Immunohistochemical and morphometric evaluation of COX-1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis* ,**

PubMed Central

Parra, Edwin Roger; Lin, Flavia; Martins, Vanessa; Rangel, Maristela Peres; Capelozzi, Vera Luiza

2013-01-01

OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. PMID:24473763

COX-2 overexpression in resected pancreatic head adenocarcinomas correlates with favourable prognosis

PubMed Central

2014-01-01

Background Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas. Methods The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n = 92), ampullary cancer (AC, n = 62) and distal bile duct cancer (DBC, n = 76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed. Results COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p = 0.043 in PC, p = 0.011 in AC, p = 0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p = 0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model. Conclusions COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis. PMID:24950702

Bayesian multivariate hierarchical transformation models for ROC analysis.

PubMed

O'Malley, A James; Zou, Kelly H

2006-02-15

A Bayesian multivariate hierarchical transformation model (BMHTM) is developed for receiver operating characteristic (ROC) curve analysis based on clustered continuous diagnostic outcome data with covariates. Two special features of this model are that it incorporates non-linear monotone transformations of the outcomes and that multiple correlated outcomes may be analysed. The mean, variance, and transformation components are all modelled parametrically, enabling a wide range of inferences. The general framework is illustrated by focusing on two problems: (1) analysis of the diagnostic accuracy of a covariate-dependent univariate test outcome requiring a Box-Cox transformation within each cluster to map the test outcomes to a common family of distributions; (2) development of an optimal composite diagnostic test using multivariate clustered outcome data. In the second problem, the composite test is estimated using discriminant function analysis and compared to the test derived from logistic regression analysis where the gold standard is a binary outcome. The proposed methodology is illustrated on prostate cancer biopsy data from a multi-centre clinical trial.

Bayesian multivariate hierarchical transformation models for ROC analysis

PubMed Central

O'Malley, A. James; Zou, Kelly H.

2006-01-01

SUMMARY A Bayesian multivariate hierarchical transformation model (BMHTM) is developed for receiver operating characteristic (ROC) curve analysis based on clustered continuous diagnostic outcome data with covariates. Two special features of this model are that it incorporates non-linear monotone transformations of the outcomes and that multiple correlated outcomes may be analysed. The mean, variance, and transformation components are all modelled parametrically, enabling a wide range of inferences. The general framework is illustrated by focusing on two problems: (1) analysis of the diagnostic accuracy of a covariate-dependent univariate test outcome requiring a Box–Cox transformation within each cluster to map the test outcomes to a common family of distributions; (2) development of an optimal composite diagnostic test using multivariate clustered outcome data. In the second problem, the composite test is estimated using discriminant function analysis and compared to the test derived from logistic regression analysis where the gold standard is a binary outcome. The proposed methodology is illustrated on prostate cancer biopsy data from a multi-centre clinical trial. PMID:16217836

The Effect of the Multivariate Box-Cox Transformation on the Power of MANOVA.

ERIC Educational Resources Information Center

Kirisci, Levent; Hsu, Tse-Chi

Most of the multivariate statistical techniques rely on the assumption of multivariate normality. The effects of non-normality on multivariate tests are assumed to be negligible when variance-covariance matrices and sample sizes are equal. Therefore, in practice, investigators do not usually attempt to remove non-normality. In this simulation…

Quality Reporting of Multivariable Regression Models in Observational Studies: Review of a Representative Sample of Articles Published in Biomedical Journals.

PubMed

Real, Jordi; Forné, Carles; Roso-Llorach, Albert; Martínez-Sánchez, Jose M

2016-05-01

Controlling for confounders is a crucial step in analytical observational studies, and multivariable models are widely used as statistical adjustment techniques. However, the validation of the assumptions of the multivariable regression models (MRMs) should be made clear in scientific reporting. The objective of this study is to review the quality of statistical reporting of the most commonly used MRMs (logistic, linear, and Cox regression) that were applied in analytical observational studies published between 2003 and 2014 by journals indexed in MEDLINE.Review of a representative sample of articles indexed in MEDLINE (n = 428) with observational design and use of MRMs (logistic, linear, and Cox regression). We assessed the quality of reporting about: model assumptions and goodness-of-fit, interactions, sensitivity analysis, crude and adjusted effect estimate, and specification of more than 1 adjusted model.The tests of underlying assumptions or goodness-of-fit of the MRMs used were described in 26.2% (95% CI: 22.0-30.3) of the articles and 18.5% (95% CI: 14.8-22.1) reported the interaction analysis. Reporting of all items assessed was higher in articles published in journals with a higher impact factor.A low percentage of articles indexed in MEDLINE that used multivariable techniques provided information demonstrating rigorous application of the model selected as an adjustment method. Given the importance of these methods to the final results and conclusions of observational studies, greater rigor is required in reporting the use of MRMs in the scientific literature.

Application and validation of Cox regression models in a single-center series of double kidney transplantation.

PubMed

Santori, G; Fontana, I; Bertocchi, M; Gasloli, G; Magoni Rossi, A; Tagliamacco, A; Barocci, S; Nocera, A; Valente, U

2010-05-01

A useful approach to reduce the number of discarded marginal kidneys and to increase the nephron mass is double kidney transplantation (DKT). In this study, we retrospectively evaluated the potential predictors for patient and graft survival in a single-center series of 59 DKT procedures performed between April 21, 1999, and September 21, 2008. The kidney recipients of mean age 63.27 +/- 5.17 years included 16 women (27%) and 43 men (73%). The donors of mean age 69.54 +/- 7.48 years included 32 women (54%) and 27 men (46%). The mean posttransplant dialysis time was 2.37 +/- 3.61 days. The mean hospitalization was 20.12 +/- 13.65 days. Average serum creatinine (SCr) at discharge was 1.5 +/- 0.59 mg/dL. In view of the limited numbers of recipient deaths (n = 4) and graft losses (n = 8) that occurred in our series, the proportional hazards assumption for each Cox regression model with P < .05 was tested by using correlation coefficients between transformed survival times and scaled Schoenfeld residuals, and checked with smoothed plots of Schoenfeld residuals. For patient survival, the variables that reached statistical significance were donor SCr (P = .007), donor creatinine cleararance (P = .023), and recipient age (P = .047). Each significant model passed the Schoenfeld test. By entering these variables into a multivariate Cox model for patient survival, no further significance was observed. In the univariate Cox models performed for graft survival, statistical significance was noted for donor SCr (P = .027), SCr 3 months post-DKT (P = .043), and SCr 6 months post-DKT (P = .017). All significant univariate models for graft survival passed the Schoenfeld test. A final multivariate model retained SCr at 6 months (beta = 1.746, P = .042) and donor SCr (beta = .767, P = .090). In our analysis, SCr at 6 months seemed to emerge from both univariate and multivariate Cox models as a potential predictor of graft survival among DKT. Multicenter studies with larger recipient populations and more graft losses should be performed to confirm our findings. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Small artery elasticity predicts future cardiovascular events in chinese patients with angiographic coronary artery disease.

PubMed

Wan, Zhaofei; Liu, Xiaojun; Wang, Xinhong; Liu, Fuqiang; Liu, Weimin; Wu, Yue; Pei, Leilei; Yuan, Zuyi

2014-04-01

Arterial elasticity has been shown to predict cardiovascular disease (CVD) in apparently healthy populations. The present study aimed to explore whether arterial elasticity could predict CVD events in Chinese patients with angiographic coronary artery disease (CAD). Arterial elasticity of 365 patients with angiographic CAD was measured. During follow-up (48 months; range 6-65), 140 CVD events occurred (including 34 deaths). Univariate Cox analysis demonstrated that both large arterial elasticity and small arterial elasticity were significant predictors of CVD events. Multivariate Cox analysis indicated that small arterial elasticity remained significant. Kaplan-Meier analysis showed that the probability of having a CVD event/CVD death increased with a decrease of small arterial elasticity (P < .001, respectively). Decreased small arterial elasticity independently predicts the risk of CVD events in Chinese patients with angiographic CAD.

Actinic cheilitis: epithelial expression of COX-2 and its association with mast cell tryptase and PAR-2.

PubMed

Rojas, I Gina; Martínez, Alejandra; Brethauer, Ursula; Grez, Patricia; Yefi, Roger; Luza, Sandra; Marchesani, Francisco J

2009-03-01

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies, including oral cancers. Recent studies have shown that mast cell-derived protease tryptase can induce COX-2 expression by the cleavage of proteinase-activated receptor-2 (PAR-2). Actinic cheilitis (AC) is a premalignant form of lip cancer characterized by an increased density of tryptase-positive mast cells. To investigate the possible contribution of tryptase to COX-2 overexpression during early lip carcinogenesis, normal lip (n=24) and AC (n=45) biopsies were processed for COX-2, PAR-2 and tryptase detection, using RT-PCR and immunohistochemistry. Expression scores were obtained for each marker and tested for statistical significance using Mann-Whitney and Spearmann's correlation tests as well as multivariate logistic regression analysis. Increased epithelial co-expression of COX-2 and PAR-2, as well as, elevated subepithelial density of tryptase-positive mast cells were found in AC as compared to normal lip (P<0.001). COX-2 overexpression was found to be a significant predictor of AC (P<0.034, forward stepwise, Wald), and to be correlated with both tryptase-positive mast cells and PAR-2 expression (P<0.01). The results suggest that epithelial COX-2 overexpression is a key event in AC, which is associated with increased tryptase-positive mast cells and PAR-2. Therefore, tryptase may contribute to COX-2 up-regulation by epithelial PAR-2 activation during early lip carcinogenesis.

A multivariate analysis of prognostic factors for melanoma patients with lesions greater than or equal to 3.65 mm in thickness. The importance of revealing alternative Cox models.

PubMed Central

Day, C L; Lew, R A; Mihm, M C; Sober, A J; Harris, M N; Kopf, A W; Fitzpatrick, T B; Harrist, T J; Golomb, F M; Postel, A; Hennessey, P; Gumport, S L; Raker, J W; Malt, R A; Cosimi, A B; Wood, W C; Roses, D F; Gorstein, F; Rigel, D; Friedman, R J; Mintzis, M M; Grier, R W

1982-01-01

Fourteen prognostic factors were examined in 79 patients with clinical Stage I melanoma greater than or equal to 3.65 mm in thickness. All nine patients with melanoma of the hands or feet died of melanoma. A Cox proportional hazards (multivariate) analysis of the remaining 70 patients showed that a combination of the following four variables best predicted bony or visceral metastases: 1) a nearly absent or minimal lymphocyte response at the base of the tumor, 2) histologic type other than superficial spreading melanoma, 3) location on the trunk, and 4) positive nodes or no initial node dissection. Ulceration and/or ulceration width were not useful in predicting outcome either singly or in combination with other variables. Patients with negative lymph nodes and primary tumors of the trunk, hands, and feet did not do better than patients with positive nodes at those sites. Conversely, non of 16 patients with negative lymph nodes and extremity melanomas (excluding the hands and feet) or head and neck melanomas developed visceral or bony metastases (i.e., five-year disease-free survival rate 100%). PMID:7055383

Impact of Blood Type, Functional Polymorphism (T-1676C) of the COX-1 Gene Promoter and Clinical Factors on the Development of Peptic Ulcer during Cardiovascular Prophylaxis with Low-Dose Aspirin

PubMed Central

Wang, Pin-Yao; Chen, Hsiu-Ping; Chen, Angela; Tsay, Feng-Woei; Kao, Sung-Shuo; Peng, Nan-Jing; Tseng, Hui-Hwa; Hsu, Ping-I

2014-01-01

Aims. To investigate the impact of blood type, functional polymorphism (T-1676C) of the COX-1 gene promoter, and clinical factors on the development of peptic ulcer during cardiovascular prophylaxis with low-dose aspirin. Methods. In a case-control study including 111 low-dose aspirin users with peptic ulcers and 109 controls (asymptomatic aspirin users), the polymorphism (T-1676C) of the COX-1 gene promoter was genotyped, and blood type, H pylori status, and clinical factors were assessed. Results. Univariate analysis showed no significant differences in genotype frequencies of the COX-1 gene at position -1676 between the peptic ulcer group and control group. Multivariate analysis revealed that blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID were the independent risk factors for the development of peptic ulcer with the odds ratios of the 2.1, 3.1, 27.6, and 2.9, respectively. Conclusion. The C-1676T polymorphism in the COX-1 gene promoter is not a risk factor for ulcer formation during treatment with low-dose aspirin. Blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID are of independent significance in predicting peptic ulcer development during treatment with low-dose aspirin. PMID:25243161

[Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

PubMed

Yang, D H; Su, Z Q; Chen, Y; Chen, Z B; Ding, Z N; Weng, Y Y; Li, J; Li, X; Tong, Q L; Han, Y X; Zhang, X

2016-03-08

To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR <1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR>1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P<0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P<0.001) and MGFA clinical classification (P<0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P<0.001) and MGFA clinical classification were related to myasthenia crisis. The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

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.

Prognostic factors in multiple myeloma: selection using Cox's proportional hazard model.

PubMed

Pasqualetti, P; Collacciani, A; Maccarone, C; Casale, R

1996-01-01

The pretreatment characteristics of 210 patients with multiple myeloma, observed between 1980 and 1994, were evaluated as potential prognostic factors for survival. Multivariate analysis according to Cox's proportional hazard model identified in the 160 dead patients with myeloma, among 26 different single prognostic variables, the following factors in order of importance: beta 2-microglobulin; bone marrow plasma cell percentage, hemoglobinemia, degree of lytic bone lesions, serum creatinine, and serum albumin. By analysis of these variables a prognostic index (PI), that considers the regression coefficients derived by Cox's model of all significant factors, was obtained. Using this it was possible to separate the whole patient group into three stages: stage I (PI < 1.485, 67 patients), stage II (PI: 1.485-2.090, 76 patients), and stage III (PI > 2.090, 67 patients), with a median survivals of 68, 36 and 13 months (P < 0.0001), respectively. Also the responses to therapy (P < 0.0001) and the survival curves (P < 0.00001) presented significant differences among the three subgroups. Knowledge of these factors could be of value in predicting prognosis and in planning therapy in patients with multiple myeloma.

Prognostic Value of Pretherapeutic Tumor-to-Blood Standardized Uptake Ratio in Patients with Esophageal Carcinoma.

PubMed

Bütof, Rebecca; Hofheinz, Frank; Zöphel, Klaus; Stadelmann, Tobias; Schmollack, Julia; Jentsch, Christina; Löck, Steffen; Kotzerke, Jörg; Baumann, Michael; van den Hoff, Jörg

2015-08-01

Despite ongoing efforts to develop new treatment options, the prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. The aim of this work was to investigate whether PET can provide independent prognostic information in such a patient group and whether the tumor-to-blood standardized uptake ratio (SUR) can improve the prognostic value of tracer uptake values. (18)F-FDG PET/CT was performed in 130 consecutive patients (mean age ± SD, 63 ± 11 y; 113 men, 17 women) with newly diagnosed esophageal cancer before definitive radiochemotherapy. In the PET images, the metabolically active tumor volume (MTV) of the primary tumor was delineated with an adaptive threshold method. The blood standardized uptake value (SUV) was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as the ratio of tumor SUV and blood SUV. Uptake values were scan-time-corrected to 60 min after injection. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant metastases-free survival (DM), and locoregional tumor control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. In multivariate Cox regression with respect to OS, including T stage, N stage, and smoking state, MTV- and SUR-based parameters were significant prognostic factors for OS with similar effect size. Multivariate analysis with respect to DM revealed smoking state, MTV, and all SUR-based parameters as significant prognostic factors. The highest hazard ratios (HRs) were found for scan-time-corrected maximum SUR (HR = 3.9) and mean SUR (HR = 4.4). None of the PET parameters was associated with LRC. Univariate Cox regression with respect to LRC revealed a significant effect only for N stage greater than 0 (P = 0.048). PET provides independent prognostic information for OS and DM but not for LRC in patients with locally advanced esophageal carcinoma treated with definitive radiochemotherapy in addition to clinical parameters. Among the investigated uptake-based parameters, only SUR was an independent prognostic factor for OS and DM. These results suggest that the prognostic value of tracer uptake can be improved when characterized by SUR instead of SUV. Further investigations are required to confirm these preliminary results. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Multivariate analysis of prognostic factors in synovial sarcoma.

PubMed

Koh, Kyoung Hwan; Cho, Eun Yoon; Kim, Dong Wook; Seo, Sung Wook

2009-11-01

Many studies have described the diversity of synovial sarcoma in terms of its biological characteristics and clinical features. Moreover, much effort has been expended on the identification of prognostic factors because of unpredictable behaviors of synovial sarcomas. However, with the exception of tumor size, published results have been inconsistent. We attempted to identify independent risk factors using survival analysis. Forty-one consecutive patients with synovial sarcoma were prospectively followed from January 1997 to March 2008. Overall and progression-free survival for age, sex, tumor size, tumor location, metastasis at presentation, histologic subtype, chemotherapy, radiation therapy, and resection margin were analyzed, and standard multivariate Cox proportional hazard regression analysis was used to evaluate potential prognostic factors. Tumor size (>5 cm), nonlimb-based tumors, metastasis at presentation, and a monophasic subtype were associated with poorer overall survival. Multivariate analysis showed metastasis at presentation and monophasic tumor subtype affected overall survival. For the progression-free survival, monophasic subtype was found to be only 1 prognostic factor. The study confirmed that histologic subtype is the single most important independent prognostic factors of synovial sarcoma regardless of tumor stage.

Predictors of unsuccessful outcome in cemented femoral revisions using bone impaction grafting; Cox regression analysis of 208 cases.

PubMed

Te Stroet, Martijn A J; Rijnen, Wim H C; Gardeniers, Jean W M; Schreurs, B Willem; Hannink, Gerjon

2016-09-29

Despite improvements in the technique of femoral impaction bone grafting, reconstruction failures still can occur. Therefore, the aim of our study was to determine risk factors for the endpoint re-revision for any reason. We used prospectively collected demographic, clinical and surgical data of all 202 patients who underwent 208 femoral revisions using the X-change Femoral Revision System (Stryker-Howmedica), fresh-frozen morcellised allograft and a cemented polished Exeter stem in our department from 1991 to 2007. Univariable and multivariable Cox regression analyses were performed to identify potential factors associated with re-revision. The mean follow-up was 10.6 (5-21) years. The cumulative re-revision rate was 6.3% (13/208). After univariable selection, sex, age, body mass index (BMI), American Association of Anesthesiologists (ASA) classification, type of removed femoral component, and mesh used for reconstruction were included in multivariable regression analysis.In the multivariable analysis, BMI was the only factor that was significantly associated with the risk of re-revision after bone impaction grafting (BMI ≥30 vs. BMI <30, HR = 6.54 [95% CI 1.89-22.65]; p = 0.003). BMI was the only factor associated with the risk of re-revision for any reason. Besides BMI also other factors, such as Endoklinik score and the type of removed femoral component, can provide guidance in the process of preclinical decision making. With the knowledge obtained from this study, preoperative patient selection, informed consent, and treatment protocols can be better adjusted to the individual patient who needs to undergo a femoral revision with impaction bone grafting.

Nomogram Prediction of Overall Survival After Curative Irradiation for Uterine Cervical Cancer

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

Seo, YoungSeok; Yoo, Seong Yul; Kim, Mi-Sook

Purpose: The purpose of this study was to develop a nomogram capable of predicting the probability of 5-year survival after radical radiotherapy (RT) without chemotherapy for uterine cervical cancer. Methods and Materials: We retrospectively analyzed 549 patients that underwent radical RT for uterine cervical cancer between March 1994 and April 2002 at our institution. Multivariate analysis using Cox proportional hazards regression was performed and this Cox model was used as the basis for the devised nomogram. The model was internally validated for discrimination and calibration by bootstrap resampling. Results: By multivariate regression analysis, the model showed that age, hemoglobin levelmore » before RT, Federation Internationale de Gynecologie Obstetrique (FIGO) stage, maximal tumor diameter, lymph node status, and RT dose at Point A significantly predicted overall survival. The survival prediction model demonstrated good calibration and discrimination. The bootstrap-corrected concordance index was 0.67. The predictive ability of the nomogram proved to be superior to FIGO stage (p = 0.01). Conclusions: The devised nomogram offers a significantly better level of discrimination than the FIGO staging system. In particular, it improves predictions of survival probability and could be useful for counseling patients, choosing treatment modalities and schedules, and designing clinical trials. However, before this nomogram is used clinically, it should be externally validated.« less

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.

Application of multivariate Gaussian detection theory to known non-Gaussian probability density functions

NASA Astrophysics Data System (ADS)

Schwartz, Craig R.; Thelen, Brian J.; Kenton, Arthur C.

1995-06-01

A statistical parametric multispectral sensor performance model was developed by ERIM to support mine field detection studies, multispectral sensor design/performance trade-off studies, and target detection algorithm development. The model assumes target detection algorithms and their performance models which are based on data assumed to obey multivariate Gaussian probability distribution functions (PDFs). The applicability of these algorithms and performance models can be generalized to data having non-Gaussian PDFs through the use of transforms which convert non-Gaussian data to Gaussian (or near-Gaussian) data. An example of one such transform is the Box-Cox power law transform. In practice, such a transform can be applied to non-Gaussian data prior to the introduction of a detection algorithm that is formally based on the assumption of multivariate Gaussian data. This paper presents an extension of these techniques to the case where the joint multivariate probability density function of the non-Gaussian input data is known, and where the joint estimate of the multivariate Gaussian statistics, under the Box-Cox transform, is desired. The jointly estimated multivariate Gaussian statistics can then be used to predict the performance of a target detection algorithm which has an associated Gaussian performance model.

A FORTRAN program for multivariate survival analysis on the personal computer.

PubMed

Mulder, P G

1988-01-01

In this paper a FORTRAN program is presented for multivariate survival or life table regression analysis in a competing risks' situation. The relevant failure rate (for example, a particular disease or mortality rate) is modelled as a log-linear function of a vector of (possibly time-dependent) explanatory variables. The explanatory variables may also include the variable time itself, which is useful for parameterizing piecewise exponential time-to-failure distributions in a Gompertz-like or Weibull-like way as a more efficient alternative to Cox's proportional hazards model. Maximum likelihood estimates of the coefficients of the log-linear relationship are obtained from the iterative Newton-Raphson method. The program runs on a personal computer under DOS; running time is quite acceptable, even for large samples.

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.

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

Comparison of Weibull and Lognormal Cure Models with Cox in the Survival Analysis Of Breast Cancer Patients in Rafsanjan.

PubMed

Hoseini, Mina; Bahrampour, Abbas; Mirzaee, Moghaddameh

2017-02-16

Breast cancer is the most common cancer after lung cancer and the second cause of death. In this study we compared Weibull and Lognormal Cure Models with Cox regression on the survival of breast cancer. A cohort study. The current study retrospective cohort study was conducted on 140 patients referred to Ali Ibn Abitaleb Hospital, Rafsanjan southeastern Iran from 2001 to 2015 suffering from breast cancer. We determined and analyzed the effective survival causes by different models using STATA14. According to AIC, log-normal model was more consistent than Weibull. In the multivariable Lognormal model, the effective factors like smoking, second -hand smoking, drinking herbal tea and the last breast-feeding period were included. In addition, using Cox regression factors of significant were the disease grade, size of tumor and its metastasis (p-value<0.05). As Rafsanjan is surrounded by pistachio orchards and pesticides applied by farmers, people of this city are exposed to agricultural pesticides and its harmful consequences. The effect of the pesticide on breast cancer was studied and the results showed that the effect of pesticides on breast cancer was not in agreement with the models used in this study. Based on different methods for survival analysis, researchers can decide how they can reach a better conclusion. This comparison indicates the result of semi-parametric Cox method is closer to clinical experiences evidences.

Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure　- Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.

PubMed

Miura, Masanobu; Sugimura, Koichiro; Sakata, Yasuhiko; Miyata, Satoshi; Tadaki, Soichiro; Yamauchi, Takeshi; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Oikawa, Takuya; Kasahara, Shintaro; Nochioka, Kotaro; Takahashi, Jun; Shimokawa, Hiroaki

2016-05-25

It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (P<0001). Furthermore, on IPTW multivariate Cox modeling for multiple treatments, both low-dose (<40 mg/day) and high-dose (≥40 mg/day) loop diuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both P<0.001). Triple blockade with RAS inhibitor(s), mineral corticoid (aldosterone) receptor antagonist(s) (MRA), and β-blocker(s) was significantly associated with better prognosis in those on low-dose but not on high-dose loop diuretics. Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

Marital status and survival in patients with renal cell carcinoma.

PubMed

Li, Yan; Zhu, Ming-Xi; Qi, Si-Hua

2018-04-01

Previous studies have shown that marital status is an independent prognostic factor for survival in several types of cancer. In this study, we investigated the effects of marital status on survival outcomes among renal cell carcinoma (RCC) patients.We identified patients diagnosed with RCC between 1973 and 2013 from the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier analysis and Cox regression were used to identify the effects of marital status on overall survival (OS) and cancer-specific survival (CSS).We enrolled 97,662 eligible RCC patients, including 64,884 married patients, and 32,778 unmarried (9831 divorced/separated, 9692 widowed, and 13,255 single) patients at diagnosis. The 5-year OS and CSS rates of the married, separated/divorced, widowed, and single patients were 73.7%, 69.5%, 58.3%, and 73.2% (OS), and 82.2%, 80.7%, 75.7%, and 83.3% (CSS), respectively. Multivariate Cox regression showed that, compared with married patients, widowed individuals showed poorer OS (hazard ratio, 1.419; 95% confidence interval, 1.370-1.469) and CSS (hazard ratio, 1.210; 95% confidence interval, 1.144-1.279). Stratified analyses and multivariate Cox regression showed that, in the insured and uninsured groups, married patients had better survival outcomes while widowed patients suffered worse OS outcomes; however, this trend was not significant for CSS.In RCC patients, married patients had better survival outcomes while widowed patients tended to suffer worse survival outcomes in terms of both OS and CSS.

Marital status and survival in patients with renal cell carcinoma

PubMed Central

Li, Yan; Zhu, Ming-xi; Qi, Si-hua

2018-01-01

Abstract Previous studies have shown that marital status is an independent prognostic factor for survival in several types of cancer. In this study, we investigated the effects of marital status on survival outcomes among renal cell carcinoma (RCC) patients. We identified patients diagnosed with RCC between 1973 and 2013 from the Surveillance, Epidemiology and End Results (SEER) database. Kaplan–Meier analysis and Cox regression were used to identify the effects of marital status on overall survival (OS) and cancer-specific survival (CSS). We enrolled 97,662 eligible RCC patients, including 64,884 married patients, and 32,778 unmarried (9831 divorced/separated, 9692 widowed, and 13,255 single) patients at diagnosis. The 5-year OS and CSS rates of the married, separated/divorced, widowed, and single patients were 73.7%, 69.5%, 58.3%, and 73.2% (OS), and 82.2%, 80.7%, 75.7%, and 83.3% (CSS), respectively. Multivariate Cox regression showed that, compared with married patients, widowed individuals showed poorer OS (hazard ratio, 1.419; 95% confidence interval, 1.370–1.469) and CSS (hazard ratio, 1.210; 95% confidence interval, 1.144–1.279). Stratified analyses and multivariate Cox regression showed that, in the insured and uninsured groups, married patients had better survival outcomes while widowed patients suffered worse OS outcomes; however, this trend was not significant for CSS. In RCC patients, married patients had better survival outcomes while widowed patients tended to suffer worse survival outcomes in terms of both OS and CSS. PMID:29668592

Reporting and methodological quality of survival analysis in articles published in Chinese oncology journals

PubMed Central

Zhu, Xiaoyan; Zhou, Xiaobin; Zhang, Yuan; Sun, Xiao; Liu, Haihua; Zhang, Yingying

2017-01-01

Abstract Survival analysis methods have gained widespread use in the filed of oncology. For achievement of reliable results, the methodological process and report quality is crucial. This review provides the first examination of methodological characteristics and reporting quality of survival analysis in articles published in leading Chinese oncology journals. To examine methodological and reporting quality of survival analysis, to identify some common deficiencies, to desirable precautions in the analysis, and relate advice for authors, readers, and editors. A total of 242 survival analysis articles were included to be evaluated from 1492 articles published in 4 leading Chinese oncology journals in 2013. Articles were evaluated according to 16 established items for proper use and reporting of survival analysis. The application rates of Kaplan–Meier, life table, log-rank test, Breslow test, and Cox proportional hazards model (Cox model) were 91.74%, 3.72%, 78.51%, 0.41%, and 46.28%, respectively, no article used the parametric method for survival analysis. Multivariate Cox model was conducted in 112 articles (46.28%). Follow-up rates were mentioned in 155 articles (64.05%), of which 4 articles were under 80% and the lowest was 75.25%, 55 articles were100%. The report rates of all types of survival endpoint were lower than 10%. Eleven of 100 articles which reported a loss to follow-up had stated how to treat it in the analysis. One hundred thirty articles (53.72%) did not perform multivariate analysis. One hundred thirty-nine articles (57.44%) did not define the survival time. Violations and omissions of methodological guidelines included no mention of pertinent checks for proportional hazard assumption; no report of testing for interactions and collinearity between independent variables; no report of calculation method of sample size. Thirty-six articles (32.74%) reported the methods of independent variable selection. The above defects could make potentially inaccurate, misleading of the reported results, or difficult to interpret. There are gaps in the conduct and reporting of survival analysis in studies published in Chinese oncology journals, severe deficiencies were noted. More endorsement by journals of the report guideline for survival analysis may improve articles quality, and the dissemination of reliable evidence to oncology clinicians. We recommend authors, readers, reviewers, and editors to consider survival analysis more carefully and cooperate more closely with statisticians and epidemiologists. PMID:29390340

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.

Differential cyclooxygenase-2 expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

PubMed

Kim, Yong Bae; Kim, Gwi Eon; Pyo, Hong Ryull; Cho, Nam Hoon; Keum, Ki Chang; Lee, Chang Geol; Seong, Jinsil; Suh, Chang Ok; Park, Tchan Kyu

2004-11-01

To determine the differential expression of cyclooxygenase-2 (COX-2) in patients with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the uterine cervix and the prognostic significance of COX-2 expression in these histologic types. A total of 105 International Federation of Gynecology and Obstetrics Stage IIB uterine cervical cancer patients were screened for COX-2 expression immunohistochemically. COX-2 expression was determined in invasive cervical SCC (n = 84) and invasive cervical ADC (n = 21). To determine the clinical significance of COX-2 expression by histologic type, the patients were arbitrarily divided into four groups: SCC/COX-2 negative (n = 64); SCC/COX-2 positive (n = 20); ADC/COX-2 negative (n = 9); and ADC/COX-2 positive (n = 12). The clinical response to treatment, patterns of treatment failure, and survival data by COX-2 expression were compared for these two major histologic types. Univariate and multivariate analyses were performed to identify the prognostic factors influencing survival. Immunohistochemical examination showed that COX-2 expression was more frequently observed in ADC than in SCC (57% vs. 24%, p = 0.007). Moreover, COX-2 expression was an important predictor of treatment response, irrespective of the histologic type. All COX-2-negative patients achieved complete remission after initial treatment; 17% of SCC patients and 33% of ADC patients with COX-2 expression did not have complete remission after the initial treatment. The incidence of local failure for those with COX-2 expression was significantly greater than for COX-2-negative patients, regardless of histologic type. With a minimal follow-up of 60 months, the overall 5-year actuarial survival rate for SCC and ADC patients was 79% and 62%, respectively (p = 0.05). The 5-year disease-free survival rate for SCC and ADC patients was 73% and 56%, respectively (p = 0.13). Irrespective of the pathologic type, COX-2-positive patients had an unfavorable prognosis. The overall 5-year actuarial survival rate was 57% for COX-2-positive patients and 83% for COX-2-negative patients (p = 0.001). When patients were stratified into the four groups according to histologic type and COX-2 expression status, ADC/COX-2-positive patients had the worst prognosis, with an overall 5-year actuarial survival rate of 49% compared with 78% for ADC/COX-2-negative patients, 62% for SCC/COX-2-positive, and 84% for SCC/COX-2-negative patients (p = 0.007, log-rank test). Irrespective of histologic type, COX-2 expression was an independent prognostic factor by univariate and multivariate analyses. In uterine cervical cancer, COX-2 was expressed in a greater proportion of ADC patients than SCC patients. COX-2 expression was also identified as a major determiner of a poor response to treatment and of an unfavorable prognosis, irrespective of the histologic type, reflecting the importance of the COX-2 protein in the acquisition of biologic aggressiveness and more malignant phenotype or increased resistance to the standard chemotherapy and radiotherapy in both histologic types. Given these observations, we believe that that ADC/COX-2-positive patients might be appropriate candidates for future trials of selective COX-2 inhibitor adjunctive therapy.

Multivariate analysis of risk factors for long-term urethroplasty outcome.

PubMed

Breyer, Benjamin N; McAninch, Jack W; Whitson, Jared M; Eisenberg, Michael L; Mehdizadeh, Jennifer F; Myers, Jeremy B; Voelzke, Bryan B

2010-02-01

We studied the patient risk factors that promote urethroplasty failure. Records of patients who underwent urethroplasty at the University of California, San Francisco Medical Center between 1995 and 2004 were reviewed. Cox proportional hazards regression analysis was used to identify multivariate predictors of urethroplasty outcome. Between 1995 and 2004, 443 patients of 495 who underwent urethroplasty had complete comorbidity data and were included in analysis. Median patient age was 41 years (range 18 to 90). Median followup was 5.8 years (range 1 month to 10 years). Stricture recurred in 93 patients (21%). Primary estimated stricture-free survival at 1, 3 and 5 years was 88%, 82% and 79%. After multivariate analysis smoking (HR 1.8, 95% CI 1.0-3.1, p = 0.05), prior direct vision internal urethrotomy (HR 1.7, 95% CI 1.0-3.0, p = 0.04) and prior urethroplasty (HR 1.8, 95% CI 1.1-3.1, p = 0.03) were predictive of treatment failure. On multivariate analysis diabetes mellitus showed a trend toward prediction of urethroplasty failure (HR 2.0, 95% CI 0.8-4.9, p = 0.14). Length of urethral stricture (greater than 4 cm), prior urethroplasty and failed endoscopic therapy are predictive of failure after urethroplasty. Smoking and diabetes mellitus also may predict failure potentially secondary to microvascular damage. Copyright 2010 American Urological Association. Published by Elsevier Inc. All rights reserved.

Tunnelled haemodialysis catheter and haemodialysis outcomes: a retrospective cohort study in Zagreb, Croatia.

PubMed

Pašara, Vedran; Maksimović, Bojana; Gunjača, Mihaela; Mihovilović, Karlo; Lončar, Andrea; Kudumija, Boris; Žabić, Igor; Knotek, Mladen

2016-05-17

Studies have reported that the tunnelled dialysis catheter (TDC) is associated with inferior haemodialysis (HD) patient survival, in comparison with arteriovenous fistula (AVF). Since many cofactors may also affect survival of HD patients, it is unclear whether the greater risk for survival arises from TDC per se, or from associated conditions. Therefore, the aim of this study was to determine, in a multivariate analysis, the long-term outcome of HD patients, with respect to vascular access (VA). Retrospective cohort study. This retrospective cohort study included all 156 patients with a TDC admitted at University Hospital Merkur, from 2010 to 2012. The control group consisted of 97 patients dialysed via AVF. The groups were matched according to dialysis unit and time of VA placement. The site of choice for the placement of the TDC was the right jugular vein. Kaplan-Meier analysis with log-rank test was used to assess patient survival. Multivariate Cox regression analysis was used to determine independent variables associated with patient survival. Patient survival with respect to VA. The cumulative 1-year survival of patients who were dialysed exclusively via TDC was 86.4% and of those who were dialysed exclusively via AVF, survival was 97.1% (p=0.002). In multivariate Cox regression analysis, male sex and older age were independently negatively associated with the survival of HD patients, while shorter HD vintage before the creation of the observed VA, hypertensive renal disease and glomerulonephritis were positively associated with survival. TDC was an independent risk factor for survival of HD patients (HR 23.0, 95% CI 6.2 to 85.3). TDC may be an independent negative risk factor for HD patient survival. 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/

Identifying prognostic intratumor heterogeneity using pre- and post-radiotherapy 18F-FDG PET images for pancreatic cancer patients.

PubMed

Yue, Yong; Osipov, Arsen; Fraass, Benedick; Sandler, Howard; Zhang, Xiao; Nissen, Nicholas; Hendifar, Andrew; Tuli, Richard

2017-02-01

To stratify risks of pancreatic adenocarcinoma (PA) patients using pre- and post-radiotherapy (RT) PET/CT images, and to assess the prognostic value of texture variations in predicting therapy response of patients. Twenty-six PA patients treated with RT from 2011-2013 with pre- and post-treatment 18F-FDG-PET/CT scans were identified. Tumor locoregional texture was calculated using 3D kernel-based approach, and texture variations were identified by fitting discrepancies of texture maps of pre- and post-treatment images. A total of 48 texture and clinical variables were identified and evaluated for association with overall survival (OS). The prognostic heterogeneity features were selected using lasso/elastic net regression, and further were evaluated by multivariate Cox analysis. Median age was 69 y (range, 46-86 y). The texture map and temporal variations between pre- and post-treatment were well characterized by histograms and statistical fitting. The lasso analysis identified seven predictors (age, node stage, post-RT SUVmax, variations of homogeneity, variance, sum mean, and cluster tendency). The multivariate Cox analysis identified five significant variables: age, node stage, variations of homogeneity, variance, and cluster tendency (with P=0.020, 0.040, 0.065, 0.078, and 0.081, respectively). The patients were stratified into two groups based on the risk score of multivariate analysis with log-rank P=0.001: a low risk group (n=11) with a longer mean OS (29.3 months) and higher texture variation (>30%), and a high risk group (n=15) with a shorter mean OS (17.7 months) and lower texture variation (<15%). Locoregional metabolic texture response provides a feasible approach for evaluating and predicting clinical outcomes following treatment of PA with RT. The proposed method can be used to stratify patient risk and help select appropriate treatment strategies for individual patients toward implementing response-driven adaptive RT.

A multivariate analysis of clinical and morphological prognostic factors in squamous cell carcinoma of the vulva.

PubMed

Smyczek-Gargya, B; Volz, B; Geppert, M; Dietl, J

1997-01-01

Clinical and histological data of 168 patients with squamous cell carcinoma of the vulva were analyzed with respect to survival. 151 patients underwent surgery, 12 patients were treated with primary radiation and in 5 patients no treatment was performed. Follow-up lasted from at least 2 up to 22 years' posttreatment. In univariate analysis, the following factors were highly significant: presurgery lymph node status, tumor infiltration beyond the vulva, tumor grading, histological inguinal lymph node status, pre- and postsurgery tumor stage, depth of invasion and tumor diameter. In the multivariate analysis (Cox regression), the most powerful factors were shown to be histological inguinal lymph node status, tumor diameter and tumor grading. The multivariate logistic regression analysis worked out as main prognostic factors for metastases of inguinal lymph nodes: presurgery inguinal lymph node status, tumor size, depth of invasion and tumor grading. Based on these results, tumor biology seems to be the decisive factor concerning recurrence and survival. Therefore, we suggest a more conservative treatment of vulvar carcinoma. Patients with confined carcinoma to the vulva, with a tumor diameter up to 3 cm and without clinical suspected lymph nodes, should be treated by wide excision/partial vulvectomy with ipsilateral lymphadenectomy.

A simple prognostic model for overall survival in metastatic renal cell carcinoma.

PubMed

Assi, Hazem I; Patenaude, Francois; Toumishey, Ethan; Ross, Laura; Abdelsalam, Mahmoud; Reiman, Tony

2016-01-01

The primary purpose of this study was to develop a simpler prognostic model to predict overall survival for patients treated for metastatic renal cell carcinoma (mRCC) by examining variables shown in the literature to be associated with survival. We conducted a retrospective analysis of patients treated for mRCC at two Canadian centres. All patients who started first-line treatment were included in the analysis. A multivariate Cox proportional hazards regression model was constructed using a stepwise procedure. Patients were assigned to risk groups depending on how many of the three risk factors from the final multivariate model they had. There were three risk factors in the final multivariate model: hemoglobin, prior nephrectomy, and time from diagnosis to treatment. Patients in the high-risk group (two or three risk factors) had a median survival of 5.9 months, while those in the intermediate-risk group (one risk factor) had a median survival of 16.2 months, and those in the low-risk group (no risk factors) had a median survival of 50.6 months. In multivariate analysis, shorter survival times were associated with hemoglobin below the lower limit of normal, absence of prior nephrectomy, and initiation of treatment within one year of diagnosis.

A simple prognostic model for overall survival in metastatic renal cell carcinoma

PubMed Central

Assi, Hazem I.; Patenaude, Francois; Toumishey, Ethan; Ross, Laura; Abdelsalam, Mahmoud; Reiman, Tony

2016-01-01

Introduction: The primary purpose of this study was to develop a simpler prognostic model to predict overall survival for patients treated for metastatic renal cell carcinoma (mRCC) by examining variables shown in the literature to be associated with survival. Methods: We conducted a retrospective analysis of patients treated for mRCC at two Canadian centres. All patients who started first-line treatment were included in the analysis. A multivariate Cox proportional hazards regression model was constructed using a stepwise procedure. Patients were assigned to risk groups depending on how many of the three risk factors from the final multivariate model they had. Results: There were three risk factors in the final multivariate model: hemoglobin, prior nephrectomy, and time from diagnosis to treatment. Patients in the high-risk group (two or three risk factors) had a median survival of 5.9 months, while those in the intermediate-risk group (one risk factor) had a median survival of 16.2 months, and those in the low-risk group (no risk factors) had a median survival of 50.6 months. Conclusions: In multivariate analysis, shorter survival times were associated with hemoglobin below the lower limit of normal, absence of prior nephrectomy, and initiation of treatment within one year of diagnosis. PMID:27217858

Misspecification of Cox regression models with composite endpoints

PubMed Central

Wu, Longyang; Cook, Richard J

2012-01-01

Researchers routinely adopt composite endpoints in multicenter randomized trials designed to evaluate the effect of experimental interventions in cardiovascular disease, diabetes, and cancer. Despite their widespread use, relatively little attention has been paid to the statistical properties of estimators of treatment effect based on composite endpoints. We consider this here in the context of multivariate models for time to event data in which copula functions link marginal distributions with a proportional hazards structure. We then examine the asymptotic and empirical properties of the estimator of treatment effect arising from a Cox regression model for the time to the first event. We point out that even when the treatment effect is the same for the component events, the limiting value of the estimator based on the composite endpoint is usually inconsistent for this common value. We find that in this context the limiting value is determined by the degree of association between the events, the stochastic ordering of events, and the censoring distribution. Within the framework adopted, marginal methods for the analysis of multivariate failure time data yield consistent estimators of treatment effect and are therefore preferred. We illustrate the methods by application to a recent asthma study. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22736519

[Negative prognostic impact of female gender on oncological outcomes following radical cystectomy].

PubMed

Dabi, Y; Rouscoff, Y; Delongchamps, N B; Sibony, M; Saighi, D; Zerbib, M; Peyraumore, M; Xylinas, E

2016-02-01

To confirm gender specific differences in pathologic factors and survival rates of urothelial bladder cancer patients treated with radical cystectomy. We conducted a retrospective monocentric study on 701 patients treated with radical cystectomy and pelvic lymphadenectomy for muscle invasive bladder cancer. Impact of gender on recurrence rate, specific and non-specific mortality rate were evaluated using Cox regression models in univariate and multivariate analysis. We collected data on 553 males (78.9%) and 148 females (21.1%) between 1998 and 2011. Both groups were comparable at inclusion regarding age, pathologic stage, nodal status and lymphovascular invasion. Mean follow-up time was 45 months (interquartile 23-73) and by that time, 163 patients (23.3%) had recurrence of their tumor and 127 (18.1%) died from their disease. In multivariable Cox regression analyses, female gender was independently associated with disease recurrence (RR: 1.73; 95% CI 1.22-2.47; P=0.02) and cancer-specific mortality (RR=2.50, 95% CI=1.71-3.68; P<0.001). We confirmed female gender to be an independent negative prognosis factor for patients following a radical cystectomy and lymphadenectomy for an invasive muscle bladder cancer. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract

PubMed Central

Seneca, Sara; De Rademaeker, Marjan; Sermon, Karen; De Rycke, Martine; De Vos, Michel; Haentjens, Patrick; Devroey, Paul; Liebaers, Ingeborg

2010-01-01

Purpose This study aims to analyze the relationship between trinucleotide repeat length and reproductive outcome in a large cohort of DM1 patients undergoing ICSI and PGD. Methods Prospective cohort study. The effect of trinucleotide repeat length on reproductive outcome per patient was analyzed using bivariate analysis (T-test) and multivariate analysis using Kaplan-Meier and Cox regression analysis. Results Between 1995 and 2005, 205 cycles of ICSI and PGD were carried out for DM1 in 78 couples. The number of trinucleotide repeats does not have an influence on reproductive outcome when adjusted for age, BMI, basal FSH values, parity, infertility status and male or female affected. Cox regression analysis indicates that cumulative live birth rate is not influenced by the number of trinucleotide repeats. The only factor with a significant effect is age (p < 0.05). Conclusion There is no evidence of an effect of trinucleotide repeat length on reproductive outcome in patients undergoing ICSI and PGD. PMID:20221684

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

Impact of Pacemaker Lead Characteristics on Pacemaker Related Infection and Heart Perforation: A Nationwide Population-Based Cohort Study.

PubMed

Lin, Yu-Sheng; Chen, Tien-Hsing; Hung, Sheng-Ping; Chen, Dong Yi; Mao, Chun-Tai; Tsai, Ming-Lung; Chang, Shih-Tai; Wang, Chun-Chieh; Wen, Ming-Shien; Chen, Mien-Cheng

2015-01-01

Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications. Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07-0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08-0.83; P = 0.023). There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.

Expression of miR-146a-5p in patients with intracranial aneurysms and its association with prognosis.

PubMed

Zhang, H-L; Li, L; Cheng, C-J; Sun, X-C

2018-02-01

The study aims to detect the association of miR-146a-5p with intracranial aneurysms (IAs). The expression of miR-146a-5p was compared from plasma samples between 72 patients with intracranial aneurysms (IAs) and 40 healthy volunteers by quantitative Real-time polymerase chain reaction (qRT-PCR). Statistical analysis was performed to analyze the relationship between miR-146a-5p expression and clinical data and overall survival (OS) time of IAs patients. Univariate and multivariate Cox proportional hazards have also been performed. Notably, higher miR-146a-5p expression was found in plasma samples from 72 patients with intracranial aneurysms (IAs) compared with 40 healthy controls. Higher miR-146a-5p expression was significantly associated with rupture and Hunt-Hess level in IAs patients. Kaplan-Meier survival analysis verified that higher miR-146a-5p expression predicted a shorter overall survival (OS) compared with lower miR-146a-5p expression in IAs patients. Univariate and multivariate Cox proportional hazards demonstrated that higher miR-146a-5p expression, rupture, and Hunt-Hess were independent risk factors of OS in patients with intracranial aneurysms (IAs). MiR-146a-5p expression may serve as a biomarker for predicting prognosis in patients with IAs.

Type 2 diabetes is an independent negative prognostic factor in patients undergoing surgical resection of a WHO grade I meningioma.

PubMed

Nayeri, Arash; Chotai, Silky; Prablek, Marc A; Brinson, Philip R; Douleh, Diana G; Weaver, Kyle D; Thompson, Reid C; Chambless, Lola

2016-10-01

In recent years, there has been increased recognition of the relationship between type 2 diabetes mellitus (DM) and poor outcomes following a variety of surgical procedures. We sought to study the role of type 2 DM as a prognostic factor affecting the long-term survival of patients undergoing surgical resection of a WHO Grade I meningioma. We conducted a retrospective cohort study on 196 patients who had a WHO Grade I meningioma resected at our institution between 2001 and 2013. The medical record was reviewed to identify a pre-existing diagnosis of type 2 DM. Patient mortality was reviewed by medical record and Social Security Death Index (SSDI). Variables associated with survival in a univariate analysis were included in the multivariate Cox model if P<0.10. Variables with probability values >0.05 were then removed from the multivariate model in a step-wise fashion. 33 (17%) patients had pre-existing diagnoses of type 2 DM prior to clinical presentation. Mean survival time in diabetic patients was 52.1 months compared to 160.9 months in non-diabetics. The decreased survival rate and time in patients with type 2 DM were found to be statistically significant (p=0.008 and p<0.0001, respectively). In a multivariate Cox analysis, a pre-existing history of type 2 DM was independently associated with decreased survival following the resection of a WHO Grade I meningioma (HR=2.6, p=0.045). A pre-existing diagnosis of type 2 DM is an independent negative prognostic indicator following the resection of a WHO Grade I meningioma. Copyright © 2016 Elsevier B.V. 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.

Lack of Thy1 (CD90) expression in neuroblastomas is correlated with impaired survival.

PubMed

Fiegel, Henning C; Kaifi, Jussuf T; Quaas, Alexander; Varol, Emine; Krickhahn, Annika; Metzger, Roman; Sauter, Guido; Till, Holger; Izbicki, Jakob R; Erttmann, Rudolf; Kluth, Dietrich

2008-01-01

Neuroblastoma (NBL) is the most common solid tumor in children. Tumors in advanced stage or with positive risk factors still have a poor prognosis. Thy1 (CD90) is a membrane glycoprotein expressed in thymus, retinal ganglionic cells, and several types of stem cells. The aim of this study was to assess Thy1 expression in NBL and analyze the correlation with clinical outcome. Sixty-three specimens of NBL were stained for Thy1 on a tissue microarray by immunohistochemistry. Fresh frozen tumor tissues were used for RNA isolation, and RT-PCR analysis for Thy1-mRNA expression was performed. Patients' survival data were correlated with Thy1 status using a log rank test and a Cox regression multivariate analysis. Thy1 was expressed on 51 (81%) of the tumors. Kaplan-Meier survival analysis showed a significantly impaired survival in patients with NBL missing Thy1 (P < 0.005 by log-rank test). A multivariate Cox regression showed an independent prognostic value of Thy1 status for overall survival (P < 0.05). In addition, the frequency of events and deaths was significantly higher in the group of patients with Thy1 negative tumors, as assessed by ANOVA analysis (P < 0.05 by F-test). The data showed that Thy1-negative NBL patients have a significantly impaired overall survival compared with Thy1-positive NBL patients. Thus, Thy1 seemed to be a marker with a specific prognostic value in NBL patients. Future studies are aiming at the biological role of this marker in the tumor cell differentiation.

Preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs and 30-day stroke mortality.

PubMed

Schmidt, Morten; Hováth-Puhó, Erzsébet; Christiansen, Christian Fynbo; Petersen, Karin L; Bøtker, Hans Erik; Sørensen, Henrik Toft

2014-11-25

To examine whether preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) influenced 30-day stroke mortality. We conducted a nationwide population-based cohort study. Using medical databases, we identified all first-time stroke hospitalizations in Denmark between 2004 and 2012 (n = 100,043) and subsequent mortality. We categorized NSAID use as current (prescription redemption within 60 days before hospital admission), former, and nonuse. Current use was further classified as new or long-term use. Cox regression was used to compute hazard ratios (HRs) of death within 30 days, controlling for potential confounding through multivariable adjustment and propensity score matching. The adjusted HR of death for ischemic stroke was 1.19 (95% confidence interval [CI]: 1.02-1.38) for current users of selective cyclooxygenase (COX)-2 inhibitors compared with nonusers, driven by the effect among new users (1.42, 95% CI: 1.14-1.77). Comparing the different COX-2 inhibitors, the HR was driven by new use of older traditional COX-2 inhibitors (1.42, 95% CI: 1.14-1.78) among which it was 1.53 (95% CI: 1.02-2.28) for etodolac and 1.28 (95% CI: 0.98-1.68) for diclofenac. The propensity score-matched analysis supported the association between older COX-2 inhibitors and ischemic stroke mortality. There was no association for former users. Mortality from intracerebral hemorrhage was not associated with use of nonselective NSAIDs or COX-2 inhibitors. Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke. Use of nonselective NSAIDs at time of admission was not associated with mortality from ischemic stroke or intracerebral hemorrhage. © 2014 American Academy of Neurology.

Prediction of all-cause death in hemodialysis patients using elevated postdialysis pulse wave velocity.

PubMed

Fu, Xiaohong; Yang, Jihong; Fan, Zhaoxin; Chen, Xianguang; Wu, Jie; Li, Jie; Wu, Hua

2016-02-01

To identify the relationship between predialysis pulse wave velocity (PWV), postdialysis PWV during 1 hemodialysis (HD) session, and deaths in maintenance HD patients. 43 patients were recruited. PWV was measured before and after one HD session and dialysis- related data were recorded. Clinical data such as blood pressure, blood lipids, and blood glucose, were carefully observed and managed in a 5-year follow-up. The association between all-cause death, predialysis PWV, postdialysis PWV, change of PWV (ΔPWV), and other related variables were analyzed. After 5 years, 17 patients (39.5%) died. Univariate Cox regression analysis showed that all-cause death of the patients significantly correlated with age, postdialysis PWV, and ΔPWV. Multivariate Cox regression analysis revealed that postdialysis PWV was an independent predictor for all-cause death in these patients (HR: 1.377, 95% CI: 1.146 - 1.656, p = 0.001). Elevated postdialysis PWV significantly correlated with and was an independent predictor for all-cause death in maintenance HD patients.

Survival in Adult Lung Transplant Recipients Receiving Pediatric Versus Adult Donor Allografts.

PubMed

Hayes, Don; Whitson, Bryan A; Ghadiali, Samir N; Lloyd, Eric A; Tobias, Joseph D; Mansour, Heidi M; Black, Sylvester M

2015-10-01

Recent evidence showed that pediatric donor lungs increased rates of allograft failure in adult lung transplant recipients; however, the influence on survival is unclear. The United Network for Organ Sharing (UNOS) database was queried from 2005 to 2013 for adult lung transplant recipients (≥18 years) to assess survival differences among donor age categories (<18 years, 18 to 29 years, 30 to 59 years, ≥60 years). Of 12,297 adult lung transplants, 12,209 were used for univariate Cox models and Kaplan-Meier (KM) analysis and 11,602 for multivariate Cox models. A total of 1,187 adult recipients received pediatric donor lungs compared with 11,110 receiving adult donor organs. Univariate and multivariate Cox models found no difference in survival between donor ages 0 to 17 and donor ages 18 to 29, whereas donor ages 60 and older were significantly associated with increased mortality hazard, relative to the modal category of donor ages 30 to 59 (adjusted hazard ratio = 1.381; 95% confidence interval = 1.188% to 1.606%; p < 0.001). Interactions between recipient and donor age range found that the oldest donor age range was negatively associated with survival among middle-aged (30 to 59) and older (≥60) lung transplant recipients. Pediatric donor lung allografts were not negatively associated with survival in adult lung transplant recipients; however, the oldest donor age range was associated with increased mortality hazard for adult lung transplant recipients. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Co-expression of COX-2 and 5-LO in primary glioblastoma is associated with poor prognosis.

PubMed

Wang, Xingfu; Chen, Yupeng; Zhang, Sheng; Zhang, Lifeng; Liu, Xueyong; Zhang, Li; Li, Xiaoling; Chen, Dayang

2015-11-01

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) are important factors in tumorigenesis and malignant progression; however, studies of their roles in glioblastoma have produced conflicting results. To define the frequencies of COX-2 and 5-LO expression and their correlation with clinicopathological features and prognosis, tumor tissues from 76 cases of newly diagnosed primary ordinary glioblastoma were examined for COX-2 and 5-LO expression by immunohistochemistry. The expression levels of COX-2 and 5-LO and the relationships between the co-expression of COX-2/5-LO and patient age and gender, edema index (EI), Karnofsky Performance Scale and overall survival (OS) were analyzed. COX-2 and 5-LO were expressed in 73.7 % (56/76) and 92.1 % (70/76) of the samples, respectively. Among the clinicopathological characteristics, only age (>60 years) exhibited a significant association with the high expression of COX-2. No statistically significant correlations were found in the 5-LO cohort. A significant positive correlation was revealed between the COX-2 and 5-LO scores (r = 0.374; p = 0.001). The elevated co-expression of COX-2 and 5-LO was observed primarily in the patients over the age of 60 years. Patients with a high expression of COX-2 had a significantly shorter OS (p < 0.01), whereas the immunoexpression of 5-LO was not associated with the OS of patients with glioblastoma. Survival analysis indicated that simultaneous high levels of COX-2 and 5-LO expression were significantly correlated with poor OS and, conversely, that a low/low expression pattern of these two proteins was significantly associated with better OS (p < 0.05). Moreover, the Cox multivariable proportional hazard model showed that a high expression of COX-2, high co-expression of COX-2 and 5-LO, and a high Ki-67 index were significant predictors of shorter OS in primary glioblastoma, independent of age, gender, EI, 5-LO expression and p53 status. The hazard ratios for OS were 2.347 (95 % CI 1.30-4.25, p = 0.005), 1.900 (95 % CI 1.30-2.78, p = 0.001), and 2.210 (95 % CI 1.19-4.09, p = 0.011), respectively. These results suggest that COX-2 and 5-LO play roles in tumorigenesis and the progression of primary glioblastoma and that the co-expression pattern of COX-2/5-LO may be used as an independent prognostic factor in this disease.

Effects of cicletanine in the left circumflex coronary artery occlusion-reperfusion canine model of sudden death: analysis of 107 experiments using Cox's proportional hazards model.

PubMed

Jouve, R; Puddu, P E; Langlet, F; Lanti, M; Guillen, J C; Rolland, P H; Serradimigni, A

1988-01-01

Multivariate analysis of survival using Cox's proportional hazards model demonstrates that several clinically measurable covariates are determinants of life-threatening arrhythmias following left circumflex coronary artery occlusion-reperfusion in 107 dogs. These are heart rate, ST segment elevation and mean aortic pressure immediately (3 min) following occlusion, and the presence of early (0-10 min) post-occlusion sustained ventricular tachycardia. The risk of occlusion-reperfusion ventricular fibrillation was determined according to Cox's solution based on ST segment elevation, thus enabling quantification of the role of cicletanine. Since cicletanine-treated dogs had reduced mean ST segment elevation at 3 min post-occlusion, lower incidence of early post-occlusion (0-10 min) sustained ventricular tachycardia, and increased endogenous production of prostacyclin, and the latter was inversely correlated with the level of ST segment elevation, it is concluded that such favourable effects on the ischaemic myocardium were contributory to the improved outcome in these experiments. These effects on the ischaemic myocardium obtained in spite of a hypotensive action in the experimental setting might be regarded as desirable and it is therefore suggested that they should be further investigated by pharmacodynamic studies in human subjects.

The TP53 gene polymorphisms and survival of sporadic breast cancer patients.

PubMed

Bišof, V; Salihović, M Peričić; Narančić, N Smolej; Skarić-Jurić, T; Jakić-Razumović, J; Janićijević, B; Rudan, P

2012-06-01

The TP53 gene polymorphisms, Arg72Pro and PIN3 (+16 bp), can have prognostic and predictive value in different cancers including breast cancer. The aim of the present study is to investigate a potential association between different genotypes of these polymorphisms and clinicopathological variables with survival of breast cancer patients in Croatian population. Ninety-four women with sporadic breast cancer were retrospectively analyzed. Median follow-up period was 67.9 months. The effects of basic clinical and histopathological characteristics of tumor on survival were tested by Cox's proportional hazards regression analysis. The TNM stage was associated with overall survival by Kaplan-Meier analysis, univariate, and multivariate Cox's proportional hazards regression analysis, while grade was associated with survival by Kaplan-Meier analysis and univariate Cox's proportional hazards regression analysis. Different genotypes of the Arg72Pro and PIN3 (+16 bp) polymorphisms had no significant impact on survival in breast cancer patients. However, in subgroup of patients treated with chemotherapy without anthracycline, the A2A2 genotype of the PIN3 (+16 bp) polymorphism was associated with poorer overall survival than other genotypes by Kaplan-Meier analysis (P = 0.048). The TP53 polymorphisms, Arg72Pro and PIN3 (+16 bp), had no impact on survival in unselected sporadic breast cancer patients in Croatian population. However, the results support the role of the A2A2 genotype of the PIN3 (+16 bp) polymorphism as a marker for identification of patients that may benefit from anthracycline-containing chemotherapy.

Reporting and methodological quality of survival analysis in articles published in Chinese oncology journals.

PubMed

Zhu, Xiaoyan; Zhou, Xiaobin; Zhang, Yuan; Sun, Xiao; Liu, Haihua; Zhang, Yingying

2017-12-01

Survival analysis methods have gained widespread use in the filed of oncology. For achievement of reliable results, the methodological process and report quality is crucial. This review provides the first examination of methodological characteristics and reporting quality of survival analysis in articles published in leading Chinese oncology journals.To examine methodological and reporting quality of survival analysis, to identify some common deficiencies, to desirable precautions in the analysis, and relate advice for authors, readers, and editors.A total of 242 survival analysis articles were included to be evaluated from 1492 articles published in 4 leading Chinese oncology journals in 2013. Articles were evaluated according to 16 established items for proper use and reporting of survival analysis.The application rates of Kaplan-Meier, life table, log-rank test, Breslow test, and Cox proportional hazards model (Cox model) were 91.74%, 3.72%, 78.51%, 0.41%, and 46.28%, respectively, no article used the parametric method for survival analysis. Multivariate Cox model was conducted in 112 articles (46.28%). Follow-up rates were mentioned in 155 articles (64.05%), of which 4 articles were under 80% and the lowest was 75.25%, 55 articles were100%. The report rates of all types of survival endpoint were lower than 10%. Eleven of 100 articles which reported a loss to follow-up had stated how to treat it in the analysis. One hundred thirty articles (53.72%) did not perform multivariate analysis. One hundred thirty-nine articles (57.44%) did not define the survival time. Violations and omissions of methodological guidelines included no mention of pertinent checks for proportional hazard assumption; no report of testing for interactions and collinearity between independent variables; no report of calculation method of sample size. Thirty-six articles (32.74%) reported the methods of independent variable selection. The above defects could make potentially inaccurate, misleading of the reported results, or difficult to interpret.There are gaps in the conduct and reporting of survival analysis in studies published in Chinese oncology journals, severe deficiencies were noted. More endorsement by journals of the report guideline for survival analysis may improve articles quality, and the dissemination of reliable evidence to oncology clinicians. We recommend authors, readers, reviewers, and editors to consider survival analysis more carefully and cooperate more closely with statisticians and epidemiologists. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis.

PubMed

Brozek, Wolfgang; Manhardt, Teresa; Kállay, Enikö; Peterlik, Meinrad; Cross, Heide S

2012-07-26

Previous studies on the significance of vitamin D insufficiency and chronic inflammation in colorectal cancer development clearly indicated that maintenance of cellular homeostasis in the large intestinal epithelium requires balanced interaction of 1,25-(OH)2D3 and prostaglandin cellular signaling networks. The present study addresses the question how colorectal cancer pathogenesis depends on alterations of activities of vitamin D hydroxylases, i.e., CYP27B1-encoded 25-hydroxyvitamin D-1a-hydroxylase and CYP24A1-encoded 25-hydroxyvitamin D-24-hydroxylase, and inflammation-induced cyclooxygenase-2 (COX-2). Data from 105 cancer patients on CYP27B1, VDR, CYP24A1, and COX-2 mRNA expression in relation to tumor grade, anatomical location, gender and age were fit into a multivariate model of exploratory factor analysis. Nearly identical results were obtained by the principal factor and the maximum likelihood method, and these were confirmed by hierarchical cluster analysis: Within the eight mutually dependent variables studied four independent constellations were found that identify different features of colorectal cancer pathogenesis: (i) Escape of COX-2 activity from restraints by the CYP27B1/VDR system can initiate cancer growth anywhere in the colorectum regardless of age and gender; (ii) variations in COX-2 expression are mainly responsible for differences in cancer incidence in relation to tumor location; (iii) advancing age has a strong gender-specific influence on cancer incidence; (iv) progression from well differentiated to undifferentiated cancer is solely associated with a rise in CYP24A1 expression.

Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis

PubMed Central

Brozek, Wolfgang; Manhardt, Teresa; Kállay, Enikö; Peterlik, Meinrad; Cross, Heide S.

2012-01-01

Previous studies on the significance of vitamin D insufficiency and chronic inflammation in colorectal cancer development clearly indicated that maintenance of cellular homeostasis in the large intestinal epithelium requires balanced interaction of 1,25-(OH)2D3 and prostaglandin cellular signaling networks. The present study addresses the question how colorectal cancer pathogenesis depends on alterations of activities of vitamin D hydroxylases, i.e., CYP27B1-encoded 25-hydroxyvitamin D-1α-hydroxylase and CYP24A1-encoded 25-hydroxyvitamin D-24-hydroxylase, and inflammation-induced cyclooxygenase-2 (COX-2). Data from 105 cancer patients on CYP27B1, VDR, CYP24A1, and COX-2 mRNA expression in relation to tumor grade, anatomical location, gender and age were fit into a multivariate model of exploratory factor analysis. Nearly identical results were obtained by the principal factor and the maximum likelihood method, and these were confirmed by hierarchical cluster analysis: Within the eight mutually dependent variables studied four independent constellations were found that identify different features of colorectal cancer pathogenesis: (i) Escape of COX-2 activity from restraints by the CYP27B1/VDR system can initiate cancer growth anywhere in the colorectum regardless of age and gender; (ii) variations in COX-2 expression are mainly responsible for differences in cancer incidence in relation to tumor location; (iii) advancing age has a strong gender-specific influence on cancer incidence; (iv) progression from well differentiated to undifferentiated cancer is solely associated with a rise in CYP24A1 expression. PMID:24213465

Impact of Donor Arterial Partial Pressure of Oxygen on Outcomes After Lung Transplantation in Adult Cystic Fibrosis Recipients.

PubMed

Hayes, Don; Kopp, Benjamin T; Kirkby, Stephen E; Reynolds, Susan D; Mansour, Heidi M; Tobias, Joseph D; Tumin, Dmitry

2016-08-01

Donor PaO2 levels are used for assessing organs for lung transplantation (LTx), but survival implications of PaO2 levels in adult cystic fibrosis (CF) patients receiving LTx are unclear. UNOS registry data spanning 2005-2013 were used to test for associations of donor PaO2 with patient survival and bronchiolitis obliterans syndrome (BOS) in adult (age ≥ 18 years) first-time LTx recipients diagnosed with CF. The analysis included 1587 patients, of whom 1420 had complete data for multivariable Cox models. No statistically significant differences among donor PaO2 categories of ≤200, 201-300, 301-400, or >400 mmHg were found in univariate survival analysis (log-rank test p = 0.290). BOS onset did not significantly differ across donor PaO2 categories (Chi-square p = 0.480). Multivariable Cox models of patient survival supported the lack of difference across donor PaO2 categories. Interaction analysis found a modest difference in survival between the two top categories of donor PaO2 when examining patients with body mass index (BMI) in the lowest decile (≤16.5 kg/m(2)). Donor PaO2 was not associated with survival or BOS onset in adult CF patients undergoing LTx. Notwithstanding statistically significant interactions between donor PaO2 and BMI, there was no evidence of post-LTx survival risk associated with donor PaO2 below conventional thresholds in any subgroup of adults with CF.

Radical Surgery Improves Survival in Patients with Stage 4 Neuroblastoma.

PubMed

Vollmer, Katherin; Gfroerer, Stefan; Theilen, Till-Martin; Bochennek, Konrad; Klingebiel, Thomas; Rolle, Udo; Fiegel, Henning

2018-06-01

Neuroblastoma (NBL) is the most common extracranial solid tumor in children. Despite a good overall prognosis in NBL patients, the outcome of children with stage 4 disease, even with multimodal intensive therapy, remains poor. The role of extended surgical resection of the primary tumor is in numerous studies controversial. The aim of this study was to retrospectively analyze the impact of radical surgical resection on the overall- and event-free survival of stage 4 NBL patients. We retrospectively analyzed patient charts of 40 patients with stage 4 NBL treated in our institution between January 1990 and May 2012. All clinical and pathological findings of stage 4 NBL patients were included. Extent of surgery was assessed from the operation records and was classified as non-radical (tumor biopsy, partial 50-90% resection) or radical (near-complete >90% resection, complete resection). Overall- (OS) and event-free (EFS) survival was assessed using the Kaplan-Meier analysis and log-rank test. A multivariate Cox regression analysis was used to demonstrate independency. In total, 29/40 patients were operated radically (>90% resection), whereas 11 patients received subtotal resection or biopsy only. OS and EFS were significantly increased in patients with radical operation compared with non-radical resection (p = 0.0003 for OS, p = 0.004 for EFS; log-rank test). A multivariate Cox regression analysis revealed radical operation as a significant and independent parameter for OS and EFS. Our data indicate that radical (over 90% resection) surgery improves OS and EFS in stage 4 NBL patients.

The result of adjuvant chemotherapy for localized pT3 upper urinary tract carcinoma in a multi-institutional study.

PubMed

Kawashima, Atsunari; Nakai, Yasutomo; Nakayama, Masashi; Ujike, Takeshi; Tanigawa, Go; Ono, Yutaka; Kamoto, Akihito; Takada, Tsuyosi; Yamaguchi, Yuichiro; Takayama, Hitoshi; Nishimura, Kazuo; Nonomura, Norio; Tsujimura, Akira

2012-10-01

To determine through the analysis of our multi-institutional database whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma (UUTC) is beneficial. A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study. Clinical features evaluated were sex, tumor location, adjuvant chemotherapy status, tumor pathology (histology, grade, infiltrating growth, lymphovascular invasion (LVI)), and cause of death. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis. In pT3 patients, overall 5-year CSS rate was 68.4% and median CSS time was 31 months (range 3-114 months). In the adjuvant chemotherapy group, 5-year CSS rate was 80.8%, whereas 5-year CSS rate was 64.4% in the non-adjuvant chemotherapy group. By multivariate analysis, adjuvant chemotherapy status was significantly associated with CSS (P = 0.008) were sex, tumor grade, tumor histology, and LVI presence. This study, although it was retrospective study, revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis. Prospective studies evaluating adjuvant therapy regimens for UTTC are required.

Natural history definition and a suggested clinical approach to Buerger's disease: a case-control study with survival analysis.

PubMed

Fazeli, Bahare; Ravari, Hassan; Assadi, Reza

2012-08-01

The aim of this study was first to describe the natural history of Buerger's disease (BD) and then to discuss a clinical approach to this disease based on multivariate analysis. One hundred eight patients who corresponded with Shionoya's criteria were selected from 2000 to 2007 for this study. Major amputation was considered the ultimate adverse event. Survival analyses were performed by Kaplan-Meier curves. Independent variables including gender, duration of smoking, number of cigarettes smoked per day, minor amputation events and type of treatments, were determined by multivariate Cox regression analysis. The recorded data demonstrated that BD may present in four forms, including relapsing-remitting (75%), secondary progressive (4.6%), primary progressive (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses within the six years after diagnosis of BD. In multivariate analysis, duration of smoking of more than 20 years had a significant relationship with further major amputation among patients with BD. Smoking cessation programs with experienced psychotherapists are strongly recommended for those areas in which Buerger's disease is common. Patients who have smoked for more than 20 years should be encouraged to quit smoking, but should also be recommended for more advanced treatment for limb salvage.

Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

PubMed Central

Ma, Wen-Juan; Wang, Xing; Yan, Wen-Ting; Zhou, Zhong-Guo; Pan, Zhi-Zhong; Chen, Gong; Zhang, Rong-Xin

2018-01-01

AIM To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 (IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer (CRC) patients. METHODS We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival (OS) outcomes. RESULTS The expression of nuclear IDO1 was significantly correlated with body mass index (P < 0.001), and IDO1 expression displayed no association with sex, age, tumor differentiation, T stage, N stage, carcinoembryonic antigen, cancer antigen 19-9, CD3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1 (P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio (HR) = 2.044, 95% confidence interval (CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2 (HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2 (HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1 (P = 0.041), nuclear/cytoplasmic IDO1 (HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2 (HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC (HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients (HR = 3.210, 95%CI: 1.074-9.590, P = 0.037). CONCLUSION Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC. PMID:29853736

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.

Long non-coding RNA PVT1 as a novel potential biomarker for predicting the prognosis of colorectal cancer.

PubMed

Fan, Heng; Zhu, Jian-Hua; Yao, Xue-Qing

2018-05-01

Long non-coding RNA (lncRNA) plays a very important role in the occurrence and development of various tumors, and is a potential biomarker for cancer diagnosis and prognosis. The purpose of this study was to investigate the relationship between the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and the prognostic significance in patients with colorectal cancer. The expression of PVT1 was measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in cancerous and adjacent tissues of 210 colorectal cancer patients. The disease-free survival and overall survival of colorectal cancer patients were evaluated by Kaplan-Meier analysis, and univariate and multivariate analysis were performed by Cox proportional-hazards model. Our results revealed that PVT1 expression in cancer tissues of colorectal cancer was significantly higher than that of adjacent tissues ( P<0.001). High PVT1 expression was increased by 51.4% (108/210), which was significantly correlated with the tumor differentiation, the depth of invasion, the stage of tumor, node, metastasis (TNM), and lymphatic metastasis. The Kaplan-Meier analysis showed that high PVT1 expression resulted in a shorter disease-free survival (Log-rank test P<0.001) and overall survival (Log-rank test P<0.001) compared with the low PVT1 expression group in colorectal cancer patients, whether at TNM I/II stage or at TNM III/IV stage. A multivariate Cox regression analysis demonstrated that high PVT1 expression was an independent predictor of poor prognosis in colorectal cancer patients. Our results suggest that high PVT1 expression might be a potential biomarker for assessing tumor recurrence and prognosis in colorectal cancer patients.

[Neutrophil to lymphocyte ratio in peripheral blood: a novel independent prognostic factor in patients with head and neck squamous cell carcinoma].

PubMed

Wu, F; Wu, L L; Zhu, L X

2017-01-23

Objective: To investigate whether neutrophil to lymphocyte ratio (NLR) in peripheral blood can be an independent prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Clinical data of 97 HNSCC patients who received surgical treatment in our department between January 2008 and January 2012 were analyzed retrospectively. The 97 patients were divided into low NLR group (NLR≤5, n =69) and high NLR group (NLR>5, n =28) according to the NLR in preoperative peripheral blood. The relationships of NLR and clinicopathological features were analyzed. Kaplan-Meier method was used for univariate survival analysis and Cox proportional hazard model for multivariate survival analysis. Results: The clinical stages were significantly different between high NLR group and low NLR group ( P <0.05), however, the age, gender, location, lymph node metastasis, smoking and alcohol of the two groups showed no significant differences ( P > 0.05 of all). Univariate survival analysis showed that smoking, lymph node metastasis, clinical stage and NLR value were risk factors for 3-year overall survival (OS) rate and relapse-free survival (RFS) rate of HNSCC patients ( P <0.05). The OS rate of high NLR and low NLR groups was 42.9% and 91.3%, and the RFS rate was 44.2% and 80.1%, respectively, with a statistically significant difference ( P <0.05 for both). Cox multivariate survival analysis showed that clinical stage and NLR were independent factors for prognostic evaluation of HNSCC patients ( P <0.05 for both). Conclusions: NLR level is significantly associated with clinical stage of HNSCC. High NLR is an independent prognostic rick factor and plays an important role in prognostic evaluation of HNSCC patients.

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

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.

Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery.

PubMed

Zolal, Amir; Juratli, Tareq A; Linn, Jennifer; Podlesek, Dino; Sitoci Ficici, Kerim Hakan; Kitzler, Hagen H; Schackert, Gabriele; Sobottka, Stephan B; Rieger, Bernhard; Krex, Dietmar

2016-05-01

Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis.

Dual oxidase 1: A predictive tool for the prognosis of hepatocellular carcinoma patients.

PubMed

Chen, Shengsen; Ling, Qingxia; Yu, Kangkang; Huang, Chong; Li, Ning; Zheng, Jianming; Bao, Suxia; Cheng, Qi; Zhu, Mengqi; Chen, Mingquan

2016-06-01

Dual oxidase 1 (DUOX1), which is the main source of reactive oxygen species (ROS) production in the airway, can be silenced in human lung cancer and hepatocellular carcinomas. However, the prognostic value of DUOX1 expression in hepatocellular carcinoma patients is still unclear. We investigated the prognostic value of DUOX1 expression in liver cancer patients. DUOX1 mRNA expression was determined in tumor tissues and non-tumor tissues by real‑time PCR. For evaluation of the prognostic value of DUOX1 expression, Kaplan-Meier method and Cox's proportional hazards model (univariate analysis and multivariate analysis) were employed. A simple risk score was devised by using significant variables obtained from the Cox's regression analysis to further predict the HCC patient prognosis. We observed a reduced DUOX1 mRNA level in the cancer tissues in comparison to the non‑cancer tissues. More importantly, Kaplan-Meier analysis showed that patients with high DUOX1 expression had longer disease-free survival and overall survival compared with those with low expression of DUOX1. Cox's regression analysis indicated that DUOX1 expression, age, and intrahepatic metastasis may be significant prognostic factors for disease-free survival and overall survival. Finally, we found that patients with total scores of >2 and >1 were more likely to relapse and succumb to the disease than patients whose total scores were ≤2 and ≤1. In conclusion, DUOX1 expression in liver tumors is a potential prognostic tool for patients. The risk scoring system is useful for predicting the survival of liver cancer patients after tumor resection.

Increased fibroblast density in actinic cheilitis: association with tryptase-positive mast cells, actinic elastosis and epithelial p53 and COX-2 expression.

PubMed

Rojas, Isolde G; Boza, Yadira V; Spencer, Maria Loreto; Flores, Maritza; Martínez, Alejandra

2012-01-01

Actinic cheilitis (AC) is characterized by epithelial and connective tissue alterations caused by ultraviolet sunlight overexposure known as photodamage. Fibroblasts have been linked to photodamage and tumor progression during skin carcinogenesis; however, their role in early lip carcinogenesis remains unknown. The aim of this study was to assess the density of fibroblasts in AC and normal lip (NL) samples and determine their association with markers of lip photodamage. Fibroblasts, mast cells, p53, COX-2, and elastin were detected in NL (n = 20) and AC (n = 28) biopsies using immunohistochemistry/histochemistry. Mast cell and fibroblast density and epithelial p53 and COX-2 expression scores were then obtained. Elastosis was scored 1-4 according to elastin fiber density and tortuosity. Fibroblasts, mast cells, p53, COX-2, and elastosis were increased in AC as compared to NL (P < 0.001). Multivariate analysis showed an association between fibroblast and mast cell density at the papillary and reticular areas of AC and NL (P < 0.05). Papillary fibroblast density was also associated with epithelial p53 and COX-2 expression (P < 0.05). Increased fibroblast density, both papillary and reticular, was found in the high elastosis group (scores 3-4) as compared to the low elastosis group (scores 1-2) (P < 0.01). Increased reticular mast cell density was detected only in the high elastosis group (P < 0.01). Fibroblasts are increased in AC, and they are associated with mast cell density, epithelial p53 and COX-2 expression, and actinic elastosis. Therefore, fibroblasts may contribute to lip photodamage and could be considered useful markers of early lip carcinogenesis. © 2011 John Wiley & Sons A/S.

Applying Additive Hazards Models for Analyzing Survival in Patients with Colorectal Cancer in Fars Province, Southern Iran

PubMed

Madadizadeh, Farzan; Ghanbarnejad, Amin; Ghavami, Vahid; Zare Bandamiri, Mohammad; Mohammadianpanah, Mohammad

2017-04-01

Introduction: Colorectal cancer (CRC) is a commonly fatal cancer that ranks as third worldwide and third and the fifth in Iranian women and men, respectively. There are several methods for analyzing time to event data. Additive hazards regression models take priority over the popular Cox proportional hazards model if the absolute hazard (risk) change instead of hazard ratio is of primary concern, or a proportionality assumption is not made. Methods: This study used data gathered from medical records of 561 colorectal cancer patients who were admitted to Namazi Hospital, Shiraz, Iran, during 2005 to 2010 and followed until December 2015. The nonparametric Aalen’s additive hazards model, semiparametric Lin and Ying’s additive hazards model and Cox proportional hazards model were applied for data analysis. The proportionality assumption for the Cox model was evaluated with a test based on the Schoenfeld residuals and for test goodness of fit in additive models, Cox-Snell residual plots were used. Analyses were performed with SAS 9.2 and R3.2 software. Results: The median follow-up time was 49 months. The five-year survival rate and the mean survival time after cancer diagnosis were 59.6% and 68.1±1.4 months, respectively. Multivariate analyses using Lin and Ying’s additive model and the Cox proportional model indicated that the age of diagnosis, site of tumor, stage, and proportion of positive lymph nodes, lymphovascular invasion and type of treatment were factors affecting survival of the CRC patients. Conclusion: Additive models are suitable alternatives to the Cox proportionality model if there is interest in evaluation of absolute hazard change, or no proportionality assumption is made. Creative Commons Attribution License

MiR-221, a potential prognostic biomarker for recurrence in papillary thyroid cancer.

PubMed

Dai, Lei; Wang, Yaozong; Chen, Liangliang; Zheng, Jueru; Li, Jianjun; Wu, Xianjiang

2017-01-07

Many studies have reported several transcriptionally deregulated microRNAs (miRNAs) in papillary thyroid cancer (PTC) tissue in comparison with benign thyroid nodules and normal thyroid tissues. However, the correlation between miRNA expressions and PTC recurrence still remains unclear. The PTC patients who scheduled to undergo total thyroidectomy by the same surgical team in Ningbo NO.2 Hospital from March 1998 to March 2008 were enrolled in this study. The clinical and pathological characteristics of each patient were recorded in detail. The selected miRNA expressions were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Potential predictive factors for cancer recurrence were evaluated by univariate and multivariate Cox proportional hazard analysis. A total of 78 patients were enrolled with 49 females at a mean age of 45.8 years. Enrolled patients were divided into two groups: nonrecurrent group (n = 54) and recurrent group (n = 24). The results from the univariate Cox proportional hazard analysis revealed that primary tumor size, TNM stage, extrathyroid extension, miR-221, and miR-222 expressions were significantly associated with PTC recurrence (P < 0.05). The tissue expression of miR-221 was the only independent risk factor for PTC recurrence (HR 1.41; 95%CI 1.14-1.95, P = 0.007) by multiple Cox proportional hazard analysis. This study identified the potential role of miR-221 as a prognostic biomarker for the recurrence in PTC.

Redo surgery risk in patients with cardiac prosthetic valve dysfunction

PubMed Central

Maciejewski, Marek; Piestrzeniewicz, Katarzyna; Bielecka-Dąbrowa, Agata; Piechowiak, Monika; Jaszewski, Ryszard

2011-01-01

Introduction The aim of the study was to analyse the risk factors of early and late mortality in patients undergoing the first reoperation for prosthetic valve dysfunction. Material and methods A retrospective observational study was performed in 194 consecutive patients (M = 75, F = 119; mean age 53.2 ±11 years) with a mechanical prosthetic valve (n = 103 cases; 53%) or bioprosthesis (91; 47%). Univariate and multivariate Cox statistical analysis was performed to determine risk factors of early and late mortality. Results The overall early mortality was 18.6%: 31.4% in patients with symptoms of NYHA functional class III-IV and 3.4% in pts in NYHA class I-II. Multivariate analysis identified symptoms of NYHA class III-IV and endocarditis as independent predictors of early mortality. The overall late mortality (> 30 days) was 8.2% (0.62% year/patient). Multivariate analysis identified age at the time of reoperation as a strong independent predictor of late mortality. Conclusions Reoperation in patients with prosthetic valves, performed urgently, especially in patients with symptoms of NYHA class III-IV or in the case of endocarditis, bears a high mortality rate. Risk of planned reoperation, mostly in patients with symptoms of NYHA class I-II, does not differ from the risk of the first operation. PMID:22291767

Quantifying parameter uncertainty in stochastic models using the Box Cox transformation

NASA Astrophysics Data System (ADS)

Thyer, Mark; Kuczera, George; Wang, Q. J.

2002-08-01

The Box-Cox transformation is widely used to transform hydrological data to make it approximately Gaussian. Bayesian evaluation of parameter uncertainty in stochastic models using the Box-Cox transformation is hindered by the fact that there is no analytical solution for the posterior distribution. However, the Markov chain Monte Carlo method known as the Metropolis algorithm can be used to simulate the posterior distribution. This method properly accounts for the nonnegativity constraint implicit in the Box-Cox transformation. Nonetheless, a case study using the AR(1) model uncovered a practical problem with the implementation of the Metropolis algorithm. The use of a multivariate Gaussian jump distribution resulted in unacceptable convergence behaviour. This was rectified by developing suitable parameter transformations for the mean and variance of the AR(1) process to remove the strong nonlinear dependencies with the Box-Cox transformation parameter. Applying this methodology to the Sydney annual rainfall data and the Burdekin River annual runoff data illustrates the efficacy of these parameter transformations and demonstrate the value of quantifying parameter uncertainty.

Expression of ARs in triple negative breast cancer tumors: a potential prognostic factor?

PubMed

Giannos, Aris; Filipits, Martin; Zagouri, Flora; Brandstetter, Anita; Tsigginou, Alexandra; Sotiropoulou, Maria; Papaspyrou, Irene; Sergentanis, Theodoros N; Psaltopoulou, Theodora; Rodolakis, Alexandros; Antsaklis, Aris; Dimopoulos, Meletios-Athanasios; Dimitrakakis, Constantine

2015-01-01

In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26-1.70, P=0.393). AR expression does not seem to play a prognostic role in TNBC.

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.

Revisiting the role of pathological analysis in transarterial chemoembolization-treated hepatocellular carcinoma after transplantation

PubMed Central

Vasuri, Francesco; Malvi, Deborah; Rosini, Francesca; Baldin, Pamela; Fiorentino, Michelangelo; Paccapelo, Alexandro; Ercolani, Giorgio; Pinna, Antonio Daniele; Golfieri, Rita; Morselli-Labate, Antonio Maria; Grigioni, Walter Franco; D’Errico-Grigioni, Antonia

2014-01-01

AIM: To define the histopathological features predictive of post-transplant hepatocellular carcinoma (HCC) recurrence after transarterial chemoembolization, applicable for recipient risk stratification. METHODS: We retrospectively reviewed the specimens of all suspicious nodules (total 275) from 101 consecutive liver transplant recipients which came to our Pathology Unit over a 6-year period. All nodules were sampled and analyzed, and follow-up data were collected. We finally considered 11 histological variables for each patient: total number of nodules, number of viable nodules, size of the major nodule, size of the major viable nodule, occurrence of microscopic vascular invasion, maximum Edmondson's grade, clear cell/sarcomatous changes, and the residual neoplastic volume. Survival data were computed by means of the Kaplan-Meier procedure and analyzed by means of the Cox proportional hazards model. The multivariate linear regression and a k-means cluster analysis were also used in order to compute the standardized histological score. RESULTS: The total number of nodules, the residual neoplastic volume (the total volume of all evaluated nodules minus the necrotic portion) and the microvascular invasion entered the Cox multivariate hazard model with HCC recurrence as dependent variable. The histological score was therefore computed and a cluster analysis sorted recipients into 3 risk groups, with 3.3%, 18.5% and 53.8% respectively of tumor recurrence rates and 1.6%, 11.1% and 38.5% of tumor-related mortality respectively at the end of follow-up. CONCLUSION: The histological score allows a reliable stratification of HCC recurrence risk, especially in those recipients found out to be beyond the Milan criteria after orthotopic liver transplantation (OLT). PMID:25309084

Decoy receptor 3 is a prognostic factor in renal cell cancer.

PubMed

Macher-Goeppinger, Stephan; Aulmann, Sebastian; Wagener, Nina; Funke, Benjamin; Tagscherer, Katrin E; Haferkamp, Axel; Hohenfellner, Markus; Kim, Sunghee; Autschbach, Frank; Schirmacher, Peter; Roth, Wilfried

2008-10-01

Decoy receptor 3 (DcR3) is a soluble protein that binds to and inactivates the death ligand CD95L. Here, we studied a possible association between DcR3 expression and prognosis in patients with renal cell carcinomas (RCCs). A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples was generated. Decoy receptor 3 expression in tumors of 560 patients was examined by immunohistochemistry. The effect of DcR3 expression on disease-specific survival and progression-free survival was assessed using univariate analysis and multivariate Cox regression analysis. Decoy receptor 3 serum levels were determined by ELISA. High DcR3 expression was associated with high-grade (P = .005) and high-stage (P = .048) RCCs. The incidence of distant metastasis (P = .03) and lymph node metastasis (P = .002) was significantly higher in the group with high DcR3 expression. Decoy receptor 3 expression correlated negatively with disease-specific survival (P < .001) and progression-free survival (P < .001) in univariate analyses. A multivariate Cox regression analysis retained DcR3 expression as an independent prognostic factor that outperformed the Karnofsky performance status. In patients with high-stage RCCs expressing DcR3, the 2-year survival probability was 25%, whereas in patients with DcR3-negative tumors, the survival probability was 65% (P < .001). Moreover, DcR3 serum levels were significantly higher in patients with high-stage localized disease (P = .007) and metastatic disease (P = .001). DcR3 expression is an independent prognostic factor of RCC progression and mortality. Therefore, the assessment of DcR3 expression levels offers valuable prognostic information that could be used to select patients for adjuvant therapy studies.

Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

PubMed

Hoffmann, Christian; Distel, Luitpold; Knippen, Stefan; Gryc, Thomas; Schmidt, Manuel Alexander; Fietkau, Rainer; Putz, Florian

2018-01-22

Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis.

PubMed

Zhao, Fu; Zhang, Jing; Li, Peng; Zhou, Qiangyi; Zhang, Shun; Zhao, Chi; Wang, Bo; Yang, Zhijun; Li, Chunde; Liu, Pinan

2018-04-23

Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.

Calorie intake and patient outcomes in severe acute kidney injury: findings from The Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study trial

PubMed Central

2014-01-01

Introduction Current practice in the delivery of caloric intake (DCI) in patients with severe acute kidney injury (AKI) receiving renal replacement therapy (RRT) is unknown. We aimed to describe calorie administration in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study and to assess the association between DCI and clinical outcomes. Methods We performed a secondary analysis in 1456 patients from the RENAL trial. We measured the dose and evolution of DCI during treatment and analyzed its association with major clinical outcomes using multivariable logistic regression, Cox proportional hazards models, and time adjusted models. Results Overall, mean DCI during treatment in ICU was low at only 10.9 ± 9 Kcal/kg/day for non-survivors and 11 ± 9 Kcal/kg/day for survivors. Among patients with a lower DCI (below the median) 334 of 729 (45.8%) had died at 90-days after randomization compared with 316 of 727 (43.3%) patients with a higher DCI (above the median) (P = 0.34). On multivariable logistic regression analysis, mean DCI carried an odds ratio of 0.95 (95% confidence interval (CI): 0.91-1.00; P = 0.06) per 100 Kcal increase for 90-day mortality. DCI was not associated with significant differences in renal replacement (RRT) free days, mechanical ventilation free days, ICU free days and hospital free days. These findings remained essentially unaltered after time adjusted analysis and Cox proportional hazards modeling. Conclusions In the RENAL study, mean DCI was low. Within the limits of such low caloric intake, greater DCI was not associated with improved clinical outcomes. Trial registration ClinicalTrials.gov number, NCT00221013 PMID:24629036

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.

Prognostic predictors of patients with carcinoma of the gastric cardia.

PubMed

Zhang, Ming; Li, Zhigao; Ma, Yan; Zhu, Guanyu; Zhang, Hongfeng; Xue, Yingwei

2012-05-01

This study gives insight into survival predictors and clinicopathological features of carcinoma of the gastric cardia. The study included 233 patients who underwent operation for carcinoma of the gastric cardia. Clinicopathological prognostic variables were evaluated as predictors of long-term survival by univariate and multivariate analysis. Cox regression was used for multivariate analysis and survival curves were drawn by the Kaplan- Meier method. Carcinoma of the gastric cardia was characterized by positive lymph node metastasis (77.3%), serosal invasion (83.3%) and more stage III or IV tumors (72.5%). Overall 5-year survival rate was 21.9% and median survival period was 24 months. The 5-year survival rate was influenced by tumor size, depth on invasion, lymph node metastasis, extent of lymph node dissection, disease stage, operation methods and resection margin. The absent of serosal invasion and lymph node metastasis, curative resection should be considered to be the favourable predictors of long-term survival of patients with carcinoma of the gastric cardia.

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.

Prognostic value of inflammation-based scores in patients with osteosarcoma

PubMed Central

Liu, Bangjian; Huang, Yujing; Sun, Yuanjue; Zhang, Jianjun; Yao, Yang; Shen, Zan; Xiang, Dongxi; He, Aina

2016-01-01

Systemic inflammation responses have been associated with cancer development and progression. C-reactive protein (CRP), Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS) have been shown to be independent risk factors in various types of malignant tumors. This retrospective analysis of 162 osteosarcoma cases was performed to estimate their predictive value of survival in osteosarcoma. All statistical analyses were performed by SPSS statistical software. Receiver operating characteristic (ROC) analysis was generated to set optimal thresholds; area under the curve (AUC) was used to show the discriminatory abilities of inflammation-based scores; Kaplan-Meier analysis was performed to plot the survival curve; cox regression models were employed to determine the independent prognostic factors. The optimal cut-off points of NLR, PLR, and LMR were 2.57, 123.5 and 4.73, respectively. GPS and NLR had a markedly larger AUC than CRP, PLR and LMR. High levels of CRP, GPS, NLR, PLR, and low level of LMR were significantly associated with adverse prognosis (P < 0.05). Multivariate Cox regression analyses revealed that GPS, NLR, and occurrence of metastasis were top risk factors associated with death of osteosarcoma patients. PMID:28008988

A flexible model for multivariate interval-censored survival times with complex correlation structure.

PubMed

Falcaro, Milena; Pickles, Andrew

2007-02-10

We focus on the analysis of multivariate survival times with highly structured interdependency and subject to interval censoring. Such data are common in developmental genetics and genetic epidemiology. We propose a flexible mixed probit model that deals naturally with complex but uninformative censoring. The recorded ages of onset are treated as possibly censored ordinal outcomes with the interval censoring mechanism seen as arising from a coarsened measurement of a continuous variable observed as falling between subject-specific thresholds. This bypasses the requirement for the failure times to be observed as falling into non-overlapping intervals. The assumption of a normal age-of-onset distribution of the standard probit model is relaxed by embedding within it a multivariate Box-Cox transformation whose parameters are jointly estimated with the other parameters of the model. Complex decompositions of the underlying multivariate normal covariance matrix of the transformed ages of onset become possible. The new methodology is here applied to a multivariate study of the ages of first use of tobacco and first consumption of alcohol without parental permission in twins. The proposed model allows estimation of the genetic and environmental effects that are shared by both of these risk behaviours as well as those that are specific. 2006 John Wiley & Sons, Ltd.

ESC guidelines adherence is associated with improved survival in patients from the Norwegian Heart Failure Registry.

PubMed

De Blois, Jonathan; Fagerland, Morten Wang; Grundtvig, Morten; Semb, Anne Grete; Gullestad, Lars; Westheim, Arne; Hole, Torstein; Atar, Dan; Agewall, Stefan

2015-01-01

To assess the adherence to heart failure (HF) guidelines for angiotensin-converting enzyme-I (ACE-I), angiotensin II receptor blockers (ARB), and β-blockers and the possible association of ACE-I or ARB, β-blockers, and statins with survival in the large contemporary Norwegian Heart Failure Registry. The study included 5761 outpatients who were diagnosed with HF of any aetiology (mean left ventricular ejection fraction 32% ± 11%) from January 2000 to January 2010 and followed up until death or February 2010. Adherence to treatment according to the guidelines was high. Cox regression analysis to identify risk factors for all-cause mortality, after adjustment for many factors, showed that ACE-I ≥ 50% of target dose, use of beta-blockers, and statins were significantly related to improved survival (P = 0.003, P < 0.001, and P < 0.001, respectively). Propensity scoring showed the same benefit for these variables. Both multivariable and propensity scoring analyses showed survival benefits with β-blockers, statins, and adequate doses of ACE-I in this contemporary HF cohort. This study stresses the importance of guidelines adherence, even in the context of high levels of adherence to guidelines. Moreover, respecting the recommended target doses of ACE-I appears to have a crucial role in survival improvement and, in the multivariate Cox regression analysis, ARB treatment was not significantly associated with a lower all-cause mortality. Published on behalf of the European Society of Cardiology. All rights reserved. ©The Author 2015. For permissions please email: journals.permissions@oup.com.

MicroRNA-34c-5p is related to recurrence in laryngeal squamous cell carcinoma.

PubMed

Re, Massimo; Çeka, Artan; Rubini, Corrado; Ferrante, Luigi; Zizzi, Antonio; Gioacchini, Federico M; Tulli, Michele; Spazzafumo, Liana; Sellari-Franceschini, Stefano; Procopio, Antonio D; Olivieri, Fabiola

2015-09-01

Altered microRNA expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). We investigated the association of LSCC-related miR-34c-5p with disease-free survival and overall survival. Retrospective cohort study. Expression levels of miR-34c-5p were detected in 90 LSCC formalin-fixed paraffin-embedded tissues by reverse-transcription quantitative polymerase chain reaction. Overall survival and disease-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. A downregulation of miR-34c-5p expression significantly correlated with worse disease-free and overall survival. In the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. A downregulation of miR-34c-5p in LSCC is independently associated with unfavorable disease-free survival, suggesting that miR-34c-5p might be a promising marker for evaluating the risk of recurrences. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Genetic Polymorphisms in RNA Binding Proteins Contribute to Breast Cancer Survival

PubMed Central

Upadhyay, Rohit; Sanduja, Sandhya; Kaza, Vimala; Dixon, Dan A.

2012-01-01

The RNA-binding proteins TTP and HuR control expression of numerous genes associated with breast cancer pathogenesis by regulating mRNA stability. However, the role of genetic variation in TTP (ZFP36) and HuR (ELAVL1) genes is unknown in breast cancer prognosis. A total of 251 breast cancer patients (170 Caucasians and 81 African-Americans) were enrolled and followed-up from 2001 to 2011 (or until death). Genotyping was performed for 10 SNPs in ZFP36 and 7 in ELAVL1 genes. On comparing both races with one another, significant differences were found for clinical and genetic variables. The influence of genetic polymorphisms on survival was analyzed by using Cox-regression, Kaplan-Meier analysis, and the log-rank test. Univariate (Kaplan-Meier/Cox-regression) and multivariate (Cox-regression) analysis showed that the TTP gene polymorphism ZFP36*2 A>G was significantly associated with poor prognosis of Caucasian patients (HR = 2.03; 95% CI = 1.09–3.76; P = 0.025; log-rank P = 0.022). None of the haplotypes, but presence of more than six risk genotypes in Caucasian patients, was significantly associated with poor prognosis (HR=2.42; 95% CI=1.17–4.99; P = 0.017; log-rank P = 0.007). The effect of ZFP36*2 A>G on gene expression was evaluated from patients' tissue samples. Both TTP mRNA and protein expression was significantly decreased in ZFP36*2 G allele carriers compared to A allele homozygotes. Conversely, upregulation of the TTP-target gene COX-2 was observed ZFP36*2 G allele carriers. Through its ability to attenuate TTP gene expression, the ZFP36*2 A>G gene polymorphism has appeared as a novel prognostic breast cancer marker in Caucasian patients. PMID:22907529

A generalized multivariate regression model for modelling ocean wave heights

NASA Astrophysics Data System (ADS)

Wang, X. L.; Feng, Y.; Swail, V. R.

2012-04-01

In this study, a generalized multivariate linear regression model is developed to represent the relationship between 6-hourly ocean significant wave heights (Hs) and the corresponding 6-hourly mean sea level pressure (MSLP) fields. The model is calibrated using the ERA-Interim reanalysis of Hs and MSLP fields for 1981-2000, and is validated using the ERA-Interim reanalysis for 2001-2010 and ERA40 reanalysis of Hs and MSLP for 1958-2001. The performance of the fitted model is evaluated in terms of Pierce skill score, frequency bias index, and correlation skill score. Being not normally distributed, wave heights are subjected to a data adaptive Box-Cox transformation before being used in the model fitting. Also, since 6-hourly data are being modelled, lag-1 autocorrelation must be and is accounted for. The models with and without Box-Cox transformation, and with and without accounting for autocorrelation, are inter-compared in terms of their prediction skills. The fitted MSLP-Hs relationship is then used to reconstruct historical wave height climate from the 6-hourly MSLP fields taken from the Twentieth Century Reanalysis (20CR, Compo et al. 2011), and to project possible future wave height climates using CMIP5 model simulations of MSLP fields. The reconstructed and projected wave heights, both seasonal means and maxima, are subject to a trend analysis that allows for non-linear (polynomial) trends.

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

Functional Gain After Inpatient Stroke Rehabilitation: Correlates and Impact on Long-Term Survival.

PubMed

Scrutinio, Domenico; Monitillo, Vincenzo; Guida, Pietro; Nardulli, Roberto; Multari, Vincenzo; Monitillo, Francesco; Calabrese, Gianluigi; Fiore, Pietro

2015-10-01

Prediction of functional outcome after stroke rehabilitation (SR) is a growing field of interest. The association between SR and survival still remains elusive. We sought to investigate the factors associated with functional outcome after SR and whether the magnitude of functional improvement achieved with rehabilitation is associated with long-term mortality risk. The study population consisted of 722 patients admitted for SR within 90 days of stroke onset, with an admission functional independence measure (FIM) score of <80 points. We used univariable and multivariable linear regression analyses to assess the association between baseline variables and FIM gain and univariable and multivariable Cox analyses to assess the association of FIM gain with long-term mortality. Age (P<0.001), marital status (P=0.003), time from stroke onset to rehabilitation admission (P<0.001), National Institutes of Health Stroke Scale score at rehabilitation admission (P<0.001), and aphasia (P=0.021) were independently associated with FIM gain. The R2 of the model was 0.275. During a median follow-up of 6.17 years, 36.9% of the patients died. At multivariable Cox analysis, age (P<0.0001), coronary heart disease (P=0.018), atrial fibrillation (P=0.042), total cholesterol (P=0.015), and total FIM gain (P<0.0001) were independently associated with mortality. The adjusted hazard ratio for death significantly decreased across tertiles of increasing FIM gain. Several factors are independently associated with functional gain after SR. Our findings strongly suggest that the magnitude of functional improvement is a powerful predictor of long-term mortality in patients admitted for SR. © 2015 American Heart Association, Inc.

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.

Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer.

PubMed

Beard, C J; Chen, M H; Cote, K; Loffredo, M; Renshaw, A A; Hurwitz, M; D'Amico, A V

2004-01-01

To investigate the risk of postradiotherapy prostate-specific antigen (PSA) failure on the basis of pretreatment risk factors in prostate cancer patients with and without perineural invasion (PNI) in prostate biopsy specimens and to explain the observation that otherwise low-risk patients with PNI experience decreased freedom from PSA failure after external beam radiotherapy (RT). The study cohort consisted of 381 patients who underwent RT between 1989 and 2000 for clinically localized prostate cancer. A single genitourinary pathologist scored the absence or presence of PNI on all prostate biopsy specimens. Patients were divided into low-, intermediate- and high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and multivariate analyses were performed to evaluate whether the presence or absence of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure for patients in each pretreatment risk group. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. Cox regression univariate analysis revealed that PNI was a significant predictor of the time to PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5-year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk patients, 70% vs. 75% (p = 0.72) in intermediate-risk patients, and 29% vs. 53% (p = 0.03) in high-risk patients with and without PNI, respectively. Cox regression multivariate analysis within the high-risk group revealed that a PSA level > or =20 ng/mL (p = 0.01) and Gleason score > or =8 (p = 0.02), but not PNI, were the only significant predictors of the time to PSA failure after RT. However, an association was found between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association was stronger between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 7-10 (p = 0. 033). A decrement in PSA outcome after RT for low-risk patients with PNI-positive biopsy specimens was found. The association between PNI and high Gleason score provides a possible explanation for the loss of statistical significance of PNI in the Cox regression multivariate analysis of the high-risk cohort. The data suggest that PNI found in the biopsy specimen of an otherwise low-risk patient predicts for occult high-grade disease that is missed owing to the sampling error associated with prostate biopsy. The association between PNI and a high Gleason score argues for the use of more aggressive therapy, such as hormonal therapy with RT and/or dose escalation, in these select patients.

Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: A multi-institutional study.

PubMed

Lee, Young Chan; Na, Se Young; Park, Gi Cheol; Han, Ju Hyun; Kim, Seung Woo; Eun, Young Gyu

2017-02-01

The impact of occult lymph node metastasis on regional recurrence after prophylactic central neck dissection for preoperative, nodal-negative papillary thyroid cancer is controversial. We investigated risk factors for regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Analysis was according to clinicopathologic characteristics and occult lymph node metastasis patterns. This multicenter study enrolled 211 consecutive patients who underwent total thyroidectomy with bilateral prophylactic central neck dissection for papillary thyroid cancer without evidence of central lymph node metastasis on preoperative imaging. Clinicopathologic features and central lymph node metastasis patterns were analyzed for predicting regional recurrence. Multivariate Cox regression analysis was used to identify independent factors for recurrence. Median follow-up time was 43 months (24-95 months). Ten patients (4.7%) showed regional lymph node recurrence. The estimated 5-year, regional recurrence-free survival was 95.2%. Tumor size ≥1 cm, central lymph node metastasis, lymph node ratio, and prelaryngeal lymph node metastasis were associated with regional recurrence in univariate analysis (P < .05). In multivariate analysis, a lymph node ratio ≥ 0.26 was a significant risk factor for regional lymph node recurrence (odds ratio = 11.63, P = .003). Lymph node ratio ≥ 0.26 was an independent predictor of worse recurrence-free survival on Cox regression analysis (hazard ratio = 11.49, P = .002). Although no significant association was observed between the presence of occult lymph node metastasis and regional recurrence, lymph node ratio ≥ 0.26 was an independent predictor of regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemokine-like factor-like MARVEL transmembrane domain-containing 3 expression is associated with a favorable prognosis in esophageal squamous cell carcinoma.

PubMed

Han, Tianci; Shu, Tianci; Dong, Siyuan; Li, Peiwen; Li, Weinan; Liu, Dali; Qi, Ruiqun; Zhang, Shuguang; Zhang, Lin

2017-05-01

Decreased expression of human chemokine-like factor-like MARVEL transmembrane domain-containing 3 (CMTM3) has been identified in a number of human tumors and tumor cell lines, including gastric and testicular cancer, and PC3, CAL27 and Tca-83 cell lines. However, the association between CMTM3 expression and the clinicopathological features and prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. The aim of the present study was to investigate the correlation between CMTM3 expression and clinicopathological parameters and prognosis in ESCC. CMTM3 mRNA and protein expression was analyzed in ESCC and paired non-tumor tissues by quantitative real-time polymerase chain reaction, western blotting and immunohistochemical analysis. The Kaplan-Meier method was used to plot survival curves and the Cox proportional hazards regression model was also used for univariate and multivariate survival analysis. The results revealed that CMTM3 mRNA and protein expression levels were lower in 82.5% (30/40) and 75% (30/40) of ESCC tissues, respectively, when compared with matched non-tumor tissues. Statistical analysis demonstrated that CMTM3 expression was significantly correlated with lymph node metastasis (P=0.002) and clinical stage (P<0.001) in ESCC tissues. Furthermore, the survival time of ESCC patients exhibiting low CMTM3 expression was significantly shorter than that of ESCC patients exhibiting high CMTM3 expression (P=0.01). In addition, Kaplan-Meier survival analysis revealed that the overall survival time of patients exhibiting low CMTM3 expression was significantly decreased compared with patients exhibiting high CMTM3 expression (P=0.010). Cox multivariate analysis indicated that CMTM3 protein expression was an independent prognostic predictor for ESCC after resection. This study indicated that CMTM3 expression is significantly decreased in ESCC tissues and CMTM3 protein expression in resected tumors may present an effective prognostic biomarker.

Kidney transplantation from deceased donors with elevated serum creatinine.

PubMed

Gallinat, Anja; Leerhoff, Sabine; Paul, Andreas; Molmenti, Ernesto P; Schulze, Maren; Witzke, Oliver; Sotiropoulos, Georgios C

2016-12-01

Elevated donor serum creatinine has been associated with inferior graft survival in kidney transplantation (KT). The aim of this study was to evaluate the impact of elevated donor serum creatinine on short and long-term outcomes and to determine possible ways to optimize the use of these organs. All kidney transplants from 01-2000 to 12-2012 with donor creatinine ≥ 2 mg/dl were considered. Risk factors for delayed graft function (DGF) were explored with uni- and multivariate regression analyses. Donor and recipient data were analyzed with uni- and multivariate cox proportional hazard analyses. Graft and patient survival were calculated using the Kaplan-Meier method. Seventy-eight patients were considered. Median recipient age and waiting time on dialysis were 53 years and 5.1 years, respectively. After a median follow-up of 6.2 years, 63 patients are alive. 1, 3, and 5-year graft and patient survival rates were 92, 89, and 89 % and 96, 93, and 89 %, respectively. Serum creatinine level at procurement and recipient's dialysis time prior to KT were predictors of DGF in multivariate analysis (p = 0.0164 and p = 0.0101, respectively). Charlson comorbidity score retained statistical significance by multivariate regression analysis for graft survival (p = 0.0321). Recipient age (p = 0.0035) was predictive of patient survival by multivariate analysis. Satisfactory long-term kidney transplant outcomes in the setting of elevated donor serum creatinine ≥2 mg/dl can be achieved when donor creatinine is <3.5 mg/dl, and the recipient has low comorbidities, is under 56 years of age, and remains in dialysis prior to KT for <6.8 years.

Prognostic Impact of Neutrophil/Lymphocyte Ratio, Platelet Count, CRP, and Albumin Levels in Metastatic Colorectal Cancer Patients Treated with FOLFIRI-Bevacizumab.

PubMed

Artaç, Mehmet; Uysal, Mükremin; Karaağaç, Mustafa; Korkmaz, Levent; Er, Zehra; Güler, Tunç; Börüban, Melih Cem; Bozcuk, Hakan

2017-06-01

Metastatic colorectal cancer (mCRC) is a lethal disease and fluorouracil-leucovorin-irinotecan (FOLFIRI) plus bevacizumab (bev) is a standard approach. Hence, there is a strong need for identifying new prognostic factors to show the efficacy of FOLFIRI-bev. This is a retrospective study including patients (n = 90) with mCRC from two centers in Turkey. Neutrophil/lymphocyte (N/L) ratio, platelet count, albumin, and C-reactive protein (CRP) were recorded before FOLFIRI-bev therapy. The efficacy of these factors on progression-free survival (PFS) was analyzed with Kaplan Meier and Cox regression analysis. And the cutoff value of N/L ratio was analyzed with ROC analysis. The median age was 56 years (range 21-80). Forty-seven percent of patients with N/L ratio >2.5 showed progressive disease versus 43 % in patients with N/L ratio <2.5 (p = 0.025). The median PFS was 8.1 months for the patients with N/L ratio >2.5 versus 13.5 months for the patients with N/L ratio <2.5 (p = 0.025). At univariate Cox regression analysis, high baseline neutrophil count, LDH, N/L ratio, and CRP were all significantly associated with poor prognosis. At multivariate Cox regression analysis, CRP was confirmed to be a better independent prognostic factor. CRP variable was divided into above the upper limit of normal (ULN) and normal value. The median PFSs of the patients with normal and above ULN were 11.3 versus 5.8 months, respectively (p = 0.022). CRP and N/L ratio are potential predictors for advanced mCRC treated with FOLFIRI-bev.

Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort.

PubMed

López-Cortés, L E; Almirante, B; Cuenca-Estrella, M; Garnacho-Montero, J; Padilla, B; Puig-Asensio, M; Ruiz-Camps, I; Rodríguez-Baño, J

2016-08-01

We compared the clinical efficacy of fluconazole and echinocandins in the treatment of candidemia in real practice. The CANDIPOP study is a prospective, population-based cohort study on candidemia carried out between May 2010 and April 2011 in 29 Spanish hospitals. Using strict inclusion criteria, we separately compared the impact of empirical and targeted therapy with fluconazole or echinocandins on 30-day mortality. Cox regression, including a propensity score (PS) for receiving echinocandins, stratified analysis on the PS quartiles and PS-based matched analyses, were performed. The empirical and targeted therapy cohorts comprised 316 and 421 cases, respectively; 30-day mortality was 18.7% with fluconazole and 33.9% with echinocandins (p 0.02) in the empirical therapy group and 19.8% with fluconazole and 27.7% with echinocandins (p 0.06) in the targeted therapy group. Multivariate Cox regression analysis including PS showed that empirical therapy with fluconazole was associated with better prognosis (adjusted hazard ratio 0.38; 95% confidence interval 0.17-0.81; p 0.01); no differences were found within each PS quartile or in cases matched according to PS. Targeted therapy with fluconazole did not show a significant association with mortality in the Cox regression analysis (adjusted hazard ratio 0.77; 95% confidence interval 0.41-1.46; p 0.63), in the PS quartiles or in PS-matched cases. The results were similar among patients with severe sepsis and septic shock. Empirical or targeted treatment with fluconazole was not associated with increased 30-day mortality compared to echinocandins among adults with candidemia. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Back to Normal! Gaussianizing posterior distributions for cosmological probes

NASA Astrophysics Data System (ADS)

Schuhmann, Robert L.; Joachimi, Benjamin; Peiris, Hiranya V.

2014-05-01

We present a method to map multivariate non-Gaussian posterior probability densities into Gaussian ones via nonlinear Box-Cox transformations, and generalizations thereof. This is analogous to the search for normal parameters in the CMB, but can in principle be applied to any probability density that is continuous and unimodal. The search for the optimally Gaussianizing transformation amongst the Box-Cox family is performed via a maximum likelihood formalism. We can judge the quality of the found transformation a posteriori: qualitatively via statistical tests of Gaussianity, and more illustratively by how well it reproduces the credible regions. The method permits an analytical reconstruction of the posterior from a sample, e.g. a Markov chain, and simplifies the subsequent joint analysis with other experiments. Furthermore, it permits the characterization of a non-Gaussian posterior in a compact and efficient way. The expression for the non-Gaussian posterior can be employed to find analytic formulae for the Bayesian evidence, and consequently be used for model comparison.

Multivariate probability distribution for sewer system vulnerability assessment under data-limited conditions.

PubMed

Del Giudice, G; Padulano, R; Siciliano, D

2016-01-01

The lack of geometrical and hydraulic information about sewer networks often excludes the adoption of in-deep modeling tools to obtain prioritization strategies for funds management. The present paper describes a novel statistical procedure for defining the prioritization scheme for preventive maintenance strategies based on a small sample of failure data collected by the Sewer Office of the Municipality of Naples (IT). Novelty issues involve, among others, considering sewer parameters as continuous statistical variables and accounting for their interdependences. After a statistical analysis of maintenance interventions, the most important available factors affecting the process are selected and their mutual correlations identified. Then, after a Box-Cox transformation of the original variables, a methodology is provided for the evaluation of a vulnerability map of the sewer network by adopting a joint multivariate normal distribution with different parameter sets. The goodness-of-fit is eventually tested for each distribution by means of a multivariate plotting position. The developed methodology is expected to assist municipal engineers in identifying critical sewers, prioritizing sewer inspections in order to fulfill rehabilitation requirements.

Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes.

PubMed

Cobleigh, Melody A; Tabesh, Bita; Bitterman, Pincas; Baker, Joffre; Cronin, Maureen; Liu, Mei-Lan; Borchik, Russell; Mosquera, Juan-Miguel; Walker, Michael G; Shak, Steven

2005-12-15

This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer patients. Patients with >or=10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS. Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.

Seven protective miRNA signatures for prognosis of cervical cancer.

PubMed

Liu, Bei; Ding, Jin-Feng; Luo, Jian; Lu, Li; Yang, Fen; Tan, Xiao-Dong

2016-08-30

Cervical cancer is the second cause of cancer death in females in their 20s and 30s, but there were limited studies about its prognosis. This study aims to identify miRNA related to prognosis and study their functions. TCGA data of patients with cervical cancer were used to build univariate Cox's model with single clinical parameter or miRNA expression level. Multivariate Cox's model was built using both clinical information and miRNA expression levels. At last, STRING was used to enrich gene ontology or pathway for validated targets of significant miRNAs, and visualize the interactions among them. Using univariate Cox's model with clinical parameters, we found that two clinical parameters, tobacco use and clinical stage, and seven miRNAs were highly correlated with the survival status. Only using the expression level of miRNA signatures, the model could separate patients into high-risk and low-risk groups successfully. An optimal feature-selected model was proposed based on two clinical parameters and seven miRNAs. Functional analysis of these seven miRNAs showed they were associated to various pathways related to cancer, including MAPK, VEGF and P53 pathways. These results helped the research of identifying targets for targeted therapy which could potentially allow tailoring of treatment for cervical cancer patients.

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.

Incidence and risk factors of postoperative pneumonia following cancer surgery in adult patients with selected solid cancer: results of "Cancer POP" study.

PubMed

Jung, Jiwon; Moon, Song Mi; Jang, Hee-Chang; Kang, Cheol-In; Jun, Jae-Bum; Cho, Yong Kyun; Kang, Seung-Ji; Seo, Bo-Jeong; Kim, Young-Joo; Park, Seong-Beom; Lee, Juneyoung; Yu, Chang Sik; Kim, Sung-Han

2018-01-01

The aim of this study was to investigate the incidence and risk factors of postoperative pneumonia (POP) within 1 year after cancer surgery in patients with the five most common cancers (gastric, colorectal, lung, breast cancer, and hepatocellular carcinoma [HCC]) in South Korea. This was a multicenter and retrospective cohort study performed at five nationwide cancer centers. The number of cancer patients in each center was allocated by the proportion of cancer surgery. Adult patients were randomly selected according to the allocated number, among those who underwent cancer surgery from January to December 2014 within 6 months after diagnosis of cancer. One-year cumulative incidence of POP was estimated using Kaplan-Meier analysis. An univariable Cox's proportional hazard regression analysis was performed to identify risk factors for POP development. As a multivariable analysis, confounders were adjusted using multiple Cox's PH regression model. Among the total 2000 patients, the numbers of patients with gastric cancer, colorectal cancer, lung cancer, breast cancer, and HCC were 497 (25%), 525 (26%), 277 (14%), 552 (28%), and 149 (7%), respectively. Overall, the 1-year cumulative incidence of POP was 2.0% (95% CI, 1.4-2.6). The 1-year cumulative incidences in each cancer were as follows: lung 8.0%, gastric 1.8%, colorectal 1.0%, HCC 0.7%, and breast 0.4%. In multivariable analysis, older age, higher Charlson comorbidity index (CCI) score, ulcer disease, history of pneumonia, and smoking were related with POP development. In conclusions, the 1-year cumulative incidence of POP in the five most common cancers was 2%. Older age, higher CCI scores, smoker, ulcer disease, and previous pneumonia history increased the risk of POP development in cancer patients. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Predictors of clinical outcome in pediatric oligodendroglioma: meta-analysis of individual patient data and multiple imputation.

PubMed

Wang, Kevin Yuqi; Vankov, Emilian R; Lin, Doris Da May

2018-02-01

OBJECTIVE Oligodendroglioma is a rare primary CNS neoplasm in the pediatric population, and only a limited number of studies in the literature have characterized this entity. Existing studies are limited by small sample sizes and discrepant interstudy findings in identified prognostic factors. In the present study, the authors aimed to increase the statistical power in evaluating for potential prognostic factors of pediatric oligodendrogliomas and sought to reconcile the discrepant findings present among existing studies by performing an individual-patient-data (IPD) meta-analysis and using multiple imputation to address data not directly available from existing studies. METHODS A systematic search was performed, and all studies found to be related to pediatric oligodendrogliomas and associated outcomes were screened for inclusion. Each study was searched for specific demographic and clinical characteristics of each patient and the duration of event-free survival (EFS) and overall survival (OS). Given that certain demographic and clinical information of each patient was not available within all studies, a multivariable imputation via chained equations model was used to impute missing data after the mechanism of missing data was determined. The primary end points of interest were hazard ratios for EFS and OS, as calculated by the Cox proportional-hazards model. Both univariate and multivariate analyses were performed. The multivariate model was adjusted for age, sex, tumor grade, mixed pathologies, extent of resection, chemotherapy, radiation therapy, tumor location, and initial presentation. A p value of less than 0.05 was considered statistically significant. RESULTS A systematic search identified 24 studies with both time-to-event and IPD characteristics available, and a total of 237 individual cases were available for analysis. A median of 19.4% of the values among clinical, demographic, and outcome variables in the compiled 237 cases were missing. Multivariate Cox regression analysis revealed subtotal resection (p = 0.007 [EFS] and 0.043 [OS]), initial presentation of headache (p = 0.006 [EFS] and 0.004 [OS]), mixed pathologies (p = 0.005 [EFS] and 0.049 [OS]), and location of the tumor in the parietal lobe (p = 0.044 [EFS] and 0.030 [OS]) to be significant predictors of tumor progression or recurrence and death. CONCLUSIONS The use of IPD meta-analysis provides a valuable means for increasing statistical power in investigations of disease entities with a very low incidence. Missing data are common in research, and multiple imputation is a flexible and valid approach for addressing this issue, when it is used conscientiously. Undergoing subtotal resection, having a parietal tumor, having tumors with mixed pathologies, and suffering headaches at the time of diagnosis portended a poorer prognosis in pediatric patients with oligodendroglioma.

Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model

PubMed Central

Li, Fang-Hui; Li, Tao; Ai, Jing-Yi; Sun, Lei; Min, Zhu; Duan, Rui; Zhu, Ling; Liu, Yan-ying; Liu, Timon Cheng-Yi

2018-01-01

The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (1H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague–Dawley rats were separated into three groups: sedentary control (SED), MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio) in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1H NMR spectroscopy and multivariate statistical analysis identified 11 metabolites in plasma, among which fine significantly and similarly changed after both HIIT and MICT, while BCAAs isoleucine, leucine, and valine and glutamine were changed only after HIIT. Together, these data indicate distinct differences in specific metabolites and autophagy and mitochondrial markers following HIIT vs. MICT and highlight the value of metabolomic analysis in providing more detailed insight into the metabolic adaptations to exercise training. PMID:29875683

Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model.

PubMed

Li, Fang-Hui; Li, Tao; Ai, Jing-Yi; Sun, Lei; Min, Zhu; Duan, Rui; Zhu, Ling; Liu, Yan-Ying; Liu, Timon Cheng-Yi

2018-01-01

The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance ( 1 H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague-Dawley rats were separated into three groups: sedentary control (SED), MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1 H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio) in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1 H NMR spectroscopy and multivariate statistical analysis identified 11 metabolites in plasma, among which fine significantly and similarly changed after both HIIT and MICT, while BCAAs isoleucine, leucine, and valine and glutamine were changed only after HIIT. Together, these data indicate distinct differences in specific metabolites and autophagy and mitochondrial markers following HIIT vs. MICT and highlight the value of metabolomic analysis in providing more detailed insight into the metabolic adaptations to exercise training.

The relationship between the effect of pravastatin and risk factors for coronary heart disease in Japanese patients with hypercholesterolemia.

PubMed

Ishikawa, Toshitsugu; Mizuno, Kyoichi; Nakaya, Noriaki; Ohashi, Yasuo; Tajima, Naoko; Kushiro, Toshio; Teramoto, Tamio; Uchiyama, Shinichiro; Nakamura, Haruo

2008-10-01

Several epidemiologic studies in Japan have shown the risk factors for coronary heart disease (CHD) in the general population. The present analysis determined the risk factors for CHD in the MEGA Study, a large primary prevention trial with pravastatin in Japanese with hypercholesterolemia. The relationship between each baseline characteristic and the risk of CHD for the 5-year study period were evaluated using the Cox proportional hazard model. The multivariable predictors of CHD were sex, age, high-density lipoprotein-cholesterol (HDL-C), diabetes mellitus (DM), hypertension (HT), and history of smoking. Serum total and low-density lipoprotein-cholesterol were not independent risk factors for CHD in the current analysis. In addition, the effect of pravastatin was evaluated by subgroups in each risk factor using the interaction in a Cox model. Diet plus pravastatin treatment reduced CHD risk by 14-43% compared with diet alone, regardless of the presence or absence of risk factors. The risk factors for CHD were sex, age, DM, HT, smoking, and low HDL-C in the MEGA Study. The pravastatin treatment was effective for reducing the risk of CHD, regardless of the presence of risk factors.

Chemotherapy Versus Chemoradiation for Node-Positive Bladder Cancer: Practice Patterns and Outcomes from the National Cancer Data Base

PubMed Central

Haque, Waqar; Verma, Vivek; Butler, E. Brian; Teh, Bin S.

2017-01-01

Background: Management of clinically node-positive bladder cancer (cN+ BC) is poorly defined; national guidelines recommend chemotherapy (CT) alone or chemoradiation (CRT). Objective: Using a large, contemporary dataset, we evaluated national practice patterns and outcomes of CT versus CRT to elucidate the optimal therapy for this patient population. Methods: The National Cancer Data Base (NCDB) was queried (2004–2013) for patients diagnosed with cTanyN1-3M0 BC. Patients were divided into two groups: CT alone or CRT. Statistics included multivariable logistic regression to determine factors predictive of receiving additional radiotherapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. Propensity score matching was performed to assess groups in a balanced manner while reducing indication biases. Results: Of 1,783 total patients, 1,388 (77.8%) underwent CT alone, and 395 (22.2%) CRT. Although patients receiving CRT tended to be of higher socioeconomic status, they were more likely older (p = 0.053), higher T stage, N1 (versus N2) disease, squamous histology, and treated at a non-academic center (p < 0.05). Median overall survival (OS) was 19.0 months and 13.8 months (p < 0.001) for patients receiving CRT or CT, respectively. On Cox multivariate analysis, receipt of CRT was independently associated with improved survival (p < 0.001). Outcome improvements with CRT persisted on evaluation of propensity-matched populations (p < 0.001). Conclusions: CRT is underutilized in the United States for cN+ BC but is independently associated with improved survival despite being preferentially administered to a somewhat higher-risk population. PMID:29152552

The relationship of age-adjusted Charlson comorbidity ındex and diurnal variation of blood pressure.

PubMed

Kalaycı, Belma; Erten, Yunus Turgay; Akgün, Tunahan; Karabag, Turgut; Kokturk, Furuzan

2018-03-05

Charlson Comorbidity index (CCI) is a scoring system to predict prognosis and mortality. It exhibits better utility when combined with age, age-adjusted Charlson Comorbidity Index (ACCI). The aim of this study was to evaluate the relationship between ACCI and diurnal variation of blood pressure parameters in hypertensive patients and normotensive patients. We enrolled 236 patients. All patients underwent a 24-h ambulatory blood pressure monitoring (ABPM) for evaluation of dipper or non-dipper pattern. We searched the correlation between ACCI and dipper or non-dipper pattern and other ABPM parameters. To further investigate the role of these parameters in predicting survival, a multivariate analysis using the Cox proportional hazard model was performed. 167 patients were in the hypertensive group (87 patients in non-dipper status) and 69 patients were in the normotensive group (41 patients in non-dipper status) of all study patients. We found a significant difference and negative correlation between AACI and 24-h diastolic blood pressure (DBP), awake DBP, awake mean blood pressure (MBP) and 24-h MBP and awake systolic blood pressure(SBP). Night decrease ratio of blood pressure had also a negative correlation with ACCI (p = 0.003, r = -0.233). However, we found a relationship with non-dipper pattern and ACCI in the hypertensive patients (p = 0.050). In multivariate Cox analysis sleep MBP was found related to mortality like ACCI (p = 0.023, HR = 1.086, %95 CI 1.012-1.165) Conclusion: ACCI was statistically significantly higher in non-dipper hypertensive patients than dipper hypertensive patients while ACCI had a negative correlation with blood pressure. Sleep MBP may predict mortality.

Marital status and survival of patients with oral cavity squamous cell carcinoma: a population-based study.

PubMed

Shi, Xiao; Zhang, Ting-Ting; Hu, Wei-Ping; Ji, Qing-Hai

2017-04-25

The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187-1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266-1.392, P < 0.001). Multivariate logistic regression showed married patients were more likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P < 0.001). Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role.

Marital status and survival of patients with oral cavity squamous cell carcinoma: a population-based study

PubMed Central

Shi, Xiao; Zhang, Ting-ting; Hu, Wei-ping; Ji, Qing-hai

2017-01-01

Background The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Results Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187–1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266–1.392, P < 0.001). Multivariate logistic regression showed married patients were more likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P < 0.001). Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). Materials and Methods 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. Conclusions Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role. PMID:28415710

Herpes zoster could be an early manifestation of undiagnosed human immunodeficiency virus infection.

PubMed

Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu; Chen, Wen-Chi

2016-05-01

No formal epidemiological research based on systematic analysis has focused on the relationship between herpes zoster and immunodeficiency virus (HIV) infection in Taiwan. Our aim was to explore whether herpes zoster is an early manifestation of undiagnosed human HIV infection in Taiwan. This was a retrospective cohort study using the database of the Taiwan National Health Insurance Program. A total of 35,892 individuals aged ≤ 84 years with newly diagnosed herpes zoster from 1998 to 2010 were assigned to the herpes zoster group, whereas 143,568 sex-matched and age-matched, randomly selected individuals without herpes zoster served as the non-herpes zoster group. The incidence of HIV diagnosis at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence interval (CI) for risk of HIV diagnosis associated with herpes zoster and other comorbidities including drug dependence and venereal diseases. The overall incidence of HIV diagnosis was 4.19-fold greater in the herpes zoster group than that in the non-herpes zoster group (3.33 per 10,000 person-years vs. 0.80 per 10,000 person-years, 95% CI 4.04-4.35). The multivariable Cox proportional hazards regression analysis revealed that the adjusted hazard ratio of HIV diagnosis was 4.37 (95% CI 3.10-6.15) for individuals with herpes zoster and without comorbidities, as compared with individuals without herpes zoster and without comorbidities. Herpes zoster is associated with HIV diagnosis. Patients who have risk behaviors of HIV infection should receive regular surveillance for undiagnosed HIV infection when they present with herpes zoster. Copyright © 2015. Published by Elsevier B.V.

Body weight changes in patients undergoing chemotherapy for ovarian cancer influence progression-free and overall survival.

PubMed

Mardas, Marcin; Stelmach-Mardas, Marta; Madry, Radosław

2017-03-01

The aim of this study was to evaluate whether body weight changes in patients undergoing chemotherapy for epithelial ovarian cancer (EOC) influence progression-free survival (PFS) and overall survival (OS). An analysis of 190 patients diagnosed with ovarian cancer after first-line chemotherapy was conducted. Changes in body weight were assessed by comparing measurements at baseline to those of the third and sixth cycles of chemotherapy. PFS and OS were calculated with the Kaplan-Meier method and multivariate Cox model. Significant reduction in body weight in advanced EOC was observed with no changes in early EOC. Significant differences in PFS were observed in advanced EOC patients that lost more than 5 % of their body weight (6 months), maintained weight (13 months), or gained more than 5 % of their body weight (15 months). Similarly, significant differences in OS were noted in advanced EOC at the following time points: 24.3, 42.4, and 66.2 months. No effect was reported for early EOC patients. The multivariate Cox analysis showed significant body weight changes from the first to the sixth chemotherapy cycle for PFS (HR = 0.97; 95 % CI 0.95-0.99) and OS (HR = 0.94; 95 % CI 0.91-0.97) as well as from the first to the third chemotherapy cycle for OS (HR = 0.93; 95 % CI 0.88-0.98). Body weight changes can be recognized as a prognostic factor for PFS and OS in advanced EOC patients undergoing chemotherapy. Weight loss is associated with poorer survival while weight gain improved outcomes.

Combined caveolin-1 and epidermal growth factor receptor expression as a prognostic marker for breast cancer.

PubMed

Liang, Ya-Nan; Liu, Yu; Wang, Letian; Yao, Guodong; Li, Xiaobo; Meng, Xiangning; Wang, Fan; Li, Ming; Tong, Dandan; Geng, Jingshu

2018-06-01

Previous studies have indicated that caveolin-1 (Cav-1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav-1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav-1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan-Meier estimator curves and the log-rank test. Stromal Cav-1 was downregulated in 38.56% (118/306) of tumor tissues, whereas cytoplasmic EGFR and Cav-1 were overexpressed in 53.92% (165/306) and 44.12% (135/306) of breast cancer tissues, respectively. EGFR expression was positively associated with cytoplasmic Cav-1 and not associated with stromal Cav-1 expression in breast cancer samples; however, low expression of stromal Cav-1 was negatively associated with cytoplasmic Cav-1 expression in total tumor tissues, and analogous results were identified in the chemotherapy group. Multivariate Cox's proportional hazards model analysis revealed that, for patients in the estrogen receptor (ER)(+) group, the expression of stromal Cav-1 alone was a significant prognostic marker of breast cancer. However, in the chemotherapy, human epidermal growth factor receptor 2 (HER-2)(-), HER-2(+) and ER(-) groups, the use of combined markers was more effective prognostic marker. Stromal Cav-1 has a tumor suppressor function, and the combined marker stromal Cav-1/EGFR expression was identified as an improved prognostic marker in the diagnosis of breast cancer. Parenchymal expression of Cav-1 is able to promote EGFR signaling in breast cancer, potentially being required for EGFR-mediated initiation of mitosis.

Characteristics and Outcomes of Patients with Ewing Sarcoma Over 40 Years of Age at Diagnosis

PubMed Central

Karski, Erin E.; Matthay, Katherine K.; Neuhaus, John M.; Goldsby, Robert E.; DuBois, Steven G.

2012-01-01

Background The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥ 40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. Methods This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥ 40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan-Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Results Patients ≥ 40 years of age were more likely to have extra-skeletal tumors (66.1% v 31.7%; p<0.001), axial tumors (64.0% v 57.2%; p=0.01), and metastatic disease at diagnosis (35.5% v 30.0%; p=0.04) compared to younger patients. Five-year survival for those age ≥ 40 and age < 40 were 40.6% and 54.3%, respectively (p<0.0001). A Cox multivariable model controlling for differences between groups confirmed inferior survival for older patients (hazard ratio for death of 2.04; 95% CI 1.63 - 2.54; p < 0.0001); though treatment data were unavailable and not controlled for in the model. A competing risks analysis confirmed increased risk of cancer-related death in older patients. Conclusion Patients ≥ 40 years at diagnosis with EWS are more likely to have extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate. PMID:22959474

Characteristics and outcomes of patients with Ewing sarcoma over 40 years of age at diagnosis.

PubMed

Karski, Erin E; Matthay, Katherine K; Neuhaus, John M; Goldsby, Robert E; Dubois, Steven G

2013-02-01

The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan-Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Patients ≥40 years of age were more likely to have extra-skeletal tumors (66.1% vs. 31.7%; p < 0.001), axial tumors (64.0% vs. 57.2%; p = 0.01), and metastatic disease at diagnosis (35.5% vs. 30.0%; p = 0.04) compared to younger patients. Five-year survival for those age ≥40 and age <40 were 40.6% and 54.3%, respectively (p < 0.0001). A Cox multivariable model controlling for differences between groups confirmed inferior survival for older patients (hazard ratio for death of 2.04; 95% CI 1.63-2.54; p < 0.0001); though treatment data were unavailable and not controlled for in the model. A competing risks analysis confirmed increased risk of cancer-related death in older patients. Patients ≥40 years at diagnosis with EWS are more likely to have extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate. Copyright © 2012 Elsevier Ltd. All rights reserved.

Undernutrition as independent predictor of early mortality in elderly cancer patients.

PubMed

Martucci, Renata B; Barbosa, Mariana V; D'Almeida, Cristiane A; Rodrigues, Viviane D; Bergmann, Anke; de Pinho, Nivaldo B; Thuler, Luiz Claudio S

2017-02-01

The aim of this study was to evaluate the 1-y survival of elderly patients with cancer and the association between undernutrition and mortality. This was a cohort study with elderly patients ages ≥65 y admitted between September and October 2014. A nutritionist performed a Mini Nutritional Assessment-Short Form (MNA-SF) assessment during 48 h of hospital admission and collected data about potential confounding variables (comorbidities, stage of cancer, treatment in the previous 3 mo, and reason for hospitalization). Vital status was determined from the medical records or public records office. Overall survival was estimated using the Kaplan-Meier method. Cox regression was performed to estimate unadjusted hazard ratios. Variables with P < 0.20 by univariate analysis were selected for multivariate analysis. P < 0.05 was considered statistically significant. Of the 136 patients (mean age, 73.1 y; 52.2% men), 29.4%, 41.2%, and 29.4% were classified as normal, at risk for undernutrition, and undernutrition, respectively, according to the MNA-SF. The mortality rate was 31.6% after 12 mo. One-year mortality was higher among the undernourished patients, followed by patients at risk for undernutrition. After adjustment for confounding variables, the multivariate regression Cox model showed that being undernourished according to the MNA-SF increased the risk for death at 1 y (hazard ratio, 5.59; 95% confidence interval, 1.8-17.3; P < 0.001). The results showed that the MNA-SF can be a useful tool in identifying elderly patients at higher risk for 1-y mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

The incidence and prevalence of pterygium in South Korea: A 10-year population-based Korean cohort study.

PubMed

Rim, Tyler Hyungtaek; Kang, Min Jae; Choi, Moonjung; Seo, Kyoung Yul; Kim, Sung Soo

2017-01-01

Although numerous population-based studies have reported the prevalences and risk factors for pterygium, information regarding the incidence of pterygium is scarce. This population-based cohort study aimed to evaluate the South Korean incidence and prevalence of pterygium. We retrospectively obtained data from a nationally representative sample of 1,116,364 South Koreans in the Korea National Health Insurance Service National Sample Cohort (NHIS-NSC). The associated sociodemographic factors were evaluated using multivariable Cox regression analysis, and the hazard ratios and confidence intervals were calculated. Pterygium was defined based on the Korean Classification of Diseases code, and surgically removed pterygium was defined as cases that required surgical removal. We identified 21,465 pterygium cases and 8,338 surgically removed pterygium cases during the study period. The overall incidences were 2.1 per 1,000 person-years for pterygium and 0.8 per 1,000 person-years for surgically removed pterygium. Among subjects who were ≥40 years old, the incidences were 4.3 per 1,000 person-years for pterygium and 1.7 per 1,000 person-years for surgically removed pterygium. The overall prevalences were 1.9% for pterygium and 0.6% for surgically removed pterygium, and the prevalences increased to 3.8% for pterygium and 1.4% for surgically removed pterygium among subjects who were ≥40 years old. The incidences of pterygium decreased according to year. The incidence and prevalence of pterygium were highest among 60-79-year-old individuals. Increasing age, female sex, and living in a relatively rural area were associated with increased risks of pterygium and surgically removed pterygium in the multivariable Cox regression analysis. Our analyses of South Korean national insurance claims data revealed a decreasing trend in the incidence of pterygium during the study period.

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.

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

Prognostic nutritional index is associated with survival after total gastrectomy for patients with gastric cancer.

PubMed

Ishizuka, Mitsuru; Oyama, Yusuke; Abe, Akihito; Tago, Kazuma; Tanaka, Genki; Kubota, Keiichi

2014-08-01

To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC). One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival. Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (≤ 72/>72), carcinoembryonic antigen (≤ 20/>20) (ng/ml), white blood cell count (≤ 9.5/>9.5) (× 10(3)/mm(3)), prognostic nutritional index (PNI) (≤ 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (≤ 45) (p<0.001). PNI is associated with postoperative survival of patients undergoing TG for GC and is able to divide such patients into two independent groups before surgery. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Prognostic impact of intestinal wall thickening in hospitalized patients with heart failure.

PubMed

Ikeda, Yuki; Ishii, Shunsuke; Fujita, Teppei; Iida, Yuichiro; Kaida, Toyoji; Nabeta, Takeru; Maekawa, Emi; Yanagisawa, Tomoyoshi; Koitabashi, Toshimi; Takeuchi, Ichiro; Inomata, Takayuki; Ako, Junya

2017-03-01

Intestine-cardiovascular relationship has been increasingly recognized as a key factor in patients with heart disease. We aimed to identify the relationships among intestinal wall edema, cardiac function, and adverse clinical events in hospitalized heart failure (HF) patients. Abdominal computed tomographic images of 168 hospitalized HF patients were retrospectively investigated for identification of average colon wall thickness (CWT) from the ascending to sigmoid colon. Relationships between average CWT and echocardiographic parameters, blood sampling data, and primary outcomes including readmission for deteriorated HF and all-cause mortality were evaluated. Among the echocardiographic parameters, lower left ventricular diastolic function was correlated with higher average CWT. In multivariate analysis, higher logarithmic C-reactive protein level, lower estimated glomerular filtration rate, lower peripheral blood lymphocyte count, higher E/E' ratio, and extremely higher/lower defecation frequency were independently correlated with higher average CWT. Multivariate Cox-hazard analysis demonstrated that higher average CWT was independently related to higher incidence of primary outcomes. In hospitalized HF patients, increased CWT was associated with lower cardiac performance, and predicted poorer long-term clinical outcomes. Copyright © 2016. Published by Elsevier B.V.

Charlson comorbidity index as a predictor of periodontal disease in elderly participants

PubMed Central

2018-01-01

Purpose This study investigated the validity of the Charlson comorbidity index (CCI) as a predictor of periodontal disease (PD) over a 12-year period. Methods Nationwide representative samples of 149,785 adults aged ≥60 years with PD (International Classification of Disease, 10th revision [ICD-10], K052–K056) were derived from the National Health Insurance Service-Elderly Cohort during 2002–2013. The degree of comorbidity was measured using the CCI (grade 0–6), including 17 diseases weighted on the basis of their association with mortality, and data were analyzed using multivariate Cox proportional-hazards regression in order to investigate the associations of comorbid diseases (CDs) with PD. Results The multivariate Cox regression analysis with adjustment for sociodemographic factors (sex, age, household income, insurance status, residence area, and health status) and CDs (acute myocardial infarction, congestive heart failure, peripheral vascular disease, cerebral vascular accident, dementia, pulmonary disease, connective tissue disorders, peptic ulcer, liver disease, diabetes, diabetes complications, paraplegia, renal disease, cancer, metastatic cancer, severe liver disease, and human immunodeficiency virus [HIV]) showed that the CCI in elderly comorbid participants was significantly and positively correlated with the presence of PD (grade 1: hazard ratio [HR], 1.11; P<0.001; grade ≥2: HR, 1.12, P<0.001). Conclusions We demonstrated that a higher CCI was a significant predictor of greater risk for PD in the South Korean elderly population. PMID:29770238

Transplant center volume and outcomes in lung transplantation for cystic fibrosis.

PubMed

Hayes, Don; Sweet, Stuart C; Benden, Christian; Kopp, Benjamin T; Goldfarb, Samuel B; Visner, Gary A; Mallory, George B; Tobias, Joseph D; Tumin, Dmitry

2017-04-01

Transplant volume represents lung transplant (LTx) expertise and predicts outcomes, so we sought to determine outcomes related to center volumes in cystic fibrosis (CF). United Network for Organ Sharing data were queried for patients with CF in the United States (US) receiving bilateral LTx from 2005 to 2015. Multivariable Cox regression was used to model survival to 1 year and long-term (>1 year) survival, conditional on surviving at least 1 year. A total of 2025 patients and 67 centers were included in the analysis. The median annual LTx volumes were three in CF [interquartile range (IQR): 2, 6] and 17 in non-CF (IQR: 8, 33). Multivariable Cox regression in cases with complete data and surviving at least 1 year (n = 1510) demonstrated that greater annual CF LTx volume (HR per 10 LTx = 0.66; 95% CI: 0.49, 0.89; P = 0.006) but not greater non-CF LTx volume (HR = 1.00; 95% CI: 0.96, 1.05; P = 0.844) was associated with improved long-term survival in LTx recipients with CF. A Wald interaction test confirmed that CF LTx volume was more strongly associated with long-term outcomes than non-CF LTx volume (P = 0.012). In a US cohort, center volume was not associated with 1-year survival. CF-specific expertise predicted improved long-term outcomes of LTx for CF, whereas general LTx expertise was unassociated with CF patients' survival. © 2016 Steunstichting ESOT.

The Multidisciplinary Swallowing Team Approach Decreases Pneumonia Onset in Acute Stroke Patients.

PubMed

Aoki, Shiro; Hosomi, Naohisa; Hirayama, Junko; Nakamori, Masahiro; Yoshikawa, Mineka; Nezu, Tomohisa; Kubo, Satoshi; Nagano, Yuka; Nagao, Akiko; Yamane, Naoya; Nishikawa, Yuichi; Takamoto, Megumi; Ueno, Hiroki; Ochi, Kazuhide; Maruyama, Hirofumi; Yamamoto, Hiromi; Matsumoto, Masayasu

2016-01-01

Dysphagia occurs in acute stroke patients at high rates, and many of them develop aspiration pneumonia. Team approaches with the cooperation of various professionals have the power to improve the quality of medical care, utilizing the specialized knowledge and skills of each professional. In our hospital, a multidisciplinary participatory swallowing team was organized. The aim of this study was to clarify the influence of a team approach on dysphagia by comparing the rates of pneumonia in acute stroke patients prior to and post team organization. All consecutive acute stroke patients who were admitted to our hospital between April 2009 and March 2014 were registered. We analyzed the difference in the rate of pneumonia onset between the periods before team organization (prior period) and after team organization (post period). Univariate and multivariate analyses were performed using a Cox proportional hazards model to determine the predictors of pneumonia. We recruited 132 acute stroke patients from the prior period and 173 patients from the post period. Pneumonia onset was less frequent in the post period compared with the prior period (6.9% vs. 15.9%, respectively; p = 0.01). Based on a multivariate analysis using a Cox proportional hazards model, it was determined that a swallowing team approach was related to pneumonia onset independent from the National Institutes of Health Stroke Scale score on admission (adjusted hazard ratio 0.41, 95% confidence interval 0.19-0.84, p = 0.02). The multidisciplinary participatory swallowing team effectively decreased the pneumonia onset in acute stroke patients.

Use of Diuretics is not associated with mortality in patients admitted to the emergency department: results from a cross-sectional study.

PubMed

Haider, Dominik G; Lindner, Gregor; Wolzt, Michael; Leichtle, Alexander Benedikt; Fiedler, Georg-Martin; Sauter, Thomas C; Fuhrmann, Valentin; Exadaktylos, Aristomenis K

2016-02-01

Patients with diuretic therapy are at risk for drug-induced adverse reactions. It is unknown if presence of diuretic therapy at hospital emergency room admission is associated with mortality. In this cross sectional analysis, all emergency room patients 2010 and 2011 at the Inselspital Bern, Switzerland were included. A multivariable logistic regression model was performed to assess the association between pre-existing diuretic medication and 28 day mortality. Twenty-two thousand two hundred thirty-nine subjects were included in the analysis. A total of 8.5%, 2.5%, and 0.4% of patients used one, two, or three or more diuretics. In univariate analysis spironolactone, torasemide and chlortalidone use were associated with 28 day mortality (all p < 0.05). In a multivariate cox regression model no association with mortality was detectable (p > 0.05). No difference existed between patients with or without diuretic therapy (P > 0.05). Age and creatinine were independent risk factors for mortaliy (both p < 0.05). Use of diuretics is not associated with mortality in an unselected cohort of patients presenting in an emergency room.

Impact of loneliness and depression on mortality: results from the Longitudinal Ageing Study Amsterdam.

PubMed

Holwerda, Tjalling J; van Tilburg, Theo G; Deeg, Dorly J H; Schutter, Natasja; Van, Rien; Dekker, Jack; Stek, Max L; Beekman, Aartjan T F; Schoevers, Robert A

2016-08-01

Loneliness is highly prevalent among older people, has serious health consequences and is an important predictor of mortality. Loneliness and depression may unfavourably interact with each other over time but data on this topic are scarce. To determine whether loneliness is associated with excess mortality after 19 years of follow-up and whether the joint effect with depression confers further excess mortality. Different aspects of loneliness were measured with the De Jong Gierveld scale and depression with the Centre for Epidemiologic Studies Depression Scale in a cohort of 2878 people aged 55-85 with 19 years of follow-up. Excess mortality hypotheses were tested with Kaplan-Meier and Cox proportional hazard analyses controlling for potential confounders. At follow-up loneliness and depression were associated with excess mortality in older men and women in bivariate analysis but not in multivariate analysis. In multivariate analysis, severe depression was associated with excess mortality in men who were lonely but not in women. Loneliness and depression are important predictors of early death in older adults. Severe depression has a strong association with excess mortality in older men who were lonely, indicating a lethal combination in this group. © The Royal College of Psychiatrists 2016.

An open cohort study of bone metastasis incidence following surgery in breast cancer patients.

PubMed

Koizumi, Mitsuru; Yoshimoto, Masataka; Kasumi, Fujio; Iwase, Takuji

2010-07-21

To help design clinical trials of adjuvant bisphosphonate therapy for breast cancer, the temporal incidence of bone metastasis was investigated in a cohort of patients. We have tried to draw the criteria to use adjuvant bisphosphonate. Consecutive breast cancer patients undergoing surgery between 1988 and 1998 (5459 patients) were followed up regarding bone metastasis until December 2006. Patients' characteristics at the time of surgery were analyzed by Cox's method, with bone metastasis as events. Patient groups were assigned according to Cox's analysis, and were judged either to require the adjuvant bisphosphonate or not, using the tentative criteria: high risk (>3% person-year), medium risk (1-3%), and low risk (<1%). Bone metastasis incidence was constant between 1.0 and 2.8% per person-year more than 10 years. Non-invasive cancer was associated with a very low incidence of bone metastasis (1/436). Multivariate Cox's analysis indicated important factors for bone metastasis were tumor grade (T), nodal grade (pN), and histology. Because T and pN were important factors for bone metastasis prediction, subgroups were made by pTNM stage. Patients at stages IIIA, IIIB and IV had an incidence of >3% per person-year, patients with stage I <1% per person-year, and those with stages II were between 1 and 3%. Further analysis with histology in stage II patients showed that stage IIB with high risk histology also had a high incidence (3% person year), whereas stage IIA with medium risk histology were <1%. Bone metastasis incidence remained constant for many years. Using pN, T, and histopathology, patients could be classified into high, medium, and low risk groups.

Fibroblast Growth Factor 2-A Predictor of Outcome for Patients Irradiated for Stage II-III Non-Small-Cell Lung Cancer

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

Rades, Dirk, E-mail: Rades.Dirk@gmx.net; Setter, Cornelia; Dahl, Olav

2012-01-01

Purpose: The prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients with non-small-cell lung cancer (NSCLC) is unclear. The present study investigated the effect of tumor cell expression of FGF-2 on the outcome of 60 patients irradiated for Stage II-III NSCLC. Methods and Materials: The effect of FGF-2 expression and 13 additional factors on locoregional control (LRC), metastasis-free survival (MFS), and overall survival (OS) were retrospectively evaluated. These additional factors included age, gender, Karnofsky performance status, histologic type, histologic grade, T and N category, American Joint Committee on Cancer stage, surgery, chemotherapy, pack-years,more » smoking during radiotherapy, and hemoglobin during radiotherapy. Locoregional failure was identified by endoscopy or computed tomography. Univariate analyses were performed with the Kaplan-Meier method and the Wilcoxon test and multivariate analyses with the Cox proportional hazard model. Results: On univariate analysis, improved LRC was associated with surgery (p = .017), greater hemoglobin levels (p = .036), and FGF-2 negativity (p <.001). On multivariate analysis of LRC, surgery (relative risk [RR], 2.44; p = .037), and FGF-2 expression (RR, 5.06; p <.001) maintained significance. On univariate analysis, improved MFS was associated with squamous cell carcinoma (p = .020), greater hemoglobin levels (p = .007), and FGF-2 negativity (p = .001). On multivariate analysis of MFS, the hemoglobin levels (RR, 2.65; p = .019) and FGF-2 expression (RR, 3.05; p = .004) were significant. On univariate analysis, improved OS was associated with a lower N category (p = .048), greater hemoglobin levels (p <.001), and FGF-2 negativity (p <.001). On multivariate analysis of OS, greater hemoglobin levels (RR, 4.62; p = .002) and FGF-2 expression (RR, 3.25; p = .002) maintained significance. Conclusions: Tumor cell expression of FGF-2 appeared to be an independent negative predictor of LRC, MFS, and OS.« less

A pretreatment nomogram for prediction of biochemical failure after primary cryoablation of the prostate.

PubMed

Elshafei, Ahmed; Kovac, Evan; Dhar, Nivedita; Levy, David; Polascik, Thomas; Mouraviev, Vladimir; Yu, Changhong; Jones, J Stephen

2015-09-01

To create a predictive nomogram for biochemical failure following primary whole-gland cryoablation of the prostate for localized prostate cancer (LPCa). We retrospectively analyzed 2,242 patients from the Cryo On-Line Database (COLD) who were treatment naive and had undergone primary whole gland cryoablation of the prostate for biopsy-confirmed LPCa. Kaplan-Meier (KM) curves estimating 5 year biochemical progression-free survival (bPFS) were generated. Multivariable Cox proportional hazards analysis (CoxPH) was performed in order to construct the nomogram. The nomogram was internally validated using the bootstrap technique. Overall, the KM estimated 5 year bPFS was 72.8%. Stratified by D'Amico risk, The KM estimated 5 year bPFS was 82.6%, 71.1%, and 57.8% for low-, intermediate-, and high-risk groups, respectively. Statistically significant predictors of biochemical outcomes from CoxPH analysis were pre-treatment prostate specific antigen (PTPSA) (P < 0.001), total prostate volume (P = 0.004), clinical stage (P = 0.034), and Gleason score (0.004). A nomogram for predicted 5 year biochemical progression free probability was constructed with a concordance index of 0.652. An online risk calculator was also generated. To the best of our knowledge, this is the first predictive nomogram for biochemical outcomes after primary whole gland cryoablation of the prostate using socio-demographic, pretreatment, clinical, and prostate biopsy data. Our nomogram and online risk calculator can guide both patients and urologists for shared decision making regarding definitive treatment options. © 2015 Wiley Periodicals, Inc.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein evaluates liver function and predicts prognosis in liver cirrhosis.

PubMed

Xu, Wen Ping; Wang, Ze Rui; Zou, Xia; Zhao, Chen; Wang, Rui; Shi, Pei Mei; Yuan, Zong Li; Yang, Fang; Zeng, Xin; Wang, Pei Qin; Sultan, Sakhawat; Zhang, Yan; Xie, Wei Fen

2018-04-01

Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA + -M2BP) is a novel glycobiomarker for evaluating liver fibrosis, but less is known about its role in liver cirrhosis (LC). This study aimed to investigate the utility of WFA + -M2BP in evaluating liver function and predicting prognosis of cirrhotic patients. We retrospectively included 197 patients with LC between 2013 and 2016. Serum WFA + -M2BP and various biochemical parameters were measured in all patients. With a median follow-up of 23 months, liver-related complications and deaths of 160 patients were recorded. The accuracy of WFA + -M2BP in evaluating liver function, predicting decompensation and mortality were measured by the receiver operating characteristic (ROC) curve, logistic and Cox's regression analyses, respectively. WFA + -M2BP levels increased with elevated Child-Pugh classification, especially in patients with hepatitis B virus (HBV) infection. ROC analysis confirmed the high reliability of WFA + -M2BP for the assessment of liver function using Child-Pugh classification. WFA + -M2BP was also significantly positively correlated with the model for end-stage liver disease (MELD) score. Multivariate logistic regression analysis indicated WFA + -M2BP as an independent predictor of clinical decompensation for compensated patients (odds ratio 11.958, 95% confidence interval [CI] 1.876-76.226, P = 0.009), and multivariate Cox's regression analysis verified WFA + -M2BP as an independent risk factor for liver-related death in patients with HBV infection (hazards ratio 10.596, 95% CI 1.356-82.820, P = 0.024). Serum WFA + -M2BP is a reliable predictor of liver function and prognosis in LC and could be incorporated into clinical surveillance strategies for LC patients, especially those with HBV infection. © 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Yonsei nomogram: A predictive model of new-onset chronic kidney disease after on-clamp partial nephrectomy in patients with T1 renal tumors.

PubMed

Abdel Raheem, Ali; Shin, Tae Young; Chang, Ki Don; Santok, Glen Denmer R; Alenzi, Mohamed Jayed; Yoon, Young Eun; Ham, Won Sik; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

2018-06-19

To develop a predictive nomogram for chronic kidney disease-free survival probability in the long term after partial nephrectomy. A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end-points were to identify independent risk factors for new-onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease-free survival probability after partial nephrectomy. The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new-onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease-free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new-onset chronic kidney disease. The C-index for chronic kidney disease-free survival was 0.853 (95% confidence interval 0.815-0.895). We developed a novel nomogram for predicting the 5-year chronic kidney disease-free survival probability after on-clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision-making and follow-up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered. © 2018 The Japanese Urological Association.

Clinical efficacy analysis of Ahmed glaucoma valve implantation in neovascular glaucoma and influencing factors

PubMed Central

He, Ye; Tian, Ying; Song, Weitao; Su, Ting; Jiang, Haibo; Xia, Xiaobo

2017-01-01

Abstract This study aimed to evaluate the efficacy of Ahmed glaucoma valve (AGV) implantation in treating neovascular glaucoma (NVG) and to analyze the factors influencing the surgical success rate. This is a retrospective review of 40 eyes of 40 NVG patients who underwent AGV implantation at Xiangya Hospital of Central South University, China, between January 2014 and December 2016. Pre- and postoperative intraocular pressure (IOP), visual acuity, surgical success rate, medications, and complications were observed. Surgical success criteria were defined as IOP ≤21 and >6 mm Hg with or without additional medications. Kaplan–Meier survival curves and Multivariate cox regression analysis were used to examine success rates and risk factors for surgical outcomes. The mean follow-up period was 8.88 ± 3.12 months (range: 3–17). IOP declined at each visit postoperatively and it was statistically significant (P < .001). An average of 3.55 ± 0.86 drugs was applied preoperatively, while an average of 0.64 ± 0.90 drugs was used postoperatively, with the difference being of statistical significance (P < .05). The complete surgical success rate of 3, 6, and 12 months after the operation was 85%, 75%, and 65%, respectively. Meanwhile, the qualified success rate of 3, 6, and 12 months after the operation was 85%, 80%, and 77.5%, respectively. The multivariate cox regression analysis showed that age (hazard ratio: 3.717, 7.246; 95% confidence interval: 1.149–12.048, 1.349–38.461; P = .028, .021) was influencing factors for complete success rate and qualified success rate among all NVG patients. Gender, previous operation history, primary disease, and preoperative IOP were found to be not significant. AGV implantation is an effective and safe surgical method to treat NVG. Age is an important factor influencing the surgical success rate. PMID:29049253

Forkhead-box series expression network is associated with outcome of clear-cell renal cell carcinoma.

PubMed

Jia, Zhongwei; Wan, Fangning; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Dai, Bo; Ye, Dingwei

2018-06-01

Previous studies have demonstrated that several members of the Forkhead-box (FOX) family of genes are associated with tumor progression and metastasis. The objective of the current study was to screen candidate FOX family genes identified from analysis of molecular networks in clear cell renal cell carcinoma (ccRCC). The expression of FOX family genes as well as FOX family-associated genes was examined, and Kaplan-Meier survival analysis was performed in The Cancer Genome Atlas (TCGA) cohort (n=525). Patient characteristics, including sex, age, tumor diameter, laterality, tumor-node-metastasis, tumor grade, stage, white blood cell count, platelet count, the levels of hemoglobin, overall survival (OS) and disease-free survival (DFS), were collected for univariate and multivariate Cox proportional hazards ratio analyses. A total of seven candidate FOX family genes were selected from the TCGA database subsequent to univariate and multivariate Cox proportional hazards ratio analyses. FOXA1, FOXA2, FOXD1, FOXD4L2, FOXK2 and FOXL1 were associated with poor OS time, while FOXA1, FOXA2, FOXD1 and FOXK2 were associated with poor DFS time (P<0.05). FOXN2 was associated with favorable outcomes for overall and disease-free survival (P<0.05). In the gene cluster network analysis, the expression of FOX family-associated genes, including nuclear receptor coactivator ( NCOA ) 1 , NADH-ubiquinone oxidoreductase flavoprotein 3 ( NDUFV3 ), phosphatidylserine decarboxylase ( PISD ) and pyruvate kinase liver and red blood cell ( PKLR ), were independent prognostic factors for OS in patients with ccRCC. Results of the present study revealed that the expression of FOX family genes, including FOXA1, FOXA2, FOXD1, FOXD4L2, FOXK2 and FOXL1 , and FOX family-associated genes, including NCOA1, NDUFV3, PISD and PKLR , are independent prognostic factors for patients with ccRCC.

Clinicopathological significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas.

PubMed

González-Arriagada, Wilfredo A; Lozano-Burgos, Carlos; Zúñiga-Moreta, Rodrigo; González-Díaz, Paulina; Coletta, Ricardo D

2018-05-24

Head and neck squamous cell carcinoma shows high prevalence of lymph node metastasis at diagnosis, and despite the advances in treatment, the overall 5-year survival is still under 50%. Chemokine receptors have a role in the development and progression of cancer, but their effect in head and neck carcinoma remains poorly characterised. This study aimed to assess the prognostic value of CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4 in head and neck squamous cell carcinomas. Immunohistochemical expression of chemokine receptors was evaluated in a retrospective cohort of 76 cases of head and neck squamous cell carcinoma. Clinicopathological associations were analysed using the chi-square test, survival curves were analysed according to the Kaplan-Meier method, and the Cox proportional hazard model was applied for multivariate survival analysis. The chemokine receptors were highly expressed in primary carcinomas, except for CCR1 and CCR3. Significant associations were detected, including the associations between CCR5 expression and lymph node metastasis (N stage, P = .03), advanced clinical stage (P = .003), poor differentiation of tumours (P = .05) and recurrence (P = .01). The high expression of CCR5 was also associated with shortened disease-free survival (HR: 2.85, 95% CI: 1.09-8.14, P = .05), but the association did not withstand the Cox multivariate survival analysis. At univariate analysis, high expression of CCR7 was associated with disease-free survival and low levels of CXCR4 were significantly associated with both disease-specific and disease-free survival. These findings show that chemokine receptors may have an important role in head and neck squamous cell carcinoma progression, regional lymph node metastasis and recurrence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association of Protein Translation and Extracellular Matrix Gene Sets with Breast Cancer Metastasis: Findings Uncovered on Analysis of Multiple Publicly Available Datasets Using Individual Patient Data Approach.

PubMed

Chowdhury, Nilotpal; Sapru, Shantanu

2015-01-01

Microarray analysis has revolutionized the role of genomic prognostication in breast cancer. However, most studies are single series studies, and suffer from methodological problems. We sought to use a meta-analytic approach in combining multiple publicly available datasets, while correcting for batch effects, to reach a more robust oncogenomic analysis. The aim of the present study was to find gene sets associated with distant metastasis free survival (DMFS) in systemically untreated, node-negative breast cancer patients, from publicly available genomic microarray datasets. Four microarray series (having 742 patients) were selected after a systematic search and combined. Cox regression for each gene was done for the combined dataset (univariate, as well as multivariate - adjusted for expression of Cell cycle related genes) and for the 4 major molecular subtypes. The centre and microarray batch effects were adjusted by including them as random effects variables. The Cox regression coefficients for each analysis were then ranked and subjected to a Gene Set Enrichment Analysis (GSEA). Gene sets representing protein translation were independently negatively associated with metastasis in the Luminal A and Luminal B subtypes, but positively associated with metastasis in Basal tumors. Proteinaceous extracellular matrix (ECM) gene set expression was positively associated with metastasis, after adjustment for expression of cell cycle related genes on the combined dataset. Finally, the positive association of the proliferation-related genes with metastases was confirmed. To the best of our knowledge, the results depicting mixed prognostic significance of protein translation in breast cancer subtypes are being reported for the first time. We attribute this to our study combining multiple series and performing a more robust meta-analytic Cox regression modeling on the combined dataset, thus discovering 'hidden' associations. This methodology seems to yield new and interesting results and may be used as a tool to guide new research.

Association of Protein Translation and Extracellular Matrix Gene Sets with Breast Cancer Metastasis: Findings Uncovered on Analysis of Multiple Publicly Available Datasets Using Individual Patient Data Approach

PubMed Central

Chowdhury, Nilotpal; Sapru, Shantanu

2015-01-01

Introduction Microarray analysis has revolutionized the role of genomic prognostication in breast cancer. However, most studies are single series studies, and suffer from methodological problems. We sought to use a meta-analytic approach in combining multiple publicly available datasets, while correcting for batch effects, to reach a more robust oncogenomic analysis. Aim The aim of the present study was to find gene sets associated with distant metastasis free survival (DMFS) in systemically untreated, node-negative breast cancer patients, from publicly available genomic microarray datasets. Methods Four microarray series (having 742 patients) were selected after a systematic search and combined. Cox regression for each gene was done for the combined dataset (univariate, as well as multivariate – adjusted for expression of Cell cycle related genes) and for the 4 major molecular subtypes. The centre and microarray batch effects were adjusted by including them as random effects variables. The Cox regression coefficients for each analysis were then ranked and subjected to a Gene Set Enrichment Analysis (GSEA). Results Gene sets representing protein translation were independently negatively associated with metastasis in the Luminal A and Luminal B subtypes, but positively associated with metastasis in Basal tumors. Proteinaceous extracellular matrix (ECM) gene set expression was positively associated with metastasis, after adjustment for expression of cell cycle related genes on the combined dataset. Finally, the positive association of the proliferation-related genes with metastases was confirmed. Conclusion To the best of our knowledge, the results depicting mixed prognostic significance of protein translation in breast cancer subtypes are being reported for the first time. We attribute this to our study combining multiple series and performing a more robust meta-analytic Cox regression modeling on the combined dataset, thus discovering 'hidden' associations. This methodology seems to yield new and interesting results and may be used as a tool to guide new research. PMID:26080057

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

Assessment of the prognostic and predictive utility of the Breast Cancer Index (BCI): an NCIC CTG MA.14 study.

PubMed

Sgroi, Dennis C; Chapman, Judy-Anne W; Badovinac-Crnjevic, T; Zarella, Elizabeth; Binns, Shemeica; Zhang, Yi; Schnabel, Catherine A; Erlander, Mark G; Pritchard, Kathleen I; Han, Lei; Shepherd, Lois E; Goss, Paul E; Pollak, Michael

2016-01-04

Biomarkers that can be used to accurately assess the residual risk of disease recurrence in women with hormone receptor-positive breast cancer are clinically valuable. We evaluated the prognostic value of the Breast Cancer Index (BCI), a continuous risk index based on a combination of HOXB13:IL17BR and molecular grade index, in women with early breast cancer treated with either tamoxifen alone or tamoxifen plus octreotide in the NCIC MA.14 phase III clinical trial (ClinicalTrials.gov Identifier NCT00002864; registered 1 November 1999). Gene expression analysis of BCI by real-time polymerase chain reaction was performed blinded to outcome on RNA extracted from archived formalin-fixed, paraffin-embedded tumor samples of 299 patients with both lymph node-negative (LN-) and lymph node-positive (LN+) disease enrolled in the MA.14 trial. Our primary objective was to determine the prognostic performance of BCI based on relapse-free survival (RFS). MA.14 patients experienced similar RFS on both treatment arms. Association of gene expression data with RFS was evaluated in univariate analysis with a stratified log-rank test statistic, depicted with a Kaplan-Meier plot and an adjusted Cox survivor plot. In the multivariate assessment, we used stratified Cox regression. The prognostic performance of an emerging, optimized linear BCI model was also assessed in a post hoc analysis. Of 299 samples, 292 were assessed successfully for BCI for 146 patients accrued in each MA.14 treatment arm. BCI risk groups had a significant univariate association with RFS (stratified log-rank p = 0.005, unstratified log-rank p = 0.007). Adjusted 10-year RFS in BCI low-, intermediate-, and high-risk groups was 87.5 %, 83.9 %, and 74.7 %, respectively. BCI had a significant prognostic effect [hazard ratio (HR) 2.34, 95 % confidence interval (CI) 1.33-4.11; p = 0.004], although not a predictive effect, on RFS in stratified multivariate analysis, adjusted for pathological tumor stage (HR 2.22, 95 % CI 1.22-4.07; p = 0.01). In the post hoc multivariate analysis, higher linear BCI was associated with shorter RFS (p = 0.002). BCI had a strong prognostic effect on RFS in patients with early-stage breast cancer treated with tamoxifen alone or with tamoxifen and octreotide. BCI was prognostic in both LN- and LN+ patients. This retrospective study is an independent validation of the prognostic performance of BCI in a prospective trial.

Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

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

Mestre, Francisco; Gutiérrez, Antonio, E-mail: antoniom.gutierrez@ssib.es; Rodriguez, Jose

Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2more » defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.« less

Predictors of retention in community-based methadone maintenance treatment program in Pearl River Delta, China

PubMed Central

2013-01-01

Background The aims were to identify predictors of treatment retention in methadone maintenance treatment (MMT) clinics in Pearl River Delta, China. Methods Retrospective longitudinal study. Participants: 6 MMT clinics in rural and urban area were selected. Statistical analysis: Stratified random sampling was employed, and the data were analyzed using Kaplan-Meier survival curves and life table method. Protective or risk factors were explored using Cox’s proportional hazards model. Independent variables were enrolled in univariate analysis and among which significant variables were analyzed by multivariate analysis. Results A total of 2728 patients were enrolled. The median of the retention duration was 13.63 months, and the cumulative retention rates at 1,2,3 years were 53.0%, 35.0%, 20.0%, respectively. Multivariate Cox analysis showed: age, relationship with family, live on support from family or friends, income, considering treatment cost suitable, considering treatment open time suitable, addiction severity (daily expense for drug), communication with former drug taking peer, living in rural area, daily treatment dosage, sharing needles, re-admission and history of being arrested were predictors for MMT retention. Conclusions MMT retention rate in Guangdong was low and treatment skills and quality should be improved. Meanwhile, participation of family and society should be encouraged. PMID:23497263

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.

Prognostic molecular markers with no impact on decision-making: the paradox of gliomas based on a prospective study.

PubMed

Wager, M; Menei, P; Guilhot, J; Levillain, P; Michalak, S; Bataille, B; Blanc, J-L; Lapierre, F; Rigoard, P; Milin, S; Duthe, F; Bonneau, D; Larsen, C-J; Karayan-Tapon, L

2008-06-03

This study assessed the prognostic value of several markers involved in gliomagenesis, and compared it with that of other clinical and imaging markers already used. Four-hundred and sixteen adult patients with newly diagnosed glioma were included over a 3-year period and tumour suppressor genes, oncogenes, MGMT and hTERT expressions, losses of heterozygosity, as well as relevant clinical and imaging information were recorded. This prospective study was based on all adult gliomas. Analyses were performed on patient groups selected according to World Health Organization histoprognostic criteria and on the entire cohort. The endpoint was overall survival, estimated by the Kaplan-Meier method. Univariate analysis was followed by multivariate analysis according to a Cox model. p14(ARF), p16(INK4A) and PTEN expressions, and 10p 10q23, 10q26 and 13q LOH for the entire cohort, hTERT expression for high-grade tumours, EGFR for glioblastomas, 10q26 LOH for grade III tumours and anaplastic oligodendrogliomas were found to be correlated with overall survival on univariate analysis and age and grade on multivariate analysis only. This study confirms the prognostic value of several markers. However, the scattering of the values explained by tumour heterogeneity prevents their use in individual decision-making.

EVALUATION OF P53, E-CADHERIN, COX-2, AND EGFR PROTEIN IMUNNOEXPRESSION ON PROGNOSTIC OF RESECTED GALLBLADDER CARCINOMA

PubMed Central

PAIS-COSTA, Sergio Renato; FARAH, José Francisco de Matos; ARTIGIANI-NETO, Ricardo; MARTINS, Sandro José; GOLDENBERG, Alberto

2014-01-01

Background Gallbladder carcinoma presents a dismal prognosis. Choice treatment is surgical resection that is associated a high levels of both morbidity and mortality. Best knowledgement of prognostic factors may result a better selection of patients either for surgical or multimodal treatment. Aim To evaluate tecidual immunoexpression of P53, E-cadherin, Cox-2, and EGFR proteins and to correlate these findings with resected gallbladder adenocarcinoma survival. Methods Clinical, laboratorial, surgical, and anatomopathological reports of a series of gallbladder adenocarcinoma patients were collected by individualized questionary. Total sample was 42 patients. Median of age was 72 years (35-87). There were seven men and 35 women. Lesion distribuition in according TNM state was the following: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Twenty-three patients underwent radical resection (R0), while 19 palliative surgery (R1-R2). A block of tissue microarray with neoplasic tissue of each patient was confected. It was performed evaluation of P53, E-Caderine, COX-2, and EGFR proteins imunoexpression. These findings were correlated with overall survival. Results Five-year survival was 28%. The median of global survival was eight months. Only immunoexpression of EGFR protein was considered independent variable at multivariated analysis. Conclusion Final prognosis was influenced by over-expression of EGFR protein in tumoral tissue. PMID:25004291

Men and women show similar survival outcome in stage IV breast cancer.

PubMed

Wu, San-Gang; Zhang, Wen-Wen; Liao, Xu-Lin; Sun, Jia-Yuan; Li, Feng-Yan; Su, Jing-Jun; He, Zhen-Yu

2017-08-01

To evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC). Patients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS). A total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50-69 years and with estrogen receptor-positive disease. There was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of smoking history on the outcomes of women with early-stage breast cancer: a secondary analysis of a randomized study.

PubMed

Abdel-Rahman, Omar; Cheung, Winson Y

2018-04-11

To assess the impact of smoking history on the outcomes of early-stage breast cancer patients treated with sequential anthracyclines-taxanes in a randomized study. This is a secondary analysis of patient-level data of 1242 breast cancer patients referred for adjuvant chemotherapy in the BCIRG005 clinical trial. Overall survival was assessed according to smoking history through Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses of factors affecting overall and relapse-free survival were subsequently conducted. Factors that were evaluated included: age, performance status, number of chemotherapy cycles, T stage, lymph node ratio, estrogen receptor status, adjuvant radiotherapy and smoking history. Kaplan-Meier analysis of overall survival according to smoking status (ever smoker vs. never smoker) was conducted. There was a trend toward a better overall survival among never smokers compared to ever smokers; however, it was not statistically significant (P = 0.098). The following factors were associated with better overall survival in multivariate analysis: older age (P = 0.011), complete chemotherapy course (P = 0.002), lower T stage (P < 0.0001), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P = 0.006). Otherwise, the following factors were associated with better relapse-free survival in multivariate analysis: older age (P = 0.001), never smoking status (P = 0.021), lower T stage (P = 0.028), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P < 0.0001). Early-stage breast cancer patients with a positive smoking history experienced worse relapse-free survival compared to never smokers. Physicians managing breast cancer patients should prioritize discussion about the benefits of smoking cessation when counseling their patients.

Comparison of DNA aneuploidy, chromosome 1 abnormalities, MYCN amplification and CD44 expression as prognostic factors in neuroblastoma.

PubMed

Christiansen, H; Sahin, K; Berthold, F; Hero, B; Terpe, H J; Lampert, F

1995-01-01

A comparison of the prognostic impact of five molecular variables in a large series was made, including tests of their nonrandom association and multivariate analysis. Molecular data were available for 377 patients and MYCN amplification, cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA ploidy and CD44 expression were investigated. Their interdependence and influence on event-free survival was tested uni- and multivariately using Pearson's chi 2-test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN amplification was present in 18% (58/322) of cases and predicted poorer prognosis in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease. CD44 expression was found in 86% (127/148) of cases, and was a marker for favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value. Most factors of prognostic significance were associated with each other. By multivariate analysis, MYCN was selected as the only relevant factor. Risk estimation of high discriminating power is, therefore, possible for patients with localised and metastatic neuroblastoma using stage and MYCN.

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.

Quantitative Analysis of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy

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

Cui, Yi; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo; Song, Jie

Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board–approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT {sup 18}F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162more » robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6). Conclusion: Quantitative analysis identified novel {sup 18}F-fluorodeoxyglucose positron emission tomography image features that showed improved prognostic value over conventional imaging metrics. If validated in large, prospective cohorts, the new prognostic signature might be used to identify patients for individualized risk-adaptive therapy.« less

Evaluation of the environmental contamination at an abandoned mining site using multivariate statistical techniques--the Rodalquilar (Southern Spain) mining district.

PubMed

Bagur, M G; Morales, S; López-Chicano, M

2009-11-15

Unsupervised and supervised pattern recognition techniques such as hierarchical cluster analysis, principal component analysis, factor analysis and linear discriminant analysis have been applied to water samples recollected in Rodalquilar mining district (Southern Spain) in order to identify different sources of environmental pollution caused by the abandoned mining industry. The effect of the mining activity on waters was monitored determining the concentration of eleven elements (Mn, Ba, Co, Cu, Zn, As, Cd, Sb, Hg, Au and Pb) by inductively coupled plasma mass spectrometry (ICP-MS). The Box-Cox transformation has been used to transform the data set in normal form in order to minimize the non-normal distribution of the geochemical data. The environmental impact is affected mainly by the mining activity developed in the zone, the acid drainage and finally by the chemical treatment used for the benefit of gold.

[Value of Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio for Prognostic Evaluation of Diffuse Large B-cell Lymphoma].

PubMed

Ni, Jing; Wang, Yong-Qing; Zhang, Ying-Ping; Wu, Wei; Zeng, Qing-Shu; Yang, Ming-Zhen; Xia, Rui-Xiang

2016-04-01

To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) for the patients with diffuse large B-cell lymphoma (DLBCL). The clinical data of 57 DLBCL patients admitted in the First Affiliated hospital of Anhui Medical University were analyzed retrospectively. According to ROC curve, the cut-off value for NLR and PLR was deterimined, and the patients were divided into high and low NLR/PLR groups before first chamotherapy. Then the relation of NLR and PLR with overall survival (OS) and progression-free survival (PFS) was analyzed by univariate and multivariate COX regression. The optimal cut-off value for NLR and PLR was 2.915 and 270.27, respectively. NLR at the diagnosis was found to be an independent predictor for OS and PFS by univariate and multivariate analysis, while the PLR was an independent predictor for PFS, but did not affect the OS. NLR and PLR may provide additional prognostic information for DLBCL patients.

Risk factors for early failure after peripheral endovascular intervention: application of a reliability engineering approach.

PubMed

Meltzer, Andrew J; Graham, Ashley; Connolly, Peter H; Karwowski, John K; Bush, Harry L; Frazier, Peter I; Schneider, Darren B

2013-01-01

We apply an innovative and novel analytic approach, based on reliability engineering (RE) principles frequently used to characterize the behavior of manufactured products, to examine outcomes after peripheral endovascular intervention. We hypothesized that this would allow for improved prediction of outcome after peripheral endovascular intervention, specifically with regard to identification of risk factors for early failure. Patients undergoing infrainguinal endovascular intervention for chronic lower-extremity ischemia from 2005 to 2010 were identified in a prospectively maintained database. The primary outcome of failure was defined as patency loss detected by duplex ultrasonography, with or without clinical failure. Analysis included univariate and multivariate Cox regression models, as well as RE-based analysis including product life-cycle models and Weibull failure plots. Early failures were distinguished using the RE principle of "basic rating life," and multivariate models identified independent risk factors for early failure. From 2005 to 2010, 434 primary endovascular peripheral interventions were performed for claudication (51.8%), rest pain (16.8%), or tissue loss (31.3%). Fifty-five percent of patients were aged ≥75 years; 57% were men. Failure was noted after 159 (36.6%) interventions during a mean follow-up of 18 months (range, 0-71 months). Using multivariate (Cox) regression analysis, rest pain and tissue loss were independent predictors of patency loss, with hazard ratios of 2.5 (95% confidence interval, 1.6-4.1; P < 0.001) and 3.2 (95% confidence interval, 2.0-5.2, P < 0.001), respectively. The distribution of failure times for both claudication and critical limb ischemia fit distinct Weibull plots, with different characteristics: interventions for claudication demonstrated an increasing failure rate (β = 1.22, θ = 13.46, mean time to failure = 12.603 months, index of fit = 0.99037, R(2) = 0.98084), whereas interventions for critical limb ischemia demonstrated a decreasing failure rate, suggesting the predominance of early failures (β = 0.7395, θ = 6.8, mean time to failure = 8.2, index of fit = 0.99391, R(2) = 0.98786). By 3.1 months, 10% of interventions failed. This point (90% reliability) was identified as the basic rating life. Using multivariate analysis of failure data, independent predictors of early failure (before 3.1 months) included tissue loss, long lesion length, chronic total occlusions, heart failure, and end-stage renal disease. Application of a RE framework to the assessment of clinical outcomes after peripheral interventions is feasible, and potentially more informative than traditional techniques. Conceptualization of interventions as "products" permits application of product life-cycle models that allow for empiric definition of "early failure" may facilitate comparative effectiveness analysis and enable the development of individualized surveillance programs after endovascular interventions. Copyright © 2013 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Prognostic Value of Protocadherin10 (PCDH10) Methylation in Serum of Prostate Cancer Patients.

PubMed

Deng, Qiu-Kui; Lei, Yong-Gang; Lin, Ying-Li; Ma, Jian-Guo; Li, Wen-Ping

2016-02-16

BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.

Community-Based Management of Child Malnutrition in Zambia: HIV/AIDS Infection and Other Risk Factors on Child Survival.

PubMed

Moramarco, Stefania; Amerio, Giulia; Ciarlantini, Clarice; Chipoma, Jean Kasengele; Simpungwe, Matilda Kakungu; Nielsen-Saines, Karin; Palombi, Leonardo; Buonomo, Ersilia

2016-07-01

(1) BACKGROUND: Supplementary feeding programs (SFPs) are effective in the community-based treatment of moderate acute malnutrition (MAM) and prevention of severe acute malnutrition (SAM); (2) METHODS: A retrospective study was conducted on a sample of 1266 Zambian malnourished children assisted from 2012 to 2014 in the Rainbow Project SFPs. Nutritional status was evaluated according to WHO/Unicef methodology. We performed univariate and multivariate Cox proportional risk regression to identify the main predictors of mortality. In addition, a time-to event analysis was performed to identify predictors of failure and time to cure events; (3) RESULTS: The analysis included 858 malnourished children (19 months ± 9.4; 49.9% males). Program outcomes met international standards with a better performance for MAM compared to SAM. Cox regression identified SAM (3.8; 2.1-6.8), HIV infection (3.1; 1.7-5.5), and WAZ <-3 (3.1; 1.6-5.7) as predictors of death. Time to event showed 80% of children recovered by SAM/MAM at 24 weeks. (4) CONCLUSIONS: Preventing deterioration of malnutrition, coupled to early detection of HIV/AIDS with adequate antiretroviral treatment, and extending the duration of feeding supplementation, could be crucial elements for ensuring full recovery and improve child survival in malnourished Zambian children.

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.

Costs associated with Eribulin treatment for patients with metastatic breast cancer in a comprehensive cancer center in France.

PubMed

Hurtaud, Aline; Donnadieu, Anne; Escalup, Laurence; Cottu, Paul H; Baffert, Sandrine

2016-12-01

There is no standard recommendation for metastatic breast cancer treatment (MBC) after two chemotherapy regimens. Eribulin (Halaven ® ) has shown a significant improvement in overall survival (OS) in this setting. Its use may however be hampered by its cost, which is up to three times the cost of other standard drugs. We report the clinical outcomes and health care costs of a large series of consecutive MBC patients treated with Eribulin. A monocentric retrospective study was conducted at Institut Curie over 1 year (August 2012 to August 2013). Data from patient's medical records were extracted to estimate treatment and outcome patterns, and direct medical costs until the end of treatment were measured. Factors affecting cost variability were identified by multiple linear regressions and factors linked to OS by a multivariate Cox model. We included 87 MBC patients. The median OS was 10.7 months (95%CI = 8.0-13.3). By multivariate Cox analysis, independent factors of poor prognosis were an Eastern Cooperative Oncology Group (ECOG) performance status of 3, a number of metastatic sites ≥ 4 and the need for hospitalization. Per-patient costs during whole treatment were €18,694 [CI 95%: 16,028-21,360], and €2581 [CI 95%: 2226-3038] per month. Eribulin administration contributed to 79% of per-patient costs. Innovative and expensive drugs often appear to be the main cost drivers in cancer treatment, particularly for MBC. There is an urgent need to assess clinical practice benefits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer.

PubMed

Singla, Nirmish; Haddad, Ahmed Q; Passoni, Niccolo M; Meissner, Matthew; Lotan, Yair

2017-01-01

To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non-aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.

Selecting risk factors: a comparison of discriminant analysis, logistic regression and Cox's regression model using data from the Tromsø Heart Study.

PubMed

Brenn, T; Arnesen, E

1985-01-01

For comparative evaluation, discriminant analysis, logistic regression and Cox's model were used to select risk factors for total and coronary deaths among 6595 men aged 20-49 followed for 9 years. Groups with mortality between 5 and 93 per 1000 were considered. Discriminant analysis selected variable sets only marginally different from the logistic and Cox methods which always selected the same sets. A time-saving option, offered for both the logistic and Cox selection, showed no advantage compared with discriminant analysis. Analysing more than 3800 subjects, the logistic and Cox methods consumed, respectively, 80 and 10 times more computer time than discriminant analysis. When including the same set of variables in non-stepwise analyses, all methods estimated coefficients that in most cases were almost identical. In conclusion, discriminant analysis is advocated for preliminary or stepwise analysis, otherwise Cox's method should be used.

Jaundice: an important, poorly recognized risk factor for diminished survival in patients with adenocarcinoma of the head of the pancreas

PubMed Central

Strasberg, Steven M; Gao, Feng; Sanford, Dominic; Linehan, David C; Hawkins, William G; Fields, Ryan; Carpenter, Danielle H; Brunt, Elizabeth M; Phillips, Carolyn

2014-01-01

Objectives: Jaundice impairs cellular immunity, an important defence against the dissemination of cancer. Jaundice is a common mode of presentation in pancreatic head adenocarcinoma. The purpose of this study was to determine whether there is an association between preoperative jaundice and survival in patients who have undergone resection of such tumours. Methods: Thirty possible survival risk factors were evaluated in a database of over 400 resected patients. Univariate analysis was used to determine odds ratio for death. All factors for which a P-value of <0.30 was obtained were entered into a multivariate analysis using the Cox model with backward selection. Results: Preoperative jaundice, age, positive node status, poor differentiation and lymphatic invasion were significant indicators of poor outcome in multivariate analysis. Absence of jaundice was a highly favourable prognostic factor. Interaction emerged between jaundice and nodal status. The benefit conferred by the absence of jaundice was restricted to patients in whom negative node status was present. Five-year overall survival in this group was 66%. Jaundiced patients who underwent preoperative stenting had a survival advantage. Conclusions: Preoperative jaundice is a negative risk factor in adenocarcinoma of the pancreas. Additional studies are required to determine the exact mechanism for this effect. PMID:23600768

Influence of the site of origin on the outcome of squamous cell carcinoma of the maxilla-oral versus sinus.

PubMed

Bobinskas, A M; Wiesenfeld, D; Chandu, A

2014-02-01

The maxilla may be affected by squamous cell carcinoma (SCC) from both oral and sinus sites. We sought to determine whether the site of origin of the maxillary tumour, oral as compared to sinus, influences survival. Univariate Kaplan-Meier and multivariate Cox proportional hazard models analysis of 58 patients with SCC involving the maxilla, treated with curative intent, was conducted. The overall 5-year disease-free survival for the group was 41.7%. Five-year disease-free survival for oral subsite SCC was 56.8%, while for sinus subsite was only 21.6%. Univariate analysis found SCC of sinus origin to be associated with a poorer prognosis, however this was not confirmed on multivariate analysis. T-stage and positive margins were found to be the only independent risk factors. For SCC of the maxilla, sinus origin of the tumour per se does not confer a poorer prognosis; however, as a result of the complex anatomy of the midface, these tumours can present at an advanced stage, while surgical control of the disease can be more difficult, especially posteriorly. Tumour size and positive margins were the determinants of a poor prognosis in this group of patients with maxillary SCC. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Multidisciplinary therapy for patients with locally oligo-recurrent pelvic malignancies.

PubMed

Sole, Claudio V; Calvo, Felipe A; de Sierra, Pedro Alvarez; Herranz, Rafael; Gonzalez-Bayon, Luis; García-Sabrido, Jose Luis

2014-07-01

To analyze prognostic factors and long-term outcomes in patients with locally recurrent pelvic cancer (LRPC) treated with a multidisciplinary approach. From January 1995 to December 2011, 81 patients [rectal (47 %); gynecologic (39 %); retroperitoneal sarcoma (14 %)] underwent extended surgery [multiorgan (58 %), bone (35 %), vascular (9 %), soft tissue (63 %)] and intraoperative electron beam radiation therapy (IOERT) to treat recurrent tumors in the pelvic region. Thirty-five patients (43 %) received external beam radiotherapy (EBRT). Survival was estimated using the Kaplan-Meier method, and risk factors were identified using univariate and multivariate analysis. Median follow-up was 39 months (6-189 months); the 1- 3- and 5-year rates of locoregional control (LRC) were 83, 53, and 41 %, respectively. Univariate Cox proportional hazard analysis revealed worse LRC in patients who did not receive integrated EBRT as rescue treatment of pelvic recurrence (p = 0.003) or underwent non-radical resection (p = 0.01). In the multivariate analysis EBRT, non-radical resection, and tumor fragmentation retained significance (p = 0.002, p = 0.004, and p = 0.05, respectively). Radical resection, absence of tumor fragmentation and addition of EBRT for rescue are associated with improved LRC in patients with LRPC. Our results suggest that this group can benefit from EBRT combined with extended surgical resection and IOERT.

High serum uric acid concentration predicts poor survival in patients with breast cancer.

PubMed

Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

2017-10-01

Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Bootstrapping Cox’s Regression Model.

DTIC Science & Technology

1985-11-01

crucial points a multivariate martingale central limit theorem. Involved in this is a p x p covariance matrix Z with elements T j2= f {2(s8 ) - s(l)( s ,8o...1980). The statistical analaysis of failure time data. Wiley, New York. Meyer, P.-A. (1971). Square integrable martingales, a survey. Lecture Notes

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.

Outcomes of surgery for gastric cancer with distant metastases: a retrospective study from the SEER database

PubMed Central

Weng, Shanshan; Dong, Caixia; Zhu, Lizhen; Yang, Ziru; Zhong, Jing; Yuan, Ying

2017-01-01

Background The role of surgical therapy in gastric cancer patients with distant metastases remains controversial. This retrospective analysis was performed to identify whether gastric cancer patients with distant metastases might benefit from surgery. Patients and methods A total of 5185 patients from the SEER database who were initially diagnosed with histologically confirmed gastric cancer with distant metastases from 2004 to 2009 were included. Patients were divided into the following three groups: patients who underwent resection of both the primary tumor and distant metastatic tumors (‘PMTR’ group), patients who only underwent resection of the primary tumor (‘PTR’ group) and patients who did not undergo any surgery (‘No surgery’ group). We employed the Kaplan-Meier analysis, the log-rank test and multivariate Cox proportional hazards regression models to estimate the survival time of the different groups. Results A total of 5185 patients had a median survival time (MST) of 9.0 months. The improvement in survival of the ‘PMTR’ and ‘PTR’ groups was significantly different compared with that of the ‘No surgery’ group (MST, 12.0 vs 12.0 vs 9.0 months, respectively, P<0.001; 1-year survival rate, 49.6% vs 49.1% vs 30.1%, respectively, P<0.001; 3-year survival rate, 12.5% vs 15.1% vs 5.8%, respectively, P<0.001), whereas no significant difference was found between the ‘PMTR’ group and ‘PTR’ group (P=0.642). Multivariate Cox proportional analysis showed that surgery was an independent prognostic factor (‘PMTR’, hazard ratio (HR) =0.648, 95% confidence interval (CI) 0.574-0.733, P<0.001; ‘PTR’, HR=0.631, 95% CI 0.583-0.684, P<0.001). Conclusions This retrospective analysis demonstrated that combined PTR and metastasectomy or PTR alone were independent prognostic factors for survival improvement in gastric cancer patients with distant metastases. Because no statistically significant difference in survival was observed between the ‘PMTR’ group and ‘PTR’ group, PTR, which is a more minor surgery, might be more appropriate than PMTR in clinical practice for gastric cancer patients with distant metastases. PMID:28008147

Risk Factors for Upper Gastrointestinal Bleeding in Patients Taking Selective COX-2 Inhibitors: A Nationwide Population-Based Cohort Study.

PubMed

Lin, Xi-Hsuan; Young, Shih-Hao; Luo, Jiing-Chyuan; Peng, Yen-Ling; Chen, Ping-Hsien; Lin, Chung-Chi; Chen, Wei-Ming; Hou, Ming-Chih; Lee, Fa-Yauh

2018-02-01

Cyclooxygenase-2 inhibitors (coxibs) are associated with less upper gastrointestinal bleeding (UGIB) than traditional nonsteroidal anti-inflammatory drugs (tNSAIDs). However, they also increase the risk of UGIB in high-risk patients. We aimed to identify the risk factors of UGIB in coxibs users. Retrospective cohort study. 2000-2010 National Health Insurance Research Database of Taiwan. Patients taking coxibs as the study group and patients not taking any coxibs as controls. After age, gender, and comorbidity matching by propensity score, 12,145 coxibs users and 12,145 matched controls were extracted for analysis. The primary end point was the occurrence of UGIB. Cox multivariate proportional hazard regression models were used to determine the risk factors for UGIB among all the enrollees and coxibs users. During a mean follow-up of three years, coxibs users had significantly higher incidence of UGIB than matched controls (P < 0.001, log-rank test). Cox regression analysis showed that coxibs increased risk of UGIB in all participants (hazard ratio = 1.37, 95% confidence interval = 1.19-1.55, P < 0.001). Independent risk factors for UGIB among coxibs users were age, male gender, diabetes, chronic renal disease, cirrhosis, history of peptic ulcer disease, PU bleeding (PUB), Helicobacter pylori (H. pylori) infection, and concomitant use of tNSAIDs, acetylsalicylic acid, or thienopyridines. Among coxibs users, H. pylori infection and history of PUB were especially important risk factors for UGIB. Further studies are needed to determine whether proton pump inhibitors might play a protective role in these at-risk patients. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Prognostic value of FDG PET/CT-based metabolic tumor volumes in metastatic triple negative breast cancer patients

PubMed Central

Marinelli, Brett; Espinet-Col, Carina; Ulaner, Gary A; McArthur, Heather L; Gonen, Mithat; Jochelson, Maxine; Weber, Wolfgang A

2016-01-01

FDG PET/CT-based measures of tumor burden show promise to predict survival in patients with metastatic breast cancer, but the patient populations studied so far are heterogeneous. The reports may have been confounded by the markedly different prognosis of the various subtypes of breast cancer. The purpose of this study is to evaluate the correlation between tumor burden on FDG PET/CT and overall survival (OS) in patients within a defined population: metastatic triple negative breast cancer (MTNBC). FDG PET/CT scans of 47 consecutive MTNBC patients (54±12 years-old) with no other known malignancies were analyzed. A total 393 lesions were identified, and maximum standardized uptake value (SUVmax), mean SUV, metabolic tumor volume (MTV), total lesion number (TLN) and total lesion glycolysis (TLG), were measured and correlated with patient survival by Mantel-Cox tests and Cox regression analysis. At a median follow-up time of 12.4 months, 41 patients died with a median OS of 12.1 months. Patients with MTV less than 51.5 ml lived nearly three times longer (22 vs 7.1 months) than those with a higher MTV (χ2=21.3, P<0.0001). In a multivariate Cox regression analysis only TLN and MTV were significantly correlated with survival. Those with an MTV burden in the 75th percentile versus the 25th percentile had a hazard ratio of 6.94 (p=0.001). In patients with MTNBC, MTV appears to be a strong prognostic factor. If validated in prospective studies, MTV may be a valuable tool for risk stratification of MTNBC patients in clinical trials and to guide patient management. PMID:27186439

Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease

PubMed Central

Kempny, Aleksander; Diller, Gerhard-Paul; Alonso-Gonzalez, Rafael; Uebing, Anselm; Rafiq, Isma; Li, Wei; Swan, Lorna; Hooper, James; Donovan, Jackie; Wort, Stephen J; Gatzoulis, Michael A; Dimopoulos, Konstantinos

2015-01-01

Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown. Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis. Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death. Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population. PMID:25736048

Overall and Comparative Risk of Herpes Zoster With Pharmacotherapy for Inflammatory Bowel Diseases: A Nationwide Cohort Study.

PubMed

Khan, Nabeel; Patel, Dhruvan; Trivedi, Chinmay; Shah, Yash; Lichtenstein, Gary; Lewis, James; Yang, Yu-Xiao

2018-01-05

Patients with inflammatory bowel disease (IBD) might be at increased risk for herpes zoster infection. We sought to quantify the risk of herpes zoster in patients with IBD and evaluate the effects of IBD and IBD medications on the risk of herpes zoster. We conducted 2 retrospective studies of populations of Veterans, from January 2000 through June 2016. In study 1, we compared the incidence of herpes zoster among patients with IBD receiving 5-ASA alone vs matched patients without IBD. In study 2, we compared the incidence of herpes zoster among patients with IBD treated with only 5-ASA, with thiopurines, with antagonists of tumor necrosis factor (TNF), with a combination of thiopurines and TNF antagonists, and with vedolizumab. We used multivariable Cox regression to estimate the hazard ratios and 95% CIs for herpes zoster associated with IBD in study 1 and with different treatments in study 2. We also estimated the incidence rate of herpes zoster based on age and IBD medication subgroups. Compared to no IBD, ulcerative colitis (UC) and Crohn's disease (CD) were each associated with significantly increased risk of herpes zoster infection. In multivariable Cox regression (compared to no IBD), UC, CD, or IBD treated with 5-ASA treatment alone was associated with significantly increased risk of herpes zoster, with adjusted HRs (AHR) of 1.81 for UC (95% CI, 1.56-2.11), 1.56 for CD (95% CI, 1.28-1.91), and 1.72 for treated IBD (95% CI, 1.51-1.96). In multivariable Cox regression analysis, compared to exposure to 5-ASA alone, exposure to thiopurines (AHR, 1.47; 95% CI, 1.31-1.65) or a combination of thiopurines and TNF antagonists (AHR, 1.65; 95% CI, 1.22-2.23) was associated with increased risk of herpes zoster. However, exposure to TNF antagonists alone (AHR, 1.15; 95% CI, 0.96-1.38) was not associated with increased risk of herpes zoster. The incidence rates of herpes zoster in all age groups and all IBD medication subgroups were substantially higher than that in the oldest group of patients without IBD (older than 60 years). In 2 retrospective studies of Veteran populations, we associated IBD and treatment with thiopurines, alone or in combination with TNF antagonists, with increased risk of herpes zoster. With the approval of a new and potentially safer vaccine for herpes zoster, the effects of immunization of patients with IBD should be investigated. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

The HOVON68 CLL trial revisited: performance status and comorbidity affect survival in elderly patients with chronic lymphocytic leukemia.

PubMed

Vojdeman, Fie Juhl; Van't Veer, Mars B; Tjønnfjord, Geir E; Itälä-Remes, Maija; Kimby, Eva; Polliack, Aaron; Wu, Ka L; Doorduijn, Jeanette K; Alemayehu, Wendimagegn G; Wittebol, Shulamiet; Kozak, Tomas; Walewski, Jan; Abrahamse-Testroote, Martine C J; van Oers, Marinus H J; Geisler, Christian Hartmann

2017-03-01

In the HOVON68 CLL trial, patients 65 to 75 years of age had no survival benefit from the addition of low-dose alemtuzumab to fludarabine and cyclophosphamide (FC) in contrast to younger patients. The reasons are explored in this 5-year trial update using both survival analysis and competing risk analysis on non-CLL-related mortality. Elderly FCA patients died more frequently from causes not related to CLL, and more often related to comorbidity (mostly cardiovascular) than to infection. In a Cox multivariate analysis, del(17p), performance status >0, and comorbidity were associated with a higher non-CLL-related mortality in the elderly independent of the treatment modality. Thus, while the 'fit' elderly with no comorbidity or performance status of 0 might potentially benefit from chemo-immunotherapy with FC, caution is warranted, when considering alemtuzumab treatment in elderly patients with cardiovascular comorbidity.

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.

Effect of late HIV diagnosis on HIV-related mortality among adults in general hospitals of Central Zone Tigray, northern Ethiopia: a retrospective cohort study.

PubMed

Belay, Hadera; Alemseged, Fessahaye; Angesom, Teklit; Hintsa, Solomon; Abay, Mebrahtu

2017-01-01

The global incidence of HIV infection is not significantly decreasing, especially in sub-Saharan African countries, including Ethiopia. Though there is availability and accessibility of free HIV services, people are not being diagnosed early for HIV, and hence patients are still dying of HIV-related causes. This research is aimed at verifying the effect of late diagnosis of HIV on HIV-related mortality in Central Zone Tigray, Ethiopia. A retrospective cohort study among adult (≥15 years old) HIV patients in three general hospitals of Tigray was conducted. Record reviews were carried out retrospectively from 2010 to 2015. Sample size was determined using stpower Cox in Stata software. Data were entered into EpiData version 3.1 software and transferred to Stata version 12 for analysis. Both bivariable and multivariable analyses were performed using Cox regression model to compare the HIV-related mortality of exposed (cluster of differentiation 4 cells count <350 cells/mm 3 ) and nonexposed (≥350 cells/mm 3 ) patients using adjusted hazard ratio (AHR) at 95% confidence interval (CI). In all, 638 HIV patients were analyzed, contributing 2,105.6 person-years. Forty-eight (7.5%) patients died of HIV-related causes with a mortality rate of 2.28 per 100 person-years. In the multivariable Cox regression model, patients with late diagnosis of HIV had a higher risk of mortality (AHR =3.22, 95% CI: 1.17-8.82) than patients with early diagnosis of HIV. Rural residence (AHR =1.96, 95% CI: 1.05-3.68), unemployment (AHR =2.70, 95% CI: 1.03-7.08), bedridden patients (AHR =2.98, 95% CI: 1.45-6.13), ambulatory patients (AHR =2.54, 95% CI: 1.05-6.15), and baseline hemoglobin level of <11 mg/dL (AHR =3.06, 95% CI: 1.51-6.23) were other independent predictors of mortality. Late diagnosis of HIV increased HIV-related mortality. Rural residence, unemployment, bedridden and ambulatory patients, and baseline hemoglobin level <11 mg/dL were also independent predictors of HIV-related mortality.

Fractals and self-organized criticality in anti-inflammatory drugs

NASA Astrophysics Data System (ADS)

Phillips, J. C.

2014-12-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) act through inhibiting prostaglandin synthesis, a catalytic activity possessed by two distinct cyclooxygenase (COX-1 and COX-2) isozymes encoded by separate genes. The discovery of COX-2 launched a new era in NSAID pharmacology, resulting in the synthesis, marketing, and widespread use of COX-2 selective inhibitors. Extensive structural studies of the biology of prostaglandin synthesis and inhibition have explained some of the differences between COX-1 and COX-2 functionality, but others are still unexplained. Notably these include molecular differences that cause COX-1 inhibitors to produce a slight decrease, and COX-2 inhibitors to induce a significant increase, in heart attacks and strokes. These differences were unexpected because of the 60% overall COX-1 and COX-2 sequence similarity and the 1-2 conservation of catalytic sites. Hydropathic analysis shows important bicyclic differences between COX-1 and COX-2 on a large scale outside the catalytic pocket. These differences involve much stronger amphiphilic interactions in COX-2 than in COX-1, and may explain the selective antiplatelet effectiveness of COX-2. Success of the non-Euclidean structural analysis is the result of using the new Brazilian hydropathicity scale based on self-organized criticality (SOC) of universal protein modules.

Refusal of postoperative radiotherapy and its association with survival in head and neck cancer.

PubMed

Schwam, Zachary G; Husain, Zain; Judson, Benjamin L

2015-11-01

Administering postoperative radiotherapy (PORT) is associated with improved survival and slower disease progression in select head and neck cancer patients. Predictive factors for PORT refusal have not been described in this population. Retrospective analysis of 6127 head and neck cancer patients who received or refused PORT in the National Cancer Database (2003-2006) was performed. Statistical analysis included Chi-square, multivariable logistic regression, Kaplan-Meier, and Cox proportional hazards analysis. In total, 247 patients (4.0%) refused PORT. Three-year overall survival was 62.8% versus 53.4% for those who received and refused PORT, respectively. PORT refusers were more likely to have negative nodes than those who underwent PORT (37.4% versus 20.1%, p<.001). In multivariate analysis, predictive factors for refusing PORT included living far from the treatment facility (OR 1.92), having negative nodes (OR 2.14), and Charlson score of ⩾ 2 (OR 2.14) (all p ⩽.001). PORT refusal was associated with increased mortality (hazard ratio 1.20, p=.044). A significant proportion of head and neck cancer patients refused PORT; this was associated with compromised overall survival. Predictive factors for PORT refusal included socioeconomic, demographic, and pathologic variables. Elucidating root causes of refusal may lead to interventions that improve long-term outcomes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Blood neutrophil-lymphocyte ratio predicts survival in locally advanced cancer stomach treated with neoadjuvant chemotherapy FOLFOX 4.

PubMed

el Aziz, Lamiss Mohamed Abd

2014-12-01

Accurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy FOLFOX 4 as neoadjuvant chemotherapy. We enrolled 70 patients with stage III-IV cancer stomach in this study. Patients received FOLFOX 4 as neoadjuvant chemotherapy. Blood sample was collected before chemotherapy. The NLR was divided into two groups: high (>3) and low (≤ 3). Univariate analysis on progression-free survival (PFS) and overall survival (OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. The toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria. The univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 28 and 44 months, respectively, P = 0.001; median OS 30 and 48 months, P = 0.001). Multivariate analysis showed that NLRs before chemotherapy were independent prognostic factors of OS but not for progression-free survival. NLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy. The FOLFOX 4 demonstrated an acceptable toxicity.

Reduced miR-300 expression predicts poor prognosis in patients with laryngeal squamous cell carcinoma.

PubMed

He, F-Y; Liu, H-J; Guo, Q; Sheng, J-L

2017-02-01

miR-300 has been demonstrated to play an important role in the progression of several tumors, but its role in tumorigenesis of laryngeal squamous cell carcinoma (LSCC) is still unclear. The purpose of this study was to explore miR-300 expression in LSCC patients and analyze its association with clinicopathological factors and prognosis. In the present study, we measured the expression level of miR-300 in LSCC tissues by RT-PCR. Associations between miRNA-300 expressions and various clinicopathological characteristics were analyzed. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. The univariate and multivariate analysis were performed using the Cox proportional hazard analysis. miR-300 expression was significantly increased in LSCC tissues compared with that in adjacent non-cancerous tissues (p < 0.01). In addition, lymph node metastasis (p = 0.004) and TNM stage (p = 0.001) were obvious influence factors for the expression of miR-300. More importantly, Kaplan-Meier analysis showed that LSCC patients with low miR-300 expression tended to have shorter overall survival (p < 0.001). Finally, multivariate analysis revealed that miR-300 expression was an independent prognostic factor for LSCC patients. Our results pointed to miR-300 as a powerful prognostic marker in LSCC and as a novel target for tumor-suppressive therapy.

The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients.

PubMed

Chen, Jian-Wu; Zhou, Chang-Fu; Lin, Zhi-Xiong

2015-09-15

Although age is thought to correlate with the prognosis of glioma patients, the most appropriate age-group classification standard to evaluate prognosis had not been fully studied. This study aimed to investigate the influence of age-group classification standards on the prognosis of patients with high-grade hemispheric glioma (HGG). This retrospective study of 125 HGG patients used three different classification standards of age-groups (≤ 50 and >50 years old, ≤ 60 and >60 years old, ≤ 45 and 45-65 and ≥ 65 years old) to evaluate the impact of age on prognosis. The primary end-point was overall survival (OS). The Kaplan-Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. Univariate analysis showed a significant correlation between OS and all three classification standards of age-groups as well as between OS and pathological grade, gender, location of glioma, and regular chemotherapy and radiotherapy treatment. Multivariate analysis showed that the only independent predictors of OS were classification standard of age-groups ≤ 50 and > 50 years old, pathological grade and regular chemotherapy. In summary, the most appropriate classification standard of age-groups as an independent prognostic factor was ≤ 50 and > 50 years old. Pathological grade and chemotherapy were also independent predictors of OS in post-operative HGG patients. Copyright © 2015. Published by Elsevier B.V.

Predicting Outcomes After Chemo-Embolization in Patients with Advanced-Stage Hepatocellular Carcinoma: An Evaluation of Different Radiologic Response Criteria

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

Gunn, Andrew J., E-mail: agunn@uabmc.edu; Sheth, Rahul A.; Luber, Brandon

2017-01-15

PurposeThe purpse of this study was to evaluate the ability of various radiologic response criteria to predict patient outcomes after trans-arterial chemo-embolization with drug-eluting beads (DEB-TACE) in patients with advanced-stage (BCLC C) hepatocellular carcinoma (HCC).Materials and methodsHospital records from 2005 to 2011 were retrospectively reviewed. Non-infiltrative lesions were measured at baseline and on follow-up scans after DEB-TACE according to various common radiologic response criteria, including guidelines of the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and modified RECIST (mRECIST). Statistical analysis was performed to see which,more » if any, of the response criteria could be used as a predictor of overall survival (OS) or time-to-progression (TTP).Results75 patients met inclusion criteria. Median OS and TTP were 22.6 months (95 % CI 11.6–24.8) and 9.8 months (95 % CI 7.1–21.6), respectively. Univariate and multivariate Cox analyses revealed that none of the evaluated criteria had the ability to be used as a predictor for OS or TTP. Analysis of the C index in both univariate and multivariate models showed that the evaluated criteria were not accurate predictors of either OS (C-statistic range: 0.51–0.58 in the univariate model; range: 0.54–0.58 in the multivariate model) or TTP (C-statistic range: 0.55–0.59 in the univariate model; range: 0.57–0.61 in the multivariate model).ConclusionCurrent response criteria are not accurate predictors of OS or TTP in patients with advanced-stage HCC after DEB-TACE.« less

Predicting Outcomes After Chemo-Embolization in Patients with Advanced-Stage Hepatocellular Carcinoma: An Evaluation of Different Radiologic Response Criteria.

PubMed

Gunn, Andrew J; Sheth, Rahul A; Luber, Brandon; Huynh, Minh-Huy; Rachamreddy, Niranjan R; Kalva, Sanjeeva P

2017-01-01

The purpse of this study was to evaluate the ability of various radiologic response criteria to predict patient outcomes after trans-arterial chemo-embolization with drug-eluting beads (DEB-TACE) in patients with advanced-stage (BCLC C) hepatocellular carcinoma (HCC). Hospital records from 2005 to 2011 were retrospectively reviewed. Non-infiltrative lesions were measured at baseline and on follow-up scans after DEB-TACE according to various common radiologic response criteria, including guidelines of the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and modified RECIST (mRECIST). Statistical analysis was performed to see which, if any, of the response criteria could be used as a predictor of overall survival (OS) or time-to-progression (TTP). 75 patients met inclusion criteria. Median OS and TTP were 22.6 months (95 % CI 11.6-24.8) and 9.8 months (95 % CI 7.1-21.6), respectively. Univariate and multivariate Cox analyses revealed that none of the evaluated criteria had the ability to be used as a predictor for OS or TTP. Analysis of the C index in both univariate and multivariate models showed that the evaluated criteria were not accurate predictors of either OS (C-statistic range: 0.51-0.58 in the univariate model; range: 0.54-0.58 in the multivariate model) or TTP (C-statistic range: 0.55-0.59 in the univariate model; range: 0.57-0.61 in the multivariate model). Current response criteria are not accurate predictors of OS or TTP in patients with advanced-stage HCC after DEB-TACE.

THE AFRICAN DESCENT AND GLAUCOMA EVALUATION STUDY (ADAGES): PREDICTORS OF VISUAL FIELD DAMAGE IN GLAUCOMA SUSPECTS

PubMed Central

Khachatryan, Naira; Medeiros, Felipe A.; Sharpsten, Lucie; Bowd, Christopher; Sample, Pamela A.; Liebmann, Jeffrey M.; Girkin, Christopher A.; Weinreb, Robert N.; Miki, Atsuya; Hammel, Na’ama; Zangwill, Linda M.

2015-01-01

Purpose To evaluate racial differences in the development of visual field (VF) damage in glaucoma suspects. Design Prospective, observational cohort study. Methods Six hundred thirty six eyes from 357 glaucoma suspects with normal VF at baseline were included from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES). Racial differences in the development of VF damage were examined using multivariable Cox Proportional Hazard models. Results Thirty one (25.4%) of 122 African descent participants and 47 (20.0%) of 235 European descent participants developed VF damage (p=0.078). In multivariable analysis, worse baseline VF mean deviation, higher mean arterial pressure during follow up, and a race *mean intraocular pressure (IOP) interaction term were significantly associated with the development of VF damage suggesting that racial differences in the risk of VF damage varied by IOP. At higher mean IOP levels, race was predictive of the development of VF damage even after adjusting for potentially confounding factors. At mean IOPs during follow-up of 22, 24 and 26 mmHg, multivariable hazard ratios (95%CI) for the development of VF damage in African descent compared to European descent subjects were 2.03 (1.15–3.57), 2.71 (1.39–5.29), and 3.61 (1.61–8.08), respectively. However, at lower mean IOP levels (below 22 mmHg) during follow-up, African descent was not predictive of the development of VF damage. Conclusion In this cohort of glaucoma suspects with similar access to treatment, multivariate analysis revealed that at higher mean IOP during follow-up, individuals of African descent were more likely to develop VF damage than individuals of European descent. PMID:25597839

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.

Association between atherogenic dyslipidemia and recurrent stroke risk in patients with different subtypes of ischemic stroke.

PubMed

Zhao, Lu; Wang, Ruihao; Song, Bo; Tan, Song; Gao, Yuan; Fang, Hui; Lu, Jie; Xu, Yuming

2015-07-01

The association between atherogenic dyslipidemia and stroke recurrence remains unclear, and may be influenced by different subtypes of ischemic stroke. We aimed to investigate whether atherogenic dyslipidemia contributed to stroke recurrence in ischemic stroke patients and in those with certain subtypes of ischemic stroke. We conducted a prospective hospital-based study enrolling patients with acute ischemic stroke. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol <40 mg/dl and triglycerides ≥200 mg/dl. Ischemic stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The patients were followed up at 3, 6, 12 and 24 months after stroke onset. The association between atherogenic dyslipidemia and stroke recurrence was analyzed by using multivariable Cox regression model. In the 510 ischemic stroke patients, 64 patients (12·5%) had atherogenic dyslipidemia, and 66 patients (12·9%) experienced stroke recurrence events within 24 months. Kaplan-Meier analysis revealed that stroke recurrence rate was significantly higher in patients with atherogenic dyslipidemia than those without in all the stroke patients (20·3% vs. 11·9%; P = 0·048), and more evident in those of large-artery atherosclerosis subtype (31·0% vs. 14·1%; P = 0·014), but not in the other subtypes. Multivariable Cox regression analysis revealed that atherogenic dyslipidemia was associated with higher stroke recurrence risk among stroke patients of large-artery atherosclerosis subtype (hazard ratio, 2·79; 95% confidence interval, 1·24-6·28), but not significant in all the stroke patients (hazard ratio, 1·69; 95% confidence interval, 0·85-3·37). Atherogenic dyslipidemia is associated with higher risk of stroke recurrence in ischemic stroke patients. Such association might be more pronounced in large-artery atherosclerosis subtype and needs further investigation to establish such relationship. © 2015 World Stroke Organization.

Bio-psychosocial determinants of time lost from work following non life threatening acute orthopaedic trauma

PubMed Central

2010-01-01

Background To determine factors predicting the duration of time away from work following acute orthopaedic non life threatening trauma Methods Prospective cohort study conducted at four hospitals in Victoria, Australia. The cohort comprised 168 patients aged 18-64 years who were working prior to the injury and sustained a range of acute unintentional orthopaedic injuries resulting in hospitalization. Baseline data was obtained by survey and medical record review. Multivariate Cox proportional hazards regression analysis was used to examine the association between potential predictors and the duration of time away from work during the six month study. The study achieved 89% follow-up. Results Of the 168 participants recruited to the study, 68% returned to work during the six month study. Multivariate Cox proportional hazards regression analysis identified that blue collar work, negative pain attitudes with respect to work, high initial pain intensity, injury severity, older age, initial need for surgery, the presence of co-morbid health conditions at study entry and an orthopaedic injury to more than one region were associated with extended duration away from work following the injury. Participants in receipt of compensation who reported high social functioning at two weeks were 2.58 times more likely to have returned to work than similar participants reporting low social functioning. When only those who had returned to work were considered, the participant reported reason for return to work " to fill the day" was a significant predictor of earlier RTW [RR 2.41 (95% C.I 1.35-4.30)] whereas "financial security" and "because they felt able to" did not achieve significance. Conclusions Many injury-related and psycho social factors affect the duration of time away from work following orthopaedic injury. Some of these are potentially modifiable and may be amenable to intervention. Further consideration of the reasons provided by participants for returning to work may provide important opportunities for social marketing approaches designed to alleviate the financial and social burden associated with work disability. PMID:20051124

Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis-a proof of principle and exploratory trial: is dose tapering practical in good responders?

PubMed

Ibrahim, Fowzia; Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

2017-11-01

RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6-12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0-6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6-12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

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.

Hypomagnesemia Is Associated with Increased Mortality among Peritoneal Dialysis Patients.

PubMed

Cai, Kedan; Luo, Qun; Dai, Zhiwei; Zhu, Beixia; Fei, Jinping; Xue, Congping; Wu, Dan

2016-01-01

Hypomagnesemia has been associated with an increase in mortality among the general population as well as patients with chronic kidney disease or those on hemodialysis. However, this association has not been thoroughly studied in patients undergoing peritoneal dialysis. The aim of this study was to evaluate the association between serum magnesium concentrations and all-cause and cardiovascular mortalities in peritoneal dialysis patients. This single-center retrospective study included 253 incident peritoneal dialysis patients enrolled between July 1, 2005 and December 31, 2014 and followed to June 30, 2015. Patient's demographic characteristics as well as clinical and laboratory measurements were collected. Of 253 patients evaluated, 36 patients (14.2%) suffered from hypomagnesemia. During a median follow-up of 29 months (range: 4-120 months), 60 patients (23.7%) died, and 35 (58.3%) of these deaths were attributed to cardiovascular causes. Low serum magnesium was positively associated with peritoneal dialysis duration (r = 0.303, p < 0.001) as well as serum concentrations of albumin (r = 0.220, p < 0.001), triglycerides (r = 0.160, p = 0.011), potassium (r = 0.156, p = 0.013), calcium(r = 0.299, p < 0.001)and phosphate (r = 0.191, p = 0.002). Patients in the hypomagnesemia group had a lower survival rate than those in the normal magnesium groups (p < 0.001). In a multivariate Cox proportional hazards regression analysis, serum magnesium was an independent negative predictor of all-cause mortality (hazard ratio [HR] = 0.075, p = 0.011) and cardiovascular mortality (HR = 0.003, p < 0.001), especially in female patients. However, in univariate and multivariate Cox analysis, △Mg(difference between 1-year magnesium and baseline magnesium) was not an independent predictor of all-cause mortality and cardiovascular mortality. Hypomagnesemia was common among peritoneal dialysis patients and was independently associated with all-cause mortality and cardiovascular mortality.

IMPACT OF STAGE MIGRATION AND PRACTICE CHANGES ON HIGH RISK PROSTATE CANCER: RESULTS FROM PATIENTS TREATED WITH RADICAL PROSTATECTOMY OVER THE LAST TWO DECADES

PubMed Central

Fossati, N.; Passoni, N. M.; Moschini, M.; Gandaglia, G.; Larcher, A.; Freschi, M.; Guazzoni, G.; Sjoberg, D. D.; Vickers, A. J.; Montorsi, F.; Briganti, A.

2016-01-01

Background Phenotype of prostate cancer at diagnosis has changed through the years. We aim to evaluate the impact of year of surgery on clinical, pathologic and oncologic outcomes of high-risk prostate cancer patients. Patients and methods We evaluated 1,033 clinically high-risk patients, defined as the presence of at least one of the following risk factors: pre-operative prostate specific antigen (PSA) level >20 ng/ml, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single Institution. Year-per-year trends of clinical and pathologic characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncologic outcomes. Results We observed a decrease over time in the proportion of high-risk patients with a pre-operative PSA level >20 ng/ml or clinical stage cT3. An opposite trend was seen for biopsy Gleason score ≥8. We observed a considerable increase in the median number of lymph nodes removed that was associated with an increased rate of LNI. At multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (HR per 5-year: 0.90; 95% CI: 0.84–0.96; p=0.01) and distant metastasis (HR per 5-year: 0.91; 95% CI: 0.83–0.99; p=0.039), after adjusting for age, pre-operative PSA, pathologic stage, lymph node invasion, surgical margin status, and pathological Gleason score. Conclusions In this single center study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. High-risk patients selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed. PMID:25787671

Bio-psychosocial determinants of time lost from work following non life threatening acute orthopaedic trauma.

PubMed

Clay, Fiona J; Newstead, Stuart V; Watson, Wendy L; Ozanne-Smith, Joan; McClure, Roderick J

2010-01-05

To determine factors predicting the duration of time away from work following acute orthopaedic non life threatening trauma Prospective cohort study conducted at four hospitals in Victoria, Australia. The cohort comprised 168 patients aged 18-64 years who were working prior to the injury and sustained a range of acute unintentional orthopaedic injuries resulting in hospitalization. Baseline data was obtained by survey and medical record review. Multivariate Cox proportional hazards regression analysis was used to examine the association between potential predictors and the duration of time away from work during the six month study. The study achieved 89% follow-up. Of the 168 participants recruited to the study, 68% returned to work during the six month study. Multivariate Cox proportional hazards regression analysis identified that blue collar work, negative pain attitudes with respect to work, high initial pain intensity, injury severity, older age, initial need for surgery, the presence of co-morbid health conditions at study entry and an orthopaedic injury to more than one region were associated with extended duration away from work following the injury. Participants in receipt of compensation who reported high social functioning at two weeks were 2.58 times more likely to have returned to work than similar participants reporting low social functioning. When only those who had returned to work were considered, the participant reported reason for return to work " to fill the day" was a significant predictor of earlier RTW [RR 2.41 (95% C.I 1.35-4.30)] whereas "financial security" and "because they felt able to" did not achieve significance. Many injury-related and psycho social factors affect the duration of time away from work following orthopaedic injury. Some of these are potentially modifiable and may be amenable to intervention. Further consideration of the reasons provided by participants for returning to work may provide important opportunities for social marketing approaches designed to alleviate the financial and social burden associated with work disability.

ALK gene copy number gain and its clinical significance in hepatocellular carcinoma.

PubMed

Jia, Shou-Wei; Fu, Sha; Wang, Fang; Shao, Qiong; Huang, Hong-Bing; Shao, Jian-Yong

2014-01-07

To examine the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in hepatocellular carcinoma (HCC) patients. A total of 213 cases of HCC were examined by fluorescent in situ hybridization using dual color break-apart ALK probes for the detection of chromosomal translocation and gene copy number gain. HCC tissue microarrays were constructed, and the correlation between the ALK status and clinicopathological variables was assessed by χ(2) test or Fisher's exact test. Survival analysis was estimated using the Kaplan-Meier approach with a Log-rank test. Univariate and multivariate analyses of clinical variables were performed using the Cox proportional hazards regression model. ALK gene translocation was not observed in any of the HCC cases included in the present study. ALK gene copy number gain (ALK/CNG) (≥ 4 copies/cell) was detected in 28 (13.15%) of the 213 HCC patients. The 3-year progression-free-survival (PFS) rate for ALK/CNG-positive HCC patients was significantly poorer than ALK/CNG-negative patients (27.3% vs 42.5%, P = 0.048), especially for patients with advanced stage III/IV (0% vs 33.5%, P = 0.007), and patients with grade III disease (24.8% vs 49.9%, P = 0.023). ALK/CNG-positive HCC patients had a significantly poorer prognosis than ALK/CNG-negative patients in the subgroup that was negative for serum hepatitis B virus DNA, with significantly different 3-year overall survival rates (18.2% vs 63.6%, P = 0.021) and PFS rates (18.2% vs 46.9%, P = 0.019). Multivariate Cox proportional hazards regression analysis suggested that ALK/CNG prevalence can predict death in HCC (HR = 1.596; 95%CI: 1.008-2.526, P = 0.046). ALK/CNG, but not translocation of ALK, is present in HCC and may be an unfavorable prognostic predictor.

ALK gene copy number gain and its clinical significance in hepatocellular carcinoma

PubMed Central

Jia, Shou-Wei; Fu, Sha; Wang, Fang; Shao, Qiong; Huang, Hong-Bing; Shao, Jian-Yong

2014-01-01

AIM: To examine the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in hepatocellular carcinoma (HCC) patients. METHODS: A total of 213 cases of HCC were examined by fluorescent in situ hybridization using dual color break-apart ALK probes for the detection of chromosomal translocation and gene copy number gain. HCC tissue microarrays were constructed, and the correlation between the ALK status and clinicopathological variables was assessed by χ2 test or Fisher’s exact test. Survival analysis was estimated using the Kaplan-Meier approach with a Log-rank test. Univariate and multivariate analyses of clinical variables were performed using the Cox proportional hazards regression model. RESULTS: ALK gene translocation was not observed in any of the HCC cases included in the present study. ALK gene copy number gain (ALK/CNG) (≥ 4 copies/cell) was detected in 28 (13.15%) of the 213 HCC patients. The 3-year progression-free-survival (PFS) rate for ALK/CNG-positive HCC patients was significantly poorer than ALK/CNG-negative patients (27.3% vs 42.5%, P = 0.048), especially for patients with advanced stage III/IV (0% vs 33.5%, P = 0.007), and patients with grade III disease (24.8% vs 49.9%, P = 0.023). ALK/CNG-positive HCC patients had a significantly poorer prognosis than ALK/CNG-negative patients in the subgroup that was negative for serum hepatitis B virus DNA, with significantly different 3-year overall survival rates (18.2% vs 63.6%, P = 0.021) and PFS rates (18.2% vs 46.9%, P = 0.019). Multivariate Cox proportional hazards regression analysis suggested that ALK/CNG prevalence can predict death in HCC (HR = 1.596; 95%CI: 1.008-2.526, P = 0.046). CONCLUSION: ALK/CNG, but not translocation of ALK, is present in HCC and may be an unfavorable prognostic predictor. PMID:24415871

Hypomagnesemia Is Associated with Increased Mortality among Peritoneal Dialysis Patients

PubMed Central

Dai, Zhiwei; Zhu, Beixia; Fei, Jinping; Xue, Congping; Wu, Dan

2016-01-01

Objective Hypomagnesemia has been associated with an increase in mortality among the general population as well as patients with chronic kidney disease or those on hemodialysis. However, this association has not been thoroughly studied in patients undergoing peritoneal dialysis. The aim of this study was to evaluate the association between serum magnesium concentrations and all-cause and cardiovascular mortalities in peritoneal dialysis patients. Methods This single-center retrospective study included 253 incident peritoneal dialysis patients enrolled between July 1, 2005 and December 31, 2014 and followed to June 30, 2015. Patient’s demographic characteristics as well as clinical and laboratory measurements were collected. Results Of 253 patients evaluated, 36 patients (14.2%) suffered from hypomagnesemia. During a median follow-up of 29 months (range: 4–120 months), 60 patients (23.7%) died, and 35 (58.3%) of these deaths were attributed to cardiovascular causes. Low serum magnesium was positively associated with peritoneal dialysis duration (r = 0.303, p < 0.001) as well as serum concentrations of albumin (r = 0.220, p < 0.001), triglycerides (r = 0.160, p = 0.011), potassium (r = 0.156, p = 0.013), calcium(r = 0.299, p < 0.001)and phosphate (r = 0.191, p = 0.002). Patients in the hypomagnesemia group had a lower survival rate than those in the normal magnesium groups (p < 0.001). In a multivariate Cox proportional hazards regression analysis, serum magnesium was an independent negative predictor of all-cause mortality (hazard ratio [HR] = 0.075, p = 0.011) and cardiovascular mortality (HR = 0.003, p < 0.001), especially in female patients. However, in univariate and multivariate Cox analysis, △Mg(difference between 1-year magnesium and baseline magnesium) was not an independent predictor of all-cause mortality and cardiovascular mortality. Conclusion Hypomagnesemia was common among peritoneal dialysis patients and was independently associated with all-cause mortality and cardiovascular mortality. PMID:27023783

Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis—a proof of principle and exploratory trial: is dose tapering practical in good responders?

PubMed Central

Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

2017-01-01

Abstract Objectives RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. Methods We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0–6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6–12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Results Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0–6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6–12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Conclusion Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. Trail registration EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701 PMID:28968858

Comparison of Outcomes of Acute Coronary Syndrome in Patients ≥80 Years Versus Those <80 Years in Israel from 2000 to 2013.

PubMed

Shechter, Michael; Rubinstein, Roy; Goldenberg, Ilan; Matetzki, Shlomi

2017-10-15

Although patients ≥80 years old constitute the fastest-growing segment of the population and have a high prevalence of coronary artery disease, few data exist regarding the outcome of octogenarians with acute coronary syndrome (ACS). In a retrospective study based on data of 13,432 ACS patients who were enrolled in the ACS Israel Survey, we first evaluated the clinical outcome of 1,731 ACS patients ≥80 years (13%) compared with 11,701 ACS patients <80 years (87%) hospitalized during 2000 to 2013. Second, we evaluated the clinical outcome of patients ≥80 years hospitalized during the 2000 to 2006 ("early") period (n = 1,037) compared with those of the same age group of patients hospitalized during the 2008 to 2013 ("late") period (n = 694). Implementation of the ACS AHA/ACC/ESC therapeutic guidelines was lower in ACS patients ≥80 years compared with patients <80 years. Multivariate Cox regression analysis demonstrated a worse 1-year survival rate in the ACS patients ≥80 years compared with those <80 years. During the late period, patients ≥80 years were more frequently treated with guideline-recommended therapies compared with patients from the same age group who were hospitalized in the early period. Multivariate Cox regression analysis demonstrated a better 1-year survival rate of patients ≥80 years during the late period compared with the early period (hazard ratio 1.17, 95% confidence interval 1.15 to 1.61; p = 0.01). In addition, adverse outcome rates of ACS patients ≥80 years were significantly higher compared with those of patients <80 years. However, survival rates of ACS patients ≥80 years were improved over the 200 to 2013 period. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study).

PubMed

Bang, Casper N; Greve, Anders M; La Cour, Morten; Boman, Kurt; Gohlke-Bärwolf, Christa; Ray, Simon; Pedersen, Terje; Rossebø, Anne; Okin, Peter M; Devereux, Richard B; Wachtell, Kristian

2015-12-15

Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

The influence of individual socioeconomic status on the clinical outcomes in ischemic stroke patients with different neighborhood status in Shanghai, China

PubMed Central

Yan, Han; Liu, Baoxin; Meng, Guilin; Shang, Bo; Jie, Qiqiang; Wei, Yidong; Liu, Xueyuan

2017-01-01

Objective: Socioeconomic status (SES) is being recognized as an important factor in both social and medical problems. The aim of present study is to examine the relationship between SES and ischemic stroke and investigate whether SES is a predictor of clinical outcomes among patients with different neighborhood status from Shanghai, China. Methods: A total of 471 first-ever ischemic stroke patients aged 18-80 years were enrolled in this retrospective study. The personal SES of each patient was evaluated using a summed score derived from his or her educational level, household income, occupation, and medical reimbursement rate. Clinical adverse events and all-cause mortality were analyzed to determine whether SES was a prognostic factor, its prognostic impact was then assessed based on different neighborhood status using multivariable Cox proportional hazard models after adjusting for other covariates. Results: The individual SES showed a significant positive correlation with neighborhood status (r = 0.370; P < 0.001). The incidence of clinical adverse events and mortality were significantly higher in low SES patients compared with middle and high SES patients (P = 0.001 and P = 0.037, respectively). After adjusting other risk factors and neighborhood status, Kaplan-Meier analysis showed clinical adverse events and deaths were still higher in the low SES patients (all P < 0.05). Multivariate Cox regression analysis demonstrated that both personal SES and neighborhood status are independent prognostic factors for ischemic stroke (all P < 0.05). Besides, among patients with low and middle neighborhood status, lower individual SES was significantly associated with clinical adverse events and mortality (all P < 0.05). Conclusion: Both individual SES and neighborhood status are significantly associated with the prognosis after ischemic stroke. A lower personal SES as well as poorer neighborhood status may significantly increase risk for adverse clinical outcomes among ischemic stroke patients. PMID:28138313

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

Targeted deletion and lipidomic analysis identify epithelial cell COX-2 as a major driver of chemically induced skin cancer.

PubMed

Jiao, Jing; Ishikawa, Tomo-O; Dumlao, Darren S; Norris, Paul C; Magyar, Clara E; Mikulec, Carol; Catapang, Art; Dennis, Edward A; Fischer, Susan M; Herschman, Harvey R

2014-11-01

Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX-2) plays a critical role in DMBA/TPA-induced skin tumor induction. Although many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell type-specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared with littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2-expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell type-specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biologic responses. Cox-2 gene deletion demonstrates that intrinsic COX-2 expression in initiated keratinocytes is a principal driver of skin carcinogenesis; lipidomic analysis identifies likely prostanoid effectors. ©2014 American Association for Cancer Research.

Experiments to Determine Whether Recursive Partitioning (CART) or an Artificial Neural Network Overcomes Theoretical Limitations of Cox Proportional Hazards Regression

NASA Technical Reports Server (NTRS)

Kattan, Michael W.; Hess, Kenneth R.; Kattan, Michael W.

1998-01-01

New computationally intensive tools for medical survival analyses include recursive partitioning (also called CART) and artificial neural networks. A challenge that remains is to better understand the behavior of these techniques in effort to know when they will be effective tools. Theoretically they may overcome limitations of the traditional multivariable survival technique, the Cox proportional hazards regression model. Experiments were designed to test whether the new tools would, in practice, overcome these limitations. Two datasets in which theory suggests CART and the neural network should outperform the Cox model were selected. The first was a published leukemia dataset manipulated to have a strong interaction that CART should detect. The second was a published cirrhosis dataset with pronounced nonlinear effects that a neural network should fit. Repeated sampling of 50 training and testing subsets was applied to each technique. The concordance index C was calculated as a measure of predictive accuracy by each technique on the testing dataset. In the interaction dataset, CART outperformed Cox (P less than 0.05) with a C improvement of 0.1 (95% Cl, 0.08 to 0.12). In the nonlinear dataset, the neural network outperformed the Cox model (P less than 0.05), but by a very slight amount (0.015). As predicted by theory, CART and the neural network were able to overcome limitations of the Cox model. Experiments like these are important to increase our understanding of when one of these new techniques will outperform the standard Cox model. Further research is necessary to predict which technique will do best a priori and to assess the magnitude of superiority.

[A SAS marco program for batch processing of univariate Cox regression analysis for great database].

PubMed

Yang, Rendong; Xiong, Jie; Peng, Yangqin; Peng, Xiaoning; Zeng, Xiaomin

2015-02-01

To realize batch processing of univariate Cox regression analysis for great database by SAS marco program. We wrote a SAS macro program, which can filter, integrate, and export P values to Excel by SAS9.2. The program was used for screening survival correlated RNA molecules of ovarian cancer. A SAS marco program could finish the batch processing of univariate Cox regression analysis, the selection and export of the results. The SAS macro program has potential applications in reducing the workload of statistical analysis and providing a basis for batch processing of univariate Cox regression analysis.

Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with stage III and IV colorectal cancer

PubMed Central

Kim, Jae Hyun; Lee, Jun Yeop; Kim, Hae Koo; Lee, Jin Wook; Jung, Sung Gyu; Jung, Kyoungwon; Kim, Sung Eun; Moon, Won; Park, Moo In; Park, Seun Ja

2017-01-01

AIM To evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC). METHODS Between April 1996 and December 2010, medical records from a total of 1868 patients with CRC were retrospectively reviewed. The values of simple inflammatory markers including NLR and PLR in predicting the long-term outcomes of these patients were evaluated using Kaplan-Meier curves and Cox regression models. RESULTS The median follow-up duration was 46 mo (interquartile range, 22-73). The estimation of NLR and PLR was based on the time of diagnosis. In multivariate Cox regression analysis, high NLR (≥ 3.0) and high PLR (≥ 160) were independent risk factors predicting poor long-term outcomes in patients with stage III and IV CRC. However, high NLR and high PLR were not prognostic factors in patients with stage I and II CRC. CONCLUSION In this study, we identified that high NLR (≥ 3.0) and high PLR (≥ 160) are useful prognostic factors to predict long-term outcomes in patients with stage III and IV CRC. PMID:28210087

Body mass index and mortality in patients with type 2 diabetes mellitus: A prospective cohort study of 11,449 participants.

PubMed

Liu, Hui; Wu, Shouling; Li, Yun; Sun, Lixia; Huang, Zhe; Lin, Liming; Liu, Yan; Ji, Chunpeng; Zhao, Hualing; Li, Chunhui; Song, Lu; Cong, Hongliang

2017-02-01

To investigate the association between body-mass index and mortality in Chinese adults T2DM. 11,449 participants of Kailuan Study with T2DM were included in this prospective cohort study. All-cause mortality was calculated using Kaplan-Meier analysis. Cox proportional hazards analysis was used to estimate the association between BMI and mortality. During a mean follow-up period of 7.25±1.42years, 1254 deaths occurred. The number of deaths of the underweight, normal weight, overweight, and obese group was 23, 389, 557, and 285; the corresponding mortality was 25.0%, 13.4%, 10.3%, and 9.4%, respectively. The obese group had the lowest all-cause mortality rate (log-rank chi-square=48.430, P<0.001). After adjusting for age, sex, fasting blood glucose, smoking status, systolic blood pressure, history of hypertension, stroke, cancer and myocardial infarction, compared with the normal weight group, Multivariate Cox proportional hazard regression analysis showed that HR (95% CI) of all-cause mortality in the underweight, overweight, and obese group was 1.497 (0.962, 2.330), 0.833 (0.728, 0.952), and 0.809 (0.690, 0.949). After stratifying for age tertiles, this trend remained. In T2DM patients in north China, the risk for all-cause mortality was lower in the overweight and the obese groups than those in the normal weight and the underweight groups. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic Factors in Amyotrophic Lateral Sclerosis: A Population-Based Study.

PubMed

Moura, Mirian Conceicao; Novaes, Maria Rita Carvalho Garbi; Eduardo, Emanoel Junio; Zago, Yuri S S P; Freitas, Ricardo Del Negro Barroso; Casulari, Luiz Augusto

2015-01-01

To determine the prognostic factors associated with survival in amyotrophic lateral sclerosis at diagnosis. This retrospective population-based study evaluated 218 patients treated with riluzole between 2005 and 2014 and described their clinical and demographic profiles after the analysis of clinical data and records from the mortality information system in the Federal District, Brazil. Cox multivariate regression analysis was conducted for the parameters found. The study sample consisted of 132 men and 86 women with a mean age at disease onset of 57.2±12.3 years; 77.6% of them were Caucasian. The mean periods between disease onset and diagnosis were 22.7 months among men and 23.5 months among women, and the mean survival periods were 45.7±47.0 months among men and 39.3±29.8 months among women. In addition, 80.3% patients presented non-bulbar-onset amyotrophic lateral sclerosis, and 19.7% presented bulbar-onset. Cox regression analysis indicated worse prognosis for body mass index (BMI) <25 kg/m2 (relative risk [RR]: 3.56, 95% confidence interval [CI]: 1.44-8.86), age >75 years (RR: 12.47, 95% CI: 3.51-44.26), and bulbar-onset (RR: 4.56, 95% CI: 2.06-10.12). Electromyography did not confirm the diagnosis in 55.6% of the suspected cases and in 27.9% of the bulbar-onset cases. The factors associated with lower survival in amyotrophic lateral sclerosis were age >75 years, BMI <25 kg/m2, and bulbar-onset.

Malignant Peritoneal Mesothelioma: Prognostic Factors and Oncologic Outcome Analysis

PubMed Central

Magge, Deepa; Zenati, Mazen S.; Austin, Frances; Mavanur, Arun; Sathaiah, Magesh; Ramalingam, Lekshmi; Jones, Heather; Zureikat, Amer H.; Holtzman, Matthew; Ahrendt, Steven; Pingpank, James; Zeh, Herbert J.; Bartlett, David L.; Choudry, Haroon A.

2014-01-01

Background Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM. Methods We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan–Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. Results Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001). Conclusions Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC. PMID:24322529

Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections.

PubMed

Kutob, Leila F; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

2016-11-01

There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for <14 days at Palmetto Health Hospitals in Columbia, SC, from 1 January 2010 through 31 December 2013 and discharged on oral antibiotics were included in this study. The cohort was stratified into three groups based on bioavailability of oral antibiotics prescribed (high, ≥95%; moderate, 75-94%; and low, <75%). Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine treatment failure. Among the 362 patients, high, moderate and low bioavailability oral antibiotics were prescribed to 106, 179 and 77 patients, respectively, for definitive therapy of Gram-negative BSI. Mean patient age was 63 years, 217 (59.9%) were women and 254 (70.2%) had a urinary source of infection. Treatment failure rates were 2%, 12% and 14% in patients receiving oral antibiotics with high, moderate and low bioavailability, respectively (P = 0.02). Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Conditional Survival in Anal Carcinoma Using the National Population-Based Survey of Epidemiology and End Results Database (1988-2012).

PubMed

Kim, Ellen; Kim, Jong S; Choi, Mehee; Thomas, Charles R

2016-04-01

Conditional survival can provide valuable information for both patients and healthcare providers about the changing prognosis in surviving patients over time. This study estimated conditional survival for patients with anal cancer in the United States through analysis of a national population-based cancer registry. Log-rank test identified significant covariates of cause-specific survival (defined as time from diagnosis until death from anal cancer). Significant covariates were considered in the multivariable regression of cause-specific survival using Cox proportional hazards models. Covariates included cancer stage and demographic variables. Patients in Surveillance, Epidemiology, and End Results regions diagnosed with anal squamous cell carcinoma as their first and only cancer diagnosis from 1988 to 2012 were selected from this database, and 5145 patients were included in the retrospective cohort study. Five-year conditional survival stratified by each variable in the final Cox models was measured : The final multivariable models of overall and cause-specific survivals included stage, grade, sex, age, race, and relationship status. Over the first 6 years after diagnosis, conditional survival of distant stage increased from 37% to 89%, whereas regional stage increased from 65% to 93% and localized stage increased from 84% to 96%. The other variables had increasing prognosis as well, but the subgroups increased at a more similar rate over time. The data source used does not include information on chemotherapy treatment, patient comorbidities, or socioeconomic status. Conditional survival showed improvement over time. Patients with advanced stage had the greatest improvement in conditional survival. This is the first study to provide specific conditional survival probabilities for patients with anal cancer.

New simple radiological criteria proposed for multiple primary lung cancers.

PubMed

Matsunaga, Takeshi; Suzuki, Kenji; Takamochi, Kazuya; Oh, Shiaki

2017-11-01

Controversies remain as to the differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IM) in lung cancers. We have investigated the clinical criteria for MPLC and here propose a set of new and simple criteria from the stand point of prognosis. A retrospective study was conducted on 588 consecutive patients with resected lung cancer of clinical Stage IA between 2009 and 2012. Multiple lung cancers (MLCs) were observed in 103 (17.5%) of the 588 patients. All main and other tumors were divided into solid tumor (ST) and non-solid tumor (non-ST). We defined Group A as MLCs having at least one non-ST and Group B as all tumors being ST. Cox's proportional hazard model was used for the multivariate analyses to investigate the preoperative prognostic factors. We divided the MLCs into MPLC and IM based on the preoperative prognostic factors, and survival was estimated by the Kaplan-Meier method. A multivariate analysis with Cox's proportional hazards model revealed that Group A independently predicted good overall survival (HR = 0.165, 95% CI: 0.041-0.672).Differences in the 3- and 5-year overall survivals between Groups A and B were statistically significant (96.3%/92.2% vs. 70.0%/60.0%, Pvalue = 0.0002). We suggest that Group A, defined as the presence of at least one tumor with a ground glass opacity component and clinical N0, should be excluded from the conventional concept of multiple lung cancers based on the criteria of Martini and Melamed as it has a very good prognosis. This group would be considered to be radiological MPLC. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Risk factors of flare in rheumatoid arthritis patients with both clinical and ultrasonographic remission: a retrospective study from China.

PubMed

Han, Jingjing; Geng, Yan; Deng, Xuerong; Zhang, Zhuoli

2017-08-01

Ultrasonographic remission in addition to clinical remission is probably becoming a new target in the treatment of rheumatoid arthritis. The current study aimed to investigate the risk factors of flare in RA patients who achieved both clinical and ultrasonographic remission. RA patients fulfilled both clinical remission and ultrasonographic remissions were retrospectively enrolled in this study. Baseline clinical, laboratory, and ultrasonographic data were collected. Durations of clinical remission before enrollment and medication strategy during follow-up were recorded. Differences between the flare and the non-flare group were analyzed. Risk factors of flare were assessed with univariate and multivariate Cox proportional hazards models. One hundred and twenty-one RA patients were included. Forty-eight patients relapsed during a median follow-up period of 12.3 months. The flare group had higher percentage of females, shorter duration of clinical remission before enrollment, higher baseline ESR and DAS28 (ESR), and lower baseline gray scale score. Univariate Cox regression revealed female, short duration of remission, high DAS28 (ESR), and failure to achieve 2010 ACR/EULAR remission criteria were risk factors of flare. Furthermore, multivariate analysis showed short duration of remission was the only independent risk factor of flare (HR 0.93, 95% CI 0.88-0.98, P = 0.007). One more month in duration of remission led to a reduction in flare of 7.3%. Short duration of remission at baseline could be an independent risk factor of flare in RA patients who achieved both clinical and ultrasonographic remission, which implicates the significance of sustained remission in the prognosis of RA patients.

The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

PubMed

Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

2017-08-01

To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

Impact of cannabis and other drugs on age at onset of psychosis.

PubMed

González-Pinto, Ana; Vega, Patricia; Ibáñez, Berta; Mosquera, Fernando; Barbeito, Sara; Gutiérrez, Miguel; Ruiz de Azúa, Sonia; Ruiz, Iván; Vieta, Eduard

2008-08-01

The aim of this study was to investigate the relationship between age and cannabis use in patients with a first psychotic episode, and to analyze the mediating effect of comorbid use of other drugs and sex on age at onset of psychosis. All consenting patients (aged 15 to 65 years) with a first psychotic episode needing inpatient psychiatric treatment during a 2-year period between February 1997 and January 1999 were considered, confirming a total of 131 patients. Subjects were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders, and clinical and demographic data were collected. We used general linear models with age at onset as the response variable and survival Cox models to confirm the results. Both a multivariate linear model and the corresponding Cox model were fitted with a covariate that summarizes the most significant contributors that seemed to decrease age at onset. Regarding the effect of cannabis use, a significant gradual reduction on age at onset was found as dependence on cannabis increased, consisting in a decrement of 7, 8.5, and 12 years for users, abusers, and dependents, respectively, with respect to nonusers (p = .004, p < .001, and p < .001, respectively). Multivariate analysis showed a clear effect of cannabis use on age at onset, which was not explained by the use of other drugs or by gender. The finding was similar in the youngest patients, suggesting that this effect was not due to chance. The major contribution of this investigation is the independent and strong link between cannabis use and early age at onset of psychosis, and the slight or nonexistent effect of sex and comorbid substance abuse in this variable. These results point to cannabis as a dangerous drug in young people at risk of developing psychosis.

Duration of Mechanical Ventilation in the Emergency Department.

PubMed

Angotti, Lauren B; Richards, Jeremy B; Fisher, Daniel F; Sankoff, Jeffrey D; Seigel, Todd A; Al Ashry, Haitham S; Wilcox, Susan R

2017-08-01

Due to hospital crowding, mechanically ventilated patients are increasingly spending hours boarding in emergency departments (ED) before intensive care unit (ICU) admission. This study aims to evaluate the association between time ventilated in the ED and in-hospital mortality, duration of mechanical ventilation, ICU and hospital length of stay (LOS). This was a multi-center, prospective, observational study of patients ventilated in the ED, conducted at three academic Level I Trauma Centers from July 2011 to March 2013. All consecutive adult patients on invasive mechanical ventilation were eligible for enrollment. We performed a Cox regression to assess for a mortality effect for mechanically ventilated patients with each hour of increasing LOS in the ED and multivariable regression analyses to assess for independently significant contributors to in-hospital mortality. Our primary outcome was in-hospital mortality, with secondary outcomes of ventilator days, ICU LOS and hospital LOS. We further commented on use of lung protective ventilation and frequency of ventilator changes made in this cohort. We enrolled 535 patients, of whom 525 met all inclusion criteria. Altered mental status without respiratory pathology was the most common reason for intubation, followed by trauma and respiratory failure. Using iterated Cox regression, a mortality effect occurred at ED time of mechanical ventilation > 7 hours, and the longer ED stay was also associated with a longer total duration of intubation. However, adjusted multivariable regression analysis demonstrated only older age and admission to the neurosciences ICU as independently associated with increased mortality. Of interest, only 23.8% of patients ventilated in the ED for over seven hours had changes made to their ventilator. In a prospective observational study of patients mechanically ventilated in the ED, there was a significant mortality benefit to expedited transfer of patients into an appropriate ICU setting.

Serum thymidine kinase 1 levels predict cancer-free survival following neoadjuvant, surgical and adjuvant treatment of patients with locally advanced breast cancer

PubMed Central

CHEN, FEIYU; TANG, LILI; XIA, TING; HE, ELLEN; HU, GUOZHU; LI, YUAN; ZHANG, MING; ZHOU, JI; ERIKSSON, STAFFAN; SKOG, SVEN

2013-01-01

In this study, the use of serum thymidine kinase 1 protein (STK1p) concentration for the prognosis of the overall survival of patients with locally advanced breast cancer (n=51) following routine treatment (neoadjuvant treatment, surgery and chemotherapy) was investigated. The patients were followed up for 44 months and the STK1p values were determined by a high-sensitivity enhanced chemiluminescence (ECL) dot blot assay. The variables investigated in relation to metastasis and survival were STK1p, clinical stage, tumor size and age, by the Kaplan-Meier method, the log-rank test and Cox uni- and multivariate analyses. Patients with high STK1p values (≥2.0 pM) 3–6 months after surgery exhibited a positive correlation to clinical stage, tumor size, occurrence of metastasis and survival. The hazard risk for the development of metastatic disease and mortality among breast cancer patients was 11–12 times higher in patients with high compared to those with low STK1p values (<2.0 pM). Notably, patients with stage III/IV disease and low STK1p values exhibited statistically significantly improved survival compared to patients with high STK1p values. A multivariate Cox analysis demonstrated that the STK1p levels 6 months after surgery was the only independent prognostic factor for metastasis and survival. In conclusion, STK1p is a prognostic marker in patients with locally advanced breast cancer and it may help identify a subgroup of stage III/IV patients with improved cancer-free survival expectancy, enabling personalized treatment. PMID:24649267

Mutations in TP53 are a prognostic factor in colorectal hepatic metastases undergoing surgical resection.

PubMed

Molleví, David G; Serrano, Teresa; Ginestà, Mireia M; Valls, Joan; Torras, Jaume; Navarro, Matilde; Ramos, Emilio; Germà, Josep R; Jaurrieta, Eduardo; Moreno, Víctor; Figueras, Joan; Capellà, Gabriel; Villanueva, Alberto

2007-06-01

The aim of this study was to analyze the prognostic value of TP53 mutations in a consecutive series of patients with hepatic metastases (HMs) from colorectal cancer undergoing surgical resection. Ninety-one patients with liver metastases from colorectal carcinoma were included. Mutational analysis of TP53, exons 4-10, was performed by single-strand conformation polymorphism and sequencing. P53 and P21 protein immunostaining was assessed. Multivariate Cox models were adjusted for gender, number of metastasis, resection margin, presence of TP53 mutations and chemotherapy treatment. Forty-six of 91 (50.05%) metastases showed mutations in TP53, observed mainly in exons 5-8, although 14.3% (n = 13) were located in exons 9 and 10. Forty percent (n = 22) were protein-truncating mutations. TP53 status associated with multiple (> or =3) metastases (65.6%, P = 0.033), advanced primary tumor Dukes' stage (P = 0.011) and younger age (<57 years old, P = 0.03). Presence of mutation associated with poor prognosis in univariate (P = 0.017) and multivariate Cox model [hazard ratio (HR) = 1.80, 95% confidence interval (CI) = 1.07-3.06, P = 0.028]. Prognostic value was maintained in patients undergoing radical resection (R0 series, n = 79, P = 0.014). Mutation associated with a worse outcome in chemotherapy-treated patients (HR = 2.54, 95% CI = 1.12-5.75, P = 0.026). The combination of > or =3 metastases and TP53 mutation identified a subset of patients with very poor prognosis (P = 0.009). P53 and P21 protein immunostaining did not show correlation with survival. TP53 mutational status seems to be an important prognostic factor in patients undergoing surgical resection of colorectal cancer HMs.

Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: a SEER population-based retrospective analysis.

PubMed

Feng, Jianhua; Shen, Fei; Cai, Wensong; Gan, Xiaoxiong; Deng, Xingyan; Xu, Bo

2018-06-16

Patients younger than 55 years of age with papillary thyroid carcinoma (PTC) have excellent survival. Diffuse sclerosing variant (DSV) and tall cell variant (TCV) of PTC are associated with aggressiveness; the survival of patients <55 years of age with these variants is still unclear. We aim to investigate the clinicopathological features and survival of these variants in the age group <55 years. All adult patients (<55 years old) with DSV, TCV and conventional PTC (CPTC) came from the Surveillance, Epidemiology, and End Results program (1988-2013). Kaplan-Meier method and log-rank test were used to analyze the survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression. There were 280 DSV, 615 TCV, and 56287 CPTC in the age group <55 years. DSV and TCV were associated with multifocality, extrathyroidal extension, lymph node and distant metastasis (all p < 0.05). The 10-year disease-specific survival (DSS) of TCV was worse than CPTC (96.3 vs. 99.4%, p < 0.01), but there was no significant difference between DSV and CPTC (99.5 vs. 99.4%, p > 0.05). Cox multivariate regression showed TCV was the independent predictor of DSS (HR: 5.39, p < 0.01). In the age group <55 years, DSV and TCV are more likely to exhibit aggressive characteristics than CPTC. Patient <55 years of age with DSV have excellent survival likewise, while patients <55 years of age with TCV carry worse survival. Further investigation for the recurrence risk of patients <55 years with these variants would contribute to optimal clinical management making.

DNA mismatch repair gene polymorphisms affect survival in pancreatic cancer.

PubMed

Dong, Xiaoqun; Li, Yanan; Hess, Kenneth R; Abbruzzese, James L; Li, Donghui

2011-01-01

DNA mismatch repair (MMR) maintains genomic stability and mediates cellular response to DNA damage. We aim to demonstrate whether MMR genetic variants affect overall survival (OS) in pancreatic cancer. Using the Sequenom method in genomic DNA, we retrospectively genotyped 102 single-nucleotide polymorphisms (SNPs) of 13 MMR genes from 706 patients with pancreatic adenocarcinoma seen at The University of Texas MD Anderson Cancer Center. Association between genotype and OS was evaluated using multivariable Cox proportional hazard regression models. At a false discovery rate of 1% (p ≤ .0015), 15 SNPs of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, TP73, and TREX1 in patients with localized disease (n = 333) and 6 SNPs of MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease (n = 373) were significantly associated with OS. In multivariable Cox proportional hazard regression models, SNPs of EXO1, MSH2, MSH3, PMS2L3, and TP73 in patients with localized disease, MSH2, MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease, and EXO1, MGMT, MSH2, MSH3, MSH6, PMS2L3, and TP73 in all patients remained significant predictors for OS (p ≤ .0015) after adjusting for all clinical predictors and all SNPs with p ≤ .0015 in single-locus analysis. Sixteen haplotypes of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, RECQL, TP73, and TREX1 significantly correlated with OS in all patients (p ≤ .001). MMR gene variants may have potential value as prognostic markers for OS in pancreatic cancer patients.

Hospital of diagnosis and probability of having surgical treatment for resectable gastric cancer.

PubMed

van Putten, M; Verhoeven, R H A; van Sandick, J W; Plukker, J T M; Lemmens, V E P P; Wijnhoven, B P L; Nieuwenhuijzen, G A P

2016-02-01

Gastric cancer surgery is increasingly being centralized in the Netherlands, whereas the diagnosis is often made in hospitals where gastric cancer surgery is not performed. The aim of this study was to assess whether hospital of diagnosis affects the probability of undergoing surgery and its impact on overall survival. All patients with potentially curable gastric cancer according to stage (cT1/1b-4a, cN0-2, cM0) diagnosed between 2005 and 2013 were selected from The Netherlands Cancer Registry. Multilevel logistic regression was used to examine the probability of undergoing surgery according to hospital of diagnosis. The effect of variation in probability of undergoing surgery among hospitals of diagnosis on overall survival during the intervals 2005-2009 and 2010-2013 was examined by using Cox regression analysis. A total of 5620 patients with potentially curable gastric cancer, diagnosed in 91 hospitals, were included. The proportion of patients who underwent surgery ranged from 53.1 to 83.9 per cent according to hospital of diagnosis (P < 0.001); after multivariable adjustment for patient and tumour characteristics it ranged from 57.0 to 78.2 per cent (P < 0.001). Multivariable Cox regression showed that patients diagnosed between 2010 and 2013 in hospitals with a low probability of patients undergoing curative treatment had worse overall survival (hazard ratio 1.21; P < 0.001). The large variation in probability of receiving surgery for gastric cancer between hospitals of diagnosis and its impact on overall survival indicates that gastric cancer decision-making is suboptimal. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation.

PubMed

Mai, Hoa Le; Treilhaud, Michèle; Ben-Arye, Shani Leviatan; Yu, Hai; Perreault, Hélène; Ang, Evelyn; Trébern-Launay, Katy; Laurent, Julie; Malard-Castagnet, Stéphanie; Cesbron, Anne; Nguyen, Thi Van Ha; Brouard, Sophie; Rostaing, Lionel; Houssel-Debry, Pauline; Legendre, Christophe; Girerd, Sophie; Kessler, Michèle; Morelon, Emmanuel; Sicard, Antoine; Garrigue, Valérie; Karam, Georges; Chen, Xi; Giral, Magali; Padler-Karavani, Vered; Soulillou, Jean Paul

2018-04-01

End-stage renal failure occurs in a substantial number of patients having received a nonrenal transplantation (NRT), for whom a kidney transplantation is needed. The medical strategy regarding the use of immunosuppression (IS) for a kidney graft in patients after an NRT is not well established. The prekidney grafts long-term IS advocates for a mild induction, such as using anti-IL-2R antibodies, whereas addition of new incompatibilities and anti-HLA preimmunization may suggest using stronger IS such as induction by polyclonal antithymocyte globulins (ATG). We performed Cox multivariate and propensity score analysis of our validated transplant database to study the impact of the type of induction therapy on kidney graft survival of recipients of a kidney graft after NRT. We report here that kidney transplantation after NRT treated with an ATG induction has a poorer outcome (kidney and recipient survival) than that with an anti-IL-2R induction. After accounting for potential baseline differences with a multivariate Cox model, or by adjusting on a propensity score, we found that despite patients having received ATG cumulate more risk factors, ATG appears independently involved. As animal-derived biotherapeutics induce antiglycan antibodies and particularly anti-N-glycolylneuraminic acid (Neu5Gc) IgGs which may activate endothelial cells in patients and grafts, we also investigated the magnitude and the nature of the anti-Neu5Gc elicited by the induction and showed that induction was associated with a shift in anti-Neu5Gc IgG repertoire. Possible reasons and mechanisms of a deleterious ATG usage in these patients are discussed. Our study suggests that ATG induction after a kidney transplantation in recipients already under maintenance IS for a NRT should be used cautiously.

KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma.

PubMed

Nadal, Ernest; Chen, Guoan; Prensner, John R; Shiratsuchi, Hiroe; Sam, Christine; Zhao, Lili; Kalemkerian, Gregory P; Brenner, Dean; Lin, Jules; Reddy, Rishindra M; Chang, Andrew C; Capellà, Gabriel; Cardenal, Felipe; Beer, David G; Ramnath, Nithya

2014-10-01

The aim of this study was to examine the effects of KRAS mutant subtypes on the outcome of patients with resected lung adenocarcinoma (AC). Using clinical and sequencing data, we identified 179 patients with resected lung AC for whom KRAS mutational status was determined. A multivariate Cox model was used to identify factors associated with disease-free survival (DFS) and overall survival (OS). Publicly available mutation and gene-expression data from lung cancer cell lines and lung AC were used to assess whether distinct KRAS mutant variants have a different profile. Patients with KRAS mutation had a significantly shorter DFS compared with those with KRAS wild-type (p = 0.009). Patients with KRAS-G12C mutant tumors had significantly shorter DFS compared with other KRAS mutants and KRAS wild-type tumors (p < 0.001). In the multivariate Cox model, KRAS-G12C remained as an independent prognostic marker for DFS (Hazard ratio = 2.46, 95% confidence interval 1.51-4.00, p < 0.001) and for OS (Hazard ratio = 2.35, 95% confidence interval 1.35-4.10, p = 0.003). No genes were statistically significant when comparing the mutational or transcriptional profile of lung cancer cell lines and lung AC harboring KRAS-G12C with other KRAS mutant subtypes. Gene set enrichment analysis revealed that KRAS-G12C mutants overexpressed epithelial to mesenchymal transition genes and expressed lower levels of genes predicting KRAS dependency. KRAS-G12C mutation is associated with worse DFS and OS in resected lung AC. Gene-expression profiles in lung cancer cell lines and surgically resected lung AC revealed that KRAS-G12C mutants had an epithelial to mesenchymal transition and a KRAS-independent phenotype.

Grading the neuroendocrine tumors of the lung: an evidence-based proposal.

PubMed

Rindi, G; Klersy, C; Inzani, F; Fellegara, G; Ampollini, L; Ardizzoni, A; Campanini, N; Carbognani, P; De Pas, T M; Galetta, D; Granone, P L; Righi, L; Rusca, M; Spaggiari, L; Tiseo, M; Viale, G; Volante, M; Papotti, M; Pelosi, G

2014-02-01

Lung neuroendocrine tumors are catalogued in four categories by the World Health Organization (WHO 2004) classification. Its reproducibility and prognostic efficacy was disputed. The WHO 2010 classification of digestive neuroendocrine neoplasms is based on Ki67 proliferation assessment and proved prognostically effective. This study aims at comparing these two classifications and at defining a prognostic grading system for lung neuroendocrine tumors. The study included 399 patients who underwent surgery and with at least 1 year follow-up between 1989 and 2011. Data on 21 variables were collected, and performance of grading systems and their components was compared by Cox regression and multivariable analyses. All statistical tests were two-sided. At Cox analysis, WHO 2004 stratified patients into three major groups with statistically significant survival difference (typical carcinoid vs atypical carcinoid (AC), P=0.021; AC vs large-cell/small-cell lung neuroendocrine carcinomas, P<0.001). Optimal discrimination in three groups was observed by Ki67% (Ki67% cutoffs: G1 <4, G2 4-<25, G3 ≥25; G1 vs G2, P=0.021; and G2 vs G3, P≤0.001), mitotic count (G1 ≤2, G2 >2-47, G3 >47; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001), and presence of necrosis (G1 absent, G2 <10% of sample, G3 >10% of sample; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001) at uni and multivariable analyses. The combination of these three variables resulted in a simple and effective grading system. A three-tiers grading system based on Ki67 index, mitotic count, and necrosis with cutoffs specifically generated for lung neuroendocrine tumors is prognostically effective and accurate.

Hilar fat infiltration: A new prognostic factor in metastatic clear cell renal cell carcinoma with first-line sunitinib treatment.

PubMed

Kammerer-Jacquet, Solène-Florence; Brunot, Angelique; Bensalah, Karim; Campillo-Gimenez, Boris; Lefort, Mathilde; Bayat, Sahar; Ravaud, Alain; Dupuis, Frantz; Yacoub, Mokrane; Verhoest, Gregory; Peyronnet, Benoit; Mathieu, Romain; Lespagnol, Alexandra; Mosser, Jean; Edeline, Julien; Laguerre, Brigitte; Bernhard, Jean-Christophe; Rioux-Leclercq, Nathalie

2017-10-01

The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib. In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect. HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival. HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

In Silico Analysis of the Potential of the Active Compounds Fucoidan and Alginate Derived from Sargassum Sp. as Inhibitors of COX-1 and COX-2

PubMed Central

Dewi, Lestari

2016-01-01

Introduction: The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. Aim: The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. Material and methods: The study was conducted by means of a computational (in silico) method. It was performed in two main stages, the docking between COX-1 and COX-2 with Fucoidan, alginate and aspirin (for comparison) and the analysis of the amount of interactions formed and the residues directly involved in the process of interaction. Results: Our results showed that both Fucoidan and alginate had an excellent potential as inhibitors of COX-1 and COX-2. Fucoidan had a better potential as an inhibitor of COX than alginate. COX inhibition was expected to provide a more favorable effect on inflammation-related pathological conditions. Conclusion: The active compounds Fucoidan and alginate derived from Sargassum sp. were suspected to possess a good potential as inhibitors of COX-1 and COX-2. PMID:27594740

In Silico Analysis of the Potential of the Active Compounds Fucoidan and Alginate Derived from Sargassum Sp. as Inhibitors of COX-1 and COX-2.

PubMed

Dewi, Lestari

2016-06-01

The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. The study was conducted by means of a computational (in silico) method. It was performed in two main stages, the docking between COX-1 and COX-2 with Fucoidan, alginate and aspirin (for comparison) and the analysis of the amount of interactions formed and the residues directly involved in the process of interaction. Our results showed that both Fucoidan and alginate had an excellent potential as inhibitors of COX-1 and COX-2. Fucoidan had a better potential as an inhibitor of COX than alginate. COX inhibition was expected to provide a more favorable effect on inflammation-related pathological conditions. The active compounds Fucoidan and alginate derived from Sargassum sp. were suspected to possess a good potential as inhibitors of COX-1 and COX-2.

Association Between Treatment at High-Volume Facilities and Improved Overall Survival in Soft Tissue Sarcomas.

PubMed

Venigalla, Sriram; Nead, Kevin T; Sebro, Ronnie; Guttmann, David M; Sharma, Sonam; Simone, Charles B; Levin, William P; Wilson, Robert J; Weber, Kristy L; Shabason, Jacob E

2018-03-15

Soft tissue sarcomas (STS) are rare malignancies that require complex multidisciplinary management. Therefore, facilities with high sarcoma case volume may demonstrate superior outcomes. We hypothesized that STS treatment at high-volume (HV) facilities would be associated with improved overall survival (OS). Patients aged ≥18 years with nonmetastatic STS treated with surgery and radiation therapy at a single facility from 2004 through 2013 were identified from the National Cancer Database. Facilities were dichotomized into HV and low-volume (LV) cohorts based on total case volume over the study period. OS was assessed using multivariable Cox regression with propensity score-matching. Patterns of care were assessed using multivariable logistic regression analysis. Of 9025 total patients, 1578 (17%) and 7447 (83%) were treated at HV and LV facilities, respectively. On multivariable analysis, high educational attainment, larger tumor size, higher grade, and negative surgical margins were statistically significantly associated with treatment at HV facilities; conversely, black race and non-metropolitan residence were negative predictors of treatment at HV facilities. On propensity score-matched multivariable analysis, treatment at HV facilities versus LV facilities was associated with improved OS (hazard ratio, 0.87, 95% confidence interval, 0.80-0.95; P = .001). Older age, lack of insurance, greater comorbidity, larger tumor size, higher tumor grade, and positive surgical margins were associated with statistically significantly worse OS. In this observational cohort study using the National Cancer Database, receipt of surgery and radiation therapy at HV facilities was associated with improved OS in patients with STS. Potential sociodemographic disparities limit access to care at HV facilities for certain populations. Our findings highlight the importance of receipt of care at HV facilities for patients with STS and warrant further study into improving access to care at HV facilities. Copyright © 2017 Elsevier Inc. All rights reserved.

Reassessment of the relationship between M-protein decrement and survival in multiple myeloma.

PubMed

Palmer, M; Belch, A; Hanson, J; Brox, L

1989-01-01

The relationship between percentage M-protein decrement and survival is assessed in 134 multiple myeloma patients. The correlation did not achieve statistical significance (P = 0.069). Multivariate analysis using the Cox proportional hazards model, including a number of previously recognised prognostic factors, showed only percentage M-protein decrement, creatinine and haemoglobin to be significantly correlated with survival. However, the R'-statistic for each of these variables was low, indicating that their prognostic power is weak. We conclude that neither the percentage M-protein decrement nor the response derived from it can be used as an accurate means of assessing the efficacy of treatment in myeloma. Mature survival data alone should be used for this purpose.

Reassessment of the relationship between M-protein decrement and survival in multiple myeloma.

PubMed Central

Palmer, M.; Belch, A.; Hanson, J.; Brox, L.

1989-01-01

The relationship between percentage M-protein decrement and survival is assessed in 134 multiple myeloma patients. The correlation did not achieve statistical significance (P = 0.069). Multivariate analysis using the Cox proportional hazards model, including a number of previously recognised prognostic factors, showed only percentage M-protein decrement, creatinine and haemoglobin to be significantly correlated with survival. However, the R'-statistic for each of these variables was low, indicating that their prognostic power is weak. We conclude that neither the percentage M-protein decrement nor the response derived from it can be used as an accurate means of assessing the efficacy of treatment in myeloma. Mature survival data alone should be used for this purpose. PMID:2757916

Prospective Validation of a Screening Biomarker Approach Combining Amino-Terminal Pro-Brain Natriuretic Peptide With Galectin-3 Predicts Death and Cardiovascular Events in Asymptomatic Hemodialysis Patients.

PubMed

Voroneanu, Luminita; Siriopol, Dimitrie; Apetrii, Mugurel; Hogas, Simona; Onofriescu, Mihai; Nistor, Ionut; Kanbay, Mehmet; Dumea, Raluca; Cusai, Silvia; Cianga, Petru; Constantinescu, Daniela; Covic, Adrian

2018-05-01

Cardiovascular (CV) disease is a major cause of death in hemodialysis patients. Biomarkers used to identify high-risk asymptomatic patients would allow early evaluation of cardiac dysfunction and appropriate therapeutic intervention. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 (Gal-3) may serve this purpose. Plasma levels of NT-proBNP and Gal-3 were measured in 173 patients. Patients were prospectively followed for occurrences of major CV events or death. The association of NT-proBNP and Gal-3 with outcome was analyzed. The prognostic abilities for the combined outcome of Gal-3 and/or NT-proBNP were evaluated. During a median follow-up of 36 months, there were 47 incident outcomes (death and CV events). In the univariable Cox analysis, age, hypertension, albumin, phosphorus levels, and combined elevation of NT-proBNP with Gal-3 above the median (hazard ratio [HR] = 3.65, 95% confidence interval [CI] = 1.45-9.21) were associated with outcomes. In multivariable Cox analysis, both NT-proBNP and Gal-3 values above the median remained associated with outcomes (HR = 3.34, 95% CI = 1.30-8.56). In clinically asymptomatic dialysis patients, combined use of NT-proBNP and Gal-3 may improve risk stratification for death and CV events.

Longitudinal relationship between traumatic brain injury and the risk of incident optic neuropathy: A 10-year follow-up nationally representative Taiwan survey

PubMed Central

Chen, Ying-Jen; Liang, Chang-Min; Tai, Ming-Cheng; Chang, Yun-Hsiang; Lin, Tzu-Yu; Chung, Chi-Hsiang; Lin, Fu-Huang; Tsao, Chang-Huei; Chien, Wu-Chien

2017-01-01

Accumulating evidences had shown that traumatic brain injury was associated with visual impairment or vision loss. However, there were a limited number of empirical studies regarding the longitudinal relationship between traumatic brain injury and incident optic neuropathy. We studied a cohort from the Taiwanese National Health Insurance data comprising 553918 participants with traumatic brain injury and optic neuropathy-free in the case group and 1107836 individuals without traumatic brain injury in the control group from 1st January 2000. After the index date until the end of 2010, Cox proportional hazards analysis was used to compare the risk of incident optic neuropathy. During the follow-up period, case group was more likely to develop incident optic neuropathy (0.24%) than the control group (0.11%). Multivariate Cox regression analysis demonstrated that the case group had a 3-fold increased risk of optic neuropathy (HR = 3.017, 95% CI = 2.767–3.289, p < 0.001). After stratification by demographic information, traumatic brain injury remained a significant factor for incident optic neuropathy. Our study provided evidence of the increased risk of incident optic neuropathy after traumatic brain injury during a 10-year follow-up period. Patients with traumatic brain injury required periodic and thorough eye examinations for incident optic neuropathy to prevent potentially irreversible vision loss. PMID:29156847

Longitudinal relationship between traumatic brain injury and the risk of incident optic neuropathy: A 10-year follow-up nationally representative Taiwan survey.

PubMed

Chen, Ying-Jen; Liang, Chang-Min; Tai, Ming-Cheng; Chang, Yun-Hsiang; Lin, Tzu-Yu; Chung, Chi-Hsiang; Lin, Fu-Huang; Tsao, Chang-Huei; Chien, Wu-Chien

2017-10-17

Accumulating evidences had shown that traumatic brain injury was associated with visual impairment or vision loss. However, there were a limited number of empirical studies regarding the longitudinal relationship between traumatic brain injury and incident optic neuropathy. We studied a cohort from the Taiwanese National Health Insurance data comprising 553918 participants with traumatic brain injury and optic neuropathy-free in the case group and 1107836 individuals without traumatic brain injury in the control group from 1st January 2000. After the index date until the end of 2010, Cox proportional hazards analysis was used to compare the risk of incident optic neuropathy. During the follow-up period, case group was more likely to develop incident optic neuropathy (0.24%) than the control group (0.11%). Multivariate Cox regression analysis demonstrated that the case group had a 3-fold increased risk of optic neuropathy (HR = 3.017, 95% CI = 2.767-3.289, p < 0.001). After stratification by demographic information, traumatic brain injury remained a significant factor for incident optic neuropathy. Our study provided evidence of the increased risk of incident optic neuropathy after traumatic brain injury during a 10-year follow-up period. Patients with traumatic brain injury required periodic and thorough eye examinations for incident optic neuropathy to prevent potentially irreversible vision loss.

[Psychiatric readmissions: individual and organizational factors].

PubMed

Plancke, Laurent; Amariei, Alina; Flament, Clara; Dumesnil, Chloé

2017-01-01

Psychiatric readmission often constitutes a criterion to assess the effects of various therapies, as well as the impact of organizational changes in the healthcare system. It is used to characterize relapse or decompensation. The purpose of this study was to determine readmission rates and identify individual and organizational factors associated with significant variations in these rates. Adult psychiatric readmissions were identified from the full-time hospital stays registered in psychiatric wards in 2011-2012 in the Nord and Pas-de-Calais departments of France, available in the medical the RimP psychiatric admission database. Readmission rates for various follow-up periods after discharge were measured by Kaplan-Meier survival analysis and multivariate analysis was conducted using the Cox proportional hazards model. Approximately 30,000 adults were hospitalized full-time in psychiatric units of the region during the study period. The 24-month readmission rate was 51.6% (95%CI: 50.8-52.3%). The Cox model showed that a diagnosis of schizophrenia (F2 - HR = 1.72 - 95%CI: 1.61-1.84 - p < 0.001) and personality disorder (F6 - HR = 1.45 - 95%CI: 1.32-1.58 - p < 0.001) was associated with a higher readmission rate. Readmission rates were higher among dependent patients in non-profit private hospitals. Psychiatric readmission is a very frequent event and is linked to organizational as well as individual factors.

Success and duration of dynamic bracing for pectus carinatum: A four-year prospective study.

PubMed

Emil, Sherif; Sévigny, Marika; Montpetit, Kathleen; Baird, Robert; Laberge, Jean-Martin; Goyette, Jade; Finlay, Ian; Courchesne, Guylaine

2017-01-01

This study sought to establish factors that can prognosticate outcomes of bracing for pectus carinatum (PC). Prospective data were collected on all patients enrolled in a dynamic bracing protocol from July 2011 to July 2015. Pressure of correction (POC) was measured at initiation of treatment, and pressure of treatment (POT) was measured pre- and post-adjustment at every follow-up visit. Univariate and Cox regression analysis tested the following possible determinants of success and bracing duration: age, sex, symmetry, POC, and POT drop during the first two follow-up visits. Of 114 patients, 64 (56%) succeeded, 33 (29%) were still in active bracing, and 17 (15%) failed or were lost to follow-up. In successful patients, active and maintenance bracing was 5.66±3.81 and 8.80±3.94months, respectively. Asymmetry and older age were significantly associated with failure. Multivariable Cox proportional hazard analysis of time-to-maintenance showed that asymmetry (p=0.01) and smaller first drop in POT (p=0.02) were associated with longer time to reach maintenance. Pressure of correction does not predict failure of bracing, but older age, asymmetry, and smaller first drop in pressure of treatment are associated with failure and longer bracing duration. Prospective Study/Level of Evidence IV. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio as an associated factor of high risk plaque on coronary computed tomography in patients without coronary artery disease.

PubMed

Nagahara, Yasuomi; Motoyama, Sadako; Sarai, Masayoshi; Ito, Hajime; Kawai, Hideki; Takakuwa, Yoko; Miyagi, Meiko; Shibata, Daisuke; Takahashi, Hiroshi; Naruse, Hiroyuki; Ishii, Junichi; Ozaki, Yukio

2016-07-01

Coronary computed tomography angiography (CCTA)-verified high risk plaque (HRP) characteristics including positive remodeling and low attenuation plaque have been associated with acute coronary syndromes. Several studies reported that the n-3 polyunsaturated fatty acids have been associated with cardiovascular events. However, the relationship between serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio and CCTA-verified HRP in patients without known coronary artery disease (CAD) is unclear. We aimed at investigating the relation between EPA/AA and CCTA-verified HRP in patients without known CAD. We included 193 patients undergoing CCTA without known CAD (65.5 ± 12.0 years, 55.0% male). No patient has been treated with EPA. The relation of coronary risk factors, lipid profile, high-sensitivity C-reactive protein, coronary artery calcification score (CACS), number of vessel disease, plaque burden, and EPA/AA with the presence of HRP was evaluated by logistic regression analysis. Incremental value of EPA/AA to predict HRP was also analyzed by C-index, NRI, and IDI. A Cox proportional hazards model was used to estimate the time to cardiovascular event. HRP was observed in 37 (19%) patients. Multivariable logistic regression analysis revealed that current smoking (OR 2.58; p=0.046), number of vessel disease (OR 1.87; p=0.031), and EPA/AA ratio (OR 0.65; p=0.0006) were independent associated factors of HRP on CCTA. Although the addition of EPA/AA to the baseline model did not significantly improve C-index, both NRI (0.60, p=0.0049) and IDI (0.054, p=0.0072) were significantly improved. Patients with HRP had significantly higher rate of events compared with patients without HRP (14% vs. 3%, Logrank p=0.0004). On multivariable Cox hazard analysis, baseline EPA/AA ratio was an independent predictor (HR 0.57, p=0.047). Low EPA/AA was an associated factor of HRP on CCTA in patients without CAD. In addition to conventional coronary risk factors and CACS, EPA/AA and CCTA might be useful for risk stratification of CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

PubMed Central

Pascual, Julio; Samaniego, Milagros D.; Torrealba, José R.; Odorico, Jon S.; Djamali, Arjang; Becker, Yolanda T.; Voss, Barbara; Leverson, Glen E.; Knechtle, Stuart J.; Sollinger, Hans W.; Pirsch, John D.

2008-01-01

The prevalence, risk factors, and outcome of antibody-mediated rejection (AMR) of the kidney after simultaneous pancreas-kidney transplantation are unknown. In 136 simultaneous pancreas-kidney recipients who were followed for an average of 3.1 yr, 21 episodes of AMR of the kidney allograft were identified. Eight episodes occurred early (≤90 d) after transplantation, and 13 occurred later. Histologic evidence of concomitant acute cellular rejection was noted in 12 cases; the other nine had evidence only of humoral rejection. In 13 cases, clinical rejection of the pancreas was diagnosed simultaneously, and two of these were biopsy proven and were positive for C4d immunostaining. Multivariate analysis identified only one significant risk factor: Female patients were three times more likely to experience AMR. Nearly all early episodes resolved with treatment and did not predict graft loss, but multivariate Cox models revealed that late AMR episodes more than tripled the risk for kidney and pancreas graft loss; therefore, new strategies are needed to prevent and to treat late AMR in simultaneous pancreas-kidney transplant recipients. PMID:18235091

Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease.

PubMed

Zhou, Bing-Yang; Guo, Yuan-Lin; Wu, Na-Qiong; Zhu, Cheng-Gang; Gao, Ying; Qing, Ping; Li, Xiao-Lin; Wang, Yao; Dong, Qian; Liu, Geng; Xu, Rui Xia; Cui, Chuan-Jue; Sun, Jing; Li, Jian-Jun

2017-03-01

Big endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear. A total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group (n=189) and non-events group (n=2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099-2.496, p=0.016). Additionally, the Kaplan-Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival (p=0.016). The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Causes of death in long-term lung cancer survivors: a SEER database analysis.

PubMed

Abdel-Rahman, Omar

2017-07-01

Long-term (>5 years) lung cancer survivors represent a small but distinct subgroup of lung cancer patients and information about the causes of death of this subgroup is scarce. The Surveillance, Epidemiology and End Results (SEER) database (1988-2008) was utilized to determine the causes of death of long-term survivors of lung cancer. Survival analysis was conducted using Kaplan-Meier analysis and multivariate analysis was conducted using a Cox proportional hazard model. Clinicopathological characteristics and survival outcomes were assessed for the whole cohort. A total of 78,701 lung cancer patients with >5 years survival were identified. This cohort included 54,488 patients surviving 5-10 years and 24,213 patients surviving >10 years. Among patients surviving 5-10 years, 21.8% were dead because of primary lung cancer, 10.2% were dead because of other cancers, 6.8% were dead because of cardiac disease and 5.3% were dead because of non-malignant pulmonary disease. Among patients surviving >10 years, 12% were dead because of primary lung cancer, 6% were dead because of other cancers, 6.9% were dead because of cardiac disease and 5.6% were dead because of non-malignant pulmonary disease. On multivariate analysis, factors associated with longer cardiac-disease-specific survival in multivariate analysis include younger age at diagnosis (p < .0001), white race (vs. African American race) (p = .005), female gender (p < .0001), right-sided disease (p = .003), adenocarcinoma (vs. large cell or small cell carcinoma), histology and receiving local treatment by surgery rather than radiotherapy (p < .0001). The probability of death from primary lung cancer is still significant among other causes of death even 20 years after diagnosis of lung cancer. Moreover, cardiac as well as non-malignant pulmonary causes contribute a considerable proportion of deaths in long-term lung cancer survivors.

Development and validation of prognostic models in metastatic breast cancer: a GOCS study.

PubMed

Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Machiavelli, M; Leone, B; Romero, A; Rodriguez, R; Cuevas, M; Dansky, C

1992-01-01

The significance of several prognostic factors and the magnitude of their influence on response rate and survival were assessed by means of uni- and multivariate analyses in 362 patients with stage IV (UICC) breast carcinoma receiving combination chemotherapy as first systemic treatment over an 8-year period. Univariate analyses identified performance status and prior adjuvant radiotherapy as predictors of objective regression (OR), whereas the performance status, prior chemotherapy and radiotherapy (adjuvants), white blood cells count, SGOT and SGPT levels, and metastatic pattern were significantly correlated to survival. In multivariate analyses favorable characteristics associated to OR were prior adjuvant radiotherapy, no prior chemotherapy and postmenopausal status. Regarding survival, the performance status and visceral involvement were selected by the Cox model. The predictive accuracy of the logistic and the proportional hazards models was retrospectively tested in the training sample, and prospectively in a new population of 126 patients also receiving combined chemotherapy as first treatment for metastatic breast cancer. A certain overfitting to data in the training sample was observed with the regression model for response. However, the discriminative ability of the Cox model for survival was clearly confirmed.

Adjuvant chemotherapy and overall survival in adult medulloblastoma.

PubMed

Kann, Benjamin H; Lester-Coll, Nataniel H; Park, Henry S; Yeboa, Debra N; Kelly, Jacqueline R; Baehring, Joachim M; Becker, Kevin P; Yu, James B; Bindra, Ranjit S; Roberts, Kenneth B

2017-02-01

Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Prognostic factors in patients with malignant pleural effusion: Is it possible to predict mortality in patients with good performance status?

PubMed

Abrao, Fernando Conrado; Peixoto, Renata D'Alpino; de Abreu, Igor Renato Louro Bruno; Janini, Maria Cláudia; Viana, Geisa Garcia; de Oliveira, Mariana Campello; Younes, Riad Naim

2016-04-01

The aim of this study was to identify predictors of mortality only in patients with malignant pleural effusion (MPE) showing good performance status which required pleural palliative procedures. All patients with MPE submitted to pleural palliative procedure were enrolled in a prospective study between 2013 and 2014. Patients with Eastern cooperative oncology group (ECOG) score zero, one, and two were considered with good performance status. The possible prognostic factors were tested for significance using the log-rank test (Kaplan-Meier method) and those with significance on univariate analysis were entered into a multivariable Cox model. A total of 64 patients were included in the analysis. Median follow-up time for surviving patients was 263 days. Median survival for the entire cohort was not reached yet. In the multivariate analysis, gastrointestinal primary site (P = 0.006), low albumin concentration in the pleural fluid (P = 0.017), and high serum NLR (P = 0.007) were associated with mortality. In our cohort of ECOG 0-2 patients with MPE submitted to pleural palliative procedures, gastrointestinal malignancy compared to other sites, low pleural fluid albumin and high NLR were significantly associated with mortality. The identification of these prognostic factors may assist the choice of the optimal palliative technique. J. Surg. Oncol. 2016;113:570-574. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma.

PubMed

Atanasov, Georgi; Schierle, Katrin; Hau, Hans-Michael; Dietel, Corinna; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Englisch, Julianna Paulina; Robson, Simon C; Reutzel-Selke, Anja; Pascher, Andreas; Jonas, Sven; Pratschke, Johann; Benzing, Christian; Schmelzle, Moritz

2017-02-01

Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies.

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.

Conditional survival estimates improve over time for patients with advanced melanoma: results from a population-based analysis.

PubMed

Xing, Yan; Chang, George J; Hu, Chung-Yuan; Askew, Robert L; Ross, Merrick I; Gershenwald, Jeffrey E; Lee, Jeffrey E; Mansfield, Paul F; Lucci, Anthony; Cormier, Janice N

2010-05-01

Conditional survival (CS) has emerged as a clinically relevant measure of prognosis for cancer survivors. The objective of this analysis was to provide melanoma-specific CS estimates to help clinicians promote more informed patient decision making. Patients with melanoma and at least 5 years of follow-up were identified from the Surveillance Epidemiology and End Results registry (1988-2000). By using the methods of Kaplan and Meier, stage-specific, 5-year CS estimates were independently calculated for survivors for each year after diagnosis. Stage-specific multivariate Cox regression models including baseline survivor functions were used to calculate adjusted melanoma-specific CS for different subgroups of patients further stratified by age, gender, race, marital status, anatomic tumor location, and tumor histology. Five-year CS estimates for patients with stage I disease remained constant at 97% annually, while for patients with stages II, III, and IV disease, 5-year CS estimates from time 0 (diagnosis) to 5 years improved from 72% to 86%, 51% to 87%, and 19% to 84%, respectively. Multivariate CS analysis revealed that differences in stages II through IV CS based on age, gender, and race decreased over time. Five-year melanoma-specific CS estimates improve dramatically over time for survivors with advanced stages of disease. These prognostic data are critical to patients for both treatment and nontreatment related life decisions. (c) 2010 American Cancer Society.

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.

[Effect of TNF-alpha gene polymorphism on outcome of thalidomide-based regimens for multiple myeloma].

PubMed

DU, Juan; Yuan, Zhen-Gang; Zhang, Chun-Yang; Fu, Wei-Jun; Jiang, Hua; Chen, Bao-An; Hou, Jian

2009-10-01

To evaluate the effect of polymorphism at the -238 and -308 position of the TNF-alpha promotor region on the clinical outcome of thalidomide (Thal)-based regimens for the treatment of multiple myeloma (MM). The polymorphism at the -238 and -308 position of the TNF-alpha promotor region of 168 MM patients treated with Thal-based regimens were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were tested for association with overall response by logistic regression, and survival was evaluated by univariate and multivariate analysis. In TNF-alpha -238 position, 11 (6.5%) patients had GA genotype and 1 (0.6%) AA genotype. In TNF-alpha -308 position, 19 (11.3%) had GA genotype and 1 (0.6%) AA genotype. In univariate analysis, the TNF-alpha -238 GA + AA genotypes were associated with a significantly prolonged progression free survival (PFS) (P = 0.017), and a better overall survival (OS) (P = 0.150). Multivariate COX regression analysis showed that TNF-alpha -238 polymorphic status was an independent prognostic factor for prolonged PFS (P = 0.049). The TNF-alpha -238 polymorphic status is associated with a favorable clinical outcome in MM patients treated with thalidomide-based regimen. The polymorphism status of TNF-alpha gene might be of promise for developing a more informative stratification system for MM.

Impact of triple-negative phenotype on prognosis of patients with breast cancer brain metastases.

PubMed

Xu, Zhiyuan; Schlesinger, David; Toulmin, Sushila; Rich, Tyvin; Sheehan, Jason

2012-11-01

To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor. Copyright © 2012 Elsevier Inc. 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.

Impact of age on the survival of patients with liver cancer: an analysis of 27,255 patients in the SEER database.

PubMed

Zhang, Wenjie; Sun, Beicheng

2015-01-20

The risk of liver cancer (LC) is regarded as age dependent. However, the influence of age on its prognosis is controversial. The aim of our study was to compare the long-term survival of younger versus older patients with LC. In this retrospective study, we searched Surveillance, Epidemiology, and End-RESULTS (SEER) population-based data and identified 27,255 patients diagnosed with LC between 1988 and 2003. These patients were categorized into younger (45 years and under) and older age (over 45 years of age) groups. Five-year cancer specific survival data was obtained. Kaplan-Meier methods and multivariable Cox regression models were used to analyze long-term survival outcomes and risk factors. There were significant differences between groups with regards to pathologic grading, histologic type, stage, and tumor size (p < 0.001). The 5-year liver cancer specific survival (LCSS) rates in the younger and older age groups were 14.5% and 8.4%, respectively (p < 0.001 by univariate and multivariate analysis). A stratified analysis of age on cancer survival showed only localized and regional stages to be validated as independent predictors, but not for advanced stages. Compared to older patients, younger patients with LC have a higher LCSS after surgery, despite the poorer biological behavior of this carcinoma.

[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.

Biologic and social determinants of sequelae and long-term survival of pediatric HIV in Romania.

PubMed

Kozinetz, Claudia A; Matusa, Rodica; Hacker, Carl S

2006-08-01

The aim of the study is to investigate the effect of social context and clinical factors on survival in a cohort of 333 children to identify issues useful in the treatment and care of human immunodeficiency virus (HIV)-infected youth in developing countries. A prospective cohort study design was used, and data were gathered at baseline and 1-year follow-up. The study cohort consisted of children given a diagnosis of HIV between 1995 and 1999 and receiving medical care in Constanta, Romania. Data were examined by means of multivariate Cox regression analysis models. The majority of the cohort were in the moderate (41%) or severe (40%) stages of HIV at baseline. Multivariate analysis indicated that social-context factors were the most significant determinants of HIV survival. The hazard for death for those with mothers or fathers with a higher level of education was approximately one quarter (relative hazard, 0.3-0.4; confidence interval, 0.1-1.0) that for a parent with a lower level of education. Subjects with employed mothers were four times more likely to survive than subjects with unemployed mothers. Results suggest that recognition of social-context risk factors for HIV disease progression and survival is important in developing countries, as it is in developed countries.

Low vascularity predicts favourable outcomes in leiomyoma patients treated with uterine artery embolization.

PubMed

Tang, Yixin; Chen, Chunlin; Duan, Hui; Ma, Ben; Liu, Ping

2016-10-01

To investigate the clinical factors predicting outcomes of leiomyoma treated with uterine artery embolization (UAE). A total of 183 uterine leiomyoma patients undergoing UAE were retrospectively analyzed. Patient age, characteristics of vascular supply in magnetic resonance imaging (MRI)/digital subtraction angiography (DSA), number, size and location of leiomyoma were recorded. Leiomyoma regrowth, new leiomyoma appearance and recurrence of any previously reported symptoms were carefully monitored over a mean follow-up of 30 months (median 32 months, range 12-80). Potential recurrence risk factors were analyzed by univariate and multivariate cox regression analysis. Twenty-three recurrences were recorded. The difference in the vascularity classification systems between MRI and DSA was not statistically significant (P = 0.059). High vascularity in MRI, high vascularity in DSA and multiple leiomyoma showed a significant risk of recurrence using univariate and multivariate analysis (P = 0.004, P < 0.001 and P = 0.023, respectively). The other factors were not significantly associated with leiomyoma recurrence (P > 0.05). Low vascularity and solitary leiomyoma indicated favourable outcomes in patients treated with UAE. • Low vascularity and solitary mass predicted favourable outcomes in UAE-treated patients. • MRI might provide information on vascularity in leiomyoma before UAE. • Variations in vascular supply, age, size, location were not associated with recurrence.

Association of pretreatment neutrophil-lymphocyte ratio and outcome in emergency colorectal cancer care.

PubMed

Palin, R P; Devine, A T; Hicks, G; Burke, D

2018-04-01

Introduction The association between the neutrophil-lymphocyte ratio (NLR) and outcome in elective colorectal cancer surgery is well established; the relationship between NLR and the emergency colorectal cancer patient is, as yet, unexplored. This paper evaluates the predictive quality of the NLR for outcome in the emergency colorectal cancer patient. Materials and Methods A total of 187 consecutive patients who underwent emergency surgery for colorectal cancer were included in the study. NLR was calculated from the haematological tests done on admission. Receiver operating characteristic analyses were used to determine the most suitable cut-off for NLR. Outcomes were assessed by mortality at 30 and 90 days using stepwise Cox proportional hazards regression. Results An NLR cut-off of 5 was found to have the highest sensitivity and specificity. At 30 days, age and time from admission to surgery were associated with increased mortality; a high NLR was associated with an increased risk of mortality in univariate but not multivariate analysis. At 90 days, age, NLR, time from admission to surgery and nodal status were all significantly associated with increased mortality on multivariate analysis. Conclusions Pre-operative NLR is a cheap, easily performed and useful clinical tool to aid prediction of outcome in the emergency colorectal cancer patient.

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).

Pattern of spread and prognosis in lower limb-onset ALS

PubMed Central

TURNER, MARTIN R.; BROCKINGTON, ALICE; SCABER, JAKUB; HOLLINGER, HANNAH; MARSDEN, RACHAEL; SHAW, PAMELA J.; TALBOT, KEVIN

2011-01-01

Our objective was to establish the pattern of spread in lower limb-onset ALS (contra- versus ipsi-lateral) and its contribution to prognosis within a multivariate model. Pattern of spread was established in 109 sporadic ALS patients with lower limb-onset, prospectively recorded in Oxford and Sheffield tertiary clinics from 2001 to 2008. Survival analysis was by univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards. Variables studied were time to next limb progression, site of next progression, age at symptom onset, gender, diagnostic latency and use of riluzole. Initial progression was either to the contralateral leg (76%) or ipsilateral arm (24%). Factors independently affecting survival were time to next limb progression, age at symptom onset, and diagnostic latency. Time to progression as a prognostic factor was independent of initial direction of spread. In a regression analysis of the deceased, overall survival from symptom onset approximated to two years plus the time interval for initial spread. In conclusion, rate of progression in lower limb-onset ALS is not influenced by whether initial spread is to the contralateral limb or ipsilateral arm. The time interval to this initial spread is a powerful factor in predicting overall survival, and could be used to facilitate decision-making and effective care planning. PMID:20001488

Downregulation of SASH1 correlates with poor prognosis in cervical cancer.

PubMed

Xie, J; Zhang, W; Zhang, J; Lv, Q-Y; Luan, Y-F

2017-10-01

The aim of this study was to analyze the association of SASH1 expression with clinicopathological features and prognosis in patients suffering cervical cancer. The expressions of SASH1 mRNA and protein in cervical cancer tissues and matched normal cervical tissues were detected by Real-time PCR and Immunohistochemistry. Based on the above findings, the association among SASH1 expression and clinicopathological features was analyzed. Overall survival was evaluated using the Kaplan-Meier method. The variables were used in univariate and multivariate analysis by the Cox proportional hazards model. The results demonstrated that both SASH1 mRNA and proteins were downregulated in cervical cancer tissues compared with those in matched normal tissues (both p < 0.05). Also, decreased SASH1 expression in cervical cancer was found to be significantly associated with high FIGO Stage (p = 0.001), lymph nodes metastasis (p = 0.003) and differentiation (p = 0.018). Furthermore, Kaplan-Meier analysis demonstrated that low SASH1 expression level was associated with poorer overall survival (p < 0.01). Univariate and multivariate analyses indicated that status of SASH1 was an independent prognostic factor for patients with cervical cancer. These findings suggested that SASH1 can be useful as a new prognostic marker and therapeutic target in cervical cancer patients.

Analysis of cohort studies with multivariate and partially observed disease classification data.

PubMed

Chatterjee, Nilanjan; Sinha, Samiran; Diver, W Ryan; Feigelson, Heather Spencer

2010-09-01

Complex diseases like cancers can often be classified into subtypes using various pathological and molecular traits of the disease. In this article, we develop methods for analysis of disease incidence in cohort studies incorporating data on multiple disease traits using a two-stage semiparametric Cox proportional hazards regression model that allows one to examine the heterogeneity in the effect of the covariates by the levels of the different disease traits. For inference in the presence of missing disease traits, we propose a generalization of an estimating equation approach for handling missing cause of failure in competing-risk data. We prove asymptotic unbiasedness of the estimating equation method under a general missing-at-random assumption and propose a novel influence-function-based sandwich variance estimator. The methods are illustrated using simulation studies and a real data application involving the Cancer Prevention Study II nutrition cohort.

Analysis of surgical outcomes of diverticular disease of the colon.

PubMed

Miyaso, Hideaki; Iwakawa, Kazuhide; Kitada, Koji; Kimura, Yuji; Isoda, Kenta; Nishie, Manabu; Hamano, Ryosuke; Tokunaga, Naoyuki; Tsunemitsu, Yosuke; Ohtsuka, Shinya; Inagawaki, Masaru; Iwagaki, Hiromi

2012-01-01

We analyzed retrospectively the surgical outcomes of diverticular diseases of the colon at the surgical division of Fukuyama Medical Center. Data were collected from 39 patients who underwent surgery for diverticular disease at Fukuyama Medical Center. Thirty-nine patients were admitted between 2005 and 2010. The mean age of the 39 patients was 63.6 years. The collected data included patient demographics, patient history, type of surgery and complications. Patients were divided into 2 groups, Elective vs. Emergent group, right vs. left colon group and laparotomy vs. laparoscopic approach. Multivariate analysis of the logistic model of morbidity revealed a significantly higher rate in the left colon and the Cox proportional hazards model clearly showed fewer postoperative hospital days with the laparoscopic approach. Surgical procedures should be decided in reference to the particular clinical and pathological features of diverticular disease to gain an acceptable morbidity and mortality rates.

IGFBP6 Regulates Cell Apoptosis and Migration in Glioma.

PubMed

Bei, Yuanqi; Huang, Qingfeng; Shen, Jianhong; Shi, Jinlong; Shen, Chaoyan; Xu, Peng; Chang, Hao; Xia, Xiaojie; Xu, Li; Ji, Bin; Chen, JianGuo

2017-07-01

The insulin-like growth factor binding protein 6 (IGFBP6), as an inhibitor of IGF-II actions, plays an important role in inhibiting survival and migration of tumor cells. In our study, we intended to demonstrate the biological function of IGFBP6 in the development of glioma and its clinical significance. Firstly, Western blot and immunohistochemistry revealed that the expression of IGFBP6 inversely correlated with glioma grade. Secondly, multivariate analysis with the Cox proportional hazards model and Kaplan-Meier analysis indicated that IGFBP6 could be an independent prognostic factor for the survival of glioma patients. In addition, overexpression of IGFBP6 induced glioma cell apoptosis, and depletion of IGFBP6 had the opposite action. Finally, overexpression of IGFBP6 inhibited migration of glioma cells, and depletion of IGFBP6 had the opposite action. Together our findings suggest that IGFBP6 might be an important regulator and prognostic factor for glioma.

Targeted Deletion and Lipidomic Analysis Identify Epithelial Cell COX-2 as a Major Driver of Chemically-induced Skin Cancer

PubMed Central

Jiao, Jing; Ishikawa, Tomo-o; Dumlao, Darren S.; Norris, Paul C.; Magyar, Clara E.; Mikulec, Carol; Catapang, Art; Dennis, Edward A.; Fischer, Susan M.; Herschman, Harvey R.

2014-01-01

Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX2) plays a critical role in DMBA/TPA-induced skin tumor induction. While many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell-type specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared to littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2 expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell-type specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biological responses. PMID:25063587

Cyclooxygenase-2 regulated by the nuclear factor-κB pathway plays an important role in endometrial breakdown in a female mouse menstrual-like model.

PubMed

Xu, Xiangbo; Chen, Xihua; Li, Yunfeng; Cao, Huizi; Shi, Cuige; Guan, Shuo; Zhang, Shucheng; He, Bin; Wang, Jiedong

2013-08-01

The role of prostaglandins (PGs) in menstruation has long been proposed. Although evidence from studies on human and nonhuman primates supports the involvement of PGs in menstruation, whether PGs play an obligatory role in the process remains unclear. Although cyclooxygenase (COX) inhibitors have been used in the treatment of irregular uterine bleeding, the mechanism involved has not been elucidated. In this study, we used a recently established mouse menstrual-like model for investigating the role of COX in endometrial breakdown and its regulation. Administration of the nonspecific COX inhibitor indomethacin and the COX-2 selective inhibitor DuP-697 led to inhibition of the menstrual-like process. Furthermore, immunostaining analysis showed that the nuclear factor (NF)κB proteins P50, P65, and COX-2 colocalized in the outer decidual stroma at 12 to 16 hours after progesterone withdrawal. Chromatin immunoprecipitation analysis showed that NFκB binding to the Cox-2 promoter increased at 12 hours after progesterone withdrawal in vivo, and real-time PCR analysis showed that the NFκB inhibitors pyrrolidine dithiocarbamate and MG-132 inhibited Cox-2 mRNA expression in vivo and in vitro, respectively. Furthermore, COX-2 and NFκB inhibitors similarly reduced endometrial breakdown, suggesting that NFκB/COX-2-derived PGs play a critical role in this process. In addition, the CD45(+) leukocyte numbers were sharply reduced following indomethacin (COX-1 and COX-2 inhibitor), DuP-697 (COX-2 inhibitor), and pyrrolidine dithiocarbamate (NFκB inhibitor) treatment. Collectively, these data indicate that NFκB/COX-2-induced PGs regulate leukocyte influx, leading to endometrial breakdown.

The Short-term Prognostic Value of the Triglyceride-to-high-density Lipoprotein Cholesterol Ratio in Acute Ischemic Stroke

PubMed Central

Wang, Huan; Lei, Leix; Zhang, Han-Qing; Gu, Zheng-Tian; Xing, Fang-Lan; Yan, Fu-Ling

2018-01-01

The triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) is a simple approach to predicting unfavorable outcomes in cardiovascular disease. The influence of TG/HDL-C on acute ischemic stroke remains elusive. The purpose of this study was to investigate the precise effect of TG/HDL-C on 3-month mortality after acute ischemic stroke (AIS). Patients with AIS were enrolled in the present study from 2011 to 2017. A total of 1459 participants from a single city in China were divided into retrospective training and prospective test cohorts. Medical records were collected periodically to determine the incidence of fatal events. All participants were followed for 3 months. Optimal cutoff values were determined using X-tile software to separate the training cohort patients into higher and lower survival groups based on their lipid levels. A survival analysis was conducted using Kaplan-Meier curves and a Cox proportional hazards regression model. A total of 1459 patients with AIS (median age 68.5 years, 58.5% male) were analyzed. Univariate Cox regression analysis confirmed that TG/HDL-C was a significant prognostic factor for 3-month survival. X-tile identified 0.9 as an optimal cutoff for TG/HDL-C. In the univariate analysis, the prognosis of the TG/HDL-C >0.9 group was markedly superior to that of TG/HDL-C ≤0.9 group (P<0.001). A multivariate Cox regression analysis showed that TG/HDL-C was independently correlated with a reduced risk of mortality (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.62; P<0.001). These results were confirmed in the 453 patients in the test cohort. A nomogram was constructed to predict 3-month case-fatality, and the c-indexes of predictive accuracy were 0.684 and 0.670 in the training and test cohorts, respectively (P<0.01). The serum TG/HDL-C ratio may be useful for predicting short-term mortality after AIS. PMID:29896437

The Short-term Prognostic Value of the Triglyceride-to-high-density Lipoprotein Cholesterol Ratio in Acute Ischemic Stroke.

PubMed

Deng, Qi-Wen; Li, Shuo; Wang, Huan; Lei, Leix; Zhang, Han-Qing; Gu, Zheng-Tian; Xing, Fang-Lan; Yan, Fu-Ling

2018-06-01

The triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) is a simple approach to predicting unfavorable outcomes in cardiovascular disease. The influence of TG/HDL-C on acute ischemic stroke remains elusive. The purpose of this study was to investigate the precise effect of TG/HDL-C on 3-month mortality after acute ischemic stroke (AIS). Patients with AIS were enrolled in the present study from 2011 to 2017. A total of 1459 participants from a single city in China were divided into retrospective training and prospective test cohorts. Medical records were collected periodically to determine the incidence of fatal events. All participants were followed for 3 months. Optimal cutoff values were determined using X-tile software to separate the training cohort patients into higher and lower survival groups based on their lipid levels. A survival analysis was conducted using Kaplan-Meier curves and a Cox proportional hazards regression model. A total of 1459 patients with AIS (median age 68.5 years, 58.5% male) were analyzed. Univariate Cox regression analysis confirmed that TG/HDL-C was a significant prognostic factor for 3-month survival. X-tile identified 0.9 as an optimal cutoff for TG/HDL-C. In the univariate analysis, the prognosis of the TG/HDL-C >0.9 group was markedly superior to that of TG/HDL-C ≤0.9 group (P<0.001). A multivariate Cox regression analysis showed that TG/HDL-C was independently correlated with a reduced risk of mortality (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.62; P<0.001). These results were confirmed in the 453 patients in the test cohort. A nomogram was constructed to predict 3-month case-fatality, and the c-indexes of predictive accuracy were 0.684 and 0.670 in the training and test cohorts, respectively (P<0.01). The serum TG/HDL-C ratio may be useful for predicting short-term mortality after AIS.

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan

PubMed Central

Lee, Cheng-Chia; Wu, Patricia W.; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei

2017-01-01

Background Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. Methods This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Results Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. Conclusions The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients. PMID:28301536

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan.

PubMed

Lu, Yueh-An; Tu, Kun-Hua; Lee, Cheng-Chia; Wu, Patricia W; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei; Chu, Pao-Hsien

2017-01-01

Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients.

The correlations between alteration of p16 gene and clinicopathological factors and prognosis in squamous cell carcinomas of the buccal mucosa.

PubMed

Dong, Yuying; Wang, Jie; Dong, Fusheng; Wang, Xu; Zhang, Yinghuai

2012-07-01

To evaluate relationships between the alteration of p16 gene and the clinical status and prognosis of the patients with squamous cell carcinoma of the buccal mucosa. Thirty buccal cancers were included in the analysis. Deletion analysis was performed by PCR. Point mutation analysis was used by PCR-SSCP and direct sequencing. Methylation-specific PCR methods were adopted for the evaluation of p16 methylation. The correlation between alteration of p16 gene and clinicopathological factors buccal cancer was evaluated by Fisher's exact test. Kaplan-Meier and Cox regression were used to investigate the relationship between p16 alteration and survival time. The frequency of p16 alteration was 63.3% in buccal carcinomas. P16 deletion was associated significantly with tumor size (P = 0.01). P16 point mutation was associated significantly with differentiation (P = 0.006). P16 methylation was associated significantly with nodes metastasis (P = 0.027). The overall survival rate of 30 buccal carcinomas was 53.3%. The Log-rank test (P = 0.021) and univariate Cox regression analysis (P = 0.030) revealed that p16 methylation was significantly associated with the overall survival rate. Multivariate analysis showed that p16 deletion, p16 mutation, and p16 methylation were not statistically significant. The alterations of p16 gene may play a major role in malignancy and development and metastases of buccal carcinoma and may be an excellent marker of aggressive clinical behavior. P16 methylation has a prognostic value in buccal carcinoma but not an independent prognosis factor. P16 point mutation and p16 deletion have not prognostic significance in buccal carcinoma. © 2012 John Wiley & Sons A/S.

Are classic predictors of voltage valid in cardiac amyloidosis? A contemporary analysis of electrocardiographic findings.

PubMed

Sperry, Brett W; Vranian, Michael N; Hachamovitch, Rory; Joshi, Hariom; McCarthy, Meghann; Ikram, Asad; Hanna, Mazen

2016-07-01

Low voltage electrocardiography (ECG) coupled with increased ventricular wall thickness is the hallmark of cardiac amyloidosis. However, patient characteristics influencing voltage in the general population, including bundle branch block, have not been evaluated in amyloid heart disease. A retrospective analysis was performed of patients with newly diagnosed cardiac amyloidosis from 2002 to 2014. ECG voltage was calculated using limb (sum of QRS complex in leads I, II and III) and precordial (Sokolow: S in V1 plus R in V5-V6) criteria. The associations between voltage and clinical variables were tested using multivariable linear regression. A Cox model assessed the association of voltage with mortality. In 389 subjects (transthyretin ATTR 186, light chain AL 203), 30% had conduction delay (QRS >120ms). In those with narrow QRS, 68% met low limb, 72% low Sokolow and 57% both criteria, with lower voltages found in AL vs ATTR. LV mass index as well as other typical factors that impact voltage (age, sex, race, hypertension, BSA, and smoking) in the general population were not associated with voltage in this cardiac amyloidosis cohort. Patients with LBBB and IVCD had similar voltages when compared to those with narrow QRS. Voltage was significantly associated with mortality (p<0.001 for both criteria) after multivariable adjustment. Classic predictors of ECG voltage in the general population are not valid in cardiac amyloidosis. In this cohort, the prevalence estimates of ventricular conduction delay and low voltage are higher than previously reported. Voltage predicts mortality after multivariable adjustment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study.

PubMed

El-Sayed, Mohamed I; Ali, Amany M; Sayed, Heba A; Zaky, Eman M

2010-12-24

We conducted a retrospective analysis to investigate treatment results and prognostic factors of pediatric neuroblastoma patients. This retrospective study was carried out analyzing the medical records of patients with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer Institute, Assiut University during the period from January 2001 and January 2010. After induction chemotherapy, response according to international neuoblastoma response criteria was assessed. Radiotherapy to patients with residual primary tumor was applied. Overall and event free survival (OAS and EFS) rates were estimated using Graphed prism program. The Log-rank test was used to examine differences in OAS and EFS rates. Cox-regression multivariate analysis was done to determine the independent prognostic factors affecting survival rates. Fifty three cases were analyzed. The median follow-up duration was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were 39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of age, N-MYC amplification, and high risk group. The majority of patients (68%) presented in high risk group, where treatment outcome was poor, as only 21% of patients survived for 3 year. Multivariate analysis confirmed only the association between survival and risk group. However, in univariate analysis, local radiation therapy resulted in significant survival improvement. Therefore, radiotherapy should be given to patients with residual tumor evident after induction chemotherapy and surgery. Future attempts to improve OAS in high risk group patients with aggressive chemotherapy and bone marrow transplantation should be considered.

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

PubMed

Li, Jie; Gong, Youling; Diao, Peng; Huang, Qingmei; Wen, Yixue; Lin, Binwei; Cai, Hongwei; Tian, Honggang; He, Bing; Ji, Lanlan; Guo, Ping; Miao, Jidong; Du, Xiaobo

2018-01-22

Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

Use of Stereotactic Radiosurgery in Elderly and Very Elderly Patients With Brain Metastases to Limit Toxicity Associated With Whole Brain Radiation Therapy.

PubMed

Chen, Linda; Shen, Colette; Redmond, Kristin J; Page, Brandi R; Kummerlowe, Megan; Mcnutt, Todd; Bettegowda, Chetan; Rigamonti, Daniele; Lim, Michael; Kleinberg, Lawrence

2017-07-15

We evaluated the toxicity associated with stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) in elderly and very elderly patients with brain metastases, as the role of SRS in geriatric patients who would traditionally receive WBRT is unclear. We conducted a retrospective review of elderly patients (aged 70-79 years) and very elderly patients (aged ≥80 years) with brain metastases who underwent RT from 2010 to 2015 at Johns Hopkins Hospital. Patients received either upfront WBRT or SRS for metastatic solid malignancies, excluding small cell lung cancer. Acute central nervous system toxicity within 3 months of RT was graded using the Radiation Therapy Oncology Group acute radiation central nervous system morbidity scale. The toxicity data between age groups and treatment modalities were analyzed using Fisher's exact test and multivariate logistic regression analysis. Kaplan-Meier curves were used to estimate the median overall survival, and the Cox proportion hazard model was used for multivariate analysis. A total of 811 brain metastases received RT in 119 geriatric patients. The median overall survival from the diagnosis of brain metastases was 4.3 months for the patients undergoing WBRT and 14.4 months for the patients undergoing SRS. On multivariate analysis, WBRT was associated with worse overall survival in this cohort of geriatric patients (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.9-7.0, P<.0001) and age ≥80 years was not. WBRT was associated with significantly greater rates of any grade 1 to 4 toxicity (OR 7.5, 95% CI 1.6-33.3, P=.009) and grade 2 to 4 toxicity (OR 2.8, 95% CI 1.0-8.1, P=.047) on multivariate analysis. Elderly and very elderly patients did not have significantly different statistically acute toxicity rates when stratified by age. WBRT was associated with increased toxicity compared with SRS in elderly and very elderly patients with brain metastases. SRS, rather than WBRT, should be prospectively evaluated in geriatric patients with the goal of minimizing treatment-related toxicity. Copyright © 2017. Published by Elsevier Inc.

Combined Analysis of COX-2 and p53 Expressions Reveals Synergistic Inverse Correlations with Microsatellite Instability and CpG Island Methylator Phenotype in Colorectal Cancer1

PubMed Central

Ogino, Shuji; Brahmandam, Mohan; Kawasaki, Takako; Kirkner, Gregory J; Loda, Massimo; Fuchs, Charles S

2006-01-01

Abstract Cyclooxygenase-2 (COX-2) overexpression and mutations of p53 (a known COX-2 regulator) are inversely associated with microsatellite instability—high (MSI-H) and CpG island methylator phenotype (CIMP), characterized by extensive promoter methylation, is associated with MSI-H. However, no studies have comprehensively examined interrelations between COX-2, p53, MSI, and CIMP. Using MethyLight, we measured DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16/INK4A), CRABP1, MLH1, and NEUROG1] in relatively unbiased samples of 751 colorectal cancer cases obtained from two large prospective cohorts; 115 (15%) tumors were CIMP-high (≥ 4 of 5 methylated promoters), 251 (33%) were CIMP-low (1 to 3 methylated promoters), and the remaining 385 (51%) were CIMP-0 (no methylated promoters). CIMP-high tumors were much less frequent in COX-2+/p53+ tumors (4.6%) than in COX-2+/p53- tumors (19%; P < .0001), COX-2-/p53+ tumors (17%; P= .04), and COX-2-/p53- tumors (28%; P < .0001). In addition, COX-2+/p53+ tumors were significantly less common in MSI-H CIMP-high tumors (9.7%) than in non-MSI-H CIMP-low/CIMP-0 tumors (44–47%; P< .0001). In conclusion, COX-2 and p53 alterations were synergistically inversely correlated with both MSI-H and CIMP-high. Our data suggest that a combined analysis of COX-2 and p53 may be more useful for the molecular classification of colorectal cancer than either COX-2 or p53 analysis alone. PMID:16820091

Low-Protein Diets in Diabetic Chronic Kidney Disease (CKD) Patients: Are They Feasible and Worth the Effort?

PubMed

Piccoli, Giorgina B; Ventrella, Federica; Capizzi, Irene; Vigotti, Federica N; Mongilardi, Elena; Grassi, Giorgio; Loi, Valentina; Cabiddu, Gianfranca; Avagnina, Paolo; Versino, Elisabetta

2016-10-21

Low-protein diets (LPDs) are often considered as contraindicated in diabetic patients, and are seldom studied. The aim of this observational study was to provide new data on this issue. It involved 149 diabetic and 300 non-diabetic patients who followed a LPD, with a personalized approach aimed at moderate protein restriction (0.6 g/day). Survival analysis was performed according to Kaplan-Meier, and multivariate analysis with Cox model. Diabetic versus non-diabetic patients were of similar age (median 70 years) and creatinine levels at the start of the diet (2.78 mg/dL vs. 2.80 mg/dL). There was higher prevalence of nephrotic proteinuria in diabetic patients (27.52% vs. 13.67%, p = 0.002) as well as comorbidity (median Charlson index 8 vs. 6 p = 0.002). Patient survival was lower in diabetic patients, but differences levelled off considering only cases with Charlson index > 7, the only relevant covariate in Cox analysis. Dialysis-free survival was superimposable in the setting of good compliance (Mitch formula: 0.47 g/kg/day in both groups): about 50% of the cases remained dialysis-free 2 years after the first finding of e-GFR (estimated glomerular filtration rate) < 15 mL/min, and 1 year after reaching e-GFR < 10 mL/min. In patients with type 2 diabetes, higher proteinuria was associated with mortality and initiation of dialysis. In conclusion, moderately restricted LPDs allow similar results in diabetic and non non-diabetic patients with similar comorbidity.

Low-Protein Diets in Diabetic Chronic Kidney Disease (CKD) Patients: Are They Feasible and Worth the Effort?

PubMed Central

Piccoli, Giorgina B.; Ventrella, Federica; Capizzi, Irene; Vigotti, Federica N.; Mongilardi, Elena; Grassi, Giorgio; Loi, Valentina; Cabiddu, Gianfranca; Avagnina, Paolo; Versino, Elisabetta

2016-01-01

Low-protein diets (LPDs) are often considered as contraindicated in diabetic patients, and are seldom studied. The aim of this observational study was to provide new data on this issue. It involved 149 diabetic and 300 non-diabetic patients who followed a LPD, with a personalized approach aimed at moderate protein restriction (0.6 g/day). Survival analysis was performed according to Kaplan–Meier, and multivariate analysis with Cox model. Diabetic versus non-diabetic patients were of similar age (median 70 years) and creatinine levels at the start of the diet (2.78 mg/dL vs. 2.80 mg/dL). There was higher prevalence of nephrotic proteinuria in diabetic patients (27.52% vs. 13.67%, p = 0.002) as well as comorbidity (median Charlson index 8 vs. 6 p = 0.002). Patient survival was lower in diabetic patients, but differences levelled off considering only cases with Charlson index > 7, the only relevant covariate in Cox analysis. Dialysis-free survival was superimposable in the setting of good compliance (Mitch formula: 0.47 g/kg/day in both groups): about 50% of the cases remained dialysis-free 2 years after the first finding of e-GFR (estimated glomerular filtration rate) < 15 mL/min, and 1 year after reaching e-GFR < 10 mL/min. In patients with type 2 diabetes, higher proteinuria was associated with mortality and initiation of dialysis. In conclusion, moderately restricted LPDs allow similar results in diabetic and non non-diabetic patients with similar comorbidity. PMID:27775639

Prolonged methylprednisolone therapy after the pulse treatment for patients with moderate-to-severe paraquat poisoning: A retrospective analysis.

PubMed

Gao, Jie; Feng, ShunYi; Wang, Jian; Yang, SiYuan; Li, Yong

2017-06-01

This retrospective study aims to evaluate the effect of prolonged methylprednisolone (MP) therapy on the mortality of patients with moderate-to-severe paraquat (PQ) poisoning after the pulse treatment.We performed a retrospective analysis of patients with acute moderate-to-severe PQ poisoning that were admitted to the emergency department from May 2012 to August 2016. Out of 138 patients, 60 were treated with pulse treatment (15 mg kg day MP for 3 days) and 78 were treated with prolonged MP therapy after pulse treatment (15 mg kg day MP for 3 days; afterward, the dosage was reduced in half every 2 days, and the MP therapy was terminated until 0.47 mg kg day). Kaplan-Meier method was used to compare the mortality between the 2 groups. Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI).The mortality of the prolonged MP therapy after pulse treatment group was lower than that of the pulse group (47.4% vs 63.3%; log-rank tests, P  =  .003). According to the multivariate Cox analysis, the prolonged MP therapy after pulse treatment was significantly associated with a lower mortality risk (HR: 0.31, 95% CI: 0.19-0.52, P < .001) compared with the pulse group. In addition, the prolonged MP therapy after pulse treatment caused more incidences of leucopenia than the pulse treatment alone (25.6% vs 11.7%, P  =  .04).The prolonged MP therapy after pulse treatment can reduce the mortality of moderate-to-severe PQ poisoning patients.

Prognostic Factors in Amyotrophic Lateral Sclerosis: A Population-Based Study

PubMed Central

Moura, Mirian Conceicao; Novaes, Maria Rita Carvalho Garbi; Eduardo, Emanoel Junio; Zago, Yuri S. S. P.; Freitas, Ricardo Del Negro Barroso; Casulari, Luiz Augusto

2015-01-01

Objective To determine the prognostic factors associated with survival in amyotrophic lateral sclerosis at diagnosis. Methods This retrospective population-based study evaluated 218 patients treated with riluzole between 2005 and 2014 and described their clinical and demographic profiles after the analysis of clinical data and records from the mortality information system in the Federal District, Brazil. Cox multivariate regression analysis was conducted for the parameters found. Results The study sample consisted of 132 men and 86 women with a mean age at disease onset of 57.2±12.3 years; 77.6% of them were Caucasian. The mean periods between disease onset and diagnosis were 22.7 months among men and 23.5 months among women, and the mean survival periods were 45.7±47.0 months among men and 39.3±29.8 months among women. In addition, 80.3% patients presented non-bulbar-onset amyotrophic lateral sclerosis, and 19.7% presented bulbar-onset. Cox regression analysis indicated worse prognosis for body mass index (BMI) <25 kg/m2 (relative risk [RR]: 3.56, 95% confidence interval [CI]: 1.44–8.86), age >75 years (RR: 12.47, 95% CI: 3.51–44.26), and bulbar-onset (RR: 4.56, 95% CI: 2.06–10.12). Electromyography did not confirm the diagnosis in 55.6% of the suspected cases and in 27.9% of the bulbar-onset cases. Conclusions The factors associated with lower survival in amyotrophic lateral sclerosis were age >75 years, BMI <25 kg/m2, and bulbar-onset. PMID:26517122

Outcome of liver transplantation for hepatocellular carcinoma -- a single center experience.

PubMed

Iacob, R; Iacob, S; Gheorghe, L; Gheorghe, C; Hrehoreţ, D; Brașoveanu, V; Croitoru, A; Herlea, V; Popescu, I

2013-01-01

Liver transplantation (LT) is a promising treatment for patients with liver cirrhosis associated with hepatocellular carcinoma (HCC). The aim of our study was to evaluate our experience regarding the clinical and pathological staging of HCC in patients who underwent LT, as well as recurrence free and overall survival. From January 2006 to December 2011, 38 patients with diagnosis of HCC, underwent LT in our Center. Demographic, clinical, imaging and pathologic information were recorded. A Cox proportional hazards survival analysis was performed in order to identify significant predictors of tumor recurrence and patient's death after LT. Eighteen patients (47.4%) in our study group were within Milan criteria. The mean follow-up was 22 months and the recurrence rate of HCC after LT was 13.2%. The 1, 3- year recurrence free survival rates were 85%, 74.3% respectively. The 1 and 3-year overall survival rates were 83.5% and 63.6% respectively. No significant predictor for HCC recurrence was identified in our study group by survival analysis, taking into account 13 different variables. As independent predictors of patient'ss death after LT for HCC however, the presence of diabetes mellitus (p=0.001), presence of more than 3 HCC nodules (p=0.03) and tumor recurrence after LT (p=0.03) were identified by multivariate Cox proportional hazards survival analysis. In our cohort HCC recurrence rate after LT was 13.2%. Diabetes mellitus, presence of more than 3 HCC nodules and HCC recurrence were significant predictors of poor overall survival after LT. Celsius.

Long-term allopurinol use decreases the risk of prostate cancer in patients with gout: a population-based study.

PubMed

Shih, H-J; Kao, M-C; Tsai, P-S; Fan, Y-C; Huang, C-J

2017-09-01

Clinical observations indicated an increased risk of developing prostate cancer in gout patients. Chronic inflammation is postulated to be one crucial mechanism for prostate carcinogenesis. Allopurinol, a widely used antigout agent, possesses potent anti-inflammation capacity. We elucidated whether allopurinol decreases the risk of prostate cancer in gout patients. We analyzed data retrieved from Taiwan National Health Insurance Database between January 2000 and December 2012. Patients diagnosed with gout during the study period with no history of prostate cancer and who had never used allopurinol were selected. Four allopurinol use cohorts (that is, allopurinol use (>365 days), allopurinol use (181-365 days), allopurinol use (91-180 days) and allopurinol use (31-90 days)) and one cohort without using allopurinol (that is, allopurinol use (No)) were included. The study end point was the diagnosis of new-onset prostate cancer. Multivariable Cox proportional hazards regression and propensity score-adjusted Cox regression models were used to estimate the association between the risk of prostate cancer and allopurinol treatment in gout patients after adjusting for potential confounders. A total of 25 770 gout patients (aged between 40 and 100 years) were included. Multivariable Cox regression analyses revealed that the risk of developing prostate cancer in the allopurinol use (>365 days) cohort was significantly lower than the allopurinol use (No) cohort (adjusted hazard ratio (HR)=0.64, 95% confidence interval (CI)=0.45-0.9, P=0.011). After propensity score adjustment, the trend remained the same (adjusted HR=0.66, 95% CI=0.46-0.93, P=0.019). Long-term (more than 1 year) allopurinol use may associate with a decreased risk of prostate cancer in gout patients.

Racial differences in the outcome of patients with urothelial carcinoma of the upper urinary tract: an international study.

PubMed

Matsumoto, Kazumasa; Novara, Giacomo; Gupta, Amit; Margulis, Vitaly; Walton, Thomas J; Roscigno, Marco; Ng, Casey; Kikuchi, Eiji; Zigeuner, Richard; Kassouf, Wassim; Fritsche, Hans-Martin; Ficarra, Vincenzo; Martignoni, Guido; Tritschler, Stefan; Rodriguez, Joaquin Carballido; Seitz, Christian; Weizer, Alon; Remzi, Mesut; Raman, Jay D; Bolenz, Christian; Bensalah, Karim; Koppie, Theresa M; Karakiewicz, Pierre I; Wood, Christopher G; Montorsi, Francesco; Iwamura, Masatsugu; Shariat, Shahrokh F

2011-10-01

•To assess the impact of differences in ethnicity on clinico-pathological characteristics and outcomes of patients with upper urinary tract urothelial carcinoma (UTUC) in a large multi-center series of patients treated with radical nephroureterectomy (RNU). •We retrospectively collected the data of 2163 patients treated with RNU at 20 academic centres in America, Asia, and Europe. •Univariable and multivariable Cox regression models addressed recurrence-free survival (RFS) and cancer-specific survival (CSS). •In all, 1794 (83%) patients were Caucasian and 369 (17%) were Japanese. All the main clinical and pathological features were significantly different between the two ethnicities. •The median follow-up of the whole cohort was 36 months. At last follow-up, 554 patients (26%) developed disease recurrence and 461 (21%) were dead from UTUC. •The 5-year RFS and CSS estimates were 71.5% and 74.2%, respectively, for Caucasian patients compared with 68.8% and 75.4%, respectively, for Japanese patients. •On univariable Cox regression analyses, ethnicity was not significantly associated with either RFS (P= 0.231) or CSS (P= 0.752). •On multivariable Cox regression analyses that adjusted for the effects of age, gender, surgical type, T stage, grade, tumour architecture, presence of concomitant carcinoma in situ, lymphovascular invasion, tumour necrosis, and lymph node status, ethnicity was not associated with either RFS (hazard ratio [HR] 1.1; P= 0.447) or CSS (HR 1.0; P= 0.908). •There were major differences in the clinico-pathological characteristics of Caucasian and Japanese patients. •However, RFS and CSS probabilities were not affected by ethnicity and race was not an independent predictor of either recurrence or cancer-related death. © 2011 THE AUTHORS; BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Spatio-temporal interpolation of precipitation during monsoon periods in Pakistan

NASA Astrophysics Data System (ADS)

Hussain, Ijaz; Spöck, Gunter; Pilz, Jürgen; Yu, Hwa-Lung

2010-08-01

Spatio-temporal estimation of precipitation over a region is essential to the modeling of hydrologic processes for water resources management. The changes of magnitude and space-time heterogeneity of rainfall observations make space-time estimation of precipitation a challenging task. In this paper we propose a Box-Cox transformed hierarchical Bayesian multivariate spatio-temporal interpolation method for the skewed response variable. The proposed method is applied to estimate space-time monthly precipitation in the monsoon periods during 1974-2000, and 27-year monthly average precipitation data are obtained from 51 stations in Pakistan. The results of transformed hierarchical Bayesian multivariate spatio-temporal interpolation are compared to those of non-transformed hierarchical Bayesian interpolation by using cross-validation. The software developed by [11] is used for Bayesian non-stationary multivariate space-time interpolation. It is observed that the transformed hierarchical Bayesian method provides more accuracy than the non-transformed hierarchical Bayesian method.

Urinary proteomics for prediction of mortality in patients with type 2 diabetes and microalbuminuria.

PubMed

Currie, Gemma E; von Scholten, Bernt Johan; Mary, Sheon; Flores Guerrero, Jose-Luis; Lindhardt, Morten; Reinhard, Henrik; Jacobsen, Peter K; Mullen, William; Parving, Hans-Henrik; Mischak, Harald; Rossing, Peter; Delles, Christian

2018-04-06

The urinary proteomic classifier CKD273 has shown promise for prediction of progressive diabetic nephropathy (DN). Whether it is also a determinant of mortality and cardiovascular disease in patients with microalbuminuria (MA) is unknown. Urine samples were obtained from 155 patients with type 2 diabetes and confirmed microalbuminuria. Proteomic analysis was undertaken using capillary electrophoresis coupled to mass spectrometry to determine the CKD273 classifier score. A previously defined CKD273 threshold of 0.343 for identification of DN was used to categorise the cohort in Kaplan-Meier and Cox regression models with all-cause mortality as the primary endpoint. Outcomes were traced through national health registers after 6 years. CKD273 correlated with urine albumin excretion rate (UAER) (r = 0.481, p = <0.001), age (r = 0.238, p = 0.003), coronary artery calcium (CAC) score (r = 0.236, p = 0.003), N-terminal pro-brain natriuretic peptide (NT-proBNP) (r = 0.190, p = 0.018) and estimated glomerular filtration rate (eGFR) (r = 0.265, p = 0.001). On multivariate analysis only UAER (β = 0.402, p < 0.001) and eGFR (β = - 0.184, p = 0.039) were statistically significant determinants of CKD273. Twenty participants died during follow-up. CKD273 was a determinant of mortality (log rank [Mantel-Cox] p = 0.004), and retained significance (p = 0.048) after adjustment for age, sex, blood pressure, NT-proBNP and CAC score in a Cox regression model. A multidimensional biomarker can provide information on outcomes associated with its primary diagnostic purpose. Here we demonstrate that the urinary proteomic classifier CKD273 is associated with mortality in individuals with type 2 diabetes and MA even when adjusted for other established cardiovascular and renal biomarkers.

Association Between Efavirenz-Based Compared With Nevirapine-Based Antiretroviral Regimens and Virological Failure in HIV-Infected Children

PubMed Central

Lowenthal, Elizabeth D.; Ellenberg, Jonas H.; Machine, Edwin; Sagdeo, Aditi; Boiditswe, Sefelani; Steenhoff, Andrew P.; Rutstein, Richard; Anabwani, Gabriel; Gross, Robert

2013-01-01

Importance Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. Objective To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. Design, Setting, and Participants Retrospective cohort study of children (aged 3–16 years) who initiated efavirenz-based (n=421) or nevirapine-based (n=383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. Main Outcomes and Measures The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. Results With a median follow-up time of 69 months (range, 6–112 months; interquartile range, 23–87 months), 57 children (13.5%; 95% CI, 10.4%–17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%–31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%–4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%–7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4–2.7; log rank P<.001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses. Conclusions and Relevance Among children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients. PMID:23632724

Genetic polymorphisms in pre-miRNAs predict the survival of non-small-cell lung cancer in Chinese population: a cohort study and a meta-analysis

PubMed Central

Xia, Lingzi; Yin, Zhihua; Li, Xuelian; Ren, Yangwu; Zhang, Haibo; Zhao, Yuxia; Zhou, Baosen

2017-01-01

Background To explore the association of genetic polymorphisms in pre-miRNA 30c-1 rs928508 and pre-miRNA 27a rs895819 with non-small-cell lung cancer prognosis. Materials and Methods 480 patients from five hospitals were enrolled in this prospective cohort study. They were followed up for five years. The association between genotypes and overall survival was assessed by Cox proportional hazards regression models. A meta-analysis was conducted to provide evidence for the effect of microRNA 27a rs895819 on cancer survival. Results G-allele containing genotypes of microRNA 30c-1 polymorphisms and C-allele containing genotypes of microRNA 27a were significantly associated with poorer overall survival. Multivariate Cox regression models indicated that these genetic polymorhpisms were independently predictive factors of poorer overall survival. In stratified analysis, the effect was observed in many strata. The significant joint effect was also observed in our study. Patients with G allele of microRNA 30c-1 rs928508 and C allele of microRNA 27a rs895819 had the poorer overall survival than patients with C allele of rs928508 and T allele of rs895819. The effect of the microRNA 27a rs895819 on non-small cell lung cancer overall survival was supported by the meta-analysis results. Conclusions The two single nucleotide polymorphisms in microRNA 30c-1 and microRNA 27a can predict the outcome of non-small cell lung cancer patients and they may decrease the sensitivity to anti-cancer drugs. PMID:29100439

A retrospective analysis of the role of proton pump inhibitors in colorectal cancer disease survival

PubMed Central

Graham, C.; Orr, C.; Bricks, C.S.; Hopman, W.M.; Hammad, N.; Ramjeesingh, R.

2016-01-01

Background Proton pump inhibitors (ppis) are a commonly used medication. A limited number of studies have identified a weak-to-moderate association between ppi use and colorectal cancer (crc) risk, but none to date have identified an effect of ppi use on crc survival. We therefore postulated that an association between ppi use and crc survival might potentially exist. Methods We performed a retrospective chart review of 1304 crc patients diagnosed from January 2005 to December 2011 and treated at the Cancer Centre of Southeastern Ontario. Kaplan–Meier analysis and Cox proportional hazards regression models were used to evaluate overall survival (os). Results We identified 117 patients (9.0%) who were taking ppis at the time of oncology consult. Those taking a ppi were also more often taking asa or statins (or both) and had a statistically significantly increased rate of cardiac disease. No identifiable difference in tumour characteristics was evident in the two groups, including tumour location, differentiation, lymph node status, and stage. Univariate analysis identified a statistically nonsignificant difference in survival, with those taking a ppi experiencing lesser 1-year (82.1% vs. 86.7%, p = 0.161), 2-year (70.1% vs. 76.8%, p = 0.111), and 5-year os (55.2% vs. 62.9%, p = 0.165). When controlling for patient demographics and tumour characteristics, multivariate Cox regression analysis identified a statistically significant effect of ppi in our patient population (hazard ratio: 1.343; 95% confidence interval: 1.011 to 1.785; p = 0.042). Conclusions Our results suggest a potential adverse effect of ppi use on os in crc patients. These results need further evaluation in prospective analyses. PMID:28050148

SCD-HeFT: Use of RR Interval Statistics for Long-term Risk Stratification for Arrhythmic Sudden Cardiac Death

PubMed Central

Au-yeung, Wan-tai M.; Reinhall, Per; Poole, Jeanne E.; Anderson, Jill; Johnson, George; Fletcher, Ross D.; Moore, Hans J.; Mark, Daniel B.; Lee, Kerry L.; Bardy, Gust H.

2015-01-01

Background In the SCD-HeFT a significant fraction of the congestive heart failure (CHF) patients ultimately did not die suddenly from arrhythmic causes. CHF patients will benefit from better tools to identify if ICD therapy is needed. Objective To identify predictor variables from baseline SCD-HeFT patients’ RR intervals that correlate to arrhythmic sudden cardiac death (SCD) and mortality and to design an ICD therapy screening test. Methods Ten predictor variables were extracted from pre-randomization Holter data from 475 patients enrolled in the SCD-HeFT ICD arm using novel and traditional heart rate variability methods. All variables were correlated to SCD using Mann Whitney-Wilcoxon test and receiver operating characteristic analysis. ICD therapy screening tests were designed by minimizing the cost of false classifications. Survival analysis, including log-rank test and Cox models, was also performed. Results α1 and α2 from detrended fluctuation analysis, the ratio of low to high frequency power, the number of PVCs per hour and heart rate turbulence slope are all statistically significant for predicting the occurrences of SCD (p<0.001) and survival (log-rank p<0.01). The most powerful multivariate predictor tool using the Cox Proportional Hazards was α2 with a hazard ratio of 0.0465 (95% CI: 0.00528 – 0.409, p<0.01). Conclusion Predictor variables from RR intervals correlate to the occurrences of SCD and distinguish survival among SCD-HeFT ICD patients. We believe SCD prediction models should incorporate Holter based RR interval analysis to refine ICD patient selection especially in removing patients who are unlikely to benefit from ICD therapy. PMID:26096609

[Study on factors influencing survival in patients with advanced gastric carcinoma after resection by Cox's proportional hazard model].

PubMed

Wang, S; Sun, Z; Wang, S

1996-11-01

A prospective follow-up study of 539 advanced gastric carcinoma patients after resection was undertaken between 1 January 1980 and 31 December 1989, with a follow-up rate of 95.36%. A multivariate analysis of possible factors influencing survival of these patients was performed, and their predicting models of survival rates was established by Cox proportional hazard model. The results showed that the major significant prognostic factors influencing survival of these patients were rate and station of lymph node metastases, type of operation, hepatic metastases, size of tumor, age and location of tumor. The most important factor was the rate of lymph node metastases. According to their regression coefficients, the predicting value (PV) of each patient was calculated, then all patients were divided into five risk groups according to PV, their predicting models of survival rates after resection were established in groups. The goodness-fit of estimated predicting models of survival rates were checked by fitting curve and residual plot, and the estimated models tallied with the actual situation. The results suggest that the patients with advanced gastric cancer after resection without lymph node metastases and hepatic metastases had a better prognosis, and their survival probability may be predicted according to the predicting model of survival rates.

Comparison and validation of statistical methods for predicting power outage durations in the event of hurricanes.

PubMed

Nateghi, Roshanak; Guikema, Seth D; Quiring, Steven M

2011-12-01

This article compares statistical methods for modeling power outage durations during hurricanes and examines the predictive accuracy of these methods. Being able to make accurate predictions of power outage durations is valuable because the information can be used by utility companies to plan their restoration efforts more efficiently. This information can also help inform customers and public agencies of the expected outage times, enabling better collective response planning, and coordination of restoration efforts for other critical infrastructures that depend on electricity. In the long run, outage duration estimates for future storm scenarios may help utilities and public agencies better allocate risk management resources to balance the disruption from hurricanes with the cost of hardening power systems. We compare the out-of-sample predictive accuracy of five distinct statistical models for estimating power outage duration times caused by Hurricane Ivan in 2004. The methods compared include both regression models (accelerated failure time (AFT) and Cox proportional hazard models (Cox PH)) and data mining techniques (regression trees, Bayesian additive regression trees (BART), and multivariate additive regression splines). We then validate our models against two other hurricanes. Our results indicate that BART yields the best prediction accuracy and that it is possible to predict outage durations with reasonable accuracy. © 2011 Society for Risk Analysis.

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.

[Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with 
Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma].

PubMed

Ren, Hongliang; Xu, Wengui; You, Jian; Song, Xiuyu; Huang, Hui; Zhao, Ning; Ren, Xiubao; Zhang, Xinwei

2016-04-20

Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Approximately 80%-85% of cases are NSCLC which includes three main types: adenocarcinoma (40%), squamous cell carcinoma (SCC) (20%-30%), and large cell carcinoma (10%). Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET)/computed tomography (CT) has emerged as an accurate staging modality in lung cancer diagnosis. The aim of this study is to investigate the role of maximum standardized uptake value (SUVmax) on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. One hundred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. The patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months; P=0.022). There was remarkable correlation between SUVmax and gender, tumor size, tumor-node-metastasis (TNM) stage, neutrophil, NLR, hemoglobin (P<0.05). Multivariate Cox analysis demonstrated that SUVmax (HR=1.714, 95%CI: 1.021-2.876, P=0.042), TNM stage (HR=1.677, 95%CI: 1.231-2.284, P=0.001) were independent predictors for survival. Furthermore, univariate survival analysis showed significant difference by SUVmax in patients of stage I (P=0.045). SUVmax may be of importance prognostic factor independent of TNM stage, which was considerable for risk stratification in patients with TNM stage. Besides, there was correlation between SUVmax of primary tumor and clinicopathological characteristics.
.

Multicenter retrospective analysis of cardiovascular risk factors affecting long-term outcome of de novo cardiac transplant recipients.

PubMed

Kobashigawa, Jon A; Starling, Randall C; Mehra, Mandeep R; Kormos, Robert L; Bhat, Geetha; Barr, Mark L; Sigouin, Chris S; Kolesar, June; Fitzsimmons, William

2006-09-01

Previous risk factor studies in cardiac transplant patients have analyzed pre-transplant risk factors as they relate to outcomes. This study is the first in-depth multicenter assessment of ongoing post-transplant risk factors in heart transplant patients and their impact on 5-year outcomes. We reviewed 280 heart transplant patients who survived > 1 year for the impact of post-transplant risk factors (hyperlipidemia, hypertension, diabetes, body mass index [BMI] and renal dysfunction: 8 to 18 possible measurements over 5 years) on outcomes, including death, cardiac allograft vasculopathy (CAV) and non-fatal major adverse cardiac events (NF-MACE). Upon multivariate Cox regression analysis, significant findings were high total-cholesterol for NF-MACE (relative risk [RR] = 4.34, confidence interval [CI] 1.35 to 13.98, p = 0.01), presence of diabetes for NF-MACE (RR = 3.96, CI 1.24 to 12.65, p = 0.02) and high serum creatinine for graft death (RR = 1.59, CI 1.35 to 1.87, p < 0.001). No covariates were found to be significant for CAV. Other significant risk factors by univariate Cox regression models with time-dependent covariates included BMI > or = 33 for graft death. Post-transplant risk factors of hypercholesterolemia and diabetes are associated with NF-MACE, whereas high serum creatinine and BMI > or = 33 are associated with graft death. Risk factor modification, including direct therapy to minimize risk factors, should be considered.

Prediction of Mortality with A Body Shape Index in Young Asians: Comparison with Body Mass Index and Waist Circumference.

PubMed

Lee, Da-Young; Lee, Mi-Yeon; Sung, Ki-Chul

2018-06-01

This paper investigated the impact of A Body Shape Index (ABSI) on the risk of all-cause mortality compared with the impact of waist circumference (WC) and body mass index (BMI). This paper reviewed data of 213,569 Korean adults who participated in health checkups between 2002 and 2012 at Kangbuk Samsung Hospital in Seoul, Korea. A multivariate Cox proportional hazard analysis was performed on the BMI, WC, and ABSI z score continuous variables as well as quintiles. During 1,168,668.7 person-years, 1,107 deaths occurred. As continuous variables, a significant positive relationship with the risk of all-cause death was found only in ABSI z scores after adjustment for age, sex, current smoking, alcohol consumption, regular exercise, presence of diabetes or hypertension, and history of cardiovascular diseases. In Cox analysis of quintiles, quintile 5 of the ABSI z score showed significantly increased hazard ratios (HRs) for mortality risk (HR [95% CI] was 1.32 [1.05-1.66]), whereas the risk for all-cause mortality, on the other hand, decreased in quintiles 3 through 5 of BMI and WC compared with their first quintiles after adjusting for several confounders. This study showed that the predictive value of ABSI for mortality risk was strong for a sample of young Asian participants and that its usefulness was better than BMI or WC. © 2018 The Obesity Society.

Box-Cox transformation of firm size data in statistical analysis

NASA Astrophysics Data System (ADS)

Chen, Ting Ting; Takaishi, Tetsuya

2014-03-01

Firm size data usually do not show the normality that is often assumed in statistical analysis such as regression analysis. In this study we focus on two firm size data: the number of employees and sale. Those data deviate considerably from a normal distribution. To improve the normality of those data we transform them by the Box-Cox transformation with appropriate parameters. The Box-Cox transformation parameters are determined so that the transformed data best show the kurtosis of a normal distribution. It is found that the two firm size data transformed by the Box-Cox transformation show strong linearity. This indicates that the number of employees and sale have the similar property as a firm size indicator. The Box-Cox parameters obtained for the firm size data are found to be very close to zero. In this case the Box-Cox transformations are approximately a log-transformation. This suggests that the firm size data we used are approximately log-normal distributions.

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

Model-Based Clustering and Data Transformations for Gene Expression Data

DTIC Science & Technology

2001-04-30

transformation parameters, e.g. Andrews, Gnanadesikan , and Warner (1973). Aitchison tests: Aitchison (1986) tested three aspects of the data for...N in the Box-Cox transformation in Equation (5) is estimated by maximum likelihood using the observa- tions (Andrews, Gnanadesikan , and Warner 1973...Compositional Data. Chapman and Hall. Andrews, D. F., R. Gnanadesikan , and J. L. Warner (1973). Methods for assessing multivari- ate normality. In P. R

A Bayesian joint probability modeling approach for seasonal forecasting of streamflows at multiple sites

NASA Astrophysics Data System (ADS)

Wang, Q. J.; Robertson, D. E.; Chiew, F. H. S.

2009-05-01

Seasonal forecasting of streamflows can be highly valuable for water resources management. In this paper, a Bayesian joint probability (BJP) modeling approach for seasonal forecasting of streamflows at multiple sites is presented. A Box-Cox transformed multivariate normal distribution is proposed to model the joint distribution of future streamflows and their predictors such as antecedent streamflows and El Niño-Southern Oscillation indices and other climate indicators. Bayesian inference of model parameters and uncertainties is implemented using Markov chain Monte Carlo sampling, leading to joint probabilistic forecasts of streamflows at multiple sites. The model provides a parametric structure for quantifying relationships between variables, including intersite correlations. The Box-Cox transformed multivariate normal distribution has considerable flexibility for modeling a wide range of predictors and predictands. The Bayesian inference formulated allows the use of data that contain nonconcurrent and missing records. The model flexibility and data-handling ability means that the BJP modeling approach is potentially of wide practical application. The paper also presents a number of statistical measures and graphical methods for verification of probabilistic forecasts of continuous variables. Results for streamflows at three river gauges in the Murrumbidgee River catchment in southeast Australia show that the BJP modeling approach has good forecast quality and that the fitted model is consistent with observed data.

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

Breakthrough seizures—Further analysis of the Standard versus New Antiepileptic Drugs (SANAD) study

PubMed Central

Powell, Graham A.; Tudur Smith, Catrin; Marson, Anthony G.

2017-01-01

Objectives To develop prognostic models for risk of a breakthrough seizure, risk of seizure recurrence after a breakthrough seizure, and likelihood of achieving 12-month remission following a breakthrough seizure. A breakthrough seizure is one that occurs following at least 12 months remission whilst on treatment. Methods We analysed data from the SANAD study. This long-term randomised trial compared treatments for participants with newly diagnosed epilepsy. Multivariable Cox models investigated how clinical factors affect the probability of each outcome. Best fitting multivariable models were produced with variable reduction by Akaike’s Information Criterion. Risks associated with combinations of risk factors were calculated from each multivariable model. Results Significant factors in the multivariable model for risk of a breakthrough seizure following 12-month remission were number of tonic-clonic seizures by achievement of 12-month remission, time taken to achieve 12-month remission, and neurological insult. Significant factors in the model for risk of seizure recurrence following a breakthrough seizure were total number of drugs attempted to achieve 12-month remission, time to achieve 12-month remission prior to breakthrough seizure, and breakthrough seizure treatment decision. Significant factors in the model for likelihood of achieving 12-month remission after a breakthrough seizure were gender, age at breakthrough seizure, time to achieve 12-month remission prior to breakthrough, and breakthrough seizure treatment decision. Conclusions This is the first analysis to consider risk of a breakthrough seizure and subsequent outcomes. The described models can be used to identify people most likely to have a breakthrough seizure, a seizure recurrence following a breakthrough seizure, and to achieve 12-month remission following a breakthrough seizure. The results suggest that focussing on achieving 12-month remission swiftly represents the best therapeutic aim to reduce the risk of a breakthrough seizure and subsequent negative outcomes. This will aid individual patient risk stratification and the design of future epilepsy trials. PMID:29267375

[Risk factors on the recurrence of ischemic stroke and the establishment of a Cox's regression model].

PubMed

An, Ya-chen; Chen, Yun-xia; Wang, Yu-xun; Zhao, Xiao-jing; Wang, Yan; Zhang, Jiang; Li, Chun-ling; Peng, Yan-bo; Gao, Su-ling; Chang, Li-sha; Zhang, Li; Xue, Xin-hong; Chen, Rui-ying; Wang, Da-li

2011-08-01

To investigate the risk factors and establish the Cox's regression model on the recurrence of ischemic stroke. We retrospectively reviewed consecutive patients with ischemic stroke admitted to the Neurology Department of the Hebei United University Affiliated Hospital between January 1, 2008 and December 31, 2009. Cases had been followed since the onset of ischemic stroke. The follow-up program was finished in June 30, 2010. Kaplan-Meier methods were used to describe the recurrence rate. Monovariant and multivariate Cox's proportional hazard regression model were used to analyze the risk factors associated to the episodes of recurrence. And then, a recurrence model was set up. During the period of follow-up program, 79 cases were relapsed, with the recurrence rates as 12.75% in one year and 18.87% in two years. Monovariant and multivariate Cox's proportional hazard regression model showed that the independent risk factors that were associated with the recurrence appeared to be age (X₁) (RR = 1.025, 95%CI: 1.003 - 1.048), history of hypertension (X₂) (RR = 1.976, 95%CI: 1.014 - 3.851), history of family strokes (X₃) (RR = 2.647, 95%CI: 1.175 - 5.961), total cholesterol amount (X₄) (RR = 1.485, 95%CI: 1.214 - 1.817), ESRS total scores (X₅) (RR = 1.327, 95%CI: 1.057 - 1.666) and progression of the disease (X₆) (RR = 1.889, 95%CI: 1.123 - 3.178). Personal prognosis index (PI) of the recurrence model was as follows: PI = 0.025X₁ + 0.681X₂ + 0.973X₃ + 0.395X₄ + 0.283X₅ + 0.636X₆. The smaller the personal prognosis index was, the lower the recurrence risk appeared, while the bigger the personal prognosis index was, the higher the recurrence risk appeared. Age, history of hypertension, total cholesterol amount, total scores of ESRS, together with the disease progression were the independent risk factors associated with the recurrence episodes of ischemic stroke. Both recurrence model and the personal prognosis index equation were successful constructed.

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.

Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

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

Huang Jiayi; Vicini, Frank A.; Williams, Scott G.

2012-07-15

Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleasonmore » score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National Comprehensive Cancer Network classification. Conclusions: The PPC is an independent and powerful predictor of clinical outcomes of prostate cancer after RT. A risk model replacing T stage with the PPC to reduce subjectivity demonstrated potentially improved stratification.« less

Changes in autonomic nervous system activity, body weight, and percentage fat mass in the first year postpartum and factors regulating the return to pre-pregnancy weight.

PubMed

Izumi, Mie; Manabe, Emiko; Uematsu, Sayo; Watanabe, Ayako; Moritani, Toshio

2016-10-27

Many women become obese during pregnancy and the postpartum period. Weight gain and obesity in the general population are often attributed to abnormalities of autonomic nervous system (ANS) activity. The aim of this study was to clarify change in ANS activity, body weight, percentage fat mass (%FM), and body mass index (BMI) and the factors regulating the return to the pre-pregnancy weight in the first year postpartum. This study was conducted from 2012 to 2016 at the University Hospital of the Kyoto Prefectural University of Medicine and a nearby obstetrics and gynecology clinic in Japan. Body weight and %FM were measured in 51 women using a dual-frequency body composition measuring device. Heart rate variability and R-R spectral transformation were used as indicators of ANS activity. All parameters were calculated at three postpartum time points. Repeated measure analysis of variance was used for comparisons between measurement times. A multivariable Cox proportional hazards model was conducted to determine factors associated with the return to pre-pregnancy weight. Mean body weight, %FM, and BMI decreased significantly over time after delivery (P < 0.001, P < 0.001, P < 0.001). However, ANS activity did not differ among subjects in the three time points. 25.5 % of subjects had still not returned to their pre-pregnancy body weight by 150-270 days postpartum, and 19.6 % had not by 270-360 days postpartum. Normal-weight obesity (NWO; BMI of 18.5-25 kg/m 2 and %FM of ≥30 %) was observed in several subjects at each measurement. The results of analysis using a multivariable Cox proportional hazards model suggest that ANS activity had no significant correlation with the return to pre-pregnancy weight. The management of body weight and %FM after delivery is considered important. These findings suggest that ANS activity is not associated with the return to pre-pregnancy weight, albeit that sample size was small.

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.

Survival of teeth treated with cast post and cores: A retrospective analysis over an observation period of up to 19.5 years.

PubMed

Raedel, Michael; Fiedler, Cliff; Jacoby, Stephan; Boening, Klaus W

2015-07-01

Scientific data about the long-term survival of teeth treated with cast post and cores are scarce. Retrospective studies often use different target events for their analyses. A comparison is therefore complicated. For associated tooth-, jaw-, and patient-related factors little evidence exists as to their effect on survival. The purpose of this study was to extend the knowledge on the survival of teeth treated with cast post and cores for observation periods of more than 10 years. A decrease or increase in survival times according to the presence or absence of associated parameters needs to be evaluated. A retrospective evaluation was conducted of all cast post and cores inserted in 1 university clinic between January 1992 and June 2011. A Kaplan-Meier survival analysis was carried out by using extraction as the target event. The survival curves for different tooth types, the presence or absence of adjacent teeth, and the prosthetic restoration of the respective jaws were compared by using the log-rank test (α=.05). A Cox regression model was calculated for multivariate analyses. A total of 717 cast post and cores for 343 patients were recorded. The mean survival time was 13.5 years. A statistically significant decrease in survival times was found for canines (11.9 years) and premolars (13.4 years) versus molars (14.1 years), no adjacent teeth (10.6 years) versus at least 1 adjacent tooth (13.8 years), and the restoration with removable dental prostheses (12.5 years) versus fixed dental prostheses and single crowns (13.9 years). The largest reduction in survival time was found for teeth being used as an abutment for a double crown-retained removable partial dental prosthesis (telescopic denture) (9.8 years). Tooth type and adjacent tooth status remained as significant variables within the multivariate Cox regression model. Cast post and cores have an acceptable long-term survival time. Because different factors may influence survival, considering these factors in treatment planning may increase the long-term success of these restorations. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

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.

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

Sole, Claudio V., E-mail: csole@iram.cl; School of Medicine, Complutense University, Madrid; Calvo, Felipe A.

Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-freemore » survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.« less

Diagnosis of pernicious anemia and the risk of pancreatic cancer.

PubMed

Shah, Pari; Rhim, Andrew D; Haynes, Kevin; Hwang, Wei-Ting; Yang, Yu-Xiao

2014-04-01

A number of studies have demonstrated a trophic effect of gastrin on pancreatic cancer cells in vitro. Pernicious anemia (PA) is a clinical condition characterized by chronic hypergastrinemia. The aim of this study was to determine if PA is a risk factor for pancreatic cancer. This study is a retrospective cohort study using The Health Improvement Network database, which contains comprehensive health information on 7.5 million patients in the United Kingdom from 1993 to 2009. All patients with PA in the study cohort were identified and composed of the exposed group. Each exposed patient was matched on practice site, sex, and age with up to 4 unexposed patients without PA. The outcome was incident pancreatic cancer. The hazard ratio and 95% confidence intervals were estimated using multivariable Cox regression analysis. We identified 15,324 patients with PA and 55,094 unexposed patients. Mean follow-up time was similar between groups (exposed 4.31 [SD, 3.38] years, unexposed 4.63 [SD, 3.44] years). The multivariable adjusted hazard ratio for pancreatic cancer associated with PA was 1.16 (95% confidence interval, 0.77-1.76; P = 0.47). There is no significant association between PA and the risk of pancreatic cancer.

Association of the Aspartate Aminotransferase to Alanine Aminotransferase Ratio with BNP Level and Cardiovascular Mortality in the General Population: The Yamagata Study 10-Year Follow-Up

PubMed Central

Yokoyama, Miyuki; Otaki, Yoichiro; Takahashi, Hiroki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Shibata, Yoko; Daimon, Makoto; Kayama, Takamasa; Kubota, Isao

2016-01-01

Background. Early identification of high risk subjects for cardiovascular disease in health check-up is still unmet medical need. Cardiovascular disease is characterized by the superior increase in aspartate aminotransferase (AST) to alanine aminotransferase (ALT). However, the association of AST/ALT ratio with brain natriuretic peptide (BNP) levels and cardiovascular mortality remains unclear in the general population. Methods and Results. This longitudinal cohort study included 3,494 Japanese subjects who participated in a community-based health check-up, with a 10-year follow-up. The AST/ALT ratio increased with increasing BNP levels. And multivariate logistic analysis showed that the AST/ALT ratio was significantly associated with a high BNP (≥100 pg/mL). There were 250 all-cause deaths including 79 cardiovascular deaths. Multivariate Cox proportional hazard regression analysis revealed that a high AST/ALT ratio (>90 percentile) was an independent predictor of all-cause and cardiovascular mortality after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that cardiovascular mortality was higher in subjects with a high AST/ALT ratio than in those without. Conclusions. The AST/ALT ratio was associated with an increase in BNP and was predictive of cardiovascular mortality in a general population. Measuring the AST/ALT ratio during routine health check-ups may be a simple and cost-effective marker for cardiovascular mortality. PMID:27872510

Lymph node ratio may predict relapse free survival and overall survival in patients with stage II & III colorectal carcinoma.

PubMed

Zekri, Jamal; Ahmad, Imran; Fawzy, Ehab; Elkhodary, Tawfik R; Al-Gahmi, Aboelkhair; Hassouna, Ashraf; El Sayed, Mohamed E; Ur Rehman, Jalil; Karim, Syed M; Bin Sadiq, Bakr

2015-01-01

Lymph node ratio (LNR) defined as the number of lymph nodes (LNs) involved with metastases divided by number of LNs examined, has been shown to be an independent prognostic factor in breast, stomach and various other solid tumors. Its significance as a prognostic determinant in colorectal cancer (CRC) is still under investigation. This study investigated the prognostic value of LNR in patients with resected CRC. We retrospectively ex- amined 145 patients with stage II & III CRC diagnosed and treated at a single institution during 9 years pe- riod. Patients were grouped according to LNR in three groups. Group 1; LNR < 0.05, Group 2; LNR = 0.05-0.19 & Group 3 > 0.19. Chi square, life table analysis and multivariate Cox regression were used for statistical analysis. On multivariate analysis, number of involved LNs (NILN) (HR = 1.15, 95% CI 1.055-1.245; P = 0.001) and pathological T stage (P = 0.002) were statistically significant predictors of relapse free survival (RFS). LNR as a continuous variable (but not as a categorical variable) was statistically significant predictor of RFS (P = 0.02). LNR was also a statistically significant predictor of overall survival (OS) (P = 0.02). LNR may predict RFS and OS in patients with resected stage II & III CRC. Studies with larger cohorts and longer follow up are needed to further examine and validate theprognostic value of LNR.

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

Comparison of the 7(th) and proposed 8(th) editions of the AJCC/UICC TNM staging system for non-small cell lung cancer undergoing radical surgery.

PubMed

Jin, Ying; Chen, Ming; Yu, Xinmin

2016-09-19

The present study aims to compare the 7(th) and the proposed 8(th) edition of the AJCC/UICC TNM staging system for NSCLC in a cohort of patients from a single institution. A total of 408 patients with NSCLC who underwent radical surgery were analyzed retrospectively. Survivals were analyzed using the Kaplan -Meier method and were compared using the log-rank test. Multivariate analysis was performed by the Cox proportional hazard model. The Akaike information criterion (AIC) and C-index were applied to compare the two prognostic systems with different numbers of stages. The 7(th) AJCC T categories, the proposed 8(th) AJCC T categories, N categories, visceral pleural invasion, and vessel invasion were found to have statistically significant associations with disease-free survival (DFS) on univariate analysis. In the 7(th) edition staging system as well as in the proposed 8(th) edition, T categories, N categories, and pleural invasion were independent factors for DFS on multivariate analysis. The AIC value was smaller for the 8(th) edition compared to the 7(th) edition staging system. The C-index value was larger for the 8(th) edition compared to the 7(th) edition staging system. Based on the data from our single center, the proposed 8(th) AJCC T classification seems to be superior to the 7(th) AJCC T classification in terms of DFS for patients with NSCLC underwent radical surgery.

Predictors of mortality in patients with emphysema and severe airflow obstruction.

PubMed

Martinez, Fernando J; Foster, Gregory; Curtis, Jeffrey L; Criner, Gerard; Weinmann, Gail; Fishman, Alfred; DeCamp, Malcolm M; Benditt, Joshua; Sciurba, Frank; Make, Barry; Mohsenifar, Zab; Diaz, Philip; Hoffman, Eric; Wise, Robert

2006-06-15

Limited data exist describing risk factors for mortality in patients having predominantly emphysema. A total of 609 patients with severe emphysema (ages 40-83 yr; 64.2% male) randomized to the medical therapy arm of the National Emphysema Treatment Trial formed the study group. Cox proportional hazards regression analysis was used to investigate risk factors for all-cause mortality. Risk factors examined included demographics, body mass index, physiologic data, quality of life, dyspnea, oxygen utilization, hemoglobin, smoking history, quantitative emphysema markers on computed tomography, and a modification of a recently described multifunctional index (modified BODE). Overall, high mortality was seen in this cohort (12.7 deaths per 100 person-years; 292 total deaths). In multivariate analyses, increasing age (p=0.001), oxygen utilization (p=0.04), lower total lung capacity % predicted (p=0.05), higher residual volume % predicted (p=0.04), lower maximal cardiopulmonary exercise testing workload (p=0.002), greater proportion of emphysema in the lower lung zone versus the upper lung zone (p=0.005), and lower upper-to-lower-lung perfusion ratio (p=0.007), and modified BODE (p=0.02) were predictive of mortality. FEV1 was a significant predictor of mortality in univariate analysis (p=0.005), but not in multivariate analysis (p=0.21). Although patients with advanced emphysema experience significant mortality, subgroups based on age, oxygen utilization, physiologic measures, exercise capacity, and emphysema distribution identify those at increased risk of death.

Outcome analysis of donor gender in heart transplantation.

PubMed

Al-Khaldi, Abdulaziz; Oyer, Phillip E; Robbins, Robert C

2006-04-01

Several studies have shown a detrimental effect of female donor gender on the survival of solid-organ transplant recipients, including heart, kidney and liver. We evaluated our own experience in heart transplantation in the cyclosporine era, since 1980, to determine the effect of donor gender on survival. We retrospectively reviewed 869 consecutive patients who underwent primary heart transplantation at Stanford University Medical Center between December 1980 and March 2004. Actuarial life-table data were calculated for survival and freedom from rejection and compared between groups. Multivariate Cox proportional hazard analysis was used to identify predictors of reduced long-term survival. One-year mortality in male recipients who received a female donor heart (24%) was higher than in male recipients who received male donor heart (13%) (p = 0.009). Actuarial survival rates for male recipients at 1, 5 and 10 years were 86%, 69% and 50% (with male donor), and 76%, 59% and 45% (with female donor) (p = 0.01), respectively. Donor gender had no effect on long-term survival in male recipients < 45 years of age and female recipients. Female donor gender was identified as an independent risk factor for death by multivariate analysis, with an odds ratio of 2.3 (95% confidence interval 1.5 to 3.4, p < 0.001). In heart transplantation the detrimental effect of female donor gender on recipient survival is significant but limited to male recipients > 45 years of age. These findings should be considered in the process of donor-recipient matching.

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study.

PubMed

Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming

2017-04-18

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05).

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study

PubMed Central

Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming

2017-01-01

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2− occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05). PMID:28038448

Surgical ablation for atrial fibrillation for two decades: are the results of new techniques equivalent to the Cox maze III procedure?

PubMed

Stulak, John M; Suri, Rakesh M; Burkhart, Harold M; Daly, Richard C; Dearani, Joseph A; Greason, Kevin L; Joyce, Lyle D; Park, Soon J; Schaff, Hartzell V

2014-05-01

A significant evolution has occurred in surgical ablation for atrial fibrillation (AF) toward alternate energy sources, lesion sets, and approaches, with the intent of simplifying the Cox maze III operation and maintaining similar outcomes. Because no large comparative studies with long-term follow-up exist, we have reviewed our experience. From January 1993 to January 2011, 1540 patients underwent surgical ablation for AF. The operations were performed in conjunction with repair of congenital heart disease in 351 (30%) and adult-acquired disease in 1189 patients (70%). In the 1189 patients, preoperative AF was paroxysmal in 598 (50%) and persistent in 591 (50%). The energy sources included cut and sew in 521 (44%), cryothermy in 267 (22%), radiofrequency in 262 (22%), and a combination in 139 patients (12%). The lesion sets included biatrial in 810 (68%), isolated pulmonary vein isolation in 269 (23%), and isolated left atrial in 110 (9%). AF ablation was performed during isolated mitral valve surgery in 516 patients (43%). The median follow-up was 33 months (maximum, 20.3 years), and late rhythm follow-up was available for 80%. The cut and sew Cox maze III procedure was superior at each follow-up interval (P = .01, P = .03, and P < .001). On multivariate analysis, the cut and sew maze procedure was independently associated with less risk of recurrent AF at a follow-up period of 1 to 5 years (hazard ratio, 0.4; 95% confidence interval, 0.24-0.69; P < .001) and >5 years (hazard ratio, 0.23; 95% confidence interval, 0.12-0.42; P < .001) for all patients. When performed during isolated mitral valve surgery, the cut and sew Cox maze III was also independently associated with less risk of recurrent AF at >5 years (hazard ratio, 0.23; 95% confidence interval, 0.08-0.66; P = .007). The cut and sew Cox maze III procedure appears to offer significantly greater freedom from AF without antiarrhythmic medications compared with alternate energy sources and lesion sets. Although alternate energy sources offer the advantage of quicker application and the possibility of minimally invasive applications, the Cox maze III operation arguably remains the reference standard for the surgical treatment of AF and should still be considered, especially for patients for whom AF ablation is of critical importance. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

All-cause mortality of elderly Australian veterans using COX-2 selective or non-selective NSAIDs: a longitudinal study

PubMed Central

Kerr, Stephen J; Rowett, Debra S; Sayer, Geoffrey P; Whicker, Susan D; Saltman, Deborah C; Mant, Andrea

2011-01-01

AIM To determine hazard ratios for all-cause mortality in elderly Australian veterans taking COX-2 selective and non-selective NSAIDs. METHODS Patient cohorts were constructed from claims databases (1997 to 2007) for veterans and dependants with full treatment entitlement irrespective of military service. Patients were grouped by initial exposure: celecoxib, rofecoxib, meloxicam, diclofenac, non-selective NSAID. A reference group was constructed of patients receiving glaucoma/hypothyroid medications and none of the study medications. Univariate and multivariate analyses were performed using Cox proportional hazards regression models. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for each exposure group against each of the reference group. The final model was adjusted for age, gender and co-prescription as a surrogate for cardiovascular risk. Patients were censored if the gap in supply of study prescription exceeded 30 days or if another study medication was initiated. The outcome measure in all analyses was death. RESULTS Hazard ratios and 95% CIs, adjusted for age, gender and cardiovascular risk, for each group relative to the reference group were: celecoxib 1.39 (1.25, 1.55), diclofenac 1.44 (1.28, 1.62), meloxicam 1.49 (1.25, 1.78), rofecoxib 1.58 (1.39, 1.79), non-selective NSAIDs 1.76 (1.59, 1.94). CONCLUSIONS In this large cohort of Australian veterans exposed to COX-2 selective and non-selective NSAIDs, there was a significant increased mortality risk for those exposed to either COX-2-selective or non-selective NSAIDs relative to those exposed to unrelated (glaucoma/hypothyroid) medications. PMID:21276041

Prevalence and prognosis of ventricular tachycardia/ventricular fibrillation in patients with post-infarction left ventricular aneurysm: Analysis of 575 cases.

PubMed

Ning, Xiaohui; Ye, Xuerui; Si, Yanhua; Yang, Zihe; Zhao, Yunzi; Sun, Qi; Chen, Ruohan; Tang, Min; Chen, Keping; Zhang, Xiaoli; Zhang, Shu

2018-03-21

We investigated the prevalence of ventricular tachycardia/ventricular fibrillation (VT/VF) in Post-infarction left ventricular aneurysm (PI-LVA) patients and analyze clinical outcomes in patients presenting with VT/VF. 575 PI-LVA patients were enrolled and investigated by logistic regression analysis. Patients with VT/VF were followed up, the composite primary endpoint was cardiac death and appropriate ICD/external shocks. The incidence of sustained VT/VF was 11%. Logistical regression analysis showed male gender, enlarged LV end diastolic diameter (LVEDD) and higher NYHA class were correlated with VT/VF development. During follow up of 46 ± 15 months, 19 out of 62(31%) patients reached study end point. Multivariate Cox regression analysis revealed that enlarged LVEDD and moderate/severe mitral regurgitation (MR) were independently predictive of clinical outcome. Male gender, enlarged LVEDD and higher NYHA class associated with risk of sustained VT/VF in PI-LVA patients. Among VT/VF positive patients, enlarged LVEDD and moderate/severe MR independently predicted poor clinical prognosis. Copyright © 2018. Published by Elsevier Inc.

Immortal time bias in observational studies of time-to-event outcomes.

PubMed

Jones, Mark; Fowler, Robert

2016-12-01

The purpose of the study is to show, through simulation and example, the magnitude and direction of immortal time bias when an inappropriate analysis is used. We compare 4 methods of analysis for observational studies of time-to-event outcomes: logistic regression, standard Cox model, landmark analysis, and time-dependent Cox model using an example data set of patients critically ill with influenza and a simulation study. For the example data set, logistic regression, standard Cox model, and landmark analysis all showed some evidence that treatment with oseltamivir provides protection from mortality in patients critically ill with influenza. However, when the time-dependent nature of treatment exposure is taken account of using a time-dependent Cox model, there is no longer evidence of a protective effect of treatment. The simulation study showed that, under various scenarios, the time-dependent Cox model consistently provides unbiased treatment effect estimates, whereas standard Cox model leads to bias in favor of treatment. Logistic regression and landmark analysis may also lead to bias. To minimize the risk of immortal time bias in observational studies of survival outcomes, we strongly suggest time-dependent exposures be included as time-dependent variables in hazard-based analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative assessment of metal elements using moss species as biomonitors in downwind area of lead-zinc mine.

PubMed

Balabanova, Biljana; Stafilov, Trajče; Šajn, Robert; Andonovska, Katerina Bačeva

2017-02-23

Distributions of a total of 21 elements were monitored in significantly lead-zinc polluted area using moss species (Hypnum cupressiforme and Camptothecium lutescens) used interchangeably, covering a denser sampling network. Interspecies comparison was conducted using Box-Cox transformed values, due to their skewed distribution. The median concentrations of trace elements in the both mosses examined decreased in the following order: Fe>Mn>Zn>Pb>Cu>Ni∼Cr∼As>Co>Cd>Hg. For almost all analyzed elements, H. cupressiforme revealed higher bio-accumulative abilities. For arsenic contents was obtained ER-value in favor of C. lutescens. The ER for the element contents according to the distance from the pollution source in selected areas was significantly enriched for the anthropogenic introduced elements As, Cd, Cu, Pb and Zn. After Box-Cox transformation of the content values, T B was significantly different for As (4.82), Cd (3.84), Cu (2.95), Pb (4.38), and Zn (4.23). Multivariate factor analysis singled out four elemental associations: F1 (Al-Co-Cr-Fe-Li-Ni-V), F2 (Cd-Pb-Zn), F3 (Ca-Mg-Na-P) and F4 (Cu) with a total variance of 89%. Spatial distribution visualized the hazardously higher contents of "hot spots" of Cd > 1.30 mg/kg, Cu > 22 mg/kg, Pb > 130 mg/kg and Zn > 160 mg/kg. Therefore, main approach in moss biomonitoring should be based on data management of the element distribution by reducing the effect of extreme values (considering Box-Cox data transformation); the interspecies variation in sampling media does not deviate in relation to H. cupressiforme vs. C. lutescens.

NSAIDs and spontaneous abortions – true effect or an indication bias?

PubMed Central

Daniel, Sharon; Koren, Gideon; Lunenfeld, Eitan; Levy, Amalia

2015-01-01

Aim The aim of the study was to characterize the extent of indication bias resulting from the excessive use of NSAIDs on the days preceding a spontaneous abortion to relieve pain. Methods We used data from a retrospective cohort study assessing the risk for spontaneous abortions following exposure to NSAIDs. Three definitions of exposure for cases of spontaneous abortions were compared, from the first day of pregnancy until the day of spontaneous abortion and until 3 and 2 days before a spontaneous abortion. Statistical analysis was performed using multivariate time programmed Cox regression. Results A sharp increase was observed in the dispensation of indomethacin, diclofenac and naproxen, and a milder increase was found in the use of ibuprofen during the week before a spontaneous abortion. Non- selective COX inhibitors in general and specifically diclofenac and indomethacin were found to be associated with spontaneous abortions when the exposure period was defined until the day of spontaneous abortion (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04, 1.28; HR 1.31, 95% CI 1.08, 1.59 and HR 3.33, 95% CI 2.09, 5.29, respectively). The effect disappears by excluding exposures occurring on the day before the spontaneous abortion for non-selective COX inhibitors and on the last week before the spontaneous abortion for indomethacin. In general, decreasing HRs were found with the exclusion of exposures occurring on the days immediately before the spontaneous abortion. Conclusions The increased use of NSAIDs during the last few days that preceded a spontaneous abortion to relieve pain associated with the miscarriage could bias studies assessing the association between exposure to NSAIDs and spontaneous abortions. PMID:25858169

Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Almstedt, Katrin; Heimes, Anne-Sophie; Makris, Georgios-Marios; Weyer, Veronika; Schmidt, Marcus

2016-09-01

New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p = 0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p = 0.025). The MDACC grading system (p = 0.008) but not the FIGO system (p = 0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95 % CI 1.007-2.449; p = 0.047, and HR 0.712; 95 % CI 0.476-1.066; p = 0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95 % CI 1.207-3.835; p = 0.009, and HR 1.258; 95 % CI 0.801-1.975; p = 0.319, respectively). We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system.

Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.

PubMed

Prochaska, Megan; Taylor, Eric; Vaidya, Anand; Curhan, Gary

2017-08-07

Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). Low bone density is an independent risk factor for incident kidney stone and is associated with higher 24-hour urine calcium excretion. Among participants with low bone density, bisphosphonate use was associated with lower risk of incident kidney stone but was not independently associated with 24-hour urine calcium excretion. Copyright © 2017 by the American Society of Nephrology.

Prediction of decannulation, oral intake recovery, overall survival and lung metastasis following oral malignant tumor resection and reconstruction

PubMed Central

Suzuki, Hidenori; Hyodo, Ikuo; Hasegawa, Yasuhisa

2018-01-01

The present study investigated whether tongue base and mandibular bone defects were associated with the rate of decannulation and oral intake recovery, and survival time, including overall and lung metastasis-free survival time, in patients that underwent oral malignant tumor (OMT) resection with reconstruction. A total of 105 patients that underwent OMT resection with laryngeal preservation and reconstruction were recruited. The extent of defects was classified according to Urken's classification. The rates of decannulation and oral intake recovery were assessed with the Kaplan-Meier method. It was identified that 4–5 section segmental mandibulectomy (SM) and total glossectomy (TG) were significantly associated with a lower rate of decannulation and oral intake recovery by univariate and multivariate analysis using a Cox's proportional model. Patients in the high risk group (4–5 sections or TG) were significantly less likely to achieve decannulation and unaided oral intake. Patients in the high risk group exhibited a significantly shorter overall and lung metastasis-free survival time. Following multivariate analysis adjusted for the clinical stage (IV/I–III), past history of or postoperative radiotherapy (yes/no) and age (per year), the high risk group was associated with a significantly rate of decannulation and unaided oral intake. In conclusion, TG or wide SM is a prognostic parameter for functional and survival outcomes, including lung metastasis, in OMT. PMID:29434993

Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis.

PubMed

Shimizu, Toshio; Bokuda, Kota; Kimura, Hideki; Kamiyama, Tsutomu; Nakayama, Yuki; Kawata, Akihiro; Isozaki, Eiji; Ugawa, Yoshikazu

2018-05-01

To investigate somatosensory cortex excitability and its relationship to survival prognosis in patients with amyotrophic lateral sclerosis (ALS). A total of 145 patients with sporadic ALS and 73 healthy control participants were studied. We recorded compound muscle action potential and sensory nerve action potential of the median nerve and the median nerve somatosensory evoked potential (SEP), and we measured parameters, including onset-to-peak amplitude of N13 and N20 and peak-to-peak amplitude between N20 and P25 (N20p-P25p). Clinical prognostic factors, including ALS Functional Rating Scale-Revised, were evaluated. We followed up patients until the endpoints (death or tracheostomy) and analyzed factors associated with survival using multivariate analysis in the Cox proportional hazard model. Compared to controls, patients with ALS showed a larger amplitude of N20p-P25p in the median nerve SEP. Median survival time after examination was shorter in patients with N20p-P25p ≥8 μV (0.82 years) than in those with N20p-P25p <8 μV (1.68 years, p = 0.0002, log-rank test). Multivariate analysis identified a larger N20p-P25p amplitude as a factor that was independently associated with shorter survival ( p = 0.002). Sensory cortex hyperexcitability predicts short survival in patients with ALS. © 2018 American Academy of Neurology.

Impact of scalp location on survival in head and neck melanoma: A retrospective cohort study.

PubMed

Xie, Charles; Pan, Yan; McLean, Catriona; Mar, Victoria; Wolfe, Rory; Kelly, John

2017-03-01

Scalp melanomas have more aggressive clinicopathological features than other melanomas and mortality rates more than twice that of melanoma located elsewhere. We sought to describe the survival of patients with scalp melanoma versus other cutaneous head and neck melanoma (CHNM), and explore a possible independent negative impact of scalp location on CHNM survival. A retrospective cohort study was performed of all invasive primary CHNM cases seen at a tertiary referral center over a 20-year period. Melanoma-specific survival (MSS) was compared between scalp melanoma and other invasive CHNM. Multivariable Cox proportional hazards regression was performed to determine associations with survival. On univariate analysis, patients with scalp melanoma had worse MSS than other CHNM (hazard ratio 2.22, 95% confidence interval 1.59-3.11). Scalp location was not associated with MSS in CHNM on multivariable analysis (hazard ratio 1.11, 95% confidence interval 0.77-1.61) for all tumors together, but remained independently associated with MSS for the 0.76- to 1.50-mm thickness stratum (hazard ratio 5.51, 95% confidence interval 1.55-19.59). Disease recurrence was not assessed because of unavailable data. The poorer survival of scalp melanoma is largely explained by greater Breslow thickness and a higher proportion of male patients. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

PubMed

Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Funayama, Akira; Kinoshita, Daisuke; Yokoyama, Miyuki; Takahashi, Tetsuya; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

2016-02-01

Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF. We measured N-acetyl-β-D-glucosamidase (NAG) levels and the urinary β2-microglobulin to creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR ≥ 300 μg/g or NAG ≥ 14.2 U/g. There were moderate correlations between RTD markers and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypoalbuminemia in patients with CHF. There were 134 cardiac events during a median period of 808 days. The comorbidity of RTD and hypoalbuminemia was increased with advancing New York Heart Association functional class. Multivariate Cox proportional hazard regression analysis showed that the presence of RTD and hypoalbuminemia was associated with cardiac events. The net reclassification index was significantly improved by adding RTD and hypoalbuminemia to the basic risk factors. Comorbid RTD and hypoalbuminemia are frequently observed and increase the risk for extremely poor outcome in patients with CHF.

Speed of response in ultrabrief and brief pulse width right unilateral ECT.

PubMed

Loo, Colleen K; Garfield, Joshua B B; Katalinic, Natalie; Schweitzer, Isaac; Hadzi-Pavlovic, Dusan

2013-05-01

Ultrabrief pulse width stimulation electroconvulsive therapy (ECT) results in less cognitive side-effects than brief pulse ECT, but recent work suggests that more treatment sessions may be required to achieve similar efficacy. In this retrospective analysis of subjects pooled from three research studies, time to improvement was analysed in 150 depressed subjects who received right unilateral ECT with a brief pulse width (at five times seizure threshold) or ultrabrief pulse width (at six times seizure threshold). Multivariate Cox regression analyses compared the number of treatments required for 50% reduction in depression scores (i.e. speed of response) in these two samples. The analyses controlled for clinical, demographic and treatment variables that differed between the samples or that were found to be significant predictors of speed of response in univariate analyses. In the multivariate analysis, older age predicted faster speed of response. There was a non-significant trend for faster time to 50% improvement with brief pulse ECT (p = 0.067). Remission rates were higher after brief pulse ECT than ultrabrief pulse ECT (p = 0.007) but response rates were similar. This study, the largest of its kind reported to date, suggests that fewer treatments may be needed to attain response with brief than ultrabrief pulse ECT and that remission rates are higher with brief pulse ECT. Further research with a larger randomized and blinded study is recommended.

Mandibular osteoradionecrosis in squamous cell carcinoma of the oral cavity and oropharynx: incidence and risk factors.

PubMed

Monnier, Yan; Broome, Martin; Betz, Michael; Bouferrache, Kahina; Ozsahin, Mahmut; Jaques, Bertrand

2011-05-01

Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) in head and neck cancer patients. The aim of this study was to analyze the incidence of and risk factors for mandibular ORN in squamous cell carcinoma (SCC) of the oral cavity and oropharynx. Case series with chart review. University tertiary care center for head and neck oncology. Seventy-three patients treated for stage I to IV SCC of the oral cavity and oropharynx between 2000 and 2007, with a minimum follow-up of 2 years, were included in the study. Treatment modalities included both RT with curative intent and adjuvant RT following tumor surgery. The log-rank test and Cox model were used for univariate and multivariate analyses. The incidence of mandibular ORN was 40% at 5 years. Using univariate analysis, the following risk factors were identified: oral cavity tumors (P < .01), bone invasion (P < .02), any surgery prior to RT (P < .04), and bone surgery (P < .0001). By multivariate analysis, mandibular surgery proved to be the most important risk factor and the only one reaching statistical significance (P < .0002). Mandibular ORN is a frequent long-term complication of RT for oral cavity and oropharynx cancers. Mandibular surgery before irradiation is the only independent risk factor. These aspects must be considered when planning treatment for these tumors.

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.

Marital status, treatment, and survival in patients with glioblastoma multiforme: a population based study.

PubMed

Chang, Susan M; Barker, Fred G

2005-11-01

Social factors influence cancer treatment choices, potentially affecting patient survival. In the current study, the authors studied the interrelations between marital status, treatment received, and survival in patients with glioblastoma multiforme (GM), using population-based data. The data source was the Surveillance, Epidemiology, and End Results (SEER) Public Use Database, 1988-2001, 2004 release, all registries. Multivariate logistic, ordinal, and Cox regression analyses adjusted for demographic and clinical variables were used. Of 10,987 patients with GM, 67% were married, 31% were unmarried, and 2% were of unknown marital status. Tumors were slightly larger at the time of diagnosis in unmarried patients (49% of unmarried patients had tumors larger than 45 mm vs. 45% of married patients; P = 0.004, multivariate analysis). Unmarried patients were less likely to undergo surgical resection (vs. biopsy; 75% of unmarried patients vs. 78% of married patients) and were less likely to receive postoperative radiation therapy (RT) (70% of unmarried patients vs. 79% of married patients). On multivariate analysis, the odds ratio (OR) for resection (vs. biopsy) in unmarried patients was 0.88 (95% confidence interval [95% CI], 0.79-0.98; P = 0.02), and the OR for RT in unmarried patients was 0.69 (95% CI, 0.62-0.77; P < 0.001). Unmarried patients more often refused both surgical resection and RT. Unmarried patients who underwent surgical resection and RT were found to have a shorter survival than similarly treated married patients (hazard ratio for unmarried patients, 1.10; P = 0.003). Unmarried patients with GM presented with larger tumors, were less likely to undergo both surgical resection and postoperative RT, and had a shorter survival after diagnosis when compared with married patients, even after adjustment for treatment and other prognostic factors. (c) 2005 American Cancer Society.

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.

Menopause and Risk of Kidney Stones.

PubMed

Prochaska, Megan; Taylor, Eric N; Curhan, Gary

2018-05-03

Metabolic changes due to menopause may alter urine composition and kidney stone risk but results from prior work on this association have been mixed. We examined menopause and risk of incident kidney stones and changes in 24-hour urine composition in the Nurses' Health Study II. We conducted a prospective analysis of 108,639 Nurses' Health Study II participants who provided information on menopause and kidney stones. We used multivariate adjusted Cox proportional hazards models. We also analyzed 24-hour urine collections from 658 participants who performed a collection while pre-menopausal and a repeat collection after menopause. During 22 years of follow-up, there were 3,456 incident kidney stones. The multivariate adjusted relative risk for an incident kidney stone for post-menopausal participants compared with pre-menopause was 1.27 (95% CI 1.08 to 1.46). In a stratified analysis, compared with pre-menopause, the multivariate adjusted relative risk of natural menopause was 1.27 (95% CI 1.09 to 1.48) and surgically induced menopause was 1.43 (95% CI 1.19 to 1.73). Among 74,505 post-menopausal participants, there were 1,041 incident stone events. Compared with no hormone therapy use, neither current nor past use was significantly associated with kidney stone risk. Compared with pre-menopause, the post-menopausal urine collections had lower mean calcium, citrate, phosphorus, and uric acid, and higher mean volume. Post-menopausal status is associated with higher risk of incident kidney stone. Natural and surgical menopause are each independently associated with higher risk. There are small but significant differences in urine composition between pre- and post-menopausal urine collections. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Factors affecting residual stones after percutaneous nephrolithotomy in patients with renal calculus].

PubMed

Qiao, Mingzhou; Zhang, Haifang; Zhou, Chenlong

2015-11-24

To explore the factors affecting the residual stones after percutaneous nephrolithotomy (PCNL) in patients with renal calculus. A retrospective analysis was performed for 1 200 patients who were affected by renal calculus and treated with PCNL between Jan 2008 and May 2014 in People's Hospital of Anyang City. Among those patients, 16 were diagnosed as bilateral renal stone and had two successive operations. The size, location and number of stones, previous history of surgery, the degree of hydronephrosis, urinary infection were included in the univariate analysis. Significant factors in univariate analysis were included in the multivariate analysis to determine factors affecting stone residual. A total of 385 cases developed stone residual after surgery. The overall residual rate was 31.7%. In univariate analysis, renal pelvis combined with caliceal calculus (P=0.006), stone size larger than 4 cm (P=0.005), stone number more than 4 (P=0.002), the amount of bleeding more than 200 ml (P=0.025), operation time longer than 120 minutes (P=0.028) were associated with an increased rate of stone residual. When subjected to the Cox multivariate analysis, the independent risk factors for residual stones were renal pelvis combined with caliceal calculus (P=0.049), stone size larger than 4 cm (P=0.038) and stone number more than 4 (P=0.018). Factors affecting the incidence of residual stones after PCNL are the size, location and number of stones. Larger size stone and the presence of renal pelvis combined with caliceal calculus are significantly associated with residual stones. Nevertheless, stone number less than 4 indicates an increased stone clearance rate.

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.

Expression of VEGF, VEGFR, EGFR, COX-2 and MVD in cervical carcinoma, in relation with the response to radio-chemotherapy.

PubMed

Nagy, Viorica Magdalena; Buiga, R; Brie, Ioana; Todor, N; Tudoran, Oana; Ordeanu, Claudia; Virág, Piroska; Tarta, Oana; Rus, Meda; Bălăcescu, O

2011-01-01

Despite the improvement in the treatment results due to modern irradiation techniques and to the association of chemo-radiotherapy, cervical cancer remains an unsolved problem of oncology both due to the increased rate of local failures and of the distant metastasis. Efforts to implement new therapeutic strategies in order to obtain better results in patients with cervical cancer appear justified. Neovascularization is an important step in the tumor progression and the therapeutic targeting of the tumor blood vessels appears to be a good strategy to follow in the anti-cancer treatment. Thus, even in an incipient phase of the clinical research process, the combination between the anti-angiogenic aimed therapies and the current radio-chemotherapy seems to represent a new, feasible and promising approach. The aim of the present study was to determine the prognostic and/or predictive value of some biological markers of tumor angiogenesis and of their implication in increasing the efficacy of current treatments for this cancer. So far, 54 women were included in a prospective trial: 44 having an advanced cervical carcinoma and 10 healthy women, as controls. A tumor biopsy and a blood sample were obtained from each patient before the start of therapy. The density of microvascularization was assessed using CD34 monoclonal antibody (hot spot technique), the expression of angiogenic factors VEGFR, EGFR and COX-2 were determined in tumor biopsies by specific immunohistochemistry techniques, using primary antibodies anti-EGFR, anti-VEGF and anti-COX-2 respectively. The quantitative polymerase chain reaction (Real Time PCR) was employed for assessing the expression level of the genes involved. Serum VEGF was determined by quantitative ELISA technique. Among the studied clinical and molecular factors, we found to be predictive for the type of response the following factors: tumor size at diagnosis (p=0.01), VEGFR2 expression (p=0.02) and a tendency to significance for patients' age (p=0.06). From the large panel of studied markers it was observed correlation between MVD expression with stromal COX-2 (p=0.01) and a tendency with epithelial COX-2 (p=0.06). Stromal COX-2 has higher correlation with VEGFR2 (p=0.01) and MVD (p=0.01) and also has a lower correlation with tumor size (p=0.08). Univariate analysis demonstrates that the response to radio-chemotherapy in cervical cancer is related to a set of clinical and molecular factors as: the tumor size, the expression of VEGFR2 as mRNA level and the patients' age. Unfortunately, the multivariate analysis by logistic model selects only VEGFR2 expression for prediction of tumor response. The interrelations between the different biomarkers demonstrate the complexity of the tumor progression process and the necessity of further studies to identify new therapeutic targets.

Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study

PubMed Central

2010-01-01

Background We conducted a retrospective analysis to investigate treatment results and prognostic factors of pediatric neuroblastoma patients. Methods This retrospective study was carried out analyzing the medical records of patients with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer Institute, Assiut University during the period from January 2001 and January 2010. After induction chemotherapy, response according to international neuoblastoma response criteria was assessed. Radiotherapy to patients with residual primary tumor was applied. Overall and event free survival (OAS and EFS) rates were estimated using Graphed prism program. The Log-rank test was used to examine differences in OAS and EFS rates. Cox-regression multivariate analysis was done to determine the independent prognostic factors affecting survival rates. Results Fifty three cases were analyzed. The median follow-up duration was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were 39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of age, N-MYC amplification, and high risk group. The majority of patients (68%) presented in high risk group, where treatment outcome was poor, as only 21% of patients survived for 3 year. Conclusion Multivariate analysis confirmed only the association between survival and risk group. However, in univariate analysis, local radiation therapy resulted in significant survival improvement. Therefore, radiotherapy should be given to patients with residual tumor evident after induction chemotherapy and surgery. Future attempts to improve OAS in high risk group patients with aggressive chemotherapy and bone marrow transplantation should be considered. PMID:21182799

The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

PubMed

Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

2015-12-01

Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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.

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.

The Number of Recalled Leads is Highly Predictive of Lead Failure: Results From the Pacemaker and Implantable Defibrillator Leads Survival Study ("PAIDLESS").

PubMed

Kersten, Daniel J; Yi, Jinju; Feldman, Alyssa M; Brahmbhatt, Kunal; Asheld, Wilbur J; Germano, Joseph; Islam, Shahidul; Cohen, Todd J

2016-12-01

The purpose of this study was to determine if implantation of multiple recalled defibrillator leads is associated with an increased risk of lead failure. The authors of the Pacemaker and Implantable Defibrillator Leads Survival Study ("PAIDLESS") have previously reported a relationship between recalled lead status, lead failure, and patient mortality. This substudy analyzes the relationship in a smaller subset of patients who received more than one recalled lead. The specific effects of having one or more recalled leads have not been previously examined. This study analyzed lead failure and mortality of 3802 patients in PAIDLESS and compared outcomes with respect to the number of recalled leads received. PAIDLESS includes all patients at Winthrop University Hospital who underwent defibrillator lead implantation between February 1, 1996 and December 31, 2011. Patients with no recalled ICD leads, one recalled ICD lead, and two recalled ICD leads were compared using the Kaplan-Meier method and log-rank test. Sidak adjustment method was used to correct for multiple comparisons. All calculations were performed using SAS 9.4. P-values <.05 were considered statistically significant. This study included 4078 total ICD leads implanted during the trial period. There were 2400 leads (59%) in the no recalled leads category, 1620 leads (40%) in the one recalled lead category, and 58 leads (1%) in the two recalled leads category. No patient received more than two recalled leads. Of the leads categorized in the two recalled leads group, 12 experienced lead failures (21%), which was significantly higher (P<.001) than in the no recalled leads group (60 failures, 2.5%) and one recalled lead group (81 failures; 5%). Multivariable Cox's regression analysis found a total of six significant predictive variables for lead failure including the number of recalled leads (P<.001 for one and two recalled leads group). The number of recalled leads is highly predictive of lead failure. Lead-based multivariable Cox's regression analysis produced a total of six predictive variable categories for lead failure, one of which was the number of recalled leads. Kaplan-Meier analysis showed that the leads in the two recalled leads category failed faster than both the no recalled lead and one recalled lead groups. The greater the number of recalled leads to which patients are exposed, the greater the risk of lead failure.

Gender-Related and Age-Related Differences in Implantable Defibrillator Recipients: Results From the Pacemaker and Implantable Defibrillator Leads Survival Study ("PAIDLESS").

PubMed

Feldman, Alyssa M; Kersten, Daniel J; Chung, Jessica A; Asheld, Wilbur J; Germano, Joseph; Islam, Shahidul; Cohen, Todd J

2015-12-01

The purpose of this study was to investigate the influences of gender and age on defibrillator lead failure and patient mortality. The specific influences of gender and age on defibrillator lead failure have not previously been investigated. This study analyzed the differences in gender and age in relation to defibrillator lead failure and mortality of patients in the Pacemaker and Implantable Defibrillator Leads Survival Study ("PAIDLESS"). PAIDLESS includes all patients at Winthrop University Hospital who underwent defibrillator lead implantation between February 1, 1996 and December 31, 2011. Male and female patients were compared within each age decile, beginning at 15 years old, to analyze lead failure and patient mortality. Statistical analyses were performed using Wilcoxon rank-sum test, Fisher's exact test, Kaplan-Meier analysis, and multivariable Cox regression models. P<.05 was considered statistically significant. No correction for multiple comparisons was performed for the subgroup analyses. A total of 3802 patients (2812 men and 990 women) were included in the analysis. The mean age was 70 ± 13 years (range, 15-94 years). Kaplan-Meier analysis found that between 45 and 54 years of age, leads implanted in women failed significantly faster than in men (P=.03). Multivariable Cox regression models were built to validate this finding, and they confirmed that male gender was an independent protective factor of lead failure in the 45 to 54 years group (for male gender: HR, 0.37; 95% confidence interval, 0.14-0.96; P=.04). Lead survival time for women in this age group was 13.4 years (standard error, 0.6), while leads implanted in men of this age group survived 14.7 years (standard error, 0.3). Although there were significant differences in lead failure, no differences in mortality between the genders were found for any ages or within each decile. This study is the first to compare defibrillator lead failure and patient mortality in relation to gender and age deciles at a single large implanting center. Within the 45 to 54 years group, leads implanted in women failed faster than in men. Male gender was found to be an independent protective factor in lead survival. This study emphasizes the complex interplay between gender and age with respect to implantable defibrillator lead failure and mortality.

Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

PubMed

Tong, Dandan; Liang, Ya-Nan; Stepanova, A A; Liu, Yu; Li, Xiaobo; Wang, Letian; Zhang, Fengmin; Vasilyeva, N V

2017-02-01

Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p < 0.001) and RAB11FIP3 ( r = 0.165, p = 0.005) expression. The multivariate Cox proportional hazard model analysis demonstrated that the expression of Eps15 homology domain 1 alone is a significant prognostic marker of breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor.

Outcomes for Spine Stereotactic Body Radiation Therapy and an Analysis of Predictors of Local Recurrence

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

Bishop, Andrew J.; Tao, Randa; Rebueno, Neal C.

Purpose: To investigate local control, survival outcomes, and predictors of local relapse for patients treated with spine stereotactic body radiation therapy. Methods and Materials: We reviewed the records of 332 spinal metastases consecutively treated with stereotactic body radiation therapy between 2002 and 2012. The median follow-up for all living patients was 33 months (range, 0-111 months). Endpoints were overall survival and local control (LC); recurrences were classified as either in-field or marginal. Results: The 1-year actuarial LC and overall survival rates were 88% and 64%, respectively. Patients with local relapses had poorer dosimetric coverage of the gross tumor volume (GTV) compared withmore » patients without recurrence (minimum dose [Dmin] biologically equivalent dose [BED] 23.9 vs 35.1 Gy, P<.001; D98 BED 41.8 vs 48.1 Gy, P=.001; D95 BED 47.2 vs 50.5 Gy, P=.004). Furthermore, patients with marginal recurrences had poorer prescription coverage of the GTV (86% vs 93%, P=.01) compared with those with in-field recurrences, potentially because of more upfront spinal canal disease (78% vs 24%, P=.001). Using a Cox regression univariate analysis, patients with a GTV BED Dmin ≥33.4 Gy (median dose) (equivalent to 14 Gy in 1 fraction) had a significantly higher 1-year LC rate (94% vs 80%, P=.001) compared with patients with a lower GTV BED Dmin; this factor was the only significant variable on multivariate Cox analysis associated with LC (P=.001, hazard ratio 0.29, 95% confidence interval 0.14-0.60) and also was the only variable significant in a separate competing risk multivariate model (P=.001, hazard ratio 0.30, 95% confidence interval 0.15-0.62). Conclusions: Stereotactic body radiation therapy offers durable control for spinal metastases, but there is a subset of patients that recur locally. Patients with local relapse had significantly poorer tumor coverage, which was likely attributable to treatment planning directives that prioritized the spinal cord constraints over tumor coverage. When possible, we recommend maintaining a GTV Dmin above 14 Gy in 1 fraction and 21 Gy in 3 fractions.« less

Gene-Based Association Analysis for Censored Traits Via Fixed Effect Functional Regressions.

PubMed

Fan, Ruzong; Wang, Yifan; Yan, Qi; Ding, Ying; Weeks, Daniel E; Lu, Zhaohui; Ren, Haobo; Cook, Richard J; Xiong, Momiao; Swaroop, Anand; Chew, Emily Y; Chen, Wei

2016-02-01

Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, here we develop Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT), which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. © 2016 WILEY PERIODICALS, INC.

Gene-based Association Analysis for Censored Traits Via Fixed Effect Functional Regressions

PubMed Central

Fan, Ruzong; Wang, Yifan; Yan, Qi; Ding, Ying; Weeks, Daniel E.; Lu, Zhaohui; Ren, Haobo; Cook, Richard J; Xiong, Momiao; Swaroop, Anand; Chew, Emily Y.; Chen, Wei

2015-01-01

Summary Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, we develop here Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT) which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. PMID:26782979

SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma.

PubMed

Chang, Dong; Ma, Kai; Gong, Min; Cui, Yong; Liu, Zhi-hua; Zhou, Xiao-ge; Zhou, Chuan-nong; Wang, Tian-you

2010-03-01

To investigate the role of stomatin-like protein 2 (SLP-2), a novel cancer-related gene, in pulmonary squamous cell carcinoma (PSCC) and its implications. Immunohistochemical detection of SLP-2 was performed on 96 cases of PSCC with a tissue microarray. SLP-2 was overexpressed in lung cancer compared with normal lung tissue (p <0.001). High-level SLP-2 expression was significantly correlated with distant metastasis (p = 0.025), decreased overall survival (p = 0.018) and disease-free survival (p = 0.017). SLP-2 overexpression was an independent prognostic factor in multivariate analysis using the Cox regression model (p <0.05). SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in PSCC. SLP-2 could be regarded as a new significant prognostic biomarker for patients with PSCC.

Meteor localization via statistical analysis of spatially temporal fluctuations in image sequences

NASA Astrophysics Data System (ADS)

Kukal, Jaromír.; Klimt, Martin; Šihlík, Jan; Fliegel, Karel

2015-09-01

Meteor detection is one of the most important procedures in astronomical imaging. Meteor path in Earth's atmosphere is traditionally reconstructed from double station video observation system generating 2D image sequences. However, the atmospheric turbulence and other factors cause spatially-temporal fluctuations of image background, which makes the localization of meteor path more difficult. Our approach is based on nonlinear preprocessing of image intensity using Box-Cox and logarithmic transform as its particular case. The transformed image sequences are then differentiated along discrete coordinates to obtain statistical description of sky background fluctuations, which can be modeled by multivariate normal distribution. After verification and hypothesis testing, we use the statistical model for outlier detection. Meanwhile the isolated outlier points are ignored, the compact cluster of outliers indicates the presence of meteoroids after ignition.

The prognostic significance of prostate specific antigen in metastatic hormone-resistant prostate cancer.

PubMed Central

Fosså, S. D.; Waehre, H.; Paus, E.

1992-01-01

Twenty-seven of 152 patients (18%) with progressing hormone resistant prostate cancer had normal serum levels of prostate specific antigen (PSA less than or equal to 10 micrograms l-1), when referred for secondary treatment. PSA was significantly correlated with the extent of skeletal metastases (R: 0.35) and the levels of hemoglobin (R: -0.19) and serum alkaline phosphatase (R: 0.30). In a multivariate Cox regression analysis the survival of the 152 patients was not correlated with the PSA level but with the patients performance status, the level of hemoglobin, and the time between primary hormone treatment and relapse. The lack of serum PSA to predict survival may be explained by a heterogenous composition of hormone resistant prostate cancer as regards differentiated and/or PSA producing vs undifferentiated and/or PSA non-producing cells. PMID:1379059

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

Angiotensin-converting enzyme inhibitor and statin use and incident mobility limitation in community-dwelling older adults: the Health, Aging and Body Composition study.

PubMed

Gray, Shelly L; Boudreau, Robert M; Newman, Anne B; Studenski, Stephanie A; Shorr, Ronald I; Bauer, Douglas C; Simonsick, Eleanor M; Hanlon, Joseph T

2011-12-01

To evaluate whether the use of angiotensin-converting enzyme (ACE) inhibitors and statins is associated with a lower risk of incident mobility limitation in older community dwelling adults. Longitudinal cohort study. Health, Aging and Body Composition (Health ABC) study. Three thousand fifty-five participants who were well functioning at baseline (no mobility limitations). Summated standardized daily doses (low, medium, high) and duration of ACE inhibitor and statin use were computed. Mobility limitation (two consecutive self-reports of having any difficulty walking one-quarter of a mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazards analyses were conducted, adjusting for demographics, health status, and health behaviors. At baseline, 15.2% used ACE inhibitors and 12.9% used statins; use of both was greater than 25% by Year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio (HR) = 0.95, 95% confidence interval (CI) = 0.82-1.09) nor statin use (multivariate HR = 1.02, 95% CI = 0.87-1.17) was associated with lower risk of mobility limitation. Similar findings were seen in analyses examining dose-response and duration-response relationships and a sensitivity analysis restricted to those with hypertension. ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively, do not lower risk of mobility limitation, an important indicator of quality of life. © 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.

Molecular structure, spectroscopic and docking analysis of 1,3-diphenylpyrazole-4-propionic acid: A good prostaglandin reductase inhibitor

NASA Astrophysics Data System (ADS)

Kavitha, T.; Velraj, G.

2018-03-01

The molecule 1,3-diphenylpyrazole-4-propionic acid (DPPA) was optimized to its minimum energy level using density functional theory (DFT) calculations. The vibrational frequencies of DPPA were calculated along with their potential energy distribution (PED) and the obtained values are validated with the help of experimental calculations. The reactivity nature of the molecule was investigated with the aid of various DFT methods such as global reactivity descriptors, local reactivity descriptors, molecular electrostatic potential (MEP), natural bond orbitals (NBOs), etc. The prediction of activity spectra for substances (PASS) result forecast that, DPPA can be more active as a prostaglandin (PG) reductase inhibitor. The PGs are biologically synthesized by the cyclooxygenase (COX) enzyme which exists in COX1 and COX2 forms. The PGs produced by COX2 enzyme induces inflammation and fungal infections and hence the inhibition of COX2 enzyme is indispensable in anti-inflammation and anti-fungal activities. The docking analysis of DPPA with COX enzymes (both COX1 and COX2) were carried out and eventually, it was found that DPPA can selectively inhibit COX2 enzyme and can serve as a PG reductase inhibitor thereby acting as a lead compound for the treatment of inflammation and fungal diseases.

An Incident Cohort Study Comparing Survival on Home Hemodialysis and Peritoneal Dialysis (Australia and New Zealand Dialysis and Transplantation Registry)

PubMed Central

Nadeau-Fredette, Annie-Claire; Hawley, Carmel M.; Pascoe, Elaine M.; Chan, Christopher T.; Clayton, Philip A.; Polkinghorne, Kevan R.; Boudville, Neil; Leblanc, Martine

2015-01-01

Background and objectives Home dialysis is often recognized as a first-choice therapy for patients initiating dialysis. However, studies comparing clinical outcomes between peritoneal dialysis and home hemodialysis have been very limited. Design, setting, participants, & measurements This Australia and New Zealand Dialysis and Transplantation Registry study assessed all Australian and New Zealand adult patients receiving home dialysis on day 90 after initiation of RRT between 2000 and 2012. The primary outcome was overall survival. The secondary outcomes were on-treatment survival, patient and technique survival, and death-censored technique survival. All results were adjusted with three prespecified models: multivariable Cox proportional hazards model (main model), propensity score quintile–stratified model, and propensity score–matched model. Results The study included 10,710 patients on incident peritoneal dialysis and 706 patients on incident home hemodialysis. Treatment with home hemodialysis was associated with better patient survival than treatment with peritoneal dialysis (5-year survival: 85% versus 44%, respectively; log-rank P<0.001). Using multivariable Cox proportional hazards analysis, home hemodialysis was associated with superior patient survival (hazard ratio for overall death, 0.47; 95% confidence interval, 0.38 to 0.59) as well as better on-treatment survival (hazard ratio for on-treatment death, 0.34; 95% confidence interval, 0.26 to 0.45), composite patient and technique survival (hazard ratio for death or technique failure, 0.34; 95% confidence interval, 0.29 to 0.40), and death-censored technique survival (hazard ratio for technique failure, 0.34; 95% confidence interval, 0.28 to 0.41). Similar results were obtained with the propensity score models as well as sensitivity analyses using competing risks models and different definitions for technique failure and lag period after modality switch, during which events were attributed to the initial modality. Conclusions Home hemodialysis was associated with superior patient and technique survival compared with peritoneal dialysis. PMID:26068181

Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association.

PubMed

Takahashi, Jun; Nihei, Taro; Takagi, Yusuke; Miyata, Satoshi; Odaka, Yuji; Tsunoda, Ryusuke; Seki, Atsushi; Sumiyoshi, Tetsuya; Matsui, Motoyuki; Goto, Toshikazu; Tanabe, Yasuhiko; Sueda, Shozo; Momomura, Shin-ichi; Yasuda, Satoshi; Ogawa, Hisao; Shimokawa, Hiroaki

2015-01-21

Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA. A total of 1429 VSA patients (median 66 years; male/female, 1090/339) were enrolled. The primary endpoint was defined as major adverse cardiac events (MACE). The propensity score matching and multivariable Cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. Among the study patients, 695 (49%) were treated with nitrates, including conventional nitrates [e.g. nitroglycerin (GTN), isosorbide mono- and dinitrate] in 551 and nicorandil in 306. Calcium channel blockers were used in >90% of patients. During the median follow-up period of 32 months, 85 patients (5.9%) reached the primary endpoint. Propensity score-matched analysis demonstrated that the cumulative incidence of MACE was comparable between the patients with and those without nitrates [11 vs. 8% at 5 years; hazard ratio (HR): 1.28; 95% confidence interval (CI): 0.72-2.28, P = 0.40]. Although nicorandil itself had a neutral prognostic effect on VSA (HR: 0.80; 95% CI: 0.28-2.27, P = 0.67), multivariable Cox model revealed the potential harm of concomitant use of conventional nitrates and nicorandil (HR: 2.14; 95% CI: 1.02-4.47; P = 0.044), particularly when GTN and nicorandil were simultaneously administered. Chronic nitrate therapy did not improve the long-term prognosis of VSA patients when combined with CCBs. Furthermore, the VSA patients with multiple nitrates would have increased risk for cardiac events. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Squamous cell carcinoma of the breast in the United States: incidence, demographics, tumor characteristics, and survival.

PubMed

Yadav, Siddhartha; Yadav, Dhiraj; Zakalik, Dana

2017-07-01

Squamous cell carcinoma of breast accounts for less than 0.1% of all breast cancers. The purpose of this study is to describe the epidemiology and survival of this rare malignancy. Data were extracted from the National Cancer Institute's Surveillance, Epidemiology and End Results Registry to identify women diagnosed with squamous cell carcinoma of breast between 1998 and 2013. SEER*Stat 8.3.1 was used to calculate age-adjusted incidence, age-wise distribution, and annual percentage change in incidence. Kaplan-Meier curves were plotted for survival analysis. Univariate and multivariate Cox proportional hazard regression model was used to determine predictors of survival. A total of 445 cases of squamous cell carcinoma of breast were diagnosed during the study period. The median age of diagnosis was 67 years. The overall age-adjusted incidence between 1998 and 2013 was 0.62 per 1,000,000 per year, and the incidence has been on a decline. Approximately half of the tumors were poorly differentiated. Stage II was the most common stage at presentation. Majority of the cases were negative for expression of estrogen and progesterone receptor. One-third of the cases underwent breast conservation surgery while more than half of the cases underwent mastectomy (unilateral or bilateral). Approximately one-third of cases received radiation treatment. The 1-year and 5-year cause-specific survival was 81.6 and 63.5%, respectively. Excluding patient with metastasis or unknown stage at presentation, in multivariate Cox proportional hazard model, older age at diagnosis and higher tumor stage (T3 or T4) or nodal stage at presentation were significant predictors of poor survival. Our study describes the unique characteristics of squamous cell carcinoma of breast and demonstrates that it is an aggressive tumor with a poor survival. Older age and higher tumor or nodal stages at presentation were independent predictors of poor survival for loco-regional stages.

Risk of infective endocarditis in patients with systemic lupus erythematosus in Taiwan: a nationwide population-based study.

PubMed

Chang, Y S; Chang, C C; Chen, Y H; Chen, W S; Chen, J H

2017-10-01

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the control cohort. By contrast, the older systemic lupus erythematosus cohort had lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox multivariate proportional hazards analysis revealed heart disease (hazard ratio = 5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034), receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001), and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001) were independent risk factors for infective endocarditis in systemic lupus erythematosus patients. Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.

The impact of ADHD and conduct disorder in childhood on adult delinquency: a 30 years follow-up study using official crime records.

PubMed

Mordre, Marianne; Groholt, Berit; Kjelsberg, Ellen; Sandstad, Berit; Myhre, Anne Margrethe

2011-04-11

Few longitudinal studies have explored lifetime criminality in adults with a childhood history of severe mental disorders. In the present study, we wanted to explore the association between adult delinquency and several different childhood diagnoses in an in-patient population. Of special interest was the impact of disturbance of activity and attention (ADHD) and mixed disorder of conduct and emotions on later delinquency, as these disorders have been variously associated with delinquent development. Former Norwegian child psychiatric in-patients (n = 541) were followed up 19-41 years after hospitalization by record linkage to the National Register of Criminality. On the basis of the hospital records, the patients were re-diagnosed according to ICD-10. The association between diagnoses and other baseline factors and later delinquency were investigated using univariate and multivariate Cox regression analyses. At follow-up, 24% of the participants had been convicted of criminal activity. In the multivariate Cox regression analysis, conduct disorder (RR = 2.0, 95%CI = 1.2-3.4) and hyperkinetic conduct disorder (RR = 2.7, 95% CI = 1.6-4.4) significantly increased the risk of future criminal behaviour. Pervasive developmental disorder (RR = 0.4, 95%CI = 0.2-0.9) and mental retardation (RR = 0.4, 95%CI = 0.3-0.8) reduced the risk for a criminal act. Male gender (RR = 3.6, 95%CI = 2.1-6.1) and chronic family difficulties (RR = 1.3, 95% CI = 1.1-1.5) both predicted future criminality. Conduct disorder in childhood was highly associated with later delinquency both alone or in combination with hyperactivity, but less associated when combined with an emotional disorder. ADHD in childhood was no more associated with later delinquency than the rest of the disorders in the study population. Our finding strengthens the assumption that there is no direct association between ADHD and criminality.

Do Intermediate Radiation Doses Contribute to Late Rectal Toxicity? An Analysis of Data From Radiation Therapy Oncology Group Protocol 94-06

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

Tucker, Susan L., E-mail: sltucker@mdanderson.org; Dong, Lei; Michalski, Jeff M.

2012-10-01

Purpose: To investigate whether the volumes of rectum exposed to intermediate doses, from 30 to 50 Gy, contribute to the risk of Grade {>=}2 late rectal toxicity among patients with prostate cancer receiving radiotherapy. Methods and Materials: Data from 1009 patients treated on Radiation Therapy Oncology Group protocol 94-06 were analyzed using three approaches. First, the contribution of intermediate doses to a previously published fit of the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was determined. Next, the extent to which intermediate doses provide additional risk information, after taking the LKB model into account, was investigated. Third, the proportionmore » of rectum receiving doses higher than a threshold, VDose, was computed for doses ranging from 5 to 85 Gy, and a multivariate Cox proportional hazards model was used to determine which of these parameters were significantly associated with time to Grade {>=}2 late rectal toxicity. Results: Doses <60 Gy had no detectable impact on the fit of the LKB model, as expected on the basis of the small estimate of the volume parameter (n = 0.077). Furthermore, there was no detectable difference in late rectal toxicity among cohorts with similar risk estimates from the LKB model but with different volumes of rectum exposed to intermediate doses. The multivariate Cox proportional hazards model selected V75 as the only value of VDose significantly associated with late rectal toxicity. Conclusions: There is no evidence from these data that intermediate doses influence the risk of Grade {>=}2 late rectal toxicity. Instead, the critical doses for this endpoint seem to be {>=}75 Gy. It is hypothesized that cases of Grade {>=}2 late rectal toxicity occurring among patients with V75 less than approximately 12% may be due to a 'background' level of risk, likely due mainly to biological factors.« less

Hepatitis B Virus Infection Predicts Better Survival In Patients With Colorectal Liver-only Metastases Undergoing Liver Resection

PubMed Central

Zhao, Yujie; Lin, Junzhong; Peng, Jianhong; Deng, Yuxiang; Zhao, Ruixia; Sui, Qiaoqi; Lu, Zhenhai; Wan, Desen; Pan, Zhizhong

2018-01-01

Objective: Hepatitis B virus (HBV) infection has been shown to decrease the risk of liver metastasis in patients with non-metastatic colorectal cancer (CRC). However, the prognostic value of HBV infection in long-term survival of patients with colorectal liver-only metastases (CRLM) after liver resection has not yet been evaluated. This study aims to explore the association between HBV infection and survival in CRLM patients. Methods: A total of 289 CRLM patients undergoing liver resection were recruited at our center from September 1999 to August 2015. Patients were divided into an HBV infection group and a non-HBV infection group. Progression-free survival (PFS) and overall survival (OS) related to HBV infection were analyzed using both Kaplan-Meier and multivariate Cox regression methods. Results: HBV infection was found in 12.1 %(35/289) of patients. Of these patients, 31.4 %(11/35) had chronic hepatitis B (CHB), 42.9 % (15/35) were inactive hepatitis B surface antigen (HBsAg) carriers (IC) and 25.7 % (9/35) did not undergo HBV DNA detection. HBV infection was associated with more liver metastases (P = 0.025) and larger-sized liver metastases (P = 0.049). The 3-year OS and PFS rates in the HBV infection group were higher than those in the HBV non-infected group (OS: 75.0 % vs 64.8 %, P = 0.031; PFS: 55.9 % vs 39.6 %, P = 0.034). In multivariate Cox analysis, HBV infection was identified as an independent factor for better 3-year OS (hazard ratio (HR), 0.446; 95 %confidence interval (CI), 0.206-0.966; P = 0.041) but not an independent factor for 3-year PFS. Conclusions: HBV-infected CRLM patients survived longer than non-infected patients. In clinical work, therapeutic regimens and follow-up for HBsAg-positive patients may be different from that for HBsAg-negative patients, even though objective prospective studies are still needed. PMID:29760793

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

Hyperfractionated Accelerated Radiation Therapy (HART) of 70.6 Gy With Concurrent 5-FU/Mitomycin C Is Superior to HART of 77.6 Gy Alone in Locally Advanced Head and Neck Cancer: Long-term Results of the ARO 95-06 Randomized Phase III Trial

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

Budach, Volker, E-mail: volker.budach@charite.de; Stromberger, Carmen; Poettgen, Christoph

2015-04-01

Purpose: To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer. Patients and Methods: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statisticalmore » analyses were done with the log-rank test and univariate and multivariate Cox regression analyses. Results: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264). Conclusions: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.« less

Risk factors and outcomes of high peritonitis rate in continuous ambulatory peritoneal dialysis patients: A retrospective study.

PubMed

Tian, Yuanshi; Xie, Xishao; Xiang, Shilong; Yang, Xin; Zhang, Xiaohui; Shou, Zhangfei; Chen, Jianghua

2016-12-01

Peritonitis remains a major complication of peritoneal dialysis (PD). A high peritonitis rate (HPR) affects continuous ambulatory peritoneal dialysis (CAPD) patients' technique survival and mortality. Predictors and outcomes of HPR, rather than the first peritonitis episode, were rarely studied in the Chinese population. In this study, we examined the risk factors associated with HPR and its effects on clinical outcomes in CAPD patients.This is a single center, retrospective, observational cohort study. A total of 294 patients who developing at least 1 episode of peritonitis were followed up from March 1st, 2002, to July 31, 2014, in our PD center. Multivariate logistic regression was used to determine the factors associated with HPR, and the Cox proportional hazard model was conducted to assess the effects of HPR on clinical outcomes.During the study period of 2917.5 patient-years, 489 episodes of peritonitis were recorded, and the total peritonitis rate was 0.168 episodes per patient-year. The multivariate analysis showed that factors associated with HPR include a quick occurrence of peritonitis after CAPD initiation (shorter than 12 months), and a low serum albumin level at the start of CAPD. In the Cox proportional hazard model, HPR was a significant predictor of technique failure. There were no differences between HPR and low peritonitis rate (LPR) group for all-cause mortality. However, when the peritonitis rate was considered as a continuous variable, a positive correlation was observed between the peritonitis rate and mortality.We found the quick peritonitis occurrence after CAPD and the low serum albumin level before CAPD were strongly associated with an HPR. Also, our results verified that HPR was positively correlated with technique failure. More importantly, the increase in the peritonitis rate suggested a higher risk of all-cause mortality.These results may help to identify and target patients who are at higher risk of HPR at the start of CAPD and to take interventions to reduce peritonitis incidence and improve clinical outcomes.

Risk factors and outcomes of high peritonitis rate in continuous ambulatory peritoneal dialysis patients

PubMed Central

Tian, Yuanshi; Xie, Xishao; Xiang, Shilong; Yang, Xin; Zhang, Xiaohui; Shou, Zhangfei; Chen, Jianghua

2016-01-01

Abstract Peritonitis remains a major complication of peritoneal dialysis (PD). A high peritonitis rate (HPR) affects continuous ambulatory peritoneal dialysis (CAPD) patients’ technique survival and mortality. Predictors and outcomes of HPR, rather than the first peritonitis episode, were rarely studied in the Chinese population. In this study, we examined the risk factors associated with HPR and its effects on clinical outcomes in CAPD patients. This is a single center, retrospective, observational cohort study. A total of 294 patients who developing at least 1 episode of peritonitis were followed up from March 1st, 2002, to July 31, 2014, in our PD center. Multivariate logistic regression was used to determine the factors associated with HPR, and the Cox proportional hazard model was conducted to assess the effects of HPR on clinical outcomes. During the study period of 2917.5 patient-years, 489 episodes of peritonitis were recorded, and the total peritonitis rate was 0.168 episodes per patient-year. The multivariate analysis showed that factors associated with HPR include a quick occurrence of peritonitis after CAPD initiation (shorter than 12 months), and a low serum albumin level at the start of CAPD. In the Cox proportional hazard model, HPR was a significant predictor of technique failure. There were no differences between HPR and low peritonitis rate (LPR) group for all-cause mortality. However, when the peritonitis rate was considered as a continuous variable, a positive correlation was observed between the peritonitis rate and mortality. We found the quick peritonitis occurrence after CAPD and the low serum albumin level before CAPD were strongly associated with an HPR. Also, our results verified that HPR was positively correlated with technique failure. More importantly, the increase in the peritonitis rate suggested a higher risk of all-cause mortality. These results may help to identify and target patients who are at higher risk of HPR at the start of CAPD and to take interventions to reduce peritonitis incidence and improve clinical outcomes. PMID:27930566

The impact of ADHD and conduct disorder in childhood on adult delinquency: A 30 years follow-up study using official crime records

PubMed Central

2011-01-01

Background Few longitudinal studies have explored lifetime criminality in adults with a childhood history of severe mental disorders. In the present study, we wanted to explore the association between adult delinquency and several different childhood diagnoses in an in-patient population. Of special interest was the impact of disturbance of activity and attention (ADHD) and mixed disorder of conduct and emotions on later delinquency, as these disorders have been variously associated with delinquent development. Methods Former Norwegian child psychiatric in-patients (n = 541) were followed up 19-41 years after hospitalization by record linkage to the National Register of Criminality. On the basis of the hospital records, the patients were re-diagnosed according to ICD-10. The association between diagnoses and other baseline factors and later delinquency were investigated using univariate and multivariate Cox regression analyses. Results At follow-up, 24% of the participants had been convicted of criminal activity. In the multivariate Cox regression analysis, conduct disorder (RR = 2.0, 95%CI = 1.2-3.4) and hyperkinetic conduct disorder (RR = 2.7, 95% CI = 1.6-4.4) significantly increased the risk of future criminal behaviour. Pervasive developmental disorder (RR = 0.4, 95%CI = 0.2-0.9) and mental retardation (RR = 0.4, 95%CI = 0.3-0.8) reduced the risk for a criminal act. Male gender (RR = 3.6, 95%CI = 2.1-6.1) and chronic family difficulties (RR = 1.3, 95% CI = 1.1-1.5) both predicted future criminality. Conclusions Conduct disorder in childhood was highly associated with later delinquency both alone or in combination with hyperactivity, but less associated when combined with an emotional disorder. ADHD in childhood was no more associated with later delinquency than the rest of the disorders in the study population. Our finding strengthens the assumption that there is no direct association between ADHD and criminality. PMID:21481227

Hypertension Control in Adults With Diabetes Mellitus and Recurrent Cardiovascular Events: Global Results From the Trial Evaluating Cardiovascular Outcomes With Sitagliptin.

PubMed

Navar, Ann Marie; Gallup, Dianne S; Lokhnygina, Yuliya; Green, Jennifer B; McGuire, Darren K; Armstrong, Paul W; Buse, John B; Engel, Samuel S; Lachin, John M; Standl, Eberhard; Van de Werf, Frans; Holman, Rury R; Peterson, Eric D

2017-11-01

Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function. © 2017 American Heart Association, Inc.

Effect of hyperlipidemia on the incidence of cardio-cerebrovascular events in patients with type 2 diabetes.

PubMed

Fan, Dabei; Li, Li; Li, Zhizhen; Zhang, Ying; Ma, Xiaojun; Wu, Lina; Qin, Guijun

2018-05-08

This study was to explore the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. Three hundred ninety five patients with type 2 diabetes in our hospital from January 2012 to January 2016 were followed up with an average of 3.8 years. The incidence of cardio-cerebrovascular diseases between diabetes combined with hyperlipidemia group (195 patients) and diabetes group (200 patients) were made a comparison. Multivariable Cox's proportional hazards regression model was used to analyze the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. Diastolic blood pressure, systolic blood pressure, high-density lipoprotein, low-density lipoprotein, body mass index and hyper-sensitive C-reactive protein were higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). At the end of the follow-up period, all-cause mortality, cardio-cerebrovascular diseases mortality, and the incidence of myocardial infarction, cerebral infarction, cerebral hemorrhage and total cardiovascular events were significantly higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). The analysis results of multivariable Cox's proportional hazards regression model showed that the risks of myocardial infarction and total cardiovascular events in diabetes combined with hyperlipidemia group were respectively 1.54 times (95%CI 1.13-2.07) and 1.68 times (95%CI 1.23-2.24) higher than those in diabetes group. Population attributable risk percent of all-cause mortality and total cardiovascular events in patients with type 2 diabetes combined with hyperlipidemia was 9.6% and 26.8%, respectively. Hyperlipidemia may promote vascular endothelial injury, increasing the risk of cardio-cerebrovascular diseases in patients with type 2 diabetes. Medical staffs should pay attention to the control of blood lipids in patients with type 2 diabetes to delay the occurrence of cardio-cerebrovascular diseases.

The effect of rheumatoid arthritis-associated autoantibodies on the incidence of cardiovascular events in a large inception cohort of early inflammatory arthritis.

PubMed

Barra, Lillian J; Pope, Janet E; Hitchon, Carol; Boire, Gilles; Schieir, Orit; Lin, Daming; Thorne, Carter J; Tin, Diane; Keystone, Edward C; Haraoui, Boulos; Jamal, Shahin; Bykerk, Vivian P

2017-05-01

. RA is associated with an increased risk of cardiovascular events (CVEs). The objective was to estimate independent effects of RA autoantibodies on the incident CVEs in patients with early RA. Patients were enrolled in the Canadian Early Inflammatory Arthritis Cohort, a prospective multicentre inception cohort. Incident CVEs, including acute coronary syndromes and cerebrovascular events, were self-reported by the patient and partially validated by medical chart review. Seropositive status was defined as either RF or ACPA positive. Multivariable Cox proportional hazards survival analysis was used to estimate the effects of seropositive status on incident CVEs, controlling for RA clinical variables and traditional cardiovascular risk factors. . A total of 2626 patients were included: the mean symptom duration at diagnosis was 6.3 months ( s . d . 4.6), the mean age was 53 years ( s . d . 15), 72% were female and 86% met classification criteria for RA. Forty-six incident CVEs occurred over 6483 person-years [incidence rate 7.1/1000 person-years (95% confidence interval 5.3, 9.4)]. The CVE rate did not differ in seropositive vs seronegative subjects and seropositivity was not associated with incident CVEs in multivariable Cox regression models. Baseline covariates independently associated with incident CVEs were older age, a history of hypertension and a longer duration of RA symptoms prior to diagnosis. The rate of CVEs early in the course of inflammatory arthritis was low; however, delays in the diagnosis of arthritis increased the rate of CVEs. Hypertension was the strongest independent risk factor for CVEs. Results support early aggressive management of RA disease activity and co-morbidities to prevent severe complications. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Multivariate analysis of prognostic factors in male breast cancer in Serbia.

PubMed

Sipetic-Grujicic, Sandra Branko; Murtezani, Zafir Hajdar; Neskovic-Konstatinovic, Zora Borivoje; Marinkovic, Jelena Milutin; Kovcin, Vladimir Nikola; Andric, Zoran Gojko; Kostic, Sanja Vladeta; Ratkov, Isidora Stojan; Maksimovic, Jadranka Milutin

2014-01-01

The aim of this study was to analyze the demographic and clinical characteristics of male breast cancer patients in Serbia, and furthermore to determine overall survival and predictive factors for prognosis. In the period of 1996-2006 histopathological diagnosis of breast cancer was made in 84 males at the Institute for Oncology and Radiology of Serbia. For statistical analyses the Kaplan-Meier method, long-rank test and Cox proportional hazards regression model were used. The mean age at diagnosis with breast cancer was 64.3±10.5 years with a range from 35-84 years. Nearly 80% of the tumors showed ductal histology. About 44% had early tumor stages (I and II) whereas 46.4% and 9.5% of the male exhibited stages III and IV, respectively. Only 7.1% of male patients were grade one. One-fifth of all patients had tumors measuring ≤2 cm, and 14.3% larger than 5 cm. Lymph node metastasis was recorded in 40.4% patients and 47% relapse. Estrogen and progesterone receptor expression was positive in 66.7% and 58.3%, respectively. Among 14.3% of individuals tumor was HER2 positive. About two-thirds of all male patients had radical mastectomy (66.7%). Adjuvant hormonal (tamoxifene), systematic chemotherapy (CMF or FAC) and adjuvant radiotherapy were given to 59.5%, 35.7% and 29.8% patients respectively. Overall survival rates at five and ten years for male breast cancer were 55.0% and 43.9%, respectively. According to the multivariate Cox regression predictive model, a lower initial disease stage, a lower tumor grade, application of adjuvant hormone therapy and no relapse occurrence were significant independent predictors for good overall survival. Results of the treatment would be better if disease is discovered earlier and therefore health education and screening are an imperative in solving this problem.

Disease Characteristics, Patterns of Care, and Survival in Very Elderly Patients with Diffuse Large B-Cell Lymphoma

PubMed Central

Williams, Jessica N.; Rai, Ashish; Lipscomb, Joseph; Koff, Jean L.; Nastoupil, Loretta J.; Flowers, Christopher R.

2015-01-01

Background Although rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered standard therapy for diffuse large B-cell lymphoma (DLBCL), patterns of use and the impact of R-CHOP on survival in patients >80 years are less clear. Methods We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to characterize presentation, treatment, and survival patterns in DLBCL patients diagnosed from 2002–2009. Chi-squared tests compared characteristics and initial treatments of DLBCL patients >80 years and ≤80 years. Multivariable logistic regression models examined factors associated with treatment selection in patients >80 years; standard and propensity score-adjusted multivariable Cox proportional hazards models examined relationships between treatment regimen, treatment duration, and survival. Results Among 4,635 patients with DLBCL, 1,156 (25%) were >80 years. Patients >80 were less likely to receive R-CHOP and more likely to be observed or receive rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP); both p<0.0001. Marital status, stage, disease site, performance status, radiation therapy, and growth factor support were associated with initial R-CHOP in patients >80. In propensity score-matched multivariable Cox proportional hazards models examining relationships between treatment regimen and survival, R-CHOP was the only regimen associated with improved OS (hazard ratio (HR) = 0.45, 95% confidence interval (CI) = 0.33–0.62) and LRS (HR=0.58, 95% CI 0.38–0.88). Conclusions Although DLBCL patients >80 years were less likely to receive R-CHOP, this regimen conferred the longest survival and should be considered for this population. Further studies are needed to characterize the impact of DLBCL treatment on quality of life in this age group. PMID:25675909

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.

Association of nutritional status as measured by the Mini-Nutritional Assessment Short Form with changes in mobility, institutionalization and death after hip fracture.

PubMed

Nuotio, M; Tuominen, P; Luukkaala, T

2016-03-01

We examined the association of nutritional status as measured by the Mini-Nutritional Assessment Short Form (MNA-SF) with changes in mobility, institutionalization and death after hip fracture. Population-based prospective data were collected on 472 out of 693 consecutive hip fracture patients aged 65 years and over between January 2010 and December 2012. Declined vs same or improved mobility level, institutionalization and death during the 4-month follow-up were the outcomes. Age, gender, American Society of Anesthesiologists scores, pre-fracture diagnosis of a memory disorder, mobility level, living arrangements and MNA-SF scores at baseline were the independent variables. Age-adjusted and multivariate logistic regression and Cox proportional hazards models were conducted. At baseline, 41 (9%) patients were malnourished and 200 (42%) patients at risk of malnutrition according to the MNA-SF. During the follow-up, 90 (19%) had died. In the multivariate Cox proportional hazards model, malnutrition (hazard ratio 2.16; 95% confidence interval (CI) 1.07-4.34) was associated with mortality. In the multivariate binary logistic regression analyses, risk of malnutrition (odds ratios (OR) 2.42; 95% CI 1.25-4.66) and malnutrition (OR 6.10;95% CI 2.01-18.5) predicted institutionalization. Risk of malnutrition (OR 2.03; 95% CI 1.24-3.31) was associated with decline in the mobility level. Malnutrition or risk of malnutrition as measured by the MNA-SF were independent predictors of negative outcomes after hip fracture. Patients classified as being at risk of malnutrition by the MNA-SF may constitute a patient population with mild-to-moderate malnutrition and may require specific attention when nutritional interventions are designed after hip fracture.

Peripheral vascular damage in systemic lupus erythematosus: data from LUMINA, a large multi-ethnic U.S. cohort (LXIX).

PubMed

Burgos, P I; Vilá, L M; Reveille, J D; Alarcón, G S

2009-12-01

To determine the factors associated with peripheral vascular damage in systemic lupus erythematosus patients and its impact on survival from Lupus in Minorities, Nature versus Nurture, a longitudinal US multi-ethnic cohort. Peripheral vascular damage was defined by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Factors associated with peripheral vascular damage were examined by univariable and multi-variable logistic regression models and its impact on survival by a Cox multi-variable regression. Thirty-four (5.3%) of 637 patients (90% women, mean [SD] age 36.5 [12.6] [16-87] years) developed peripheral vascular damage. Age and the SDI (without peripheral vascular damage) were statistically significant (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.01-1.08; P = 0.0107 and OR = 1.30, 95% CI 0.09-1.56; P = 0.0043, respectively) in multi-variable analyses. Azathioprine, warfarin and statins were also statistically significant, and glucocorticoid use was borderline statistically significant (OR = 1.03, 95% CI 0.10-1.06; P = 0.0975). In the survival analysis, peripheral vascular damage was independently associated with a diminished survival (hazard ratio = 2.36; 95% CI 1.07-5.19; P = 0.0334). In short, age was independently associated with peripheral vascular damage, but so was the presence of damage in other organs (ocular, neuropsychiatric, renal, cardiovascular, pulmonary, musculoskeletal and integument) and some medications (probably reflecting more severe disease). Peripheral vascular damage also negatively affected survival.

Global cardiovascular mortality risk in the adult Polish population: prospective assessment of the cohorts studied in multicentre national WOBASZ and WOBASZ Senior studies.

PubMed

Piotrowski, Walerian; Waśkiewicz, Anna; Cicha-Mikołajczyk, Alicja

2016-01-01

To develop a global cardiovascular disease (CVD) mortality risk model for the Polish population and to verify these data in the context of the SCORE risk algorithm. We analysed data obtained in two multicentre national population studies, the WOBASZ study which was conducted in 2003-2005 and included 14,769 subjects aged 20-74 years, and the WOBASZ Senior study which was conducted in 2007 and included 1096 subjects above 74 years of age. All these subjects were followed for survival status until 2012 and the cause of death was determined. The mean duration of follow-up was 8.2 years for WOBASZ study participants and about 5 years for WOBASZ Senior study participants. Overall, 1436 subjects died, including 568 due to CVD. For the purpose of our analysis of overall and CVD mortality, 15 established risk factors were selected. Survival was analysed separately in WOBASZ and WOBASZ Senior study participants. Statistical methods included descriptive statistics, Kaplan-Meier curves, Cox proportional hazard models, and the SCORE risk algorithm. Measure of incompatibility of the SCORE risk model to the Polish population was determined as the difference between mortality rates by the SCORE risk quartiles and the Cox approach. During the 8-year follow-up of the WOBASZ study population, mortality due to CVD was 38% among men and 31% among women. The most common causes of CVD mortality were ischaemic heart disease (IHD, 33%) followed by cerebro-vascular disease (17%) in men, and cerebrovascular disease (31%) followed by IHD (23%) in women. We found significant differences between men and women in regard to survival curves for both overall mortality and CVD mortality (p < 0.0001). For overall mortality among men and women, nearly all selected risk factors were shown to be significant in univariate analyses, except for high density lipoprotein cholesterol (HDL-C) level and the total cholesterol/HDL-C ratio in men, and smoking status in women. In multivariate analysis, independent predictors in men included age, glucose level, systolic blood pressure, and smoking status. In women, independent predictors were age, smoking status, and diabetes. During the 5-year follow-up of the WOBASZ Senior study population, mortality due to CVD was 48% among men and 58% among women. The most common cause of CVD mortality in both men and women was IHD (29% and 24%, respectively), followed by cerebrovascular disease (16% and 21%, respectively). We found significant differences between men and women in regard to survival curves for overall mortality (p < 0.0001) but not for CVD mortality (p = 0.0755). Due to the fact that survival curves for CVD mortality did not differ between men and women, we estimated the cut-off age for no survival difference in the WOBASZ study. By selecting the oldest patients and adding them to the WOBASZ Senior cohort, we obtained the cut-off age of 70 years above which the survival curves were not significantly different between men and women. In univariate analyses, independent predictors in men were age and creatinine level. These factors remained significant in multivariate analysis. In women above 74 years of age, independent predictors in univariate analyses included age, HDL-C level, creatinine level, total cholesterol/HDL-C ratio, and smoking status. Age, HDL-C level, creatinine level, and smoking status remained independent predictors of overall mortality in multivariate analysis. For CVD mortality, significant predictors were the same as for overall mortality. In women, significant predictors in uni- and multivariate analyses were age and smoking status. Overall disagreement between CVD mortality rates by the SCORE risk model and the Cox model was 5.7% in men and 2% in women. 1. Long-term follow-up of WOBASZ and WOBASZ Senior study participants allowed assessment of the inde-pendent association of the evaluated cardiovascular risk factors with CVD mortality in the Polish population. 2. Validation of the SCORE risk algorithm to estimate individual global CVD risk in the Polish population showed a high predictive value of this algorithm.

Mutations in COA3 cause isolated complex IV deficiency associated with neuropathy, exercise intolerance, obesity, and short stature.

PubMed

Ostergaard, Elsebet; Weraarpachai, Woranontee; Ravn, Kirstine; Born, Alfred Peter; Jønson, Lars; Duno, Morten; Wibrand, Flemming; Shoubridge, Eric A; Vissing, John

2015-03-01

We investigated a subject with an isolated cytochrome c oxidase (COX) deficiency presenting with an unusual phenotype characterised by neuropathy, exercise intolerance, obesity, and short stature. Blue-native polyacrylamide gel electrophoresis (BN-PAGE) analysis showed an almost complete lack of COX assembly in subject fibroblasts, consistent with the very low enzymatic activity, and pulse-labelling mitochondrial translation experiments showed a specific decrease in synthesis of the COX1 subunit, the core catalytic subunit that nucleates assembly of the holoenzyme. Whole exome sequencing identified compound heterozygous mutations (c.199dupC, c.215A>G) in COA3, a small inner membrane COX assembly factor, resulting in a pronounced decrease in the steady-state levels of COA3 protein. Retroviral expression of a wild-type COA3 cDNA completely rescued the COX assembly and mitochondrial translation defects, confirming the pathogenicity of the mutations, and resulted in increased steady-state levels of COX1 in control cells, demonstrating a role for COA3 in the stabilisation of this subunit. COA3 exists in an early COX assembly complex that contains COX1 and other COX assembly factors including COX14 (C12orf62), another single pass transmembrane protein that also plays a role in coupling COX1 synthesis with holoenzyme assembly. Immunoblot analysis showed that COX14 was undetectable in COA3 subject fibroblasts, and that COA3 was undetectable in fibroblasts from a COX14 subject, demonstrating the interdependence of these two COX assembly factors. The mild clinical course in this patient contrasts with nearly all other cases of severe COX assembly defects that are usually fatal early in life, and underscores the marked tissue-specific involvement in mitochondrial diseases. 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.

Clinical Characteristics of Malignant Melanoma in Southwest China: A Single-Center Series of 82 Consecutive Cases and a Meta-Analysis of 958 Reported Cases

PubMed Central

Huang, Hui; Zhai, Zhifang; Shen, Zhu; Lin, Hui

2016-01-01

Purpose The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles) involving 958 patients in China. Materials and methods The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan—Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Weipu database (VIP) database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis software Results In this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4%) were classified as stage II-III. Thirty-two patients (39.0%) had acral malignant melanoma, and 31 patients (37.8%) had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis). The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis. Conclusions The clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not statistically significant. PMID:27861496

The effect of molecular subtype and body mass index on neo-adjuvant chemotherapy in breast cancer patients.

PubMed

Iwase, Toshiaki; Nakamura, Rikiya; Yamamoto, Naohito; Yoshi, Atushi; Itami, Makiko; Miyazaki, Masaru

2014-06-01

The aim of the present study was to analyze the effect of subtype and body mass index (BMI) on neo-adjuvant chemotherapy (NAC) and postoperative prognosis. Two-hundred and forty nine patients who underwent surgery after NAC were included. A multivariate analysis and survival analysis were used to clarify the relationship between BMI, subtype, and NAC. In the logistic regression model, the pCR rate had a significant relationship with the subtype and tumor stage. In the non-pCR group, more overweight patients had significantly a worse disease-free survival (DFS) compared to normal range patients (Log lank test, p < 0.05). In the Cox proportional hazards model, subtype and tumor stage were significantly associated with decreased DFS. In conclusion, patients with the ER (+), HER (-) type and a high BMI had a high risk for recurrence when they achieved non-pCR after NAC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Overexpression of COX-2 and LMP1 are correlated with lymph node in Tunisian NPC patients.

PubMed

Fendri, Ali; Khabir, Abdelmajid; Hadhri-Guiga, Boutheina; Sellami-Boudawara, Tahia; Ghorbel, Abdelmoonem; Daoud, Jamel; Frikha, Mounir; Jlidi, Rachid; Gargouri, Ali; Mokdad-Gargouri, Raja

2008-07-01

Cyclooxygenase 2 (COX-2) an inducible form of COX is frequently up-regulated in many human tumours. The expression of COX-2 in nasopharyngeal carcinoma (NPC) and its relationship to clinicopathological features were studied in Tunisian patients. COX-2 mRNA was detected in 91% of tumour tissues. Immunohistochemical analysis showed that COX-2 protein was strongly detected in tumour cells and the staining was mainly cytoplasmic. In contrast, COX-2 mRNA and protein were very low or undetectable in normal nasopharyngeal mucosa. Our result showed a significant association of COX-2 overexpression with the lymph node involvement, however, no correlation was observed with age, tumour stage, histological type and distant metastasis. Moreover, we showed that all tumour specimens co-overexpressed COX-2 and the EBV oncoprotein LMP1 corroborating the fact that LPM1 is known to induce COX-2. Altogether, our data suggests that the COX-2 is overexpressed in NPC biopsies and that is linked to the lymph node involvement.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

PubMed

Brennan, Donal J; Brändstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Pontén, Fredrik; Uhlén, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm; Jirstrom, Karin

2010-04-01

Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

PubMed Central

2010-01-01

Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens. PMID:20359358

Baseline Fourier-Domain Optical Coherence Tomography Structural Risk Factors for Visual Field Progression in the Advanced Imaging for Glaucoma Study.

PubMed

Zhang, Xinbo; Dastiridou, Anna; Francis, Brian A; Tan, Ou; Varma, Rohit; Greenfield, David S; Schuman, Joel S; Sehi, Mitra; Chopra, Vikas; Huang, David

2016-12-01

To identify baseline structural parameters that predict the progression of visual field (VF) loss in patients with open-angle glaucoma. Multicenter cohort study. Participants from the Advanced Imaging for Glaucoma (AIG) study were enrolled and followed up. VF progression is defined as either a confirmed progression event on Humphrey Progression Analysis or a significant (P < .05) negative slope for VF index (VFI). Fourier-domain optical coherence tomography (FDOCT) was used to measure optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thickness parameters. A total of 277 eyes of 188 participants were followed up for 3.7 ± 2.1 years. VF progression was observed in 83 eyes (30%). Several baseline NFL and GCC parameters, but not disc parameters, were found to be significant predictors of progression on univariate Cox regression analysis. The most accurate single predictors were the GCC focal loss volume (FLV), followed closely by NFL-FLV. An abnormal GCC-FLV at baseline increased risk of progression by a hazard ratio of 3.1. Multivariate Cox analysis showed that combining age and central corneal thickness with GCC-FLV in a composite index called "Glaucoma Composite Progression Index" (GCPI) further improved the accuracy of progression prediction. GCC-FLV and GCPI were both found to be significantly correlated with the annual rate of change in VFI. Focal GCC and NFL loss as measured by FDOCT are the strongest predictors for VF progression among the measurements considered. Older age and thinner central corneal thickness can enhance the predictive power using the composite risk model. Copyright © 2016 Elsevier Inc. All rights reserved.

Disparities in Mortality of Hispanic Cystic Fibrosis Patients in the United States: A National and Regional Cohort Study.

PubMed

Rho, Jason; Ahn, Chul; Gao, Ang; Sawicki, Gregory S; Keller, Ashley; Jain, Raksha

2018-05-09

Cystic Fibrosis (CF) patients of Hispanic origin are the largest growing minority, representing 8.5% of CF patients in the United States. No national survival analysis of this group has ever been undertaken. We aimed to determine whether Hispanic ethnicity within the CF population is associated with worse outcomes and whether any geographic differences exist. Using U.S. CF Foundation Patient Registry data from 2010-2014, we performed a retrospective cohort analysis comparing survival rates between Hispanics and non-Hispanics using Kaplan-Meier and Cox regression analysis. A subject's residence was categorized into geographic regions based on U.S. Census Bureau data: Northeast, Midwest, West and South. 29,637 patients were included in the study; 2,493 identified themselves as Hispanic. Hispanics had a lower survival probability overall, with a mean age of death of 22.4 ± 9.9 years compared to non-Hispanics of 28.1 ± 10.0 years (p < 0.0001). Multivariate cox proportional hazards modeling revealed that Hispanic CF patients had a 1.27 times higher rate of death compared to non-Hispanics (95% CI: 1.05 - 1.53) after adjusting for covariates including age, sex, genetic mutations, bacterial cultures, lung function, body mass index, use of CF respiratory therapies, low socioeconomic status, pancreatic enzyme use, and CF-related diabetes. When analyzed by region, Hispanics in the Midwest, Northeast, and West had shorter median survivals compared to Non-Hispanics, which was not demonstrated in the South. CF patients of Hispanic origin have a higher mortality rate than non-Hispanic CF patients. This pattern was seen in the Midwest, Northeast, and West but not in the South.

Determining delayed admission to intensive care unit for mechanically ventilated patients in the emergency department.

PubMed

Hung, Shih-Chiang; Kung, Chia-Te; Hung, Chih-Wei; Liu, Ber-Ming; Liu, Jien-Wei; Chew, Ghee; Chuang, Hung-Yi; Lee, Wen-Huei; Lee, Tzu-Chi

2014-08-23

The adverse effects of delayed admission to the intensive care unit (ICU) have been recognized in previous studies. However, the definitions of delayed admission varies across studies. This study proposed a model to define "delayed admission", and explored the effect of ICU-waiting time on patients' outcome. This retrospective cohort study included non-traumatic adult patients on mechanical ventilation in the emergency department (ED), from July 2009 to June 2010. The primary outcomes measures were 21-ventilator-day mortality and prolonged hospital stays (over 30 days). Models of Cox regression and logistic regression were used for multivariate analysis. The non-delayed ICU-waiting was defined as a period in which the time effect on mortality was not statistically significant in a Cox regression model. To identify a suitable cut-off point between "delayed" and "non-delayed", subsets from the overall data were made based on ICU-waiting time and the hazard ratio of ICU-waiting hour in each subset was iteratively calculated. The cut-off time was then used to evaluate the impact of delayed ICU admission on mortality and prolonged length of hospital stay. The final analysis included 1,242 patients. The time effect on mortality emerged after 4 hours, thus we deduced ICU-waiting time in ED > 4 hours as delayed. By logistic regression analysis, delayed ICU admission affected the outcomes of 21 ventilator-days mortality and prolonged hospital stay, with odds ratio of 1.41 (95% confidence interval, 1.05 to 1.89) and 1.56 (95% confidence interval, 1.07 to 2.27) respectively. For patients on mechanical ventilation at the ED, delayed ICU admission is associated with higher probability of mortality and additional resource expenditure. A benchmark waiting time of no more than 4 hours for ICU admission is recommended.

Cell cycle-related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients.

PubMed

Chen, Jinyun; Pande, Mala; Huang, Yu-Jing; Wei, Chongjuan; Amos, Christopher I; Talseth-Palmer, Bente A; Meldrum, Cliff J; Chen, Wei V; Gorlov, Ivan P; Lynch, Patrick M; Scott, Rodney J; Frazier, Marsha L

2013-02-01

Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle-related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle-related genes and 31 DNA repair-related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan-Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P < 5 × 10(-4)). Furthermore, risk modeling using CART analysis defined combinations of genotypes for these SNPs with which subjects could be classified into low-risk, moderate-risk and high-risk groups that had median ages of colorectal cancer onset of 63, 50 and 42 years, respectively. The age-associated risk of colorectal cancer in the high-risk group was more than four times the risk in the low-risk group (hazard ratio = 4.67, 95% CI = 3.16-6.92). The additional genetic markers identified may help in refining risk groups for more tailored screening and follow-up of non-Hispanic white patients with Lynch syndrome.

Cell cycle–related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients

PubMed Central

Chen, Jinyun; Pande, Mala

2013-01-01

Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle–related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle–related genes and 31 DNA repair–related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan–Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P < 5×10–4). Furthermore, risk modeling using CART analysis defined combinations of genotypes for these SNPs with which subjects could be classified into low-risk, moderate-risk and high-risk groups that had median ages of colorectal cancer onset of 63, 50 and 42 years, respectively. The age-associated risk of colorectal cancer in the high-risk group was more than four times the risk in the low-risk group (hazard ratio = 4.67, 95% CI = 3.16–6.92). The additional genetic markers identified may help in refining risk groups for more tailored screening and follow-up of non-Hispanic white patients with Lynch syndrome. PMID:23125224

Clinical Significance of MiR-137 Expression in Patients with Gastric Cancer After Radical Gastrectomy

PubMed Central

Gu, Qiaoyan; Zhang, Jun; Hu, Haifeng; Tan, Yu-e; Shi, Shengmei; Nian, Yuanyuan

2015-01-01

The dysregulation of miR-137 plays vital roles in the oncogenesis and progression of various types of cancer, but its role in prognosis of gastric cancer patients remains unknown. This study was designed to investigate the expression and prognostic significance of miR-137 in gastric cancer patients after radical gastrectomy. Quantitative real-time PCR (qRT-PCR) was performed to evaluate the expression of miR-137 in human gastric cancer cell lines and tissues in patients with gastric adenocarcinoma. Results were assessed for association with clinical factors and overall survival by using Kaplan-Meier analysis. Prognostic values of miR-137 expression and clinical outcomes were evaluated by Cox regression analysis. The results exhibited that the expression level of miR-137 was decreased in human gastric cancer cell lines and tissues, and down-regulated expression of miR-137 was associated with tumor cell differentiation, N stage, and TNM stage. Decreased miR-137 expression in gastric cancer tissues was positively correlated with poor overall survival of gastric cancer patients. Further multivariate Cox regression analysis suggested that miR-137 expression was an independent prognostic indicator for gastric cancer except for TNM stage. Applying the prognostic value of miR-137 expression to TNM stage III group showed a better risk stratification for overall survival. In conclusion, the results reinforced the critical role for the down-regulated miR-137 expression in gastric cancer and suggested that miR-137 expression could be a prognostic indicator for this disease. In addition, these patients with TNM stage III gastric cancer and low miR-137 expression might need more aggressive postoperative treatment and closer follow-up. PMID:26545111

Correlation Between Body Temperature and Survival Rate in Patients With Hospital-Acquired Bacteremia: A Prospective Observational Study.

PubMed

Dai, Yu-Tzu; Lu, Shu-Hua; Chen, Yee-Chun; Ko, Wen-Je

2015-10-01

Fever is a complex and major sign of a patient's acute response to infection. However, analysis of the risks and benefits associated with the change in body temperature of an infected host remains controversial. To examine the relationship between the intensity of the change in body temperature and the mortality of patients with hospital-acquired bacteremia. A prospective observational study. Subjects were hospitalized adult patients who developed clinical signs of infection 48 hr or more after admission and had documented bacterial growth in blood culture. The maximum body temperature (maxTe) during the early period of infection measurements (i.e., the day before, the day of, and 2 days after the day of blood culture) was used to indicate the intensity of the body temperature response. Patients were categorized as discharged alive or died in hospital. Cox regression analysis was employed to analyze the data. The cohort consisted of 502 subjects. The mean maxTe of subjects was 38.6°C, and 14.9% had a maxTe lower than 38.0°C. The in-hospital mortality rate was 18.9%. The highest in-hospital mortality was found in subjects with a maxTe lower than 38°C (30.7%). Multivariate Cox regression analysis determined that the maxTe and the severity of comorbidity are the two variables associated with in-hospital mortality. Lack of a robust febrile response may be associated with greater risk of mortality in patients with bacteremia. Clinicians must be vigilant in identifying patients at risk for a blunted febrile response to bacteremia for more intensive monitoring. © The Author(s) 2014.

Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study.

PubMed

Pérez-Beteta, Julián; Martínez-González, Alicia; Molina, David; Amo-Salas, Mariano; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Claramonte, Marta; Barcia, Juan A; Iglesias, Lidia; Avecillas, Josué; Albillo, David; Navarro, Miguel; Villanueva, José M; Paniagua, Juan C; Martino, Juan; Velásquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Delgado, María Del Carmen; Del Valle, Ana; Falkov, Anthony; Schucht, Philippe; Arana, Estanislao; Pérez-Romasanta, Luis; Pérez-García, Víctor M

2017-03-01

The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. • Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. • Patients with small width of contrast enhancing areas have better prognosis. • The irregularity of contrast enhancing areas predicts survival in glioblastoma patients.

Tranexamic acid in life-threatening military injury and the associated risk for infectious complications

PubMed Central

Lewis, C. J.; Li, P.; Stewart, L.; Weintrob, A. C.; Carson, M. L.; Murray, C. K.; Tribble, D. R.; Ross, J. D.

2015-01-01

Background Tranexamic acid (TXA) has been shown to reduce mortality from severe hemorrhage. Although recent data suggest that TXA has anti-inflammatory properties, few analyses have investigated the impact of TXA on infectious complications in trauma patients. We examined the association between TXA administration and infection risk among injured military personnel. Methods Patients administered TXA were matched by injury severity score to patients who did not receive TXA. Conditional logistic regression was used to examine risk factors associated with infections within 30 days. A Cox proportional analysis evaluated risk factors in a time-to-first infection model. Results A total of 335 TXA recipients were matched to 626 patients not administered TXA. A greater proportion of TXA recipients had an infection compared to the comparative group (P <0.001). The univariate analysis estimated an unadjusted odds ratio (OR) of 2.5 (95 per cent confidence interval [CI]: 1.8–3.4) for the association of TXA with infection risk; however, upon multivariable analysis, TXA administration was not significant (OR: 1.3; CI: 0.8–1.9). Blast injuries, intensive care unit (ICU) admission, and receipt of ≥10 units of blood within 24 hours post-injury were independently associated with infection risk. The Cox proportional model confirmed association with ICU admission and blood transfusions. Moreover, traumatic amputations were also significantly associated with a reduced time-to-first infection. Conclusion In life-threatening military injuries matched for injury severity, TXA recipients did not have a higher risk for infections nor was time to developed infections shorter than in non-recipients. Extent of blood loss, blast injuries, extremity amputations, and intensive care stay were associated with infections. PMID:26791625

The Clinicopathological Factors Associated with Disease Progression in Luminal A Breast Cancer and Characteristics of Metastasis: A Retrospective Study from A Single Center in China.

PubMed

Ye, Jingming; Wang, Wenjun; Xin, Ling; Owen, Sioned; Xu, Ling; Duan, Xuening; Cheng, Yuanjia; Zhang, Hong; Zhang, Shuang; Li, Ting; Liu, Yinhua

2017-08-01

This study investigated the clinicopathological factors associated with outcomes in patients with Luminal A breast cancer. Retrospective analysis of the association of clinicopathological factors and breast cancer outcome in 421 patients with newly-diagnosed Luminal-A breast cancer that were enrolled from January 2008 to December 2014. Clinicopathological data were analyzed to validate the relationship with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves and log-rank tests were used to analyze the value of clinicopathological factors (tumor size, node status and lymphovascular invasion), and subsequent Cox regression analysis revealed significant prognostic factors. With a median of 61 months follow-up, the 5-year DFS and 5-year OS rate were 98.3% and 99.3%. Cox multivariate regression analysis showed that clinical anatomic stage, tumor size, status of lymph nodes, lymphovascular invasion and systemic treatment are strong prognostic factors for clinical outcome in patients with Luminal-A breast cancer. Of all 413 patients with stage I-III breast cancer, 14 presented with metastasis (3.4%) during the follow up. Bone (6/14, 42.9%) was the most common site of metastasis followed by liver (5/14, 35.7%) and lung (4/14, 28.6%). The median survival time after metastasis was 20.4 months. Of all the sites of distant metastasis, liver metastasis was the only factor that affected survival time after metastasis (χ 2 =6.263, p=0.012). Patients with Luminal A breast cancer have excellent outcomes. Liver metastasis is an important factor compressing the survival time after distant metastasis presents. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Cyclooxygenase 2 gene polymorphisms and chronic periodontitis in a North Indian population: a pilot study

PubMed Central

Daing, Anika; Singh, Sarvendra Vikram; Saimbi, Charanjeet Singh; Khan, Mohammad Akhlaq

2012-01-01

Purpose Cyclooxygenase (COX) enzyme catalyzes the production of prostaglandins, which are important mediators of tissue destruction in periodontitis. Single nucleotide polymorphisms of COX2 enzyme have been associated with increasing susceptibility to inflammatory diseases. The present study evaluates the association of two single nucleotide polymorphisms in COX2 gene (-1195G>A and 8473C>T) with chronic periodontitis in North Indians. Methods Both SNPs and their haplotypes were used to explore the associations between COX2 polymorphisms and chronic periodontitis in 56 patients and 60 controls. Genotyping was done by polymerase chain reaction followed by restriction fragment length polymorphism. Chi-square test and logistic regression analysis were performed for association analysis. Results By the individual genotype analysis, mutant genotypes (GA and AA) of COX2 -1195 showed more than a two fold risk (odds ratio [OR]>2) and COX2 8473 (TC and CC) showed a reduced risk for the disease, but the findings were not statistically significant. Haplotype analysis showed that the frequency of the haplotype AT was higher in the case group and a significant association was found for haplotype AT (OR, 1.79; 95% confidence interval, 1.03 to 3.11; P=0.0370) indicating an association between the AT haplotype of COX2 gene SNPs and chronic periodontitis. Conclusions Individual genotypes of both the SNPs were not associated while haplotype AT was found to be associated with chronic periodontitis in North Indians. PMID:23185695

Monitoring of Fasciola Species Contamination in Water Dropwort by cox1 Mitochondrial and ITS-2 rDNA Sequencing Analysis.

PubMed

Choi, In-Wook; Kim, Hwang-Yong; Quan, Juan-Hua; Ryu, Jae-Gee; Sun, Rubing; Lee, Young-Ha

2015-10-01

Fascioliasis, a food-borne trematode zoonosis, is a disease primarily in cattle and sheep and occasionally in humans. Water dropwort (Oenanthe javanica), an aquatic perennial herb, is a common second intermediate host of Fasciola, and the fresh stems and leaves are widely used as a seasoning in the Korean diet. However, no information regarding Fasciola species contamination in water dropwort is available. Here, we collected 500 samples of water dropwort in 3 areas in Korea during February and March 2015, and the water dropwort contamination of Fasciola species was monitored by DNA sequencing analysis of the Fasciola hepatica and Fasciola gigantica specific mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear ribosomal internal transcribed spacer 2 (ITS-2). Among the 500 samples assessed, the presence of F. hepatica cox1 and 1TS-2 markers were detected in 2 samples, and F. hepatica contamination was confirmed by sequencing analysis. The nucleotide sequences of cox1 PCR products from the 2 F. hepatica-contaminated samples were 96.5% identical to the F. hepatica cox1 sequences in GenBank, whereas F. gigantica cox1 sequences were 46.8% similar with the sequence detected from the cox1 positive samples. However, F. gigantica cox1 and ITS-2 markers were not detected by PCR in the 500 samples of water dropwort. Collectively, in this survey of the water dropwort contamination with Fasciola species, very low prevalence of F. hepatica contamination was detected in the samples.

Liver transplantation of hepatitis B surface antigen positive donors to hepatitis B core antibody recipients: analysis of 27 patients.

PubMed

Krishnamoorthi, R; Manickam, P; Cappell, M S

2014-06-01

Shortage of donor livers is the major limiting factor for liver transplantation (LT). While livers from patients with past infection of Hepatitis-B (HBcAb+) are commonly used as donors, scant data exists on outcomes following transplantation of HBsAg+ donor livers. The impact of donor HBsAg positivity on recipient survival is currently analyzed. Post hoc analysis of all adults undergoing LT from October 1987-September 2010 registered in United Network for Organ Sharing/Organ Procurement and Transplantation Network, a concurrent, limited access database of all American LT recipients. Only recipients who were HBcAb+ were analyzed. LTs with missing donor or recipient serologic parameters for Hepatitis-B were excluded. Significant predictors of survival were determined by univariate analysis. Cox proportional hazards model was used to determine independent risk predictors in the multivariate analysis. The population consisted of 13,329 LT recipients. The mean age of donors and recipients were 40±16 years and 52±9 years respectively. The mean follow-up was 3.7 years. Study population included 27 recipients transplanted with HBsAg+ grafts, of whom 7 (28%) died. Outcomes were adjusted for donor age, recipient age, donor gender, recipient gender, type of LT, MELD score, HCV status, previous LT, and cold ischemic time. On multivariate analysis, LT recipient outcomes were not significantly different for HBsAg+ donors versus donors without prior hepatitis B infection (HR: 1.14, 95% CI: 0.93-1.39, P=0.17). Kaplan-Meier curves revealed no significant survival difference between the two groups. These results suggest that donor HBsAg positivity did not affect overall survival of LT recipients. These findings could potentially expand the pool of liver donors.

Clinical correlates and prognostic value of different metastatic sites in patients with malignant melanoma of the skin: a SEER database analysis.

PubMed

Abdel-Rahman, Omar

2018-03-01

Population-based data on the clinical correlates and prognostic value of the pattern of metastases among patients with cutaneous melanoma are needed. Surveillance, Epidemiology and End Results (SEER) database (2010-2013) has been explored through SEER*Stat program. For each of six distant metastatic sites (bone, brain, liver, lung, distant lymph nodes, and skin/subcutaneous), relevant correlation with baseline characteristics were reported. Survival analysis has been conducted through Kaplan-Meier analysis, and multivariate analysis has been conducted through a Cox proportional hazard model. A total of 2691 patients with metastatic cutaneous melanoma were identified in the period from 2010 to 2013. Patients with isolated skin/subcutaneous metastases have the best overall and melanoma-specific survival (MSS) followed by patients with isolated distant lymph node metastases followed by patients with isolated lung metastases. Patients with isolated liver, bone, or brain metastases have the worst overall and MSS (p < .0001 for both end points). Multivariate analysis revealed that age more than 70 at diagnosis (p = .012); multiple sites of metastases (p <.0001), no surgery to the primary tumor (p <.0001), and no surgery to the metastatic disease (p < .0001) were associated with worse overall survival (OS). For MSS, nodal positivity (p = .038), multiple sites of metastases (p < .0001), no surgery to the primary tumor (p < .0001), and no surgery to the metastatic disease (p < .0001) were associated with worse survival. The prognosis of metastatic cutaneous melanoma patients differs considerably according to the site of distant metastases. Further prospective studies are required to evaluate the role of local treatment in the management of metastatic disease.

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

Structural Basis for Certain Naturally Occurring Bioflavonoids to Function as Reducing Co-Substrates of Cyclooxygenase I and II

PubMed Central

Zhu, Bao Ting

2010-01-01

Background Recent studies showed that some of the dietary bioflavonoids can strongly stimulate the catalytic activity of cyclooxygenase (COX) I and II in vitro and in vivo, presumably by facilitating enzyme re-activation. In this study, we sought to understand the structural basis of COX activation by these dietary compounds. Methodology/Principal Findings A combination of molecular modeling studies, biochemical analysis and site-directed mutagenesis assay was used as research tools. Three-dimensional quantitative structure-activity relationship analysis (QSAR/CoMFA) predicted that the ability of bioflavonoids to activate COX I and II depends heavily on their B-ring structure, a moiety known to be associated with strong antioxidant ability. Using the homology modeling and docking approaches, we identified the peroxidase active site of COX I and II as the binding site for bioflavonoids. Upon binding to this site, bioflavonoid can directly interact with hematin of the COX enzyme and facilitate the electron transfer from bioflavonoid to hematin. The docking results were verified by biochemical analysis, which reveals that when the cyclooxygenase activity of COXs is inhibited by covalent modification, myricetin can still stimulate the conversion of PGG2 to PGE2, a reaction selectively catalyzed by the peroxidase activity. Using the site-directed mutagenesis analysis, we confirmed that Q189 at the peroxidase site of COX II is essential for bioflavonoids to bind and re-activate its catalytic activity. Conclusions/Significance These findings provide the structural basis for bioflavonoids to function as high-affinity reducing co-substrates of COXs through binding to the peroxidase active site, facilitating electron transfer and enzyme re-activation. PMID:20808785

Docking studies on NSAID/COX-2 isozyme complexes using Contact Statistics analysis

NASA Astrophysics Data System (ADS)

Ermondi, Giuseppe; Caron, Giulia; Lawrence, Raelene; Longo, Dario

2004-11-01

The selective inhibition of COX-2 isozymes should lead to a new generation of NSAIDs with significantly reduced side effects; e.g. celecoxib (Celebrex®) and rofecoxib (Vioxx®). To obtain inhibitors with higher selectivity it has become essential to gain additional insight into the details of the interactions between COX isozymes and NSAIDs. Although X-ray structures of COX-2 complexed with a small number of ligands are available, experimental data are missing for two well-known selective COX-2 inhibitors (rofecoxib and nimesulide) and docking results reported are controversial. We use a combination of a traditional docking procedure with a new computational tool (Contact Statistics analysis) that identifies the best orientation among a number of solutions to shed some light on this topic.

Binding Energy Calculation of Patchouli Alcohol Isomer Cyclooxygenase Complexes Suggested as COX-1/COX-2 Selective Inhibitor

PubMed Central

Mahdi, Chanif; Nurdiana, Nurdiana; Kikuchi, Takheshi; Fatchiyah, Fatchiyah

2014-01-01

To understand the structural features that dictate the selectivity of the two isoforms of the prostaglandin H2 synthase (PGHS/COX), the three-dimensional (3D) structure of COX-1/COX-2 was assessed by means of binding energy calculation of virtual molecular dynamic with using ligand alpha-Patchouli alcohol isomers. Molecular interaction studies with COX-1 and COX-2 were done using the molecular docking tools by Hex 8.0. Interactions were further visualized by using Discovery Studio Client 3.5 software tool. The binding energy of molecular interaction was calculated by AMBER12 and Virtual Molecular Dynamic 1.9.1 software. The analysis of the alpha-Patchouli alcohol isomer compounds showed that all alpha-Patchouli alcohol isomers were suggested as inhibitor of COX-1 and COX-2. Collectively, the scoring binding energy calculation (with PBSA Model Solvent) of alpha-Patchouli alcohol isomer compounds (CID442384, CID6432585, CID3080622, CID10955174, and CID56928117) was suggested as candidate for a selective COX-1 inhibitor and CID521903 as nonselective COX-1/COX-2. PMID:25484897

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.

Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy.

PubMed

Lamarca, Angela; Rigby, Christina; McNamara, Mairéad G; Hubner, Richard A; Valle, Juan W

2016-07-14

To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). SREs are common and impact on patient's morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs.

Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy

PubMed Central

Lamarca, Angela; Rigby, Christina; McNamara, Mairéad G; Hubner, Richard A; Valle, Juan W

2016-01-01

AIM: To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). CONCLUSION: SREs are common and impact on patient’s morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs. PMID:27468198

Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer.

PubMed

Mori, Keiichiro; Kimura, Takahiro; Onuma, Hajime; Kimura, Shoji; Yamamoto, Toshihiro; Sasaki, Hiroshi; Miki, Jun; Miki, Kenta; Egawa, Shin

2017-07-01

An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone. This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa. The primary outcome measure was the comparative combined progression-free survival (PFS) comprising symptomatic and/or radiographic PFS. Patients were also compared for total prostate-specific antigen (PSA)-PFS, overall survival (OS), and PSA response. The predictors of combined PFS and OS were analyzed with a backward-stepwise multivariate Cox model. Of the 69 patients, 46 received enzalutamide first, followed by abiraterone (E-A group), and 23 received abiraterone, followed by enzalutamide (A-E group). The two groups were not significantly different with regard to basic data, except for hemoglobin values. In a comparison with the E-A group, the A-E group was shown to be associated with better combined PFS in Kaplan-Meier analysis (P = 0.043). Similar results were obtained for total PSA-PFS (P = 0.049), while OS did not differ between groups (P = 0.62). Multivariate analysis demonstrated that pretreatment lactate dehydrogenase (LDH) values and age were significant predictors of longer combined PFS (P < 0.05). Likewise, multivariate analysis demonstrated that pretreatment hemoglobin values and performance status were significant predictors of longer OS (P < 0.05). The results of this study suggested the A-E sequence had longer combined PSA and total PSA-PFS compared to the E-A sequence in patients with CRPC. LDH values in sequential therapy may serve as a predictor of longer combined PFS. © 2017 Wiley Periodicals, Inc.

Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation.

PubMed

Kim, Yong-Hyub; Ahn, Sung-Ja; Kim, Young-Chul; Kim, Kyu-Sik; Oh, In-Jae; Ban, Hee-Jung; Chung, Woong-Ki; Nam, Taek-Keun; Yoon, Mee Sun; Jeong, Jae-Uk; Song, Ju-Young

2016-02-01

Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm(3) and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001). Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

PubMed

Hayman, Jonathan; Phillips, Ryan; Chen, Di; Perin, Jamie; Narang, Amol K; Trieu, Janson; Radwan, Noura; Greco, Stephen; Deville, Curtiland; McNutt, Todd; Song, Daniel Y; DeWeese, Theodore L; Tran, Phuoc T

2018-06-01

Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men. © 2018 Wiley Periodicals, Inc.

Correlated non-nuclear COX2 and low HER2 expression confers a good prognosis in colorectal cancer.

PubMed

Zhou, Fei-Fei; Huang, Rong; Jiang, Jun; Zeng, Xiao-Hong; Zou, Shu-Qian

2018-06-05

COX2 and HER2 are shown to be critical in the regulation of cancer progression. However, the prognostic value of nuclear COX2 in colorectal cancer (CRC) and its relationship with HER2 still remains unknown. In this study, the expression and biological significance of COX2 and HER2 were evaluated in CRC at mRNA and protein levels. RNA-Seq data of CRC were downloaded from TCGA, and 229 CRC and 50 non-cancerous subjects were enrolled in this study. Bioinformatics and immunohistochemistry analysis was performed based on the obtained data. Survival analysis was conducted to identify factors associated with overall survival of CRC patients. We showed that mRNA and protein levels of COX2 and HER2 were upregulated in CRC compared with the adjacent tissues. COX2 protein levels and nuclear COX2 expression were correlated with a poor prognosis of CRC patients. In addition, we also revealed that nuclear COX2 expression was positively associated with HER2 expression. Non-nuclear COX2 combined with low HER2 expression, was negatively correlated with Duke's stage and lymph node metastasis, predicting the best outcomes for CRC patients. In addition, our data indicated that non-nuclear COX2 combined with low HER2 expression is an independent prognostic factor for CRC after surgical resection. The study suggests that nuclear COX2 in combination with HER2 can serve as potential biomarkers for the clinical diagnosis and prognosis of CRC, and targeted inhibition of COX2 and HER2 might be an alternative strategy for the management of CRC.

Late Results of Cox Maze III Procedure in Patients with Atrial Fibrillation Associated with Structural Heart Disease

PubMed Central

Gomes, Gustavo Gir; Gali, Wagner Luis; Sarabanda, Alvaro Valentim Lima; da Cunha, Claudio Ribeiro; Kessler, Iruena Moraes; Atik, Fernando Antibas

2017-01-01

Background Cox-Maze III procedure is one of the surgical techniques used in the surgical treatment of atrial fibrillation (AF). Objectives To determine late results of Cox-Maze III in terms of maintenance of sinus rhythm, and mortality and stroke rates. Methods Between January 2006 and January 2013, 93 patients were submitted to the cut-and-sew Cox-Maze III procedure in combination with structural heart disease repair. Heart rhythm was determined by 24-hour Holter monitoring. Procedural success rates were determined by longitudinal methods and recurrence predictors by multivariate Cox regression models. Results Thirteen patients that obtained hospital discharge alive were excluded due to lost follow-up. The remaining 80 patients were aged 49.9 ± 12 years and 47 (58.7%) of them were female. Involvement of mitral valve and rheumatic heart disease were found in 67 (83.7%) and 63 (78.7%) patients, respectively. Seventy patients (87.5%) had persistent or long-standing persistent AF. Mean follow-up with Holter monitoring was 27.5 months. There were no hospital deaths. Sinus rhythm maintenance rates were 88%, 85.1% and 80.6% at 6 months, 24 months and 36 months, respectively. Predictors of late recurrence of AF were female gender (HR 3.52; 95% CI 1.21-10.25; p = 0.02), coronary artery disease (HR 4.73 95% CI 1.37-16.36; p = 0.01) and greater left atrium diameter (HR 1.05; 95% CI 1.01-1.09; p = 0.02). Actuarial survival was 98.5% at 12, 24 and 48 months and actuarial freedom from stroke was 100%, 100% and 97.5% in the same time frames. Conclusions The Cox-Maze III procedure, in our experience, is efficacious for sinus rhythm maintenance, with very low late mortality and stroke rates. PMID:28678926

Soluble form of receptor for advanced glycation end products and incidence of new cardiovascular events among patients with cardiovascular disease.

PubMed

Reichert, Stefan; Triebert, Ulrike; Santos, Alexander Navarrete; Hofmann, Britt; Schaller, Hans-Günter; Schlitt, Axel; Schulz, Susanne

2017-11-01

Soluble RAGE (sRAGE) serum level could be a biomarker for atherosclerosis and subsequent diseases such as cardiovascular disease (CVD). Therefore, we wanted to investigate whether peripheral sRAGE level is associated with new cardiovascular events among patients with CVD using the Cox's regression analysis. In this three-year longitudinal cohort study, 1002 in-patients with angiographically proven CVD were included. In 933 patients, sRAGE levels were determined by a commercial available ELISA kit at the time of baseline examination. The combined endpoint was defined as myocardial infarction, stroke/TIA (non-fatal, fatal), and cardiovascular death. For risk analysis, sRAGE values were distributed in quartiles. For generation of adjusted hazard ratios (HR), other risk factors for CVD, such as age, gender, current smoking, body mass index, diabetes, hypertension, dyslipoproteinemia, family history of CVD, severe periodontitis, serum levels for C-reactive protein and interleukin-6, were recorded. 886 patients completed the 3-year follow-up. The overall incidence of the combined endpoint was 16%. Patients with sRAGE levels >838.19 pg/ml (fourth quartile) had the highest incidence of recurrent CVD events (24.9% versus 13.1%, p < 0.0001). In multivariate Cox regression with respect to further confounders for CVD, the association between sRAGE and new CVD events was confirmed (HR = 1.616, 95% CI 1.027-2.544, p = 0.038). Elevated sRAGE serum level is associated with further adverse events in patients with CVD. Copyright © 2017 Elsevier B.V. All rights reserved.

The prognostic value of preoperative inflammation-based prognostic scores and nutritional status for overall survival in resected patients with nonmetastatic Siewert type II/III adenocarcinoma of esophagogastric junction.

PubMed

Zhang, Lixiang; Su, Yezhou; Chen, Zhangming; Wei, Zhijian; Han, Wenxiu; Xu, Aman

2017-07-01

Immune and nutritional status of patients have been reported to predict postoperative complications, recurrence, and prognosis of patients with cancer. Therefore, this retrospective study aimed to explore the prognostic value of preoperative inflammation-based prognostic scores [neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR)] and nutritional status [prognostic nutritional index (PNI), body mass index (BMI), hemoglobin, albumin, and prealbumin] for overall survival (OS) in adenocarcinoma of esophagogastric junction (AEG) patients. A total of 355 patients diagnosed with Siewert type II/III AEG and underwent surgery between October 2010 and December 2011 were followed up until October 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values of NLR, PLR, and PNI. Kaplan-Meier curves and Cox regression analyses were used to calculate the OS characteristics. The ideal cutoff values for predicting OS were 3.5 for NLR, 171 for PLR, and 51.3 for PNI according to the ROC curve. The patients with hemoglobin <120 g/L (P = .001), prealbumin <180 mg/L (P = .000), PNI <51.3 (P = .010), NLR >3.5 (P = .000), PLR >171 (P = .006), and low BMI group (P = .000) had shorter OS. And multivariate survival analysis using the Cox proportional hazards model showed that the tumor-node-metastasis stage, BMI, NLR, and prealbumin levels were independent risk factors for the OS. Our study demonstrated that preoperative prealbumin, BMI, and NLR were independent prognostic factors of AEG patients.

Clinical outcome and predictors of survival in patients with pneumocystis jirovecii pneumonia--results of a tertiary referral centre.

PubMed

Roembke, Felicitas; Heinzow, Hauke Sebastian; Gosseling, Thomas; Heinecke, Achim; Domagk, Dirk; Domschke, Wolfram; Meister, Tobias

2014-01-01

Pneumocystis jirovecii pneumonia also known as pneumocystis pneumonia (PCP) is an opportunistic respiratory infection in human immunodeficiency virus (HIV) patients that may also develop in non-HIV immunocompromised persons. The aim of our study was to evaluate mortality predictors of PCP patients in a tertiary referral centre. Fifty-one patients with symptomatic PCP were enrolled in the study. The patients had either HIV infection (n = 21) or other immunosuppressive conditions (n = 30). Baseline characteristics (e.g. age, sex and underlying disease) were retrieved. Kaplan-Meier analysis was employed to calculate survival. Comparisons were made by log-rank test. A multivariate analysis of factors influencing survival was carried out using the Cox regression model. Chi-squared test and Wilcoxon-Mann-Whitney test was applied as appropriate. The median survival time for the HIV group was >120 months compared with 3 months for the non-HIV group (P = 0.009). Three-month survival probability was also significantly greater in the HIV group compared with the non-HIV group (90% vs 41%, P = 0.002). In univariate log-rank test, intensive care unit (ICU) necessity, HIV negativity, age >50 years, haemoglobin <10g/dl, C-reactive protein >5 mg/dL and multiple comorbidities were significant negative predictors of survival. In the Cox regression model, ICU and HIV statuses turned out to be independent prognostic factors of survival. PCP is a serious problem in non-HIV immunocompromised patients in whom survival outcomes are worse than those in HIV patients. © 2013 John Wiley & Sons Ltd.

Usefulness of admission gamma-glutamyltransferase level for predicting new-onset heart failure in patients with acute coronary syndrome with left ventricular systolic dysfunction.

PubMed

Sarıkaya, Savaş; Aydın, Gülay; Yücel, Hasan; Kaya, Hakkı; Yıldırımlı, Kutay; Başaran, Ahmet; Zorlu, Ali; Sahin, Safak; Akyol, Lütfü; Bulut, Musa

2014-04-01

Our aim was to determine whether there is a relationship between admission gamma-glutamyltransferase (GGT) and subsequent heart failure hospitalizations in patients with acute coronary syndrome. We selected 123 patients with newly diagnosed acute coronary syndrome of ejection fraction (EF) <45%. Patients were followed 15±10 months, and the relationship between admission GGT level and hospitalization because of heart failure during the follow-up was examined. Twenty-three (18.7%) patients were hospitalized during the follow-up of 15±10 months. Receiver operating characteristic (ROC) curve analysis showed that the cut-off point of admission GGT related to predict hospitalization was 49 IU/L, with a sensitivity of 81.7% and specificity of 65.2%. Increased GGT >49 IU/L on admission, presence of hypertension and hyperlipidemia, left ventricular ejection fraction (LVEF), right ventricular dysfunction, moderate-to-severe mitral regurgitation, alanine aminotransferase level, and antiplatelet agent usage were found to have prognostic significance in univariate Cox proportional hazards analysis. In multivariate Cox proportional-hazards model, increased GGT >49 IU/L on admission (hazard ratio [HR] 2.663, p=0.047), presence of hypertension (HR 4.107, p=0.007), and LVEF (HR 0.911, p=0.002) were found to be independent factors to predict new-onset heart failure requiring hospitalization. Hospitalization in heart failure was associated with increased admission GGT levels. Increased admission GGT level in acute coronary syndrome with heart failure should be monitored closely and treated aggressively.

[Survival following the first admission in an integrated dual disorders treatment ward (IDDTW): preliminary results from a cohort study].

PubMed

Gimelfarb, Yuri; Becatel, Ety; Wolf, Aviva; Baruch, Yehuda

2014-01-01

Dual disorders (co-occurring severe mental illness [SMI] and substance abuse disorders in the same person) are extremely common among patients receiving mental health services. Dual disorders are associated with increased all-cause mortality, as compared with patients with SMI. Scientific evidence is lacking on the survival of dual disorders subjects, who had psychiatric inpatient care. To determine the long term survival rates of patients after the first admission in an IDDTW and to identify their baseline predictors. The charts of 258 subjects admitted to IDDTW during the period 2002-2004 were assessed at least 8 years after the first admission. Psychiatric diagnoses were established and grouped according to the International Statistical Classification of Diseases and Related Health Problems 10th edition (ICD-10). The Kaplan-Meier survival analysis was used to estimate the cumulative survival rates, and the predictive values of different variables were assessed by Cox proportional-hazards regression model. The cumulative 1-, 2-, 4-, 6- and 8-year survival rates of all subjects were 98.06%, 96.51%, 91.47, 86.43% and 81.78%, respectively, without statistically significant differences between subgroups of psychiatric diagnoses. Multivariate Cox regression analysis revealed that the age at death was the only independent predictor of all-cause mortality (hazard ratio = .96; 95% confidence interval .93 to .99; p < .009). Those of young age are at a particularly low risk of long term survival. More targeted health care is required to address the specific needs of this vulnerable subgroup. Further research of survival into specific risk groups is required.

NIPA-like domain containing 1 is a novel tumor-promoting factor in oral squamous cell carcinoma.

PubMed

Sasahira, Tomonori; Nishiguchi, Yukiko; Kurihara-Shimomura, Miyako; Nakashima, Chie; Kuniyasu, Hiroki; Kirita, Tadaaki

2018-05-01

In our previous global gene expression analysis, we identified NIPA-like domain containing 1 (NIPAL1), which encodes a magnesium transporter, as one of the most overexpressed genes in recurrent oral squamous cell carcinoma (OSCC). Although has been NIPAL1 linked with gout pathogenesis, little is known about its expression and function in human malignancies. In this study, we examined NIPAL1 expression in 192 cases of OSCC by immunohistochemistry and performed a functional analysis of human OSCC cells. NIPAL1 immunostaining was observed in 39 of 192 OSCC patients (20.3%). NIPAL1 expression correlated significantly with cancer cell intravsation (P = 0.0062), as well as with poorer disease-free survival in a Kaplan-Meier analysis (P < 0.0001). Moreover, a multivariate Cox proportional hazards model analysis revealed that NIPAL1 expression was an independent predictor of disease-free survival in OSCC (P < 0.0001). In a functional analysis, NIPAL1 regulated the growth and adhesion of OSCC tumor cells and endothelial cells. Our findings suggest that NIPAL1 might be a novel factor promoting OSCC tumorigenesis, as well as a useful molecular marker of OSCC.

International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study.

PubMed

Pagès, Franck; Mlecnik, Bernhard; Marliot, Florence; Bindea, Gabriela; Ou, Fang-Shu; Bifulco, Carlo; Lugli, Alessandro; Zlobec, Inti; Rau, Tilman T; Berger, Martin D; Nagtegaal, Iris D; Vink-Börger, Elisa; Hartmann, Arndt; Geppert, Carol; Kolwelter, Julie; Merkel, Susanne; Grützmann, Robert; Van den Eynde, Marc; Jouret-Mourin, Anne; Kartheuser, Alex; Léonard, Daniel; Remue, Christophe; Wang, Julia Y; Bavi, Prashant; Roehrl, Michael H A; Ohashi, Pamela S; Nguyen, Linh T; Han, SeongJun; MacGregor, Heather L; Hafezi-Bakhtiari, Sara; Wouters, Bradly G; Masucci, Giuseppe V; Andersson, Emilia K; Zavadova, Eva; Vocka, Michal; Spacek, Jan; Petruzelka, Lubos; Konopasek, Bohuslav; Dundr, Pavel; Skalova, Helena; Nemejcova, Kristyna; Botti, Gerardo; Tatangelo, Fabiana; Delrio, Paolo; Ciliberto, Gennaro; Maio, Michele; Laghi, Luigi; Grizzi, Fabio; Fredriksen, Tessa; Buttard, Bénédicte; Angelova, Mihaela; Vasaturo, Angela; Maby, Pauline; Church, Sarah E; Angell, Helen K; Lafontaine, Lucie; Bruni, Daniela; El Sissy, Carine; Haicheur, Nacilla; Kirilovsky, Amos; Berger, Anne; Lagorce, Christine; Meyers, Jeffrey P; Paustian, Christopher; Feng, Zipei; Ballesteros-Merino, Carmen; Dijkstra, Jeroen; van de Water, Carlijn; van Lent-van Vliet, Shannon; Knijn, Nikki; Mușină, Ana-Maria; Scripcariu, Dragos-Viorel; Popivanova, Boryana; Xu, Mingli; Fujita, Tomonobu; Hazama, Shoichi; Suzuki, Nobuaki; Nagano, Hiroaki; Okuno, Kiyotaka; Torigoe, Toshihiko; Sato, Noriyuki; Furuhata, Tomohisa; Takemasa, Ichiro; Itoh, Kyogo; Patel, Prabhu S; Vora, Hemangini H; Shah, Birva; Patel, Jayendrakumar B; Rajvik, Kruti N; Pandya, Shashank J; Shukla, Shilin N; Wang, Yili; Zhang, Guanjun; Kawakami, Yutaka; Marincola, Francesco M; Ascierto, Paolo A; Sargent, Daniel J; Fox, Bernard A; Galon, Jérôme

2018-05-26

The estimation of risk of recurrence for patients with colon carcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus Immunoscore assay in patients with stage I-III colon cancer. An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the Immunoscore assay in patients with TNM stage I-III colon cancer. Patients were randomly assigned to a training set, an internal validation set, or an external validation set. Paraffin sections of the colon tumour and invasive margin from each patient were processed by immunohistochemistry, and the densities of CD3+ and cytotoxic CD8+ T cells in the tumour and in the invasive margin were quantified by digital pathology. An Immunoscore for each patient was derived from the mean of four density percentiles. The primary endpoint was to evaluate the prognostic value of the Immunoscore for time to recurrence, defined as time from surgery to disease recurrence. Stratified multivariable Cox models were used to assess the associations between Immunoscore and outcomes, adjusting for potential confounders. Harrell's C-statistics was used to assess model performance. Tissue samples from 3539 patients were processed, and samples from 2681 patients were included in the analyses after quality controls (700 patients in the training set, 636 patients in the internal validation set, and 1345 patients in the external validation set). The Immunoscore assay showed a high level of reproducibility between observers and centres (r=0·97 for colon tumour; r=0·97 for invasive margin; p<0·0001). In the training set, patients with a high Immunoscore had the lowest risk of recurrence at 5 years (14 [8%] patients with a high Immunoscore vs 65 (19%) patients with an intermediate Immunoscore vs 51 (32%) patients with a low Immunoscore; hazard ratio [HR] for high vs low Immunoscore 0·20, 95% CI 0·10-0·38; p<0·0001). The findings were confirmed in the two validation sets (n=1981). In the stratified Cox multivariable analysis, the Immunoscore association with time to recurrence was independent of patient age, sex, T stage, N stage, microsatellite instability, and existing prognostic factors (p<0·0001). Of 1434 patients with stage II cancer, the difference in risk of recurrence at 5 years was significant (HR for high vs low Immunoscore 0·33, 95% CI 0·21-0·52; p<0·0001), including in Cox multivariable analysis (p<0·0001). Immunoscore had the highest relative contribution to the risk of all clinical parameters, including the American Joint Committee on Cancer and Union for International Cancer Control TNM classification system. The Immunoscore provides a reliable estimate of the risk of recurrence in patients with colon cancer. These results support the implementation of the consensus Immunoscore as a new component of a TNM-Immune classification of cancer. French National Institute of Health and Medical Research, the LabEx Immuno-oncology, the Transcan ERAnet Immunoscore European project, Association pour la Recherche contre le Cancer, CARPEM, AP-HP, Institut National du Cancer, Italian Association for Cancer Research, national grants and the Society for Immunotherapy of Cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

C-reactive protein as an adverse prognostic marker for men with castration-resistant prostate cancer (CRPC): confirmatory results

PubMed Central

Prins, Renee C.; Rademacher, Brooks L.; Mongoue-Tchokote, Solange; Alumkal, Joshi J.; Graff, Julie N.; Eilers, Kristine M.; Beer, Tomasz M.

2010-01-01

We previously reported that higher serum concentrations of C-reactive protein (CRP) are associated with shorter survival in men with castration-resistant prostate cancer (CRPC). To confirm this finding in an independent data set, we used 119 CRPC patients enrolled in 6 phase II clinical trials and examined the relationship of CRP, alkaline phosphatase, hemoglobin, age, ECOG PS, and prostate specific antigen (PSA) with survival. Median follow-up was 19.7 months (0.9–98.5 months) and 89% have died. After analyzing the form of the risk function using the generalized additive model method, univariate and multivariate Cox proportional hazard models were used to assess associations between baseline individual categorical and continuous variables. Quartiles of CRP were: 1: 0–1.0, 1.1–4.9, 5.0–17.0, and 17.1 to 311 mg/L. In a Cox multivariate model, log2(CRP) (HR 1.106 p=0.013) as well as hemoglobin and alkaline phosphatase were independently associated with survival, confirming that higher CRP is associated with shorter survival in CRPC. Since CRP is a marker of inflammation, this finding suggests that inflammation may play an important role in the natural history of advanced prostate cancer. CRP is a readily measurable biomarker that has the potential to improve prognostic models and should be validated in a prospective clinical trial. PMID:20207556

Factors Affecting Discharge to Home of Geriatric Intermediate Care Facility Residents in Japan.

PubMed

Morita, Kojiro; Ono, Sachiko; Ishimaru, Miho; Matsui, Hiroki; Naruse, Takashi; Yasunaga, Hideo

2018-04-01

To investigate factors associated with lower likelihood of discharge to home from geriatric intermediate care facilities in Japan. Retrospective cohort study. We used data from the nationwide long-term care (LTC) insurance claims database (April 2012-March 2014). Study participants were 342,758 individuals newly admitted to 3,459 geriatric intermediate care facilities during the study period. The primary outcome was discharge to home. We performed a multivariable competing-risk Cox regression with adjustment for resident-, facility-, and region-level characteristics. Resident level of care needs and several medical conditions were included as time-varying covariates. Death, admission to a hospital, and admission to another LTC facility were treated as competing risks. During the 2-year follow-up period, 19% of participants were discharged to home. In the multivariable competing-risk Cox regression, the following factors were significantly associated with lower likelihood of discharge to home: older age, higher level of care need, having several medical conditions, private ownership of the facility, more beds in the facility, and more LTC facility beds per 1,000 adults aged 65 and older in the region. Only 19% of residents were discharged to home. Our results are useful for policy-makers to promote discharge to home of older adults in geriatric intermediate care facilities. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

The roles of the cyclo-oxygenases types one and two in prostaglandin synthesis in human fetal membranes at term.

PubMed

Sawdy, R J; Slater, D M; Dennes, W J; Sullivan, M H; Bennett, P R

2000-01-01

The aim of this study was to determine the relative contributions of cyclo-oxygenase (COX) types 1 and 2 to prostaglandin synthesis at term. Fetal membranes were collected from 6 pregnancies after elective caesarean section at term, prior to labour. The presence of COX-1 and COX-2 protein was determined using Western analysis. The relative contributions of the two isoforms of COX to prostaglandin synthesis were determined by incubation of fetal membrane discs with either a COX-2 selective inhibitor, SC236, or a COX-1 selective inhibitor, SC560, and measurement of prostaglandin release during 24 h using enzyme-linked immuno-sorbent assay (ELISA). Both COX-1 and COX-2 protein were demonstrated in amnion and chorion-decidua. The COX-2 selective inhibitor, SC-236, significantly reduced prostaglandin synthesis, both in its COX-2 specific and higher, non-specific concentration ranges. The COX-1 selective inhibitor, SC-560, had no effect upon prostaglandin synthesis in its COX-1 specific concentration range, but did significantly reduce prostaglandin synthesis at higher, non-selective concentrations. Fetal membranes contain both COX-1 and COX-2 at term, but only COX-2 contributes towards prostaglandin synthesis. COX-2 selective NSAI drugs will be as effective as non-selective agents in inhibition of fetal membrane prostaglandin synthesis and may represent a new strategy for tocolysis. Copyright 2000 Harcourt Publishers Ltd.

Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma.

PubMed

Adams, Hugo J A; de Klerk, John M H; Fijnheer, Rob; Dubois, Stefan V; Nievelstein, Rutger A J; Kwee, Thomas C

2015-03-01

To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ=-0.042, P=0.765), categorized lactate dehydrogenase (LDH) ratio (ρ=0.201, P=0.156), extranodal disease in major organs (φ=-0.245, P=0.083), Ann Arbor stage III/IV disease (φ=-0.208, P=0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ=0.015, P=0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P=0.003) and overall survival (P=0.004). The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Keeping data continuous when analyzing the prognostic impact of a tumor marker: an example with cathepsin D in breast cancer.

PubMed

Bossard, N; Descotes, F; Bremond, A G; Bobin, Y; De Saint Hilaire, P; Golfier, F; Awada, A; Mathevet, P M; Berrerd, L; Barbier, Y; Estève, J

2003-11-01

The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg(-1). The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

Comparing initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care: A study of Irish National data.

PubMed

Doherty, Sarah M; Jackman, Louise M; Kirwan, John F; Dunne, Deirdre; O'Connor, Kieran G; Rouse, John M

2016-12-01

The incidence of melanoma is rising worldwide. Current Irish guidelines from the National Cancer Control Programme state suspicious pigmented lesions should not be removed in primary care. There are conflicting guidelines and research advising who should remove possible melanomas. To determine whether initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care leads to poorer survival. Analysis of data comprising 7116 cases of cutaneous malignant melanoma from the National Cancer Registry Ireland between January 2002 and December 2011. Single predictor variables were examined by the chi-square or Mann-Whitney U test. The effects of single predictor variables on survival were examined by Cox proportionate hazards modelling and a multivariate Cox model of survival based on excision in a non-hospital setting versus hospital setting was derived with adjusted and unadjusted hazard ratios. Over a 10-year period 8.5% of melanomas in Ireland were removed in a non-hospital setting. When comparing melanoma death between the hospital and non-hospital groups, the adjusted hazard ratio was 1.56 (95%CI: 1.08-2.26); (P = .02), indicating a non-inferior outcome for the melanoma cases initially treated in the non-hospital group, after adjustment for significant covariates. This study suggests that initial excision biopsy carried out in general practice does not lead to a poorer outcome. [Box: see text].

Preventive dental management of osteonecrosis of the jaws related to zoledronic acid treatment.

PubMed

Coello-Suanzes, J A; Rollon-Ugalde, V; Castaño-Seiquer, A; Lledo-Villar, E; Herce-Lopez, J; Infante-Cossio, P; Rollon-Mayordomo, A

2018-02-07

To evaluate the effect of preventive dental management on reducing the incidence and delaying the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients treated with intravenous zoledronic acid (ZA). This single-center clinical study included 255 cancer patients monitored over a 6-year period. Patients received dental treatment prior (Group A) or after (Group B) the initiation of ZA therapy. Dental treatments performed, incidence proportion (IP) and incidence rate (IR) in both groups were analyzed using significance tests. BRONJ onset were estimated using the Kaplan-Meier estimator and log-rank test. Independent risk factors to develop BRONJ were evaluated using Cox regression analysis models. 37 patients suffered from BRONJ (IP=14.5%), 7.3% in group A and 36.5% in group B (p=0.000). The IR was 0.007 patients/month in group B and 0.004 in group A. BRONJ free survival at 3 years were 97% in group A and 66% in group B. Survival curves were significant (p=0.056) according to log-rank test. Multivariate Cox models showed that dental extractions (p=0.000) were significant. BRONJ occurred significantly in patients who underwent dental extractions after the initiation of ZA and did not accomplish a preventive dental program. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Association between local inflammation and breast tissue age-related lobular involution among premenopausal and postmenopausal breast cancer patients

PubMed Central

Hanna, Mirette; Dumas, Isabelle; Orain, Michèle; Jacob, Simon; Têtu, Bernard; Sanschagrin, François; Bureau, Alexandre; Poirier, Brigitte; Diorio, Caroline

2017-01-01

Increased levels of pro-inflammatory markers and decreased levels of anti-inflammatory markers in the breast tissue can result in local inflammation. We aimed to investigate whether local inflammation in the breast tissue is associated with age-related lobular involution, a process inversely related to breast cancer risk. Levels of eleven pro- and anti-inflammatory markers were assessed by immunohistochemistry in normal breast tissue obtained from 164 pre- and postmenopausal breast cancer patients. Involution status of the breast (degree of lobular involution and the predominant lobule type) was microscopically assessed in normal breast tissue on hematoxylin-eosin stained mastectomy slides. Multivariate generalized linear models were used to assess the associations. In age-adjusted analyses, higher levels of pro-inflammatory markers IL-6, TNF-α, CRP, COX-2, leptin, SAA1 and IL-8; and anti-inflammatory marker IL-10, were inversely associated with the prevalence of complete lobular involution (all P≤0.04). Higher levels of the pro-inflammatory marker COX-2 were also associated with lower prevalence of predominant type 1/no type 3 lobules in the breast, an indicator of complete involution, in age-adjusted analysis (P = 0.017). Higher tissue levels of inflammatory markers, mainly the pro-inflammatory ones, are associated with less involuted breasts and may consequently be associated with an increased risk of developing breast cancer. PMID:28846716

A novel risk score for mortality in renal transplant recipients beyond the first posttransplant year.

PubMed

Hernández, Domingo; Sánchez-Fructuoso, Ana; González-Posada, José Manuel; Arias, Manuel; Campistol, Josep María; Rufino, Margarita; Morales, José María; Moreso, Francesc; Pérez, Germán; Torres, Armando; Serón, Daniel

2009-09-27

All-cause mortality is high after kidney transplantation (KT), but no prognostic index has focused on predicting mortality in KT using baseline and emergent comorbidity after KT. A total of 4928 KT recipients were used to derive a risk score predicting mortality. Patients were randomly assigned to two groups: a modeling population (n=2452), used to create a new index, and a testing population (n=2476), used to test this index. Multivariate Cox regression model coefficients of baseline (age, weight, time on dialysis, diabetes, hepatitis C, and delayed graft function) and emergent comorbidity within the first posttransplant year (diabetes, proteinuria, renal function, and immunosuppressants) were used to weigh each variable in the calculation of the score and allocated into risk quartiles. The probability of death at 3 years, estimated by baseline cumulative hazard function from the Cox model [P (death)=1-0.993592764 (exp(score/100)], increased from 0.9% in the lowest-risk quartile (score=40) to 4.7% in the highest risk-quartile (score=200). The observed incidence of death increased with increasing risk quartiles in testing population (log-rank analysis, P<0.0001). The overall C-index was 0.75 (95% confidence interval: 0.72-0.78) and 0.74 (95% confidence interval: 0.70-0.77) in both populations, respectively. This new index is an accurate tool to identify high-risk patients for mortality after KT.

Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

PubMed

Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

2015-09-03

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.

The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection.

PubMed

Zhao, Jing-jing; Pan, Ke; Wang, Wei; Chen, Ju-gao; Wu, Yan-heng; Lv, Lin; Li, Jian-jun; Chen, Yi-bing; Wang, Dan-dan; Pan, Qiu-zhong; Li, Xiao-dong; Xia, Jian-chuan

2012-01-01

Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs. The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis. Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00-115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients. The presence of CD15+ TINs is an independent and unfavorable factor in the prognosis of gastric adenocarcinoma patients. Targeting CD15+ TINs may be a potential intervenient therapy in the future.

The bitter barricading of prostaglandin biosynthesis pathway: understanding the molecular mechanism of selective cyclooxygenase-2 inhibition by amarogentin, a secoiridoid glycoside from Swertia chirayita.

PubMed

Shukla, Shantanu; Bafna, Khushboo; Sundar, Durai; Thorat, Sunil S

2014-01-01

Swertia chirayita, a medicinal herb inhabiting the challenging terrains and high altitudes of the Himalayas, is a rich source of essential phytochemical isolates. Amarogentin, a bitter secoiridoid glycoside from S. chirayita, shows varied activity in several patho-physiological conditions, predominantly in leishmaniasis and carcinogenesis. Experimental analysis has revealed that amarogentin downregulates the cyclooxygenase-2 (COX-2) activity and helps to curtail skin carcinogenesis in mouse models; however, there exists no account on selective inhibition of the inducible cyclooxygenase (COX) isoform by amarogentin. Hence the computer-aided drug discovery methods were used to unravel the COX-2 inhibitory mechanism of amarogentin and to check its selectivity for the inducible isoform over the constitutive one. The generated theoretical models of both isoforms were subjected to molecular docking analysis with amarogentin and twenty-one other Food and Drug Authority (FDA) approved lead molecules. The post-docking binding energy profile of amarogentin was comparable to the binding energy profiles of the FDA approved selective COX-2 inhibitors. Subsequent molecular dynamics simulation analysis delineated the difference in the stability of both complexes, with amarogentin-COX-2 complex being more stable after 40ns simulation. The total binding free energy calculated by MMGBSA for the amarogentin-COX-2 complex was -52.35 KCal/mol against a binding free energy of -8.57 KCal/mol for amarogentin-COX-1 complex, suggesting a possible selective inhibition of the COX-2 protein by the natural inhibitor. Amarogentin achieves this potential selectivity by small, yet significant, structural differences inherent to the binding cavities of the two isoforms. Hypothetically, it might block the entry of the natural substrates in the hydrophobic binding channel of the COX-2, inhibiting the cyclooxygenation step. To sum up briefly, this work highlights the mechanism of the possible selective COX-2 inhibition by amarogentin and endorses the possibility of obtaining efficient, futuristic and targeted therapeutic agents for relieving inflammation and malignancy from this phytochemical source.

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

Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer.

PubMed

Ellis, Mark A; Graboyes, Evan M; Wahlquist, Amy E; Neskey, David M; Kaczmar, John M; Schopper, Heather K; Sharma, Anand K; Morgan, Patrick F; Nguyen, Shaun A; Day, Terry A

2018-04-01

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

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.

Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

PubMed

Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

2014-02-01

Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

Retrospective Analysis of 255 Papillary Thyroid Carcinomas ≤2 cm: Clinicohistological Features and Prognostic Factors.

PubMed

Marques, Pedro; Leite, Valeriano; Bugalho, Maria João

2014-12-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The widespread use of neck ultrasound (US) and US-guided fine-needle aspiration cytology is triggering an overdiagnosis of PTC. To evaluate clinical behavior and outcomes of patients with PTCs ≤2 cm, seeking for possible prognostic factors. Clinical records of cases with histological diagnosis of PTC ≤2 cm followed at the Endocrine Department of Instituto Português de Oncologia, Lisbon between 2002 and 2006 were analyzed retrospectively. We identified 255 PTCs, 111 were microcarcinomas. Most patients underwent near-total thyroidectomy, with lymph node dissections in 55 cases (21.6%). Radioiodine therapy was administered in 184 patients. At the last evaluation, 38 (14.9%) had evidence of disease. Two deaths were attributed to PTC. Median (±SD) follow-up was 74 (±23) months. Multivariate analysis identified vascular invasion, lymph node and systemic metastases significantly associated with recurrence/persistence of disease. In addition, lymph node involvement was significantly associated with extrathyroidal extension and angioinvasion. Median (±SD) disease-free survival (DFS) was estimated as 106 (±3) months and the 5-year DFS rate was 87.5%. Univariate Cox analysis identified some relevant parameters for DFS, but multivariate regression only identified lymph node and systemic metastases as significant independent factors. The median DFS estimated for lymph node and systemic metastases was 75 and 0 months, respectively. In the setting of small PTCs, vascular invasion, extrathyroidal extension and lymph node and/or systemic metastases may confer worse prognosis, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

Prognostic value of transformer 2β expression in prostate cancer.

PubMed

Diao, Yan; Wu, Dong; Dai, Zhijun; Kang, Huafeng; Wang, Ziming; Wang, Xijing

2015-01-01

Deregulation of transformer 2β (Tra2β) has been implicated in several cancers. However, the role of Tra2β expression in prostate cancer (PCa) is unclear. Therefore, this study was to investigate the expression of Tra2β in PCa and evaluated its association with clinicopathological variables and prognosis. Thirty paired fresh PCa samples were analyzed for Tra2β expression by Western blot analysis. Immunohistochemistry (IHC) assay was performed in 160 PCa samples after radical prostatectomy and adjacent non-cancerous tissues. Tra2β protein expression was divided into high expression group and low expression group by IHC. We also investigated the association of Tra2β expression with clinical and pathologic parameters. Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the association between Tra2β protein expression and prognosis of PCa patients. Our results showed that Tra2β was significantly upregulated in PCa tissues by western blot and IHC. Our data indicated that high expression of Tra2β was significantly associated with lymph node metastasis (P=0.002), clinical stage (P=0.015), preoperative prostate-specific antigen (P=0.003), Gleason score (P=0.001), and biochemical recurrence (P=0.021). High Tra2β expression was a significant predictor of poor biochemical recurrence free survival and overall survival both in univariate and multivariate analysis. We show that Tra2β was significantly upregulated in PCa patients after radical prostatectomy, and multivariate analysis confirmed Tra2β as an independent prognostic factor.

LGE Provides Incremental Prognostic Information Over Serum Biomarkers in AL Cardiac Amyloidosis.

PubMed

Boynton, Samuel J; Geske, Jeffrey B; Dispenzieri, Angela; Syed, Imran S; Hanson, Theodore J; Grogan, Martha; Araoz, Philip A

2016-06-01

This study sought to determine the prognostic value of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) in amyloid light chain (AL) cardiac amyloidosis. Cardiac involvement is the major determinant of mortality in AL amyloidosis. CMR LGE is a marker of amyloid infiltration of the myocardium. The purpose of this study was to evaluate retrospectively the prognostic value of CMR LGE for determining all-cause mortality in AL amyloidosis and to compare the prognostic power with the biomarker stage. Seventy-six patients with histologically proven AL amyloidosis underwent CMR LGE imaging. LGE was categorized as global, focal patchy, or none. Global LGE was considered present if it was visualized on LGE images or if the myocardium nulled before the blood pool on a cine multiple inversion time (TI) sequence. CMR morphologic and functional evaluation, echocardiographic diastolic evaluation, and cardiac biomarker staging were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. There were 40 deaths, and the median study follow-up period was 34.4 months. Global LGE was associated with all-cause mortality in univariate analysis (hazard ratio = 2.93; p < 0.001). In multivariate modeling with biomarker stage, global LGE remained prognostic (hazard ratio = 2.43; p = 0.01). Diffuse LGE provides incremental prognosis over cardiac biomarker stage in patients with AL cardiac amyloidosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

Effects of Cyclooxygenase on the Urothelium of the Urinary Bladder of Mice Exposed to Pelvic Radiation.

PubMed

Ozbilgin, M Kemal; Onal, Tuna; Ozcan, Cemil; Temel, Merve; Aktas, Caner; Gareveran, Manuchehr Salehi; Uluer, Elgin Turkoz; Inan, Sevinc; Kurtman, Cengiz

2016-04-01

To determine the role of cyclooxygenase (COX) expression in the urothelium of the urinary bladder during radiation injury caused by pelvic radiotherapy for cancer therapy. Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1) and the second, third, and fourth groups were euthanized after 24 hours (Group 2), 48 hours (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Histochemical analysis using hematoxylin and eosin and immunohistochemical analysis using anti-COX-1 and COX-2 antibodies were performed on tissue samples. The immunoreactivities of the urinary bladder were quantified using H-score measurement, and statistical comparison was performed. In the immunohistochemical examination the COX-1 immunoreactivities were found to be higher in the urothelium of the bladder in the radiation exposed groups than in the normal control group (group 1) (p < 0.005). Additionally, high immunoreactivity of COX-2 molecule was established in groups 2, 3, and 4 of radiation groups as compared to group 1 (p < 0.005) in examination of the urothelium. COX-1 and COX-2 immunoreactivities in the submucosa were detected higher in group 4 than in the other groups (p < 0.005). COX-1 and COX-2 expressions in the urothelium and subepithelium of the urinary bladder were investigated in mice during the acute radiation response. The expression of COX-1 and COX-2 in the urothelium seems to prevent bladder damage from radiation, supplying differentiation and restoration of the urothelium.

QSAR analyses of conformationally restricted 1,5-diaryl pyrazoles as selective COX-2 inhibitors: application of connection table representation of ligands.

PubMed

Prasanna, S; Manivannan, E; Chaturvedi, S C

2005-04-15

As a part of our continuing efforts in discerning the structural and physicochemical requirements for selective COX-2 over COX-1 inhibition among the fused pyrazole ring systems, herein we report the QSAR analyses of the title compounds. The conformational flexibility of the title compounds was examined using a simple connection table representation. The conformational investigation was aided by calculating a connection table parameter called fraction of rotable bonds, b_rotR encompassing the number of rotable bonds and b_count, the number of bonds including implicit hydrogens of each ligand. The hydrophobic and steric correlation of the title compounds towards selective COX-2 inhibition was reported previously in one of our recent publications. In this communication, we attempt to calculate Wang-Ford charges of the non-hydrogen common atoms of AM1 optimized geometries of the title compounds. Owing to the partial conformational flexibility of title compounds, conformationally restricted and unrestricted descriptors were calculated from MOE. Correlation analysis of these 2D, 3D and Wang-Ford charges was accomplished by linear regression analysis. 2D molecular descriptor b_single, 3D molecular descriptors glob, std_dim3 showed significant contribution towards COX-2 inhibitory activity. Balaban J, a connectivity topological index showed a negative and positive contribution towards COX-1 and selective COX-2 over COX-1 inhibition, respectively. Wang-Ford charges calculated on C(7) showed a significant contribution towards COX-1 inhibitory activity whereas charges calculated on C(8) were crucial in governing the selectivity of COX-2 over COX-1 inhibition among these congeners.

Long-Term Prognostic Implications of the Admission Shock Index in Patients With Acute Myocardial Infarction Who Received Percutaneous Coronary Intervention.

PubMed

Abe, Naoyuki; Miura, Takashi; Miyashita, Yusuke; Hashizume, Naoto; Ebisawa, Soichiro; Motoki, Hirohiko; Tsujimura, Takuya; Ishihara, Takayuki; Uematsu, Masaaki; Katagiri, Toshio; Ishihara, Ryuma; Tosaka, Atsushi; Ikeda, Uichi

2017-04-01

The admission shock index (SI) enables prediction of short-term prognosis. This study investigated the prognostic implications of admission SI for predicting long-term prognoses for acute myocardial infarction (AMI). The participants were 680 patients with AMI who received percutaneous coronary intervention. Shock index is the ratio of heart rate and systolic blood pressure. Patients were classified as admission SI <0.66 (normal) and ≥0.66 (elevated; 75th percentile). The end point was 5-year major adverse cardiac events (MACEs). Elevated admission SI was seen in 176 patients. Peak creatine kinase levels were significantly higher and left ventricular ejection fraction was lower in the elevated SI group, which had a worse MACEs. In multivariate Cox regression analysis, SI ≥0.66 was a risk factor for MACE. Elevated admission SI was associated with poorer long-term prognosis.

Risk prediction and impaired tactile sensory perception among cancer patients during chemotherapy.

PubMed

Cardoso, Ana Carolina Lima Ramos; Araújo, Diego Dias de; Chianca, Tânia Couto Machado

2018-01-08

to estimate the prevalence of impaired tactile sensory perception, identify risk factors, and establish a risk prediction model among adult patients receiving antineoplastic chemotherapy. historical cohort study based on information obtained from the medical files of 127 patients cared for in the cancer unit of a private hospital in a city in Minas Gerais, Brazil. Data were analyzed using descriptive and bivariate statistics, with survival and multivariate analysis by Cox regression. 57% of the 127 patients included in the study developed impaired tactile sensory perception. The independent variables that caused significant impact, together with time elapsed from the beginning of treatment up to the onset of the condition, were: bone, hepatic and regional lymph node metastases; alcoholism; palliative chemotherapy; and discomfort in lower limbs. impaired tactile sensory perception was common among adult patients during chemotherapy, indicating the need to implement interventions designed for early identification and treatment of this condition.

Survival pattern of first accident among commercial drivers in the Greater Accra Region of Ghana.

PubMed

Nanga, Salifu; Odai, Nii Afotey; Lotsi, Anani

2017-06-01

In this study, the average accident risk of commercial drivers in the Greater Accra region of Ghana and its associated risks were examined based on a survey data collected using paper-based questionnaires from 204 commercial drivers from the Greater Accra Region of Ghana. The Cox Proportional Hazards Model was used for multivariate analysis while the Kaplan-Meier (KM) Model was used to study the survival patterns of the commercial drivers. The study revealed that the median survival time for an accident to happen is 2.50 years. Good roads provided a better chance of survival than bad roads and experienced drivers have a better chance of survival than the inexperienced drivers. Age of driver, alcohol usage of driver, marital status, condition of road and duration of driver's license were found to be related to the risk of accident. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognostic determinants of community-acquired bloodstream infection in type 2 diabetic patients in ED.

PubMed

Yo, Chia-Hung; Lee, Meng-Tse Gabriel; Gi, Weng-Tein; Chang, Shy-Shin; Tsai, Kuang-Chau; Chen, Shyr-Chyr; Lee, Chien-Chang

2014-12-01

The objective of the study is to describe the epidemiology and outcome of community-acquired bloodstream infection (BSI) in type 2 diabetic patients in emergency department (ED). All patients admitted to the ED of the university hospital from June 2010 to June 2011 with a history of type 2 diabetes mellitus and microbiologically documented BSI were retrospectively enrolled. Demographic characteristics, Charlson comorbidity index, antibiotic therapy, clinical severity, microbiological etiology, and diabetes-related complications were recorded in a standardized form. The major outcome measure was 30-day survival. χ2 Or Student t test was used for univariate analysis, and Cox proportional hazards models were used for multivariate analysis. Among 250 enrolled emergency patients with BSI, the overall 30-day mortality rate was 15.5%. Twenty-seven patients (10.7%) developed diabetic ketoacidosis (DKA), and 22 patients (8.8%) developed hyperosmolar hyperglycemic state. On univariate analysis, DKA rather than hyperosmolar hyperglycemic state was associated with adverse outcome. Other risk factors include higher mean glycated hemoglobin level, presence of underlying malignancy, long-term use of steroids, lower respiratory tract infection, and higher Charlson scores. Multivariate analysis identified 3 independent risk factors for early mortality when severity, comorbidity, age, and sex were under control: DKA (hazard ratio, 3.89; 95% confidence interval, 1.6-8.9), inappropriate antibiotics (2.25, 1.05-4.82), and chronic use of steroid (3.89, 1.1-13.2). In type 2 diabetic patients with BSI, a substantial proportion of patients developed DKA. This condition was probably underrecognized by clinicians and constituted an independent risk factor for short-term mortality. Other identified risk factors are potentially correctable and may allow preventive efforts to individuals at greatest potential benefit. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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.

Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database.

PubMed

Wei, Shenhai; Tian, Jintao; Song, Xiaoping; Wu, Bingqun; Liu, Limin

2018-01-01

To investigate the probability of death (POD) from any causes by time after diagnosis of non-small cell lung cancer (NSCLC) and the factors associated with survival for NSCLC patients. A total of 202,914 patients with NSCLC from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) and lung cancer-specific survival (LCSS) were calculated and POD from any causes at different time periods after diagnosis was explored. The predictive factors for OS, LCSS and survival from non-lung cancer deaths were investigated using multivariate analysis with Cox proportional hazards regression and competing risk regression analysis. The 5- and 10-year OS were 20.4% and 11.5%, accordingly that for LCSS were 25.5% and 18.4%, respectively. Lung cancer contributed 88.3% (n = 128,402) of the deaths. The POD from lung cancer decreased with time after diagnosis. In multivariate analysis, advanced age and advanced stage of NSCLC were associated with decreased OS and LCSS. Comparing to no surgery, any kind of resection conferred lower risk of death from lung cancer and higher risk of dying from non-lung cancer conditions except lobectomy or bilobectomy, which was associated with lower risk of death from both lung cancer and non-lung cancer conditions. Most of the patients with NSCLC died from lung cancer. Rational surveillance and treatment policies should be made for them. Early stage and lobectomy or bilobectomy were associated with improved OS and LCSS. It is reasonable to focus on early detection and optimal surgical treatment for NSCLC.

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

PubMed

Hamilton, Sarah N; Ho, Cheryl; Laskin, Janessa; Zhai, Yongliang; Mak, Paul; Wu, Jonn

2016-12-01

The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

Monotherapy versus Combination Therapy against Nonbacteremic Carbapenem-resistant Gram-negative Infections: A Retrospective Observational Study.

PubMed

Ghafur, Abdul; Devarajan, Vidyalakshmi; Raja, T; Easow, Jose; Raja, M A; Sreenivas, Sankar; Ramakrishnan, Balasubramaniam; Raman, S G; Devaprasad, Dedeepiya; Venkatachalam, Balaji; Nimmagadda, Ramesh

2017-12-01

Superiority of colistin-carbapenem combination therapy (CCCT) over colistin monotherapy (CMT) against carbapenem-resistant Gram-negative bacterial (CRGNB) infections is not conclusively proven. The aim of the current study was to analyze the effectiveness of both strategies against CRGNB nonbacteremic infections. This was a retrospective observational cohort study. Case record analysis of patients who had CRGNB nonbacteremic infections identified over a period of 4 years (January 2012-December 2015) was done by medical record review at a tertiary care center in India. P < 0.05 was considered as significant. Multivariate analysis was performed using Cox regression. Out of 153 patients (pneumonia 115, urinary tract infection 17, complicated skin and soft-tissue infection 18, intra-abdominal infection 1, and meningitis 2), 92 patients received CCCT and 61 received CMT. Univariate analysis revealed higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, pneumonia as the diagnosis, and Klebsiella as the causative organism to be the risk factors for higher 28-day mortality ( P = 0.036, 0.006, 0.016, respectively). Combination therapy had no significant impact on mortality (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.327-2.535, P = 0.857). Multivariate analysis revealed that higher APACHE II score and infection due to Klebsiella were found to be independent risk factors for higher mortality (OR = 3.16 and 4.9, 95% CI = 1.34-7.4 and 2.19-11.2, P = 0.008 and 0.0001, respectively). In our retrospective single-center series of CRGNB nonbacteremic infections, CCCT was not superior to CMT. Multicenter large observational studies or prospective randomized clinical trials are the need of the hour.

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.

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.

A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases.

PubMed

Rades, Dirk; Janssen, Stefan; Dziggel, Liesa; Blanck, Oliver; Bajrovic, Amira; Veninga, Theo; Schild, Steven E

2017-01-06

This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases. One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS). On univariate analysis of IC, type of irradiation did not significantly affect outcomes (p = 0.84). On Cox regression, brain metastases number (p < 0.001), nature of tumor (p < 0.001) and period from cancer detection to irradiation of brain metastases (p = 0.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes (p = 0.63). On multivariate analyses, OS was significantly associated with ECOG performance score (p = 0.011), nature of tumor (p = 0.035), brain metastases number (p = 0.048), extra-cerebral spread (p = 0.002) and RPA-class (p < 0.001). In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis.

Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

PubMed Central

Alejandre, Maria José; Palomino-Morales, Rogelio J.; Prados, Jose; Aránega, Antonia; Delgado, Juan R.; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M.

2015-01-01

The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease. PMID:26346854

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.

Individual and hospital-specific factors influencing medical graduates' time to medical specialization.

PubMed

Johannessen, Karl-Arne; Hagen, Terje P

2013-11-01

Previous studies of gender differences in relation to medical specialization have focused more on social variables than hospital-specific factors. In a multivariate analysis with extended Cox regression, we used register data for socio-demographic variables (gender, family and having a child born during the study period) together with hospital-specific variables (the amount of supervision available, efficiency pressure and the type of teaching hospital) to study the concurrent effect of these variables on specialty qualification among all 2474 Norwegian residents who began specialization in 1999-2001. We followed the residents until 2010. A lower proportion of women qualified for a specialty in the study period (67.9% compared with 78.7% of men, p < 0.001), and they took on average six months longer than men did to complete the specialization qualification (p < 0.01). Fewer women than men entered specialties providing emergency services and those with longer working hours, and women worked shorter hours than men in all specialties. Hospital factors were significant predictors for the timely attainment of specialization: working at university hospitals (regional) or central hospitals was associated with a reduction in the time taken to complete the specialization, whereas an increased patient load and less supervision had the opposite effect. Multivariate analysis showed that the smaller proportion of women who qualified for a specialty was explained principally by childbirth and by the number of children aged under 18 years. Copyright © 2013 Elsevier Ltd. All rights reserved.

The complexity of interpreting genomic data in patients with acute myeloid leukemia

PubMed Central

Nazha, A; Zarzour, A; Al-Issa, K; Radivoyevitch, T; Carraway, H E; Hirsch, C M; Przychodzen, B; Patel, B J; Clemente, M; Sanikommu, S R; Kalaycio, M; Maciejewski, J P; Sekeres, M A

2016-01-01

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML. PMID:27983727

The complexity of interpreting genomic data in patients with acute myeloid leukemia.

PubMed

Nazha, A; Zarzour, A; Al-Issa, K; Radivoyevitch, T; Carraway, H E; Hirsch, C M; Przychodzen, B; Patel, B J; Clemente, M; Sanikommu, S R; Kalaycio, M; Maciejewski, J P; Sekeres, M A

2016-12-16

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML.

Prognostic value of inflammation-based markers in patients with pancreatic cancer administered gemcitabine and erlotinib.

PubMed

Lee, Jae Min; Lee, Hong Sik; Hyun, Jong Jin; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck

2016-07-15

To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation-based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients' prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan-Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses.

True survival benefit of lung transplantation for cystic fibrosis patients: the Zurich experience.

PubMed

Hofer, Markus; Benden, Christian; Inci, Ilhan; Schmid, Christoph; Irani, Sarosh; Speich, Rudolf; Weder, Walter; Boehler, Annette

2009-04-01

Lung transplantation is the ultimate therapy for end-stage cystic fibrosis (CF) lung disease; however, the debate continues as to whether lung transplantation improves survival. We report post-transplant outcome in CF at our institution by comparing 5-year post-transplant survival with a calculated 5-year survival without lung transplantation, using a predictive 5-year survivorship model, and describe pre-transplant parameters influencing transplant outcome. CF patients undergoing lung transplantation at our center were included (1992 to 2007). Survival rates were calculated and compared, and univariate and multivariate Cox regression analyses were used for statistical assessment. Eighty transplants were performed in CF patients, 11 (13.8%) of whom were children. Mean age at transplant was 26.2 years (95% confidence interval: 24.4 to 28.0). The Liou raw score at transplant was -20 (95% confidence interval: -16 to -24), resulting in an estimated 5-year survival without transplantation of 33 +/- 14%, compared with a 5-year post-transplant survival of 68.2 +/- 5.6%. Further improvement was noted in the recent transplant era (since 2000), with a 5-year survival of 72.7 +/- 7.3%. Univariate analysis revealed that later year of transplant and diagnosis of diabetes influenced survival positively. Pediatric age had no negative impact. In the multivariate analysis, only diabetes influenced survival, in a positive manner. Lung transplantation performed at centers having experience with the procedure can offer a true survival benefit to patients with end-stage CF lung disease.

Percentage of positive prostate biopsies independently predicts biochemical outcome following radiation therapy for prostate cancer.

PubMed

Gabriele, Domenico; Garibaldi, Monica; Girelli, Giuseppe; Taraglio, Stefano; Duregon, Eleonora; Gabriele, Pietro; Guiot, Caterina; Bollito, Enrico

2016-06-01

This work aims to definitely show the ability of percentage of positive biopsy cores (%PC) to independently predict biochemical outcome beyond traditional pretreatment risk-factors in prostate cancer (PCa) patients treated with radiotherapy. A cohort of 2493 men belonging to the EUREKA-2 retrospective multicentric database on (PCa) and treated with external-beam radiation therapy (EBRT) as primary treatment comprised the study population (median follow-up 50 months). A Cox regression time to prostate-specific antigen (PSA) failure analysis was performed to evaluate the predictive power of %PC, both in univariate and multivariate settings, with age, pretreatment PSA, clinical-radiological staging, bioptic Gleason Score (bGS), RT dose and RT +/- ADT as covariates. P statistics for %PC is lower than 0.001 both in univariate and multivariate models. %PC as a continuous variable yields an AUC of 69% in ROC curve analysis for biochemical relapse. Four classes of %PC (1-20%, 21-50%, 51-80% and 81-100%) distinctly split patients for risk of biochemical relapse (overall log-rank test P<0.0001), with biochemical progression free survival (bPFS) at 5-years ranging from 88% to 58% and 10-years bPFS ranging from 80% to 38%. We strongly affirm the usefulness of %PC information beyond main risk factors (PSA, staging and bGS) in predicting biochemical recurrence after EBRT for PCa. The stratification of patients according to %PC may be valuable to further discriminate cases with favourable or adverse prognosis.

Prognostic implications of stress hyperglycemia in acute ST elevation myocardial infarction. Prospective observational study.

PubMed

Sanjuán, Rafael; Núñez, Julio; Blasco, M Luisa; Miñana, Gema; Martínez-Maicas, Helena; Carbonell, Nieves; Palau, Patricia; Bodí, Vicente; Sanchis, Juan

2011-03-01

In patients with acute myocardial infarction, elevation of plasma glucose levels is associated with worse outcomes. The aim of this study was to evaluate the association between stress hyperglycemia and in-hospital mortality in patients with acute myocardial infarction with ST-segment elevation (STEMI). We analyzed 834 consecutive patients admitted for STEMI to the Coronary Care Unit of our center. Association between admission glucose and mortality was assessed with Cox regression analysis. Discriminative accuracy of the multivariate model was assessed by Harrell's C statistic. Eighty-nine (10.7%) patients died during hospitalization. Optimal threshold glycemia level of 140mg/dl on admission to predict mortality was obtained by ROC curves. Those who presented glucose ≥140mg/dl showed higher rates of malignant ventricular tachyarrhythmias (28% vs. 18%, P=.001), complicative bundle branch block (5% vs. 2%, P=.005), new atrioventricular block (9% vs. 5%, P=.05) and in-hospital mortality (15% vs. 5%, P<.001). Multivariate analysis showed that those with glycemia ≥140mg/dl exhibited a 2-fold increase of in-hospital mortality risk (95% CI: 1.2-3.5, P=.008) irrespective of diabetes mellitus status (P-value for interaction=0.487 and 0.653, respectively). Stress hyperglycemia on admission is a predictor of mortality and arrhythmias in patients with STEMI and could be used in the stratification of risk in these patients. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian women and cancer study: a population-based prospective study.

PubMed

Gavrilyuk, Oxana; Braaten, Tonje; Skeie, Guri; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eiliv

2014-03-25

Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.

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.

Impaired left ventricular systolic function and increased brachial-ankle pulse-wave velocity are independently associated with rapid renal function progression.

PubMed

Chen, Szu-Chia; Lin, Tsung-Hsien; Hsu, Po-Chao; Chang, Jer-Ming; Lee, Chee-Siong; Tsai, Wei-Chung; Su, Ho-Ming; Voon, Wen-Chol; Chen, Hung-Chun

2011-09-01

Heart failure and increased arterial stiffness are associated with declining renal function. Few studies have evaluated the association between left ventricular ejection fraction (LVEF) and brachial-ankle pulse-wave velocity (baPWV) and renal function progression. The aim of this study was to assess whether LVEF<40% and baPWV are associated with a decline in the estimated glomerular filtration rate (eGFR) and the progression to a renal end point of ≥25% decline in eGFR. This longitudinal study included 167 patients. The baPWV was measured with an ankle-brachial index-form device. The change in renal function was estimated by eGFR slope. The renal end point was defined as ≥25% decline in eGFR. Clinical and echocardiographic parameters were compared and analyzed. After a multivariate analysis, serum hematocrit was positively associated with eGFR slope, and diabetes mellitus, baPWV (P=0.031) and LVEF<40% (P=0.001) were negatively associated with eGFR slope. Forty patients reached the renal end point. Multivariate, forward Cox regression analysis found that lower serum albumin and hematocrit levels, higher triglyceride levels, higher baPWV (P=0.039) and LVEF<40% (P<0.001) were independently associated with progression to the renal end point. Our results show that LVEF<40% and increased baPWV are independently associated with renal function decline and progression to the renal end point.

Molecular characterization of Taenia multiceps isolates from Gansu Province, China by sequencing of mitochondrial cytochrome C oxidase subunit 1.

PubMed

Li, Wen Hui; Jia, Wan Zhong; Qu, Zi Gang; Xie, Zhi Zhou; Luo, Jian Xun; Yin, Hong; Sun, Xiao Lin; Blaga, Radu; Fu, Bao Quan

2013-04-01

A total of 16 Taenia multiceps isolates collected from naturally infected sheep or goats in Gansu Province, China were characterized by sequences of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. The complete cox1 gene was amplified for individual T. multiceps isolates by PCR, ligated to pMD18T vector, and sequenced. Sequence analysis indicated that out of 16 T. multiceps isolates 10 unique cox1 gene sequences of 1,623 bp were obtained with sequence variation of 0.12-0.68%. The results showed that the cox1 gene sequences were highly conserved among the examined T. multiceps isolates. However, they were quite different from those of the other Taenia species. Phylogenetic analysis based on complete cox1 gene sequences revealed that T. multiceps isolates were composed of 3 genotypes and distinguished from the other Taenia species.

Molecular Characterization of Taenia multiceps Isolates from Gansu Province, China by Sequencing of Mitochondrial Cytochrome C Oxidase Subunit 1

PubMed Central

Li, Wen Hui; Jia, Wan Zhong; Qu, Zi Gang; Xie, Zhi Zhou; Luo, Jian Xun; Yin, Hong; Sun, Xiao Lin; Blaga, Radu

2013-01-01

A total of 16 Taenia multiceps isolates collected from naturally infected sheep or goats in Gansu Province, China were characterized by sequences of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. The complete cox1 gene was amplified for individual T. multiceps isolates by PCR, ligated to pMD18T vector, and sequenced. Sequence analysis indicated that out of 16 T. multiceps isolates 10 unique cox1 gene sequences of 1,623 bp were obtained with sequence variation of 0.12-0.68%. The results showed that the cox1 gene sequences were highly conserved among the examined T. multiceps isolates. However, they were quite different from those of the other Taenia species. Phylogenetic analysis based on complete cox1 gene sequences revealed that T. multiceps isolates were composed of 3 genotypes and distinguished from the other Taenia species. PMID:23710087

Redox-regulated dynamic interplay between Cox19 and the copper-binding protein Cox11 in the intermembrane space of mitochondria facilitates biogenesis of cytochrome c oxidase

PubMed Central

Bode, Manuela; Woellhaf, Michael W.; Bohnert, Maria; van der Laan, Martin; Sommer, Frederik; Jung, Martin; Zimmermann, Richard; Schroda, Michael; Herrmann, Johannes M.

2015-01-01

Members of the twin Cx9C protein family constitute the largest group of proteins in the intermembrane space (IMS) of mitochondria. Despite their conserved nature and their essential role in the biogenesis of the respiratory chain, the molecular function of twin Cx9C proteins is largely unknown. We performed a SILAC-based quantitative proteomic analysis to identify interaction partners of the conserved twin Cx9C protein Cox19. We found that Cox19 interacts in a dynamic manner with Cox11, a copper transfer protein that facilitates metalation of the Cu(B) center of subunit 1 of cytochrome c oxidase. The interaction with Cox11 is critical for the stable accumulation of Cox19 in mitochondria. Cox19 consists of a helical hairpin structure that forms a hydrophobic surface characterized by two highly conserved tyrosine-leucine dipeptides. These residues are essential for Cox19 function and its specific binding to a cysteine-containing sequence in Cox11. Our observations suggest that an oxidative modification of this cysteine residue of Cox11 stimulates Cox19 binding, pointing to a redox-regulated interplay of Cox19 and Cox11 that is critical for copper transfer in the IMS and thus for biogenesis of cytochrome c oxidase. PMID:25926683

Conservative Secondary Shell Substitution In Cyclooxygenase-2 Reduces Inhibition by Indomethacin Amides and Esters via Altered Enzyme Dynamics

PubMed Central

2015-01-01

The cyclooxygenase enzymes (COX-1 and COX-2) are the therapeutic targets of nonsteroidal anti-inflammatory drugs (NSAIDs). Neutralization of the carboxylic acid moiety of the NSAID indomethacin to an ester or amide functionality confers COX-2 selectivity, but the molecular basis for this selectivity has not been completely revealed through mutagenesis studies and/or X-ray crystallographic attempts. We expressed and assayed a number of divergent secondary shell COX-2 active site mutants and found that a COX-2 to COX-1 change at position 472 (Leu in COX-2, Met in COX-1) reduced the potency of enzyme inhibition by a series of COX-2-selective indomethacin amides and esters. In contrast, the potencies of indomethacin, arylacetic acid, propionic acid, and COX-2-selective diarylheterocycle inhibitors were either unaffected or only mildly affected by this mutation. Molecular dynamics simulations revealed identical equilibrium enzyme structures around residue 472; however, calculations indicated that the L472M mutation impacted local low-frequency dynamical COX constriction site motions by stabilizing the active site entrance and slowing constriction site dynamics. Kinetic analysis of inhibitor binding is consistent with the computational findings. PMID:26704937

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

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.

Role of cyclooxygenase isoforms in the altered excitatory motor pathways of human colon with diverticular disease.

PubMed

Fornai, M; Colucci, R; Antonioli, L; Ippolito, C; Segnani, C; Buccianti, P; Marioni, A; Chiarugi, M; Villanacci, V; Bassotti, G; Blandizzi, C; Bernardini, N

2014-08-01

The COX isoforms (COX-1, COX-2) regulate human gut motility, although their role under pathological conditions remains unclear. This study examines the effects of COX inhibitors on excitatory motility in colonic tissue from patients with diverticular disease (DD). Longitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor) or DFU (COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol- and substance P (SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis. In control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle. In control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity. © 2014 The British Pharmacological Society.

Role of cyclooxygenase isoforms in the altered excitatory motor pathways of human colon with diverticular disease

PubMed Central

Fornai, M; Colucci, R; Antonioli, L; Ippolito, C; Segnani, C; Buccianti, P; Marioni, A; Chiarugi, M; Villanacci, V; Bassotti, G; Blandizzi, C; Bernardini, N

2014-01-01

BACKGROUND AND PURPOSE The COX isoforms (COX-1, COX-2) regulate human gut motility, although their role under pathological conditions remains unclear. This study examines the effects of COX inhibitors on excitatory motility in colonic tissue from patients with diverticular disease (DD). EXPERIMENTAL APPROACH Longitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor) or DFU (COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol- and substance P (SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis. KEY RESULTS In control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle. CONCLUSIONS AND IMPLICATIONS In control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity. PMID:24758697

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.

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

PubMed Central

Finch, Natalie A.; Zasowski, Evan J.; Murray, Kyle P.; Mynatt, Ryan P.; Zhao, Jing J.; Yost, Raymond; Pogue, Jason M.

2017-01-01

ABSTRACT Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure. PMID:28923869

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

PubMed

Finch, Natalie A; Zasowski, Evan J; Murray, Kyle P; Mynatt, Ryan P; Zhao, Jing J; Yost, Raymond; Pogue, Jason M; Rybak, Michael J

2017-12-01

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24 ) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC 24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC 24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure. Copyright © 2017 American Society for Microbiology.

A statistical approach to evaluate the performance of cardiac biomarkers in predicting death due to acute myocardial infarction: time-dependent ROC curve

PubMed

Karaismailoğlu, Eda; Dikmen, Zeliha Günnur; Akbıyık, Filiz; Karaağaoğlu, Ahmet Ergun

2018-04-30

Background/aim: Myoglobin, cardiac troponin T, B-type natriuretic peptide (BNP), and creatine kinase isoenzyme MB (CK-MB) are frequently used biomarkers for evaluating risk of patients admitted to an emergency department with chest pain. Recently, time- dependent receiver operating characteristic (ROC) analysis has been used to evaluate the predictive power of biomarkers where disease status can change over time. We aimed to determine the best set of biomarkers that estimate cardiac death during follow-up time. We also obtained optimal cut-off values of these biomarkers, which differentiates between patients with and without risk of death. A web tool was developed to estimate time intervals in risk. Materials and methods: A total of 410 patients admitted to the emergency department with chest pain and shortness of breath were included. Cox regression analysis was used to determine an optimal set of biomarkers that can be used for estimating cardiac death and to combine the significant biomarkers. Time-dependent ROC analysis was performed for evaluating performances of significant biomarkers and a combined biomarker during 240 h. The bootstrap method was used to compare statistical significance and the Youden index was used to determine optimal cut-off values. Results : Myoglobin and BNP were significant by multivariate Cox regression analysis. Areas under the time-dependent ROC curves of myoglobin and BNP were about 0.80 during 240 h, and that of the combined biomarker (myoglobin + BNP) increased to 0.90 during the first 180 h. Conclusion: Although myoglobin is not clinically specific to a cardiac event, in our study both myoglobin and BNP were found to be statistically significant for estimating cardiac death. Using this combined biomarker may increase the power of prediction. Our web tool can be useful for evaluating the risk status of new patients and helping clinicians in making decisions.

Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

PubMed Central

Schultz, Nicolai A.; Christensen, Ib J.; Werner, Jens; Giese, Nathalia; Jensen, Benny V.; Larsen, Ole; Bjerregaard, Jon K.; Pfeiffer, Per; Calatayud, Dan; Nielsen, Svend E.; Yilmaz, Mette K.; Holländer, Niels H.; Wøjdemann, Morten; Bojesen, Stig E.; Nielsen, Kaspar R.; Johansen, Julia S.

2013-01-01

Purpose We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival. Patients and Methods In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay. Results Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22–5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months). Conclusions Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis. PMID:23840582

The role of whole brain radiation therapy in the management of melanoma brain metastases

PubMed Central

2014-01-01

Background Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as “radioresistant,” the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). Methods We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). Conclusions Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials. PMID:24954062

Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain

PubMed Central

Wang, Xiao-Min; Wu, Tian-Xia; Hamza, May; Ramsay, Edward S.; Wahl, Sharon M.; Dionne, Raymond A.

2007-01-01

New insights into the biological properties of cyclooxygenase-2 (COX-2) and its response pathway challenge the hypothesis that COX-2 is simply pro-inflammatory and inhibition of COX-2 solely prevents the development of inflammation and ameliorates inflammatory pain. The present study performed a comprehensive analysis of gene/protein expression induced by a selective inhibitor of COX-2, rofecoxib, compared with a non-selective COX inhibitor, ibuprofen, and placebo in a clinical model of acute inflammatory pain (the surgical extraction of impacted third molars) using microarray analysis followed by quantitative RT-PCR verification and Western blotting. Inhibition of COX-2 modulated gene expression related to inflammation and pain, the arachidonic acid pathway, apoptosis/angiogenesis, cell adhesion and signal transduction. Compared to placebo, rofecoxib treatment increased the gene expression of ANXA3 (annexin 3), SOD2 (superoxide dismutase 2), SOCS3 (suppressor of cytokine signaling 3) and IL1RN (IL1 receptor antagonist) which are associated with inhibition of phospholipase A2 and suppression of cytokine signaling cascades, respectively. Both rofecoxib and ibuprofen treatment increased the gene expression of the pro-inflammatory mediators, IL6 and CCL2 (chemokine C-C motif ligand 2), following tissue injury compared to the placebo treatment. These results indicate a complex role for COX-2 in the inflammatory cascade in addition to the well-characterized COX-dependent pathway, as multiple pathways are also involved in rofecoxib-induced anti-inflammatory and analgesic effects at the gene expression level. These findings may also suggest an alternative hypothesis for the adverse effects attributed to selective inhibition of COX-2. PMID:17070997

The Bitter Barricading of Prostaglandin Biosynthesis Pathway: Understanding the Molecular Mechanism of Selective Cyclooxygenase-2 Inhibition by Amarogentin, a Secoiridoid Glycoside from Swertia chirayita

PubMed Central

Sundar, Durai; Thorat, Sunil S.

2014-01-01

Swertia chirayita, a medicinal herb inhabiting the challenging terrains and high altitudes of the Himalayas, is a rich source of essential phytochemical isolates. Amarogentin, a bitter secoiridoid glycoside from S. chirayita, shows varied activity in several patho-physiological conditions, predominantly in leishmaniasis and carcinogenesis. Experimental analysis has revealed that amarogentin downregulates the cyclooxygenase-2 (COX-2) activity and helps to curtail skin carcinogenesis in mouse models; however, there exists no account on selective inhibition of the inducible cyclooxygenase (COX) isoform by amarogentin. Hence the computer-aided drug discovery methods were used to unravel the COX-2 inhibitory mechanism of amarogentin and to check its selectivity for the inducible isoform over the constitutive one. The generated theoretical models of both isoforms were subjected to molecular docking analysis with amarogentin and twenty-one other Food and Drug Authority (FDA) approved lead molecules. The post-docking binding energy profile of amarogentin was comparable to the binding energy profiles of the FDA approved selective COX-2 inhibitors. Subsequent molecular dynamics simulation analysis delineated the difference in the stability of both complexes, with amarogentin-COX-2 complex being more stable after 40ns simulation. The total binding free energy calculated by MMGBSA for the amarogentin-COX-2 complex was −52.35 KCal/mol against a binding free energy of −8.57 KCal/mol for amarogentin-COX-1 complex, suggesting a possible selective inhibition of the COX-2 protein by the natural inhibitor. Amarogentin achieves this potential selectivity by small, yet significant, structural differences inherent to the binding cavities of the two isoforms. Hypothetically, it might block the entry of the natural substrates in the hydrophobic binding channel of the COX-2, inhibiting the cyclooxygenation step. To sum up briefly, this work highlights the mechanism of the possible selective COX-2 inhibition by amarogentin and endorses the possibility of obtaining efficient, futuristic and targeted therapeutic agents for relieving inflammation and malignancy from this phytochemical source. PMID:24603686

Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

PubMed Central

Dash, Raju; Uddin, Mir Muhammad Nasir; Hosen, S.M. Zahid; Rahim, Zahed Bin; Dinar, Abu Mansur; Kabir, Mohammad Shah Hafez; Sultan, Ramiz Ahmed; Islam, Ashekul; Hossain, Md Kamrul

2015-01-01

Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration. PMID:26770028

Anti-inflammatory drugs and prediction of new structures by comparative analysis.

PubMed

Bartzatt, Ronald

2012-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of agents important for their analgesic, anti-inflammatory, and antipyretic properties. This study presents several approaches to predict and elucidate new molecular structures of NSAIDs based on 36 known and proven anti-inflammatory compounds. Based on 36 known NSAIDs the mean value of Log P is found to be 3.338 (standard deviation= 1.237), mean value of polar surface area is 63.176 Angstroms2 (standard deviation = 20.951 A2), and the mean value of molecular weight is 292.665 (standard deviation = 55.627). Nine molecular properties are determined for these 36 NSAID agents, including Log P, number of -OH and -NHn, violations of Rule of 5, number of rotatable bonds, and number of oxygens and nitrogens. Statistical analysis of these nine molecular properties provides numerical parameters to conform to in the design of novel NSAID drug candidates. Multiple regression analysis is accomplished using these properties of 36 agents followed with examples of predicted molecular weight based on minimum and maximum property values. Hierarchical cluster analysis indicated that licofelone, tolfenamic acid, meclofenamic acid, droxicam, and aspirin are substantially distinct from all remaining NSAIDs. Analysis of similarity (ANOSIM) produced R = 0.4947, which indicates low to moderate level of dissimilarity between these 36 NSAIDs. Non-hierarchical K-means cluster analysis separated the 36 NSAIDs into four groups having members of greatest similarity. Likewise, discriminant analysis divided the 36 agents into two groups indicating the greatest level of distinction (discrimination) based on nine properties. These two multivariate methods together provide investigators a means to compare and elucidate novel drug designs to 36 proven compounds and ascertain to which of those are most analogous in pharmacodynamics. In addition, artificial neural network modeling is demonstrated as an approach to predict numerous molecular properties of new drug designs that is based on neural training from 36 proven NSAIDs. Comprehensive and effective approaches are presented in this study for the design of new NSAID type agents which are so very important for inhibition of COX-2 and COX-1 isoenzymes.

Cox-nnet: An artificial neural network method for prognosis prediction of high-throughput omics data.

PubMed

Ching, Travers; Zhu, Xun; Garmire, Lana X

2018-04-01

Artificial neural networks (ANN) are computing architectures with many interconnections of simple neural-inspired computing elements, and have been applied to biomedical fields such as imaging analysis and diagnosis. We have developed a new ANN framework called Cox-nnet to predict patient prognosis from high throughput transcriptomics data. In 10 TCGA RNA-Seq data sets, Cox-nnet achieves the same or better predictive accuracy compared to other methods, including Cox-proportional hazards regression (with LASSO, ridge, and mimimax concave penalty), Random Forests Survival and CoxBoost. Cox-nnet also reveals richer biological information, at both the pathway and gene levels. The outputs from the hidden layer node provide an alternative approach for survival-sensitive dimension reduction. In summary, we have developed a new method for accurate and efficient prognosis prediction on high throughput data, with functional biological insights. The source code is freely available at https://github.com/lanagarmire/cox-nnet.

Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

PubMed

Kadera, Brian E; Sunjaya, Dharma B; Isacoff, William H; Li, Luyi; Hines, O Joe; Tomlinson, James S; Dawson, David W; Rochefort, Matthew M; Donald, Graham W; Clerkin, Barbara M; Reber, Howard A; Donahue, Timothy R

2014-02-01

Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. Retrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected. Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling. All 49 patients were deemed initially unresectable owing to vascular involvement. After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response. The median overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P=.007) and HP treatment response (hazard ratio, 9.0; P=.009) were most significant. Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P=.05). Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P=.04) than LN-positive patients. The candidate prognostic biomarkers, SMAD4 protein loss (P=.01) in tumor cells and microRNA-21 expression in the stroma (P=.05), also correlated with OS. On multivariate Cox proportional hazard modeling of HP and prognostic biomarkers, only SMAD4 protein loss was significant (hazard ratio, 9.3; P=.004). Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of LN-negative disease and excellent OS. After surgical resection, HP treatment response, perineural invasion, and SMAD4 status should help determine who should receive adjuvant therapy in this select subset of patients.

Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure.

PubMed

Lundström, Susanna L; Levänen, Bettina; Nording, Malin; Klepczynska-Nyström, Anna; Sköld, Magnus; Haeggström, Jesper Z; Grunewald, Johan; Svartengren, Magnus; Hammock, Bruce D; Larsson, Britt-Marie; Eklund, Anders; Wheelock, Åsa M; Wheelock, Craig E

2011-01-01

Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications. This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air. Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information. Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change. Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.