DOE Office of Scientific and Technical Information (OSTI.GOV)

Swanick, Cameron W.; Castle, Katherine O.; Vedam, Sastry

Purpose: We prospectively compared computed tomography (CT)– and magnetic resonance imaging (MRI)–based high-risk clinical target volume (HR-CTV) contours at the time of brachytherapy for cervical cancer in an effort to identify patients who might benefit most from MRI-based planning. Methods and Materials: Thirty-seven patients who had undergone a pretreatment diagnostic MRI scan were included in the analysis. We delineated the HR-CTV on the brachytherapy CT and brachytherapy MRI scans independently for each patient. We then calculated the absolute volumes for each HR-CTV and the Dice coefficient of similarity (DC, a measure of spatial agreement) for the HR-CTV contours. We identifiedmore » the clinical and tumor factors associated with (1) a discrepancy in volume between the CT HR-CTV and MRI HR-CTV contours; and (2) DC. The mean values were compared using 1-way analysis of variance or paired or unpaired t tests, as appropriate. Simple and multivariable linear regression analyses were used to model the effects of covariates on the outcomes. Results: Patients with International Federation of Gynecology and Obstetrics stage IB to IVA cervical cancer were treated with intracavitary brachytherapy using tandem and ovoid (n=33) or tandem and cylinder (n=4) applicators. The mean CT HR-CTV volume (44.1 cm{sup 3}) was larger than the mean MRI HR-CTV volume (35.1 cm{sup 3}; P<.0001, paired t test). On multivariable analysis, a higher body mass index (BMI) and tumor size ≥5 cm with parametrial invasion on the MRI scan at diagnosis were associated with an increased discrepancy in volume between the HR-CTV contours (P<.02 for both). In addition, the spatial agreement (as measured by DC) between the HR-CTV contours decreased with an increasing BMI (P=.013). Conclusions: We recommend MRI-based brachytherapy planning for patients with tumors >5 cm and parametrial invasion on MRI at diagnosis and for those with a high BMI.« less

Exploring high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for metabonomic analysis of apples.

PubMed

Vermathen, Martina; Marzorati, Mattia; Vermathen, Peter

2012-01-01

Classical liquid-state high-resolution (HR) NMR spectroscopy has proved a powerful tool in the metabonomic analysis of liquid food samples like fruit juices. In this paper the application of (1)H high-resolution magic angle spinning (HR-MAS) NMR spectroscopy to apple tissue is presented probing its potential for metabonomic studies. The (1)H HR-MAS NMR spectra are discussed in terms of the chemical composition of apple tissue and compared to liquid-state NMR spectra of apple juice. Differences indicate that specific metabolic changes are induced by juice preparation. The feasibility of HR-MAS NMR-based multivariate analysis is demonstrated by a study distinguishing three different apple cultivars by principal component analysis (PCA). Preliminary results are shown from subsequent studies comparing three different cultivation methods by means of PCA and partial least squares discriminant analysis (PLS-DA) of the HR-MAS NMR data. The compounds responsible for discriminating organically grown apples are discussed. Finally, an outlook of our ongoing work is given including a longitudinal study on apples.

Predictors of in-hospital mortality amongst octogenarians undergoing emergency general surgery: a retrospective cohort study.

PubMed

Wilson, Iain; Paul Barrett, Michael; Sinha, Ashish; Chan, Shirley

2014-11-01

Elderly patients are often judged to be fit for emergency surgery based on age alone. This study identified risk factors predictive of in-hospital mortality amongst octogenarians undergoing emergency general surgery. A retrospective review of octogenarians undergoing emergency general surgery over 3 years was performed. Parametric survival analysis using Cox multivariate regression model was used to identify risk factors predictive of in-hospital mortality. Hazard ratios (HR) and corresponding 95% confidence interval were calculated. Seventy-three patients with a median age of 84 years were identified. Twenty-eight (38%) patients died post-operatively. Multivariate analysis identified ASA grade (ASA 5 HR 23.4 95% CI 2.38-230, p = 0.007) and chronic obstructive pulmonary disease (COPD) (HR 3.35 95% CI 1.15-9.69, p = 0.026) to be the only significant predictors of in-hospital mortality. Identification of high risk surgical patients should be based on physiological fitness for surgery rather than chronological age. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Mortality and its predictors among highly active antiretroviral therapy naive hiv-infected individuals: data from prospective cohort study in Ukraine.

PubMed

Zhyvytsia, D

2014-01-01

There is little information from Ukraine about the effect of Highly active antiretroviral therapy (HAART) on survival of HIV-infected patients. Our objective was to identify predictors of mortality in HIV-infected patients initiating HAART at the Zaporizhzhya AIDS Center, Ukraine. Prospective cohort study of HIV-infected patients from January 2005 to December 2008 in a Zaporizhzhya AIDS Center, and were tracked for 60 months after start HAART. Unvaried and multivariate analysis and constructed Kaplan-Meier curves to assess predictors. To identify predictors of mortality were used to build a regression Cox proportional hazards model.Two hundred and seventy two patients were studied (mean age 34 years, 42% female, median CD4 count 120 cell/μL). In 60 months of HAART 36 patients died. The probability of survival was 87%. In the univariate analysis, mortality was strongly associated with male gender (HR 6,28; 95% CI 2,22-17,78), IDU route of HIV transmission (HR 2,90; 95% CI 1,32-6,36), WHO clinical stage 4 (HR 3,45 95% CI 1,7-7,0). Mortality was also strongly associated with anemia (HR 2,24 95% CI 1,02-4,92) and HBsAg seropositivity (HR 6,26 95% CI 3,01-13,02). In the multivariate analysis independent factors associated with mortality were WHO clinical stage 4 (HR 2,66 95% CI 1,26-5,58) and HBsAg seropositivity (HR 4,35 95% CI 2,05-9,23). HAART significantly increased probability of survival and reduced the risk of death for HIV-infected patients in Ukraine. Simple clinical and laboratory data independently predict mortality and allow for risk stratification in HIV-infected patients in Ukraine.

Hormone receptors status: a strong determinant of the kinetics of brain metastases occurrence compared with HER2 status in breast cancer.

PubMed

Darlix, Amélie; Griguolo, Gaia; Thezenas, Simon; Kantelhardt, Eva; Thomssen, Christoph; Dieci, Maria Vittoria; Miglietta, Federica; Conte, PierFranco; Braccini, Antoine Laurent; Ferrero, Jean Marc; Bailleux, Caroline; Jacot, William; Guarneri, Valentina

2018-06-01

Breast cancer (BC) metastatic behavior varies according to the hormone receptors (HR) and HER2 statuses. Indeed, patients with triple-negative (TN) and HER2+ tumors are at higher risk of brain metastases (BM). The objective of this multinational cohort was to evaluate BM kinetics depending on the BC subtype. We retrospectively analyzed a series of BC patients with BM diagnosed in four European institutions (1996-2016). The delay between BC and BM diagnoses (BM-free survival) according to tumor biology was estimated with the Kaplan-Meier method. A multivariate analysis was performed using the Cox proportional hazards regression model. 649 women were included: 32.0% HER2-/HR+, 24.8% TN, 22.2% HER2+/HR- and 21.0% HER2+/HR+ tumors. Median age at BM diagnosis was 56 (25-85). In univariate analysis, BM-free survival differed depending on tumor biology: HER2-/HR+ 5.3 years (95% CI 4.6-5.9), HER2+/HR+ 4.4 years (95% CI 3.4-5.2), HER2+/HR- 2.6 years (95% CI 2.2-3.1) and TN 2.2 years (95% CI 1.9-2.7) (p < 0.001). It was significantly different between HR+ and HR- tumors (5.0 vs. 2.5 years, p < 0.001), and between HER2+ and HER2- tumors (3.2 vs. 3.8 years, p = 0.039). In multivariate analysis, estrogen-receptors (ER) and progesterone-receptors (PR) negativity, but not HER2 status, were independently associated with BM-free survival (hazard ratio = 1.36 for ER, p = 0.013, 1.31 for PR, p = 0.021, and 1.01 for HER2+ vs. HER2- tumors, p = 0.880). HR- and HER2+ tumors are overrepresented in BC patients with BM, supporting a higher risk of BM in these biological subtypes. HR status, but not HER2 status, impacts the kinetics of BM occurrence.

Meta-analysis of prognostic value of inflammation parameter in breast cancer.

PubMed

Chen, Jie; Pan, Yuqin; He, Bangshun; Ying, Houqun; Sun, Huiling; Deng, Qiwen; Liu, Xian; Wang, Shukui

2018-01-01

Recently, increasing studies investigated the association between inflammation parameter such as neutrophil to lymphocyte ratio (NLR) and the prognosis of cancers. However, the clinical and prognostic significance of NLR in breast cancer remains controversial. This meta-analysis was conducted to establish the overall accuracy of the NLR test in the diagnosis of breast cancer. A comprehensive search of the literature was conducted using PubMed and Web of Science. Six studies dating up to July 2014 with 2267 patients were enrolled in the present study. STATA 11.0 software (STATA Corporation, College Station, TX, USA) was selected for data analysis. In order to evaluate the association between NLR and overall survival (OS), disease-free survival (DFS), recurrence-free survival or cancer-specific survival, the hazard ratios (HRs), and their 95% confidence intervals (CIs) were extracted. Subgroup analyses showed that NLR was a strong prognostic factor for OS in multivariate analysis (HR = 2.81, 95% CI = 2.13-3.71, P H = 0.992) and without metastasis (HR = 1.45, 95% CI = 0.37-5.66, P H < 0.001). Elevated NLR was associated with a high risk for DFS in subgroups of multivariate analysis (HR = 2.16, 95% CI = 1.67-2.80, P H = 0.977) and mixed metastasis (HR = 2.13, 95% CI = 1.38-3.30, P H = 0.84). In summary, NLR may be considered as a predictive factor for patients with breast cancer.

Comparison between the univariate and multivariate analysis on the partial characterization of the endoglucanase produced in the solid state fermentation by Aspergillus oryzae ATCC 10124.

PubMed

de Brito, Aila Riany; Santos Reis, Nadabe Dos; Silva, Tatielle Pereira; Ferreira Bonomo, Renata Cristina; Trovatti Uetanabaro, Ana Paula; de Assis, Sandra Aparecida; da Silva, Erik Galvão Paranhos; Aguiar-Oliveira, Elizama; Oliveira, Julieta Rangel; Franco, Marcelo

2017-11-26

Endoglucanase production by Aspergillus oryzae ATCC 10124 cultivated in rice husks or peanut shells was optimized by experimental design as a function of humidity, time, and temperature. The optimum temperature for the endoglucanase activity was estimated by a univariate analysis (one factor at the time) as 50°C (rice husks) and 60°C (peanut shells), however, by a multivariate analysis (synergism of factors), it was determined a different temperature (56°C) for endoglucanase from peanut shells. For the optimum pH, values determined by univariate and multivariate analysis were 5 and 5.2 (rice husk) and 5 and 7.6 (peanut shells). In addition, the best half-lives were observed at 50°C as 22.8 hr (rice husks) and 7.3 hr (peanut shells), also, 80% of residual activities was obtained between 30 and 50°C for both substrates, and the pH stability was improved at 5-7 (rice hulls) and 6-9 (peanut shells). Both endoglucanases obtained presented different characteristics as a result of the versatility of fungi in different substrates.

Prognostic value of stromal decorin expression in patients with breast cancer: a meta-analysis.

PubMed

Li, Shuang-Jiang; Chen, Da-Li; Zhang, Wen-Biao; Shen, Cheng; Che, Guo-Wei

2015-11-01

Numbers of studies have investigated the biological functions of decorin (DCN) in oncogenesis, tumor progression, angiogenesis and metastasis. Although many of them aim to highlight the prognostic value of stromal DCN expression in breast cancer, some controversial results still exist and a consensus has not been reached until now. Therefore, our meta-analysis aims to determine the prognostic significance of stromal DCN expression in breast cancer patients. PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literatures met out inclusion criteria. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I(2) statistic were employed to estimate the level of heterogeneity across the included studies. Sensitivity analysis was conducted to further identify the possible origins of heterogeneity. The publication bias was detected by Begg's test and Egger's test. There were three English literatures (involving 6 studies) included into our meta-analysis. On the one hand, both the summarized outcomes based on univariate analysis (HR: 0.513; 95% CI: 0.406-0.648; P<0.001) and multivariate analysis (HR: 0.544; 95% CI: 0.388-0.763; P<0.001) indicated that stromal DCN expression could promise the high cancer-specific survival (CSS) of breast cancer patients. On the other hand, both the summarized outcomes based on univariate analysis (HR: 0.504; 95% CI: 0.389-0.651; P<0.001) and multivariate analysis (HR: 0.568; 95% CI: 0.400-0.806; P=0.002) also indicated that stromal DCN expression was positively associated with high disease-free survival (DFS) of breast cancer patients. No significant heterogeneity or publication bias was observed within this meta-analysis. The present evidences indicate that high stromal DCN expression can significantly predict the good prognosis in patients with breast cancer. The discoveries from our meta-analysis have better be confirmed in the updated review pooling more relevant investigations in the future.

Risk of Colchicine-Associated Myopathy in Gout: Influence of Concomitant Use of Statin.

PubMed

Kwon, Oh Chan; Hong, Seokchan; Ghang, Byeongzu; Kim, Yong-Gil; Lee, Chang-Keun; Yoo, Bin

2017-05-01

The purpose of this study was to investigate the risk of myopathy when statins are coadministered with colchicine in patients with gout. In gout patients who received colchicine with or without statin, clinical data collected included medications and history of hypertension, chronic kidney disease, and liver cirrhosis. Myopathy was defined as the presence of muscle symptoms with elevated creatine kinase or myoglobin. Multivariate analysis was performed to identify risk factors for myopathy. Inverse probability of treatment weighting (IPTW)-adjusted analysis was used to evaluate the influence of concomitant colchicine and statin use on myopathy. Of 674 patients, 486 received colchicine alone and 188 also received statin. The incidence of myopathy was not significantly higher in those on both drugs than in those on colchicine alone (2.7% vs 1.4%, P = .330). On multivariate analysis, chronic kidney disease (hazard ratio [HR] 29.056; 95% confidence interval [CI], 4.387-192.450; P <.001), liver cirrhosis (HR 10.676; 95% CI, 1.279-89.126; P = .029), higher colchicine dose (HR 20.960; 95% CI, 1.835-239.481; P = .014), and concomitant CYP3A4 inhibitor (HR 12.027; 95% CI, 2.743-52.725; P = .001) were associated with increased risk of myopathy. Concomitant use of statins, however, was not, even after adjusting for confounders (HR 1.123; 95% CI, 0.262-4.814; P = .875; IPTW-adjusted HR 0.321; 95% CI, 0.077-1.345; P = .120). Concomitant use of statin and colchicine was not associated with increased risk of myopathy. Thus, concomitant use of statin with colchicine seems to be safe from myotoxicity in gout patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Determination of the impact of melanoma surgical timing on survival using the National Cancer Database.

PubMed

Conic, Ruzica Z; Cabrera, Claudia I; Khorana, Alok A; Gastman, Brian R

2018-01-01

The ideal timing for melanoma treatment, predominantly surgery, remains undetermined. Patient concern for receiving immediate treatment often exceeds surgeon or hospital availability, requiring establishment of a safe window for melanoma surgery. To assess the impact of time to definitive melanoma surgery on overall survival. Patients with stage I to III cutaneous melanoma and with available time to definitive surgery and overall survival were identified by using the National Cancer Database (N = 153,218). The t test and chi-square test were used to compare variables. Cox regression was used for multivariate analysis. In a multivariate analysis of patients in all stages who were treated between 90 and 119 days after biopsy (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.01-1.18) and more than 119 days (HR, 1.12; 95% CI, 1.02-1.22) had a higher risk for mortality compared with those treated within 30 days of biopsy. In a subgroup analysis of stage I, higher mortality risk was found in patients treated within 30 to 59 days (HR, 1.05; 95% CI, 1.01-1.1), 60 to 89 days (HR, 1.16; 95% CI, 1.07-1.25), 90 to 119 days (HR, 1.29; 95% CI, 1.12-1.48), and more than 119 days after biopsy (HR, 1.41; 95% CI, 1.21-1.65). Surgical timing did not affect survival in stages II and III. Melanoma-specific survival was not available. Expeditious treatment of stage I melanoma is associated with improved outcomes. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Obesity-associated metabolic changes influence resting and peak heart rate in women and men.

PubMed

Strandheim, Astrid; Halland, Hilde; Saeed, Sahrai; Cramariuc, Dana; Hetland, Trude; Lønnebakken, Mai Tone; Gerdts, Eva

2015-01-01

To study the relationship between obesity and heart rate (HR) in women and men. We studied 241 overweight and obese subjects without known heart disease. All subjects underwent ergospirometry during maximal exercise testing on treadmill and recording of body composition, electrocardiogram and clinic and ambulatory blood pressure. Women (n = 132) were slightly older and had higher fat mass, but lower weight, blood pressure and prevalence of metabolic syndrome (MetS) than men (n = 109) (all p < 0.05), while prevalences of obesity and hypertension did not differ. A significant interaction between sex and HR was demonstrated (p < 0.05). In multivariate analysis, female sex (β = 0.99, p < 0.01) predicted higher resting HR independent of confounders. Higher resting HR was particularly associated with presence of MetS, hypertension, higher insulin resistance and lower relative muscle mass in men (all p < 0.05). Female sex also predicted higher peak exercise HR (β = 0.48, p < 0.01) independent of confounders. Higher peak exercise HR was particularly associated with higher exercise capacity and lower age and self-reported physical activity in men, while lower HbA1c and absence of obesity were the main covariates in women in multivariate analyses (all p < 0.05). In our study population, obesity and obesity-associated metabolic changes influenced both resting and peak exercise HR.

Impact of heart rate in atrial fibrillation versus sinus rhythm on mortality in octogenarian patients with acute coronary syndrome.

PubMed

Li, Shijun; Barywani, Salim; Fu, Michael

2017-01-01

Association of heart rate (HR) with mortality in patients with acute coronary syndrome (ACS) and aged ≥ 80 years are underrepresented in clinical trials. We therefore aimed to investigate the association of HR in atrial fibrillation (AF) versus sinus rhythm (SR) with all-cause mortality in octogenarian patients with ACS. A total of 336 patients with ACS patients and aged ≥ 80 years were enrolled into the current study. The end point of interest was death from any cause. Association of HR in AF versus SR with mortality was analyzed by Kaplan-Meier curve following log-rank test and multivariable Cox regression analysis. In total, 63 (87.5%) of patients with AF were dead and 147 (59.8%) of patients with SR were dead during the follow-up period. The best cut-off was 80 bpm, with a sensitivity of 62% and specificity of 66%. HR ≤ 80 bpm in SR but not in AF was associated with better outcome as compared with HR > 80 bpm (Chi-Square = 26.55, Log rank P < 0.001). In SR subgroup, the hazard ratios of HR ≤ 80 bpm were 0.51(95% CI 0.37-0.70, P < 0.001) adjusted for age, 0.46 (95%CI 0.33-0.63, P < 0.001) adjusted for gender, 0.62 (95%CI 0.42- 0.93, P = 0.020) adjusted for multivariables respectively. In AF subgroup, the hazard ratios of HR ≤ 80 bpm were 0.83(95% CI 0.49-1.38, P = 0.464) adjusted for age, 0.96 (95%CI 0.59-1.58, P = 0.882) adjusted for gender, 0.72(95% CI 0.41-1.26, P = 0.249) adjusted for multivariables respectively. The current study demonstrates that heart rate is an independent prognostic predictor for all-cause mortality, and HR ≤ 80 bpm is associated with improved outcome in SR but not in AF in octogenarian patients with ACS.

Pre-operative risk factors of bleeding and stroke during left ventricular assist device support: an analysis of more than 900 HeartMate II outpatients.

PubMed

Boyle, Andrew J; Jorde, Ulrich P; Sun, Benjamin; Park, Soon J; Milano, Carmelo A; Frazier, O Howard; Sundareswaran, Kartik S; Farrar, David J; Russell, Stuart D

2014-03-11

This study sought to determine the pre-operative risk factors related to late bleeding, stroke, and pump thrombosis in patients with HeartMate II (HMII) left ventricular assist devices (LVADs) (Thoratec Corporation, Pleasanton, California) that might influence tailored improvements in patient management. Adverse events in LVAD patients remain high. It is unclear whether pre-operative characteristics influence the likelihood of the development of post-operative hemorrhagic or thrombotic complications. Knowing which patients are at greater risk might assist in tailoring anticoagulation therapy for certain patients. Advanced heart failure patients (n = 956) discharged from the hospital after LVAD implantation in the HMII bridge to transplantation (n = 405) and destination therapy (n = 551) clinical trials were retrospectively evaluated. Bleeding requiring surgery or transfusion of >2 U of packed red blood cells, stroke (hemorrhagic and ischemic), and pump thrombosis were tracked from hospital discharge until patient outcome. Adverse event rates for post-discharge bleeding (0.67 events/patient-year) were higher than those for hemorrhagic stroke (0.05), ischemic stroke (0.04), and pump thrombosis (0.03). The main sites of bleeding included gastrointestinal (45% of events), wound (12%), and epistaxis (4%). Older age (>65 years) (hazard ratio [HR]: 1.31), lower pre-operative hematocrit (≤31%) (HR: 1.31), ischemic etiology (HR: 1.35), and female (HR: 1.45) were statistically significant multivariable risk factors for bleeding. Female (HR: 1.92) and 65 years of age and younger (HR: 1.94) were multivariable risk factors for hemorrhagic stroke, whereas female (HR: 1.84) and history of diabetes (HR: 1.99) were risk factors for ischemic stroke. Female (HR: 1.90) and higher body mass index (HR: 1.71/10 kg/m(2) increase) were also multivariable risk factors for pump thrombosis. The risk of bleeding and thrombotic events during LVAD support differs by patient demographics, including sex, age, body mass index, and etiology of heart failure. Further studies should focus on the potential of tailored anticoagulation strategies in these subgroups. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer.

PubMed

Ramsey, Sara; Lamb, Gavin W A; Aitchison, Michael; Graham, John; McMillan, Donald C

2007-01-15

Recently, it was shown that an inflammation-based prognostic score, the Glasgow Prognostic Score (GPS), provides additional prognostic information in patients with advanced cancer. The objective of the current study was to examine the value of the GPS compared with established scoring systems in predicting cancer-specific survival in patients with metastatic renal cancer. One hundred nineteen patients who underwent immunotherapy for metastatic renal cancer were recruited. The Memorial Sloan-Kettering Cancer Center (MSKCC) score and the Metastatic Renal Carcinoma Comprehensive Prognostic System (MRCCPS) score were calculated as described previously. Patients who had both an elevated C-reactive protein level (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients who had only 1 of those 2 biochemical abnormalities were allocated a GPS of 1. Patients who had neither abnormality were allocated a GPS of 0. On multivariate analysis of significant individual factors, only calcium (hazard ratio [HR], 3.21; 95% confidence interval [95% CI], 1.51-6.83; P = .002), white cell count (HR, 1.66; 95% CI, 1.17-2.35; P = .004), albumin (HR, 2.63; 95% CI, 1.38-5.03; P = .003), and C-reactive protein (HR, 2.85; 95% CI; 1.49-5.45; P = .002) were associated independently with cancer-specific survival. On multivariate analysis of the different scoring systems, the MSKCC (HR, 1.88; 95% CI, 1.22-2.88; P = .004), the MRCCPS (HR, 1.42; 95% CI, 0.97-2.09; P = .071), and the GPS (HR, 2.35; 95% CI, 1.51-3.67; P < .001) were associated independently with cancer-specific survival. An inflammation-based prognostic score (GPS) predicted survival independent of established scoring systems in patients with metastatic renal cancer.

HR-MAS MR Spectroscopy of Breast Cancer Tissue Obtained with Core Needle Biopsy: Correlation with Prognostic Factors

PubMed Central

Choi, Ji Soo; Baek, Hyeon-Man; Kim, Suhkmann; Kim, Min Jung; Youk, Ji Hyun; Moon, Hee Jung; Kim, Eun-Kyung; Han, Kyung Hwa; Kim, Dong-hyun; Kim, Seung Il; Koo, Ja Seung

2012-01-01

The purpose of this study was to examine the correlation between high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy using core needle biopsy (CNB) specimens and histologic prognostic factors currently used in breast cancer patients. After institutional review board approval and informed consent were obtained for this study, CNB specimens were collected from 36 malignant lesions in 34 patients. Concentrations and metabolic ratios of various choline metabolites were estimated by HR-MAS MR spectroscopy using CNB specimens. HR-MAS spectroscopic values were compared according to histopathologic variables [tumor size, lymph node metastasis, histologic grade, status of estrogens receptor (ER), progesterone receptor (PR), HER2 (a receptor for human epidermal growth factor), and Ki-67, and triple negativity]. Multivariate analysis was performed with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA). HR-MAS MR spectroscopy quantified and discriminated choline metabolites in all CNB specimens of the 36 breast cancers. Several metabolite markers [free choline (Cho), phosphocholine (PC), creatine (Cr), taurine, myo-inositol, scyllo-inositol, total choline (tCho), glycine, Cho/Cr, tCho/Cr, PC/Cr] on HR-MAS MR spectroscopy were found to correlate with histologic prognostic factors [ER, PR, HER2, histologic grade, triple negativity, Ki-67, poor prognosis]. OPLS-DA multivariate models were generally able to discriminate the status of histologic prognostic factors (ER, PR, HER2, Ki-67) and prognosis groups. Our study suggests that HR-MAS MR spectroscopy using CNB specimens can predict tumor aggressiveness prior to surgery in breast cancer patients. In addition, it may be helpful in the detection of reliable markers for breast cancer characterization. PMID:23272149

Colorectal specialization and survival in colorectal cancer.

PubMed

Hall, G M; Shanmugan, S; Bleier, J I S; Jeganathan, A N; Epstein, A J; Paulson, E C

2016-02-01

It is recognized that higher surgeon volume is associated with improved survival in colorectal cancer. However, there is a paucity of national studies that have evaluated the relationship between surgical specialization and survival. We used the Surveillance, Epidemiology, and End Results Medicare cancer registry to examine the association between colorectal specialization (CRS) and disease-specific survival (DSS) between 2001 and 2009. A total of 21,432 colon cancer and 5893 rectal cancer patients who underwent elective surgical resection between 2001 and 2009 were evaluated. Univariate and multivariate Cox survival analysis was used to identify the association between surgical specialization and cancer-specific survival. Colorectal specialists performed 16.3% of the colon and 27% of the rectal resections. On univariate analysis, specialization was associated with improved survival in Stage II and Stage III colon cancer and Stage II rectal cancer. In multivariate analysis, however, CRS was associated with significantly improved DSS only in Stage II rectal cancer [hazard ratio (HR) 0.70, P = 0.03]. CRS was not significantly associated with DSS in either Stage I (colon HR 1.14, P = 0.39; rectal HR 0.1.26, P = 0.23) or Stage III (colon HR 1.06, P = 0.52; rectal HR 1.08, P = 0.55) disease. When analysis was limited to high volume surgeons only, the relationship between CRS and DSS was unchanged. CRS is associated with improved DSS following resection of Stage II rectal cancer. A combination of factors may contribute to long-term survival in these patients, including appropriate surgical technique, multidisciplinary treatment decisions and guideline-adherent surveillance. CRS probably contributes positively to these factors resulting in improved survival. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

p-Akt as a potential poor prognostic factor for gastric cancer: a systematic review and meta-analysis.

PubMed

Cao, Fang; Zhang, Cong; Han, Wei; Gao, Xiao-Jiao; Ma, Jun; Hu, Yong-Wei; Gu, Xing; Ding, Hou-Zhong; Zhu, Li-Xia; Liu, Qin

2017-08-29

To understand the relationship between p-Akt expression and the prognosis of patients with gastric cancer, we searched six databases, Pubmed, EMBASE, Cochrane Library, CNKI, Wanfang and CBM for relevant articles in order to conduct this metaanalysis. The pooled hazard ratios and corresponding 95%CI of overall survival were calculated to evaluate the prognostic value of p-Akt expression in patients with gastric cancer. With 2261 patients combined from 13 available studies, the pooled HR showed a poor prognosis in patients with gastric cancer in the univariate analysis (HR=1.88, 95%CI:1.45-2.43, P<0.00001), and the group "univariate analysis+estimate" (HR=1.41, 95%CI: 1.01-1.97, P=0.04), but not in multivariate analysis (HR=0.66, 95%CI: 0.29-1.52, P=0.33) and estimate (HR=1.13, 95%CI: 0.65-1.95, P=0.67). In conclusion, our results indicated that p-Akt was likely to be an indicator of poor prognosis in patients with gastric cancer.

Effect of HCV, HIV and coinfection in kidney transplant recipients: mate kidney analyses.

PubMed

Xia, Y; Friedmann, P; Yaffe, H; Phair, J; Gupta, A; Kayler, L K

2014-09-01

Reports of kidney transplantation (KTX) in recipients with hepatitis C virus (HCV+), human immunodeficiency virus (HIV+) or coinfection often do not provide adequate adjustment for donor risk factors. We evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one kidney was transplanted into a patient with viral infection (HCV+, n = 1700; HIV+, n = 243) and the other transplanted into a recipient without infection (HCV- n = 1700; HIV- n = 243) using Scientific Registry of Transplant Recipients data between 2000 and 2013. On multivariable analysis (adjusted for recipient risk factors), HCV+ conferred increased risks of death-censored graft survival (DCGS) (adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.04-1.47) and patient survival (aHR 1.24, 95% CI 1.06-1.45) compared with HCV-. HIV+ conferred similar DCGS (aHR 0.85, 95% CI 0.48-1.51) and patient survival (aHR 0.80, 95% CI 0.39-1.64) compared with HIV-. HCV coinfection was a significant independent risk factor for DCGS (aHR 2.33; 95% CI 1.06, 5.12) and patient survival (aHR 2.88; 95% CI 1.35, 6.12). On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection. Whereas KTX in HIV+ recipients were associated with similar outcomes relative to noninfected recipients, HCV monoinfection and, to a greater extent, coinfection were associated with poor patient and graft survival. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Stereotactic Body Radiation Therapy and the Influence of Chemotherapy on Overall Survival for Large (≥5 Centimeter) Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verma, Vivek; McMillan, Matthew T.; Grover, Surbhi

2017-01-01

Purpose: Stereotactic body radiation therapy (SBRT) for ≥5 cm lesions is poorly defined, largely owing to the low sample sizes in existing studies. The present analysis examined the SBRT outcomes and assessed the effect of chemotherapy in this population. Methods and Materials: The National Cancer Data Base was queried for primary non-small cell lung cancer ≥5 cm treated with SBRT (≤10 fractions). Patient, tumor, and treatment parameters were extracted. The primary outcome was overall survival (OS). Statistical methods involved Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. Results: From 2004 to 2012, data from 201 patients were analyzed. The median follow-upmore » was 41.1 months. The median tumor size was 5.5 cm (interquartile range 5.0-6.0), with cT2a, cT2b, and cT3 disease in 24.9%, 53.2%, and 21.9%, respectively. The median total SBRT dose and fractionation was 50 Gy in 4 fractions, and 92.5% of the patients underwent SBRT with ≤5 fractions. The median OS was 25.1 months. Of the 201 patients, 15% received chemotherapy. The receipt of chemotherapy was associated with longer OS (median 30.6 vs 23.4 months; P=.027). On multivariable analysis, worse OS was seen with increasing age (hazard ratio [HR] 1.03; P=.012), poorly differentiated tumors (HR 2.06; P=.049), and T3 classification (HR 2.13; P=.005). On multivariable analysis, chemotherapy remained independently associated with improved OS (HR 0.57; P=.039). Conclusions: SBRT has utility in the setting of tumors ≥5 cm, with chemotherapy associated with improved OS in this subset. These hypothesis-generating data now raise the necessity of performing prospective analyses to determine whether chemotherapy confers outcome benefits after SBRT.« less

Effect of membrane flux and dialyzer biocompatibility on survival in end-stage diabetic nephropathy.

PubMed

Götz, Angela K; Böger, Carsten A; Popal, Massoud; Banas, Bernhard; Krämer, Bernhard K

2008-01-01

We examined the effects of dialyzer membrane flux and biocompatibility on mortality in diabetic dialysis patients. We enrolled 402 prevalent chronic hemodialysis patients from 30 centers in Germany in 1999 for a prospective observational study until 2003. We compared 2 groups in post hoc analysis: high-flux (HF, n = 166) versus low-flux (LF, n = 236) membrane, and high biocompatibility (HB, n = 300) versus low biocompatibility (LB, n = 102). All-cause mortality (ACM) was the primary endpoint. Death causes were the secondary endpoints. Multivariate Cox regression analysis showed no significant difference in risk for ACM with respect to flux (hazard ratio, HR, 0.79; p = 0.08; ACM 63% in HF vs. 70% in LF dialysis) and biocompatibility level (HR 1.00; p = 0.98; ACM 67% for HB vs. 66% for LB). The multivariate analysis of different causes of death did not reveal any outcome differences dependent on flux and biocompatibility level apart from a slightly better cumulative survival regarding the death cause 'infectious' in our HF dialysis group (HR 0.48; p = 0.07, Kaplan-Meier analysis p = 0.03). Our data indicate that mortality of hemodialysis patients with type-2 diabetic nephropathy is influenced neither by dialyzer flux level nor by biocompatibility. Copyright 2008 S. Karger AG, Basel.

Prospective analysis of body mass index, physical activity and colorectal cancer risk associated with β-catenin (CTNNB1) status

PubMed Central

Morikawa, Teppei; Kuchiba, Aya; Lochhead, Paul; Nishihara, Reiko; Yamauchi, Mai; Imamura, Yu; Liao, Xiaoyun; Qian, Zhi Rong; Ng, Kimmie; Chan, Andrew T.; Meyerhardt, Jeffrey A.; Giovannucci, Edward; Fuchs, Charles S.; Ogino, Shuji

2013-01-01

Dysregulation of the WNT/β-catenin (CTNNB1) signaling pathway is implicated in colorectal carcinoma and metabolic diseases. Considering these roles and cancer prevention, we hypothesized that tumor CTNNB1 status might influence cellular sensitivity to obesity and physical activity. In clinical follow-up of 109,046 women in the Nurses' Health Study and 47,684 men in the Health Professionals Follow-up Study, there were 861 incident rectal and colon cancers with tissue immunohistochemistry data on nuclear CTNNB1 expression. Using this molecular pathological epidemiology database, we performed Cox proportional hazards regression analysis using data duplication method to assess differential associations of body mass index (BMI) or exercise activity with colorectal cancer risk according to tumor CTNNB1 status. Greater BMI was associated with a significantly higher risk of CTNNB1-negative cancer [multivariate hazard ratio (HR) =1.34; 95% confidence interval (CI), 1.18–1.53 for 5.0 kg/m2 increment; Ptrend=0.0001], but not with CTNNB1-positive cancer risk (multivariate HR =1.07; 95% CI, 0.92–1.25 for 5.0 kg/m2 increment; Ptrend=0.36; Pheterogeneity=0.027, between CTNNB1-negative and CTNNB1-positive cancer risks). Physical activity level was associated with a lower risk of CTNNB1-negative cancer (multivariate HR =0.93; 95% CI, 0.87–1.00 for 10 MET-hours/week increment; Ptrend=0.044), but not with CTNNB1-positive cancer risk (multivariate HR =0.98; 95% CI, 0.91–1.05 for 10 MET-hours/week increment; Ptrend=0.60). Our findings argue that obesity and physical inactivity are associated with a higher risk of CTNNB1-negative colorectal cancer, but not with CTNNB1-positive cancer risk. Further, they suggest that energy balance and metabolism status exerts its effect in a specific carcinogenesis pathway that is less likely dependent on WNT/CTNNB1 activation. PMID:23442321

Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer.

PubMed

Shigeta, Keisuke; Kosaka, Takeo; Yazawa, Satoshi; Yasumizu, Yota; Mizuno, Ryuichi; Nagata, Hirohiko; Shinoda, Kazunobu; Morita, Shinya; Miyajima, Akira; Kikuchi, Eiji; Nakagawa, Ken; Hasegawa, Shintaro; Oya, Mototsugu

2015-06-01

The aim of this study is to identify factors that increase the occurrence of severe neutropenia (SN) and febrile neutropenia (FN) during docetaxel treatment for castration-resistant prostate cancer (CRPC). We retrospectively reviewed 258 courses during the first three cycles among 95 patients. Docetaxel at a dose of 75 mg/m(2) was administered every 3 or 4 weeks. Patient background, laboratory data, and bone scan results were collected to assess predictive factors for SN and FN. We defined SN as an absolute neutrophil count (ANC) of <500/mm(3) and defined FN as an ANC of <1000/mm(3) with a body temperature of >38.3 °C. The mean age of the patients was 72.6 ± 6.4 years and the mean prostate-specific antigen was 135.4 ± 290.9 ng/ml. During the first three courses of treatment, SN occurred in 72.6% of patients and FN occurred in 9.5 % of patients. Univariate analysis demonstrated that age ≥ 75 years (p = 0.002), number of comorbidities ≥ 1.2 (p = 0.008 and p = 0.006) and previous external beam radiation therapy (EBRT) (p = 0.001) were predictive factors for the development of SN or FN. In multivariate analysis, significant predictors of SN or FN were age ≥ 75 years (hazard ratio [HR] 5.77; p = 0.004) and previous EBRT (HR 14.5; p = 0.012). According to the subgroup analysis dividing SN and FN separately, multivariate analysis also revealed that age ≥ 75 years and previous EBRT were also significant predictors for developing SN (HR 5.09; p = 0.023, HR 12.7; p = 0.020, respectively) and for developing FN (HR 5.45; p = 0.042, HR 7.72; p = 0.015, respectively). Patients aged ≥ 75 years and with a history of localized radiation therapy are at higher risk for significant neutropenic events and require closer surveillance.

Survival analysis of platinum-refractory patients with advanced esophageal cancer treated with docetaxel or best supportive care alone: a retrospective study.

PubMed

Moriwaki, T; Kajiwara, T; Matsumoto, T; Suzuki, H; Hiroshima, Y; Matsuda, K; Hirai, S; Yamamoto, Y; Yamada, T; Sugaya, A; Kobayashi, M; Endo, S; Ishige, K; Nishina, T; Hyodo, I

2014-01-01

The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC. © 2014 International Society for Diseases of the Esophagus.

The Cancer of the Prostate Risk Assessment (CAPRA) score predicts biochemical recurrence in intermediate-risk prostate cancer treated with external beam radiotherapy (EBRT) dose escalation or low-dose rate (LDR) brachytherapy.

PubMed

Krishnan, Vimal; Delouya, Guila; Bahary, Jean-Paul; Larrivée, Sandra; Taussky, Daniel

2014-12-01

To study the prognostic value of the University of California, San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score to predict biochemical failure (bF) after various doses of external beam radiotherapy (EBRT) and/or permanent seed low-dose rate (LDR) prostate brachytherapy (PB). We retrospectively analysed 345 patients with intermediate-risk prostate cancer, with PSA levels of 10-20 ng/mL and/or Gleason 7 including 244 EBRT patients (70.2-79.2 Gy) and 101 patients treated with LDR PB. The minimum follow-up was 3 years. No patient received primary androgen-deprivation therapy. bF was defined according to the Phoenix definition. Cox regression analysis was used to estimate the differences between CAPRA groups. The overall bF rate was 13% (45/345). The CAPRA score, as a continuous variable, was statistically significant in multivariate analysis for predicting bF (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.10-1.72, P = 0.006). There was a trend for a lower bF rate in patients treated with LDR PB when compared with those treated by EBRT ≤ 74 Gy (HR 0.234, 95% CI 0.05-1.03, P = 0.055) in multivariate analysis. In the subgroup of patients with a CAPRA score of 3-5, CAPRA remained predictive of bF as a continuous variable (HR 1.51, 95% CI 1.01-2.27, P = 0.047) in multivariate analysis. The CAPRA score is useful for predicting biochemical recurrence in patients treated for intermediate-risk prostate cancer with EBRT or LDR PB. It could help in treatment decisions. © 2013 The Authors. BJU International © 2013 BJU International.

The risk of carotid stenosis in head and neck cancer patients after radiation therapy.

PubMed

Carpenter, David J; Mowery, Yvonne M; Broadwater, Gloria; Rodrigues, Anna; Wisdom, Amy J; Dorth, Jennifer A; Patel, Pretesh R; Shortell, Cynthia K; Clough, Robert; Brizel, David M

2018-05-01

Head and neck radiotherapy (RT) is a risk factor for cerebrovascular disease. We performed a retrospective cohort study to evaluate carotid artery stenosis (CAS) incidence in head and neck cancer (HNC) patients undergoing RT, characterizing associated risk factors. Records were retrospectively reviewed for HNC patients undergoing carotid ultrasound screening after definitive or adjuvant RT between January 2000 and May 2016. CAS was defined as ≥50% stenosis on imaging, stroke, or transient ischemic attack. Actuarial CAS rates were calculated by Kaplan-Meier method. Univariate and multivariate analyses predicted CAS risk based on carotid dosimetric and clinical parameters. 366 patients met inclusion criteria. Median time from RT completion to last follow-up was 4.1 yr. Actuarial risk for CAS was 29% (95% CI 22-36%) at 8 years. Univariate analysis showed that smoking (HR 1.7; 95% CI 1.1-2.7), hyperlipidemia (HR 1.6; 95% CI 1.03-2.6), diabetes (HR 2.8; 95% CI 1.6-4.8), coronary artery disease (HR 2.4; 95% CI 1.4-4.2), and peripheral artery disease (HR 3.6; 95% CI 1.1-11.6) were significantly associated with increased CAS. In multivariate analysis, diabetes was predictive of time to CAS (HR 1.9; 95% CI 1.1-3.4). Carotid dose parameters were not significantly associated with CAS. CAS incidence is high after head and neck radiotherapy, gradually rising over time. No clear dose-response effect between carotid dose and CAS was identified for HNC patients. Carotid artery screening and preventative strategies should be employed in this high-risk patient population. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early and late mortality of spontaneous hemorrhagic transformation of ischemic stroke.

PubMed

D'Amelio, Marco; Terruso, Valeria; Famoso, Giorgia; Di Benedetto, Norma; Realmuto, Sabrina; Valentino, Francesca; Ragonese, Paolo; Savettieri, Giovanni; Aridon, Paolo

2014-04-01

Hemorrhagic transformation (HT), a complication of ischemic stroke (IS), might influence patient's prognosis. Our aim is to evaluate, in a hospital-based series of patients not treated with thrombolysis, the relationship between HT and mortality. We compared mortality of individuals with spontaneous HT with that of individuals without. Medical records of patients diagnosed with anterior IS were retrospectively reviewed. Outcome measures were 30- and 90-day survival after IS onset. Kaplan-Meier estimates were used to construct survival curves. Cox proportional hazards model was used to estimate hazard ratio (HR) for the main outcome measure (death). HT was stratified in hemorrhagic infarction and parenchymal hematoma (PH). We also evaluated the relationship between HT and the main mortality risk factors (gender, age, premorbid status, severity of stroke, and radiological features). Thirty days from stroke onset, 8.1% (19 of 233) of patients died. At multivariate analysis, PH (HR: 7.7, 95% confidence interval [CI]: 2.1, 27.8) and low level of consciousness at admission (HR: 5.0, 95% CI: 1.3, 18.6) were significantly associated with death. At 3-month follow-up, mortality rate was 12.1% (28 of 232). At multivariate analysis, large infarct size (HR: 2.7, 95% CI: 1.2, 6.0) and HT (HR: 2.3, 95% CI: 1.0, 5.4) were independent risk factors for mortality. Parenchymal hematoma was, however, the strongest predictor of late mortality (HR: 7.9, 95% CI: 2.9, 21.4). Neurological status and infarct size play a significant role, respectively, in early and late mortality after IS. Parenchymal hematoma independently predicts both early and late mortality. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Association of High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT) bone microarchitectural parameters with previous clinical fracture in older men: The Osteoporotic Fractures in Men (MrOS) study.

PubMed

Fink, Howard A; Langsetmo, Lisa; Vo, Tien N; Orwoll, Eric S; Schousboe, John T; Ensrud, Kristine E

2018-05-08

High-resolution peripheral quantitative computed tomography (HR-pQCT) assesses both volumetric bone mineral density (vBMD) and trabecular and cortical microarchitecture. However, studies of the association of HR-pQCT parameters with fracture history have been small, predominantly limited to postmenopausal women, often performed limited adjustment for potential confounders including for BMD, and infrequently assessed strength or failure measures. We used data from the Osteoporotic Fractures in Men (MrOS) study, a prospective cohort study of community-dwelling men aged ≥65 years, to evaluate the association of distal radius, proximal (diaphyseal) tibia and distal tibia HR-pQCT parameters measured at the Year 14 (Y14) study visit with prior clinical fracture. The primary HR-pQCT exposure variables were finite element analysis estimated failure loads (EFL) for each skeletal site; secondary exposure variables were total vBMD, total bone area, trabecular vBMD, trabecular bone area, trabecular thickness, trabecular number, cortical vBMD, cortical bone area, cortical thickness, and cortical porosity. Clinical fractures were ascertained from questionnaires administered every 4 months between MrOS study baseline and the Y14 visit and centrally adjudicated by masked review of radiographic reports. We used multivariate-adjusted logistic regression to estimate the odds of prior clinical fracture per 1 SD decrement for each Y14 HR-pQCT parameter. Three hundred forty-four (19.2%) of the 1794 men with available HR-pQCT measures had a confirmed clinical fracture between baseline and Y14. After multivariable adjustment, including for total hip areal BMD, decreased HR-pQCT finite element analysis EFL for each site was associated with significantly greater odds of prior confirmed clinical fracture and major osteoporotic fracture. Among other HR-pQCT parameters, decreased cortical area appeared to have the strongest independent association with prior clinical fracture. Future studies should explore associations of HR-pQCT parameters with specific fracture types and risk of incident fractures and the impact of age and sex on these relationships. Published by Elsevier Inc.

CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence.

PubMed

Kurnit, Katherine C; Kim, Grace N; Fellman, Bryan M; Urbauer, Diana L; Mills, Gordon B; Zhang, Wei; Broaddus, Russell R

2017-07-01

Although the majority of low grade, early stage endometrial cancer patients will have good survival outcomes with surgery alone, those patients who do recur tend to do poorly. Optimal identification of the subset of patients who are at high risk of recurrence and would benefit from adjuvant treatment has been difficult. The purpose of this study was to evaluate the impact of somatic tumor mutation on survival outcomes in this patient population. For this study, low grade was defined as endometrioid FIGO grades 1 or 2, while early stage was defined as endometrioid stages I or II (disease confined to the uterus). Next-generation sequencing was performed using panels comprised of 46-200 genes. Recurrence-free and overall survival was compared across gene mutational status in both univariate and multivariate analyses. In all, 342 patients were identified, 245 of which had endometrioid histology. For grades 1-2, stages I-II endometrioid endometrial cancer patients, age (HR 1.07, 95% CI 1.03-1.10), CTNNB1 mutation (HR 5.97, 95% CI 2.69-13.21), and TP53 mutation (HR 4.07, 95% CI 1.57-10.54) were associated with worse recurrence-free survival on multivariate analysis. When considering endometrioid tumors of all grades and stages, CTNNB1 mutant tumors were associated with significantly higher rates of grades 1-2 disease, lower rates of deep myometrial invasion, and lower rates of lymphatic/vascular space invasion. When both TP53 and CTNNB1 mutations were considered, presence of either TP53 mutation or CTNNB1 mutation remained a statistically significant predictor of recurrence-free survival on multivariate analysis and was associated with a more precise confidence interval (HR 4.69, 95% CI 2.38-9.24). Thus, mutational analysis of a 2 gene panel of CTNNB1 and TP53 can help to identify a subset of low grade, early stage endometrial cancer patients who are at high risk of recurrence.

Outcome and prognostic factors in patients with brain metastases from small-cell lung cancer treated with whole brain radiotherapy.

PubMed

Bernhardt, Denise; Adeberg, Sebastian; Bozorgmehr, Farastuk; Opfermann, Nils; Hoerner-Rieber, Juliane; König, Laila; Kappes, Jutta; Thomas, Michael; Herth, Felix; Heußel, Claus Peter; Warth, Arne; Debus, Jürgen; Steins, Martin; Rieken, Stefan

2017-08-01

The purpose of this study was to evaluate prognostic factors associated with overall survival (OS) and neurological progression free survival (nPFS) in small-cell lung cancer (SCLC) patients with brain metastases who received whole-brain radiotherapy (WBRT). From 2003 to 2015, 229 SCLC patients diagnosed with brain metastases who received WBRT were analyzed retrospectively. In this cohort 219 patients (95%) received a total photon dose of 30 Gy in 10 fractions. The prognostic factors evaluated for OS and nPFS were: age, Karnofsky Performance Status (KPS), number of brain metastases, synchronous versus metachronous disease, initial response to chemotherapy, the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class and thoracic radiation. Median OS after WBRT was 6 months and the median nPFS after WBRT was 11 months. Patients with synchronous cerebral metastases had a significantly better median OS with 8 months compared to patients with metachronous metastases with a median survival of 3 months (p < 0.0001; HR 0.46; 95% CI 0.31-0.67). Based on RPA classification median survival after WBRT was 17 months in RPA class I, 7 months in class II and 3 months in class III (p < 0.0001). Karnofsky performance status scale (KPS < 70%) was significantly associated with OS in both univariate (HR 2.84; p < 0.001) and multivariate analyses (HR 2.56; p = 0.011). Further, metachronous brain metastases (HR 1.8; p < 0.001), initial response to first-line chemotherapy (HR 0.51, p < 0.001) and RPA class III (HR 2.74; p < 0.001) were significantly associated with OS in univariate analysis. In multivariate analysis metachronous disease (HR 1.89; p < 0.001) and initial response to chemotherapy (HR 0.61; p < 0.001) were further identified as significant prognostic factors. NPFS was negatively significantly influenced by poor KPS (HR 2.56; p = 0.011), higher number of brain metastases (HR 1.97; p = 0.02), and higher RPA class (HR 2.26; p = 0.03) in univariate analysis. In this series, the main prognostic factors associated with OS were performance status, time of appearance of intracranial disease (synchronous vs. metachronous), initial response to chemotherapy and higher RPA class. NPFS was negatively influenced by poor KPS, multiplicity of brain metastases, and higher RPA class in univariate analysis. For patients with low performance status, metachronous disease or RPA class III, WBRT should be weighed against supportive therapy with steroids alone or palliative chemotherapy.

Impact of heart rate in atrial fibrillation versus sinus rhythm on mortality in octogenarian patients with acute coronary syndrome

PubMed Central

Li, Shijun; Barywani, Salim; Fu, Michael

2017-01-01

Introduction Association of heart rate (HR) with mortality in patients with acute coronary syndrome (ACS) and aged ≥ 80 years are underrepresented in clinical trials. We therefore aimed to investigate the association of HR in atrial fibrillation (AF) versus sinus rhythm (SR) with all-cause mortality in octogenarian patients with ACS. Methods A total of 336 patients with ACS patients and aged ≥ 80 years were enrolled into the current study. The end point of interest was death from any cause. Association of HR in AF versus SR with mortality was analyzed by Kaplan-Meier curve following log-rank test and multivariable Cox regression analysis. Results In total, 63 (87.5%) of patients with AF were dead and 147 (59.8%) of patients with SR were dead during the follow-up period. The best cut-off was 80 bpm, with a sensitivity of 62% and specificity of 66%. HR ≤ 80 bpm in SR but not in AF was associated with better outcome as compared with HR > 80 bpm (Chi-Square = 26.55, Log rank P < 0.001). In SR subgroup, the hazard ratios of HR ≤ 80 bpm were 0.51(95% CI 0.37-0.70, P < 0.001) adjusted for age, 0.46 (95%CI 0.33-0.63, P < 0.001) adjusted for gender, 0.62 (95%CI 0.42- 0.93, P = 0.020) adjusted for multivariables respectively. In AF subgroup, the hazard ratios of HR ≤ 80 bpm were 0.83(95% CI 0.49-1.38, P = 0.464) adjusted for age, 0.96 (95%CI 0.59-1.58, P = 0.882) adjusted for gender, 0.72(95% CI 0.41-1.26, P = 0.249) adjusted for multivariables respectively. Conclusion The current study demonstrates that heart rate is an independent prognostic predictor for all-cause mortality, and HR ≤ 80 bpm is associated with improved outcome in SR but not in AF in octogenarian patients with ACS. PMID:29255559

Tumor Volume Is a Prognostic Factor in Non-Small-Cell Lung Cancer Treated With Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexander, Brian M.; Othus, Megan; Caglar, Hale B.

2011-04-01

Purpose: To investigate whether primary tumor and nodal volumes defined on radiotherapy planning scans are correlated with outcome (survival and recurrence) after combined-modality treatment. Methods and Materials: A retrospective review of patients with Stage III non-small-cell lung cancer treated with chemoradiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute from 2000 to 2006 was performed. Tumor and nodal volume measurements, as computed by Eclipse (Varian, Palo Alto, CA), were used as independent variables, along with existing clinical factors, in univariate and multivariate analyses for association with outcomes. Results: For patients treated with definitive chemoradiotherapy, both nodal volume (hazard ratio [HR], 1.09;more » p < 0.01) and tumor volume (HR, 1.03; p < 0.01) were associated with overall survival on multivariate analysis. Both nodal volume (HR, 1.10; p < 0.01) and tumor volume (HR, 1.04; p < 0.01) were also associated with local control but not distant metastases. Conclusions: In addition to traditional surgical staging variables, disease burden, measured by primary tumor and nodal metastases volume, provides information that may be helpful in determining prognosis and identifying groups of patients for which more aggressive local therapy is warranted.« less

The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doll, Corinne M., E-mail: Corinne.Doll@albertahealthservices.ca; Aquino-Parsons, Christina; Pintilie, Melania

2013-03-01

Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens weremore » retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis.« less

Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH) trial.

PubMed

Teo, Koon K; Goldstein, Larry B; Chaitman, Bernard R; Grant, Shannon; Weintraub, William S; Anderson, David C; Sila, Cathy A; Cruz-Flores, Salvador; Padley, Robert J; Kostuk, William J; Boden, William E

2013-10-01

In Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, addition of extended-release niacin (ERN) to simvastatin in participants with established cardiovascular disease, low high-density lipoprotein cholesterol, and high triglycerides had no incremental benefit, despite increases in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete end point adjudication suggested increased ischemic stroke risk among participants randomized to ERN. This final analysis was conducted after complete AIM-HIGH event ascertainment to further explore potential relationship between niacin therapy and ischemic stroke risk. There was no group difference in trial primary composite end point at a mean 36-month follow-up among 3414 patients (85% men; mean age, 64±9 years) randomized to simvastatin plus ERN (1500-2000 mg/d) versus simvastatin plus matching placebo. In the intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18 (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95% confidence interval {CI}, 1.00-3.17; P=0.050). Multivariate analysis showed independent associations between ischemic stroke risk and >65 years of age (HR, 3.58; 95% CI, 1.82-7.05; P=0.0002), history of stroke/transient ischemic attack/carotid disease (HR, 2.18; 95% CI, 1.23-3.88; P=0.0079), elevated baseline Lp(a) (HR, 2.80; 95% CI, 1.25-6.27 comparing the middle with the lowest tertile; HR, 2.31; 95% CI, 1.002-5.30 comparing the highest with the lowest tertile; overall P=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI, 0.97-3.11; P=0.063). Although there were numerically more ischemic strokes with addition of ERN to simvastatin that reached nominal significance, the number was small, and multivariable analysis accounting for known risk factors did not support a significant association between niacin and ischemic stroke risk. http://www.clinicaltrials.gov. Unique identifier: NCT00120289.

Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy.

PubMed

Jackson, William; Hamstra, Daniel A; Johnson, Skyler; Zhou, Jessica; Foster, Benjamin; Foster, Corey; Li, Darren; Song, Yeohan; Palapattu, Ganesh S; Kunju, Lakshmi P; Mehra, Rohit; Feng, Felix Y

2013-09-15

The presence of Gleason pattern 5 (GP5) at radical prostatectomy (RP) has been associated with worse clinical outcome; however, this pathologic variable has not been assessed in patients receiving salvage radiation therapy (SRT) after a rising prostate-specific antigen level. A total of 575 patients who underwent primary RP for localized prostate cancer and subsequently received SRT at a tertiary medical institution were reviewed retrospectively. Primary outcomes of interest were biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM), which were assessed via univariate analysis and Fine and Grays competing risks multivariate models. On pathologic evaluation, 563 (98%) patients had a documented Gleason score (GS). The median follow-up post-SRT was 56.7 months. A total of 60 (10.7%) patients had primary, secondary, or tertiary GP5. On univariate analysis, the presence of GP5 was prognostic for BF (hazard ratio [HR] 3.3; P < .0001), DM (HR:11.1, P < .0001), and PCSM (HR:8.8, P < .0001). Restratification of the Gleason score to include GP5 as a distinct entity resulted in improved prognostic capability. Patients with GP5 had clinically worse outcomes than patients with GS8(4+4). On multivariate analysis, the presence of GP5 was the most adverse pathologic predictor of BF (HR 2.9; P < .0001), DM (HR 14.8; P < .0001), and PCSM (HR 5.7; P < .0001). In the setting of SRT for prostate cancer, the presence of GP5 is a critical pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual Gleason patterns among men receiving SRT post-RP. © 2013 American Cancer Society.

The relationship between genetic profiling, clinicopathological factors and survival in patients undergoing surgery for node-negative colorectal cancer: 10-year follow-up.

PubMed

Powell, Arfon G M T; Ferguson, Jenny; Al-Mulla, Fahd; Orange, Clare; McMillan, Donald C; Horgan, Paul G; Edwards, Joanne; Going, James J

2013-12-01

The introduction of the bowel cancer screening programme has resulted in increasing numbers of patients being diagnosed with node-negative disease. Unfortunately, approximately 30 % will develop recurrence following surgery. Given the toxicity associated with adjuvant chemotherapy, it is important to identify high-risk patients who may benefit from adjuvant therapy. This study aims to identify which clinicopathological factors and genetic profiling markers predict outcome in node-negative disease. Forty-nine microsatellite stable (MSS) patients undergoing curative resection between 1991 and 1993 were included. Local immune response was assessed by Klintrup criteria and vascular invasion status assessed through Miller's elastin staining. Comparative genomic hybridisation (CGH) on a range of loci provided data on allelic imbalance. Analysis of survival included clinicopathological and CGH data in a multivariate (Cox) model. On binary logistical regression analysis, 4p deletion was independently associated with low Klintrup score (HR 0.16; 95 % CI (0.03-0.96); P = 0.045), venous invasion (HR 4.19; 95 % CI (1.08-16.29); P = 0.039) and higher Dukes' stage (HR 6.43; 95 % CI (1.22-33.97); P = 0.028). Minimum follow-up was 109 months and there were 24 cancer deaths. On multivariate analysis, high Klintrup score (HR 0.33; 95 % CI (0.12-0.93); P = 0.036), 4p- (HR 4.01; 95 % CI (1.58-10.21); P = 0.004) and 5q- (HR 3.81; 95 % CI (1.54-9.47); P = 0.004) were significantly associated with survival. 4p-, 5q- and low Klintrup score were independently associated with poor cancer-specific survival in node-negative MSS colorectal cancer. Confirmatory work in a larger cohort is needed to determine whether these markers may be used to identify patients who may benefit from adjuvant chemotherapy.

Femoral Neck X-Ray Absorptiometry Parameters and Peripheral Quantitative Computer Tomography Tibial Cortical Density Predict Survival in Dialysis Patients.

PubMed

Yap, Natalie; Wong, Phillip; McGinn, Stella; Nery, Maria-Liza; Doyle, Jean; Wells, Lynda; Clifton-Bligh, Phillip; Clifton-Bligh, Roderick J

2017-01-01

Low bone mineral density (BMD) is a known independent predictor of mortality in the general elderly population. However, studies in patients with end-stage renal disease (ESRD) are limited. The present study evaluated mortality during long-term follow-up in a population of patients having dialysis for ESRD, in whom BMD was also measured. Fifty-eight patients with ESRD were recruited consecutively from a dialysis clinic and followed prospectively for 6 years. Baseline BMD of the lumbar spine and femoral neck (FN) were measured by X-ray absorptiometry and by peripheral quantitative CT at the radius and tibia. Serum calcium, phosphate, parathyroid hormone (PTH), and albumin were measured at baseline. During follow-up, 25 patients died. Univariate analysis showed that mortality was significantly associated with FN-BMD: hazards ratio (HR) per 0.1 g/cm2 decrease 1.50 (95% CI 1.07-2.10), p = 0.019; FN-T score: HR per 1-SD decrease 1.84 (95% CI 1.16-2.92), p = 0.009; and tibial cortical density: HR per 10 mg/cm3 decrease 1.08 (95% CI 1.02-1.14), p = 0.010. In multivariate analysis with stepwise adjustment for age, sex, transplant status, albumin, PTH, phosphate, dialysis duration, diabetes, and smoking, FN-T score remained significantly associated with mortality: HR per 1-SD decrease 1.82 (95% CI 1.02-3.24), p = 0.044, whereas the HR for FN-BMD and tibial cortical density were no longer significant. When 4 patients who had peritoneal dialysis were excluded, the HR relating FN-BMD, FN-T score, and tibial cortical density to mortality remained significant but became insignificant when albumin was included in the multivariate analysis. Reduced FN-BMD, FN-T score, and tibial cortical density were significantly associated with an increased risk of death in patients with ESRD. © 2017 S. Karger AG, Basel.

Development of a multivariate model to predict the likelihood of carcinoma in patients with indeterminate peripheral lung nodules after a nondiagnostic bronchoscopic evaluation.

PubMed

Voss, Jesse S; Iqbal, Seher; Jenkins, Sarah M; Henry, Michael R; Clayton, Amy C; Jett, James R; Kipp, Benjamin R; Halling, Kevin C; Maldonado, Fabien

2014-01-01

Studies have shown that fluorescence in situ hybridization (FISH) testing increases lung cancer detection on cytology specimens in peripheral nodules. The goal of this study was to determine whether a predictive model using clinical features and routine cytology with FISH results could predict lung malignancy after a nondiagnostic bronchoscopic evaluation. Patients with an indeterminate peripheral lung nodule that had a nondiagnostic bronchoscopic evaluation were included in this study (N = 220). FISH was performed on residual bronchial brushing cytology specimens diagnosed as negative (n = 195), atypical (n = 16), or suspicious (n = 9). FISH results included hypertetrasomy (n = 30) and negative (n = 190). Primary study end points included lung cancer status along with time to diagnosis of lung cancer or date of last clinical follow-up. Hazard ratios (HRs) were calculated using Cox proportional hazards regression model analyses, and P values < .05 were considered statistically significant. The mean age of the 220 patients was 66.7 years (range, 35-91), and most (58%) were men. Most patients (79%) were current or former smokers with a mean pack year history of 43.2 years (median, 40; range, 1-200). After multivariate analysis, hypertetrasomy FISH (HR = 2.96, P < .001), pack years (HR = 1.03 per pack year up to 50, P = .001), age (HR = 1.04 per year, P = .02), atypical or suspicious cytology (HR = 2.02, P = .04), and nodule spiculation (HR = 2.36, P = .003) were independent predictors of malignancy over time and were used to create a prediction model (C-statistic = 0.78). These results suggest that this multivariate model including test results and clinical features may be useful following a nondiagnostic bronchoscopic examination. © 2013.

Prevalence of Anal High-Risk Human Papillomavirus Infections Among HIV-Positive and HIV-Negative Men Who Have Sex With Men in Nigeria.

PubMed

Nowak, Rebecca G; Gravitt, Patti E; He, Xin; Ketende, Sosthenes; Dauda, Wuese; Omuh, Helen; Blattner, William A; Charurat, Manhattan E

2016-04-01

Prevalence estimates of anal high-risk human papillomavirus (HR-HPV) are needed in sub-Saharan Africa where HIV is endemic. This study evaluated anal HR-HPV in Nigeria among HIV-positive and HIV-negative men who have sex with men (MSM) for future immunization recommendations. We conducted a cross-sectional study to compare the prevalence of anal HR-HPV infections between 64 HIV-negative and 90 HIV-positive MSM. Multivariate Poisson regression analyses were used to examine demographic and behavioral risk factors associated with any HR-HPV infections. The median age of the 154 participants was 25 years (interquartile range, 22-28 years; range, 16-38 years), and the median age at initiation of anal sex with another man was 16 years (interquartile range, 13-18 years; range, 7-29 years). The prevalence of anal HR-HPV was higher among HIV-positive than HIV-negative MSM (91.1% vs. 40.6%, P < 0.001). In the multivariate analysis, HIV infection (adjusted prevalence ratio [aPR], 2.02; 95% confidence interval [CI], 1.49-2.72), 10 years or more since anal sexual debut (aPR, 1.26; 95% CI, 1.07-1.49), and concurrent relationships with men (aPR, 1.32; 95% CI, 1.04-1.67) were associated with increased anal HR-HPV prevalence. Anal HR-HPV infection is high for young Nigerian MSM, and rates are amplified in those coinfected with HIV. Providing universal coverage as well as catch-up immunization for young MSM may be an effective anal cancer prevention strategy in Nigeria.

Observational and Genetic Associations of Resting Heart Rate With Aortic Valve Calcium.

PubMed

Whelton, Seamus P; Mauer, Andreas C; Pencina, Karol M; Massaro, Joseph M; D'Agostino, Ralph B; Fox, Caroline S; Hoffmann, Udo; Michos, Erin D; Peloso, Gina M; Dufresne, Line; Engert, James C; Kathiresan, Sekar; Budoff, Matthew; Post, Wendy S; Thanassoulis, George; O'Donnell, Christopher J

2018-05-15

It is unknown if lifelong exposure to increased hemodynamic stress from an elevated resting heart rate (HR) may contribute to aortic valve calcium (AVC). We performed multivariate regression analyses using data from 1,266 Framingham Heart Study (FHS) Offspring cohort participants and 6,764 Multi-Ethnic Study of Atherosclerosis (MESA) participants. We constructed a genetic risk score (GRS) for HR using summary-level data in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) AVC Consortium to investigate if there was evidence in favor of a causal relation. AVC was present in 39% of FHS Offspring cohort participants and in 13% of MESA cohort participants. In multivariate adjusted models, participants in the highest resting HR quartiles had significantly greater prevalence of AVC, with a prevalence ratio of 1.19 (95% confidence interval [CI] 0.99 to 1.44) for the FHS Offspring cohort and 1.32 (95% CI 1.12 to 1.63) for the MESA cohort, compared with those in the lowest quartile. There was a similar increase in the prevalence of AVC per standard deviation increase in resting HR in both FHS Offspring (prevalence ratio 1.08, 95% CI 1.01 to 1.15) and MESA (1.10, 95% CI 1.03 to 1.17). In contrast with these observational findings, a HR associated GRS was not significantly associated with AVC. Although our observational analysis indicates that a higher resting HR is associated with AVC, our genetic results do not support a causal relation. Unmeasured environmental and/or lifestyle factors associated with both increased resting HR and AVC that are not fully explained by covariates in our observational models may account for the association between resting HR and AVC. Copyright © 2018. Published by Elsevier Inc.

SU-F-R-07: Radiomics of CT Features and Associations and Correlation with Outcomes Following Lung SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schreibmann, E; Iwinski Sutter, A; Whitaker, D

Objective: To investigate the prognostic significance of image gradients and in predicting clinical outcomes in a patients with non-small cell lung cancer treated with stereotactic body radiotherapy (SBRT) on 71 patients with 83 treated lesions. Methods: The records of patients treated with lung SBRT were retrospectively reviewed. When applicable, SBRT target volumes were modified to exclude any overlap with pleura, chestwall, or mediastinum. The ITK software package was utilized to generate quantitative measures of image intensity, inhomogeneity, shape morphology and first and second-order CT textures. Multivariate and univariate models containing CT features were generated to assess associations with clinicopathologic factors.more » Results: On univariate analysis, tumor size (HR 0.54, p=0.045) sumHU (HR 0.31, p=0.044) and short run grey level emphasis STD (HR 0.22, p=0.019) were associated with regional failure-free survival; meanHU (HR 0.30, p=0.035), long run emphasis (HR 0.21, p=0.011) and long run low grey level emphasis (HR 0.14, p=0.005) was associated with distant failure-free survival (DFFS). No features were significant on multivariate modeling however long run low grey level emphasis had a hazard ratio of 0.12 (p=0.061) for DFFS. Adenocarcinoma and squamous cell carcinoma differed with respect to long run emphasis STD (p=0.024), short run low grey level emphasis STD (p<0.001), and long run low grey level emphasis STD (p=0.024). Multivariate modeling of texture features associated with tumor histology was used to estimate histologies of 18 lesions treated without histologic confirmation. Of these, MVA suggested the same histology as a prior metachronous lung malignancy in 3/7 patients. Conclusion: Extracting radiomics features on clinical datasets was feasible with the ITK package with minimal effort to identify pre-treatment quantitative CT features with prognostic factors for distant control after lung SBRT.« less

Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma

PubMed Central

Huang, Gloria S.; Chiu, Lydia G.; Gebb, Juliana S.; Gunter, Marc J.; Sukumvanich, Paniti; Goldberg, Gary L.; Einstein, Mark H.

2009-01-01

Objective The purpose of this study was to determine the clinical utility of CA125 measurement in patients with uterine carcinosarcoma (CS). Methods Ninety-five consecutive patients treated for CS at a single institution were identified. All 54 patients who underwent preoperative CA125 measurement were included in the study. Data were abstracted from the medical records. Tests of association between preoperative CA125 and previously identified clinicopathologic prognostic factors were performed using Fisher’s exact test and Pearson chi-square test. To evaluate relationship of CA125 elevation and survival, a Cox proportional hazard model was used for multivariate analysis, incorporating all of prognostic factors identified by univariate analysis. Results Preoperative CA125 was significantly associated with the presence of extrauterine disease (P<0.001), deep myometrial invasion (P<0.001), and serous histology of the epithelial component (P=0.005). Using univariate survival analysis, stage (HR=1.808, P=0.004), postoperative CA125 level (HR=9.855, P<0.001), and estrogen receptor positivity (HR=0.314, P=0.029) were significantly associated with survival. In the multivariate model, only postoperative CA125 level remained significantly associated with poor survival (HR=5.725, P=0.009). Conclusion Preoperative CA125 elevation is a marker of extrauterine disease and deep myometrial invasion in patients with uterine CS. Postoperative CA125 elevation is an independent prognostic factor for poor survival. These findings indicate that CA125 may be a clinically useful serum marker in the management of patients with CS. PMID:17935762

The Impact of Chemoembolization Endpoints on Survival in Hepatocellular Carcinoma Patients

PubMed Central

Jin, Brian; Wang, Dingxin; Lewandowski, Robert J.; Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Larson, Andrew C.; Salem, Riad; Omary, Reed A.

2010-01-01

OBJECTIVE To investigate the relationship between angiographic embolic endpoints of transarterial chemoembolization (TACE) and survival in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study retrospectively assessed 105 patients with surgically unresectable HCC who underwent TACE. Patients were classified according to a previously established subjective angiographic chemoembolization endpoint (SACE) scale. Only one patient was classified as SACE level 1 and thus excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. Multivariate analysis with Cox’s proportional hazard regression model was used to determine independent prognostic risk factors of survival. RESULTS Overall median survival was 21.1 months (95% confidence interval [CI], 15.9–26.4). Patients embolized to SACE levels 2 and 3 were aggregated and had a significantly higher median survival (25.6 months; 95% CI, 16.2–35.0) than patients embolized to SACE level 4 (17.1 months; 95% CI, 13.3–20.9) (p = 0.035). Multivariate analysis indicated that SACE level 4 (Hazard ratio [HR], 2.49; 95% CI, 1.41–4.42; p = 0.002), European Cooperative Oncology Group performance status > 0 (HR, 1.97; 95% CI, 1.15–3.37; p = 0.013), American Joint Committee on Cancer stage 3 or 4 (HR, 2.42; 95% CI, 1.27–4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09–3.46; p = 0.025) were all independent negative prognostic indicators of survival. CONCLUSION Embolization to an intermediate, sub-stasis endpoint (SACE levels 2 and 3) during TACE improves survival compared to embolization to a higher, stasis endpoint (SACE level 4). Interventional oncologists should consider targeting these intermediate, sub-stasis angiographic endpoints during TACE. PMID:21427346

Magnetic resonance metabolic profiling of estrogen receptor-positive breast cancer: correlation with currently used molecular markers

PubMed Central

Koo, Ja Seung; Kim, Siwon; Park, Vivian Youngjean; Kim, Eun-Kyung; Kim, Suhkmann; Kim, Min Jung

2017-01-01

Estrogen receptor (ER)-positive breast cancers overall have a good prognosis, however, some patients suffer relapses and do not respond to endocrine therapy. The purpose of this study was to determine whether there are any correlations between high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) metabolic profiles of core needle biopsy (CNB) specimens and the molecular markers currently used in patients with ER-positive breast cancers. The metabolic profiling of CNB samples from 62 ER-positive cancers was performed by HR-MAS MRS. Metabolic profiles were compared according to human epidermal growth factor receptor 2 (HER2) and Ki-67 status, and luminal type, using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). In univariate analysis, the HER2-positive group was shown to have higher levels of glycine and glutamate, compared to the HER2-negative group (P<0.01, and P <0.01, respectively). The high Ki-67 group showed higher levels of glutamate than the low Ki-67 group without statistical significance. Luminal B cancers showed higher levels of glycine (P=0.01) than luminal A cancers. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the subgroups according to HER2 and Ki-67 status, and luminal type. This study showed that the metabolic profiles of CNB samples assessed by HR-MAS MRS can be used to detect potential prognostic biomarkers as well as to understand the difference in metabolic mechanism among subtypes of ER-positive breast cancer. PMID:28969000

The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

DOE Office of Scientific and Technical Information (OSTI.GOV)

Showalter, Timothy N.; Winter, Kathryn A.; Berger, Adam C., E-mail: adam.berger@jefferson.edu

2011-12-01

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluatemore » associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.« less

Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

PubMed Central

Li, Yong-Jiang; Yang, Xi; Zhang, Wen-Biao; Yi, Cheng; Wang, Feng; Li, Ping

2017-01-01

Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte–monocyte ratio (LMR), and neutrophil–platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma. PMID:29033609

Single Marital Status and Infectious Mortality in Women With Cervical Cancer in the United States.

PubMed

Machida, Hiroko; Eckhardt, Sarah E; Castaneda, Antonio V; Blake, Erin A; Pham, Huyen Q; Roman, Lynda D; Matsuo, Koji

2017-10-01

Unmarried status including single marital status is associated with increased mortality in women bearing malignancy. Infectious disease weights a significant proportion of mortality in patients with malignancy. Here, we examined an association of single marital status and infectious mortality in cervical cancer. This is a retrospective observational study examining 86,555 women with invasive cervical cancer identified in the Surveillance, Epidemiology, and End Results Program between 1973 and 2013. Characteristics of 18,324 single women were compared with 38,713 married women in multivariable binary logistic regression models. Propensity score matching was performed to examine cumulative risk of all-cause and infectious mortality between the 2 groups. Single marital status was significantly associated with young age, black/Hispanic ethnicity, Western US residents, uninsured status, high-grade tumor, squamous histology, and advanced-stage disease on multivariable analysis (all, P < 0.05). In a prematched model, single marital status was significantly associated with increased cumulative risk of all-cause mortality (5-year rate: 32.9% vs 29.7%, P < 0.001) and infectious mortality (0.5% vs 0.3%, P < 0.001) compared with the married status. After propensity score matching, single marital status remained an independent prognostic factor for increased cumulative risk of all-cause mortality (adjusted hazards ratio [HR], 1.15; 95% confidence interval [CI], 1.11-1.20; P < 0.001) and those of infectious mortality on multivariable analysis (adjusted HR, 1.71; 95% CI, 1.27-2.32; P < 0.001). In a sensitivity analysis for stage I disease, single marital status remained significantly increased risk of infectious mortality after propensity score matching (adjusted HR, 2.24; 95% CI, 1.34-3.73; P = 0.002). Single marital status was associated with increased infectious mortality in women with invasive cervical cancer.

Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

PubMed

Schofield, Penelope E; Stockler, M R; Zannino, D; Tebbutt, N C; Price, T J; Simes, R J; Wong, N; Pavlakis, N; Ransom, D; Moylan, E; Underhill, C; Wyld, D; Burns, I; Ward, R; Wilcken, N; Jefford, M

2016-01-01

Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HRs) and P values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P < 0.001) and positively with health utility (HR 0.56, P < 0.001) and hopefulness (HR 0.75, P = 0.013). In multivariable analysis, OS was also associated negatively with depression (HR 1.72, P < 0.001) and positively with health utility (HR 0.73, P = 0.014), but not with optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. Depression and health utility, but not optimism, hope or anxiety, were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities.

Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucas, John T., E-mail: jolucas@wakehealth.edu; Colmer, Hentry G.; White, Lance

Purpose: To estimate the hazard for neurologic (central nervous system, CNS) and nonneurologic (non-CNS) death associated with patient, treatment, and systemic disease status in patients receiving stereotactic radiosurgery after whole-brain radiation therapy (WBRT) failure, using a competing risk model. Patients and Methods: Of 757 patients, 293 experienced recurrence or new metastasis following WBRT. Univariate Cox proportional hazards regression identified covariates for consideration in the multivariate model. Competing risks multivariable regression was performed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for both CNS and non-CNS death after adjusting for patient, disease, and treatment factors. The resultantmore » model was converted into an online calculator for ease of clinical use. Results: The cumulative incidence of CNS and non-CNS death at 6 and 12 months was 20.6% and 21.6%, and 34.4% and 35%, respectively. Patients with melanoma histology (relative to breast) (aHR 2.7, 95% CI 1.5-5.0), brainstem location (aHR 2.1, 95% CI 1.3-3.5), and number of metastases (aHR 1.09, 95% CI 1.04-1.2) had increased aHR for CNS death. Progressive systemic disease (aHR 0.55, 95% CI 0.4-0.8) and increasing lowest margin dose (aHR 0.97, 95% CI 0.9-0.99) were protective against CNS death. Patients with lung histology (aHR 1.3, 95% CI 1.1-1.9) and progressive systemic disease (aHR 2.14, 95% CI 1.5-3.0) had increased aHR for non-CNS death. Conclusion: Our nomogram provides individual estimates of neurologic death after salvage stereotactic radiosurgery for patients who have failed prior WBRT, based on histology, neuroanatomical location, age, lowest margin dose, and number of metastases after adjusting for their competing risk of death from other causes.« less

Energetic Interrelationship between Spontaneous Low-Frequency Fluctuations in Regional Cerebral Blood Volume, Arterial Blood Pressure, Heart Rate, and Respiratory Rhythm

NASA Astrophysics Data System (ADS)

Katura, Takusige; Yagyu, Akihiko; Obata, Akiko; Yamazaki, Kyoko; Maki, Atsushi; Abe, Masanori; Tanaka, Naoki

2007-07-01

Strong spontaneous fluctuations around 0.1 and 0.3 Hz have been observed in blood-related brain-function measurements such as functional magnetic resonance imaging and optical topography (or functional near-infrared spectroscopy). These fluctuations seem to reflect the interaction between the cerebral circulation system and the systemic circulation system. We took an energetic viewpoint in our analysis of the interrelationships between fluctuations in cerebral blood volume (CBV), mean arterial blood pressure (MAP), heart rate (HR), and respiratory rhythm based on multivariate autoregressive modeling. This approach involves evaluating the contribution of each fluctuation or rhythm to specific ones by performing multivariate spectral analysis. The results we obtained show MAP and HR can account slightly for the fluctuation around 0.1 Hz in CBV, while the fluctuation around 0.3 Hz is derived mainly from the respiratory rhythm. During our presentation, we will report on the effects of posture on the interrelationship between the fluctuations and the respiratory rhythm.

Retrospective Analysis of Radiological Recurrence Patterns in Glioblastoma, Their Prognostic Value And Association to Postoperative Infarct Volume.

PubMed

Bette, Stefanie; Barz, Melanie; Huber, Thomas; Straube, Christoph; Schmidt-Graf, Friederike; Combs, Stephanie E; Delbridge, Claire; Gerhardt, Julia; Zimmer, Claus; Meyer, Bernhard; Kirschke, Jan S; Boeckh-Behrens, Tobias; Wiestler, Benedikt; Gempt, Jens

2018-03-14

Recent studies suggested that postoperative hypoxia might trigger invasive tumor growth, resulting in diffuse/multifocal recurrence patterns. Aim of this study was to analyze distinct recurrence patterns and their association to postoperative infarct volume and outcome. 526 consecutive glioblastoma patients were analyzed, of which 129 met our inclusion criteria: initial tumor diagnosis, surgery, postoperative diffusion-weighted imaging and tumor recurrence during follow-up. Distinct patterns of contrast-enhancement at initial diagnosis and at first tumor recurrence (multifocal growth/progression, contact to dura/ventricle, ependymal spread, local/distant recurrence) were recorded by two blinded neuroradiologists. The association of radiological patterns to survival and postoperative infarct volume was analyzed by uni-/multivariate survival analyses and binary logistic regression analysis. With increasing postoperative infarct volume, patients were significantly more likely to develop multifocal recurrence, recurrence with contact to ventricle and contact to dura. Patients with multifocal recurrence (Hazard Ratio (HR) 1.99, P = 0.010) had significantly shorter OS, patients with recurrent tumor with contact to ventricle (HR 1.85, P = 0.036), ependymal spread (HR 2.97, P = 0.004) and distant recurrence (HR 1.75, P = 0.019) significantly shorter post-progression survival in multivariate analyses including well-established prognostic factors like age, Karnofsky Performance Score (KPS), therapy, extent of resection and patterns of primary tumors. Postoperative infarct volume might initiate hypoxia-mediated aggressive tumor growth resulting in multifocal and diffuse recurrence patterns and impaired survival.

Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study.

PubMed

Ellin, Fredrik; Landström, Jenny; Jerkeman, Mats; Relander, Thomas

2015-07-02

Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas, but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, as well as the outcome of these patients, in a large population-based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis, disease characteristics at diagnosis independently associated with an increased risk for later CNS involvement were involvement of more than 1 extranodal site (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P = .035) and skin (HR, 3.51; 95% CI, 1.26-9.74; P = .016) and gastrointestinal involvement (HR, 3.06; 95% CI, 1.30-7.18; P = .010). The outcome of relapsed/refractory patients was very poor, and CNS involvement was not associated with a significantly worse outcome compared with relapsed/refractory patients without CNS involvement in multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P = .074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease. © 2015 by The American Society of Hematology.

[Local recurrence based on size after conservative surgery in breast cancer stage T1-T2. A population-based study].

PubMed

Martínez-Ramos, David; Fortea-Sanchis, Carlos; Escrig-Sos, Javier; Prats-de Puig, Miguel; Queralt-Martín, Raquel; Salvador-Sanchis, José Luís

2014-01-01

Conservative surgery can be regarded as the standard treatment for most early stage breast tumors. However, a minority of patients treated with conservative surgery will present local or locoregional recurrence. Therefore, it is of interest to evaluate the possible factors associated with this recurrence. A population-based retrospective study using data from the Tumor Registry of Castellón (Valencia, Spain) of patients operated on for primary nonmetastatic breast cancer between January 2000 and December 2008 was designed. Kaplan-Meier curves and log-rank test to estimate 5-year local recurrence were used. Two groups of patients were defined, one with conservative surgery and another with nonconservative surgery. Cox multivariate analysis was conducted. The total number of patients was 410. Average local recurrence was 6.8%. In univariate analysis, only tumor size and lymph node involvement showed significant differences. On multivariate analysis, independent prognostic factors were conservative surgery (hazard ratio [HR] 4.62; 95% confidence interval [CI]: 1.12-16.82), number of positive lymph nodes (HR 1.07; 95% CI: 1.01-1.17) and tumor size (in mm) (HR 1.02; 95% CI: 1.01-1.06). Local recurrence after breast-conserving surgery is higher in tumors >2 cm. Although tumor size should not be a contraindication for conservative surgery, it should be a risk factor to be considered.

Heart rate behavior during an exercise stress test in obese patients.

PubMed

Gondoni, L A; Titon, A M; Nibbio, F; Augello, G; Caetani, G; Liuzzi, A

2009-03-01

Heart rate (HR) response to exercise has not been fully described in the obese. We wanted to study the differences between obese and non-obese patients in HR behavior during an exercise stress test and to determine whether these differences influence exercise capacity. We studied 554 patients (318 females) who underwent a treadmill exercise test. All subjects were in sinus rhythm. Patients with ischemic heart disease, with reduced ejection fraction and patients taking drugs that interfere with HR were excluded. The population included 231 patients with BMI<30 kg/m(2) (group 1), 212 patients who were unfit and obese (group 2) and 111 patients who were trained obese (group 3). Resting HR was similar in the various groups. Peak HR, HR recovery and chronotropic index were lower in obese subjects, regardless of their fitness level. Multivariate analysis showed that HR related variables were associated with age, BMI, height, hypertension and various pharmacologic treatments, while exercise capacity was strongly dependent on HR behavior, as well as on sex, age, BMI and diabetes. Obese subjects have a marked impairment of HR behavior during exercise and in the recovery period, and the blunted increase in HR is the most important factor that influences exercise capacity.

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial.

PubMed

Blanchard, Pierre; Faivre, Laura; Lesaunier, François; Salem, Naji; Mesgouez-Nebout, Nathalie; Deniau-Alexandre, Elisabeth; Rolland, Frédéric; Ferrero, Jean-Marc; Houédé, Nadine; Mourey, Loïc; Théodore, Christine; Krakowski, Ivan; Berdah, Jean-François; Baciuchka, Marjorie; Laguerre, Brigitte; Davin, Jean-Louis; Habibian, Muriel; Culine, Stéphane; Laplanche, Agnès; Fizazi, Karim

2016-01-01

The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of pretreatment body mass index and survival in human papillomavirus positive oropharyngeal squamous cell carcinoma.

PubMed

Albergotti, William G; Davis, Kara S; Abberbock, Shira; Bauman, Julie E; Ohr, James; Clump, David A; Heron, Dwight E; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T; Ferris, Robert L

2016-09-01

Pretreatment body mass index (BMI) >25kg/m(2) is a positive prognostic factor in patients with head and neck cancer. Previous studies have not been adequately stratified by human papilloma virus (HPV) status or subsite. Our objective is to determine prognostic significance of pretreatment BMI on overall survival in HPV+ oropharyngeal squamous cell carcinoma (OPSCC). This is a retrospective review of patients with HPV+ OPSCC treated between 8/1/2006 and 8/31/2014. Patients were stratified by BMI status (>/<25kg/m(2)). Univariate and multivariate analyses of survival were performed. 300 patients met our inclusion/exclusion criteria. Patients with a BMI >25kg/m(2) had a longer overall survival (HR=0.49, P=0.01) as well as a longer disease-specific survival (HR=0.43, P=0.02). Overall survival remained significantly associated with high BMI on multivariate analysis (HR=0.54, P=0.04). Pre-treatment normal or underweight BMI status is associated with worse overall survival in HPV+ OPSCC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tp-Te interval predicts heart rate reduction after fingolimod administration in patients with multiple sclerosis.

PubMed

Tocci, Giuliano; Giuliani, Manuela; Canichella, Flaminia; Timpano, Jacopo; Presta, Vivianne; Francia, Pietro; Musumeci, Maria Beatrice; Fubelli, Federica; Pozzilli, Carlo; Volpe, Massimo; Ferrucci, Andrea

2016-10-15

FTY720 (Fingolimod) is an immunosuppressive drug, which provides favourable effects in patients with multiple sclerosis (MS), albeit it induces heart rate (HR) and blood pressure (BP) reductions. Therefore, we tested potential factors able to predict HR response in MS patients treated with fingolimod. We analysed patients with MS followed at our Neurology Outpatient Clinic from May 2013 to June 2015. All patients underwent BP measurements and 12-lead ECG before and 6-h after drug administration. At these time intervals, conventional and new ECG indexes for cardiac damage, including Tp-Te interval, were measured. Univariate and multivariate analyses were performed to test the outcome of HR reduction more than median difference between baseline and final observations. 69 outpatients with MS (46 males, age 35.1±9.4years, BP 119.0±12.7/73.0±9.3mmHg, HR 73.5±11.4bpm) were included. No relevant adverse reactions were reported. Fingolimod induced progressive systolic (P=0.024) and diastolic (P<0.001) BP, as well as HR (P<0.001) reductions compared to baseline. Prolonged PQ (150.4±19.5 vs. 157.0±19.5ms; P<0.001), QT (374.9±27.0 vs. 400.0±25.8ms; P<0.001), Tp-Te (1.8±0.3 vs. 1.9±0.3mm; P=0.021), and reduced QTc (414.4±24.4 vs. 404.5±24.5ms; P<0.001) intervals were also recorded at final observation. Baseline HR, QT and Tp-Te intervals provided prognostic information at univariate analysis, although Tp-Te interval resulted the best independent predictor for HR reduction at multivariate analysis [0.057 (0.005-0.660); P=0.022]. This study firstly demonstrates that prolonged Tp-Te interval may identify those MS patients treated with fingolimod at higher risk of having significant, asymptomatic HR reduction during clinical observation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, Sarah Nicole; Tyldesley, Scott; Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia

Purpose: To compare the second malignancy incidence in prostate cancer patients treated with brachytherapy (BT) relative to radical prostatectomy (RP) and to compare both groups with the cancer incidence in the general population. Methods and Materials: From 1998 to 2010, 2418 patients were treated with Iodine 125 prostate BT monotherapy at the British Columbia Cancer Agency, and 4015 referred patients were treated with RP. Cancer incidence was compared with the age-matched general population using standardized incidence ratios (SIRs). Pelvic malignancies included invasive and noninvasive bladder cancer and rectal cancer. Cox multivariable analysis was performed with adjustment for covariates to determinemore » whether treatment (RP vs BT) was associated with second malignancy risk. Results: The median age at BT was 66 years and at RP 62 years. The SIR comparing BT patients with the general population was 1.06 (95% confidence interval [CI] 0.91-1.22) for second malignancy and was 1.53 (95% CI 1.12-2.04) for pelvic malignancy. The SIR comparing RP patients with the general population was 1.11 (95% CI 0.98-1.25) for second malignancy and was 1.11 (95% CI 0.82-1.48) for pelvic malignancy. On multivariable analysis, older age (hazard ratio [HR] 1.05) and smoking (HR 1.65) were associated with increased second malignancy risk (P<.0001). Radical prostatectomy was not associated with a decreased second malignancy risk relative to BT (HR 0.90, P=.43), even when excluding patients who received postprostatectomy external beam radiation therapy (HR 1.13, P=.25). Older age (HR 1.09, P<.0001) and smoking (HR 2.17, P=.0009) were associated with increased pelvic malignancy risk. Radical prostatectomy was not associated with a decreased pelvic malignancy risk compared with BT (HR 0.57, P=.082), even when excluding postprostatectomy external beam radiation therapy patients (HR 0.87, P=.56). Conclusions: After adjustment for covariates, BT patients did not have an increased second malignancy risk compared with RP patients. Further follow-up of this cohort is needed given the potential latency of radiation-induced malignancies.« less

Prognostic value of indeterminable anaerobic threshold in heart failure.

PubMed

Agostoni, Piergiuseppe; Corrà, Ugo; Cattadori, Gaia; Veglia, Fabrizio; Battaia, Elisa; La Gioia, Rocco; Scardovi, Angela B; Emdin, Michele; Metra, Marco; Sinagra, Gianfranco; Limongelli, Giuseppe; Raimondo, Rosa; Re, Federica; Guazzi, Marco; Belardinelli, Romualdo; Parati, Gianfranco; Magrì, Damiano; Fiorentini, Cesare; Cicoira, Mariantonietta; Salvioni, Elisabetta; Giovannardi, Marta; Mezzani, Alessandro; Scrutinio, Domenico; Di Lenarda, Andrea; Mantegazza, Valentina; Ricci, Roberto; Apostolo, Anna; Iorio, Annamaria; Paolillo, Stefania; Palermo, Pietro; Contini, Mauro; Vassanelli, Corrado; Passino, Claudio; Piepoli, Massimo F

2013-09-01

In patients with heart failure (HF), during maximal cardiopulmonary exercise test, anaerobic threshold (AT) is not always identified. We evaluated whether this finding has a prognostic meaning. We recruited and prospectively followed up, in 14 dedicated HF units, 3058 patients with systolic (left ventricular ejection fraction <40%) HF in stable clinical conditions, New York Heart Association class I to III, who underwent clinical, laboratory, echocardiographic, and cardiopulmonary exercise test investigations at study enrollment. We excluded 921 patients who did not perform a maximal exercise, based on lack of achievement of anaerobic metabolism (peak respiratory quotient ≤1.05). Primary study end point was a composite of cardiovascular death and urgent cardiac transplant, and secondary end point was all-cause death. Median follow-up was 3.01 (1.39-4.98) years. AT was identified in 1935 out of 2137 patients (90.54%). At multivariable logistic analysis, failure in detecting AT resulted significantly in reduced peak oxygen uptake and higher metabolic exercise and cardiac and kidney index score value, a powerful prognostic composite HF index (P<0.001). At multivariable analysis, the following variables were significantly associated with primary study end point: peak oxygen uptake (% pred; P<0.001; hazard ratio [HR]=0.977; confidence interval [CI]=0.97-0.98), ventilatory efficiency slope (P=0.01; HR=1.02; CI=1.01-1.03), hemoglobin (P<0.05; HR=0.931; CI=0.87-1.00), left ventricular ejection fraction (P<0.001; HR=0.948; CI=0.94-0.96), renal function (modification of diet in renal disease; P<0.001; HR=0.990; CI=0.98-0.99), sodium (P<0.05; HR=0.967; CI=0.94-0.99), and AT nonidentification (P<0.05; HR=1.41; CI=1.06-1.89). Nonidentification of AT remained associated to prognosis also when compared with metabolic exercise and cardiac and kidney index score (P<0.01; HR=1.459; CI=1.09-1.10). Similar results were obtained for the secondary study end point. The inability to identify AT most often occurs in patients with severe HF, and it has an independent prognostic role in HF.

Analysis of Predictors of Resection and Survival in Locally Advanced Stage III Pancreatic Cancer: Does the Nature of Chemotherapy Regimen Influence Outcomes?

PubMed

Bednar, Filip; Zenati, Mazen S; Steve, Jennifer; Winters, Sharon; Ocuin, Lee M; Bahary, Nathan; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

2017-05-01

Locally advanced unresectable pancreatic cancer (LAPC) historically portends a poor prognosis. FOLFIRINOX and gemcitabine/nab-paclitaxel have proven effective in the metastatic setting. We sought to evaluate the outcomes of these regimens compared with older regimens in LAPC. A retrospective, single institutional review of all consecutive LAPC treated with "new" (FOLFIRINOX and/or gemcitabine/nab-paclitaxel) and "old" (gemcitabine or 5-FU) chemotherapy from 2010 to 2014 was performed. Univariate and multivariate predictors of resection and survival were determined. A total of 92 patients (new chemotherapy = 61, old chemotherapy = 31) were analyzed, of which 19 (21%) underwent eventual resection (median overall survival [OS] = 32 vs. 14.3 months for unresected patients, P = 0.0002). For the overall cohort, resection (hazard ratio [HR] 0.261, P = 0.014), radiation therapy (HR 0.458, P = 0.004), number of lines of chemotherapy (HR 0.486, P = 0.012), and new chemotherapy (HR 0.593 vs. old regimens, P = 0.065) were independent predictors of OS on multivariate analyses (MVA). On MVA, predictors of eventual resection were head and neck tumors (OR 0.307, P = 0.033) or SMA involvement (OR 0.285, P = 0.023). In nonresected patients (73), MVA showed treatment with new chemotherapy (HR 0.452, P = 0.006), radiation (HR 0.459, P = 0.006), and number of lines of CT (HR 0.705, P = 0.013) to be predictors of survival. In LAPC, use of FOLFIRNOX and/or gemcitabine/nab-paclitaxel is associated with improved survival compared with older chemotherapy regimens, regardless of eventual resection. Tumor location and relationship to certain vasculature are important determinants of resection in this cohort.

Prevalence of anal high-risk human papillomavirus infections among HIV-positive and HIV-negative men who have sex with men (MSM) in Nigeria

PubMed Central

Nowak, Rebecca G.; Gravitt, Patti E.; He, Xin; Ketende, Sosthenes; Anom, Wuese; Omuh, Helen; Blattner, William A.; Charurat, Manhattan E.

2016-01-01

Background Prevalence estimates of anal high-risk human papillomavirus (HR-HPV) are needed in sub-Saharan Africa where HIV is endemic. This study evaluated anal HR-HPV in Nigeria among HIV-positive and HIV-negative men who have sex with men (MSM) for future immunization recommendations. Methods We conducted a cross-sectional study to compare the prevalence of anal HR-HPV infections between 64 HIV-negative and 90 HIV-positive MSM. Multivariate Poisson regression analyses were used to examine demographic and behavioral risk factors associated with any HR-HPV infections. Results The median age of the 154 participants was 25 years (interquartile range [IQR]: 22-28, range: 16-38) and the median age at initiation of anal sex with another man was 16 years (IQR: 13-18, range: 7-29). The prevalence of anal HR-HPV was higher among HIV-positive than HIV-negative MSM (91.1% vs. 40.6%, p<0.001). In the multivariate analysis, HIV infection (adjusted prevalence ratio [aPR]: 2.02, 95% CI: 1.49-2.72), ten years or more since anal sexual debut (aPR: 1.26, 95% CI: 1.07-1.49), and concurrent relationships with men (aPR: 1.32, 95% CI: 1.04-1.67) were associated with increased anal HR-HPV prevalence. Conclusions Anal HR-HPV infection is high for young Nigerian MSM and rates are amplified in those co-infected with HIV. Providing universal coverage as well as catchup immunization for young MSM may be an effective anal cancer prevention strategy in Nigeria. PMID:26967301

Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma.

PubMed

Meza-Junco, Judith; Montano-Loza, Aldo J; Baracos, Vickie E; Prado, Carla M M; Bain, Vincent G; Beaumont, Crystal; Esfandiari, Nina; Lieffers, Jessica R; Sawyer, Michael B

2013-01-01

Abnormal body composition such as severe skeletal muscle depletion or sarcopenia has emerged as an independent predictor of clinical outcomes in a variety of clinical conditions. This study is the first study to report the frequency and prognostic significance of sarcopenia as a marker of nutritional status in patients with hepatocellular carcinoma (HCC). We analyzed 116 patients with HCC who were consecutively evaluated for liver transplant. Skeletal muscle cross-sectional area was measured by CT. Sarcopenia was defined using previously established cutpoints. Ninety-eight patients were males (85%), and the mean age was 58±6 years. Sarcopenia was present in 35 patients (30%). By univariate Cox analysis, male sex (HR, 3.84; P=0.02), lumbar skeletal muscle index (HR, 0.97; P=0.04), INR (HR, 8.18; P<0.001), MELD score (HR, 1.19; P<0.001), Child-Pugh (HR, 3.95; P<0.001), serum sodium (HR, 0.84; P<0.001), TNM stage (HR, 2.59; P<0.001), treatment type (HR, 0.53; P<0.001), and sarcopenia (HR, 2.27; P=0.004) were associated with increased risks of mortality. By multivariate Cox regression analysis, only MELD score (HR, 1.08; P=0.04), Child-Pugh (HR, 2.14; P=0.005), sodium (HR, 0.89; P=0.01), TNM stage (HR, 1.92; P<0.001), and sarcopenia (HR, 2.04; P=0.02) were independently associated with mortality. Median survival for sarcopenic patients was 16±6 versus 28±3 months in nonsarcopenic (P=0.003). Sarcopenia is present in almost one third of patients with HCC, and constitutes a strong and independent risk factor for mortality. Our results highlight the importance of body composition assessment in clinical practice.

Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer

PubMed Central

Chu, Michael P.; Hecht, J. Randolph; Slamon, Dennis; Wainberg, Zev A.; Bang, Yung-Jue; Hoff, Paulo M.; Sobrero, Alberto; Qin, Shukui; Afenjar, Karen; Houe, Vincent; King, Karen; Koski, Sheryl; Mulder, Karen; Hiller, Julie Price; Scarfe, Andrew; Spratlin, Jennifer; Huang, Yingjie J.; Khan-Wasti, Saba; Chua, Neil

2016-01-01

Importance Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. Objective To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. Design, Setting, and Participants This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib. Proton pump inhibitor use was identified by medication records. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with PPIs vs patients who were not. Specific subgroups were accounted for, such as younger age (<60 years), Asian ethnicity, female sex, and disease stage (metastatic/advanced) in multivariate Cox proportional hazards modeling. The TRIO-013 trial accrued and randomized patients between June 2008 and January 2012; this analysis took place in January 2014. Interventions Patients were divided based on PPI exposure. Main Outcomes and Measures Primary study outcome was PFS and OS between patients treated with PPIs vs patients who were not. Secondary outcomes included disease response rates and toxicities. Results Of the 545 patients with GEC (median age, 60 years; 406 men [74%]) included in the study, 229 received PPIs (42.0%) and were evenly distributed between arms. In the placebo arm, PPI-treated patients had poorer median PFS, 4.2 vs 5.7 months (hazard ratio [HR], 1.55; 95% CI, 1.29-1.81, P < .001); OS, 9.2 vs 11.3 months (HR, 1.34; 95% CI, 1.06-1.62; P = .04); and disease control rate (72% vs 83%; P = .02) vs patients not treated with PPIs. In multivariate analysis considering age, race, disease stage, and sex, PPI-treated patients had poorer PFS (HR, 1.68; 95% CI, 1.42-1.94; P < .001) and OS (HR, 1.41; 95% CI, 1.11-1.71; P = .001). In patients treated with CapeOx and lapatinib, PPIs had less effect on PFS (HR, 1.08; P = .54) and OS (HR, 1.26; P = .10); however, multivariate analysis in this group demonstrated a significant difference in OS (HR, 1.38; 95% CI, 1.06-1.66; P = .03). Conclusions and Relevance Proton pump inhibitors negatively effected capecitabine efficacy by possibly raising gastric pH levels, leading to altered dissolution and absorption. These results are consistent with previous erlotinib and sunitinib studies. Whether PPIs affected lapatinib is unclear given concurrent capecitabine. Given capecitabine’s prevalence in treatment breast cancer and colon cancer, further studies are under way. Trial Registration clinicaltrials.gov Identifier: NCT00680901 PMID:27737436

Prognostic Significance of POLE Proofreading Mutations in Endometrial Cancer

PubMed Central

Church, David N.; Stelloo, Ellen; Nout, Remi A.; Valtcheva, Nadejda; Depreeuw, Jeroen; ter Haar, Natalja; Noske, Aurelia; Amant, Frederic; Wild, Peter J.; Lambrechts, Diether; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Smit, Vincent T. H. B. M.; Creutzberg, Carien L.; Bosse, Tjalling

2015-01-01

Background: Current risk stratification in endometrial cancer (EC) results in frequent over- and underuse of adjuvant therapy, and may be improved by novel biomarkers. We examined whether POLE proofreading mutations, recently reported in about 7% of ECs, predict prognosis. Methods: We performed targeted POLE sequencing in ECs from the PORTEC-1 and -2 trials (n = 788), and analyzed clinical outcome according to POLE status. We combined these results with those from three additional series (n = 628) by meta-analysis to generate multivariable-adjusted, pooled hazard ratios (HRs) for recurrence-free survival (RFS) and cancer-specific survival (CSS) of POLE-mutant ECs. All statistical tests were two-sided. Results: POLE mutations were detected in 48 of 788 (6.1%) ECs from PORTEC-1 and-2 and were associated with high tumor grade (P < .001). Women with POLE-mutant ECs had fewer recurrences (6.2% vs 14.1%) and EC deaths (2.3% vs 9.7%), though, in the total PORTEC cohort, differences in RFS and CSS were not statistically significant (multivariable-adjusted HR = 0.43, 95% CI = 0.13 to 1.37, P = .15; HR = 0.19, 95% CI = 0.03 to 1.44, P = .11 respectively). However, of 109 grade 3 tumors, 0 of 15 POLE-mutant ECs recurred, compared with 29 of 94 (30.9%) POLE wild-type cancers; reflected in statistically significantly greater RFS (multivariable-adjusted HR = 0.11, 95% CI = 0.001 to 0.84, P = .03). In the additional series, there were no EC-related events in any of 33 POLE-mutant ECs, resulting in a multivariable-adjusted, pooled HR of 0.33 for RFS (95% CI = 0.12 to 0.91, P = .03) and 0.26 for CSS (95% CI = 0.06 to 1.08, P = .06). Conclusion: POLE proofreading mutations predict favorable EC prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors. This novel biomarker may help to reduce overtreatment in EC. PMID:25505230

Preoperative Toxoplasma gondii serostatus does not affect long-term survival of cardiac transplant recipients. Analysis of the Spanish Heart Transplantation Registry.

PubMed

Barge-Caballero, Eduardo; Almenar-Bonet, Luis; Crespo-Leiro, María G; Brossa-Loidi, Vicens; Rangel-Sousa, Diego; Gómez-Bueno, Manuel; Farrero-Torres, Marta; Díaz-Molina, Beatriz; Delgado-Jiménez, Juan; Martínez-Sellés, Manuel; López-Granados, Amador; De-la-Fuente-Galán, Luis; González-Costello, José; Garrido-Bravo, Iris P; Blasco-Peiró, Teresa; Rábago-Juan-Aracil, Gregorio; González-Vílchez, Francisco

2018-01-01

It's unclear whether pre-transplant T. gondii seropositivity is associated with impaired survival in heart transplant recipients. To test the above-mentioned hypothesis in the Spanish Heart Transplantation Registry. Post-transplant outcomes of 4048 patients aged >16years who underwent first, single-organ heart transplantation in 17 Spanish institutions from 1984 to 2014 were studied. Long-term post-transplant survival and survival free of cardiac death or retransplantation of 2434 (60%) T. gondii seropositive recipients and 1614 (40%) T. gondii seronegative recipients were compared. T. gondii seropositive recipients were older, had higher body mass index, and presented higher prevalence of hypertension, hypercholesterolemia, COPD and Cytomegalovirus seropositivity than T. gondii seronegative recipients. In univariable analysis, pre-transplant T. gondii seropositivity was associated with increased post-transplant all-cause mortality (non-adjusted HR 1.15; 95% CI 1.04-1.26). However, this effect was no longer statistically significant after multivariable adjustment by recipient's age and sex (adjusted HR 1.01, 95% CI 0.92-1.11). Extended multivariable adjustment by other potential confounders showed similar results (adjusted HR 0.99, 95% CI 0.89-1.11). T. gondii seropositivity had no significant effect on the composite outcome cardiac death or retransplantation (non-adjusted HR 1.08, 95% CI 0.95-1.24, p=0.235). The distribution of the causes of death was comparable in T. gondii seropositive and T. gondii seronegative recipients. No statistically significant impact of donor's T. gondii serostatus or donor-recipient T. gondii serostatus matching on post-transplant survival was observed. Our analysis did not show a significant independent effect of preoperative T. gondii serostatus on long-term outcomes after heart transplantation. Copyright © 2017 Elsevier B.V. All rights reserved.

Sudden death after pediatric heart transplantation: analysis of data from the Pediatric Heart Transplant Study Group.

PubMed

Daly, Kevin P; Chakravarti, Sujata B; Tresler, Margaret; Naftel, David C; Blume, Elizabeth D; Dipchand, Anne I; Almond, Christopher S

2011-12-01

Sudden death is a well-recognized complication of heart transplantation. Little is known about the incidence and risk factors for sudden death after transplant in children. The purpose of this study was to determine the incidence of and risk factors for sudden death. This retrospective multicenter cohort study used the Pediatric Heart Transplant Study Group (PHTS) database, an event-driven registry of children aged <18 at listing undergoing heart transplantation between 1993 and 2007. Standard Kaplan-Meier and parametric analyses were used for survival analysis. Multivariate analysis in the hazard-function domain was used to identify risk factors for sudden death after transplant. Of 604 deaths in 2,491 children who underwent heart transplantation, 94 (16%) were classified as sudden. Freedom from sudden death was 97% at 5 years, and the hazard for sudden death remained constant over time at 0.01 deaths/year. Multivariate risk factors associated with sudden death included black race (hazard ratio [HR], 2.6; p < 0.0001), United Network of Organ Sharing (UNOS) status 2 at transplant (HR, 1.8; p = 0.008), older age (HR, 1.4/10 years of age; p = 0.03), and an increased number of rejection episodes in the first post-transplant year (HR, 1.6/episode; p = 0.03). Sudden death accounts for 1 in 6 deaths after heart transplant in children. Older recipient age, recurrent rejection within the first year, black race, and UNOS status 2 at listing were associated with sudden death. Patients with 1 or more of these risk factors may benefit from primary prevention efforts. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Cardiovascular Complications and Short-term Mortality Risk in Community-Acquired Pneumonia.

PubMed

Violi, Francesco; Cangemi, Roberto; Falcone, Marco; Taliani, Gloria; Pieralli, Filippo; Vannucchi, Vieri; Nozzoli, Carlo; Venditti, Mario; Chirinos, Julio A; Corrales-Medina, Vicente F

2017-06-01

Previous reports suggest that community-acquired pneumonia (CAP) is associated with an enhanced risk of cardiovascular complications. However, a contemporary and comprehensive characterization of this association is lacking. In this multicenter study, 1182 patients hospitalized for CAP were prospectively followed for up to 30 days after their hospitalization for this infection. Study endpoints included myocardial infarction, new or worsening heart failure, atrial fibrillation, stroke, deep venous thrombosis, cardiovascular death, and total mortality. Three hundred eighty (32.2%) patients experienced intrahospital cardiovascular events (CVEs) including 281 (23.8%) with heart failure, 109 (9.2%) with atrial fibrillation, 89 (8%) with myocardial infarction, 11 (0.9%) with ischemic stroke, and 1 (0.1%) with deep venous thrombosis; 28 patients (2.4%) died for cardiovascular causes. Multivariable Cox regression analysis showed that intrahospital Pneumonia Severity Index (PSI) class (hazard ratio [HR], 2.45, P = .027; HR, 4.23, P < .001; HR, 5.96, P < .001, for classes III, IV, and V vs II, respectively), age (HR, 1.02, P = .001), and preexisting heart failure (HR, 1.85, P < .001) independently predicted CVEs. One hundred three (8.7%) patients died by day 30 postadmission. Thirty-day mortality was significantly higher in patients who developed CVEs compared with those who did not (17.6% vs 4.5%, P < .001). Multivariable Cox regression analysis showed that intrahospital CVEs (HR, 5.49, P < .001) independently predicted 30-day mortality (after adjustment for age, PSI score, and preexisting comorbid conditions). CVEs, mainly those confined to the heart, complicate the course of almost one-third of patients hospitalized for CAP. More importantly, the occurrence of CVEs is associated with a 5-fold increase in CAP-associated 30-day mortality. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Progression of liver fibrosis is associated with non‐liver‐related mortality in patients with nonalcoholic fatty liver disease

PubMed Central

Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yasuhiro; Akita, Tomoyuki; Tanaka, Junko

2017-01-01

In patients with nonalcoholic fatty liver disease (NAFLD), prognosis and outcome, especially non‐liver‐related mortality, remain incompletely elucidated. We clarified the mortality from all causes in patients with NAFLD. A total of 4,073 patients with NAFLD diagnosed by ultrasonography were enrolled. We investigated the causes of death and analyzed the mortality from non‐liver‐related diseases according to the degrees of steatosis and fibrosis using the competing risk method. We used the NAFLD fibrosis score (NFS) to assess fibrosis severity and the ultrasonography fatty liver score to evaluate steatosis severity. The numbers of patients with NFS indicating low, intermediate, and high probabilities of advanced fibrosis were 2,451 (60.2%), 1,462 (35.9%), and 160 (3.9%), respectively. Of the 4,073 patients, 179 died during follow‐up, but only nine deaths were due to liver‐related diseases. Of the remaining 170 patients who died due to non‐liver‐related diseases, 83 (48.8%), 42 (24.7%), and 45 (26.5%) patients died due to malignancies, cerebrovascular and cardiovascular diseases, and benign diseases (excluding cerebrovascular and cardiovascular diseases), respectively. Multivariate analysis showed that the intermediate and high NFS groups were independently associated with each disease category: hazard ratio (HR) 2.163 (95% confidence interval [CI], 1.354‐3.457) and HR 4.814 (95% CI, 2.323‐9.977) for malignancies; HR 2.265 (95% CI, 1.141‐4.497) and HR 8.482 (95% CI, 3.558‐20.220) for cerebrovascular and cardiovascular diseases; and HR 3.216 (95% CI, 1.641‐6.303) and HR 5.558 (95% CI, 1.923‐16.070) for benign diseases, respectively. Conversely, the status of steatosis was not associated with risk of mortality in multivariate analysis. Conclusion: Progression of liver fibrosis severity was associated with mortality from various non‐liver‐related causes in patients with NAFLD. (Hepatology Communications 2017;1:928–945) PMID:29404500

Influence of Pulmonary Hypertension on Patients With Idiopathic Pulmonary Fibrosis Awaiting Lung Transplantation.

PubMed

Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Kirkby, Stephen; Mansour, Heidi M; Whitson, Bryan A

2016-01-01

The influence of varying levels of pulmonary hypertension (PH) on survival in idiopathic pulmonary fibrosis is not well defined. The United Network for Organ Sharing database was queried from 2005 to 2013 to identify first-time lung transplant candidates listed for lung transplantation who were tracked from waitlist entry date until death or censoring to determine the influence of PH on patients with advanced lung disease. Using data for right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure of 25 mm Hg or more, and severe as 35 mm Hg or more. Of 6,657 idiopathic pulmonary fibrosis patients, 6,651 were used for univariate analysis, 6,126 for Kaplan-Meier survival function, 6,013 for multivariate Cox models, and 5,186 (mild PH) and 2,014 (severe PH) for propensity score matching, respectively. Univariate Cox proportional hazards analysis found significant differences in survival for mild PH (hazard ratio [HR] 1.689, 95% confidence interval [CI]: 1.434 to 1.988, p < 0.001) and severe PH (HR 2.068, 95% CI: 1.715 to 2.493, p < 0.001). Further assessment by multivariate Cox models identified significant risk for death for mild PH (HR 1.433, 95% CI: 1.203 to 1.706, p < 0.001) and severe PH (HR 1.597, 95% CI: 1.308 to 1.949, p < 0.001). Propensity score matching confirmed the risk for death for mild PH (HR 1.530, 95% CI: 1.189 to 1.969, p = 0.001) and severe PH (HR 2.103, 95% CI: 1.436 to 3.078, p < 0.001). The manifestation of PH, even with mild severity, is associated with significantly increased risk for death among patients with idiopathic pulmonary fibrosis awaiting lung transplantation, so referral should be considered early in the disease course. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Despite Access to Antiretrovirals for Prevention and Treatment, High Rates of Mortality Persist Among HIV-infected Infants and Young Children.

PubMed

Abrams, Elaine J; Woldesenbet, Selamawit; Soares Silva, Juliana; Coovadia, Ashraf; Black, Viviane; Technau, Karl-Günter; Kuhn, Louise

2017-06-01

Outcomes of HIV-infected children before widespread use of antiretroviral therapy (ART) for treatment and prevention of mother-to-child transmission (PMTCT) have been well characterized but less is known about children who acquire HIV infection in the context of good ART access. We enrolled newly diagnosed HIV-infected children ≤24 months of age at 3 hospitals and 2 clinics in Johannesburg, South Africa. We report ART initiation and mortality rates during 6 months from enrollment and factors associated with mortality. Of 272 children enrolled, median age 6.1 months, 69.5% were diagnosed during hospitalization. By 6 months postenrollment, 53 (19.5%) died and 73 (26.8%) were lost-to-follow-up. Using Kaplan-Meier analysis, the probability of death by 6 months after enrollment was 23.5%. The median age of death was 9.1 months [95% confidence interval (CI): 8.6-12.0]. Overall, 226 (83%) children initiated ART which was associated with a 71% reduction in risk of death [hazard ratio (HR) = 0.29 (95% CI: 0.15-0.58)]. In multivariable analysis of infant factors, weight-for-age Z score < -2 standard deviation (SD) [HR = 2.43 (95% CI: 1.03-5.73)], CD4 <20% [HR = 3.29 (95% CI: 1.60-6.76)] and identification during hospitalization [HR = 2.89 (95% CI: 1.16-7.25)] were independently associated with mortality. In multivariable analysis of maternal factors, CD4 ≤350/no maternal ART was associated with increased mortality risk [HR = 2.57 (95% CI: 1.19-5.59)] versus CD4 >350/no maternal ART; exposure to maternal/infant antiretrovirals for PMTCT was associated with reduced mortality risk [HR = 0.53 (95% CI: 0.28-0.99)] versus no PMTCT. ART initiation is highly protective against death in young children. However, despite improved access to ART, young children remain at risk for early death; innovative approaches to rapidly diagnose and initiate treatment as early in life as possible are needed.

Brachytherapy Is Associated With Improved Survival in Inoperable Stage I Endometrial Adenocarcinoma: A Population-Based Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acharya, Sahaja; Perkins, Stephanie M.; DeWees, Todd

2015-11-01

Purpose: To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause-specific survival (CSS). Methods and Materials: Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Coxmore » proportional hazards regression model. Results: A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92). Conclusion: Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.« less

Factors affecting death and progression towards next stage following modified Blalock-Taussig shunt in neonates.

PubMed

Alsoufi, Bahaaldin; Gillespie, Scott; Mori, Makoto; Clabby, Martha; Kanter, Kirk; Kogon, Brian

2016-07-01

The modified Blalock-Taussig shunt (BTS) is utilized to palliate neonates born with restrictive pulmonary blood flow including those with single ventricle (SV) or biventricular (BV) cardiac anomalies. We aim in the current study to report palliation outcomes of neonates with BTS and to examine factors affecting death and progression to the subsequent stage of palliation or repair. Between 2002 and 2012, 341 patients underwent BTS including 175 with SV and 166 with BV anomalies. Competing risk analysis modelled events after BTS (death or transplantation, transition to Glenn shunt or biventricular repair) and examined risk factors affecting outcomes. SV patients had a higher incidence of extracorporeal membrane oxygenation (ECMO) support requirement (12 vs 4%, P = 0.004) and unplanned cardiac reoperation (14 vs 7%, P = 0.051) than their BV counterparts. Additionally, hospital mortality was higher in SV than in BV patients (15 vs 3%, P < 0.001). In SV patients, competing risk analysis showed that, 2 years following BTS, 27% of patients had died or received transplantation and 73% had undergone the Glenn shunt. On multivariable analysis, factors associated with time until death or transplantation prior to Glenn were cardiopulmonary bypass [hazard ratio (HR) 3.6 (2.0-6.4), P < 0.001], unplanned cardiac reoperation [HR 2.4 (1.3-4.6), P = 0.007], pulmonary atresia [HR 2.0 (1.1-3.7), P = 0.026] and the shunt size/weight ratio [HR 1.3 (1.1-1.4) per 0.1 increase, P = 0.001]. In BV patients, competing risk analysis showed that, 2 years following BTS, 13% of patients had died or received transplantation, 85% had undergone biventricular repair and 2% were alive without biventricular repair. On multivariable analysis, factors associated with time until death or transplantation prior to biventricular repair were genetic syndromes and extracardiac malformations [HR 6.1 (2.0-18.2), P = 0.001], weight ≤2.5 kg [HR 5.6 (2.0-16.0), P = 0.001] and male gender [HR 3.4 (1.1-11.0), P = 0.041]. Palliation with BTS continues to be associated with significant operative morbidity and mortality. In addition to hospital death, there is an important interstage attrition risk prior to subsequent palliation or biventricular repair. Inherent patient characteristics (i.e. genetic syndromes and low weight) and anatomical details (i.e. SV, pulmonary atresia and concomitant cardiac anomalies) are associated with worse survival. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy.

PubMed

Fan, Bo; Hu, Bin; Yuan, Qingmin; Wen, Shuang; Liu, Tianqing; Bai, Shanshan; Qi, Xiaofeng; Wang, Xin; Yang, Deyong; Sun, Xiuzhen; Song, Xishuang

2017-07-01

Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. Recent publications have assessed the prognostic significance of tumor architecture in UTUC, but there is still controversy regarding the significance and importance of tumor architecture on disease recurrence. We retrospectively reviewed the medical records of 101 patients with clinical UTUC who had undergone surgery. Univariate and multivariate analyses were conducted to identify factors associated with disease recurrence and cancer-specific mortality. As our single center study and the limited sample size may influence the clinical significance, we further quantitatively combined the results with those of existing published literature through a meta-analysis compiled from searching several databases. At a median follow-up of 41.3 months, 25 patients experienced disease recurrence. Spearman's correlation analysis showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with sessile tumor architecture had significantly poor recurrence free survival (RFS) and cancer specific survival (CSS). Furthermore, multivariate analysis suggested that tumor architecture was independent prognostic factors for RFS (Hazard ratio, HR = 2.648) and CSS (HR = 2.072) in UTUC patients. A meta-analysis of investigating tumor architecture and its effects on UTUC prognosis was conducted. After searching PubMed, Medline, Embase, Cochrane Library and Scopus databases, 17 articles met the eligibility criteria for this analysis. The eligible studies included a total of 14,368 patients and combined results showed that sessile tumor architecture was associated with both disease recurrence with a pooled HR estimate of 1.454 and cancer-specific mortality with a pooled HR estimate of 1.416. Tumor architecture is an independent predictor for disease recurrence after radical nephroureterectomy for UTUC. Therefore, closer surveillance is necessary, especially in patients with sessile tumor architecture.

Prognostic factors and long-term outcomes of hilar cholangiocarcinoma: A single-institution experience in China

PubMed Central

Hu, Hai-Jie; Mao, Hui; Shrestha, Anuj; Tan, Yong-Qiong; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Cheng, Nan-Sheng; Li, Fu-Yu

2016-01-01

AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution. METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated by univariate and multivariate analyses. RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio (HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease (HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation (HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion (HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins (HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease (HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation (HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion (HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins (HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio (OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter (OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures (OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage (OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion (OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumor-free margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect survival outcome by influencing the tumor resection margin. PMID:26937148

Factors predicting survival in amyotrophic lateral sclerosis patients on non-invasive ventilation.

PubMed

Gonzalez Calzada, Nuria; Prats Soro, Enric; Mateu Gomez, Lluis; Giro Bulta, Esther; Cordoba Izquierdo, Ana; Povedano Panades, Monica; Dorca Sargatal, Jordi; Farrero Muñoz, Eva

2016-01-01

Non invasive ventilation (NIV) improves quality of life and extends survival in amyotrophic lateral sclerosis (ALS) patients. However, few data exist about the factors related to survival. We intended to assess the predictive factors that influence survival in patients after NIV initiation. Patients who started NIV from 2000 to 2014 and were tolerant (compliance ≥ 4 hours) were included; demographic, disease related and respiratory variables at NIV initiation were analysed. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. 213 patients were included with median survival from NIV initiation of 13.5 months. In univariate analysis, the identified risk factors for mortality were severity of bulbar involvement (HR 2), Forced Vital Capacity (FVC) % (HR 0.99) and ALSFRS-R (HR 0.97). Multivariate analysis showed that bulbar involvement (HR 1.92) and ALSFRS-R (HR 0.97) were independent predictive factors of survival in patients on NIV. In our study, the two prognostic factors in ALS patients following NIV were the severity of bulbar involvement and ALSFRS-R at the time on NIV initiation. A better assessment of bulbar involvement, including evaluation of the upper airway, and a careful titration on NIV are necessary to optimize treatment efficacy.

Outcomes following Kidney transplantation in IgA nephropathy: a UNOS/OPTN analysis.

PubMed

Kadiyala, Aditya; Mathew, Anna T; Sachdeva, Mala; Sison, Cristina P; Shah, Hitesh H; Fishbane, Steven; Jhaveri, Kenar D

2015-10-01

This study updates assessment of post-transplant outcomes in IgAN patients in the modern era of immunosuppression. Using UNOS/OPTN data, patients ≥18 yr of age with first kidney transplant (1/1/1999 to 12/31/2008) were analyzed. Multivariable Cox regression models and propensity score-based matching techniques were used to estimate hazard ratios (HRs) for death-censored allograft survival (DCGS) and patient survival in IgAN compared to non-IgAN. Results of multivariable regression were stratified by donor type (living vs. deceased). A total of 107, 747 recipients were included (4589 with IgAN and 103 158 with non-IgAN). Adjusted HR for DCGS showed no significant difference between IgAN and non-IgAN. IgAN had higher patient survival compared to non-IgAN (HR 0.54, 95% CI 0.47-0.62, p < 0.0001 for deceased donors; HR 0.42, 95% CI 0.33-0.54, p < 0.0001 for living donors). Propensity score-matched analysis was similar, with no significant difference in DCGS between matched groups and higher patient survival in IgAN patients compared to non-IgAN group (HR 0.54, 95% CI 0.47, 0.63; p-value <0.0001). IgAN patients with first kidney transplant have superior patient survival and similar graft survival compared to non-IgAN recipients. Results can be used in prognostication and informed decision-making about kidney transplantation in patients with IgAN. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High Ki-67 Immunohistochemical Reactivity Correlates With Poor Prognosis in Bladder Carcinoma

PubMed Central

Luo, Yihuan; Zhang, Xin; Mo, Meile; Tan, Zhong; Huang, Lanshan; Zhou, Hong; Wang, Chunqin; Wei, Fanglin; Qiu, Xiaohui; He, Rongquan; Chen, Gang

2016-01-01

Abstract Ki-67 is considered as one of prime biomarkers to reflect cell proliferation and immunohistochemical Ki-67 staining has been widely applied in clinical pathology. To solve the widespread controversy whether Ki-67 reactivity significantly predicts clinical prognosis of bladder carcinoma (BC), we performed a comprehensive meta-analysis by combining results from different literature. A comprehensive search was conducted in the Chinese databases of WanFang, China National Knowledge Infrastructure and Chinese VIP as well as English databases of PubMed, ISI web of science, EMBASE, Science Direct, and Wiley online library. Independent studies linking Ki-67 to cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were included in our meta-analysis. With the cut-off values literature provided, hazard ratio (HR) values between the survival distributions were extracted and later combined with STATA 12.0. In total, 76 studies (n = 13,053 patients) were eligible for the meta-analysis. It was indicated in either univariate or multivariate analysis for survival that high Ki-67 reactivity significantly predicted poor prognosis. In the univariate analysis, the combined HR for CSS, DFS, OS, PFS, and RFS were 2.588 (95% confidence interval [CI]: 1.623–4.127, P < 0.001), 2.697 (95%CI: 1.874–3.883, P < 0.001), 2.649 (95%CI: 1.632–4.300, P < 0.001), 3.506 (95%CI: 2.231–5.508, P < 0.001), and 1.792 (95%CI: 1.409–2.279, P < 0.001), respectively. The pooled HR of multivariate analysis for CSS, DFS, OS, PFS, and RFS were 1.868 (95%CI: 1.343–2.597, P < 0.001), 2.626 (95%CI: 2.089–3.301, P < 0.001), 1.104 (95%CI: 1.008–1.209, P = 0.032), 1.518 (95%CI: 1.299–1.773, P < 0.001), and 1.294 (95%CI: 1.203–1.392, P < 0.001), respectively. Subgroup analysis of univariate analysis by origin showed that Ki-67 reactivity significantly correlated with all 5 clinical outcome in Asian and European-American patients (P < 0.05). For multivariate analysis, however, the pooled results were only significant for DFS, OS, and RFS in Asian patients, for CSS, DFS, PFS, and RFS in European-American patients (P < 0.05). In the subgroup with low cut-off value (<20%), our meta-analysis indicated that high Ki-67 reactivity was significantly correlated with worsened CSS, DFS, OS, PFS, and RFS on univariate analysis (P < 0.05). For multivariate analysis, the meta-analysis of literature with low cut-off value (<20%) demonstrated that high Ki-67 reactivity predicted shorter DFS, PFS, and RFS in BC patients (P < 0.05). In the subgroup analysis of high cut-off value (≥20%), our meta-analysis indicated that high Ki-67 reactivity, in either univariate or multivariate analysis, significantly correlated with all five clinical outcomes in BC patients (P < 0.05). The meta-analysis indicates that high Ki-67 reactivity significantly correlates with deteriorated clinical outcomes in BC patients and that Ki-67 can be considered as an independent indicator for the prognosis by the meta-analyses of multivariate analysis. PMID:27082587

Prognostic factors of early metastasis and mortality in dogs with appendicular osteosarcoma after receiving surgery: an individual patient data meta-analysis.

PubMed

Schmidt, A F; Nielen, M; Klungel, O H; Hoes, A W; de Boer, A; Groenwold, R H H; Kirpensteijn, J

2013-11-01

Recently an aggregated data meta-analysis showed that serum alkaline phosphatase (SALP) and proximal humerus location are predictors for shorter survival in canine osteosarcoma. To identify additional prognostic factors of mortality and metastasis an individual patient data meta-analysis (IPDMA) was conducted. Individual patient data from 20 studies, identified via the VSSO society, were pooled. Univariable and multivariable hazard ratios (HR) for metastasis and mortality were assessed, using stratified Cox models. The study included 1405 dogs who received surgical treatment, of which the metastasis status was measured in 1155 dogs and mortality status in 1336 dogs; median survival was 256 days. High versus normal SALP and weight (kg) were associated with an increase in hazard of metastasis [HR 1.34 (95%CI 1.07; 1.68) and HR 1.02 (per kg increase) (95%CI 1.01; 1.03)] and for mortality [HR 1.43 (95%CI 1.16; 1.77) and HR 1.02 (95%CI 1.01; 1.02)]. Distal radius tumor was associated with a lower hazard of metastasis compared to other locations: HR 0.75 (95%CI 0.58; 0.96). Proximal humerus and distal femur or proximal tibia location were related with an increased mortality: HR 1.53 (95%CI 1.26; 1.84) and HR 1.23 (95%CI 1.01; 1.49) compared to other locations. Older age (years) was associated with a higher hazard for mortality [HR 1.06 per year (95%CI 1.03; 1.09)] but not for metastasis: HR 1.03 (95%CI 0.99; 1.06). These results confirm findings from a recent aggregated data meta-analysis and (in addition) showed that tumor location, SALP, weight were prognostic factors for both mortality and metastasis. Age was a prognostic factor for mortality but not for metastasis. Copyright © 2013 Elsevier B.V. All rights reserved.

High Prevalence of Anal Canal High-Risk Human Papillomavirus Infection in Patients With Crohn's Disease.

PubMed

Vuitton, Lucine; Jacquin, Elise; Parmentier, Anne-Laure; Crochet, Elise; Fein, Francine; Dupont-Gossart, Anne-Claire; Plastaras, Laurianne; Bretagne, Charles-Henri; Mauny, Frédéric; Koch, Stéphane; Prétet, Jean-Luc; Mougin, Christiane; Valmary-Degano, Séverine

2018-03-15

The increasing incidence of anal canal carcinomas requires better knowledge on anal human papillomavirus (HPV) infection. We aimed to assess anal canal HPV infection prevalence and risk factors among patients seen at a gastroenterology department in France. We analyzed anal tissue samples collected from 469 consecutive patients (median age 54 years, 52% women), including 112 who received immunosuppressant therapies and 101 with inflammatory bowel disease (70 with Crohn's disease), who underwent colonoscopy examinations from April 1, 2012 to April 30, 2015. HPV was detected and genotyped using the INNO-LiPA assay, and we collected medical and demographic data from all subjects. Risk factors for any HPV, high-risk HPV (HR-HPV) and HPV16 infection were assessed by bivariate and multivariate analysis. The primary outcomes association of HR-HPV or HPV16 with medical and demographic features. We detected HPV DNA in anal tissues from 34% of the subjects and HR-HPV in 18%. HPV16 was the most prevalent genotype (detected in 7%), followed by HPV51, HPV52, and HPV39. HR-HPV was detected in a significantly higher proportion of samples from women (23.1%) than men (12.8%) (P = .0035); HR-HPV and HPV16 were detected in a significantly higher proportion of patients with Crohn's disease (30.0%) than without (18.1%) (P = .005). Female sex, history of sexually transmitted disease, lifetime and past year-number of sexual partners, active smoking, and immunosuppressive therapies were independent risk factors for anal HR-HPV infection in multivariate analysis. One third of patients who underwent colonoscopy at a gastroenterology department were found to have anal canal HPV infection. We detected HR-HPV infection in almost 20% of patients and in a significantly higher proportion of patients with Crohn's disease than without. Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cardiovascular mortality prediction in veterans with arm exercise vs pharmacologic myocardial perfusion imaging.

PubMed

Martin, Wade H; Xian, Hong; Chandiramani, Pooja; Bainter, Emily; Klein, Andrew J P

2015-08-01

No data exist comparing outcome prediction from arm exercise vs pharmacologic myocardial perfusion imaging (MPI) stress test variables in patients unable to perform treadmill exercise. In this retrospective study, 2,173 consecutive lower extremity disabled veterans aged 65.4 ± 11.0years (mean ± SD) underwent either pharmacologic MPI (1730 patients) or arm exercise stress tests (443 patients) with MPI (n = 253) or electrocardiography alone (n = 190) between 1997 and 2002. Cox multivariate regression models and reclassification analysis by integrated discrimination improvement (IDI) were used to characterize stress test and MPI predictors of cardiovascular mortality at ≥10-year follow-up after inclusion of significant demographic, clinical, and other variables. Cardiovascular death occurred in 561 pharmacologic MPI and 102 arm exercise participants. Multivariate-adjusted cardiovascular mortality was predicted by arm exercise resting metabolic equivalents (hazard ratio [HR] 0.52, 95% CI 0.39-0.69, P < .001), 1-minute heart rate recovery (HR 0.61, 95% CI 0.44-0.86, P < .001), and pharmacologic and arm exercise delta (peak-rest) heart rate (both P < .001). Only an abnormal arm exercise MPI prognosticated cardiovascular death by multivariate Cox analysis (HR 1.98, 95% CI 1.04-3.77, P < .05). Arm exercise MPI defect number, type, and size provided IDI over covariates for prediction of cardiovascular mortality (IDI = 0.074-0.097). Only pharmacologic defect size prognosticated cardiovascular mortality (IDI = 0.022). Arm exercise capacity, heart rate recovery, and pharmacologic and arm exercise heart rate responses are robust predictors of cardiovascular mortality. Arm exercise MPI results are equivalent and possibly superior to pharmacologic MPI for cardiovascular mortality prediction in patients unable to perform treadmill exercise. Published by Elsevier Inc.

Comparison of the prognostic value of pretreatment measurements of systemic inflammatory response in patients undergoing curative resection of clear cell renal cell carcinoma.

PubMed

Lucca, Ilaria; de Martino, Michela; Hofbauer, Sebastian L; Zamani, Nura; Shariat, Shahrokh F; Klatte, Tobias

2015-12-01

Pretreatment measurements of systemic inflammatory response, including the Glasgow prognostic score (GPS), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) and the prognostic nutritional index (PNI) have been recognized as prognostic factors in clear cell renal cell carcinoma (CCRCC), but there is at present no study that compared these markers. We evaluated the pretreatment GPS, NLR, MLR, PLR and PNI in 430 patients, who underwent surgery for clinically localized CCRCC (pT1-3N0M0). Associations with disease-free survival were assessed with Cox models. Discrimination was measured with the C-index, and a decision curve analysis was used to evaluate the clinical net benefit. On multivariable analyses, all measures of systemic inflammatory response were significant prognostic factors. The increase in discrimination compared with the stage, size, grade and necrosis (SSIGN) score alone was 5.8 % for the GPS, 1.1-1.4 % for the NLR, 2.9-3.4 % for the MLR, 2.0-3.3 % for the PLR and 1.4-3.0 % for the PNI. On the simultaneous multivariable analysis of all candidate measures, the final multivariable model contained the SSIGN score (HR 1.40, P < 0.001), the GPS (HR 2.32, P < 0.001) and the MLR (HR 5.78, P = 0.003) as significant variables. Adding both the GPS and the MLR increased the discrimination of the SSIGN score by 6.2 % and improved the clinical net benefit. In patients with clinically localized CCRCC, the GPS and the MLR appear to be the most relevant prognostic measures of systemic inflammatory response. They may be used as an adjunct for patient counseling, tailoring management and clinical trial design.

An HR-MAS MR Metabolomics Study on Breast Tissues Obtained with Core Needle Biopsy

PubMed Central

Cho, Nariya; Chang, Jung Min; Koo, Hye Ryoung; Yi, Ann; Kim, Hyeonjin; Park, Sunghyouk; Moon, Woo Kyung

2011-01-01

Background Much research has been devoted to the development of new breast cancer diagnostic measures, including those involving high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopic techniques. Previous HR-MAS MR results have been obtained from post-surgery samples, which limits their direct clinical applicability. Methodology/Principal Findings In the present study, we performed HR-MAS MR spectroscopic studies on 31 breast tissue samples (13 cancer and 18 non-cancer) obtained by percutaneous core needle biopsy. We showed that cancer and non-cancer samples can be discriminated very well with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA) multivariate model on the MR spectra. A subsequent blind test showed 69% sensitivity and 94% specificity in the prediction of the cancer status. A spectral analysis showed that in cancer cells, taurine- and choline-containing compounds are elevated. Our approach, additionally, could predict the progesterone receptor statuses of the cancer patients. Conclusions/Significance HR-MAS MR metabolomics on intact breast tissues obtained by core needle biopsy may have a potential to be used as a complement to the current diagnostic and prognostic measures for breast cancers. PMID:22028780

Quality of Life in Patients with Noninfectious Uveitis Treated with or without Systemic Anti-inflammatory Therapy.

PubMed

Gui, Wei; Dombrow, Matthew; Marcus, Inna; Stowe, Meredith H; Tessier-Sherman, Baylah; Yang, Elizabeth; Huang, John J

2015-04-01

To compare vision-related (VR-QOL) and health-related quality of life (HR-QOL) in patients with noninfectious uveitis treated with systemic anti-inflammatory therapy versus nonsystemic therapy. A prospective, cross-sectional study design was employed. VR-QOL and HR-QOL were assessed by the 25-Item Visual Function Questionnaire (VFQ-25) and the Short Form 12-Item Health Survey (SF-12), respectively. Multivariate regression analysis was performed to assess the VR-QOL and HR-QOL based on treatment. Among the 80 patients, the median age was 51 years with 28 males (35%). The adjusted effect of treatment modality on VR-QOL or HR-QOL showed no statistically significant difference in all subscores of VFQ-25 or physical component score (PCS) and mental component score (MCS) of SF-12. Systemic therapy did not compromise VR-QOL or HR-QOL compared to nonsystemic therapy. Systemic therapy can be effectively used to control serious cases of noninfectious uveitis without significant relative adverse impact on quality of life.

Marital status is an independent prognostic factor for tracheal cancer patients: an analysis of the SEER database.

PubMed

Li, Mu; Dai, Chen-Yang; Wang, Yu-Ning; Chen, Tao; Wang, Long; Yang, Ping; Xie, Dong; Mao, Rui; Chen, Chang

2016-11-22

Although marital status is an independent prognostic factor in many cancers, its prognostic impact on tracheal cancer has not yet been determined. The goal of this study was to examine the relationship between marital status and survival in patients with tracheal cancer. Compared with unmarried patients (42.67%), married patients (57.33%) had better 5-year OS (25.64% vs. 35.89%, p = 0.009) and 5-year TCSS (44.58% vs. 58.75%, p = 0.004). Results of multivariate analysis indicated that marital status is an independent prognostic factor, with married patients showing better OS (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64-0.95, p = 0.015) and TCSS (HR = 0.70, 95% CI 0.54-0.91, p = 0.008). In addition, subgroup analysis suggested that marital status plays a more important role in the TCSS of patients with non-low-grade malignant tumors (HR = 0.71, 95% CI 0.53-0.93, p = 0.015). We extracted 600 cases from the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by Pearson chi-squared test, t-test, log-rank test, and multivariate Cox regression analysis. Overall survival (OS) and tracheal cancer-specific survival (TCSS) were compared between subgroups with different pathologic features and tumor stages. Marital status is an independent prognostic factor for survival in patients with tracheal cancer. For that reason, additional social support may be needed for unmarried patients, especially those with non-low-grade malignant tumors.

Gastric cancer, nutritional status, and outcome.

PubMed

Liu, Xuechao; Qiu, Haibo; Kong, Pengfei; Zhou, Zhiwei; Sun, Xiaowei

2017-01-01

We aim to investigate the prognostic value of several nutrition-based indices, including the prognostic nutritional index (PNI), performance status, body mass index, serum albumin, and preoperative body weight loss in patients with gastric cancer (GC). We retrospectively analyzed the records of 1,330 consecutive patients with GC undergoing curative surgery between October 2000 and September 2012. The relationship between nutrition-based indices and overall survival (OS) was examined using Kaplan-Meier analysis and Cox regression model. Following multivariate analysis, the PNI and preoperative body weight loss were the only nutritional-based indices independently associated with OS (hazard ratio [HR]: 1.356, 95% confidence interval [CI]: 1.051-1.748, P =0.019; HR: 1.152, 95% CI: 1.014-1.310, P =0.030, retrospectively). In stage-stratified analysis, multivariate analysis revealed that preoperative body weight loss was identified as an independent prognostic factor only in patients with stage III GC (HR: 1.223, 95% CI: 1.065-1.405, P =0.004), while the prognostic significance of PNI was not significant (all P >0.05). In patients with stage III GC, preoperative body weight loss stratified 5-year OS from 41.1% to 26.5%. When stratified by adjuvant chemotherapy, the prognostic significance of preoperative body weight loss was maintained in patients treated with surgery plus adjuvant chemotherapy and in patients treated with surgery alone ( P <0.001; P =0.003). Preoperative body weight loss is an independent prognostic factor for OS in patients with GC, especially in stage III disease. Preoperative body weight loss appears to be a superior predictor of outcome compared with other established nutrition-based indices.

Emergence and predictors of alcohol reference displays on Facebook during the first year of college

PubMed Central

Moreno, Megan A; D’Angelo, Jonathan; Kacvinsky, Lauren E.; Kerr, Bradley; Zhang, Chong; Eickhoff, Jens

2013-01-01

The purpose of this study was to investigate the emergence of displayed alcohol references on Facebook for first-year students from two universities. Graduated high school seniors who were planning to attend one of the two targeted study universities were recruited. Participants’ Facebook profiles were evaluated for displayed alcohol references at baseline and every four weeks throughout the first year of college. Profiles were categorized as Non-Displayers, Alcohol Displayers or Intoxication/Problem Drinking Displayers. Analyses included logistic regression, univariate and multivariate Cox proportional hazard analysis and multi-state Markov modeling. A total of 338 participants were recruited, 56.1% were female, 74.8% were Caucasian, and 58.8% were from University A. At baseline, 68 Facebook profiles (20.1%) included displayed alcohol references. During the first year of college, 135 (39.9%) profiles newly displayed alcohol. In multivariate Cox proportional hazard analysis, university (University B versus A, HR = 0.47, 95% CI: 0.28–0.77, p = 0.003), number of Facebook friends (HR = 1.19, 95% CI: 1.09–1.28, p < 0.001 for every 100 more friends), and average monthly status updates (HR = 1.03, 95% CI: 1.002–1.05, p = 0.033) were identified as independent predictors for new alcohol display. Findings contribute to understanding the patterns and predictors for displayed alcohol references on Facebook. PMID:24415846

Risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors.

PubMed

Song, Taejong; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

2014-09-01

The aim of this study was to identify risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors (BOTs). We performed a retrospective review of all patients treated and followed for BOTs between 1996 and 2011. Multivariate Cox proportional hazards model analysis was performed to identify independent risk factors for progression to invasive carcinoma. A total of 364 patients were identified. During the median follow-up of 53.8 months, 31 patients (8.5%) developed recurrent disease: 12 (3.3%) had recurrent disease with progression to invasive carcinoma, and 19 (5.2%) had recurrent disease with borderline histology. Disease-related deaths (7/364; 1.7%) were observed only in patients with progression to invasive carcinoma. The multivariate analysis showed that independent risk factors for progression to invasive carcinoma were advanced disease stage (hazard ratio [HR], 5.59; P = 0.005), age 65 years or older (HR, 5.13; P = 0.037), and the presence of microinvasion (HR, 3.71; P = 0.047). These 3 factors were also independently related to overall survival. Although patients with BOTs have an excellent prognosis, the risk of progression to invasive carcinoma and thereby death remains. Therefore, physicians should pay closer attention to BOT patients with these risk factors (ie, advanced disease stage, old age, and microinvasion), and more careful surveillance for progression to invasive carcinoma is needed.

Factors predictive of survival after stapler hepatectomy of hepatocellular carcinoma: a multivariate, single-center analysis.

PubMed

Hoffmann, Katrin; Müller-Bütow, Verena; Franz, Clemens; Hinz, Ulf; Longerich, Thomas; Büchler, Markus W; Schemmer, Peter

2014-02-01

New technical devices for hepatic parenchymal transection have improved perioperative safety and patient survival. The aim of the present study was to determine the oncological outcome after stapler hepatectomy in patients with HCC. Data of 95 patients who underwent stapler hepatectomy for HCC between 2001 and 2011 were analyzed retrospectively regarding clinical safety of the procedure and predictive factors for survial. Thirty-nine minor (≤2 segments) and 56 major (≥3 segments) hepatic resections were performed. The median survival was 47.5 months, after 36 months follow-up. Low grading, tumors ≥5 cm, multiple nodules and liver cirrhosis were predictors of decreased overall survival using multivariate analysis with hazard ratio(HR)=2.62, 2.41, 2.05, and 1.92 respectively. An estimated intra-operative blood loss of ≥1.2l was inversely correlated to disease free survival (HR=1.96). Stapler hepatectomy is a safe procedure in patients with HCC. Substantial intraoperative blood loss and the presence of cirrhosis independently predict the overall probability of patient survival. Intraoperative blood loss directly impacts HCC recurrence.

Outcome and prognostic factors in single brain metastases from small-cell lung cancer.

PubMed

Bernhardt, Denise; Adeberg, Sebastian; Bozorgmehr, Farastuk; Opfermann, Nils; Hörner-Rieber, Juliane; König, Laila; Kappes, Jutta; Thomas, Michael; Unterberg, Andreas; Herth, Felix; Heußel, Claus Peter; Warth, Arne; Debus, Jürgen; Steins, Martin; Rieken, Stefan

2018-02-01

Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanchard, Pierre, E-mail: pierre.blanchard@gustaveroussy.fr; University of Paris-Sud, Cancer Campus, Villejuif; Faivre, Laura

Purpose: The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Methods and Materials: Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was leftmore » to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). Results: A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. Conclusions: This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients.« less

Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a European cohort of patients with prostate cancer treated with radiotherapy.

PubMed

Langsenlehner, Tanja; Pichler, Martin; Thurner, Eva-Maria; Krenn-Pilko, Sabine; Stojakovic, Tatjana; Gerger, Armin; Langsenlehner, Uwe

2015-05-01

Recent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable marker of systemic inflammation and has been shown to represent a prognostic marker in different cancer entities. To evaluate the prognostic value of the PLR in prostate cancer, we performed the present study. Data from 374 consecutive patients with prostate cancer, treated with 3D conformal radiotherapy from 1999 to 2007, were analyzed. Distant metastases-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease-free survival, and time to salvage systemic therapy were assessed using the Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed to adjust for other covariates. Using receiver operating characteristics analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses revealed that PLR≥190 was a prognostic factor for decreased MFS (P = 0.004), CSS (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated PLR with biochemical disease-free survival (P = 0.740) and time to salvage systemic therapy (P = 0.063) was not detected. In multivariate analysis, an increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24, 95% CI: 1.06-4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19-13.4, P = 0.025), and OS (HR = 1.87, 95% CI: 1.02-3.42, P = 0.044). Our findings indicate that the PLR may predict prognosis in patients with prostate cancer and may contribute to future individual risk assessment in them. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of risk factors for central venous port failure in cancer patients

PubMed Central

Hsieh, Ching-Chuan; Weng, Hsu-Huei; Huang, Wen-Shih; Wang, Wen-Ke; Kao, Chiung-Lun; Lu, Ming-Shian; Wang, Chia-Siu

2009-01-01

AIM: To analyze the risk factors for central port failure in cancer patients administered chemotherapy, using univariate and multivariate analyses. METHODS: A total of 1348 totally implantable venous access devices (TIVADs) were implanted into 1280 cancer patients in this cohort study. A Cox proportional hazard model was applied to analyze risk factors for failure of TIVADs. Log-rank test was used to compare actuarial survival rates. Infection, thrombosis, and surgical complication rates (χ2 test or Fisher’s exact test) were compared in relation to the risk factors. RESULTS: Increasing age, male gender and open-ended catheter use were significant risk factors reducing survival of TIVADs as determined by univariate and multivariate analyses. Hematogenous malignancy decreased the survival time of TIVADs; this reduction was not statistically significant by univariate analysis [hazard ratio (HR) = 1.336, 95% CI: 0.966-1.849, P = 0.080)]. However, it became a significant risk factor by multivariate analysis (HR = 1.499, 95% CI: 1.079-2.083, P = 0.016) when correlated with variables of age, sex and catheter type. Close-ended (Groshong) catheters had a lower thrombosis rate than open-ended catheters (2.5% vs 5%, P = 0.015). Hematogenous malignancy had higher infection rates than solid malignancy (10.5% vs 2.5%, P < 0.001). CONCLUSION: Increasing age, male gender, open-ended catheters and hematogenous malignancy were risk factors for TIVAD failure. Close-ended catheters had lower thrombosis rates and hematogenous malignancy had higher infection rates. PMID:19787834

Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation.

PubMed

Hayes, Don; Kopp, Benjamin T; Tobias, Joseph D; Woodley, Frederick W; Mansour, Heidi M; Tumin, Dmitry; Kirkby, Stephen E

2015-12-01

Survival in non-cystic fibrosis (CF) bronchiectasis is not well studied. The United Network for Organ Sharing database was queried from 1987 to 2013 to compare survival in adult patients with non-CF bronchiectasis to patients with CF listed for lung transplantation (LTx). Each subject was tracked from waitlist entry date until death or censoring to determine survival differences between the two groups. Of 2112 listed lung transplant candidates with bronchiectasis (180 non-CF, 1932 CF), 1617 were used for univariate Cox and Kaplan-Meier survival function analysis, 1173 for multivariate Cox models, and 182 for matched-pairs analysis based on propensity scores. Compared to CF, patients with non-CF bronchiectasis had a significantly lower mortality by univariate Cox analysis (HR 0.565; 95 % CI 0.424, 0.754; p < 0.001). Adjusting for potential confounders, multivariate Cox models identified a significant reduction in risk for death associated with non-CF bronchiectasis who were lung transplant candidates (HR 0.684; 95 % CI 0.475, 0.985; p = 0.041). Results were consistent in multivariate models adjusting for pulmonary hypertension and forced expiratory volume in one second. Non-CF bronchiectasis with advanced lung disease was associated with significantly lower mortality hazard compared to CF bronchiectasis on the waitlist for LTx. Separate referral and listing criteria for LTx in non-CF and CF populations should be considered.

The role of adjuvant therapy in the management of head and neck merkel cell carcinoma: an analysis of 4815 patients.

PubMed

Chen, Michelle M; Roman, Sanziana A; Sosa, Julie A; Judson, Benjamin L

2015-02-01

Merkel cell carcinoma (MCC) is a rare neuroendocrine malignant neoplasm that most commonly occurs in the head and neck and is rapidly increasing in incidence. The role of adjuvant chemoradiotherapy (CRT) in the management of head and neck MCC remains controversial. To evaluate the association between different adjuvant therapies and survival in head and neck MCC. Retrospective review of adult patients with head and neck MCC who had surgery recorded in the National Cancer Data Base from 1998 to 2011. Surgical excision, adjuvant radiation therapy (RT), or adjuvant CRT. Our main outcome was overall survival (OS). Statistical analysis included χ2, t tests, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. We identified 4815 patients; 92.0% underwent standard surgical excision, and 8.0% underwent Mohs surgery. On multivariate analysis, age at least 75 years (hazard ratio [HR], 2.83 [95% CI, 1.82-4.41]), larger tumor size, positive margins (HR, 1.52 [95% CI, 1.25-1.85]), and metastatic lymph nodes (HR, 2.29 [95% CI, 1.84-2.85]) were independently associated with decreased OS. Postoperative CRT (HR, 0.62 [95% CI, 0.47-0.81]) and RT (HR, 0.80 [95% CI, 0.70-0.92]) provided a survival benefit over surgery alone. Adjuvant CRT was associated with improved OS over adjuvant RT in patients with positive margins (HR, 0.48 [95% CI, 0.25-0.93]), tumor size at least 3 cm (HR, 0.52 [95% CI, 0.30-0.90]), and male sex (HR, 0.69 [95% CI, 0.50-0.94]). To our knowledge, this the first study examining the role of adjuvant CRT in head and neck MCC. Results suggest that adjuvant CRT may help improve survival in high-risk patients, such as males and those with positive margins and larger tumors.

The impact of lungs from diabetic donors on lung transplant recipients†.

PubMed

Ambur, Vishnu; Taghavi, Sharven; Jayarajan, Senthil; Kadakia, Sagar; Zhao, Huaqing; Gomez-Abraham, Jesus; Toyoda, Yoshiya

2017-02-01

We attempted to determine if transplants of lungs from diabetic donors (DDs) is associated with increased mortality of recipients in the modern era of the lung allocation score (LAS). The United Network for Organ Sharing (UNOS) database was queried for all adult lung transplant recipients from 2006 to 2014. Patients receiving a lung from a DD were compared to those receiving a transplant from a non-DD. Multivariate Cox regression analysis using variables associated with mortality was used to examine survival. A total of 13 159 adult lung transplants were performed between January 2006 and June 2014: 4278 (32.5%) were single-lung transplants (SLT) and 8881 (67.5%) were double-lung transplants (DLT). The log-rank test demonstrated a lower median survival in the DD group (5.6 vs 5.0 years, P = 0.003). We performed additional analysis by dividing this initial cohort into two cohorts by transplant type. On multivariate analysis, receiving an SLT from a DD was associated with increased mortality (HR 1.28, 95% CI 1.07–1.54, P = 0.011). Interestingly, multivariate analysis demonstrated no difference in mortality rates for patients receiving a DLT from a DD (HR 1.12, 95% CI 0.97–1.30, P = 0.14). DLT with DDs can be performed safely without increased mortality, but SLT using DDs results in worse survival and post-transplant outcomes. Preference should be given to DLT when using lungs from donors with diabetes. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Pooled Analysis of Individual Patient Data on Concurrent Chemoradiotherapy for Stage III Non-Small-Cell Lung Cancer in Elderly Patients Compared With Younger Patients Who Participated in US National Cancer Institute Cooperative Group Studies.

PubMed

Stinchcombe, Thomas E; Zhang, Ying; Vokes, Everett E; Schiller, Joan H; Bradley, Jeffrey D; Kelly, Karen; Curran, Walter J; Schild, Steven E; Movsas, Benjamin; Clamon, Gerald; Govindan, Ramaswamy; Blumenschein, George R; Socinski, Mark A; Ready, Neal E; Akerley, Wallace L; Cohen, Harvey J; Pang, Herbert H; Wang, Xiaofei

2017-09-01

Purpose Concurrent chemoradiotherapy is standard treatment for patients with stage III non-small-cell lung cancer. Elderly patients may experience increased rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy. Patients and Methods Individual patient data were collected from 16 phase II or III trials conducted by US National Cancer Institute-supported cooperative groups of concurrent chemoradiotherapy alone or with consolidation or induction chemotherapy for stage III non-small-cell lung cancer from 1990 to 2012. Overall survival (OS), progression-free survival, and AEs were compared between patients age ≥ 70 (elderly) and those younger than 70 years (younger). Unadjusted and adjusted hazard ratios (HRs) for survival time and CIs were estimated by single-predictor and multivariable frailty Cox models. Unadjusted and adjusted odds ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable generalized linear mixed-effect models. Results A total of 2,768 patients were classified as younger and 832 as elderly. In unadjusted and multivariable models, elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95% CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly and younger patients had similar progression-free survival (HR, 1.01; 95% CI, 0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients had a higher rate of grade ≥ 3 AEs in unadjusted and multivariable models (OR, 1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively). Grade 5 AEs were significantly higher in elderly compared with younger patients (9% v 4%; P < .01). Fewer elderly compared with younger patients completed treatment (47% v 57%; P < .01), and more discontinued treatment because of AEs (20% v 13%; P < .01), died during treatment (7.8% v 2.9%; P < .01), and refused further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had a higher rate of death during treatment than younger patients.

Exploring Radiotherapy Targeting Strategy and Dose: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III Non-Small Cell Lung Cancer.

PubMed

Schild, Steven E; Fan, Wen; Stinchcombe, Thomas E; Vokes, Everett E; Ramalingam, Suresh S; Bradley, Jeffrey D; Kelly, Karen; Pang, Herbert H; Wang, Xiaofei

2018-04-21

Concurrent chemoradiotherapy(CRT) is standard therapy for locally-advanced non-small-cell lung cancer(LA-NSCLC)patients. This study was performed to examine thoracic radiotherapy(TRT) parameters and their impact on patient survival. We collected Individual patient data(IPD) from 3600LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy(elective nodal irradiation(ENI) compared to involved field TRT(IF-TRT)), total dose, and biologically effective dose(BED). Hazard ratios(HRs) for overall survival were calculated with univariable and multivariable Cox models. TRT doses ranged from 60 to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT(univariable HR,1.37;95%CI,1.24-1.51,p<0.0001;multivariable HR,1.31;95%CI,1.08-1.59,p=0.002). The median survival of the IF and ENI patients were 24 and 16 months, respectively. Patients were divided into 3 dose groups: low total dose(60 Gy), medium total dose(>60Gy-66Gy) and high total dose(>66Gy-74 Gy). With reference to the low dose group, the multivariable HR's were 1.08 for the medium dose group(95%CI=0.93-1.25) and 1.12 for the high dose group(CI=0.97-1.30).The univariate p=0.054 and multivariable p=0.17. BED was grouped as follows: low(<55.5Gy 10 ), medium(=55.5 Gy 10) , or high(>55.5 Gy 10 ). With reference to the low BED group, the HR was 1.00(95%CI=0.85-1.18) for the medium BED group and 1.10(95%CI=0.93-1.31) for the high BED group. The univariable p=0.076 and multivariable p=0.16. For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT. Copyright © 2018. Published by Elsevier Inc.

Primary fascial closure with mesh reinforcement is superior to bridged mesh repair for abdominal wall reconstruction.

PubMed

Booth, Justin H; Garvey, Patrick B; Baumann, Donald P; Selber, Jesse C; Nguyen, Alexander T; Clemens, Mark W; Liu, Jun; Butler, Charles E

2013-12-01

Many surgeons believe that primary fascial closure with mesh reinforcement should be the goal of abdominal wall reconstruction (AWR), yet others have reported acceptable outcomes when mesh is used to bridge the fascial edges. It has not been clearly shown how the outcomes for these techniques differ. We hypothesized that bridged repairs result in higher hernia recurrence rates than mesh-reinforced repairs that achieve fascial coaptation. We retrospectively reviewed prospectively collected data from consecutive patients with 1 year or more of follow-up, who underwent midline AWR between 2000 and 2011 at a single center. We compared surgical outcomes between patients with bridged and mesh-reinforced fascial repairs. The primary outcomes measure was hernia recurrence. Multivariate logistic regression analysis was used to identify factors predictive of or protective for complications. We included 222 patients (195 mesh-reinforced and 27 bridged repairs) with a mean follow-up of 31.1 ± 14.2 months. The bridged repairs were associated with a significantly higher risk of hernia recurrence (56% vs 8%; hazard ratio [HR] 9.5; p < 0.001) and a higher overall complication rate (74% vs 32%; odds ratio [OR] 3.9; p < 0.001). The interval to recurrence was more than 9 times shorter in the bridged group (HR 9.5; p < 0.001). Multivariate Cox proportional hazard regression analysis identified bridged repair and defect width > 15 cm to be independent predictors of hernia recurrence (HR 7.3; p < 0.001 and HR 2.5; p = 0.028, respectively). Mesh-reinforced AWRs with primary fascial coaptation resulted in fewer hernia recurrences and fewer overall complications than bridged repairs. Surgeons should make every effort to achieve primary fascial coaptation to reduce complications. Published by Elsevier Inc.

PROSPECT Eligibility and Clinical Outcomes: Results From the Pan-Canadian Rectal Cancer Consortium.

PubMed

Bossé, Dominick; Mercer, Jamison; Raissouni, Soundouss; Dennis, Kristopher; Goodwin, Rachel; Jiang, Di; Powell, Erin; Kumar, Aalok; Lee-Ying, Richard; Price-Hiller, Julie; Heng, Daniel Y C; Tang, Patricia A; MacLean, Anthony; Cheung, Winson Y; Vickers, Michael M

2016-09-01

The PROSPECT trial (N1048) is evaluating the selective use of chemoradiation in patients with cT2N1 and cT3N0-1 rectal cancer undergoing sphincter-sparing low anterior resection. We evaluated outcomes of PROSPECT-eligible and -ineligible patients from a multi-institutional database. Data from patients with locally advanced rectal cancer who received chemoradiation and low anterior resection from 2005 to 2014 were retrospectively collected from 5 Canadian centers. Overall survival, disease-free survival (DFS), recurrence-free survival (RFS), and time to local recurrence (LR) were estimated using the Kaplan-Meier method, and a multivariate analysis was performed adjusting for prognostic factors. A total of 566 (37%) of 1531 patients met the PROSPECT eligibility criteria. Eligible patients were more likely to have better PS (P = .0003) and negative circumferential resection margin (P < .0001). PROSPECT eligibility was associated with improved DFS (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.91), overall survival (HR, 0.73; 95% CI, 0.57-0.95), and RFS (HR, 0.68; 95% CI, 0.54-0.86) in univariate analyses. In multivariate analysis, only RFS remained significantly improved for PROSPECT-eligible patients (HR, 0.75; 95% CI, 0.57-1.00, P = .0499). The 3-year DFS and freedom from LR for PROSPECT-eligible patients were 79.1% and 97.4%, respectively, compared to 71.1% and 96.8% for PROSPECT-ineligible patients. Real-world data corroborate the eligibility criteria used in the PROSPECT study; the criteria identify a subgroup of patients in whom risk of recurrence is lower and in whom selective use of chemoradiation should be actively examined. Copyright © 2016 Elsevier Inc. All rights reserved.

Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, Kristin A., E-mail: kristin.higgins@duke.edu; Chino, Junzo P.; Berry, Mark

2012-06-01

Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non-small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non-small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995-2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meiermore » method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.« less

Ventilator-associated nosocomial pneumonia in intensive care units in Malaysia.

PubMed

Gopal Katherason, Supaletchimi; Naing, Lin; Jaalam, Kamarudin; Imran Musa, Kamarul; Nik Mohamad, Nik Abdullah; Aiyar, Subramaniar; Bhojani, Kavita; Harussani, Najah; Abdul Rahman, Aisai; Ismail, Asma

2009-10-22

The outcome indicator of nosocomial infection (NI) in the intensive care unit (ICU) is used to benchmark the quality of patient care in Malaysia. We conducted a three-year prospective study on the incidences of ventilator-associated pneumonia (VAP), risk factors, and patterns of the microorganisms isolated in three ICUs. A follow-up in prospective cohort surveillance was conducted on patients admitted to an adult medical-surgical ICU of a university hospital and two governmental hospitals in Malaysia from October 2003 to December 2006. VAP was detected using CDC criteria which included clinical manifestation and confirmed endotracheal secretion culture results. In total, 215 patients (2,306 patient-days) were enrolled into the study. The incidence of ICU-acquired device-related NI was 29.3 % (n = 63). The device-related VAP infection rate was 27.0 % (n = 58), with a mechanical ventilator utilization rate of 88.7%. The death rate due to all ICU-acquired NI including sepsis was 6.5%. The most common causative pathogen was Klebsiella pneumoniae (n = 27). Multivariate analysis using Cox regression showed that the risk factors identified were aspiration pneumonia (HR = 4.09; 95% CI = 1.24, 13.51; P = 0.021), cancer (HR = 2.51; 95% CI = 1.27, 4.97; P = 0.008), leucocytosis (HR=3.43; 95% CI= 1.60, 7.37; P=0.002) and duration of mechanical ventilation (HR=1.04; 95% CI = 1.00, 1.08; P = 0.030). Age, gender and race were not identified as risk factors in the multivariable analysis performed. The incidence of VAP was comparable to that found in the National Nosocomial Infection Surveillance (NNIS) System report of June 1998. The incidence of VAP was considered high for the three hospitals studied.

Prognostic factors and survival according to tumour subtype in women presenting with breast cancer brain metastases at initial diagnosis.

PubMed

Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

2017-03-01

The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Hence, the prognostic assessment and management of these patients is very challenging. The aim of this study was to analyse the influence of tumour subtype compared with other prognostic factors in the survival of patients with BMIBCD. We evaluated women with BMIBCD, reported to Surveillance, Epidemiology and End Results program from 2010 to 2013. Patients with other primary malignancy were excluded. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS). We included 740 patients. Median OS for the whole population was 10 months, and 20.7% of patients were alive at 36 months. Tumour subtype distribution was: 46.6% hormone receptor (HR)+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% triple-negative. Univariate analysis showed that the presence of liver metastases, lung metastases and triple-negative patients (median OS 6 months) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8), lobular histology (hazard ratio 2.08), triple-negative subtype (hazard ratio 2.25), liver metastases (hazard ratio 1.6) and unmarried patients (hazard ratio 1.39) had significantly shorter OS. Although the prognosis of patients with BMIBCD is generally poor, 20.7% were still alive 3 years after the diagnosis. There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathological complete response in breast cancer patients receiving anthracycline and taxane-based neoadjuvant chemotherapy: Evaluating the effect of race/ethnicity

PubMed Central

Chavez-MacGregor, Mariana; Litton, Jennifer; Chen, Huiqin; Giordano, Sharon H.; Hudis, Clifford A.; Wolff, Antonio C.; Valero, Vicente; Hortobagyi, Gabriel N.; Bondy, Melissa L.; Gonzalez-Angulo, Ana Maria

2010-01-01

Purpose To evaluate the influence of race/ethnicity and tumor subtype in pathological complete response (pCR) following treatment with neoadjuvant chemotherapy. Methods 2074 patients diagnosed with breast cancer between 1994 and 2008, treated with neoadjuvant anthracycline- and taxane-based chemotherapy, were included. pCR was defined as no residual invasive cancer in the breast and axilla. Kaplan-Meier product-limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome. Results Median age was 50 years, 14.6% patients were black, 15.2% Hispanic, 64.3% White, and 5.9% other race. There were no differences in pCR rates among race/ethnicity: (12.3% in black, 14.2% in Hispanics, 12.3% in whites and 11.5% in others, p=.788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse RFS and OS (p≤.0001). Differences in RFS by race/ethnicity were seen in the patients with hormone receptor-positive disease, p=.007. In multivariate analysis, Hispanics had improved RFS (HR, 95% CI 0.69; 0.49-0.97) and OS (HR, 95% CI 0.63; 0.41-0.97); blacks had a trend to worse outcomes (RFS:HR, 95% CI 1.28; 0.97-1.68, OS:HR, 1.32; 95% CI; 0.97-1.81) when compared to whites. Conclusions In this cohort of patients, race/ethnicity was not significantly associated with pCR rates. In a multivariate analysis we observed improved outcomes in Hispanics and a trend towards worse outcomes in black patients, when compared to whites. Further research is needed to explore the potential differences in biology and outcomes. PMID:20564153

Change in Health Insurance Coverage After Liver Transplantation Can Be Associated with Worse Outcomes.

PubMed

Akateh, Clifford; Tumin, Dmitry; Beal, Eliza W; Mumtaz, Khalid; Tobias, Joseph D; Hayes, Don; Black, Sylvester M

2018-06-01

Health insurance coverage changes for many patients after liver transplantation, but the implications of this change on long-term outcomes are unclear. To assess post-transplant patient and graft survival according to change in insurance coverage within 1 year of transplantation. We queried the United Network for Organ Sharing for patients between ages 18-64 years undergoing liver transplantation in 2002-2016. Patients surviving > 1 year were categorized by insurance coverage at transplantation and the 1-year transplant anniversary. Multivariable Cox regression characterized the association between coverage pattern and long-term patient or graft survival. Among 34,487 patients in the analysis, insurance coverage patterns included continuous private coverage (58%), continuous public coverage (29%), private to public transition (8%) and public to private transition (4%). In multivariable analysis of patient survival, continuous public insurance (HR 1.29, CI 1.22, 1.37, p < 0.001), private to public transition (HR 1.17, CI 1.07, 1.28, p < 0.001), and public to private transition (HR 1.14, CI 1.00, 1.29, p = 0.044), were associated with greater mortality hazard, compared to continuous private coverage. After disaggregating public coverage by source, mortality hazard was highest for patients transitioning from private insurance to Medicaid (HR vs. continuous private coverage = 1.32; 95% CI 1.14, 1.52; p < 0.001). Similar differences by insurance category were found for death-censored graft failure. Post-transplant transition to public insurance coverage is associated with higher risk of adverse outcomes when compared to retaining private coverage.

Chemotherapy-related leukopenia as a biomarker predicting survival outcomes in locally advanced cervical cancer.

PubMed

Bogani, Giorgio; Sabatucci, Ilaria; Maltese, Giuseppa; Lecce, Francesca; Signorelli, Mauro; Martinelli, Fabio; Chiappa, Valentina; Indini, Alice; Leone Roberti Maggiore, Umberto; Borghi, Chiara; Fucà, Giovanni; Ditto, Antonino; Raspagliesi, Francesco; Lorusso, Domenica

2017-01-01

To investigate the impact of hematologic toxicity and leukopenia in locally advanced cervical cancer patients undergoing neoadjuvant chemotherapy (NACT). Data of consecutive patients undergoing platinum-based NACT followed by surgery were retrospectively searched in order to evaluate the impact of chemotherapy-related toxicity on survival outcomes. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAEv.4.03). Survival outcomes were evaluated using Kaplan-Meir and Cox hazard models. Overall, 126 patients were included. Among those, 94 (74.6%) patients experienced grade2+ hematologic toxicity; while, grade2+ non-hematologic toxicity occurred in 11 (8.7%) patients. After a median follow-up of 37.1 (inter-quartile range, 12-57.5) months, 21 (16.6%) patients experienced recurrence. Via multivariate analysis, no factor was independently associated with disease-free survival; while a trend toward worse prognosis was observed for patients experiencing grade2+ leukopenia at cycle-3 (HR:3.13 (95%CI: 0.94, 10.3); p=0.06). Similarly, grade2+ leukopenia (HR:9.98 (95%CI: 1.14, 86.6); p=0.03), lymph-node positivity (HR:14.6 (95%CI:1.0, 214.4); p=0.05) and vaginal involvement (HR:5.81 (95%CI:1.43, 23.6); p=0.01) impacted on overall survival, at multivariate analysis. Magnitude of leukopenia correlated with survival (p<0.001). Although, our data have to be confirmed by prospective investigations, the present study shows an association between the occurrence of leukopenia and survival outcomes. NACT-related immunosuppression might reduce the response against the tumor, thus promoting cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison between imported versus domestic drug-eluting stents in China: A large single-center data.

PubMed

Liu, Ru; Gao, Zhan; Chen, Jue; Gao, Lijian; Song, Lei; Qiao, Shubin; Yang, Yuejin; Gao, Runlin; Xu, Bo; Yuan, Jinqing

2017-08-01

In recent years, most drug-eluting stents (DESs) were domestically produced in China, but how domestic DESs perform compared to imported DESs was still unknown. A total of 9011 consecutive cases with DESs implantation in a single center throughout 2013 were prospectively collected. Two-year clinical outcomes were evaluated between patients implanted with imported and domestic DESs. During 2-year follow-up, the rates of all-cause death, cardiac death, myocardial infarction, stroke, and stent thrombosis were not significantly different between two groups. However, the rate of revascularization was significantly higher in domestic DES group, shown as higher rates of overall revascularization, target vessel revascularization (TVR), and target lesion revascularization (TLR) (9.7% vs 6.4%, P < 0.001; 5.6% vs 3.2%, P < 0.001; 4.5% vs 2.2%, P < 0.001, respectively). Accordingly, major adverse cardiac events (MACE) rate was significantly higher in domestic DES group (12.1% vs 8.5%, P < 0.001). Multivariable Cox regression analysis indicated that domestic DES was an independent risk factor of MACE (HR [95%CI]: 1.22 [1.05-1.41]), overall revascularization (HR [95%CI]: 1.29 [1.09-1.53]), TVR (HR [95%CI]: 1.54 [1.22-1.94]), and TLR (HR [95%CI]: 1.85 [1.41-2.42]). After propensity score matching, the rates of overall revascularization, TVR, and TLR were still significantly higher in domestic DES group, and domestic DES was still predictive of overall revascularization, TVR, and TLR in multivariate Cox regression analysis. Domestic DESs showed the same safety as imported DESs in this real-world cohort. But, patients implanted with domestic DESs had a higher risk of revascularization than imported DESs. © 2017, Wiley Periodicals, Inc.

Lack of tumour pigmentation in conjunctival melanoma is associated with light iris colour and worse prognosis.

PubMed

Brouwer, Niels J; Marinkovic, Marina; Luyten, Gregorius P M; Shields, Carol L; Jager, Martine J

2018-05-18

To investigate whether differences in iris colour, skin colour and tumour pigmentation are related to clinical outcome in conjunctival melanoma. Data of 70 patients with conjunctival melanoma from the Leiden University Medical Center (Leiden, The Netherlands) and 374 patients from the Wills Eye Hospital (Philadephia, USA) were reviewed. The relation between iris colour, skin colour and tumour pigmentation versus clinical parameters and outcome was investigated using univariate and multivariate regression analyses. A light iris colour (blue, grey, green) was present in 261 (59%) patients and a dark colour (hazel, brown) in 183 (41%). A low tumour pigmentation was detected in 130 (40%) and a high pigmentation in 197 (60%) patients. Low tumour pigmentation was associated with light iris colour (p=0.021) but not related to skin colour (p=0.92). In univariate analysis, neither iris nor skin colour was related to clinical outcome, while a low tumour pigmentation was related to metastasis formation (HR 2.37, p=0.004) and death (HR 2.42, p=0.020). In multivariate analysis, low tumour pigmentation was related to the development of recurrences (HR 1.63, p=0.043), metastasis formation (HR 2.48, p=0.004) and death (HR 2.60, p=0.014). Lightly pigmented tumours occurred especially in individuals with lightly coloured irises. While iris colour or skin colour was not significantly related to clinical outcome, a low tumour pigmentation was related to a worse outcome in patients with conjunctival melanoma. The amount and type of melanin in conjunctival melanocytes may be involved in the pathogenesis and behaviour of selected conjunctival melanoma. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Locoregional treatment and overall survival of men with T1a,b,cN0M0 breast cancer: A population-based study.

PubMed

Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

2017-01-01

Male breast cancer (MaBC) is an understudied disease; information about locoregional treatment and outcomes in patients with early stage is unknown. We aimed to analyse patient characteristics, locoregional treatment and overall survival (OS) of T1a,b,cN0M0 male breast cancer. We evaluated men with T1a,b,cN0M0 breast cancer reported to Surveillance, Epidemiology, and End Results program from 1988 to 2012. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. We included 1263 patients. Median age was 66 years (range 27-103). Median follow-up was 62 months (range 1-294). OS at 5 and 10 years were 85.1% and 66.5%, respectively. Distribution according to tumour sub-stage was: T1a 6.5%, T1b 20.7% and T1c 72.8%. Mastectomy was performed in >74% of patients of each tumour size group and overall 44.1% had >5 lymph nodes examined (LNE). Univariate analysis showed that patients with T1c, no surgery and 0 LNE had worse prognosis. In multivariate analysis, older age (hazard ratio [HR] 11.09), grade 3/4 tumours (HR 1.7), no surgery (HR 3.3), 0 LNE (HR 5.1) and unmarried patients (HR 1.7) had significantly shorter OS. There were no differences in OS between breast conservation versus mastectomy and 1-5 LNE versus > 5 LNE. Men with early breast cancer have a favourable OS. However, older age, higher grade, no breast surgery, no LNE and unmarried status emerged as poor prognostic characteristics. Efforts to decrease the high rates of mastectomy and extensive LNE should be taken given similar OS observed with breast conservation and 1-5 LNE, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome

PubMed Central

Jokubaitis, Vilija G.; Trojano, Maria; Izquierdo, Guillermo; Grand’Maison, François; Oreja-Guevara, Celia; Boz, Cavit; Lugaresi, Alessandra; Girard, Marc; Grammond, Pierre; Iuliano, Gerardo; Fiol, Marcela; Cabrera-Gomez, Jose Antonio; Fernandez-Bolanos, Ricardo; Giuliani, Giorgio; Lechner-Scott, Jeannette; Cristiano, Edgardo; Herbert, Joseph; Petkovska-Boskova, Tatjana; Bergamaschi, Roberto; van Pesch, Vincent; Moore, Fraser; Vella, Norbert; Slee, Mark; Santiago, Vetere; Barnett, Michael; Havrdova, Eva; Young, Carolyn; Sirbu, Carmen-Adella; Tanner, Mary; Rutherford, Michelle; Butzkueven, Helmut

2012-01-01

Objectives We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS). Methods The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation. Results A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation. Conclusion In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation. PMID:22768046

Survival Outcomes of Whole-Pelvic Versus Prostate-Only Radiation Therapy for High-Risk Prostate Cancer Patients With Use of the National Cancer Data Base

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amini, Arya; Jones, Bernard L.; Yeh, Norman

Purpose/Objectives: The addition of whole pelvic (WP) compared with prostate-only (PO) radiation therapy (RT) for clinically node-negative prostate cancer remains controversial. The purpose of our study was to evaluate the survival benefit of adding WPRT versus PO-RT for high-risk, node-negative prostate cancer, using the National Cancer Data Base (NCDB). Methods and Materials: Patients with high-risk prostate cancer treated from 2004 to 2006, with available data for RT volume, coded as prostate and pelvis (WPRT) or prostate alone (PO-RT) were included. Multivariate analysis (MVA) and propensity-score matched analysis (PSM) were performed. Recursive partitioning analysis (RPA) based on overall survival (OS) usingmore » Gleason score (GS), T stage, and pretreatment prostate-specific antigen (PSA) was also conducted. Results: A total of 14,817 patients were included: 7606 (51.3%) received WPRT, and 7211 (48.7%) received PO-RT. The median follow-up time was 81 months (range, 2-122 months). Under MVA, the addition of WPRT for high-risk patients had no OS benefit compared with PO-RT (HR 1.05; P=.100). On subset analysis, patients receiving dose-escalated RT also did not benefit from WPRT (HR 1.01; P=.908). PSM confirmed no survival benefit with the addition of WPRT for high-risk patients (HR 1.05; P=.141). In addition, RPA was unable to demonstrate a survival benefit of WPRT for any subset. Other prognostic factors for inferior OS under MVA included older age (HR 1.25; P<.001), increasing comorbidity scores (HR 1.46; P<.001), higher T stage (HR 1.17; P<.001), PSA (HR 1.81; P<.001), and GS (HR 1.29; P<.001), and decreasing median county household income (HR 1.15; P=.011). Factors improving OS included the addition of androgen deprivation therapy (HR 0.92; P=.033), combination external beam RT plus brachytherapy boost (HR 0.71; P<.001), and treatment at an academic/research institution (HR 0.84; P=.002). Conclusion: In the largest reported analysis of WPRT for patients with high-risk prostate cancer treated in the dose-escalated era, the addition of WPRT demonstrated no survival advantage compared with PO-RT.« less

Prospective evaluation of Ki-67 system in histological grading of soft tissue sarcomas in the Japan Clinical Oncology Group Study JCOG0304.

PubMed

Tanaka, Kazuhiro; Hasegawa, Tadashi; Nojima, Takayuki; Oda, Yoshinao; Mizusawa, Junki; Fukuda, Haruhiko; Iwamoto, Yukihide

2016-04-18

The correct clinical staging of soft tissue sarcomas (STS) is critical for the selection of treatments. The staging system consists of histological grade of the tumors and French Federation of Cancer Center (FNCLCC) system based on mitotic count is widely used for the grading. In this study, we compared the validity and usefulness of Ki-67 grading system with FNCLCC system in JCOG0304 trial which investigated the efficacy and safety of perioperative chemotherapy with doxorubicin and ifosfamide for STS. All 70 eligible patients with STS in the extremities treated by perioperative chemotherapy in JCOG0304 were analyzed. Univariate and multivariate Cox regression analyses were conducted to investigate an influence on overall survival. The reproducibility of Ki-67 grading system in the histological grading of STS was higher than FNCLCC system (κ = 0.54 [95 % CI 0.39-0.71], and 0.46 [0.32-0.62], respectively). Although FNCLCC grade was not associated with overall survival (OS) in univariate analysis (HR 2.80 [0.74-10.55], p = 0.13), Ki-67 grading system had a tendency to associate with OS in univariate analysis (HR 4.12 [0.89-19.09], p = 0.07) and multivariate analysis with backward elimination (HR 3.51 [0.75-16.36], p = 0.11). This is the first report demonstrating the efficacy of Ki-67 grading system for the patients with STS in the prospective trial. The results indicate that Ki-67 grading system might be useful for the evaluation of histological grade of STS.

The Risk of Developing Diabetes Mellitus in Patients with Psoriatic Arthritis: A Cohort Study.

PubMed

Eder, Lihi; Chandran, Vinod; Cook, Richard; Gladman, Dafna D

2017-03-01

To estimate the prevalence of diabetes mellitus (DM) in patients with psoriatic arthritis (PsA) in comparison with the general population and to assess whether the level of disease activity over time predicts the development of DM in these patients. A cohort analysis was conducted in patients followed in a large PsA clinic from 1978 to 2014. The prevalence of DM in the patients was compared with the general population of Ontario, Canada, and the age-standardized prevalence ratio (SPR) was calculated. For the assessment of risk factors for DM, time-weighted arithmetic mean (AM) levels of PsA-related disease activity measures were assessed as predictors for the development of DM. Multivariable Cox proportional hazards models were used to compute HR for incident DM after controlling for potential confounders. A total of 1305 patients were included in the analysis. The SPR of DM in PsA compared with the general population in Ontario was 1.43 (p = 0.002). Of the 1065 patients who were included in the time-to-event analysis, 73 patients were observed to develop DM. Based on multivariable analyses, AM tender joint count (HR 1.53, 95% CI 1.08-2.18, p = 0.02) and AM erythrocyte sedimentation rate (HR 1.21, 95% CI 1.03-1.41, p = 0.02) predicted the development of DM. The prevalence of DM is higher in patients with PsA compared with the general population. Patients with elevated levels of disease activity are at higher risk of developing DM.

Renal transplantation outcome and social deprivation in the French healthcare system: a cohort study using the European Deprivation Index.

PubMed

Châtelet, Valérie; Bayat-Makoei, Sahar; Vigneau, Cécile; Launoy, Guy; Lobbedez, Thierry

2018-04-02

The study objective was to estimate the effect of social deprivation estimated by the European Deprivation Index (EDI) on the risk of death and graft failure on renal transplantation in France. EDI was calculated for 8701 of 9205 patients receiving a first renal transplantation between 2010 and 2014. Patients were separated in EDI quintiles of the general population. A Cox model (cs-HR: cause-specific hazard ratio of death or graft failure) and a Fine and Gray model (sd-HR: subdistribution hazard ratio of death and graft failure) were used for the analysis. The 5th quintile group (most deprived) accounted for 32% of patients [2818 of 8701]. In the multivariate analysis, compared with quintile 1, the risk of death was higher for the 5 th quintile group in the complete cohort [cs-HR: 1.31, 95% CI: (1.01-1.70), sd-HR: 1.29, 95% CI: (1.00-1.68)], in the deceased donor group [cs-HR: 1.31, 95% CI: (1.00-1.71), sd-HR: 1.30, 95% CI: (1.00-1.70)] but not in living donor transplant patients. There was no association between the EDI groups and the risk of transplant failure. Social deprivation estimated by the EDI is associated with an increased risk of death in transplantation in France but not with the chance of allograft loss. © 2018 Steunstichting ESOT.

[Epidemiology of febrile neutropenia in patients with hematological disease-a prospective multicentre survey in China].

PubMed

Yan, C H; Xu, T; Zheng, X Y; Sun, J; Duan, X L; Gu, J L; Zhao, C L; Zhu, J; Wu, Y H; Wu, D P; Hu, J D; Huang, H; Jiang, M; Li, J; Hou, M; Wang, C; Shao, Z H; Liu, T; Hu, Y; Huang, X J

2016-03-01

To investigate the incidence, clinical and microbiological features of febrile, and risk factors during neutropenia periods in patients with hematological diseases. From October 20, 2014 to March 20, 2015, consecutive patients who had hematological diseases and developed neutropenia during hospitalization were enrolled in the prospective, multicenter and observational study. A total of 784 episodes of febrile occurred in 1 139 neutropenic patients with hematological diseases. The cumulative incidence of febrile was 81.9% at 21 days after neutropenia. Multivariate analysis suggested that central venous catheterization (P<0.001, HR=3.407, 95% CI 2.276-4.496), gastrointestinal mucositis (P<0.001, HR=10.548, 95% CI 3.245-28.576), previous exposure to broad-spectrum antibiotics within 90 days (P<0.001, HR=3.582, 95% CI 2.387-5.770) and duration of neutropenia >7 days (P<0.001,HR=4.194, 95% CI 2.572-5.618) were correlated with higher incidence of febrile during neutropenia. With the increase of the risk factors, the incidence of febrile increased gradually (35.4%, 69.2%, 86.1%, 95.6%, P<0.001). Of 784 febrile cases, 253 (32.3%) were unknown origin, 429 (54.7% )of clinical documented infections and 102(13.0%) of microbiological documented infections. The most common sites of infection were pulmonary (49.5%), upper respiratory (16.0%), crissum (9.8%), blood stream (7.7%). The most common pathogens were gram-negative bacteria (44.54%), followed by gram-positive bacteria (37.99% ) and fungi (17.47% ). There was no significant difference in mortality rates between cases with febrile and cases without febrile (9.2% vs 4.8%, P=0.099). Multivariate analysis also suggested that >40 years old (P=0.047, HR=5.000, 95% CI 0.853-28.013), hemodynamic instability (P=0.001, HR=13.185, 95% CI 2.983-54.915), prior colonization or infection by resistant pathogens (P=0.005, HR=28.734, 95% CI 2.921-313.744), blood stream infection (P=0.038, HR=9.715, 95% CI 1.110-81.969) and pulmonary infection (P=0.031, HR=25.905, 95% CI 1.381-507.006) were correlated with higher mortality rate in cases with febrile. Febrile was the common complication during neutropenia periods in patients with hematological disease. There was different distribution of organisms in different sites of infection. Moreove, the duration of neutropenia >7 days, central venous catheterization, gastrointestinal mucositis and previous exposure to broad-spectrum antibiotics within 90 days were the risk factors for the higher incidence of febrile.

Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.

PubMed

Lakatos, Peter Laszlo; Golovics, Petra Anna; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Horvath, Agnes; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Veres, Gabor; Lovasz, Barbara Dorottya; Szathmari, Miklos; Kiss, Lajos S; Lakatos, Laszlo

2012-04-01

Medical therapy for Crohn's disease (CD) has changed significantly over the past 20 years with increasing use of immunosuppressives. In contrast, surgery rates are still high and there is little evidence that disease outcomes for CD have changed over the past decades. The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprem province database. Data of 506 incident CD patients were analyzed (age at diagnosis: 31.5 years, s.d. 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups by the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). Overall, azathioprine (AZA), systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1- and 5-year probability of AZA use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In a multivariate Cox-regression analysis, decade of diagnosis (P < 0.001, hazard ratio (HR)(cohorts B-C): 2.88-6.53), age at onset (P = 0.008, HR: 1.76), disease behavior at diagnosis (P < 0.001, HR(complicated): 1.76-2.07), and need for systemic steroids (P < 0.001, HR: 2.71) were significantly associated with the time to initiation of AZA therapy. Early AZA use was significantly associated with the time to intestinal surgery in CD patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for AZA use (HR: 0.42, 95% CI: 0.26-0.67). This population-based inception cohort has shown that the recent reduction in surgical rates was independently associated with increased and earlier AZA use.

Breast Cancer Laterality Does Not Influence Survival in a Large Modern Cohort: Implications for Radiation-Related Cardiac Mortality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rutter, Charles E., E-mail: charles.rutter@yale.edu; Chagpar, Anees B.; Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine, New Haven, Connecticut

2014-10-01

Objectives: Radiation therapy for left-sided breast cancer has been associated with an elevated risk of cardiac mortality, based on studies predating treatment planning based on computed tomography. This study assessed the impact of tumor laterality on overall survival (OS) in a large cohort treated with modern techniques, to indirectly determine whether left-sided treatment remains associated with increased cardiac mortality. Methods and Materials: Patients treated for breast cancer with breast conserving surgery and adjuvant external beam radiation therapy were identified in the National Cancer Database, and OS was compared based on tumor laterality using Kaplan-Meier analysis. Separate analyses were performed formore » noninvasive and invasive carcinoma and for breast-only and breast plus regional nodal radiation therapy. Multivariate regression analysis of OS was performed with demographic, pathologic, and treatment variables as covariates to adjust for factors associated with breast cancer–specific survival. Results: We identified 344,831 patients whose cancer was diagnosed from 1998 to 2006 with a median follow-up time of 6.04 years (range, 0-14.17 years). Clinical, tumor, and treatment characteristics were similar between laterality groups. Regional nodal radiation was used in 14.2% of invasive cancers. No OS difference was noted based on tumor laterality for patients treated with breast-only (hazard ratio [HR] 0.984, P=.132) and breast plus regional nodal radiation therapy (HR 1.001, P=.957). In multivariate analysis including potential confounders, OS was identical between left and right sided cancers (HR 1.002, P=.874). No significant OS difference by laterality was observed when analyses were restricted to patients with at least 10 years of follow-up (n=27,725), both in patients treated with breast-only (HR 0.955, P=.368) and breast plus regional nodal radiation therapy (HR 0.859, P=.155). Conclusions: Radiation therapy for left-sided breast cancer does not appear to increase the risk of death in this national database relative to right-sided tumors. Consequently, radiation therapy–induced cardiac disease may be less prominent than previously demonstrated.« less

Echocardiographic predictors of survival in dogs with myxomatous mitral valve disease.

PubMed

Sargent, Julia; Muzzi, Ruthnea; Mukherjee, Rajat; Somarathne, Sharlene; Schranz, Katherine; Stephenson, Hannah; Connolly, David; Brodbelt, David; Fuentes, Virginia Luis

2015-03-01

To evaluate vena contracta and other echocardiographic measures of myxomatous mitral valve disease (MMVD) severity in a multivariable analysis of survival in dogs. 70 dogs diagnosed with MMVD from stored echocardiographic images that met study inclusion criteria. Left heart dimensions were measured as well as mitral regurgitant jet area/left atrial area (JAR), early mitral filling velocity (Evel), extent of mitral valve prolapse in right and left views (ProlR, ProlL), Prol indexed to aortic diameter (ProlR:Ao, ProlL:Ao), presence of a flail leaflet (FlailR, FlailL), and mitral regurgitation vena contracta diameter (VCR, VCL) indexed to aortic diameter (VCR:Ao, VCL:Ao). Follow-up from referring veterinarians was obtained by questionnaire or telephone to determine survival times. Inter- and intra-observer agreement was evaluated with Bland-Altman plots and weighted Kappa analysis. Survival was analyzed using Kaplan-Meier curves, logrank tests and Cox's proportional hazards. Logrank analysis showed VCL:Ao, VCR:Ao, FlailL, ProlR:Ao, ProlL:Ao, left ventricular internal dimension in diastole indexed to aortic diameter (LVIDD:Ao) >2.87, left atrium to aorta ratio (LA/Ao) >1.6, and Evel >1.4 m/s were predictors of cardiac mortality. In a multivariable analysis, the independent predictors of cardiac mortality were Evel >1.4 m/s [hazard ratio (HR) 5.0, 95% confidence interval (CI) 2.5-10.3], FlailL (HR 3.1, 95% CI 1.3-7.9), and ProlR:Ao (HR 2.8, 95% CI 1.3-6.3). Echocardiographic measures of mitral regurgitation severity and mitral valve pathology provide valuable prognostic information independent of chamber enlargement in dogs with MMVD. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios on Survival in Patients with Extrahepatic Cholangiocarcinoma.

PubMed

Kitano, Yuki; Yamashita, Yo-Ichi; Yamamura, Kensuke; Arima, Kota; Kaida, Takayoshi; Miyata, Tatsunori; Nakagawa, Shigeki; Mima, Kosuke; Imai, Katsunori; Hashimoto, Daisuke; Chikamoto, Akira; Baba, Hideo

2017-06-01

As indicators of systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict prognoses for various cancers. This study investigated their prognostic significance in extrahepatic cholangiocarcinoma (ECC). We analyzed 120 patients who underwent surgery for ECC between 2000 and 2014. We calculated preoperative NLR and PLR and evaluated their correlations with patients' clinicopathological features and prognosis. Although high NLR was not associated with worse recurrence-free survival (RFS) (hazard ratio (HR)=1.32, p=0.26), cancer-specific survival (CSS) (HR=1.35, p=0.31) and overall survival (OS) (HR=1.19, p=0.52), high PLR was significantly associated with worse RFS (HR=1.85, p=0.01), CSS (HR=2.38, p=0.002) and OS (HR=1.98, p=0.008). In multivariate analysis, high PLR (HR=1.89, p=0.02) and lymph node metastasis (HR=1.78, p=0.03) were independent prognostic factors for OS. A high PLR had more liver recurrences (p=0.04) and recurrences within 1 year (HR=2.38, p=0.02) than low PLR. High preoperative PLR was an independent predictor of poor prognosis for patients with ECC who underwent resections. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children.

PubMed

Kann, Benjamin H; Park, Henry S; Lester-Coll, Nataniel H; Yeboa, Debra N; Benitez, Viviana; Khan, Atif J; Bindra, Ranjit S; Marks, Asher M; Roberts, Kenneth B

2016-12-01

Postoperative radiotherapy to the craniospinal axis is standard-of-care for pediatric medulloblastoma but is associated with long-term morbidity, particularly in young children. With the advent of modern adjuvant chemotherapy strategies, postoperative radiotherapy deferral has gained acceptance in children younger than 3 years, although it remains controversial in older children. To analyze recent postoperative radiotherapy national treatment patterns and implications for overall survival in patients with medulloblastoma ages 3 to 8 years. Using the National Cancer Data Base, patients ages 3 to 8 years diagnosed as having histologically confirmed medulloblastoma in 2004 to 2012, without distant metastases, who underwent surgery and adjuvant chemotherapy with or without postoperative radiotherapy at facilities nationwide accredited by the Commission on Cancer were identified. Patients were designated as having "postoperative radiotherapy upfront" if they received radiotherapy within 90 days of surgery or "postoperative radiotherapy deferred" otherwise. Factors associated with postoperative radiotherapy deferral were identified using multivariable logistic regression. Overall survival (OS) was compared using Kaplan-Meier analysis with log-rank tests and multivariable Cox regression. Statistical tests were 2-sided. Postoperative radiotherapy utilization and overall survival. Among 816 patients, 123 (15.1%) had postoperative radiotherapy deferred, and 693 (84.9%) had postoperative radiotherapy upfront; 36.8% of 3-year-olds and 4.1% of 8-year-olds had postoperative radiotherapy deferred (P < .001). On multivariable logistic regression, variables associated with postoperative radiotherapy deferral were age (odds ratio [OR], 0.57 per year; 95% CI, 0.49-0.67 per year) and year of diagnosis (OR, 1.18 per year; 95% CI, 1.08-1.29 per year). On survival analysis, with median follow-up of 4.8 years, OS was improved for those receiving postoperative radiotherapy upfront vs postoperative radiotherapy deferred (5-year OS: 82.0% vs 63.4%; P < .001). On multivariable analysis, variables associated with poorer OS were postoperative radiotherapy deferral (hazards ratio [HR], 1.95; 95% CI, 1.15-3.31); stage M1-3 disease (HR, 1.86; 95% CI, 1.10-3.16), and low facility volume (HR, 1.75; 95% CI, 1.04-2.94). Our national database analysis reveals a higher-than-expected and increasing rate of postoperative radiotherapy deferral in children with medulloblastoma ages 3 to 8 years. The analysis suggests that postoperative radiotherapy deferral is associated with worse survival in this age group, even in the modern era of chemotherapy.

Prognostic significance of pre-resection albumin/fibrinogen ratio in patients with non-small cell lung cancer: A propensity score matching analysis.

PubMed

Chen, Shuaishuai; Yan, Haixi; Du, Juping; Li, Jun; Shen, Bo; Ying, Haijian; Zhang, Ying; Chen, Shiyong

2018-07-01

Nutrition and coagulation play important roles in cancer progression. This study was aimed to investigate the value of the albumin/fibrinogen ratio (AFR) in non-small cell lung cancer (NSCLC) patients, through a propensity score matching (PSM) method. We retrospectively analyzed 529 NSCLC patients underwent surgical resection from 2010 to 2015. PSM was used to eliminate possible biases. A Cox proportional hazards regression model was performed to evaluate the prognostic value of AFR in NSCLC. The optimal value was 9.67 for the AFR by ROC (receiver operating characteristic) curve. The AFR was statistically significantly associated with age, sex, smoking history, histological subtype, tumor size, pathological stage and adjuvant therapy (p < 0.05). Multivariate analysis indicated that the pathological stage and pre-resection AFR were independent prognostic factors for patients with NSCLC. Additionally, elevated AFR indicated a better outcome, and patients with higher AFR had lower risk for overall death (OS) (HR 0.512, 95% CI 0.316-0.829, p = 0.006) as well as disease-free death (DFS) (HR 0.561, 95% CI 0.399-0.787, p = 0.001). The propensity score model identified 120 patients from each group that were balanced for age, sex, smoking history, histological subtype, tumor size, stage distribution and adjuvant therapy. In multivariable regression analysis of PSM groups, the result indicated that the AFR was predictive for OS (HR 0.392, 95% CI 0.225-0.683, p < 0.001) and DFS (HR 0.526, 95% CI 0.344-0.805, p = 0.003). Pre-resection AFR can be considered as an independent prognostic factor in NSCLC patients, and higher AFR may enhance OS and DFS of NSCLC patients. Copyright © 2018 Elsevier B.V. All rights reserved.

A multi-institutional analysis of the untreated course of cerebral dural arteriovenous fistulas.

PubMed

Gross, Bradley A; Albuquerque, Felipe C; McDougall, Cameron G; Jankowitz, Brian T; Jadhav, Ashutosh P; Jovin, Tudor G; Du, Rose

2017-12-15

OBJECTIVE The rarity of cerebral dural arteriovenous fistulas (dAVFs) has precluded analysis of their natural history across large cohorts. Investigators from a considerable proportion of the few reports that do exist have evaluated heterogeneous groups of untreated and partially treated lesions. In the present study, the authors exclusively evaluated the untreated course of dAVFs across a multi-institutional data set to delineate demographic, angiographic, and natural history data. METHODS A multi-institutional database of dAVFs was queried for demographic and angiographic data as well as untreated disease course. After dAVFs were stratified by Djindjian type, annual nonhemorrhagic neurological deficit (NHND) and hemorrhage rates were derived, as were risk factors for each. A multivariable Cox proportional-hazards regression model was used to calculate hazard ratios. RESULTS Two hundred ninety-five dAVFs had at least 1 month of untreated follow-up. For 126 Type I dAVFs, there were no episodes of NHND or hemorrhage over 177 lesion-years. Respective annualized NHND and hemorrhage rates were 4.5% and 3.4% for Type II, 6.0% and 4.0% for Type III, and 4.5% and 9.1% for Type IV dAVFs. The respective annualized NHND and hemorrhage rates were 2.3% and 2.9% for asymptomatic Type II-IV dAVFs, 23.1% and 3.3% for dAVFs presenting with NHND, and 0% and 46.2% for lesions presenting with hemorrhage. On multivariate analysis, NHND presentation (HR 11.49, 95% CI 3.19-63) and leptomeningeal venous drainage (HR 5.03, 95% CI 0.42-694) were significant risk factors for NHND; hemorrhagic presentation (HR 17.67, 95% CI 2.99-117) and leptomeningeal venous drainage (HR 10.39, 95% CI 1.11-1384) were significant risk factors for hemorrhage. CONCLUSIONS All Type II-IV dAVFs should be considered for treatment. Given the high risk of rebleeding, lesions presenting with NHND and/or hemorrhage should be treated expediently.

Clostridium difficile infection is associated with graft loss in solid organ transplant recipients.

PubMed

Cusini, A; Béguelin, C; Stampf, S; Boggian, K; Garzoni, C; Koller, M; Manuel, O; Meylan, P; Mueller, N J; Hirsch, H H; Weisser, M; Berger, C; van Delden, C

2018-01-19

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to improve the management of SOT recipients. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Cystic Fibrosis Associated with Worse Survival After Liver Transplantation.

PubMed

Black, Sylvester M; Woodley, Frederick W; Tumin, Dmitry; Mumtaz, Khalid; Whitson, Bryan A; Tobias, Joseph D; Hayes, Don

2016-04-01

Survival in cystic fibrosis patients after liver transplantation and liver-lung transplantation is not well studied. To discern survival rates after liver transplantation and liver-lung transplantation in patients with and without cystic fibrosis. The United Network for Organ Sharing database was queried from 1987 to 2013. Univariate Cox proportional hazards, multivariate Cox models, and propensity score matching were performed. Liver transplant and liver-lung transplant were performed in 212 and 53 patients with cystic fibrosis, respectively. Univariate Cox proportional hazards regression identified lower survival in cystic fibrosis after liver transplant compared to a reference non-cystic fibrosis liver transplant cohort (HR 1.248; 95 % CI 1.012, 1.541; p = 0.039). Supplementary analysis found graft survival was similar across the 3 recipient categories (log-rank test: χ(2) 2.68; p = 0.262). Multivariate Cox models identified increased mortality hazard among cystic fibrosis patients undergoing liver transplantation (HR 2.439; 95 % CI 1.709, 3.482; p < 0.001) and liver-lung transplantation (HR 2.753; 95 % CI 1.560, 4.861; p < 0.001). Propensity score matching of cystic fibrosis patients undergoing liver transplantation to non-cystic fibrosis controls identified a greater mortality hazard in the cystic fibrosis cohort using a Cox proportional hazards model stratified on matched pairs (HR 3.167; 95 % CI 1.265, 7.929, p = 0.014). Liver transplantation in cystic fibrosis is associated with poorer long-term patient survival compared to non-cystic fibrosis patients, although the difference is not due to graft survival.

Gene modules associated with breast cancer distant metastasis-free survival in the PAM50 molecular subtypes.

PubMed

Liu, Rong; Zhang, Wei; Liu, Zhao-Qian; Zhou, Hong-Hao

2016-04-19

To identify PAM50 subtype-specific associations between distant metastasis-free survival (DMFS) in breast cancer (BC) patients and gene modules describing potentially targetable oncogenic pathways, a comprehensive analysis evaluating the prognostic efficacy of published gene signatures in 2027 BC patients from 13 studies was conducted. We calculated 21 gene modules and computed hazard ratios (HRs) for DMFS for one-unit increases in module score, with and without adjustment for clinical characteristics. By comparing gene expression to survival outcomes, we derived four subtype-specific prognostic signatures for BC. Univariate and multivariate analyses showed that in the luminal A subgroup, E2F3, PTEN and GGI gene module scores were associated with clinical outcome. In the luminal B tumors, RAS was associated with DMFS and in the basal-like tumors, ER was associated with DMFS. Our defined gene modules predicted high-risk patients in multivariate analyses for the basal-like (HR: 2.19, p=2.5×10-4), luminal A (HR: 3.03, p=7.2×10-5), luminal B (HR: 3.00, p=2.4×10-10) and HER2+ (HR: 5.49, p=9.7×10-10) subgroups. We found that different modules are associated with DMFS in different BC subtypes. The results of this study could help to identify new therapeutic strategies for specific molecular subgroups of BC, and could enhance efforts to improve patient-specific therapy options.

Long-Term Mortality in Patients Operated for Perforated Peptic Ulcer: Factors Limiting Longevity are Dominated by Older Age, Comorbidity Burden and Severe Postoperative Complications.

PubMed

Thorsen, K; Søreide, J A; Søreide, K

2017-02-01

Perforated peptic ulcer (PPU) is a surgical emergency associated with high short-term mortality. However, studies on long-term outcomes are scarce. Our aim was to investigate long-term survival after surgery for PPU. A population-based, consecutive cohort of patients who underwent surgery for PPU between 2001 and 2014 was reviewed, and the long-term mortality was assessed. Survival was investigated by univariate analysis (log-rank test) and displayed using Kaplan-Meier survival curves. Multivariable analysis of risk factors for long-term mortality was assessed by Cox proportional hazards regression and reported as hazard ratio (HR) with 95 % confidence intervals (CI). A total of 234 patients were available for the calculation of ninety-day, one-year and two-year mortality, and the results showed rates of 19.2 % (45/234), 22.6 % (53/234) and 24.8 % (58/234), respectively. At the end of follow-up, a total of 109 of the 234 patients (46.6 %) had died. Excluding 37 (15.2 %) patients who died within 30 days of surgery, 197 patients had long-term follow-up (median 57 months, range 1-168) of which 36 % (71/197) died during the follow-up period. In multivariable analyses, age >60 years (HR 3.95, 95 % CI 1.81-8.65), active cancer (HR 3.49, 95 % CI 1.73-7.04), hypoalbuminemia (HR 1.65, 95 % CI 0.99-2.73), pulmonary disease (HR 2.06, 95 % CI 1.14-3.71), cardiovascular disease (HR 1.67, 95 % CI 1.01-2.79) and severe postoperative complications (HR 1.76, 95 % CI 1.07-2.89) during the initial stay for PPU were all independently associated with an increased risk of long-term mortality. Cause of long-term mortality was most frequently (18 of 71; 25 %) attributed to new onset sepsis and/or multiorgan failure. The long-term mortality after surgery for PPU is high. One in every three patients died during follow-up. Older age, comorbidity and severe postoperative complications were risk factors for long-term mortality.

DOE Office of Scientific and Technical Information (OSTI.GOV)

VanderWalde, Noam A.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Meyer, Anne Marie

Purpose: The purpose of this study was to compare chemoradiation therapy (CRT) with radiation therapy (RT) only in an older patient population with head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2007), we identified a retrospective cohort of nonmetastatic HNSCC patients and divided them into treatment groups. Comparisons were made between CRT and RT cohorts. Propensity scores for CRT were estimated from covariates associated with receipt of treatment using multivariable logistic regression. Standardized mortality ratio weights (SMRW) were created from the propensity scores and used to balance groupsmore » on measured confounders. Multivariable and SMR-weighted Cox proportional hazard models were used to estimate the hazard ratio (HR) of death for receipt of CRT versus RT among the whole group and for separate patient and tumor categories. Results: The final cohort of 10,599 patients was 68% male and 89% white. Median age was 74 years. Seventy-four percent were treated with RT, 26% were treated with CRT. Median follow-up points for CRT and RT survivors were 4.6 and 6.3 years, respectively. On multivariable analysis, HR for death with CRT was 1.13 (95% confidence interval [CI]: 1.07-1.20; P<.01). Using the SMRW model, the HR for death with CRT was 1.08 (95% CI: 1.02-1.15; P=.01). Conclusions: Although the addition of chemotherapy to radiation has proven efficacious in many randomized controlled trials, it may be less effective in an older patient population treated outside of a controlled trial setting.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Bhavana V.; Gill, Beant S.; Viswanathan, Akila N.

Purpose: Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base. Methods and Materials: Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis. Results: We identified 3075 patients withmore » a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range [IQR] 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio [HR] 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779). Conclusions: Patients with vulvar squamous cell carcinoma and positive surgical margins derive an OS benefit from aRT with a seemingly optimal dose in the range of 54.0 to 59.9 Gy.« less

Positron emission tomography–computed tomography predictors of progression after DA-R-EPOCH for PMBCL

PubMed Central

Ng, Andrea K.; Dabaja, Bouthaina S.; Milgrom, Sarah A.; Gunther, Jillian R.; Fuller, C. David; Smith, Grace L.; Abou Yehia, Zeinab; Qiao, Wei; Wogan, Christine F.; Akhtari, Mani; Mawlawi, Osama; Medeiros, L. Jeffrey; Chuang, Hubert H.; Martin-Doyle, William; Armand, Philippe; LaCasce, Ann S.; Oki, Yasuhiro; Fanale, Michelle; Westin, Jason; Neelapu, Sattva; Nastoupil, Loretta

2018-01-01

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [18F]fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning–derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance (P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis (P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression. PMID:29895624

Positron emission tomography-computed tomography predictors of progression after DA-R-EPOCH for PMBCL.

PubMed

Pinnix, Chelsea C; Ng, Andrea K; Dabaja, Bouthaina S; Milgrom, Sarah A; Gunther, Jillian R; Fuller, C David; Smith, Grace L; Abou Yehia, Zeinab; Qiao, Wei; Wogan, Christine F; Akhtari, Mani; Mawlawi, Osama; Medeiros, L Jeffrey; Chuang, Hubert H; Martin-Doyle, William; Armand, Philippe; LaCasce, Ann S; Oki, Yasuhiro; Fanale, Michelle; Westin, Jason; Neelapu, Sattva; Nastoupil, Loretta

2018-06-12

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [ 18 F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning-derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance ( P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis ( P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression. © 2018 by The American Society of Hematology.

Using computer assisted image analysis to determine the optimal Ki67 threshold for predicting outcome of invasive breast cancer

PubMed Central

Tay, Timothy Kwang Yong; Thike, Aye Aye; Pathmanathan, Nirmala; Jara-Lazaro, Ana Richelia; Iqbal, Jabed; Sng, Adeline Shi Hui; Ye, Heng Seow; Lim, Jeffrey Chun Tatt; Koh, Valerie Cui Yun; Tan, Jane Sie Yong; Yeong, Joe Poh Sheng; Chow, Zi Long; Li, Hui Hua; Cheng, Chee Leong; Tan, Puay Hoon

2018-01-01

Background Ki67 positivity in invasive breast cancers has an inverse correlation with survival outcomes and serves as an immunohistochemical surrogate for molecular subtyping of breast cancer, particularly ER positive breast cancer. The optimal threshold of Ki67 in both settings, however, remains elusive. We use computer assisted image analysis (CAIA) to determine the optimal threshold for Ki67 in predicting survival outcomes and differentiating luminal B from luminal A breast cancers. Methods Quantitative scoring of Ki67 on tissue microarray (TMA) sections of 440 invasive breast cancers was performed using Aperio ePathology ImmunoHistochemistry Nuclear Image Analysis algorithm, with TMA slides digitally scanned via Aperio ScanScope XT System. Results On multivariate analysis, tumours with Ki67 ≥14% had an increased likelihood of recurrence (HR 1.941, p=0.021) and shorter overall survival (HR 2.201, p=0.016). Similar findings were observed in the subset of 343 ER positive breast cancers (HR 2.409, p=0.012 and HR 2.787, p=0.012 respectively). The value of Ki67 associated with ER+HER2-PR<20% tumours (Luminal B subtype) was found to be <17%. Conclusion Using CAIA, we found optimal thresholds for Ki67 that predict a poorer prognosis and an association with the Luminal B subtype of breast cancer. Further investigation and validation of these thresholds are recommended. PMID:29545924

PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer

PubMed Central

Lotan, Tamara L.; Wei, Wei; Morais, Carlos L.; Hawley, Sarah T.; Fazli, Ladan; Hurtado-Coll, Antonio; Troyer, Dean; McKenney, Jesse K.; Simko, Jeffrey; Carroll, Peter R.; Gleave, Martin; Lance, Raymond; Lin, Daniel W.; Nelson, Peter S.; Thompson, Ian M.; True, Lawrence D.; Feng, Ziding; Brooks, James D.

2015-01-01

Background PTEN is the most commonly deleted tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes and ERG gene rearrangement. Objective We tested whether PTEN loss is associated with shorter recurrence-free survival (RFS) in surgically treated PCa patients with known ERG status. Design, setting, and participants A genetically validated, automated PTEN immunohistochemistry (IHC) protocol was used for 1275 primary prostate tumors from the Canary Foundation retrospective PCa tissue microarray cohort to assess homogeneous (in all tumor tissue sampled) or heterogeneous (in a subset of tumor tissue sampled) PTEN loss. ERG status as determined by a genetically validated IHC assay was available for a subset of 938 tumors. Outcome measurements and statistical analysis Associations between PTEN and ERG status were assessed using Fisher’s exact test. Kaplan-Meier and multivariate weighted Cox proportional models for RFS were constructed. Results and limitations When compared to intact PTEN, homogeneous (hazard ratio [HR] 1.66, p = 0.001) but not heterogeneous (HR 1.24, p = 0.14) PTEN loss was significantly associated with shorter RFS in multivariate models. Among ERG-positive tumors, homogeneous (HR 3.07, p < 0.0001) but not heterogeneous (HR 1.46, p = 0.10) PTEN loss was significantly associated with shorter RFS. Among ERG-negative tumors, PTEN did not reach significance for inclusion in the final multivariate models. The interaction term for PTEN and ERG status with respect to RFS did not reach statistical significance (p = 0.11) for the current sample size. Conclusions These data suggest that PTEN is a useful prognostic biomarker and that there is no statistically significant interaction between PTEN and ERG status for RFS. Patient summary We found that loss of the PTEN tumor suppressor gene in prostate tumors as assessed by tissue staining is correlated with shorter time to prostate cancer recurrence after radical prostatectomy. PMID:27617307

Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

PubMed

Walker, Steven M; Knight, Laura A; McCavigan, Andrena M; Logan, Gemma E; Berge, Viktor; Sherif, Amir; Pandha, Hardev; Warren, Anne Y; Davidson, Catherine; Uprichard, Adam; Blayney, Jaine K; Price, Bethanie; Jellema, Gera L; Steele, Christopher J; Svindland, Aud; McDade, Simon S; Eden, Christopher G; Foster, Chris; Mills, Ian G; Neal, David E; Mason, Malcolm D; Kay, Elaine W; Waugh, David J; Harkin, D Paul; Watson, R William; Clarke, Noel W; Kennedy, Richard D

2017-10-01

Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Influence of semi-quantitative oestrogen receptor expression on adjuvant endocrine therapy efficacy in ductal and lobular breast cancer - a TEAM study analysis.

PubMed

van de Water, Willemien; Fontein, Duveken B Y; van Nes, Johanna G H; Bartlett, John M S; Hille, Elysée T M; Putter, Hein; Robson, Tammy; Liefers, Gerrit-Jan; Roumen, Rudi M H; Seynaeve, Caroline; Dirix, Luc Y; Paridaens, Robert; Kranenbarg, Elma Meershoek-Klein; Nortier, Johan W R; van de Velde, Cornelis J H

2013-01-01

Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC). However, data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by Allred score was also investigated. Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized to exemestane (25mg daily) alone or following tamoxifen (20mg daily) for 5 years. Inclusion was restricted to IDC and ILC patients. Histological subtype was assessed locally; ER expression was centrally reviewed according to Allred score (ER-poor (<7; n=235); ER-rich (7; n=1789)). Primary end-point was relapse-free survival (RFS), which was the time from randomization to disease relapse. Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for exemestane was 0.83 (95%confidence interval (CI) 0.67-1.03)), and ILC (HR 0.69 (95%CI 0.45-1.06)). Irrespective of histological subtype, patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS (multivariable HR 0.71 (95%CI 0.56-0.89)). In contrast, patients with ER-poor Allred scores allocated to exemestane had a worse RFS (multivariable HR 2.33 (95%CI 1.32-4.11)). Significant effect modification by ER-Allred score was confirmed (multivariable p=0.003). Efficacy of endocrine therapy regimens was similar for IDC and ILC. However, ER-rich patients showed superior efficacy to upfront exemestane, while ER-poor patients had better outcomes with sequential therapy, irrespective of histological subtype, emphasising the relevance of quantification of ER expression. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Analysis of risk factors for all cause-mortality in Chinese emergency atrial fibrillation patients].

PubMed

Wang, Juan; Yang, Yan-min; Zhu, Jun; Zhang, Han; Shao, Xing-hui; Huang, Bi; Tian, Li

2013-09-24

To explore the independent risk factors associated with one-year mortality in patients with atrial fibrillation (AF). This study consecutively enrolled AF patients presenting to an emergency department at 20 Chinese hospitals from November 2008 to October 2011. Their baseline data and therapies were recorded. They were followed up for one year. Their major cardiovascular outcomes were recorded. And the predictors of one-year mortality were identified by uni- and multi-variate Cox regression analysis with baseline, therapy variables and follow-up therapy variables. The one-year all-cause mortality was 13.8% among a total of 2016 AF patients. They were divided into mortality group (A, n = 279) and survival group (B, n = 1737). The baseline data of two groups were analyzed. The group A patients were older ((76.1 ± 11.6) vs (67.2 ± 13.1) years, P < 0.01) and had smaller body mass index compared with group B ((23.7 ± 3.6) vs (22.3 ± 3.4) kg/m(2), P < 0.01); the proportion of permanent AF and CHADS2 score ≥ 2 points was higher in the group A (71.8% vs 47.5%, P < 0.01). History of heart failure, previous stroke, left ventricular systolic dysfunction, diabetes, dementia and chronic obstructive pulmonary disease (COPD) were in a higher proportion of group A (51.2% vs 35.1%, 26.3% vs 17.6%, 26.7% vs 17.9%, 21.0% vs 14.6%, 6.0% vs 1.6%, 21.4% vs 10.1%, all P < 0.01). With regards to drug treatment, usage of diuretics, digoxin and other anticoagulants (heparin, etc), the values were greater in group A (50.9% vs 42.2%, 41.3% vs 34.7%, 10.0% vs 5.9%, all P < 0.01). The Kaplan-Meier survival curves showed that the mortality rate increased along with rising CHADS2 score. Multi-variate Cox regression analysis showed that age (HR = 1.053, 95%CI: 1.040-1.066), permanent AF (HR = 1.374, 95%CI: 1.003-1.883), history of heart failure (HR = 1.385, 95%CI: 1.009-1.901), previous stroke (HR = 1.345, 95%CI: 1.009-1.795), COPD (HR = 1.379, 95%CI: 1.030-1.848), unused angiotensin II receptor blocker (ARB) (HR = 1.955, 95%CI: 1.349-2.832), aspirin unused (HR = 1.770, 95%CI: 1.375-2.278) and warfarin unused (HR = 3.262, 95%CI:1.824-5.834) were independent risk factors for one-year mortality of AF patients. Age, history of heart failure, previous stroke, COPD history, ARB unused, aspirin and warfarin unused are independent risk factors for one-year all-cause mortality of AF patients.

Repetition of self-harm and suicide following self-harm in children and adolescents: findings from the Multicentre Study of Self-harm in England.

PubMed

Hawton, Keith; Bergen, Helen; Kapur, Navneet; Cooper, Jayne; Steeg, Sarah; Ness, Jennifer; Waters, Keith

2012-12-01

Self-harm (intentional self-poisoning and self-injury) in children and adolescents is often repeated and is associated with increased risk of future suicide. We have investigated factors associated with these outcomes. We used data collected in the Multicentre Study of Self-harm in England on all self-harm hospital presentations by individuals aged 10-18 years between 2000 and 2007, and national death information on these individuals to the end of 2010. Cox hazard proportional models were used to identify independent and multivariable predictors of repetition of self-harm and of suicide. Repetition of self-harm occurred in 27.3% of individuals (N = 3920) who presented between 2000 and 2005 and were followed up until 2007. Multivariate analysis showed that repetition was associated with age, self-cutting, and previous self-harm and psychiatric treatment. Of 51 deaths in individuals who presented between 2000 and 2007 and were followed up to 2010 (N = 5133) half (49.0%) were suicides. The method used was usually different to that used for self-harm. Multivariate analysis showed that suicide was associated with male gender [Hazard ratio (HR) = 2.4, 95% CI 1.2-4.8], self-cutting (HR = 2.1, 95% CI 1.1-3.7) and prior psychiatric treatment at initial presentation (HR = 4.2, 95% CI 1.7-10.5). It was also associated with self-cutting and history of psychiatric treatment at the last episode before death, and history of previous self harm. Self-cutting as a method of self-harm in children and adolescents conveys greater risk of suicide (and repetition) than self-poisoning although different methods are usually used for suicide. The findings underline the need for psychosocial assessment in all cases. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Use and Effectiveness of Adjuvant Endocrine Therapy for Hormone Receptor-Positive Breast Cancer in Men.

PubMed

Venigalla, Sriram; Carmona, Ruben; Guttmann, David M; Jain, Varsha; Freedman, Gary M; Clark, Amy S; Shabason, Jacob E

2018-05-24

Although adjuvant endocrine therapy confers a survival benefit among females with hormone receptor (HR)-positive breast cancer, the effectiveness of this treatment among males with HR-positive breast cancer has not been rigorously investigated. To investigate trends, patterns of use, and effectiveness of adjuvant endocrine therapy among men with HR-positive breast cancer. This retrospective cohort study identified patients in the National Cancer Database with breast cancer who had received treatment from 2004 through 2014. Inclusion criteria for the primary study cohort were males at least 18 years old with nonmetastatic HR-positive invasive breast cancer who underwent surgery with or without adjuvant endocrine therapy. A cohort of female patients was also identified using the same inclusion criteria for comparative analyses by sex. Data analysis was conducted from October 1, 2017, to December 15, 2017. Receipt of adjuvant endocrine therapy. Patterns of adjuvant endocrine therapy use were assessed using multivariable logistic regression analyses. Association between adjuvant endocrine therapy use and overall survival was assessed using propensity score-weighted multivariable Cox regression models. The primary study cohort comprised 10 173 men with HR-positive breast cancer (mean [interquartile range] age, 66 [57-75] years). The comparative cohort comprised 961 676 women with HR-positive breast cancer (mean [interquartile range] age, 62 [52-72] years). The median follow-up for the male cohort was 49.6 months (range, 0.1-142.5 months). Men presented more frequently than women with HR-positive disease (94.0% vs 84.3%, P < .001). However, eligible men were less likely than women to receive adjuvant endocrine therapy (67.3% vs 79.0%; OR, 0.61; 95% CI, 0.58-0.63; P < .001). Treatment at academic facilities (odds ratio, 1.13; 95% CI, 1.02-1.25; P = .02) and receipt of adjuvant radiotherapy (odds ratio, 2.83; 95% CI, 2.55-3.15; P < .001) or chemotherapy (odds ratio, 1.20; 95% CI, 1.07-1.34; P < .001) were statistically significantly associated with adjuvant endocrine therapy use in men. A propensity score-weighted analysis indicated that relative to no use, adjuvant endocrine therapy use in men was associated with improved overall survival (hazard ratio, 0.70; 95% CI, 0.63-0.77; P < .001). There is a sex disparate underuse of adjuvant endocrine therapy among men with HR-positive breast cancer despite the use of this treatment being associated with improved overall survival. Further research and interventions may be warranted to bridge gaps in care in this population.

Dietary Protein Sources and All-Cause and Cause-Specific Mortality: The Golestan Cohort Study in Iran.

PubMed

Farvid, Maryam S; Malekshah, Akbar F; Pourshams, Akram; Poustchi, Hossein; Sepanlou, Sadaf G; Sharafkhah, Maryam; Khoshnia, Masoud; Farvid, Mojtaba; Abnet, Christian C; Kamangar, Farin; Dawsey, Sanford M; Brennan, Paul; Pharoah, Paul D; Boffetta, Paolo; Willett, Walter C; Malekzadeh, Reza

2017-02-01

Dietary protein comes from foods with greatly different compositions that may not relate equally with mortality risk. Few cohort studies from non-Western countries have examined the association between various dietary protein sources and cause-specific mortality. Therefore, the associations between dietary protein sources and all-cause, cardiovascular disease, and cancer mortality were evaluated in the Golestan Cohort Study in Iran. Among 42,403 men and women who completed a dietary questionnaire at baseline, 3,291 deaths were documented during 11 years of follow up (2004-2015). Cox proportional hazards models estimated age-adjusted and multivariate-adjusted hazard ratios (HRs) and 95% CIs for all-cause and disease-specific mortality in relation to dietary protein sources. Data were analyzed from 2015 to 2016. Comparing the highest versus the lowest quartile, egg consumption was associated with lower all-cause mortality risk (HR=0.88, 95% CI=0.79, 0.97, p trend =0.03). In multivariate analysis, the highest versus the lowest quartile of fish consumption was associated with reduced risk of total cancer (HR=0.79, 95% CI=0.64, 0.98, p trend =0.03) and gastrointestinal cancer (HR=0.75, 95% CI=0.56, 1.00, p trend =0.02) mortality. The highest versus the lowest quintile of legume consumption was associated with reduced total cancer (HR=0.72, 95% CI=0.58, 0.89, p trend =0.004), gastrointestinal cancer (HR=0.76, 95% CI=0.58, 1.01, p trend =0.05), and other cancer (HR=0.66, 95% CI=0.47, 0.93, p trend =0.04) mortality. Significant associations between total red meat and poultry intake and all-cause, cardiovascular disease, or cancer mortality rate were not observed among all participants. These findings support an association of higher fish and legume consumption with lower cancer mortality, and higher egg consumption with lower all-cause mortality. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

Dietary Protein Sources and All-Cause and Cause-Specific Mortality: The Golestan Cohort Study in Iran

PubMed Central

Farvid, Maryam S.; Malekshah, Akbar F.; Pourshams, Akram; Poustchi, Hossein; Sepanlou, Sadaf G.; Sharafkhah, Maryam; Khoshnia, Masoud; Farvid, Mojtaba; Abnet, Christian C.; Kamangar, Farin; Dawsey, Sanford M.; Brennan, Paul; Pharoah, Paul D.; Boffetta, Paolo; Willett, Walter C.; Malekzadeh, Reza

2016-01-01

Introduction Dietary protein comes from foods with greatly different compositions that may not relate equally with mortality risk. Few cohort studies from non-Western countries have examined the association between various dietary protein sources and cause-specific mortality. Therefore, the associations between dietary protein sources and all-cause, cardiovascular disease, and cancer mortality were evaluated in the Golestan Cohort Study in Iran. Methods Among 42,403 men and women who completed a dietary questionnaire at baseline, 3,291 deaths were documented during 11 years of follow up (2004–2015). Cox proportional hazards models estimated age-adjusted and multivariate-adjusted hazard ratios (HRs) and 95% CIs for all- cause and disease-specific mortality in relation to dietary protein sources. Data were analyzed from 2015 to 2016. Results Comparing the highest versus the lowest quartile, egg consumption was associated with lower all-cause mortality risk (HR=0.88, 95% CI=0.79, 0.97, ptrend=0.03). In multivariate analysis, the highest versus the lowest quartile of fish consumption was associated with reduced risk of total cancer (HR=0.79, 95% CI=0.64, 0.98, ptrend=0.03) and gastrointestinal cancer (HR=0.75, 95% CI=0.56, 1.00, ptrend=0.02) mortality. The highest versus the lowest quintile of legume consumption was associated with reduced total cancer (HR=0.72, 95% CI=0.58, 0.89, ptrend=0.004), gastrointestinal cancer (HR=0.76, 95% CI=0.58, 1.01, ptrend=0.05), and other cancer (HR=0.66, 95% CI=0.47, 0.93, ptrend=0.04) mortality. Significant associations between total red meat and poultry intake and all- cause, cardiovascular disease, or cancer mortality rate were not observed among all participants. Conclusions These findings support an association of higher fish and legume consumption with lower cancer mortality, and higher egg consumption with lower all-cause mortality. PMID:28109460

The prognostic value of sST2 and galectin-3 considering different aetiologies in non-ischaemic heart failure.

PubMed

Binas, David; Daniel, Hanna; Richter, Anette; Ruppert, Volker; Schlüter, Klaus-Dieter; Schieffer, Bernhard; Pankuweit, Sabine

2018-01-01

Several studies indicate a prognostic value of sST2 and galectin-3 in heart failure (HF). While previous studies focused on ischaemic cause of HF, we investigated the role of sST2 and galectin-3 in patients with non-ischaemic dilated cardiomyopathy (DCM). sST2 and galectin-3 serum concentrations were measured in 262 subjects with DCM. Survival rates were determined for all-cause mortality (ACM) and cardiac mortality (CM). In a univariate model, sST2 as a continuous variable was a predictor of ACM (HR 1.05; 95% CI 1.03 to 1.07, P<0.001) and CM (HR 1.03; 95% CI 1.00 to 1.06, P=0.040). In the subgroup of patients with inflammatory and/or viral DCM (DCMi⋎viral), the endpoints ACM (HR 1.10; 95% CI 1.05 to 1.17, P<0.001) and CM (HR 1.10; 95% CI 1.02 to 1.18, P=0.013) were significant. In the subgroup of patients with idiopathic DCM, the endpoint ACM (HR 1.04; 95% CI 1.01 to 1.07, P=0.019) was significant. In a multivariate model, the prognostic value of the sST2 main group remained intact for ACM (HR 1.04; 95% CI 1.02 to 1.07, P=0.003).Univariate and multivariate analysis of galectin-3 as continuous variable did not show any significant result. However, in a quartile model, intermediate values of galectin-3 were significantly associated with a lower event rate of ACM and CM. The study revealed that sST2 predicts ACM and CM in patients with non-ischaemic HF and could be useful especially in patients with inflammatory background. Our findings that intermediate levels of galectin-3 allow for better prognosis were new and different to other investigations. NCT03090425; Results.

Does human resource management improve family planning service quality? Analysis from the Kenya Service Provision Assessment 2010.

PubMed

Thatte, Nandita; Choi, Yoonjoung

2015-04-01

Human resource (HR) management is a priority for health systems strengthening in developing countries, yet few studies have empirically examined associations with service quality. The purpose of this study was to assess the relationship between HR management and family planning (FP) service quality. Data came from the 2010 Kenya Service Provision Assessment, a nationally representative health facility assessment. In total, 912 FP consultations from 301 facilities were analysed. Four indices were created to measure quality on reproductive history taking, physical examination, sexually transmitted infections prevention and pill/injectable specific counselling. HR management variables included training in the past year, any and supportive (i.e. with feedback, technical updates and discussion) in-person supervision in the past 6 months and having a written job description. Multivariate linear regression analyses were conducted to estimate coefficients of HR management variables on each of the four quality indices, adjusting for background characteristics of clients, provider and facilities. The level of service quality ranged from 16 to 53 out of a maximum score of 100 across the indices. Fifty-two per cent of consultations were done by providers who received supportive in-person supervision in the previous 6 months. In 23% and 38% of consultations, the provider was trained in the past year and had a written job description, respectively. Multivariate analyses indicated that having a written job description was associated with higher service quality in history taking, physical examination and the pill/injectable specific counselling. Other HR management variables were not significantly associated with service quality. Having a written job description was significantly associated with higher service quality and may be a useful tool for strengthening management practices. The details of such job descriptions and the quality of other management indicators should be explored to better understand the relationship between HR management and FP service quality. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

PubMed

Morera-Sendra, Natalia; Tejera-Vaquerizo, Antonio; Traves, Víctor; Requena, Celia; Bolumar, Isidro; Pla, Angel; Vázquez, Carlos; Soriano, Virtudes; Nagore, Eduardo

2016-01-01

The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

Tamoxifen therapy improves overall survival in luminal A subtype of ductal carcinoma in situ: a study based on nationwide Korean Breast Cancer Registry database.

PubMed

Hwang, Ki-Tae; Kim, Eun-Kyu; Jung, Sung Hoo; Lee, Eun Sook; Kim, Seung Il; Lee, Seokwon; Park, Heung Kyu; Kim, Jongjin; Oh, Sohee; Kim, Young A

2018-06-01

To determine the prognostic role of tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) according to molecular subtypes. Data of 14,944 patients with DCIS were analyzed. Molecular subtypes were classified into four categories based on expression of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Kaplan-Meier estimator was used for overall survival analysis while Cox proportional hazards model was used for univariate and multivariate analyses. Luminal A subtype (ER/PR+, HER2-) showed higher (P = .009) survival rate than triple-negative (TN) subtype. Tamoxifen therapy group showed superior (P < .001) survival than no-tamoxifen therapy group. It had survival benefit only for luminal A subtype (P = .001). Tamoxifen therapy resulted in higher survival rate in subgroups with positive ER (P = .006), positive PR (P = .009), and negative HER2 (P < .001). In luminal A subtype, tamoxifen therapy showed lower hazard ratio (HR) compared to no-tamoxifen therapy (HR, 0.420; 95% CI 0.250-0.705; P = .001). Tamoxifen therapy was a significant independent factor by multivariate analysis (HR, 0.538; 95% CI 0.306-0.946; P = .031) as well as univariate analysis. Tamoxifen therapy group showed superior prognosis than the no-tamoxifen therapy group. Its prognostic influence was only effective for luminal A subtype. Patients with luminal A subtype showed higher survival rate than those with TN subtype. Active tamoxifen therapy is recommended for DCIS patients with luminal A subtype, and routine tests for ER, PR, and HER2 should be considered for DCIS.

Intake of Fiber and Nuts during Adolescence and Incidence of Proliferative Benign Breast Disease

PubMed Central

Su, Xuefen; Tamimi, Rulla M.; Collins, Laura C.; Baer, Heather J.; Cho, Eunyoung; Sampson, Laura; Willett, Walter C.; Schnitt, Stuart J.; Connolly, James L.; Rosner, Bernard A.; Colditz, Graham A.

2011-01-01

Objective We examined the association between adolescent fiber intake and proliferative BBD, a marker of increased breast cancer risk, in the Nurses’ Health Study II. Methods Among 29,480 women who completed a high school diet questionnaire in 1998, 682 proliferative BBD cases were identified and confirmed by centralized pathology review between 1991 and 2001. Multivariate-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Women in the highest quintile of adolescent fiber intake had a 25% lower risk of proliferative BBD (multivariate HR (95% CI): 0.75 (0.59, 0.96), p-trend = 0.01) than women in the lowest quintile. High school intake of nuts and apples was also related to significantly reduced BBD risk. Women consuming ≥2 servings of nuts/week had a 36% lower risk (multivariate HR (95% CI): 0.64 (0.48, 0.85), p-trend < 0.01) than women consuming <1 serving/month. Results were essentially the same when the analysis was restricted to prospective cases (n = 142) diagnosed after return of the high school diet questionnaire. Conclusions These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influence subsequent risk of breast disease and may suggest a viable means for breast cancer prevention. PMID:20229245

Optimal Timing for Elective Early Primary Repair of Tetralogy of Fallot: Analysis of Intermediate Term Outcomes.

PubMed

Cunningham, Michael E A; Donofrio, Mary T; Peer, Syed Murfad; Zurakowski, David; Jonas, Richard A; Sinha, Pranava

2017-03-01

We have previously demonstrated that early primary repair of tetralogy of Fallot with pulmonary stenosis (TOF) can be safely performed without increase in hospital resource utilization or compromise to surgical technical performance scores (TPS). We sought to identify the optimal timing for elective early primary repair of TOF with respect to intermediate-term reintervention. Retrospective review of all patients with TOF undergoing elective primary repair between September 2004 and December 2013 was performed. Patients were stratified into reintervention group or no reintervention group. Multivariable Cox regression analysis identified independent predictors of reintervention. Youden's J-index in receiver operating characteristic analysis identified optimal age cutoff predictive of reintervention. Kaplan-Meier analysis with the log-rank test compared reintervention rates stratified by age and TPS. A total of 129 patients with median (interquartile range) age and weight of 78 days (56 to 111) and 5 kg (4.1 to 5.7), respectively, underwent primary repair. After a median (interquartile range) follow-up of 2.3 years (0.1 to 4.6), 18 patients (14%) required a total of 22 reinterventions. Youden's J-index revealed significantly lower risk of intermediate-term reintervention when repaired after 55 days of age (8% for >55 days old versus 31% for ≤55 days of age). Multivariable Cox regression identified age 55 days and younger (hazard ratio [HR] 4.5, 95% confidence interval [CI] 1.6 to 12.8, p = 0.004), valve sparing repair (HR 15.3, 95% CI 1.8 to 128.5, p < 0.001), residual right ventricular outflow tract (RVOT) gradient (HR 1.11, 95% CI 1.1 to 1.2, p < 0.001), and inadequate TPS (HR 21.5, 95% CI 7.4 to 63, p < 0.001) as independent predictors of overall intermediate-term reintervention. Elective repair in patients greater than 55 days of age, irrespective of size of the patient, can be safely performed without any increase in reintervention rates. Both residual peak RVOT gradient and TPS are effective in identifying patients at increased risk of reintervention. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Cancer Liver Metastases.

PubMed

Wang, Jane; Margonis, Georgios Antonios; Amini, Neda; Andreatos, Nikolaos; Yuan, Chunhui; Damaskos, Christos; Antoniou, Efstathios; Garmpis, Nikolaos; Buettner, Stefan; Barbon, Carlotta; Deshwar, Amar; He, Jin; Burkhart, Richard; Pawlik, Timothy M; Wolfgang, Christopher L; Weiss, Matthew J

2018-04-09

Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm. Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins. Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin. Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P < 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and HR 2.14, 1.46-3.16; P < 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41-2.65; P < 0.001). Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm should perhaps be employed by future studies.

Impact of extent of resection and recurrent surgery on clinical outcome and overall survival in a consecutive series of 170 patients for glioblastoma in intraoperative high field magnetic resonance imaging.

PubMed

Coburger, Jan; Wirtz, Christian R; König, Ralph W

2017-06-01

In patients with a glioblastoma (GBM), few unselected data exists using actual standard adjuvant treatment and contemporary surgical techniques like iMRI. Aim of study is to assess impact of EoR and recurrent surgery on survival and outcome. We assessed a consecutive unselected series of 170 surgeries for GBM (2008-2014) applying intraoperative MRI (iMRI). All patients received adjuvant radio-chemo-therapy. Overall-survival (OS), progression free survival (PFS), complications and new permanent neurological deficits (nPND) were assessed. Uni- and multivariate-cox-regression-models were calculated. Mean follow-up was 40mo. GTR was intended in 82% and achieved in 77% of these cases. A nPND was found in 7% of patients. In multivariate cox-regression, GTR (HR:0.6, P<0.024) and absence of MGMT methylation (HR:1.6, P<0.042) was significantly associated with PFS. We found no difference in PFS after primary surgery and recurrent surgery. Concerning OS, in multivariate assessment an un-methylated MGMT-promotor (HR2.0, P<0.01) and presence of a complication (HR1.7, P<0.06) were negative prognosticators. Only GTR was significantly beneficial for OS (HR0.4, P<0.028) compared to a failed GTR and a STR. Repeated surgery for recurrent disease was positively associated with OS (HR0.6, P<0.06). Surgery in a contemporary setup using iMRI, brain mapping and modern adjuvant treatment, has a higher OS and lower complication rates as previously published. A maximum but safe resection should be the goal of surgery since a perioperative complication significantly decreases OS. Recurrent surgery has a beneficial effect on OS without an increase of complications.

Tumor deposits counted as positive lymph nodes in TNM staging for advanced colorectal cancer: a retrospective multicenter study.

PubMed

Li, Jun; Yang, Shengke; Hu, Junjie; Liu, Hao; Du, Feng; Yin, Jie; Liu, Sai; Li, Ci; Xing, Shasha; Yuan, Jiatian; Lv, Bo; Fan, Jun; Leng, Shusheng; Zhang, Xin; Wang, Bing

2016-04-05

We investigated the possibility of counting tumor deposits (TDs) as positive lymph nodes (pLNs) in the pN category and evaluated its prognostic value for colorectal cancer (CRC) patients. A new pN category (npN category) was calculated using the numbers of pLNs plus TDs. The npN category included 4 tiers: npN1a (1 tumor node), npN1b (2-3 tumor nodes), npN2a (4-6 tumor nodes), and npN2b (≥7 tumor nodes). We identified 4,121 locally advanced CRC patients, including 717 (11.02%) cases with TDs. Univariate and multivariate analyses were performed to evaluate the disease-free and overall survival (DFS and OS) for npN and pN categories. Multivariate analysis showed that the npN and pN categories were both independent prognostic factors for DFS (HR 1.614, 95% CI 1.541 to 1.673; HR 1.604, 95% CI 1.533 to 1.679) and OS (HR 1.633, 95% CI 1.550 to 1.720; HR 1.470, 95% CI 1.410 to 1.532). However, the npN category was superior to the pN category by Harrell's C statistic. We conclude that it is thus feasible to consider TDs as positive lymph nodes in the pN category when evaluating the prognoses of CRC patients, and the npN category is potentially superior to the TNM (7th edition) pN category for predicting DFS and OS among advanced CRC patients.

Propensity score analysis of recurrence for neutrophil-to-lymphocyte ratio in colorectal cancer.

PubMed

Balde, Alpha I; Fang, Suzhen; He, Linyun; Cai, Zhai; Han, Shuai; Wang, Weiwei; Li, Zhou; Kang, Liang

2017-11-01

The perioperative serum neutrophil-to-lymphocyte ratio (NLR) has been proposed to predict adverse prognosis in colorectal cancer (CRC). However, its interpretation remains unclear. The present study aimed to clarify the prognostic value of NLR in predicting survival among CRC patients. A single-centre, retrospective, propensity score-matched study of adenocarcinoma patients who underwent D3 lymphadenectomy via laparoscopic or open surgery between 2010 and 2016 was conducted. A cutoff of 3.5 was used based on the receiver operating characteristic curve. To overcome selection biases, we performed a 1:1 match using six covariates. The high-preoperative NLR group had a higher recurrence rate than the low group (P < 0.001). Univariate analysis showed that increased NLR (P < 0.001), N1 (P = 0.016), and N2 (P < 0.001) were associated with worse recurrence-free survival (RFS). Multivariate analysis showed that N2 (hazard ratio [HR], 2.492; P = 0.008) was an adverse prognostic factor for RFS. Univariate analysis for overall survival (OS) revealed that high perioperative NLR (P = 0.001), N1 (P = 0.01), N2 (P < 0.001), and distant metastasis (P < 0.001) were adverse prognostic factors. Subsequent multivariate analysis showed that M1 (HR, 3.973; P < 0.001) and N2 (HR, 2.381; P = 0.013) were highly adverse factors for OS. Clinical assessments performed during a 21.14 (±16.20)-mo follow-up revealed that OS (P = 0.001) and RFS (P < 0.001) were worse in the high-perioperative group than in the low group between the matched groups. An elevated preoperative NLR is a strong predictor of worse RFS and OS in CRC patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk factors associated with recurrent hemorrhage after the initial improvement of colonic diverticular bleeding.

PubMed

Nishikawa, Hiroki; Maruo, Takanori; Tsumura, Takehiko; Sekikawa, Akira; Kanesaka, Takashi; Osaki, Yukio

2013-03-01

We elucidated risk factors contributing to recurrent hemorrhage after initial improvement of colonic diverticular bleeding. 172 consecutive hospitalized patients diagnosed with colonic diverticular bleeding were analyzed. Recurrent hemorrhage after initial improvement of colonic diverticular bleeding is main outcome measure. We analyzed factors contributing to recurrent hemorrhage risk in univariate and multivariate analyses. The length of the observation period after improvement of colonic diverticular bleeding was 26.4 +/- 14.6 months (range, 1-79 months). The cumulative recurrent hemorrhage rate in all patients at 1 and 2 years was 34.8% and 41.8%, respectively. By univariate analysis, age > 70 years (P = 0.021), BMI > 25 kg/m2 (P = 0.013), the use of anticoagulant drugs (P = 0.034), the use of NSAIDs (P = 0.040), history of hypertension (P = 0.011), history of smoking (P = 0.030) and serum creatinine level > 1.5 mg/dL (P < 0.001) were found to be significant risk factors for recurrent colonic diverticular bleeding. By multivariate analysis, age > 70 years (Hazard ratio (HR), 1.905, 95% confidence interval (CI), 1.067-3.403, P = 0.029), history of hypertension (HR, 0.493, 95% CI, 0.245-0.993, P = 0.048) and serum creatinine level > 1.5 mg/dL (HR, 95% CI, 0.288-0.964, P = 0.044) were shown to be significant independent risk factors. Close observation after the initial improvement of colonic diverticular bleeding is needed, especially in elderly patients or patients with history of hypertension or renal deficiency.

Impact of FAB classification on predicting outcome in acute myeloid leukemia, not otherwise specified, patients undergoing allogeneic stem cell transplantation in CR1: An analysis of 1690 patients from the acute leukemia working party of EBMT.

PubMed

Canaani, Jonathan; Beohou, Eric; Labopin, Myriam; Socié, Gerard; Huynh, Anne; Volin, Liisa; Cornelissen, Jan; Milpied, Noel; Gedde-Dahl, Tobias; Deconinck, Eric; Fegueux, Nathalie; Blaise, Didier; Mohty, Mohamad; Nagler, Arnon

2017-04-01

The French, American, and British (FAB) classification system for acute myeloid leukemia (AML) is extensively used and is incorporated into the AML, not otherwise specified (NOS) category in the 2016 WHO edition of myeloid neoplasm classification. While recent data proposes that FAB classification does not provide additional prognostic information for patients for whom NPM1 status is available, it is unknown whether FAB still retains a current prognostic role in predicting outcome of AML patients undergoing allogeneic stem cell transplantation. Using the European Society of Blood and Bone Marrow Transplantation registry we analyzed outcome of 1690 patients transplanted in CR1 to determine if FAB classification provides additional prognostic value. Multivariate analysis revealed that M6/M7 patients had decreased leukemia free survival (hazard ratio (HR) of 1.41, 95% confidence interval (CI), 1.01-1.99; P = .046) in addition to increased nonrelapse mortality (NRM) rates (HR, 1.79; 95% CI, 1.06-3.01; P = .028) compared with other FAB types. In the NPM1 wt AML, NOS cohort, FAB M6/M7 was also associated with increased NRM (HR, 2.17; 95% CI, 1.14-4.16; P = .019). Finally, in FLT3-ITD + patients, multivariate analyses revealed that specific FAB types were tightly associated with adverse outcome. In conclusion, FAB classification may predict outcome following transplantation in AML, NOS patients. © 2017 Wiley Periodicals, Inc.

Association between ERCC1 and TS mRNA levels and disease free survival in colorectal cancer patients receiving oxaliplatin and fluorouracil (5-FU) adjuvant chemotherapy.

PubMed

Li, Sheng; Zhu, Liangjun; Yao, Li; Xia, Lei; Pan, Liangxi

2014-08-29

Aim was to explore the association of ERCC1 and TS mRNA levels with the disease free survival (DFS) in Chinese colorectal cancer (CRC) patients receiving oxaliplatin and 5-FU based adjuvant chemotherapy. Total 112 Chinese stage II-III CRC patients were respectively treated by four different chemotherapy regimens after curative operation. The TS and ERCC1 mRNA levels in primary tumor were measured by real-time RT-PCR. Kaplan-Meier curves and log-rank tests were used for DFS analysis. The Cox proportional hazards model was used for prognostic analysis. In univariate analysis, the hazard ratio (HR) for the mRNA expression levels of TS and ERCC1 (logTS: HR = 0.820, 95% CI = 0.600 - 1.117, P = 0.210; logERCC1: HR = 1.054, 95% CI = 0.852 - 1.304, P = 0.638) indicated no significant association of DFS with the TS and ERCC1 mRNA levels. In multivariate analyses, tumor stage (IIIc: reference, P = 0.083; IIb: HR = 0.240, 95% CI = 0.080 - 0.724, P = 0.011; IIc: HR < 0.0001, P = 0.977; IIIa: HR = 0.179, 95% CI = 0.012 - 2.593, P = 0.207) was confirmed to be the independent prognostic factor for DFS. Moreover, the Kaplan-Meier DFS curves showed that TS and ERCC1 mRNA levels were not significantly associated with the DFS (TS: P = 0.264; ERCC1: P = 0.484). The mRNA expression of ERCC1 and TS were not applicable to predict the DFS of Chinese stage II-III CRC patients receiving 5-FU and oxaliplatin based adjuvant chemotherapy.

Anti-carbamylated protein autoantibodies associated with mortality in Spanish rheumatoid arthritis patients

PubMed Central

Vidal-Bralo, Laura; Perez-Pampin, Eva; Regueiro, Cristina; Montes, Ariana; Varela, Rosana; Boveda, Maria Dolores; Gomez-Reino, Juan J.

2017-01-01

Patients with rheumatoid arthritis (RA) have an increased mortality rate that is associated with the presence of RA-specific autoantibodies in many studies. However, the relative role of rheumatoid factor (RF), anti-CCP antibodies and the most recently established RA-autoantibodies, directed against carbamylated proteins (anti-CarP antibodies), is unclear. Here, we have assessed the role of these three antibodies in 331 patients with established RA recruited from 2001 to 2009 and followed until November 2015. During this time, 124 patients died (37.5%). This death rate corresponds to a mortality rate 1.53 (95% CI 1.26 to 1.80) folds the observed in the reference population. We used for analysis of all-cause mortality the Cox proportional hazard regression model with adjustment for age, sex and smoking. It showed a trend for association with increased mortality of each of the three RA autoantibodies in antibody-specific analysis (hazards ratio (HR) from 1.37 to 1.79), but only the HR of the anti-CarP antibodies was significant (HR = 1.79, 95% CI 1.23 to 2.61, p = 0.002). In addition, the multivariate analysis that included all autoantibodies showed a marked decrease in the HR of RF and of anti-CCP antibodies, whereas the HR of anti-CarP remained significant. This increase was specific of respiratory system causes of death (HR = 3.19, 95% CI 1.52 to 6.69, p = 0.002). Therefore, our results suggest a specific relation of anti-CarP antibodies with the increased mortality in RA, and drive attention to their possible connection with respiratory diseases. PMID:28672020

Mortality among people living with HIV on antiretroviral treatment in Bali, Indonesia: incidence and predictors.

PubMed

Utami, Sri; Sawitri, Anak Agung Sagung; Wulandari, Luh Putu Lila; Artawan Eka Putra, I Wayan Gede; Astuti, Putu Ayu Swandewi; Wirawan, Dewa Nyoman; Causer, Louise; Mathers, Bradley

2017-10-01

Indonesia has the third highest number of people living with HIV/AIDS (PLWH) and the greatest increase in proportion of AIDS-related mortality in the Asia Pacific region between 2005 and 2013. Longitudinal mortality data among PLWH in Indonesia are limited. We conducted a retrospective cohort study from medical records of antiretroviral treatment (ART) recipients attending Badung General Hospital (BGH) and Bali Medica Clinic (BMC) between 2006 and 2014. We explored incidence of mortality by Kaplan-Meier analysis and identified predictors using a Cox proportional hazard model. In total, 575 patients were included in the analysis; the majority were male. The overall mortality rate was 10% per year. Multivariate analysis suggested that being male (adjusted hazard ratio [aHR]: 2.74; 95% confidence interval [CI]: 1.34-5.59), having a lower education (aHR: 2.17; 95%CI: 1.31-3.61), having heterosexual (aHR: 7.40; 95% CI: 2.61-21.00) or injecting drug use (aHR: 13.20; 95% CI: 3.17-55.00) as the likely transmission risk category, starting treatment with low CD4 cell counts (aHR: 3.18; 95% CI: 1.16-8.69), and not having a treatment supervisor (aHR: 4.02; 95% CI: 2.44-6.65) were independent predictors of mortality. The mortality was high, particularly in the first three months after initiating ART. These findings highlight the need to encourage HIV testing and early diagnosis and prompt treatment. Applying aspects of BMCs targeted HIV services model in more generalised services such as BGH may be beneficial. Providing adherence support as part of ART services is key to promoting adherence to ART.

New breast cancer prognostic factors identified by computer-aided image analysis of HE stained histopathology images

PubMed Central

Chen, Jia-Mei; Qu, Ai-Ping; Wang, Lin-Wei; Yuan, Jing-Ping; Yang, Fang; Xiang, Qing-Ming; Maskey, Ninu; Yang, Gui-Fang; Liu, Juan; Li, Yan

2015-01-01

Computer-aided image analysis (CAI) can help objectively quantify morphologic features of hematoxylin-eosin (HE) histopathology images and provide potentially useful prognostic information on breast cancer. We performed a CAI workflow on 1,150 HE images from 230 patients with invasive ductal carcinoma (IDC) of the breast. We used a pixel-wise support vector machine classifier for tumor nests (TNs)-stroma segmentation, and a marker-controlled watershed algorithm for nuclei segmentation. 730 morphologic parameters were extracted after segmentation, and 12 parameters identified by Kaplan-Meier analysis were significantly associated with 8-year disease free survival (P < 0.05 for all). Moreover, four image features including TNs feature (HR 1.327, 95%CI [1.001 - 1.759], P = 0.049), TNs cell nuclei feature (HR 0.729, 95%CI [0.537 - 0.989], P = 0.042), TNs cell density (HR 1.625, 95%CI [1.177 - 2.244], P = 0.003), and stromal cell structure feature (HR 1.596, 95%CI [1.142 - 2.229], P = 0.006) were identified by multivariate Cox proportional hazards model to be new independent prognostic factors. The results indicated that CAI can assist the pathologist in extracting prognostic information from HE histopathology images for IDC. The TNs feature, TNs cell nuclei feature, TNs cell density, and stromal cell structure feature could be new prognostic factors. PMID:26022540

Validation of the ICON-S staging for HPV-associated oropharyngeal carcinoma using a pre-defined treatment policy.

PubMed

Porceddu, Sandro V; Milne, Rob; Brown, Elizabeth; Bernard, Anne; Rahbari, Reza; Cartmill, Bena; Foote, Matthew; McGrath, Margaret; Coward, Jermaine; Panizza, Benedict

2017-03-01

To determine whether the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) for HPV associated oropharyngeal carcinoma (HPV+OPC) is a better discriminator of overall survival (OS), compared with the 7th edition (7th Ed) AJCC/UICC TNM staging following curative radiotherapy (RT). The 5-year OS for all patients with non-metastatic (M0) p16-confirmed OPC treated between 2005 and 2015 was determined and grouped based on the 7th Ed AJCC/UICC TNM and ICON-S staging. A total of 279 patients met the inclusion criteria. The 5-year OS with the 7th Ed TNM classification were Stage I/II 88.9% (95% CI; 70.6-100%), Stage III 93.8% (95% CI; 85.9-100%), Stage IVa 86.4% (95% CI; 81.6-91.5%) and Stage IVb 62.3% (95% CI; 46.8-82.8%). On multivariate Cox regression analysis there was no statistically significant OS difference when comparing Stage I/II with, Stage III (p=0.98, HR=0.97, 95% CI; 0.11-8.64), IVa (p=0.67, HR=1.56, 95% CI; 0.2-11.94) and IVb (p=0.11, HR=5.54, 95% CI; 0.69-44.52), respectively. The 5-year OS with ICON-S staging were Stage I 93.6% (95% CI; 89.4-98.0%), Stage II 81.9% (95% CI; 73.7-91.1%) and Stage III 69.1% (95%; 57.9-82.6%). There was a consistent decrease of OS with increasing stage. On multivariate Cox regression analysis, when compared to Stage I, OS was significantly lower for stage II (p=0.007, HR=2.84, 95% CI; 1.33-6.05) and stage III (p<0.001, HR=3.78, 95% CI; 1.81-7.92), respectively. The ICON-S staging provides better OS stratification for HPV+OPC following RT compared with the 7th Ed TNM staging. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

Validation of methods to control for immortal time bias in a pharmacoepidemiologic analysis of renin-angiotensin system inhibitors in type 2 diabetes.

PubMed

Yang, Xilin; Kong, Alice Ps; Luk, Andrea Oy; Ozaki, Risa; Ko, Gary Tc; Ma, Ronald Cw; Chan, Juliana Cn; So, Wing Yee

2014-01-01

Pharmacoepidemiologic analysis can confirm whether drug efficacy in a randomized controlled trial (RCT) translates to effectiveness in real settings. We examined methods used to control for immortal time bias in an analysis of renin-angiotensin system (RAS) inhibitors as the reference cardioprotective drug. We analyzed data from 3928 patients with type 2 diabetes who were recruited into the Hong Kong Diabetes Registry between 1996 and 2005 and followed up to July 30, 2005. Different Cox models were used to obtain hazard ratios (HRs) for cardiovascular disease (CVD) associated with RAS inhibitors. These HRs were then compared to the HR of 0.92 reported in a recent meta-analysis of RCTs. During a median follow-up period of 5.45 years, 7.23% (n = 284) patients developed CVD and 38.7% (n = 1519) were started on RAS inhibitors, with 39.1% of immortal time among the users. In multivariable analysis, time-dependent drug-exposure Cox models and Cox models that moved immortal time from users to nonusers both severely inflated the HR, and time-fixed models that included immortal time deflated the HR. Use of time-fixed Cox models that excluded immortal time resulted in a HR of only 0.89 (95% CI, 0.68-1.17) for CVD associated with RAS inhibitors, which is closer to the values reported in RCTs. In pharmacoepidemiologic analysis, time-dependent drug exposure models and models that move immortal time from users to nonusers may introduce substantial bias in investigations of the effects of RAS inhibitors on CVD in type 2 diabetes.

The oral iron chelator deferasirox might improve survival in allogeneic hematopoietic cell transplant (alloHSCT) recipients with transfusional iron overload.

PubMed

Sivgin, Serdar; Baldane, Suleyman; Akyol, Gulsah; Keklik, Muzaffer; Kaynar, Leylagül; Kurnaz, Fatih; Pala, Cigdem; Zararsiz, Gokmen; Cetin, Mustafa; Eser, Bulent; Unal, Ali

2013-10-01

Iron overload (IO) has been shown to be an important cause of mortality and morbidity in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). This study aimed to evaluate the possible effect of oral iron-chelation treatment (deferasirox) on survival in alloHSCT recipients in the posttransplant period. A total of 80 alloHSCT recipients with IO were analyzed, retrospectively. Pretransplant and posttransplant data were obtained from the patients' files. Patients were divided into two groups. Group 1; patients who did not receive any chelator treatment due to side effects or compliance problems. These patients were treated by phlebotomy. Group 2 consisted of patients who received deferasirox treatment. The median treatment duration with deferasirox was 122 days (min-max:91-225). The iron chelating treatment significantly reduced serum ferritin levels administered at a dosage of 20-30 mg/kg/day (p<0.001). The median OS in Group 1 was found 16.0 (min-max:1.0-63.0) months and 25.0 (min-max:3.0-72.0) months in Group 2. In univariate and multivariate analysis, patients in Group 1 showed poorer OS compared to those in Group 2 with an increase in risk of death (HR:3.22, min-max:1.67-6.23, p=0.001 and HR:3.51,, min-max:1.75-6.99, p<0.001; respectively). The median DFS in Group 1 was found 11.0 (min-max:3.0-24.0) months and 22.0 (min-max:8.0-43.0) months in Group 2. The difference was found statistically significant (p=0.023). The other factors that we found significant difference in multivariate analysis between groups were; presence of acute GVHD (patients with aGVHD had increased risk of death compared to patients without aGVHD (HR:2.49, min-max: 1.32-4.69, p=0.005), chronic GVHD (HR:2.57, min-max:1.23-5.41, p=0.013), median interval to tx (HR: 2.23, min-max:1.17-4.26, p=0.015) and HLA match (HR:3.01, min-max:1.35-6.73, p=0.007) CONCLUSION: Oral deferasirox (Exjade) treatment may improve survival in patients with iron overload who underwent alloHSCT. Copyright © 2013 Elsevier Ltd. All rights reserved.

Single-Fraction Proton Beam Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hattangadi-Gluth, Jona A.; Chapman, Paul H.; Kim, Daniel

2014-06-01

Purpose/Objective(s): To evaluate the obliteration rate and potential adverse effects of single-fraction proton beam stereotactic radiosurgery (PSRS) in patients with cerebral arteriovenous malformations (AVMs). Methods and Materials: From 1991 to 2010, 248 consecutive patients with 254 cerebral AVMs received single-fraction PSRS at our institution. The median AVM nidus volume was 3.5 cc (range, 0.1-28.1 cc), 23% of AVMs were in critical/deep locations (basal ganglia, thalamus, or brainstem), and the most common prescription dose was 15 Gy(relative biological effectiveness [RBE]). Univariable and multivariable analyses were performed to assess factors associated with obliteration and hemorrhage. Results: At a median follow-up time of 35 months (range, 6-198 months),more » 64.6% of AVMs were obliterated. The median time to total obliteration was 31 months (range, 6-127 months), and the 5-year and 10-year cumulative incidence of total obliteration was 70% and 91%, respectively. On univariable analysis, smaller target volume (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.86-0.93, P<.0001), smaller treatment volume (HR 0.93, 95% CI 0.90-0.96, P<.0001), higher prescription dose (HR 1.16, 95% CI 1.07-1.26, P=.001), and higher maximum dose (HR 1.14, 95% CI 1.05-1.23, P=.002) were associated with total obliteration. Deep/critical location was also associated with decreased likelihood of obliteration (HR 0.68, 95% CI 0.47-0.98, P=.04). On multivariable analysis, critical location (adjusted HR [AHR] 0.42, 95% CI 0.27-0.65, P<.001) and smaller target volume (AHR 0.81, 95% CI 0.68-0.97, P=.02) remained associated with total obliteration. Posttreatment hemorrhage occurred in 13 cases (5-year cumulative incidence of 7%), all among patients with less than total obliteration, and 3 of these events were fatal. The most common complication was seizure, controlled with medications, both acutely (8%) and in the long term (9.1%). Conclusions: The current series is the largest modern series of PSRS for cerebral AVMs. PSRS can achieve a high obliteration rate with minimal morbidity. Post-treatment hemorrhage remains a potentially fatal risk among patients who have not yet responded to treatment.« less

The Risk of TB in Patients With Type 2 Diabetes Initiating Metformin vs Sulfonylurea Treatment.

PubMed

Pan, Sheng-Wei; Yen, Yung-Feng; Kou, Yu Ru; Chuang, Pei-Hung; Su, Vincent Yi-Fong; Feng, Jia-Yih; Chan, Yu-Jiun; Su, Wei-Juin

2017-12-16

Metformin and the sulfonylureas are common initial antidiabetic agents; the former has demonstrated anti-TB action in in vitro and animal studies. The comparative effect of metformin vs the sulfonylureas on TB risk in patients with type 2 diabetes mellitus (T2DM) remains unclear. In this retrospective cohort study, patients without chronic kidney disease who received a T2DM diagnosis during 2003 to 2013 were identified from the Taiwan National Health Insurance Research Database. Participants with ≥ 2 years of follow-up were reviewed and observed for TB until December 2013. Patients receiving metformin ≥ 60 cumulative defined daily dose (cDDD) and sulfonylureas < 15 cDDD in the initial 2 years were defined as metformin majors; it was the inverse for sulfonylurea majors. The two groups were matched 1:1 by propensity score and compared for TB risk by multivariate Cox regression analysis. Among 40,179 patients with T2DM, 263 acquired TB (0.65%) over a mean follow-up of 6.1 years. In multivariate analysis, the initial 2-year dosage of metformin, but not that of the sulfonylureas, was an independent predictor of TB (60-cDDD increase (adjusted hazard ratio [HR], 0.931; 95% CI, 0.877-0.990) after adjustment by cofactors, including adapted diabetes complication severity index. Metformin majors had a significantly lower TB risk than that of sulfonylurea majors before and after matching (HR, 0.477; 95% CI, 0.268-0.850 and HR, 0.337; 95% CI, 0.169-0.673; matched pairs, n = 3,161). Compared with the reference group (initial 2-year metformin < 60 cDDD), metformin treatment showed a dose-dependent association with TB risk (60-219 cDDD; HR, 0.860; 95% CI, 0.637-1.161; 220-479 cDDD, HR, 0.706; 95% CI, 0.485-1.028; ≥ 480 cDDD, HR, 0.319; 95% CI, 0.118-0.863). Metformin use in the initial 2 years was associated with a decreased risk of TB, and metformin users had a reduced risk compared with their sulfonylurea comparators. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Appraising stroke risk in maintenance hemodialysis patients: a large single-center cohort study.

PubMed

Power, Albert; Chan, Kakit; Singh, Seema K; Taube, David; Duncan, Neill

2012-02-01

Stroke incidence in hemodialysis patients is up to 10 times greater than in the general population and is associated with a worse prognosis. Factors influencing stroke risk by subtype and subsequent prognosis are poorly described in the literature. Retrospective single-center cohort study. 2,384 established maintenance hemodialysis patients at a single center from January 1, 2002, to June 1, 2009. Patient demographics, comorbid conditions. Incidence of acute stroke (International Classification of Diseases, 9th Revision codes 430, 431, 432.9, 433.1, and 434.1 with evidence of compatible neuroimaging), patient survival. Cumulative patient survival, incidence of acute fatal and nonfatal stroke. 127 strokes occurred during 9,541 total patient-years of follow-up. First (incident) stroke occurred at a rate of 14.9/1,000 patient years (95% CI, 12.2-17.9) with a predominance of ischemic compared with hemorrhagic subtypes (11.2 vs 3.7/1,000 patient-years). 54% of hemorrhagic strokes occurred in patients of South Asian ethnicity compared with ischemic strokes, which occurred predominantly in white patients (45% of events). Diabetes mellitus (HR, 1.92; 95% CI, 1.29-2.85; P = 0.001) and prior cerebrovascular disease (HR, 4.54; 95% CI, 3.07-6.72; P < 0.001) were independently associated with incident cerebrovascular accident on multivariate analysis. Acute stroke was associated with worse patient survival (HR, 3.26; 95% CI, 2.47-4.30; P < 0.001) and overall 1-year mortality of 24%, which was significantly worse in patients with hemorrhagic events (39% vs 19% mortality for ischemic subtypes). Serum albumin level >3.5 g/L (HR, 0.38; 95% CI, 0.19-0.76; P = 0.007) and C-reactive protein level >3.0 mg/l (HR, 1.36; 95% CI, 1.12-1.64; P = 0.002) influenced survival after stroke on multivariate analysis. Retrospective analysis of data cannot prove causality. The high incidence of stroke in hemodialysis patients is associated with high mortality, especially hemorrhagic subtypes. Strict management of hypertension, better appreciation of hemodialysis anticoagulation, and large-scale interventional studies are urgently required to direct prevention and treatment of this significant disease. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Prognostic value of MLH1 promoter methylation in male patients with esophageal squamous cell carcinoma.

PubMed

Wu, Dongping; Chen, Xiaoying; Xu, Yan; Wang, Haiyong; Yu, Guangmao; Jiang, Luping; Hong, Qingxiao; Duan, Shiwei

2017-04-01

The DNA mismatch repair (MMR) gene MutL homolog 1 ( MLH1 ) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC.

Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

PubMed

Wan, Guo-Xing; Chen, Ping; Cai, Xiao-Jun; Li, Lin-Jun; Yu, Xiong-Jie; Pan, Dong-Feng; Wang, Xian-He; Wang, Xuan-Bin; Cao, Feng-Jun

2016-01-15

The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Gastroduodenal Ulcers and ABO Blood Group: the Japan Nurses' Health Study (JNHS).

PubMed

Alkebsi, Lobna; Ideno, Yuki; Lee, Jung-Su; Suzuki, Shosuke; Nakajima-Shimada, Junko; Ohnishi, Hiroshi; Sato, Yasunori; Hayashi, Kunihiko

2018-01-05

Although several studies have shown that blood type O is associated with increased risk of peptic ulcer, few studies have investigated these associations in Japan. We sought to investigate the association between the ABO blood group and risk of gastroduodenal ulcers (GDU) using combined analysis of both retrospective and prospective data from a large cohort study of Japanese women, the Japan Nurses' Health Study (JNHS; n = 15,019). The impact of the ABO blood group on GDU risk was examined using Cox regression analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI), with adjustment for potential confounders. Compared with women with non-O blood types (A, B, and AB), women with blood type O had a significantly increased risk of GDU from birth (multivariable-adjusted HR 1.18; 95% CI, 1.04-1.34). Moreover, the highest cumulative incidence of GDU was observed in women born pre-1956 with blood type O. In a subgroup analysis stratified by birth year (pre-1956 or post-1955), the multivariable-adjusted HR of women with blood type O was 1.22 (95% CI, 1.00-1.49) and 1.15 (95% CI, 0.98-1.35) in the pre-1956 and post-1955 groups, respectively. In this large, combined, ambispective cohort study of Japanese women, older women with blood type O had a higher risk of developing GDU than those with other blood types.

Risk factors associated with refractoriness to esophageal dilatation for benign dysphagia.

PubMed

Rodrigues-Pinto, Eduardo; Pereira, Pedro; Ribeiro, Armando; Lopes, Susana; Moutinho-Ribeiro, Pedro; Silva, Marco; Peixoto, Armando; Gaspar, Rui; Macedo, Guilherme

2016-06-01

Benign esophageal strictures need repeated dilatations to relieve dysphagia. Literature is scarce on the risk factors for refractoriness of these strictures. This study aimed to assess the risk factors associated with refractory strictures. This is a retrospective study of patients with benign esophageal strictures who were referred for esophageal dilatation over a period of 3 years. A total of 327 esophageal dilatations were performed in 103 patients; 53% of the patients reported dysphagia for liquids. Clinical success was achieved in 77% of the patients. There was a need for further dilatations in 54% of patients, being more frequent in patients with dysphagia for liquids [78 vs. 64%, P=0.008, odds ratio (OR) 1.930], in those with caustic strictures (89 vs. 70%, P=0.007, OR 3.487), and in those with complex strictures (83 vs. 70%, P=0.047, OR 2.132). Caustic strictures, peptic strictures, and complex strictures showed statistical significance in the multivariate analysis. Time until subsequent dilatations was less in patients with dysphagia for liquids (49 vs. 182 days, P<0.001), in those with peptic strictures (49 vs. 98 days, P=0.004), in those with caustic strictures (49 vs. 78 days, P=0.005), and in patients with complex strictures (47 vs. 80 days P=0.009). In multivariate analysis, further dilatations occurred earlier in patients with dysphagia for liquids [hazard ratio (HR) 1.506, P=0.004], in those with peptic strictures (HR 1.644, P=0.002), in those with caustic strictures (HR 1.581, P=0.016), and in patients with complex strictures (HR 1.408, P=0.046). Caustic, peptic, and complex strictures were associated with a greater need for subsequent dilatations. Time until subsequent dilatations was less in patients with dysphagia for liquids and in those with caustic, peptic, and complex strictures.

Prognostic factors in patients with hepatitis B virus-related hepatocellular carcinoma undergoing nucleoside analog antiviral therapy

PubMed Central

NISHIKAWA, HIROKI; NISHIJIMA, NORIHIRO; ARIMOTO, AKIRA; INUZUKA, TADASHI; KITA, RYUICHI; KIMURA, TORU; OSAKI, YUKIO

2013-01-01

In the present era of entecavir (ETV) use for chronic hepatitis B (CHB), the prognostic factors in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. The aims of the present study were to investigate the prognostic factors in patients with HBV-related HCC treated with ETV who underwent curative therapy. A total of 74 HBV-related HCC patients treated with ETV who underwent curative therapy were analyzed. Predictive factors associated with overall survival (OS) and recurrence-free survival (RFS) were examined using univariate and multivariate analysis. Our study population included 49 males and 25 females with a median age of 62 years. The median observation period was 3.4 years (range, 0.2–11.5 years). The 1-, 3- and 5-year cumulative OS rates were 100, 89.8 and 89.8%, respectively. The corresponding RFS rates were 82.8, 52.1 and 25.6%, respectively. In this study, 73 patients (98.6%) achieved an HBV DNA level of <400 copies/ml during the follow-up period. No viral breakthrough hepatitis, as defined by 1 log increase from nadir, was observed during ETV therapy. According to multivariate analysis, only hepatitis B e antigen (HBeAg) positivity was significantly associated with OS [hazard ratio (HR), 0.058; 95% confidence interval (CI), 0.005–0.645; P=0.020)], whereas HCC stage (HR, 0.359; 95% CI, 0.150–0.859; P=0.021), HBeAg positivity (HR, 0.202; 95% CI, 0.088–0.463; P<0.001) and γ-glutamyl transpeptidase ≥50 IU/l (HR, 0.340; 95% CI, 0.152–0.760; P=0.009) were significant predictive factors linked to RFS. In conclusion, HBeAg positivity was significantly associated with OS and RFS in HBV-related HCC patients treated with ETV who underwent curative therapy. In such patients, close observation is required, even after curative therapy for HCC. PMID:24179497

The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan

Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels aftermore » NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.« less

Outcome and toxicity of intensity modulated radiotherapy with simultaneous integrated boost in locally advanced non-small cell lung cancer patients.

PubMed

Fondevilla Soler, A; López-Guerra, J L; Dzugashvili, M; Sempere Rincón, P; Sautbaet, A; Castañeda, P; Díaz, J M; Praena-Fernandez, J M; Rivin Del Campo, E; Azinovic, I

2017-12-01

The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients. A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction. The median follow-up was 16 months (range, 1-70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022). This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy.

HLA-G 3'UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment.

PubMed

Garziera, Marica; Bidoli, Ettore; Cecchin, Erika; Mini, Enrico; Nobili, Stefania; Lonardi, Sara; Buonadonna, Angela; Errante, Domenico; Pella, Nicoletta; D'Andrea, Mario; De Marchi, Francesco; De Paoli, Antonino; Zanusso, Chiara; De Mattia, Elena; Tassi, Renato; Toffoli, Giuseppe

2015-01-01

An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host's immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3'UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3'UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3'UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3'UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3'UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38-0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26-0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19-5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16-6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3'UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G.

Age and Other Risk Factors Influencing Long-Term Mortality in Patients With Traumatic Cervical Spine Fracture.

PubMed

Bank, Matthew; Gibbs, Katie; Sison, Cristina; Kutub, Nawshin; Paptheodorou, Angelos; Lee, Samuel; Stein, Adam; Bloom, Ona

2018-01-01

To identify clinical or demographic variables that influence long-term mortality, as well as in-hospital mortality, with a particular focus on the effects of age. Cervical spine fractures with or without spinal cord injury (SCI) disproportionately impact the elderly who constitute an increasing percentage of the US population. We analyzed data collected for 10 years at a state-designated level I trauma center to identify variables that influenced in-hospital and long-term mortality among elderly patients with traumatic cervical spine fracture with or without SCI. Acute in-hospital mortality was determined from hospital records and long-term mortality within the study period (2003-2013) was determined from the National Death Index. Univariate and multivariate regression analyses were used to identify factors influencing survival. Data from patients (N = 632) with cervical spine fractures were analyzed, the majority (66%) of whom were geriatric (older than age 64). Most patients (62%) had a mild/moderate injury severity score (ISS; median, interquartile range: 6, 5). Patients with SCI had significantly longer lengths of stay (14.1 days), days on a ventilator (3.5 days), and higher ISS (14.9) than patients without SCI ( P < .0001 for all). Falls were the leading mechanism of injury for patients older than age 64. Univariate analysis identified that long-term survival decreased significantly for all patients older than age 65 (hazard ratio [HR]: 1.07; P < .0001). Multivariate analysis demonstrated age (HR: 1.08; P < .0001), gender (HR: 1.60; P < .0007), and SCI status (HR: 1.45, P < .02) significantly influenced survival during the study period. This study identified age, gender, and SCI status as significant variables for this study population influencing long-term survival among patients with cervical spine fractures. Our results support the growing notion that cervical spine injuries in geriatric patients with trauma may warrant additional research.

Age and Other Risk Factors Influencing Long-Term Mortality in Patients With Traumatic Cervical Spine Fracture

PubMed Central

Bank, Matthew; Gibbs, Katie; Sison, Cristina; Kutub, Nawshin; Paptheodorou, Angelos; Lee, Samuel; Stein, Adam; Bloom, Ona

2018-01-01

Objective: To identify clinical or demographic variables that influence long-term mortality, as well as in-hospital mortality, with a particular focus on the effects of age. Summary and Background Data: Cervical spine fractures with or without spinal cord injury (SCI) disproportionately impact the elderly who constitute an increasing percentage of the US population. Methods: We analyzed data collected for 10 years at a state-designated level I trauma center to identify variables that influenced in-hospital and long-term mortality among elderly patients with traumatic cervical spine fracture with or without SCI. Acute in-hospital mortality was determined from hospital records and long-term mortality within the study period (2003-2013) was determined from the National Death Index. Univariate and multivariate regression analyses were used to identify factors influencing survival. Results: Data from patients (N = 632) with cervical spine fractures were analyzed, the majority (66%) of whom were geriatric (older than age 64). Most patients (62%) had a mild/moderate injury severity score (ISS; median, interquartile range: 6, 5). Patients with SCI had significantly longer lengths of stay (14.1 days), days on a ventilator (3.5 days), and higher ISS (14.9) than patients without SCI (P < .0001 for all). Falls were the leading mechanism of injury for patients older than age 64. Univariate analysis identified that long-term survival decreased significantly for all patients older than age 65 (hazard ratio [HR]: 1.07; P < .0001). Multivariate analysis demonstrated age (HR: 1.08; P < .0001), gender (HR: 1.60; P < .0007), and SCI status (HR: 1.45, P < .02) significantly influenced survival during the study period. Conclusion: This study identified age, gender, and SCI status as significant variables for this study population influencing long-term survival among patients with cervical spine fractures. Our results support the growing notion that cervical spine injuries in geriatric patients with trauma may warrant additional research. PMID:29760965

Elevated resting heart rate in heart transplant recipients: innocent bystander or adverse prognostic indicator?

PubMed

Wachter, S Blake; McCandless, Sean P; Gilbert, Edward M; Stoddard, Gregory J; Kfoury, Abdallah G; Reid, Bruce B; McKellar, Stephen H; Nativi-Nicolau, Jose; Saidi, Abdulfattah; Barney, Jacob; McCreath, Lauren; Koliopoulou, Antigone; Wright, Spencer E; Fang, James C; Stehlik, Josef; Selzman, Craig H; Drakos, Stavros G

2015-09-01

The elevated baseline heart rate (HR) of a heart transplant recipient has previously been considered inconsequential. However, we hypothesized that a resting HR above 100 beats per minute (bpm) may be associated with morbidity and mortality. The U.T.A.H. Cardiac Transplant Program studied patients who received a heart transplant between 2000 and 2011. Outpatient HR values for each patient were averaged during the first year post-transplant. The study cohort was divided into two groups: the tachycardic (TC) (HR > 100 bpm) and the non-TC group (HR ≤ 100 bpm) in which mortality, incidence of rejection, and cardiac allograft vasculopathy were compared. Three hundred and ten patients were included as follows: 73 in the TC and 237 in the non-TC group. The TC group had a higher risk of a 10-yr all-cause mortality (p = 0.004) and cardiovascular mortality (p = 0.044). After adjustment for donor and recipient characteristics in multivariable logistic regression analysis, the hazard ratio was 3.9, (p = 0.03, CI: 1.2-13.2) and 2.6 (p = 0.02, CI: 1.2-5.5) for cardiovascular mortality and all-cause mortality, respectively. Heart transplant recipients with elevated resting HR appear to have higher mortality than those with lower resting HR. Whether pharmacologically lowering the HR would result in better outcomes warrants further investigation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Marital status and survival in patients with rectal cancer: An analysis of the Surveillance, Epidemiology and End Results (SEER) database.

PubMed

Wang, Xiangyang; Cao, Weilan; Zheng, Chenguo; Hu, Wanle; Liu, Changbao

2018-06-01

Marital status has been validated as an independent prognostic factor for survival in several cancer types, but is controversial in rectal cancer (RC). The objective of this study was to investigate the impact of marital status on the survival outcomes of patients with RC. We extracted data of 27,498 eligible patients diagnosed with RC between 2004 and 2009 from the Surveillance, Epidemiology and End Results (SEER) database. Patients were categorized into married, never married, divorced/separated and widowed groups.We used Chi-square tests to compare characteristics of patients with different marital status.Rectal cancer specific survival was compared using the Kaplan-Meier method,and multivariate Cox regression analyses was used to analyze the survival outcome risk factors in different marital status. The widowed group had the highest percentage of elderly patients and women,higher proportion of adenocarcinomas, and more stage I/II in tumor stage (P < 0.05),but with a lower rate of surgery compared to the married group (76.7% VS 85.4%). Compared with the married patients, the never married (HR 1.40), widowed (HR 1.61,) and divorced/separated patients (HR 1.16) had an increased overall 5-year mortality. A further analysis showed that widowed patients had an increased overall 5-year cause-specific survival(CSS) compared with married patients at stage I(HR 1.92),stage II (HR 1.65),stage III (HR 1.73),and stage IV (HR 1.38). Our study showed marriage was associated with better outcomes of RC patients, but unmarried RC patients, especially widowed patients,are at greater risk of cancer specific mortality. Copyright © 2018 Elsevier Ltd. All rights reserved.

Predictive value of night-time heart rate for cardiovascular events in hypertension. The ABP-International study.

PubMed

Palatini, Paolo; Reboldi, Gianpaolo; Beilin, Lawrence J; Eguchi, Kazuo; Imai, Yutaka; Kario, Kazuomi; Ohkubo, Takayoshi; Pierdomenico, Sante D; Saladini, Francesca; Schwartz, Joseph E; Wing, Lindon; Verdecchia, Paolo

2013-09-30

Data from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting. To investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52 ± 16 years from Italy, U.S.A., Japan, and Australia, included in the 'ABP-International' registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine. During a median follow-up of 5.0 years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24h HR (p=0.007 and =0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p=0.07 and =0.18, respectively). The hazard ratio of the fatal combined with nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04-1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05-1.25) or subjects who had an event within 5 years after enrollment (hazard ratio, 1.23; 95% CI, 1.05-1.45) were excluded from analysis. At variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia.

PubMed

De Stefano, Valerio; Za, Tommaso; Rossi, Elena; Vannucchi, Alessandro M; Ruggeri, Marco; Elli, Elena; Micò, Caterina; Tieghi, Alessia; Cacciola, Rossella R; Santoro, Cristina; Gerli, Giancarla; Guglielmelli, Paola; Pieri, Lisa; Scognamiglio, Francesca; Rodeghiero, Francesco; Pogliani, Enrico M; Finazzi, Guido; Gugliotta, Luigi; Leone, Giuseppe; Barbui, Tiziano

2010-02-01

There is evidence that leukocytosis is associated with an increased risk of first thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Whether it is a risk factor for recurrent thrombosis too is currently unknown. In the frame of a multicenter retrospective cohort study, we recruited 253 patients with PV (n = 133) or ET (n = 120), who were selected on the basis of a first arterial (70%) or venous major thrombosis (27.6%) or both (2.4%), and who were not receiving cytoreduction at the time of thrombosis. The probability of recurrent thrombosis associated with the leukocyte count recorded at the time of the first thrombosis was estimated by a receiver operating characteristic analysis and a multivariable Cox proportional hazards regression model. Thrombosis recurred in 78 patients (30.7%); multivariable analysis showed an independent risk of arterial recurrence (hazard ratio [HR] 2.16, 95% CI 1.12-4.18) in patients with a leukocyte count that was >12.4 x 10(9)/L at the time of the first thrombotic episode. The prognostic role for leukocytosis was age-related, as it was only significant in patients that were aged <60 years (HR for arterial recurrence 3.35, 95% CI 1.22-9.19).

The real-world outcomes of treating Polycythemia Vera: Physician adherence to treatment guidelines.

PubMed

Jackson Chornenki, Nicholas L; Chai-Adisaksopha, Chatree; Leong, Darryl P; Siegal, Deborah M; Hillis, Christopher M

2018-06-04

Therapy in Polycythemia Vera (PV), a myeloproliferative neoplasm, focuses on reducing cardiovascular (CV) risk without increasing bleeding or hematological progression. However, the real-world practice of treating PV in North America is understudied. We performed a retrospective cohort study of newly diagnosed PV (JAK2V617F mutation positive) patients in Hamilton, Canada to fill this knowledge gap. Out of 108 patients included, (n = 45, 41.7%) patients did not receive therapy consistent with contemporary treatment guidelines. Multivariable analysis showed increased white blood cell count at diagnosis (HR, 1.09; 95% CI, 1.04-1.14; p < 0.001), older age (HR, 1.15; 95% CI, 1.07-1.23; p < 0.001) and diabetic history (HR, 3.71; 95% CI, 1.27-10.78; p = 0.012) associated with greater mortality. Not receiving pharmacological treatment according to guidelines was also independently associated with increased mortality (HR, 3.12; 95% CI, 1.13-8.65; p = 0.029). Copyright © 2018 Elsevier Ltd. All rights reserved.

Endometrial cancer risk factors among Lynch syndrome women: a retrospective cohort study

PubMed Central

Staff, Synnöve; Aaltonen, Mari; Huhtala, Heini; Pylvänäinen, Kirsi; Mecklin, Jukka-Pekka; Mäenpää, Johanna

2016-01-01

Background: Lynch syndrome (LS) is associated with a significant lifetime risk of endometrial cancer (EC). There are limited data on factors modifying the EC risk in LS patients. Methods: The study cohort included 136 LS mutation-positive women. Exposure data were collected by postal questionnaires. Cox regression model was used to estimate the associations between lifestyle, hormonal, reproductive and medical factors and the risk of EC. Results: Increased EC risk was associated with type II diabetes and hypercholesterolaemia in univariable (HR 3.21, (95% CI 1.34–7.78), P=0.009 and HR 2.08, (95% CI 1.11–3.90), P=0.02; respectively) and with diabetes and duration of hormone replacement therapy (HRT) in multivariable analysis (HR 4.18 (95% CI 1.52–11.52), P=0.006 and HR 1.07 (95% CI 1.02–1.13), P=0.010; respectively). Conclusions: Prevention of diabetes and avoiding long-duration HRT are potential targets for reduction of EC risk in women with LS. PMID:27336600

Anxiety and mortality risk in community-dwelling elderly people.

PubMed

Carrière, Isabelle; Ryan, Joanne; Norton, Joanna; Scali, Jacqueline; Stewart, Robert; Ritchie, Karen; Ancelin, Marie Laure

2013-09-01

There are conflicting data on the role of anxiety in predicting mortality. To evaluate the 10-year mortality risk associated with anxiety in community-dwelling elderly people. Using data from 718 men and 1046 women aged 65 years and over, gender-stratified associations of anxiety symptoms (Spielberger State-Trait Anxiety Inventory, third tertile) and current DSM-IV anxiety disorder including generalised anxiety disorder (GAD) and phobia with all-cause and cardiovascular mortality were determined. In women, mortality risk was increased for anxiety disorder and GAD in multivariate Cox models (hazard ratio (HR) = 1.53, 95% CI 1.02-2.27 and HR = 2.04, 95% CI 1.08-3.86 respectively), whereas for phobia it was nearly significant (HR = 1.52, 95% CI 0.94-2.47). Anxiety trait symptoms became non-significant as a result of the confounding effect of depressive symptoms. Anxiety disorder was associated with cardiovascular mortality in univariate analysis (HR = 2.42, 95% CI 1.16-5.07). No significant associations were found in men. Our study suggests a gender-specific association of anxiety and mortality.

Alpha-Fetoprotein Slope >7.5 ng/mL per Month Predicts Microvascular Invasion and Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma.

PubMed

Giard, Jeanne-Marie; Mehta, Neil; Dodge, Jennifer L; Roberts, John P; Yao, Francis Y

2018-05-01

Rising alpha-fetoprotein (AFP) is a potential marker of worse prognosis after liver transplant (LT) for hepatocellular carcinoma (HCC), but prior studies relied on only 2 data points and were imprecise in assessing AFP slope. The aim of this study was to examine the association between AFP slope and post-LT HCC recurrence, with AFP slope estimated from multiple data points over time. Our cohort included 336 patients undergoing LT with Model for End Stage Liver Disease exception for HCC within Milan criteria from 2003 to 2013. Most (98%) had pre-LT locoregional therapy. AFP slope was estimated by fitting a regression line to the AFP levels over time. The 1- and 5-year post-LT survivals were 94% and 77% and 1- and 5-year recurrence-free probabilities were 95% and 86%, respectively. In univariate analysis, HCC recurrence was significantly associated with microvascular invasion (hazard ratio [HR], 13.1; P<0.001), tumor grade (HR, 1.8; P<0.001), pathologic stage >Milan criteria (HR, 8.9; P<0.001), 3 tumor nodules (HR, 5.5; P=0.002), AFP slope greater than 7.5 ng/mL per month (HR, 3.9; P=0.005), and female sex (HR, 2.3; P=0.01). In multivariable analysis of factors known before LT, 3 tumor nodules (HR, 7.6; P<0.001), female sex (HR, 2.5; P=0.01), and AFP slope >7.5 (HR, 3.0; P=0.03) were significantly associated with HCC recurrence. AFP slope greater than 7.5 was also associated with microvascular invasion (odds ratio, 6.8; P=0.008). AFP slope increasing greater than 7.5 ng/mL per month despite locoregional therapy is associated with post-LT HCC recurrence and may serve as a surrogate for microvascular invasion. These findings support incorporating changes in the AFP into candidate selection for LT.

Key donor factors associated with graft loss among liver transplant recipients with human immunodeficiency virus.

PubMed

Campos-Varela, Isabel; Dodge, Jennifer L; Stock, Peter G; Terrault, Norah A

2016-09-01

Human immunodeficiency virus (HIV)-infected liver transplant (LT) recipients have higher risk of graft loss than HIV-uninfected recipients. As the original donor risk index excluded HIV-positive patients, donor factors associated with graft loss in HIV-positive recipients are unknown. Identifying all HIV-positive patients in the Scientific Registry of Transplant Recipients, supplemented by all HIV-infected patients in the solid organ transplantation in HIV: Multi-Site Study (HIV-TR), we evaluated donor factors associated with graft loss among HIV-positive recipients transplanted between March 2002 and August 2012. A total of 249 HIV-positive LT recipients were followed for median 2.4 (interquartile range [IQR]: 0.8-4.9) years. In univariate analysis, donor diabetes (HR=2.09; P=.002) and donor hypertension (HR=1.43; P=.048) were significantly associated with graft loss, and African-American (AA) recipient:non-AA donor race mismatch (HR=1.60; P=.07), other cause of donor death compared to trauma (HR=2.02; P=.09), and donor age 30 years or older (HR=1.53; P=.05) were of borderline significance. In multivariate analysis, donor diabetes (HR=2.12; 95% CI: 1.33-3.38; P=.002) was the only significant predictor of graft loss. In HIV-positive LT recipients, risk of graft loss is strongly influenced by donor diabetes. This information may be useful to transplant physicians seeking to optimize overall graft survival in their HIV-positive LT recipients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of clinical outcome after autologous stem cell transplantation between patients with peripheral T-cell lymphomas and diffuse large B-cell lymphoma.

PubMed

Sohn, B S; Park, I; Kim, E K; Yoon, D H; Lee, S S; Kang, B W; Jang, G; Choi, Y H; Kim, C; Lee, D H; Kim, S; Huh, J; Suh, C

2009-09-01

Although patients with T-cell phenotype lymphomas are generally accepted to have worse prognosis than B-cell phenotype lymphomas, the studies comparing outcomes after autologous stem cell transplantation (ASCT) between peripheral T-cell lymphomas (PTCLs) and with diffuse large B-cell lymphoma (DLBCL) are few. In this study, we compared outcomes after ASCT between 23 patients with PTCLs and 54 patients with DLBCL. Univariate analysis showed that the timing of ASCT, complete response (CR) at ASCT, favorable lactate dehydrogenase/performance/stage, low/low-intermediate (L-LI) International Prognostic Index (IPI) and L-LI age-adjusted IPI (aaIPI) at ASCT were significant predictors of both OS and EFS. Multivariate analysis showed that CR and L-LI aaIPI at ASCT were favorable for both OS (hazard ratio (HR), 0.34; 95% CI, 0.14-0.81; P=0.016 and HR, 0.27; 95% CI, 0.12-0.57; P=0.001) and EFS (HR, 0.38; 95% CI, 0.17-0.85; P=0.020 and HR, 0.36; 95% CI, 0.17-0.77; P=0.008). B-cell or T-cell phenotype, however, had no impact on OS (HR, 0.56; 95% CI, 0.27-1.18; P=0.126) or EFS (HR, 0.62; 95% CI, 0.30-1.30; P=0.206). In conclusion, when compared to patients with DLBCL, patients with PTCLs did not have inferior outcomes after ASCT. T-cell phenotype itself may not have an effect on outcomes of PTCL patients who underwent ASCT.

Lower Performance in Orientation to Time and Place Associates with Greater Risk of Cardiovascular Events and Mortality in the Oldest Old: Leiden 85-Plus Study.

PubMed

Rostamian, Somayeh; van Buchem, Mark A; Jukema, J Wouter; Gussekloo, Jacobijn; Poortvliet, Rosalinde K E; de Cren, Anton J M; Sabayan, Behnam

2017-01-01

Background: Impairment in orientation to time and place is commonly observed in community-dwelling older individuals. Nevertheless, the clinical significance of this has been not fully explored. In this study, we investigated the link between performance in orientation domains and future risk of cardiovascular events and mortality in a non-hospital setting of the oldest old adults. Methods: We included 528 subjects free of myocardial infarction (Group A), 477 individuals free of stroke/transient ischemic attack (Group B), and 432 subjects free of both myocardial infarction and stroke/transient ischemic attack (Group C) at baseline from the population-based Leiden 85-plus cohort study. Participants were asked to answer five questions related to orientation to time and five questions related to orientation to place. 5-year risks of first-time fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, as well as cardiovascular and non-cardiovascular mortality, were estimated using the multivariate Cox regression analysis. Results: In the multivariable analyses, adjusted for sociodemographic characteristics and cardiovascular risk factors, each point lower performance in "orientation to time" was significantly associated with higher risk of first-time myocardial infarction (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.09-1.67, P = 0.007), first-time stroke (HR 1.35, 95% CI 1.12-1.64, P = 0.002), cardiovascular mortality (HR 1.28, 95% CI 1.06-1.54, P = 0.009) and non-cardiovascular mortality (HR 1.37, 95% CI 1.20-1.56, P < 0.001). Similarly, each point lower performance in "orientation to place" was significantly associated with higher risk of first-time myocardial infarction (HR 1.67, 95% CI 1.25-2.22, P = 0.001), first-time stroke (HR 1.39, 95% CI 1.05-1.82, P = 0.016), cardiovascular mortality (HR 1.35, 95% CI 1.00-1.82, P = 0.054) and non-cardiovascular mortality (HR 1.45, 95% CI 1.20-1.77, P < 0.001). Conclusions: Lower performance in orientation to time and place in advanced age is independently related to higher risk of myocardial infarction, stroke and mortality. Impaired orientation might be an early sign of covert vascular injuries, putting subjects at greater risk of cardiovascular events and mortality.

Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis.

PubMed

Gunia, Sven; Kakies, Christoph; Erbersdobler, Andreas; Hakenberg, Oliver W; Koch, Stefan; May, Matthias

2012-03-01

To evaluate the role of p53, p21 and cyclin D1 expression in patients with penile cancer (PC). Paraffin-embedded tissues from PC specimens from six pathology departments were subjected to a central histopathological review performed by one pathologist. The tissue microarray technique was used for immunostaining which was evaluated by two independent pathologists and correlated with cancer-specific survival (CSS). κ-statistics were used to assess interobserver variability. Uni- and multivariable Cox proportional hazards analysis was applied to assess the independent effects of several prognostic factors on CSS over a median of 32 months (IQR 6-66 months). Specimens and clinical data from 110 men treated surgically for primary PC were collected. p53 staining was positive in 30 and negative in 62 specimens. κ-statistics showed substantial interobserver reproducibility of p53 staining evaluation (κ=0.73; p<0.001). The 5-year CSS rate for the entire study cohort was 74%. Five-year CSS was 84% in p53-negative and 51% in p53-positive PC patients (p=0.003). Multivariable analysis showed p53 (HR=3.20; p=0.041) and pT-stage (HR=4.29; p<0.001) as independent significant prognostic factors for CSS. Cyclin D1 and p21 expression were not correlated with survival. However, incorporating p21 into a multivariable Cox model did contribute to improved model quality for predicting CSS. In patients with PC, the expression of p53 in the primary tumour specimen can be reproducibly assessed and is negatively associated with cancer specific survival.

Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears.

PubMed

Ren, Chenchen; Zhu, Yuanhang; Yang, Li; Zhang, Xiaoan; Liu, Ling; Ren, Chunying

2018-02-01

The aim of this study was to investigate the clinical performance of high risk (HR) HPV E6/E7 mRNA assay in detecting cervical high-grade intraepithelial neoplasia and cancer among women with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smears. A total of 160 patients with ASCUS who underwent HR-HPV DNA assay, HR-HPV E6/E7 mRNA assay and colposcopy biopsy at Third Affiliated Hospital of Zhengzhou University, China, from December 2015 to March 2017, were enrolled. Logistic regression analysis was used to evaluate the relationship between pathological results with clinical biologic factors. Univariate analysis showed that the qualitative results of HR-HPV DNA, qualitative results of HR-HPV E6/E7 mRNA and expression levels of HR-HPV E6/E7 mRNA were risk factors of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (all P < 0.05). Multivariable analysis found that only the expression levels of HR-HPV E6/E7 mRNA was associated with high-grade CIN and cervical cancer (OR = 8.971, 95% CI = 2.572-31.289, P = 0.001). An optimal cut-off value of ≥ 558.26 copies/ml was determined using receiver operating characteristic curve, and specificity of cut-off value were higher than E6/E7 mRNA qualitative assay and DNA qualitative assay. HPV E6/E7 mRNA quantitative assay may be a valuable tool in triage of ASCUS pap smears. A high specificity of E6/E7 mRNA quantitative assay as a triage test in women with ASCUS can be translated into a low referral for colposcopy.

Stereotactic Body Radiotherapy for Early-stage Non-small-cell Lung Cancer in Patients 80 Years and Older: A Multi-center Analysis.

PubMed

Cassidy, Richard J; Patel, Pretesh R; Zhang, Xinyan; Press, Robert H; Switchenko, Jeffrey M; Pillai, Rathi N; Owonikoko, Taofeek K; Ramalingam, Suresh S; Fernandez, Felix G; Force, Seth D; Curran, Walter J; Higgins, Kristin A

2017-09-01

Stereotactic body radiotherapy (SBRT) is the standard of care for medically inoperable early-stage non-small-cell lung cancer. Despite the limited number of octogenarians and nonagenarians on trials of SBRT, its use is increasingly being offered in these patients, given the aging cancer population, medical fragility, or patient preference. Our purpose was to investigate the efficacy, safety, and survival of patients ≥ 80 years old treated with definitive lung SBRT. Patients who underwent SBRT were reviewed from 2009 to 2015 at 4 academic centers. Patients diagnosed at ≥ 80 years old were included. Kaplan-Meier and multivariate logistic regression and Cox proportional hazard regression analyses were performed. Recursive partitioning analysis was done to determine a subgroup of patients most likely to benefit from therapy. A total of 58 patients were included, with a median age of 84.9 years (range, 80.1-95.2 years), a median follow-up time of 19.9 months (range, 6.9-64.9 months), a median fraction size of 10.0 Gy (range, 7.0-20.0 Gy), and a median number of fractions of 5.0 (range, 3.0-8.0 fractions). On multivariate analysis, higher Karnofsky performance status (KPS) was associated with higher local recurrence-free survival (hazard ratio [HR], 0.92; P < .01), regional recurrence-free survival (HR, 0.94; P < .01), and overall survival (HR, 0.91; P < .01). On recursive partitioning analysis, patients with KPS ≥ 75 had improved 3-year cancer-specific and overall survival (99.4% and 91.9%, respectively) compared with patients with KPS < 75 (47.8% and 23.6%, respectively; P < .01). Definitive lung SBRT for early-stage non-small-cell lung cancer was efficacious and safe in patients ≥ 80 years old. Patients with a KPS of ≥ 75 derived the most benefit from therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Periprosthetic Joint Infection in Hip Arthroplasty: Is There an Association Between Infection and Bearing Surface Type?

PubMed

Pitto, Rocco P; Sedel, Laurent

2016-10-01

Preliminary studies have raised the question of whether certain prosthetic biomaterials used in total hip arthroplasty (THA) bearings are associated with increased risk of periprosthetic joint infection (PJI). For example, some observational data suggest the risk of PJI is higher with metal-on-metal bearings. However, it is not known whether other bearings-including ceramic bearings or metal-on-polyethylene bearings-may be associated with a higher or lower risk of PJI. The objective of this study was to use a national arthroplasty registry to assess whether the choice of bearings-metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), ceramic-on-ceramic (CoC), or metal-on-metal (MoM)-is associated with differences in the risk of revision for deep infection, either (1) within 6 months or (2) over the entire period of observation, which spanned 15 years. Data from primary THAs were extracted from the New Zealand Joint Registry over a 15-year period. A total of 97,889 hips were available for analysis. Inclusion criterion was degenerative joint disease; exclusion criteria were previous surgery, trauma, and any other diagnosis (12,566 hips). We also excluded a small group of ceramic-on-metal THAs (429) with short followup. The median observation period of the selected group of hips (84,894) was 9 years (range, 1-15 years). The mean age of patients was 68 years (SD ± 11 years), and 52% were women. There were 54,409 (64%) MoP, 16,503 (19%) CoP, 9051 (11%) CoC, and 4931 (6%) MoM hip arthroplasties. Four hundred one hips were revised for deep infection. A multivariate assessment was carried out including the following risks factors available for analysis: age, sex, operating room type, use of body exhaust suits, THA fixation mode, and surgeon volume. Because of late introduction of data collection in the Registry, we were unable to include body mass index (BMI, recording started 2010) and medical comorbidities according to the American Society of Anesthesiologists class (ASA, recording started 2005) in the multivariate analysis. The rate of early PJI (< 6 months) did not differ by bearing surface. In contrast, we observed a difference over the total observation period. Within the first 6 months after the index surgery, CoC THAs were not associated with a lower risk of revision for PJI (p = 0.118) when compared with CoP (hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.50-3.41), MoP (HR, 2.10; CI, 0.91-4.82), and MoM (HR, 2.04; CI, 0.69-6.09). When the whole observation period was considered, CoC hips were associated with a lower risk of revision for deep infection when compared with CoP (HR, 1.30; CI, 0.78-2.18; p = 0.01), MoP (HR, 1.75; CI, 1.07-2.86; p = 0.02), and MoM (HR, 2.12; CI, 1.23-3.65; p = 0.008). Our finding associating CoC THA bearings with a lower risk of infection after THA must be considered very preliminary, and we caution readers against attributing all of the observed difference to the bearing surface. It is possible that some or all of the observed difference associated with bearing type may have been driven by other factors such as ASA and BMI, which could not be included in our multivariate analysis, and so future registry studies on this topic must assess those variables carefully. Level III, therapeutic study.

Genetic risk score and cardiovascular mortality in a southern european population with coronary artery disease.

PubMed

Pereira, Andreia; Mendonca, Maria Isabel; Sousa, Ana Célia; Borges, Sofia; Freitas, Sónia; Henriques, Eva; Rodrigues, Mariana; Freitas, Ana Isabel; Guerra, Graça; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Palma Dos Reis, Roberto

2017-06-01

Several genetic risk scores (GRS) have been associated with cardiovascular disease; their role, however, in survival from proven coronary artery disease (CAD) have yielded conflicting results. The objective of this study was to evaluate long-term cardiovascular mortality according to the genetic risk score in a Southern European population with CAD. A cohort of 1464 CAD patients with angiographic proven CAD were followed up prospectively for up to 58.3 (interquartile range: 25.8-88.1) months. Genotyping of 32 single-nucleotide polymorphisms previously associated with CAD was performed using oligonucleotides probes marked with fluorescence for each allele. GRS was constructed according to the additive model assuming codominance and categorised using the median (=26). Cox Regression analysis was performed to determine independent multivariate predictors of cardiovascular mortality. Kaplan-Meier survival curves compared high vs low GRS using log-rank test. C-index was done for our population, as a measure of discrimination in survival analysis model. During a mean follow-up of 58.3 months, 156 patients (10.7%) died, 107 (7.3%) of CV causes. High GRS (≥26) was associated with reduced cardiovascular survival. Survival analysis with Cox regression model adjusted for 8 variables showed that high GRS, dyslipidemia, diabetes and 3-vessel disease were independent risk factors for cardiovascular mortality (HR=1.53, P=.037; HR=3.64, P=.012; HR=1.75, P=.004; HR=2.97, P<.0001, respectively). At the end of follow-up, the estimated survival probability was 70.8% for high GRS and 80.8% for low GRS (Log-rank test 5.6; P=.018). C-Index of 0.71 was found when GRS was added to a multivariate survival model of diabetes, dyslipidemia, smoking, hypertension and 3 vessel disease, stable angina and dual antiplatelet therapy. Besides the classical risk factors management, this work highlights the relevance of the genetic profile in survival from CAD. It is expected that new therapies will be dirsected to gene targets with proven value in cardiovascular survival. © 2017 John Wiley & Sons Ltd.

Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

PubMed

Park, Sehhoon; Park, Seongyeol; Lee, Se-Hoon; Suh, Beomseok; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Kim, Young Whan; Heo, Dae Seog

2016-11-01

Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control.

PubMed

Schrem, Harald; Schneider, Valentin; Kurok, Marlene; Goldis, Alon; Dreier, Maren; Kaltenborn, Alexander; Gwinner, Wilfried; Barthold, Marc; Liebeneiner, Jan; Winny, Markus; Klempnauer, Jürgen; Kleine, Moritz

2016-01-01

The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33-3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age <52.3 years (p = 0.007, Hazard ratio (HR): 0.82), age >62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (p<0.001, HR: 1.04), ADPKD (p = 0.008, HR: 1.26) and diabetic nephropathy (p = 0.004, HR = 1.51). G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05). Risk-adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm signals to trigger Kaizen events and audits for root-cause analysis of relevant detection rate changes. Further, comparative G-chart analysis would enable benchmarking of cancer surveillance processes between centers.

Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control

PubMed Central

Kurok, Marlene; Goldis, Alon; Dreier, Maren; Kaltenborn, Alexander; Gwinner, Wilfried; Barthold, Marc; Liebeneiner, Jan; Winny, Markus; Klempnauer, Jürgen; Kleine, Moritz

2016-01-01

Background The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. Patients and Methods 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Results Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33–3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age <52.3 years (p = 0.007, Hazard ratio (HR): 0.82), age >62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (p<0.001, HR: 1.04), ADPKD (p = 0.008, HR: 1.26) and diabetic nephropathy (p = 0.004, HR = 1.51). G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05). Conclusions Risk-adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm signals to trigger Kaizen events and audits for root-cause analysis of relevant detection rate changes. Further, comparative G-chart analysis would enable benchmarking of cancer surveillance processes between centers. PMID:27398803

Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation

NASA Technical Reports Server (NTRS)

Makikallio, T. H.; Hoiber, S.; Kober, L.; Torp-Pedersen, C.; Peng, C. K.; Goldberger, A. L.; Huikuri, H. V.

1999-01-01

A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.

Patients with chronic lymphocytic leukemia and complex karyotype show an adverse outcome even in absence of TP53/ATM FISH deletions

PubMed Central

Puiggros, Anna; Collado, Rosa; Calasanz, Maria José; Ortega, Margarita; Ruiz-Xivillé, Neus; Rivas-Delgado, Alfredo; Luño, Elisa; González, Teresa; Navarro, Blanca; García-Malo, MaDolores; Valiente, Alberto; Hernández, José Ángel; Ardanaz, María Teresa; Piñan, María Ángeles; Blanco, María Laura; Hernández-Sánchez, María; Batlle-López, Ana; Salgado, Rocío; Salido, Marta; Ferrer, Ana; Abrisqueta, Pau; Gimeno, Eva; Abella, Eugènia; Ferrá, Christelle; Terol, María José; Ortuño, Francisco; Costa, Dolors; Moreno, Carol; Carbonell, Félix; Bosch, Francesc; Delgado, Julio; Espinet, Blanca

2017-01-01

Genomic complexity identified by chromosome banding analysis (CBA) predicts a worse clinical outcome in CLL patients treated either with standard or new treatments. Herein, we analyzed the clinical impact of complex karyotypes (CK) with or without high-risk FISH deletions (ATM and/or TP53, HR-FISH) in a cohort of 1045 untreated MBL/CLL patients. In all, 99/1045 (9.5%) patients displayed a CK. Despite ATM and TP53 deletions were more common in CK (25% vs 7%; P < 0.001; 40% vs 5%; P < 0.001, respectively), only 44% (40/90) patients with TP53 deletions showed a CK. CK group showed a significant higher two-year cumulative incidence of treatment (48% vs 20%; P < 0.001), as well as a shorter overall survival (OS) (79 mo vs not reached; P < 0.001). When patients were categorized regarding CK and HR-FISH, those with both characteristics showed the worst median OS (52 mo) being clearly distinct from those non-CK and non-HR-FISH (median not reached), but no significant differences were detected between cases with only CK or HR-FISH. Both CK and TP53 deletion remained statistically significant in the multivariate analysis for OS. In conclusion, CK group is globally associated with advanced disease and poor prognostic markers. Further investigation in larger cohorts with CK lacking HR-FISH is needed to elucidate which mechanisms underlie the poor outcome of this subgroup. PMID:28903342

Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.

PubMed

Kang, S H; Lee, Y B; Lee, J-H; Nam, J Y; Chang, Y; Cho, H; Yoo, J-J; Cho, Y Y; Cho, E J; Yu, S J; Kim, M Y; Kim, Y J; Baik, S K; Yoon, J-H

2017-11-01

Rifaximin might decrease the risk of portal hypertension-related complications by controlling small intestinal bacterial overgrowth. To evaluate whether rifaximin was associated with the risk of death and cirrhotic complications. We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non-HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding. In the non-HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio [aHR], 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile-associated diarrhoea was not different between the groups (aHR, 0.028; P = .338). In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy. © 2017 John Wiley & Sons Ltd.

Outcomes and Prognostic Factors in Women With 1 to 3 Breast Cancer Brain Metastases Treated With Definitive Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, T. Jonathan; Oh, Jung Hun; Folkert, Michael R.

2014-11-01

Background: With the continuing increase in the use of definitive stereotactic radiosurgery (SRS) for patients with limited brain metastases (BM), clinicians need more specific prognostic tools. We investigated clinical predictors of outcomes in patients with limited breast cancer BM treated with SRS alone. Methods and Materials: We identified 136 patients with breast cancer and 1-3 BM who underwent definitive SRS for 186 BM between 2000 and 2012. The Kaplan-Meier method was used to assess overall survival (OS), regional failure (RF), and local failure (LF). Associations between clinical factors and outcomes were tested using Cox regression. A point scoring system wasmore » used to stratify patients based on OS, and the predictive power was tested with concordance probability estimate (CPE). Results: The median OS was 17.6 months. The 12-month RF and LF rates were 45% and 10%, respectively. On multivariate analysis, >1 lesion (hazard ratio [HR] = 1.6, P=.02), triple-negative (TN) disease (HR=2.0, P=.006), and active extracranial disease (ED) (HR=2.7, P<.0001) were significantly associated with worse OS. The point score system was defined using proportional simplification of the multivariate Cox proportional hazards regression function. The median OS for patients with 3.0-4.0 points (n=37), 4.5-5.5 points (n=28), 6.0-6.5 points (n=37), and 8-8.5 points (n=34) were 9.2, 15.6, 25.1, and 45.1 months, respectively (P<.0001, CPE = 0.72). Active ED (HR=2.4, P=.0007) was significantly associated with RF. Higher risk for LF was significantly associated with larger BM size (HR=3.1, P=.0001). Conclusion: Patients with >1 BM, active ED, and TN had the highest risk of death after SRS. Active ED is an important prognostic factor for OS and intracranial control.« less

Validation of a Radiosensitivity Molecular Signature in Breast Cancer

PubMed Central

Eschrich, Steven A.; Fulp, William J.; Pawitan, Yudi; Foekens, John A.; Smid, Marcel; Martens, John W. M.; Echevarria, Michelle; Kamath, Vidya; Lee, Ji-Hyun; Harris, Eleanor E.; Bergh, Jonas; Torres-Roca, Javier F.

2014-01-01

Purpose Previously, we developed a radiosensitivity molecular signature (RSI) that was clinically-validated in three independent datasets (rectal, esophageal, head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT) treated breast cancer patients. Experimental Design RSI was tested in two previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n=159) and Erasmus Medical Center (n=344). RSI was applied as previously described. Results We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5 yr relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, p=0.0212) but there was no difference between RS/RR patients treated without RT (71% vs. 77%, p=0.6744), consistent with RSI being RT-specific (interaction term RSIxRT, p=0.05). Similarly, in the Erasmus dataset RT-treated RS patients had an improved 5-year distant-metastasis-free survival over RR patients (77% vs. 64%, p=0.0409) but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, p=0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, HR=5.53, p=0.0987, Erasmus, HR=1.64, p=0.0758) and in backward selection (removal alpha of 0.10) RSI was the only variable remaining in the final model. Finally, RSI is an independent predictor of outcome in RT-treated ER+ patients (Erasmus, multivariable analysis, HR=2.64, p=0.0085). Conclusions RSI is validated in two independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in five independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology. PMID:22832933

Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours.

PubMed

Zandee, Wouter T; van Adrichem, Roxanne C; Kamp, Kimberly; Feelders, Richard A; van Velthuysen, Marie-Louise F; de Herder, Wouter W

2017-08-01

Serotonin secretion occurs in approximately 1%-4% of patients with a pancreatic neuroendocrine tumour (PNET), but the incidence is not well defined. The aim of this study was to determine the incidence of serotonin secretion with and without carcinoid syndrome and the prognostic value for overall survival (OS). Data were collected from 255 patients with a PNET if 24-hours urinary 5-hydroxyindoleacetic acid excretion (5-HIAA) was assessed. Patients were diagnosed with serotonin secretion if 24-hours urinary 5-HIAA excretion was more than 3× the upper limit of normal (ULN) of 50 μmol/24 hours during follow-up. The effect of serotonin secretion on OS was estimated with uni- and multivariate analyses using a Cox regression. Two (0.8%) patients were diagnosed with carcinoid syndrome, and another 20 (7.8%) had a serotonin-secreting PNET without symptoms. These patients mostly had ENETS stage IV disease with high chromogranin A (CgA). Serotonin secretion was a negative prognostic factor in univariate analysis (HR 2.2, 95% CI: 1.27-3.81), but in multivariate analysis, only CgA>10× ULN (HR: 1.81, 95% CI: 1.10-2.98) and neuron-specific enolase (NSE) >ULN (HR: 3.51, 95% CI: 2.26-5.46) were predictors for OS. Immunohistochemical staining for serotonin was positive in 28.6% of serotonin-secreting PNETs (one with carcinoid syndrome) and negative in all controls. Carcinoid syndrome is rare in patients with a PNET, but serotonin secretion occurs often. This is a negative prognostic factor for OS, but after correction for CgA and NSE, it is no longer a predictor and probably only a "not-so innocent bystander" in patients with high tumour burden. © 2017 John Wiley & Sons Ltd.

Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis.

PubMed

Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro; Romero, Alberto Omar; Machiavelli, Mario Raúl; Pérez, Juan Eduardo; Leone, Julieta; Leone, José Pablo

2017-02-01

To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM). We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM. We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2- tumors, triple-negative and HR-/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases. There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

Anal Human Papillomavirus (HPV) Prevalences and Factors Associated with Abnormal Anal Cytology in HIV-Infected Women in an Urban Cohort from Rio de Janeiro, Brazil

PubMed Central

Luz, Paula M.; Lake, Jordan E.; Levi, José Eduardo; Coutinho, José Ricardo; de Andrade, Angela; Heinke, Thais; Derrico, Mônica; Veloso, Valdilea G.; Friedman, Ruth K.; Grinsztejn, Beatriz

2015-01-01

Abstract Identifying factors, including human papillomavirus (HPV) genotypes, associated with abnormal anal cytology in HIV-infected women have implications for anal squamous cell cancer (SCC) prevention in HIV-infected women. Anal and cervical samples were collected for cytology, and tested for high-(HR-HPV) and low-risk HPV (LR-HPV) genotypes in a cross-sectional analysis of the IPEC Women's HIV Cohort (Rio de Janeiro, Brazil). Multivariate log-binomial regression models estimated prevalence ratios for factors associated with abnormal anal cytology [≥atypical squamous cells of undetermined significance, (ASC-US)]. Characteristics of the 863 participants included: median age 42 years, 57% non-white, 79% current CD4+ T-cell count >350 cells/mm3, 53% HIV-1 viral load <50 copies/mL, median ART duration 5.8 years. Fifty-one percent of anal specimens contained ≥1 HR-HPV genotype; 31% had abnormal anal cytology [14% ASC-US, 11% low-grade squamous intra-epithelial lesion, (LSIL); 2% atypical squamous cells-cannot exclude high-grade SIL (ASC-H); 4% high-grade SIL/cancer (HSIL+)]. In multivariate analysis, cervical LSIL+, nadir CD4+ T-cell count ≤50 cells/mm3, HIV-1 viral load ≥50 copies/mL, and anal HPV 6, 11, 16, 18, 33, 45, 52, 56, and 58 were associated with ≥anal ASC-US (p<0.05). Abnormal anal cytology and HR-HPV prevalences were high. HIV-infected women with cervical LSIL+, low nadir CD4+ counts, or detectable HIV-1 viral loads should be a particular focus for enhanced anal SCC screening efforts. PMID:25361401

Risk Factors and Mortality Associated with Default from Multidrug-Resistant Tuberculosis Treatment

PubMed Central

Franke, Molly F.; Appleton, Sasha C.; Bayona, Jaime; Arteaga, Fernando; Palacios, Eda; Llaro, Karim; Shin, Sonya S.; Becerra, Mercedes C.; Murray, Megan B.; Mitnick, Carole D.

2008-01-01

Background Completing treatment for multidrug-resistant (MDR) tuberculosis (TB) may be more challenging than completing first-line TB therapy, especially in resource poor settings. The objectives of this study were to (1) identify risk factors for default from MDR TB therapy; (2) quantify mortality among patients who default; and (3) identify risk factors for death following default. Methods We performed a retrospective chart review to identify risk factors for default and conducted home visits to assess mortality among patients who defaulted. Results 67 of 671 patients (10.0%) defaulted. The median time to default was 438 days (interquartile range [IQR]: 152−710), and 40.3% of patients had culture-positive sputum at the time of default. Substance use (hazard ratio [HR]: 2.96, 95% confidence interval [CI]: [1.56, 5.62], p-value [p]=0.001), substandard housing conditions (HR: 1.83, CI: [1.07, 3.11], p=0.03), later year of enrollment (HR: 1.62, CI: [1.09, 2.41], p=0.02) and health district (p=0.02) predicted default in a multivariable analysis. Severe adverse events did not predict default. Of 47 (70.1%) patients who defaulted and were successfully traced, 25 (53.2%) had died. Poor bacteriologic response, less than a year of treatment at default, low education level, and diagnosis with a psychiatric disorder significantly predicted death after default in a multivariable analysis. Conclusions The proportion of patients who defaulted from MDR TB treatment was relatively low. The large proportion of patients who defaulted while culture-positive underscores the public health importance of minimizing default. Prognosis for patients who defaulted was poor. Interventions aimed at preventing default may reduce TB-related mortality. PMID:18462099

Statin Use and Serum Lipid Levels Are Associated With Survival Outcomes After Surgery for Renal Cell Carcinoma.

PubMed

Haddad, Ahmed Q; Jiang, Lai; Cadeddu, Jeffrey A; Lotan, Yair; Gahan, Jeffrey C; Hynan, Linda S; Gupta, Neil; Raj, Ganesh V; Sagalowsky, Arthur I; Margulis, Vitaly

2015-12-01

To evaluate the association of statin use and preoperative serum lipid parameters with oncologic outcomes following surgery for renal cell carcinoma. A total of 850 patients who underwent surgery for localized renal cell carcinoma at our institution from 2000 to 2012 were included. Use of statins, preoperative serum lipid profile, and comprehensive clinicopathologic features were retrospectively recorded. Kaplan-Meier analysis and multivariate Cox proportional hazards model were employed to compare survival outcomes. There were 342 statin users and 508 non-users. Median follow-up was 25.0 months. Statin users were older, had greater body mass index, and had worse performance status than non-users. Tumor pathologic characteristics were balanced between groups. Five-year recurrence free survival (RFS) was 77.9% for non-users compared with 87.6% for statin users (P = .004). After adjustment for clinicopathologic variables, statin use was independently associated with improved RFS (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.33-0.86, P = .011) and overall survival (HR 0.45, 95%CI 0.28-0.71, P = .001). In patients with available serum lipid parameters (n = 193), 5-year RFS was 83.8% for patients with triglycerides <250 mg/dL compared with 33.3% for those with triglycerides >250 mg/dL (P <.0001). Elevated serum triglycerides (>250 mg/dL) was independently associated with worse RFS (HR 2.69, 95%CI 1.22-5.93, P = .015) on multivariate analysis. Statin use was independently associated with improved survival, whereas elevated serum triglyceride levels correlated with worse oncologic outcomes in this cohort. These findings warrant validation in prospective studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Ethnicity and association with disease manifestations and mortality in Behçet's disease.

PubMed

Savey, Lea; Resche-Rigon, Mathieu; Wechsler, Bertrand; Comarmond, Cloé; Piette, Jean Charles; Cacoub, Patrice; Saadoun, David

2014-03-27

Behçet's disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups. We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis. 535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015). We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis.

Ethnicity and association with disease manifestations and mortality in Behçet’s disease

PubMed Central

2014-01-01

Background Behçet’s disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups. Methods We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis. Results 535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015). Conclusion We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis. PMID:24674137

Risk factors and outcomes of acute lower gastrointestinal bleeding in intestinal Behçet's disease.

PubMed

Park, Jihye; Cheon, Jae Hee; Park, Yong Eun; Lee, Yoon Jee; Lee, Hyun Jung; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho

2017-05-01

Intestinal Behçet's disease (BD) can cause acute lower gastrointestinal bleeding, which is sometimes fatal. We aimed to identify the risk factors and outcomes of acute lower gastrointestinal bleeding and factors associated with rebleeding in intestinal BD patients. Of the total of 588 intestinal BD patients, we retrospectively reviewed the medical records of 66 (11.2%) patients with acute lower gastrointestinal bleeding and compared them with those of 132 matched patients without bleeding. The baseline characteristics were comparable between the bleeding group (n = 66) and the non-bleeding group (n = 132). On multivariate analysis, the independent factors significantly associated with lower gastrointestinal bleeding were older age (>52 years) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.058-4.684, p = 0.035) and a nodular ulcer margin (HR 7.1, 95% CI 2.084-24.189, p = 0.002). Rebleeding occurred in 23 patients (34.8%). Female patients (p = 0.044) and those with previous use of corticosteroids or azathioprine (p = 0.034) were more likely to develop rebleeding. On multivariate analysis, only use of steroids or azathioprine was significantly associated with rebleeding (HR 3.2, 95% CI 1.070-9.462, p = 0.037). Age >52 years and the presence of a nodular margin of the ulcer were found to be related to increased risk of bleeding in patients with intestinal BD. Rebleeding is not uncommon and not effectively prevented with currently available medications. Further studies are warranted to identify effective measures to decrease rebleeding in intestinal BD.

Serum prognostic biomarkers in head and neck cancer patients.

PubMed

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J; Tainsky, Michael A

2014-08-01

A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Prospective cohort study. A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient's serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Poor overall survival was associated with African Americans (hazard ratio [HR] for death = 2.61; 95% confidence interval [CI]: 1.58-4.33; P = .000), advanced stage (HR = 2.79; 95% CI: 1.40-5.57; P = .004), and recurrent disease (HR = 6.66; 95% CI: 2.54-17.44; P = .000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Serum Prognostic Biomarkers in Head and Neck Cancer Patients

PubMed Central

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S.; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H.; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J.; Tainsky, Michael A.

2014-01-01

Objectives/Hypothesis A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Study Design Prospective cohort study. Methods A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient’s serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Results Poor overall survival was associated with African Americans (hazard ratio [HR] for death =2.61; 95% confidence interval [CI]: 1.58–4.33; P =.000), advanced stage (HR =2.79; 95% CI: 1.40–5.57; P =.004), and recurrent disease (HR =6.66; 95% CI: 2.54–17.44; P =.000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. Conclusions The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. PMID:24347532

High Center Volume Does Not Mitigate Risk Associated with Using High Donor Risk Organs in Liver Transplantation.

PubMed

Beal, Eliza W; Black, Sylvester M; Mumtaz, Khalid; Hayes, Don; El-Hinnawi, Ashraf; Washburn, Kenneth; Tumin, Dmitry

2017-09-01

High-risk donor allografts increase access to liver transplant, but potentially reduce patient and graft survival. It is unclear whether the risk associated with using marginal donor livers is mitigated by increasing center experience. The United Network for Organ Sharing registry was queried for adult first-time liver transplant recipients between 2/2002 and 12/2015. High donor risk was defined as donor risk index >1.9, and 1-year patient and graft survival were compared according to donor risk index in small and large centers. Multivariable Cox regression estimated the hazard ratio (HR) associated with using high-risk donor organs, according to a continuous measure of annual center volume. The analysis included 51,770 patients. In 67 small and 67 large centers, high donor risk index predicted increased mortality (p = 0.001). In multivariable analysis, high-donor risk index allografts predicted greater mortality hazard at centers performing 20 liver transplants per year (HR 1.35; 95% CI 1.22, 1.49; p < 0.001) and, similarly, at centers performing 70 per year (HR 1.35; 95% CI 1.26, 1.43; p < 0.001). The interaction between high donor risk index and center volume was not statistically significant (p = 0.747), confirming that the risk associated with using marginal donor livers was comparable between smaller and larger centers. Results were consistent when examining graft loss. At both small and large centers, high-risk donor allografts were associated with reduced patient and graft survival after liver transplant. Specific strategies to mitigate the risk of liver transplant involving high-risk donors are needed, in addition to accumulation of center expertise.

High-risk human papillomavirus among HIV-infected women with normal cervical cytology: a pilot study in Jos, Nigeria.

PubMed

Musa, Jonah; Taiwo, Babafemi; Achenbach, Chad; Olugbenga, Silas; Berzins, Baiba; Sagay, Atiene S; Idoko, John A; Kanki, Phyllis J; Murphy, Robert L

2013-12-01

Cervical cancer is strongly linked to high-risk human papillomavirus (HR-HPV) and is typically preceded by cytological abnormalities. Less is known in patients with normal cervical cytology (NCC). We investigated the epidemiology of HR-HPV among HIV-infected women with NCC. We conducted a cross-sectional study between January and June 2011 among HIV-infected women with NCC at an adult HIV clinic in Jos, Nigeria. Cervical sampling and analysis for HR-HPV by hybrid capture (HC2) with signal amplification was done to determine presence of one or more of the following HR-HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68. Epidemiologic factors associated with HR-HPV were determined using bivariate statistics and multivariate logistic regression. We evaluated 103 HIV-infected women with Pap cytology. The median age of the women was 32 years (range 21-49). Ninety-seven (94.2%) had NCC. Cervical samples for HR-HPV DNA testing were available from 89/97 (91.8%) of the HIV-infected women with NCC. Of the 89 women with cervical samples for HR-HPV DNA testing, 40 (44.9%) had detectable HR-HPV by HC2 giving a HR-HPV prevalence of 44.9% (95% CI 33.9-55.5%). Age < 30 years was associated with HR-HPV (OR 2.69 [95% CI 1.05-6.91, p = 0.039]) while history of previous abortion showed an inverse association with HR-HPV (OR 0.33[95% CI 0.15-0.94, p = 0.039]). The prevalence of HR-HPV is seemingly high among HIV-infected women with NCC in our clinical setting. These data provide support for further investigation of the clinical implications of positive HR-HPV among HIV-infected women with NCC report in cervical cancer prevention programs in Nigeria.

Metric substage according to micro and extensive lamina propria invasion improves prognostics in T1 bladder cancer.

PubMed

Fransen van de Putte, Elisabeth E; Otto, Wolfgang; Hartmann, Arndt; Bertz, Simone; Mayr, Roman; Bründl, Johannes; Breyer, Johannes; Manach, Quentin; Compérat, Eva M; Boormans, Joost L; Bosschieter, Judith; Jewett, Michael A S; Stoehr, Robert; van Leenders, Geert J L H; Nieuwenhuijzen, Jakko A; Zlotta, Alexandre R; Hendricksen, Kees; Rouprêt, Morgan; Burger, Maximilian; van der Kwast, Theo H; van Rhijn, Bas W G

2018-06-04

Reliable prognosticators for T1 bladder cancer (T1BC) are urgently needed. To compare the prognostic value of 2 substage systems for T1BC in patients treated by transurethral resection (TUR) and adjuvant bacillus Calmette-Guérin therapy. The slides of 601 primary T1BCs from four institutes were reviewed by 2 uropathologists and substaged according to 2 classifications: metric substage according to T1 microinvasive (T1m-lamina propria invasion <0.5mm) and T1 extensive invasive (pT1e-invasion ≥ 0.5mm), and according to invasion of the muscularis mucosae (MM) (T1a-invasion above or into MM/T1b). Multivariable analyses for progression-free (PFS) and cancer-specific survival (CSS) were performed including substage, size, multiplicity, carcinoma in situ, sex, age, WHO-grade 1973, and WHO-grade 2004 as variables. Median follow-up was 5.9 years (interquartile range: 3.3-9.0). Progression to T2BC was observed in 148 (25%) patients and 94 (16%) died of BC. The MM was not present at the invasion front in 135 (22%) of tumors. Slides were substaged as follows: 213 T1m and 388 T1e and 281 T1a and 320 T1b. On multivariable analysis, T1m/e substage and WHO 1973 grade were the strongest prognosticators for PFS (hazard ratio [HR] = 3.8 and HR = 1.8) and CSS (HR = 2.7 and HR = 2.6), respectively. Other prognostic factors for CSS were age (HR = 1.03), and tumor size (HR = 1.8). Substage according to MM-invasion was not significant. Our study was limited by its retrospective design and that standard re-TUR was not performed if TUR was macroscopically complete and muscularis propria was present in resected specimens. Metric substaging of T1BC was possible in all cases of 601 T1BC patients and it was a strong independent prognosticator of both PFS and CSS. Copyright © 2018 Elsevier Inc. All rights reserved.

Validation of Methods to Control for Immortal Time Bias in a Pharmacoepidemiologic Analysis of Renin–Angiotensin System Inhibitors in Type 2 Diabetes

PubMed Central

Yang, Xilin; Kong, Alice PS; Luk, Andrea OY; Ozaki, Risa; Ko, Gary TC; Ma, Ronald CW; Chan, Juliana CN; So, Wing Yee

2014-01-01

Background Pharmacoepidemiologic analysis can confirm whether drug efficacy in a randomized controlled trial (RCT) translates to effectiveness in real settings. We examined methods used to control for immortal time bias in an analysis of renin–angiotensin system (RAS) inhibitors as the reference cardioprotective drug. Methods We analyzed data from 3928 patients with type 2 diabetes who were recruited into the Hong Kong Diabetes Registry between 1996 and 2005 and followed up to July 30, 2005. Different Cox models were used to obtain hazard ratios (HRs) for cardiovascular disease (CVD) associated with RAS inhibitors. These HRs were then compared to the HR of 0.92 reported in a recent meta-analysis of RCTs. Results During a median follow-up period of 5.45 years, 7.23% (n = 284) patients developed CVD and 38.7% (n = 1519) were started on RAS inhibitors, with 39.1% of immortal time among the users. In multivariable analysis, time-dependent drug-exposure Cox models and Cox models that moved immortal time from users to nonusers both severely inflated the HR, and time-fixed models that included immortal time deflated the HR. Use of time-fixed Cox models that excluded immortal time resulted in a HR of only 0.89 (95% CI, 0.68–1.17) for CVD associated with RAS inhibitors, which is closer to the values reported in RCTs. Conclusions In pharmacoepidemiologic analysis, time-dependent drug exposure models and models that move immortal time from users to nonusers may introduce substantial bias in investigations of the effects of RAS inhibitors on CVD in type 2 diabetes. PMID:24747198

Impact of interleukin-10 polymorphisms (-1082 and -3575) on the survival of patients with lymphoid neoplasms.

PubMed

Domingo-Domènech, Eva; Benavente, Yolanda; González-Barca, Eva; Montalban, Carlos; Gumà, Josep; Bosch, Ramón; Wang, Sophia S; Lan, Qing; Whitby, Denise; Fernández de Sevilla, Alberto; Rothman, Nathaniel; de Sanjosé, Sílvia

2007-11-01

Single-nucleotide polymorphisms (SNP) in interleukin-10 (IL-10) genes can influence immune responses, which may affect the outcome of patients with lymphoid neoplasms. The aim of this study was to explore the association between polymorphisms of IL-10-(1082A>G) and IL-10-(3575T>A) with the overall survival in patients with lymphoid neoplasms. We analyzed two IL-10 SNP (-1082 and -3575) in 472 consecutive cases with lymphoid neoplasms. Genotypes were tested for association with overall survival and classical prognostic factors by multivariate analysis. Haplotype analysis was carried out using the haplostats package implemented in R software. The implications for survival of patients with lymphoma were evaluated using multivariate analysis. Lymphoma patients with the IL-10-(3575T>A) genotype had a better overall survival (p= 0.002), as did the subgroup with non-Hodgkin's lymphoma (NHL) (p=0.05). Patients with the IL10(-1082GG) genotype had a better median overall survival (p=0.05). When both genotypes were included in a multivariate analysis, IL-10(-3575AA) genotype was the only independent prognostic factor for survival (HR=0.20, 95%CI 0.05-0.92). Patients with the IL-10(-1082) and (-3575) G-A/G-A diplotype had a longer overall survival (p=0.003) and this combination appeared to be an independent prognostic factor for survival (HR:0.26; 95%CI 0.08-0.83). The IL-10(-3575A/A) genotype was identified as a marker of favorable survival. Because the IL-10(-1082) and (-3575) G-A/G-A diplotype was also identified as an indicator of longer survival, we cannot exclude the potential additive role of the IL-10(-1082GG) genotype. These results need to be replicated in larger series and examined in different NHL subtypes.

Factors associated to hypertensive heart disease development: a prospective cohort study in Bayamo, Cuba.

PubMed

Álvarez Aliaga, Alexis; González Aguilera, Julio César; Maceo Gómez, Liliana Del Rosario

2016-07-07

Among the conditions resulting from target organ damage by arterial hypertension, hypertensive cardiopathy is the one that exhibits the highest morbidity and mortality rates. Its prevention should be a target of all high blood pressure medical care programs. To identify risk factors for the development of hypertensive cardiopathy. A prospective cohort study was carried out in hypertensive patients assisted at the specialized arterial hypertension physicians’ offices of the “Carlos Manuel de Céspedes” Specialty Policlinic attached to the General University Hospital, Bayamo Municipality, Granma Province, Cuba, from January 1st, 2000 to December 31st, 2009. Multivariate analysis done to estimate the hazard rate (HR) of developing hypertensive cardiopathy, showed significant independent statistic association for most factors. The first place was occupied by lack of blood pressure control (HR=2.022; 95% CI: 1.659-2.465; p<0.005), followed by hypertension stage 2 (HR=2.015; 95% CI: 1.715-2.366; p<0.005). Another factors with significant HRs were microalbuminuria (HR=1.9; 95% CI: 1.6-2.2) and age over 60 years (HR=1.6; 95% CI: 1.4-1.9). Several risk factors must be considered for the prevention of hypertensive heart disease in high blood pressure patients.

Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial.

PubMed

Sonnenblick, Amir; Agbor-Tarh, Dominique; Bradbury, Ian; Di Cosimo, Serena; Azim, Hatem A; Fumagalli, Debora; Sarp, Severine; Wolff, Antonio C; Andersson, Michael; Kroep, Judith; Cufer, Tanja; Simon, Sergio D; Salman, Pamela; Toi, Masakazu; Harris, Lyndsay; Gralow, Julie; Keane, Maccon; Moreno-Aspitia, Alvaro; Piccart-Gebhart, Martine; de Azambuja, Evandro

2017-05-01

Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) -positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination. In this substudy, we evaluated whether patients with diabetes at study entry-with or without metformin treatment-were associated with different disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) compared with patients without diabetes. Results A total of 8,381 patients were included in the current analysis: 7,935 patients (94.7%) had no history of diabetes at diagnosis, 186 patients (2.2%) had diabetes with no metformin treatment, and 260 patients (3.1%) were diabetic and had been treated with metformin. Median follow-up was 4.5 years (0.16 to 6.31 years), at which 1,205 (14.38%), 929 (11.08%), and 528 (6.3%) patients experienced DFS, DDFS, and OS events, respectively. Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004). This effect was limited to hormone receptor-positive patients. Whereas insulin treatment was associated with a detrimental effect, metformin had a salutary effect in patients with diabetes who had HER2-positive and hormone receptor-positive breast cancer. Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor-positive breast cancer.

Cruciferous Vegetable Intake Is Inversely Associated with Lung Cancer Risk among Current Nonsmoking Men in the Japan Public Health Center (JPHC) Study.

PubMed

Mori, Nagisa; Shimazu, Taichi; Sasazuki, Shizuka; Nozue, Miho; Mutoh, Michihiro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Inoue, Manami; Takachi, Ribeka; Sunami, Ayaka; Ishihara, Junko; Sobue, Tomotaka; Tsugane, Shoichiro

2017-05-01

Background: Cruciferous vegetables, a rich source of isothiocyanates, have been reported to lower the risk of several types of cancer, including lung cancer. However, evidence from prospective observations of populations with a relatively high intake of cruciferous vegetables is sparse. Objective: We investigated the association between cruciferous vegetable intake and lung cancer risk in a large-scale population-based prospective study in Japan. Methods: We studied 82,330 participants (38,663 men; 43,667 women) aged 45-74 y without a past history of cancer. Participants were asked to respond to a validated questionnaire that included 138 food items. The association between cruciferous vegetable intake and lung cancer incidence was assessed with the use of Cox proportional hazard regression analysis to estimate HRs and 95% CIs (with adjustments for potential confounding factors). Results: After 14.9 y of follow-up, a total of 1499 participants (1087 men; 412 women) were diagnosed with lung cancer. After deleting early-diagnosed cancer and adjusting for confounding factors, we observed a nonsignificant inverse trend between cruciferous vegetable intake and lung cancer risk in men in the highest compared with the lowest quartiles (multivariate HR: 0.85; 95% CI: 0.69, 1.06; P -trend = 0.13). Stratified analysis by smoking status revealed a significant inverse association between cruciferous vegetable intake and lung cancer risk among those who were never smokers and those who were past smokers after deleting lung cancer cases in the first 3 y of follow-up [multivariate HR for never smokers: 0.49 (95% CI: 0.27, 0.87; P -trend = 0.04); multivariate HR for past smokers: 0.59 (95% CI: 0.35, 0.99; P -trend = 0.10)]. No association was noted in men who were current smokers and women who were never smokers. Conclusion: This study suggests that cruciferous vegetable intake may be associated with a reduction in lung cancer risk among men who are currently nonsmokers. © 2017 American Society for Nutrition.

Impact of socioeconomic status on survival of colorectal cancer patients.

PubMed

Zhang, Qian; Wang, Yufu; Hu, Hanqing; Huang, Rui; Xie, Lei; Liu, Enrui; Chen, Ying-Gang; Wang, Guiyu; Wang, Xishan

2017-12-01

Socioeconomic status (SES) has an impact on the survival of various cancers, but it has not been fully understood in colorectal cancer (CRC). The Surveillance, Epidemiology and End Results database was adopted to detect the role of SES in the survival outcomes of CRC. A total of 184,322 eligible patients were included and SES status was analyzed. The multivariable analysis showed that Non-Hispanic Black (HR, 1.20; 95% CI, 1.15-1.24), being widowed (HR, 1.04; 95% CI, 1.01-1.07), any Medicaid (HR, 1.36; 95% CI, 1.33-1.39) and the lowest education level group patients had relative poorer prognosis. Besides, sex, tumor location, age, differentiation level and American Joint Committee on Cancer stage also had significant effects on overall survival of CRC. The individuals were further divided into five groups according to the number of survival-adverse factors. All of the four groups containing adverse factors showed impaired survival outcomes compared with the group containing no adverse factor.

Hormonal Contraception, Pregnancy, Breastfeeding, and Risk of HIV Disease Progression Among Zambian Women.

PubMed

Wall, Kristin M; Kilembe, William; Haddad, Lisa; Vwalika, Bellington; Lakhi, Shabir; Khu, Naw Htee; Brill, Ilene; Chomba, Elwyn; Mulenga, Joseph; Tichacek, Amanda; Allen, Susan

2016-03-01

Some studies suggest that hormonal contraception, pregnancy, and/or breastfeeding may influence rates of HIV disease progression. From 1994 to 2012, HIV discordant couples recruited at couples' voluntary HIV counseling and testing centers in Lusaka were followed 3-monthly. Multivariate survival analyses explored associations between time-varying contraception, pregnancy, and breastfeeding and 2 outcomes among HIV-positive women: (1) time to death and (2) time to antiretroviral treatment (ART) initiation. Among 1656 female seropositive, male seronegative couples followed for 3359 person-years (PY), 224 women died [6.7/100 PY; 95% confidence interval (CI): 5.8 to 7.6]. After 2003, 290 women initiated ART (14.5/100 PY; 95% CI: 12.9 to 16.2). In a multivariate model of time to death, hormonal implant [adjusted hazard ratio (aHR) = 0.30; 95% CI: 0.10 to 0.98] and injectable (aHR = 0.59; 95% CI: 0.36 to 0.97) were significantly protective relative to nonhormonal method use, whereas oral contraceptive pill (OCP) use was not (aHR = 1.08; 95% CI: 0.74 to 1.57) controlling for baseline HIV disease stage, time-varying pregnancy, time-varying breastfeeding, and year of enrollment. In a multivariate model of time-to-ART initiation, implant was significantly protective (aHR = 0.54; 95% CI: 0.31 to 0.95), whereas OCP (aHR = 0.70; 95% CI: 0.44 to 1.10) and injectable (aHR = 0.85; 95% CI: 0.55 to 1.32) were not relative to nonhormonal method use controlling for variables above, woman's age, and literacy. Pregnancy was not significantly associated with death (aHR = 1.07; 95% CI: 0.68 to 1.66) or ART initiation (aHR = 1.24; 95% CI: 0.83 to 1.86), whereas breastfeeding was protective for death (aHR = 0.34; 95% CI: 0.19 to 0.62) and ART initiation (aHR = 0.49; 95% CI: 0.29 to 0.85). Hormonal implants and injectables significantly predicted lower mortality; implants were protective for ART initiation. OCPs and pregnancy were not associated with death or ART initiation, whereas breastfeeding was protective for both. Findings from this 18-year cohort study suggest that (1) HIV-positive women desiring pregnancy can be counseled to do so and breastfeed and (2) all effective contraceptive methods, including injectables and implants, should be promoted to prevent unintended pregnancy.

Leflunomide in the treatment of rheumatoid arthritis. An analysis of predictors for treatment continuation.

PubMed

van Roon, E N; Hoekstra, M; Tobi, H; Jansen, T L Th A; Bernelot Moens, H J; Brouwers, J R B J; van de Laar, M A F J

2005-09-01

To determine factors predictive for leflunomide drug survival in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. A standard dataset was collected from medical records of consecutive outpatients on leflunomide treatment for rheumatoid arthritis between January 2000 and June 2003. The dataset consisted of patient, disease and treatment characteristics at the start of leflunomide treatment, and data on leflunomide use. Leflunomide was started in 279 patients and 173 patients (62.0%) withdrew from treatment during follow-up. From univariate analysis, concomitant systemic corticosteroid use [hazard ratio (HR) (95% confidence interval) 1.35 (1.00, 1.83)] and an erythrocyte sedimentation rate <35 mm h(-1)[HR 1.38 (1.01, 1.88)] at start of leflunomide were found to be predictive for better leflunomide survival. Furthermore, the attending rheumatologist was correlated with leflunomide drug survival. Hazard ratios varied, depending on the individual rheumatologist, from 0.60 to 2.66. Multivariate analysis suggested attending rheumatologist (HR varying from 0.54 to 2.30 depending on the individual rheumatologist), concomitant systemic corticosteroid use [HR 1.58 (1.14 2.21)] and erythrocyte sedimentation rate <35 mm h(-1)[HR 1.42 (1.03, 1.96)] at start of leflunomide to be associated with leflunomide survival. Concomitant systemic corticosteroid use, erythrocyte sedimentation rate at the start of treatment and attending rheumatologist were found to be predictive for leflunomide survival. Information on these predictors at the start of leflunomide therapy may offer information on which patients are at an increased risk of withdrawal from leflunomide. Whether this information leads to optimization of leflunomide treatment outcomes remains to be studied.

Quantitative monitoring of tamoxifen in human plasma extended to 40 metabolites using liquid-chromatography high-resolution mass spectrometry: new investigation capabilities for clinical pharmacology.

PubMed

Dahmane, Elyes; Boccard, Julien; Csajka, Chantal; Rudaz, Serge; Décosterd, Laurent; Genin, Eric; Duretz, Bénédicte; Bromirski, Maciej; Zaman, Khalil; Testa, Bernard; Rochat, Bertrand

2014-04-01

Liquid-chromatography (LC) high-resolution (HR) mass spectrometry (MS) analysis can record HR full scans, a technique of detection that shows comparable selectivity and sensitivity to ion transitions (SRM) performed with triple-quadrupole (TQ)-MS but that allows de facto determination of "all" ions including drug metabolites. This could be of potential utility in in vivo drug metabolism and pharmacovigilance studies in order to have a more comprehensive insight in drug biotransformation profile differences in patients. This simultaneous quantitative and qualitative (Quan/Qual) approach has been tested with 20 patients chronically treated with tamoxifen (TAM). The absolute quantification of TAM and three metabolites in plasma was realized using HR- and TQ-MS and compared. The same LC-HR-MS analysis allowed the identification and relative quantification of 37 additional TAM metabolites. A number of new metabolites were detected in patients' plasma including metabolites identified as didemethyl-trihydroxy-TAM-glucoside and didemethyl-tetrahydroxy-TAM-glucoside conjugates corresponding to TAM with six and seven biotransformation steps, respectively. Multivariate analysis allowed relevant patterns of metabolites and ratios to be associated with TAM administration and CYP2D6 genotype. Two hydroxylated metabolites, α-OH-TAM and 4'-OH-TAM, were newly identified as putative CYP2D6 substrates. The relative quantification was precise (<20 %), and the semiquantitative estimation suggests that metabolite levels are non-negligible. Metabolites could play an important role in drug toxicity, but their impact on drug-related side effects has been partially neglected due to the tremendous effort needed with previous MS technologies. Using present HR-MS, this situation should evolve with the straightforward determination of drug metabolites, enlarging the possibilities in studying inter- and intra-patients drug metabolism variability and related effects.

Elevated postvoid residual urine volume predicting recurrence of urinary tract infections in toilet-trained children.

PubMed

Chang, Shang-Jen; Tsai, Li-Ping; Hsu, Chun-Kai; Yang, Stephen S

2015-07-01

The aim of this study was to examine whether toilet-trained children with a history of febrile urinary tract infection (fUTI) and elevated postvoid residual (PVR) urine volume according to a recently published PVR nomogram were at greater risk of UTI recurrence. One month after recovery from febrile UTI, constipation was diagnosed according to the Rome III criteria, and lower urinary tract (LUT) function was evaluated with two sets of uroflowmetry and PVR by ultrasonography. For children aged ≦ 6 and ≧ 7 years, elevated PVR is defined as >20 and >10 ml, respectively. Cox proportion hazards regression was used to evaluate the risk factors for recurrence of UTI. Between 2005 and 2011, 60 children aged 6.5 ± 2.5 years (boy:girl ratio 27:33) were enrolled for analysis. Univariate analysis showed that recurrent febrile UTI was more commonly observed in children with elevated PVR [repetitive elevated PVR: hazard ratio (HR) 5.75, 95% confidence interval (CI) 1.41-23.4; one elevated PVR: HR 4.53, 95% CI 1.01-20.2] and high-grade vesicoureteral reflux (VUR; HR 4.53, 95% CI 1.46-14.07). Multivariate analysis showed that younger age (HR 1.37, 95% CI 1.03-1.82, p < 0.01) and elevated PVR (HR 2.88, 95% CI 1.44-5.73, p = 0.01) were significant, independent risk factors for recurrent febrile UTI--but not gender, presence of high-grade VUR and constipation. Elevated PVR defined by the new PVR nomogram predicted recurrent UTI in children with history of febrile UTI. Care should be taken to manage children with elevated PVR.

Optimizing D'Amico risk groups in radical prostatectomy through the addition of magnetic resonance imaging data.

PubMed

Algarra, R; Zudaire, B; Tienza, A; Velis, J M; Rincón, A; Pascual, I; Zudaire, J

2014-11-01

To improve the predictive efficacy of the D'Amico risk classification system with magnetic resonance imaging (MRI) of the pelvis. We studied 729 patients from a series of 1310 radical prostatectomies for T1-T2 prostate cancer who underwent staging pelvic MRI. Each patient was classified with T2, T3a or T3b MRI, and N (+) patients were excluded. We identified the therapeutic factors that affected the biochemical progression-free survival (BPFS) time (prostate specific antigen [PSA] levels>0.4ng/mL) using a univariate and multivariate study with Cox models. We attempted to improve the predictive power of the D'Amico model (low risk: T1; Gleason 2-6; PSA levels<10ng/mL; intermediate risk: T2 or Gleason 7 or PSA levels 10-20ng/mL; high risk: T3 or Gleason 8-10 or PSA levels>20ng/mL). In the univariate study, the clinical factors that influenced BPFS were the following: Gleason 7 (HR: 1.7); Gleason 8-10 (HR: 2.9); T2 (HR: 1.6); PSA levels 10-20 (HR: 2); PSA levels>20 (HR: 4.3); D'Amico intermediate (HR: 2.1) and high (HR: 4.8) risk; T3a MRI (HR: 2.3) and T3b MRI (HR: 4.5). In the multivariate study, the only variables that affected BPFS were the following: D'Amico intermediate risk (HR: 2; 95% CI 1.2-3.3); D'Amico high risk (HR: 4.1; 95% CI 2.4-6.8); T3a MRI (HR: 1.9; 95% CI 1.2-2.9) and T3b MRI (HR: 3.9; 95% CI 2.5-6.1). Predictive model: Using the multivariate Cox models, we assessed the weight of each variable. A value of 1 was given to D'Amico low risk and T2 MRI; a value of 2 was given to D'Amico intermediate risk and T3a MRI and a value 3 was given to D'Amico high risk and T3b MRI. Each patient had a marker that varied between 2 and 6. The best model included 3 groups, as follows: 494 (67.7%) patients in group 1, with a score of 2-3 points (HR, 1), a BPFS of 86%±2% and 79%±2% at 5 and 10 years, respectively; 179 (24.6%) patients in group 2, with a score of 4 points (HR, 3), a BPFS of 60%±4% and 54%±5% at 5 and 10 years, respectively; and 56 (7.7%) patients in group 3, with a score of 5-6 points (HR, 9.3), a BPFS of 29%±8% and 19%±7% at 5 and 10 years, respectively. The median BPFS time was 1.5 years. MRI data significantly improves the predictive capacity of BPFS when using the D'Amico model data. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Muscular strength and incident hypertension in normotensive and prehypertensive men.

PubMed

Maslow, Andréa L; Sui, Xuemei; Colabianchi, Natalie; Hussey, Jim; Blair, Steven N

2010-02-01

The protective effects of cardiorespiratory fitness (CRF) on hypertension (HTN) are well known; however, the association between muscular strength and incidence of HTN has yet to be examined. This study evaluated the strength-HTN association with and without accounting for CRF. Participants were 4147 men (age = 20-82 yr) in the Aerobics Center Longitudinal Study for whom an age-specific composite muscular strength score was computed from measures of a one-repetition maximal leg and a one-repetition maximal bench press. CRF was quantified by maximal treadmill exercise test time in minutes. Cox proportional hazards regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals of incident HTN events according to exposure categories. During a mean follow-up of 19 yr, there were 503 incident HTN cases. Multivariable-adjusted (excluding CRF) HR of HTN in normotensive men comparing middle- and high-strength thirds to the lowest third were not significant at 1.17 and 0.84, respectively. Multivariable-adjusted (excluding CRF) HR of HTN in baseline prehypertensive men comparing middle- and high-strength thirds to the lowest third were significant at 0.73 and 0.72 (P = 0.01 each), respectively. The association between muscular strength and incidence of HTN in baseline prehypertensive men was no longer significant after control for CRF (P = 0.26). The study indicated that middle and high levels of muscular strength were associated with a reduced risk of HTN in prehypertensive men only. However, this relationship was no longer significant after controlling for CRF.

Impact of tumor grade on prognosis in pancreatic cancer: should we include grade in AJCC staging?

PubMed

Wasif, Nabil; Ko, Clifford Y; Farrell, James; Wainberg, Zev; Hines, Oscar J; Reber, Howard; Tomlinson, James S

2010-09-01

AJCC staging of pancreatic cancer (PAC) is used to determine prognosis, yet survival within each stage shows wide variation and remains unpredictable. We hypothesized that tumor grade might be responsible for some of this variation and that the addition of grade to current AJCC staging would provide improved prognostication. The Surveillance, Epidemiology, and End Results (SEER) database (1991-2005) was used to identify 8082 patients with resected PAC. The impact of grade on overall and stage-specific survival was assessed using Cox regression analysis. Variables in the model were age, sex, tumor size, lymph node status, and tumor grade. For each AJCC stage, survival was significantly worse for high-grade versus low-grade tumors. On multivariate analysis, high tumor grade was an independent predictor of survival for the entire cohort (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.31-1.48) as well as for stage I (HR 1.28, 95% CI 1.07-1.54), stage IIA (HR 1.43, 95% CI 1.26-1.61), stage IIB (HR 1.38, 95% CI 1.27-1.50), stage III (HR 1.28, 95% CI 1.02-1.59), and stage IV (HR 1.58, 95% CI 1.21-2.05) patients. The addition of grade to staging results in a statistically significant survival discrimination between all stages. Tumor grade is an important prognostic variable of survival in PAC. We propose a novel staging system incorporating grade into current AJCC staging for pancreas cancer. The improved prognostication is more reflective of tumor biology and may impact therapy decisions and stratification of future clinical trials.

Clinical and electrocardiographic characteristics for prediction of new-onset atrial fibrillation in asymptomatic patients with atrial premature complexes.

PubMed

Im, Sung Il; Park, Dong Hyun; Kim, Bong Joon; Cho, Kyoung Im; Kim, Hyun Su; Heo, Jung Ho

2018-06-01

Identification of precursors of atrial fibrillation (AF) may lead to early detection and prevent associated morbidity and mortality. Atrial premature complexes (APCs) are commonly seen in healthy subjects. However, there was limited data about the clinical and electrocardiographic (ECG) characteristics for prediction of new-onset AF in asymptomatic patients with APCs in the long-term follow up. The Kosin University (No. 2014-02-04) 24-h holter monitoring, echocardiography, ECG database were reviewed from 2008 to 2016 to identify new- onset AF in patients with APCs. We analyzed demographic and clinical features and the nature of the APCs by ECG according to new-onset AF in those patients. Among 652 patients who underwent 24-h holter monitoring, 226 (34.4%) patients had new-onset AF. There was no difference of the baseline characteristics between new-onset AF group and non-AF group. In univariate analysis, hypertension (HTN), renal failure (CRF), high APC burdens, fastest APC running heart rate (HR), minimal HR, left ventricular ejection fraction (LVEF), left atrial volume index, peak mitral flow velocity of the early rapid filling wave and tricuspid regurgitation grade were significantly associated with new-onset AF. In multivariate analysis, higher APCs burden ( P  = 0.047), higher fastest APCs running HR ( P  = 0.034) and lower minimal HR ( P  = 0.025) were independent risk factors for new-onset AF in asymptomatic patients with APCs. Higher APCs burden, higher fastest APCs running HR and lower minimal HR were associated with new-onset AF in asymptomatic patients with APCs in the long-term follow up.

Introducing ICD-resistant mortality as an end point to evaluate the clinical efficacy of an implantable cardioverter-defibrillator in ischaemic cardiomyopathy.

PubMed

Floré, Vincent; Vandenberk, Bert; Belmans, Ann; Garweg, Christophe; Ector, Joris; Willems, Rik

2018-02-01

A new end point called ICD-resistant mortality was evaluated to assess the clinical efficacy of ICD implantations. In 302 ICD patients with ischaemic cardiomyopathy, we investigated which clinical parameters predicted useful ICD implantations using cumulative incidence competing risk analysis. Implantation was deemed clinically useful when the ICD provided appropriate therapy and the patient survived implantation by 1 year and the first shock by 30 days. ICD-resistant mortality (ICDRM) was defined as death within 30 days after the first shock, within 1 year of implantation or without previous appropriate ICD therapy. After 5 years, ICDRM occurred in 23% of implantations, while 36% were clinically useful. After multivariable analysis, ICDRM was associated with LVEF <35% (HR: 2.63; p = .005), beta-blocker dose <50% (HR: 2.0; p = .01) and anterior or diffuse infarct location (HR: 3.61; p = .001 and HR: 2.89; p = .02). Useful ICD implantations were associated with beta-blocker dose <50% (HR: 1.64; p = .02) and non-anterior infarct location (HR: 3.22 vs anterior and 1.59 vs diffuse; combined p<.001). Five years after implantation, an ICD could be classified as useful in 1 out of 3, while ICDRM occurred in one out of four patients. At 10 years, up to 80% of implantations could be categorized. Lower LVEF was related with significantly higher incidence of ICDRM. Anterior infarcts were associated with more ICDRM and less useful implantations than non-anterior infarcts. Future risk stratification for ICD should focus more on the discrimination between arrhythmic risk, probably preventable by ICDs and ICD-resistant mortality risk.

Serum cholinesterase is an important prognostic factor in chronic heart failure.

PubMed

Sato, Takamasa; Yamauchi, Hiroyuki; Suzuki, Satoshi; Yoshihisa, Akiomi; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

2015-03-01

We determine the importance of indicators of nutrition including lymphocyte, total protein, albumin, cholinesterase and body mass index, and compare the prognostic significance in chronic heart failure (CHF). We examined consecutive 465 CHF patients (376 males, age 62 ± 14 years) who underwent cardiopulmonary exercise testing, echocardiography and blood examination including indicators of nutrition at the same time in our hospital. The patients were followed up [median period 766 days (interquartile range 500-1060)] to register cardiac deaths and rehospitalization due to worsening heart failure. There were 180 cardiac events during the follow-up periods. Patients with cardiac events had lower cholinesterase level than those without events (P < 0.001). On the receiver operating characteristic analysis, the best cut-off value for cholinesterase was 240 U/l (area under the curve 0.720). In the Kaplan-Meier analysis, patients with cholinesterase <240 U/l had significantly higher cardiac event rates than those with cholinesterase >240 U/l. Multivariable Cox proportional hazards model demonstrated that NYHA class III [hazard ratio (HR): 1.688, 95 % confidence interval (CI) 1.062-2.684, P = 0.027], eGFR (HR: 0.983, 95 % CI 0.971-0.995, P = 0.006), sodium concentration (HR: 0.947, 95 % CI 0.897-0.999, P < 0.046), log BNP (HR: 1.880, 95 % CI 1.509-2.341, P < 0.001), cholinesterase (HR: 0.996, 95 % CI 0.993-0.998, P = 0.002) and exertional periodic breathing (HR: 1.619, 95 % CI 1.098-2.388, P = 0.015) were independent factors to predict adverse clinical outcomes. Serum cholinesterase level was an important prognostic factor in CHF.

Results of a 25 Year Longitudinal Analysis of the Serologic Incidence of Syphilis in a Cohort of HIV Infected Patients with Unrestricted Access to Care

PubMed Central

Ganesan, Anuradha; Fieberg, Ann; Agan, Brian K.; Lalani, Tahaniyat; Landrum, Michael L.; Wortmann, Glenn; Crum-Cianflone, Nancy F.; Lifson, Alan. R.; Macalino, Grace

2013-01-01

Background The well described biological and epidemiologic associations of syphilis and HIV are particularly relevant to the military, as service members are young and at risk for sexually transmitted infections. We therefore used the results of serial serologic testing to determine the prevalence, incidence, and risk factors for incident syphilis in a cohort of HIV-infected Department of Defense beneficiaries. Methods Participants with a positive non-treponemal test at HIV diagnosis that was confirmed on treponemal testing were categorized as prevalent cases, whereas participants with an initial negative non-treponemal test who subsequently developed a confirmed positive non-treponemal test as incident cases. Results At HIV diagnosis the prevalence of syphilis was 5.8% (n=202). 4239 participants contributed 27,192 person years (PY) to the incidence analysis and 347 (8%) developed syphilis (rate 1.3/100 PY; [1.1, 1.4]). Syphilis incidence was highest during the calendar years 2006 - 2009 (2.5/100 PY; [2.0, 2.9]). In multivariate analyses, younger age (per 10 year increase HR 0.8;[0.8-0.9]); male gender (HR 5.6; [2.3-13.7]); non European-American ethnicity (African-American (HR 3.2; [2.5-4.2]; Hispanic HR 1.9; [1.2-3.0]); history of hepatitis B (HR 1.5; [1.2-1.9]) or gonorrhea (HR 1.4; [1.1 −1.8]) were associated with syphilis. Conclusions The significant burden of disease both at and after HIV diagnosis, observed in this cohort, suggests that the cost-effectiveness of extending syphilis screening to at risk military members should be assessed. In addition, HIV infected persons continue to acquire syphilis, emphasizing the continued importance of prevention for positive programs. PMID:22592829

Validating fatty acid intake as estimated by an FFQ: how does the 24 h recall perform as reference method compared with the duplicate portion?

PubMed

Trijsburg, Laura; de Vries, Jeanne Hm; Hollman, Peter Ch; Hulshof, Paul Jm; van 't Veer, Pieter; Boshuizen, Hendriek C; Geelen, Anouk

2018-05-08

To compare the performance of the commonly used 24 h recall (24hR) with the more distinct duplicate portion (DP) as reference method for validation of fatty acid intake estimated with an FFQ. Intakes of SFA, MUFA, n-3 fatty acids and linoleic acid (LA) were estimated by chemical analysis of two DP and by on average five 24hR and two FFQ. Plasma n-3 fatty acids and LA were used to objectively compare ranking of individuals based on DP and 24hR. Multivariate measurement error models were used to estimate validity coefficients and attenuation factors for the FFQ with the DP and 24hR as reference methods. Wageningen, the Netherlands. Ninety-two men and 106 women (aged 20-70 years). Validity coefficients for the fatty acid estimates by the FFQ tended to be lower when using the DP as reference method compared with the 24hR. Attenuation factors for the FFQ tended to be slightly higher based on the DP than those based on the 24hR as reference method. Furthermore, when using plasma fatty acids as reference, the DP showed comparable to slightly better ranking of participants according to their intake of n-3 fatty acids (0·33) and n-3:LA (0·34) than the 24hR (0·22 and 0·24, respectively). The 24hR gives only slightly different results compared with the distinctive but less feasible DP, therefore use of the 24hR seems appropriate as the reference method for FFQ validation of fatty acid intake.

Gastroduodenal Ulcers and ABO Blood Group: the Japan Nurses’ Health Study (JNHS)

PubMed Central

Ideno, Yuki; Lee, Jung-Su; Suzuki, Shosuke; Nakajima-Shimada, Junko; Ohnishi, Hiroshi; Sato, Yasunori; Hayashi, Kunihiko

2018-01-01

Background Although several studies have shown that blood type O is associated with increased risk of peptic ulcer, few studies have investigated these associations in Japan. We sought to investigate the association between the ABO blood group and risk of gastroduodenal ulcers (GDU) using combined analysis of both retrospective and prospective data from a large cohort study of Japanese women, the Japan Nurses’ Health Study (JNHS; n = 15,019). Methods The impact of the ABO blood group on GDU risk was examined using Cox regression analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI), with adjustment for potential confounders. Results Compared with women with non-O blood types (A, B, and AB), women with blood type O had a significantly increased risk of GDU from birth (multivariable-adjusted HR 1.18; 95% CI, 1.04–1.34). Moreover, the highest cumulative incidence of GDU was observed in women born pre-1956 with blood type O. In a subgroup analysis stratified by birth year (pre-1956 or post-1955), the multivariable-adjusted HR of women with blood type O was 1.22 (95% CI, 1.00–1.49) and 1.15 (95% CI, 0.98–1.35) in the pre-1956 and post-1955 groups, respectively. Conclusion In this large, combined, ambispective cohort study of Japanese women, older women with blood type O had a higher risk of developing GDU than those with other blood types. PMID:29093357

The FIB-4 score predicts postoperative short-term outcomes of hepatocellular carcinoma fulfilling the milan criteria.

PubMed

Dong, J; Xu, X-h; Ke, M-y; Xiang, J-x; Liu, W-y; Liu, X-m; Wang, B; Zhang, X-f; Lv, Y

2016-05-01

The fibrosis score 4 (FIB-4) score is a useful tool to determine the degree of hepatic fibrosis. Liver fibrosis and cirrhosis are well-known predictors of postoperative complications after hepatectomy. This study examined the impact of FIB-4 on postoperative short-term outcomes of patients with hepatocellular carcinoma (HCC). Three hundred and fifty patients undergoing hepatectomy for HCC between 2008 and 2013 were enrolled. The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the FIB-4. Univariate and multivariate analysis was performed to identify the risk factors. The correlation of the preoperative FIB-4 value with clinicopathological parameters was examined. Postoperative complications were observed in 202 (57.7%) patients. The optimal cutoff value of the FIB-4 was set at 2.88 and 3.85 for postoperative complications and intraoperative blood loss respectively. It was also an independent prognostic factor for postoperative complications (hazard ratio [HR], 1.202; 95% CI, 1.076-1.344; P = 0.001) and intraoperative blood loss (HR, 1.196; 95% CI, 1.091-1.343; P < 0.001) by multivariate analysis. The FIB-4 was significantly correlated with age, liver function, coagulation function, blood loss, intraoperative blood transfusion (all P < 0.05). Preoperative FIB-4 is a useful index to predict postoperative outcomes in patients with HCC. The FIB-4 should be assessed routinely for hepatocellular carcinoma patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study.

PubMed

Stocker, Gertraud; Hacker, Ulrich T; Fiteni, Frédéric; John Mahachie, Jestinah; Roth, Arnaud D; Van Cutsem, Eric; Peeters, Marc; Lordick, Florian; Mauer, Murielle

2018-06-12

Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy. Survival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m 2 ), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed - versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were conducted to adjust for baseline prognostic factors using Cox regression model. 13.4% (280 of 2094 patients) had a BMI ≥ 30 kg/m 2 , and 5.3% had both a BMI ≥ 30 kg/m 2 and a body surface area (BSA) ≥2 m 2 . Dose reductions occurred in 16.1% of patients with a BMI ≥ 30 kg/m 2 and 32.4% with BMI ≥ 30 kg/m 2 and BSA ≥ 2 m 2 , respectively. In patients with BMI ≥ 30 kg/m 2 , multivariate analysis demonstrated a trend towards better RFS in the fully dosed compared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43-1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI ≥ 30 kg/m 2 and BSA ≥ 2 m 2 , multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27-0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28-1.01; p = 0.052). This group comprised predominantly of men. Data support the recommendation of using fully dosed chemotherapy for the adjuvant treatment in obese patients with colon cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparative analysis of the effect of prostatic invasion patterns on cancer-specific mortality after radical cystectomy in pT4a urothelial carcinoma of the bladder.

PubMed

Vallo, Stefan; Gilfrich, Christian; Burger, Maximilian; Volkmer, Björn; Boehm, Katharina; Rink, Michael; Chun, Felix K; Roghmann, Florian; Novotny, Vladimir; Mani, Jens; Brisuda, Antonin; Mayr, Roman; Stredele, Regina; Noldus, Joachim; Schnabel, Marco; May, Matthias; Fritsche, Hans-Martin; Pycha, Armin; Martini, Thomas; Wirth, Manfred; Roigas, Jan; Bastian, Patrick J; Nuhn, Philipp; Dahlem, Roland; Haferkamp, Axel; Fisch, Margit; Aziz, Atiqullah

2016-10-01

To evaluate the prognostic relevance of different prostatic invasion patterns in pT4a urothelial carcinoma of the bladder (UCB) after radical cystectomy. Our study comprised a total of 358 men with pT4a UCB. Patients were divided in 2 groups-group A with stromal infiltration of the prostate via the prostatic urethra with additional muscle-invasive UCB (n = 121, 33.8%) and group B with continuous infiltration of the prostate through the entire bladder wall (n = 237, 66.2%). The effect of age, tumor grade, carcinoma in situ, lymphovascular invasion, soft tissue surgical margin, lymph node metastases, administration of adjuvant chemotherapy, and prostatic invasion patterns on cancer-specific mortality (CSM) was evaluated using competing-risk regression analysis. Decision curve analysis was used to evaluate the net benefit of including the variable invasion pattern within our model. The estimated 5-year CSM-rates for group A and B were 50.1% and 66.0%, respectively. In multivariable competing-risk analysis, lymph node metastases (hazard ratio [HR] = 1.73, P<0.001), lymphovascular invasion (HR = 1.62, P = 0.0023), soft tissue surgical margin (HR = 1.49, P = 0.026), absence of adjuvant chemotherapy (HR = 2.11, P<0.001), and tumor infiltration of the prostate by continuous infiltration of the entire bladder wall (HR = 1.37, P = 0.044) were significantly associated with a higher risk for CSM. Decision curve analysis showed a net benefit of our model including the variable invasion pattern. Continuous infiltration of the prostate through the entire bladder wall showed an adverse effect on CSM. Besides including these patients into clinical trials for an adjuvant therapy, we recommend including prostatic invasion patterns in predictive models in pT4a UCB in men. Copyright © 2016 Elsevier Inc. All rights reserved.

Pseudomonas aeruginosa Bacteremia among Immunocompetent and Immunocompromised Patients: Relation to Initial Antibiotic Therapy and Survival.

PubMed

Migiyama, Yohei; Yanagihara, Katsunori; Kaku, Norihito; Harada, Yosuke; Yamada, Koichi; Nagaoka, Kentaro; Morinaga, Yoshitomo; Akamatsu, Norihiko; Matsuda, Junichi; Izumikawa, Koichi; Kohrogi, Hirotsugu; Kohno, Shigeru

2016-01-01

Pseudomonas aeruginosa bacteremia occurs mainly in immunocompromised patients. However, P. aeruginosa bacteremia in immunocompetent patients has also been reported. The aim of this study was to evaluate the clinical characteristics of P. aeruginosa bacteremia in relation to the immune status of the patients. The medical records of 126 adult patients with P. aeruginosa bacteremia in Nagasaki University Hospital were retrospectively reviewed between January 2003 and December 2012. Of 126 patients with P. aeruginosa bacteremia, 60 patients (47.6%) were classified as immunocompetent. Mortality in immunocompetent patients tended to be lower than in immunocompromised patients (7-day mortality, 8% vs. 30%, P < 0.01; 30-day mortality, 23% vs. 39%, P = 0.053). Multivariate analysis showed that a higher sequential organ failure assessment score (hazard ratio [HR]: 1.27, P < 0.01) and underlying malignancies (HR: 3.33, P < 0.01) were independently associated with 30-day mortality. Initial antibiotic therapy (HR: 0.21, P < 0.01) and patients' immune status (HR: 0.29, P = 0.02) also had a significant impact on survival. However, there was a significant interaction between these 2 variables (P = 0.03 for interaction). A subgroup analysis showed that in immunocompromised, but not immunocompetent patients, initial appropriate antibiotic therapy was associated with lower mortality (30-day mortality 20.5% vs. 66.7%, P < 0.01 by log-rank test).

Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population.

PubMed

Tao, Li; Chu, Laura; Wang, Lisa I; Moy, Lisa; Brammer, Melissa; Song, Chunyan; Green, Marjorie; Kurian, Allison W; Gomez, Scarlett L; Clarke, Christina A

2016-09-01

To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression. We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of Stage IV versus Stage I-III breast cancer; Cox proportional hazards regression was used to assess relative hazard (RH) of mortality. Five percent of invasive breast cancer was metastatic at diagnosis. Compared to patients with earlier stage disease, patients with de novo metastatic disease were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI 1.17-1.42; HR-/HER2+: OR 1.40, 95 %CI 1.25-1.57, vs. HR+/HER2-). Median survival improved over time, but varied substantially across race/ethnicity (Asians: 34 months; African Americans: 6 months), neighborhood socioeconomic status (SES) (highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45 months; triple negative: 12 months). In a multivariable model, triple negative (RH 2.85, 95 % CI 2.50-3.24) and HR-/HER2+ (RH 1.60, 95 % CI 1.37-1.87) had worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2- breast cancer. De novo metastatic breast cancer was more likely to be HER2+. Among metastatic tumors, those that were HER2+ had better survival than other subtypes.

Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, Tai-Chung, E-mail: lamtaichung@gmail.com; Uno, Hajime; Krishnan, Monica

2015-10-01

Purpose: Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. Methods and Materials: At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomaticmore » vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. Results: The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS ≥11 (HR=2.5 , 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. Conclusion: In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS ≥11 and SF RT were associated with a higher rate of SAEs.« less

Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd

2014-10-01

Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. Amore » P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.« less

Analysis of the Influence of HLA-A Matching Relative to HLA-B and -DR Matching on Heart Transplant Outcomes

PubMed Central

Ansari, David; Bućin, Dragan; Höglund, Peter; Ohlsson, Mattias; Andersson, Bodil; Nilsson, Johan

2015-01-01

Background There are conflicting reports on the effect of donor-recipient HLA matching on outcomes in heart transplantation. The objective of this study was to investigate the effects of HLA-A matching relative to HLA-B and -DR matching on long-term survival in heart transplantation. Methods A total of 25 583 patients transplanted between 1988 and 2011 were identified from the International Society for Heart and Lung Transplantation registry. Transplants were divided into 2 donor-recipient matching groups: HLA-A–compatible (no HLA-A mismatches) and HLA-A–incompatible (1-2 HLA-A mismatches). Primary outcome was all-cause mortality. Secondary outcomes were graft failure-, cardiovascular-, infection-, or malignancy-related deaths. Results The risk of all-cause mortality 15 years after transplantation was higher for HLA-A–compatible (vs HLA-A–incompatible) grafts in patients who had HLA-B–, HLA-DR–, or HLA-B,DR–incompatible grafts (P = 0.027, P = 0.007, and P = 0.002, respectively) but not in HLA-B– and/or HLA-DR–compatible grafts. This was confirmed in multivariable Cox regression analysis where HLA-A compatibility (vs HLA-A incompatibility) was associated with higher mortality in transplants incompatible for HLA-DR or HLA-B and -DR (hazard ratio [HR], 1.59; 95% confidence interval [95% CI], 1.11-2.28; P = 0.012 and HR, 1.69; 95% CI, 1.17-2.43; P = 0.005, respectively). In multivariable analysis, the largest compromise in survival for HLA-A compatibility (vs HLA-incompatibility) was for chronic rejection in HLA-B– and -DR–incompatible grafts (HR, 1.91; 95% CI, 1.22-3.01; P = 0.005). Conclusions Decreased long-term survival in heart transplantation was associated with HLA-A compatibility in HLA-B,DR–incompatible grafts. PMID:27500238

Prognostic Significance of Nodal Location and Ratio in Stage IIIC Endometrial Carcinoma Among a Multi-Institutional Academic Collaboration.

PubMed

Mayadev, Jyoti; Elshaikh, Mohamed A; Christie, Alana; Nagel, Christa; Kennedy, Vanessa; Khan, Nadia; Lea, Jayanthi; Ghanem, Ahmad; Miller, David; Xie, Xian-Jin; Folkert, Michael; Albuquerque, Kevin

2018-04-20

Stage IIIC endometrial carcinoma (EC) represents pathologically heterogenous patients with single/multiple pelvic (stage IIIC1) or paraaortic (stage IIIC2) lymph nodes (LNs). There is an increasing trend to offer adjuvant chemotherapy (CT) +/- radiation (RT) uniformly to these patients, regardless of substage. We investigate the prognostic significance of positive LN (pLN) number, ratio (%pLN), location (IIC1 vs. IIC2), and adjuvant treatment on patterns of failure and survival in a large collaborative multi-institutional series. Clinical data for stage III EC patients such as patient characteristics, surgery/pathologic details, adjuvant therapies (including CT, RT, and chemotherapy and radiation), and outcomes (including pelvic control [PC], disease-free survival [DFS], distant DFS, and overall survival [OS]) were collected from 3 academic institutions. Log-rank analyses, Cox regression univariate and multivariate analyses were performed. Of the 264 patients queried for stage III disease, 237 (73%) had pLN, and complete LN sampling for analysis. The mean number of pLN in the combined data were 3.9, with 26.1% of all LN sampled positive; 121 patients (51%) staged IIIC1, and 116 patients (49%) staged IIIC2. There was a significant difference in number of pLN (P=0.0006) and total LN sampled by institution (range, 13 to 35; P=0.0004), without a difference in %pLN (P=0.35). Ninety-seven of 220 (44.1%) have ≥20% pLN. While controlling for substage and institution, a decrease in DFS (hazard ratio [HR], 1.1; P=0.007), and OS (HR, 1.1; P=0.01) was observed with every increase of 10% in the pLN ratio. There was a significant difference in DFS (HR, 1.8; P=0.003), PC (HR, 1.9; P=0.004), and distant DFS (HR, 1.6; P=0.03), as well as a trend for decreased OS (HR, 1.6; P=0.08) for substage IIIC2 versus IIIC1 disease; 5 years DFS 40% versus 45%, OS 50% versus 57%. Patients received no adjuvant therapy (10%), CT alone (27%), RT alone (16%), or chemotherapy and radiation (47%). There was no significant difference in PC, DFS, or OS between the various treatment regimens. On univariate analysis, while pLN was significant, treatment type did not impact DFS or OS. On multivariate analysis for DFS, patient age, race, and IIIC1 versus IIIC2 substage retained significance (HR, 0.56; P=0.01). Stage III EC patients with substage IIIC2 disease have a significantly increased risk of local and distant disease recurrence and death from EC. A decrease in DFS and OS was observed with every increase of 10% in the pLN ratio. Stage IIIC2 patients represent a high-risk subpopulation for whom clinical trials, or targeted regimens should be explored to achieve improved oncologic outcomes.

Cross-sectional time series and multivariate adaptive regression splines models using accelerometry and heart rate predict energy expenditure of preschoolers

USDA-ARS?s Scientific Manuscript database

Prediction equations of energy expenditure (EE) using accelerometers and miniaturized heart rate (HR) monitors have been developed in older children and adults but not in preschool-aged children. Because the relationships between accelerometer counts (ACs), HR, and EE are confounded by growth and ma...

Outcome predictors in the management of intramedullary classic ependymoma: An integrative survival analysis.

PubMed

Wang, Yinqing; Cai, Ranze; Wang, Rui; Wang, Chunhua; Chen, Chunmei

2018-06-01

This is a retrospective study.The aim of this study was to illustrate the survival outcomes of patients with classic ependymoma (CE) and identify potential prognostic factors.CE is the most common category of spinal ependymomas, but few published studies have discussed predictors of the survival outcome.A Boolean search of the PubMed, Embase, and OVID databases was conducted by 2 investigators independently. The objects were intramedullary grade II ependymoma according to 2007 WHO classification. Univariate Kaplan-Meier analysis and Log-Rank tests were performed to identify variables associated with progression-free survival (PFS) or overall survival (OS). Multivariate Cox regression was performed to assess hazard ratios (HRs) with 95% confidence intervals (95% CIs). Statistical analysis was performed by SPSS version 23.0 (IBM Corp.) with statistical significance defined as P < .05.A total of 35 studies were identified, including 169 cases of CE. The mean follow-up time across cases was 64.2 ± 51.5 months. Univariate analysis showed that patients who had undergone total resection (TR) had better PFS and OS than those with subtotal resection (STR) and biopsy (P = .002, P = .004, respectively). Within either univariate or multivariate analysis (P = .000, P = .07, respectively), histological type was an independent prognostic factor for PFS of CE [papillary type: HR 0.002, 95% CI (0.000-0.073), P = .001, tanycytic type: HR 0.010, 95% CI (0.000-0.218), P = .003].It was the first integrative analysis of CE to elucidate the correlation between kinds of factors and prognostic outcomes. Definite histological type and safely TR were foundation of CE's management. 4.

Influence of diabetes on the risk of urothelial cancer according to body mass index: a 10-year nationwide population-based observational study.

PubMed

Bae, Woong Jin; Choi, Jin Bong; Moon, Hyong Woo; Park, Young Hyun; Cho, Hyuk Jin; Hong, Sung-Hoo; Lee, Ji Youl; Kim, Sae Woong; Han, Kyung-Do; Ha, U-Syn

2018-01-01

To examine the association between obesity and urothelial cancer, we used a representative data from the National Health Insurance System (NHIS). Participants included 826,170 men aged 20 years and older who experienced a health examination at least one time between 2004 and 2008. The study thus excluded people aged <20 years and women. We used a multivariate adjusted Cox regression analysis to examine the association between urothelial cancer and body mass index (BMI) via a hazard ratio (HR) and 95% confidence interval (CI). The age- or multivariable-adjusted HR for urothelial cancer was stratified by BMI. Men with a higher BMI were more likely to acquire urothelial cancer independent of variables. In the population with diabetes, there showed a considerable, increasing trend in the risk of urothelial cancer in the overweight and obesity group, compared to the group with the same BMI but without diabetes. This population-based study showed evidence of an association between obesity and the development of urothelial cancer, where the presence of diabetes increased the risk of urothelial cancer. Additionally, the higher the BMI, the higher the risk for urothelial cancer.

Utility and Clinical Profile of Dexmedetomidine in Pediatric Cardiac Catheterization Procedures: A Matched Controlled Analysis.

PubMed

Riveros, Ricardo; Makarova, Natalya; Riveros-Perez, Efrain; Chodavarapu, Praneeta; Saasouh, Wael; Yılmaz, Hüseyin Oğuz; Cuko, Evis; Babazade, Rovnat; Kimatian, Stephen; Turan, Alparslan

2017-12-01

Dexmedetomidine is increasingly used in children undergoing cardiac catheterization procedures. We compared the percentage of surgical time with hemodynamic instability and the incidence of postoperative agitation between pediatric cardiac catheterization patients who received dexmedetomidine infusion and those who did not and the incidence of postoperative agitation. We matched 653 pediatric patients scheduled for cardiac catheterization. Two separate multivariable linear mixed models were used to assess the association between dexmedetomidine use and intraoperative blood pressure and heart rate instability. A multivariate logistic regression was used for relationship between dexmedetomidine and postoperative agitation. No difference between the study groups was found in the duration of MAP ( P = .867) or heart rate (HR) instabilities ( P = .224). The relationship between dexmedetomidine use and the duration of negative hemodynamic effects does not depend on any of the considered CHD types (all P > .001) or intervention ( P = .453 for MAP and P = .023 for HR). No difference in postoperative agitation was found between the study groups ( P = .590). Our study demonstrated no benefit in using dexmedetomidine infusion compared with other general anesthesia techniques to maintain hemodynamic stability or decrease agitation in pediatric patients undergoing cardiac catheterization procedures.

Impact of Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression on Prognosis After Surgical Resection for Biliary Carcinoma.

PubMed

Toyota, Kazuhiro; Murakami, Yoshiaki; Kondo, Naru; Uemura, Kenichiro; Nakagawa, Naoya; Takahashi, Shinya; Sueda, Taijiro

2017-06-01

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that influences chemotherapy effectiveness and prognosis. The aim of this study was to investigate whether SPARC expression correlates with the postoperative survival of patients treated with surgical resection for biliary carcinoma. SPARC expression in resected biliary carcinoma specimens was investigated immunohistochemically in 175 patients. The relationship between SPARC expression and prognosis after surgery was evaluated using univariate and multivariate analyses. High SPARC expression in peritumoral stroma was found in 61 (35%) patients. In all patients, stromal SPARC expression was significantly associated with overall survival (OS) (P = 0.006). Multivariate analysis revealed that high stromal SPARC expression was an independent risk factor for poor OS (HR 1.81, P = 0.006). Moreover, high stromal SPARC expression was independently associated with poor prognosis in a subset of 118 patients treated with gemcitabine-based adjuvant chemotherapy (HR 2.04, P = 0.010) but not in the 57 patients who did not receive adjuvant chemotherapy (P = 0.21). Stromal SPARC expression correlated with the prognosis of patients with resectable biliary carcinoma, and its significance was enhanced in patients treated with adjuvant gemcitabine-based chemotherapy.

FAS ligand expression in inflammatory infiltrate lymphoid cells as a prognostic marker in oral squamous cell carcinoma.

PubMed

Peterle, G T; Santos, M; Mendes, S O; Carvalho-Neto, P B; Maia, L L; Stur, E; Agostini, L P; Silva, C V M; Trivilin, L O; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-09-22

Currently, the most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of regional lymph node metastases, which correlates with a 50% reduction in life expectancy. We have previously observed that expression of hypoxia genes in the tumor inflammatory infiltrate is statistically related to prognosis in OSCC. FAS and FASL expression levels in OSCC have previously been related to patient survival. The present study analyzed the relationship between FASL expression in the inflammatory infiltrate lymphoid cells and clinical variables, tumor histology, and prognosis of OSCC. Strong FASL expression was significantly associated with lymph node metastases (P = 0.035) and disease-specific death (P = 0.014), but multivariate analysis did not confirm FASL expression as an independent death risk factor (OR = 2.78, 95%CI = 0.81-9.55). Disease-free and disease-specific survival were significantly correlated with FASL expression (P = 0.016 and P = 0.005, respectively). Multivariate analysis revealed that strong FASL expression is an independent marker for earlier disease relapse and disease-specific death, with approximately 2.5-fold increased risk compared with weak expression (HR = 2.24, 95%CI = 1.08-4.65 and HR = 2.49, 95%CI = 1.04-5.99, respectively). Our results suggest a potential role for this expression profile as a tumor prognostic marker in OSCC patients.

Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Jakobi, Sina; Steetskamp, Joscha; Makris, Georgios; Sicking, Isabel; Weyer, Veronika; Schmidt, Marcus

2014-07-01

The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.

Association of vegetable and fruit intake with gastric cancer risk among Japanese: a pooled analysis of four cohort studies.

PubMed

Shimazu, T; Wakai, K; Tamakoshi, A; Tsuji, I; Tanaka, K; Matsuo, K; Nagata, C; Mizoue, T; Inoue, M; Tsugane, S; Sasazuki, S

2014-06-01

Prospective evidence is inconsistent regarding the association between vegetable/fruit intake and the risk of gastric cancer. In an analysis of original data from four population-based prospective cohort studies encompassing 191 232 participants, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of gastric cancer incidence according to vegetable and fruit intake and conducted a meta-analysis of HRs derived from each study. During 2 094 428 person-years of follow-up, 2995 gastric cancer cases were identified. After adjustment for potential confounders, we found a marginally significant decrease in gastric cancer risk in relation to total vegetable intake but not total fruit intake: the multivariate-adjusted HR (95% CI; P for trend) for the highest versus the lowest quintile of total vegetable intake was 0.89 (0.77-1.03; P for trend = 0.13) among men and 0.83 (0.67-1.03; P for trend = 0.40) among women. For distal gastric cancer, the multivariate HR for the highest quintile of total vegetable intake was 0.78 (0.63-0.97; P for trend = 0.02) among men. This pooled analysis of data from large prospective studies in Japan suggests that vegetable intake reduces gastric cancer risk, especially the risk of distal gastric cancer among men. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The Role of Polymerase Chain Reaction of High-Risk Human Papilloma Virus in the Screening of High-Grade Squamous Intraepithelial Lesions in the Anal Mucosa of Human Immunodeficiency Virus-Positive Males Having Sex with Males

PubMed Central

Hidalgo-Tenorio, Carmen; Rivero-Rodriguez, Mar; Gil-Anguita, Concepción; Esquivias, Javier; López-Castro, Rodrigo; Ramírez-Taboada, Jessica; de Hierro, Mercedes López; López-Ruiz, Miguel A.; Martínez, R. Javier; Llaño, Juan P.

2015-01-01

Objectives To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM). Methods This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation. Results Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82). Conclusions When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV-positive patients. HPV suppression with treatment protects against the appearance of HSIL. PMID:25849412

Pretreatment Endorectal Coil Magnetic Resonance Imaging Findings Predict Biochemical Tumor Control in Prostate Cancer Patients Treated With Combination Brachytherapy and External-Beam Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riaz, Nadeem; Afaq, Asim; Akin, Oguz

Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes.more » The median follow-up was 49 months (range, 1-13 years). Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients.« less

The role of polymerase chain reaction of high-risk human papilloma virus in the screening of high-grade squamous intraepithelial lesions in the anal mucosa of human immunodeficiency virus-positive males having sex with males.

PubMed

Hidalgo-Tenorio, Carmen; Rivero-Rodriguez, Mar; Gil-Anguita, Concepción; Esquivias, Javier; López-Castro, Rodrigo; Ramírez-Taboada, Jessica; de Hierro, Mercedes López; López-Ruiz, Miguel A; Martínez, R Javier; Llaño, Juan P

2015-01-01

To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM). This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation. Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82). When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV suppression with treatment protects against the appearance of HSIL [corrected].

Locoregional treatments before liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry.

PubMed

Pommergaard, Hans-Christian; Rostved, Andreas Arendtsen; Adam, René; Thygesen, Lau Caspar; Salizzoni, Mauro; Gómez Bravo, Miguel Angel; Cherqui, Daniel; De Simone, Paolo; Boudjema, Karim; Mazzaferro, Vincenzo; Soubrane, Olivier; García-Valdecasas, Juan Carlos; Fabregat Prous, Joan; Pinna, Antonio D; O'Grady, John; Karam, Vincent; Duvoux, Christophe; Rasmussen, Allan

2018-05-01

Locoregional treatment while on the waiting list for liver transplantation (Ltx) for hepatocellular carcinoma (HCC) has been shown to improve survival. However, the effect of treatment type has not been investigated. We investigate the effect of locoregional treatment type on survival after Ltx for HCC. We investigated patients registered in the European Liver Transplant Registry database using multivariate Cox regression survival analysis. Information on locoregional therapy was registered for 4978 of 23 124 patients and was associated with improved overall survival [hazard ratio (HR) 0.84 (0.73-0.96)] and HCC-specific survival [HR 0.76 (0.59-0.98)]. Radiofrequency ablation (RFA) was the one monotherapy associated with improved overall survival [HR 0.51 (0.40-0.65)]. In addition, the combination of RFA and transarterial chemoembolization also improved survival [HR 0.74 (0.55-0.99)]. Adjusting for factors related to prognosis, disease severity, and tumor aggressiveness, RFA was highly beneficial for overall and HCC-specific survival. The effect may represent a selection of patients with favorable tumor biology; however, the treatment may be effective per se by halting tumor progression. Clinicaltrials.gov number: NCT02995096. © 2018 Steunstichting ESOT.

The importance of extent of choroid plexus cauterization in addition to endoscopic third ventriculostomy for infantile hydrocephalus: a retrospective North American observational study using propensity score-adjusted analysis.

PubMed

Fallah, Aria; Weil, Alexander G; Juraschka, Kyle; Ibrahim, George M; Wang, Anthony C; Crevier, Louis; Tseng, Chi-Hong; Kulkarni, Abhaya V; Ragheb, John; Bhatia, Sanjiv

2017-12-01

OBJECTIVE Combined endoscopic third ventriculostomy (ETC) and choroid plexus cauterization (CPC)-ETV/CPC- is being investigated to increase the rate of shunt independence in infants with hydrocephalus. The degree of CPC necessary to achieve improved rates of shunt independence is currently unknown. METHODS Using data from a single-center, retrospective, observational cohort study involving patients who underwent ETV/CPC for treatment of infantile hydrocephalus, comparative statistical analyses were performed to detect a difference in need for subsequent CSF diversion procedure in patients undergoing partial CPC (describes unilateral CPC or bilateral CPC that only extended from the foramen of Monro [FM] to the atrium on one side) or subtotal CPC (describes CPC extending from the FM to the posterior temporal horn bilaterally) using a rigid neuroendoscope. Propensity scores for extent of CPC were calculated using age and etiology. Propensity scores were used to perform 1) case-matching comparisons and 2) Cox multivariable regression, adjusting for propensity score in the unmatched cohort. Cox multivariable regression adjusting for age and etiology, but not propensity score was also performed as a third statistical technique. RESULTS Eighty-four patients who underwent ETV/CPC had sufficient data to be included in the analysis. Subtotal CPC was performed in 58 patients (69%) and partial CPC in 26 (31%). The ETV/CPC success rates at 6 and 12 months, respectively, were 49% and 41% for patients undergoing subtotal CPC and 35% and 31% for those undergoing partial CPC. Cox multivariate regression in a 48-patient cohort case-matched by propensity score demonstrated no added effect of increased extent of CPC on ETV/CPC survival (HR 0.868, 95% CI 0.422-1.789, p = 0.702). Cox multivariate regression including all patients, with adjustment for propensity score, demonstrated no effect of extent of CPC on ETV/CPC survival (HR 0.845, 95% CI 0.462-1.548, p = 0.586). Cox multivariate regression including all patients, with adjustment for age and etiology, but not propensity score, demonstrated no effect of extent of CPC on ETV/CPC survival (HR 0.908, 95% CI 0.495-1.664, p = 0.755). CONCLUSIONS Using multiple comparative statistical analyses, no difference in need for subsequent CSF diversion procedure was detected between patients in this cohort who underwent partial versus subtotal CPC. Further investigation regarding whether there is truly no difference between partial versus subtotal extent of CPC in larger patient populations and whether further gain in CPC success can be achieved with complete CPC is warranted.

Prognostic impact of the level of nodal involvement: retrospective analysis of patients with advanced oral squamous cell carcinoma.

PubMed

Murakami, R; Nakayama, H; Semba, A; Hiraki, A; Nagata, M; Kawahara, K; Shiraishi, S; Hirai, T; Uozumi, H; Yamashita, Y

2017-01-01

We retrospectively evaluated the prognostic impact of the level of nodal involvement in patients with advanced oral squamous cell carcinoma (SCC). Between 2005 and 2010, 105 patients with clinical stage III or IV oral SCC had chemoradiotherapy preoperatively. Clinical (cN) and pathological nodal (pN) involvement was primarily at levels Ib and II. We defined nodal involvement at levels Ia and III-V as anterior and inferior extensions, respectively, and recorded such findings as extensive. With respect to pretreatment variables (age, clinical stage, clinical findings of the primary tumour, and nodal findings), univariate analysis showed that extensive cN was the only significant factor for overall survival (hazard ratio [HR], 3.27; 95% CI 1.50 to 7.13; p=0.001). Univariate analysis showed that all pN findings, including the nodal classification (invaded nodes, multiple, and contralateral) and extensive involvement were significant, and multivariate analysis confirmed that extensive pN (HR 4.71; 95% CI 1.85 to 11.97; p=0.001) and multiple pN (HR 2.59; 95% CI 1.10 to 6.09; p=0.029) were independent predictors of overall survival. Assessment based on the level of invaded neck nodes may be a better predictor of survival than the current nodal classification. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction.

PubMed

Domínguez, Eloy; Palau, Patricia; Núñez, Eduardo; Ramón, José María; López, Laura; Melero, Joana; Bellver, Alejandro; Santas, Enrique; Chorro, Francisco J; Núñez, Julio

2018-03-24

The mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR) response to exercise is associated to functional capacity in patients with symptomatic HFpEF. We prospectively studied 74 HFpEF patients [35.1% New York Heart Association Class III, 53% female, age (mean ± standard deviation) 72.5 ± 9.1 years, and 59.5% atrial fibrillation]. Functional performance was assessed by peak oxygen consumption (peak VO 2 ). The mean (standard deviation) peak VO 2 was 10 ± 2.8 mL/min/kg. The following chronotropic parameters were calculated: Delta-HR (HR at peak exercise - HR at rest), chronotropic index (CI) = (HR at peak exercise - resting HR)/[(220 - age) - resting HR], and CI according to the equation developed by Keteyian et al. (CIK) (HR at peak exercise - HR at rest)/[119 + (HR at rest/2) - (age/2) - 5 - HR at rest]. In a bivariate setting, peak VO 2 was positively and significantly correlated with Delta-HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P = 0.055). In a multivariable linear regression analysis that included clinical, analytical, echocardiographic, and functional capacity covariates, the chronotropic parameters were positively associated with peak VO 2 . We found a linear relationship between Delta-HR and peak VO 2 (β coefficient of 0.03; 95% confidence interval: 0.004-0.05; P = 0.030); conversely, the association among CIs and peak VO 2 was exponentially shaped. In patients with chronic HFpEF, the HR response to exercise was positively associated to patient's functional capacity. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Persistence in Therapy With Risperidone and Aripiprazole in Pediatric Outpatients: A 2-Year Naturalistic Comparison.

PubMed

Pozzi, Marco; Pisano, Simone; Bertella, Silvana; Capuano, Annalisa; Rizzo, Renata; Antoniazzi, Stefania; Auricchio, Fabiana; Carnovale, Carla; Cattaneo, Dario; Ferrajolo, Carmen; Gentili, Marta; Guastella, Giuseppe; Mani, Elisa; Rafaniello, Concetta; Riccio, Maria Pia; Scuderi, Maria Grazia; Sperandeo, Serena; Sportiello, Liberata; Villa, Laura; Radice, Sonia; Clementi, Emilio; Rossi, Francesco; Pascotto, Antonio; Bernardini, Renato; Molteni, Massimo; Bravaccio, Carmela

2016-12-01

The practical effectiveness of second-generation antipsychotics in children and adolescents is an understudied issue. It is a crucial area of study, though, because such patients are often treated for long-lasting disorders. We carried out a 24-month (March 2012-March 2014) observational study on an unselected population of pediatric outpatients treated with risperidone, aripiprazole, olanzapine, or quetiapine aiming to (1) describe drug use, (2) compare post hoc the discontinuation rates due to specific causes and dose adjustments by Kaplan-Meier analyses between drugs, and (3) analyze predictors influencing these outcomes by Cox multivariate models. Among 184 pediatric patients, 77% patients were prescribed risperidone, and 18% were prescribed aripiprazole. Olanzapine or quetiapine were scantly used; therefore, they were excluded from analyses. Risperidone was prevalent in younger, male patients with disruptive behavioral disorders; aripiprazole, in patients with tic disorders. Overall, discontinuations occurred mostly in the first 6 months, and, at 24 months, the discontinuation numbers were similar between users of risperidone and aripiprazole (41.5% vs 39.4%). In univariate analyses, dose reduction was higher for aripiprazole (P = .033). Multivariate analyses yielded the following predictors: for all-cause discontinuation, baseline severity (hazard ratio [HR] = 1.48, P = .001) and dose increase (HR = 3.55, P = .001); for patient-decided discontinuation, dose change (increase: HR = 6.43, P = .004; reduction: HR = 7.89, P = .049) and the presence of concomitant drugs (HR = 4.03, P = .034), while autistic patients discontinued less (HR = 0.23, P = .050); for clinician-decided discontinuation due to adverse drug reactions, baseline severity (HR = 1.96, P = .005) and dose increase (HR = 5.09, P = .016); for clinician-decided discontinuation due to inefficacy, baseline severity (HR = 2.88, P = .014) and the use of aripiprazole (HR = 5.55, P = .013); for dose increase, none; for dose reduction, the occurrence of adverse drug reactions (HR = 4.74, P = .046), while dose reduction was less probable in autistic patients (HR = 0.22, P = .042). The findings of this study show a similarity between the overall effectiveness of risperidone and aripiprazole in a real-life pediatric outpatient setting. © Copyright 2016 Physicians Postgraduate Press, Inc.

Preoperative Erythrocyte Sedimentation Rate Independently Predicts Overall Survival in Localized Renal Cell Carcinoma following Radical Nephrectomy

PubMed Central

Cross, Brian W.; Johnson, Timothy V.; DeRosa, Austin B.; Ogan, Kenneth; Pattaras, John G.; Nieh, Peter T.; Kucuk, Omer; Harris, Wayne B.; Master, Viraj A.

2012-01-01

Objectives. To determine the relationship between preoperative erythrocyte sedimentation rate (ESR) and overall survival in localized renal cell carcinoma (RCC) following nephrectomy. Methods. 167 patients undergoing nephrectomy for localized RCC had ESR levels measured preoperatively. Receiver Operating Characteristics curves were used to determine Area Under the Curve and relative sensitivity and specificity of preoperative ESR in predicting overall survival. Cut-offs for low (0.0–20.0 mm/hr), intermediate (20.1–50.0 mm/hr), and high risk (>50.0 mm/hr) groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based groups on overall survival. Univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results. Overall, 55.2% were low risk, while 27.0% and 17.8% were intermediate and high risk, respectively. Median (95% CI) survival was 44.1 (42.6–45.5) months, 35.5 (32.3–38.8) months, and 32.1 (25.5–38.6) months, respectively. After controlling for other patient and tumor characteristics, intermediate and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735–27.649) and 18.5-fold (HR: 18.531, 95% CI: 2.117–162.228) increased risk of overall mortality, respectively. Conclusion. Preoperative ESR values represent a robust predictor of overall survival following nephrectomy in localized RCC. PMID:22900160

Alcohol Intake and Risk of Incident Melanoma: A Pooled Analysis of Three Prospective Studies in the U.S

PubMed Central

Rivera, Andrew; Nan, Hongmei; Li, Tricia; Qureshi, Abrar; Cho, Eunyoung

2016-01-01

Background Alcohol consumption is associated with increased risk of numerous cancers, but existing evidence for an association with melanoma is equivocal. No study has evaluated the association with different anatomic locations of melanoma. Methods We used data from three large prospective cohort studies to investigate whether alcohol intake was associated with risk of melanoma. Alcohol intake was assessed repeatedly by food-frequency questionnaires. A Cox proportional hazards model was used to calculate multivariate-adjusted hazard ratios (HRs). Results A total of 1,374 cases of invasive melanoma were documented during 3,855,706 person-years of follow-up. There was an association between higher alcohol intake and incidence of invasive melanoma (pooled multivariate HR 1.14; 95% confidence interval [CI]: 1.00–1.29] per drink/d, p trend = 0.04). Among alcoholic beverages, white wine consumption was associated with an increased risk of melanoma (pooled multivariate HR 1.13 [95% CI: 1.04–1.24] per drink/d, p trend <0.01) after adjusting for other alcoholic beverages. The association between alcohol consumption and melanoma risk was stronger for melanoma in relatively UV-spared sites (trunk) versus more UV-exposed sites (head, neck, or extremities). Compared to non-drinkers, the pooled multivariate-adjusted HRs for ≥20g/d of alcohol were 1.02 (95% CI: 0.64–1.62; P trend =0.25) for melanomas of the head, neck, and extremities and 1.73 (95% CI: 1.25–2.38; P trend =0.02) for melanomas of the trunk. Conclusions Alcohol intake was associated with a modest increase in the risk of melanoma, particularly in UV-protected sites. Impact These findings further support American Cancer Society Guidelines for Cancer Prevention to limit alcohol intake. PMID:27909090

Body Size Indicators and Risk of Gallbladder Cancer: Pooled Analysis of Individual-Level Data from 19 Prospective Cohort Studies.

PubMed

Campbell, Peter T; Newton, Christina C; Kitahara, Cari M; Patel, Alpa V; Hartge, Patricia; Koshiol, Jill; McGlynn, Katherine A; Adami, Hans-Olov; Berrington de González, Amy; Beane Freeman, Laura E; Bernstein, Leslie; Buring, Julie E; Freedman, Neal D; Gao, Yu-Tang; Giles, Graham G; Gunter, Marc J; Jenab, Mazda; Liao, Linda M; Milne, Roger L; Robien, Kim; Sandler, Dale P; Schairer, Catherine; Sesso, Howard D; Shu, Xiao-Ou; Weiderpass, Elisabete; Wolk, Alicja; Xiang, Yong-Bing; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Gapstur, Susan M

2017-04-01

Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking. Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist-height ratio (WHtR), hip circumference (HC), and waist-hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI). Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m 2 , HR: 1.24; 95% CI, 1.13-1.35), young adult BMI (per 5 kg/m 2 , HR: 1.12; 95% CI, 1.00-1.26), adult weight gain (per 5 kg, HR: 1.07; 95% CI, 1.02-1.12), height (per 5 cm, HR: 1.10; 95% CI, 1.03-1.17), WC (per 5 cm, HR: 1.09; 95% CI, 1.02-1.17), WHtR (per 0.1 unit, HR: 1.24; 95% CI, 1.00-1.54), and HC (per 5 cm, HR: 1.13; 95% CI, 1.04-1.22), but not WHR (per 0.1 unit, HR: 1.03; 95% CI, 0.87-1.22), were associated with higher risks of gallbladder cancer, and results did not differ meaningfully by sex or other demographic/lifestyle factors. Conclusions: These findings indicate that measures of overall and central excess body weight are associated with higher gallbladder cancer risks. Impact: Excess body weight is an important, and potentially preventable, gallbladder cancer risk factor. Cancer Epidemiol Biomarkers Prev; 26(4); 597-606. ©2017 AACR . ©2017 American Association for Cancer Research.

Neutrophil-lymphocyte ratio predicts survival in patients with advanced cholangiocarcinoma on chemotherapy.

PubMed

Lee, Ban Seok; Lee, Sang Hyub; Son, Jun Hyuk; Jang, Dong Kee; Chung, Kwang Hyun; Lee, Yoon Suk; Paik, Woo Hyun; Ryu, Ji Kon; Kim, Yong-Tae

2016-02-01

The blood neutrophil-to-lymphocyte ratio (NLR) is reported to be a prognostic marker in several cancers. However, the prognostic role of NLR in patients with advanced cholangiocarcinoma on chemotherapy is unknown. A total of 221 patients with pathologically confirmed locally advanced or metastatic cholangiocarcinoma receiving first-line palliative chemotherapy were enrolled. Associations between baseline clinical and laboratory variables including NLR and survival were investigated. Patients were classified into two groups according to the NLR level (≤ 5 vs. >5). Median overall survival (OS) and time to progression (TTP) in patients with NLR ≤ 5 were 10.9 and 6.7 months, respectively, and 6.8 and 4.1 months in patients with NLR > 5 (P < 0.001, P = 0.002, respectively). In multivariate analysis, number of cycles of chemotherapy was a significant predictor of longer OS (HR 0.86, P < 0.001), whereas adverse prognostic factors for OS were CA 19-9 > 300 (HR 1.43, P = 0.025), CEA > 5 (HR 1.44, P = 0.029), higher stage (HR 1.69, P = 0.004), and NLR > 5 (HR 1.87, P < 0.001). NLR > 5 was also associated with reduced TTP (HR 1.66, P = 0.007). Among 50 patients with initial NLR > 5, 33 patients had NLR ≤ 5 after two cycles of chemotherapy and they had significantly better survival than the others (HR 0.48, P = 0.015). NLR independently predicts survival in patients with advanced cholangiocarcinoma undergoing chemotherapy. Considering cost-effectiveness and easy availability, NLR may be a useful biomarker for prognosis prediction.

Postoperative Morbidity and Mortality of Perforated Peptic Ulcer: Retrospective Cohort Study of Risk Factors among Black Africans in Côte d'Ivoire.

PubMed

Gona, Soro Kountele; Alassan, Mahassadi Kouamé; Marcellin, Koffi Gnangoran; Henriette, Kissi Ya; Adama, Coulibaly; Toussaint, Assohoun; Manuela, Ehua Adjoba; Sylvain, Seu Gagon; Anthony, Afum-Adjei Awuah; Francis, Ehua Somian

2016-01-01

Introduction. Surgical treatment of perforated peptic ulcer (PPU) is a challenge for surgeons in Africa. Aim. To determine risk factors of postoperative complications or mortality among black Ivoirian patients with PPU. Methods. All 161 patients (median age = 34 years, 90.7 male) operated on for PPU in the visceral and general surgery unit were enrolled in a retrospective cohort study. Variables were studied with Kaplan Meier and Cox proportional hazard models. Results. Among 161 patients operated on for PPU, 36 (27.5%) experienced complications and 31 (19.3%) died. Follow-up results were the incidence of complications and mortality of 6.4 (95% CI: 4.9-8.0) per 100 person-days and 3.0 (95% CI: 1.9-4.0) per 100 person-days for incidence of mortality. In multivariate analysis, risk factors of postoperative complications or mortality were comorbidities (HR = 2.1, P = 0.03), tachycardia (pulse rate > 100/minutes) (HR = 2.4, P = 0.02), purulent intra-abdominal fluid collection (HR = 2.1, P = 0.04), hyponatremia (median value ≤ 134 mEq/L) (HR = 2.3, P = 0.01), delayed time of hospital admission > 72 hours (HR = 2.6, P < 0.0001), and delayed time of surgical intervention between 24 and 48 hours (HR = 3.8, P < 0.0001). Conclusion. The delayed hospital admission or surgical intervention and hyponatremia may be considered as additional risk of postoperative complications or mortality in Black African patients with PPU.

Coffee consumption and mortality in three Eastern European countries: results from the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study.

PubMed

Grosso, Giuseppe; Stepaniak, Urszula; Micek, Agnieszka; Stefler, Denes; Bobak, Martin; Pajak, Andrzej

2017-01-01

To test the association between coffee consumption and risk of all-cause, CVD and cancer death in a European cohort. Prospective cohort study. Cox proportional hazards models with adjustment for potential confounders to estimate multivariable hazard ratios (HR) and 95 % CI were used. Czech Republic, Russia and Poland. A total of 28561 individuals followed for 6·1 years. A total of 2121 deaths (43·1 % CVD and 35·7 % cancer mortality) occurred during the follow-up. Consumption of 3-4 cups coffee/d was associated with lower mortality risk in men (HR=0·83; 95 % CI 0·71, 0·99) and women (HR=0·63; 95 % CI 0·47, 0·84), while further intake showed non-significant reduced risk estimates (HR=0·71; 95 % CI 0·49, 1·04 and HR=0·51; 95 % CI 0·24, 1·10 in men and women, respectively). Decreased risk of CVD mortality was also found in men (HR=0·71; 95 % CI 0·54, 0·93) for consumption of 3-4 cups coffee/d. Stratified analysis revealed that consumption of a similar amount of coffee was associated with decreased risk of all-cause (HR=0·61; 95 % CI 0·43, 0·87) and cancer mortality (HR=0·59; 95 % CI 0·35, 0·99) in non-smoking women and decreased risk of all-cause mortality for >4 cups coffee/d in men with no/moderate alcohol intake. Coffee consumption was associated with decreased risk of mortality. The protective effect was even stronger when stratification by smoking status and alcohol intake was performed.

Disparities in completion rates of the medical prerenal transplant evaluation by race or ethnicity and gender.

PubMed

Monson, Rebecca S; Kemerley, Patricia; Walczak, Douglas; Benedetti, Enrico; Oberholzer, Jose; Danielson, Kirstie K

2015-01-01

A significant number of potential kidney transplant candidates do not complete the required medical evaluation after referral to a transplant program. Factors associated with rate of completion of the renal transplant evaluation were analyzed using a retrospective chart review of patients first seen between October 1, 2009, and September 30, 2010 (n=256). The primary endpoint was completion in 12 months. Independent variables included socioeconomic, demographic, and medical factors. Mean age was 50.7 years; 49.6% were black, 28.5% Hispanic, and 21.9% white and other; 26.3% did not require dialysis. During follow-up, 23.4% did not complete the evaluation. Multivariable analysis indicated that slower rates of completion were associated with needing a greater number of medical tests (compared to 0-2: 3-5 tests, hazard ratio [HR]=0.65, P=0.02; ≥ 6 tests, HR=0.47, P=0.0005) and requiring more than one hospitalization (compared to none: HR=0.37, P=0.0008). A significant interaction between race or ethnicity and gender on completion was found: compared to black men, Hispanic men (HR=2.75, P<0.0001), Hispanic women (HR=1.96, P=0.006), and white men (HR=1.99, P=0.005) showed a more rapid completion. In comparison, black and white women (HR=1.38, P=0.16; HR=0.94, P=0.83, respectively) were not significantly different from black men in rates of completion. Differences by race or ethnicity and gender were not confounded by socioeconomic variables or social support. To lessen barriers and facilitate renal transplantation, black men and women, white women, and patients needing multiple medical tests and requiring several hospitalizations may benefit from additional assistance during the medical evaluation process.

Contraceptive method and pregnancy incidence among African women in HIV-1 serodiscordant partnerships

PubMed Central

NGURE, Kenneth; HEFFRON, Renee; MUGO, Nelly R.; CELUM, Connie; COHEN, Craig R.; ODOYO, Josephine; REES, Helen; KIARIE, James N.; WERE, Edwin; BAETEN, Jared M.

2014-01-01

Background Effective contraception reduces unintended pregnancies and is a central strategy to reduce vertical HIV-1 transmission for HIV-1 infected women. Methods Among 2269 HIV-1 seropositive and 1085 seronegative women from 7 African countries who were members of HIV-1 serodiscordant heterosexual partnerships and who were participating in an HIV-1 prevention clinical trial, we assessed pregnancy incidence for women using various contraceptive methods using multivariate Andersen-Gill analysis. Results Compared with women using no contraceptive method, pregnancy incidence was significantly reduced among HIV-1 seropositive and seronegative women using injectable contraception (adjusted hazard ratio (aHR) 0.24, p=0.001 and aHR 0.25, p<0.001, respectively). Oral contraceptives significantly reduced pregnancy risk only among HIV-1 seropositive women (aHR 0.51, p=0.004) but not seronegative women (aHR 0.64, p=0.3), and, for both seropositive and seronegative women, oral contraceptive pill users were more likely to become pregnant than injectable contraceptive users (aHR 2.22, p=0.01 for HIV-1 seropositive women and aHR 2.65, p=0.09 for HIV-1 seronegative women). Condoms, when reported as being used as the primary contraceptive method, marginally reduced pregnancy incidence (aHR 0.85, p=0.1 for seropositive women and aHR 0.67, p=0.02 for seronegative women). There were no pregnancies among women using intrauterine devices, implantable methods or who had undergone surgical sterilization, although these methods were used relatively infrequently. Conclusions Family planning programs and HIV-1 prevention trials need innovative ways to motivate uptake and sustained use of longer acting, less user-dependent contraception for women who do not desire pregnancy. PMID:22156966

Contraceptive method and pregnancy incidence among women in HIV-1-serodiscordant partnerships.

PubMed

Ngure, Kenneth; Heffron, Renee; Mugo, Nelly R; Celum, Connie; Cohen, Craig R; Odoyo, Josephine; Rees, Helen; Kiarie, James N; Were, Edwin; Baeten, Jared M

2012-02-20

Effective contraception reduces unintended pregnancies and is a central strategy to reduce vertical HIV-1 transmission for HIV-1-infected women. Among 2269 HIV-1-seropositive and 1085-seronegative women from seven African countries who were members of HIV-1-serodiscordant heterosexual partnerships and who were participating in an HIV-1 prevention clinical trial, we assessed pregnancy incidence according to contraceptive method using multivariate Andersen-Gill analysis. Compared with women using no contraceptive method, pregnancy incidence was significantly reduced among HIV-1-seropositive and HIV-1-seronegative women using injectable contraception [adjusted hazard ratio (aHR) 0.24, P = 0.001 and aHR 0.25, P < 0.001, respectively). Oral contraceptives significantly reduced pregnancy risk only among HIV-1-seropositive women (aHR 0.51, P = 0.004) but not seronegative women (aHR 0.64, P = 0.3), and, for both seropositive and seronegative women, oral contraceptive pill users were more likely to become pregnant than injectable contraceptive users (aHR 2.22, P = 0.01 for HIV-1-seropositive women and aHR 2.65, P = 0.09 for HIV-1-seronegative women). Condoms, when reported as being used as the primary contraceptive method, marginally reduced pregnancy incidence (aHR 0.85, P = 0.1 for seropositive women and aHR 0.67, P = 0.02 for seronegative women). There were no pregnancies among women using intrauterine devices, implantable methods or who had undergone surgical sterilization, although these methods were used relatively infrequently. Family planning programs and HIV-1 prevention trials need innovative ways to motivate uptake and sustained use of longer acting, less user-dependent contraception for women who do not desire pregnancy.

The prognostic role of hemoglobin levels in patients undergoing concurrent chemo-radiation for anal cancer.

PubMed

Franco, Pierfrancesco; Montagnani, Francesco; Arcadipane, Francesca; Casadei, Chiara; Andrikou, Kalliopi; Martini, Stefania; Iorio, Giuseppe Carlo; Scartozzi, Mario; Mistrangelo, Massimiliano; Fornaro, Lorenzo; Cassoni, Paola; Cascinu, Stefano; Ricardi, Umberto; Casadei Gardini, Andrea

2018-05-02

Concurrent chemo-radiation (CT-RT) is a standard therapy for squamous cell carcinoma of anal canal. Different clinical and biological factors may potentially affect outcome. We investigated the prognostic role of baseline hemoglobin (Hb) in a cohort of anal cancer patients submitted to CT-RT with 5-fluorouracil and mitomycin C. Up to 161 patients with clinical stage T1-T4/N0-N3/M0 were treated. Response was assessed at 6 weeks and thereafter at 3, 6 and 12 months. Two different approaches were used:a)simultaneous integrated boost following RTOG 05-29 indications;b)first sequence of 45Gy/25 fractions to the pelvis followed by 9-14.4 Gy/5-8 fractions to the macroscopic disease. Primary endpoints were progression-free survival (PFS) and overall survival (OS). On multivariate analysis, pre-treatment Hb level had a significant correlation to OS (HR:0.53;95% CI:0.33-0.87; p = 0.001), but not to PFS (HR:0.78;95% CI:0.53-1.15; p = 0.12) Patients with pre-treatment Hb ≥ 12 g/dl had 5-year PFS and OS of 82.2%, compared to 29.3% and 32.8% for those below the threshold. The likelihood to achieve a complete remission increased by 5.6% for every single-unit (g/dl) increase in baseline Hb level over 11 g/dl. On multivariate analysis, response to treatment had a significant correlation to PFS (incomplete vs complete response - HR:5.43;95% CI:2.75-10.7; p < 0.0001) and OS (HR: 6.96;95% CI:2.96-16.5; p < 0.0001). We showed that baseline Hb level is a strong indicator for poor response to RT-CT in anal cancer patients. A close clinical monitoring for incomplete response to treatment should be advised in patients with low pre-treatment Hb. The hypothesis that the preservation of adequate Hb level during treatment may lead to a better outcome needs prospective evaluation.

Medullary Thyroid Carcinoma in MEN2A: ATA Moderate- or High-Risk RET Mutations Do Not Predict Disease Aggressiveness.

PubMed

Voss, Rachel K; Feng, Lei; Lee, Jeffrey E; Perrier, Nancy D; Graham, Paul H; Hyde, Samuel M; Nieves-Munoz, Frances; Cabanillas, Maria E; Waguespack, Steven G; Cote, Gilbert J; Gagel, Robert F; Grubbs, Elizabeth G

2017-08-01

High-risk RET mutations (codon 634) are associated with earlier development of medullary thyroid carcinoma (MTC) and presumed increased aggressiveness compared with moderate-risk RET mutations. To determine whether high-risk RET mutations are more aggressive. Retrospective cohort study using institutional multiple endocrine neoplasia type 2 registry. Tertiary cancer care center. Patients with MTC and moderate- or high-risk germline RET mutation. None (observational study). Proxies for aggressiveness were overall survival (OS) and time to distant metastatic disease (DMD). A total of 127 moderate-risk and 135 high-risk patients were included (n = 262). Median age at diagnosis was 42.3 years (range, 6.4 to 86.4 years; mean, 41.6 years) for moderate-risk mutations and 23.0 years (range, 3.7 to 66.8 years; mean, 25.6 years) for high-risk mutations (P < 0.0001). Moderate-risk patients had more T3/T4 tumors at diagnosis (P = 0.03), but there was no significant difference for N or M stage and no significant difference in OS (P = 0.40). From multivariable analysis for OS, increasing age [hazard ratio (HR), 1.05/y; 95% confidence interval (CI), 1.03 to 1.08], T3/T4 tumor (HR, 2.73; 95% CI, 1.22 to 6.11), and M1 status at diagnosis (HR, 3.93; 95% CI, 1.61 to 9.59) were significantly associated with worse OS but high-risk mutation was not (P = 0.40). No significant difference was observed for development of DMD (P = 0.33). From multivariable analysis for DMD, only N1 status at diagnosis was significant (HR, 2.10; 95% CI, 1.03 to 4.27). Patients with high- and moderate-risk RET mutations had similar OS and development of DMD after MTC diagnosis and therefore similarly aggressive clinical courses. High-risk connotes increased disease aggressiveness; thus, future guidelines should consider RET mutation classification by disease onset (early vs late) rather than by risk (high vs moderate). Copyright © 2017 Endocrine Society

Association between body mass index and outcomes after percutaneous coronary intervention in multiethnic South East Asian population: a retrospective analysis of the Malaysian National Cardiovascular Disease Database-Percutaneous Coronary Intervention (NCVD-PCI) registry.

PubMed

Azhari, Zaid; Ismail, Muhammad Dzafir; Zuhdi, Ahmad Syadi Mahmood; Md Sari, Norashikin; Zainal Abidin, Imran; Wan Ahmad, Wan Azman

2017-11-09

To examine the relationship between body mass index (BMI) and outcomes after percutaneous coronary intervention (PCI) in a multiethnic South East Asian population. Fifteen participating cardiology centres contributed to the Malaysian National Cardiovascular Disease Database-Percutaneous Coronary Intervention (NCVD-PCI) registry. 28 742 patients from the NCVD-PCI registry who had their first PCI between January 2007 and December 2014 were included. Those without their BMI recorded or BMI <11 kg/m 2 or >70 kg/m 2 were excluded. In-hospital death, major adverse cardiovascular events (MACEs), vascular complications between different BMI groups were examined. Multivariable-adjusted HRs for 1-year mortality after PCI among the BMI groups were also calculated. The patients were divided into four groups; underweight (BMI <18.5 kg/m 2 ), normal BMI (BMI 18.5 to <23 kg/m 2 ), overweight (BMI 23 to <27.5 kg/m 2 ) and obese (BMI ≥27.5 kg/m 2 ). Comparison of their baseline characteristics showed that the obese group was younger, had lower prevalence of smoking but higher prevalence of diabetes, hypertension and dyslipidemia. There was no difference found in terms of in-hospital death, MACE and vascular complications after PCI. Multivariable Cox proportional hazard regression analysis showed that compared with normal BMI group the underweight group had a non-significant difference (HR 1.02, p=0.952), while the overweight group had significantly lower risk of 1-year mortality (HR 0.71, p=0.005). The obese group also showed lower HR but this was non-significant (HR 0.78, p=0.056). Using Asian-specific BMI cut-off points, the overweight group in our study population was independently associated with lower risk of 1-year mortality after PCI compared with the normal BMI group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Racial differences in the development of de-novo donor-specific antibodies and treated antibody-mediated rejection after heart transplantation.

PubMed

Cole, Robert Townsend; Gandhi, Jonathan; Bray, Robert A; Gebel, Howard M; Yin, Michael; Shekiladze, Nikolaz; Young, An; Grant, Aubrey; Mahoney, Ian; Laskar, S Raja; Gupta, Divya; Bhatt, Kunal; Book, Wendy; Smith, Andrew; Nguyen, Duc; Vega, J David; Morris, Alanna A

2018-04-01

Despite improvements in outcomes after heart transplantation, black recipients have worse survival compared with non-black recipients. The source of such disparate outcomes remains largely unknown. We hypothesize that a propensity to generate de-novo donor-specific antibodies (dnDSA) and subsequent antibody-mediated rejection (AMR) may account for racial differences in sub-optimal outcomes after heart transplant. In this study we aimed to determine the role of dnDSA and AMR in racial disparities in post-transplant outcomes. This study was a single-center, retrospective analysis of 137 heart transplant recipients (81% male, 48% black) discharged from Emory University Hospital. Patients were classified as black vs non-black for the purpose of our analysis. Kaplan-Meier and Cox regression analyses were used to evaluate the association between race and selected outcomes. The primary outcome was the development of dnDSA. Secondary outcomes included treated AMR and a composite of all-cause graft dysfunction or death. After 3.7 years of follow-up, 39 (28.5%) patients developed dnDSA and 19 (13.8%) were treated for AMR. In multivariable models, black race was associated with a higher risk of developing dnDSA (hazard ratio [HR] 3.65, 95% confidence interval [CI] 1.54 to 8.65, p = 0.003) and a higher risk of treated AMR (HR 4.86, 95% CI 1.26 to 18.72, p = 0.021) compared with non-black race. Black race was also associated with a higher risk of all-cause graft dysfunction or death in univariate analyses (HR 2.10, 95% CI 1.02 to 4.30, p = 0.044). However, in a multivariable model incorporating dnDSA, black race was no longer a significant risk factor. Only dnDSA development was significantly associated with all-cause graft dysfunction or death (HR 4.85, 95% CI 1.89 to 12.44, p = 0.001). Black transplant recipients are at higher risk for the development of dnDSA and treated AMR, which may account for racial disparities in outcomes after heart transplantation. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org; Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center, Tampa, Florida; Fulp, William J.

Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSImore » and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and molecular subtype could be useful in guiding radiation therapy–based decisions in breast cancer.« less

Survival rates and worker compensation expenses in a national cohort of Mexican workers with permanent occupational disability caused by diabetes.

PubMed

Ascencio-Montiel, Iván de Jesús; Kumate-Rodríguez, Jesús; Borja-Aburto, Víctor Hugo; Fernández-Garate, José Esteban; Konik-Comonfort, Selene; Macías-Pérez, Oliver; Campos-Hernández, Ángel; Rodríguez-Vázquez, Héctor; López-Roldán, Verónica Miriam; Zitle-García, Edgar Jesús; Solís-Cruz, María Del Carmen; Velázquez-Ramírez, Ismael; Aguilar-Jiménez, Miriam; Villa-Caballero, Leonel; Cisneros-González, Nelly

2016-09-01

Permanent occupational disability is one of the most severe consequences of diabetes that impedes the performance of usual working activities among economically active individuals. Survival rates and worker compensation expenses have not previously been examined among Mexican workers. We aimed to describe the worker compensation expenses derived from pension payments and also to examine the survival rates and characteristics associated with all-cause mortality, in a cohort of 34,014 Mexican workers with permanent occupational disability caused by diabetes during the years 2000-2013 at the Mexican Institute of Social Security. A cross-sectional analysis study was conducted using national administrative records data from the entire country, regarding permanent occupational disability medical certification, pension payment and vital status. Survival rates were estimated using the Kaplan-Meier method. Multivariate Cox proportional hazard model was used to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (95 % CI) in order to assess the cohort characteristics and all-cause mortality risk. Total expenses derived from pension payments for the period were accounted for in U.S. dollars (USD, 2013). There were 12,917 deaths in 142,725.1 person-years. Median survival time was 7.26 years. After multivariate adjusted analysis, males (HR, 1.39; 95 % CI, 1.29-1.50), agricultural, forestry, and fishery workers (HR, 1.41; 95 % CI, 1.15-1.73) and renal complications (HR, 3.49; 95 % CI, 3.18-3.83) had the highest association with all-cause mortality. The all-period expenses derived from pension payments amounted to $777.78 million USD (2013), and showed a sustained increment: from $58.28 million USD in 2000 to $111.62 million USD in 2013 (percentage increase of 91.5 %). Mexican workers with permanent occupational disability caused by diabetes had a median survival of 7.26 years, and those with renal complications showed the lowest survival in the cohort. Expenses derived from pension payments amounted to $ 777 million USD and showed an important increase from 2000 to 2013.

Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merrell, Kenneth W.; Haddock, Michael G.; Quevedo, J. Fernando

Purpose: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). Methods and Materials: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gymore » in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. Results: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). Conclusions: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as adjuvant locoregional treatment following pancreatic cancer resection.« less

Relationship Between Persistent Pain and 5-Year Mortality: A Population-Based Prospective Cohort Study

PubMed Central

Shega, Joseph W.; Andrew, Melissa; Kotwal, Ashwin; Lau, Denys T.; Herr, Keela; Ersek, Mary; Weiner, Debra K.; Chin, Marshall H.; Dale, William

2014-01-01

OBJECTIVES To assess the association between self-reported noncancer pain and 5-year mortality. DESIGN Cohort. SETTING Community-dwelling older adults. PARTICIPANTS Canadian Study of Health and Aging 1996 wave. MEASUREMENTS Registrar of Vital Statistics–established 5-year mortality. Noncancer pain was assessed using the 5-point verbal descriptor scale, dichotomized into no or very mild versus moderate, severe, or very severe pain. Frailty was the accumulation of health deficits. Cognitive status (Modified Mini-Mental State Examination) and depressed mood (five-item mental health screening questionnaire) were also assessed. Multivariable logistic regression and Cox proportional hazards were used to analyze the relationship between pain and 5-year mortality. RESULTS Of 5,703 participants, 4,694 (82.3%) had complete data for analysis; 1,663 of these (35.4%) reported moderate, severe, or very severe pain, and 1,343 (28.6%) had died at 5-year follow-up. Four hundred ninety-six of those who died (29.8%) reported moderate, severe, or very severe pain and 847 (27.9%) no or very mild pain. Multivariate logistic analysis found that individuals with moderate, severe, or very severe pain had lower odds of 5-year mortality than those with no or very mild pain (odds ratio = 0.78, 95% confidence interval (CI) = 0.66–0.92; P < .001). The risk of death was lower in persons reporting moderate or greater pain than in those with no or very mild pain (HR = 0.85, 95% CI = 0.75–0.96; P = .01). An interaction between pain and sex explained this effect. Men with pain were not significantly more likely than men without pain to die (HR = 1.00, 95% CI = 0.84–1.19; P = .99), whereas women without pain (HR = 0.54, 95% CI = 0.47–0.63; P < 0.01) and women with pain (HR = 0.40; CI = 0.33–0.47; P < .01) had less risk of death than men without and with pain, respectively. CONCLUSION Older women with pain were less likely to die within 5 years than older women without pain, men in pain, or men without pain. PMID:24320761

An evaluation of the impact of donor BMI on survival and post-transplant obesity in pediatric liver transplant recipients

PubMed Central

Perito, Emily Rothbaum; Rhee, Sue; Glidden, Dave; Roberts, John Paul; Rosenthal, Philip

2012-01-01

Introduction In adult liver transplant recipients, donor BMI is associated with post-transplant obesity but not graft or patient survival. Given the U.S. obesity epidemic and already-limited supply of liver donors, clarifying whether donor BMI affects pediatric outcomes is important. Methods UNOS data on pediatric U.S. liver transplants 1990-2010 was evaluated. Data on transplants 2004-2010 (n=3788) was used for survival analysis with Kaplan-Meier and Cox proportional hazards models and for post-transplant obesity analysis with generalized estimating equations. Results For children receiving adult donor livers, donor BMI 25-35 kg/m2 was not associated with graft or patient survival in univariate or multivariate analyses. Donor BMI>35 kg/m2 increased the risk of graft loss (HR 2.54, 95%CI 1.29-5.01, p=0.007) and death (HR 3.56, 95%CI 1.64-7.72, p=0.001). For pediatric donors, donor BMI was not associated with graft loss or mortality in univariate or multivariate analysis. Donor overweight/obesity was not a risk factor for post-transplant obesity. Conclusions Overweight/obesity is common among liver transplant donors. This analysis suggests that for adult donors, BMI 25-35 should not by itself be a contraindication to liver donation. Severe obesity (BMI>35) in adult donors increased the risk of graft loss and mortality, even after adjustment for recipient, donor, and transplant risk factors. Post-transplant obesity was not associated with donor BMI in this analysis. Further research is needed to clarify the impact of donor obesity on pediatric liver transplant recipients. PMID:22467594

Effect of age on rates of palliative surgery and chemotherapy use in patients with locally advanced or metastatic gastric cancer.

PubMed

Nelen, S D; van Putten, M; Lemmens, V E P P; Bosscha, K; de Wilt, J H W; Verhoeven, R H A

2017-12-01

This study assessed trends in the treatment and survival of palliatively treated patients with gastric cancer, with a focus on age-related differences. For this retrospective, population-based, nationwide cohort study, all patients diagnosed between 1989 and 2013 with non-cardia gastric cancer with metastasized disease or invasion into adjacent structures were selected from the Netherlands Cancer Registry. Trends in treatment and 2-year overall survival were analysed and compared between younger (age less than 70 years) and older (aged 70 years or more) patients. Analyses were done for five consecutive periods of 5 years, from 1989-1993 to 2009-2013. Multivariable logistic regression analysis was used to examine the probability of undergoing surgery. Multivariable Cox regression analysis was used to identify independent risk factors for death. Palliative resection rates decreased significantly in both younger and older patients, from 24·5 and 26·2 per cent to 3·0 and 5·0 per cent respectively. Compared with patients who received chemotherapy alone, both younger (21·6 versus 6·3 per cent respectively; P < 0·001) and older (14·7 versus 4·6 per cent; P < 0·001) patients who underwent surgery had better 2-year overall survival rates. Multivariable analysis demonstrated that younger and older patients who received chemotherapy alone had worse overall survival than patients who had surgery only (younger: hazard ratio (HR) 1·22, 95 per cent c.i. 1·12 to 1·33; older: HR 1·12, 1·01 to 1·24). After 2003 there was no association between period of diagnosis and overall survival in younger or older patients. Despite changes in the use of resection and chemotherapy as palliative treatment, overall survival rates of patients with advanced and metastatic gastric cancer did not improve. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Health-related Quality of Life After Radical Cystectomy: A Cross-sectional Study With Matched-pair Analysis on Ileal Conduit vs Ileal Orthotopic Neobladder Diversion.

PubMed

Cerruto, Maria Angela; D'Elia, Carolina; Siracusano, Salvatore; Saleh, Omar; Gacci, Mauro; Cacciamani, Giovanni; De Marco, Vincenzo; Porcaro, Antonio Benito; Balzarro, Matteo; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Serni, Sergio; Carini, Marco; Verze, Paolo; Artibani, Walter

2017-10-01

To examine the different and health-related quality of life (HR-QoL) outcomes between ileal conduit (IC) and ileal orthotopic neobladder (IONB) in patients who underwent radical cystectomy (RC), by using validated self-reported cancer-specific instruments. This retrospective, cross-sectional, multicenter cohort study included 148 and 171 patients with either IC or IONB. HR-QoL was evaluated with Quality of Life Core Questionnaire and bladder module (BLM)-30 European Organisation for Research and Treatment of Cancer questionnaires. Baseline HR-QoL scores were dichotomized at the median to give "good" or "poor" score profiles. A matched-pair analysis compared HR-QoL aspects between 79 IC patients and 79 IONB patients. At univariate analysis IONB resulted favorable for physical functioning, emotional functioning, cognitive functioning (CF), fatigue, dyspnea, appetite loss, constipation (CO), and abdominal bloating flatulence (AB). At multivariate analyses, IONB showed better scores for emotional functioning (85 vs 79, P = .023), CF (93 vs 85, P <.001), CO (16 vs 31, P <.001), and AB (12 vs 25, P <.001). A significant worsening of sexual and urinary function was observed for IONB patients in the long-term. At matched-pair analysis, global health status was similar (65 vs 62, P = .385). Significantly better scores were observed in the IONB group for the following items: CF (P = .007), fatigue (P = .003), pain (P = .019), dyspnea (P = .016), CO (P = .001), and AB (P = .00). IONB and IC after RC were similar in terms of global health status. IONB provides better results in some aspects of HR-QoL related to bowel function, but a worsening of urinary and sexual functions. Further randomized controlled trials are needed to confirm these data. Copyright © 2017 Elsevier Inc. All rights reserved.

[A clinical study on the relationship of autonomic nervous function and arteriosclerosis in patients with essential hypertension].

PubMed

Zhao, G; Li, S H; Tan, X

2016-03-01

To investigate the relationship between autonomic nervous function and arteriosclerosis in patients with essential hypertension. From January 2011 to December 2013, a total of 269 patients with essential hypertension hospitalized in Chang'an Branch of First People's Hospital of Liangshan were divided into normal PWV group (PWV<9 m/s, n=178) and high PWV group (PWV≥9 m/s, n=91) via the results of carotid-femoral pulse wave velocity (PWV). Synchronic 24 hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed for all participants to simultaneously monitor the heart rate variability (HRV) and blood pressure variability (BPV) in these patients. Pearson single factor analysis and multivariate logistic regression analysis were performed to define the relationship between PWV and HRV, BPV respectively. The level of nHR/dHR (index of heart rate variability), 24 hour'sSSD, dSSD, nSSD (indexes of blood pressure variability) increased significantly (all P<0.05), while the level of SDANN (index of heart rate variability) decreased significantly (P<0.05) in high PWV group compared with normal PWV group. Multiple linear regression analysis showed that PWV was positively correlated with 24 hour'sSSD, 24 hour'sPP, LF, LF/HF and night/day heart rate ratio (all P<0.05). HRV (LF, LF/HF, nHR/dHR) and BPV (24 hours'SSD, dSSD, nSSD) are positively correlated to arteriosclerosis in patients with essential hypertension. Our results show that sympathetic activation and vascular injury are closely related in patients with essential hypertension.

Homoarginine and all-cause mortality: A systematic review and meta-analysis.

PubMed

Zinellu, Angelo; Paliogiannis, Panagiotis; Carru, Ciriaco; Mangoni, Arduino A

2018-05-28

Homoarginine, a basic amino acid and analogue of L-arginine, has been shown to exert salutary effects on vascular homoeostasis, possibly through interaction with the enzymes nitric oxide synthase and arginase. This might translate into improved survival outcomes, particularly in subjects with moderate-high cardiovascular risk. We conducted a systematic review and meta-analysis to investigate the association between circulating homoarginine concentrations and all-cause mortality in observational studies of human cohorts. Studies reporting baseline circulating homoarginine concentrations and all-cause mortality as outcome were searched using the MEDLINE, Scopus and Cochrane databases until January 2018. Hazard ratios (HRs) with 95% confidence intervals (CIs) derived from multivariate Cox's proportional-hazards analysis were extracted from individual studies. A total of 13 studies in 11 964 participants were included in the final analysis. Homoarginine concentrations were inversely associated with all-cause mortality (HR 0.64, 95% CI 0.57-0.73). This association remained significant in participant sub-groups with predominant cardiovascular disease (HR 0.64, 95% CI 0.55-0.76) and renal disease (HR 0.60, 95% CI 0.46-0.68). This meta-analysis of observational studies showed an inverse association between circulating homoarginine concentrations and all-cause mortality. Further research is warranted to investigate the direct effects of homoarginine on cardiovascular homoeostasis, the associations between homoarginine and all-cause mortality in other population groups, and the effects of interventions on homoarginine concentrations on clinical outcomes. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus.

PubMed

Fasano, Serena; Pierro, Luciana; Pantano, Ilenia; Iudici, Michele; Valentini, Gabriele

2017-07-01

Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE. Patients consecutively admitted to our center who, at admission, satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus Collaborating Clinics classification criteria for SLE, and had not experienced any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c-HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ associated with a lower incidence of CVE. Cox regression analysis served to identify factors associated with a first CVE. For the study, 189 patients with SLE were enrolled and monitored for 13 years (median). Ten CVE occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047, respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR 18.054) increased the risk of a first CVE. Our results suggest that prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional evidence for its continued use in patients with SLE.

A traditional Sami diet score as a determinant of mortality in a general northern Swedish population.

PubMed

Nilsson, Lena Maria; Winkvist, Anna; Brustad, Magritt; Jansson, Jan-Håkan; Johansson, Ingegerd; Lenner, Per; Lindahl, Bernt; Van Guelpen, Bethany

2012-05-04

To examine the relationship between "traditional Sami" dietary pattern and mortality in a general northern Swedish population. Population-based cohort study. We examined 77,319 subjects from the Västerbotten Intervention Program (VIP) cohort. A traditional Sami diet score was constructed by adding 1 point for intake above the median level of red meat, fatty fish, total fat, berries and boiled coffee, and 1 point for intake below the median of vegetables, bread and fibre. Hazard ratios (HR) for mortality were calculated by Cox regression. Increasing traditional Sami diet scores were associated with slightly elevated all-cause mortality in men [Multivariate HR per 1-point increase in score 1.04 (95% CI 1.01-1.07), p=0.018], but not for women [Multivariate HR 1.03 (95% CI 0.99-1.07), p=0.130]. This increased risk was approximately equally attributable to cardiovascular disease and cancer, though somewhat more apparent for cardiovascular disease mortality in men free from diabetes, hypertension and obesity at baseline [Multivariate HR 1.10 (95% CI 1.01-1.20), p=0.023]. A weak increased all-cause mortality was observed in men with higher traditional Sami diet scores. However, due to the complexity in defining a "traditional Sami" diet, and the limitations of our questionnaire for this purpose, the study should be considered exploratory, a first attempt to relate a "traditional Sami" dietary pattern to health endpoints. Further investigation of cohorts with more detailed information on dietary and lifestyle items relevant for traditional Sami culture is warranted.

The joint relationship between organizational design factors and HR practice factors on direct care workers' job satisfaction and turnover intent.

PubMed

Kim, Jungyoon; Wehbi, Nizar; Dellifraine, Jami L; Brannon, Diane

2014-01-01

Human resource (HR) practices, such as training and communication, have been linked to positive employee job commitment and lower turnover intent for direct care workers (DCWs). Not many studies have looked at the combined interaction of HR practices and organizational structure. The aim of this study is to examine the relationship between organizational structure (centralization, formalization, and span of control) and HR practices (training, horizontal communication, and vertical communication) on DCW's job satisfaction and turnover intent. Data were collected from 58 long-term care facilities in five states. We used latent class analysis to group facility characteristics into three sets of combinations: "organic," "mechanistic," and "minimalist." We used multivariate regression to test the relationship of each of these groups on DCW's job satisfaction and turnover intent. After controlling for state, organizational, and individual covariates, the organic group, which represents decentralized and less formalized structures and high levels of job training and communication, was positively related to job satisfaction and negatively related to intent to leave. On the other hand, the minimalist group, which is characterized by low levels of job-related training and communication, showed no significant differences from the mechanistic group (referent) on job satisfaction and intent to leave. These findings imply that managers in long-term care facilities may want to consider adopting organic, decentralized structures and HR practices to retain DCWs.

Predictive biomarkers for death and rehospitalization in comorbid frail elderly heart failure patients.

PubMed

Pacho, Cristina; Domingo, Mar; Núñez, Raquel; Lupón, Josep; Núñez, Julio; Barallat, Jaume; Moliner, Pedro; de Antonio, Marta; Santesmases, Javier; Cediel, Germán; Roura, Santiago; Pastor, M Cruz; Tor, Jordi; Bayes-Genis, Antoni

2018-05-09

Heart failure (HF) is associated with a high rate of readmissions within 30 days post-discharge and in the following year, especially in frail elderly patients. Biomarker data are scarce in this high-risk population. This study assessed the value of early post-discharge circulating levels of ST2, NT-proBNP, CA125, and hs-TnI for predicting 30-day and 1-year outcomes in comorbid frail elderly patients with HF with mainly preserved ejection fraction (HFpEF). Blood samples were obtained at the first visit shortly after discharge (4.9 ± 2 days). The primary endpoint was the composite of all-cause mortality or HF-related rehospitalization at 30 days and at 1 year. All-cause mortality alone at one year was also a major endpoint. HF-related rehospitalizations alone were secondary end-points. From February 2014 to November 2016, 522 consecutive patients attending the STOP-HF Clinic were included (57.1% women, age 82 ± 8.7 years, mean Barthel index 70 ± 25, mean Charlson comorbidity index 5.6 ± 2.2). The composite endpoint occurred in 8.6% patients at 30 days and in 38.5% at 1 year. In multivariable analysis, ST2 [hazard ratio (HR) 1.53; 95% CI 1.19-1.97; p = 0.001] was the only predictive biomarker at 30 days; at 1 year, both ST2 (HR 1.34; 95% CI 1.15-1.56; p < 0.001) and NT-proBNP (HR 1.19; 95% CI 1.02-1.40; p = 0.03) remained significant. The addition of ST2 and NT-proBNP into a clinical predictive model increased the AUC from 0.70 to 0.75 at 30 days (p = 0.02) and from 0.71 to 0.74 at 1 year (p < 0.05). For all-cause death at 1 year, ST2 (HR 1.50; 95% CI 1.26-1.80; p < 0.001), and CA125 (HR 1.41; 95% CI 1.21-1.63; p < 0.001) remained independent predictors in multivariable analysis. The addition of ST2 and CA125 into a clinical predictive model increased the AUC from 0.74 to 0.78 (p = 0.03). For HF-related hospitalizations, ST2 was the only predictive biomarker in multivariable analyses, both at 30 days and at 1 year. In a comorbid frail elderly population with HFpEF, ST2 outperformed NT-proBNP for predicting the risk of all-cause mortality or HF-related rehospitalization. ST2, a surrogate marker of inflammation and fibrosis, may be a better predictive marker in high-risk HFpEF.

Improved Heart Rate Recovery After Marked Weight Loss Induced by Gastric Bypass Surgery: 2 Year Follow Up in the Utah Obesity Study

PubMed Central

Wasmund, Stephen L.; Yanowitz, Frank G.; Adams, Ted D.; Hunt, Steven C.; Hamdan, Mohamed H.; Litwin, Sheldon E.

2010-01-01

Background Obesity is associated with significantly increased cardiovascular mortality that has been attributed, in part, to sympathetic activation. Gastric bypass surgery (GBS) appears to increase long-term survival in the severely obese, but mechanisms responsible for this increase are still being sought. Heart rate (HR) recovery after exercise reflects the balance of cardiac autonomic input from the sympathetic and parasympathetic systems. Blunted HR recovery is a very powerful predictor of increased mortality while enhanced HR recovery portends a good prognosis. Objectives To evaluate the effect of marked weight loss achieved via GBS on HR recovery. Methods Severely obese patients underwent submaximal exercise testing (80% predicted maximum HR) at baseline and 2 years after GBS (n=153) or nonsurgical treatment (n=188). Results Patients in the GBS group lost an average of 100±37 lbs compared to 3±22 lbs in the nonsurgical group (p<0.001, GBS vs. nonsurgical). Resting HR decreased from 73 beats/minute (bpm) to 60 bpm in the GBS group and from 74 bpm to 68 bpm in nonsurgical patients (p<0.001). Heart rate recovery improved by 13 bpm in the GBS group and did not change in the nonsurgical group (p<0.001 GBS vs. nonsurgical). In multivariable analysis, the independent correlates of HR recovery at the 2-year time point were resting HR, treadmill time, age, body mass index and HOMA-IR. Conclusion Marked weight loss 2 years after GBS resulted in a significant decrease in resting HR and an enhancement in HR recovery after exercise. These changes are likely attributable to improvement in insulin sensitivity and cardiac autonomic balance. Whether and to what extent this contributes to a reduction in cardiovascular mortality with GBS remains to be determined. PMID:20970524

Population-based cohort study investigating the correlation of diabetes mellitus with pleural empyema in adults in Taiwan.

PubMed

Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

2017-09-01

We assessed the association between diabetes mellitus and the risk of pleural empyema in Taiwan.A population-based retrospective cohort study was conducted using the database of the Taiwan National Health Insurance Program. There were 28,802 subjects aged 20 to 84 years who were newly diagnosed with diabetes mellitus from 2000 to 2010 as the diabetes group and 114,916 randomly selected subjects without diabetes mellitus as the non-diabetes group. The diabetes group and the non-diabetes group were matched by sex, age, comorbidities, and the year of index date. The incidence of pleural empyema at the end of 2011 was estimated. A multivariable Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for pleural empyema associated with diabetes mellitus.The overall incidence of pleural empyema was 1.65-fold higher in the diabetes group than that in the non-diabetes group (1.58 vs 0.96 per 10,000 person-years, 95% CI 1.57-1.72). After adjusting for confounders, a multivariable Cox proportional hazards regression model revealed that the adjusted HR of pleural empyema was 1.71 in subjects with diabetes mellitus (95% CI 1.16-2.51), compared with those without diabetes mellitus. In further analysis, even in the absence of any comorbidity, the adjusted HR was 1.99 for subjects with diabetes mellitus alone (95% CI 1.18-3.38).Diabetic patients confer a 1.71-fold increased hazard of developing pleural empyema. Even in the absence of any comorbidity, the risk remains existent.

Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy

PubMed Central

Wang, H. M.; Liao, Z. X.; Komaki, R.; Welsh, J. W.; O'Reilly, M. S.; Chang, J. Y.; Zhuang, Y.; Levy, L. B.; Lu, C.; Gomez, D. R.

2013-01-01

Background Preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor. Patients and methods We retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Results In univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P < 0.01), DFS (P < 0.01), and OS (P = 0.01), but not LRPFS (P = 0.33) compared with patients not taking beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63). Conclusion Beta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes. PMID:23300016

Dose to heart substructures is associated with non-cancer death after SBRT in stage I-II NSCLC patients.

PubMed

Stam, Barbara; Peulen, Heike; Guckenberger, Matthias; Mantel, Frederick; Hope, Andrew; Werner-Wasik, Maria; Belderbos, Jose; Grills, Inga; O'Connell, Nicolette; Sonke, Jan-Jakob

2017-06-01

To investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). 803 patients with early stage NSCLC received SBRT with predominant schedules of 3×18Gy (59%) or 4×12Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively. Median follow-up was 34.8months. Two year Kaplan-Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5Gy EQD2, range=0.009-197, HR=1.005, p-value=0.035), and the dose to 90% of the superior vena cava (median 0.59Gy EQD2, range=0.003-70, HR=1.025, p-value=0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria+vessels) to be significantly associated with non-cancer death. Doses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied. Copyright © 2017 Elsevier B.V. All rights reserved.

Multivariate Brain Prediction of Heart Rate and Skin Conductance Responses to Social Threat.

PubMed

Eisenbarth, Hedwig; Chang, Luke J; Wager, Tor D

2016-11-23

Psychosocial stressors induce autonomic nervous system (ANS) responses in multiple body systems that are linked to health risks. Much work has focused on the common effects of stress, but ANS responses in different body systems are dissociable and may result from distinct patterns of cortical-subcortical interactions. Here, we used machine learning to develop multivariate patterns of fMRI activity predictive of heart rate (HR) and skin conductance level (SCL) responses during social threat in humans (N = 18). Overall, brain patterns predicted both HR and SCL in cross-validated analyses successfully (r HR = 0.54, r SCL = 0.58, both p < 0.0001). These patterns partly reflected central stress mechanisms common to both responses because each pattern predicted the other signal to some degree (r HR→SCL = 0.21 and r SCL→HR = 0.22, both p < 0.01), but they were largely physiological response specific. Both patterns included positive predictive weights in dorsal anterior cingulate and cerebellum and negative weights in ventromedial PFC and local pattern similarity analyses within these regions suggested that they encode common central stress mechanisms. However, the predictive maps and searchlight analysis suggested that the patterns predictive of HR and SCL were substantially different across most of the brain, including significant differences in ventromedial PFC, insula, lateral PFC, pre-SMA, and dmPFC. Overall, the results indicate that specific patterns of cerebral activity track threat-induced autonomic responses in specific body systems. Physiological measures of threat are not interchangeable, but rather reflect specific interactions among brain systems. We show that threat-induced increases in heart rate and skin conductance share some common representations in the brain, located mainly in the vmPFC, temporal and parahippocampal cortices, thalamus, and brainstem. However, despite these similarities, the brain patterns that predict these two autonomic responses are largely distinct. This evidence for largely output-measure-specific regulation of autonomic responses argues against a common system hypothesis and provides evidence that different autonomic measures reflect distinct, measurable patterns of cortical-subcortical interactions. Copyright © 2016 the authors 0270-6474/16/3611987-12$15.00/0.

Anthropometrics and prognosis in diffuse large B-cell lymphoma: a multicentre study of 653 patients.

PubMed

Bendtsen, Mette Dahl; Munksgaard, Peter Svenssen; Severinsen, Marianne Tang; Bekric, Eric; Brieghel, Christian; Nielsen, Kristina Buchardi; Brown, Peter de Nully; Dybkaer, Karen; Johnsen, Hans Erik; Bøgsted, Martin; El-Galaly, Tarec Christoffer

2017-04-01

The impact of body mass index (BMI) and body surface area (BSA) on survival in diffuse large B-cell lymphoma (DLBCL) is controversial. Recent studies show superior outcomes for overweight and obese patients. A total of 653 R-CHOP(-like)-treated DLBCL patients were included in this retrospective cohort study. Patients, baseline clinicopathologic characteristics and treatment information were retrieved from the Danish Lymphoma Registry. Anthropometric measures were obtained from chemotherapy prescription charts. Underweight (BMI <18.5 kg/m 2 ) was associated with significantly worse progression-free survival (PFS) for male patients only in sex-stratified analyses (HR 3.92, 95% CI: 1.57-9.75, P = 0.003, for males; HR 1.65, 95% CI: 0.90-3.02, P = 0.107, for females). In multivariate analyses, underweight was associated with worse PFS for both sexes (HR 5.34, 95% CI: 2.07-13.79, P = 0.001, for males; HR 2.14, 95% CI: 1.12-4.08, P = 0.021, for females). Similar results were obtained in analyses of overall survival. In crude analyses, BSA <1.8 m 2 was associated with worse PFS for men and women (HR 1.65, 95% CI: 1.03-2.65, P = 0.039, for men; HR 1.62, 95% CI: 1.03-2.56, P = 0.037, for women). In multivariate analyses, however, these associations diminished. Our study demonstrates that underweight DLBCL patients have worse outcomes following R-CHOP as compared to normal as well as overweight patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of care at comprehensive cancer centers on outcome: Results from a population-based study.

PubMed

Wolfson, Julie A; Sun, Can-Lan; Wyatt, Laura P; Hurria, Arti; Bhatia, Smita

2015-11-01

Rigorous processes ensure quality of research and clinical care at National Cancer Institute-designated comprehensive cancer centers (NCICCCs). Unmeasurable elements of structure and process of cancer care delivery warrant evaluation. To the authors' knowledge, the impact of NCICCC care on survival and access to NCICCCs for vulnerable subpopulations remain unstudied. The current study's population-based cohort of 69,579 patients had newly diagnosed adult-onset (aged 22-65 years) cancers reported to the Los Angeles County cancer registry between 1998 and 2008. Geographic information systems were used for geospatial analysis. With regard to overall survival across multiple diagnoses, patients not receiving their first planned treatment at NCICCCs experienced poorer outcomes compared with those treated at NCICCCs; differences persisted on multivariable analyses after adjusting for clinical and sociodemographic factors (hepatobiliary: hazard ratio [HR], 1.5; 95% confidence interval [95% CI], 1.4-1.7 [P<.001]; lung: HR, 1.4; 95% CI, 1.3-1.6 [P<.001]; pancreatic: HR, 1.5; 95% CI, 1.3-1.7 [P<.001]; gastric: HR, 1.3; 95% CI, 1.1-1.7 [P = .01]; breast: HR, 1.3; 95% CI, 1.1-1.5 [P<.001]; and colorectal: HR, 1.2; 95% CI, 1.0-1.4 [P = .05]). With regard to barriers to care, multivariable analyses revealed that a lower likelihood of treatment at NCICCCs was associated with race/ethnicity (African-American: OR range across diagnoses: 0.4-0.7 [P<.03]; Hispanic: OR range, 0.5-0.7 [P<.04]); lack of private insurance (public: OR range, 0.6-0.8 [P<.004]; uninsured: OR range, 0.1-0.5 [P<.04]); less than high socioeconomic status (high-middle: OR range, 0.4-0.7 [P<.02]; middle: OR range, 0.3-0.5 [P<.001]; and low: OR range, 0.2-0.6 [P<.01]), and residing >9 miles from the nearest NCICCC (OR range, 0.5-0.7 [P<.02]). Among individuals aged 22 to 65 years residing in Los Angeles County with newly diagnosed adult-onset cancer, those who were treated at NCICCCs experienced superior survival compared with those treated at non-NCICCC facilities. Barriers to care at NCICCCs included race/ethnicity, insurance, socioeconomic status, and distance to an NCICCC. © 2015 American Cancer Society.

Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis

PubMed Central

Mbogning, Cyprien; Link, Jenny; Ryner, Malin; Ramanujam, Ryan; Auer, Michael; Hyldgaard Jensen, Poul Erik; Koch-Henriksen, Nils; Warnke, Clemens; Ingenhoven, Kathleen; Buck, Dorothea; Grummel, Verena; Lawton, Andy; Donnellan, Naoimh; Hincelin-Mery, Agnès; Sikkema, Dan; Pallardy, Marc; Kieseier, Bernd; Hemmer, Bernard; Hartung, Hans Peter; Soelberg Sorensen, Per; Deisenhammer, Florian; Dönnes, Pierre; Davidson, Julie; Fogdell-Hahn, Anna; Broët, Philippe

2016-01-01

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9–8.4 and pooled HR = 8.7, 95% CI 6.6–11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4–2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1–1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1–2.4 and HR = 2.4, 95% CI 1.5–3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0–1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0–2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers. PMID:27806057

Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis.

PubMed

Bachelet, Delphine; Hässler, Signe; Mbogning, Cyprien; Link, Jenny; Ryner, Malin; Ramanujam, Ryan; Auer, Michael; Hyldgaard Jensen, Poul Erik; Koch-Henriksen, Nils; Warnke, Clemens; Ingenhoven, Kathleen; Buck, Dorothea; Grummel, Verena; Lawton, Andy; Donnellan, Naoimh; Hincelin-Mery, Agnès; Sikkema, Dan; Pallardy, Marc; Kieseier, Bernd; Hemmer, Bernard; Hartung, Hans Peter; Soelberg Sorensen, Per; Deisenhammer, Florian; Dönnes, Pierre; Davidson, Julie; Fogdell-Hahn, Anna; Broët, Philippe

2016-01-01

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.

Impact of time from diagnosis to initiation of curative chemotherapy on survival of patients with diffuse large B-cell lymphoma.

PubMed

Hay, Kevin; Lee, Benny; Goktepe, Ozge; Connors, Joseph M; Sehn, Laurie H; Savage, Kerry J; Klasa, Richard; Shenkier, Tamara; Gerrie, Alina; Villa, Diego

2015-06-19

Although it is generally regarded appropriate to start chemotherapy promptly after a diagnosis of diffuse large B-cell lymphoma (DLBCL), the optimal time from diagnosis to treatment (TDT) is unknown. A total of 689 patients diagnosed with DLBCL and treated with ≥ 1 cycle of CHOP-R with curative intent during 2003-2008 in British Columbia were identified: 347 (50%) TDT ≤ 4 weeks, 277 (40%) TDT 5-8 weeks, 65 (10%) TDT > 8 weeks. For the respective TDT groups, 5-year OS estimates were 61%, 74%, 63% (p = 0.006); 5-year PFS 57%, 70%, 61% (p = 0.006); and 5-year DSS 64%, 80%, 77% (p <0.001). In multivariate analysis, TDT >8 weeks was associated with worse OS (HR 1.20 (95% CI 1.03, 1.41), p = 0.020), PFS (HR 1.33 (95% CI 1.15, 1.54), p < 0.001), and DSS (HR 1.40 (95% CI 1.10, 1.78), p = 0.006). Clinicians should endeavor to initiate curative chemotherapy as soon as possible after a diagnosis of DLBCL is established.

Comparison of Adjuvant Radiation Therapy Alone and Chemotherapy Alone in Surgically Resected Low-Grade Gliomas: Survival Analyses of 2253 Cases from the National Cancer Data Base.

PubMed

Wu, Jing; Neale, Natalie; Huang, Yuqian; Bai, Harrison X; Li, Xuejun; Zhang, Zishu; Karakousis, Giorgos; Huang, Raymond; Zhang, Paul J; Tang, Lei; Xiao, Bo; Yang, Li

2018-04-01

It is becoming increasingly common to incorporate chemotherapy (CT) with radiotherapy (RT) in the treatment of low-grade gliomas (LGGs) after surgical resection. However, there is a lack of literature comparing survival of patients who underwent RT or CT alone. The U.S. National Cancer Data Base was used to identify patients with histologically confirmed, World Health Organization grade 2 gliomas who received either RT alone or CT alone after surgery from 2004 to 2013. Overall survival (OS) was evaluated by Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and propensity-score-matched analysis. In total, 2253 patients with World Health Organization grade 2 gliomas were included, of whom 1466 (65.1%) received RT alone and 787 (34.9%) CT alone. The median OS was 98.9 months for the RT alone group and 125.8 months for the CT alone group. On multivariable analysis, CT alone was associated with a significant OS benefit compared with RT alone (hazard ratio [HR], 0.405; 95% confidence interval, 0.277-0.592; P < 0.001). On subgroup analyses, the survival advantage of CT alone over RT alone persisted across all age groups, and for the subtotal resection and biopsy groups, but not in the gross total resection group. In propensity-score-matched analysis, CT alone still showed significantly improved OS compared with RT alone (HR, 0.612; 95% confidence interval, 0.506-0.741; P < 0.001). Our results suggest that CT alone was independently associated with longer OS compared with RT alone in patients with LGGs who underwent surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

FAILURE OF RADIOACTIVE IODINE IN TREATMENT OF HYPERTHYROIDISM

PubMed Central

Schneider, David F.; Sonderman, Philip E.; Jones, Michaela F.; Ojomo, Kristin A.; Chen, Herbert; Jaume, Juan C.; Elson, Diane F.; Perlman, Scott B.; Sippel, Rebecca S.

2015-01-01

Introduction Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common, and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism. Methods We conducted a retrospective review of patients treated with RAI from 2007–2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p < 0.05) variables from the univariate analysis. Results Of the 325 patients analyzed, 74 patients (22.8%) failed initial RAI treatment. 53 (71.6%) received additional RAI, 13 (17.6%) received additional RAI followed by surgery, and the remaining 8 (10.8%) were cured after thyroidectomy. The percentage of patients who failed decreased in a step-wise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses < 12.5 mCi were associated with failure while initial T3 and free T4 levels of at least 4.5 pg/mL and 2.3 ng/dL, respectively, were associated with failure. In the final multivariate analysis, higher T4 (HR 1.13, 95% CI 1.02–1.26, p=0.02) and methimazole treatment (HR 2.55, 95% CI 1.22–5.33, p=0.01) were associated with failure. Conclusions Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients. PMID:25001092

Failure of radioactive iodine in the treatment of hyperthyroidism.

PubMed

Schneider, David F; Sonderman, Philip E; Jones, Michaela F; Ojomo, Kristin A; Chen, Herbert; Jaume, Juan C; Elson, Diane F; Perlman, Scott B; Sippel, Rebecca S

2014-12-01

Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism. We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p < 0.05) variables from the univariate analysis. Of the 325 patients analyzed, 74 patients (22.8 %) failed initial RAI treatment, 53 (71.6 %) received additional RAI, 13 (17.6 %) received additional RAI followed by surgery, and the remaining 8 (10.8 %) were cured after thyroidectomy. The percentage of patients who failed decreased in a stepwise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses <12.5 mCi were associated with failure while initial T3 and free T4 levels of at least 4.5 pg/mL and 2.3 ng/dL, respectively, were associated with failure. In the final multivariate analysis, higher T4 (hazard ratio [HR] 1.13; 95 % confidence interval [CI] 1.02-1.26; p = 0.02) and methimazole treatment (HR 2.55; 95 % CI 1.22-5.33; p = 0.01) were associated with failure. Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients.

Long-term outcomes and prognostic factors for patients with esophageal cancer following radiotherapy

PubMed Central

Chen, Chuang-Zhen; Chen, Jian-Zhou; Li, De-Rui; Lin, Zhi-Xiong; Zhou, Ming-Zhen; Li, Dong-Sheng; Chen, Zhi-Jian

2013-01-01

AIM: To evaluate long-term outcomes and prognostic factors for esophageal squamous cell carcinoma (SCC) treated with three dimensional conformal radiotherapy (3D-CRT). METHODS: Between January 2005 and December 2006, 153 patients (120 males, 33 females) with pathologically confirmed esophageal SCC and treated with 3D-CRT in Cancer Hospital of Shantou University were included in this retrospective analysis. Median age was 60 years (range: 37-84 years). The proportion of tumor location was as follows: upper thorax (including the cervical region), 73 (48%); middle thorax, 73 (48%); lower thorax, 7 (5%), respectively. The median radiation dose was 64 Gy (range: 50-74 Gy). Fifty four cases (35%) received cisplatin-based concurrent chemotherapy. Univariate and multivariate analysis were performed to determine the association between the correlative factors and prognosis. RESULTS: The five-year overall survival rate was 26.3%, with a median follow-up of 49 mo (range: 3-66 mo) for patients who were still alive. On univariate analysis, lesion location, lesion length by barium esophagogram, computed tomography imaging characteristics including Y diameter (anterior-posterior, AP, extent of tumor), gross tumor volume of primary lesion (GTV-E), volume of positive lymph nodes (GTV-LN), and the total target volume (GTV-T = GTV-E + GTV-LN) were prognostic for overall survival. By multivariate analysis, only the Y diameter [hazard ratio (HR) 2.219, 95%CI 1.141-4.316, P = 0.019] and the GTV-T (HR 1.372, 95%CI 1.044-1.803, P = 0.023) were independent prognostic factors for survival. CONCLUSION: The overall survival of esophageal carcinoma patients undergoing 3D-CRT was promising. The best predictors for survival were GTV-T and Y diameter. PMID:23539205

Long-term outcomes and prognostic factors for patients with esophageal cancer following radiotherapy.

PubMed

Chen, Chuang-Zhen; Chen, Jian-Zhou; Li, De-Rui; Lin, Zhi-Xiong; Zhou, Ming-Zhen; Li, Dong-Sheng; Chen, Zhi-Jian

2013-03-14

To evaluate long-term outcomes and prognostic factors for esophageal squamous cell carcinoma (SCC) treated with three dimensional conformal radiotherapy (3D-CRT). Between January 2005 and December 2006, 153 patients (120 males, 33 females) with pathologically confirmed esophageal SCC and treated with 3D-CRT in Cancer Hospital of Shantou University were included in this retrospective analysis. Median age was 60 years (range: 37-84 years). The proportion of tumor location was as follows: upper thorax (including the cervical region), 73 (48%); middle thorax, 73 (48%); lower thorax, 7 (5%), respectively. The median radiation dose was 64 Gy (range: 50-74 Gy). Fifty four cases (35%) received cisplatin-based concurrent chemotherapy. Univariate and multivariate analysis were performed to determine the association between the correlative factors and prognosis. The five-year overall survival rate was 26.3%, with a median follow-up of 49 mo (range: 3-66 mo) for patients who were still alive. On univariate analysis, lesion location, lesion length by barium esophagogram, computed tomography imaging characteristics including Y diameter (anterior-posterior, AP, extent of tumor), gross tumor volume of primary lesion (GTV-E), volume of positive lymph nodes (GTV-LN), and the total target volume (GTV-T = GTV-E + GTV-LN) were prognostic for overall survival. By multivariate analysis, only the Y diameter [hazard ratio (HR) 2.219, 95%CI 1.141-4.316, P = 0.019] and the GTV-T (HR 1.372, 95%CI 1.044-1.803, P = 0.023) were independent prognostic factors for survival. The overall survival of esophageal carcinoma patients undergoing 3D-CRT was promising. The best predictors for survival were GTV-T and Y diameter.

Rates and risk factors of hypertension in adolescents and adults with sickle cell anaemia in Tanzania: 10 years' experience.

PubMed

Makubi, Abel; Mmbando, Bruno P; Novelli, Enrico M; Lwakatare, Johnson; Soka, Deogratius; Marik, Harvest; Tibarazwa, Kemi; Ngaeje, Mariam; Newton, Charles R; Gladwin, Mark T; Makani, Julie

2017-06-01

Data on the magnitude and risk factors for hypertension in sickle cell anaemia (SCA) are limited. A retrospective analysis of individuals with SCA aged ≥15 years enrolled from 2004-2014 at Muhimbili National Hospital, Tanzania was conducted to determine the prevalence, incidence and risk factors for hypertension. A total of 1013 individuals with SCA were analysed, of whom 571(56%) were females. The median age [interquartile range] was 17 [15-22] years. Four hundred and forty-one (44%) of the patients had relative hypertension [systolic blood pressure (SBP) 120-139 mmHg or diastolic blood pressure (DBP) 70-89 mmHg], and 79 (8%) had hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). The incidence of hypertension was 64/1000 person years of observation and the 5-year survival rate was 0·71 [95% confidence interval (CI): 0·67-0·75]. In multivariate analysis, age>18 years, Hazard ratio (HR) 1·50 (95% CI: 1·03-2·18); pulse pressure, HR 0·64 (95% CI: 0·42 to 0·98); pulse rate, 1·02 (95% CI: 1·01-1·03); body mass index (BMI), HR 1·08 (95% CI: 1·03-1·13); blood transfusion, HR 2·50 (95% CI: 1·01-6·21) and haemoglobin, HR 1·12 (95% CI: 1·05-1·33) were independently associated with hypertension. In conclusion, despite the younger age, hypertension in this population was higher than that reported in others studies. Age, BMI, pulse pressure and haemoglobin were independently associated with hypertension in SCA. © 2016 John Wiley & Sons Ltd.

Risk of rupture of unruptured cerebral aneurysms in elderly patients

PubMed Central

Date, Isao; Tokunaga, Koji; Tominari, Shinjiro; Nozaki, Kazuhiko; Shiokawa, Yoshiaki; Houkin, Kiyohiro; Murayama, Yuichi; Ishibashi, Toshihiro; Takao, Hiroyuki; Kimura, Toshikazu; Nakayama, Takeo; Morita, Akio

2015-01-01

Objectives: The aim of this study was to identify risk factors for rupture of unruptured cerebral aneurysms (UCAs) in elderly Japanese patients aged 70 years or older. Methods: The participants included all patients 70 years of age or older in 3 prospective studies in Japan (the Unruptured Cerebral Aneurysm Study of Japan [UCAS Japan], UCAS II, and the prospective study at the Jikei University School of Medicine). A total of 1,896 patients aged 70 years or older with 2,227 UCAs were investigated. The median and mean follow-up periods were 990 and 802.7 days, respectively. Results: The mean aneurysm size was 6.2 ± 3.9 mm. Sixty-eight patients (3.6%) experienced subarachnoid hemorrhage during the follow-up period. Multivariable analysis per patient revealed that in patients aged 80 years or older (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.16–3.49, p = 0.012), aneurysms 7 mm or larger (HR, 3.08; 95% CI, 1.35–7.03, p = 0.007 for 7–9 mm; HR, 7.82; 95% CI, 3.60–16.98, p < 0.001 for 10–24 mm; and HR, 43.31; 95% CI, 12.55–149.42, p < 0.001 for ≥25 mm) and internal carotid–posterior communicating artery aneurysms (HR, 2.45; 95% CI, 1.23–4.88, p = 0.011) were independent predictors for UCA rupture in elderly patients. Conclusions: In our pooled analysis of prospective cohorts in Japan, patient age and aneurysm size and location were significant risk factors for UCA rupture in elderly patients. PMID:26511450

Increase in overall mortality risk in patients with type 2 diabetes receiving glipizide, glyburide or glimepiride monotherapy versus metformin: a retrospective analysis.

PubMed

Pantalone, K M; Kattan, M W; Yu, C; Wells, B J; Arrigain, S; Jain, A; Atreja, A; Zimmerman, R S

2012-09-01

It remains uncertain if differences in mortality risk exist among the sulfonylureas, especially in patients with documented coronary artery disease (CAD). The purpose of this study was to assess the overall mortality risk of the individual sulfonylureas versus metformin in a large cohort of patients with type 2 diabetes. A retrospective cohort study was conducted using an academic health centre enterprise-wide electronic health record (EHR) system to identify 23 915 patients with type 2 diabetes who initiated monotherapy with metformin (N = 12774), glipizide (N = 4325), glyburide (N = 4279) or glimepiride (N = 2537), ≥ 18 years of age, with and without a history of CAD, and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. An increase in overall mortality risk was observed in the entire cohort with glipizide (HR 1.64; 95% CI 1.39-1.94), glyburide (HR 1.59; 95% CI 1.35-1.88), and glimepiride (HR 1.68; 95% CI 1.37-2.06) versus metformin; however, in those patients with documented CAD, a statistically significant increase in overall mortality risk was only found with glipizide (HR 1.41; 95% CI 1.07-1.87) and glyburide (HR 1.38; 95% CI 1.04-1.83) versus metformin. Glipizide, glyburide and glimepiride are associated with an increased risk of overall mortality versus metformin. Our results suggest that if a sulfonylurea is required to obtain glycaemic control, glimepiride may be the preferred sulfonylurea in those with underlying CAD. © 2012 Blackwell Publishing Ltd.

Overall survival and self-reported fatigue in patients with esophageal cancer.

PubMed

Stauder, M C; Romero, Y; Kabat, B; Atherton, P J; Geno, D; Deschamps, C; Jatoi, A; Sloan, J A; Botros, M; Jung, K W; Arora, A S; Miller, R C

2013-02-01

A prospective cohort study was conducted to analyze whether self-reported fatigue predicts overall survival in patients with esophageal cancer. Patients enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry between September 2001 and January 2009 who completed a baseline quality of life instrument were eligible for evaluation. The fatigue component was scored on a 0-10 scale, with 0 as extreme fatigue. Patients were categorized as having a decreased energy level if they reported a score of ≤ 5. Fatigue scores ≥ 6 reflect normal levels of energy. Data from a total of 659 enrolled patients were analyzed. A total of 392 (59 %) and 267 (41 %) patients reported decreased and normal energy, respectively. Univariate analysis indicates patients with normal energy had improved 5-year survival compared to patients with decreased energy (37 vs 28 %, hazard ratio (HR) 0.74, p = 0.006). Among the patients with locally advanced disease, the same relationship was seen (28 vs 17 %, HR = 0.67, p = 0.003); this remained significant on multivariate analysis (HR = 0.71, p = 0.015). A decreased energy level is associated with poor survival in patients with esophageal cancer. Thus, patients with high levels of fatigue should be referred for psychological support and be considered for therapy aimed at amelioration of fatigue symptoms.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy.

PubMed

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-12-01

The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02-6.80, P=0.04), SLPECC inferior RNFLT (per -1 μm, HR=1.38, 95% CI: 1.02-2.2, P=0.02), and TDOCT inferior RNFLT (per -1 μm, HR=1.11, 95% CI: 1.04-1.2, P=0.001) had significant HRs for SAP progression. Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

PubMed Central

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-01-01

Purpose The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Methods Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Results Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02–6.80, P=0.04), SLPECC inferior RNFLT (per −1 μm, HR=1.38, 95% CI: 1.02–2.2, P=0.02), and TDOCT inferior RNFLT (per −1 μm, HR=1.11, 95% CI: 1.04–1.2, P=0.001) had significant HRs for SAP progression. Conclusion Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes. PMID:23060026

Association Between Radiation Necrosis and Tumor Biology After Stereotactic Radiosurgery for Brain Metastasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Jacob A.; Bennett, Elizabeth E.; Xiao, Roy

Background: The primary dose-limiting toxicity of stereotactic radiosurgery (SRS) is radiation necrosis (RN), which occurs after approximately 5% to 10% of treatments. This adverse event may worsen neurologic deficits, increase the frequency and cost of imaging, and necessitate prolonged treatment with steroids or antiangiogenic agents. Previous investigations have primarily identified lesion size and dosimetric constraints as risk factors for RN in small populations. We hypothesized that disease histology, receptor status, and mutational status are associated with RN. Methods and Materials: All patients presenting with brain metastasis between 1997 and 2015 who underwent SRS and subsequent radiographic follow-up at a singlemore » tertiary-care institution were eligible for inclusion. The primary outcome was the cumulative incidence of radiographic RN. Multivariate competing risks regression was used to identify biological risk factors for RN. Results: 1939 patients (5747 lesions) were eligible for inclusion; 285 patients (15%) experienced radiographic RN after the treatment of 427 (7%) lesions. After SRS, the median time to RN was 7.6 months. After multivariate analysis, graded prognostic assessment, renal pathology, lesion diameter, and the heterogeneity index remained independently predictive of RN in the pooled cohort. In subset analyses of individual pathologies, HER2-amplified status (hazard ratio [HR] 2.05, P=.02), BRAF V600+ mutational status (HR 0.33, P=.04), lung adenocarcinoma histology (HR 1.89, P=.04), and ALK rearrangement (HR 6.36, P<.01) were also associated with RN. Conclusions: In the present investigation constituting the largest series of RN, several novel risk factors were identified, including renal histology, lung adenocarcinoma histology, HER2 amplification, and ALK/BRAF mutational status. These risk factors may be used to guide clinical trial design incorporating biological risk stratification or dose escalation. Future studies determining the optimal timing of targeted therapies are warranted to further define the risk of RN.« less

Adjuvant Chemotherapy After Radical Cystectomy for Urothelial Bladder Cancer: Outcome and Prognostic Factors for Survival in a French Multicenter, Contemporary Cohort.

PubMed

Pouessel, Damien; Bastuji-Garin, Sylvie; Houédé, Nadine; Vordos, Dimitri; Loriot, Yohann; Chevreau, Christine; Sevin, Emmanuel; Beuzeboc, Philippe; Taille, Alexandre de la; Le Thuaut, Aurélie; Allory, Yves; Culine, Stéphane

2017-02-01

In the past decade, adjuvant chemotherapy (AC) after radical cystectomy (RC) was preferred worldwide for patients with muscle-invasive urothelial bladder cancer. In this study we aimed to determine the outcome of patients who received AC and evaluated prognostic factors associated with survival. We retrospectively analyzed 226 consecutive patients treated in 6 academic hospitals between 2000 and 2009. Multivariate Cox proportional hazards regression adjusted for center to estimate adjusted hazard ratios (HRs) with 95% confidence intervals were used. The median age was 62.4 (range, 35-82) years. Patients had pT3/pT4 and/or pN+ in 180 (79.6%) and 168 patients (74.3%), respectively. Median lymph node (LN) density was 25% (range, 3.1-100). Median time between RC and AC was 61.5 (range, 18-162) days. Gemcitabine with cisplatin, gemcitabine with carboplatin, and MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimens were delivered in 161 (71.2%), 49 (21.7%), and 12 patients (5.3%) of patients, respectively. The median number of cycles was 4 (range, 1-6). Thirteen patients (5.7%) with LN metastases also received adjuvant pelvic radiotherapy (ART). After a median follow-up of 4.2 years, 5-year overall survival (OS) was 40.7%. In multivariate analysis, pT ≥3 stage (HR, 1.73; P = .05), LN density >50% (HR, 1.94; P = .03), and number of AC cycles <4 (HR, 4.26; P = .001) were adverse prognostic factors for OS. ART (HR, 0.30; P = .05) tended to provide survival benefit. Classical prognostic features associated with survival are not modified by the use of AC. Patients who derived benefit from AC had a low LN density and received at least 4 cycles of treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: Exploratory analyses of AFFIRM and PREVAIL studies.

PubMed

Beer, Tomasz M; Miller, Kurt; Tombal, Bertrand; Cella, David; Phung, De; Holmstrom, Stefan; Ivanescu, Cristina; Skaltsa, Konstantina; Naidoo, Shevani

2017-12-01

Our exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC). HRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Multivariate analyses evaluated the prognostic significance of baseline and time-dependent scores after adjusting for treatment and clinical/demographic variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) represented the hazard of rPFS or OS per minimally important difference (MID) score change in HRQoL variables. In baseline and time-dependent multivariate analyses, OS was independently associated with multiple HRQoL measures across both studies. In time-dependent analyses, a 10-point (upper bound of MID range) increase (improvement) in FACT-P total score was associated with reductions in mortality risk of 19% in AFFIRM (HR 0.81 [95% CI 0.78-0.84]) and 21% in PREVAIL (HR 0.79 [0.76-0.83]). For baseline analyses, a 10-point increase in FACT-P total score was associated with reductions in mortality risk of 12% (HR 0.88 [0.84-0.93]) and 10% (HR 0.90 [0.86-0.95]) in AFFIRM and PREVAIL, respectively. rPFS was associated with a subset of HRQoL domains in both studies. Several baseline HRQoL domains were prognostic for rPFS and OS in patients with mCRPC, and this association was maintained during treatment, indicating that changes in HRQoL are informative for patients' expected survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

Marital Status and Survival in Patients with Carcinoid Tumors.

PubMed

Greenleaf, Erin K; Cooper, Amanda B; Hollenbeak, Christopher S

2016-01-01

Marital status is a known prognostic factor in overall and disease-specific survival in several types of cancer. The impact of marital status on survival in patients with carcinoid tumors remains unknown. We hypothesized that married patients have higher rates of survival than similar unmarried patients with carcinoid tumors. Using the Surveillance, Epidemiology, and End Results database, we identified 23,126 people diagnosed with a carcinoid tumor between 2000 and 2011 and stratified them according to marital status. Univariate and multivariable analyses were performed to compare the characteristics and outcomes between patient cohorts. Overall and cancer-related survival were analyzed using the Kaplan-Meier method. Multivariable survival analyses were performed using Cox proportional hazards models (hazards ratio [HR]), controlling for demographics and tumor-related and treatment-related variables. Propensity score analysis was performed to determine surgical intervention distributions among married and unmarried (ie, single, separated, divorced, widowed) patients. Marital status was significantly related to both overall and cancer-related survival in patients with carcinoid tumors. Divorced and widowed patients had worse overall survival (HR, 1.33 [95% confidence interval {CI}, 1.08-1.33] and 1.34 [95% CI, 1.22-1.46], respectively) and cancer-related survival (HR, 1.15 [95% CI, 1.00-1.31] and 1.15 [95% CI, 1.03-1.29], respectively) than married patients over five years. Single and separated patients had worse overall survival (HR, 1.20 [95% CI, 1.08-1.33] and 1.62 [95% CI, 1.25-2.11], respectively) than married patients over five years, but not worse cancer-related survival. Unmarried patients were more likely than matched married patients to undergo definitive surgical intervention (62.67% vs 53.11%, respectively, P < 0.0001). Even after controlling for other prognostic factors, married patients have a survival advantage after diagnosis of any carcinoid tumor, potentially reflecting better social support and financial means than patients without partners.

Metastatic Lymph Node Burden and Survival in Oral Cavity Cancer

PubMed Central

Kim, Sungjin; Tighiouart, Mourad; Gudino, Cynthia; Mita, Alain; Scher, Kevin S.; Laury, Anna; Prasad, Ravi; Shiao, Stephen L.; Van Eyk, Jennifer E.; Zumsteg, Zachary S.

2017-01-01

Purpose Current staging systems for oral cavity cancers incorporate lymph node (LN) size and laterality, but place less weight on the total number of positive metastatic nodes. We investigated the independent impact of numerical metastatic LN burden on survival. Methods Adult patients with oral cavity squamous cell carcinoma undergoing upfront surgical resection for curative intent were identified in the National Cancer Data Base between 2004 and 2013. A neck dissection of a minimum of 10 LNs was required. Multivariable models were constructed to assess the association between the number of metastatic LNs and survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Results Overall, 14,554 patients met inclusion criteria (7,906 N0 patients; 6,648 node-positive patients). Mortality risk escalated continuously with increasing number of metastatic nodes without plateau, with the effect most pronounced with up to four LNs (HR, 1.34; 95% CI, 1.29 to 1.39; P < .001). Extranodal extension (HR, 1.41; 95% CI, 1.20 to 1.65; P < .001) and lower neck involvement (HR, 1.16; 95% CI, 1.06 to 1.27; P < .001) also predicted increased mortality. Increasing number of nodes examined was associated with improved survival, plateauing at 35 LNs (HR, 0.98; 95% CI, 0.98 to 0.99; P < .001). In multivariable models accounting for the number of metastatic nodes, contralateral LN involvement (N2c status) and LN size were not associated with mortality. A novel nodal staging system derived by recursive partitioning analysis exhibited greater concordance than the American Joint Committee on Cancer (8th edition) system. Conclusion The number of metastatic nodes is a critical predictor of oral cavity cancer mortality, eclipsing other features such as LN size and contralaterality in prognostic value. More robust incorporation of numerical metastatic LN burden may augment staging and better inform adjuvant treatment decisions. PMID:28880746

Increased Prognostic Value of Query Amyloid Late Enhancement Score in Light-Chain Cardiac Amyloidosis.

PubMed

Wan, Ke; Sun, Jiayu; Han, Yuchi; Liu, Hong; Yang, Dan; Li, Weihao; Wang, Jie; Cheng, Wei; Zhang, Qing; Zeng, Zhi; Chen, Yucheng

2018-02-23

Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112-2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9. The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

Racial differences in colorectal cancer survival at a safety net hospital.

PubMed

Tapan, Umit; Lee, Shin Yin; Weinberg, Janice; Kolachalama, Vijaya B; Francis, Jean; Charlot, Marjory; Hartshorn, Kevan; Chitalia, Vipul

2017-08-01

While racial disparity in colorectal cancer survival have previously been studied, whether this disparity exists in patients with metastatic colorectal cancer receiving care at safety net hospitals (and therefore of similar socioeconomic status) is poorly understood. We examined racial differences in survival in a cohort of patients with stage IV colorectal cancer treated at the largest safety net hospital in the New England region, which serves a population with a majority (65%) of non-Caucasian patients. Data was extracted from the hospital's electronic medical record. Survival differences among different racial and ethnic groups were examined graphically using Kaplan-Meier analysis. A univariate cox proportional hazards model and a multivariable adjusted model were generated. Black patients had significantly lower overall survival compared to White patients, with median overall survival of 1.9 years and 2.5 years respectively. In a multivariate analysis, Black race posed a significant hazard (HR 1.70, CI 1.01-2.90, p=0.0467) for death. Though response to therapy emerged as a strong predictor of survival (HR=0.4, CI=0.2-0.7, p=0.0021), it was comparable between Blacks and Whites. Despite presumed equal access to healthcare and socioeconomic status within a safety-net hospital system, our results reinforce findings from previous studies showing lower colorectal cancer survival in Black patients, and also point to the importance of investigating other factors such as genetic and pathologic differences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relation of dyspnea in patients unable to perform exercise stress testing to outcome and myocardial ischemia.

PubMed

Bernheim, Alain M; Kittipovanonth, Maytinee; Scott, Christopher G; McCully, Robert B; Tsang, Teresa S; Pellikka, Patricia A

2009-07-15

Limited information exists regarding the significance of dyspnea in patients who are unable to exercise and the contribution of myocardial ischemia to this symptom. To assess this, we evaluated results of dobutamine stress echocardiography (DSE) and long-term outcome of patients with dyspnea referred for DSE. We studied 6,376 consecutive patients who were unable to perform an exercise test and were referred for DSE. Patients were classified according to presenting symptoms and followed for 5.5 +/- 2.8 years. End points were cardiac ischemic events (myocardial infarction or revascularization), hospitalization for heart failure (HF), and death. Dobutamine stress echocardiogram was positive for ischemia in 19% of patients with dyspnea versus 24% (p = 0.002) of those with typical angina and 17% (p = 0.2) of asymptomatic patients. In multivariate analysis, risk of death was increased in dyspneic patients versus asymptomatic patients (hazard ratio [HR] 1.14, p = 0.02) and patients with chest pain (HR 1.20, p <0.001). Hospitalization for HF occurred more often in patients with dyspnea (HR 1.26, p = 0.05 vs asymptomatic; HR 1.24, p = 0.06 vs chest pain), especially in the subset without previous HF (HR 1.45, p = 0.006 vs chest pain). Risk of cardiac ischemic events in patients with dyspnea was similar versus asymptomatic patients (HR 0.92, p = 0.39) and decreased versus patients with chest pain (HR 0.70, p <0.001). In conclusion, in patients referred for DSE, dyspnea was associated with a poor outcome. This increased hazard seems not to be linked to myocardial ischemia, but instead to HF and death.

Incidence of high dosage buprenorphine and methadone shopping behavior in a retrospective cohort of opioid-maintained patients in France.

PubMed

Delorme, Jessica; Chenaf, Chouki; Kabore, Jean-Luc; Pereira, Bruno; Mulliez, Aurélien; Tremey, Aurore; Brousse, Georges; Zenut, Marie; Laporte, Catherine; Authier, Nicolas

2016-05-01

Opioid Substitution Treatment (OST) misuse and diversion have significantly increased worldwide. Obtaining OST prescriptions from multiple prescribers, known as doctor shopping, is a way in which opioids may be diverted. The aim of this study was to assess the incidence of OST (high dosage buprenorphine (HDB) and methadone (MTD)) shopping behavior and identify associated risk factors, and its impact on mortality. A retrospective cohort of patients treated by OST between April 1, 2004 and December 31, 2012 from a sample of the French Health Insurance database was established. Doctor shopping was defined as ≥1 day of overlapping prescriptions written by ≥2 different prescribers and filled in ≥3 different pharmacies. A total of 2043 patients were enrolled, 1450HDB and 593 MTD. The one-year incidence of shopping behavior was 8.4% (95% CI: 7.0-10.1) in HDB group and 0% in MTD group, compared to 0.2% (95% CI: 0.1-0.2) for diuretics. On multivariate analysis, factors associated with HDB shopping behavior were: male gender HR: 1.74 (95% CI: 1.20-2.54); low-income status HR: 2.95 (95% CI: 2.07-4.44); mental health disorders HR: 1.43 (95% CI: 1.06-1.94); concurrent hypnotics use HR: 1.90 (95% CI: 1.39-2.61); concurrent use of weak opioids HR: 1.48 (95% CI: 1.09-1.99) and morphine HR: 1.69 (95% CI: 1.02-2.80). HDB shoppers had a higher, yet non-significant risk of death (HR: 1.56 (95% CI: 0.64-3.81)) than non HDB shoppers. Shopping behavior was only found in high dosage buprenorphine patients and concerned almost one out ten patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impact of postoperative complications on overall survival of patients with hepatoblastoma.

PubMed

Becker, Kristina; Furch, Christiane; Schmid, Irene; von Schweinitz, Dietrich; Häberle, Beate

2015-01-01

Complete resection of hepatoblastoma (HB) is a demanding procedure in advanced tumors. Perioperative complications are still common. The influence of complication rates on course of disease and survival of patients with HB has not been analyzed yet. Patients with high risk (HR) HB and standard-risk (SR) HB registered from 1999 to 2008 to the German prospective multicenter study HB99 were evaluated regarding perioperative complications, reasons (e.g., tumor size and vessel involvement) and impact on further treatment and overall survival (OS). Surgical data from 126 patients were available (47 HR-HB, 79 SR-HB). Postoperative complications occurred in 26 (21%) patients consisting of biliary leakage (n = 9), cholestasis (n = 5), deficit of liver perfusion (n = 5) and others (n = 7). Twenty of these 26 patients (77%) required a second operation. The rate of postoperative complications was higher in the HR-group (26%) compared to the SR-group (17%). Patients with vessel involvement had significantly more complications (17% vs. 54%, P = 0.01). Patients with PRETEXT I/II-tumors had the same rate of postoperative complications (19% vs. 20%) as patients with PRETEXT III/IV. Patients of HR-group with postoperative complications showed delayed start in adjuvant chemotherapy (>21 d) (75% vs. 25%, n.s.) combined with significant lower 5-year-OS (75% vs. 50%, P = 0.02). In multivariate analysis postoperative complications were an independent negative prognostic factor for HR-patients (HR 3.1, P = 0.04). Postoperative complications after HB resection are frequent and associated with worsened OS of patients with HR-HB. One possible reason is delay in postoperative chemotherapy. The approach to precarious liver resection should be carefully planned and executed by specialists. © 2014 Wiley Periodicals, Inc.

Prognostic Factors for Mortality among Day +100 Survivors after Allogeneic Hematopoietic Cell Transplantation.

PubMed

Patel, Sagar S; Rybicki, Lisa A; Corrigan, Donna; Bolwell, Brian; Dean, Robert; Liu, Hien; Gerds, Aaron T; Hanna, Rabi; Hill, Brian; Jagadeesh, Deepa; Kalaycio, Matt; Pohlman, Brad; Sobecks, Ronald; Majhail, Navneet S; Hamilton, Betty K

2018-05-01

Although day +100 survival among allogeneic hematopoietic cell transplantation (HCT) recipients has improved over time, longer-term survival remains a challenge. The aim of this study was to identify prognostic factors for survival among patients surviving longer than 100 days using baseline characteristics and factors identified within the first 100 days after transplantation. Of 413 patients undergoing a first allogeneic HCT between 2006 and 2014, 335 survived >100 days post-transplantation. The majority underwent a myeloablative transplantation (75%) with a bone marrow (BM) (52%) graft source. One-year all-cause mortality (ACM) was 29%, with 16% relapse mortality (RM) and 12% nonrelapse mortality. In multivariable analysis, high-risk disease (hazard ratio [HR], 1.55; P = .003), non-cytomegalovirus infection (HR, 1.79; P = .003), more days hospitalized (HR, 1.16; P < .001), and relapse (HR, 4.38; P < .001) within the first 100 days were associated with increased risk of ACM. Patients with higher income (HR, .89; P = .024) and those who received BM (HR, .52; P < .001) or umbilical cord blood (HR, .40; P = .002) relative to peripheral blood stem cells had lower risk of ACM. Our study identifies risk factors for adverse long-term survival in 100-day survivors, a time point when patients frequently are discharged from transplantation centers. In addition to disease- and transplantation-related factors, low socioeconomic status was associated with worse long-term survival, highlighting the need for focused efforts to improve outcomes in vulnerable patient populations. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Dietary Patterns and Risk of Esophageal Cancer Mortality: The Japan Collaborative Cohort Study.

PubMed

Okada, Emiko; Nakamura, Koshi; Ukawa, Shigekazu; Sakata, Kiyomi; Date, Chigusa; Iso, Hiroyasu; Tamakoshi, Akiko

2016-01-01

Several case-control studies have associated dietary patterns with esophageal cancer (EC) risk, but prospective studies are scarce. We investigated dietary pattern and EC mortality risk associations by smoking status. Participants were 26,562 40- to 79-yr-old Japanese men, who enrolled in the Japan Collaborative Cohort Study between 1988 and 1990. Hazard ratios (HRs) and 95% confidence intervals (CIs) for EC mortality in nonsmokers and smokers were estimated using Cox proportional models. During follow-up (1988-2009), 132 participants died of EC. Using a baseline food frequency questionnaire and factor analysis, vegetable, animal, and dairy product food patterns were identified. EC risk decreased significantly with a higher factor score for the dairy product pattern (Ptrend = 0.042) and was more pronounced in smokers [multivariable HR (4th vs. 1st quartiles) = 0.57, 95% CI: 0.30, 1.09; Ptrend = 0.021]. Neither vegetable nor animal food patterns were significant overall; however, EC risk increased with a higher factor score for the animal food pattern in nonsmokers [multivariable HR (4th vs. 1st quartiles) = 6.01, 95% CI: 1.17, 30.88; Ptrend = 0.021], although the small number of events was a limitation. Our findings suggest a dairy product pattern may reduce EC risk in Japanese men, especially smokers.

FABP4 and Cardiovascular Events in Peripheral Arterial Disease.

PubMed

Höbaus, Clemens; Herz, Carsten Thilo; Pesau, Gerfried; Wrba, Thomas; Koppensteiner, Renate; Schernthaner, Gerit-Holger

2018-05-01

Fatty acid-binding protein 4 (FABP4) is a possible biomarker of atherosclerosis. We evaluated FABP4 levels, for the first time, in patients with peripheral artery disease (PAD) and the possible association between baseline FABP4 levels and cardiovascular events over time. Patients (n = 327; mean age 69 ± 10 years) with stable PAD were enrolled in this study. Serum FABP4 was measured by bead-based multiplex assay. Cardiovascular events were analyzed by FABP4 tertiles using Kaplan-Meier and Cox regression analyses after 5 years. Serum FABP4 levels showed a significant association with the classical 3-point major adverse cardiovascular event (MACE) end point (including death, nonlethal myocardial infarction, or nonfatal stroke) in patients with PAD ( P = .038). A standard deviation increase of FABP4 resulted in a hazard ratio (HR) of 1.33 (95% confidence interval [95% CI]: 1.03-1.71) for MACE. This association increased (HR: 1.47, 95% CI: 1.03-1.71) after multivariable adjustment ( P = .020). Additionally, in multivariable linear regression analysis, FABP4 was linked to estimated glomerular filtration rate ( P < .001), gender ( P = .005), fasting triglycerides ( P = .048), and body mass index ( P < .001). Circulating FABP4 may be a useful additional biomarker to evaluate patients with stable PAD at risk of major cardiovascular complications.

Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration.

PubMed

Margulis, Vitaly; Shariat, Shahrokh F; Matin, Surena F; Kamat, Ashish M; Zigeuner, Richard; Kikuchi, Eiji; Lotan, Yair; Weizer, Alon; Raman, Jay D; Wood, Christopher G

2009-03-15

The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified. Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria. Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high-grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) -positive. Over a mean follow-up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5-year recurrence-free and cancer-specific survival probabilities (+/-SD) were 69%+/-1% and 73%+/-1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P<.001), advancing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.8, P<.001), infiltrative growth pattern (HR: 1.5, P<.001), and LVI (HR: 1.2, P=.041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P=.001), high tumor grade (HR: 1.7, P=.001), increasing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.7, P<.001), sessile architecture (HR: 1.5, P=.002), and LVI (HR: 1.4, P=.02) were independently associated with cancer-specific survival. Radical nephroureterectomy provided durable local control and cancer-specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy. Copyright (c) 2009 American Cancer Society.

Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study.

PubMed

Taylor, Fiona G M; Quirke, Philip; Heald, Richard J; Moran, Brendan J; Blomqvist, Lennart; Swift, Ian R; Sebag-Montefiore, David; Tekkis, Paris; Brown, Gina

2014-01-01

The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR). Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates. Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis. High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM-based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.

Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial

PubMed Central

Smyth, Elizabeth C.; Fassan, Matteo; Cunningham, David; Allum, William H.; Okines, Alicia F.C.; Lampis, Andrea; Hahne, Jens C.; Rugge, Massimo; Peckitt, Clare; Nankivell, Matthew; Langley, Ruth; Ghidini, Michele; Braconi, Chiara; Wotherspoon, Andrew; Grabsch, Heike I.

2016-01-01

Purpose The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as a standard of care for patients with resectable esophagogastric cancer. However, identification of patients at risk for relapse remains challenging. We evaluated whether pathologic response and lymph node status after neoadjuvant chemotherapy are prognostic in patients treated in the MAGIC trial. Materials and Methods Pathologic regression was assessed in resection specimens by two independent pathologists using the Mandard tumor regression grading system (TRG). Differences in overall survival (OS) according to TRG were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards method established the relationships among TRG, clinical-pathologic variables, and OS. Results Three hundred thirty resection specimens were analyzed. In chemotherapy-treated patients with a TRG of 1 or 2, median OS was not reached, whereas for patients with a TRG of 3, 4, or 5, median OS was 20.47 months. On univariate analysis, high TRG and lymph node metastases were negatively related to survival (Mandard TRG 3, 4, or 5: hazard ratio [HR], 1.94; 95% CI, 1.11 to 3.39; P = .0209; lymph node metastases: HR, 3.63; 95% CI, 1.88 to 7.0; P < .001). On multivariate analysis, only lymph node status was independently predictive of OS (HR, 3.36; 95% CI, 1.70 to 6.63; P < .001). Conclusion Lymph node metastases and not pathologic response to chemotherapy was the only independent predictor of survival after chemotherapy plus resection in the MAGIC trial. Prospective evaluation of whether omitting postoperative chemotherapy and/or switching to a noncross-resistant regimen in patients with lymph node-positive disease whose tumor did not respond to preoperative epirubicin, cisplatin, and fluorouracil may be appropriate. PMID:27298411

The effect of single and repeated UVB radiation on rabbit cornea.

PubMed

Fris, Miroslav; Tessem, May-Britt; Cejková, Jitka; Midelfart, Anna

2006-12-01

Cumulative effect of ultraviolet radiation (UVR) is an important aspect of UV corneal damage. The purpose of this study was to apply high resolution magic angle spinning proton nuclear magnetic resonance (HR-MAS 1H NMR) spectroscopy to evaluate the effect of single and repeated UV radiation exposure of the same overall dose on the rabbit cornea. Corneal surfaces of 24 normal rabbit eyes were examined for the effects of UVB exposure (312 nm). In the first group (UVB1), animals were irradiated with a single dose (3.12 J/cm2; 21 min) of UVB radiation. The animals in the second group (UVB2) were irradiated three times for 7 min every other day (dose of 1.04 J/cm2; days 1, 3, 5) to give the same overall dose (3.12 J/cm2). The third group served as an untreated control group. One day after the last irradiation, the animals were sacrificed, and the corneas were removed and frozen. HR-MAS 1H NMR spectra from intact corneas were obtained. Special grouping patterns among the tissue samples and the relative percentage changes in particular metabolite concentrations were evaluated using modern statistical methods (multivariate analysis, one-way ANOVA). The metabolic profile of both groups of UVB-irradiated samples was significantly different from the control corneas. Substantial decreases in taurine, hypo-taurine and choline-derivatives concentrations and substantial elevation in glucose and betaine levels were observed following the UVR exposure. There was no significant difference between the effect of a single and repeated UVB irradiation of the same overall dose. For the first time, the effects of single and repeated UVR doses on the metabolic profile of the rabbit cornea were analysed and compared. The combination of HR-MAS 1H NMR spectroscopy and modern statistical methods (multivariate analysis, one-way ANOVA) proved suitable to assess the overall view of the metabolic alterations in the rabbit corneal tissue following UVB radiation exposure.

Role of late gadolinium enhancement cardiovascular magnetic resonance in the risk stratification of hypertrophic cardiomyopathy.

PubMed

Ismail, Tevfik F; Jabbour, Andrew; Gulati, Ankur; Mallorie, Amy; Raza, Sadaf; Cowling, Thomas E; Das, Bibek; Khwaja, Jahanzaib; Alpendurada, Francisco D; Wage, Ricardo; Roughton, Michael; McKenna, William J; Moon, James C; Varnava, Amanda; Shakespeare, Carl; Cowie, Martin R; Cook, Stuart A; Elliott, Perry; O'Hanlon, Rory; Pennell, Dudley J; Prasad, Sanjay K

2014-12-01

Myocardial fibrosis identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM) is associated with adverse cardiovascular events, but its value as an independent risk factor for sudden cardiac death (SCD) is unknown. We investigated the role of LGE-CMR in the risk stratification of HCM. We conducted a prospective cohort study in a tertiary referral centre. Consecutive patients with HCM (n=711, median age 56.3 years, IQR 46.7-66.6; 70.0% male) underwent LGE-CMR and were followed for a median 3.5 years. The primary end point was SCD or aborted SCD. Overall, 471 patients (66.2%) had myocardial fibrosis (median 5.9% of left ventricular mass, IQR: 2.2-13.3). Twenty-two (3.1%) reached the primary end point. The extent but not the presence of fibrosis was a significant univariable predictor of the primary end point (HR per 5% LGE: 1.24, 95% CI 1.06 to 1.45; p=0.007 and HR for LGE: 2.69, 95% CI 0.91 to 7.97; p=0.073, respectively). However, on multivariable analysis, only LV-EF remained statistically significant (HR: 0.92, 95% CI 0.89 to 0.95; p<0.001). For the secondary outcome of cardiovascular mortality/aborted SCD, the presence and the amount of fibrosis were significant predictors on univariable but not multivariable analysis after adjusting for LV-EF and non-sustained ventricular tachycardia. The amount of myocardial fibrosis was a strong univariable predictor of SCD risk. However, this effect was not maintained after adjusting for LV-EF. Further work is required to elucidate the interrelationship between fibrosis and traditional predictors of outcome in HCM. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The significance of serum urea and renal function in patients with heart failure.

PubMed

Gotsman, Israel; Zwas, Donna; Planer, David; Admon, Dan; Lotan, Chaim; Keren, Andre

2010-07-01

Renal function and urea are frequently abnormal in patients with heart failure (HF) and are predictive of increased mortality. The relative importance of each parameter is less clear. We prospectively compared the predictive value of renal function and serum urea on clinical outcome in patients with HF. Patients hospitalized with definite clinical diagnosis of HF (n = 355) were followed for short-term (1 yr) and long-term (mean, 6.5 yr) survival and HF rehospitalization. Increasing tertiles of discharge estimated glomerular filtration rate (eGFR) were an independent predictor of increased long-term survival (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.47-0.91; p = 0.01) but not short-term survival. Admission and discharge serum urea and blood urea nitrogen (BUN)/creatinine ratio were predictors of reduced short- and long-term survival on multivariate Cox regression analysis. Increasing tertiles of discharge urea were a predictor of reduced 1-year survival (HR, 2.13; 95% CI, 1.21-3.73; p = 0.009) and long-term survival (HR, 1.93; 95% CI, 1.37-2.71; p < 0.0001). Multivariate analysis including discharge eGFR and serum urea demonstrated that only serum urea remained a significant predictor of long-term survival; however, eGFR and BUN/creatinine ratio were both independently predictive of survival. Urea was more discriminative than eGFR in predicting long-term survival by area under the receiver operating characteristic curve (0.803 vs. 0.787; p = 0.01). Increasing tertiles of discharge serum urea and BUN/creatinine were independent predictors of HF rehospitalization and combined death and HF rehospitalization. This study suggests that serum urea is a more powerful predictor of survival than eGFR in patients with HF. This may be due to urea's relation to key biological parameters including renal, hemodynamic, and neurohormonal parameters pertaining to the overall clinical status of the patient with chronic HF.

Excellent real-world outcomes of adults with Burkitt lymphoma treated with CODOX-M/IVAC plus or minus rituximab.

PubMed

Zhu, Katie Y; Song, Kevin W; Connors, Joseph M; Leitch, Heather; Barnett, Michael J; Ramadan, Khaled; Slack, Graham W; Abou Mourad, Yasser; Forrest, Donna L; Hogge, Donna E; Nantel, Stephen H; Narayanan, Sujaatha; Nevill, Thomas J; Power, Maryse M; Sanford, David S; Sutherland, Heather J; Tucker, Tracy; Toze, Cynthia L; Sehn, Laurie H; Broady, Raewyn; Gerrie, Alina S

2018-06-01

Treatment of Burkitt lymphoma (BL) with intensive, multi-agent chemotherapy with aggressive central nervous system (CNS) prophylaxis results in high cure rates, although no regimen is standard of care. We examined population-based survival outcomes of adults with BL treated with a modified combination of cyclophosphamide, vincristine, doxorubicin, prednisone and systemic high-dose methotrexate (MTX) (CODOX-M) with IVAC (ifosfamide, mesna, etoposide, cytarabine and intrathecal MTX) (CODOX-M/IVAC) ± rituximab over a 15-year period in British Columbia. For the 81 patients identified (including 8 with CNS involvement and 18 with human immunodeficiency virus-associated BL), 5-year progression-free survival (PFS) and overall survival (OS) were 75% [95% confidence interval (CI): 63-83%] and 77% (95% CI: 66-85%), respectively, with no treatment-related deaths. Those who completed the regimen per protocol (n = 38) had significantly improved 5-year PFS 86% (P = 0·04) and OS 92% (P = 0·008), as did those under 60 years with 5-year PFS 82% (P = 0·005) and OS 86% (P = 0·002), which remained significant in multivariate analysis [PFS: hazard ratio (HR) 3·36, P = 0·018; OS HR 4·03, P = 0·012]. Incorporation of high-dose systemic methotrexate also significantly affected multivariate survival outcomes (OS HR 0·28, P = 0·025). Stem cell transplant in first remission had no effect on OS or PFS. This large, real-world analysis of BL patients treated with CODOX-M/IVAC ± rituximab demonstrates excellent survival outcomes comparable to clinical trials. These results help to serve as a benchmark when comparing curative therapies for BL patients as novel regimens are incorporated into clinical practice. © 2018 John Wiley & Sons Ltd.

The Prognostic Significance of Sentinel Lymph Node Status for Patients with Thick Melanoma.

PubMed

Bello, Danielle M; Han, Gang; Jackson, Laura; Bulloch, Kaleigh; Ariyan, Stephan; Narayan, Deepak; Rothberg, Bonnie Gould; Han, Dale

2016-12-01

Sentinel lymph node biopsy (SLNB) is recommended for patients with intermediate-thickness melanoma, but the use of SLNB for patients with thick melanoma is debated. This report presents a single-institution study investigating factors predictive of sentinel lymph node (SLN) metastasis and outcome for thick-melanoma patients . A retrospective review of a single-institution database from 1997 to 2012 identified 147 patients with thick primary cutaneous melanoma (≥4 mm) who had an SLNB. Clinicopathologic characteristics were correlated with nodal status and outcome. The median age of the patients was 67 years, and 61.9 % of the patients were men. The median tumor thickness was 5.5 mm, and 54 patients (36.7 %) had a positive SLN. Multivariable analysis showed that only tumor thickness significantly predicted SLN metastasis (odds ratio 1.14; 95 % confidence interval (CI) 1.02-1.28; P = 0.02). The overall median follow-up period was 34.6 months. Overall survival (OS) and melanoma-specific survival (MSS) were significantly worse for the positive versus negative-SLN patients. Multivariable analysis showed that age [hazard ratio (HR) 1.04; 95 % CI 1.01-1.07; P = 0.02] and SLN status (HR 2.24; 95 % CI 1.03-4.88; P = 0.04) significantly predicted OS, whereas only SLN status (HR 3.85; 95 % CI 2.13-6.97; P < 0.01) significantly predicted MSS. Tumor thickness predicts SLN status in thick melanomas. Furthermore, SLN status is prognostic for OS and MSS in thick-melanoma patients, with positive-SLN patients having significantly worse OS and MSS. These findings show that SLNB should be recommended for thick-melanoma patients, particularly because detection of SLN metastasis can identify patients for potential systemic therapy and treatment of nodal disease at a microscopic stage.

Ibrutinib versus previous standard of care: an adjusted comparison in patients with relapsed/refractory chronic lymphocytic leukaemia.

PubMed

Hansson, Lotta; Asklid, Anna; Diels, Joris; Eketorp-Sylvan, Sandra; Repits, Johanna; Søltoft, Frans; Jäger, Ulrich; Österborg, Anders

2017-10-01

This study explored the relative efficacy of ibrutinib versus previous standard-of-care treatments in relapsed/refractory patients with chronic lymphocytic leukaemia (CLL), using multivariate regression modelling to adjust for baseline prognostic factors. Individual patient data were collected from an observational Stockholm cohort of consecutive patients (n = 144) diagnosed with CLL between 2002 and 2013 who had received at least second-line treatment. Data were compared with results of the RESONATE clinical trial. A multivariate Cox proportional hazards regression model was used which estimated the hazard ratio (HR) of ibrutinib versus previous standard of care. The adjusted HR of ibrutinib versus the previous standard-of-care cohort was 0.15 (p < 0.0001) for progression-free survival (PFS) and 0.36 (p < 0.0001) for overall survival (OS). A similar difference was observed also when patients treated late in the period (2012-) were compared separately. Multivariate analysis showed that later line of therapy, male gender, older age and poor performance status were significant independent risk factors for worse PFS and OS. Our results suggest that PFS and OS with ibrutinib in the RESONATE study were significantly longer than with previous standard-of-care regimens used in second or later lines in routine healthcare. The approach used, which must be interpreted with caution, compares patient-level data from a clinical trial with outcomes observed in a daily clinical practice and may complement results from randomised trials or provide preliminary wider comparative information until phase 3 data exist.

PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer.

PubMed

Lotan, Tamara L; Wei, Wei; Morais, Carlos L; Hawley, Sarah T; Fazli, Ladan; Hurtado-Coll, Antonio; Troyer, Dean; McKenney, Jesse K; Simko, Jeffrey; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Feng, Ziding; Brooks, James D

2016-06-01

PTEN is the most commonly deleted tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes and ERG gene rearrangement. We tested whether PTEN loss is associated with shorter recurrence-free survival (RFS) in surgically treated PCa patients with known ERG status. A genetically validated, automated PTEN immunohistochemistry (IHC) protocol was used for 1275 primary prostate tumors from the Canary Foundation retrospective PCa tissue microarray cohort to assess homogeneous (in all tumor tissue sampled) or heterogeneous (in a subset of tumor tissue sampled) PTEN loss. ERG status as determined by a genetically validated IHC assay was available for a subset of 938 tumors. Associations between PTEN and ERG status were assessed using Fisher's exact test. Kaplan-Meier and multivariate weighted Cox proportional models for RFS were constructed. When compared to intact PTEN, homogeneous (hazard ratio [HR] 1.66, p = 0.001) but not heterogeneous (HR 1.24, p = 0.14) PTEN loss was significantly associated with shorter RFS in multivariate models. Among ERG-positive tumors, homogeneous (HR 3.07, p < 0.0001) but not heterogeneous (HR 1.46, p = 0.10) PTEN loss was significantly associated with shorter RFS. Among ERG-negative tumors, PTEN did not reach significance for inclusion in the final multivariate models. The interaction term for PTEN and ERG status with respect to RFS did not reach statistical significance ( p = 0.11) for the current sample size. These data suggest that PTEN is a useful prognostic biomarker and that there is no statistically significant interaction between PTEN and ERG status for RFS. We found that loss of the PTEN tumor suppressor gene in prostate tumors as assessed by tissue staining is correlated with shorter time to prostate cancer recurrence after radical prostatectomy.

Gender-specific Differences in Recurrence of Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

PubMed

Uhlig, Annemarie; Strauss, Arne; Seif Amir Hosseini, Ali; Lotz, Joachim; Trojan, Lutz; Schmid, Marianne; Uhlig, Johannes

2017-09-06

The incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non-muscle-invasive UCB. To conduct a meta-analysis evaluating gender-specific differences in recurrence of non-muscle-invasive urinary bladder cancer (NMIBC). An unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggeŕs test. Of 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01-1.23, p=0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13-2.39, p=0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32-2.15, p<0.001). Sensitivity analyses confirmed female patients at increased risk for UCB recurrence. Women are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses. In this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Radiation modality use and cardiopulmonary mortality risk in elderly patients with esophageal cancer.

PubMed

Lin, Steven H; Zhang, Ning; Godby, Joy; Wang, Jingya; Marsh, Gary D; Liao, Zhongxing; Komaki, Ritsuko; Ho, Linus; Hofstetter, Wayne L; Swisher, Stephen G; Mehran, Reza J; Buchholz, Thomas A; Elting, Linda S; Giordano, Sharon H

2016-03-15

It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC). The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment. Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims. In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC. © 2015 American Cancer Society.

Safety of concurrent adjuvant radiotherapy and chemotherapy for locally advanced soft tissue sarcoma.

PubMed

Greto, Daniela; Loi, Mauro; Saieva, Calogero; Muntoni, Cristina; Delli Paoli, Camilla; Becherini, Carlotta; Ciabatti, Cinzia; Perna, Marco; Campanacci, Domenico; Terziani, Francesca; Beltrami, Giovanni; Scoccianti, Guido; Bonomo, Pierluigi; Meattini, Icro; Desideri, Isacco; Simontacchi, Gabriele; Mangoni, Monica; Livi, Lorenzo

2018-04-01

This retrospective study analyzes the safety and feasibility of concurrent chemoradiotherapy (CRT) in adjuvant treatment of soft tissue sarcoma (STS). A total of 158 patients with STS were retrospectively analyzed. Anthracycline-based computed tomography was performed in high-risk patients. Acute radiotherapy toxicity and chemotherapy-related toxicity were assessed according to the Common Terminology Criteria for Adverse Events 4.0; late radiotherapy toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Fifty-four (34.2%) patients received CRT. Mean follow up was 5.4 years (range .2-21.1 years). Local DFS-recurrence-free survival, distant DFS-relapse-free survival, and overall survival were 79.1%, 76.4%, and 64.6%, respectively, at last follow-up. Leukopenia occurred in 11.4% of patients. Skin acute toxicity developed in 60.1% of patients and determined interruption of radiotherapy treatment in 19 (12%) patients. Nineteen patients (12%) experienced moderate fibrosis (grade 2). Mild and moderate joint stiffness was recorded in 16 (10.1%) patients. Size ≥5 cm was the only predictor of local recurrence at multivariate analysis (hazard ratio [HR] 9.65, 95% confidence interval [CI] 1.28-72.83, p = .028). Age and stage resulted as independent distant relapse predictors (HR 4.77, 95% CI 1.81-12.58, p = .002 and HR 4.83, CI 1.41-16.57, p = .012, respectively). At Cox regression univariate analysis, Karnofsky Performance Status, size, and stage were significant survival predictors (HR 2.23, 95% CI 1.02-4.87, p = .045; HR 2.88, 95% CI 1.10-7.52, p = .031; HR 2.59, 95% CI 1.11-6.04, p = .028). Concurrent CRT is a well-tolerated treatment option with no additional toxicity compared to exclusive radiotherapy or sequential CRT.

A gender based analysis of predictors of all cause death after transcatheter aortic valve implantation.

PubMed

Conrotto, Federico; D'Ascenzo, Fabrizio; Salizzoni, Stefano; Presbitero, Patrizia; Agostoni, Pierfrancesco; Tamburino, Corrado; Tarantini, Giuseppe; Bedogni, Francesco; Nijhoff, Freek; Gasparetto, Valeria; Napodano, Massimo; Ferrante, Giuseppe; Rossi, Marco Luciano; Stella, Pieter; Brambilla, Nedy; Barbanti, Marco; Giordana, Francesca; Grasso, Costanza; Biondi Zoccai, Giuseppe; Moretti, Claudio; D'Amico, Maurizio; Rinaldi, Mauro; Gaita, Fiorenzo; Marra, Sebastiano

2014-10-15

The impact of gender-related pathophysiologic features of severe aortic stenosis on transcatheter aortic valve implantation (TAVI) outcomes remains to be determined, as does the consistency of predictors of mortality between the genders. All consecutive patients who underwent TAVI at 6 institutions were enrolled in this study and stratified according to gender. Midterm all-cause mortality was the primary end point, with events at 30 days and at midterm as secondary end points. All events were adjudicated according to Valve Academic Research Consortium definitions. Eight hundred thirty-six patients were enrolled, 464 (55.5%) of whom were female. At midterm follow-up (median 365 days, interquartile range 100 to 516) women had similar rates of all-cause mortality compared with men (18.1% vs 22.6%, p = 0.11) and similar incidence of myocardial infarction and cerebrovascular accident. Gender did not affect mortality also on multivariate analysis. Among clinical and procedural features, glomerular filtration rate <30 ml/min/1.73 m(2) (hazard ratio [HR] 2.55, 95% confidence interval [CI] 1.36 to 4.79) and systolic pulmonary arterial pressure >50 mm Hg (HR 2.26, 95% CI 1.26 to 4.02) independently predicted mortality in women, while insulin-treated diabetes (HR 3.45, 95% CI 1.47 to 8.09), previous stroke (HR 3.42, 95% CI 1.43 to 8.18), and an ejection fraction <30% (HR 3.82, 95% CI 1.41 to 10.37) were related to mortality in men. Postprocedural aortic regurgitation was independently related to midterm mortality in the 2 groups (HR 11.19, 95% CI 3.3 to 37.9). In conclusion, women and men had the same life expectancy after TAVI, but different predictors of adverse events stratified by gender were demonstrated. These findings underline the importance of a gender-tailored clinical risk assessment in TAVI patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevalence of Pulmonary Hypertension and its Influence on Survival in Patients With Advanced Chronic Obstructive Pulmonary Disease Prior to Lung Transplantation.

PubMed

Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Mansour, Heidi M; Whitson, Bryan A

2016-01-01

Prevalence of pulmonary hypertension (PH) and its influence on survival in chronic obstructive pulmonary disease (COPD) are not well studied in the lung allocation score (LAS) era. The UNOS database was queried from 2005 to 2013 to identify first-time adult lung transplant candidates with COPD who were tracked from wait list entry date until death or censoring to determine both prevalence and influence of PH. Using right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg and severe ≥ 35 mmHg. Of 1315 COPD candidates not transplanted, 1243 were used for survival analysis using Cox proportional hazards models, and 1010 (mild PH) and 244 (severe PH) were used for propensity score matching, respectively. A total of 52% (652) of subjects had PH mPAP ≥ 25 mmHg. Univariate analysis revealed significant differences in survival for mild PH (HR = 1.769; 95% CI: 1.331, 2.351; p < 0.001) and severe PH (HR = 3.271; 95% CI: 2.311, 4.630; p < 0.001). Kaplan-Meier survival function demonstrated significant disparities for mild PH (Log-rank test: Chi-square1: 15.87, p < 0.0001) and severe PH (Log-rank test: Chi-square1: 50.13, p < 0.0001). Multivariate Cox models identified significant risk for death for mild PH (HR = 1.987; 95% CI: 1.484, 2.662; p < 0.001) and severe PH (HR = 3.432; 95% CI: 2.410, 4.888; p < 0.001). Propensity score matching confirmed increased mortality hazard associated with mild PH (HR = 2.280; 95% CI: 1.425, 3.649; p = 0.001) and severe PH (HR = 7.000; 95% CI: 2.455, 19.957; p < 0.001). PH is highly prevalent in advanced COPD and associated with a significantly higher risk for mortality.

Overall Graft Loss Versus Death-Censored Graft Loss: Unmasking the Magnitude of Racial Disparities in Outcomes Among US Kidney Transplant Recipients.

PubMed

Taber, David J; Gebregziabher, Mulugeta; Payne, Elizabeth H; Srinivas, Titte; Baliga, Prabhakar K; Egede, Leonard E

2017-02-01

Black kidney transplant recipients experience disproportionately high rates of graft loss. This disparity has persisted for 40 years, and improvements may be impeded based on the current public reporting of overall graft loss by US regulatory organizations for transplantation. Longitudinal cohort study of kidney transplant recipients using a data set created by linking Veterans Affairs and US Renal Data System information, including 4918 veterans transplanted between January 2001 and December 2007, with follow-up through December 2010. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). Three thousand three hundred six non-Hispanic whites (67%) were compared with 1612 non-Hispanic black (33%) recipients with 6.0 ± 2.2 years of follow-up. In the unadjusted analysis, black recipients were significantly more likely to have overall graft loss (hazard ratio [HR], 1.19; 95% confidence interval [95% CI], 1.07-1.33), death-censored graft loss (HR, 1.67; 95% CI, 1.45-1.92), and lower mortality (HR, 0.83; 95% CI, 0.72-0.96). In fully adjusted models, only death-censored graft loss remained significant (HR, 1.38; 95% CI, 1.12-1.71; overall graft loss [HR, 1.08; 95% CI, 0.91-1.28]; mortality [HR, 0.84; 95% CI, 0.67-1.06]). A composite definition of graft loss reduced the magnitude of disparities in blacks by 22%. Non-Hispanic black kidney transplant recipients experience a substantial disparity in graft loss, but not mortality. This study of US data provides evidence to suggest that researchers should focus on using death-censored graft loss as the primary outcome of interest to facilitate a better understanding of racial disparities in kidney transplantation.

Baseline participant characteristics and risk for dropout from ten obesity randomized controlled trials: a pooled analysis of individual level data.

PubMed

Kaiser, Kathryn A; Affuso, Olivia; Desmond, Renee; Allison, David B

Understanding participant demographic characteristics that inform the optimal design of obesity RCTs have been examined in few studies. The objective of this study was to investigate the association of individual participant characteristics and dropout rates (DORs) in obesity randomized controlled trials (RCT) by pooling data from several publicly available datasets for analyses. We comprehensively characterize DORs and patterns in obesity RCTs at the individual study level, and describe how such rates and patterns vary as a function of individual-level characteristics. We obtained and analyzed nine publicly-available, obesity RCT datasets that examined weight loss or weight gain prevention as a primary or secondary endpoint. Four risk factors for dropout were examined by Cox proportional hazards including sex, age, baseline BMI, and race/ethnicity. The individual study data were pooled in the final analyses with a random effect for study, and HR and 95% CIs were computed. Results of the multivariate analysis indicated that the risk of dropout was significantly higher for females compared to males (HR= 1.24, 95% CI = 1.05, 1.46). Hispanics and Non-Hispanic blacks had a significantly higher dropout rate compared to non-Hispanic whites (HR= 1.62, 95% CI = 1.37, 1.91; HR= 1.22, 95% CI = 1.11, 1.35, respectively). There was a significantly increased risk of dropout associated with advancing age (HR= 1.02, 95% CI = 1.01, 1.02) and increasing BMI (HR= 1.03, 95% CI = 1.03, 1.04). As more studies may focus on special populations, researchers designing obesity RCTs may wish to oversample in certain demographic groups if attempting to match comparison groups based on generalized estimates of expected dropout rates, or otherwise adjust a priori power estimates. Understanding true reasons for dropout may require additional methods of data gathering not generally employed in obesity RCTs, e.g. time on treatment.

Sex and SUVmax: sex-dependent prognostication in early non-small cell lung cancer.

PubMed

Wainer, Zoe; Daniels, Marissa G; Callahan, Jason; Binns, David; Hicks, Rodney J; Antippa, Phillip; Russell, Prudence A; Alam, Naveed Z; Conron, Matthew; Solomon, Benjamin; Wright, Gavin M

2012-11-01

The identification of robust prognostic factors for patients with early-stage non-small cell lung cancer (NSCLC) is clinically important. The International Association for the Study of Lung Cancer has identified both sex and the maximum standardized uptake value (SUVmax) of (18)F-FDG in the primary tumor as measured by PET as potential prognostic variables. We examined the prognostic value of SUVmax in a surgical cohort of patients with NSCLC and disaggregated the findings by sex. Patients who had undergone a preoperative PET/CT scan and surgical resection with curative intent from 2001 to 2009 were identified from a prospective database. An SUVmax cutoff was calculated using receiver-operating-characteristic curves. Overall survival was correlated with SUVmax for the whole cohort and disaggregated by sex. Inclusion criteria were met by 189 patients: 127 (67%) men and 62 (33%) women. Five-year survival was 54.6% for the whole cohort, 47.7% for men, and 68.2% for women. SUVmax correlated negatively with survival in a univariate analysis for the whole cohort (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.54-4.09; P < 0.001) and men (HR, 3.42; 95% CI, 1.94-6.05; P < 0.001) but not for women (HR, 1.61; 95% CI, 0.43-3.12; P = 0.77), using 8 as a cutoff. In multivariate analysis, SUVmax correlated with overall survival for the whole cohort (HR, 1.70; 95% CI, 1.05-2.99; P = 0.05) and men (HR, 2.40; 95% CI, 1.32-4.37; P = 0.004) but not for women (HR, 0.80; 95% CI, 0.15-4.47; P = 0.80). SUVmax independently predicted overall survival for men but not for women in this surgical cohort. Our results suggest that SUVmax is an independent prognostic variable in men with surgically treated early NSCLC.

Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin

2013-03-15

Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likelymore » to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.« less

Prognostic impact of early nutritional support in patients affected by locally advanced and metastatic pancreatic ductal adenocarcinoma undergoing chemotherapy.

PubMed

Trestini, Ilaria; Carbognin, Luisa; Sperduti, Isabella; Bonaiuto, Clelia; Auriemma, Alessandra; Melisi, Davide; Salvatore, Lisa; Bria, Emilio; Tortora, Giampaolo

2018-05-01

The aim of this analysis was to determine the risk of malnutrition and the prognostic value of nutritional intervention in patients affected by pancreatic ductal adenocarcinoma (PDAC) undergoing chemotherapy. Clinical-pathological and nutritional data were correlated with overall survival (OS) using a Cox model. Nutritional status was determined by Malnutrition Universal Screening Tool (MUST), body mass index, weight loss in the past 6 months, presence of nutrition-related symptoms, and current energy intake. Nutritional intervention included appropriate individual dietary counseling. Data from 109 patients were gathered (median age 63 years). The majority of patients (64.2%) presented a MUST value of ≥ 2, corresponding to a high risk of malnutrition. At multivariate analysis for OS in locally advanced and metastatic PDAC patients, the time between the diagnosis and the nutritional intervention (HR 2.22, p = 0.017), the performance status (HR 1.38, p = 0.075), the surgery of the primary (HR 5.89, p = 0.005), and the response to the first line (HR 5.9, p = 0.03) were independent significant predictors of outcome. Furthermore, a weight gain > 2% from the baseline weight was correlated with the time between the diagnosis and the nutritional intervention (p = 0.021): in patients receiving a nutritional support within 3 months from diagnosis, a 2% weight gain was associated with a 2-year OS benefit (50.3% vs. 33.0%, p = 0.04). This analysis suggests that the early nutritional support may contribute to influence the prognosis of patients affected by advanced PDAC undergoing chemotherapy.

Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis.

PubMed

Tomasello, Gianluca; Barni, Sandro; Turati, Luca; Ghidini, Michele; Pezzica, Ezio; Passalacqua, Rodolfo; Petrelli, Fausto

2018-02-15

CDX2 is a homeobox gene encoding transcriptional factors for intestinal organogenesis and represents a specific marker of colorectal adenocarcinoma (CRC) differentiation. We have evaluated if CDX2 expression is associated with better overall and disease-free survival (OS and DFS) in patients with CRC. PubMed, SCOPUS, EMBASE, The Cochrane Library, and Web of Science (from inception to July 2017) were systematically reviewed for relevant studies on adult patients with CRC where OS and DFS were calculated according to CDX2 expression in uni- or multivariate analysis were included. Hazard ratio (HR) for mortality and/or disease progression was calculated. The search produced 16 studies suitable for inclusion (6291 individual patients). The meta-analysis showed a reduced risk of death for patients with CDX2-positive CRC in 14 studies (HR, 0.5; 95% confidence interval [CI], 0.38-0.66; P < .001 according to random effect model). In 6 studies where only DFS data was available, CDX2 expression led to a 52% lower risk of relapse or death (HR, 0.48; 95% CI, 0.39-0.59; P < .001 according to random effect model). The results did not change as a function of ethnicity, type of study, CDX2 detection modality, or stage. Interestingly, in stages II to III, CDX2 expression was associated with a 70% lower risk of death (HR, 0.3; 95% CI, 0.12-0.77; P = .01). CDX2 expression confirms to be a strong prognostic factor in stage II and III CRC. In this setting, along with other clinical and pathologic factors, the lack of expression of CDX2 may be considered an important variable when deciding for adjuvant chemotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers

PubMed Central

Peng, Li; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui

2017-01-01

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients. PMID:27926484

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers.

PubMed

Peng, Li; Yuan, Xiao-Qing; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui; Li, Guan-Cheng

2017-01-03

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients.

Vision Loss Following Episcleral Brachytherapy for Uveal Melanoma: Development of a Vision Prognostication Tool.

PubMed

Aziz, Hassan A; Singh, Nakul; Bena, James; Wilkinson, Allan; Singh, Arun D

2016-06-01

Vision loss following episcleral brachytherapy for uveal melanoma is difficult to predict for individual patients. To generate a risk calculator for vision loss following episcleral brachytherapy for uveal melanoma. A retrospective review of data was conducted at a multispecialty tertiary care center in Cleveland, Ohio. All patients with primary ciliary body or choroidal melanoma treated with iodine 125 or ruthenium 106 episcleral brachytherapy between January 1, 2004, and December 30, 2013, were included. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log-rank analyses) were used to estimate freedom from vision loss. Bootstrap resampling was performed to bias correct this estimate. Vision loss (to visual acuity [VA] worse than 20/50 and worse than 20/200). A total of 311 patients were included in the study, with a mean (SD) age of 62 (14.7) years at start of treatment and a median follow-up of 36 months (interquartile range, 18-60 months). At presentation, VA was better than or equal to 20/50 in 199 patients (64%) and better than or equal to 20/200 in 289 patients (93%). By Kaplan-Meier analysis, VA less than 20/200 at 3 years was not associated with sex, diabetes, systemic hypertension, or hypercholesterolemia but was associated with history of ocular comorbidities, type of isotope (ruthenium 106 or iodine 125), and initial VA ( >20/50 or <20/50). By multivariable analysis, age (hazard ratio [HR], 0.97; 95% CI, 0.94-1.00; P = .06), largest basal diameter (HR, 1.25; 95% CI, 1.16-1.34; P = <.001), total radiation dose to the fovea (HR, 1.03; 95% CI, 1.01-1.04; P = .001) and optic disc (HR, 1.01; 95% CI, 1.00-1.01; P = .005), and initial VA worse than 20/50 (HR, 1.85; 95% CI, 1.20-2.85; P = .005) were predictive of vision loss to a VA of less than 20/200. The concordance index for the full data set was 0.77. Using these data, an online risk calculator was developed to predict vision loss following episcleral brachytherapy. The vision prognostication tool presented herein needs to be validated by independent data sets. This tool may improve counseling for patients being evaluated for episcleral brachytherapy. At-risk individuals identified by this tool could be considered for inclusion into trials exploring prevention or treatment of radiation retinopathy and alternative therapies of uveal melanoma.

The Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification independently predicts wound healing in diabetic foot ulcers.

PubMed

Hicks, Caitlin W; Canner, Joseph K; Mathioudakis, Nestoras; Sherman, Ronald; Malas, Mahmoud B; Black, James H; Abularrage, Christopher J

2018-04-02

Previous studies have reported correlation between the Wound, Ischemia, and foot Infection (WIfI) classification system and wound healing time on unadjusted analyses. However, in the only multivariable analysis to date, WIfI stage was not predictive of wound healing. Our aim was to examine the association between WIfI classification and wound healing after risk adjustment in patients with diabetic foot ulcers (DFUs) treated in a multidisciplinary setting. All patients presenting to our multidisciplinary DFU clinic from June 2012 to July 2017 were enrolled in a prospective database. A Cox proportional hazards model accounting for patients' sociodemographics, comorbidities, medication profiles, and wound characteristics was used to assess the association between WIfI classification and likelihood of wound healing at 1 year. There were 310 DFU patients enrolled (mean age, 59.0 ± 0.7 years; 60.3% male; 60.0% black) with 709 wounds, including 32.4% WIfI stage 1, 19.9% stage 2, 25.2% stage 3, and 22.4% stage 4. Mean wound healing time increased with increasing WIfI stage (stage 1, 96.9 ± 8.3 days; stage 4, 195.1 ± 10.6 days; P < .001). Likelihood of wound healing at 1 year was 94.1% ± 2.0% for stage 1 wounds vs 67.4% ± 4.4% for stage 4 (P < .001). After risk adjustment, increasing WIfI stage was independently associated with poor wound healing (stage 4 vs stage 1: hazard ratio, [HR] 0.44; 95% confidence interval, 0.33-0.59). Peripheral artery disease (HR, 0.73), increasing wound area (HR, 0.99 per square centimeter), and longer time from wound onset to first assessment (HR, 0.97 per month) also decreased the likelihood of wound healing, whereas use of clopidogrel was protective (HR, 1.39; all, P ≤ .04). The top three predictors of poor wound healing were WIfI stage 4 (z score, -5.40), increasing wound area (z score, -3.14), and WIfI stage 3 (z score, -3.11), respectively. Among patients with DFU, the WIfI classification system predicts wound healing at 1 year in both crude and risk-adjusted analyses. This is the first study to validate the WIfI score as an independent predictor of wound healing using multivariable analysis. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Time-varying associations of suicide with deployments, mental health conditions, and stressful life events among current and former US military personnel: a retrospective multivariate analysis.

PubMed

Shen, Yu-Chu; Cunha, Jesse M; Williams, Thomas V

2016-11-01

US military suicides have increased substantially over the past decade and currently account for almost 20% of all military deaths. We investigated the associations of a comprehensive set of time-varying risk factors with suicides among current and former military service members. We did a retrospective multivariate analysis of all US military personnel between 2001 and 2011 (n=110 035 573 person-quarter-years, representing 3 795 823 service members). Outcome was death by suicide, either during service or post-separation. We used Cox proportional hazard models at the person-quarter level to examine associations of deployment, mental disorders, history of unlawful activity, stressful life events, and other demographic and service factors with death by suicide. The strongest predictors of death by suicide were current and past diagnoses of self-inflicted injuries, major depression, bipolar disorder, substance use disorder, and other mental health conditions (compared with service members with no history of diagnoses, the hazard ratio [HR] ranged from 1·4 [95% CI 1·14-1·72] to 8·34 [6·71-10·37]). Compared with service members who were never deployed, hazard rates of suicide (which represent the probability of death by suicide in a specific quarter given that the individual was alive in the previous quarter) were lower among the currently deployed (HR 0·50, 95% CI 0·40-0·61) but significantly higher in the quarters following first deployment (HR 1·51 [1·17-1·96] if deployed in the previous three quarters; 1·14 [1·06-1·23] if deployed four or more quarters ago). The hazard rate of suicide increased within the first year of separation from the military (HR 2·49, 95% CI 2·12-2·91), and remained high for those who had separated from the military 6 or more years ago (HR 1·63, 1·45-1·82). The increased hazard rate of death by suicide for military personnel varies by time since exposure to deployment, mental health diagnoses, and other stressful life events. Continued monitoring is especially needed for these high-risk individuals. Additional information should be gathered to address the persistently raised risk of suicide among service members after separation. Partly funded by the Naval Research Program. Copyright © 2016 Elsevier Ltd. All rights reserved.

Individual and Combined Effects of Dietary Factors on Risk of Incident Hypertension: Prospective Analysis From the NutriNet-Santé Cohort.

PubMed

Lelong, Helene; Blacher, Jacques; Baudry, Julia; Adriouch, Solia; Galan, Pilar; Fezeu, Leopold; Hercberg, Serge; Kesse-Guyot, Emmanuelle

2017-10-01

Dietary intake is pointed as one of the major determinants in hypertension development. Data in the area are mostly obtained from cross-sectional studies. We aimed to investigate the prospective association between (1) individual nutritional factors and (2) adherence to the Dietary Approach to Stop Hypertension and the risk of incident hypertension in a large cohort study. We prospectively examined the incidence of hypertension among 80 426 French adults participating in the NutriNet-Santé cohort study. Self-reported sociodemographic, lifestyle health questionnaires and dietary consumption assessed by three 24-hour records were completed at baseline and yearly thereafter. Associations between quartiles (Q) of nutrients and food groups and adherence to Dietary Approach to Stop Hypertension diet and hypertension risk were assessed by multivariable Cox proportional hazards models. During a mean follow-up of 3.4±2.1 years, 2413 cases of incident hypertension were documented. Dietary intakes of sodium (Q4 versus Q1): hazard ratio (HR)=1.17 (95% confidence interval [CI], 1.02-1.35), potassium: HR=0.82 (95% CI, 0.72-0.94), animal protein: HR=1.26 (95% CI, 1.11-1.43), vegetable protein: HR=0.85 (95% CI, 0.75-0.95), fiber: HR =0.81 (95% CI, 0.71-0.93), magnesium: HR=0.77 (95% CI, 0.67-0.89), fruit and vegetables: HR=0.85 (95% CI, 0.74-0.97), whole grain: HR=0.84(95% CI, 0.76-0.93), nuts: HR=0.72 (95% CI, 0.63-0.83), and red and processed meat: HR=1.25 (95% CI, 1.11-0.42) were associated with risk of hypertension. Besides, adherence to the Dietary Approach to Stop Hypertension was strongly inversely associated with incident hypertension: (Q4 versus Q1) HR=0.66 (95% CI, 0.58-0.75). Our results confirmed the association of several nutritional factors intake and incident hypertension and highlighted that adopting a global healthy diet could strongly contribute to the prevention of hypertension. © 2017 American Heart Association, Inc.

Pulmonic stenosis in dogs: survival and risk factors in a retrospective cohort of patients.

PubMed

Locatelli, C; Spalla, I; Domenech, O; Sala, E; Brambilla, P G; Bussadori, C

2013-09-01

To assess survival and risk factors in dogs with pulmonic stenosis. A retrospective review of medical case records of all cases of pulmonic stenosis >50 mmHg, undergoing pulmonary balloon valvuloplasty or not. Survival curves and multivariate analysis were calculated in the overall population and in subgroups. One hundred and seventy-two cases were included. Factors negatively affecting survival were clinical signs [hazard ratio (HR) 3 · 44, P < 0 · 001], younger age at diagnosis (HR 3 · 96, P = 0 · 001) and valve morphology type B (HR 3 · 33, P = 0 · 001) in the overall population. In those that had pulmonary balloon valvuloplasty group only clinical signs was significant (HR 3 · 44, P < 0 · 001). In cases that did not undergo pulmonary balloon valvuloplasty group Doppler gradient (HR 1 · 02, P < 0 · 001), clinical signs (HR 5 · 41, P = 0 · 002), valve morphology type B (HR 10 · 20, P = 0 · 001) and younger age at diagnosis (HR 12 · 82, P < 0 · 001) negatively affected survival. Dogs with severe pulmonic stenosis undergoing pulmonary balloon valvuloplasty (HR 0 · 47, P = 0 · 047) and asymptomatic dogs with moderate pulmonic stenosis (HR 0 · 10, P = 0 · 042) had a better outcome. Younger age at diagnosis was correlated with poorer outcome in right-sided congestive heart failure dogs (HR 14 · 02, P = 0 · 01). Clinical signs, valve morphology type B and age at diagnosis are risk factors in pulmonic stenosis patients. Pulmonary balloon valvuloplasty is a reasonable treatment choice in dogs with severe pulmonic stenosis. © 2013 British Small Animal Veterinary Association.

Prognostic value of systolic mitral annular velocity measured with Doppler tissue imaging in patients with chronic heart failure caused by left ventricular systolic dysfunction

PubMed Central

Nikitin, N P; Loh, P H; de Silva, R; Ghosh, J; Khaleva, O Y; Goode, K; Rigby, A S; Alamgir, F; Clark, A L; Cleland, J G F

2006-01-01

Objective To assess the prognostic value of various conventional and novel echocardiographic indices in patients with chronic heart failure (CHF) caused by left ventricular (LV) systolic dysfunction. Methods 185 patients with a mean (SD) age of 67 (11) years with CHF and LV ejection fraction < 45% despite optimal pharmacological treatment were prospectively enrolled. The patients underwent two dimensional echocardiography with tissue harmonic imaging to assess global LV systolic function and obtain volumetric data. Transmitral flow was assessed with conventional pulse wave Doppler. Systolic (Sm), early, and late diastolic mitral annular velocities were measured with the use of colour coded Doppler tissue imaging. Results During a median follow up of 32 months (range 24–38 months in survivors), 34 patients died and one underwent heart transplantation. Sm velocity (hazard ratio (HR) 0.648, 95% confidence interval (CI) 0.463 to 0.907, p  =  0.011), diastolic arterial pressure (HR 0.965, 95% CI 0.938 to 0.993, p  =  0.015), serum creatinine (HR 1.006, 95% CI 1.001 to 1.011, p  =  0.023), LV ejection fraction (HR 0.945, 95% CI 0.899 to 0.992, p  =  0.024), age (HR 1.035, 95% CI 1.000 to 1.071, p  =  0.052), LV end systolic volume index (HR 1.009, 95% CI 0.999 to 1.019, p  =  0.067), and restrictive pattern of transmitral flow (HR 0.543, 95% CI 0.278 to 1.061, p  =  0.074) predicted the outcome of death or transplantation on univariate analysis. On multivariate analysis, only Sm velocity (HR 0.648, 95% CI 0.460 to 0.912, p  =  0.013) and diastolic arterial pressure (HR 0.966, 95% CI 0.938 to 0.994, p  =  0.016) emerged as independent predictors of outcome. Conclusions In patients with CHF and LV systolic dysfunction despite optimal pharmacological treatment, the strongest independent echocardiographic predictor of prognosis was Sm velocity measured with quantitative colour coded Doppler tissue imaging. PMID:16251233

Long-Term Exposure to Particulate Matter and Self-Reported Hypertension: A Prospective Analysis in the Nurses' Health Study.

PubMed

Zhang, Zhenyu; Laden, Francine; Forman, John P; Hart, Jaime E

2016-09-01

Studies have suggested associations between elevated blood pressure and short-term air pollution exposures, but the evidence is mixed regarding long-term exposures on incidence of hypertension. We examined the association of hypertension incidence with long-term residential exposures to ambient particulate matter (PM) and residential distance to roadway. We estimated 24-month and cumulative average exposures to PM10, PM2.5, and PM2.5-10 and residential distance to road for women participating in the prospective nationwide Nurses' Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for incident hypertension from 1988 to 2008 using Cox proportional hazards models adjusted for potential confounders. We considered effect modification by age, diet, diabetes, obesity, region, and latitude. Among 74,880 participants, 36,812 incident cases of hypertension were observed during 960,041 person-years. In multivariable models, 10-μg/m3 increases in 24-month average PM10, PM2.5, and PM2.5-10 were associated with small increases in the incidence of hypertension (HR: 1.02, 95% CI: 1.00, 1.04; HR: 1.04, 95% CI: 1.00, 1.07; and HR: 1.03, 95% CI: 1.00, 1.07, respectively). Associations were stronger among women < 65 years of age (HR: 1.04, 95% CI: 1.01, 1.06; HR: 1.07, 95% CI: 1.02, 1.12; and HR: 1.05, 95% CI: 1.01, 1.09, respectively) and the obese (HR: 1.07, 95% CI: 1.04, 1.12; HR: 1.15, 95% CI: 1.07, 1.23; and HR: 1.13, 95% CI: 1.07, 1.19, respectively), with p-values for interaction < 0.05 for all models except age and PM2.5-10. There was no association with roadway proximity. Long-term exposure to particulate matter was associated with small increases in risk of incident hypertension, particularly among younger women and the obese. Zhang Z, Laden F, Forman JP, Hart JE. 2016. Long-term exposure to particulate matter and self-reported hypertension: a prospective analysis in the Nurses' Health Study. Environ Health Perspect 124:1414-1420; http://dx.doi.org/10.1289/EHP163.

Serum lactate dehydrogenase with a systemic inflammation score is useful for predicting response and survival in patients with newly diagnosed diffuse large B-cell lymphoma.

PubMed

Jung, Sung-Hoon; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

2015-01-01

We evaluated the relationship between serum lactate dehydrogenase (LDH) level with systemic inflammation score and survival in 213 patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. The patients were classified into 3 groups based on LDH with the Glasgow Prognostic Score (L-GPS). A score of 2 was assigned to patients with elevated C-reactive protein, hypoalbuminemia and elevated LDH, a score of 1 to those with one or two abnormalities and a score of 0 to those with no abnormality. In multivariate analysis, independent poor prognostic factors for progression-free survival were L-GPS 2 [hazard ratio (HR) 5.415, p = 0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR 3.504, p = 0.001) and bulky lesion (HR 2.030, p = 0.039). Independent poor prognostic factors for overall survival were L-GPS 2 (HR 5.898, p = 0.001) and ECOG PS ≥2 (HR 3.525, p = 0.001). The overall response rate for the R-CHOP chemotherapy decreased according to the L-GPS; it was 96.7% at L-GPS 0, 87% at L-GPS 1 and 75% at L-GPS 2 (p = 0.009). L-GPS based on systemic inflammatory indicators may be a useful clinical prognostic indicator for survival, and predicts the response for R-CHOP chemotherapy in patients with newly diagnosed DLBCL. © 2014 S. Karger AG, Basel.

Risk factors for colonization and infection by Pseudomonas aeruginosa in patients hospitalized in intensive care units in France.

PubMed

Hoang, S; Georget, A; Asselineau, J; Venier, A-G; Leroyer, C; Rogues, A M; Thiébaut, R

2018-01-01

To assess the role of environment, medical care and individual risks factors for P. aeruginosa colonization and infection. A French multicentric prospective study involved ten ICUs for a five months period. Every adult patient newly hospitalized in ICUs with no P. aeruginosa carriage up to 48 hours after admission was included and weekly screened before discharge or death. Screening swabs were either rectal, sputum or oropharyngeal samples. Hydric environment was also sampled each week. Data on patient clinical features, environmental and device exposures, and antibiotics supports were regularly collected. Multivariate analysis was performed with a multistate model. The overall prevalence of P. aeruginosa carriage was 15.3% (201/1314). Risk factors associated with patient colonization were: use of inactive antibiotics against P. aeruginosa (HR = 1.60 [1.15-2.21] p<0.01), tap water contamination at the entry in the room (HR = 1.66 [1.01-2.27] p<0.05) and mechanical invasive ventilation (HR = 4.70 [2.66-8.31] p<0.0001). Active antibiotics prevented from colonization (HR = 0.67 [0.48-0.93] p = 0.02) and from infection (HR = 0.64 [0.41-1.01] p = 0.05). Interaction between hydric environment antibiotics support was not statistically associated with patient colonization. Hydric contamination and antibiotics pressure seem to remain key independent risk factors in P. aeruginosa colonization. These results advocate the need to carry on preventive and targeted interventions toward healthcare associated infections.

Living alone, obesity, and smoking increase risk for suicide independently of depressive mood findings from the population-based MONICA/KORA Augsburg cohort study.

PubMed

Schneider, Barbara; Lukaschek, Karoline; Baumert, Jens; Meisinger, Christa; Erazo, Natalia; Ladwig, Karl-Heinz

2014-01-01

Suicide is strongly associated with mental disorders, particularly with depression. There is insufficient knowledge to what extent sociodemographic and behavioral characteristics contribute to suicide risk. A population-based cohort study on three independent cross-sectional MONICA/KORA Augsburg surveys with 12,888 subjects (6456 men, 6432 women) was followed up on average for 12.0 years. Information on sociodemographic characteristics, chronic disease conditions, smoking habits, alcohol consumption, depressive symptoms, personality type, and other psychodiagnostic parameters was assessed by standardized interviews. Cox proportional hazards regression analyses were used to compute hazard ratios (HRs) as estimates of relative risks for suicide mortality. Additionally, population-attributable risks were calculated. Within the follow-up period, a total of 1449 persons had died, 38 of them by suicide. Although several variables were associated with increased risk in the basic analyses, only obesity (HR=2.73), smoking (HR=2.23), and living alone (HR=2.19) remained significantly associated with suicide additionally to male sex (HR=3.57) and depressed mood (HR=2.01) in a multivariate analysis. The generalization of our findings to countries with different social, economic or cultural conditions may be questioned. Our findings extend the knowledge about sociodemographic and behavioral risk factors for suicide in the general population: Suicide prevention measures should not consider only subjects with mental disorders but also address other adverse conditions. © 2013 Published by Elsevier B.V.

Chlamydia Retesting Among Safety-Net Clinic Patients: Infertility Prevention Project.

PubMed

McArdle, Breanna J; Buser, Genevieve L; Hedberg, Katrina; Schafer, Sean

2018-04-25

Due to high reinfection rates, the Centers for Disease Control and Prevention (CDC) recommend retesting everyone diagnosed with chlamydia after treatment. However, retesting rates are often low, and research on retesting is limited. Infertility Prevention Project (IPP) was a national chlamydia screening and treatment project in the United States. We completed a retrospective longitudinal analysis using IPP testing data from 8,266 women with at least 1 positive test result from 2010 to 2013. We calculated the proportion of women retested 2-12 months after a chlamydia diagnosis and used Cox proportional hazards models to explore associated factors. Only 32% of women had evidence of retesting by 12 months of follow-up. Being younger (multivariate hazard ratio [mHR]: 0.96; 95% confidence interval [CI]: 0.95-0.96), black (mHR: 1.29; 95% CI: 1.12-1.50), or attending a county sexually transmitted diseases (STD; mHR: 1.91; 95% CI: 1.68-2.17), county family planning (mHR: 1.53; 95% CI: 1.39-1.69), or school-based (mHR: 2.34; 95% CI: 2.07-2.65) clinic relative to a nonprofit community health clinic were associated with increased retesting rates. Less than one-third of women are retested. Our results show that some clinic settings may have systematic differences which facilitate retesting, such as use of automated reminders, closed patient populations, and makeup of patient populations. Investigation of clinical environments through site visits and further data analyses may be keys to improving retesting rates.

New insights into the effect of haemodiafiltration on mortality: the Romanian experience.

PubMed

Siriopol, Dimitrie; Canaud, Bernard; Stuard, Stefano; Mircescu, Gabriel; Nistor, Ionut; Covic, Adrian

2015-02-01

Haemodiafiltration (HDF), by successfully removing the larger solutes and protein-bound compounds, may offer a feasible approach to improve dialysis outcomes. Recently, three large, randomized, controlled trials have tested this hypothesis, but only one showed an improved survival associated with HDF treatment, when compared with haemodialysis (HD). This is a retrospective analysis of the entire Romanian dialysed population from the European Clinical Database (EUCLID) Fresenius Medical Care Database. We conducted two types of analysis. First, we used an intention-to-treat approach including all patients who were in dialysis (either HDF or HD) at 1 March 2010--'prevalent cohort analysis'. We then considered only the incident patients who started dialysis (either HDF or HD) after 1 March 2010--'incident cohort analysis'. In both analyses, patients were followed until 31 April 2013. In the prevalent cohort, we included 1546 patients who were already performing dialysis at the first time point-1322 on HD and 224 on HDF. When compared with HD, HDF treatment was associated with reduced mortality in both univariate and multivariate survival analysis (HR = 0.67, 95% CI 0.46-0.96 and HR = 0.58, 95% CI 0.36-0.93, respectively). In the incident cohort, 2447 patients started dialysis (2181 HD and 266 HDF) during the observation period. Patients in the HDF group maintained a reduced risk for all-cause mortality (HR = 0.20, 95% CI 0.11-0.38 for the univariate and HR = 0.24, 95% CI 0.13-0.46 for the fully adjusted model). This study suggests that HDF treatment could reduce all-cause mortality in incident and prevalent patients even after correction for different confounders. Interestingly, an additional survival benefit could be observed in incident patients. However, as with any observational study, there could have been other unmeasured confounders that could have influenced our final results. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Adherence to recommendations of the German food pyramid and risk of chronic diseases: results from the EPIC-Potsdam study.

PubMed

von Ruesten, A; Illner, A-K; Buijsse, B; Heidemann, C; Boeing, H

2010-11-01

The German food pyramid was set up to foster and communicate healthy food choices. The adherence to recommendations of the food pyramid was translated into an index (German Food Pyramid Index (GFPI)) by scoring the ratio of consumed and recommended daily servings of eight food groups, wherein higher scores indicated greater adherence. The GFPI was calculated for 23 531 subjects who participated in the European Prospective Investigation into Cancer and Nutrition-Potsdam study and were recruited between 1994 and 1998. Associations between quintiles of GFPI scores and risk of incident cardiovascular diseases (CVD), type-2 diabetes (T2D) and cancer were evaluated using Cox proportional hazard regression models. During 183 740 person-years of follow-up, 363 incident cases of CVD (myocardial infarction or stroke), 837 incident cases of T2D and 844 incident cases of cancer occurred. The GFPI was inversely related to CVD risk in men (multivariable-adjusted hazard ratio (HR) for highest versus lowest quintiles=0.56; 95% confidence interval (CI): 0.34-0.94) but not in women (HR=1.39; 95% CI: 0.76-2.55). No association between GFPI and cancer was observed. An inverse relation between GFPI and T2D (men: HR= 0.71 (0.52-0.97); women: HR= 0.69 (0.50-0.96)) in age-adjusted models was substantially attenuated after multivariable adjustments, particularly by body mass index (BMI) (men: HR=0.94 (0.69-1.30); women: HR=1.09 (0.77-1.54)). The same was observed for overall major chronic disease risk (CVD, T2D and total cancer). Adherence to the German food pyramid recommendations is not associated with a decreased risk of chronic diseases when considering BMI as confounder, except of CVD in men.

Low Body Mass Index, Serum Creatinine, and Cause of Death in Patients Undergoing Percutaneous Coronary Intervention.

PubMed

Goel, Kashish; Gulati, Rajiv; Reeder, Guy S; Lennon, Ryan J; Lewis, Bradley R; Behfar, Atta; Sandhu, Gurpreet S; Rihal, Charanjit S; Singh, Mandeep

2016-10-31

Low body mass index (BMI) and serum creatinine are surrogate markers of frailty and sarcopenia. Their relationship with cause-specific mortality in elderly patients undergoing percutaneous coronary intervention is not well studied. We determined long-term cardiovascular and noncardiovascular mortality in 9394 consecutive patients aged ≥65 years who underwent percutaneous coronary intervention from 2000 to 2011. BMI and serum creatinine were divided into 4 categories. During a median follow-up of 4.2 years (interquartile range 1.8-7.3 years), 3243 patients (33.4%) died. In the multivariable model, compared with patients with normal BMI, patients with low BMI had significantly increased all-cause mortality (hazard ratio [HR] 1.4, 95% CI 1.1-1.7), which was related to both cardiovascular causes (HR 1.4, 95% CI 1.0-1.8) and noncardiovascular causes (HR 1.4, 95% CI 1.06-1.9). Compared with normal BMI, significant reduction was noted in patients who were overweight and obese in terms of cardiovascular mortality (overweight: HR 0.77, 95% CI 0.67-0.88; obese: HR 0.80, 95% CI 0.70-0.93) and noncardiovascular mortality (overweight: HR 0.85, 95% CI 0.74-0.97; obese: HR 0.82, 95% CI 0.72-0.95). In a multivariable model, in patients with normal BMI, low creatinine (≤0.70 mg/dL) was significantly associated with increased all-cause mortality (HR 1.8, 95% CI 1.3-2.5) and cardiovascular mortality (HR 2.3, 95% CI 1.4-3.8) compared with patients with normal creatinine (0.71-1.0 mg/dL); however, this was not observed in other BMI categories. We identified a new subgroup of patients with low serum creatinine and normal BMI that was associated with increased all-cause mortality and cardiovascular mortality in elderly patients undergoing percutaneous coronary intervention. Low BMI was associated with increased cardiovascular and noncardiovascular mortality. Nutritional support, resistance training, and weight-gain strategies may have potential roles for these patients undergoing percutaneous coronary intervention. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection

PubMed Central

Schirripa, M; Bergamo, F; Cremolini, C; Casagrande, M; Lonardi, S; Aprile, G; Yang, D; Marmorino, F; Pasquini, G; Sensi, E; Lupi, C; De Maglio, G; Borrelli, N; Pizzolitto, S; Fasola, G; Bertorelle, R; Rugge, M; Fontanini, G; Zagonel, V; Loupakis, F; Falcone, A

2015-01-01

Background: Despite major advances in the management of metastatic colorectal cancer (mCRC) with liver-only involvement, relapse rates are high and reliable prognostic markers are needed. Methods: To assess the prognostic impact of BRAF and RAS mutations in a large series of liver-resected patients, medical records of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially curative liver resection were selected. BRAF and RAS mutational status was tested on primary and/or metastases by means of pyrosequencing and mass spectrometry genotyping assay. Primary endpoint was relapse-free survival (RFS). Results: In the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt) patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7, 11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043). At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09–4.87; P=0.029) and to RAS mutant (multivariate HR=2.06; 95% CI, 1.02–4.14; P=0.044). Similar results were obtained in terms of overall survival. Compared with all wt patients, RAS mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05–2.07; P=0.025), but such effect was lost at multivariate analyses. Conclusions: BRAF mutation is associated with an extremely poor median RFS after liver resection and with higher probability of relapse and death. Knowledge of BRAF mutational status may optimise clinical decision making in mCRC patients potentially candidate to hepatic surgery. RAS status as useful marker in this setting might require further studies. PMID:25942399

Importance of recurrence rating, morphology, hernial gap size, and risk factors in ventral and incisional hernia classification.

PubMed

Dietz, U A; Winkler, M S; Härtel, R W; Fleischhacker, A; Wiegering, A; Isbert, C; Jurowich, Ch; Heuschmann, P; Germer, C-T

2014-02-01

There is limited evidence on the natural course of ventral and incisional hernias and the results of hernia repair, what might partially be explained by the lack of an accepted classification system. The aim of the present study is to investigate the association of the criteria included in the Wuerzburg classification system of ventral and incisional hernias with postoperative complications and long-term recurrence. In a retrospective cohort study, the data on 330 consecutive patients who underwent surgery to repair ventral and incisional hernias were analyzed. The following four classification criteria were applied: (a) recurrence rating (ventral, incisional or incisional recurrent); (b) morphology (location); (c) size of the hernial gap; and (d) risk factors. The primary endpoint was the occurrence of a recurrence during follow-up. Secondary endpoints were incidence of postoperative complications. Independent association between classification criteria, type of surgical procedures and postoperative complications was calculated by multivariate logistic regression analysis and between classification criteria, type of surgical procedures and risk of long-term recurrence by Cox regression analysis. Follow-up lasted a mean 47.7 ± 23.53 months (median 45 months) or 3.9 ± 1.96 years. The criterion "recurrence rating" was found as predictive factor for postoperative complications in the multivariate analysis (OR 2.04; 95 % CI 1.09-3.84; incisional vs. ventral hernia). The criterion "morphology" had influence neither on the incidence of the critical event "recurrence during follow-up" nor on the incidence of postoperative complications. Hernial gap "width" predicted postoperative complications in the multivariate analysis (OR 1.98; 95 % CI 1.19-3.29; ≤5 vs. >5 cm). Length of the hernial gap was found to be an independent prognostic factor for the critical event "recurrence during follow-up" (HR 2.05; 95 % CI 1.25-3.37; ≤5 vs. >5 cm). The presence of 3 or more risk factors was a consistent predictor for "recurrence during follow-up" (HR 2.25; 95 % CI 1.28-9.92). Mesh repair was an independent protective factor for "recurrence during follow-up" compared to suture (HR 0.53; 95 % CI 0.32-0.86). The ventral and incisional hernia classification of Dietz et al. employs a clinically proven terminology and has an open classification structure. Hernial gap size and the number of risk factors are independent predictors for "recurrence during follow-up", whereas recurrence rating and hernial gap size correlated significantly with the incidence of postoperative complications. We propose the application of these criteria for future clinical research, as larger patient numbers will be needed to refine the results.

Age-related changes in bone strength from HR-pQCT derived microarchitectural parameters with an emphasis on the role of cortical porosity.

PubMed

Vilayphiou, Nicolas; Boutroy, Stephanie; Sornay-Rendu, Elisabeth; Van Rietbergen, Bert; Chapurlat, Roland

2016-02-01

The high resolution peripheral computed tomography (HR-pQCT) technique has seen recent developments with regard to the assessment of cortical porosity. In this study, we investigated the role of cortical porosity on bone strength in a large cohort of women. The distal radius and distal tibia were scanned by HR-pQCT. We assessed bone strength by estimating the failure load by microfinite element analysis (μFEA), with isotropic and homogeneous material properties. We built a multivariate model to predict it, using a few microarchitecture variables including cortical porosity. Among 857 Caucasian women analyzed with μFEA, we found that cortical and trabecular properties, along with the failure load, impaired slightly with advancing age in premenopausal women, the correlations with age being modest, with |rage| ranging from 0.14 to 0.38. After the onset of the menopause, those relationships with age were stronger for most parameters at both sites, with |rage| ranging from 0.10 to 0.64, notably for cortical porosity and failure load, which were markedly deteriorated with increasing age. Our multivariate model using microarchitecture parameters revealed that cortical porosity played a significant role in bone strength prediction, with semipartial r(2)=0.22 only at the tibia in postmenopausal women. In conclusion, in our large cohort of women, we observed a small decline of bone strength at the tibia before the onset of menopause. We also found an age-related increase of cortical porosity at both scanned sites in premenopausal women. In postmenopausal women, the relatively high increase of cortical porosity accounted for the decline in bone strength only at the tibia. Copyright © 2015 Elsevier Inc. All rights reserved.

The impact of colorectal screening program on the detection of right-sided colorectal cancer. A 5-year cohort study in the Mantua District.

PubMed

Asteria, Corrado R; Pucciarelli, Salvatore; Gerard, Leonardo; Mantovani, Nicola; Pagani, Mauro; Boccia, Luigi; Ricci, Paolo; Troiano, Luigi; Lucchini, Giuseppe; Pulica, Coriolano

2015-12-01

High rates of advanced colorectal cancer (CRC) are still diagnosed in the right side of the colon. This study aimed to investigate whether screening programs increase CRC detection and whether tumor location is associated with survival outcome. Patients affected by CRC, aged from 50 to 69 years and operated on from 2005 to 2009 were reviewed. Other than patient-, disease-, and treatment-related factors, detection mode and tumor location were recorded. Overall (OS) and disease-free survival (DFS) were investigated, using univariate and multivariate analyses. Mean age of 386 patients included was 62.0 years, 59 % were males. CRC was detected by screening in 17 % of cases, and diagnosis was made from symptoms in 67 % and emergency surgery for 16 %. Screen-detected CRCs were located in the left colon (59 %), then in rectum (25 %) and in proximal colon (16 %) (p = 0.02). Most of CRC patients urgently operated on had cancer located in proximal colon (45 %), then in the left colon (36 %) and in rectum (18 %) (p = 0.001). Right-sided CRC demonstrated higher pTNM stage (p = 0.001), adequate harvest count nodes (p = 0.0001), metastatic nodes (p = 0.02), and poor differentiation grading (p = 0.0001). With multivariate analysis, poor differentiation grade was independently associated with both worse OS (HR 3.6, p = 0.05) and worse DFS (HR 8.1, p = 0.0001), while distant recurrence was associated with worse OS (HR 20.1, p = 0.0001). Low rates of right-sided CRC are diagnosed following screening program. Proximal CRC demonstrates aggressive behavior without impact on outcome. These findings prompt concern about population awareness for CRC screening.

Lymph Node Yield as a Predictor of Survival in Pathologically Node Negative Oral Cavity Carcinoma.

PubMed

Lemieux, Aaron; Kedarisetty, Suraj; Raju, Sharat; Orosco, Ryan; Coffey, Charles

2016-03-01

Even after a pathologically node-negative (pN0) neck dissection for oral cavity squamous cell carcinoma (SCC), patients may develop regional recurrence. In this study, we (1) hypothesize that an increased number of lymph nodes removed (lymph node yield) in patients with pN0 oral SCC predicts improved survival and (2) explore predictors of survival in these patients using a multivariable model. Case series with chart review. Administrative database analysis. The SEER database was queried for patients diagnosed with all-stage oral cavity SCC between 1988 and 2009 who were determined to be pN0 after elective lymph node dissection. Demographic and treatment variables were extracted. The association of lymph node yield with 5-year all-cause survival was studied with multivariable survival analyses. A total of 4341 patients with pN0 oral SCC were included in this study. The 2 highest lymph node yield quartiles (representing >22 nodes removed) were found to be significant predictors of overall survival (22-35 nodes: hazard ratio [HR] = 0.854, P = .031; 36-98 nodes: HR = 0.827, P = .010). Each additional lymph node removed during neck dissection was associated with increased survival (HR = 0.995, P = .022). These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Childhood internalizing and externalizing problems predict the onset of clinical panic attacks over adolescence: the TRAILS study.

PubMed

Mathyssek, Christina M; Olino, Thomas M; Verhulst, Frank C; van Oort, Floor V A

2012-01-01

Panic attacks are a source of individual suffering and are an independent risk factor for later psychopathology. However, much less is known about risk factors for the development of panic attacks, particularly during adolescence when the incidence of panic attacks increases dramatically. We examined whether internalizing and externalizing problems in childhood predict the onset of panic attacks in adolescence. This study is part of the TRacking Adolescents' Individual Lives Survey (TRAILS), a Dutch longitudinal population cohort study (N = 1,584). Internalizing and Externalizing Problems were collected using the Youth Self-Report (YSR) and the parent-report Child Behavior Checklist (CBCL) at baseline (age 10-12). At age 18-20, DSM-IV defined panic attacks since baseline were assessed with the Composite International Diagnostic Interview (CIDI). We investigated whether early adolescent Internalizing and Externalizing Problems predicted panic attacks between ages 10-20 years, using survival analysis in univariate and multivariate models. There were N = 314 (19.8%) cases who experienced at least one DSM-IV defined panic attack during adolescence and N = 18 (1.2%) who developed panic disorder during adolescence. In univariate analyses, CBCL Total Problems, Internalizing Problems and three of the eight syndrome scales predicted panic attack onset, while on the YSR all broad-band problem scales and each narrow-band syndrome scale predicted panic attack onset. In multivariate analyses, CBCL Social Problems (HR 1.19, p<.05), and YSR Thought Problems (HR 1.15, p<.05) and Social Problems (HR 1.26, p<.01) predicted panic attack onset. Risk indicators of panic attack include the wide range of internalizing and externalizing problems. Yet, when adjusted for co-occurring problem behaviors, Social Problems were the most consistent risk factor for panic attack onsets in adolescence.

Obesity and Risk of Biochemical Failure for Patients Receiving Salvage Radiotherapy After Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Christopher R.; Spiotto, Michael T.; Kapp, Daniel S.

Purpose: Obesity has been proposed as an independent risk factor for patients undergoing surgery or radiotherapy (RT) for prostate cancer. Using body mass index (BMI) as a measure of obesity, we tested its role as a risk factor for patients receiving salvage RT after prostatectomy. Methods and Materials: Rates of subsequent biochemical relapse were examined in 90 patients who underwent salvage RT between 1984 and 2004 for biochemical failure after radical prostatectomy. Median follow-up was 3.7 years. The BMI was tested as a continuous and categorical variable (stratified as <25, 25-<30, and {>=}30 kg/m{sup 2}). Univariate and multivariate proportional hazardsmore » regression analyses were performed for clinical, pathologic, and treatment factors associated with time to relapse after salvage RT. Results: There were 40 biochemical failures after salvage RT with a median time to failure of 1.2 years. The BMI was not associated with adverse clinical, pathologic, or treatment factors. On multivariate analysis, obesity was independently significant (hazard ratio [HR], 1.2; p = 0.01), along with RT dose (HR, 0.7; p = 0.003) and pre-RT prostate-specific antigen level (HR, 1.2; p = 0.0003). Conclusions: This study is weakly suggestive that obesity may be a risk factor for salvage RT patients. Whether this results from greater biologic aggressiveness or technical inadequacies cannot be answered by this study. Given the very high failure rate observed for severely obese patients, we propose that technical difficulties with RT are at play. This hypothesis is supported by the RT literature and could be prospectively investigated. Techniques that optimize targeting, especially in obese patients, perhaps seem warranted at this time.« less

Risk of falling in a stroke unit after acute stroke: The Fall Study of Gothenburg (FallsGOT).

PubMed

Persson, Carina U; Kjellberg, Sigvar; Lernfelt, Bodil; Westerlind, Ellen; Cruce, Malin; Hansson, Per-Olof

2018-03-01

This study aimed to investigate incidence of falls and different baseline variables and their association with falling during hospitalization in a stroke unit among patients with acute stroke. Prospective observational study. A stroke unit at a university hospital. A consecutive sample of stroke patients, out of which 504 were included, while 101 declined participation. The patients were assessed a mean of 1.7 days after admission and 3.8 days after stroke onset. The primary end-point was any fall, from admission to the stroke unit to discharge. Factors associated with falling were analysed using univariable and multivariable Cox hazard regression analyses. Independent variables were related to function, activity and participation, as well as personal and environmental factors. In total, 65 patients (13%) fell at least once. Factors statistically significantly associated with falling in the multivariable analysis were male sex (hazard ratio (HR): 1.88, 95% confidence interval (CI): 1.13-3.14, P = 0.015), use of a walking aid (HR: 2.11, 95% CI: 1.24-3.60, P = 0.006) and postural control as assessed with the modified version of the Postural Assessment Scale for Stroke Patients (SwePASS). No association was found with age, cognition or stroke severity, the HR for low SwePASS scores (⩽24) was 9.33 (95% CI: 2.19-39.78, P = 0.003) and for medium SwePASS scores (25-30) was 6.34 (95% CI: 1.46-27.51, P = 0.014), compared with high SwePASS scores (⩾31). Postural control, male sex and use of a walking aid are associated with falling during hospitalization after acute stroke.

Impact of academic facility type and volume on post-surgical outcomes following diagnosis of glioblastoma.

PubMed

Hauser, Alan; Dutta, Sunil W; Showalter, Timothy N; Sheehan, Jason P; Grover, Surbhi; Trifiletti, Daniel M

2018-01-01

To identify if facility type and/or facility volume impact overall survival (OS) following diagnosis of glioblastoma (GBM). We also sought to compare early post-surgical outcomes based on these factors. The National Cancer Database was queried for patients with GBM diagnosed from 2004 to 2013 with known survival. Patients were grouped based on facility type and facility volume. Multivariable analyses were performed to investigate factors associated OS following diagnosis and Chi-square tests were used to compare early post-surgical outcomes. 89,839 patients met inclusion criteria. Factors associated with improved OS on multivariable analysis included younger patient age, female gender, race, lower comorbidity score, higher performance score, smaller tumor size, unifocal tumors, MGMT hypermethylation, fully resected tumors, radiotherapy, and chemotherapy (each p < .001). Also, OS was improved among patients treated at centers averaging at least 30.2 cases per year (HR 0.948, compared to <7.4 cases/year, p < .001), and patients treated at Academic/Research programs had improved survival compared to those treated at Comprehensive Community Cancer programs (HR 1.069, p < .001) and Integrated Network Cancer programs (HR 1.126, p < .001). Similarly, Academic/Research programs and high volume centers demonstrated improved 30- and 90-day morality as well as 30-day readmission rates (p < .001). This study suggests that patients treated in Academic/Research programs and high patient-volume centers have increased survival and more favorable early-postsurgical outcomes. The extent to which differences in patient populations, socioeconomic factors, and/or provider expertise play into this cause will be areas of future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiple barriers delay care among women with abnormal cancer screening despite patient navigation.

PubMed

Ramachandran, Ambili; Freund, Karen M; Bak, Sharon M; Heeren, Timothy C; Chen, Clara A; Battaglia, Tracy A

2015-01-01

While there is widespread dissemination of patient navigation programs in an effort to reduce delays in cancer care, little is known about the impact of barriers to care on timely outcomes. We conducted a secondary analysis of the Boston Patient Navigation Research Program (PNRP) to examine the effect that the presence of barriers had on time to diagnostic resolution of abnormal breast or cervical cancer screening tests. We used multivariable Cox proportional hazards regression with time to diagnostic resolution as the outcome to examine the effect of the number of barriers, controlling for demographic covariates and clustered by patients' primary navigator. There were 1481 women who received navigation; mean age was 39 years; 32% were White, 27% Black, and 31% Hispanic; 28% had private health insurance; and 38% did not speak English. Overall, half (n=745, 50%) had documentation of one or more barriers to care. Women with barriers were more likely to be older, non-White, non-English language speakers, and on public or no health insurance compared with women without barriers. In multivariable analyses, we found less timely diagnostic resolution as the number of barriers increased (one barrier, adjusted hazard ratio [aHR] 0.81 [95% CI 0.56-1.17], p=0.26; two barriers, aHR 0.55 [95% CI 0.37-0.81], p=0.0025; three or more barriers, aHR 0.31 [95% CI 0.21-0.46], p<0.0001)]. Within a patient navigation program proven to reduce delays in care, we found that navigated patients with documented barriers to care experience less timely resolution of abnormal cancer screening tests.

Markers of vitamin B6 status and metabolism as predictors of incident cancer: the Hordaland Health Study.

PubMed

Zuo, Hui; Ueland, Per M; Eussen, Simone J P M; Tell, Grethe S; Vollset, Stein E; Nygård, Ottar; Midttun, Øivind; Meyer, Klaus; Ulvik, Arve

2015-06-15

Dietary intake and/or circulating concentrations of vitamin B6 have been associated with risk of cancer, but results are inconsistent and mechanisms uncertain. Pyridoxal 5'-phosphate (PLP) is the most commonly used marker of B6 status. We recently proposed the ratio 3-hydroxykynurenine/xanthurenic acid (HK/XA) as an indicator of functional vitamin B6 status, and the 4-pyridoxic acid (PA) /(pyridoxal (PL) +PLP) ratio (PAr) as a marker of vitamin B6 catabolism during inflammation. We compared plasma PLP, HK/XA and PAr as predictors of cancer incidence in a prospective community-based cohort in Norway. This study included 6,539 adults without known cancer at baseline (1998-99) from the Hordaland Health Study (HUSK). HR and 95% CI were calculated for the risk of overall and site-specific cancers using multivariate Cox proportional hazards regression with adjustment for potential confounders. After a median follow-up time of 11.9 years, 963 cancer cases (501 men and 462 women) were identified. Multivariate-adjusted Cox-regression showed no significant relation of plasma PLP or HK/XA with risk of incident cancer. In contrast, PAr was significantly associated with risk of cancer with HR (95% CI) = 1.31 (1.12-1.52) per two standard deviation (SD) increment (p < 0.01). Further analysis showed that PAr was a particular strong predictor of lung cancer with HR (95% CI) = 2.46 (1.49-4.05) per two SD increment (p < 0.01). The present results indicate that associations of vitamin B6 with cancer may be related to increased catabolism of vitamin B6, in particular for lung cancer where inflammation may be largely involved in carcinogenesis. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer.

PubMed

De Marchi, Tommaso; Liu, Ning Qing; Stingl, Cristoph; Timmermans, Mieke A; Smid, Marcel; Look, Maxime P; Tjoa, Mila; Braakman, Rene B H; Opdam, Mark; Linn, Sabine C; Sweep, Fred C G J; Span, Paul N; Kliffen, Mike; Luider, Theo M; Foekens, John A; Martens, John W M; Umar, Arzu

2016-01-01

Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity in complex tumor tissue was reduced using laser capture microdissection (LCM). In the current study, we performed high resolution proteomic analysis on two cohorts of ER positive breast tumors derived from patients who either manifested good or poor outcome to tamoxifen treatment upon recurrence. A total of 112 fresh frozen tumors were collected from multiple medical centers and divided into two sets: an in-house training and a multi-center test set. Epithelial tumor cells were enriched with LCM and analyzed by nano-LC Orbitrap mass spectrometry (MS), which yielded >3000 and >4000 quantified proteins in the training and test sets, respectively. Raw data are available via ProteomeXchange with identifiers PXD000484 and PXD000485. Statistical analysis showed differential abundance of 99 proteins, of which a subset of 4 proteins was selected through a multivariate step-down to develop a predictor for tamoxifen treatment outcome. The 4-protein signature significantly predicted poor outcome patients in the test set, independent of predictive histopathological characteristics (hazard ratio [HR] = 2.17; 95% confidence interval [CI] = 1.15 to 4.17; multivariate Cox regression p value = 0.017). Immunohistochemical (IHC) staining of PDCD4, one of the signature proteins, on an independent set of formalin-fixed paraffin-embedded tumor tissues provided and independent technical validation (HR = 0.72; 95% CI = 0.57 to 0.92; multivariate Cox regression p value = 0.009). We hereby report the first validated protein predictor for tamoxifen treatment outcome in recurrent ER-positive breast cancer. IHC further showed that PDCD4 is an independent marker. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, James X.; Rose, Steven; White, Sarah B.

PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Coxmore » proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.« less

Radiation therapy dose is associated with improved survival for unresected anaplastic thyroid carcinoma: Outcomes from the National Cancer Data Base.

PubMed

Pezzi, Todd A; Mohamed, Abdallah S R; Sheu, Tommy; Blanchard, Pierre; Sandulache, Vlad C; Lai, Stephen Y; Cabanillas, Maria E; Williams, Michelle D; Pezzi, Christopher M; Lu, Charles; Garden, Adam S; Morrison, William H; Rosenthal, David I; Fuller, Clifton D; Gunn, G Brandon

2017-05-01

The outcomes of patients with unresected anaplastic thyroid carcinoma (ATC) from the National Cancer Data Base (NCDB) were assessed, and potential correlations were explored between radiation therapy (RT) dose and overall survival (OS). The study cohort was comprised of patients who underwent either no surgery or grossly incomplete resection. Correlates of OS were explored using univariate analysis and multivariable analysis (MVA). In total, 1288 patients were analyzed. The mean patient age was 70.2 years, 59.7% of patients were women, and 47.6% received neck RT. The median OS was 2.27 months, and 11% of patients remained alive at 1 year. A positive RT dose-survival correlation was observed for the entire study cohort, for those who received systemic therapy, and for those with stage IVA/IVB and IVC disease. On MVA, older age (hazard ratio [HR], 1.317; 95% confidence interval [CI], 1.137-1.526), ≥ 1 comorbidity (HR, 1.587; 95% CI, 1.379-1.827), distant metastasis (HR, 1.385; 95% CI, 1.216-1.578), receipt of systemic therapy (HR, 0.637; 95% CI, 0.547-0.742), and receipt of RT compared with no RT (<45 grays [Gy]:HR, 0.843; 95% CI, 0.718-0.988; 45-59.9 Gy: HR, 0.596; 95% CI, 0.479-0.743; 60-75 Gy: HR, 0.419; 95% CI, 0.339-0.517) correlated with OS. The RT dose-survival correlation for patients who received higher (60-75 Gy) versus lower (45-59.9 Gy) therapeutic doses was confirmed by propensity-score matching. Survival was poor in this cohort of patients with unresected ATC, and more effective therapies are needed. However, the association of RT dose with OS highlights the importance of identifying patients with unresected ATC who may still yet benefit from multimodal locoregional treatment that incorporates higher dose RT. Cancer 2017;123:1653-1661. © 2017 American Cancer Society. © 2016 American Cancer Society.

Marijuana Use Is Not Associated With Progression to Advanced Liver Fibrosis in HIV/Hepatitis C Virus–coinfected Women

PubMed Central

Kelly, Erin M.; Dodge, Jennifer L.; Sarkar, Monika; French, Audrey L.; Tien, Phyllis C.; Glesby, Marshall J.; Golub, Elizabeth T.; Augenbraun, Michael; Plankey, Michael; Peters, Marion G.

2016-01-01

Background. Marijuana (hereafter “tetrahydrocannabinol [THC]”) use has been associated with liver fibrosis progression in retrospective analyses of patients with chronic hepatitis C (HCV). We studied long-term effects of THC on fibrosis progression in women coinfected with human immunodeficiency virus (HIV)/HCV enrolled in the Women's Interagency HIV Study (WIHS). Methods. Liver fibrosis was categorized according to FIB-4 scores as none, moderate, or significant. THC and alcohol use were quantified as average exposure per week. Associations between THC use and progression to significant fibrosis were assessed using Cox proportional hazards regression. Results. Among 575 HIV/HCV-coinfected women followed for a median of 11 (interquartile range, 6–17) years, 324 (56%) reported no THC use, 141 (25%) less than weekly use, 70 (12%) weekly use, and 40 (7%) daily use at WIHS entry. In univariable analysis, entry FIB-4 score (hazard ratio [HR], 2.26 [95% confidence interval {CI}, 1.88–2.73], P < .001), log HCV RNA (HR, 1.19 [95% CI, 1.02–1.38], P = .02), tobacco use (HR, 1.37 [95% CI, 1.02–1.85], P = .04), CD4+ count (risk per 100-cell increase: HR, 0.90 [95% CI, .86–.95], P < .001), and log HIV RNA (HR, 1.18 [95% CI, 1.05–1.32], P = .005) were associated with progression to significant fibrosis, as was cumulative alcohol use in follow-up (HR, 1.03 [95% CI, 1.02–1.04], P < .001). In multivariable analysis, entry FIB-4, entry CD4+ count, and cumulative alcohol use remained significant. Cumulative THC use was not associated with fibrosis progression (HR, 1.01 [95% CI, .92–1.10], P = .83). Conclusions. In this large cohort of HIV/HCV-coinfected women, THC was not associated with progression to significant liver fibrosis. Alcohol use was independently associated with liver fibrosis, and may better predict fibrosis progression in HIV/HCV-coinfected women. PMID:27225241

Creation of a Prognostic Index for Spine Metastasis to Stratify Survival in Patients Treated With Spinal Stereotactic Radiosurgery: Secondary Analysis of Mature Prospective Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Chad; Hess, Kenneth; Bishop, Andrew J.

Purpose: There exists uncertainty in the prognosis of patients following spinal metastasis treatment. We sought to create a scoring system that stratifies patients based on overall survival. Methods and Materials: Patients enrolled in 2 prospective trials investigating stereotactic spine radiation surgery (SSRS) for spinal metastasis with ≥3-year follow-up were analyzed. A multivariate Cox regression model was used to create a survival model. Pretreatment variables included were race, sex, age, performance status, tumor histology, extent of vertebrae involvement, previous therapy at the SSRS site, disease burden, and timing of diagnosis and metastasis. Four survival groups were generated based on the model-derivedmore » survival score. Results: Median follow-up in the 206 patients included in this analysis was 70 months (range: 37-133 months). Seven variables were selected: female sex (hazard ratio [HR] = 0.7, P=.02), Karnofsky performance score (HR = 0.8 per 10-point increase above 60, P=.007), previous surgery at the SSRS site (HR = 0.7, P=.02), previous radiation at the SSRS site (HR = 1.8, P=.001), the SSRS site as the only site of metastatic disease (HR = 0.5, P=.01), number of organ systems involved outside of bone (HR = 1.4 per involved system, P<.001), and >5 year interval from initial diagnosis to detection of spine metastasis (HR = 0.5, P<.001). The median survival among all patients was 25.5 months and was significantly different among survival groups (in group 1 [excellent prognosis], median survival was not reached; group 2 reached 32.4 months; group 3 reached 22.2 months; and group 4 [poor prognosis] reached 9.1 months; P<.001). Pretreatment symptom burden was significantly higher in the patient group with poor survival than in the group with excellent survival (all metrics, P<.05). Conclusions: We developed the prognostic index for spinal metastases (PRISM) model, a new model that identified patient subgroups with poor and excellent prognoses.« less

Prognostic factors and survival of colorectal cancer in Kurdistan province, Iran: A population-based study (2009-2014).

PubMed

Rasouli, Mohammad Aziz; Moradi, Ghobad; Roshani, Daem; Nikkhoo, Bahram; Ghaderi, Ebrahim; Ghaytasi, Bahman

2017-02-01

Colorectal cancer (CRC) survival varies at individual and geographically level. This population-based study aimed to evaluating various factors affecting the survival rate of CRC patients in Kurdistan province.In a retrospective cohort study, patients diagnosed as CRC were collected through a population-based study from March 1, 2009 to 2014. The data were collected from Kurdistan's Cancer Registry database. Additional information and missing data were collected reference to patients' homes, medical records, and pathology reports. The CRC survival was calculated from the date of diagnosis to the date of cancer-specific death or the end of follow-up (cutoff date: October 2015). Kaplan-Meier method and log-rank test were used for the univariate analysis of survival in various subgroups. The proportional-hazard model Cox was also used in order to consider the effects of different factors on survival including age at diagnosis, place of residence, marital status, occupation, level of education, smoking, economic status, comorbidity, tumor stage, and tumor grade.A total number of 335 patients affected by CRC were assessed and the results showed that 1- and 5-year survival rate were 87% and 33%, respectively. According to the results of Cox's multivariate analysis, the following factors were significantly related to CRC survival: age at diagnosis (≥65 years old) (HR 2.08, 95% CI: 1.17-3.71), single patients (HR 1.62, 95% CI: 1.10-2.40), job (worker) (HR 2.09, 95% CI: 1.22-3.58), educational level: diploma or below (HR 0.61, 95% CI: 0.39-0.92), wealthy economic status (HR 0.51, 95% CI: 0.31-0.82), tumor grade in poorly differentiated (HR 2.25, 95% CI: 1.37-3.69), and undifferentiated/anaplastic grade (HR 2.90, 95% CI: 1.67-4.98).We found that factors such as low education, inappropriate socioeconomic status, and high tumor grade at the time of disease diagnosis were effective in the poor survival of CRC patients in Kurdistan province; this, which need more attention.

Prognostic factors and survival of colorectal cancer in Kurdistan province, Iran

PubMed Central

Rasouli, Mohammad Aziz; Moradi, Ghobad; Roshani, Daem; Nikkhoo, Bahram; Ghaderi, Ebrahim; Ghaytasi, Bahman

2017-01-01

Abstract Colorectal cancer (CRC) survival varies at individual and geographically level. This population-based study aimed to evaluating various factors affecting the survival rate of CRC patients in Kurdistan province. In a retrospective cohort study, patients diagnosed as CRC were collected through a population-based study from March 1, 2009 to 2014. The data were collected from Kurdistan's Cancer Registry database. Additional information and missing data were collected reference to patients’ homes, medical records, and pathology reports. The CRC survival was calculated from the date of diagnosis to the date of cancer-specific death or the end of follow-up (cutoff date: October 2015). Kaplan–Meier method and log-rank test were used for the univariate analysis of survival in various subgroups. The proportional-hazard model Cox was also used in order to consider the effects of different factors on survival including age at diagnosis, place of residence, marital status, occupation, level of education, smoking, economic status, comorbidity, tumor stage, and tumor grade. A total number of 335 patients affected by CRC were assessed and the results showed that 1- and 5-year survival rate were 87% and 33%, respectively. According to the results of Cox's multivariate analysis, the following factors were significantly related to CRC survival: age at diagnosis (≥65 years old) (HR 2.08, 95% CI: 1.17–3.71), single patients (HR 1.62, 95% CI: 1.10–2.40), job (worker) (HR 2.09, 95% CI: 1.22–3.58), educational level: diploma or below (HR 0.61, 95% CI: 0.39–0.92), wealthy economic status (HR 0.51, 95% CI: 0.31–0.82), tumor grade in poorly differentiated (HR 2.25, 95% CI: 1.37–3.69), and undifferentiated/anaplastic grade (HR 2.90, 95% CI: 1.67–4.98). We found that factors such as low education, inappropriate socioeconomic status, and high tumor grade at the time of disease diagnosis were effective in the poor survival of CRC patients in Kurdistan province; this, which need more attention. PMID:28178134

Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis.

PubMed

Kreuter, Michael; Bonella, Francesco; Maher, Toby M; Costabel, Ulrich; Spagnolo, Paolo; Weycker, Derek; Kirchgaessler, Klaus-Uwe; Kolb, Martin

2017-02-01

Data are conflicting regarding the possible effects of statins in patients with idiopathic pulmonary fibrosis (IPF). This post hoc analysis assessed the effects of statin therapy on disease-related outcomes in IPF. Patients randomised to placebo (n=624) in three controlled trials of pirfenidone in IPF (CAPACITY 004 and 006, ASCEND) were categorised by baseline statin use. Outcomes assessed during the 1-year follow-up included disease progression, mortality, hospitalisation and composite outcomes of death or ≥10% absolute decline in FVC and death or ≥50 m decline in 6-minute walk distance (6MWD). At baseline, 276 (44%) patients were statin users versus 348 (56%) non-users. Baseline characteristics were similar between groups, except statin users were older and had higher prevalence of cardiovascular disease and risk factors. In multivariate analyses adjusting for differences in baseline characteristics, statin users had lower risks of death or 6MWD decline (HR 0.69; 95% CI 0.48 to 0.99, p=0.0465), all-cause hospitalisation (HR 0.58; 95% CI 0.35 to 0.94, p=0.0289), respiratory-related hospitalisation (HR 0.44; 95% CI 0.25 to 0.80, p=0.0063) and IPF-related mortality (HR 0.36; 95% CI 0.14 to 0.95, p=0.0393) versus non-users. Non-significant treatment effects favouring statin use were observed for disease progression (HR 0.75; 95% CI 0.52 to 1.07, p=0.1135), all-cause mortality (HR 0.54; 95% CI 0.24 to 1.21, p=0.1369) and death or FVC decline (HR 0.71; 95% CI 0.48 to 1.07, p=0.1032). This post hoc analysis supports the hypothesis that statins may have a beneficial effect on clinical outcomes in IPF. Prospective clinical trials are required to validate these observations. NCT01366209, NCT00287729 and NCT00287716. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Impact of CTLA4 genotype and other immune response gene polymorphisms on outcomes after single umbilical cord blood transplantation.

PubMed

Cunha, Renato; Zago, Marco A; Querol, Sergio; Volt, Fernanda; Ruggeri, Annalisa; Sanz, Guillermo; Pouthier, Fabienne; Kogler, Gesine; Vicario, José L; Bergamaschi, Paola; Saccardi, Riccardo; Lamas, Carmen H; Díaz-de-Heredia, Cristina; Michel, Gerard; Bittencourt, Henrique; Tavella, Marli; Panepucci, Rodrigo A; Fernandes, Francisco; Pavan, Julia; Gluckman, Eliane; Rocha, Vanderson

2017-01-26

We evaluated the impact of recipient and cord blood unit (CBU) genetic polymorphisms related to immune response on outcomes after unrelated cord blood transplantations (CBTs). Pretransplant DNA samples from 696 CBUs with malignant diseases were genotyped for NLRP1, NLRP2, NLRP3, TIRAP/Mal, IL10, REL, TNFRSF1B, and CTLA4. HLA compatibility was 6 of 6 in 10%, 5 of 6 in 39%, and ≥4 of 6 in 51% of transplants. Myeloablative conditioning was used in 80%, and in vivo T-cell depletion in 81%, of cases. The median number of total nucleated cells infused was 3.4 × 10 7 /kg. In multivariable analysis, patients receiving CBUs with GG-CTLA4 genotype had poorer neutrophil recovery (hazard ratio [HR], 1.33; P = .02), increased nonrelapse mortality (NRM) (HR, 1.50; P < .01), and inferior disease-free survival (HR, 1.41; P = .02). We performed the same analysis in a more homogeneous subset of cohort 1 (cohort 2, n = 305) of patients who received transplants for acute leukemia, all given a myeloablative conditioning regimen, and with available allele HLA typing (HLA-A, -B, -C, and -DRB1). In this more homogeneous but smaller cohort, we were able to demonstrate that GG-CTLA4-CBU was associated with increased NRM (HR, 1.85; P = .01). Use of GG-CTLA4-CBU was associated with higher mortality after CBT, which may be a useful criterion for CBU selection, when multiple CBUs are available. © 2017 by The American Society of Hematology.

Impact and outcomes of nutritional support team intervention in patients with gastrointestinal disease in the intensive care unit.

PubMed

Park, Yong Eun; Park, Soo Jung; Park, Yehyun; Cheon, Jae Hee; Kim, Tae Il; Kim, Won Ho

2017-12-01

Nutritional support has become an important intervention for critically ill patients. Many studies have reported on the effects of nutritional support for the patients within the intensive care unit (ICU); however, no studies have specifically assessed patients with gastrointestinal diseases who may have difficulty absorbing enteral nutrition (EN) in the ICU.Sixty-two patients with gastrointestinal disease were admitted to the ICU between August 2014 and August 2016 at a single tertiary university hospital. We analyzed 2 different patient groups in a retrospective cohort study: those who received nutritional support team (NST) intervention and those who did not.Forty-four (71.0%) patients received nutritional support in ICU and 18 (29.0%) did not. Variables including male sex, high albumin or prealbumin level at the time of ICU admission, and short transition period into EN showed statistically significant association with lower mortality on the univariate analysis (all P < .05). Multivariate analysis revealed that longer length of hospital stay (P = .013; hazard ratio [HR], 0.972; 95% confidence interval [CI], 0.951-0.994), shorter transition into EN (P = .014; HR, 1.040; 95% CI, 1.008-1.072), higher prealbumin level (P = .049; HR, 0.988; 95% CI, 0.976-1.000), and NST intervention (P = .022; HR, 0.356; 95% CI, 0.147-0.862) were independent prognostic factors for lower mortality.In conclusion, NST intervention related to early initiated EN, and high prealbumin levels are beneficial to decrease mortality in the acutely ill patients with GI disease.

Prognostic value of CD44 expression in non-small cell lung cancer: a systematic review.

PubMed

Luo, Zhuang; Wu, Rong-Rong; Lv, Liang; Li, Peng; Zhang, Li-Yan; Hao, Qing-Lin; Li, Wei

2014-01-01

CD44 is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has been reported to correlate with poor prognosis of NSCLC in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and prognosis and clinicopathological features in NSCLC. Relevant literatures were identified using PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases (up to February 2014). Data from eligible studies were extracted and included into meta-analysis using a random effects model. Studies were pooled. Summary hazard ratios (HR) and clinical parameters were calculated. We performed a final analysis of 1772 patients from 23 evaluable studies for Prognostic Value and 2167 patients from 28 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD44-V6 for overall survival in NSCLC was 1.63 [95% confidence interval (CI): 1.20-2.21] by univariate analysis and 1.29 (95% CI: 0.71-2.37) by multivariate analysis.The pooled HR of overexprssion panCD44 for overall survival in NSCLC was 1.53 (95% CI: 0.58-4.04) by univariate analysis and 3.00 (95% CI: 1.53-5.87) by multivariate analysis. Overexpression of CD44-V6 is associated with tumor differentiation (poor differentiation, OR = 1.66, 95% CI: 1.12-2.45), tumor histological type [squamous cell carcinomas (SCC), OR = 2.6, 95% CI: 1.63-5.02], clinical TMN stage (TMN stage III, OR = 2.22, 95% CI: 1.44-3.43) and lymph node metastasis (N1-3, 3.52, 95% CI: 2.08-5.93) in patients with NSCLC. However, there was no significant association between CD44-V6 and tumor size [T category, OR = 1.42, 95% CI: 0.73-2.78]. Our meta-analysis showed that CD44-V6 is an efficient prognostic factor for NSCLC. Overexpression of CD44-V6 was significantly associated with tumor differentiation, tumor histological type, clinical TMN stage and lymph node metastasis. However, there was no significant association between CD44-V6 and tumor size. Large prospective studies are now needed to confirm the clinical utility of CD44 as an independent prognostic marker.

Factors predictive of locoregional recurrence following neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancer: An analysis of the EORTC 10994/BIG 1-00 study.

PubMed

Gillon, Pauline; Touati, Nathan; Breton-Callu, Christel; Slaets, Leen; Cameron, David; Bonnefoi, Hervé

2017-07-01

Identification of clinicopathological factors predicting for a locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC) could help to decide on the optimal locoregional radiotherapy. The objective of this trial is to identify those factors in the context of a phase III trial (European Organisation for Research and Treatment of Cancer 10994). Patients received NAC followed by surgery with or without radiotherapy. Radiotherapy was administered according to pre-specified guidelines. Patients with hormone receptor positive tumours received adjuvant hormonal therapy. A proportion of patients with human epidermal growth factor receptor 2 (HER2) positive cancer received adjuvant trastuzumab. The predictive factors for LRR were identified by multivariate analysis with time to LRR as first event as the primary end-point. The median follow-up was 4.4 years. In 1553 eligible patients, there were 76 LRRs with a 5-year cumulative incidence of 4.9% (95% confidence interval, CI [3.76-6.04]). In multivariate analysis, breast cancer subtype was a significant predictor of LRR (p < 0.0001): hazard ratio (HR) 6.44 (95% CI [2.83-14.69]) for triple negative, 6.26 (95% CI [2.81-13.93]) for HER2+ without trastuzumab (T) and 3.37 (95% CI [1.10-10.34]) for HER2+ with T cancers, all compared to luminal A patients. Lack of pathological response was also associated with significantly higher LRR risk in case of ≥4 pathologically positive nodes, HR 2.43 (95% CI [1.34-4.40], p < 0.0001). Breast cancer subtype and lack of pathological response are predictive factors for high LRR after NAC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer: Oncologic and Functional Outcomes from the COLD Registry.

PubMed

Tay, Kae Jack; Polascik, Thomas J; Elshafei, Ahmed; Cher, Michael L; Given, Robert W; Mouraviev, Vladimir; Ross, Ashley E; Jones, J Stephen

2016-01-01

To evaluate the oncological and functional outcomes of primary cryotherapy in men with clinically localized, high-grade prostate cancer. We included all men with biopsy Gleason score ≥8, localized (cT1-2) disease with a serum prostate-specific antigen (PSA) ≤50 ng/mL from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2 ng/mL). Secondary outcomes of continence (defined as strictly no leak) and potency (able to have intercourse) were patient reported. Factors influencing BPFS were evaluated individually using Kaplan Meier and in a multivariate model using Cox regression. Altogether, 300 men were included for analysis. The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months. Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2% and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of men and this tended to occur in men with larger prostates, likely as a technical consideration for downsizing before cryosurgery. At multivariate analysis, the presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA nadir of ≥0.4 ng/mL (HR 5.7) were the only significant variables associated with biochemical progression using Cox regression. Complete continence was noted in 90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence of rectourethral fistulae and urinary retention requiring intervention beyond temporary catheterization was 1.3% and 3.3%, respectively. Primary cryotherapy appears to be effective and safe in the community setting for high-grade, clinically localized prostate cancer in the short term.

Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis.

PubMed

Damman, Kevin; Valente, Mattia A E; Voors, Adriaan A; O'Connor, Christopher M; van Veldhuisen, Dirk J; Hillege, Hans L

2014-02-01

Chronic kidney disease (CKD) and worsening renal function (WRF) have been associated with poor outcome in heart failure (HF). Articles were identified by literature search of MEDLINE (from inception to 1 July 2012) and Cochrane. We included studies on HF patients and mortality risk with CKD and/or WRF. In a secondary analysis, we selected studies investigating predictors of WRF. We retrieved 57 studies (1,076,104 patients) that investigated CKD and 28 studies (49,890 patients) that investigated WRF. The prevalence of CKD was 32% and associated with all-cause mortality: odds ratio (OR) 2.34, 95% confidence interval (CI) 2.20-2.50, P < 0.001). Worsening renal function was present in 23% and associated with unfavourable outcome (OR 1.81, 95% CI 1.55-2.12, P < 0.001). In multivariate analysis, moderate renal impairment: hazard ratio (HR) 1.59, 95% CI 1.49-1.69, P < 0.001, severe renal impairment, HR 2.17, 95% CI 1.95-2.40, P < 0.001, and WRF, HR 1.95, 95% CI 1.45-2.62, P < 0.001 were all independent predictors of mortality. Across studies, baseline CKD, history of hypertension and diabetes, age, and diuretic use were significant predictors for the occurrence of WRF. Across all subgroups of patients with HF, CKD, and WRF are prevalent and associated with a strongly increased mortality risk, especially CKD. Specific conditions may predict the occurrence of WRF and thereby poor prognosis.

Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults.

PubMed

Moore, Steven C; Lee, I-Min; Weiderpass, Elisabete; Campbell, Peter T; Sampson, Joshua N; Kitahara, Cari M; Keadle, Sarah K; Arem, Hannah; Berrington de Gonzalez, Amy; Hartge, Patricia; Adami, Hans-Olov; Blair, Cindy K; Borch, Kristin B; Boyd, Eric; Check, David P; Fournier, Agnès; Freedman, Neal D; Gunter, Marc; Johannson, Mattias; Khaw, Kay-Tee; Linet, Martha S; Orsini, Nicola; Park, Yikyung; Riboli, Elio; Robien, Kim; Schairer, Catherine; Sesso, Howard; Spriggs, Michael; Van Dusen, Roy; Wolk, Alicja; Matthews, Charles E; Patel, Alpa V

2016-06-01

Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood. To determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking. We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015. Leisure-time physical activity of a moderate to vigorous intensity. Incident cancer during follow-up. A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16-1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers. Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.

Risk factors for infections due to carbapenem-resistant Klebsiella pneumoniae after open heart surgery.

PubMed

Salsano, Antonio; Giacobbe, Daniele Roberto; Sportelli, Elena; Olivieri, Guido Maria; Brega, Carlotta; Di Biase, Carlo; Coppo, Erika; Marchese, Anna; Del Bono, Valerio; Viscoli, Claudio; Santini, Francesco

2016-11-01

Patients undergoing major surgery are at increased risk of developing infections due to resistant organisms, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp). In this study, we assessed risk factors for CR-Kp infections after open heart surgery in a teaching hospital in northern Italy. A retrospective study was conducted from January to December 2014. The primary outcome measure was postoperative CR-Kp infection, defined as a time-to-event end-point. The effect of potentially related variables was assessed by univariable and multivariable analyses. Secondary end-points were in-hospital mortality and 180-day postoperative mortality. Among 553 patients undergoing open heart surgery, 32 developed CR-Kp infections (6%). In the final multivariable model, CR-Kp colonization [hazard ratio (HR) 227.45, 95% confidence intervals (CI) 67.13-1225.20, P < 0.001], cardiopulmonary bypass time in minutes (HR 1.01, 95% CI 1.01-1.02, P < 0.001), chronic obstructive pulmonary disease (HR 3.99, 95% CI 1.61-9.45, P = 0.004), SOFA score (HR 1.29, 95% CI 1.08-1.53, P = 0.007), preoperative mechanical ventilation (HR 8.10, 95% CI 1.31-48.57, P = 0.026), prolonged mechanical ventilation (HR 2.48, 95% CI 1.08-6.15, P = 0.032) and female sex (HR 2.08, 95% CI 1.00-4.36, P = 0.049) were associated with the development of CR-Kp infection. Increased in-hospital mortality and 180-day mortality were observed in patients who developed CR-Kp infections in comparison with those who did not. In our cohort, CR-Kp colonization was an important predictor of CR-Kp infection after open heart surgery. CR-Kp infection after surgery significantly affected survival. Preventing colonization is conceivably the most effective current strategy to reduce the impact of CR-Kp. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

The Impact of Epidemiological Factors and Treatment Interventions on Survival in Patients With Signet Ring Cell Carcinoma of the Pancreas.

PubMed

Patel, Mausam; Hans, Harliv S; Pan, Kelsey; Khan, Humza; Donath, Elie; Caldera, Humberto

2018-04-18

Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P<0.05). On multivariable analysis; radiation improved OS and DSS (adjusted hazard ratio [aHR], 0.592 and 0.589, respectively), pancreatectomy improved OS and DSS (aHR, 0.360 and 0.355, respectively), and combination therapy improved OS and DSS (aHR, 0.295 and 0.286, respectively). Age, site, and stage were also independent predictors of OS and DSS. Subgroup analysis demonstrated treatment to be an independent predictor of OS and DSS in localized/regional disease, in distant disease, and in patients diagnosed between 2000 and 2013. Age, site, stage, and treatment independently predict OS and DSS in pancreatic SRCC.

Single-fraction stereotactic body radiotherapy for spinal metastases from renal cell carcinoma.

PubMed

Balagamwala, Ehsan H; Angelov, Lilyana; Koyfman, Shlomo A; Suh, John H; Reddy, Chandana A; Djemil, Toufik; Hunter, Grant K; Xia, Ping; Chao, Samuel T

2012-12-01

Stereotactic body radiotherapy (SBRT) has emerged as an important treatment option for spinal metastases from renal cell carcinoma (RCC) as a means to overcome RCC's inherent radioresistance. The authors reviewed the outcomes of SBRT for the treatment of RCC metastases to the spine at their institution, and they identified factors associated with treatment failure. Fifty-seven patients (88 treatment sites) with RCC metastases to the spine received single-fraction SBRT. Pain relief was based on the Brief Pain Inventory and was adjusted for narcotic use according to the Radiation Therapy Oncology Group protocol 0631. Toxicity was scored according to Common Toxicity Criteria for Adverse Events version 4.0. Radiographic failure was defined as infield or adjacent (within 1 vertebral body [VB]) failure on follow-up MRI. Multivariate analyses were performed to correlate outcomes with the following variables: epidural, paraspinal, single-level, or multilevel disease (2-5 sites); neural foramen involvement; and VB fracture prior to SBRT. Kaplan-Meier analysis and Cox proportional hazards modeling were used for statistical analysis. The median follow-up and survival periods were 5.4 months (range 0.3-38 months) and 8.3 months (range 1.5-38 months), respectively. The median time to radiographic failure and unadjusted pain progression were 26.5 and 26.0 months, respectively. The median time to pain relief (from date of simulation) and duration of pain relief (from date of treatment) were 0.9 months (range 0.1-4.4 months) and 5.4 months (range 0.1-37.4 months), respectively. Multivariate analyses demonstrated that multilevel disease (hazard ratio [HR] 3.5, p = 0.02) and neural foramen involvement (HR 3.4, p = 0.02) were correlated with radiographic failure; multilevel disease (HR 2.3, p = 0.056) and VB fracture (HR 2.4, p = 0.046) were correlated with unadjusted pain progression. One patient experienced Grade 3 nausea and vomiting; no other Grade 3 or 4 toxicities were observed. Twelve treatment sites (14%) were complicated by subsequent vertebral fractures. Stereotactic body radiotherapy for RCC metastases to the spine offers fast and durable pain relief with minimal toxicity. Stereotactic body radiotherapy seems optimal for patients who have solitary or few spinal metastases. Patients with neural foramen involvement are at an increased risk for failure.

[Role of locoregional radiation therapy in breast cancer patients with negative lymph nodes after preoperative chemotherapy and mastectomy. The Institut Curie-Hôpital René-Huguenin experience].

PubMed

Le Scodan, R; Bruant, S; Selz, J; Bollet, M-A; Daveau, C; de la Lande, B; Lerebours, F; Labib, A; Stevens, D

2011-12-01

Neoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease and challenges the standard indications of adjuvant postmastectomy radiation therapy. We retrospectively evaluated the impact of postmastectomy radiation therapy in breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy. Among 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 134 patients had pN0 status after neoadjuvant chemotherapy and mastectomy. Demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The impact of postmastectomy radiation therapy on locoregional recurrence-free survival and overall survival was evaluated by multivariate analysis including known prognostic factors. Among 134 eligible patients, 78 patients (58.2%) received postmastectomy radiation therapy, and 56 patients (41.8%) did not. With a median follow-up time of 91.4 months, the 10-year locoregional recurrence-free survival and overall survival rates were 96.2% and 77.2% with postmastectomy radiation therapy and 86.8% and 87.7% without radiation therapy, respectively (no significant difference). In multivariate analysis, there was a trend towards poorer overall survival among patients who did not have a pathologically complete primary tumour response after neoadjuvant chemotherapy (hazard ratio [HR], 6.65; 95% CI, 0.82-54.12; P=0.076). Postmastectomy radiation therapy had no effect on either locoregional recurrence-free survival (HR, 0.37; 95% CI, 0.09-1.61; P=0.18) or overall survival (HR, 2.06; 95% CI, 0.71-6; P=0.18). There was a trend towards poorer overall survival among patients who did not have pathologically complete in-breast tumour response after neoadjuvant chemotherapy (HR, 6.65; 95% CI, 0.82-54.12; P=0.076). This retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence or death when postmastectomy radiation therapy was omitted in breast cancer patients with pN0 status after neoadjuvant chemotherapy and mastectomy. Whether the omission of postmastectomy radiation therapy is acceptable for these patients should be addressed prospectively. Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Predictive factors for the diagnosis of irritable bowel syndrome in a large cohort of 440,822 young adults.

PubMed

Carter, Dan; Beer-Gabel, Marc; Tzur, Dorit; Levy, Gad; Derazne, Estela; Novis, Ben; Afek, Arnon

2015-04-01

The prevalence of irritable bowel syndrome (IBS) in the community has been reported in numerous cross-sectional surveys. However, little is known about the incidence and predictive factors for the clinical diagnosis of IBS. We examined the association of socioeconomic, anthropometric, and occupational factors with the incidence of IBS in a cohort of 440,822 young Israeli adults aged 18 to 39 who served in active military service during the years 2005 to 2011. During the follow-up of 1,925,003 person-years, IBS was diagnosed de novo in 976 patients, giving an incidence rate of 221:100,000 (0.2%) person-years for the diagnosis of IBS. On multivariable Cox analysis, higher socioeconomic status [hazard ratio (HR) 1.629; 95% confidence interval (CI), 1.328-1.999; P<0.0001], Israeli birth (HR 1.362; 95% CI, 1.084-1.712; P=0.008), Jewish ethnicity (HR 2.089; 95% CI, 1.344-3.248; P=0.001), education ≥than 11 years (HR 1.674; 95% CI, 1.019-2.751; P=0.042), and a noncombat military position (HR 1.196; 95% CI, 1.024-1.397; P=0.024) were found to be risk factors for the diagnosis or for the worsening of IBS. Overweight (HR 0.744; 95% CI, 0.589-0.941; P=0.014), obesity (HR 0.698; 95% CI, 0.510-0.95; P=0.025), living in a rural settlement (HR 0.705; 95% CI, 0.561-0.886; P=0.003), and Middle Eastern (HR 0.739; 95% CI, 0.617-0.884; P=0.001,) or North African and Ethiopian origin (HR 0.702; 95% CI, 0.585-0.842; P<0.001) were found to be protective for the diagnosis or the worsening of IBS. This study provides novel data on the socioeconomic, anthropometric, and occupational factors predictive for IBS development. The predictive factors for IBS diagnosis may point to the fact that stress had a lower impact on IBS incidence in our study cohort.

A comprehensive approach to the prevention of central venous catheter complications: results of 10-year prospective surveillance in pediatric hematology-oncology patients.

PubMed

Cesaro, Simone; Cavaliere, Mara; Pegoraro, Anna; Gamba, Piergiorgio; Zadra, Nicola; Tridello, Gloria

2016-04-01

We report our decennial experience with 1161 newly-placed long-term central venous catheters inserted in 919 hematology-oncology patients for a total of 413,901 CVC-days of observation. Most of the CVCs were partially-implanted, open-ended, Broviac-Hickman type of CVC (95 %). One thousand and twenty-four complications were recorded equal to 2.47 per 1000 CVC-days. The frequency of complications per CVC, the rate of episodes per 1000 CVC-days, and removal rate were malfunction/occlusion 42 %, 1.18/1000, and 2.3 %; mechanical (dislodgement/rupture/kinking) 18.3 %, 0.51/1000, and 77.4 %; bacteremia 14.8 %, 0.42/1000, and 18.6 %; exit-site/tunnel infection 11.5 %, 0.32/1000, and 9.7 %; thrombosis 0.86 %, 0.02/1000, and 30 %; pneumothorax 0.52 %, 0.01/1000, and 0. In multivariate analysis, the risk factors were for mechanical complications, a younger age <6.1 years at CVC insertion (HR 1.8, p = 0.0006); for bacteremia, a double lumen CVC (HR 3.1, p < 0.0001) and the surgical modality of CVC insertion (HR 1.5, p = 0.03); for exit-site/tunnel infection, a double lumen CVC (HR 2.1, p = 0.0003) and a diagnosis of leukemia or lymphoma (HR 1.8, p = 0.01); for malfunction/occlusion, an age <6.1 years (HR 1.6, p = 0.0003), the diagnosis of leukemia or lymphoma (HR 1.9, p < 0.0001) and double lumen CVC (HR 1.33, p = 0.023). The cumulative incidence of premature CVC removal was 29.2 % and the risk factors associated with this event were the surgical modality of CVC insertion (HR 1.4, p = 0.0153) and an age at CVC positioning less than 6.1 years (HR 1.6, p = 0.0025). We conclude that a best-practice set of rules resulted in reduced CVC complications.

Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study.

PubMed

Robak, Tadeusz; Huang, Huiqiang; Jin, Jie; Zhu, Jun; Liu, Ting; Samoilova, Olga; Pylypenko, Halyna; Verhoef, Gregor; Siritanaratkul, Noppadol; Osmanov, Evgenii; Pereira, Juliana; Mayer, Jiri; Hong, Xiaonan; Okamoto, Rumiko; Pei, Lixia; Rooney, Brendan; van de Velde, Helgi; Cavalli, Franco

2017-06-05

The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m 2 /cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m 2 /cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.

[Metabolic Syndrome as a marker of cardiovascular events in hypertensives in primary prevention].

PubMed

Costa, José Antonio; Rodilla, Enrique; Cardona, Joaquín; González, Carmen; Pascual, José María

2012-07-07

The aim of this study was to assess the impact of metabolic syndrome (MS) as a predictor of cardiovascular events (CVE) in hypertensives in primary prevention. This retrospective study involved 2410 non-diabetic, hypertensive patients (52% women, 43% with MS), without previous CVE. The total follow-up was 13096 patient-years with a median of 4,5 years (IIQ; 2,2-7,3). Patients with metabolic syndrome did not have more risk of CVE (HR 1,19; CI 95%:0,89-1,58; p=0,292), 183 patients had a CVE, 88 in patients with MS (15,4; CI 95%:12,4-19,0 patients-years), and 95 in patients without MS (13,0; CI 95%:10,5-15,9 patients/years) (p=0,279). In a multivariate analysis corrected for other factors, only age (HR 1,08; CI 95%: 1,07-1,10; p=0,001), male gender (HR 1,77; CI 95%: 1,27-2,45; p=0,001), smoking (HR 2,95; CI 95%: 2,01-4,34; p=0,001) at the beginning, and values of systolic arterial pressure ≥160 mm Hg (HR 1,83; CI 95%: 1,17-2,89; p=0,009) and cholesterol-low density lipoproteins ≥160 mg/dl (HR 1,58; CI 95%: 1,05-2,38; p=0,029) during the follow-up, were associated with new CVE. In hypertensive non-diabetic patients in primary prevention the diagnosis of metabolic syndrome did not add any significant prediction about future CVE over the traditional risk factors. Systolic arterial pressure ≥160 mm Hg and cholesterol-low density lipoproteins ≥160 mg/dl, respectively, during the follow up were factors related to new CVE. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Saving lives, money and resources: drug and CABG/PCI use after myocardial infarction in a Swedish record-linkage study.

PubMed

Wilhelmsen, Lars; Welin, Lennart; Odén, Anders; Björnberg, Arne

2010-04-01

Drug costs are increasing despite the introduction of cheaper generic drugs. The aim of the present study was to analyse the entire costs of hospital care, out-patient care, and the cost of drugs for 16 months following a myocardial infarction (MI) to see to what extent drug costs contribute to the overall costs of care. Diagnoses and costs for care as well as mortality data obtained from the Västra Götaland Region, Sweden, and drug costs from the Swedish Board of Health and Welfare, were merged in a computer file. Patients registered from 1 July 2005 to 30 June 2006 were followed from 28 days after an MI, with follow-up until 31 October 2006. Of 4,725 patients, 711 died before the start of the study and 721 during follow-up. Higher age [hazard ratio (HR, 95%CI) = 1.06 (1.05-1.07)], previous MI [HR = 1.31 (1.13-1.53)] and diabetes mellitus [HR = 1.34 (1.13-1.58)] were associated with increased mortality, which decreased with coronary interventions: CABG/PCI [HR = 0.19 (0.14-0.27)]. In a multivariable analysis, mortality was lower for patients taking simvastatin [HR = 0.62 (0.50-0.76)] and clopidogrel [HR = 0.58 (0.46-0.74)]. Costs for out-patient care accounted for 25% and drugs for 5% of total costs. If patients not treated with simvastatin or clopidogrel had received these drugs, an additional 154-306 lives might have been saved. Drug costs would be higher, but total costs lower. Thus, even expensive drugs may reduce overall costs.

1,25 Dihydroxyvitamin D circulating levels, calcitriol administration, and incidence of acute rejection, CMV infection, and polyoma virus infection in renal transplant recipients.

PubMed

Moscarelli, Luciano; Antognoli, Giulia; Buti, Elisa; Dervishi, Egrina; Fani, Filippo; Caroti, Leonardo; Tsalouchos, Aris; Romoli, Elena; Ghiandai, Giulia; Minetti, Enrico

2016-10-01

Observation that 1,25-Dihydroxyvitamin-D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy-proven acute rejection, CMV infection, BKV infection, with 1,25-Dihydroxyvitamin-D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids. During the first year, the incidence of BPAR (4% vs 11%, P=.04), CMV infection (3% vs 9%, P=.04), and BKV infection (6% vs 19%, P=.04) was significantly lower in users compared to controls. By multivariate Cox regression analysis, 1,25-Dihydroxyvitamin-D3 deficiency and no calcitriol exposure were independent risk factors for BPAR (HR=4.30, P<.005 and HR=3.25, P<.05), for CMV infection (HR=2.33, P<.05 and HR=2.31, P=.001), and for BKV infection (HR=2.41, P<.05 and HR=2.45, P=.001). After one year, users had a better renal function: eGFR was 62.5±6.7 mL/min vs 51.4±7.6 mL/min (P<.05). Only one user developed polyomavirus-associated nephropathy vs 15 controls. Two users lost their graft vs 11 controls. 1,25(OH)2-D3 deficiency circulating levels increased the risk of BPAR, CMV infection, BKV infection after kidney transplantation. Administration of calcitriol is a way to obtain adequate 1,25(OH)2-D3 circulating levels. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

BIOBEHAVIORAL PROGNOSTIC FACTORS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: Results from the INSPIRE-II Trial

PubMed Central

Blumenthal, James A.; Smith, Patrick J.; Durheim, Michael; Mabe, Stephanie; Emery, Charles F.; Martinu, Tereza; Diaz, Philip T.; Babyak, Michael; Welty-Wolf, Karen; Palmer, Scott

2015-01-01

Objective To examine the prognostic value of select biobehavioral factors in patients with chronic obstructive pulmonary disease (COPD) in a secondary analysis of participants from the INSPIRE-II trial. Methods Three hundred twenty six outpatients with COPD underwent assessments of pulmonary function, physical activity, body mass index, inflammation, pulmonary symptoms, depression, and pulmonary quality of life, and were followed for up to 5.4 years for subsequent clinical events. The prognostic value of each biobehavioral factor, considered individually and combined, also was examined in the context of existing Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 risk stratification. Results Sixty-nine individuals experienced a hospitalization or died over a mean follow-up time period of 2.4 (interquartile range = 1.6) years. GOLD classification was associated with an increased risk of clinical events (HR = 2.72 [95% CI 1.63, 4.54], per stage); Six Minute Walk (HR = 0.50 [0.34, 0.73] per 500 feet), total steps (HR = 0.82 [0.71, 0.94] per 1,000 steps), hsC-reactive protein (HR = 1.44 [1.01, 2.06] per 4.5 mg/L), depression (HR = 1.12 [1.01, 1.25] per 4 points), and pulmonary quality of life (HR = 1.73 [1.14, 2.63] per 25 points) were each predictive over and above the GOLD assessment. However, only GOLD group and Six Minute Walk were predictive of all-cause mortality and COPD hospitalization when all biobehavioral variables were included together in a multivariable model. Conclusion Biobehavioral factors provide added prognostic information over and above measures of COPD severity in predicting adverse events in patients with COPD. PMID:26780299

The World Health Organization 1973 classification system for grade is an important prognosticator in T1 non-muscle-invasive bladder cancer.

PubMed

van de Putte, Elisabeth E Fransen; Bosschieter, Judith; van der Kwast, Theo H; Bertz, Simone; Denzinger, Stefan; Manach, Quentin; Compérat, Eva M; Boormans, Joost L; Jewett, Michael A S; Stoehr, Robert; van Leenders, Geert J L H; Nieuwenhuijzen, Jakko A; Zlotta, Alexandre R; Hendricksen, Kees; Rouprêt, Morgan; Otto, Wolfgang; Burger, Maximilian; Hartmann, Arndt; van Rhijn, Bas W G

2018-04-10

To compare the prognostic value of the World Health Organization (WHO) 1973 and 2004 classification systems for grade in T1 bladder cancer (T1-BC), as both are currently recommended in international guidelines. Three uro-pathologists re-revised slides of 601 primary (first diagnosis) T1-BCs, initially managed conservatively (bacille Calmette-Guérin) in four hospitals. Grade was defined according to WHO1973 (Grade 1-3) and WHO2004 (low-grade [LG] and high-grade [HG]). This resulted in a lack of Grade 1 tumours, 188 (31%) Grade 2, and 413 (69%) Grade 3 tumours. There were 47 LG (8%) vs 554 (92%) HG tumours. We determined the prognostic value for progression-free survival (PFS) and cancer-specific survival (CSS) in Cox-regression models and corrected for age, sex, multiplicity, size and concomitant carcinoma in situ. At a median follow-up of 5.9 years, 148 patients showed progression and 94 died from BC. The WHO1973 Grade 3 was negatively associated with PFS (hazard ratio [HR] 2.1) and CSS (HR 3.4), whilst WHO2004 grade was not prognostic. On multivariable analysis, WHO1973 grade was the only prognostic factor for progression (HR 2.0). Grade 3 tumours (HR 3.0), older age (HR 1.03) and tumour size >3 cm (HR 1.8) were all independently associated with worse CSS. The WHO1973 classification system for grade has strong prognostic value in T1-BC, compared to the WHO2004 system. Our present results suggest that WHO1973 grade cannot be replaced by the WHO2004 classification in non-muscle-invasive BC guidelines. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Effects of sex and the common ADRB1 389 genetic polymorphism on the hemodynamic response to dobutamine.

PubMed

Yogev, Dotan; Basheer, Maamoun; Blotnick, Simcha; Caraco, Yoseph; Muszkat, Mordechai

2015-11-01

The ADRB1 389 polymorphism affects responses to the β-1 adrenergic receptor (β1AR) agonist in vitro. Previous studies on its effect on the response to dobutamine stress echocardiography were conflicting. In addition, sex differences in the response to dobutamine have been suggested. The aim of this study was to determine whether the ADRB1 389 polymorphism affects the hemodynamic response to dobutamine in healthy individuals including men and women. Healthy individuals were recruited according to their ADRB1 49 and 389 genotypes [15 Arg389Arg, 10 Gly389Arg, and 10 Gly389Gly individuals, (all Ser49Ser), 21 men and 14 women]. Dobutamine was infused at 2, 4, and 6 mcg/kg/min. Standardized exercise was performed during the last minute of each infusion. Resting heart rate (HR) response to 6 mcg/kg/min dobutamine (ΔHR) was 4.7-fold larger in Arg389Arg than in Gly389Gly [(mean ± SD) 12.95 ± 6.99, 2.75 ± 1.65 bpm, respectively, PANOVA=0.012]. Renin response to dobutamine (ΔRenin) was 3.9-fold greater in Arg389Arg than in Gly389Gly (PANOVA=0.032). Among Arg389Gly heterozygotes, ΔHR and ΔRenin were not significantly different from either homozygote group. In multivariate analysis for ΔHR variance, significant contributions were observed for genotype (P=0.011), baseline HR (P=0.011), and borderline effect for sex (P=0.049). In healthy individuals, HR and renin responses to dobutamine were more than three-fold greater among ADRB1 Arg389 compared with Gly389 homozygotes. Future studies on the effect of the ADRB1 389 polymorphism on dobutamine stress echocardiography should compare Arg389 and Gly389 homozygotes.

VEGETARIAN DIETS AND THE INCIDENCE OF CANCER IN A LOW-RISK POPULATION

PubMed Central

Tantamango-Bartley, Yessenia; Jaceldo-Siegl, Karen; Fan, Jing; Fraser, Gary

2012-01-01

Background Cancer is the second leading cause of death in the US. Dietary factors account for at least 30% of all cancers in Western countries. Since people do not consume individual foods but rather combinations of them, the assessment of dietary patterns may offer valuable information when determining associations between diet and cancer risk. Methods We examined the association between dietary patterns (non-vegetarians, lacto, pesco, vegan, and semi-vegetarian) and the overall cancer incidence among 69,120 participants of the Adventist Health Study-2. Cancer cases were identified by matching to cancer registries. Cox-proportional hazard regression analysis was performed to estimate hazard ratios, with “attained age” as the time variable. Results 2,939 incident cancer cases were identified. The multivariate HR of overall cancer risk among vegetarians compared to non-vegetarians was statistically significant (HR=0.92; 95%CI: 0.85, 0.99) for both genders combined. Also, a statistically significant association was found between vegetarian diet and cancers of the gastrointestinal tract (HR=0.76; 95%CI: 0.63, 0.90). When analyzing the association of specific vegetarian dietary patterns, vegan diets showed statistically significant protection for overall cancer incidence (HR=0.84; 95%CI: 0.72, 0.99) in both genders combined and for female-specific cancers (HR=0.66; 95%CI: 0.47, 0.92). Lacto-ovo-vegetarians appeared to be associated with decreased risk of cancers of the gastrointestinal system (HR=0.75; 95%CI: 0.60, 0.92). Conclusion Vegetarian diets seem to confer protection against cancer. Impact Vegan diet seems to confer lower risk for overall and female-specific cancer compared to other dietary patterns. The lacto-ovo-vegetarian diets seem to confer protection from cancers of the gastrointestinal tract. PMID:23169929

Health-Related Quality of Life in Children and Adolescents with Hereditary Bleeding Disorders and in Children and Adolescents with Stroke: Cross-Sectional Comparison to Siblings and Peers

PubMed Central

Neuner, Bruno; von Mackensen, Sylvia; Holzhauer, Susanne; Funk, Stephanie; Klamroth, Robert; Kurnik, Karin; Krümpel, Anne; Halimeh, Susan; Reinke, Sarah; Frühwald, Michael; Nowak-Göttl, Ulrike

2016-01-01

Objectives. To investigate self-reported health-related quality of life (HrQoL) in children and adolescents with chronic medical conditions compared with siblings/peers. Methods. Group 1 (6 treatment centers) consisted of 74 children/adolescents aged 8–16 years with hereditary bleeding disorders (HBD), 12 siblings, and 34 peers. Group 2 (one treatment center) consisted of 70 children/adolescents with stroke/transient ischemic attack, 14 siblings, and 72 peers. HrQoL was assessed with the “revised KINDer Lebensqualitätsfragebogen” (KINDL-R) questionnaire. Multivariate analyses within groups were done by one-way ANOVA and post hoc pairwise single comparisons by Student's t-tests. Adjusted pairwise comparisons were done by hierarchical linear regressions with individuals nested within treatment centers (group 1) and by linear regressions (group 2), respectively. Results. No differences were found in multivariate analyses of self-reported HrQoL in group 1, while in group 2 differences occurred in overall wellbeing and all subdimensions. These differences were due to differences between patients and peers. After adjusting for age, gender, number of siblings, and treatment center these differences persisted regarding self-worth (p = .0040) and friend-related wellbeing (p < .001). Conclusions. In children with HBD, HrQoL was comparable to siblings and peers. In children with stroke/TIA HrQoL was comparable to siblings while peers, independently of relevant confounder, showed better self-worth and friend-related wellbeing. PMID:27294108

Prognostic Factors for Survival in Patients with Advanced Intrahepatic Cholangiocarcinoma Treated with Gemcitabine plus Cisplatin as First-Line Treatment.

PubMed

Ishimoto, Utako; Kondo, Shunsuke; Ohba, Akihiro; Sasaki, Mitsuhito; Sakamoto, Yasunari; Morizane, Chigusa; Ueno, Hideki; Okusaka, Takuji

2018-01-01

Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials. © 2017 S. Karger AG, Basel.

Precipitating Factors for Acute Heart Failure Hospitalization and Long-Term Survival

PubMed Central

Berkovitch, Anat; Maor, Elad; Sabbag, Avi; Chernomordik, Fernando; Elis, Avishay; Arbel, Yaron; Goldenberg, Ilan; Grossman, Ehud; Klempfner, Robert

2015-01-01

Abstract Heart failure (HF) patients have frequent exacerbations leading to high consumption of medical services and recurrent hospitalizations. Different precipitating factors have various effects on long-term survival. We investigated 2212 patients hospitalized with a diagnosis of either acute HF or acute exacerbation of chronic HF. Patients were divided into 2 primary precipitant groups: ischemic (N = 979 [46%]) and nonischemic (N = 1233 [54%]). The primary endpoint was all-cause mortality. Multivariate analysis demonstrated that the presence of a nonischemic precipitant was associated with a favorable in-hospital outcome (OR 0.64; CI 0.43–0.94), but with a significant increase in the risk of 10-year mortality (HR 1.12; CI 1.01–1.21). Consistently, the cumulative probability of 10-year mortality was significantly higher among patients with a nonischemic versus ischemic precipitant (83% vs 90%, respectively; Log-rank P value <0.001). Subgroup analysis showed that among the nonischemic precipitant, the presence of renal dysfunction and infection were both associated with poor short-term outcomes (OR 1.56, [P < 0.001] and OR 1.35 [P < 0.001], respectively), as well as long-term (HR 1.59 [P < 0.001] and HR 1.24 [P < 0.001], respectively). Identification of precipitating factors for acute HF hospitalization has important short- and long-term implications that can be used for improved risk stratification and management. PMID:26717369

Health-related fitness profiles in adolescents with complex congenital heart disease.

PubMed

Klausen, Susanne Hwiid; Wetterslev, Jørn; Søndergaard, Lars; Andersen, Lars L; Mikkelsen, Ulla Ramer; Dideriksen, Kasper; Zoffmann, Vibeke; Moons, Philip

2015-04-01

This study investigates whether subgroups of different health-related fitness (HrF) profiles exist among girls and boys with complex congenital heart disease (ConHD) and how these are associated with lifestyle behaviors. We measured the cardiorespiratory fitness, muscle strength, and body composition of 158 adolescents aged 13-16 years with previous surgery for a complex ConHD. Data on lifestyle behaviors were collected concomitantly between October 2010 and April 2013. A cluster analysis was conducted to identify profiles with similar HrF. For comparisons between clusters, multivariate analyses of covariance were used to test the differences in lifestyle behaviors. Three distinct profiles were formed: (1) Robust (43, 27%; 20 girls and 23 boys); (2) Moderately Robust (85, 54%; 37 girls and 48 boys); and (3) Less robust (30, 19%; 9 girls and 21 boys). The participants in the Robust clusters reported leading a physically active lifestyle and participants in the Less robust cluster reported leading a sedentary lifestyle. Diagnoses were evenly distributed between clusters. The cluster analysis attributed some of the variability in cardiorespiratory fitness among adolescents with complex ConHD to lifestyle behaviors and physical activity. Profiling of HrF offers a valuable new option in the management of person-centered health promotion. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bilbao, Cristina, E-mail: cbilbao@dbbf.ulpgc.e; Department of Radiation Oncology, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Canary Islands; Lara, Pedro Carlos

Purpose: To elucidate whether microsatellite instability (MSI) predicts clinical outcome in radiation-treated endometrioid endometrial cancer (EEC). Methods and Materials: A consecutive series of 93 patients with EEC treated with extrafascial hysterectomy and postoperative radiotherapy was studied. The median clinical follow-up of patients was 138 months, with a maximum of 232 months. Five quasimonomorphic mononucleotide markers (BAT-25, BAT-26, NR21, NR24, and NR27) were used for MSI classification. Results: Twenty-five patients (22%) were classified as MSI. Both in the whole series and in early stages (I and II), univariate analysis showed a significant association between MSI and poorer 10-year local disease-free survival,more » disease-free survival, and cancer-specific survival. In multivariate analysis, MSI was excluded from the final regression model in the whole series, but in early stages MSI provided additional significant predictive information independent of traditional prognostic and predictive factors (age, stage, grade, and vascular invasion) for disease-free survival (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.01-10.49; p = 0.048) and cancer-specific survival (HR 4.20, 95% CI 1.23-14.35; p = 0.022) and was marginally significant for local disease-free survival (HR 3.54, 95% CI 0.93-13.46; p = 0.064). Conclusions: These results suggest that MSI may predict radiotherapy response in early-stage EEC.« less

Does Peak Urine Flow Rate Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from REDUCE.

PubMed

Simon, Ross M; Howard, Lauren E; Moreira, Daniel M; Roehrborn, Claus; Vidal, Adriana; Castro-Santamaria, Ramiro; Freedland, Stephen J

2017-09-01

We determined whether decreased peak urine flow is associated with future incident lower urinary tract symptoms in men with mild to no lower urinary tract symptoms. Our population consisted of 3,140 men from the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial with mild to no lower urinary tract symptoms, defined as I-PSS (International Prostate Symptom Score) less than 8. REDUCE was a randomized trial of dutasteride vs placebo for prostate cancer prevention in men with elevated prostate specific antigen and negative biopsy. I-PSS measures were obtained every 6 months throughout the 4-year study. The association between peak urine flow rate and progression to incident lower urinary tract symptoms, defined as the first of medical treatment, surgery or sustained and clinically significant lower urinary tract symptoms, was tested by multivariable Cox models, adjusting for various baseline characteristics and treatment arm. On multivariable analysis as a continuous variable, decreased peak urine flow rate was significantly associated with an increased risk of incident lower urinary tract symptoms (p = 0.002). Results were similar in the dutasteride and placebo arms. On univariable analysis when peak flow was categorized as 15 or greater, 10 to 14.9 and less than 10 ml per second, flow rates of 10 to 14.9 and less than 10 ml per second were associated with a significantly increased risk of incident lower urinary tract symptoms (HR 1.39, p = 0.011 and 1.67, p <0.001, respectively). Results were similar on multivariable analysis, although in the 10 to 14.9 ml per second group findings were no longer statistically significant (HR 1.26, p = 0.071). In men with mild to no lower urinary tract symptoms a decreased peak urine flow rate is independently associated with incident lower urinary tract symptoms. If confirmed, these men should be followed closer for incident lower urinary tract symptoms. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Lymphopenia Association With Gross Tumor Volume and Lung V5 and Its Effects on Non-Small Cell Lung Cancer Patient Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Chad; Liao, Zhongxing, E-mail: zliao@mdanderson.org; Gomez, Daniel

2014-08-01

Purpose: Radiation therapy (RT) can both suppress and stimulate the immune system. We sought to investigate the mechanisms underlying radiation-induced lymphopenia and its associations with patient outcomes in non-small cell lung cancer (NSCLC). Methods and Materials: Subjects consisted of 711 patients who had received definitive RT for NSCLC. A lymphocyte nadir was calculated as the minimum lymphocyte value measured during definitive RT. Associations between gross tumor volumes (GTVs) and lung dose-volume histogram (DVH) parameters with lymphocyte nadirs were assessed with Spearman correlation coefficients. Relationships between lymphocyte nadirs with overall survival (OS) and event free survival (EFS) were evaluated with Kaplan-Meiermore » analysis and compared with log-rank test results. Multivariate regressions were conducted with linear and Cox regression analyses. All variables were analyzed as continuous if possible. Results: Larger GTVs were correlated with lower lymphocyte nadirs regardless of concurrent chemotherapy receipt (with concurrent: r = −0.26, P<.0001; without: r = −0.48, P<.0001). Analyses of lung DVH parameters revealed significant correlations at lower doses (lung V5-V10: P<.0001) that incrementally decreased and became nonsignificant at higher doses (lung V60-V70: P>.05). Of note, no significant associations were detected between GTV and lung DVH parameters with total leukocyte, neutrophil, or monocyte nadirs during RT or with lymphocyte count prior to RT. Multivariate analysis revealed larger GTV (P<.0001), receipt of concurrent chemotherapy (P<.0001), twice-daily radiation fractionation (P=.02), and stage III disease (P=.05) to be associated with lower lymphocyte nadirs. On univariate analysis, patients with higher lymphocyte nadirs exhibited significantly improved OS (hazard ratio [HR] = 0.51 per 10{sup 3} lymphocytes/μL, P=.01) and EFS (HR = 0.46 per 10{sup 3} lymphocytes/μL, P<.0001). These differences held on multivariate analyses, controlling for common disease and treatment characteristics including GTV. Conclusions: Lower lymphocyte nadirs during definitive RT were associated with larger GTVs and worse patient outcomes.« less

Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations

PubMed Central

Janjigian, Yelena Y.; Park, Bernard J.; Zakowski, Maureen F.; Ladanyi, Marc; Pao, William; D’Angelo, Sandra P.; Kris, Mark G.; Shen, Ronglai; Zheng, Junting; Azzoli, Christopher G.

2013-01-01

Background Patients with stage IV lung adenocarcinoma and EGFR mutation derive clinical benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown. Methods Data were analyzed from a surgical database of patients with resected lung adenocarcinoma harboring EGFR exon 19 or 21 mutations. In a multivariate analysis, we evaluated the impact of treatment with adjuvant TKI. Results The cohort consists of 167 patients with completely resected stage I–III lung adenocarcinoma. 93 patients (56%) had exon 19 del, 74 patients (44%) had exon 21 mutations, 56 patients (33%) received perioperative TKI. In a multivariate analysis controlling for sex, stage, type of surgery and adjuvant platinum chemotherapy, the 2-year DFS was 89% for patients treated with adjuvant TKI compared with 72% in control group (hazard ratio [HR] = 0.53; 95% confidence interval [CI] 0.28 to 1.03; p = 0.06). The 2-year OS was 96% with adjuvant EGFR TKI and 90% in the group that did not receive TKI (HR 0.62; 95% CI 0.26 to 1.51; p = 0.296). Conclusions Compared to patients who did not receive adjuvant TKI, we observed a trend toward improvement in disease free survival among individuals with resected stages I–III lung adenocarcinomas harboring mutations in EGFR exons 19 or 21 who received these agents as adjuvant therapy. Based on these data, 320 patients are needed for a randomized trial to prospectively validate this DFS benefit. PMID:21150674

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

PubMed

Jin, Zhaohui; Hartgers, Mindy L; Sanhueza, Cristobal T; Shubert, Christopher R; Alberts, Steven R; Truty, Mark J; Muppa, Prasuna; Nagorney, David M; Smyrk, Thomas C; Hassan, Mohamed; Mahipal, Amit

2018-05-01

Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Cerebral venous thrombosis in Behçet's disease.

PubMed

Saadoun, D; Wechsler, B; Resche-Rigon, M; Trad, S; Le Thi Huong, D; Sbai, A; Dormont, D; Amoura, Z; Cacoub, P; Piette, J C

2009-04-15

To analyze the clinical findings, treatment, outcome, and prevalence of cerebral venous thrombosis (CVT) in a large cohort of patients with Behçet's disease (BD) from a single center. We reported a series of 64 consecutive patients with CVT who fulfilled the international criteria for BD. Multivariate analysis was performed to define factors that affect prognosis. Among a cohort of 820 patients with BD, CVT was present in 64 (7.8%). Compared with BD patients without CVT, those with CVT had lower parenchymal central nervous system involvement (4.7% versus 28.7%; P = 0.0001) and higher extraneurologic vascular lesions (62.5% versus 38.8%; P = 0.03). Up to 90% of patients responded to anticoagulation therapy without severe hemorrhagic complications. Neither steroid nor immunosuppressant use provided better outcome. Severe visual loss due to optic atrophy was the main complication of CVT, being found in 15% of patients. In multivariate analysis, papilledema (odds ratio [OR] 7.1, 95% confidence interval [95% CI] 1.6-31.9) and concurrent prothrombotic risk factors (OR 4.6, 95% CI 1.1-20.2) were independently associated with the occurrence of sequelae. Factors associated with relapse of thrombosis were concurrent prothrombotic risk factors (hazard ratio [HR] 4.9, 95% CI 1.5-15.4) and a peripheral venous thrombosis (HR 2.8, 95% CI 0.7-10.5). After a mean +/- SD followup of 8.2 +/- 6.9 years, 4 deaths unrelated to CVT were noted. CVT in patients with BD may result in serious neurologic outcomes. Anticoagulation represents a safe and effective therapy. Extensive investigation of prothrombotic disorders should be considered.

Risk of acute myocardial infarction in upper tract urothelial carcinoma patients receiving radical nephroureterectomy: a population-based cohort study

PubMed Central

Lin, Shih-Yi; Lin, Cheng-Li; Chang, Chao-Hsiang; Wu, His-Chin; Wang, I-Kuan; Chou, Che-Yi; Liang, Ji-An

2017-01-01

Background The outcomes of upper tract urothelial carcinoma (UTUC) receiving radical nephroureterectomy were usually limited to small sample size, case-control studies, and often focused on cancer progression. Risk of acute myocardial infarction (AMI) in these patients was never investigated. Results The overall incidences of AMI were 3.39, 1.44, and 1.70 per 10,000 person-years in the radical nephroureterectomy, nonnephroureterectomy, and non-UTUC cohorts, respectively. Multivariable Cox proportional hazard regression analysis revealed a significantly higher AMI risk in the radical nephroureterectomy cohort [adjusted HR (aHR) = 1.83, 95% confidence interval (CI) = 1.08–3.11], compared with non-UTUC cohorts. The risk of mortality were the highest in patients with UTUC who had undergone radical nephroureterectomy [adjusted HR (aHR) = 5.37, 95% confidence interval (CI) = 4.80–6.02]. Materials and Methods From the Taiwan National Health Insurance claims data, 1,359 patients with UTUC who had undergone radical nephroureterectomy and 3,154 patients with UTUC who had undergone nephron sparing surgery and were newly diagnosed between 2000 and 2010 were identified. For each patient, 4 individuals without UTUC were randomly selected and frequency matched by age, sex, and diagnosis year. Conclusions Patients with UTUC who have undergone radical nephroureterectomy are at a higher risk of developing AMI, compared with those receiving nephron sparing surgery. PMID:29108329

Temporal Patterns of Exposure to Asbestos and Risk of Asbestosis: An Analysis of a Cohort of Asbestos Textile Workers.

PubMed

Farioli, Andrea; Violante, Francesco S; La Vecchia, Carlo; Negri, Eva; Pelucchi, Claudio; Spatari, Giovanna; Boffetta, Paolo; Pira, Enrico

2018-01-12

The aim of the study was to assess the risk of asbestosis death based on the temporal pattern of exposure to asbestos. We followed up a cohort of asbestos textile workers, employed in 1946 to 1984, until November 2013. We measured the duration of the employment, the time since last employment (TSLE), the age, and the year of first employment. Hazard ratios (HR) were estimated through multivariable Cox regression models. We observed 51 asbestosis deaths among 1823 workers. The HR of asbestosis death increased with exposure duration (HR 2.4 for ≥15 years compared with <5 years, P trend = 0.014) and declined with TSLE (HR 0.3 for ≥25 compared with <5 years, P = 0.004). The risk of asbestosis mortality strongly declined for exposure starting after 1968. The risk of asbestosis death strongly declines in the decades after cessation of the exposure.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

Surgical Management and Prognostic Factors of Vulvovaginal Melanoma.

PubMed

Ditto, Antonino; Bogani, Giorgio; Martinelli, Fabio; Di Donato, Violante; Laufer, Joel; Scasso, Santiago; Chiappa, Valentina; Signorelli, Mauro; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

2016-07-01

The aim of the study was to evaluate the surgical management and the role of different prognostic factors on survival outcomes of women affected by genital (i.e., vulvar and vaginal) melanoma. Data of patients undergoing primary surgical treatment for genital melanoma were evaluated in this retrospective study. Baseline, pathological, and postoperative variables were tested to identify prognostic factors. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox proportional hazards models. Overall, 98 patients met the inclusion criteria. Sixty-seven (68%) and 31 (32%) patients in this study population were diagnosed with vulvar and vaginal melanoma, respectively. Median (range) DFS and OS were 12 (1-70) and 22 (1-70) months, respectively. Considering factors influencing DFS, we observed that at multivariate analysis, only vaginal localization (hazard ratio [HR] = 3.72; 95% CI = 1.05-13.2) and number of mitoses (HR = 1.24; 95% CI = 1.11-1.39) proved to be associated with worse DFS. Nodal status was the only independent factor influencing 5-year OS in patients with vulvar (HR = 1.76; 95% CI = 1.22-2.54; p = .002) and vaginal (HR = 3.65; 95% CI = 1.08-12.3; p = .03) melanoma. Genital melanomas are characterized by a poor prognosis. Number of mitoses and lymph node status are the main factors influencing survival. Surgery is the mainstay of treatment. A correct and prompt diagnosis is paramount.

Initial heart rate and cardiovascular outcomes in patients presenting with acute coronary syndrome.

PubMed

Asaad, Nidal; El-Menyar, Ayman; AlHabib, Khalid F; Shabana, Adel; Alsheikh-Ali, Alawi A; Almahmeed, Wael; Al Faleh, Hussam; Hersi, Ahmad; Al Saif, Shukri; Al-Motarreb, Ahmed; Sulaiman, Kadhim; Al Nemer, Khalid; Amin, Haitham; Al Suwaidi, Jassim

2014-06-01

To assess the impact of on-admission heart rate (HR) in patients presenting with acute coronary syndrome (ACS). Data were collected retrospectively from the second Gulf Registry of Acute Coronary Events. Patients were divided according to their initial HR into: (I: < 60, II: 60-69, III: 70-79, IV: 80-89 and V: ≥ 90 bpm). Patients' characteristics and hospital and one- and 12-month outcomes were analyzed and compared. Among 7939 consecutive ACS patients, groups I to V represented 7%, 13%, 20%, 23.5%, and 37%, respectively. Mean age was higher in groups I and V. Group V were more likely males, diabetic and hypertensive. ST-elevation myocardial infarction was the main presentation in groups I and V. Reperfusion therapies were less likely given to group V. Beta blockers were more frequently prescribed to group III in comparison to groups with higher HR. Groups I and V were associated with worse hospital outcomes. Multivariate analysis showed initial tachycardia as an independent predictor for heart failure (OR 2.2; 95%CI: 1.39-3.32), while bradycardia was independently associated with higher one-month mortality (OR 2.0; 95%CI: 1.04-3.85) CONCLUSION: The majority of ACS patients present with tachycardia. However, low or high HR is a marker of high risk that needs more attention and management.

Periodontal Disease, Tooth Loss and Cancer Risk in a Prospective Study of Male Health Professionals

PubMed Central

Michaud, Dominique S.; Liu, Yan; Meyer, Mara; Giovannucci, Edward; Joshipura, Kaumudi

2008-01-01

SUMMARY Background A number of studies suggest that tooth loss and periodontal disease may increase the risk of various cancers; however, it has been difficult to tease apart the role of oral health from that of smoking. We conducted an analysis to examine whether periodontal disease or tooth loss is associated with cancer risk. Methods The analysis was conducted in a prospective study of U.S. male health professionals aged 40 to 75 years. For this analysis, 48,375 men and 18 years of follow-up were available (1986 to January 31, 2004; median follow-up is 17.7 yrs), during which time 5720 incident cancer cases were documented (excluding nonmelanoma skin cancer and nonaggressive prostate cancer); the five most common cancers were colorectal (n=1043), melanoma of the skin (n=698), lung (n=678), bladder (n=543), and advanced prostate (n=541). Endpoints for this study were total cancer and individual cancers with more than 100 cases. Multivariate hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models. Findings After adjusting for known risk factors, including detailed smoking history and dietary factors, periodontal disease history was associated with an increased risk of total cancer (HR = 1.14, 95% CI = 1.07–1.22, compared with no history of periodontal disease); by cancer site, statistically significant associations were observed for lung (HR = 1.36, 95% CI = 1.15–1.60), kidney (HR = 1.49, 95% CI = 1.12–1.97), pancreatic (HR = 1.54, 95% CI = 1.16–2.04; results previously published), and hematopoietic cancers (HR = 1.30, 95% CI = 1.11–1.53). Fewer teeth at baseline (0–16) was associated with a non-significant increase in risk of total cancer (HR = 1.09, 95% CI = 0.99–1.20, compared to 25–32 teeth); a statistically significant association was observed for lung cancer (HR = 1.70, 95% CI = 1.37–2.11, for 0–16 vs. 25–32 teeth). Among never smokers, periodontal disease was associated with statistically significant increases in total and hematopoietic cancers (HR = 1.21, 95% CI = 1.06–1.39, HR = 1.35, 95% CI = 1.01–1.81, respectively); in contrast, no association was observed for lung cancer (HR = 0.96, 95% CI = 0.46–1.98). Interpretation Periodontal disease was associated with a small, but statistically significant, increase in overall cancer risk which persisted among never smokers. The associations observed for lung cancer are likely to be due to residual confounding by smoking. The increased risks observed for hematopoietic, kidney and pancreatic cancers require confirmation but suggest that periodontal disease may either be a marker of a susceptible immune system or may directly effect cancer risk. PMID:18462995

A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Jeremy P.; Murphy, James D.; Hanlon, Alexandra L.

2014-03-15

Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC frommore » 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.« less

Risk factors for postneonatal, infant, child and under-5 mortality in Nigeria: a pooled cross-sectional analysis

PubMed Central

Ezeh, Osita Kingsley; Agho, Kingsley Emwinyore; Dibley, Michael John; Hall, John Joseph; Page, Andrew Nicolas

2015-01-01

Objectives To identify common factors associated with post-neonatal, infant, child and under-5 mortality in Nigeria. Design, setting and participants A cross-sectional data of three Nigeria Demographic and Health Surveys (NDHS) for the years 2003, 2008 and 2013 were used. A multistage, stratified, cluster random sampling method was used to gather information on 63 844 singleton live-born infants of the most recent birth of a mother within a 5-year period before each survey was examined using cox regression models. Main outcome measures Postneonatal mortality (death between 1 and 11 months), infant mortality (death between birth and 11 months), child mortality (death between 12 and 59 months) and under-5 mortality (death between birth and 59 months). Results Multivariable analyses indicated that children born to mothers with no formal education was significantly associated with mortality across all four age ranges (adjusted HR=1.30, 95% CI 1.01 to 1.66 for postneonatal; HR=1.38, 95% CI 1.11 to 1.84 for infant; HR=2.13, 95% CI 1.56 to 2.89 for child; HR=1.19, 95% CI 1.02 to 1.41 for under-5). Other significant factors included living in rural areas (HR=1.48, 95% CI 1.16 to 1.89 for postneonatal; HR=1.23, 95% CI 1.03 to 1.47 for infant; HR=1.52, 95% CI 1.16 to 1.99 for child; HR=1.29, 95% CI 1.11 to 1.50 for under-5), and poor households (HR=2.47, 95% CI 1.76 to 3.47 for postneonatal; HR=1.40, 95% CI 1.10 to 1.78 for infant; HR=1.72, 95% CI 1.19 to 2.49 for child; HR=1.43, 95% CI 1.17 to 1.76 for under-5). Conclusions This study found that no formal education, poor households and living in rural areas increased the risk of postneonatal, infant, child and under-5 mortality among Nigerian children. Community-based interventions for reducing under-5 deaths are needed and should target children born to mothers of low socioeconomic status. PMID:25818271

Risk factors for postneonatal, infant, child and under-5 mortality in Nigeria: a pooled cross-sectional analysis.

PubMed

Ezeh, Osita Kingsley; Agho, Kingsley Emwinyore; Dibley, Michael John; Hall, John Joseph; Page, Andrew Nicolas

2015-03-27

To identify common factors associated with post-neonatal, infant, child and under-5 mortality in Nigeria. A cross-sectional data of three Nigeria Demographic and Health Surveys (NDHS) for the years 2003, 2008 and 2013 were used. A multistage, stratified, cluster random sampling method was used to gather information on 63,844 singleton live-born infants of the most recent birth of a mother within a 5-year period before each survey was examined using cox regression models. Postneonatal mortality (death between 1 and 11 months), infant mortality (death between birth and 11 months), child mortality (death between 12 and 59 months) and under-5 mortality (death between birth and 59 months). Multivariable analyses indicated that children born to mothers with no formal education was significantly associated with mortality across all four age ranges (adjusted HR=1.30, 95% CI 1.01 to 1.66 for postneonatal; HR=1.38, 95% CI 1.11 to 1.84 for infant; HR=2.13, 95% CI 1.56 to 2.89 for child; HR=1.19, 95% CI 1.02 to 1.41 for under-5). Other significant factors included living in rural areas (HR=1.48, 95% CI 1.16 to 1.89 for postneonatal; HR=1.23, 95% CI 1.03 to 1.47 for infant; HR=1.52, 95% CI 1.16 to 1.99 for child; HR=1.29, 95% CI 1.11 to 1.50 for under-5), and poor households (HR=2.47, 95% CI 1.76 to 3.47 for postneonatal; HR=1.40, 95% CI 1.10 to 1.78 for infant; HR=1.72, 95% CI 1.19 to 2.49 for child; HR=1.43, 95% CI 1.17 to 1.76 for under-5). This study found that no formal education, poor households and living in rural areas increased the risk of postneonatal, infant, child and under-5 mortality among Nigerian children. Community-based interventions for reducing under-5 deaths are needed and should target children born to mothers of low socioeconomic status. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Neovascular glaucoma after proton beam therapy of choroidal melanoma: incidence and risk factors.

PubMed

Riechardt, Aline I; Pilger, Daniel; Cordini, Dino; Seibel, Ira; Gundlach, Enken; Hager, Annette; Joussen, Antonia M

2017-11-01

To analyze the risk factors for the development of neovascular glaucoma (NVG) of patients with choroidal melanoma after proton beam therapy (PBT). Clinical case series, retrospective study. We evaluated 629 consecutive patients receiving proton beam therapy for the treatment of a choroidal melanoma at the oncology service at Charité, Berlin and Helmholtz-Zentrum, Berlin between 05/1998 and 11/2008 regarding the development and risk factors of NVG. Patients with tumor resection, salvage proton beam therapy for recurrent disease and known glaucoma of other origin were excluded from the cohort. Of the 629 patients matching the inclusion criteria, 20.8% developed neovascularization of the iris after a mean time of 2.0 years (range 0.45 to 8.4 years) after PBT. Forty-seven percent of the patients with a neovascularization of the iris developed NVG after a mean time of 2.0 years after PBT, ranging from 5 months to 11.6 years. Univariate analysis revealed tumor height [p < 0.001, hazard ratio (HR): 2.71, 95% confidence interval (CI): 1.36-5.35 for tumors >6 mm ≤9 mm and 11.32 (4.03-31.73) for tumors >9 mm], distance of the tumor to the optic disc (p < 0.001, HR: 0.43, 95% CI: 0.24-0.77 for >0 mm ≤3 mm and HR: 0.13, 95% CI: 0.04-0.37 for >3 mm), dose to the ciliary body (p < 0.001, HR: 9.21, 95% CI: 5.08-16.71 (21-40 cobalt gray equivalents (CGE), HR 27.23, 95% CI: 6.33-116.97 (41-60 CGE)), dose to the optic disc (p < 0.001, HR: 3.53, 95% CI: 1.11-11.27 (21-40CGE), HR: 5.37, 95% CI: 2.72-10.63 (41-60CGE)), the irradiated length of the optic nerve (p < 0.001, HR: 4.48, 95% CI: 2.47-8.13) and diabetes mellitus (p < 0.05, HR: 2.53, 95% CI: 1.4-4.5) were found to be risk factors for the development of NVG. Multivariate regression analysis identified the dose to the ciliary body [p < 0.001, HR: 4.39, 95% CI: 2.28-8.44 (21-40 CGE), HR: 11.04, 95% CI: 1.97-61.69 (41-60 CGE)], the irradiated length of the optic nerve (p < 0.001, HR: 3.88, 95% CI: 2.11-7.16), the existence of diabetes mellitus (p < 0.01, HR: 1.28, 95% CI: 1.24-4.21) and tumor height [p < 0.05, HR: 2.28, 95% CI: 1.17-4.83 (>6 mm ≤9 mm), HR: 3.74, 95% CI: 1.05-13.23, (>9 mm)] to be independent risk factors for the development of NVG. In the present analysis we found tumor height, dose to the ciliary body, irradiated length of the optic nerve and diabetes mellitus to be risk factors for the development of NVG. Whenever possible, critical structures of the anterior and posterior segment should be spared by beam shaping or changing of the beam entry angle.

Impact of Postmastectomy Radiation on Locoregional Recurrence in Breast Cancer Patients With 1-3 Positive Lymph Nodes Treated With Modern Systemic Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tendulkar, Rahul D., E-mail: tendulr@ccf.org; Rehman, Sana; Shukla, Monica E.

2012-08-01

Purpose: Postmastectomy radiation therapy (PMRT) remains controversial for patients with 1-3 positive lymph nodes (LN+). Methods and Materials: We conducted a retrospective review of all 369 breast cancer patients with 1-3 LN+ who underwent mastectomy without neoadjuvant systemic therapy between 2000 and 2007 at Cleveland Clinic. Results: We identified 271 patients with 1-3 LN+ who did not receive PMRT and 98 who did receive PMRT. The median follow-up time was 5.2 years, and the median number of LN dissected was 11. Of those not treated with PMRT, 79% received adjuvant chemotherapy (of whom 70% received a taxane), 79% received hormonalmore » therapy, and 5% had no systemic therapy. Of the Her2/neu amplified tumors, 42% received trastuzumab. The 5-year rate of locoregional recurrence (LRR) was 8.9% without PMRT vs 0% with PMRT (P=.004). For patients who did not receive PMRT, univariate analysis showed 6 risk factors significantly (P<.05) correlated with LRR: estrogen receptor/progesterone receptor negative (hazard ratio [HR] 2.6), lymphovascular invasion (HR 2.4), 2-3 LN+ (HR 2.6), nodal ratio >25% (HR 2.7), extracapsular extension (ECE) (HR 3.7), and Bloom-Richardson grade III (HR 3.1). The 5-year LRR rate was 3.4% (95% confidence interval [CI], 0.1%-6.8%] for patients with 0-1 risk factor vs 14.6% [95% CI, 8.4%-20.9%] for patients with {>=}2 risk factors (P=.0006), respectively. On multivariate analysis, ECE (HR 4.3, P=.0006) and grade III (HR 3.6, P=.004) remained significant risk factors for LRR. The 5-year LRR was 4.1% in patients with neither grade III nor ECE, 8.1% with either grade III or ECE, and 50.4% in patients with both grade III and ECE (P<.0001); the corresponding 5-year distant metastasis-free survival rates were 91.8%, 85.4%, and 59.1% (P=.0004), respectively. Conclusions: PMRT offers excellent control for patients with 1-3 LN+, with no locoregional failures to date. Patients with 1-3 LN+ who have grade III disease and/or ECE should be strongly considered for PMRT.« less

Association Between Coffee Intake After Diagnosis of Colorectal Cancer and Reduced Mortality.

PubMed

Hu, Yang; Ding, Ming; Yuan, Chen; Wu, Kana; Smith-Warner, Stephanie A; Hu, Frank B; Chan, Andrew T; Meyerhardt, Jeffrey A; Ogino, Shuji; Fuchs, Charles S; Giovannucci, Edward L; Song, Mingyang

2018-03-01

Few studies have examined the association between coffee intake and survival after diagnosis of colorectal cancer (CRC). We performed a prospective study to investigate the association between coffee intake after a diagnosis of CRC and mortality. We collected data from the Nurses' Health Study (1984-2012) and Health Professionals Follow-up Study (1986-2012), following 1599 patients diagnosed with stage 1, 2, or 3 CRC. CRC was reported on questionnaires and ascertained by review of medical records and pathology reports; intake of food and beverages was determined from responses to semi-quantitative food frequency questionnaires. Participants were asked how often during the previous year that they consumed coffee, with 1 cup as the standard portion size. The first questionnaire response collected at least 6 months but not more than 4 years after diagnosis was used for assessment of post-diagnostic intake (median time from diagnosis to the dietary assessment, 2.2 years). The last semi-quantitative food frequency questionnaire prior to diagnosis was used to assess pre-diagnostic dietary intake. During a median of 7.8 years of follow-up, we documented 803 deaths, of which 188 were because of CRC. In the multivariable adjusted models, compared with nondrinkers, patients who consumed at least 4 cups of coffee per day had a 52% lower risk of CRC-specific death (hazard ratio [HR] 0.48; 95% CI, 0.28-0.83; P for trend=.003) and 30% reduced risk of all-cause death (HR, 0.70; 95% CI, 0.54-0.91; P for trend <.001). High intake of caffeinated and decaffeinated coffee (2 or more cups/day) was associated with lower risk of CRC-specific mortality and all-cause mortality. When coffee intake before vs after CRC diagnosis were examined, compared with patients consistently consuming low amounts (less than 2 cups/day), those who maintained a high intake (2 or more cups/day) had a significantly lower risk of CRC-specific death (multivariable HR, 0.63; 95% CI, 0.44-0.89) and death from any cause (multivariable HR, 0.71; 95% CI, 0.60-0.85). In an analysis data from the Nurses' Health Study and Health Professionals Follow-up Study, we associated intake of caffeinated and decaffeinated coffee after diagnosis of CRC with lower risk of CRC-specific death and overall death. Studies are needed to determine the mechanisms by which coffee might reduce CRC progression. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients.

PubMed

Serrano, Oscar K; Friedmann, Patricia; Ahsanuddin, Sayeeda; Millan, Carlos; Ben-Yaacov, Almog; Kayler, Liise K

2015-11-06

Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time. A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; n=5521) or antithymocyte globulin (ATG; n=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003-2005, 2006-2008, ≥2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts. On multivariate analysis of DCGS there was a significant interaction between AZ and era (P<0.001). AZ was significantly associated with inferior DCGS in the earliest 2003-2005 era (adjusted hazard ratio [aHR], 2.21; 95% confidence interval [95% CI], 1.72 to 2.84) but not in the middle 2006-2008 era (aHR, 1.14; 95% CI, 0.96 to 1.36) or the most recent 2009-2014 era (aHR, 1.08; 95% CI, 0.90 to 1.29) compared with ATG. Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (P=0.13 and P=0.06, respectively). Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time. Copyright © 2015 by the American Society of Nephrology.

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

PubMed Central

Serrano, Oscar K.; Friedmann, Patricia; Ahsanuddin, Sayeeda; Millan, Carlos; Ben-Yaacov, Almog

2015-01-01

Background and objectives Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time. Design, setting, participants, & measurements A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; n=5521) or antithymocyte globulin (ATG; n=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003–2005, 2006–2008, ≥2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts. Results On multivariate analysis of DCGS there was a significant interaction between AZ and era (P<0.001). AZ was significantly associated with inferior DCGS in the earliest 2003–2005 era (adjusted hazard ratio [aHR], 2.21; 95% confidence interval [95% CI], 1.72 to 2.84) but not in the middle 2006–2008 era (aHR, 1.14; 95% CI, 0.96 to 1.36) or the most recent 2009–2014 era (aHR, 1.08; 95% CI, 0.90 to 1.29) compared with ATG. Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (P=0.13 and P=0.06, respectively). Conclusions Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time. PMID:26342042

Loss to follow-up in the Australian HIV Observational Database

PubMed Central

McManus, Hamish; Petoumenos, Kathy; Brown, Katherine; Baker, David; Russell, Darren; Read, Tim; Smith, Don; Wray, Lynne; Giles, Michelle; Hoy, Jennifer; Carr, Andrew; Law, Matthew

2015-01-01

Background Loss to follow-up (LTFU) in HIV-positive cohorts is an important surrogate for interrupted clinical care which can potentially influence the assessment of HIV disease status and outcomes. After preliminary evaluation of LTFU rates and patient characteristics, we evaluated the risk of mortality by LTFU status in a high resource setting. Methods Rates of LTFU were measured in the Australian HIV Observational Database for a range of patient characteristics. Multivariate repeated measures regression methods were used to identify determinants of LTFU. Mortality by LTFU status was ascertained using linkage to the National Death Index. Survival following combination antiretroviral therapy initiation was investigated using the Kaplan-Meier (KM) method and Cox proportional hazards models. Results Of 3,413 patients included in this analysis, 1,632 (47.8%) had at least one episode of LTFU after enrolment. Multivariate predictors of LTFU included viral load (VL)>10,000 copies/ml (Rate ratio (RR) 1.63 (95% confidence interval (CI):1.45–1.84) (ref ≤400)), time under follow-up (per year) (RR 1.03 (95% CI: 1.02–1.04)) and prior LTFU (per episode) (RR 1.15 (95% CI: 1.06–1.24)). KM curves for survival were similar by LTFU status (p=0.484). LTFU was not associated with mortality in Cox proportional hazards models (univariate hazard ratio (HR) 0.93 (95% CI: 0.69–1.26) and multivariate HR 1.04 (95% CI: 0.77–1.43)). Conclusions Increased risk of LTFU was identified amongst patients with potentially higher infectiousness. We did not find significant mortality risk associated with LTFU. This is consistent with timely re-engagement with treatment, possibly via high levels of unreported linkage to other health care providers. PMID:25377928

Loss to follow-up in the Australian HIV Observational Database.

PubMed

McManus, Hamish; Petoumenos, Kathy; Brown, Katherine; Baker, David; Russell, Darren; Read, Tim; Smith, Don; Wray, Lynne; Giles, Michelle; Hoy, Jennifer; Carr, Andrew; Law, Matthew G

2015-01-01

Loss to follow-up (LTFU) in HIV-positive cohorts is an important surrogate for interrupted clinical care, which can potentially influence the assessment of HIV disease status and outcomes. After preliminary evaluation of LTFU rates and patient characteristics, we evaluated the risk of mortality by LTFU status in a high-resource setting. Rates of LTFU were measured in the Australian HIV Observational Database for a range of patient characteristics. Multivariate repeated measures regression methods were used to identify determinants of LTFU. Mortality by LTFU status was ascertained using linkage to the National Death Index. Survival following combination antiretroviral therapy initiation was investigated using the Kaplan-Meier (KM) method and Cox proportional hazards models. Of 3,413 patients included in this analysis, 1,632 (47.8%) had at least one episode of LTFU after enrolment. Multivariate predictors of LTFU included viral load (VL)>10,000 copies/ml (rate ratio [RR] 1.63; 95% CI 1.45, 1.84; ref ≤400), time under follow-up (per year; RR 1.03; 95% CI 1.02, 1.04) and prior LTFU (per episode; RR 1.15; 95% CI 1.06, 1.24). KM curves for survival were similar by LTFU status (P=0.484). LTFU was not associated with mortality in Cox proportional hazards models (univariate hazard ratio [HR] 0.93; 95% CI 0.69, 1.26) and multivariate HR 1.04 (95% CI 0.77, 1.43). Increased risk of LTFU was identified amongst patients with potentially higher infectiousness. We did not find significant mortality risk associated with LTFU. This is consistent with timely re-engagement with treatment, possibly via high levels of unreported linkage to other health-care providers.

Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org; Guerrero, Araceli; Maldonado, Xavier

Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research andmore » Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. Conclusion: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.« less

Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDowell, Lachlan J.; Huang, Shao Hui; Xu, Wei

Purpose: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). Methods and Materials: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodalmore » irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. Results: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). Conclusions: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.« less

Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease.

PubMed

Badani, Ketan K; Reddy, Balaji N; Moskowitz, Eric J; Paulucci, David J; Beksac, Alp Tuna; Martini, Alberto; Whalen, Michael J; Skarecky, Douglas W; Huynh, Linda My; Ahlering, Thomas E

2018-06-01

Seminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer. Modifications to the pelvic lymph node dissection (PLND) during radical prostatectomy (RP) have been reported to have a therapeutic benefit. The present study is the first to determine if lymph node yield (LNY) is associated with a lower risk of biochemical recurrence (BCR) for men with SVI. A total of 220 patients from 2 high-volume institutions who underwent RP without adjuvant treatment between 1990 and 2015 and had prostate cancer with SVI (i.e., pT3b) were identified, and 21 patients did not undergo lymph node dissection. BCR was defined as a postoperative PSA>0.2ng/mL, or use of salvage androgen deprivation therapy (ADT) or radiation. Multivariable Cox proportional hazards models were used to determine whether LNY was predictive of BCR, controlling for PSA, pathologic Gleason Score, pathologic lymph node status, NCCN risk category, etc. The Kaplan-Meier method was used to determine 3-year freedom from BCR. Median number of lymph nodes sampled were 7 (IQR: 3-12; range: 0-35) and 90.5% underwent PLND. The estimated 3-year BCR rate was 43.9%. Results from multivariable analysis demonstrated that LNY was not significantly associated with risk of BCR overall (HR = 1.00, 95% CI: 0.98-1.03; P = 0.848) for pN0 (HR = 0.99, 95% CI: 0.97-1.03; P = 0.916) or pN1 patients (HR = 0.96, 95% CI: 0.88-1.06; P = 0.468). Overall, PSA (HR = 1.02, P<0.001) and biopsy Gleason sum ≥ 8 (HR = 1.81, P = 0.001) were associated with an increased risk of BCR, and increasing LNY increased the likelihood of detecting>2 positive lymph nodes (OR = 1.27, 95% CI: 1.06-1.65, P = 0.023). Seminal vesicle invasion is associated with an increased risk of BCR at 3 years, primarily due to pathologic Gleason score and PSA. Although greater lymph node yield is diagnostic and facilitates more accurate pathologic staging, our data do not show a therapeutic benefit in reducing BCR. Copyright © 2018 Elsevier Inc. All rights reserved.

Febrile urinary tract infections after ureteroneocystostomy and subureteral injection of dextranomer/hyaluronic acid for vesicoureteral reflux--do choice of procedure and success matter?

PubMed

Dwyer, Moira E; Husmann, Douglas A; Rathbun, Suzanne R; Weight, Christopher J; Kramer, Stephen A

2013-01-01

Despite success rates favoring ureteroneocystostomy over subureteral injection of dextranomer/hyaluronic acid for correction of vesicoureteral reflux, the reported incidence of postoperative febrile urinary tract infection favors the latter. We evaluated contemporary treatment cohorts for an association between correction of vesicoureteral reflux and risk of postoperative febrile urinary tract infection. We retrospectively reviewed the records of 396 consecutive patients who underwent ureteroneocystostomy or subureteral injection of dextranomer/hyaluronic acid between 1994 and 2008. Time to event multivariate analyses included preoperative grade of vesicoureteral reflux and bladder/bowel dysfunction. Of 316 patients meeting study criteria 210 underwent ureteroneocystostomy (356 ureters) and 106 underwent subureteral injection of dextranomer/hyaluronic acid (167). Median patient age was 5.7 years (IQR 3.4 to 8.3). Median followup was 28 months (IQR 8 to 61). Ureteral success was significantly greater after ureteroneocystostomy (88%, 314 of 356 cases) vs subureteral injection of dextranomer/hyaluronic acid (74%, 124 of 167, p = 0.0001). When controlling for preoperative grade of vesicoureteral reflux and bladder/bowel dysfunction, the risk of persistent reflux was 2.8 times greater after subureteral injection of dextranomer/hyaluronic acid (95% CI 1.7-4.7, p <0.0001). The incidence of febrile urinary tract infection did not significantly differ between ureteroneocystostomy (8%, 16 of 210 cases) and subureteral injection of dextranomer/hyaluronic acid (4%, 4 of 106; HR 1.96, 95% CI 0.64-5.9, p = 0.24) even when controlling for preoperative grade of vesicoureteral reflux, a predictor of postoperative febrile urinary tract infection on multivariate analysis (HR 2.2 per increase in grade, 95% CI 1.3-3.6, p = 0.0022). Persistent reflux was not a predictor of postoperative febrile urinary tract infection (HR 0.81, 95% CI 0.22-2.9, p = 0.75 for ureteroneocystostomy vs HR 1.8, 95% CI 0.2-17.3, p = 0.6 for subureteral injection of dextranomer/hyaluronic acid and HR 1.8, 95% CI 0.3-3.3, p = 0.6 for both). The incidence of postoperative febrile urinary tract infection may be independent of radiographic procedural success. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Long-term Outcomes of Hypofractionation Versus Conventional Radiation Therapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ of the Breast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lalani, Nafisha; Paszat, Lawrence; Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario

Purpose: Whole-breast radiation therapy (XRT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) may decrease the risk of local recurrence, but the optimal dose regimen remains unclear. Past studies administered 50 Gy in 25 fractions (conventional); however, treatment pattern studies report that hypofractionated (HF) regimens (42.4 Gy in 16 fractions) are frequently used. We report the impact of HF (vs conventional) on the risk of local recurrence after BCS for DCIS. Methods and Materials: All women with DCIS treated with BCS and XRT in Ontario, Canada from 1994 to 2003 were identified. Treatment and outcomes were assessed through administrative databasesmore » and validated by chart review. Survival analyses were performed. To account for systematic differences between women treated with alternate regimens, we used a propensity score adjustment approach. Results: We identified 1609 women, of whom 971 (60%) received conventional regimens and 638 (40%) received HF. A total of 489 patients (30%) received a boost dose, of whom 143 (15%) received conventional radiation therapy and 346 (54%) received HF. The median follow-up time was 9.2 years. The median age at diagnosis was 56 years (interquartile range [IQR], 49-65 years). On univariate analyses, the 10-year actuarial local recurrence–free survival was 86% for conventional radiation therapy and 89% for HF (P=.03). On multivariable analyses, age <45 years (hazard ratio [HR] = 2.4; 95% CI: 1.6-3.4; P<.0001), high (HR=2.9; 95% CI: 1.2-7.3; P=.02) or intermediate nuclear grade (HR=2.7; 95% CI: 1.1-6.6; P=.04), and positive resection margins (HR=1.4; 95% CI: 1.0-2.1; P=.05) were associated with an increased risk of local recurrence. HF was not significantly associated with an increased risk of local recurrence compared with conventional radiation therapy on multivariate analysis (HR=0.8; 95% CI: 0.5-1.2; P=.34). Conclusions: The risk of local recurrence among individuals treated with HF regimens after BCS for DCIS was similar to that among individuals treated with conventional radiation therapy.« less

Racial and Ethnic Differences in Patient Navigation: Results from the Patient Navigation Research Program

PubMed Central

Ko, Naomi Y; Snyder, Frederick R; Raich, Peter C; Paskett, Electra D.; Dudley, Donald; Lee, Ji-Hyun; Levine, Paul H.; Freund, Karen M

2016-01-01

Purpose Patient navigation was developed to address barriers to timely care and reduce cancer disparities. This study explores navigation and racial and ethnic differences in time to diagnostic resolution of a cancer screening abnormality. Patients and Methods We conducted an analysis of the multi-site Patient Navigation Research Program. Participants with an abnormal cancer screening test were allocated to either navigation or control. Unadjusted median time to resolution was calculated for each racial and ethnic group by navigation and control. Multivariable Cox proportional hazards models were fit, adjusting for sex, age, cancer abnormality type, and health insurance, stratifying by center of care. Results Among a sample of 7,514 participants, 29% were Non-Hispanic White, 43% Hispanic, and 28% Black. In the control group Blacks had a longer median time to diagnostic resolution (108 days) than Non-Hispanic Whites (65 days) or Hispanics (68 days) (p< .0001). In the navigated groups, Blacks had a reduction in median time to diagnostic resolution (97 days) (p <.0001). In the multivariable models, among controls, Black race was associated with increased delay to diagnostic resolution (HR=0.77; 95% CI: 0.69, 0.84) compared to the Non-Hispanic Whites, which was reduced in the navigated arm (HR=0.85; 95% CI: 0.77, 0.94). Conclusion Patient navigation had its greatest impact for Black patients who had the greatest delays in care. PMID:27227342

High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis.

PubMed

Wikberg, Maria L; Edin, Sofia; Lundberg, Ida V; Van Guelpen, Bethany; Dahlin, Anna M; Rutegård, Jörgen; Stenling, Roger; Oberg, Ake; Palmqvist, Richard

2013-04-01

An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85-90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1.72; 95 % CI 1.07-2.77, p = 0.025). FAP expression in the tumor front, though more frequent than in the tumor center, was not associated with prognosis. FAP expression in the tumor center was more common in specimens with positive microsatellite instability (MSI) screening status and in patients with high CpG island methylator phenotype (CIMP) status. However, inclusion of MSI screening status and CIMP status in the multivariate analysis strengthened the risk estimates for high FAP expression in the tumor center (HR = 1.89; 95 % CI 1.13-3.14; p = 0.014), emphasizing the role of FAP as an independent prognostic factor. Stromal FAP expression is common in colorectal cancer, and we conclude that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.

Surveillance for Hepatocellular Carcinoma Reduces Mortality: an Inverse Probability of Treatment Weighted Analysis.

PubMed

Chaiteerakij, Roongruedee; Chattieng, Piyanat; Choi, Jonggi; Pinchareon, Nutcha; Thanapirom, Kessirin; Geratikornsupuk, Nopavut

Evidence supporting benefit of hepatocellular carcinoma (HCC) surveillance in reducing mortality is not well-established. The effect of HCC surveillance in reducing mortality was assessed by an inverse probability of treatment weighting (IPTW)-based analysis controlled for inherent bias and confounders in observational studies. This retrospective cohort study was conducted on 446 patients diagnosed with HCC between 2007 and 2013 at a major referral center. Surveillance was defined as having at least 1 ultrasound test within a year before HCC diagnosis. Primary outcome was survival estimated using the Kaplan-Meier method with lead-time bias adjustment and compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (CI) were computed using conventional Cox and weighted Cox proportional hazards analysis with IPTW adjustment. Of the 446 patients, 103 (23.1%) were diagnosed with HCC through surveillance. The surveillance group had more patients with the Barcelona-Clinic Liver Cancer stage A (80.6% vs. 33.8%, P < 0.0001), more patients eligible for potentially curative treatment (73.8% vs. 44.9%, P < 0.0001), and longer median survival (49.6 vs. 15.9 months, P < 0.0001). By conventional multivariate Cox analysis, HR (95% CI) of surveillance was 0.63 (0.45-0.87), P = 0.005. The estimated effect of surveillance remained similar in the IPTW-adjusted Cox analysis (HR: 0.57; 95% CI: 0.43-0.76, P < 0.001). HCC surveillance by ultrasound is associated with a 37% reduction in mortality. Even though surveillance is recommended in all guidelines, but in practice, it is underutilized. Interventions are needed to increase surveillance rate for improving HCC outcome.

Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.

PubMed

Blute, Michael L; Rushmer, Timothy J; Shi, Fangfang; Fuller, Benjamin J; Abel, E Jason; Jarrard, David F; Downs, Tracy M

2015-11-01

Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04). Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT).

PubMed

Schetelig, Johannes; de Wreede, Liesbeth C; Andersen, Niels S; Moreno, Carol; van Gelder, Michel; Vitek, Antonin; Karas, Michal; Michallet, Mauricette; Machaczka, Maciej; Gramatzki, Martin; Beelen, Dietrich; Finke, Jürgen; Delgado, Julio; Volin, Liisa; Passweg, Jakob; Dreger, Peter; Schaap, Nicolaas; Wagner, Eva; Henseler, Anja; van Biezen, Anja; Bornhäuser, Martin; Iacobelli, Simona; Putter, Hein; Schönland, Stefan O; Kröger, Nicolaus

2017-08-01

The best approach for allogeneic haematopoietic stem cell transplantations (alloHCT) in patients with chronic lymphocytic leukaemia (CLL) is unknown. We therefore analysed the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study. Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analysed by multivariable Cox proportional hazards models with a frailty component to investigate unexplained centre heterogeneity. Five-year EFS of the whole cohort was 37% (95% confidence interval [CI], 34-42%). Larger numbers of CLL alloHCTs (hazard ratio [HR] 0·96, P = 0·002), certification of quality management (HR 0·7, P = 0·045) and a higher gross national income per capita (HR 0·4, P = 0·04) improved EFS. In vivo T-cell depletion (TCD) with alemtuzumab compared to no TCD (HR 1·5, P = 0·03), and a female donor compared to a male donor for a male patient (HR 1·4, P = 0·02) had a negative impact on EFS, but not non-myeloablative versus more intensive conditioning. After correcting for patient-, procedure- and centre-characteristics, significant variation in centre outcomes persisted. In conclusion, further research on the impact of centre and procedural characteristics is warranted. Non-myeloablative conditioning appears to be the preferable approach for patients with CLL. © 2017 John Wiley & Sons Ltd.

Decreasing Efficacy of Antimalarial Combination Therapy in Uganda Explained by Decreasing Host Immunity Rather than Increasing Drug Resistance

PubMed Central

Greenhouse, Bryan; Slater, Madeline; Njama-Meya, Denise; Nzarubara, Bridget; Maiteki-Sebuguzi, Catherine; Clark, Tamara D.; Staedke, Sarah G.; Kamya, Moses R.; Hubbard, Alan; Rosenthal, Philip J.; Dorsey, Grant

2009-01-01

Background Improved control efforts are reducing the burden of malaria in Africa, but may result in decreased antimalarial immunity. Methods A cohort of 129 children aged 1–10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for 396 episodes of uncomplicated malaria over a 29 month period as part of a longitudinal clinical trial. Results The risk of treatment failure increased over the course of the study from 5% to 21% (HR=2.4/yr, 95%CI=1.3–4.3). Parasite genetic polymorphisms were associated with an increased risk of failure, but their prevalence did not change over time. Three markers of antimalarial immunity were associated with a decreased risk of treatment failure: increased age (HR=0.5/5yrs, 95%CI=0.2–1.2), living in an area of higher malaria incidence (HR=0.26, 95%CI=0.11–0.64), and recent asymptomatic parasitemia (HR=0.06, 95%CI=0.01–0.36). In multivariate analysis, adjustment for recent asymptomatic parasitemia, but not parasite polymorphisms, removed the association between calendar time and the risk of treatment failure (HR=1.5/yr, 95%CI=0.7–3.4), suggesting that worsening treatment efficacy was best explained by decreasing host immunity. Conclusion Declining immunity in our study population appeared to be the primary factor underlying decreased efficacy of amodiaquine+sulfadoxine-pyrimethamine. With improved malaria control efforts, decreasing immunity may unmask resistance to partially efficacious drugs. PMID:19199542

Long-term exposure to ambient air pollution and mortality in a Chinese tuberculosis cohort.

PubMed

Peng, Zhuoxin; Liu, Cong; Xu, Biao; Kan, Haidong; Wang, Weibing

2017-02-15

Evidence for the relationship between exposure to ambient air pollution and the mortality of tuberculosis (TB) patients is limited. We analyzed the association between long-term exposure to particulate matter <2.5μm in diameter (PM 2.5 ) and cause-specific mortality in a Chinese TB patients cohort from 2003 to 2013. Data from the Global Burden of Disease 2013 estimate were used to assess yearly average concentrations of PM 2.5 and ozone at the household addresses of participants. Cox regression was used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cause-specific mortality, controlling for demographic and other TB-related factors. There were 4444 eligible subjects, including 891 deaths, over a median follow-up of 2464days. Per an interquartile range increase (2.06μg/m 3 ), multivariable analysis indicated that exposure to PM 2.5 was significantly associated with overall mortality (aHR=1.30, 95% CI: 1.19, 1.42), mortality from TB (aHR=1.46, 95% CI: 1.15, 1.85), respiratory cancers (aHR=1.72, 95% CI: 1.36, 2.19), other respiratory diseases (aHR=1.19, 95% CI: 1.02, 1.38), and other cancers (aHR=1.76, 95% CI: 1.33, 2.32). Long-term exposure to PM 2.5 increases the risk of death from TB and other diseases among TB patients. It suggests that the control of ambient air pollution may help decreasing the mortality caused by TB. Copyright © 2016 Elsevier B.V. All rights reserved.

Patterns of Care and Comparative Effectiveness of Intensified Adjuvant Therapy for Resected Oropharyngeal Squamous Cell Carcinoma in the Human Papillomavirus Era.

PubMed

Sher, David J; Nedzi, Lucien; Khan, Saad; Hughes, Randy; Sumer, Baran D; Myers, Larry L; Truelson, John M; Koshy, Matthew

2016-08-01

There is a growing debate on the relative benefits of adjuvant chemoradiotherapy (CRT) and boost doses of postoperative radiotherapy (B-PORT) in oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery, especially for patients with human papillomavirus (HPV)-driven disease. To characterize the recent patterns of care in and overall survival (OS) outcomes following the use of adjuvant CRT and B-PORT after primary surgery for OPSCC. Retrospective analysis of patients in the National Cancer Database with stage III to IVA-B OPSCC treated with surgery and adjuvant radiotherapy between 2010 and 2012 at Commission on Cancer-accredited facilities. The data analysis was performed between June 15, 2015, and May 4, 2016. The primary outcomes were prevalence of CRT and B-PORT, and OS. The primary predictors were HPV positivity and high-risk pathologic features (HRPFs) (extracapsular extension and positive surgical margins). Of the 1409 patients (1153 [82%] male; median age, 57 [interquartile range {IQR}, 51-63] years), 873 (62%) and 789 (56%) patients received CRT and B-PORT, respectively; most patients (n = 583 [79%]) with HRPFs received CRT, and many patients (n = 227 [40%]) without HRPFs received CRT. Multivariable predictors of CRT included adverse pathologic features (extracapsular extension [OR, 6.99; 95% CI, 5.22-9.35], positive surgical margins [OR, 2.07; 95% CI, 1.50-2.87], ≥6 involved nodes [OR, 2.34; 95% CI, 1.39-3.92], or low-neck disease [OR, 1.52; 95% CI, 1.01-2.28]), and treatment at a nonacademic institution (OR, 1.59 [95% CI, 1.21-2.10] for comprehensive community cancer center vs academic program). Patients with HPV-positive disease (OR, 0.47; 95% CI, 0.33-0.68) were less likely to receive CRT; this decrease was limited to absent HRPF treated at academic institutions (n = 173, 44 [25%] received CRT). With a median follow-up of surviving patients of 27 (IQR, 21-33) months, the 2-year OS probability was 92% (95% CI, 90%-94%). Multivariable analysis including age, sex, pathologic T stage, 6 or more positive nodes, and educational status confirmed the prognostic impact of HPV positivity (hazard ratio [HR], 0.41; 95% CI, 0.21-0.80) and HRPFs (positive surgical margins [HR, 2.15; 95% CI, 1.27-3.66] and ≥6 involved nodes [HR, 2.11; 95% CI, 1.13-3.93]), but neither CRT (HR, 1.27; 95% CI, 0.70-2.30) nor B-PORT (HR, 1.04; 95% CI, 0.63-1.73) was associated with improved OS. Postoperative CRT and B-PORT following resection of OPSCC were dependent on factors beyond HRPFs, including HPV status and treatment at an academic institution. No benefit was seen with intensified adjuvant therapy, supporting enrollment of the HPV-positive population into deintensification trials.

Neighborhood socioeconomic deprivation, tumor subtypes, and causes of death after non-metastatic invasive breast cancer diagnosis: a multilevel competing-risk analysis.

PubMed

Lian, Min; Pérez, Maria; Liu, Ying; Schootman, Mario; Frisse, Ann; Foldes, Ellen; Jeffe, Donna B

2014-10-01

The purpose of this study is to examine the associations of neighborhood socioeconomic deprivation and triple-negative breast cancer (TNBC) subtype with causes of death [breast cancer (BC)-specific and non-BC-specific] among non-metastatic invasive BC patients. We identified 3,312 patients younger than 75 years (mean age 53.5 years; 621 [18.8 %] TNBC) with first primary BC treated at an academic medical center from 1999 to 2010. We constructed a census-tract-level socioeconomic deprivation index using the 2000 U.S. Census data and performed a multilevel competing-risk analysis to estimate the hazard ratios (HR) and 95 % confidence intervals (CI) of BC-specific and non-BC-specific mortality associated with neighborhood socioeconomic deprivation and TNBC subtype. The adjusted models controlled for patient sociodemographics, health behaviors, tumor characteristics, comorbidity, and cancer treatment. With a median 62-month follow-up, 349 (10.5 %) patients died; 233 died from BC. In the multivariate models, neighborhood socioeconomic deprivation was independently associated with non-BC-specific mortality (the most- vs. the least-deprived quartile: HR = 2.98, 95 % CI = 1.33-6.66); in contrast, its association with BC-specific mortality was explained by the aforementioned patient-level covariates, particularly sociodemographic factors (HR = 1.15, 95 % CI = 0.71-1.87). TNBC subtype was independently associated with non-BC-specific mortality (HR = 2.15; 95 % CI = 1.20-3.84), while the association between TNBC and BC-specific mortality approached significance (HR = 1.42; 95 % CI = 0.99-2.03, P = 0.057). Non-metastatic invasive BC patients who lived in more socioeconomically deprived neighborhoods were more likely to die as a result of causes other than BC compared with those living in the least socioeconomically deprived neighborhoods. TNBC was associated with non-BC-specific mortality but not BC-specific mortality.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shinohara, Eric T.; Mitra, Nandita; Guo Mengye

Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The medianmore » age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of IHC.« less

Predictors of inguinal hernia after radical prostatectomy.

PubMed

Rabbani, Farhang; Yunis, Luis Herran; Touijer, Karim; Brady, Mary S

2011-02-01

To determine the significant independent predictors of inguinal hernia development after radical prostatectomy (RP) so that prophylactic measures can be undertaken in those at increased risk. Although inguinal hernia is a recognized complication after RP, the risk factors have not been well elucidated. From January 1999 to June 2007, 4592 consecutive patients underwent open retropubic RP or laparoscopic RP without previous radiotherapy. The median follow-up was 36.9 months (interquartile range 20.3, 60.6). Comorbidities were recorded, as well as the occurrence of inguinal hernia, wound infection, and bladder neck contracture. Cox proportional hazards analysis was performed for the predictors of inguinal hernia after RP on multivariate analysis. Inguinal hernia developed after RP in 68 men (1.5%) men at a median follow-up of 7.9 months (interquartile range 4.3, 18.1). The laterality was bilateral in 7, right in 27, left in 24, and not documented in 10 patients. The significant independent predictors of inguinal hernia included age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.01-1.09, P = .016), body mass index (HR 0.91, 95% CI 0.85-0.98, P = .011), history of inguinal hernia repair (HR 3.9, 95% CI 1.8-8.2, P <.001), and bladder neck contracture (HR 2.8, 95% CI 1.3-5.9, P = .007) but not the RP approach (HR 1.08, 95% CI 0.60-1.96, P = .80 for laparoscopic RP vs retropubic RP). The results of our study have indicated that older patients, thinner patients, those with previous inguinal hernia repair, and those developing bladder neck contracture are at increased risk of developing an inguinal hernia. These factors might identify a subset for whom evaluation for subclinical hernia might allow prophylactic inguinal hernia repair at RP. Copyright © 2011 Elsevier Inc. All rights reserved.

Neighborhood Socioeconomic Deprivation, Tumor Subtypes, and Causes of Death after Non-Metastatic Invasive Breast Cancer Diagnosis: A Multilevel Competing-Risk Analysis

PubMed Central

Lian, Min; Pérez, Maria; Liu, Ying; Schootman, Mario; Frisse, Ann; Foldes, Ellen; Jeffe, Donna B.

2014-01-01

Purpose To examine the associations of neighborhood socioeconomic deprivation and triple-negative breast cancer (TNBC) subtype with causes of death (breast cancer [BC]-specific and non-BC-specific) among non-metastatic invasive BC patients. Methods We identified 3,312 patients younger than 75 years (mean age 53.5 years; 621 [18.8%] TNBC) with first primary BC treated at an academic medical center from 1999–2010. We constructed a census-tract-level socioeconomic deprivation index using the 2000 U.S. Census data and performed a multilevel competing-risk analysis to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of BC-specific and non-BC-specific mortality associated with neighborhood socioeconomic deprivation and TNBC subtype. The adjusted models controlled for patient sociodemographics, health behaviors, tumor characteristics, comorbidity, and cancer treatment. Results With a median 62-month follow-up, 349 (10.5%) patients died; 233 died from BC. In the multivariate models, neighborhood socioeconomic deprivation was independently associated with non-BC-specific mortality (the most- vs. the least-deprived quartile: HR=2.98, 95% CI=1.33–6.66); in contrast, its association with BC-specific mortality was explained by the aforementioned patient-level covariates, particularly sociodemographic factors (HR=1.15, 95% CI=0.71–1.87). TNBC subtype was independently associated with non-BC-specific mortality (HR=2.15; 95% CI=1.20–3.84), while the association between TNBC and BC-specific mortality approached significance (HR=1.42; 95% CI=0.99–2.03, P=0.057). Conclusions Non-metastatic invasive BC patients who lived in more socioeconomically deprived neighborhoods were more likely to die as a result of causes other than breast cancer compared with those living in the least socioeconomically deprived neighborhoods. TNBC was associated with non-BC-specific mortality but not BC-specific mortality. PMID:25234843

Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation.

PubMed

Lip, G Y H; Frison, L; Grind, M

2008-07-01

To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF). Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study. The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052). In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Impact of Blood Transfusions on Survival of Locally Advanced Cervical Cancer Patients Undergoing Neoadjuvant Chemotherapy Plus Radical Surgery.

PubMed

Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Lopez, Carlos; Indini, Alice; Leone Roberti Maggiore, Umberto; Sabatucci, Ilaria; Lorusso, Domenica; Raspagliesi, Francesco

2017-03-01

Transfusions represent one of the main progresses of modern medicine. However, accumulating evidence supports that transfusions correlate with worse survival outcomes in patients affected by solid cancers. In the present study, we aimed to investigate the effects of perioperative blood transfusion in locally advanced cervical cancer. Data of consecutive patients affected by locally advanced cervical cancer scheduled to undergo neoadjuvant chemotherapy plus radical surgery were retrospectively searched to test the impact of perioperative transfusions on survival outcomes. Five-year survival outcomes were evaluated using Kaplan-Meier and Cox models. The study included 275 patients. Overall, 170 (62%) patients had blood transfusion. Via univariate analysis, we observed that transfusion correlated with an increased risk of developing recurrence (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.09-4.40; P = 0.02). Other factors associated with 5-year disease-free survival were noncomplete clinical response after neoadjuvant chemotherapy (HR, 2.99; 95% CI, 0.92-9.63; P = 0.06) and pathological (P = 0.03) response at neoadjuvant chemotherapy as well as parametrial (P = 0.004), vaginal (P < 0.001), and lymph node (P = 0.002) involvements. However, via multivariate analysis, only vaginal (HR, 3.07; 95% CI, 1.20-7.85; P = 0.01) and lymph node involvements (HR, 2.4; 95% CI, 1.00-6.06; P = 0.05) correlate with worse disease-free survival. No association with worse outcomes was observed for patients undergoing blood transfusion (HR, 2.71; 95% CI, 0.91-8.03; P = 0.07). Looking at factors influencing overall survival, we observed that lymph node status (P = 0.01) and vaginal involvement (P = 0.06) were independently associated with survival. The role of blood transfusions in increasing the risk of developing recurrence in LAAC patients treated by neoadjuvant chemotherapy plus radical surgery remains unclear; further prospective studies are warranted.

Sex difference in appropriate shocks but not mortality during long-term follow-up in patients with implantable cardioverter-defibrillators

PubMed Central

Seegers, Joachim; Conen, David; Jung, Klaus; Bergau, Leonard; Dorenkamp, Marc; Lüthje, Lars; Sohns, Christian; Sossalla, Samuel T.; Fischer, Thomas H.; Hasenfuss, Gerd; Friede, Tim; Zabel, Markus

2016-01-01

Abstract Aims Implantable cardioverter-defibrillators (ICDs) have been shown to improve survival, although a considerable number of patients never receive therapy. Implantable cardioverter-defibrillators are routinely implanted regardless of sex. There is continuing controversy whether major outcomes differ between men and women. Methods and results In this retrospective single-centre study, 1151 consecutive patients (19% women) undergoing ICD implantation between 1998 and 2010 were followed for mortality and first appropriate ICD shock over 4.9 ± 2.7 years. Sex-related differences were investigated using multivariable Cox models adjusting for potential confounders. During follow-up, 318 patients died, a rate of 5.9% per year among men and 4.6% among women (uncorrected P = 0.08); 266 patients received a first appropriate ICD shock (6.3% per year among men vs. 3.6% among women, P = 0.002). After multivariate correction, independent predictors of all-cause mortality were age (hazard ratio, HR = 1.04 per year of age, 95% confidence interval (CI) [1.03–1.06], P < 0.001), left ventricular ejection fraction (HR = 0.98 per %, 95% CI [0.97–1.00], P = 0.025), renal function (HR = 0.99 per mL/min/1.73 m2, 95% CI [0.99–1.00], P = 0.009), use of diuretics (HR = 1.81, 95% CI [1.29–2.54], P = 0.0023), peripheral arterial disease (HR = 2.21, 95% CI [1.62–3.00], P < 0.001), and chronic obstructive pulmonary disease (HR = 1.48, 95% CI [1.13–1.94], P = 0.029), but not sex. Female sex (HR = 0.51, 95% CI [0.33–0.81], P = 0.013), older age (HR = 0.98, 95% CI [0.97–0.99], P < 0.001), and primary prophylactic ICD indication (HR = 0.69, 95% CI [0.52–0.93], P = 0.043) were independent predictors for less appropriate shocks. Conclusion Women receive 50% less appropriate shocks than men having similar mortality in this large single-centre population. These data may pertain to individually improved selection of defibrillator candidates using risk factors, e.g. sex as demonstrated in this study. PMID:26622054

Increased long-term recreational physical activity is associated with older age at natural menopause among heavy smokers: the California Teachers Study.

PubMed

Emaus, Aina; Dieli-Conwright, Christina; Xu, Xinxin; Lacey, James V; Ingles, Sue A; Reynolds, Peggy; Bernstein, Leslie; Henderson, Katherine D

2013-03-01

Although physical activity modulates the hypothalamic-pituitary-ovarian axis, the few studies that have investigated whether physical activity is associated with age at natural menopause have yielded mixed results. We set out to determine whether physical activity is associated with the timing of natural menopause in a large cohort of California women overall and by smoking history. We investigated the association between long-term physical activity (h/wk/y) and age at natural menopause among 97,945 women in the California Teachers Study. Multivariable Cox proportional hazards regression methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). The impact of cigarette smoking (never smoker, former light smoker, former heavy smoker, current light smoker, and current heavy smoker) as an effect modifier was evaluated. In a multivariable model adjusted for body mass index at age 18 years, age at menarche, race/ethnicity, and age at first full-term pregnancy, increased physical activity was statistically significantly associated with older age at natural menopause (P(trend) = 0.005). Higher body mass index at age 18 years (P(trend) = 0.0003) and older age at menarche (P(trend) = 0.0003) were also associated with older age at natural menopause. Hispanic ethnicity (vs non-Hispanic whites; HR, 1.17; 95% CI, 1.09-1.26), current smokers (vs never smokers; HR, 1.68; 95% CI, 1.60-1.75 for current light smokers; HR, 1.38; 95% CI, 1.33-1.44 for current heavy smokers), and older age at first full-term pregnancy (HR(≥29, 2+ full-term pregnancies) vs HR(<29, 2+ full-term pregnancies), 1.10; 95% CI, 1.06-1.14) were associated with earlier age at natural menopause. Upon stratification by smoking history, increased physical activity was statistically significantly associated with older age at natural menopause among heavy smokers only (HR(highest quartile) vs HR(lowest quartile), 0.88; 95% CI, 0.81-0.97; P(trend) = 0.02 for former heavy smokers; HR(highest quartile) vs HR(lowest quartile), 0.89; 95% CI, 0.80-0.99; P(trend) = 0.04 for current heavy smokers). Age at natural menopause is a complex trait; the determinants of age at natural menopause, including physical activity, may differ by smoking status.

Dedifferentiated chondrosarcoma: A survival analysis of 159 cases from the SEER database (2001-2011).

PubMed

Strotman, Patrick K; Reif, Taylor J; Kliethermes, Stephanie A; Sandhu, Jasmin K; Nystrom, Lukas M

2017-08-01

Dedifferentiated chondrosarcoma is a rare malignancy with reported 5-year overall survival rates ranging from 7% to 24%. The purpose of this investigation is to determine the overall survival of dedifferentiated chondrosarcoma in a modern patient series and how it is impacted by patient demographics, tumor characteristics, and surgical treatment factors. This is a retrospective review of the Surveillance, Epidemiology, and End Results (SEER) database from 2001 to 2011. Kaplan Meier analyses were used for overall and disease-specific survival. Univariable and multivariable cox regression models were used to identify prognostic factors. Five year overall- and disease-specific survival was 18% (95% CI: 12-26%) and 28% (95% CI: 18-37%), respectively. Individuals with extremity tumors had a worse prognosis than individuals with a primary tumor in the chest wall or axial skeleton (HR 0.20, 95% CI: 0.07-0.56; P = 0.002 and HR 0.60, 95% CI: 0.36-0.99; P = 0.04, respectively). Patients with AJCC stage III or IV disease (HR 2.51, 95% CI: 1.50-4.20; P = 0.001), tumors larger than 8 cm (HR 2.17, 95% CI: 1.11-4.27; P = 0.046), metastatic disease at diagnosis (HR 3.25, 95% CI: 1.98-5.33; P < 0.001), and those treated without surgical resection (amputation: HR 0.43, 95% CI 0.23-0.80; P = 0.01; limb salvage/non-amputation resection: HR 0.41, 95% CI: 0.24-0.69; P = 0.001) had a significant increase in risk of mortality. The overall prognosis of dedifferentiated chondrosarcoma is poor with a 5-year overall survival of 18%. Patients with a primary tumor located in the chest wall had a better prognosis. Tumors larger than 8 cm, presence of metastases at diagnosis, and treatment without surgical resection were significant predictors of mortality. © 2017 Wiley Periodicals, Inc.

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

PubMed Central

van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II–IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

[Pre-surgical period and non-work-related sickness absence due to inguinal hernia].

PubMed

Ruiz-Moraga, Montserrat; Catalina-Romero, Carlos; Martínez-Muñoz, Paloma; Cobo-Santiago, María Dolores; González-López, Maite; Cabrera-Sierra, Martha; Porrero-Carro, José Luis; Calvo-Bonacho, Eva

2014-04-01

To analyze non-work-related sickness absence (NWR-SA) due to inguinal hernia and the factors related to its duration, paying particular attention to the pre-surgical period of NWR-SA. Prospective cohort study was conducted on 1,003 workers with an episode of NWR-SA due to an inguinal hernia, belonging to the insured population of a mutual insurance company. We assessed the duration of the NWR-SA episodes and the main demographic, occupational and clinical variables potentially related to it. Cox regression analyses were conducted to establish the predictors of NWR-SA duration. The mean duration of NWR-SA due to inguinal hernia was 68.6 days. After multivariate analysis (Cox regression), having a pre-surgical period of NWR-SA (HR = 0.35; 95%CI: 0.28-0.43), manual occupations (HR=0.68; 95%CI: 0.49-0.95), construction sector (HR=0.71; 95%CI: 0.58-0.88), direct payment methods by a Mutual Insurance Company during sick leave in self-employed workers (HR=0.58; 95%CI, 0.41-0.82), or employees (HR=0.51; 95%CI: 0.36-0.72), comorbidity (HR=0.45; 95%CI:0.34-0.59), and surgery performed under an entity other than the Public Health System or a mutual insurance company (HR=0,76; 95%CI: 0.59-0.97) were associated with longer NWR-SA. The Mutual Insurance Company always performed the surgery when a pre-surgery period of NWR-SA existed (mean duration=47 ±39.6 days); that was associated with shorter periods of post-surgical NWR-SA (P=.001). The NWR-SA due to inguinal hernia is a multifactorial phenomenon in which the pre-surgery period plays an important role. The collaboration between organizations involved in the management of NWR-SA seems to be an effective strategy for reducing its duration. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Effect of femoral head size and surgical approach on risk of revision for dislocation after total hip arthroplasty

PubMed Central

Zijlstra, Wierd P; De Hartog, Bas; Van Steenbergen, Liza N; Scheurs, B Willem; Nelissen, Rob G H H

2017-01-01

Background and purpose Recurrent dislocation is the commonest cause of early revision of a total hip arthropasty (THA). We examined the effect of femoral head size and surgical approach on revision rate for dislocation, and for other reasons, after total hip arthroplasty (THA). Patients and methods We analyzed data on 166,231 primary THAs and 3,754 subsequent revision THAs performed between 2007 and 2015, registered in the Dutch Arthroplasty Register (LROI). Revision rate for dislocation, and for all other causes, were calculated by competing-risk analysis at 6-year follow-up. Multivariable Cox proportional hazard regression ratios (HRs) were used for comparisons. Results Posterolateral approach was associated with higher dislocation revision risk (HR =1) than straight lateral, anterolateral, and anterior approaches (HR =0.5–0.6). However, the risk of revision for all other reasons (especially stem loosening) was higher with anterior and anterolateral approaches (HR =1.2) and lowest with posterolateral approach (HR =1). For all approaches, 32-mm heads reduced the risk of revision for dislocation compared to 22- to 28-mm heads (HR =1 and 1.6, respectively), while the risk of revision for other causes remained unchanged. 36-mm heads increasingly reduced the risk of revision for dislocation but only with the posterolateral approach (HR =0.6), while the risk of revision for other reasons was unchanged. With the anterior approach, 36-mm heads increased the risk of revision for other reasons (HR =1.5). Interpretation Compared to the posterolateral approach, direct anterior and anterolateral approaches reduce the risk of revision for dislocation, but at the cost of more stem revisions and other revisions. For all approaches, there is benefit in using 32-mm heads instead of 22- to 28-mm heads. For the posterolateral approach, 36-mm heads can safely further reduce the risk of revision for dislocation. PMID:28440704

Serum total cholesterol levels and all-cause mortality in a home-dwelling elderly population: a six-year follow-up

PubMed Central

Tuikkala, Päivi; Hartikainen, Sirpa; Korhonen, Maarit J.; Lavikainen, Piia; Kettunen, Raimo; Sulkava, Raimo; Enlund, Hannes

2010-01-01

Objective To investigate the association between serum total cholesterol and all-cause mortality in elderly individuals aged ≥ 75 years. Design A prospective cohort study with a six-year follow-up. Setting and subjects A random sample (n = 700) of all persons aged ≥ 75 years living in Kuopio, Finland. After exclusion of participants living in institutional care and participants using lipid-modifying agents or missing data on blood pressure and cholesterol levels, the final study population consisted of 490 home-dwelling elderly persons with clinical examination. We used the Cox proportional hazard model and the propensity score (PS) method. Main outcome measure All-cause mortality. Results In an age- and sex-adjusted analysis, participants with S-TC ≥ 6mmol/l had the lowest risk of death (hazard ratio, HR = 0.48, 95% CI 0.33–0.70) compared with those with S-TC < 5 mmol/l. HR of death for a 1 mmol increase in S-TC was 0.78. In multivariate analyses, the HR of death for a 1 mmol increase in S-TC was 0.82 and using S-TC < 5 mmol/l as a reference, the HR of death for S-TC ≥ 6 mmol/l was 0.59 (95% CI 0.39–0.89) and for S-TC 5.0–5.9 mmol/l, the HR was 0.62 (95% CI 0.42–0.93). In a PS-adjusted model using S-TC < 5 mmol/l as a reference, the HR of death for S-TC ≥ 6 mmol/l was 0.42 (95% CI 0.28–0.62) and for S-TC 5.0–5.9 mmol/l, the HR was 0.57 (95% CI 0.38–0.84). Conclusions. Participants with low serum total cholesterol seem to have a lower survival rate than participants with an elevated cholesterol level, irrespective of concomitant diseases or health status. PMID:20470020

Interactions and relevance of blast percentage and treatment strategy among younger and older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)

PubMed Central

DiNardo, Courtney D.; Garcia-Manero, Guillermo; Pierce, Sherry; Nazha, Aziz; Bueso-Ramos, Carlos; Jabbour, Elias; Ravandi, Farhad; Cortes, Jorge; Kantarjian, Hagop

2017-01-01

Acute myeloid leukemia (AML) is defined as ≥20% myeloblasts, representing a change from original guidelines where ≤30% blasts were considered as myelodysplastic syndromes (MDS), and 20–29% blasts classified as refractory anemia with excess blasts in transformation (RAEB-T). Whether the diagnostic bone marrow blast percentage has current value with regards to patient prognostication or identification of optimal treatment strategies is unclear. We retrospectively studied 1652 treatment-naïve adults with MDS or AML and ≥10% blasts from January 2000 to April 2014. Patients with 20–29% blasts were more similar to MDS patients in terms of advanced age, increased frequency of poor-risk cytogenetics, lower WBC count, and less frequent NPM1 and FLT3-ITD mutations. Median overall survival of MDS and RAEB-T were similar, 16.0 and 16.0 months, compared to 13.5 months for AML with ≥30% blasts (P =0.045). Multivariate analysis showed inferior survival with increased age (HR 1.81 age 60–69, HR 2.68 age ≥70, P < 0.0005); poor-risk cytogenetics (HR 2.25, P < 0.0005); therapy-related disease (HR 1.44, P < 0.0005); and markers of proliferative disease including WBC ≥25 × 109/L (HR 1.35, P = 0.0003), elevated LDH count (HR 1.24, P =0.0015), and peripheral blasts (HR 1.25, P =0.004). Among younger patients (≤60 years), intensive AML-type therapy resulted in similar outcomes regardless of blast percentage, suggesting this to be optimal therapy in this context. Among older patients (≥70 years), patients with 20–29% blasts had similar outcomes to patients with <20% blasts, and better than those with ≥30% blasts. In addition, among older patients, epigenetic therapy provided at least equivalent outcome to intensive chemotherapy. PMID:26799610

Interactions and relevance of blast percentage and treatment strategy among younger and older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

PubMed

DiNardo, Courtney D; Garcia-Manero, Guillermo; Pierce, Sherry; Nazha, Aziz; Bueso-Ramos, Carlos; Jabbour, Elias; Ravandi, Farhad; Cortes, Jorge; Kantarjian, Hagop

2016-02-01

Acute myeloid leukemia (AML) is defined as ≥20% myeloblasts, representing a change from original guidelines where ≤30% blasts were considered as myelodysplastic syndromes (MDS), and 20-29% blasts classified as refractory anemia with excess blasts in transformation (RAEB-T). Whether the diagnostic bone marrow blast percentage has current value with regards to patient prognostication or identification of optimal treatment strategies is unclear. We retrospectively studied 1652 treatment-naïve adults with MDS or AML and ≥10% blasts from January 2000 to April 2014. Patients with 20-29% blasts were more similar to MDS patients in terms of advanced age, increased frequency of poor-risk cytogenetics, lower WBC count, and less frequent NPM1 and FLT3-ITD mutations. Median overall survival of MDS and RAEB-T were similar, 16.0 and 16.0 months, compared to 13.5 months for AML with ≥30% blasts (P = 0.045). Multivariate analysis showed inferior survival with increased age (HR 1.81 age 60-69, HR 2.68 age ≥70, P < 0.0005); poor-risk cytogenetics (HR 2.25, P < 0.0005); therapy-related disease (HR 1.44, P < 0.0005); and markers of proliferative disease including WBC ≥25 × 10(9) /L (HR 1.35, P = 0.0003), elevated LDH count (HR 1.24, P = 0.0015), and peripheral blasts (HR 1.25, P = 0.004). Among younger patients (≤60 years), intensive AML-type therapy resulted in similar outcomes regardless of blast percentage, suggesting this to be optimal therapy in this context. Among older patients (≥70 years), patients with 20-29% blasts had similar outcomes to patients with <20% blasts, and better than those with ≥30% blasts. In addition, among older patients, epigenetic therapy provided at least equivalent outcome to intensive chemotherapy. © 2015 Wiley Periodicals, Inc.

Serum Gamma-Glutamyl-Transferase Independently Predicts Outcome After Transarterial Chemoembolization of Hepatocellular Carcinoma: External Validation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr; Deschamps, Frederic; Boulin, Mathieu

Purpose: An Asian study showed that gamma glutamyl transpeptidase (GGT) can predict survival after transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). This study was designed to validate in a European population this biomarker as an independent predictor of outcome after TACE of HCC and to determine a threshold value for clinical use. Methods: In 88 consecutive patients treated by TACE for HCC, the optimal threshold for GGT serum level was determined by a ROC analysis. Endpoints were time-to-treatment failure (TTTF) and overall survival (OS). All multivariate models were internally validated using bootstrapping (90 replications). Results: Median follow-up lasted 373 days,more » and median overall survival was 748 days. The optimal threshold for GGT was 165 U/L (sensitivity: 89.3%; specificity: 56.7%; area under the ROC curve: 0.7515). Median TTTF was shorter when GGT was {>=}165 U/L (281 days vs. 850 days; P < 0.001). GGT {>=}165 U/L (hazard ratio (HR) = 2.06; P = 0.02), WHO PS of 2 (HR = 5.4; P = 0.002), and tumor size (HR = 1.12; P = 0.014) were independently associated with shorter TTTF. Median OS was shorter when GGT was {>=}165 U/L (508 days vs. not reached; P < 0.001). GGT {>=} 165 U/L (HR = 3.05; P = 0.029), WHO PS of 2 (HR = 12.95; P < 0.001), alfa-fetoprotein (HR = 2.9; P = 0.01), and tumor size (HR = 1.096; P = 0.013) were independently associated with shorter OS. The results were confirmed by bootstrapping. Conclusions: Our results provide in a European population the external validation of GGT as an independent predictor of outcome after TACE of HCC. A serum level of GGT {>=} 165 U/L is independently associated with both shorter TTTF and OS.« less

Prevalence of preoperative anemia, abnormal mean corpuscular volume and red cell distribution width among surgical patients in Singapore, and their influence on one year mortality

PubMed Central

Wee, Hide Elfrida; Ang, Ai Leen; Ranjakunalan, Niresh; Ong, Biauw Chi; Abdullah, Hairil Rizal

2017-01-01

Introduction Preoperative anemia and high red cell distribution width (RDW) are associated with higher perioperative mortality. Conditions with high RDW levels can be categorized by mean corpuscular volume (MCV). The relationship between RDW, anemia and MCV may explain causality between high RDW levels and outcomes. We aim to establish the prevalence of preoperative anemia and distribution of RDW and MCV among pre-surgical patients in Singapore. In addition, we aim to investigate the association between preoperative anemia, RDW and MCV levels with one-year mortality after surgery. Methods Retrospective review of 97,443 patients aged > = 18 years who underwent cardiac and non-cardiac surgeries under anesthesia between January 2012 and October 2016. Patient demographics, comorbidities, priority of surgery, surgical risk classification, perioperative transfusion, preoperative hemoglobin, RDW, MCV were collected. WHO anemia classification was used. High RDW was defined as >15.7%. Multivariate regression analyses were done to identify independent risk factors for mild or moderate/severe anemia and high RDW (>15.7). Multivariate cox regression analysis was done to determine the effect of preoperative anemia, abnormal RDW and MCV values on 1-year mortality. Results Our cohort comprised of 94.7% non-cardiac and 5.3% cardiac surgeries. 88.7% of patients achieved 1 year follow-up. Anemia prevalence was 27.8%—mild anemia 15.3%, moderate anemia 12.0% and severe anemia 0.5%. One-year mortality was 3.5%. Anemia increased with age in males, while in females, anemia was more prevalent between 18–49 years and > = 70 years. Most anemics were normocytic. Normocytosis and macrocytosis increased with age, while microcytosis decreased with age. Older age, male gender, higher ASA-PS score, anemia (mild- aHR 1.98; moderate/severe aHR 2.86), macrocytosis (aHR 1.47), high RDW (aHR 2.34), moderate-high risk surgery and emergency surgery were associated with higher hazard ratios of one-year mortality. Discussion Preoperative anemia is common. Anemia, macrocytosis and high RDW increases one year mortality. PMID:28777814

Alpha-fetoprotein and (18)F-FDG positron emission tomography predict tumor recurrence better than Milan criteria in living donor liver transplantation.

PubMed

Hong, Geun; Suh, Kyung-Suk; Suh, Suk-Won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Paeng, Jin Chul; Yi, Nam-Joon; Lee, Kwang-Woong

2016-04-01

Given the organ shortage for liver transplantation (LT) and the limitations of the current morphology-based selection criteria, improved criteria are needed to achieve the maximum benefit of LT for hepatocellular carcinoma (HCC). We hypothesized that a combination of biological markers may better predict the prognosis than the Milan criteria. HCC patients (n=123) with preoperative data on serum alpha-fetoprotein (AFP) levels and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) positivity underwent live-donor LT between January 2003 and December 2009. The cut-off values for serum AFP levels (200 ng/ml) and (18)F-FDG PET positivity (1.10) for tumor recurrence were determined by c-statistics using receiver operating characteristic curves. Univariate and multivariate analyses with preoperative variables were performed to find pre-transplant prognostic factors. Disease-free survival rates and overall survival rates were analysed with regard to serum AFP levels and (18)F-FDG PET positivity. The 5-year disease-free survival rates and overall survival rates were 80.3% and 81.6% respectively. (18)F-FDG PET positivity (hazard ratio (HR) 9.766, 95% CI 3.557-26.816; p<0.001) and serum AFP level (HR 6.234, 95% CI 2.643-14.707; p<0.001) were the only significant pre-transplant prognostic factors in the multivariate analysis; tumor number and size were not significant. A combination of criteria showed that the biologically high-risk group (AFP level ⩾200 ng/ml and PET-positive) had an HR of 29.069 (95% CI 8.797-96.053; p<0.001) compared with the double-negative group. Use of the Milan criteria yielded an HR of 1.351 (95% CI 0.500-3.652; p=0.553). The combination of the serum AFP level and (18)F-FDG PET data predicted better outcomes than those using the Milan criteria, improving objectivity when adult-to-adult living donor LT is contemplated. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Association between smoking at diagnosis and cause-specific survival in patients with rectal cancer: Results from a population-based analysis of 10,794 cases.

PubMed

Sharp, Linda; McDevitt, Joseph; Brown, Christopher; Carsin, Anne-Elie; Comber, Harry

2017-07-01

Currently, the 5-year survival rate for rectal cancer remains at <60%. The identification of potentially modifiable prognostic factors would be of considerable public health importance. A few studies have suggested associations between smoking and survival in rectal cancer; however, the evidence is inconsistent, and most of these studies were relatively small. In a large population-based cohort study, we investigated whether smoking at diagnosis is an independent prognostic factor for cancer-specific survival in rectal cancer and whether the association varies by sex, age, or treatment. Rectal cancers (ICD10 C19-20) diagnosed between 1994 and 2012 were abstracted from the National Cancer Registry Ireland and classified by smoking status at diagnosis. Follow-up was for 5 years or until December 31, 2012. Multivariable Cox proportional hazards models were used to compare cancer-specific death rates in current smokers, ex-smokers, and never smokers. Subgroup analyses by age at diagnosis, sex, and treatment were conducted. A total of 10,794 rectal cancers were diagnosed. At diagnosis, 25% were current smokers, 24% were ex-smokers, and 51% were never smokers. Compared with never smokers, current smokers had a significantly greater rate of death from cancer (multivariable hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.06-1.24), but ex-smokers did not (HR, 1.02; 95% CI, 0.94-1.11). The association was slightly stronger in men (current versus never smokers: HR = 1.13, 95% CI, 1.02-1.24) than females (HR, 1.05; 95% CI, 0.90-1.23), but the test for interaction was not significant (P = .75). The effect of smoking was not modified by age or receipt of tumor-directed surgery, radiotherapy, or chemotherapy. Rectal cancer patients who smoke at diagnosis have a statistically significant increased cancer death rate. Elucidation of the underlying mechanisms is urgently required. Cancer 2017;123:2543-50. © 2017 American Cancer Society. © 2017 American Cancer Society.

APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.

PubMed

Freedman, Barry I; Pastan, Stephen O; Israni, Ajay K; Schladt, David; Julian, Bruce A; Gautreaux, Michael D; Hauptfeld, Vera; Bray, Robert A; Gebel, Howard M; Kirk, Allan D; Gaston, Robert S; Rogers, Jeffrey; Farney, Alan C; Orlando, Giuseppe; Stratta, Robert J; Mohan, Sumit; Ma, Lijun; Langefeld, Carl D; Bowden, Donald W; Hicks, Pamela J; Palmer, Nicholette D; Palanisamy, Amudha; Reeves-Daniel, Amber M; Brown, W Mark; Divers, Jasmin

2016-01-01

Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLA match, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 × 10), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.

The Association of Visual Impairment With Clinical Outcomes in Hemodialysis Patients.

PubMed

Hong, Yu Ah; Kim, Suk Young; Kim, Su-Hyun; Kim, Young Ok; Jin, Dong Chan; Song, Ho Chul; Choi, Euy Jin; Kim, Yong-Lim; Kim, Yon-Su; Kang, Shin-Wook; Kim, Nam-Ho; Yang, Chul Woo; Kim, Yong Kyun

2016-05-01

Visual impairment limits people's ability to perform daily tasks and affects their quality of life. We evaluated the impact of visual impairment on clinical outcomes in hemodialysis (HD) patients.HD patients were selected from the Clinical Research Center registry a prospective cohort study on dialysis patients in Korea. Visual impairment was defined as difficulty in daily life due to decreased visual acuity or blindness. The primary outcome was all-cause mortality and the secondary outcomes were cardiovascular and infection-related hospitalization.A total of 3250 patients were included. Seven hundred thirty (22.5%) of the enrolled patients had visual impairment. The median follow-up period was 30 months. The Kaplan-Meier curve and log-rank test showed that all-cause mortality rates (P < 0.001) as well as cardiovascular and infection-related hospitalization rates (P < 0.001 and P < 0.001) were significantly higher in patients with visual impairment than in patients without visual impairment. In the multivariable analysis, visual impairment had significant predictive power for all-cause mortality (Hazard ratio [HR], 1.77, 95% confidence interval [CI], 1.21-2.61, P = 0.004) and cardiovascular hospitalization (HR 1.45 [1.00-1.90], P = 0.008) after adjusting for confounding variables. Of these 3250 patients, 634 patients from each group were matched by propensity scores. In the propensity score matched analysis, patients with visual impairment had independently significant associations with increased all-cause mortality (HR 1.69 [1.12-2.54], P = 0.01) and cardiovascular hospitalization (HR 1.48 [1.08-2.02], P = 0.01) compared with patients without visual impairment after adjustment for confounding variables.Our data demonstrated that visual impairment was an independent risk factor for clinical adverse outcomes in HD patients.

Additive effect of congenital heart disease and early developmental disorders on attention-deficit/hyperactivity disorder and autism spectrum disorder: a nationwide population-based longitudinal study.

PubMed

Tsao, Pei-Chen; Lee, Yu-Sheng; Jeng, Mei-Jy; Hsu, Ju-Wei; Huang, Kai-Lin; Tsai, Shih-Jen; Chen, Mu-Hong; Soong, Wen-Jue; Kou, Yu Ru

2017-11-01

In this retrospective nationwide population-based case-control study, we investigated the impact of congenital heart disease (CHD) on the development of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), which remains unclear. Children aged <18 years that were diagnosed with CHD (n = 3552) between January 1, 1997 and December 31, 2009 were identified from the National Health Insurance Research Database in Taiwan. Non-CHD controls (n = 14,208) matched for age and sex (1:4) were selected from the same dataset. All subjects were observed until December 31, 2011 or their death. Comorbid perinatal conditions and early developmental disorders (EDD) that were diagnosed before ADHD and ASD diagnosis were also analyzed. The incidence rates of perinatal comorbidities, EDD, ADHD, and ASD were higher in the CHD group than in the control group. Multivariate Cox regression analysis revealed that the CHD group had an increased risk of developing ADHD (adjusted hazard ratio [aHR] 2.52, 95% confidence interval CI 1.96-3.25) and ASD (aHR 1.97, 95% CI 1.11-3.52) after adjusting for confounding comorbidities. EDD, but not perinatal comorbidities were also independent risk factors for ADHD and ASD after adjustment. Subgroup analysis indicated that the risk for ADHD (HR 16.59, 95% CI 12.17-22.60) and ASD (HR 80.68, 95% CI 39.96-176.12) was greatly increased in CHD subjects with EDD than in non-CHD subjects without EDD. These findings suggested that CHD at birth and EDD during early childhood were two independent risk factors for ADHD and ASD and that concurrent CHD and EDD might additively increase these risks.

The incidence of cerebrovascular accidents and second brain tumors in patients with pituitary adenoma: a population-based study.

PubMed

Brown, Paul D; Blanchard, Miran; Jethwa, Krishan; Flemming, Kelly D; Brown, Cerise A; Kline, Robert W; Jacobson, Debra J; St Sauver, Jennifer; Pollock, Bruce E; Garces, Yolanda I; Stafford, Scott L; Link, Michael J; Erickson, Dana; Foote, Robert L; Laack, Nadia N I

2014-03-01

To assess the risk of cerebrovascular accidents (CVAs) and second brain tumors (SBTs) in patients with pituitary adenoma after surgery or radiotherapy. A cohort of 143 people from Olmsted County, who were diagnosed with pituitary adenoma between 1933 and 2000, was studied. Only patients from Olmsted County were included because of the unique nature of medical care in Olmsted County, which allows the ascertainment of virtually all cases of pituitary adenoma for this community's residents and comparisons to the general population in the county. Surgical resection was performed in 76 patients, 29 patients underwent radiotherapy (with 21 undergoing both surgery and radiotherapy), 5 patients were reirradiated, and 59 patients were managed conservatively and observed. Median follow-up was 15.5 years. There was no difference in CVA-free survival between treatment groups. On univariate analysis age > 60 years (hazard ratio [HR], 11.93; 95% CI, 6.26-23.03; P < .001); male sex (HR, 3.67; 95% CI, 2.03-6.84; P < .001), and reirradiation (HR, 3.41; 95% CI, 1.05-9.68; P = .04) were associated with worse CVA-free survival. In multivariate analysis, only age > 60 years was associated with worse CVA-free survival. Compared with the general population, there was a 4-fold increase in the rate of CVAs in pituitary adenoma patients (HR, 4.2; 95% CI, 2.8-6.1). Two patients developed SBT (an irradiated patient and a surgically managed patient). CVA is a significant risk for patients with pituitary tumors, but treatment does not seem to impact the risk. Even with long-term follow-up, SBTs are a rare event regardless of treatment modality.

The incidence of cerebrovascular accidents and second brain tumors in patients with pituitary adenoma: a population-based study

PubMed Central

Brown, Paul D.; Blanchard, Miran; Jethwa, Krishan; Flemming, Kelly D.; Brown, Cerise A.; Kline, Robert W.; Jacobson, Debra J.; St. Sauver, Jennifer; Pollock, Bruce E.; Garces, Yolanda I.; Stafford, Scott L.; Link, Michael J.; Erickson, Dana; Foote, Robert L.; Laack, Nadia N.I.

2014-01-01

Background To assess the risk of cerebrovascular accidents (CVAs) and second brain tumors (SBTs) in patients with pituitary adenoma after surgery or radiotherapy. Methods A cohort of 143 people from Olmsted County, who were diagnosed with pituitary adenoma between 1933 and 2000, was studied. Only patients from Olmsted County were included because of the unique nature of medical care in Olmsted County, which allows the ascertainment of virtually all cases of pituitary adenoma for this community's residents and comparisons to the general population in the county. Surgical resection was performed in 76 patients, 29 patients underwent radiotherapy (with 21 undergoing both surgery and radiotherapy), 5 patients were reirradiated, and 59 patients were managed conservatively and observed. Results Median follow-up was 15.5 years. There was no difference in CVA-free survival between treatment groups. On univariate analysis age > 60 years (hazard ratio [HR], 11.93; 95% CI, 6.26–23.03; P < .001); male sex (HR, 3.67; 95% CI, 2.03–6.84; P < .001), and reirradiation (HR, 3.41; 95% CI, 1.05–9.68; P = .04) were associated with worse CVA-free survival. In multivariate analysis, only age > 60 years was associated with worse CVA-free survival. Compared with the general population, there was a 4-fold increase in the rate of CVAs in pituitary adenoma patients (HR, 4.2; 95% CI, 2.8–6.1). Two patients developed SBT (an irradiated patient and a surgically managed patient). Conclusion CVA is a significant risk for patients with pituitary tumors, but treatment does not seem to impact the risk. Even with long-term follow-up, SBTs are a rare event regardless of treatment modality. PMID:26034611

Sex-dependent difference in the effect of metformin on colorectal cancer-specific mortality of diabetic colorectal cancer patients

PubMed Central

Park, Jung Won; Lee, Jin Ha; Park, Ye Hyun; Park, Soo Jung; Cheon, Jae Hee; Kim, Won Ho; Kim, Tae Il

2017-01-01

AIM To assess factors associated with the higher effect of metformin on mortality in diabetic colorectal cancer (CRC) patients, since the factors related to the effectiveness of metformin have not been identified yet. METHODS Between January 2000 and December 2010, 413 patients diagnosed with both stage 3/4 CRC and diabetes mellitus were identified. Patients’ demographics and clinical characteristics were analyzed. The effect of metformin on CRC-specific mortality and the interactions between metformin and each adjusted factor were evaluated. RESULTS Total follow-up duration was median 50 mo (range: 1-218 mo). There were 85 deaths (45.9%) and 72 CRC-specific deaths (38.9%) among 185 patients who used metformin, compared to 130 total deaths (57.0%) and 107 CRC-specific deaths (46.9%) among 228 patients who did not use metformin. In multivariate analysis, survival benefit associated with metformin administration was identified (HR = 0.985, 95%CI: 0.974-0.997, P = 0.012). Interaction test between metformin and sex after adjustment for relevant factors revealed that female CRC patients taking metformin exhibited a significantly lower CRC-specific mortality rate than male CRC patients taking metformin (HR = 0.369, 95%CI: 0.155-0.881, P = 0.025). Furthermore, subgroup analysis revealed significant differences in CRC-specific mortality between the metformin and non-metformin groups in female patients (HR = 0.501, 95%CI: 0.286-0.879, P = 0.013) but not male patients (HR = 0.848, 95%CI: 0.594-1.211, P = 0.365). There were no significant interactions between metformin and other adjusted factors on CRC-specific mortality. CONCLUSION We showed a strong sex-dependent difference in the effect of metformin on CRC-specific mortality in advanced stage CRC patients with diabetes. PMID:28811714

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muijs, Christina, E-mail: c.t.muijs@umcg.nl; Smit, Justin; Karrenbeld, Arend

Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis wasmore » performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.« less

Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study.

PubMed

Floegel, Anna; Pischon, Tobias; Bergmann, Manuela M; Teucher, Birgit; Kaaks, Rudolf; Boeing, Heiner

2012-04-01

Early studies suggested that coffee consumption may increase the risk of chronic disease. We investigated prospectively the association between coffee consumption and the risk of chronic diseases, including type 2 diabetes (T2D), myocardial infarction (MI), stroke, and cancer. We used data from 42,659 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study. Coffee consumption was assessed by self-administered food-frequency questionnaire at baseline, and data on medically verified incident chronic diseases were collected by active and passive follow-up procedures. HRs and 95% CIs were calculated with multivariate Cox regression models and compared by competing risk analysis. During 8.9 y of follow-up, we observed 1432 cases of T2D, 394 of MI, 310 of stroke, and 1801 of cancer as first qualifying events. Caffeinated (HR: 0.94; 95% CI: 0.84, 1.05) or decaffeinated (HR: 1.05; 95% CI: 0.84, 1.31) coffee consumption (≥4 cups/d compared with <1 cup/d; 1 cup was defined as 150 mL) was not associated with the overall risk of chronic disease. A lower risk of T2D was associated with caffeinated (HR: 0.77; 95% CI: 0.63, 0.94; P-trend 0.009) and decaffeinated (HR: 0.70; 95% CI: 0.46, 1.06; P-trend: 0.043) coffee consumption (≥4 cups/d compared with <1 cup/d), but cardiovascular disease and cancer risk were not. The competing risk analysis showed no significant differences between the risk associations of individual diseases. Our findings suggest that coffee consumption does not increase the risk of chronic disease, but it may be linked to a lower risk of T2D.

Predictive value of early brain atrophy on response in patients treated with interferon β

PubMed Central

Pérez-Miralles, Francisco Carlos; Vidal-Jordana, Angela; Río, Jordi; Auger, Cristina; Pareto, Deborah; Tintoré, Mar; Rovira, Alex; Montalban, Xavier

2015-01-01

Objective: To investigate the association between brain volume loss during the first year of interferon treatment and clinical outcome at 4 years. Methods: Patients with multiple sclerosis initiating interferon β were clinically evaluated every 6 months for the presence of relapses and assessment of global disability using the Expanded Disability Status Scale (EDSS). MRI scans were performed at baseline and after 12 months, and the percentage of brain volume change (PBVC), brain parenchymal volume change (BPVc%), gray matter volume change (GMVc%), and white matter volume change (WMVc%) were estimated. Patients were divided based on the cutoff values for predicting confirmed EDSS worsening obtained by receiver operating characteristic analysis for all atrophy measurements. Survival curves and Cox proportional hazards regression to predict disability worsening at last observation were applied, adjusting for demographic, clinical, and radiologic variables. Results: Larger PBVC and WMVc% decreases were observed in patients with disability worsening at 4 years of follow-up, whereas no differences were found in BPVc% or GMVc%. Cutoff points were obtained for PBVC (−0.86%; sensitivity 65.5%, specificity 71.4%) and WMVc% (−2.49%; sensitivity 85.3%, specificity 43.8%). Patients with decreases of PBVC and WMVc% below cutoff values were more prone to develop disability worsening (unadjusted hazard ratio [HR] 3.875, p = 0.005; HR 4.246, p = 0.004, respectively). PBVC (HR 4.751, p = 0.008) and the interaction of new T2 lesions with WMVc% (HR 1.086, p = 0.005) were found to be independent predictors of disability worsening in the multivariate analysis. Conclusions: At the patient level, whole-brain and white matter volume changes in the first year of interferon β therapy are predictive of subsequent clinical evolution under treatment. PMID:26185778

Predictive value of early brain atrophy on response in patients treated with interferon β.

PubMed

Pérez-Miralles, Francisco Carlos; Sastre-Garriga, Jaume; Vidal-Jordana, Angela; Río, Jordi; Auger, Cristina; Pareto, Deborah; Tintoré, Mar; Rovira, Alex; Montalban, Xavier

2015-08-01

To investigate the association between brain volume loss during the first year of interferon treatment and clinical outcome at 4 years. Patients with multiple sclerosis initiating interferon β were clinically evaluated every 6 months for the presence of relapses and assessment of global disability using the Expanded Disability Status Scale (EDSS). MRI scans were performed at baseline and after 12 months, and the percentage of brain volume change (PBVC), brain parenchymal volume change (BPVc%), gray matter volume change (GMVc%), and white matter volume change (WMVc%) were estimated. Patients were divided based on the cutoff values for predicting confirmed EDSS worsening obtained by receiver operating characteristic analysis for all atrophy measurements. Survival curves and Cox proportional hazards regression to predict disability worsening at last observation were applied, adjusting for demographic, clinical, and radiologic variables. Larger PBVC and WMVc% decreases were observed in patients with disability worsening at 4 years of follow-up, whereas no differences were found in BPVc% or GMVc%. Cutoff points were obtained for PBVC (-0.86%; sensitivity 65.5%, specificity 71.4%) and WMVc% (-2.49%; sensitivity 85.3%, specificity 43.8%). Patients with decreases of PBVC and WMVc% below cutoff values were more prone to develop disability worsening (unadjusted hazard ratio [HR] 3.875, p = 0.005; HR 4.246, p = 0.004, respectively). PBVC (HR 4.751, p = 0.008) and the interaction of new T2 lesions with WMVc% (HR 1.086, p = 0.005) were found to be independent predictors of disability worsening in the multivariate analysis. At the patient level, whole-brain and white matter volume changes in the first year of interferon β therapy are predictive of subsequent clinical evolution under treatment.

Pretreatment Serum Lactate Dehydrogenase and N Classification Predict Long-Term Survival and Distant Metastasis in Patients With Nasopharyngeal Carcinoma Who Have A Positive Family History of Cancer

PubMed Central

Zhang, Wenna; Chen, Yupei; Zhou, Guanqun; Liu, Xu; Chen, Lei; Tang, Linglong; Mao, Yanping; Sun, Ying; Ma, Jun

2015-01-01

Abstract The purpose of the present study was to evaluate prognostic factors in patients with nasopharyngeal carcinoma (NPC) from the endemic area of southern China who have a positive family history (FH) of cancer. Retrospective analysis of 600 patients with nondisseminated NPC and a positive FH was conducted. The prognostic value of different factors for overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and local relapse-free survival (LRFS) were assessed using Cox regression models. The 3-year OS, DMFS, DFS, and LRFS rates were 93.8%, 91.3%, 86.3%, and 93.8%, respectively. The FH tumor type was NPC for 226/600 (37.7%) patients and other cancers for 374/600 (62.3%) patients. The 3-year OS and DMFS rates for patients with an FH of NPC were 91.2% and 89.8%, respectively. Thirty of 600 (5.0%) patients had elevated pretreatment serum lactate dehydrogenase (LDH >245.0 IU/L). In multivariate analysis, N classification (HR 4.56, 95% CI 2.13–9.74, P < 0.0001) and elevated pretreatment serum LDH (HR 2.87, 95% CI 1.08–7.62, P = 0.034) were independent prognosticators for OS. Female patients (HR 0.42, 95% CI 0.19–0.95, P = 0.037) and patients with normal pretreatment serum LDH (HR 2.42, 95% CI 1.02–5.78, P = 0.046) had better DMFS. Elevated pretreatment serum LDH and N classification are independent prognostic factors for poorer survival in patients with NPC who have a positive FH of cancer. PMID:26376394

Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers.

PubMed

O'Grady, M R; O'Sullivan, M L; Minors, S L; Horne, R

2009-01-01

Angiotensin converting enzyme inhibitors (ACEIs) are recommended in people to treat asymptomatic (occult) dilated cardiomyopathy (DCM). Efficacy of therapy in occult DCM in dogs is unknown. ACEIs, specifically benazepril hydrochloride (BH), will delay the onset of overt DCM in Doberman Pinschers. Ninety-one Doberman Pinschers were studied, 57 dogs received BH, and 34 dogs no ACEI. Retrospective study of the medical records of all Doberman Pinschers with occult DCM that received BH or no ACEI between April 1989 and February 2003. Two criteria of left ventricular enlargement were used for enrollment: one independent of body weight (BW) (C1) and the other indexed to BW (C2). Cox proportional hazards analyses were used to identify variables associated with the onset of overt DCM. On univariate analysis the median time to onset of overt DCM was significantly longer for the benazepril group (for C1: 425 days for BH, 95% confidence interval [CI] 264-625 days; 339 days for no ACEI, CI 172-453 days, P= .02; for C2: 454 days for BH, CI 264-628 days; 356 days for no ACEI, CI 181-547 days, P= .02). The hazard ratio (HR) (benazepril/no ACEI) was 0.57, CI 0.35-0.94, P= .03 for C1; HR = 0.56, CI 0.34-0.93, P= .02 for C2. On multivariate analysis, BH significantly delayed onset of overt DCM (HR [benazepril/no ACEI] = 0.45, CI 0.26-0.78, P < .01, for C1; HR = 0.36, CI 0.21-0.63, P < .01, for C2). BH in particular and ACEIs in general might delay the progression of occult DCM. Prospective studies are warranted to test this theory.

The Impact of Demographic and Socioeconomic Factors on Major Salivary Gland Cancer Survival.

PubMed

Olarte, Lucia S; Megwalu, Uchechukwu C

2014-06-01

This study aimed to investigate the impact of demographic and socioeconomic factors on survival in patients with major salivary gland malignancies. Population-based study using the Surveillance, Epidemiology, and End Results (SEER) cancer database. The study cohort consisted of 10,735 men and women ages 20 and older who were diagnosed with major salivary gland carcinoma from 1973 to 2009. Kaplan-Meier analysis revealed that the overall and disease-specific survival was higher for women than for men (P < .001). Overall and disease-specific survival decreased with increasing age (P < .001) and differed by race (P < .001) and marital status (P < .001). Patients residing in counties with higher rates of high school completion had higher overall and disease-specific survival (P < .001). Patients residing in counties with higher median household incomes had better overall and disease-specific survival than patients from lower income counties (P < .001). On multivariable analysis, male sex (hazard ratio [HR] = 1.41; 95% confidence interval [CI], 1.32-1.50), increasing age, and single status (HR = 1.36; 95% CI, 1.27-1.44) had poor prognostic impact on overall survival. Male sex (HR = 1.38; 95% CI, 1.27-1.49), increasing age, and single status (HR = 1.29; 95% CI, 1.19-1.39) had poor prognostic impact on disease-specific survival. For patients with salivary gland malignancies, there is a survival benefit for younger patients, female patients, and married patients. This highlights the significance of demographic factors on survival outcomes for patients with salivary gland malignancies and highlights areas for further research on health disparities. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Risk factors for adverse drug reactions in pediatric inpatients: A cohort study.

PubMed

Andrade, Paulo Henrique Santos; Lobo, Iza Maria Fraga; da Silva, Wellington Barros

2017-01-01

The present study aims to identify the risk factors for adverse drug reactions (ADR) in pediatric inpatients. A prospective cohort study in one general pediatric ward in a hospital in Northeast Brazil was conducted in two stages: the first stage was conducted between August 17th and November 6th, 2015, and the second one between March 1st and August 25th, 2016. We included children aged 0-14 years 11 months hospitalized with a minimum stay of 48 hours. Observed outcomes were the ADR occurrence and the time until the first ADR observed. In the univariate analysis, the time to the first ADR was compared among groups using a log-rank test. For the multivariate analysis, the Cox regression model was used. A total of 173 children (208 admissions) and 66 ADR classified as "definite" and "probable" were identified. The incidence rate was 3/100 patient days. The gastro-intestinal system disorders were the main ADR observed (28.8%). In addition, 22.7% of the ADR were related to antibacterials for systemic use and 15.2% to general anesthesia. Prior history of ADR of the child [hazard ratio (HR) 2.44; 95% confidence interval (CI) 1.19-5.00], the use of meglumine antimonate (HR 4.98; 95% CI 1.21-20.54), antibacterial for systemic use (HR 2.75; 95% CI 1.08-6.98) and antiepileptic drugs (HR 3.84; 95% CI 1.40-10.56) were identified risk factors for ADR. We identified as risk factors the prior history of ADR of the child and the use of meglumine antimonate, antibacterial for systemic use and antiepileptic drugs.

A pooled analysis of the association of isolated low levels of high-density lipoprotein cholesterol with cardiovascular mortality in Japan.

PubMed

Hirata, Takumi; Sugiyama, Daisuke; Nagasawa, Shin-Ya; Murakami, Yoshitaka; Saitoh, Shigeyuki; Okayama, Akira; Iso, Hiroyasu; Irie, Fujiko; Sairenchi, Toshimi; Miyamoto, Yoshihiro; Yamada, Michiko; Ishikawa, Shizukiyo; Miura, Katsuyuki; Ueshima, Hirotsugu; Okamura, Tomonori

2017-07-01

Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

Mesorectal Invasion Depth in Rectal Carcinoma Is Associated With Low Survival.

PubMed

Lino-Silva, Leonardo S; Loaeza-Belmont, Reynaldo; Gómez Álvarez, Miguel A; Vela-Sarmiento, Itzel; Aguilar-Romero, José M; Domínguez-Rodríguez, Jorge A; Salcedo-Hernández, Rosa A; Ruiz-García, Erika B; Maldonado-Martínez, Héctor A; Herrera-Gómez, Ángel

2017-03-01

Most cases of rectal cancer (RC) in our institution are in pathologic stage T3. They are a heterogeneous group but have been classified in a single-stage category. We performed the present study to validate the prognostic significance of the mesorectal extension depth (MED) in T3 RC measured in millimeters beyond the muscularis propria plane. We performed a retrospective analysis of 104 patients with T3 RC who had undergone curative surgery after a course of preoperative chemoradiotherapy at a tertiary referral cancer hospital. The patients were grouped by MED (T3a, < 1 mm; T3b, 1-5 mm; T3c > 5-10 mm; and T3d > 10 mm). The clinicopathologic data and disease-free survival were analyzed. The 5-year disease-free survival rate according to the T3 subclassification was 87.5% for those with T3a, 57.9% for T3b, 38.7% for T3c, and 40.3% for those with T3d tumors (P = .050). On univariate and multivariate analysis, the prognostic factors affecting survival were overall recurrence (hazard ratio [HR], 3.670; 95% confidence interval [CI], 1.710-7.837; P = .001), histologic grade (HR, 2.204; 95% CI, 1.156-4.199; P = .016), mesorectal invasion depth (HR, 1.885; 95% CI, 1.164-3.052; P = .010), and lymph node metastasis (HR, 1.211; 95% CI, 1.015-1.444; P = .033). MED is a significant prognostic factor in patients with T3 RC who have undergone neoadjuvant chemoradiotherapy, especially when the MED is > 5 mm. The MED could be as important as other clinicopathologic factors in predicting disease-specific survival. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk factors for infection by oncogenic human papillomaviruses in HIV-positive MSM patients in the ART era (2010-2016).

PubMed

Hidalgo-Tenorio, Carmen; Gil-Anguita, Concepción; Ramírez-Taboada, Jessica; Esquivias, Javier; López-Ruz, Miguel A; Balgahata, Omar Mohamed; Javier-Martinez, Rosario; Pasquau, Juan

2017-09-01

Squamous cell carcinoma of anus (SCCA) is one of the most frequent non-AIDS-defining diseases in HIV patients, mainly in men who have sex with men (MSM), and it is associated with human papillomavirus (HPV) infection.To determine the prevalence of high-risk HPV (HR-HPV) genotypes, premalignant lesions (HSIL) and SCCA in a cohort of HIV-positive MSM; to study the distribution of HPV genotypes according to anal histology results; and to analyze risk factors for this infection.This prospective single-center study was conducted between May 2010 and September 2016. At the study visit, cotton swabs were used to collect anal samples for cytology study in ThinPrep Pap Test liquid medium (Thin Prep Processor 2000, Hologic Corp, USA), and for HPV PCR (Linear Array HPV Genotyping Test). After, high-resolution anoscopy (HRA) (Zeiss 150 fc) was carried out. Logistic regression analysis was performed to identify risk factors for HR-HPV infection.The study included 319 patients, with mean age of 36.7 years; HR-HPV was detected in 81.3%. The prevalence of HSIL was 13.5% and SCCA was 0.3%. With regard to the distribution of HPV genotypes according to histology results, HPV 16 was the most frequent genotype in normal anal mucosa (26.7%), in LSILs (36.9%), and in HSILs (38%). In multivariate analysis, CD4 nadir < 200 cells/μL was the factor associated with infection by HR-HPV (OR 3.66, 95% CI 1.05%-12.75%).HIV-positive MSM showed a high prevalence of HSIL+ lesions and of infection by oncogenic HPV, which appears to be favored by a deficient immune system. HPV 16 was the most frequently isolated genotype in anal mucosa, regardless of lesion type.

Lead-Dependent Infective Endocarditis: The Role of Factors Predisposing to Its Development in an Analysis of 414 Clinical Cases.

PubMed

Polewczyk, Anna; Jacheć, Wojciech; Janion, Marianna; Podlaski, Rafał; Kutarski, Andrzej

2015-07-01

Lead-dependent infective endocarditis (LDIE) is a serious and insidious infective disease spreading along the leads to valve leaflets and endocardial surface. LDIE is still a lesser known disease with unclear risk factors, most often evaluated jointly for all infectious complications. Clinical data from 414 patients with the diagnosis of LDIE according to the Modified Duke Leads Criteria were analyzed. Patients with LDIE were identified in a population of 1,426 subjects submitted to transvenous lead extraction (TLE) in the Reference Center on Lead Extraction in Lublin, Poland, between March 2006 and July 2013 due to infectious (619 patients-43.4%) and noninfectious (807-56.6% of patients) reasons. During the period of 2006-2011, the analysis was conducted retrospectively; from early 2012 on, patients were enrolled prospectively. The effect of potential risk factors on the development of the disease was evaluated in a comparative analysis of clinical data from the LDIE patients and from 807 subjects with noninfectious indications for TLE. Additionally, in order to identify the factors predisposing to the development of LDIE, the population of infectious patients was divided into three subgroups: with isolated LDIE (157 patients), with LDIE and pocket infection (PI; 257 patients), and with isolated PI (205 patients). The groups and subgroups were analyzed for the presence of patient-dependent risk factors (age, gender, accompanying diseases, anticoagulation, or antiplatelet therapy) and procedure-related risk factors (the number and lead dwell time, pacing system, prior procedures, lead loops, and intracardiac abrasion of the leads). Furthermore, microbes' identification was conducted. The LDIE patients were older (67.3 vs 62.3; P = 0.001) and were more frequently male (68.6% vs 55.0%; P = 0.001) as compared with patients submitted to TLE for noninfectious reasons, but not in comparison with subjects diagnosed with isolated LDIE. In univariate analysis, the independent prognostic factors of LDIE were: type 2 diabetes-increase of risk by 37.7% (hazard ratio [HR] = 1,377; 95% confidence interval [CI] [1,088-1,742]), elevated above 2 mg% creatinine level-increase of risk by 61.5% (HR = 1,615; 95% CI [1,96-2,182]), antiplatelet therapy (HR = 1,285; 95% CI [1,052-1,057]), number of intracardiac leads prior to TLE (HR = 1,199; 95% CI [1,075-1,337]), intracardiac device with implantable cardioverter defibrillator (ICD) lead (HR = 1,909; 95% CI [1,492-2,444]), intracardiac device with coronary sinus lead (HR = 1,411; 95% CI [1,099-1,810]), number of procedures prior to TLE (HR = 1,092; 95% CI [1,017-1,172]), and abrasion of intracardiac leads (HR = 1,350; 95% CI [1,097-1,662]). Multivariate logistic regression demonstrated that the independent risk factors of LDIE were: chronic renal failure (HR = 1,406; 95% CI [1,033-1,915]), number of intracardiac leads prior to TLE (HR = 1,152; 95% CI [1,017-1,305]), intracardiac devices with ICD leads (HR = 1,719; 95% CI [1,330-2,223]), and presence of abrasion of intracardiac leads (HR = 1,405; 95% CI [1,129-1,750]). Microbiological analysis showed the domination of coagulase-negative staphylococci with relative advantage of Staphylococcus epidermidis in pathogenesis of LDIE. The factors predisposing to LDIE are mainly related to procedures performed on the patients. LDIE develops more frequently in patients with multiple leads, especially ICD. An important, until now lesser known, risk factor for LDIE is intracardiac abrasion of the leads strongly connected with procedural agents and properties of specific kind of bacteries. A new concept of the pathogenesis of LDIE was proposed on the basis of present analysis. ©2015 Wiley Periodicals, Inc.

Lung and gastrointestinal complications are leading causes of death in SCORE, a multi-ethnic Singapore systemic sclerosis cohort.

PubMed

Santosa, A; Tan, C S; Teng, G G; Fong, W; Lim, A; Law, W G; Chan, G; Ng, S C; Low, Ahl

2016-11-01

To assess contemporary outcomes and predictors of mortality in the well-characterized multi-ethnic systemic sclerosis cohort Singapore (SCORE). From 2008, patients diagnosed with systemic sclerosis (SSc) fulfilling the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) or Very Early Diagnosis of Systemic Sclerosis (VEDOSS) criteria were recruited from three major tertiary rheumatology centres in Singapore. Mortality was verified with the Singapore National Registry of Deaths and in-hospital cause of death was determined by two independent reviewers, up to 10 December 2013. A Cox proportional hazard (PH) regression analysis was used to examine the association between demographic and clinical indices and mortality, controlling for age and race. Of the 349 patients (86.8% female; 77.7% Chinese), 97.4% fulfilled the ACR/EULAR 2013 criteria. The mean age at diagnosis was 46.2 years. The prevalence of limited (lcSSc), diffuse (dcSSc) cutaneous SSc, and SSc-overlap syndromes was 34.4, 37.1, and 26.8%, respectively. Thirty-five patients died after a mean follow-up of 2.1 years (743.6 person-years). Fifty-seven per cent of deaths were attributed to SSc, with pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and gastrointestinal (GI) complications as the leading causes of death. Multivariate analysis (n = 275) showed that smoking [hazard ratio (HR) 4.0, 95% confidence interval (CI) 1.5-10.6], SSc-overlap (HR 6.0, 95% CI 1.8-19.1), baseline renal involvement (HR 2.5, 95% CI 1.1-6.0), pulmonary artery systolic pressure (PASP) ≥ 40 mmHg on echocardiography (HR 5.1, 95% CI 2.2-11.7), treatment for peripheral vasculopathy (HR 2.6, 95% CI 1.1-6.5), and parenteral nutrition (HR 8.8, 95% CI 2.2-34.3) were independent predictors of mortality. PAH, ILD, and GI complications were leading causes of death in this cohort. We identified a high-risk group of patients who would benefit from closer monitoring and early intervention.

Role of adjuvant radiotherapy for localized extrahepatic bile duct cancer

PubMed Central

Kim, Yi-Jun; Min, Seog Ki; Nam, Eun Mi

2017-01-01

Objective: To evaluate the benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic bile duct (EHBD) cancer. Methods: From 1997 to 2015, 59 patients with EHBD cancer were the subject of this study; 36 patients not undergoing adjuvant treatment after surgery (observation group) and 23 patients receiving adjuvant RT (RT group) were compared. Microscopic residual disease (R1) was in 9 (25%) patients and 5 (22%) patients, and macroscopic residual disease (R2) was in 2 (6%) patients and 6 (26%) patients in the observation and RT groups, respectively. Adjuvant RT was delivered to the tumour bed and regional lymph nodes up to 50.4 Gy (range, 45–61 Gy). Results: With a median follow-up of 19 months, local recurrence was observed in 10 (28%) patients and 2 (9%) patients in the observation and RT groups, respectively. On univariate analysis, the 5-year local recurrence-free survival (LRFS) rates were 50% in the observation group and 54% in the RT group (p = 0.401). The 5-year overall survival (OS) rates were 29.3% in the observation group and 26.3% in the RT group (p = 0.602). On multivariable analysis, however, adjuvant RT significantly improved LRFS [hazard ratio (HR), 0.310; 95% confidence interval (CI), 0.100–0.963; p = 0.043] and had a trend towards increased OS (HR, 0.491; 95% CI, 0.219–1.102; p = 0.085). Resection margin (RM) status was also correlated with LRFS (HR for R1 6.134, 95% CI 2.051–18.344; and HR for R2 18.551, 95% CI 3.680–93.520; p < 0.001) and OS (HR for R1 1.816, 95% CI 0.853–3.867; and HR for R2 3.564, 95% CI 1.175–10.809; p = 0.054). Conclusion: RM status was a significant prognosticator of EHBD cancer, and adjuvant RT improved local control rate; thereby, survival rate might be increased. Advances in knowledge: The benefit of adjuvant RT in EHBD cancer was demonstrated via comparison with observation group. PMID:28118028

Correlation between the severity of cetuximab-induced skin rash and clinical outcome for head and neck cancer patients: The XXXX experience

PubMed Central

Bar-Ad, Voichita; Zhang, Qiang (Ed); Harari, Paul M.; Axelrod, Rita; Rosenthal, David I.; Trotti, Andy; Jones, Christopher U.; Garden, Adam S.; Song, Guobin; Foote, Robert L.; Raben, David; Shenouda, George; Spencer, Sharon A.; Harris, Jonathan; Le, Quynh-Thu

2016-01-01

Purpose The purpose of the present study was to evaluate severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy and cetuximab. Materials & Methods Analysis included patients who received loading dose and ≥ 1cetuximab dose concurrent with definitive chemoradiotherapy (70Gy + cisplatin) or postoperative chemoradiotherapy (60–66Gy + docetaxel or cisplatin). Results Six hundred two patients were analyzed; 383 (63.6%) developed Grade 2–4 cetuximab rash. Patients manifesting Grade 2–4 rash had younger age (p<0.001), fewer pack-years smoking history (p<0.001), were more likely to be males (p=0.04), and had p16-negative (p=0.04) oropharyngeal tumors (p=0.003). In univariate analysis, Grade 2–4 rash was associated with better overall survival (OS) (hazard ratio [HR] 0.58, p<0.001) and progression-free survival (PFS) (HR 0.75, p=0.02), and reduced distant metastasis (DM) rate (HR 0.61, p=0.03), but not local-regional failure (LRF) (HR 0.79, p=0.16) relative to Grade 0–1 rash. In multivariable analysis, HRs for OS, PFS, DM, and LRF were 0.68 (p=0.008), 0.85 (p=0.21), 0.64 (p=0.06), and 0.89 (p=0.48). Grade ≥2 rash was associated with improved survival in p16 negative patients (HR 0.28 (0.11–0.74)) but not in p16 positive patients (HR 1.10 (0.42–2.89)) (p=0.05 for interaction). Twenty-five percent of patients with Grade 2–4 acute in-field radiation dermatitis experienced Grade 2–4 late skin fibrosis vs. 14% of patients with Grade 0–1 acute in-field radiation dermatitis (p=0.002). Conclusion Grade 2–4 cetuximab rash was associated with better survival possibly due to reduction of distant metastasis. This observation was noted mainly in p16 negative patients. Grade 2–4 acute in-field radiation dermatitis was associated with higher rate of late Grade 2–4 skin fibrosis. PMID:27212198

Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bar-Ad, Voichita, E-mail: voichita.bar-ad@jefferson.edu; Zhang, Qiang; Harari, Paul M.

Purpose: To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab. Methods and Materials: Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin). Results: Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and hadmore » p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002). Conclusion: Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.« less

Centre characteristics associated with the risk of peritonitis in peritoneal dialysis: a hierarchical modelling approach based on the data of the French Language Peritoneal Dialysis Registry.

PubMed

Béchade, Clémence; Guillouët, Sonia; Verger, Christian; Ficheux, Maxence; Lanot, Antoine; Lobbedez, Thierry

2017-06-01

This study investigated the centre effect on the risk of peritonitis in peritoneal dialysis (PD) patients. This was a retrospective cohort study based on data from the French Language Peritoneal Dialysis Registry. We analysed 5017 incident patients starting PD between January 2008 and December 2012 in 127 PD centres. The end of the observation period was 1 January 2014. The event of interest was the first peritonitis episode. The analysis was performed with a multilevel Cox model and a Fine and Gray model. Among the 5017 patients, 3190 peritonitis episodes occurred in 1796 patients. There was significant heterogeneity between centres (variance of the random effect: 0.11). The variance of the centre effect was reduced by 9% after adjusting for patient characteristics and by 35% after adjusting on centre covariate. In the multivariate analysis with a multilevel Cox model, centre with a nurse specialized in PD or centre providing home visits before dialysis initiation decreased the centre effect on peritonitis. Patients treated in centres with a nurse specialized in PD or in centres providing home visits before dialysis initiation had a lower risk of peritonitis [cause-specific hazard ratio (cs-HR): 0.75 (95% confidence interval, CI, 0.67-0.83) and cs-HR: 0.87 (95% CI 0.76-0.97), respectively]. The data show that neither centre type nor centre volume influenced peritonitis risk. In the competing risk analysis, centre with a nurse specialized in PD and centre with home visits had a protective effect on peritonitis [sub-distribution HR (sd-HR): 0.77 (95% CI 0.70-0.85) and sd-HR: 0.85 (95% CI 0.77-0.94), respectively]. There is a significant centre effect on the risk of peritonitis that can be decreased by home visits before dialysis initiation and by the presence of a nurse specialized in PD. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study

PubMed Central

Chess, James; Do, Jun-Young; Noh, Hyunjin; Lee, Hi-Bahl; Kim, Yong-Lim; Summers, Angela; Williams, Paul Ford; Davison, Sara; Dorval, Marc

2016-01-01

Background and Objectives Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. Methods and Materials We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients), with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis. Results The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (β = -0.007, 95%CI -0.010, -0.004) and decreased with higher serum sodium (β = 0.002, 95%CI 0.0005, 0.003) in incident patients and increased with dialysate glucose (β = -0.0002, 95%CI -0.0004, -0.00006) in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6–10 compared with <6, Incident group HR 0.92, 95%CI 0.58, 1.46, Prevalent group HR 1.42, 95%CI 0.86, 2.34). Conclusions In prevalent non-diabetic patients, random glucose levels at a diabetic level are under-recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses. PMID:27249020

The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery.

PubMed

Rutten, I J G; Ubachs, J; Kruitwagen, R F P M; van Dijk, D P J; Beets-Tan, R G H; Massuger, L F A G; Olde Damink, S W M; Van Gorp, T

2017-04-01

Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS). Ovarian cancer patients (n = 216) treated with PDS were enrolled retrospectively. Total skeletal muscle surface area was measured on axial computed tomography at the level of the third lumbar vertebra. Optimum stratification was used to find the optimal skeletal muscle index cut-off to define sarcopenia (≤38.73 cm 2 /m 2 ). Cox-regression and Kaplan-Meier analysis were used to analyse the relationship between sarcopenia and OS. The effect of sarcopenia on the development of major surgical complications was studied with logistic regression. Kaplan-Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p = 0.010). Sarcopenia univariably predicted OS (HR 1.536 (95% CI 1.105-2.134), p = 0.011) but was not significant in multivariable Cox-regression analysis (HR 1.362 (95% CI 0.968-1.916), p = 0.076). Significant predictors for OS in multivariable Cox-regression analysis were complete PDS, treatment in a specialised centre and the development of major complications. Sarcopenia was not predictive of major complications. Sarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery. However a strong trend towards a survival disadvantage for patients with sarcopenia was seen. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival. Complete cytoreduction remains the strongest predictor of ovarian cancer survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Impact of treatment and insurance on socioeconomic disparities in survival after adolescent and young adult Hodgkin lymphoma: A population-based study

PubMed Central

Keegan, Theresa H.M.; DeRouen, Mindy C.; Parsons, Helen M.; Clarke, Christina A.; Goldberg, Debbie; Flowers, Christopher R.; Glaser, Sally L.

2015-01-01

Background Previous studies documented racial/ethnic and socioeconomic disparities in survival after Hodgkin lymphoma (HL) among adolescents and young adults (AYAs), but did not consider the influence of combined-modality treatment and health insurance. Methods Data for 9,353 AYA patients aged 15–39 when diagnosed with HL during 1988–2011 were obtained from the California Cancer Registry. Using multivariate Cox proportional hazards regression, we examined the impact of socio-demographic characteristics (race/ethnicity, neighborhood socioeconomic status (SES), and health insurance), initial combined-modality treatment, and subsequent cancers on survival. Results Over the 24-year study period, we observed improvements in HL-specific survival by diagnostic period and differences in survival by race/ethnicity, neighborhood SES and health insurance for a subset of more recently diagnosed patients (2001–2011). In multivariable analyses, HL-specific survival was worse for Blacks than Whites with early-stage (Hazard Ratio (HR): 1.68; 95% Confidence Interval (CI): 1.14, 2.49) and late-stage disease (HR: 1.68; 95% CI: 1.17, 2.41) and for Hispanics than Whites with late-stage disease (HR: 1.58; 95% CI: 1.22, 2.04). AYAs diagnosed with early-stage disease experienced worse survival if they also resided in lower SES neighborhoods (HR: 2.06; 95% CI: 1.59, 2.68). Furthermore, more recently diagnosed AYAs with public health insurance or who were uninsured experienced worse HL-specific survival (HR: 2.08; 95% CI: 1.52, 2.84). Conclusion Our findings identify several subgroups of HL patients at higher risk for HL mortality. Impact Identifying and reducing barriers to recommended treatment and surveillance in these AYAs at much higher risk of mortality is essential to ameliorating these survival disparities. PMID:26826029

Predicting survival of men with recurrent prostate cancer after radical prostatectomy.

PubMed

Dell'Oglio, Paolo; Suardi, Nazareno; Boorjian, Stephen A; Fossati, Nicola; Gandaglia, Giorgio; Tian, Zhe; Moschini, Marco; Capitanio, Umberto; Karakiewicz, Pierre I; Montorsi, Francesco; Karnes, R Jeffrey; Briganti, Alberto

2016-02-01

To develop and externally validate a novel nomogram aimed at predicting cancer-specific mortality (CSM) after biochemical recurrence (BCR) among prostate cancer (PCa) patients treated with radical prostatectomy (RP) with or without adjuvant external beam radiotherapy (aRT) and/or hormonal therapy (aHT). The development cohort included 689 consecutive PCa patients treated with RP between 1987 and 2011 with subsequent BCR, defined as two subsequent prostate-specific antigen values >0.2 ng/ml. Multivariable competing-risks regression analyses tested the predictors of CSM after BCR for the purpose of 5-year CSM nomogram development. Validation (2000 bootstrap resamples) was internally tested. External validation was performed into a population of 6734 PCa patients with BCR after treatment with RP at the Mayo Clinic from 1987 to 2011. The predictive accuracy (PA) was quantified using the receiver operating characteristic-derived area under the curve and the calibration plot method. The 5-year CSM-free survival rate was 83.6% (confidence interval [CI]: 79.6-87.2). In multivariable analyses, pathologic stage T3b or more (hazard ratio [HR]: 7.42; p = 0.008), pathologic Gleason score 8-10 (HR: 2.19; p = 0.003), lymph node invasion (HR: 3.57; p = 0.001), time to BCR (HR: 0.99; p = 0.03) and age at BCR (HR: 1.04; p = 0.04), were each significantly associated with the risk of CSM after BCR. The bootstrap-corrected PA was 87.4% (bootstrap 95% CI: 82.0-91.7%). External validation of our nomogram showed a good PA at 83.2%. We developed and externally validated the first nomogram predicting 5-year CSM applicable to contemporary patients with BCR after RP with or without adjuvant treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long term impact of hyperleukocytosis in newly diagnosed acute myeloid leukemia patients undergoing allogeneic stem cell transplantation: An analysis from the acute leukemia working party of the EBMT.

PubMed

Canaani, Jonathan; Labopin, Myriam; Socié, Gerard; Nihtinen, Anne; Huynh, Anne; Cornelissen, Jan; Deconinck, Eric; Gedde-Dahl, Tobias; Forcade, Edouard; Chevallier, Patrice; Bourhis, Jean H; Blaise, Didier; Mohty, Mohamad; Nagler, Arnon

2017-07-01

Up to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3-ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the European Society of Blood and Marrow Transplantation. A cohort of 357 patients with hyperleukocytosis (159 patients with white blood count [WBC] 50 K-100 K, 198 patients with WBC ≥ 100 K) was compared to 918 patients without hyperleukocytosis. Patients with hyperleukocytosis were younger, had an increased rate of favorable risk cytogenetics, and more likely to be FLT3 and NPM1 mutated. In multivariate analysis, hyperleukocytosis was independently associated with increased relapse incidence (hazard ratio [HR] of 1.55, 95% confidence interval [CI], 1.14-2.12; P = .004), decreased leukemia-free survival (HR of 1.38, 95% CI, 1.07-1.78; P = .013), and inferior overall survival (HR of 1.4, 95% CI, 1.07-1.84; P = .013). Hyperleukocytosis retains a significant prognostic role for AML patients undergoing HSCT. © 2017 Wiley Periodicals, Inc.

Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study

PubMed Central

Citgez, Emanuel; van der Palen, Job; Koehorst-ter Huurne, Kirsten; Movig, Kris; van der Valk, Paul; Brusse-Keizer, Marjolein

2016-01-01

Background Both chronic inflammation and cardiovascular comorbidity play an important role in the morbidity and mortality of patients with chronic obstructive pulmonary disease (COPD). Statins could be a potential adjunct therapy. The additional effects of statins in COPD are, however, still under discussion. The aim of this study is to further investigate the association of statin use with clinical outcomes in a well-described COPD cohort. Methods 795 patients of the Cohort of Mortality and Inflammation in COPD (COMIC) study were divided into statin users or not. Statin use was defined as having a statin for at least 90 consecutive days after inclusion. Outcome parameters were 3-year survival, based on all-cause mortality, time until first hospitalisation for an acute exacerbation of COPD (AECOPD) and time until first community-acquired pneumonia (CAP). A sensitivity analysis was performed without patients who started a statin 3 months or more after inclusion to exclude immortal time bias. Results Statin use resulted in a better overall survival (corrected HR 0.70 (95% CI 0.51 to 0.96) in multivariate analysis), but in the sensitivity analysis this association disappeared. Statin use was not associated with time until first hospitalisation for an AECOPD (cHR 0.95, 95% CI 0.74 to 1.22) or time until first CAP (cHR 1.1, 95% CI 0.83 to 1.47). Conclusions In the COMIC study, statin use is not associated with a reduced risk of all-cause mortality, time until first hospitalisation for an AECOPD or time until first CAP in patients with COPD. PMID:27403321

Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study.

PubMed

Citgez, Emanuel; van der Palen, Job; Koehorst-Ter Huurne, Kirsten; Movig, Kris; van der Valk, Paul; Brusse-Keizer, Marjolein

2016-01-01

Both chronic inflammation and cardiovascular comorbidity play an important role in the morbidity and mortality of patients with chronic obstructive pulmonary disease (COPD). Statins could be a potential adjunct therapy. The additional effects of statins in COPD are, however, still under discussion. The aim of this study is to further investigate the association of statin use with clinical outcomes in a well-described COPD cohort. 795 patients of the Cohort of Mortality and Inflammation in COPD (COMIC) study were divided into statin users or not. Statin use was defined as having a statin for at least 90 consecutive days after inclusion. Outcome parameters were 3-year survival, based on all-cause mortality, time until first hospitalisation for an acute exacerbation of COPD (AECOPD) and time until first community-acquired pneumonia (CAP). A sensitivity analysis was performed without patients who started a statin 3 months or more after inclusion to exclude immortal time bias. Statin use resulted in a better overall survival (corrected HR 0.70 (95% CI 0.51 to 0.96) in multivariate analysis), but in the sensitivity analysis this association disappeared. Statin use was not associated with time until first hospitalisation for an AECOPD (cHR 0.95, 95% CI 0.74 to 1.22) or time until first CAP (cHR 1.1, 95% CI 0.83 to 1.47). In the COMIC study, statin use is not associated with a reduced risk of all-cause mortality, time until first hospitalisation for an AECOPD or time until first CAP in patients with COPD.

Clinical prognostic value of metastasis-associated lung adenocarcinoma transcript 1 in various human cancers: an updated meta-analysis.

PubMed

Li, Yang; Yang, Ze; Wan, Xiaoya; Zhou, Jianguo; Zhang, Yu; Ma, Hu; Bai, Yuju

2016-05-28

Many studies have investigated the prognostic value of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in human cancers. However, these studies were often limited by small sample sizes. Therefore, we performed this updated meta-analysis to summarize the potential value of MALAT1 as a biomarker for early treatment and to predict survival in various human malignant neoplasms, through the inclusion of the latest literature and improved methodology. Twelve eligible articles were systematically obtained from PubMed, Medline, Embase, Web of Science, China National Knowledge Infrastructure and the Cochrane Library, from inception up to June 30, 2015. Survival was assessed using pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs). By combining the results of 12 studies, we found elevated MALAT1 expression was associated with poor survival in most cancers, with a pooled HR of 1.90 (95% CI, 1.56-2.30) for overall survival (OS) and 3.06 (95% CI, 2.06-4.56) for recurrence-free survival/disease-free survival. Subgroup analyses according to ethnicity, tumor type, assay method, sample size, HR-calculation method and analysis type did not affect the predictive role of MALAT1 for OS in various cancer types. Further, by combining results from studies that used multivariate analyses, we found elevated MALAT1 was an independent prognostic factor for OS (HR = 1.98; 95% CI, 1.58-2.48). MALAT1 could serve as a potential prognostic biomarker in various cancers and may be a potential therapeutic target for the treatment and early detection of recurrence.

E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx.

PubMed

Li, Yuncheng; Sturgis, Erich M; Zhu, Lijun; Cao, Xiaoli; Wei, Qingyi; Zhang, Hua; Li, Guojun

2017-04-01

Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1 008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, P < 0.001) and lower SCCOP recurrence risk (HR, 0.4, 95% CI, 0.3-0.6 and HR, 0.3, 95% CI, 0.2-0.5, respectively) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, those with common homozygous genotypes of E2F2-rs2742976 and E2F2-rs3218123 had better disease-free survival rates (both log-rank, P < 0.001) and lower recurrence risk (HR, 0.1, 95% CI, 0.1-0.4 and HR, 0.1, 95% CI, 0.0-0.2, respectively) than patients with variant genotypes. However, no significant differences were found for the other three polymorphisms. After combining the risk genotypes of the five polymorphisms and using the high-risk group (2-5 risk genotypes) as the reference group, we found that the low-risk groups (0 or 1 risk genotype) had significantly lower recurrence risk among all patients (HR, 0.4, 95% CI, 0.3-0.6) and among HPV16-positive patients (HR, 0.2, 95% CI, 0.1-0.5). Our findings suggest that E2F2 polymorphisms may individually or jointly modify SCCOP recurrence risk, particularly for SCCOP patients with HPV16-positive tumors. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effect of hypertension on preoperative neutrophil-lymphocyte ratio evaluation of prognosis of renal cell carcinoma.

PubMed

Sun, Jia; Ning, Hao; Sun, Jintang; Qu, Xun

2016-05-01

As an indicator of inflammatory reaction of immune system, the neutrophil-lymphocyte ratio (NLR) is a significantly independent prognostic factor of renal cell carcinoma (RCC). However, the NLR was not added in any well-established prognostic models. Many physiologic factors were also associated with NLR, such as hypertension. As such, we evaluated the effect of hypertension on NLR evaluation of prognosis of RCC. Hematological parameters and clinicopathological data during diagnosis were retrospectively recorded for 401 patients with RCC between the years 1999 and 2009. The standardized cutoff-finder algorithm was used to find the suitable NLR cutoff value for recurrence. The Log-rank test and Kaplan-Meier method were used to compare and estimate the recurrence-free survival. Univariate and multivariate Cox regression analyses were used to evaluate the association between NLR and clinicopathologic outcomes. In the analysis of total subjects, recurrence-free survival was significantly worse among patients with a preoperative NLR (>3.139 [21.9%] vs.≤3.139 [78.1%]; P<0.001). High NLR value was associated with high pathological TNM stage (P = 0.009, 0.018, 0.001, respectively). In the normotensive subgroup, recurrence-free survival was also significantly worse among patients with a preoperative NLR (>3.139 [22.6%] vs.≤3.139 [77.4%]; P<0.001). However, in the subgroup with hypertension, the difference of recurrence-free survival was not significant between patients with preoperative NLR (>3.139 [21.2%] vs.≤3.139 [78.8%]; P = 0.093). Moreover, multivariate analysis identified increased NLR as a poor prognosis index for recurrence-free survival in total group (hazard ratio [HR] = 2.27; 95% CI: 1.50-3.44; P<0.001) and normotensive subgroup (HR = 2.97; 95% CI: 1.74-5.07; P<0.001), but not in hypertensive subgroup (HR = 1.25; 95% CI: 0.59-2.65; P = 0.566). Hypertension is a disturbance factor in the evaluation of prognosis of RCC by preoperative NLR. Copyright © 2016 Elsevier Inc. All rights reserved.

High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ost, Piet, E-mail: piet.ost@ugent.be; Cozzarini, Cesare; De Meerleer, Gert

2012-07-01

Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was leftmore » at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.« less

The correlation of the lifestyle and medical conditions with the vaginal infections and production of 2-phenylethanol.

PubMed

Findri-Guštek, Stefica; Petek, Maja Jelena; Sarajlija, Hrvoje; Mršić, Gordan; Džepina, Ana Mlinarić; Oreščanin, Višnja

2012-09-01

The objective of this study was determination of causative factors of the genital infections and their correlation with various predictor variables. Secondary objectives included: (1) determination of the presence and the type of low molecular weight metabolites in the samples of vaginal secretion formed in vivo, (2) determination of the concentration of 2-phenylethanol formed in vitro for each Candida species, (3) determination of the relationship between fungal/bacterial/viral infections with the metabolites formed in vivo using multivariate analysis. One hundred and ninety-seven women in the age range from 18 to 65 years were included in the study. After the completion of questionnaire, all the patients were subjected to Pap test, cervical swabs for the presence of aerobic bacteria, yeasts, Ureaplasma urealyticum, Chlamydia trachomatis, Mycoplasma, and hrHPV DNA. The presence and the concentration of low-molecular weight metabolites in vitro and in vivo were determined by gas chromatography-mass spectrometry (GC-MS) method. Multivariate analysis methods were used for statistical evaluation. The most important risk factors of fungal/bacterial/viral infections were determined. The presence of 2-phenylethanol in vivo was confirmed in 14 of 74 tested samples and connected with the Candida species. The presence of symptoms, hrHPV DNA and Ureaplasma urealyticum are the predictor variables with the highest influence on the formation of the metabolite in vivo. The results in vitro confirmed that various Candida species produced 2-phenylethanol with the concentrations ranging from 0.6 to 4.64 μg/mL. The medical exposure to irradiation, marital status, and number of partners as well as stress factors (miscarriages, chronic, viral, or tumor illnesses) had the highest influence on the development of the bacterial/fungal/viral infections. The formation of 2-phenylethanol, both in vivo and in vitro, was confirmed and connected with Candida species. Besides, according to statistical tests, it seems that presence of symptoms, hrHPV DNA, and Ureaplasma urealyticum had also significant role on the formation of 2-phenylethanol in vivo.