Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

PubMed Central

Fejzo, Marlena S.; Magtira, Aromalyn; Schoenberg, Frederic Paik; MacGibbon, Kimber; Mullin, Patrick; Romero, Roberto; Tabsh, Khalil

2014-01-01

Objective The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. Study design This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. Results Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhy- dramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. Conclusion Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy. PMID:23751910

Modified Weekly Cisplatin-Based Chemotherapy Is Acceptable in Postoperative Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer

PubMed Central

Lu, Hsueh-Ju; Yang, Chao-Chun; Wang, Ling-Wei; Chu, Pen-Yuan; Tai, Shyh-Kuan; Chen, Ming-Huang; Yang, Muh-Hwa; Chang, Peter Mu-Hsin

2015-01-01

Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT) has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC). We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT. Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed. Results. Median follow-up time was 30.0 (3.1–73.0) months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%). Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%). No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively. Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC. PMID:25793192

An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

PubMed

Chronowski, Gregory M; Wilder, Richard B; Tucker, Susan L; Ha, Chul S; Sarris, Andreas H; Hagemeister, Fredrick B; Barista, Ibrahim; Hess, Mark A; Cabanillas, Fernando; Cox, James D

2002-12-15

The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10998

Primary central nervous system lymphoma in immunocompetent individuals: a single center experience.

PubMed

Aki, Hilal; Uzunaslan, Didem; Saygin, Caner; Batur, Sebnem; Tuzuner, Nukhet; Kafadar, Ali; Ongoren, Seniz; Oz, Buge

2013-01-01

Primary central nervous system lymphoma (PCNSL) is defined as the involvement of brain, leptomeninges, eyes or spinal cord by non-Hodgkin lymphoma. The role of various prognostic markers in predicting adverse outcome is debated. To investigate the clinical and immunohistochemical findings of immunocompetent PCNSL cases (39 cases) diagnosed at the study center, and evaluate the influence of potential prognostic factors on overall survival (OS) of patients. Data regarding patient characteristics, neuroimaging, pathological and immunohistochemical features and follow-up were obtained from patient records. The influence of potential prognostic parameters on OS was investigated by log-rank test and Cox regression analysis. Patients who received combined chemotherapy and radiotherapy had a significantly better OS when compared to chemotherapy alone. Other variables included in this study were not associated with a significant survival advantage. In this study, we failed to demonstrate a relationship between different clinicopathological variables and OS of patients. Prospective studies with large patient series are needed to investigate other potential prognostic factors.

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

PubMed

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

2017-11-01

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

Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis.

PubMed

Lee, Yee Mei; Lang, Dora; Lockwood, Craig

Increasing numbers of studies identify new prognostic factors for categorising chemotherapy-induced febrile neutropenia adult cancer patients into high- or low-risk groups for adverse outcomes. These groupings are used to tailor therapy according to level of risk. However many emerging factors with prognostic significance remain controversial, being based on single studies only. A systematic review was conducted to determine the strength of association of all identified factors associated with the outcomes of chemotherapy-induced febrile neutropenia patients. The participants included were adults of 15 years old and above, with a cancer diagnosis and who underwent cancer treatment.The review focused on clinical factors and their association with the outcomes of cancer patients with chemotherapy-induced febrile neutropenia at presentation of fever.All quantitative studies published in English which investigated clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia were considered.The primary outcome of interest was to identify the clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia. Electronic databases searched from their respective inception date up to December 2011 include MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Science-Direct, Scopus and Mednar. The quality of the included studies was subjected to assessment by two independent reviewers. The standardised critical appraisal tool from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used to assess the following criteria: representativeness of study population; clearly defined prognostic factors and outcomes; whether potential confounders were addressed and appropriate statistical analysis was undertaken for the study design. Data extraction was performed using a modified version of the standardised extraction tool from the JBI-MAStARI. Prognostic factors and the accompanying odds ratio reported for the significance of these factors that were identified by multivariate regression, were extracted from each included study. Studies results were pooled in statistical meta-analysis using Review Manager 5.1. Where statistical pooling was not possible, the findings were presented in narrative form. Seven studies (four prospective cohort and three retrospective cohort) investigating 22 factors in total were included. Fixed effects meta-analysis showed: hypotension [OR=1.66, 95%CI, 1.14-2.41, p=0.008] and thrombocytopenia [OR=3.92, 95%CI, 2.19-7.01, p<0.00001)] were associated with high-risk of adverse outcomes for febrile neutropenia. Other factors that were statistically significant from single studies included: age of patients, clinical presentation at fever onset, presence or absence of co-morbidities, infections, duration and severity of neutropenia state. Five prognostic factors failed to demonstrate an association between the variables and the outcomes measured and they include: presence of pneumonia, total febrile days, median days to fever, recovery from neutropenia and presence of moderate clinical symptoms in association with Gram-negative bacteraemia. Despite the overall limitations identified in the included studies, this review has provided a synthesis of the best available evidence for the prognostic factors used in risk stratification of febrile neutropenia patients. However, the dynamic aspects of prognostic model development, validation and utilisation have not been addressed adequately thus far. Given the findings of this review, it is timely to address these issues and improve the utilisation of prognostic models in the management of febrile neutropenia patients. The identified factors are similar to the factors in current prognostic models. However, additional factors that were reported to be statistically significant in this review (thrombocytopenia, presence of central venous catheter, and duration and severity of neutropenia) have not previously been included in prognostic models. This review has found these factors may improve the performance of current models by adding or replacing some of the factors. The role of risk stratification of chemotherapy-induced febrile neutropenia patients continues to evolve as the practice of risk-based therapy has been demonstrated to be beneficial to patients, clinicians and health care organisations. Further research to identify new factors /markers is needed to develop a new model which is reliable and accurate for these patients, regardless of cancer types. A robust and well-validated prognostic model is the key to enhance patient safety in the risk-based management of cancer patients with chemotherapy-induced febrile neutropenia.

CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer

PubMed Central

Yoshida, Kazumichi; Tsujimoto, Hironori; Matsumura, Kouji; Kinoshita, Manabu; Takahata, Risa; Matsumoto, Yusuke; Hiraki, Shuichi; Ono, Satoshi; Seki, Shuhji; Yamamoto, Junji; Hase, Kazuo

2015-01-01

CD47 is an antiphagocytic molecule that acts via ligation to signal regulatory protein alpha on phagocytes; its enhanced expression and therapeutic targeting have recently been reported for several malignancies. However, CD47 expression in gastric cancer is not well documented. Immunohistochemical expression of CD47 in surgical specimens was investigated. Expression of CD47 and CD44, a known gastric cancer stem cell marker, were investigated in gastric cancer cell lines by flow cytometry. MKN45 and MKN74 gastric cancer cells were sorted by fluorescence-activated cell sorting according to CD44 and CD47 expression levels, and their in vitro proliferation, spheroid-forming capacity, and in vivo tumorigenicity were studied. In vitro phagocytosis of cancer cells by human macrophages in the presence of a CD47 blocking monoclonal antibody (B6H12) and the survival of immunodeficient mice intraperitoneally engrafted with MKN45 cells and B6H12 were compared to experiments using control antibodies. Immunohistochemistry of the clinical specimens indicated that CD47 was positive in 57 out of 115 cases, and its positivity was an independent adverse prognostic factor. Approximately 90% of the MKN45 and MKN74 cells expressed CD47 and CD44. CD47hi gastric cancer cells showed significantly higher proliferation and spheroid colony formation than CD47lo, and CD44hiCD47hi cells showed the highest proliferation in vitro and tumorigenicity in vivo. B6H12 significantly enhanced in vitro phagocytosis of cancer cells by human macrophages and prolonged the survival of intraperitoneal cancer dissemination in mice compared to control antibodies. In conclusion, CD47 is an adverse prognostic factor and promising therapeutic target in gastric cancer. PMID:26077800

Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

PubMed

Sanjay, Pandanaboyana; de Figueiredo, Rodrigo S; Leaver, Heather; Ogston, Simon; Kulli, Christoph; Polignano, Francesco M; Tait, Iain S

2012-03-10

There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

Prognostic Significance of Human Apurinic/Apyrimidinic Endonuclease (APE/Ref-1) Expression in Rectal Cancer Treated With Preoperative Radiochemotherapy

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

Kim, Jun-Sang, E-mail: k423j@cnu.ac.kr; Cancer Research Institute, Chungnam National University, Daejeon; Kim, Jin-Man

Purpose: Human apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair of radiation-induced DNA lesions and regulates transcription via redox-based activation. We investigated the predictive and prognostic significance of APE/Ref-1 expression in pretreatment biopsy specimens in locally advanced rectal cancer (LARC) (cT3-T4 or N+). Methods and Materials: APE/Ref-1 expression was analyzed by immunohistochemistry in pretreatment biopsy specimens obtained from 83 patients with LARC. Patients received preoperative radiotherapy of 50.4 Gy in 28 fractions, combined with oral capecitabine and leucovorin chemotherapy, followed by curative surgery. The prognostic significance of various clinicopathologic characteristics, including APE/Ref-1 protein expression, was evaluated. Results: APE/Ref-1 was expressed inmore » 97% of patient samples. Exclusive APE/Ref-1 nuclear staining was observed in 49 of 83 samples (59%), and mixed nuclear and cytoplasmic staining was observed in 31 samples (37%). APE/Ref-1 nuclear expression levels were low in 49 patients (59%) and high in 34 patients (41%). The level of APE/Ref-1 nuclear expression was not a prognostic factor for overall and disease-free survival. Cytoplasmic expression of APE/Ref-1 was a borderline-significant predictive factor for pathologic tumor response (p = 0.08) and a significant prognostic factor for disease-free survival, as shown by univariate analysis (p = 0.037). Multivariate analysis confirmed that cytoplasmic localization of APE/Ref-1 is a significant predictor of disease-free survival (hazard ratio, 0.45; p = 0.046). Conclusions: APE/Ref-1 was expressed in a majority of pretreatment biopsy specimens from patients with LARC. The level of APE/Ref-1 nuclear expression was not a significant predictive and prognostic factor; however, cytoplasmic localization of the protein was negatively associated with disease-free survival. These results indicate that cytoplasmic expression of APE/Ref-1 represents an adverse prognostic factor for LARC patients who receive preoperative radiochemotherapy.« less

Prognostic Impact of Calcium Score after Transcatheter Aortic Valve Implantation Performed With New Generation Prosthesis.

PubMed

Akodad, Mariama; Lattuca, Benoit; Agullo, Audrey; Macia, Jean-Christophe; Gandet, Thomas; Marin, Grégory; Iemmi, Anaïs; Vernhet, Hélène; Schmutz, Laurent; Nagot, Nicolas; Albat, Bernard; Cayla, Guillaume; Leclercq, Florence

2018-05-15

Calcium score (CS) is a well-known prognostic factor after transcatheter aortic valve implantation (TAVI) performed with first generation prosthesis but few data are available concerning new generation valves. The aim of this study was to evaluate if CS remains a prognostic factor after Sapien 3 and Evolut R valves implantation. Agatston CS was evaluated on multislice computed tomography before TAVI in 346 patients implanted with Sapien XT (n = 61), CoreValve (n = 57) devices, (group 1, n = 118), and with new generation Sapien 3 (n = 147), Evolut R (n = 81) prosthesis, (group 2, n = 228). Major adverse cardiovascular events and aortic regurgitation (AR) were evaluated at 1 month. The 2 groups were similar at baseline except for logistic Euroscore (20.1% in group 1 vs 15.0 % in group 2; p = 0.001), chronic renal failure (44.1% vs 37.2% respectively, p = 0.007) and preprocedural CS (4,092 ± 2,176 vs 3,682 ± 2,109 respectively, p = 0.022). In group 1, 28 patients (23.7%) had adverse clinical events vs 21 (9.2%) in group 2 (p <0.01). In multivariate analysis, a higher CS was predictive of adverse events in group 1 (5,785 ± 3,285 vs 3,565 ± 1,331 p <0.0001) but not in group 2 (p = 0.28). A higher CS was associated with AR in group 1 (6,234 ± 2711 vs 3,429 ± 1,505; p <0.001) and in patients implanted with an Evolut R device from group 2 (4,085 ± 3,645 vs 2,551 ± 1,356; p = 0.01). In conclusion, CS appears as an important prognostic factor of major events after TAVI with first generation valves but not with new generation devices. CS remains associated with AR only with new generation self-expandable Evolut R devices. Copyright © 2018 Elsevier Inc. All rights reserved.

Prognostic Factors and Expression of MDM2 in Patients with Primary Extremity Liposarcoma

PubMed Central

Júnior, Rosalvo Zósimo Bispo; de Camargo, Olavo Pires; de Oliveira, Cláudia Regina G. C. M.; Filippi, Renée Zon; Baptista, André Mathias; Caiero, Marcelo Tadeu

2008-01-01

OBJECTIVE The objective of this study was to investigate MDM2 (murine double minute 2) protein expression and evaluate its relationship with some anatomical and pathological aspects, aiming also to identify prognostic factors concerning local recurrence-free survival, metastasis-free survival and overall survival in patients with primary liposarcomas of the extremities. MATERIALS AND METHODS Of 50 patients with primary liposarcomas of the extremities admitted to a Reference Service, between 1968 and 2004, 25 were enrolled in the study, following eligibility and exclusion criteria. RESULTS The adverse factors that influenced the risk for local recurrence in the univariant analysis included male sex (P = 0.023), pleomorphic histological subtype (P = 0.027), and high histological grade (P = 0.007). Concerning metastasis-free survival, age less than 50 years (P = 0.040), male sex (P = 0.040), pleomorphic subtype (P < 0.001), and high histological grade (P = 0.003) had a worse prognosis. Adverse factors for overall survival were age under 50 years (P = 0.040), male sex (P = 0.040), pleomorphic subtype (P < 0.001), and high histological grade (P = 0.003). CONCLUSIONS There was no correlation between immunohistochemically observed MDM2 protein expressions and the anatomical and pathological variables studied. The immunohistochemical expression of MDM2 protein was not considered to have a prognostic value for any of the surviving patients in this study (local recurrence-free survival, metastasis-free survival, or overall survival). The immunoexpression of MDM2 protein was a frequent event in the different subtypes of liposarcomas. PMID:18438568

A new prognostic model for chemotherapy-induced febrile neutropenia.

PubMed

Ahn, Shin; Lee, Yoon-Seon; Lee, Jae-Lyun; Lim, Kyung Soo; Yoon, Sung-Cheol

2016-02-01

The objective of this study was to develop and validate a new prognostic model for febrile neutropenia (FN). This study comprised 1001 episodes of FN: 718 for the derivation set and 283 for the validation set. Multivariate logistic regression analysis was performed with unfavorable outcome as the primary endpoint and bacteremia as the secondary endpoint. In the derivation set, risk factors for adverse outcomes comprised age ≥ 60 years (2 points), procalcitonin ≥ 0.5 ng/mL (5 points), ECOG performance score ≥ 2 (2 points), oral mucositis grade ≥ 3 (3 points), systolic blood pressure <90 mmHg (3 points), and respiratory rate ≥ 24 breaths/min (3 points). The model stratified patients into three severity classes, with adverse event rates of 6.0 % in class I (score ≤ 2), 27.3 % in class II (score 3-8), and 67.9 % in class III (score ≥ 9). Bacteremia was present in 1.1, 11.5, and 29.8 % of patients in class I, II, and III, respectively. The outcomes of the validation set were similar in each risk class. When the derivation and validation sets were integrated, unfavorable outcomes occurred in 5.9 % of the low-risk group classified by the new prognostic model and in 12.2 % classified by the Multinational Association for Supportive Care in Cancer (MASCC) risk index. With the new prognostic model, we can classify patients with FN into three classes of increasing adverse outcomes and bacteremia. Early discharge would be possible for class I patients, short-term observation could safely manage class II patients, and inpatient admission is warranted for class III patients.

Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma.

PubMed

Chao, Angel; Lai, Chyong-Huey; Wang, Tzu-Hao; Jung, Shih-Ming; Lee, Yun-Shien; Chang, Wei-Yang; Yang, Lan-Yang; Ku, Fei-Chun; Huang, Huei-Jean; Chao, An-Shine; Wang, Chin-Jung; Chang, Ting-Chang; Wu, Ren-Chin

2018-05-03

We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.

Clinical factors affecting pathological fracture and healing of unicameral bone cysts

PubMed Central

2014-01-01

Background Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. Methods We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. Results The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. Conclusion The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery. PMID:24884661

Clinical factors affecting pathological fracture and healing of unicameral bone cysts.

PubMed

Urakawa, Hiroshi; Tsukushi, Satoshi; Hosono, Kozo; Sugiura, Hideshi; Yamada, Kenji; Yamada, Yoshihisa; Kozawa, Eiji; Arai, Eisuke; Futamura, Naohisa; Ishiguro, Naoki; Nishida, Yoshihiro

2014-05-17

Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery.

A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma.

PubMed

Perry, Anamarija M; Cardesa-Salzmann, Teresa M; Meyer, Paul N; Colomo, Luis; Smith, Lynette M; Fu, Kai; Greiner, Timothy C; Delabie, Jan; Gascoyne, Randy D; Rimsza, Lisa; Jaffe, Elaine S; Ott, German; Rosenwald, Andreas; Braziel, Rita M; Tubbs, Raymond; Cook, James R; Staudt, Louis M; Connors, Joseph M; Sehn, Laurie H; Vose, Julie M; López-Guillermo, Armando; Campo, Elias; Chan, Wing C; Weisenburger, Dennis D

2012-09-13

Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.

Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

PubMed

Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

2016-01-01

The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution.

PubMed

Zhang, Shengting; Wang, Li; Yu, Dong; Shen, Yang; Cheng, Shu; Zhang, Li; Qian, Ying; Shen, Zhixiang; Li, Qinyu; Zhao, Weili

2015-08-15

Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.

Prognostic Value of Coronary Computed Tomography Imaging in Patients at High Risk Without Symptoms of Coronary Artery Disease.

PubMed

Dedic, Admir; Ten Kate, Gert-Jan R; Roos, Cornelis J; Neefjes, Lisan A; de Graaf, Michiel A; Spronk, Angela; Delgado, Victoria; van Lennep, Jeanine E Roeters; Moelker, Adriaan; Ouhlous, Mohamed; Scholte, Arthur J H A; Boersma, Eric; Sijbrands, Eric J G; Nieman, Koen; Bax, Jeroen J; de Feijter, Pim J

2016-03-01

At present, traditional risk factors are used to guide cardiovascular management of asymptomatic subjects. Intensified surveillance may be warranted in those identified as high risk of developing cardiovascular disease (CVD). This study aims to determine the prognostic value of coronary computed tomography (CT) angiography (CCTA) next to the coronary artery calcium score (CACS) in patients at high CVD risk without symptoms suspect for coronary artery disease (CAD). A total of 665 patients at high risk (mean age 56 ± 9 years, 417 men), having at least one important CVD risk factor (diabetes mellitus, familial hypercholesterolemia, peripheral artery disease, or severe hypertension) or a calculated European systematic coronary risk evaluation of >10% were included from outpatient clinics at 2 academic centers. Follow-up was performed for the occurrence of adverse events including all-cause mortality, nonfatal myocardial infarction, unstable angina, or coronary revascularization. During a median follow-up of 3.0 (interquartile range 1.3 to 4.1) years, adverse events occurred in 40 subjects (6.0%). By multivariate analysis, adjusted for age, gender, and CACS, obstructive CAD on CCTA (≥50% luminal stenosis) was a significant predictor of adverse events (hazard ratio 5.9 [CI 1.3 to 26.1]). Addition of CCTA to age, gender, plus CACS, increased the C statistic from 0.81 to 0.84 and resulted in a total net reclassification index of 0.19 (p <0.01). In conclusion, CCTA has incremental prognostic value and risk reclassification benefit beyond CACS in patients without CAD symptoms but with high risk of developing CVD. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical presentation and management of drug-induced agranulocytosis.

PubMed

Andrès, Emmanuel; Zimmer, Jacques; Mecili, Mustapha; Weitten, Thierry; Alt, Martine; Maloisel, Frédéric

2011-04-01

In this article, we report and discuss the clinical presentation and management of idiosyncratic drug-induced agranulocytosis (neutrophil count <0.5 × 10(9)/l). Idiosyncratic drug-induced agranulocytosis remains a potentially serious adverse event owing to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia and septic shock in approximately two-thirds of all hospitalized patients. However, several prognostic factors have recently been identified that may be helpful in practice to identify 'susceptible' patients. Old age (>65 years), septicemia or shock, metabolic disorders such as renal failure and a neutrophil count below 0.1 × 10(9)/l are currently consensually accepted as poor prognostic factors. In this potentially life-threatening disorder, modern management with broad-spectrum antibiotics and hematopoietic growth factors (particularly granulocyte colony-stimulating factor) is likely to improve prognosis. Thus, with appropriate management, the mortality rate from idiosyncratic drug-induced agranulocytosis is currently approximately 5%.

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.

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

Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

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

Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Galbreath, Robert W.

Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate sizemore » for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.« less

Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan.

PubMed

Matsumoto, Ryuji; Abe, Takashige; Ishizaki, Junji; Kikuchi, Hiroshi; Harabayashi, Toru; Minami, Keita; Sazawa, Ataru; Mochizuki, Tango; Akino, Tomoshige; Murakumo, Masashi; Osawa, Takahiro; Maruyama, Satoru; Murai, Sachiyo; Shinohara, Nobuo

2018-06-25

The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

Prognostic significance of extranodal extension in head and neck squamous cell carcinoma cN0 patients with occult metastatic neck nodes.

PubMed

Lop, Joan; Rigó, Antoni; Codina, Alberto; de Juan, Julia; Quer, Miquel; León, Xavier

Extranodal extension in nodal metastases is an independent adverse prognostic factor in head and neck squamous cell carcinoma patients. However, few studies specifically address the subgroup of patients with no clinical evidence of nodal disease. We retrospectively analysed data from 348 head and neck squamous cell carcinoma patients without any previous treatment and lacking clinical or radiological evidence of neck node metastases during the initial workup, treated with an elective neck dissection between 1992-2014. The incidence of occult metastatic neck nodes with extranodal extension and the impact of extranodal extension in survival were evaluated. The proportion of patients with occult neck node metastases was 33%. Of these, 23.5% had at least one metastatic neck node with extranodal extension. There were significant differences in the disease-specific survival rate according to neck node status. Five-year disease-specific survival for patients without histopathological metastases was 90%, for patients with occult neck node metastases without extranodal extension it was 71.2%, and for patients with occult neck node metastases with extranodal extension it was 25.9% (P=.0001). The multivariate analysis revealed that the presence of occult node metastases with extranodal extension was the factor with strongest impact on survival. The inclusion of the extranodal extension as a criterion of histopathological evaluation in the 8th TNM classification edition improves the prognostic capacity compared to previous TNM editions. Appearance of metastatic neck nodes with extranodal extension is an adverse prognostic factor in head and neck squamous cell carcinoma patients without clinical evidence of regional disease during the initial workup of the tumour. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Prognostic significance of SRSF2 mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia: a meta-analysis.

PubMed

Arbab Jafari, Pourya; Ayatollahi, Hossein; Sadeghi, Ramin; Sheikhi, Maryam; Asghari, Amir

2018-05-14

Serine/arginine-rich splicing factor 2 (SRSF2) mutations were detected frequently in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients. However, its prognostic value has not yet been fully clarified. In this meta-analysis, Hazard Ratio (HR) and 95% confidence interval (CI) for overall-survival (OS) were chosen to evaluate the prognostic impact of SRSF2 mutations and to compare SRSF2 mutations to those with wild-type. A total of 2056 patients from 12 studies were obtained. The pooled HRs for OSsuggested that patients with MDS had a poorer prognosis (HR = 1.780, 95% CI (1.410-2.249)), while analysis on SRSF2 mutations revealed no significant effect on the prognosis of CMML patients (HR = 1.091, 95% CI (0.925-1.286)). The frequency of SRSF2 mutations was found to be 11.5% and 39.8% in patients with MDS and CMML, respectively. This meta-analysis suggests that SRSF2 has a poor prognosis in patients with MDS, but no prognosis impact on patients with CMML. In conclusion, SRSF2 mutations were significantly related to the shorter OS in patients with MDS which may consider as an adverse prognostic risk factor. Whereas, analysis did not show any prognostic effect on OS of CMML patients with SRSF2 mutations.

Transcription factor activating protein 4 is synthetically lethal and a master regulator of MYCN-amplified neuroblastoma. | Office of Cancer Genomics

Cancer.gov

Despite the identification of MYCN amplification as an adverse prognostic marker in neuroblastoma, MYCN inhibitors have yet to be developed. Here, by integrating evidence from a whole-genome shRNA library screen and the computational inference of master regulator proteins, we identify transcription factor activating protein 4 (TFAP4) as a critical effector of MYCN amplification in neuroblastoma, providing a novel synthetic lethal target.

Neuroblastoma in children: Update on clinicopathologic and genetic prognostic factors.

PubMed

Ahmed, Atif A; Zhang, Lei; Reddivalla, Naresh; Hetherington, Maxine

2017-04-01

Neuroblastoma is the most common extracranial solid tumor in childhood accounting for 8-10% of all childhood malignancies. The tumor is characterized by a spectrum of histopathologic features and a heterogeneous clinical phenotype. Modern multimodality therapy results in variable clinical response ranging from cure in localized tumors to limited response in aggressive metastatic disease. Accurate clinical staging and risk assessment based on clinical, surgical, biologic and pathologic criteria are of pivotal importance in assigning prognosis and planning effective treatment approaches. Numerous studies have analyzed the presence of several clinicopathologic and biologic factors in association with the patient's prognosis and outcome. Although patient's age, tumor stage, histopathologic classification, and MYCN amplification are the most commonly validated prognostic markers, several new gene mutations have been identified in sporadic and familial neuroblastoma cases that show association with an adverse outcome. Novel molecular studies have also added data on chromosomal segmental aberrations in MYCN nonamplified tumors. In this review, we provide an updated summary of the clinical, serologic and genetic prognostic indicators in neuroblastoma including classic factors that have consistently played a role in risk stratification of patients as well as newly discovered biomarkers that may show a potential significance in patients' management.

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

An Examination of Commercial Aviation Accidents and Incidents Related to Integrated Vehicle Health Management

NASA Technical Reports Server (NTRS)

Reveley, Mary S.; Briggs, Jeffrey L.; Thomas, Megan A.; Evans, Joni K.; Jones, Sharon M.

2011-01-01

The Integrated Vehicle Health Management (IVHM) Project is one of the four projects within the National Aeronautics and Space Administration's (NASA) Aviation Safety Program (AvSafe). The IVHM Project conducts research to develop validated tools and technologies for automated detection, diagnosis, and prognosis that enable mitigation of adverse events during flight. Adverse events include those that arise from system, subsystem, or component failure, faults, and malfunctions due to damage, degradation, or environmental hazards that occur during flight. Determining the causal factors and adverse events related to IVHM technologies will help in the formulation of research requirements and establish a list of example adverse conditions against which IVHM technologies can be evaluated. This paper documents the results of an examination of the most recent statistical/prognostic accident and incident data that is available from the Aviation Safety Information Analysis and Sharing (ASIAS) System to determine the causal factors of system/component failures and/or malfunctions in U.S. commercial aviation accidents and incidents.

Risk factors and screening instruments to predict adverse outcomes for undifferentiated older emergency department patients: a systematic review and meta-analysis.

PubMed

Carpenter, Christopher R; Shelton, Erica; Fowler, Susan; Suffoletto, Brian; Platts-Mills, Timothy F; Rothman, Richard E; Hogan, Teresita M

2015-01-01

A significant proportion of geriatric patients experience suboptimal outcomes following episodes of emergency department (ED) care. Risk stratification screening instruments exist to distinguish vulnerable subsets, but their prognostic accuracy varies. This systematic review quantifies the prognostic accuracy of individual risk factors and ED-validated screening instruments to distinguish patients more or less likely to experience short-term adverse outcomes like unanticipated ED returns, hospital readmissions, functional decline, or death. A medical librarian and two emergency physicians conducted a medical literature search of PubMed, EMBASE, SCOPUS, CENTRAL, and ClinicalTrials.gov using numerous combinations of search terms, including emergency medical services, risk stratification, geriatric, and multiple related MeSH terms in hundreds of combinations. Two authors hand-searched relevant specialty society research abstracts. Two physicians independently reviewed all abstracts and used the revised Quality Assessment of Diagnostic Accuracy Studies instrument to assess individual study quality. When two or more qualitatively similar studies were identified, meta-analysis was conducted using Meta-DiSc software. Primary outcomes were sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for predictors of adverse outcomes at 1 to 12 months after the ED encounters. A hypothetical test-treatment threshold analysis was constructed based on the meta-analytic summary estimate of prognostic accuracy for one outcome. A total of 7,940 unique citations were identified yielding 34 studies for inclusion in this systematic review. Studies were significantly heterogeneous in terms of country, outcomes assessed, and the timing of post-ED outcome assessments. All studies occurred in ED settings and none used published clinical decision rule derivation methodology. Individual risk factors assessed included dementia, delirium, age, dependency, malnutrition, pressure sore risk, and self-rated health. None of these risk factors significantly increased the risk of adverse outcome (LR+ range = 0.78 to 2.84). The absence of dependency reduces the risk of 1-year mortality (LR- = 0.27) and nursing home placement (LR- = 0.27). Five constructs of frailty were evaluated, but none increased or decreased the risk of adverse outcome. Three instruments were evaluated in the meta-analysis: Identification of Seniors at Risk, Triage Risk Screening Tool, and Variables Indicative of Placement Risk. None of these instruments significantly increased (LR+ range for various outcomes = 0.98 to 1.40) or decreased (LR- range = 0.53 to 1.11) the risk of adverse outcomes. The test threshold for 3-month functional decline based on the most accurate instrument was 42%, and the treatment threshold was 61%. Risk stratification of geriatric adults following ED care is limited by the lack of pragmatic, accurate, and reliable instruments. Although absence of dependency reduces the risk of 1-year mortality, no individual risk factor, frailty construct, or risk assessment instrument accurately predicts risk of adverse outcomes in older ED patients. Existing instruments designed to risk stratify older ED patients do not accurately distinguish high- or low-risk subsets. Clinicians, educators, and policy-makers should not use these instruments as valid predictors of post-ED adverse outcomes. Future research to derive and validate feasible ED instruments to distinguish vulnerable elders should employ published decision instrument methods and examine the contributions of alternative variables, such as health literacy and dementia, which often remain clinically occult. © 2014 by the Society for Academic Emergency Medicine.

Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

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

Gold, Douglas G.; Miller, Robert C.; Haddock, Michael G.

2009-09-01

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. Onmore » univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.« less

Is definitive concurrent chemoradiotherapy effective for locally advanced head and neck cancer in the elderly aged ≥ 75 years: A single-institute, retrospective, cohort study.

PubMed

Lai, Kuan-Ming; Lin, Jen-Tsun; Lu, Hsueh-Ju; Liang, Chia-Chun; Chen, Mu-Kuan

2018-06-01

Definitive chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck cancer (HNC). However, for very elderly patients, the comparison of benefit/risk between definitive radiotherapy (RT) with and without systemic chemotherapy was equivocal. The study was a single-institute, retrospective, cohort study. Seventy patients aged ≥75 years who had a locally advanced HNC were enrolled. The patients were divided into those with CRT and those with RT alone. Survival, compliance/adverse events and independent prognostic factors were analyzed. For baseline characteristics, the patients who received RT alone had worse performance status, comorbidity score and neutrophil-to-lymphocyte ratio. However, during definitive therapy, the CRT group had more adverse events such as neutropenia, febrile neutropenia and thrombocytopenia. There were no significant differences in disease-specific survival (DSS) and overall survival (OS) (P = 0.864 and 0.788, respectively). As to OS, several independent prognostic factors were identified. Performance status (hazard ratio [HR], 2.312; confidence interval [CI], 1.176-4.546; P = 0.015), clinical T staging (HR, 2.240; 95% CI, 1.021-4.913; P = 0.004) and total RT dose (HR, 2.555; 95% CI, 1.246-5.238; P = 0.010) were independent prognostic factors of OS. Definitive RT with or without systemic chemotherapy did not significantly influence DSS and OS for very elderly patients. Therefore, for elderly patients aged ≥ 75 years who have HNC, conservative RT might be sufficient for treatment purposes. © 2017 John Wiley & Sons Australia, Ltd.

Incidental gallbladder cancer after routine cholecystectomy: when should we suspect it preoperatively and what are predictors of patient survival?

PubMed Central

Ahn, Yongchel; Hwang, Shin; Jang, Hyuk-Jai; Choi, Kun-Moo; Lee, Sung-Gyu

2016-01-01

Purpose In about 1% of cases, incidental gallbladder cancers (iGBC) are found after routine cholecystectomy. The aim of this study is to compare clinical features of iGBC with benign GB disease and to evaluate factors affecting recurrence and survival. Methods Between January 1998 and March 2014, 4,629 patients received cholecystectomy and 73 iGBC patients (1.6%) were identified. We compared clinical features of 4,556 benign GB disease patients with 73 iGBC patients, and evaluated operative outcomes and prognostic factors in 56 eligible patients. Results The iGBC patients were older and concomitant diseases such as hypertension and anemia were more common than benign ones. And an age of more than 65 years was the only risk factor of iGBC. Adverse prognostic factors affecting patients' survival were age over 65, advanced histology, lymph node metastasis, and lymphovascular invasion on multivariate analysis. Age over 65 years, lymph node involvement, and lymphovascular invasion were identified as unfavorable factors affecting survival in subgroup analysis of extended cholecystectomy with bile duct resection (EC with BDR, n = 22). Conclusion Prior to routine cholecystectomy, incidental GB cancer should be suspected especially in elderly patients. And advanced age, lymph node metastasis, and lymphovascular invasion are important prognostic factors in EC with BDR cohorts. PMID:26942156

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

PubMed

Lau, Kui Kai; Wong, Yuen Kwun; Chan, Yap Hang; Teo, Kay Cheong; Chan, Koon Ho; Wai Li, Leonard Sheung; Cheung, Raymond Tak Fai; Siu, Chung Wah; Ho, Shu Leong; Tse, Hung Fat

2014-07-01

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Prognostic factors and risk stratification in patients with castration-resistant prostate cancer receiving docetaxel-based chemotherapy.

PubMed

Yamashita, Shimpei; Kohjimoto, Yasuo; Iguchi, Takashi; Koike, Hiroyuki; Kusumoto, Hiroki; Iba, Akinori; Kikkawa, Kazuro; Kodama, Yoshiki; Matsumura, Nagahide; Hara, Isao

2016-03-22

While novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for castration-resistant prostate cancer (CRPC) patients. Despite the excellent anti-tumor effect of docetaxel, its severe adverse effects sometimes distress patients. Therefore, it would be very helpful to predict the efficacy of docetaxel before treatment. The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy. This study included 79 patients with CRPC treated with docetaxel. The variables, including patient characteristics at diagnosis and at the start of chemotherapy, were retrospectively collected. Prognostic factors predicting OS were analyzed using the Cox proportional hazard model. Risk stratification for overall survival was determined based on the results of multivariate analysis. PSA response ≥50 % was observed in 55 (69.6 %) of all patients, and the median OS was 22.5 months. The multivariate analysis showed that age, serum PSA level at the start of chemotherapy, and Hb were independent prognostic factors for OS. In addition, ECOG performance status (PS) and the CRP-to-albumin ratio were not significant but were considered possible predictors for OS. Risk stratification according to the number of these risk factors could effectively stratify CRPC patients treated with docetaxel in terms of OS. Age, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS. ECOG PS and the CRP-to-albumin ratio were not significant, but were considered possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating overall survival.

Prognostic role of cardiac power index in ambulatory patients with advanced heart failure.

PubMed

Grodin, Justin L; Mullens, Wilfried; Dupont, Matthias; Wu, Yuping; Taylor, David O; Starling, Randall C; Tang, W H Wilson

2015-07-01

Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (<0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P < 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Atypical and Malignant Meningioma: Outcome and Prognostic Factors in 119 Irradiated Patients. A Multicenter, Retrospective Study of the Rare Cancer Network

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

Pasquier, David; Bijmolt, Stefan; Veninga, Theo

2008-08-01

Purpose: To retrospectively analyze and assess the outcomes and prognostic factors in a large number of patients with atypical and malignant meningiomas. Methods and Materials: Ten academic medical centers participating in this Rare Cancer Network contributed 119 cases of patients with atypical or malignant meningiomas treated with external beam radiotherapy (EBRT) after surgery or for recurrence. Eligibility criteria were histologically proven atypical or anaplastic (malignant) meningioma (World Health Organization Grade 2 and 3) treated with fractionated EBRT after initial resection or for recurrence, and age >18 years. Sex ratio (male/female) was 1.3, and mean ({+-}SD) age was 57.6 {+-} 12more » years. Surgery was macroscopically complete (Simpson Grades 1-3) in 71% of patients; histology was atypical and malignant in 69% and 31%, respectively. Mean dose of EBRT was 54.6 {+-} 5.1 Gy (range, 40-66 Gy). Median follow-up was 4.1 years. Results: The 5- and 10-year actuarial overall survival rates were 65% and 51%, respectively, and were significantly influenced by age >60 years (p = 0.005), Karnofsky performance status (KPS) (p = 0.01), and high mitotic rate (p = 0.047) on univariate analysis. On multivariate analysis age >60 years (p = 0.001) and high mitotic rate (p = 0.02) remained significant adverse prognostic factors. The 5- and 10-year disease-free survival rates were 58% and 48%, respectively, and were significantly influenced by KPS (p 0.04) and high mitotic rate (p = 0.003) on univariate analysis. On multivariate analysis only high mitotic rate (p = 0.003) remained a significant prognostic factor. Conclusions: In this multicenter retrospective study, age, KPS, and mitotic rate influenced outcome. Multicenter prospective studies are necessary to clarify the management and prognostic factors of such a rare disease.« less

Hypoparathyroidism after total thyroidectomy: prospective evaluation and relation with early hypocalcemia.

PubMed

D'Alessandro, Nicola; Tramutola, Giuseppe; Fasano, Giovanni Michele; Gilio, Francesco; Iside, Giovanni; Izzo, Maria Lucia; Loffredo, Andrea; Pici, Mariano; Pinto, Margherita; Tramontano, Salvatore; Citro, Giuseppe

2016-01-01

Definitive hypoparathyrodism (hypo-PTH) represents one of the most dangerous complication after total thyroidectomy. Partial or total lesion or accidental removal of parathyroid glands is an unpredictable adverse event, although real incidence is not well defined, such as management of this deficit. We started a prospective evaluation of patients treated with total thyroidectomy in our centre, to identify incidence of hypo-PTH, symptomatic or not, in relation to incidence of early postoperative hypocalcemia in our experience. We prospectively evaluated 177 patients treated for benign and malign pathology, measuring calcium before surgery and calcium and PTH at least three months after surgery. Postoperative hypocalcemia was observed in 37.3% of cases. Eight patients (4.5% of cohort) presented low level of PTH, at mean follow-up of 9.1 months. Positive predictive value for postoperative hypocalcemia was 12.1%, while negative predictive was 95.4%; confirming high sensitivity (100%) and low specificity (65.4%) for detecting hypo-PTH. All patients with late hypo-PTH presented hypocalcemia on early analysis, while no case with normal postoperative calcemia accounted with hypo-PTH: this may indicate calcemia as valid prognostic factor of good gland production, when is in the range. Moreover, isolated analysis is too limited to determine real predictability. Technical standardization represents the best method for prevention of hypo-PTH. Early hypocalcemia is a prognostic factor, even with a low specificity, of deficit of PTH-production. This observation must be related to other known prognostic factors. Postoperative normal calcemia should be a positive prognostic factor of an acceptable PTHfunction, supported by large cohorts. Hypocalcemia, Parathormone, Thyroidectomy.

Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation.

PubMed

Fenske, Timothy S; Ahn, Kwang W; Graff, Tara M; DiGilio, Alyssa; Bashir, Qaiser; Kamble, Rammurti T; Ayala, Ernesto; Bacher, Ulrike; Brammer, Jonathan E; Cairo, Mitchell; Chen, Andy; Chen, Yi-Bin; Chhabra, Saurabh; D'Souza, Anita; Farooq, Umar; Freytes, Cesar; Ganguly, Siddhartha; Hertzberg, Mark; Inwards, David; Jaglowski, Samantha; Kharfan-Dabaja, Mohamed A; Lazarus, Hillard M; Nathan, Sunita; Pawarode, Attaphol; Perales, Miguel-Angel; Reddy, Nishitha; Seo, Sachiko; Sureda, Anna; Smith, Sonali M; Hamadani, Mehdi

2016-07-01

For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non-relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS) <80, chemoresistance, autoHCT to alloHCT interval <1-year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS<80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS, including KPS<80 (4 points), autoHCT to alloHCT interval <1-year (2 points) and chemoresistant disease at alloHCT (5 points). This CIBMTR prognostic model classified patients into four groups: low-risk (0 points), intermediate-risk (2-5 points), high-risk (6-9 points) or very high-risk (11 points), predicting 3-year PFS of 40, 32, 11 and 6%, respectively, with 3-year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long-term survival with alloHCT after a failed prior autoHCT. © 2016 John Wiley & Sons Ltd.

Non-O blood groups can be a prognostic marker of in-hospital and long-term major adverse cardiovascular events in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Cetin, Mehmet Serkan; Ozcan Cetin, Elif Hande; Aras, Dursun; Topaloglu, Serkan; Temizhan, Ahmet; Kisacik, Halil Lutfi; Aydogdu, Sinan

2015-09-01

Recent studies have suggested ABO blood type locus as an inherited predictor of thrombosis, cardiovascular risk factors, myocardial infarction. However, data is scarce about the impact of non-O blood groups on prognosis in patients with ST-elevation myocardial infarction (STEMI). Therefore, we aimed to evaluate the prognostic importance of non-O blood groups in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI) METHODS: 1835 consecutive patients who were admitted with acute STEMI between 2010 and 2015 were included and followed-up for a median of 35.6months. The prevalence of hyperlipidemia, total cholesterol, LDL, peak CKMB and no-reflow as well as hospitalization duration were higher in patients with non-O blood groups. Gensini score did not differ between groups. During the in-hospital and long-term follow-up period, MACE, the prevalence of stent thrombosis, non-fatal MI, and mortality were higher in non-O blood groups. In multivariate logistic regression analysis, non-0 blood groups were demonstrated to be independent predictors of in-hospital (OR:2.085 %CI: 1.328-3.274 p=0.001) and long term MACE (OR:2.257 %CI: 1.325-3.759 p<0.001). Kaplan-Meier analysis according to the long-term MACE free survival revealed a higher occurrence of MACE in non-O blood group compared with O blood group (p<0.001, Chi-square: 22.810). Non-O blood groups were determined to be significant prognostic indicators of short- and long-term cardiovascular adverse events and mortality in patients with STEMI undergoing pPCI. In conjunction with other prognostic factors, evaluation of this parameter may improve the risk categorization and tailoring the individual therapy and follow-up in STEMI patient population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Additive prognostic value of interleukin-6 at peak phase of dobutamine stress echocardiography in patients with coronary artery disease. A 6-year follow-up study.

PubMed

Ikonomidis, Ignatios; Athanassopoulos, George; Stamatelopoulos, Kimon; Lekakis, John; Revela, Ioanna; Venetsanou, Kiriaki; Marinou, Margarita; Monaco, Claudia; Cokkinos, Dennis V; Nihoyannopoulos, Petros

2008-08-01

Interleukin-6 (IL-6) and tissue factor (TF) are elevated after myocardial ischemia during dobutamine stress echo (DSE). We examined the incremental prognostic value of IL-6 or TF measured during DSE over echocardiographic and clinical factors in patients with chronic coronary artery disease (CAD). We studied 106 patients with angiographically documented CAD. IL-6 and TF were measured at rest, peak, and during recovery. A wall motion score index was calculated. Fifty-seven (54%) patients had ischemia at DSE. During follow-up (63.7 +/- 20 months), 36 patients (33%) had an adverse event (12 cardiac deaths, 24 acute coronary events). Patients with events had a higher peak IL-6 (P = .02) but similar rest and recovery IL-6 than those without. Patients with peak IL-6 > or =3.14 pg/mL (upper tertile) had a hazard ratio of 2.7 (95% CI 1.44-5.37) (P < .01 for an adverse event). The addition of peak wall motion score index in a multivariable model including risk factors, ejection fraction, revascularization, and multivessel disease increased the model's c statistic from 0.66 to 0.70 (P = .04). The addition of peak IL-6 further increased the model's c statistic to 0.75 (P = .04). Tissue factor was not related with cardiac events. Interleuikin-6 levels measured during the peak phase of DSE incrementally contribute to risk stratification in patients with chronic CAD.

Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

PubMed

Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

2010-01-01

Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal dysfunction patients had 8.5-fold increased risk for adverse outcomes. Although IC is often self-limited, our data warrants special attention and aggressive therapy in treating these patients.

Prognostic significance of KIT exon 11 deletion mutation in intermediate-risk gastrointestinal stromal tumor.

PubMed

Quek, Richard; Farid, Mohamad; Kanjanapan, Yada; Lim, Cindy; Tan, Iain Beehuat; Kesavan, Sittampalam; Lim, Tony Kiat Hon; Oon, Lynette Lin-Ean; Goh, Brian Kp; Chan, Weng Hoong; Teo, Melissa; Chung, Alexander Yf; Ong, Hock Soo; Wong, Wai Keong; Tan, Patrick; Yip, Desmond

2017-06-01

Benefit of adjuvant imatinib therapy following curative resection in patients with intermediate-risk gastrointestinal stromal tumor (GIST) is unclear. GIST-specific exon mutations, in particular exon 11 deletions, have been shown to be prognostic. We hypothesize that specific KIT mutations may improve risk stratification in patients with intermediate-risk GIST, identifying a subgroup of patients who may benefit from adjuvant therapy. In total, 142 GIST patients with complete clinicopathologic and mutational data from two sites were included. Risk classification was based on the modified National Institute of Health (NIH) criteria. In this cohort, 74% (n = 105) of patients harbored a KIT mutation; 61% (n = 86) were found in exon 11 of which nearly 70% were KIT exon 11 deletions (n = 60). A total of 18% (n = 25) of cases were classified as having intermediate-risk disease. Univariate analysis confirmed tumor size, mitotic index, nongastric origin, presence of tumor rupture and modified NIH criteria were adversely prognostic for relapse-free survival (RFS). Among KIT/PDGFRA mutants, KIT exon 11 deletions had a significantly worse prognosis (hazard ratio 2.31; 95% confidence interval, 1.30-4.10; P = 0.003). Multivariate analysis confirmed KIT exon 11 deletion (P = 0.003) and clinical risk classification (P < 0.001) as independent adverse prognostic factors for RFS. Intermediate-risk patients harboring KIT exon 11 deletions had RFS outcomes similar to high-risk patients. The presence of KIT exon 11 deletion mutation in patients with intermediate-risk GIST is associated with an inferior clinical outcome with RFS similar to high-risk patients. © 2016 John Wiley & Sons Australia, Ltd.

Association of maternal serum PAPP-A levels, nuchal translucency and crown-rump length in first trimester with adverse pregnancy outcomes: retrospective cohort study.

PubMed

Bilagi, Ashwini; Burke, Danielle L; Riley, Richard D; Mills, Ian; Kilby, Mark D; Katie Morris, R

2017-07-01

Are first trimester serum pregnancy-associated plasma protein-A (PAPP-A), nuchal translucency (NT) and crown-rump length (CRL) prognostic factors for adverse pregnancy outcomes? Retrospective cohort, women, singleton pregnancies (UK 2011-2015). Unadjusted and multivariable logistic regression. small for gestational age (SGA), pre-eclampsia (PE), preterm birth (PTB), miscarriage, stillbirth, perinatal mortality and neonatal death (NND). A total of 12 592 pregnancies: 852 (6.8%) PTB, 352 (2.8%) PE, 1824 (14.5%) SGA, 73 (0.6%) miscarriages, 37(0.3%) stillbirths, 73 perinatal deaths (0.6%) and 38 (0.30%) NND. Multivariable analysis: lower odds of SGA [adjusted odds ratio (aOR) 0.88 (95% CI 0.85,0.91)], PTB [0.92 (95%CI 0.88,0.97)], PE [0.91 (95% CI 0.85,0.97)] and stillbirth [0.71 (95% CI 0.52,0.98)] as PAPP-A increases. Lower odds of SGA [aOR 0.79 (95% CI 0.70,0.89)] but higher odds of miscarriage [aOR 1.75 95% CI (1.12,2.72)] as NT increases, and lower odds of stillbirth as CRL increases [aOR 0.94 95% CI (0.89,0.99)]. Multivariable analysis of three factors together demonstrated strong associations: a) PAPP-A, NT, CRL and SGA, b) PAPP-A and PTB, c) PAPP-A, CRL and PE, d) NT and miscarriage. Pregnancy-associated plasma protein-A, NT and CRL are independent prognostic factors for adverse pregnancy outcomes, particularly PAPP-A and SGA with lower PAPP-A associated with increased risk. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

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

Bhatia, Sumita; Miller, Robert C.; Haddock, Michael G.

2006-10-01

Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis includedmore » lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.« less

Hypoglycorrhachia in Adults with Community-Acquired Meningitis: Etiologies and Prognostic Significance

PubMed Central

Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

2015-01-01

Study objectives Hypoglycorrhachia (CSF glucose < 45mg/dL) has been identified as a prognostic factor in patients with meningitis. We analyzed the differential diagnosis of hypoglycorrhachia and its clinical significance. Methods Retrospective study of 620 adult patients with community acquired meningitis [CSF WBC >5 cells/mm3, absence of a CSF shunt or recent neurosurgical procedure (< 1 month)] at 8 Memorial Hermann Hospitals in Houston, TX from January, 2005 to December, 2010. An adverse clinical outcome was defined as a Glasgow outcome scale of 4 or less. Results Out of 620 patients with meningitis, 116 (19%) had hypoglycorrachia. Etiologies of hypoglycorrhachia were idiopathic (40), bacterial (27), cryptococcal (26), viral (15), and tuberculous (4). Patients with hypoglycorrachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status and focal neurological deficits compared to those patients without hypoglycorrachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions and abnormal cranial imaging (p<005). Furthermore, patients with hypoglycorrachia had more adverse clinical outcomes [26 out of 116 (22.4%) vs. 45 out of 504 (8.9%)] (p< 0.001). Conclusion Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis. PMID:26299186

Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer. Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy

PubMed Central

Maiorano, Eugenio; Regan, Meredith M.; Viale, Giuseppe; Mastropasqua, Mauro G.; Colleoni, Marco; Castiglione-Gertsch, Monica; Price, Karen N.; Gelber, Richard D.; Goldhirsch, Aron; Coates, Alan S.

2013-01-01

Purpose A minority of early invasive breast cancers show a pattern of central necrosis and fibrosis (CNF). Previous studies have documented an adverse prognostic impact and association with other adverse pathological features, but its predictive importance for therapy selection is unknown. Methods We examined the prognostic and predictive value of CNF in two randomized clinical trials comparing chemoendocrine therapy with endocrine therapy alone in patients with node-negative breast cancer. A total of 1850 patients randomly assigned to treatment groups comparing endocrine with chemoendocrine therapy, and with centrally-assessed CNF, ER, PgR and HER2 were included in the analytic cohort. The median follow up was 10 years. Results CNF was present in 84 of 1850 trial patients (4.5%). It was associated with tumor characteristics suggesting poor outcome, but was an independent adverse factor for disease-free survival. In the presence of CNF outcome was worse regardless of tumor grade, whereas in the absence of CNF, patients with grade 3 tumors had poorer outcome than those with grade 1-2 tumors. Among patients with estrogen receptor-absent tumors chemoendocrine therapy was superior to endocrine therapy alone only in the absence of CNF [HR (chemoendocrine:endocrine)=0.46 in CNF-absent, 0.90 in CNF-present], while among those with receptor-positive disease chemoendocrine therapy was beneficial only in the presence of CNF [HR=0.34 CNF-present, 0.96 CNF-absent]. Conclusion The results suggest that the presence of CNF reflects a biological difference in early breast cancer that is important in modulating the efficacy of standard therapies. Accordingly we believe that its presence should be routinely reported. PMID:19280340

Prognostic significance of interventricular septal thickness in patients with AL amyloidosis.

PubMed

Cho, Hyunsoo; Kim, Soo-Jeong; Shim, Chi Young; Hong, Geu-Ru; Ha, Jong-Won; Kim, Yu Ri; Yang, Woo Ick; Chung, Haerim; Jang, Ji Eun; Cheong, June-Won; Min, Yoo Hong; Kim, Jin Seok

2017-09-01

The major prognostic determinant of immunoglobulin light chain (AL) amyloidosis is cardiac involvement. However, the role of interventricular septal thickness (IVST), which reflects the extent of cardiac involvement, remains unclear. Therefore, we analyzed 77 patients with newly diagnosed AL amyloidosis and evaluated the prognostic role of IVST. Fifty patients (64.9%) had cardiac involvement and 17 patients (22.1%) showed IVST >15mm. Among all patients, the revised Mayo Clinic Stage III-IV and IVST >15mm were independently associated with inferior overall survival (OS) in a multivariable analysis. IVST >15mm was also adversely prognostic for OS in a subgroup of advanced-stage (revised Mayo Clinic stage III-IV) patients in a multivariable analysis (P<0.001). Furthermore, advanced-stage patients with IVST >15mm did not show survival benefit from treatment with bortezomib-based regimens and/or autologous stem-cell transplantation (ASCT). Our study demonstrated that IVST >15mm is adversely prognostic independent of the revised Mayo Clinic staging system in patients with AL amyloidosis. In addition, the degree of IVST might be used as a useful prognostic indicator that can guide the management of patients with AL amyloidosis especially at an advanced stage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intrahepatic cholangiocarcinoma prognostic determination using pre-operative serum C-reactive protein levels.

PubMed

Lin, Zi-Ying; Liang, Zhen-Xing; Zhuang, Pei-Lin; Chen, Jie-Wei; Cao, Yun; Yan, Li-Xu; Yun, Jing-Ping; Xie, Dan; Cai, Mu-Yan

2016-10-12

Serum C-reactive protein (CRP), an acute inflammatory response biomarker, has been recognized as an indicator of malignant disease progression. However, the prognostic significance of CRP levels collected before tumor removal in intrahepatic cholangiocarcinoma requires further investigation. We sampled the CRP levels in 140 patients with intrahepatic cholangiocarcinoma who underwent hepatectomies with regional lymphadenectomies between 2006 and 2013. A retrospective analysis of the clinicopathological data was performed. We focused on the impact of serum CRP on the patients' cancer-specific survival and recurrence-free survival rates. High levels of preoperative serum CRP were significantly associated with well-established clinicopathologic features, including gender, advanced tumor stage, and elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P < 0.05). Univariate analysis demonstrated a significant association between high levels of serum CRP and adverse cancer-specific survival (P = 0.001) and recurrence-free survival (P < 0.001). In patients with stage I/II intrahepatic cholangiocarcinoma, the serum CRP level was a prognostic indicator for cancer-specific survival. In patients with stage I/II or stage III/IV, the serum CRP level was a prognostic indicator for recurrence-free survival (P < 0.05). Additionally, multivariate analysis identified serum CRP level in intrahepatic cholangiocarcinoma as an independent prognostic factor (P < 0.05). We confirmed a significant association of elevated pre-operative CRP levels with poor clinical outcomes for the tested patients with intrahepatic cholangiocarcinoma. Our results indicate that the serum CRP level may represent a useful factor for patient stratification in intrahepatic cholangiocarcinoma management.

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

PubMed Central

Han, Donghee; Hartaigh, Bríain Ó; Gransar, Heidi; Lee, Ji Hyun; Rizvi, Asim; Baskaran, Lohendran; Schulman-Marcus, Joshua; Dunning, Allison; Achenbach, Stephan; Al-Mallah, Mouaz H; Berman, Daniel S; Budoff, Matthew J; Cademartiri, Filippo; Maffei, Erica; Callister, Tracy Q; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp A; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Kim, Yong-Jin; Leipsic, Jonathon; Feuchtner, Gudrun; Cury, Ricardo C; Pontone, Gianluca; Andreini, Daniele; Marques, Hugo; Rubinshtein, Ronen; Hindoyan, Niree; Jones, Erica C; Gomez, Millie; Lin, Fay Y; Chang, Hyuk-Jae; Min, James K

2018-01-01

Abstract Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1–49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18–41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults. PMID:28977374

Community-Acquired Meningitis in Older Adults: Clinical Features, Etiology, and Prognostic Factors

PubMed Central

Wang, Amy Y.; Machicado, Jorge D.; Khoury, Nabil T.; Wootton, Susan H.; Salazar, Lucrecia; Hasbun, Rodrigo

2014-01-01

Background Bacterial meningitis in older adults is a well-studied and serious disease, but few studies have investigated the epidemiology and outcomes of community-acquired meningitis in older adults. Methods We conducted a retrospective study of 619 adults in Houston, Texas, with community-acquired meningitis hospitalized between January 1, 2005, and January 1, 2010. Patients were categorized as older if age ≥65 (N=54) and younger if age 18–64 (N=565). An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Results Older patients consisted of 8.7% (54/619) of the total cohort and had higher rates of comorbidities, abnormal neurological and laboratory findings, abnormalities on computed tomography and magnetic resonance imaging of the head and adverse clinical outcomes (ACO) (p<0.05). The majority of patients (65.8%) had meningitis of unknown etiology. Bacterial meningitis was an infrequent cause (7.4%). Of the known causes, bacterial meningitis and West Nile virus were more common in older patients. In contrast, younger patients more frequently had cryptococcal and viral meningitis. On logistic regression, female gender was predictive of a poor outcome in the older patients, whereas abnormal neurologic exam, fever, and CSF glucose <45mg/dLwere significant poor prognostic factors in younger patients (p<0.05). Conclusion Most cases of community-acquired meningitis are of unknown origin. Older patients are more likely to have bacterial meningitis and West Nile virus infection when a cause can be identified. They also have more neurologic abnormalities, laboratory and imaging abnormalities, as well as adverse clinical outcomes. PMID:25370434

BIOBEHAVIORAL PROGNOSTIC FACTORS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: Results from the INSPIRE-II Trial

PubMed Central

Blumenthal, James A.; Smith, Patrick J.; Durheim, Michael; Mabe, Stephanie; Emery, Charles F.; Martinu, Tereza; Diaz, Philip T.; Babyak, Michael; Welty-Wolf, Karen; Palmer, Scott

2015-01-01

Objective To examine the prognostic value of select biobehavioral factors in patients with chronic obstructive pulmonary disease (COPD) in a secondary analysis of participants from the INSPIRE-II trial. Methods Three hundred twenty six outpatients with COPD underwent assessments of pulmonary function, physical activity, body mass index, inflammation, pulmonary symptoms, depression, and pulmonary quality of life, and were followed for up to 5.4 years for subsequent clinical events. The prognostic value of each biobehavioral factor, considered individually and combined, also was examined in the context of existing Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 risk stratification. Results Sixty-nine individuals experienced a hospitalization or died over a mean follow-up time period of 2.4 (interquartile range = 1.6) years. GOLD classification was associated with an increased risk of clinical events (HR = 2.72 [95% CI 1.63, 4.54], per stage); Six Minute Walk (HR = 0.50 [0.34, 0.73] per 500 feet), total steps (HR = 0.82 [0.71, 0.94] per 1,000 steps), hsC-reactive protein (HR = 1.44 [1.01, 2.06] per 4.5 mg/L), depression (HR = 1.12 [1.01, 1.25] per 4 points), and pulmonary quality of life (HR = 1.73 [1.14, 2.63] per 25 points) were each predictive over and above the GOLD assessment. However, only GOLD group and Six Minute Walk were predictive of all-cause mortality and COPD hospitalization when all biobehavioral variables were included together in a multivariable model. Conclusion Biobehavioral factors provide added prognostic information over and above measures of COPD severity in predicting adverse events in patients with COPD. PMID:26780299

Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: results from a prospective study with long-term follow-up.

PubMed

Ding, Chao; Fan, Wenting; Gu, Lili; Tian, Hongliang; Ge, Xiaolong; Gong, Jianfeng; Nie, Yongzhan; Li, Ning

2018-05-01

Gut microbiota may contribute to regulate colonic motility, which is involved in the etiology of constipation. Fecal microbiota transplantation (FMT) has been demonstrated to restore intestinal homeostasis. The aim of this study was to evaluate the clinical outcomes and prognostic factors of FMT for the treatment of slow transit constipation (STC). Fifty-two patients with STC received standardized FMT and were followed up for 6 months. Bowel habit, colonic transit time, constipation-related symptoms (PAC-SYM score), quality of life (PAC-QOL score), treatment satisfaction scores and adverse events were monitored. The primary efficacy endpoint was the proportion of patients having on average three or more complete spontaneous bowel movements (CSBMs) per week. The primary efficacy endpoint was achieved in 50.0%, 38.5% and 32.7% of patients over week intervals 3-4, 9-12 and 21-24, respectively ( P  < 0.01 for all comparisons). Significant improvements were also observed in other bowel movement assessments, colonic transit time, constipation-related symptoms and quality of life; but all improvements diminished at weeks 12 and 24. Incompleteness of evacuation served as the only factor associated with efficacy. No serious treatment-related adverse events were observed. This study suggested FMT was effective and safe for STC, while a late loss of efficacy was also observed. A lower degree of sensation of incompleteness predicted a better outcome.

[Usefulness of scoring risk for adverse outcomes in older patients with the Identification of Seniors at Risk scale and the Triage Risk Screening Tool: a meta-analysis].

PubMed

Rivero-Santana, Amado; Del Pino-Sedeño, Tasmania; Ramallo-Fariña, Yolanda; Vergara, Itziar; Serrano-Aguilar, Pedro

2017-02-01

A considerable proportion of the geriatric population experiences unfavorable outcomes of hospital emergency department care. An assessment of risk for adverse outcomes would facilitate making changes in clinical management by adjusting available resources to needs according to an individual patient's risk. Risk assessment tools are available, but their prognostic precision varies. This systematic review sought to quantify the prognostic precision of 2 geriatric screening and risk assessment tools commonly used in emergency settings for patients at high risk of adverse outcomes (revisits, functional deterioration, readmissions, or death): the Identification of Seniors at Risk (ISAR) scale and the Triage Risk Screening Tool (TRST). We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and SCOPUS, with no date limits, to find relevant studies. Quality was assessed with the QUADAS-2 checklist (for quality assessment of diagnostic accuracy studies). We pooled data for prognostic yield reported for the ISAR and TRST scores for each short- and medium-term outcome using bivariate random-effects modeling. The sensitivity of the ISAR scoring system as a whole ranged between 67% and 99%; specificity fell between 21% and 41%. TRST sensitivity ranged between 52% and 75% and specificity between 39% and 51%.We conclude that the tools currently used to assess risk of adverse outcomes in patients of advanced age attended in hospital emergency departments do not have adequate prognostic precision to be clinically useful.

NEDD9, an independent good prognostic factor in intermediate-risk acute myeloid leukemia patients

PubMed Central

Pallarès, Victor; Hoyos, Montserrat; Chillón, M. Carmen; Barragán, Eva; Conde, M. Isabel Prieto; Llop, Marta; Céspedes, María Virtudes; Nomdedeu, Josep F.; Brunet, Salut; Sanz, Miguel Ángel; González-Díaz, Marcos; Sierra, Jorge; Casanova, Isolda; Mangues, Ramon

2017-01-01

Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated. Nevertheless, previous work has established an important role for the CAS family members NEDD9 or BCAR1 in the migratory and dissemination capacities of myeloid cells. On this basis, we hypothesized that NEDD9 or BCAR1 expression levels could associate with survival in IR-AML patients and become new prognostic markers. To that purpose, we assessed BCAR1 and NEDD9 gene expression in a cohort of 73 adult AML patients validating the results in an independent cohort (n = 206). We have identified NEDD9, but not BCAR1, as a new a marker for longer overall and disease-free survival, and for lower cumulative incidence of relapse. In summary, NEDD9 gene expression is an independent prognostic factor for favourable prognosis in IR-AML patients. PMID:29100287

High clinical and morphologic response using 90Y-DOTA-octreotate sequenced with 177Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours.

PubMed

Kong, Grace; Callahan, Jason; Hofman, Michael S; Pattison, David A; Akhurst, Tim; Michael, Michael; Eu, Peter; Hicks, Rodney J

2017-03-01

Bulky disease is an adverse prognostic factor for 177 Lu-DOTA-octreotate ( 177 Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). 90 Y-DOTA-octreotate ( 90 Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than 177 Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of 90 Y-DOTATATE followed by 2-3 cycles of 177 Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq 90 Y-DOTATATE, and 21 GBq 177 Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with 90 Y -DOTATATE followed by 177 Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either agent used alone or other approved treatments, particularly given the adverse prognostic features of this cohort.

Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and prognostic significance.

PubMed

Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

2015-10-01

Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose <45 mg/dl) has been identified as a prognostic factor in patients with meningitis. The differential diagnosis of hypoglycorrhachia and its clinical significance was analyzed in the present study. This was a retrospective study of 620 adult patients with community-acquired meningitis (CSF white blood cell count >5 × 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (<1 month)) at eight Memorial Hermann hospitals in Houston, Texas, from January 2005 to December 2010. An adverse clinical outcome was defined as a Glasgow outcome scale score of ≤ 4. Out of 620 patients with meningitis, 116 (19%) had hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40), bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4). Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status, and focal neurological deficits compared to those patients without hypoglycorrhachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions, and abnormal cranial imaging (p<0.05). Furthermore, patients with hypoglycorrhachia had more adverse clinical outcomes (26/116 (22.4%) vs. 45/504 (8.9%); p<0.001). Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole.

PubMed

Viale, Giuseppe; Giobbie-Hurder, Anita; Regan, Meredith M; Coates, Alan S; Mastropasqua, Mauro G; Dell'Orto, Patrizia; Maiorano, Eugenio; MacGrogan, Gaëtan; Braye, Stephen G; Ohlschlegel, Christian; Neven, Patrick; Orosz, Zsolt; Olszewski, Wojciech P; Knox, Fiona; Thürlimann, Beat; Price, Karen N; Castiglione-Gertsch, Monica; Gelber, Richard D; Gusterson, Barry A; Goldhirsch, Aron

2008-12-01

To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.

Prognostic value of tripartite motif containing 29 expression in patients with gastric cancer following surgical resection.

PubMed

Wang, Chenghu; Zhou, Yi; Chen, Beibei; Yuan, Weiwei; Huang, Jinxi

2018-04-01

Tripartite motif containing 29 (TRIM29) dysregulation serves an important function in the progression of numerous types of cancer, but its function in the prognosis of patients with gastric cancer remains unknown. The present study assessed the prognostic value of TRIM29 in patients with gastric cancer following surgical resection. A total of 243 fresh gastric adenocarcinoma and adjacent normal tissues were continuously retrieved from patients who underwent curative surgery for gastric cancer at the Cancer Hospital of Henan Province (Zhengzhou, China) between January 2005 and December 2011. The reverse transcription-quantitative polymerase chain reaction was performed to assess TRIM29 expression. The association between TRIM29 expression and clinicopathological features and prognosis was subsequently evaluated. The results of the present study revealed that the expression of TRIM29 was increased in the gastric cancer tissues compared with the normal adjacent tissues, and that upregulated expression of TRIM29 was associated with tumor cell differentiation, tumor stage, lymph node metastasis, and tumor-node-metastasis (TNM) stage. In the training and validation data, high TRIM29 expression was associated with poor overall survival in patients with gastric cancer. Furthermore, multivariate analysis identified that TRIM29 expression was an independent prognostic factor for overall survival, in addition to TNM stage and Lauren classification. Combining TRIM29 expression with the TNM staging system generated a novel predictive model that exhibited improved prognostic accuracy for overall survival in patients with gastric cancer. The present study revealed that TRIM29 was an independent adverse prognostic factor in patients with gastric cancer. Incorporating TRIM29 expression level into the TNM staging system may improve risk stratification and render prognosis more accurate in patients with gastric cancer.

Value of the prognostic nutritional index in advanced gastric cancer treated with preoperative chemotherapy.

PubMed

Sun, Jianyi; Wang, Donghai; Mei, Ying; Jin, Hailong; Zhu, Kankai; Liu, Xiaosun; Zhang, Qing; Yu, Jiren

2017-03-01

The prognostic nutritional index (PNI) is a useful parameter indicating the immune and nutritional status of cancer patients; this study investigated the prognostic value of the PNI in advanced gastric cancer patients treated with preoperative chemotherapy. We retrospectively reviewed 117 advanced gastric cancer patients who met the inclusion criteria for preoperative chemotherapy and underwent surgical resection from July 2004 to December 2011. The patients were divided into PNI-high (PNI ≥ 45) and PNI-low (PNI < 45) groups. Clinicopathologic features, chemotherapy adverse events, and surgical complications were compared between the prechemotherapy PNI-high and PNI-low groups using the chi-square test. Survival analysis was performed using the Kaplan-Meier method and log-rank test. The Cox proportional hazard model was used to identify prognostic factors. Overall survival was better in the prechemotherapy PNI-high group than in the PNI-low group (hazard ratio [HR] = 2.237, 95% confidence interval [CI]: 1.271-3.393, P = 0.005), while there was no significant difference in Overall survival between the postchemotherapy PNI-high and PNI-low groups (P > 0.05). Cox regression analysis indicated that yield pathologic T (ypT), yield pathologic N (ypN) stage, and prechemotherapy PNI were independent prognostic factors (ypT: HR = 2.914, 95% CI = 1.312-6.470, P = 0.009; ypN: HR = 4.909, 95% CI = 1.764-13.660, P = 0.003; prechemotherapy PNI: HR = 1.963, 95% CI = 1.101-3.499, P = 0.022). The prechemotherapy PNI is a useful predictor of the long-term outcome of patients with advanced gastric cancer treated with preoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of Stage and Clinical/Prognostic Factors for Lung Cancer from SEER Registries: AJCC Staging and Collaborative Stage Data Collection System

PubMed Central

Chen, Vivien W.; Ruiz, Bernardo A.; Hsieh, Mei-Chin; Wu, Xiao-Cheng; Ries, Lynn; Lewis, Denise R.

2014-01-01

Introduction The American Joint Committee on Cancer (AJCC) 7th edition introduced major changes in the staging of lung cancer, including Tumor (T), Node (N), Metastasis (M) (TNM) system and new stage/prognostic site-specific factors (SSFs), collected under the Collaborative Stage Version 2 (CSv2) Data Collection System. The intent was to improve the stage precision which could guide treatment options and ultimately lead to better survival. This report examines stage trends, the change in stage distributions from the AJCC 6th to the 7th edition, and findings of the prognostic SSFs for 2010 lung cancer cases. Methods Data were from the November 2012 submission of 18 Surveillance, Epidemiology, and End Results (SEER) Program population-based registries. A total of 344 797 cases of lung cancer, diagnosed in 2004–2010, were analyzed. Results The percentages of small tumors and early stage lung cancer cases increased from 2004 to 2010. The AJCC 7th edition, implemented for 2010 diagnosis year, subclassified tumor size and reclassified multiple tumor nodules, pleural effusions, and involvement of tumors in the contralateral lung, resulting in a slight decrease in stage IB and stage IIIB and a small increase in stage IIA and stage IV. Overall about 80% of cases remained the same stage group in AJCC 6th and 7th editions. About 21% of lung cancer patients had separate tumor nodules in the ipsilateral (same) lung, and 23% of the surgically resected patients had visceral pleural invasion, both adverse prognostic factors. Conclusion It is feasible for high quality population-based registries such as the SEER Program to collect more refined staging and prognostic SSFs that allows better categorization of lung cancer patients with different clinical outcomes and to assess their survival. PMID:25412390

Age distribution and age-related outcomes of olfactory neuroblastoma: a population-based analysis.

PubMed

Yin, Zhenzhen; Wang, Youyou; Wu, Yuemei; Zhang, Ximei; Wang, Fengming; Wang, Peiguo; Tao, Zhen; Yuan, Zhiyong

2018-01-01

The objective of the study was to describe the age distribution and to evaluate the role of prognostic value of age on survival in patients diagnosed with olfactory neuroblastoma (ONB). A population-based retrospective analysis was conducted. The population-based study of patients in the Surveillance, Epidemiology, and End Results (SEER) tumor registry, who were diagnosed with ONB from 1973 to 2014, were retrospectively analyzed. The cohort included 876 patients with a median age of 54 years. There was a unimodal distribution of age and ONBs most frequently occurred in the fifth to sixth decades of life. Kaplan-Meier analysis demonstrated overall survival (OS) and cancer-specific survival (CSS) rates of 69% and 78% at 5 years. Multivariable Cox regression analysis showed that age, SEER stage, and surgery were independent prognostic factors for CSS. The risk of overall death and cancer-specific death increased 3.1% and 1.6% per year, respectively. Patients aged >60 years presented significantly poor OS and CSS compared with patients aged ≤60 years, even in patients with loco-regional disease or in those treated with surgery. This study highlights the growing evidence that there is a unimodal age distribution of ONB and that age is an important adverse prognostic factor.

Prognostic significance of smoking in addition to established risk factors in patients with Dukes B and C colorectal cancer: a retrospective analysis.

PubMed

Diamantis, N; Xynos, I D; Amptulah, S; Karadima, M; Skopelitis, H; Tsavaris, N

2013-01-01

To investigate the prognostic significance of smoking in addition to established risk factors in patients with Dukes stage B and C colorectal cancer (CRC). 291 consecutive non-selected CRC patients were studied retrospectively. Twenty-three variables were examined using a regression statistical model to identify relevant prognostic factors related to disease free survival (DFS) and overall survival (OS). On multivariate analysis DFS was found to be negatively affected in patients with a smoking history of ≤10 pack-years vs. non-smokers (p<0.016). Additionally, performance status (PS)<90 (p<0.001), Dukes stage C (p<0.001) and elevated tumor markers (p<0.001) at the time of diagnosis were found to adversely affect DFS. Smoking also had a significant association with relapse. Patients with a smoking history of ≤10 pack-years had 2.45 (p<0.018) higher risk of recurrence compared to patients with no smoking history. OS was influenced by Karnofsky performance status (PS), Dukes stage, and elevated tumor markers. In particular patients with PS< 90 had a 4.69-fold higher risk of death (p<0.001) than patients with better PS. Stage C disease was associated with 2.27-fold higher risk of death (p<0.001) than stage B disease, and patients with elevated tumor markers at the time of diagnosis had 2.74-fold higher risk of death (p<0.014) when compared to those whose tumor markers were normal at presentation. Our study associates smoking and relapse incidence in non-clinical- trial CRC patients and reiterates the prognostic significance of PS, stage and tumor markers at the time of diagnosis.

Comprehensive analysis and validation of contemporary survival prognosticators in Korean patients with metastatic renal cell carcinoma treated with targeted therapy: prognostic impact of pretreatment neutrophil-to-lymphocyte ratio.

PubMed

Koo, Kyo Chul; Lee, Kwang Suk; Cho, Kang Su; Rha, Koon Ho; Hong, Sung Joon; Chung, Byung Ha

2016-06-01

In line with the era of targeted therapy (TT), an increasing number of prognosticators are becoming available for patients with metastatic renal cell carcinoma (mRCC). Here, potential prognosticators of cancer-specific survival (CSS) were identified based on the contemporary literature and were comprehensively validated in an independent cohort of patients treated for mRCC. Data were collected from 478 patients treated with TT for mRCC between January 1999 and July 2013 at a single institution. The analysis included 25 clinicopathological covariates that included both traditional and contemporary prognosticators. Multivariate Cox regression models were used to quantify the effect of covariates on CSS. Median survival from the initial diagnosis of metastasis was 24.5 (IQR, 11.5-55.7) months. There were 303 (63.4 %) cancer-specific deaths, yielding a 2-year CSS rate of 62.5 %. Low Karnofsky performance status (KPS), hypercalcemia, neutrophil-to-lymphocyte ratio (NLR), the number of metastatic sites (≥2), and the presence of brain metastases were independent adverse prognosticators of CSS. The C-index of the model was 0.78. Patients with at least one adverse prognosticator demonstrated lower 2-year CSS rates compared to those with no prognosticators (53.9 vs. 70.6 %; log rank p < 0.001). Together with traditional prognosticators such as KPS, hypercalcemia, and the number and location of metastases, the NLR was an independent predictor of CSS in patients with mRCC treated with TT. Our findings could be useful for guiding clinical decision making including stratification of patients for TT and inclusion in clinical trials.

Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI.

PubMed

Delgado, Julio; Doubek, Michael; Baumann, Tycho; Kotaskova, Jana; Molica, Stefano; Mozas, Pablo; Rivas-Delgado, Alfredo; Morabito, Fortunato; Pospisilova, Sarka; Montserrat, Emili

2017-04-01

Rai and Binet staging systems are important to predict the outcome of patients with chronic lymphocytic leukemia (CLL) but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients' outcome. We devised a biomarkers-only CLL prognostic system based on the two most important prognostic parameters in CLL (i.e., IGHV mutational status and fluorescence in situ hybridization [FISH] cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV + no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either unmutated IGHV or adverse FISH cytogenetics) and (3) high-risk (unmutated IGHV + adverse FISH cytogenetics). In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76%-88%), 52% (45%-62%), and 27% (17%-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials. © 2017 Wiley Periodicals, Inc.

Sarcopenia is a risk factor for complications and an independent predictor of hospital length of stay in trauma patients.

PubMed

DeAndrade, James; Pedersen, Mark; Garcia, Luis; Nau, Peter

2018-01-01

Sarcopenia is an independent risk factor for adverse outcomes in critically ill patients. The impact of sarcopenia on morbidity and length of stay in a trauma population has not been completely defined. This project evaluated the influence of sarcopenia on patients admitted to the trauma service. A retrospective review of 778 patients presenting as a trauma alert at a single institution from 2012-2014 was completed. Records were abstracted for comorbidities and hospital complications. The Hounsfield Unit Area Calculation was collected from admission computed tomography scans. Criteria for sarcopenia were based on the lowest 25th percentile of muscle density measurements. Relationships to patient outcomes were evaluated by univariate and multivariable regression or analyses of variance, when applicable. A total of 432 (55.6%) patients suffered a complication. Sarcopenia was associated with overall complications (P < 0.0001, relative risk 2.54, confidence interval 1.78-3.61) and was an independent risk factor for catheter-associated urinary tract infections (P = 0.011), wound infections (P = 0.011), need for reintubation (P = 0.0062), and length of hospitalization (P = 0.0007). Incorporating sarcopenia into a novel length of stay calculator showed increased prognostic ability for prolonged length of stay over Abbreviated Injury Scale alone (P = 0.0002). Sarcopenia is an independent risk factor for adverse outcomes and increased length of stay in trauma patients. Prognostic algorithms incorporating sarcopenia better predict hospital length of stay. Identification of patients at risk may allow for targeted interventions early in the patient's hospital course. Copyright © 2017 Elsevier Inc. All rights reserved.

FDG-PET/CT at the end of immuno-chemotherapy in follicular lymphoma: the prognostic role of the ratio between target lesion and liver SUVmax (rPET).

PubMed

Annunziata, Salvatore; Cuccaro, Annarosa; Tisi, Maria Chiara; Hohaus, Stefan; Rufini, Vittoria

2018-06-01

To retrospectively investigate the prognostic role of the ratio between target lesion and liver SUV max (rPET) in patients with follicular lymphoma (FL) submitted to FDG-PET/CT at the end of immuno-chemotherapy (PI-PET), and to compare rPET with International Harmonization Project criteria (IHP), Deauville Score (5p-DS) and FL International Prognostic Index at diagnosis (FLIPI). Eighty-nine patients with FL undergoing PI-PET were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point of rPET with respect to 5-years progression free survival (PFS). The prognostic significance of rPET was compared with IHP, DS and FLIPI. Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of adverse events as gold standard. The ROC analysis for rPET as predictor of progression showed an optimal rPET cut-point of 0.98. Patients with positive values of IHP, DS and rPET had a PFS of 50, 30 and 31%. PPV were of 56, 80 and 80%, NPV of 83, 86 and 88%, respectively. DS and rPET differed only in two patients. FLIPI was not predictive of progression and relapse. rPET is a prognostic factor in patients with FL submitted to PI-PET. Although it has a similar prognostic power as DS, it can have methodological advantages over visual analysis. PI-PET with different evaluation systems has a stronger prognostic power than FLIPI at diagnosis, so it could be useful to identify patients with FL at risk for early relapse after immuno-chemotherapy.

Fasting blood glucose is a novel prognostic indicator for extranodal natural killer/T-cell lymphoma, nasal type

PubMed Central

Cai, Q; Luo, X; Liang, Y; Rao, H; Fang, X; Jiang, W; Lin, T; Lin, T; Huang, H

2013-01-01

Background: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease with poor prognosis, requiring risk stratification. However, the prognosis of ENKTL is not fully defined and needs supplementation. We hypothesised that fasting blood glucose (FBG) may be a new prognostic factor for ENKTL. Methods: We retrospectively analysed 130 patients newly diagnosed with ENKTL. Results: Both univariate analysis and multivariate analysis revealed that FBG >100 mg dl−1 was associated with a poor outcome. Patients with FBG >100 mg dl−1 at diagnosis had more adverse clinical features, achieved lower complete remission rates (P=0.003) and had worse overall survival (P<0.001) and progression-free survival (P<0.001) compared with low-FBG patients. Measurement of FBG was helpful in differentiating between low-risk patients using the International Prognostic Index (IPI) and Prognosis Index for peripheral T-cell lymphoma (PIT) scoring and patients in a different category using the Korean Prognostic Index (KPI) scores with different survival outcomes (P<0.05). Conclusion: Our data suggest that measuring FBG levels at diagnosis is a novel, independent predictor of prognosis in ENKTL and helps to distinguish low-risk patients with poor survival, and this holds true in patients considered low-risk by IPI, PIT and KPI. PMID:23299534

Residual tumor after neoadjuvant chemoradiation outside the radiation therapy target volume: a new prognostic factor for survival in esophageal cancer.

PubMed

Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet; Mul, Veronique; van Dam, Go; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

2014-03-15

The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities. Copyright © 2014 Elsevier Inc. All rights reserved.

High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study

PubMed Central

Langer, Christian; Radmacher, Michael D.; Ruppert, Amy S.; Whitman, Susan P.; Paschka, Peter; Mrózek, Krzysztof; Baldus, Claudia D.; Vukosavljevic, Tamara; Liu, Chang-Gong; Ross, Mary E.; Powell, Bayard L.; de la Chapelle, Albert; Kolitz, Jonathan E.; Larson, Richard A.; Marcucci, Guido

2008-01-01

BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile. PMID:18378853

Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden.

PubMed

Kozlowski, Piotr; Lennmyr, Emma; Ahlberg, Lucia; Bernell, Per; Hulegårdh, Erik; Karbach, Holger; Karlsson, Karin; Tomaszewska-Toporska, Beata; Åström, Maria; Hallböök, Heléne

2017-08-01

Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012. Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B- and T-ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status ≥2 influenced the choice of palliation. Intensive, palliative, and both approaches resulted in complete remission rate 83/16/70% and 3-year overall survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With intensive treatment, platelet count ≤35×10 9 /L and age ≥75 years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year age-group. We report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph-negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment. © 2017 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

Outcome of severe adult thrombotic microangiopathies in the intensive care unit.

PubMed

Pene, Frédéric; Vigneau, Cécile; Auburtin, Marc; Moreau, Delphine; Zahar, Jean-Ralph; Coste, Joël; Heshmati, Farhad; Mira, Jean-Paul

2005-01-01

Thrombotic microangiopathies, namely thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, are uncommon microvascular occlusive diseases. Despite the dramatic improvement in the outcome by exogenous plasma supply, either through plasma infusion or through plasma exchange, patients frequently require support in the intensive care unit. In the present study, we evaluated the outcome of a large cohort of patients with severe thrombotic microangiopathies. A retrospective multicenter study from January 1998 to June 2001. Fourteen French university hospital medical intensive care units. Sixty three adult patients with severe thrombotic microangiopathies. Of the 63 patients, 19 had a clinical presentation of thrombotic thrombocytopenic purpura, 18 had hemolytic uremic syndrome and 26 had combined neurologic and renal failures. Infections were the main etiology associated with thrombotic microangiopathies. The mortality rate was 35%. Of the survivors, all achieved complete remission. Whereas neurologic failure assessed through the Glasgow coma scale was an independent predictor of mortality [HR=0.845 (CI 95%: 0.759-0.940), P=0.002], renal impairment did not appear to be an adverse prognostic factor. The use of plasma exchange was independently associated with survival [HR=0.269 (CI 95%: 0.104-0.691), P=0.006]. Thrombotic microangiopathies with severe organ dysfunctions leading to hospitalization in the intensive care unit are associated with high mortality. Neurologic impairment appears to be the main adverse prognostic factor correlated to mortality, and the study confirms the importance of plasma exchange in the treatment of high-risk patients.

Epirubicin in the adjuvant treatment of splenic hemangiosarcoma in dogs: 59 cases (1997-2004).

PubMed

Kim, Stanley E; Liptak, Julius M; Gall, Trent T; Monteith, Gabrielle J; Woods, J Paul

2007-11-15

To determine the efficacy and toxic effects of epirubicin for the adjuvant treatment of dogs with splenic hemangiosarcoma and identify prognostic factors. Retrospective case series. 59 client-owned dogs that underwent splenectomy for splenic hemangiosarcoma treated with or without epirubicin. Medical records were examined for signalment, clinical signs, diagnostic and surgical findings, and postoperative outcome. For dogs treated with epirubicin, dose numbers, intervals, and reductions and type and severity of toxic effects were recorded. Dogs were allotted to 2 groups: splenectomy alone and splenectomy with adjuvant epirubicin treatment. 18 dogs received epirubicin (30 mg/m(2)) every 3 weeks for up to 4 to 6 treatments. Forty-one dogs were treated with splenectomy alone. The overall median survival time was significantly longer in dogs treated with splenectomy and epirubicin (144 days), compared with splenectomy alone (86 days). Median survival time for dogs with stage I disease (345 days) was significantly longer than for dogs with either stage II (93 days) or III disease (68 days). Seven of 18 dogs treated with epirubicin were hospitalized for signs of adverse gastrointestinal effects. Inappetence, long duration of clinical signs, thrombocytopenia, neutrophilia, and high mitotic rate were negative prognostic factors. Epirubicin may be as efficacious as adjuvant doxorubicin-based protocols, but may result in a higher incidence of adverse gastrointestinal effects. Epirubicin should be considered as an alternative to doxorubicin in dogs with preexisting cardiac disease, as clinical epirubicin cardiotoxicity was not diagnosed in treated dogs.

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

PubMed Central

Gönen, Mithat; Sun, Zhuoxin; Figueroa, Maria E.; Patel, Jay P.; Abdel-Wahab, Omar; Racevskis, Janis; Ketterling, Rhett P.; Fernandez, Hugo; Rowe, Jacob M.; Tallman, Martin S.; Melnick, Ari; Levine, Ross L.

2012-01-01

We determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25POS myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25POS patients had inferior complete remission rates (P = .0005) and overall survival (P < .0001) compared with CD25NEG cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of FLT3-ITDPOS AML was restricted to CD25POS patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25POS status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25POS status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML. PMID:22855599

Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study.

PubMed

Carr, Brian I; Pancoska, Petr; Branch, Robert A

2009-12-24

967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end point. We found that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated AFP or bilirubin, or alkaline phosphatase, were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, even in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient sub groups based on liver function and tumor characteristics and found clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant factors. We also used a purely mathematical approach to derive subgroups and a prognostic model for individual patients. Interestingly, the two approaches gave similar predictive information, which opens the possibility of a more detailed mathematical analysis in the future. The results of this large dataset show that amongst non-surgical HCC patients, there are clear subsets with longer survival. The data supports the concept of heterogeneity of HCC. The three factors, bilirubin, AFP, and PVT predominate in prognosis.

Outcomes of 50 Patients With Ewing Sarcoma Family of Tumors Treated at a Single Institution in Taiwan

PubMed Central

Lee, Chih-Ying; Yen, Chueh-Chuan; Yen, Hsiu-Ju; Shiau, Cheng-Ying; Chao, Ta-Chung; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul Chih-Hsueh; Wu, Hung-Ta Hondar; Chiou, Hong-Jen; Chen, Chao-Chun; Hung, Giun-Yi; Chen, Wei-Ming

2016-01-01

Abstract To identify the prognostic factors and long-term outcome of the Ewing sarcoma family of tumors (ESFT), data on 50 patients with ESFT treated at Taipei Veterans General Hospital between February 1991 and March 2014 were retrospectively considered. The influence of patient demographics, tumor features, and clinical and therapeutic parameters on overall survival (OS) and progression-free survival (PFS) rates were assessed. The results revealed that 21 of the 50 patients (42%) were metastatic at diagnosis. The median follow-up time was 1.8 years. The 5-year OS and PFS for patients who were nonmetastatic were 61.6% and 55.5%, respectively, and 18.8% and 15.4% for patients who were metastatic, respectively. The key adverse prognostic factor was metastasis at diagnosis. Radiotherapy for local control was associated with improved PFS. The high rate of primary metastasis and poorer outcomes of nonmetastatic ESFT compared with results from Western studies, along with previously reported low rates of ESFT in Taiwanese people, suggest that genetic factors play a role in the pathogenesis of ESFT and chemotherapy pharmacokinetics and pharmacodynamics. Radiotherapy in local treatment should be considered more aggressively in Taiwanese patients with ESFT. PMID:27258529

Patient Attitudinal and Behavioral Factors Associated with Warfarin Non-adherence at Outpatient Anticoagulation Clinics

PubMed Central

Localio, A. Russell; Platt, Alec B.; Brensinger, Colleen M.; Christie, Jason D.; Gross, Robert; Parker, Catherine S.; Price, Maureen; Metlay, Joshua P.; Cohen, Abigail; Newcomb, Craig W.; Strom, Brian L.; Kimmel, Stephen E.

2010-01-01

Background Warfarin is an anticoagulant effective in preventing stroke, but it has a narrow therapeutic range requiring optimal adherence to achieve the most favorable effects. Purpose The goal of this study was to examine specific patient factors that might help explain warfarin non-adherence at outpatient anticoagulation clinics. Method In a prospective cohort study of 156 adults, we utilized logistic regression analyses to examine the relationship between the five Treatment Prognostics scales from the Millon Behavioral Medicine Diagnostic (MBMD), as well as three additional MBMD scales (Depression, Future Pessimism, and Social Isolation), and daily warfarin non-adherence assessed using electronic medication event monitoring systems caps over a median of 139 days. Results Four of the five Treatment Prognostic scales and greater social isolation were associated with warfarin non-adherence. When controlling for pertinent demographic and medical variables, the Information Discomfort scale remained significantly associated with warfarin non-adherence over time. Conclusion Although several factors were related to warfarin non-adherence, patients reporting a lack of receptivity to details regarding their medical illness seemed most at risk for warfarin non-adherence. This information might aid in the development of interventions to enhance warfarin adherence and perhaps reduce adverse medical events. PMID:19579066

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

PubMed Central

Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

2010-01-01

Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

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.

Added clinical value of applying myocardial deformation imaging to assess right ventricular function.

PubMed

Sokalskis, Vladislavs; Peluso, Diletta; Jagodzinski, Annika; Sinning, Christoph

2017-06-01

Right heart dysfunction has been found to be a strong prognostic factor predicting adverse outcome in various cardiopulmonary diseases. Conventional echocardiographic measurements can be limited by geometrical assumptions and impaired reproducibility. Speckle tracking-derived strain provides a robust quantification of right ventricular function. It explicitly evaluates myocardial deformation, as opposed to tissue Doppler-derived strain, which is computed from tissue velocity gradients. Right ventricular longitudinal strain provides a sensitive tool for detecting right ventricular dysfunction, even at subclinical levels. Moreover, the longitudinal strain can be applied for prognostic stratification of patients with pulmonary hypertension, pulmonary embolism, and congestive heart failure. Speckle tracking-derived right atrial strain, right ventricular longitudinal strain-derived mechanical dyssynchrony, and three-dimensional echocardiography-derived strain are emerging imaging parameters and methods. Their application in research is paving the way for their clinical use. © 2017, Wiley Periodicals, Inc.

Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system.

PubMed

Snozek, C L H; Katzmann, J A; Kyle, R A; Dispenzieri, A; Larson, D R; Therneau, T M; Melton, L J; Kumar, S; Greipp, P R; Clark, R J; Rajkumar, S V

2008-10-01

To determine if the serum free light chain (FLC) ratio has prognostic value in patients with symptomatic multiple myeloma (MM), baseline serum samples from a well-characterized cohort of 790 newly diagnosed MM patients were tested with the FLC assay. FLC ratio was calculated as kappa/lambda (reference range 0.26-1.65). On the basis of the distribution of values, a cutpoint kappa/lambda FLC ratio of <0.03 or >32 was chosen for further analysis. Overall survival was significantly inferior in patients with an abnormal FLC ratio of <0.03 or >32 (n=479) compared with those with an FLC ratio between 0.03 and 32 (n=311), with median survival of 30 versus 39 months, respectively. We incorporated abnormal FLC ratio with the International Staging System (ISS) risk factors (that is, albumin <3.5 g/dl and serum beta(2)-microglobulin >or=3.5 g/l), to create a risk stratification model with improved prognostic capabilities. Patients with 0, 1, 2 or 3 adverse risk factors had significantly different overall survival, with median survival times of 51, 39, 30 and 22 months, respectively (P<0.001). These findings suggest that the serum FLC ratio at initial diagnosis is an important predictor of prognosis in myeloma, and can be incorporated into the ISS for improved risk stratification.

Controversies in breast cancer: adjuvant and neoadjuvant therapy.

PubMed

Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

2005-06-01

Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

Long-term outcome for immune suppression and immune related lymphoproliferative disorder: prospective data from the United Kingdom Children's Leukaemia and Cancer Group registry 1994-2004.

PubMed

Taj, Mary M; Hadzic, Nedim; Height, Susan E; Wotherspoon, Andrew; Burke, Margaret; Hobson, Rachel; Viskaduraki, Maria; Pinkerton, C Ross

2012-05-01

Prospective national registry data on 98 patients were studied to determine the long-term outcome of immune related lymphoproliferative disease (LPD) and define prognostic factors. Seventy-three developed LPD following organ transplant (26 liver, 21 heart, 15 kidney, nine bone marrow [BM], two bowel). Twenty-five had non-transplant related immunosuppression. Age was 1.1-17 years (median 8.6). Fifty-eight patients had lymphomatous, 21 systemic and 17 lymphadenopathic disease. Sixty (73%) were disseminated and 22 (27%) localized. Thirty-three (54%) were monoclonal. Seventy-three (83%) were Epstein-Barr virus (EBV) positive. Median follow-up was 7.6 years. LPD developed earlier after liver and BM as compared to heart or kidney transplant. Five-year overall survival (OS) was 58%. Prognosis was best after liver and kidney transplant (OS >77%). Mortality was higher following heart (2.5 times) and BM transplant (5 times). Adverse prognostic factors were disseminated or lymphomatous disease and lack of reduction of immunosuppression. With appropriate reduction of immunosuppression, rituximab and low-dose chemotherapy, long-term survival is high.

The clinical significance of c-Kit mutations in metastatic oral mucosal melanoma in China.

PubMed

Ma, Xuhui; Wu, Yunteng; Zhang, Tian; Song, Hao; Jv, Houyu; Guo, Wei; Ren, Guoxin

2017-10-10

c-Kit mutations are frequently detected in mucosal melanomas, but their clinical significance in metastatic oral mucosal melanomas (OMM) remains unclear. The main purpose of this study was to investigate the clinical and pathological features of metastatic OMMs with c-Kit mutations and the efficiency of the tyrosine kinase inhibitor imatinib in treating metastatic OMMs. We found thatresidual primary lesion and neck lymph nodes could act as independent prognostic factors in metastatic OMM patients. c-Kit mutations were detected in 22 out of 139 (15.8%) metastatic OMM patients. Under chemotherapy, the overall survival (OS) of c-Kit mutant patients was significantly shorter than that of wild-type patients. The Ki67 expression was significantly higher in c-Kit mutant patients than in wild-type patients. In distant metastatic OMM patients with c-Kit mutations, the treatment with c-Kit inhibitor resulted in a better OS. In conclusion, residual primary lesion, cervical lymph nodes and c-Kit mutations act as adverse prognostic factors of metastatic OMMs. The Kit inhibitor imatinib could benefit metastatic OMM patients with c-Kit mutations.

Prognosis Research Strategy (PROGRESS) 2: prognostic factor research.

PubMed

Riley, Richard D; Hayden, Jill A; Steyerberg, Ewout W; Moons, Karel G M; Abrams, Keith; Kyzas, Panayiotis A; Malats, Núria; Briggs, Andrew; Schroter, Sara; Altman, Douglas G; Hemingway, Harry

2013-01-01

Prognostic factor research aims to identify factors associated with subsequent clinical outcome in people with a particular disease or health condition. In this article, the second in the PROGRESS series, the authors discuss the role of prognostic factors in current clinical practice, randomised trials, and developing new interventions, and explain why and how prognostic factor research should be improved.

The outcome of surgical resection versus assignment to the liver transplant waiting list for hepatocellular carcinoma.

PubMed

Pierie, Jean-Pierre E N; Muzikansky, Alona; Tanabe, Kenneth K; Ott, Mark J

2005-07-01

Optimal management of patients with hepatocellular carcinoma (HCC) is controversial. This study was conducted to evaluate the outcome of tumor resection versus assignment to a liver transplant waiting list (WL) in patients with HCC. Prospectively collected patient data from 1970 to 1997 on 313 patients with HCC were retrospectively analyzed by multivariate analysis to determine the effect of liver disease, method of treatment, and tumor-related factors on survival. A total of 199 patients underwent nonsurgical palliative care (PC), 81 underwent partial liver resection (LR), and 33 were assigned to a liver transplant WL, of which 22 received a donor liver. A total of 91%, 53%, and 91% of the patients had cirrhotic livers in the PC, LR, and WL groups, respectively (P < .001). In the LR group, the absence of a tumor capsule (P < .0001) and a poorly differentiated tumor (P = .027) were both adverse prognostic factors. In the WL group, hepatitis B (P = .02) and American Joint Committee on Cancer tumor stage III (P = .019) were adverse prognostic factors. The 3-year survival rates were 4%, 33%, and 38% for the PC, LR, and WL patients, respectively (P < .0001). The 3-year survival rate in the LR patients was 51% in patients without cirrhosis and 15% in patients with cirrhosis (P < .0001). Patients with locally unresectable tumors, distant disease, or both will continue to receive PC. Patients assigned to liver transplant WLs run the risk of not receiving a donor liver, in which case their survival is predicted to be poor. Survival after resection in a group of patients with advanced tumors is worse than that after transplantation; however, shortages of donor livers presently preclude transplantation in this population of patients.

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

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

Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months,more » the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.« less

Three-Gene Immunohistochemical Panel Adds to Clinical Staging Algorithms to Predict Prognosis for Patients With Esophageal Adenocarcinoma

PubMed Central

Ong, Chin-Ann J.; Shapiro, Joel; Nason, Katie S.; Davison, Jon M.; Liu, Xinxue; Ross-Innes, Caryn; O'Donovan, Maria; Dinjens, Winand N.M.; Biermann, Katharina; Shannon, Nicholas; Worster, Susannah; Schulz, Laura K.E.; Luketich, James D.; Wijnhoven, Bas P.L.; Hardwick, Richard H.; Fitzgerald, Rebecca C.

2013-01-01

Purpose Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor long-term survival. Despite growing knowledge of its biology, no molecular biomarkers are currently used in routine clinical practice to determine prognosis or aid clinical decision making. Hence, this study set out to identify and validate a small, clinically applicable immunohistochemistry (IHC) panel for prognostication in patients with EAC. Patients and Methods We recently identified eight molecular prognostic biomarkers using two different genomic platforms. IHC scores of these biomarkers from a UK multicenter cohort (N = 374) were used in univariate Cox regression analysis to determine the smallest biomarker panel with the greatest prognostic power with potential therapeutic relevance. This new panel was validated in two independent cohorts of patients with EAC who had undergone curative esophagectomy from the United States and Europe (N = 666). Results Three of the eight previously identified prognostic molecular biomarkers (epidermal growth factor receptor [EGFR], tripartite motif-containing 44 [TRIM44], and sirtuin 2 [SIRT2]) had the strongest correlation with long-term survival in patients with EAC. Applying these three biomarkers as an IHC panel to the validation cohort segregated patients into two different prognostic groups (P < .01). Adjusting for known survival covariates, including clinical staging criteria, the IHC panel remained an independent predictor, with incremental adverse overall survival (OS) for each positive biomarker (hazard ratio, 1.20; 95% CI, 1.03 to 1.40 per biomarker; P = .02). Conclusion We identified and validated a clinically applicable IHC biomarker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and provides additional prognostic information to current survival predictors such as stage. PMID:23509313

Prognostic Implications of Monosomies in Patients With Multiple Myeloma.

PubMed

Shin, Sang-Yong; Eom, Hyeon-Seok; Sohn, Ji Yeon; Lee, Hyewon; Park, Boram; Joo, Jungnam; Jang, Ja-Hyun; Lee, Mi-Na; Kim, Jung Kwon; Kong, Sun-Young

2017-03-01

Cytogenetic analysis aides in risk stratification for patients with multiple myeloma (MM). Although several cytogenetic aberrations have been reported to be prognostic, less is known about the association between the presence of monosomies and prognosis. The present study evaluated the prevalence and prognostic implications of monosomies in patients with MM. Karyotypes were determined using conventional cytogenetics and fluorescence in situ hybridization (FISH). The prognostic effect of monosomies was evaluated by comparison with the clinical factors in MM patients with normal karyotypes. Karyotypes were successfully determined in 167 of the 170 patients with MM. Of these 167 patients, 52 (31.1%) had abnormal karyotypes. Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14, and loss of X detected by metaphase analysis were each associated with reduced progression-free survival (P < .05 for each). Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14 detected by metaphase analysis and FISH-determined RB1 (13q)/TP53 (17p) deletion were each associated with reduced overall survival (P < .05 for each). Multivariable analysis showed that hypodiploidy detected by metaphase analysis was independently prognostic of shorter progression-free survival (P < .05 for each) and that hypodiploidy, monosomy 16, and loss of Y chromosome and FISH-determined TP53 (17p) deletion were associated with reduced overall survival (P < .05 for each). In addition to known cytogenetic abnormalities, such as monosomy 13, hypodiploidy, and TP53 (17p) deletion, monosomy 16 and loss of the Y chromosome have adverse prognostic implications in patients with MM. Copyright © 2016 Elsevier Inc. All rights reserved.

Lower body mass index predicts worse cancer-specific prognosis in octogenarians with colorectal cancer.

PubMed

Adachi, Tomohiro; Hinoi, Takao; Kinugawa, Yusuke; Enomoto, Toshiyuki; Maruyama, Satoshi; Hirose, Hajime; Naito, Masanori; Tanaka, Keitaro; Miyake, Yasuhiro; Watanabe, Masahiko

2016-08-01

High body mass index (BMI) is a risk factor for colorectal cancer. However, the prognostic impact of BMI and other factors may differ between elderly and younger colorectal cancer patients. We analyze here prognostic factors in the surgical management of octogenarians with colorectal cancer and clarify the prognostic impact of BMI. Cox regression analysis and propensity score methods were used to retrospectively examine the association of BMI with mortality in 1613 octogenarian patients who underwent curative surgery for stage 0-III colorectal cancer. In the Cox regression analysis, lower BMI (<18.5 kg/m(2); p = 0.001), age ≥83 years (p = 0.008), American Society of Anesthesiology class ≥3: (p = 0.001), performance status ≥2 (p = 0.003), Union for International Cancer Control (UICC) stage ≥III (p = 0.001), and postoperative adverse events (p = 0.001) were independently associated with decreased overall survival. Lower BMI (p = 0.001) and UICC stage ≥III (p = 0.001) were independently associated with decreased cancer-specific survival. After covariate adjustment, lower BMI was a risk factor for overall [hazard ratio (HR) 1.62; 95 % confidence interval (CI) 1.26-2.05; p = 0.0004] and cancer-specific survival (HR 2.00; 95 % CI 1.39-2.87; p = 0.0038) compared with normal BMI (18.5-24.9 kg/m(2)). Lower BMI is significantly and independently associated with increased mortality risk in octogenarians who undergo curative surgery for colorectal cancer. Lower BMI should be used for prognosis assessment in octogenarians with colorectal cancer.

Expression of Vascular Notch Ligand Delta-Like 4 and Inflammatory Markers in Breast Cancer

PubMed Central

Jubb, Adrian M.; Soilleux, Elizabeth J.; Turley, Helen; Steers, Graham; Parker, Andrew; Low, Irene; Blades, Jennifer; Li, Ji-Liang; Allen, Paul; Leek, Russell; Noguera-Troise, Irene; Gatter, Kevin C.; Thurston, Gavin; Harris, Adrian L.

2010-01-01

Delta-like ligand 4 (Dll4) is a Notch ligand that is predominantly expressed in the endothelium. Evidence from xenografts suggests that inhibiting Dll4 may overcome resistance to antivascular endothelial growth factor therapy. The aims of this study were to characterize the expression of Dll4 in breast cancer and assess whether it is associated with inflammatory markers and prognosis. We examined 296 breast adenocarcinomas and 38 ductal carcinoma in situ tissues that were represented in tissue microarrays. Additional whole sections representing 10 breast adenocarcinomas, 10 normal breast tissues, and 16 angiosarcomas were included. Immunohistochemistry was then performed by using validated antibodies against Dll4, CD68, CD14, Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN), CD123, neutrophil elastase, CD31, and carbonic anhydrase 9. Dll4 was selectively expressed by intratumoral endothelial cells in 73% to 100% of breast adenocarcinomas, 18% of in situ ductal carcinomas, and all lactating breast cases, but not normal nonlactating breast. High intensity of endothelial Dll4 expression was a statistically significant adverse prognostic factor in univariate (P = 0.002 and P = 0.01) and multivariate analyses (P = 0.03 and P = 0.04) of overall survival and relapse-free survival, respectively. Among the inflammatory markers, only CD68 and DC-SIGN were significant prognostic factors in univariate (but not multivariate) analyses of overall survival (P = 0.01 and 0.002, respectively). In summary, Dll4 was expressed by endothelium associated with breast cancer cells. In these retrospective subset analyses, endothelial Dll4 expression was a statistically significant multivariate prognostic factor. PMID:20167860

Prognostic significance of surgical extranodal extension in head and neck squamous cell carcinoma patients.

PubMed

Matsumoto, Fumihiko; Mori, Taisuke; Matsumura, Satoko; Matsumoto, Yoshifumi; Fukasawa, Masahiko; Teshima, Masanori; Kobayashi, Kenya; Yoshimoto, Seiichi

2017-08-01

Lymph node metastasis with extranodal extension represents one of the most important adverse prognostic factors for survival in patients with head and neck squamous cell carcinoma. We propose that extranodal extension occurs to differing extents. The aim of this study was to determine the prognostic significance of extranodal extension in patients with head and neck squamous cell carcinoma. Two hundred and ninety-eight patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection were included. Cervical lymph nodes were classified into four categories: (i) pathological N negative, (ii) extranodal extension negative, (iii) non-surgical extranodal extension and (iv) surgical extranodal extension. Lymph node metastases were detected in 67.1% of laryngeal/hypopharyngeal cancer patients and 52.7% of oral cancer patients. The 3-year disease-specific survival rates for patients in the pathological N negative, extranodal extension negative, non-surgical extranodal extension and surgical extranodal extension groups were 90.9%, 79.6%, 63.8% and 48.3%, respectively. In laryngeal/hypopharyngeal cancer patients, surgical extranodal extension was associated with a significantly poorer disease-specific survival than a pathological N negative, extranodal extension negative or non-surgical extranodal extension status. In oral cancer patients, no significant differences were observed between the non-surgical and surgical extranodal extension groups. However, non-surgical extranodal extension was associated with a poorer disease-specific survival than a pathological N negative or extranodal extension negative status. Surgical extranodal extension was a poor prognostic factor in patients with head and neck squamous cell carcinoma. The prognostic significance of surgical extranodal extension differed between laryngeal/hypopharyngeal and oral cancer patients. The clinical significance of surgical extranodal extension was much greater for patients with laryngeal/hypopharyngeal cancer than oral cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Nutrition support can bring survival benefit to high nutrition risk gastric cancer patients who received chemotherapy.

PubMed

Qiu, Miaozhen; Zhou, Yi-xin; Jin, Yin; Wang, Zi-xian; Wei, Xiao-li; Han, Hong-yu; Ye, Wen-feng; Zhou, Zhi-wei; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Yang, Da-jun; Xu, Rui-hua

2015-07-01

The aim of our study is firstly to evaluate the prevalence and prognostic value of nutrition risk in gastric cancer patients and secondly to explore whether the nutrition support can prolong the survival of advanced gastric cancer patients. It contained two study periods. In the first period, we prospectively evaluated the nutritional risk of gastric adenocarcinoma patients from 2009 to 2011 using the method of European Nutritional Risk Screening (NRS) 2002. The Kaplan-Meier method and log-rank test were used to evaluate the prognostic value of high nutrition risk. The second period was between 2012 and 2013. We prospectively gave the nutrition support to stage IV gastric cancer patients whose NRS is ≥3. There were 830 patients in the first period, 50.7% patients with a NRS ≥ 3. Patients with NRS ≥ 3 presented a significantly higher percentage of stage IV diseases, elevated values of C-reactive protein, and hypoproteinemia. The median survival was significantly higher in NRS < 3 patients (31.9 vs. 25.7 months, P < 0.001). Multivariate analysis confirmed that NRS status was an independent prognostic factor. There were 347 patients in the second period. Young, male, and good response to chemotherapy were more likely to have the NRS shift to <3 after nutrition support. The median survival was 14.3 and 9.6 months for patients with and without NRS shift, respectively, P = 0.001. NRS ≥ 3 was an independent adverse prognostic factor in gastric cancer patients. For stage IV patients whose NRS ≥ 3, the nutrition support might be helpful to improve the prognosis.

Progranulin Is a Novel Independent Predictor of Disease Progression and Overall Survival in Chronic Lymphocytic Leukemia

PubMed Central

Göbel, Maria; Eisele, Lewin; Möllmann, Michael; Hüttmann, Andreas; Johansson, Patricia; Scholtysik, René; Bergmann, Manuela; Busch, Raymonde; Döhner, Hartmut; Hallek, Michael; Seiler, Till; Stilgenbauer, Stephan; Klein-Hitpass, Ludger; Dührsen, Ulrich; Dürig, Jan

2013-01-01

Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38+ZAP-70+ as compared to indolent CD38−ZAP-70− chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p-) as detected by flourescence in situ hybridization (FISH) and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163). Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13–3.76, p = 0.018), unmutated IGHV status (HR = 5.63, 95%-CI = 3.05–10.38, p<0.001), high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09–3.89, p = 0.026) but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA. PMID:24009671

Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia.

PubMed

Göbel, Maria; Eisele, Lewin; Möllmann, Michael; Hüttmann, Andreas; Johansson, Patricia; Scholtysik, René; Bergmann, Manuela; Busch, Raymonde; Döhner, Hartmut; Hallek, Michael; Seiler, Till; Stilgenbauer, Stephan; Klein-Hitpass, Ludger; Dührsen, Ulrich; Dürig, Jan

2013-01-01

Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38(+)ZAP-70(+) as compared to indolent CD38(-)ZAP-70(-) chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p-) as detected by flourescence in situ hybridization (FISH) and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163). Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13-3.76, p = 0.018), unmutated IGHV status (HR = 5.63, 95%-CI = 3.05-10.38, p<0.001), high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09-3.89, p = 0.026) but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA.

Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

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

Krishnan, Sunil; Rana, Vishal; Evans, Douglas B.

2008-03-01

Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies weremore » used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.« less

Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications

PubMed Central

Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2015-01-01

The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671

Clinical relevance of sentinel lymph node status examined with conventional histology and molecular biology.

PubMed

Micciolo, Rocco; Boi, Sebastiana; Paoli, Loredana; Cristofolini, Paolo; Girlando, Salvatore; Dalla Palma, Paolo; Cristofolini, Mario

2009-01-01

The presence of nodal metastases in patients with primary cutaneous melanoma adversely affects the biological behavior and is related to a poor prognosis. The role of sentinel lymph node biopsy is still debated. The aim of this study was to evaluate the prognostic role of sentinel lymph node biopsy with respect to disease-free period and overall survival. Patients with invasive cutaneous melanoma who underwent sentinel lymph node biopsy in the Santa Chiara Hospital of Trento between October 1997 and December 2002 were evaluated. The lymph nodes were examined with conventional histology, S100 and tyrosinase in immunohistochemistry, and tyrosinase in molecular biology. There were 144 patients with 198 sentinel lymph nodes. A significant association was found in conventional histology with Clark level and Breslow thickness. The prognostic role of sentinel lymph node status was independent of the other considered variables. However, no significant association was found with the molecular biology test. A significant excess of positive results at molecular biology was found. Sentinel lymph node biopsy is an important independent prognostic factor for invasive cutaneous melanoma, but only when evaluated with conventional histology. As a result of this study, we stopped performing the tyrosinase test in molecular biology.

Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: results from the MAGGIC individual patient data meta-analysis.

PubMed

Berry, C; Poppe, K K; Gamble, G D; Earle, N J; Ezekowitz, J A; Squire, I B; McMurray, J J V; McAlister, F A; Komajda, M; Swedberg, K; Maggioni, A P; Ahmed, A; Whalley, G A; Doughty, R N; Tarantini, L

2016-06-01

Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). Individual person data meta-analysis. Patients with haemoglobin (Hb) data from the MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l in men. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazard modelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-cause mortality. Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HF-PEF and aHR 2.49 (2.13-2.90) in HF-REF. Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adjuvant Chemotherapy After Radical Cystectomy for Urothelial Bladder Cancer: Outcome and Prognostic Factors for Survival in a French Multicenter, Contemporary Cohort.

PubMed

Pouessel, Damien; Bastuji-Garin, Sylvie; Houédé, Nadine; Vordos, Dimitri; Loriot, Yohann; Chevreau, Christine; Sevin, Emmanuel; Beuzeboc, Philippe; Taille, Alexandre de la; Le Thuaut, Aurélie; Allory, Yves; Culine, Stéphane

2017-02-01

In the past decade, adjuvant chemotherapy (AC) after radical cystectomy (RC) was preferred worldwide for patients with muscle-invasive urothelial bladder cancer. In this study we aimed to determine the outcome of patients who received AC and evaluated prognostic factors associated with survival. We retrospectively analyzed 226 consecutive patients treated in 6 academic hospitals between 2000 and 2009. Multivariate Cox proportional hazards regression adjusted for center to estimate adjusted hazard ratios (HRs) with 95% confidence intervals were used. The median age was 62.4 (range, 35-82) years. Patients had pT3/pT4 and/or pN+ in 180 (79.6%) and 168 patients (74.3%), respectively. Median lymph node (LN) density was 25% (range, 3.1-100). Median time between RC and AC was 61.5 (range, 18-162) days. Gemcitabine with cisplatin, gemcitabine with carboplatin, and MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimens were delivered in 161 (71.2%), 49 (21.7%), and 12 patients (5.3%) of patients, respectively. The median number of cycles was 4 (range, 1-6). Thirteen patients (5.7%) with LN metastases also received adjuvant pelvic radiotherapy (ART). After a median follow-up of 4.2 years, 5-year overall survival (OS) was 40.7%. In multivariate analysis, pT ≥3 stage (HR, 1.73; P = .05), LN density >50% (HR, 1.94; P = .03), and number of AC cycles <4 (HR, 4.26; P = .001) were adverse prognostic factors for OS. ART (HR, 0.30; P = .05) tended to provide survival benefit. Classical prognostic features associated with survival are not modified by the use of AC. Patients who derived benefit from AC had a low LN density and received at least 4 cycles of treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

[Prognostic value of first fasting glucose measurement compared with admission glucose level in patients with acute coronary syndrome].

PubMed

Vivas, David; García-Rubira, Juan C; González-Ferrer, Juan J; Núñez-Gil, Iván; del Prado, Náyade; Fernández-Ortiz, Antonio; Macaya, Carlos

2008-05-01

The admission plasma glucose (APG) level is a recognized prognostic factor in patients with acute coronary syndrome (ACS). However, little is known about the prognostic value of the first fasting plasma glucose (FPG) measurement. The aim of this study was to determine the prognostic value of the first FPG measurement relative to that of the APG level in patients with ACS. The study involved 547 consecutive patients who were admitted to our center with a diagnosis of ACS in 2006. Patients were divided into three groups according to their first FPG or APG level (i.e., <126 mg/dL, 126-200 mg/dL, or >200 mg/dL). The primary endpoint was the combined outcome of death or reinfarction during hospitalization. The primary endpoint was observed in 46 patients, 25 of whom died. Patients in this group were older, were more often diabetics or smokers, more often had had a prior myocardial infarction, were in a higher admission Killip class, showed more than one vessel disease on catheterization, had a lower left ventricular ejection fraction, and had higher admission creatinine, APG, and first FPG levels. Multivariate analysis, adjusted for previously identified factors, revealed that the first FPG level was an independent risk factor for death or reinfarction (126-200 mg/dL, odds ratio [OR]=5.26; 95% confidence interval [CI], 1.09-25.45; >200 mg/dL, OR=6.66; 95% CI, 2.05-21.63), but that the APG level was not (126-200 mg/dL, OR=0.84; 95% CI, 0.63-1.05; >200 mg/dL, OR=1.14; 95% CI, 0.29-4.51). The first FPG level was found to be a better predictor of an adverse outcome (i.e., death or reinfarction) during hospitalization in ACS patients than the APG level.

Red blood cell distribution width as a predictor of survival in nasal-type, extranodal natural killer/T-cell lymphoma

PubMed Central

He, Qiao; Cai, Shaolei; Li, Shi; Zeng, Jian; Zhang, Qing; Gao, Yu; Yu, Sisi

2017-01-01

We retrospectively enrolled 191 nasal-type, extranodal natural killer/T-cell lymphoma (ENKTL) patients newly diagnosed from 2008 to 2016 at the Sichuan Cancer Hospital, in order to evaluate the relationship between disease outcomes, demographic and clinical factors, and red blood cell distribution width (RDW). C-index, fisher's exact test, univariate analysis, and cox regression analysis were applied. The median age of patients was 44 years and 134 (70%) were men. The cutoff of RDW was 46.2 fL determined by Cutoff Finder. Patients with RDW≤46.2 fL had significantly better progression-free survival (PFS) (3-year PFS, 80.4% vs. 63.1%; P=0.01) and overall survival (OS) (3-year OS, 83.2% vs. 65.5%; P=0.004) than those with RDW>46.2 fL. Multivariate analysis demonstrated that elevated RDW is an independent adverse predictor of OS (P=0.021, HR=2.04). RDW is an independent predictor of survival outcomes in ENKTL, which we found to be superior to both the prognostic index of natural killer lymphoma (PINK) and the Korean Prognostic Index (KPI) in discriminating patients with different outcomes in low-risk and high-risk groups (all P < 0.05). The new models combining RDW with the International Prognostic Index (IPI), KPI, and PINK showed more powerful prognostic value than corresponding original models. RDW represents an easily available and inexpensive marker for risk stratification in patients with ENKTL treated with radiotherapy-based treatment. Further prospective studies are warranted to confirm the prognostic value of RDW in ENKTL. PMID:29190934

Red blood cell distribution width as a predictor of survival in nasal-type, extranodal natural killer/T-cell lymphoma.

PubMed

Luo, Huaichao; Quan, Xiaoying; Song, Xiao-Yu; Zhang, Li; Yin, Yilin; He, Qiao; Cai, Shaolei; Li, Shi; Zeng, Jian; Zhang, Qing; Gao, Yu; Yu, Sisi

2017-11-03

We retrospectively enrolled 191 nasal-type, extranodal natural killer/T-cell lymphoma (ENKTL) patients newly diagnosed from 2008 to 2016 at the Sichuan Cancer Hospital, in order to evaluate the relationship between disease outcomes, demographic and clinical factors, and red blood cell distribution width (RDW). C-index, fisher's exact test, univariate analysis, and cox regression analysis were applied. The median age of patients was 44 years and 134 (70%) were men. The cutoff of RDW was 46.2 fL determined by Cutoff Finder. Patients with RDW≤46.2 fL had significantly better progression-free survival (PFS) (3-year PFS, 80.4% vs. 63.1%; P =0.01) and overall survival (OS) (3-year OS, 83.2% vs. 65.5%; P =0.004) than those with RDW>46.2 fL. Multivariate analysis demonstrated that elevated RDW is an independent adverse predictor of OS ( P =0.021, HR=2.04). RDW is an independent predictor of survival outcomes in ENKTL, which we found to be superior to both the prognostic index of natural killer lymphoma (PINK) and the Korean Prognostic Index (KPI) in discriminating patients with different outcomes in low-risk and high-risk groups (all P < 0.05). The new models combining RDW with the International Prognostic Index (IPI), KPI, and PINK showed more powerful prognostic value than corresponding original models. RDW represents an easily available and inexpensive marker for risk stratification in patients with ENKTL treated with radiotherapy-based treatment. Further prospective studies are warranted to confirm the prognostic value of RDW in ENKTL.

Prognostic value of bone marrow involvement by clonal immunoglobulin gene rearrangements in follicular lymphoma

PubMed Central

Berget, Ellen; Helgeland, Lars; Liseth, Knut; Løkeland, Turid; Molven, Anders; Vintermyr, Olav Karsten

2014-01-01

Aims We aimed to evaluate the prognostic value of routine use of PCR amplification of immunoglobulin gene rearrangements in bone marrow (BM) staging in patients with follicular lymphoma (FL). Methods Clonal rearrangements were assessed by immunoglobulin heavy and light-chain gene rearrangement analysis in BM aspirates from 96 patients diagnosed with FL and related to morphological detection of BM involvement in biopsies. In 71 patients, results were also compared with concurrent flow cytometry analysis. Results BM involvement was detected by PCR in 34.4% (33/96) of patients. The presence of clonal rearrangements by PCR was associated with advanced clinical stage (I–III vs IV; p<0.001), high FL International Prognostic Index (FLIPI) score (0–1, 2 vs ≥3; p=0.003), and detection of BM involvement by morphology and flow cytometry analysis (p<0.001 for both). PCR-positive patients had a significantly poorer survival than PCR-negative patients (p=0.001, log-rank test). Thirteen patients positive by PCR but without morphologically detectable BM involvement, had significantly poorer survival than patients with negative morphology and negative PCR result (p=0.002). The poor survival associated with BM involvement by PCR was independent of the FLIPI score (p=0.007, Cox regression). BM involvement by morphology or flow cytometry did not show a significant impact on survival. Conclusions Our results showed that routine use of PCR-based clonality analysis significantly improved the prognostic impact of BM staging in patients with FL. BM involvement by PCR was also an independent adverse prognostic factor. PMID:25233852

Depressive symptoms, functional measures and long-term outcomes of high-risk ST-elevated myocardial infarction patients treated by primary angioplasty.

PubMed

Compostella, Leonida; Lorenzi, Sonia; Russo, Nicola; Setzu, Tiziana; Compostella, Caterina; Vettore, Elia; Isabella, Giambattista; Tarantini, Giuseppe; Iliceto, Sabino; Bellotto, Fabio

2017-02-01

The presence of major depressive symptoms is usually considered a negative long-term prognostic factor after an acute myocardial infarction (AMI); however, most of the supporting research was conducted before the era of immediate reperfusion by percutaneous coronary intervention. The aims of this study are to evaluate if depression still retains long-term prognostic significance in our era of immediate coronary reperfusion, and to study possible correlations with clinical parameters of physical performance. In 184 patients with recent ST-elevated AMI (STEMI), treated by immediate reperfusion, moderate or severe depressive symptoms (evaluated by Beck Depression Inventory version I) were present in 10 % of cases. Physical performance was evaluated by two 6-min walk tests and by a symptom-limited cardiopulmonary exercise test: somatic/affective (but not cognitive/affective) symptoms of depression and perceived quality of life (evaluated by the EuroQoL questionnaire) are worse in patients with lower levels of physical performance. Follow-up was performed after a median of 29 months by means of telephone interviews; 32 major adverse cardiovascular events (MACE) occurred. The presence of three vessels disease and low left ventricle ejection fraction are correlated with a greater incidence of MACE; only somatic/affective (but not cognitive/affective) symptoms of depression correlate with long-term outcomes. In patients with recent STEMI treated by immediate reperfusion, somatic/affective but not cognitive/affective symptoms of depression show prognostic value on long-term MACE. Depression symptoms are not predictors "per se" of adverse prognosis, but seem to express an underlying worse cardiac efficiency, clinically reflected by poorer physical performance.

High truncated-O-glycan score predicts adverse clinical outcome in patients with localized clear-cell renal cell carcinoma after surgery.

PubMed

NguyenHoang, SonTung; Liu, Yidong; Xu, Le; Zhou, Lin; Chang, Yuan; Fu, Qiang; Liu, Zheng; Lin, Zongming; Xu, Jiejie

2017-10-03

Truncated O-glycans, including Tn-antigen, sTn-antigen, T-antigen, sT-antigen, are incomplete glycosylated structures and their expression occur frequently in tumor tissue. The study aims to evaluate the abundance of each truncated O-glycans and its clinical significance in postoperative patients with localized clear-cell renal cell carcinoma (ccRCC). We used immunohistochemical testing to analyze the expression of truncated O-glycans in tumor specimens from 401 patients with localized ccRCC. Truncated-O-glycan score was built by integrating the expression level of Tn-, sTn- and sT-antigen. Kaplan-Meier survival and Cox regression analysis were done to compare clinical outcomes in subgroups. Receiver operating characteristic (ROC) was applied to assess the impact of prognostic factors on overall survival (OS) and recurrence-free survival (RFS). The results identified Tn-, sTn-, sT-antigen as independent prognosticators. The OS and RFS were shortened among the 198 (49.4%) patients with high Truncated-O-glycan score than among the 203 (50.6%) patients with low score (hazard ratio for OS, 7.060; 95% confidence interval [CI]: 2.765 to 18.027; p <0.001; for RFS, 4.612; 95% CI: 2.141 to 9.931; p <0.001). There is no difference between low-risk patients and high-risk patients in low score group ( p = 0.987). High-risk patients with low score showed a better prognosis than low-risk patient with high score ( p = 0.029). The Truncated-O-glycan score showed better prognostic value for OS (AUC: 0.739, p = 0.003) and RFS (AUC: 0.719, p = 0.003) than TNM stage. In summary, the high Truncated-O-glycan score could predict adverse clinical outcome in localized ccRCC patients after surgery.

Advanced Methods for Determining Prediction Uncertainty in Model-Based Prognostics with Application to Planetary Rovers

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Sankararaman, Shankar

2013-01-01

Prognostics is centered on predicting the time of and time until adverse events in components, subsystems, and systems. It typically involves both a state estimation phase, in which the current health state of a system is identified, and a prediction phase, in which the state is projected forward in time. Since prognostics is mainly a prediction problem, prognostic approaches cannot avoid uncertainty, which arises due to several sources. Prognostics algorithms must both characterize this uncertainty and incorporate it into the predictions so that informed decisions can be made about the system. In this paper, we describe three methods to solve these problems, including Monte Carlo-, unscented transform-, and first-order reliability-based methods. Using a planetary rover as a case study, we demonstrate and compare the different methods in simulation for battery end-of-discharge prediction.

Homoarginine—A prognostic indicator in adolescents and adults with complex congenital heart disease?

PubMed Central

Mueller, Marieke; Meinitzer, Andreas; Maerz, Winfried; Dschietzig, Thomas

2017-01-01

Background Homoarginine (hArg) has been shown to be of prognostic value in patients with chronic left heart failure. The present study aims to assess the clinical utility and prognostic value of hArg levels in patients with complex congenital heart disease (CHD). Methods Plasma hArg levels were measured in 143 patients with complex CHD and compared to clinical status, echocardiographic and laboratory parameters as well as the occurrence of adverse cardiac events. Results Median hArg levels were 1.5 μmol/l in CHD patients as compared to 1.70 μmol/l in healthy controls (p = 0.051). Median hArg levels were lowest in patients with Fontan palliation (1.27 μmol/l) and Eisenmenger physiology (0.99 μmol/l) and decreased with the severity of adverse cardiac events with lowest values found in patients prior to death or overt heart failure (0.89 μmol/l). According to ROC analysis, the most important predictors of adverse cardiac events were hArg levels (AUC 0.837, p<0.001, CI 0.726–0.947), NYHA class (AUC 0.800, p<0.001, CI 0.672–0.928) and NT-proBNP levels (AUC 0.780, p<0.001, CI 0.669–0.891). The occurrence of overt heart failure or death due to progressive heart failure were best predicted by NYHA class (AUC 0.945, p<0.001, CI 0.898–0.992), hArg levels (AUC 0.911, p<0.001, CI 0.850–0.971) and NT-proBNP levels (AUC 0.877, p<0.001, CI 0.791–0.962), respectively. Conclusion In patients with complex CHD, hArg levels can predict adverse cardiac events as reliably as or even better than NT-proBNP levels and thus might be of prognostic value in this subset of patients. PMID:28886170

Prognostic risk stratification derived from individual patient level data for men with advanced penile squamous cell carcinoma receiving first-line systemic therapy.

PubMed

Pond, Gregory R; Di Lorenzo, Giuseppe; Necchi, Andrea; Eigl, Bernhard J; Kolinsky, Michael P; Chacko, Raju T; Dorff, Tanya B; Harshman, Lauren C; Milowsky, Matthew I; Lee, Richard J; Galsky, Matthew D; Federico, Piera; Bolger, Graeme; DeShazo, Mollie; Mehta, Amitkumar; Goyal, Jatinder; Sonpavde, Guru

2014-05-01

Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (P<0.001) and ECOG PS ≥ 1 (P<0.001) for both PFS and OS. A risk stratification model constructed with 0, 1, and both poor prognostic factors was internally validated and demonstrated moderate discriminatory ability (c-statistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including these factors exhibited moderate discriminatory ability for outcomes and warrants external validation. Patients receiving cisplatin-based regimens exhibited better outcomes compared with noncisplatin-based regimens after adjusting for prognostic factors. © 2013 Published by Elsevier Inc.

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

Dinshaw, Ketayun A.; Budrukkar, Ashwini N.; Chinoy, Roshan F.

Purpose: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. Methods and Materials: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). Results: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women.more » The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age {<=}40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). Conclusion: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment.« less

Ambulatory blood pressure and cardiovascular events in chronic kidney disease

PubMed Central

Agarwal, Rajiv

2007-01-01

Purpose of review Hypertension is an important risk factor for adverse cardiovascular and renal outcomes particularly in patients with chronic kidney disease. This review compares blood pressure measurements obtained in the clinic with those obtained outside the clinic to predict cardiovascular and renal injury and outcomes. Recent findings Data are accumulating that suggest that ambulatory blood pressure monitoring is a superior prognostic marker compared to blood pressures obtained in the clinic. Use of ambulatory blood pressure monitoring can detect white coat hypertension and masked hypertension which results in less misclassification of blood pressures. Ambulatory blood pressure monitoring is a marker of cardiovascular end points in CKD. Non dipping is associated with proteinuria and lower GFR. Although non-dipping is associated with more ESRD and cardiovascular events, adjustment for other risk factors removes the prognostic significance of non-dipping. For patients with CKD, not on dialysis, 24 hour ambulatory BP of <125/75 mm Hg, daytime ambulatory of <130/85 mm Hg and nighttime ambulatory BP of <110/70 mm Hg appear to be reasonable goal BP targets. In the management of hypertension in patients with CKD, control of hypertension is important. Ambulatory BP monitoring may be useful to assign more aggressive treatment to patients with masked hypertension and withdraw antihypertensive therapy in patients with white-coat hypertension. Summary Ambulatory blood pressure monitoring can refine cardiovascular and renal risk assessment in all stages of chronic kidney disease. The independent prognostic role of non-dipping is unclear. PMID:17868791

Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study

PubMed Central

2010-01-01

Background We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. Methods Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5%) satisfied the selection criteria. Results Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2%) which was followed by nasal cavity (n = 30, 23.3%), genitourinary (n = 21, 16.3%), oral cavity (n = 14, 10.9%), upper gastrointestinal tract (n = 6, 4.7%) and maxillary sinus (n = 5, 3.9%) in the order of frequency. With the median 64.5 (range 4.3-213.0) months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5) for all patients, and 34.6 (95% CI 24.5-44.7) months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin), and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04). Conclusion Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome. PMID:20426858

[Pregnancy-Associated Breast Cancer: An analytical observational study].

PubMed

Baulies, Sonia; Cusidó, Maite; Tresserra, Francisco; Rodríguez, Ignacio; Ubeda, Belén; Ara, Carmen; Fábregas, Rafael

2014-03-04

Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy and up to one year postpartum. A retrospective, analytical, observational study comparing 56 cases of breast cancer and pregnancy (PABC) diagnosed 1976-2008 with 73 patients with breast cancer not associated with pregnancy (non-PABC) was performed. Demographic data, prognostic factors, treatment and survival were reviewed and compared. The prevalence of PABC in our center is 8.3/10,000. The highest frequency (62%) appeared during the postpartum period. The stages are higher in PABC, being 31.3% advanced (EIII and EIV) in PABC versus 13.3% in non-PABC (P < .05). Regarding prognostic factors, 27.3% in PABC had a tumoral grade 3 versus 15.8% of non-PABC. Among women with PABC, 33.3% had negative estrogen receptors, 48.7% negative progesterone receptors and 34.5% positive Her2Neu compared with 22.2, 24.1 and 31%, respectively of non-PABC patients. Finally, positive lymph nodes were found in 52.8% of PABC, versus 33.8% non-PABC (P < .05). Overall and disease-free survival rate at 5 years for PABC was 63.7 and 74.2%, respectively. The poorer survival observed is possibly due to the presence of adverse prognostic features such as lymph node metastases, negative hormone receptors, tumoral grade iii, as well as a delay in diagnosis with a higher rate of advanced stages. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Non-chemotherapy drug-induced neutropenia - an update.

PubMed

Andrès, Emmanuel; Mourot-Cottet, Rachel

2017-11-01

To date, non-chemotherapy drug-induced severe neutropenia (neutrophil count of ≤0.5 x 10 9 /L) also called idiosyncratic drug-induced agranulocytosis is little discussed in the literature. In the present paper, we report and discuss the clinical data and management of this rare disorder. Areas covered: To do this, we carried out a review of the literature using PubMed database of the US National Library of Medicine. We also used data from the American Society of Hematology educational books, textbooks of Hematology and Internal medicine, and information gleaned from international meetings. Expert opinion: Idiosyncratic agranulocytosis remains a potentially serious adverse event due to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia, and septic shock in approximately two-thirds of all hospitalized patients. In this context, several prognostic factors have been identified that may be helpful when identifying 'susceptible' patients. Old age (>65 years), septicemia or shock, renal failure, and a neutrophil count ≤0.1 × 10 9 /L have been consensually accepted as poor prognostic factors. In our experience, modern management with pre-established procedures, intravenous broad-spectrum antibiotics and hematopoietic growth factors (particularly G-CSF) is likely to improve the prognosis. Thus with appropriate management, the mortality rate is currently between 5 to 10%.

Type 1 IGF Receptor Localization in Paediatric Gliomas: Significant Association with WHO Grading and Clinical Outcome.

PubMed

Clément, Florencia; Martin, Ayelen; Venara, Marcela; de Luján Calcagno, Maria; Mathó, Cecilia; Maglio, Silvana; Lombardi, Mercedes García; Bergadá, Ignacio; Pennisi, Patricia A

2018-06-01

Nuclear localization of insulin-like growth factor receptor type 1 (IGF-1R) has been described as adverse prognostic factor in some cancers. We studied the expression and localization of IGF-1R in paediatric patients with gliomas, as well as its association with World Health Organization (WHO) grading and survival. We conducted a single cohort, prospective study of paediatric patients with gliomas. Samples were taken at the time of the initial surgery; IGF-1R expression and localization were characterized by immunohistochemistry (IHC), subcellular fractionation and western blotting. Tumours (47/53) showed positive staining for IGF-1R by IHC. IGF-1R nuclear labelling was observed in 10/47 cases. IGF-1R staining was mostly non-nuclear in low-grade tumours, while IGF-1R nuclear labelling was predominant in high-grade gliomas (p = 0.0001). Survival was significantly longer in patients with gliomas having non-nuclear IGF-1R localization than in patients with nuclear IGF-1R tumours (p = 0.016). In gliomas, IGF-1R nuclear localization was significantly associated with both high-grade tumours and increased risk of death. Based on a prospective design, we provide evidence of a potential usefulness of intracellular localization of IGF-1R as prognostic factor in paediatric patients with gliomas.

High Phosphohistone H3 Expression Correlates with Adverse Clinical, Biological, and Pathological Factors in Neuroblastomas

PubMed Central

Ramani, Pramila; Taylor, Scott; Miller, Elizabeth; Sowa-Avugrah, Emile; May, Margaret T.

2015-01-01

Phosphohistone H3 (pHH3), a biomarker of the late G2- and M-phase of the cell cycle, provides a powerful indication of the proliferative state of many cancers. We investigated the prognostic significance of pHH3 by immunostaining 80 neuroblastomas and counting the average number of strongly stained nuclei and mitotic figures. The median and 75th percentile pHH3 proliferation indices (PIs) were 0.54% and 1.06% (range, 0.01% to 2.23%) respectively. pHH3 expression was significantly higher in neuroblastomas from patients with adverse clinical characteristics, all unfavorable pathological factors including high mitosis karyorrhexis index (MKI), and adverse biological factors including MYCN oncogene amplification. High pHH3-PIs, at 1% threshold, were significantly associated with a shorter overall survival (OS) and event-free survival (EFS) in the univariable Cox regression analyses. In the multivariable models, high pHH3 counts were significantly associated with worse OS after adjustment for age but were not independent of either high MKI or MYCN amplification. In children less than 18 months of age, high MKIs and high PHH3-PIs were associated with significantly worse OS and EFS. In conclusion, high pHH3 expression correlates strongly with high MKI and MYCN amplification and indicates poor prognosis in neuroblastomas. PMID:25711230

Factors associated with differential response to online cognitive behavioural therapy.

PubMed

Button, Katherine S; Wiles, Nicola J; Lewis, Glyn; Peters, Tim J; Kessler, David

2012-05-01

Patients differ in their response to treatments. There is obvious clinical utility in establishing patient characteristics that are associated with differential treatment responses (i.e., are effect modifiers or moderators of treatment response). Factors that moderate response to cognitive behavioural therapy (CBT) remain unclear. This study investigates whether factors prognostic of general depression outcome generally are also moderators of response to online CBT in a sample of depressed patients recruited through U.K. general practices. Secondary analysis of a randomised controlled trial, internet-based psychotherapy for depression. A total of 297 patients referred from 55 U.K. general practices and suffering from depression were randomly allocated to receive either online CBT or waiting list control. Treatment effect was measured by comparing depression score at 4 months between randomization groups. Treatment effect modification was assessed using regression analyses focusing on interactions between treatment effect and putative moderator variables. Pretreatment severity and marital status moderated treatment response. More severe patients, and patients who were separated, widowed, or divorced, benefited most from the intervention. Weak evidence suggested that treatment effectiveness diminished with increasing recent adverse life events. No evidence was found to suggest that educational attainment, age, and history of depression-moderated treatment response. Secondary analyses of trials comparing two or more treatments allow factors that may moderate treatment response to be distinguished from more general prognostic indicators, although caution is needed in interpreting such exploratory analyses.

Prognostic accuracy of cerebroplacental ratio and middle cerebral artery Doppler for adverse perinatal outcome: systematic review and meta‐analysis

PubMed Central

De Boer, M. A.; Heymans, M. W.; Schoonmade, L. J.; Bossuyt, P. M. M.; Mol, B. W. J.; De Groot, C. J. M.; Bax, C. J.

2018-01-01

ABSTRACT Objective Doppler ultrasonographic assessment of the cerebroplacental ratio (CPR) and middle cerebral artery (MCA) is widely used as an adjunct to umbilical artery (UA) Doppler to identify fetuses at risk of adverse perinatal outcome. However, reported estimates of its accuracy vary considerably. The aim of this study was to review systematically the prognostic accuracies of CPR and MCA Doppler in predicting adverse perinatal outcome, and to compare these with UA Doppler, in order to identify whether CPR and MCA Doppler evaluation are of added value to UA Doppler. Methods PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, from inception to June 2016, for studies on the prognostic accuracy of UA Doppler compared with CPR and/or MCA Doppler in the prediction of adverse perinatal outcome in women with a singleton pregnancy of any risk profile. Risk of bias and concerns about applicability were assessed using the QUADAS‐2 (Quality Assessment of Diagnostic Accuracy Studies‐2) tool. Meta‐analysis was performed for multiple adverse perinatal outcomes. Using hierarchal summary receiver–operating characteristics meta‐regression models, the prognostic accuracy of CPR vs MCA Doppler was compared indirectly, and CPR and MCA Doppler vs UA Doppler compared directly. Results The search identified 4693 articles, of which 128 studies (involving 47 748 women) were included. Risk of bias or suboptimal reporting was detected in 120/128 studies (94%) and substantial heterogeneity was found, which limited subgroup analyses for fetal growth and gestational age. A large variation was observed in reported sensitivities and specificities, and in thresholds used. CPR outperformed UA Doppler in the prediction of composite adverse outcome (as defined in the included studies) (P < 0.001) and emergency delivery for fetal distress (P = 0.003), but was comparable to UA Doppler for the other outcomes. MCA Doppler performed significantly worse than did UA Doppler in the prediction of low Apgar score (P = 0.017) and emergency delivery for fetal distress (P = 0.034). CPR outperformed MCA Doppler in the prediction of composite adverse outcome (P < 0.001) and emergency delivery for fetal distress (P = 0.013). Conclusion Calculating the CPR with MCA Doppler can add value to UA Doppler assessment in the prediction of adverse perinatal outcome in women with a singleton pregnancy. However, it is unclear to which subgroup of pregnant women this applies. The effectiveness of the CPR in guiding clinical management needs to be evaluated in clinical trials. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. PMID:28708272

Diagnosis-Specific Prognostic Factors, Indexes, and Treatment Outcomes for Patients With Newly Diagnosed Brain Metastases: A Multi-Institutional Analysis of 4,259 Patients

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

Sperduto, Paul W., E-mail: psperduto@mropa.co; Chao, Samuel T.; Sneed, Penny K.

2010-07-01

Purpose: Controversy endures regarding the optimal treatment of patients with brain metastases (BMs). Debate persists, despite many randomized trials, perhaps because BM patients are a heterogeneous population. The purpose of the present study was to identify significant diagnosis-specific prognostic factors and indexes (Diagnosis-Specific Graded Prognostic Assessment [DS-GPA]). Methods and Materials: A retrospective database of 5,067 patients treated for BMs between 1985 and 2007 was generated from 11 institutions. After exclusion of the patients with recurrent BMs or incomplete data, 4,259 patients with newly diagnosed BMs remained eligible for analysis. Univariate and multivariate analyses of the prognostic factors and outcomes bymore » primary site and treatment were performed. The significant prognostic factors were determined and used to define the DS-GPA prognostic indexes. The DS-GPA scores were calculated and correlated with the outcomes, stratified by diagnosis and treatment. Results: The significant prognostic factors varied by diagnosis. For non-small-cell lung cancer and small-cell lung cancer, the significant prognostic factors were Karnofsky performance status, age, presence of extracranial metastases, and number of BMs, confirming the original GPA for these diagnoses. For melanoma and renal cell cancer, the significant prognostic factors were Karnofsky performance status and the number of BMs. For breast and gastrointestinal cancer, the only significant prognostic factor was the Karnofsky performance status. Two new DS-GPA indexes were thus designed for breast/gastrointestinal cancer and melanoma/renal cell carcinoma. The median survival by GPA score, diagnosis, and treatment were determined. Conclusion: The prognostic factors for BM patients varied by diagnosis. The original GPA was confirmed for non-small-cell lung cancer and small-cell lung cancer. New DS-GPA indexes were determined for other histologic types and correlated with the outcome, and statistical separation between the groups was confirmed. These data should be considered in the design of future randomized trials and in clinical decision-making.« less

Adverse prognostic value of MYBL2 overexpression and association with microRNA-30 family in acute myeloid leukemia patients.

PubMed

Fuster, Oscar; Llop, Marta; Dolz, Sandra; García, Paloma; Such, Esperanza; Ibáñez, Mariam; Luna, Irene; Gómez, Inés; López, María; Cervera, José; Montesinos, Pau; Moscardó, Federico; Cordón, Lourdes; Solves, Pilar; de Juan, Inmaculada; Palanca, Sarai; Bolufer, Pascual; Sanz, Miguel Ángel; Barragán, Eva

2013-12-01

The MYBL2 gene encodes a transcription factor implicated in cell proliferation and maturation whose amplification or overexpression has been associated with different human malignancies, suggesting that it could be implicated in tumorigenesis. We analyzed MYBL2 expression and its prognostic value in 291 patients with de novo acute myeloid leukemia (AML) and we also evaluated its association with microRNAs 29 and 30 families. MYBL2 expression in AML patients was increased relative to CD34+ cells. Moreover, MYBL2 overexpression was associated with lower expression of miR-30a (P=0.024), miR-30b (P=0.021) and miR-30c (P=0.009). Multivariate analysis showed that MYBL2 expression was an independent factor for disease-free survival (HR 3.0, 95% CI 1.5-6.0, P=0.002) and cumulative incidence of relapse (HR 2.6, 95% CI 1.2-5.6, P=0.015) in patients with an intermediate-risk karyotype. In conclusion, our data showed that MYBL2 expression analysis could be useful to define subgroups of patients with poor prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Oestrogen receptor status, treatment and breast cancer prognosis in Icelandic BRCA2 mutation carriers.

PubMed

Jonasson, Jon G; Stefansson, Olafur A; Johannsson, Oskar T; Sigurdsson, Helgi; Agnarsson, Bjarni A; Olafsdottir, Gudridur H; Alexiusdottir, Kristin K; Stefansdottir, Hrefna; Munoz Mitev, Rodrigo; Olafsdottir, Katrin; Olafsdottir, Kristrun; Arason, Adalgeir; Stefansdottir, Vigdis; Olafsdottir, Elinborg J; Barkardottir, Rosa B; Eyfjord, Jorunn E; Narod, Steven A; Tryggvadóttir, Laufey

2016-09-27

The impact of an inherited BRCA2 mutation on the prognosis of women with breast cancer has not been well documented. We studied the effects of oestrogen receptor (ER) status, other prognostic factors and treatments on survival in a large cohort of BRCA2 mutation carriers. We identified 285 breast cancer patients with a 999del5 BRCA2 mutation and matched them with 570 non-carrier patients. Clinical information was abstracted from patient charts and pathology records and supplemented by evaluation of tumour grade and ER status using archived tissue specimens. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. The effects of various therapies were studied in patients treated from 1980 to 2012. Among mutation carriers, positive ER status was associated with higher risk of death than negative ER status (HR=1.94; 95% CI=1.22-3.07, P=0.005). The reverse association was seen for non-carriers (HR=0.71; 95% CI: 0.51-0.97; P=0.03). Among BRCA2 carriers, ER-positive status is an adverse prognostic factor. BRCA2 carrier status should be known at the time when treatment decisions are made.

Admission factors can predict the need for ICU monitoring in gallstone pancreatitis.

PubMed

Arnell, T D; de Virgilio, C; Chang, L; Bongard, F; Stabile, B E

1996-10-01

The purpose was 1) to prospectively determine the prevalence of adverse events necessitating intensive care unit (ICU) monitoring in gallstone pancreatitis (GP) and 2) To identify admission prognostic indicators that predict the need for ICU unit monitoring. Prospective laboratory data, physiologic parameters, and APACHE II scores were gathered on 102 patients with GP over 14 months. Adverse events were defined as cardiac, respiratory, or renal failure, gastrointestinal bleeding, stroke, sepsis, and necrotizing pancreatitis. Patients were divided into Group 1 (no adverse events, n=95) and Group 2 (adverse events, n=7). There were no deaths and 7 (7%) adverse events, including necrotizing pancreatitis (3), cholangitis (2), and cardiac (2). APACHE 11 > or = 5 (P < 0.005), blood urea nitrogen (BUN) > or = 12 mmol/L (P < 0.005), white blood cell count (WBC) > or = 14.5 x 10(9)/L, (P < 0.001), heart rate > or = 100 bpm (P < 0.001), and glucose > or = 150 mg/dL (P < 0.005) were each independent predictors of adverse events. The sensitivity and specificity of these criteria for predicting severe complications requiring ICU care varied from 71 to 86 per cent and 78 to 87 per cent, respectively. The prevalence of adverse events necessitating ICU care in GP patients is low. Glucose, BUN, WBC, heart rate, and APACHE II scores are independent predictors of adverse events necessitating ICU care. Single criteria predicting the need for ICU care on admission are readily available on admission.

Hyponatremia is Associated with Fluid Imbalance and Adverse Renal Outcome in Chronic Kidney Disease Patients Treated with Diuretics.

PubMed

Lim, Lee Moay; Tsai, Ni-Chin; Lin, Ming-Yen; Hwang, Daw-Yang; Lin, Hugo You-Hsien; Lee, Jia-Jung; Hwang, Shang-Jyh; Hung, Chi-Chih; Chen, Hung-Chun

2016-11-14

Chronic kidney disease (CKD) is frequently complicated with hyponatremia, probably because of fluid overload or diuretic usage. Hyponatremia in CKD population is associated with increased mortality, but the effect on renal outcome was unknown. We investigated whether hyponatremia is associated with fluid status and is a prognostic indicator for adverse outcomes in a CKD cohort of 4,766 patients with 1,009 diuretic users. We found that diuretic users had worse clinical outcomes compared with diuretic non-users. Hyponatremia (serum sodium <135 mEq/L) was associated with excessive volume and volume depletion, measured as total body water by bioimpedance analysis, in diuretic users, but not in diuretic non-users. Furthermore, in Cox survival analysis, hyponatremia was associated with an increased risk for renal replacement therapy (hazard ratio, 1.45; 95% CI, 1.13-1.85, P < 0.05) in diuretic users, but not in diuretic non-users (P for interaction <0.05); restricted cubic spline model also showed a similar result. Hyponatremia was not associated with all-cause mortality or cardiovascular event whereas hypernatremia (serum sodium >141 mEq/L) was associated with an increased risk for all-cause mortality. Thus, hyponatremia is an indicator of fluid imbalance and also a prognostic factor for renal replacement therapy in CKD patients treated with diuretics.

Hyponatremia is Associated with Fluid Imbalance and Adverse Renal Outcome in Chronic Kidney Disease Patients Treated with Diuretics

PubMed Central

Lim, Lee Moay; Tsai, Ni-Chin; Lin, Ming-Yen; Hwang, Daw-Yang; Lin, Hugo You-Hsien; Lee, Jia-Jung; Hwang, Shang-Jyh; Hung, Chi-Chih; Chen, Hung-Chun

2016-01-01

Chronic kidney disease (CKD) is frequently complicated with hyponatremia, probably because of fluid overload or diuretic usage. Hyponatremia in CKD population is associated with increased mortality, but the effect on renal outcome was unknown. We investigated whether hyponatremia is associated with fluid status and is a prognostic indicator for adverse outcomes in a CKD cohort of 4,766 patients with 1,009 diuretic users. We found that diuretic users had worse clinical outcomes compared with diuretic non-users. Hyponatremia (serum sodium <135 mEq/L) was associated with excessive volume and volume depletion, measured as total body water by bioimpedance analysis, in diuretic users, but not in diuretic non-users. Furthermore, in Cox survival analysis, hyponatremia was associated with an increased risk for renal replacement therapy (hazard ratio, 1.45; 95% CI, 1.13–1.85, P < 0.05) in diuretic users, but not in diuretic non-users (P for interaction <0.05); restricted cubic spline model also showed a similar result. Hyponatremia was not associated with all-cause mortality or cardiovascular event whereas hypernatremia (serum sodium >141 mEq/L) was associated with an increased risk for all-cause mortality. Thus, hyponatremia is an indicator of fluid imbalance and also a prognostic factor for renal replacement therapy in CKD patients treated with diuretics. PMID:27841359

Prognostic Utility of Novel Biomarkers of Cardiovascular Stress: The Framingham Heart Study

PubMed Central

Wang, Thomas J.; Wollert, Kai C.; Larson, Martin G.; Coglianese, Erin; McCabe, Elizabeth L.; Cheng, Susan; Ho, Jennifer E.; Fradley, Michael G.; Ghorbani, Anahita; Xanthakis, Vanessa; Kempf, Tibor; Benjamin, Emelia J.; Levy, Daniel; Vasan, Ramachandran S.; Januzzi, James L.

2013-01-01

Background Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. Methods and Results To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3,428 participants (mean age 59, 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a “multimarker” score composed of the 3 biomarkers, in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each endpoint (p<0.001) except for coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2, 95% CI, 2.2–4.7; p<0.001), 6-fold risk of heart failure (6.2, 95% CI, 2.6–14.8; p<0.001), and 2-fold risk of cardiovascular events (1.9, 95% CI, 1.3–2.7; p=0.001). Addition of the multimarker score to clinical variables led to significant increases in the c-statistic (p=0.007 or lower) and net reclassification improvement (p=0.001 or lower). Conclusions Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals, and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure. PMID:22907935

High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma

PubMed Central

Raso, Alessandro; Mascelli, Samantha; Biassoni, Roberto; Nozza, Paolo; Kool, Marcel; Pistorio, Angela; Ugolotti, Elisabetta; Milanaccio, Claudia; Pignatelli, Sara; Ferraro, Manuela; Pavanello, Marco; Ravegnani, Marcello; Cama, Armando; Garrè, Maria Luisa; Capra, Valeria

2011-01-01

The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative– polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P= .007) and in those with metastasis (P= .03). Kaplan–Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P= .0004 and P= .002, for OS and PFS for all cases, respectively; P= .002 and P= .008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P= .008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P= .019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting. PMID:21486962

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

Muijs, Christina, E-mail: c.t.muijs@umcg.nl; Smit, Justin; Karrenbeld, Arend

Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis wasmore » performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.« less

Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.

PubMed

Wang, Thomas J; Wollert, Kai C; Larson, Martin G; Coglianese, Erin; McCabe, Elizabeth L; Cheng, Susan; Ho, Jennifer E; Fradley, Michael G; Ghorbani, Anahita; Xanthakis, Vanessa; Kempf, Tibor; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Januzzi, James L

2012-09-25

Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3428 participants (mean age, 59 years; 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a "multimarker" score composed of the 3 biomarkers in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each end point (P<0.001) except coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2; 95% confidence interval, 2.2-4.7; P<0.001), 6-fold risk of heart failure (6.2; 95% confidence interval, 2.6-14.8; P<0.001), and 2-fold risk of cardiovascular events (1.9; 95% confidence interval, 1.3-2.7; P=0.001). Addition of the multimarker score to clinical variables led to significant increases in the c statistic (P=0.005 or lower) and net reclassification improvement (P=0.001 or lower). Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.

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

PubMed

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

2015-03-01

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

Predictive factors for long-term survival in patients with clinically significant portal hypertension following resection of hepatocellular carcinoma.

PubMed

Choi, Gi H; Park, Jun Y; Hwang, Ho K; Kim, Dong H; Kang, Chang M; Choi, Jin S; Park, Young N; Kim, Do Y; Ahn, Sang H; Han, Kwang-Hyub; Chon, Chae Y; Lee, Woo J

2011-04-01

Hepatic resection for hepatocellular carcinoma (HCC) is not currently recommended for patients with clinically significant portal hypertension (PHT); however, recent studies have shown similar post-operative outcomes between patients with and without clinically significant PHT. To clarify the post-operative prognostic relevance of clinically significant PHT in Child-Pugh A cirrhotic patients. A total of 100 Child-Pugh A cirrhotic patients who underwent curative resection of HCC were eligible for this analysis. Patients were divided into two groups: PHT group (n=47) and non-PHT group (n=53). Clinicopathological variables showed no significant differences except for prothrombine time. Liver-related complications were significantly higher in the PHT group (P=0.015), and the 5-year overall survival rate was significantly higher in the non-PHT group (78.7 vs. 37.9%, P<0.001). The proportion of patients who died because of complications of cirrhosis was significantly higher in the PHT group (P=0.001). Multivariate analysis indicated that the presence of clinically significant PHT was the most powerful adverse prognostic factor for overall survival. Multivariate analysis of the 47 patients with clinically significant PHT indicated that gross vascular invasion and non-single nodular type were poor prognostic factors. The 5-year survival rate of patients with single nodular type and without gross vascular invasion (n=17) was 78.4%. In Child-Pugh A cirrhotic patients, the presence of clinically significant PHT was significantly associated with post-operative hepatic decompensation and poor prognosis after resection of HCC. However, in patients with clinically significant PHT, those with single nodular tumours lacking gross vascular invasion may be good surgical candidates. © 2011 John Wiley & Sons A/S.

Differential Prognostic Value of Coronary Computed Tomography Angiography in Relation to Exercise Electrocardiography in Asymptomatic Subjects

PubMed Central

Lee, Sang-Eun; Cho, Iksung; Hong, Geu-Ru; Sung, Ji Min; Cho, In-Jeong; Shim, Chi Young; Choi, Byoung Wook; Chung, Namsik

2015-01-01

Background To explore the prognostic performance of coronary computed tomography angiography (CCTA) and exercise electrocardiography (XECG) in asymptomatic subjects. Methods We retrospectively enrolled 812 (59 ± 9 years, 60.8% male) asymptomatic subjects who underwent CCTA and XECG concurrently from 2003 through 2009. Subjects were followed-up for major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, unstable angina, and revascularization after 90 days from index CCTA. Results The prevalence of occult coronary artery disease (CAD) detected by CCTA was 17.5% and 120 subjects (14.8%) had positive XECG. During a mean follow-up of 37 ± 16 months, nine subjects experienced MACE. In multivariable Cox-regression analysis, only the presence of CAD by CCTA independently predicted future MACE (p = 0.002). Moreover, CAD by CCTA improved the predictive value when added to a clinical risk factor model using the likelihood ratio test (p < 0.001). Notably, the prognostic value of CCTA persisted in the moderate-to-high-risk group as classified by the Duke treadmill score (p = 0.040), but not in the low-risk group (p = 0.991). Conclusion CCTA provides incremental prognostic benefit over and above XECG in an asymptomatic population, especially for those in a moderate-to-high-risk group as classified by the Duke treadmill score. Risk stratification using XECG may prove valuable for identifying asymptomatic subjects who can benefit from CCTA. PMID:26755933

Prevalence and Impact of Co-morbidity Burden as Defined by the Charlson Co-morbidity Index on 30-Day and 1- and 5-Year Outcomes After Coronary Stent Implantation (from the Nobori-2 Study).

PubMed

Mamas, Mamas A; Fath-Ordoubadi, Farzin; Danzi, Gian B; Spaepen, Erik; Kwok, Chun Shing; Buchan, Iain; Peek, Niels; de Belder, Mark A; Ludman, Peter F; Paunovic, Dragica; Urban, Philip

2015-08-01

Co-morbidities have typically been considered as prevalent cardiovascular risk factors and cardiovascular diseases rather than systematic measures of general co-morbidity burden in patients who underwent percutaneous coronary intervention (PCI). Charlson co-morbidity index (CCI) is a measure of co-morbidity burden providing a means of quantifying the prognostic impact of 22 co-morbid conditions on the basis of their number and prognostic impact. The study evaluated the impact of the CCI on cardiac mortality and major adverse cardiovascular events (MACE) after PCI through analysis of the Nobori-2 study. The prognostic impact of CCI was studied in 3,067 patients who underwent PCI in 4,479 lesions across 125 centers worldwide on 30-day and 1- and 5-year cardiac mortality and MACE. Data were adjusted for potential confounders using stepwise logistic regression; 2,280 of 3,067 patients (74.4%) had ≥1 co-morbid conditions. CCI (per unit increase) was independently associated with an increase in both cardiac death (odds ratio [OR] 1.47 95% confidence interval [CI] 1.20 to 1.80, p = 0.0002) and MACE (OR 1.29 95% CI 1.14 to 1.47, p ≤0.0011) at 30 days, with similar observations recorded at 1 and 5 years. CCI score ≥2 was independently associated with increased 30-day cardiac death (OR 4.25, 95% CI 1.24 to 14.56, p = 0.02) at 1 month, and this increased risk was also observed at 1 and 5 years. In conclusion, co-morbid burden, as measured using CCI, is an independent predictor of adverse outcomes in the short, medium, and long term. Co-morbidity should be considered in the decision-making process when counseling patients regarding the periprocedural risks associated with PCI, in conjunction with traditional risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma

PubMed Central

Ok, Chi Young; Tzankov, Alexandar; Manyam, Ganiraju C.; Sun, Ruifan; Visco, Carlo; Zhang, Mingzhi; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Møller, Michael B.; Wang, Jinfeng; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Pham, Lan V.; Medeiros, L. Jeffrey; Young, Ken H.

2015-01-01

Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-κB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2− activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-κB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications. PMID:26324762

Idiosyncratic drug-induced agranulocytosis or acute neutropenia.

PubMed

Andrès, Emmanuel; Maloisel, Frédéric

2008-01-01

Idiosyncratic drug-induced agranulocytosis or acute neutropenia is an adverse event resulting in a neutrophil count of under 0.5 x 10/l. Patients with such severe neutropenia are likely to experience life-threatening and sometimes fatal infections. Over the last 20 years, the incidence of idiosyncratic drug-induced agranulocytosis or acute neutropenia has remained stable at 2.4-15.4 cases per million, despite the emergence of new causative drugs: antibiotics (beta-lactam and cotrimoxazole), antiplatelet agents (ticlopidine), antithyroid drugs, sulfasalazine, neuroleptics (clozapine), antiepileptic agents (carbamazepine), nonsteroidal anti-inflammatory agents and dipyrone. Drug-induced agranulocytosis remains a serious adverse event due to the occurrence of severe sepsis with severe deep infections (such as pneumonia), septicemia and septic shock in around two thirds of patients. In this setting, old age (>65 years), septicemia or shock, metabolic disorders such as renal failure, and a neutrophil count under 0.1 x 10/l are poor prognostic factors. Nevertheless with appropriate management using preestablished procedures, with intravenous broad-spectrum antibiotic therapy and hematopoietic growth factors, the mortality rate is currently around 5%. Given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, healthcare professionals should be aware of this adverse event and its management.

A novel H-FABP assay and a fast prognostic score for risk assessment of normotensive pulmonary embolism.

PubMed

Dellas, Claudia; Tschepe, Merle; Seeber, Valerie; Zwiener, Isabella; Kuhnert, Katherina; Schäfer, Katrin; Hasenfuß, Gerd; Konstantinides, Stavros; Lankeit, Mareike

2014-05-05

We tested whether heart-type fatty acid binding protein (H-FABP) measured by a fully-automated immunoturbidimetric assay in comparison to ELISA provides additive prognostic value in patients with pulmonary embolism (PE), and validated a fast prognostic score in comparison to the ESC risk prediction model and the simplified Pulmonary Embolism Severity Index (sPESI). We prospectively examined 271 normotensive patients with PE; of those, 20 (7%) had an adverse 30-day outcome. H-FABP levels determined by immunoturbidimetry were higher (median, 5.2 [IQR; 2.7-9.8] ng/ml) than those by ELISA (2.9 [1.1-5.4] ng/ml), but Bland-Altman plot demonstrated a good agreement of both assays. The area under the curve for H-FABP was greater for immunoturbidimetry than for ELISA (0.82 [0.74-0.91] vs 0.78 [0.68-0.89]; P=0.039). H-FABP measured by immunoturbidimetry (but not by ELISA) provided additive prognostic information to other predictors of 30-day outcome (OR, 12.4 [95% CI, 1.6-97.6]; P=0.017). When H-FABP determined by immunoturbidimetry was integrated into a novel prognostic score (H-FABP, Syncope, and Tachycardia; FAST score), the score provided additive prognostic information by multivariable analysis (OR, 14.2 [3.9-51.4]; p<0.001; c-index, 0.86) which were superior to information obtained by the ESC model (c-index, 0.62; net reclassification improvement (NRI), 0.39 [0.21-0.56]; P<0.001) or the sPESI (c-index, 0.68; NRI, 0.24 [0.05-0.43]; P=0.012). In conclusion, determination of H-FABP by immunoturbidimetry provides prognostic information superior to that of ELISA and, if integrated in the FAST score, appears more suitable to identify patients with an adverse 30-day outcome compared to the ESC model and sPESI.

Clinical significance of residual platelet reactivity in patients treated with platelet P2Y12 inhibitors.

PubMed

Thomas, Mark R; Storey, Robert F

2016-09-01

Platelet P2Y12 inhibitors have become an essential component of the treatment strategy for patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention. It is now well-established that approximately 30% of patients treated with the P2Y12 inhibitor clopidogrel display high residual platelet reactivity despite treatment. Patients with high on-treatment platelet reactivity have approximately 2-3-fold greater risk of adverse cardiovascular events and stent thrombosis than those without high platelet reactivity. Conversely, clopidogrel-treated patients with low platelet reactivity display approximately 1.7-fold increased risk of major bleeding. High platelet reactivity is uncommon during treatment with prasugrel and ticagrelor, which achieve a greater reduction in adverse cardiovascular events compared to clopidogrel in ACS patients treated with PCI. This is at the expense of an increase in spontaneous bleeding, however. Minor bleeding events, such as skin haematomas, are more common in prasugrel- and ticagrelor-treated patients that have particularly low platelet reactivity values. These minor bleeding events may occasionally prompt discontinuation of therapy, but their overall prognostic impact is uncertain. However, risk factors for bleeding tend to overlap with risk factors for adverse cardiovascular events. Therefore, patients with these minor bleeding events may also be at higher risk of adverse cardiovascular events, conferring a benefit from low platelet reactivity. Further work is needed to determine the optimal level of platelet reactivity in individuals by taking into account their risk of subsequent adverse cardiovascular events and bleeding. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of time to return of spontaneous circulation on neuroprotective effect of targeted temperature management at 33 or 36 degrees in comatose survivors of out-of hospital cardiac arrest.

PubMed

Kjaergaard, Jesper; Nielsen, Niklas; Winther-Jensen, Matilde; Wanscher, Michael; Pellis, Tommaso; Kuiper, Michael; Hartvig Thomsen, Jakob; Wetterslev, Jørn; Cronberg, Tobias; Bro-Jeppesen, John; Erlinge, David; Friberg, Hans; Søholm, Helle; Gasche, Yvan; Horn, Janneke; Hovdenes, Jan; Stammet, Pascal; Wise, Matthew P; Åneman, Anders; Hassager, Christian

2015-11-01

Time to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33°C over 36°C on the prognostic importance of time to ROSC. In predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days. Prolonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01-1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1-2) and mRS (p=0.17, mRS 0-3) with no significant interaction with level of TTM. Time to ROSC remains a significant prognostic factor in comatose OHCA patients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33°C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36°C. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Vehicle Integrated Prognostic Reasoner (VIPR) 2010 Annual Final Report

NASA Technical Reports Server (NTRS)

Hadden, George D.; Mylaraswamy, Dinkar; Schimmel, Craig; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

2011-01-01

Honeywell's Central Maintenance Computer Function (CMCF) and Aircraft Condition Monitoring Function (ACMF) represent the state-of-the art in integrated vehicle health management (IVHM). Underlying these technologies is a fault propagation modeling system that provides nose-to-tail coverage and root cause diagnostics. The Vehicle Integrated Prognostic Reasoner (VIPR) extends this technology to interpret evidence generated by advanced diagnostic and prognostic monitors provided by component suppliers to detect, isolate, and predict adverse events that affect flight safety. This report describes year one work that included defining the architecture and communication protocols and establishing the user requirements for such a system. Based on these and a set of ConOps scenarios, we designed and implemented a demonstration of communication pathways and associated three-tiered health management architecture. A series of scripted scenarios showed how VIPR would detect adverse events before they escalate as safety incidents through a combination of advanced reasoning and additional aircraft data collected from an aircraft condition monitoring system. Demonstrating VIPR capability for cases recorded in the ASIAS database and cross linking them with historical aircraft data is planned for year two.

Preoperative prognostic factors for mortality in peptic ulcer perforation: a systematic review.

PubMed

Møller, Morten Hylander; Adamsen, Sven; Thomsen, Reimar Wernich; Møller, Ann Merete

2010-08-01

Mortality and morbidity following perforated peptic ulcer (PPU) is substantial and probably related to the development of sepsis. During the last three decades a large number of preoperative prognostic factors in patients with PPU have been examined. The aim of this systematic review was to summarize available evidence on these prognostic factors. MEDLINE (January 1966 to June 2009), EMBASE (January 1980 to June 2009), and the Cochrane Library (Issue 3, 2009) were screened for studies reporting preoperative prognostic factors for mortality in patients with PPU. The methodological quality of the included studies was assessed. Summary relative risks with 95% confidence intervals for the identified prognostic factors were calculated and presented as Forest plots. Fifty prognostic studies with 37 prognostic factors comprising a total of 29,782 patients were included in the review. The overall methodological quality was acceptable, yet only two-thirds of the studies provided confounder adjusted estimates. The studies provided strong evidence for an association of older age, comorbidity, and use of NSAIDs or steroids with mortality. Shock upon admission, preoperative metabolic acidosis, tachycardia, acute renal failure, low serum albumin level, high American Society of Anaesthesiologists score, and preoperative delay >24 h were associated with poor prognosis. In patients with PPU, a number of negative prognostic factors can be identified prior to surgery, and many of these seem to be related to presence of the sepsis syndrome.

Accumulation of FOXP3+T-cells in the tumor microenvironment is associated with an epithelial-mesenchymal-transition-type tumor budding phenotype and is an independent prognostic factor in surgically resected pancreatic ductal adenocarcinoma

PubMed Central

Wartenberg, Martin; Zlobec, Inti; Perren, Aurel; Koelzer, Viktor Hendrik; Gloor, Beat; Lugli, Alessandro; Eva, Karamitopoulou

2015-01-01

Here we explore the role of the interplay between host immune response and epithelial-mesenchymal-transition (EMT)-Type tumor-budding on the outcome of pancreatic adenocarcinoma (PDAC). CD4+, CD8+, and FOXP3+T-cells as well as iNOS+ (M1) and CD163+-macrophages (M2) were assessed on multipunch tissue-microarrays containing 120 well-characterized PDACs, precursor lesions (PanINs) and corresponding normal tissue. Counts were normalized for the percentage of tumor/spot and associated with the clinico-pathological features, including peritumoral (PTB) and intratumoral (ITB) EMT-Type tumor-budding and outcome. Increased FOXP3+T-cell-counts and CD163-macrophages and decreased CD8+T-cell-counts were observed in PDACs compared with normal tissues and PanINs (p < 0.0001). Increased peritumoral FOXP3+T-cell-counts correlated significantly with venous invasion, distant metastasis, R1-status, high-grade ITB, PTB and independently with reduced survival. Increased intratumoral FOXP3+T-cells correlated with lymphatic invasion, N1-stage, PTB and marginally with adverse outcome. High peritumoral CD163-counts correlated with venous invasion, PTB and ITB. High intratumoral CD163-counts correlated with higher T-stage and PTB. PDAC-microenvironment displays a tumor-favoring immune-cell composition especially in the immediate environment of the tumor-buds that promotes further growth and indicates a close interaction of the immune response with the EMT-process. Increased peritumoral FOXP3+T-cell density is identified as an independent adverse prognostic factor in PDAC. Patients with phenotypically aggressive PDACs may profit from targeted immunotherapy against FOXP3. PMID:25669968

Prognostic value of depression, anxiety, and anger in hospitalized cardiovascular disease patients for predicting adverse cardiac outcomes.

PubMed

Nakamura, Shunichi; Kato, Koji; Yoshida, Asuka; Fukuma, Nagaharu; Okumura, Yasuyuki; Ito, Hiroto; Mizuno, Kyoichi

2013-05-15

Although attention has recently been focused on the role of psychosocial factors in patients with cardiovascular disease (CVD), the factors that have the greatest influence on prognosis have not yet been elucidated. The aim of this study was to evaluate the effects of depression, anxiety, and anger on the prognosis of patients with CVD. Four hundred fourteen consecutive patients hospitalized with CVD were prospectively enrolled. Depression was evaluated using the Patient Health Questionnaire, anxiety using the Generalized Anxiety Disorder Questionnaire, and anger using the Spielberger Trait Anger Scale. Cox proportional-hazards regression was used to examine the individual effects of depression, anxiety, and anger on a combined primary end point of cardiac death or cardiac hospitalization and on a combined secondary end point of all-cause death or hospitalization during follow-up (median 14.2 months). Multivariate analysis showed that depression was a significant risk factor for cardiovascular hospitalization or death after adjusting for cardiac risk factors and other psychosocial factors (hazard ratio 2.62, p = 0.02), whereas anxiety was not significantly associated with cardiovascular hospitalization or death after adjustment (hazard ratio 2.35, p = 0.10). Anger was associated with a low rate of cardiovascular hospitalization or death (hazard ratio 0.34, p <0.01). In conclusion, depression in hospitalized patients with CVD is a stronger independent risk factor for adverse cardiac events than either anxiety or anger. Anger may help prevent adverse outcomes. Routine screening for depression should therefore be performed in patients with CVD, and the potential effects of anger in clinical practice should be reconsidered. Copyright © 2013 Elsevier Inc. All rights reserved.

Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning.

PubMed

Tang, Weidong; Ruan, Feng; Chen, Qi; Chen, Suping; Shao, Xuebo; Gao, Jianbo; Zhang, Mao

2016-07-01

Acute organophosphorus pesticide poisoning (AOPP) is becoming a significant problem and a potential cause of human mortality because of the abuse of organophosphate compounds. This study aims to determine the independent prognostic factors of AOPP by using multivariate logistic regression analysis. The clinical data for 71 subjects with AOPP admitted to our hospital were retrospectively analyzed. This information included the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, admission blood cholinesterase levels, 6-h post-admission blood cholinesterase levels, cholinesterase activity, blood pH, and other factors. Univariate analysis and multivariate logistic regression analyses were conducted to identify all prognostic factors and independent prognostic factors, respectively. A receiver operating characteristic curve was plotted to analyze the testing power of independent prognostic factors. Twelve of 71 subjects died. Admission blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, blood pH, and APACHE II scores were identified as prognostic factors for AOPP according to the univariate analysis, whereas only 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, and blood pH were independent prognostic factors identified by multivariate logistic regression analysis. The receiver operating characteristic analysis suggested that post-admission 6-h lactate clearance rates were of moderate diagnostic value. High 6-h post-admission blood lactate levels, low blood pH, and low post-admission 6-h lactate clearance rates were independent prognostic factors identified by multivariate logistic regression analysis. Copyright © 2016 by Daedalus Enterprises.

Factors predicting survival following complete surgical remission of pulmonary metastasis in osteosarcoma

PubMed Central

SALAH, SAMER; TOUBASI, SAMAR

2015-01-01

Pulmonary metastasectomy (PM) is associated with improved survival of patients with metastatic osteosarcoma; however, the factors affecting survival following achievement of complete surgical remission remain controversial. The main objective of this study was to report the outcomes and prognostic factors of osteosarcoma patients who achieved complete remission (CR) following PM. We analyzed the effect of demographic and disease-related characteristics on the overall survival (OS) of consecutive patients with metastatic osteosarcoma who were treated at a single institution and achieved CR following PM, through univariate and multivariate analyses. Between January, 2000 and August, 2013, 62 patients with metastatic osteosarcoma were treated and followed up at our institution. A total of 25 patients achieved CR following PM and were included in this analysis. The 5-year OS and disease-free survival following PM were 30 and 21%, respectively. The factors correlated with inferior OS in the univariate analysis included chondroblastic subtype, post-chemotherapy necrosis <90% in the primary tumor, metastasis detected during neoadjuvant or adjuvant chemotherapy and pathological identification of tumor cells reaching the visceral pleural surface of any of the resected nodules. In the multivariate analysis, the chondroblastic subtype was the sole independent adverse prognostic factor (HR=4.6, 95% CI: 1.0–21.3, P=0.044). Therefore, factors associated with tumor biology, including poor tumor necrosis in the primary tumor and detection of metastasis during primary chemotherapy, are associated with poor post-metastasectomy survival. In addition, chondroblastic subtype and visceral pleural involvement predicted poor prognosis in our series. PMID:25469287

Vehicle Integrated Prognostic Reasoner (VIPR) Final Report

NASA Technical Reports Server (NTRS)

Bharadwaj, Raj; Mylaraswamy, Dinkar; Cornhill, Dennis; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

2013-01-01

A systems view is necessary to detect, diagnose, predict, and mitigate adverse events during the flight of an aircraft. While most aircraft subsystems look for simple threshold exceedances and report them to a central maintenance computer, the vehicle integrated prognostic reasoner (VIPR) proactively generates evidence and takes an active role in aircraft-level health assessment. Establishing the technical feasibility and a design trade-space for this next-generation vehicle-level reasoning system (VLRS) is the focus of our work.

The Children's Hepatic tumors International Collaboration (CHIC): Novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model

PubMed Central

Czauderna, Piotr; Haeberle, Beate; Hiyama, Eiso; Rangaswami, Arun; Krailo, Mark; Maibach, Rudolf; Rinaldi, Eugenia; Feng, Yurong; Aronson, Daniel; Malogolowkin, Marcio; Yoshimura, Kenichi; Leuschner, Ivo; Lopez-Terrada, Dolores; Hishiki, Tomoro; Perilongo, Giorgio; von Schweinitz, Dietrich; Schmid, Irene; Watanabe, Kenichiro; Derosa, Marisa; Meyers, Rebecka

2016-01-01

Introduction Contemporary state-of-the-art management of cancer is increasingly defined by individualized treatment strategies. For very rare tumors, like hepatoblastoma, the development of biologic markers, and the identification of reliable prognostic risk factors for tailoring treatment, remains very challenging. The Children's Hepatic tumors International Collaboration (CHIC) is a novel international response to this challenge. Methods Four multicenter trial groups in the world, who have performed prospective controlled studies of hepatoblastoma over the past two decades (COG; SIOPEL; GPOH; and JPLT), joined forces to form the CHIC consortium. With the support of the data management group CINECA, CHIC developed a centralized online platform where data from eight completed hepatoblastoma trials were merged to form a database of 1605 hepatoblastoma cases treated between 1988 and 2008. The resulting dataset is described and the relationships between selected patient and tumor characteristics, and risk for adverse disease outcome (event-free survival; EFS) are examined. Results Significantly increased risk for EFS-event was noted for advanced PRETEXT group, macrovascular venous or portal involvement, contiguous extrahepatic disease, primary tumor multifocality and tumor rupture at enrollment. Higher age (≥8 years), low AFP (<100 ng/ml) and metastatic disease were associated with the worst outcome. Conclusion We have identified novel prognostic factors for hepatoblastoma, as well as confirmed established factors, that will be used to develop a future common global risk stratification system. The mechanics of developing the globally accessible web-based portal, building and refining the database, and performing this first statistical analysis has laid the foundation for future collaborative efforts. This is an important step for refining of the risk based grouping and approach to future treatment stratification, thus we think our collaboration offers a template for others to follow in the study of rare tumors and diseases. PMID:26655560

The Children's Hepatic tumors International Collaboration (CHIC): Novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model.

PubMed

Czauderna, Piotr; Haeberle, Beate; Hiyama, Eiso; Rangaswami, Arun; Krailo, Mark; Maibach, Rudolf; Rinaldi, Eugenia; Feng, Yurong; Aronson, Daniel; Malogolowkin, Marcio; Yoshimura, Kenichi; Leuschner, Ivo; Lopez-Terrada, Dolores; Hishiki, Tomoro; Perilongo, Giorgio; von Schweinitz, Dietrich; Schmid, Irene; Watanabe, Kenichiro; Derosa, Marisa; Meyers, Rebecka

2016-01-01

Contemporary state-of-the-art management of cancer is increasingly defined by individualized treatment strategies. For very rare tumors, like hepatoblastoma, the development of biologic markers, and the identification of reliable prognostic risk factors for tailoring treatment, remains very challenging. The Children's Hepatic tumors International Collaboration (CHIC) is a novel international response to this challenge. Four multicenter trial groups in the world, who have performed prospective controlled studies of hepatoblastoma over the past two decades (COG; SIOPEL; GPOH; and JPLT), joined forces to form the CHIC consortium. With the support of the data management group CINECA, CHIC developed a centralized online platform where data from eight completed hepatoblastoma trials were merged to form a database of 1605 hepatoblastoma cases treated between 1988 and 2008. The resulting dataset is described and the relationships between selected patient and tumor characteristics, and risk for adverse disease outcome (event-free survival; EFS) are examined. Significantly increased risk for EFS-event was noted for advanced PRETEXT group, macrovascular venous or portal involvement, contiguous extrahepatic disease, primary tumor multifocality and tumor rupture at enrollment. Higher age (≥ 8 years), low AFP (<100 ng/ml) and metastatic disease were associated with the worst outcome. We have identified novel prognostic factors for hepatoblastoma, as well as confirmed established factors, that will be used to develop a future common global risk stratification system. The mechanics of developing the globally accessible web-based portal, building and refining the database, and performing this first statistical analysis has laid the foundation for future collaborative efforts. This is an important step for refining of the risk based grouping and approach to future treatment stratification, thus we think our collaboration offers a template for others to follow in the study of rare tumors and diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Systematic review of prognostic factors predicting outcome in non-surgically treated patients with sciatica.

PubMed

Verwoerd, A J H; Luijsterburg, P A J; Lin, C W C; Jacobs, W C H; Koes, B W; Verhagen, A P

2013-09-01

Identification of prognostic factors for surgery in patients with sciatica is important to be able to predict surgery in an early stage. Identification of prognostic factors predicting persistent pain, disability and recovery are important for better understanding of the clinical course, to inform patient and physician and support decision making. Consequently, we aimed to systematically review prognostic factors predicting outcome in non-surgically treated patients with sciatica. A search of Medline, Embase, Web of Science and Cinahl, up to March 2012 was performed for prospective cohort studies on prognostic factors for non-surgically treated sciatica. Two reviewers independently selected studies for inclusion and assessed the risk of bias. Outcomes were pain, disability, recovery and surgery. A best evidence synthesis was carried out in order to assess and summarize the data. The initial search yielded 4392 articles of which 23 articles reporting on 14 original cohorts met the inclusion criteria. High clinical, methodological and statistical heterogeneity among studies was found. Reported evidence regarding prognostic factors predicting the outcome in sciatica is limited. The majority of factors that have been evaluated, e.g., age, body mass index, smoking and sensory disturbance, showed no association with outcome. The only positive association with strong evidence was found for leg pain intensity at baseline as prognostic factor for subsequent surgery. © 2013 European Federation of International Association for the Study of Pain Chapters.

Early prognostic factors of outcomes in monochorionic twin pregnancy: systematic review and meta-analysis.

PubMed

Mackie, Fiona L; Hall, Matthew J; Morris, R Katie; Kilby, Mark D

2018-05-12

Assess ability of first trimester pregnancy related factors (ultrasound measurements, maternal characteristics, biomarkers) to predict complications in monochorionic twin pregnancies DATA SOURCES: MEDLINE, EMBASE, ISI Web of Science, CINAHL, the Cochrane Central Registration of Controlled Trials and Research Registers, and Google Scholar, from inception to 12 May 2017. Grey literature and bibliographies of articles were checked. Studies that reported ultrasound measurements, maternal characteristics, or potential biomarkers, measured in the first trimester in monochorionic diamniotic twin pregnancies, where the potential prognostic ability between the variable and twin-twin transfusion syndrome, growth restriction, or intrauterine fetal death could be assessed. Quality assessment was evaluated using the STROBE checklist by 2 reviewers independently. For meta-analysis, odds ratios using a random effects model, or standardized mean difference were calculated. If a moderate association was found, the prognostic ability was evaluated by calculating the sensitivity and specificity. Risk of heterogeneity was reported as I 2 and publication bias was visually assessed by funnel plots and quantitatively by Egger's test. Forty-eight studies were eligible for inclusion. Twenty meta-analyses could be performed. A moderate association was demonstrated in 3 meta-analyses, between: NT>95th centile in one/both fetuses and TTTS (OR 2.29 [95%CI 1.05, 4.96] I 2 =6.6%, 4 studies, 615 pregnancies); CRL discordance ≥10% and TTTS (OR 2.43 [95%CI 1.13, 5.21] I 2 =14.1%, 3 studies, 708 pregnancies); and maternal ethnicity and TTTS (OR 2.12 [95%CI 1.17, 3.83] I 2 =0.0%, 5 studies, 467 pregnancies), but none demonstrated a prognostic ability for any outcome under investigation. It is not currently possible to predict adverse outcomes in monochorionic twin pregnancies. We have revealed a lack of research investigating first trimester biomarkers in monochorionic twin pregnancies. Different assessment methods and definitions of each variable and outcome were an issue and this highlights the need for a large cohort study to evaluate these factors. Copyright © 2018 Elsevier Inc. All rights reserved.

Tumour-marker levels and prognosis in malignant teratoma of the testis.

PubMed Central

Germa-Lluch, J. R.; Begent, R. H.; Bagshawe, K. D.

1980-01-01

The effect of 6 putative prognostic factors on survival was studied in patients with Stages III and IV malignant teratoma of the testis. Differences between survival curves were tested for statistical significance. A diameter greater than 5 cm in the largest tumour mass, and greater than 8 pulmonary metastases were adverse prognostic factors (P = 0.004 and 0.008 respectively). Patients with malignant teratoma, trophoblastic, fared worse than those with malignant teratoma, undifferentiated, and malignant teratoma, intermediate (P = 0.011 and 0.023 respectively). Previous chemotherapy or radiotherapy had no significant effect. Serum alpha-foetoprotein (AFP) above 10(3) MRC u/ml and serum beta subunit of human chorionic gonadotrophin (hCG) above 10(5) miu/ml, were found to predict a poor prognosis (P = 0.010 and 0.001 respectively). A combination of measurements of the tumour markers gave the most consistent indication of prognosis, in that patients with either AFP greater than 10(3) MRC u/ml or hCG greater than 10(5) miu/ml, or both, fared much worse than those with neither factor (P = 0.001). Serum concentrations of AFP and hCG should be stated in reports of treatment of testicular teratoma in order to provide a basis for comparison with other series. Regular and frequent measurements of these markers are appropriate throughout the clinical management of patients with malignant teratoma. PMID:6161630

Predictive and Prognostic Factors in Definition of Risk Groups in Endometrial Carcinoma

PubMed Central

Sorbe, Bengt

2012-01-01

Background. The aim was to evaluate predictive and prognostic factors in a large consecutive series of endometrial carcinomas and to discuss pre- and postoperative risk groups based on these factors. Material and Methods. In a consecutive series of 4,543 endometrial carcinomas predictive and prognostic factors were analyzed with regard to recurrence rate and survival. The patients were treated with primary surgery and adjuvant radiotherapy. Two preoperative and three postoperative risk groups were defined. DNA ploidy was included in the definitions. Eight predictive or prognostic factors were used in multivariate analyses. Results. The overall recurrence rate of the complete series was 11.4%. Median time to relapse was 19.7 months. In a multivariate logistic regression analysis, FIGO grade, myometrial infiltration, and DNA ploidy were independent and statistically predictive factors with regard to recurrence rate. The 5-year overall survival rate was 73%. Tumor stage was the single most important factor with FIGO grade on the second place. DNA ploidy was also a significant prognostic factor. In the preoperative risk group definitions three factors were used: histology, FIGO grade, and DNA ploidy. Conclusions. DNA ploidy was an important and significant predictive and prognostic factor and should be used both in preoperative and postoperative risk group definitions. PMID:23209924

Do the key prognostic factors for non-specific neck pain have moderation effects? - A study protocol.

PubMed

Balasundaram, Arun Prasad; Robinson, Hilde Stendal; Vøllestad, Nina Køpke

2018-05-01

Neck pain is one of the common musculoskeletal conditions prevalent in the general population in Norway. Patients with neck pain, seek treatment from different health professionals such as general practitioners, physiotherapists, chiropractors and alternative medicine practitioners. The interventions for neck pain are typically provided in a primary care or specialised healthcare setting depending on the general practitioners' referral patterns. Clinicians are interested to know the various prognostic factors that can explain the recovery from neck pain. In order to know this, studies have explored and reported on a range of prognostic factors that contribute to the outcomes in patients with neck pain. This information is currently available only for neck pain following whiplash injury that has a traumatic origin. There is limited information on the role of prognostic factors specifically for non-specific neck pain without a traumatic episode. Moreover, there is a lack of data on whether there are interactions (moderation effects) between the prognostic factors. Therefore, we propose a hypothesis to elucidate whether the same set of prognostic factors found in neck pain associated with whiplash injuries are also identified in patients with neck pain without trauma. Additionally, we hypothesize that the association between a prognostic factor and the outcome variable (s) would be dependent on the third variable, thereby confirming the moderation effects. Clinicians could make informed decisions in the clinical management of neck pain with the knowledge of prognostic factors that explain the outcomes. It could also be used for the development of new interventions or for modifying the existing ones. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prognostic factors in patients with spinal metastasis: a systematic review and meta-analysis.

PubMed

Luksanapruksa, Panya; Buchowski, Jacob M; Hotchkiss, William; Tongsai, Sasima; Wilartratsami, Sirichai; Chotivichit, Areesak

2017-05-01

Incidence of symptomatic spinal metastasis has increased owing to improvement in treatment of the disease. One of the key factors that influences decision-making is expected patient survival. To our knowledge, no systematic reviews or meta-analysis have been conducted that review independent prognostic factors in spinal metastases. This study aimed to determine independent prognostic factors that affect outcome in patients with metastatic spine disease. This is a systematic literature review and meta-analysis of publications for prognostic factors in spinal metastatic disease. Pooled patient results from cohort and observational studies. Meta-analysis for poor prognostic factors as determined by hazard ratio (HR) and 95% confidential interval (95% CI). We systematically searched relevant publications in PubMed and Embase. The following search terms were used: ("'spinal metastases'" OR "'vertebral metastases'" OR "spinal metastasis" OR 'vertebral metastases') AND ('"prognostic factors"' OR "'survival'"). Inclusion criteria were prospective and retrospective cohort series that report HR and 95% CI of independent prognostic factors from multivariate analysis. Two reviewers independently assessed all papers. The quality of included papers was assessed by using Newcastle-Ottawa Scale for cohort studies and publication bias was assessed by using funnel plot, Begg test, and Egger test. The prognostic factors that were mentioned in at least three publications were pooled. Meta-analysis was performed using HR and 95% CI as the primary outcomes of interest. Heterogeneity was assessed using the I 2 method. A total of 3,959 abstracts (1,382 from PubMed and 2,577 from Embase) were identified through database search and 40 publications were identified through review of cited publications. The reviewers selected a total of 51 studies for qualitative synthesis and 43 studies for meta-analysis. Seventeen poor prognostic factors were identified. These included presence of a neurologic deficit before surgery, non-ambulatory status before radiotherapy (RT), non-ambulatory status before surgery, presence of bone metastases, presence of multiple bone metastases (>2 sites), presence of multiple spinal metastases (>3 sites), development of motor deficit in <7 days before initiating RT, development of motor deficit in <14 days before initiating RT, time interval from cancer diagnosis to RT <15 months, Karnofsky Performance Score (KPS) 10-40, KPS 50-70, KPS<70, Eastern Cooperative Oncology Group (ECOG) grade 3-4, male gender, presence of visceral metastases, moderate growth tumor on Tomita score (TS) classification, and rapid growth tumor on TS classification. Seventeen independent poor prognostic factors were identified in this study. These can be categorized into cancer-specific and nonspecific prognostic factors. A tumor-based prognostic scoring system that combines all specific and general factors may enhance the accuracy of survival prediction in patients with metastatic spine disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Retrospective cohort study of prognostic factors in patients with oral cavity and oropharyngeal squamous cell carcinoma.

PubMed

Carrillo, José F; Carrillo, Liliana C; Cano, Ana; Ramirez-Ortega, Margarita C; Chanona, Jorge G; Avilés, Alejandro; Herrera-Goepfert, Roberto; Corona-Rivera, Jaime; Ochoa-Carrillo, Francisco J; Oñate-Ocaña, Luis F

2016-04-01

Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma (SCC) are debated. The purpose of this study was to investigate the association of prognostic factors with oncologic outcomes. Patients with oral cavity and oropharyngeal SCC treated from 1997 to 2012 were included in this retrospective cohort study. Associations of prognostic factors with locoregional recurrence (LRR) or overall survival (OS) were analyzed using the logistic regression and the Cox models. Six hundred thirty-four patients were included in this study; tumor size, surgical margins, and N classification were associated with LRR (p < .0001); considering histopathology: perineural invasion, lymphocytic infiltration, infiltrative borders, and N classification were significant determinants of LRR. Tumor size, N classification, alcoholism, and surgical margins were associated with OS (p < .0001); considering pathologic prognostic factors, perivascular invasion, islands borders, and surgical margins were independently associated with OS (p < .0001). Surgical margins, perineural and perivascular invasion, lymphocytic infiltration, and infiltrative patterns of tumor invasion are significant prognostic factors in oral cavity and oropharyngeal SCC. © 2015 Wiley Periodicals, Inc.

Contribution of artificial intelligence to the knowledge of prognostic factors in laryngeal carcinoma.

PubMed

Zapater, E; Moreno, S; Fortea, M A; Campos, A; Armengot, M; Basterra, J

2000-11-01

Many studies have investigated prognostic factors in laryngeal carcinoma, with sometimes conflicting results. Apart from the importance of environmental factors, the different statistical methods employed may have influenced such discrepancies. A program based on artificial intelligence techniques is designed to determine the prognostic factors in a series of 122 laryngeal carcinomas. The results obtained are compared with those derived from two classical statistical methods (Cox regression and mortality tables). Tumor location was found to be the most important prognostic factor by all methods. The proposed intelligent system is found to be a sound method capable of detecting exceptional cases.

The predictive value of resting heart rate following osmotherapy in brain injury: back to basics.

PubMed

Hasanpour Mir, Mahsa; Yousefshahi, Fardin; Abdollahi, Mohammad; Ahmadi, Arezoo; Nadjafi, Atabak; Mojtahedzadeh, Mojtaba

2012-12-30

The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia.To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS). By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed. After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07). Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury.

Association of the type of 5q loss with complex karyotype, clonal evolution, TP53 mutation status, and prognosis in acute myeloid leukemia and myelodysplastic syndrome.

PubMed

Volkert, Sarah; Kohlmann, Alexander; Schnittger, Susanne; Kern, Wolfgang; Haferlach, Torsten; Haferlach, Claudia

2014-05-01

We analyzed 1,200 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) harboring a 5q deletion in order to clarify whether the type of 5q loss is associated with other biological markers and prognosis. We investigated all patients by chromosome banding analysis, FISH with a probe for EGR1 (5q31) and, if necessary, to resolve complex karyotypes with 24-color-FISH. Moreover, 420 patients were analyzed for mutations in the TP53 gene. The patient cohort was subdivided based on type of 5q loss: Patients with interstitial deletions and patients with 5q loss due to unbalanced rearrangements or monosomy 5. Loss of the long arm of chromosome 5 due to an unbalanced rearrangement occurred more often in AML (286/627; 45.6%) than MDS (188/573; 32.8%; P < 0.001). In both entities, patients with 5q loss due to unbalanced translocations showed complex karyotypes more frequently (MDS: 179/188; 95.2% vs. 124/385; 32.2%; P < 0.001; AML: 274/286; 95.8% vs. 256/341; 75.1%; P < 0.001). Moreover, in MDS unbalanced 5q translocations were associated with clonal evolution (109/188; 58.0% vs. 124/385; 32.2%; P < 0.001), mutation of TP53 (64/67; 95.5% vs. 40/120; 40.0%; P < 0.001), and shorter survival (15.3 months vs. not reached; P < 0.001). In MDS, complex karyotype was an independent adverse prognostic factor (HR = 5.34; P = 0.032), whereas in AML presence of TP53 mutations was the strongest adverse prognostic factor (HR = 2.21; P = 0.026). In conclusion, in AML and MDS, loss of the long arm of chromosome 5 due to unbalanced translocations is associated with complex karyotype and in MDS, moreover, with clonal evolution, mutations in the TP53 gene and adverse prognosis. Copyright © 2014 Wiley Periodicals, Inc.

Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

PubMed

Nickolas, Thomas L; Schmidt-Ott, Kai M; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C; Barasch, Jonathan

2012-01-17

This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Diagnostic and Prognostic Stratification in the Emergency Department Using Urinary Biomarkers of Nephron Damage

PubMed Central

Nickolas, Thomas L.; Schmidt-Ott, Kai M.; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J.; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C.; Barasch, Jonathan

2012-01-01

Objectives This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Background Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. Methods In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. Results All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Conclusion Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. PMID:22240130

Role of pelvic radiotherapy for locally advanced rectal cancer and synchronous unresectable distant metastases.

PubMed

Liu, K T; Wan, J F; Zhu, J; Li, G C; Sun, W J; Shen, L J; Cai, S J; Gu, W L; Lian, P; Zhang, Z

2016-12-01

To evaluate the efficacy and safety of pelvic irradiation combined systematic chemotherapy in patients with locally advanced (cT3-T4 and/or cN+) rectal cancer and synchronous unresectable distant metastases. A total of 76 eligible patients who received pelvic radiotherapy and concurrent capecitabine-based chemotherapy were retrospectively reviewed. Patients survival curves were constructed using the Kaplan-Meier method, and a multivariate analysis was performed to identify independent prognostic factors. Most of the adverse events were mild during the period of combined chemoradiotherapy. Twenty-two patients experienced resection of primary tumour and 16 patients underwent radical surgery of all lesions. Only five patients had pelvic progression during the follow-up period. The median progression-free survival and median overall survival were 13 and 30 months, respectively. Radical surgery of all lesions following chemoradiotherapy was found to be an independent prognostic factor according to multivariate analysis. Pelvic irradiation combined with systematic chemotherapy in patients with locally advanced rectal cancer and synchronous unresectable distant metastases is effective and tolerable, both for pelvic and distant control. A curative resection following chemoradiotherapy was associated with prolonged survival. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

PubMed

Garibaldi, Elisabetta; Gabriele, Domenico; Maggio, Angelo; Delmastro, Elena; Garibaldi, Monica; Russo, Filippo; Bresciani, Sara; Stasi, Michele; Gabriele, Pietro

2017-09-01

The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.

Long-term outcome in patients with germ cell tumours treated with POMB/ACE chemotherapy: comparison of commonly used classification systems of good and poor prognosis.

PubMed Central

Hitchins, R. N.; Newlands, E. S.; Smith, D. B.; Begent, R. H.; Rustin, G. J.; Bagshawe, K. D.

1989-01-01

We analysed outcome in 206 consecutive male patients treated for metastatic non-seminomatous germ cell tumour (NSGCT) of testicular or extragonadal origin treated with the POMB/ACE (cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide, etoposide) regimen after division into prognostic groups by commonly used clinical classification systems and definitions of adverse prognosis. The adverse prognostic groups of all classification systems and definitions examined showed similar, but only moderate, sensitivity (71-81%) and specificity (52-56%) in predicting death. A simple definition of poor prognosis based on raised initial levels of serum tumour markers alpha fetoprotein (aFP) and human chorionic gonadotrophin (hCG) proved at least as useful (sensitivity 80%, specificity 55%) as other more complicated systems in predicting failure to achieve long-term survival. Comparison of survival between ultra-high dose cisplatin-based combination chemotherapy and patients treated with POMB/ACE shows no advantage from this more toxic approach. This suggests that good results in adverse prognosis patients can be achieved using conventional dose regimens administered intensively. PMID:2467682

Traditional and emerging molecular markers in neuroblastoma prognosis: the good, the bad and the ugly.

PubMed

Poremba, C; Hero, B; Goertz, H G; Scheel, C; Wai, D; Schaefer, K L; Christiansen, H; Berthold, F; Juergens, H; Boecker, W; Dockhorn-Dworniczak, B

2001-01-01

Neuroblastomas (NB) are a heterogeneous group of childhood tumours with a wide range of likelihood for tumour progression. As traditional parameters do not ensure completely accurate prognostic grouping, new molecular markers are needed for assessing the individual patient's prognosis more precisely. 133 NB of all stages were analysed in blind-trial fashion for telomerase activity (TA), expression of surviving, and MYCN status. These data were correlated with other traditional prognostic indicators and disease outcome. TA is a powerful independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative "favourable" clinical or biological subgroups of NB patients. High surviving expression is associated with an adverse outcome, but is more difficult to interprete than TA because survivin expression needs to be accurately quantified to be of predictive value. We propose an extended progression model for NB including emerging prognostic markers, with emphasis on telomerase activity.

Host genetic variants of ABCB1 and IL15 influence treatment outcome in paediatric acute lymphoblastic leukaemia

PubMed Central

Lu, Y; Kham, S K Y; Ariffin, H; Oei, A M I; Lin, H P; Tan, A M; Quah, T C; Yeoh, A E J

2014-01-01

Background: Host germline variations and their potential prognostic importance is an emerging area of interest in paediatric ALL. Methods: We investigated the associations between 20 germline variations and various clinical end points in 463 children with ALL. Results: After adjusting for known prognostic factors, variants in two genes were found to be independently associated with poorer EFS: ABCB1 T/T at either 2677 (rs2032582) or 3435 (rs1045642) position (P=0.003) and IL15 67276493G/G (rs17015014; P=0.022). These variants showed a strong additive effect affecting outcome (P<0.001), whereby patients with both risk genotypes had the worst EFS (P=0.001), even after adjusting for MRD levels at the end of remission induction. The adverse effect of ABCB1 T/T genotypes was most pronounced in patients with favourable cytogenetics (P=0.011) while the IL15 67276493G/G genotype mainly affected patients without common chromosomal abnormalities (P=0.022). In both cytogenetic subgroups, increasing number of such risk genotypes still predicted worsening outcome (P<0.001 and=0.009, respectively). Conclusion: These results point to the prognostic importance of host genetic variants, although the specific mechanisms remain unclarified. Inclusion of ABCB1 and IL15 variants may help improve risk assignment strategies in paediatric ALL. PMID:24434428

The relationship of transversus abdominis and lumbar multifidus activation and prognostic factors for clinical success with a stabilization exercise program: a cross-sectional study.

PubMed

Hebert, Jeffrey J; Koppenhaver, Shane L; Magel, John S; Fritz, Julie M

2010-01-01

Hebert JJ, Koppenhaver SL, Magel JS, Fritz JM. The relationship of transversus abdominis and lumbar multifidus activation and prognostic factors for clinical success with a stabilization exercise program: a cross-sectional study. To examine the relationship between prognostic factors for clinical success with a stabilization exercise program and lumbar multifidus (LM) and transversus abdominis (TrA) muscle activation assessed using rehabilitative ultrasound imaging (RUSI). Cross-sectional study. Outpatient physical therapy clinic. Volunteers with current low back pain (N=40). Not applicable. We examined the relationship between prognostic factors associated with clinical success with a stabilization exercise program (positive prone instability test, age <40y, aberrant movements, straight leg raise >91 degrees , presence of lumbar hypermobility) and degree of TrA and LM muscle activation assessed by RUSI. Significant univariate relationships were identified between LM muscle activation and the number of prognostic factors present (Pearson correlation coefficient [r] =-.558, P=.001), as well as the individual factors of a positive prone instability test (point biserial correlation coefficient [r(pbis)]=.376, P=.018) and segmental hypermobility (r(pbis)=.358, P=.025). The multivariate analyses indicated that after controlling for other variables, the addition of the variable "number of prognostic factors present" resulted in a significant increase in R(2) (P=.006). No significant univariate or multivariate relationships were observed between the prognostic factors and TrA muscle activation. Decreased LM muscle activation, but not TrA muscle activation, is associated with the presence of factors predictive of clinical success with a stabilization exercise program. Our findings provide researchers and clinicians with evidence regarding the construct validity of the prognostic factors examined in this study, as well as the potential clinical importance of the LM muscle as a target for stabilization exercises. Copyright (c) 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer.

PubMed

Gagnon, B; Abrahamowicz, M; Xiao, Y; Beauchamp, M-E; MacDonald, N; Kasymjanova, G; Kreisman, H; Small, D

2010-03-30

C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption). We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC). In the Cox's PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03-1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP.

Adjusted Analyses in Studies Addressing Therapy and Harm: Users' Guides to the Medical Literature.

PubMed

Agoritsas, Thomas; Merglen, Arnaud; Shah, Nilay D; O'Donnell, Martin; Guyatt, Gordon H

2017-02-21

Observational studies almost always have bias because prognostic factors are unequally distributed between patients exposed or not exposed to an intervention. The standard approach to dealing with this problem is adjusted or stratified analysis. Its principle is to use measurement of risk factors to create prognostically homogeneous groups and to combine effect estimates across groups.The purpose of this Users' Guide is to introduce readers to fundamental concepts underlying adjustment as a way of dealing with prognostic imbalance and to the basic principles and relative trustworthiness of various adjustment strategies.One alternative to the standard approach is propensity analysis, in which groups are matched according to the likelihood of membership in exposed or unexposed groups. Propensity methods can deal with multiple prognostic factors, even if there are relatively few patients having outcome events. However, propensity methods do not address other limitations of traditional adjustment: investigators may not have measured all relevant prognostic factors (or not accurately), and unknown factors may bias the results.A second approach, instrumental variable analysis, relies on identifying a variable associated with the likelihood of receiving the intervention but not associated with any prognostic factor or with the outcome (other than through the intervention); this could mimic randomization. However, as with assumptions of other adjustment approaches, it is never certain if an instrumental variable analysis eliminates bias.Although all these approaches can reduce the risk of bias in observational studies, none replace the balance of both known and unknown prognostic factors offered by randomization.

Diagnostic and prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with chronic aortic regurgitation.

PubMed

Weber, Michael; Hausen, Michael; Arnold, Roman; Moellmann, Helge; Nef, Holger; Elsaesser, Albrecht; Mitrovic, Vesselin; Hamm, Christian

2008-07-21

BNP and its N-terminal fragment NT-proBNP have proven to be of diagnostic and prognostic value in patients with valvular aortic stenosis. Data regarding those biomarkers in patients with chronic aortic regurgitation (AR) are sparse. Thus it was the aim of the present study to evaluate the diagnostic and the long term prognostic value of NT-proBNP in patients presenting with AR. This study included 60 patients with isolated AR of varying severity (AR I mild, AR II moderate and AR III severe) and preserved left ventricular function. Patients were followed over a median period of 824 (770-921) days. NT-proBNP at baseline was related to disease severity and to functional status (161 (70-456) pg/ml in AR I, 226 (100-666) pg/ml in AR II and 1268 (522-5446) pg/ml in AR III (p=0.003)). Patients (n=6) experiencing an adverse event had higher NT-proBNP values at baseline as event free survivors (1271 (613-2992) pg/ml vs. 215 (92-534) pg/ml; p=0.034). The AUC of the ROC curve for NT-proBNP as a predictor for an adverse event was 0.76 (p<0.036) with an optimised cut-off value of 602 pg/ml. Consequently, in Kaplan-Meier analysis NT-proBNP values dichotomised at this cut-off were able to discriminate patients with an adverse outcome in the entire study group (Log rank 9.98, p=0.0016) and even better in the conservative group (Log rank 26.92, p<0.001). NT-proBNP is linked to disease severity in patients with chronic aortic regurgitation reflecting hemodynamic stress due to volume overload. It provides prognostic information for the clinical outcome and thus might be a useful biomarker for risk stratification.

Late renal transplant failure: an adverse prognostic factor at initiation of peritoneal dialysis.

PubMed

Sasal, J; Naimark, D; Klassen, J; Shea, J; Bargman, J M

2001-01-01

Early renal transplant failure necessitating a return to dialysis has been shown to be a poor prognostic factor for survival. Little is known about the outcome of patients with late transplant failure returning to dialysis. It was our clinical impression that late transplant failure (>2 months) carries an increased morbidity and mortality risk in patients returning to dialysis. To determine whether patients with a failed renal transplant have an outcome different to those on dialysis who have never received a kidney transplant. Peritoneal dialysis (PD) unit in a teaching hospital. All failed renal transplant patients (fTx) in the Toronto Hospital Peritoneal Dialysis program between 1989 and 1996 were identified. This cohort of 42 fTx patients was compared with a cohort of randomly selected never-transplanted PD patients (non-Tx). The PD program was selected because of the availability of well-documented patient archival material. The non-Tx group was matched for age and presence of diabetes. Data were collected until retransplantation, change of dialysis modality or center, death, or until June 1998. There was no difference at initiation of PD between groups in serum albumin, residual renal function, or mean serum parathyroid hormone level. The mean low-density lipoprotein level was significantly higher in the fTx cohort. The duration of dialysis before Tx in fTx patients accounted for the increased total length of dialysis in fTx (mean 15 months). However, post-Tx the duration of PD was similar for both groups (30.7 months for fTx vs 31.6 months for non-Tx). The fTx group had a considerably worse outcome than the non-Tx group. The time to first peritonitis, subsequent episodes of peritonitis, catheter change, or transfer to hemodialysis occurred at a much faster rate in fTx patients. The most dramatic difference was in survival. There were 3 deaths in the non-Tx group and 12 in the fTx group (p < 0.01). The mean age at time of death in the fTx group was 47.5 years. Deaths were due mainly to gram-negative peritonitis and cardiovascular disease. We conclude that late failed renal transplant patients starting dialysis are at increased risk of complications and have strikingly higher mortality rates than non-Tx patients. A previously failed kidney transplant can be considered an adverse prognostic factor for patients commencing PD; these patients need to be closely monitored. Although this study was limited to PD patients, the same principles likely apply to fTx patients returning to any form of renal replacement therapy.

Prognostic factors in canine appendicular osteosarcoma – a meta-analysis

PubMed Central

2012-01-01

Background Appendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease. This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g. age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies. Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma. The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance. Results A literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI). The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers. Conclusions Elevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma. PMID:22587466

Prognostic factors in canine appendicular osteosarcoma - a meta-analysis.

PubMed

Boerman, Ilse; Selvarajah, Gayathri T; Nielen, Mirjam; Kirpensteijn, Jolle

2012-05-15

Appendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease. This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g. age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies. Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma. The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance. A literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI). The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers. Elevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma.

The Prognostic Value of Late Gadolinium-Enhanced Cardiac Magnetic Resonance Imaging in Nonischemic Dilated Cardiomyopathy: A Review and Meta-Analysis.

PubMed

Becker, Marthe A J; Cornel, Jan H; van de Ven, Peter M; van Rossum, Albert C; Allaart, Cornelis P; Germans, Tjeerd

2018-04-13

This review and meta-analysis reviews the prognostic value of cardiac magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (DCM). Late gadolinium-enhanced (LGE) CMR is a noninvasive method to determine the underlying cause of DCM and previous studies reported the prognostic value of the presence of LGE to identify patients at risk of major adverse cardiovascular events. PubMed was searched for studies describing the prognostic implication of LGE in patients with DCM for the specified endpoints cardiovascular mortality, major ventricular arrhythmic events including appropriate implantable cardioverter-defibrillator therapy, rehospitalization for heart failure, and left ventricular reverse remodeling. Data from 34 studies were included, with a total of 4,554 patients. Contrast enhancement was present in 44.8% of DCM patients. Patients with LGE had increased cardiovascular mortality (odds ratio [OR]: 3.40; 95% confidence interval [CI]: 2.04 to 5.67), ventricular arrhythmic events (OR: 4.52; 95% CI: 3.41 to 5.99), and rehospitalization for heart failure (OR: 2.66; 95% CI: 1.67 to 4.24) compared with those without LGE. Moreover, the absence of LGE predicted left ventricular reverse remodeling (OR: 0.15; 95% CI: 0.06 to 0.36). The presence of LGE on CMR substantially worsens prognosis for adverse cardiovascular events in DCM patients, and the absence indicates left ventricular reverse remodeling. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients].

PubMed

Yébenes-Ramírez, Manuel; Serrano, Josefina; Martínez-Losada, Carmen; Sánchez-García, Joaquín

2016-09-02

Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. Overall survival (OS) of the series was 3.7%±2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic-molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Outcome Analysis of Patients With Oral Cavity Cancer and Extracapsular Spread in Neck Lymph Nodes

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

Liao, Chun-Ta, E-mail: liaoct@adm.cgmh.org.tw; Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Lee, Li-Yu

Purpose: Extracapsular spread (ECS) in neck lymph nodes is a major adverse prognostic factor in patients with oral cavity squamous cell carcinoma (OSCC). We conducted a retrospective analysis of prognostic factors in this patient group and tried to identify a subset of patients with a worse prognosis suitable for more aggressive therapeutic interventions. Methods and Materials: Enrolled in the study were 255 OSCC patients with ECS in neck nodes and without evidence of distant metastasis. All participants were followed-up for at least 2 years or censored at last follow-up. The 5-year rates of control, distant metastasis, and survival were themore » main outcome measures. Results: Level IV/V lymph node metastases and tumor depth {>=}12 mm were independent predictors of 5-year survival and identified three prognostic groups. In the low-risk group (no level IV/V metastases and tumor depth <12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 60%, 66%, and 50%, respectively. In the intermediate-risk group (no level IV/V metastases and tumor depth {>=}12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 39%, 41%, and 28%, respectively. In the high-risk group (evidence of level IV/V metastases), the 5-year disease-free, disease-specific, and overall survival rates were 14%, 12%, and 10%, respectively. Conclusions: Among OSCC patients with ECS, those with level IV/V metastases appear to have the worst prognosis followed by without level IV/V metastases and tumor depth {>=}12 mm. An aggressive therapeutic approach may be suitable for intermediate- and high-risk patients.« less

Reduced high-density lipoprotein cholesterol: A valuable, independent prognostic marker in peripheral arterial disease.

PubMed

Martinez-Aguilar, Esther; Orbe, Josune; Fernández-Montero, Alejandro; Fernández-Alonso, Sebastián; Rodríguez, Jose A; Fernández-Alonso, Leopoldo; Páramo, Jose A; Roncal, Carmen

2017-11-01

The prognosis of patients with peripheral arterial disease (PAD) is characterized by an exceptionally high risk for myocardial infarction, ischemic stroke, and death; however, studies in search of new prognostic biomarkers in PAD are scarce. Even though low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with higher risk of cardiovascular (CV) complications and death in different atherosclerotic diseases, recent epidemiologic studies have challenged its prognostic utility. The aim of this study was to test the predictive value of HDL-C as a risk factor for ischemic events or death in symptomatic PAD patients. Clinical and demographic parameters of 254 symptomatic PAD patients were recorded. Amputation, ischemic coronary disease, cerebrovascular disease, and all-cause mortality were recorded during a mean follow-up of 2.7 years. Multivariate analyses showed that disease severity (critical limb ischemia) was significantly reduced in patients with normal HDL-C levels compared with the group with low HDL-C levels (multivariate analysis odds ratio, 0.09; 95% confidence interval [CI], 0.03-0.24). A decreased risk for mortality (hazard ratio, 0.46; 95% CI, 0.21-0.99) and major adverse CV events (hazard ratio, 0.38; 95% CI, 0.16-0.86) was also found in patients with normal vs reduced levels of HDL-C in both Cox proportional hazards models and Kaplan-Meier estimates, after adjustment for confounding factors. Reduced HDL-C levels were significantly associated with higher risk for development of CV complications as well as with mortality in PAD patients. These findings highlight the usefulness of this simple test for early identification of PAD patients at high risk for development of major CV events. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Phosphorylated 4EBP1 is associated with tumor progression and poor prognosis in Xp11.2 translocation renal cell carcinoma

PubMed Central

Qu, Yuanyuan; Zhao, Rui; Wang, Hongkai; Chang, Kun; Yang, Xiaoqun; Zhou, Xiaoyan; Dai, Bo; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Ye, Dingwei

2016-01-01

Two main signaling pathways, PI3K-AKT-mTOR and RAS-MAPK, are involved in transmitting the proliferative signals which play critical roles in human cancers. However, the functions of these pathways in Xp11.2 RCC remain undefined. This study aimed to explore the expression of mTOR and MAPK cascades in Xp11.2 RCC and to assess the prognostic significance of proteins evaluated. Immunohistochemistry was performed to evaluate the expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K and p-MAPK in 36 adult Xp11.2 RCC patients who were confirmed by FISH assay. Cox regression models were used to evaluate the prognostic value of all covariates. Among 36 assessed patients, 14 (38.9%), 26 (72.2%), 16 (44.4%), 19 (52.8%), and 9 (25.0%) patients showed high expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K, and p-MAPK, respectively. We noted that p-4EBP1 expression was significantly correlated with lymph node metastases (P = 0.027). Multivariate analysis showed that high p-4EBP1 expression was an independent adverse prognostic factor for both PFS (HR = 33.750, P = 0.017) and OS (HR = 56.111, P = 0.026). Our findings suggest that p-4EBP1 may serve as a funnel factor that converge the upstream proliferative oncogenic signals. Effective inhibition of the pathways responsible for 4E-BP1 phosphorylation might be a useful strategy to improve the outcome of Xp11.2 RCC patients. PMID:27026382

Phosphorylated 4EBP1 is associated with tumor progression and poor prognosis in Xp11.2 translocation renal cell carcinoma.

PubMed

Qu, Yuanyuan; Zhao, Rui; Wang, Hongkai; Chang, Kun; Yang, Xiaoqun; Zhou, Xiaoyan; Dai, Bo; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Ye, Dingwei

2016-03-30

Two main signaling pathways, PI3K-AKT-mTOR and RAS-MAPK, are involved in transmitting the proliferative signals which play critical roles in human cancers. However, the functions of these pathways in Xp11.2 RCC remain undefined. This study aimed to explore the expression of mTOR and MAPK cascades in Xp11.2 RCC and to assess the prognostic significance of proteins evaluated. Immunohistochemistry was performed to evaluate the expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K and p-MAPK in 36 adult Xp11.2 RCC patients who were confirmed by FISH assay. Cox regression models were used to evaluate the prognostic value of all covariates. Among 36 assessed patients, 14 (38.9%), 26 (72.2%), 16 (44.4%), 19 (52.8%), and 9 (25.0%) patients showed high expression of 4EBP1, p-4EBP1, p-mTOR, p-S6K, and p-MAPK, respectively. We noted that p-4EBP1 expression was significantly correlated with lymph node metastases (P = 0.027). Multivariate analysis showed that high p-4EBP1 expression was an independent adverse prognostic factor for both PFS (HR = 33.750, P = 0.017) and OS (HR = 56.111, P = 0.026). Our findings suggest that p-4EBP1 may serve as a funnel factor that converge the upstream proliferative oncogenic signals. Effective inhibition of the pathways responsible for 4E-BP1 phosphorylation might be a useful strategy to improve the outcome of Xp11.2 RCC patients.

High-sensitivity human papilloma virus genotyping reveals near universal positivity in anal squamous cell carcinoma: different implications for vaccine prevention and prognosis.

PubMed

Baricevic, Ivona; He, Xiaotong; Chakrabarty, Bipasha; Oliver, Anthony W; Bailey, Charles; Summers, Jeff; Hampson, Lynne; Hampson, Ian; Gilbert, Duncan C; Renehan, Andrew G

2015-04-01

Characterisation of human papilloma virus (HPV) infection in anal squamous cell carcinoma (ASCC) may have dual importance: first, aetiological; second, prognostic, informing outcome after chemo-radiotherapy (CRT). We undertook HPV genotyping, and allelic characterisations, to evaluate the aetiological role of HPV while simultaneously evaluating the impact of HPV genotyping on relapse-free (RFS) and overall survival (OS). Dual-primer HPV genotyping (subtypes 6, 11, 16, 18, 31, 33, 45, 52, 58) and DNA sequencing of HPV 16 positive tumours were analysed in 151 consecutively referred ASCCs, previously characterised by immunohistochemistry for p16 expression. In 110 patients treated with CRT, factors influencing RFS and OS were evaluated using univariate and multivariate models. HPV positivity was observed in 95%. HPV 16 accounted for 89%; of these, 64% harboured the T350G E6 variant. HPV 16 positivity was significantly correlated with improved 5-year RFS (62% versus 40%; p = 0.027) and OS (59% versus 38%; p = 0.019). p16 expression was also significantly correlated with improved 5-year RFS (positive versus negative: 65% versus 16%; p < 0.0001) and OS (63% versus 13%; p < 0.0001). In multivariable models that included HPV 16 status, p16 status, sex, and age, p16 expression remained an independent prognostic factor for RFS (p < 0.0001) and OS (p = 0.002). In ASCC, near-universal HPV detection rates were demonstrated, higher than generally reported in the literature, and supporting the development of multivalent HPV vaccinations for prevention. By contrast, p16 negatively, but not HPV 16 genotype, is an independent adverse prognosticator after chemo-radiotherapy in patients with ASCC. Copyright © 2015. Published by Elsevier Ltd.

Prognostic factors of clinical endpoints in elderly patients with atrial fibrillation during a 2-year follow-up in China

PubMed Central

Wang, Hao; Wang, Hai-Jun; Chen, Ya-Dong; Tao, Tao; Guo, Yu-Tao; Zhao, Xiao-Ning; Liu, Hong-Bin; Wang, Yu-Tang

2017-01-01

Abstract This study aimed to reveal the incidence of clinical endpoints in elderly patients with atrial fibrillation (AF) during a 2-year follow-up and evaluate the related prognostic factors of these endpoints. In total, 200 elderly patients with AF and 400 age- and sex-matched patients without AF were enrolled in this prospective observational cohort study. The incidence of clinical endpoints, including thromboembolism, hemorrhage, and all-cause death, during the 2-year follow-up was analyzed. Other follow-up data, including disease history, laboratory examinations, medication status, and other clinical endpoints, were collected. The prognostic factors of these clinical endpoints were then evaluated by Cox-survival analysis. In addition, the predicative role of C-reactive protein (CRP) and platelet-activating factor (PAF) on these clinical endpoints was analyzed. The incidence of clinical endpoints, including thromboembolism, hemorrhage, and all-cause death, was significantly higher in patients with AF than in those without AF (27.8% vs 9.8%, 29.4% vs 12.7%, and 28.7% vs 11.6%, respectively; all P < .001). Antithrombotic therapy significantly reduced the incidences of all-cause deaths (P < .05). Body mass index (BMI) and digoxin were prognostic risk factors of thromboembolism; age, massive hemorrhage history, and digoxin were prognostic risk factors of hemorrhage and age, renal insufficiency history, massive hemorrhage history, and digoxin were prognostic risk factors of all-cause death (P < .05). Further, both CRP and PAF were prognostic risk factors of thromboembolism and massive hemorrhage (P < .05). Age, BMI, massive hemorrhage history, and digoxin appear to be prognostic risk factors of clinical endpoints in elderly patients with AF. Appropriate drug use during follow-up may be beneficial in preventing the occurrence of clinical endpoints in elderly patients with AF. Trial registration number: ChiCTR-OCH-13003479. PMID:28816946

Prognostic significance of biomarkers in predicting outcome in patients with coronary artery disease and left ventricular dysfunction: results of the biomarker substudy of the Surgical Treatment for Ischemic Heart Failure trials.

PubMed

Feldman, Arthur M; Mann, Douglas L; She, Lilin; Bristow, Michael R; Maisel, Alan S; McNamara, Dennis M; Walsh, Ryan; Lee, Dorellyn L; Wos, Stanislaw; Lang, Irene; Wells, Gretchen; Drazner, Mark H; Schmedtje, John F; Pauly, Daniel F; Sueta, Carla A; Di Maio, Michael; Kron, Irving L; Velazquez, Eric J; Lee, Kerry L

2013-05-01

Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-α receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: χ(2)=40.6; P<0.0001 and sTNFR-1: χ(2)=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ(2)=30.3) and sTNFR-1 (χ(2)=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ(2)=6.0; P=0.049) and sTNFR-1 (χ(2)=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.

Treatment-Related Predictive and Prognostic Factors in Trimodality Approach in Stage IIIA/N2 Non-Small Cell Lung Cancer.

PubMed

Jeremić, Branislav; Casas, Francesc; Dubinsky, Pavol; Gomez-Caamano, Antonio; Čihorić, Nikola; Videtic, Gregory; Igrutinovic, Ivan

2018-01-01

While there are no established pretreatment predictive and prognostic factors in patients with stage IIIA/pN2 non-small cell lung cancer (NSCLC) indicating a benefit to surgery as a part of trimodality approach, little is known about treatment-related predictive and prognostic factors in this setting. A literature search was conducted to identify possible treatment-related predictive and prognostic factors for patients for whom trimodality approach was reported on. Overall survival was the primary endpoint of this study. Of 30 identified studies, there were two phase II studies, 5 "prospective" studies, and 23 retrospective studies. No study was found which specifically looked at treatment-related predictive factors of improved outcomes in trimodality treatment. Of potential treatment-related prognostic factors, the least frequently analyzed factors among 30 available studies were overall pathologic stage after preoperative treatment and UICC downstaging. Evaluation of treatment response before surgery and by pathologic tumor stage after induction therapy were analyzed in slightly more than 40% of studies and found not to influence survival. More frequently studied factors-resection status, degree of tumor regression, and pathologic nodal stage after induction therapy as well as the most frequently studied factor, the treatment (in almost 75% studies)-showed no discernible impact on survival, due to conflicting results. Currently, it is impossible to identify any treatment-related predictive or prognostic factors for selecting surgery in the treatment of patients with stage IIIA/pN2 NSCLC.

Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma.

PubMed

Huang, Jia-Jia; Li, Ya-Jun; Xia, Yi; Wang, Yu; Wei, Wen-Xiao; Zhu, Ying-Jie; Lin, Tong-Yu; Huang, Hui-Qiang; Jiang, Wen-Qi; Li, Zhi-Ming

2013-05-03

Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL.

Validation of EORTC Prognostic Factors for Adults With Low-Grade Glioma: A Report Using Intergroup 86-72-51

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

Daniels, Thomas B.; Brown, Paul D., E-mail: Brown.paul@mayo.edu; Felten, Sara J.

2011-09-01

Purpose: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). Methods and Materials: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-riskmore » group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. Results: On univariate analysis, the following were statistically significant (p < 0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p < 0.0001) and PFS (6.2 years vs. 1.9 years, p < 0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p = 0.03). Conclusions: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of histology and tumor size. Co-deletion of 1p19q is a prognostic factor. Future studies are needed to develop a more refined prognostic system that combines clinical prognostic features with more robust molecular and genetic data.« less

Coronary artery calcium scoring does not add prognostic value to standard 64-section CT angiography protocol in low-risk patients suspected of having coronary artery disease.

PubMed

Kwon, Sung Woo; Kim, Young Jin; Shim, Jaemin; Sung, Ji Min; Han, Mi Eun; Kang, Dong Won; Kim, Ji-Ye; Choi, Byoung Wook; Chang, Hyuk-Jae

2011-04-01

To evaluate the prognostic outcome of cardiac computed tomography (CT) for prediction of major adverse cardiac events (MACEs) in low-risk patients suspected of having coronary artery disease (CAD) and to explore the differential prognostic values of coronary artery calcium (CAC) scoring and coronary CT angiography. Institutional review committee approval and informed consent were obtained. In 4338 patients who underwent 64-section CT for evaluation of suspected CAD, both CAC scoring and CT angiography were concurrently performed by using standard scanning protocols. Follow-up clinical outcome data regarding composite MACEs were procured. Multivariable Cox proportional hazards models were developed to predict MACEs. Risk-adjusted models incorporated traditional risk factors for CAC scoring and coronary CT angiography. During the mean follow-up of 828 days ± 380, there were 105 MACEs, for an event rate of 3%. The presence of obstructive CAD at coronary CT angiography had independent prognostic value, which escalated according to the number of stenosed vessels (P < .001). In the receiver operating characteristic curve (ROC) analysis, the superiority of coronary CT angiography to CAC scoring was demonstrated by a significantly greater area under the ROC curve (AUC) (0.892 vs 0.810, P < .001), whereas no significant incremental value for the addition of CAC scoring to coronary CT angiography was established (AUC = 0.892 for coronary CT angiography alone vs 0.902 with addition of CAC scoring, P = .198). Coronary CT angiography is better than CAC scoring in predicting MACEs in low-risk patients suspected of having CAD. Furthermore, the current standard multisection CT protocol (coronary CT angiography combined with CAC scoring) has no incremental prognostic value compared with coronary CT angiography alone. Therefore, in terms of determining prognosis, CAC scoring may no longer need to be incorporated in the cardiac CT protocol in this population. © RSNA, 2011.

High Expression of EphA4 Predicted Lesser Degree of Tumor Regression after Neoadjuvant Chemoradiotherapy in Rectal Cancer.

PubMed

Lin, Ching-Yih; Lee, Ying-En; Tian, Yu-Feng; Sun, Ding-Ping; Sheu, Ming-Jen; Lin, Chen-Yi; Li, Chien-Feng; Lee, Sung-Wei; Lin, Li-Ching; Chang, I-Wei; Wang, Chieh-Tien; He, Hong-Lin

2017-01-01

Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression. Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed. Results: EphA4 expression was significantly associated with vascular invasion ( P =0.015), post-treatment depth of tumor invasion ( P =0.006), pre-treatment and post-treatment lymph node metastasis ( P =0.004 and P =0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT ( P =0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival ( P =0.0009) and metastasis-free survival ( P =0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651; P =0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601; P =0.003). Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.

Methodological issues and recommendations for systematic reviews of prognostic studies: an example from cardiovascular disease.

PubMed

Dretzke, Janine; Ensor, Joie; Bayliss, Sue; Hodgkinson, James; Lordkipanidzé, Marie; Riley, Richard D; Fitzmaurice, David; Moore, David

2014-12-03

Prognostic factors are associated with the risk of future health outcomes in individuals with a particular health condition. The prognostic ability of such factors is increasingly being assessed in both primary research and systematic reviews. Systematic review methodology in this area is continuing to evolve, reflected in variable approaches to key methodological aspects. The aim of this article was to (i) explore and compare the methodology of systematic reviews of prognostic factors undertaken for the same clinical question, (ii) to discuss implications for review findings, and (iii) to present recommendations on what might be considered to be 'good practice' approaches. The sample was comprised of eight systematic reviews addressing the same clinical question, namely whether 'aspirin resistance' (a potential prognostic factor) has prognostic utility relative to future vascular events in patients on aspirin therapy for secondary prevention. A detailed comparison of methods around study identification, study selection, quality assessment, approaches to analysis, and reporting of findings was undertaken and the implications discussed. These were summarised into key considerations that may be transferable to future systematic reviews of prognostic factors. Across systematic reviews addressing the same clinical question, there were considerable differences in the numbers of studies identified and overlap between included studies, which could only partially be explained by different study eligibility criteria. Incomplete reporting and differences in terminology within primary studies hampered study identification and selection process across reviews. Quality assessment was highly variable and only one systematic review considered a checklist for studies of prognostic questions. There was inconsistency between reviews in approaches towards analysis, synthesis, addressing heterogeneity and reporting of results. Different methodological approaches may ultimately affect the findings and interpretation of systematic reviews of prognostic research, with implications for clinical decision-making.

Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study

PubMed Central

Klamroth, Robert; Scharf, Rüdiger E.; Trappe, Ralf U.; Holstein, Katharina; Huth-Kühne, Angela; Gottstein, Saskia; Geisen, Ulrich; Schenk, Joachim; Scholz, Ute; Schilling, Kristina; Neumeister, Peter; Miesbach, Wolfgang; Manner, Daniela; Greil, Richard; von Auer, Charis; Krause, Manuela; Leimkühler, Klaus; Kalus, Ulrich; Blumtritt, Jan-Malte; Werwitzke, Sonja; Budde, Eva; Koch, Armin; Knöbl, Paul

2015-01-01

Acquired hemophilia A (AHA) is caused by autoantibodies against factor VIII (FVIII). Immunosuppressive treatment (IST) results in remission of disease in 60% to 80% of patients over a period of days to months. IST is associated with frequent adverse events, including infections as a leading cause of death. Predictors of time to remission could help guide IST intensity but have not been established. We analyzed prognostic factors in 102 prospectively enrolled patients treated with a uniform IST protocol. Partial remission (PR; defined as no active bleeding, FVIII restored >50 IU/dL, hemostatic treatment stopped >24 hours) was achieved by 83% of patients after a median of 31 days (range 7-362). Patients with baseline FVIII <1 IU/dL achieved PR less often and later (77%, 43 days) than patients with ≥1 IU/dL (89%, 24 days). After adjustment for other baseline characteristics, low FVIII remained associated with a lower rate of PR (hazard ratio 0.52, 95% confidence interval 0.33-0.81, P < .01). In contrast, PR achieved on steroids alone within ≤21 days was more common in patients with FVIII ≥1 IU/dL and inhibitor concentration <20 BU/mL (odds ratio 11.2, P < .0001). Low FVIII was also associated with a lower rate of complete remission and decreased survival. In conclusion, presenting FVIII and inhibitor concentration are potentially useful to tailor IST in AHA. PMID:25525118

Co-expression of midkine and pleiotrophin predicts poor survival in human glioma.

PubMed

Ma, Jinyang; Lang, Bojuan; Wang, Xiongwei; Wang, Lei; Dong, Yuanxun; Hu, Huojun

2014-11-01

The aim of this study was to investigate whether co-expression of midkine (MK) and pleiotrophin (PTN) has prognostic relevance in human gliomas. Immunohistochemistry was used to investigate the expression of MK and PTN proteins in 168 patients with gliomas. The levels of MK and PTN mRNA in glioma tissues and paratumor tissues were evaluated in 45 paired cases by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis was performed to assess prognostic significance. The expression levels of MK and PTN proteins in glioma tissue were both significantly higher (both p<0.001) than those in paratumor tissues on immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of either MK or PTN was significantly associated with the World Health Organization Grade (p=0.001 and 0.034, respectively), low Karnofsky Performance Status (KPS) score (p=0.022 and 0.001, respectively), time to recurrence (p=0.043 and 0.011, respectively) and poor overall survival (p=0.018 and 0.001, respectively). Multivariate Cox proportional-hazards regression analysis revealed that increased expressions of MK and PTN were both independent prognostic factors for poor overall survival (p=0.030 and 0.022, respectively). Furthermore, the co-expression of MK and PTN was more significantly (p=0.003) associated with adverse prognosis in patients with gliomas than the respective expression of MK or PTN alone. To our knowledge, these findings are the first to indicate that the co-expression of MK and PTN is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker. Copyright © 2014 Elsevier Ltd. All rights reserved.

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer

PubMed Central

Gagnon, B; Abrahamowicz, M; Xiao, Y; Beauchamp, M-E; MacDonald, N; Kasymjanova, G; Kreisman, H; Small, D

2010-01-01

Background: C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption). Methods: We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC). Results: In the Cox's PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03–1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. Conclusion: Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP. PMID:20234363

The predictive value of resting heart rate following osmotherapy in brain injury: back to basics

PubMed Central

2012-01-01

Background The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia. To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS). Method By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed. Results After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07). Conclusion Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury. PMID:23351393

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.

Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

PubMed

Riley, Richard D; Elia, Eleni G; Malin, Gemma; Hemming, Karla; Price, Malcolm P

2015-07-30

A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points). © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

An internally validated new clinical and inflammation-based prognostic score for patients with advanced hepatocellular carcinoma treated with sorafenib.

PubMed

Diaz-Beveridge, R; Bruixola, G; Lorente, D; Caballero, J; Rodrigo, E; Segura, Á; Akhoundova, D; Giménez, A; Aparicio, J

2018-03-01

Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis. To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management. Retrospective review of 145 pts bNLR, overall toxicity, early toxicity rates and overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the coefficients found in the Cox analysis. ROC curves and pseudoR2 index were used for internal validation. Discrimination ability and calibration were tested by Harrel's c-index (HCI) and Akaike criteria (AIC). The optimal bNLR cut-off for the prediction of OS was 4 (AUC 0.62). Independent prognostic factors in multivariate analysis for OS were performance status (PS) (p < .0001), Child-Pugh (C-P) score (p = 0.005), early-onset diarrhoea (p = 0.006) and BNLR (0.011). The prognostic score based on these four variables was found efficient (HCI = 0.659; AIC = 1.180). Four risk groups for OS could be identified: a very low-risk (median OS = 48.6 months), a low-risk (median OS = 11.6 months), an intermediate-risk (median OS = 8.3 months) and a high-risk group (median OS = 4.4 months). PS and C-P score were the main prognostic factors for OS, followed by early-onset diarrhoea and bNLR. We identified four risk groups for OS depending on these parameters. This prognostic model could be useful for patient stratification, but an external validation is needed.

Single nucleotide polymorphisms in long noncoding RNA, ANRIL, are not associated with severe periodontitis but with adverse cardiovascular events among patients with cardiovascular disease.

PubMed

Schulz, S; Seitter, L; Werdan, K; Hofmann, B; Schaller, H-G; Schlitt, A; Reichert, S

2018-05-06

Biological plausibility of an association between severe periodontitis and cardiovascular disease (CVD) has been proven. Genetic characteristics play an important role in both complex inflammatory diseases. Polymorphisms (single nucleotide polymorphisms [SNPs]) in the long noncoding RNA, antisense noncoding RNA in the INK4 locus (ANRIL), were shown to play a leading role in both diseases. The primary objectives of the study were to assess, among cardiovascular (CV angiographically proven ≥50% stenosis of a main coronary artery) patients, the impact of ANRIL SNPs rs133049 and rs3217992 on the severity of periodontitis and the previous history of coronary events, as well as on the occurrence of further adverse CV events. The prevalence of severe periodontitis was analyzed in 1002 CV patients. ANRIL SNPs rs133049 and rs3217992 were genotyped. The prognostic value of both ANRIL SNPs for combined CV endpoint (stroke/transient ischemic attack [TIA], myocardial infarction, death from a CV-related event, death from stroke) was evaluated after a 3-year follow-up period. Hazard ratios (HRs) were adjusted for established CV risk factors applying Cox regression. ANRIL SNPs rs133049 and rs3217992 were not associated with severe periodontitis or history of CVD in CV patients. In the Kaplan-Meier survival curve including the log rank-test (P = .036) and Cox regression (hazard ratio = 1.684, P = .009) the AA genotype of rs3217992 was shown to be an independent predictor for adverse CV events after 3 years of follow-up. SNPs in ANRIL are not risk modulators for severe periodontitis and history of CVD in CV patients. The AA genotype of ANRIL SNPs rs3217992 possesses prognostic power for further CV events within 3 years of follow-up. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pneumococcal pneumonia - Are the new severity scores more accurate in predicting adverse outcomes?

PubMed

Ribeiro, C; Ladeira, I; Gaio, A R; Brito, M C

2013-01-01

The site-of-care decision is one of the most important factors in the management of patients with community-acquired pneumonia. The severity scores are validated prognostic tools for community-acquired pneumonia mortality and treatment site decision. The aim of this paper was to compare the discriminatory power of four scores - the classic PSI and CURB65 ant the most recent SCAP and SMART-COP - in predicting major adverse events: death, ICU admission, need for invasive mechanical ventilation or vasopressor support in patients admitted with pneumococcal pneumonia. A five year retrospective study of patients admitted for pneumococcal pneumonia. Patients were stratified based on admission data and assigned to low-, intermediate-, and high-risk classes for each score. Results were obtained comparing low versus non-low risk classes. We studied 142 episodes of hospitalization with 2 deaths and 10 patients needing mechanical ventilation and vasopressor support. The majority of patients were classified as low risk by all scores - we found high negative predictive values for all adverse events studied, the most negative value corresponding to the SCAP score. The more recent scores showed better accuracy for predicting ICU admission and need for ventilation or vasopressor support (mostly for the SCAP score with higher AUC values for all adverse events). The rate of all adverse outcomes increased directly with increasing risk class in all scores. The new gravity scores appear to have a higher discriminatory power in all adverse events in our study, particularly, the SCAP score. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Prognosis research: why is Dr. Lydgate still waiting?

PubMed

Hemingway, Harry

2006-12-01

Understanding prognosis--the future risk of adverse outcomes among people with existing disease--plays third fiddle behind clinical research into therapeutic interventions and novel diagnostic technologies. Diseases show marked variations in a wide range of prognostic outcomes, yet these variations have seldom been the subject of systematic and sustained epidemiologic and multidisciplinary research. This is important to prioritize hypotheses for testing in intervention studies in groups, and to refine tools for prognostication in individuals. Methodologic standards for the design, conduct, analysis and reporting of prognosis research are required. Training is needed for the clinicians, policymakers, and payers who use prognostic information. Here, arguments detracting from the potential scope of prognosis research are rebutted and misconceptions addressed with the aim of stimulating debate on the evolving role of prognosis research.

Prognostic Factors for Mortality among Day +100 Survivors after Allogeneic Hematopoietic Cell Transplantation.

PubMed

Patel, Sagar S; Rybicki, Lisa A; Corrigan, Donna; Bolwell, Brian; Dean, Robert; Liu, Hien; Gerds, Aaron T; Hanna, Rabi; Hill, Brian; Jagadeesh, Deepa; Kalaycio, Matt; Pohlman, Brad; Sobecks, Ronald; Majhail, Navneet S; Hamilton, Betty K

2018-05-01

Although day +100 survival among allogeneic hematopoietic cell transplantation (HCT) recipients has improved over time, longer-term survival remains a challenge. The aim of this study was to identify prognostic factors for survival among patients surviving longer than 100 days using baseline characteristics and factors identified within the first 100 days after transplantation. Of 413 patients undergoing a first allogeneic HCT between 2006 and 2014, 335 survived >100 days post-transplantation. The majority underwent a myeloablative transplantation (75%) with a bone marrow (BM) (52%) graft source. One-year all-cause mortality (ACM) was 29%, with 16% relapse mortality (RM) and 12% nonrelapse mortality. In multivariable analysis, high-risk disease (hazard ratio [HR], 1.55; P = .003), non-cytomegalovirus infection (HR, 1.79; P = .003), more days hospitalized (HR, 1.16; P < .001), and relapse (HR, 4.38; P < .001) within the first 100 days were associated with increased risk of ACM. Patients with higher income (HR, .89; P = .024) and those who received BM (HR, .52; P < .001) or umbilical cord blood (HR, .40; P = .002) relative to peripheral blood stem cells had lower risk of ACM. Our study identifies risk factors for adverse long-term survival in 100-day survivors, a time point when patients frequently are discharged from transplantation centers. In addition to disease- and transplantation-related factors, low socioeconomic status was associated with worse long-term survival, highlighting the need for focused efforts to improve outcomes in vulnerable patient populations. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma

PubMed Central

2013-01-01

Background Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Methods Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. Results The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. Conclusion The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL. PMID:23638998

Prognostic Value of the Apparent Diffusion Coefficient in Newborns with Hypoxic-Ischaemic Encephalopathy Treated with Therapeutic Hypothermia.

PubMed

Heursen, Eva-Marie; Zuazo Ojeda, Amaya; Benavente Fernández, Isabel; Jimenez Gómez, Gema; Campuzano Fernández-Colima, Rosalía; Paz-Expósito, José; Lubián López, Simón Pedro

2017-01-01

Apparent diffusion coefficient (ADC) quantification has been proven to be of prognostic value in term newborns with hypoxic-ischaemic encephalopathy (HIE) who were treated under normothermia. To evaluate the prognostic value of ADC in standardized brain regions in neonates with HIE who were treated with therapeutic hypothermia (TH). This prospective cohort study included 54 term newborns who were admitted with HIE and treated with TH. All magnetic resonance imaging examinations were performed between days 4 and 6 of life, and ADC values were measured in 13 standardized regions of the brain. At 2 years of age we explored whether ADC values were related to composite outcomes (death or survival with abnormal neurodevelopment). The severity of HIE is inversely related to ADC values in different brain regions. We found that lower ADC values in the posterior limb of the internal capsule (PLIC), the thalami, the semioval centre, and frontal and parietal white matter were related to adverse outcomes. ADC values in the PLIC and thalami are good predictors of adverse outcomes (AUC 0.86 and 0.76). Low ADC values in the PLIC, thalamus, semioval centre, and frontal and parietal white matter in full-term infants with HIE treated with TH were associated with a poor outcome. © 2017 S. Karger AG, Basel.

Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients

PubMed Central

Martin, Stewart G.; Lebot, Marie N.; Sukkarn, Bhudsaban; Ball, Graham; Green, Andrew R.; Rakha, Emad A.; Ellis, Ian O.; Storr, Sarah J.

2018-01-01

G protein-coupled oestrogen receptor 1 (GPER), also called G protein-coupled receptor 30 (GPR30), is attracting considerable attention for its potential role in breast cancer development and progression. Activation by oestrogen (17β-oestradiol; E2) initiates short term, non-genomic, signalling events both in vitro and in vivo. Published literature on the prognostic value of GPER protein expression in breast cancer indicates that further assessment is warranted. We show, using immunohistochemistry on a large cohort of primary invasive breast cancer patients (n=1245), that low protein expression of GPER is not only significantly associated with clinicopathological and molecular features of aggressive behaviour but also significantly associated with adverse survival of breast cancer patients. Furthermore, assessment of GPER mRNA levels in the METABRIC cohort (n=1980) demonstrates that low GPER mRNA expression is significantly associated with adverse survival of breast cancer patients. Using artificial neural networks, genes associated with GPER mRNA expression were identified; these included notch-4 and jagged-1. These results support the prognostic value for determination of GPER expression in breast cancer. PMID:29899833

High levels of bcl-2 protein expression do not correlate with genetic abnormalities but predict worse prognosis in patients with lymphoblastic lymphoma.

PubMed

Gu, Yajun; Pan, Yi; Meng, Bin; Guan, Bingxin; Fu, Kai; Sun, Baocun; Zheng, Fang

2013-06-01

We aimed to investigate bcl-2, bcl-6, and c-myc rearrangements in patients with lymphoblastic lymphoma (LBL), especially focus on the correlation of protein expression with genetic abnormalities. Moreover, their prognostic significance was further analyzed in LBL. Protein expression and genetic abnormalities of bcl-2, bcl-6, and c-myc were investigated in microarrayed tumors from 33 cases of T cell LBL and eight cases of B cell lineage. Immunohistochemical (IHC) staining was performed to evaluate protein expression, including bcl-2, bcl-6, c-myc, TdT, CD1α, CD34, Ki-67, PAX-5, CD2, CD3, CD4, CD8, and CD20. Genetic abnormalities of bcl-2, bcl-6, and c-myc were detected by dual color fluorescence in situ hybridization (FISH). Bcl-2 protein was positive in 51.2 % (21/41) of the patients, bcl-6 protein in 7.3 % (three out of 41), and c-myc protein in 78.0 % (32/41). Bcl-2 breakpoint was found in two cases by FISH analysis. There was no evidence of bcl-6 or c-myc rearrangement in patients with LBL. However, both gene gain and loss events occurred in bcl-2, bcl-6, and c-myc. A univariate analysis showed that stage III or IV, elevated lactate dehydrogenase (LDH), and positivity for bcl-2 protein were associated with shorter survival (p<0.05). Enhanced protein expression and detectable genetic abnormalities of bcl-2, bcl-6, and c-myc were observed in patients with LBL. No statistical correlation was found between IHC results and cytogenetic findings. Stage III or IV, elevated LDH, and positivity for bcl-2 protein were identified as adverse prognostic factors. The patients with more adverse factors would have increasingly worse prognosis.

Relationship between p53 dysfunction, CD38 expression, and IgV(H) mutation in chronic lymphocytic leukemia.

PubMed

Lin, Ke; Sherrington, Paul D; Dennis, Michael; Matrai, Zoltan; Cawley, John C; Pettitt, Andrew R

2002-08-15

Established adverse prognostic factors in chronic lymphocytic leukemia (CLL) include CD38 expression, relative lack of IgV(H) mutation, and defects of the TP53 gene. However, disruption of the p53 pathway can occur through mechanisms other than TP53 mutation, and we have recently developed a simple screening test that detects p53 dysfunction due to mutation of the genes encoding either p53 or ATM, a kinase that regulates p53. The present study was conducted to examine the predictive value of this test and to establish the relationship between p53 dysfunction, CD38 expression, and IgV(H) mutation. CLL cells from 71 patients were examined for IgV(H) mutation, CD38 expression, and p53 dysfunction (detected as an impaired p53/p21 response to ionizing radiation). Survival data obtained from 69 patients were analyzed according to each of these parameters. Relative lack of IgV(H) mutation (less than 5%; n = 45), CD38 positivity (antigen expressed on more than 20% of malignant cells; n = 19), and p53 dysfunction (n = 19) were independently confirmed as adverse prognostic factors. Intriguingly, all p53-dysfunctional patients and all but one of the CD38(+) patients had less [corrected] than 5% IgV(H) mutation. Moreover, patients with p53 dysfunction and/or CD38 positivity (n = 31) accounted for the short survival of the less mutated group. These findings indicate that the poor outcome associated with having less than 5% IgV(H) mutation may be due to the overrepresentation of high-risk patients with p53 dysfunction and/or CD38 positivity within this group, and that CD38(-) patients with functionally intact p53 may have a prolonged survival regardless of the extent of IgV(H) mutation.

The N2 paradox: similar outcomes of pre- and postoperatively identified single-zone N2a positive non-small-cell lung cancer.

PubMed

Tsitsias, Thomas; Boulemden, Anas; Ang, Keng; Nakas, Apostolos; Waller, David A

2014-05-01

Resection of N2a non-small-cell lung cancer (NSCLC) diagnosed preoperatively is controversial but there is support for resection of unexpected N2 disease discovered at surgery. Since the seventh TNM edition, we have intentionally resected clinical N2a disease. To validate this policy, we determined prognostic factors associated with all resected N2 disease. From a prospective database of 1131 consecutive patients undergoing elective resection for primary lung cancer over a period of 8 years, we identified 68 patients (35 females (51.4%), mean age 66 years, standard deviation (SD) 9 years) who had pathological N2 disease. All patients had positron emission computed tomography (CT-PET) staging and selective mediastinoscopy. A Cox-regression analysis was performed to identify prognostic factors. At a median follow-up of 38.7 months (standard error 10, 95% confidence interval (CI) 19.0-58.4), the overall median survival was 22.2 months (95% CI 14.6-29.8) with 1-, 2- and 5-year survival rates of 63.3, 46.6 and 13.2%, respectively. Survival after resection of pN2 disease is adversely affected by the need for pneumonectomy, multizone pN2b involvement and by non-compliance with adjuvant chemotherapy. Pathological involvement of the subcarinal zone but no other zone appears to be associated with an adverse prognosis (hazard ratio (HR) 1.87, P = 0.063). Importantly, long-term survival is not different between those patients who have a negative preoperative PET-CT scan and yet are found to have pN2 after resection, and those who are single-zone cN2a positive before resection on PET-CT scan (HR 1.37, P = 0.335). Our results support a policy of intentionally resecting single-zone N2a NSCLC identified preoperatively as part of a multimodality therapy.

Prognostic importance of DNA ploidy in non-endometrioid, high-risk endometrial carcinomas.

PubMed

Sorbe, Bengt

2016-03-01

The present study investigated the predictive and prognostic impact of DNA ploidy together with other well-known prognostic factors in a series of non-endometrioid, high-risk endometrial carcinomas. From a complete consecutive series of 4,543 endometrial carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stages I-IV, 94 serous carcinomas, 48 clear cell carcinomas and 231 carcinosarcomas were selected as a non-endometrioid, high-risk group for further studies regarding prognosis. The impact of DNA ploidy, as assessed by flow cytometry, was of particular focus. The age of the patients, FIGO stage, depth of myometrial infiltration and tumor expression of p53 were also included in the analyses (univariate and multivariate). In the complete series of cases, the recurrence rate was 37%, and the 5-year overall survival rate was 39% with no difference between the three histological subtypes. The primary cure rate (78%) was also similar for all tumor types studied. DNA ploidy was a significant predictive factor (on univariate analysis) for primary tumor cure rate, and a prognostic factor for survival rate (on univariate and multivariate analyses). The predictive and prognostic impact of DNA ploidy was higher in carcinosarcomas than in serous and clear cell carcinomas. In the majority of multivariate analyses, FIGO stage and depth of myometrial infiltration were the most important predictive (tumor recurrence) and prognostic (survival rate) factors. DNA ploidy status is a less important predictive and prognostic factor in non-endometrioid, high-risk endometrial carcinomas than in the common endometrioid carcinomas, in which FIGO and nuclear grade also are highly significant and important factors.

Prognostic Factors for Recovery After Anterior Debridement/Bone Grafting and Posterior Instrumentation for Lumbar Spinal Tuberculosis.

PubMed

Yao, Yuan; Zhang, Huiyu; Liu, Huan; Zhang, Zhengfeng; Tang, Yu; Zhou, Yue

2017-08-01

Anterior debridement/bone grafting/posterior instrumentation is a common selection for the treatment of lumbar spinal tuberculosis (LST). To date, no study has focused on the prognostic factors for recovery after this surgery. We included 144 patients who experienced anterior debridement/bone grafting/posterior instrumentation for LST. The recovery rate based on the Japanese Orthopedic Association (JOA) score was used to assess recovery. The Kaplan-Meier method and Cox regression analysis were used to identify the prognostic factors for recovery postoperatively. For the prognostic factors worth further consideration, the changes in JOA scores within the 24-month follow-up period were identified by repeated-measures analysis of variance. Paralysis/nonparalysis, duration of symptoms (≥3/<3 months), number of involved vertebrae (>2/≤2), and posterior open/percutaneous instrumentation were identified as prognostic factors for recovery postoperatively. The prognostic factor of open/percutaneous instrumentation was then further compared for potential clinical application. Patients in the percutaneous instrumentation group achieved higher JOA scores than those in the open instrumentation group in the early stages postoperatively (1-3 months), but this effect equalized at 6 months postoperatively. Patients in the open instrumentation group experienced longer operation time and less cost than those in the percutaneous instrumentation group. Nonparalysis, shorter symptom duration, fewer involved vertebrae, and posterior percutaneous instrumentation (compared with open instrumentation) are considered favorable prognostic factors. Patients in the percutaneous instrumentation group achieved higher JOA scores than those in the open instrumentation group in the early stages postoperatively (1-3 months), but no significant difference was observed in long-term JOA scores (6-24 months). Copyright © 2017. Published by Elsevier Inc.

A systematic review of prognostic factors for return to work following work-related traumatic hand injury.

PubMed

Shi, Qiyun; Sinden, Kathryn; MacDermid, Joy C; Walton, David; Grewal, Ruby

2014-01-01

Systematic review. Traumatic hand injuries are frequent cause of work related injuries and can result in prolonged durations of time loss from work. To systematically review available evidence to determine which prognostic factors predict return-to-work (RTW) following work-related traumatic hand injuries. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO from 1980 to September 2013 and reference lists of articles. Studies investigating any prognostic factors of RTW after traumatic hand injury were included. Two reviewers performed study selection, assessment of methodological quality and data extraction independently of each other. Identified factors were grouped into conceptual prognostic factor categories. We assessed 8 studies, which addressed 11 potential prognostic factors (i.e., sociodemographic factors, occupation, work compensation status, treatment related factors, impairment severity, location of injury, etc.). The quality of the studies was low to moderate. Across all included studies, RTW (original or modified work) occurred in over 60% of individuals by 6 months. There was consistent low-moderate quality evidence that individuals with more severe impairments and lower pre-injury income were less likely to RTW, and low-moderate quality evidence that age, gender and level of education had no impact on RTW. Evidence on other commonly cited prognostic factors were limited in the literature. Impairment severity and lower pre-injury income showed a consistent association with RTW following occupational hand injury, while other factors demonstrated no or variable effects across studies. Additional high-quality studies are warranted toward improving our understanding of the complex factors that mediate RTW following a traumatic work-related hand injury. 2a. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Prognostic factors and scoring system for survival in colonic perforation.

PubMed

Komatsu, Shuhei; Shimomatsuya, Takumi; Nakajima, Masayuki; Amaya, Hirokazu; Kobuchi, Taketsune; Shiraishi, Susumu; Konishi, Sayuri; Ono, Susumu; Maruhashi, Kazuhiro

2005-01-01

No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.

Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplantation.

PubMed

Bitan, Menachem; Ahn, Kwang Woo; Millard, Heather R; Pulsipher, Michael A; Abdel-Azim, Hisham; Auletta, Jeffery J; Brown, Valerie; Chan, Ka Wah; Diaz, Miguel Angel; Dietz, Andrew; Vincent, Marta González; Guilcher, Gregory; Hale, Gregory A; Hayashi, Robert J; Keating, Amy; Mehta, Parinda; Myers, Kasiani; Page, Kristin; Prestidge, Tim; Shah, Nirali N; Smith, Angela R; Woolfrey, Ann; Thiel, Elizabeth; Davies, Stella M; Eapen, Mary

2017-09-01

We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML, n = 790) and acute lymphoblastic leukemia (ALL, n = 1096) who underwent transplantation between 2000 and 2010 and who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease-, and transplantation characteristics and acute and chronic graft-versus-host disease (GVHD) was performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival. We did not identify any prognostic factors beyond 4 years after transplantation for AML and beyond 3 years for ALL. Risk score for survival for AML includes age, disease status at transplantation, cytogenetic risk group, and chronic GVHD. For ALL, the risk score includes age at transplantation and chronic GVHD. The 10-year probabilities of OS for AML with good (score 0, 1, or 2), intermediate (score 3), and poor risk (score 4, 5, 6, or 7) were 94%, 87%, and 68%, respectively. The 10-year probabilities of OS for ALL were 89% and 80% for good (score 0 or 1) and poor risk (score 2), respectively. Identifying children at risk for late mortality with early intervention may mitigate some excess late mortality. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer.

PubMed

Wu, Xinhong; Luo, Bo; Wei, Shaozhong; Luo, Yan; Feng, Yaojun; Xu, Juan; Wei, Wei

2013-11-01

To investigate the treatment efficiency of whole brain irradiation combined with precise radiotherapy on triple-negative (TN) phenotype breast cancer patients with brain metastases and their survival times. A total of 112 metastatic breast cancer patients treated with whole brain irradiation and intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT) were analyzed. Thirty-seven patients were of TN phenotype. Objective response rates were compared. Survival times were estimated by using the Kaplan-Meier method. Log-rank test was used to compare the survival time difference between the TN and non-TN groups. Potential prognostic factors were determined by using a Cox proportional hazard regression model. The efficiency of radiotherapy treatment on TN and non-TN phenotypes was 96.2% and 97%, respectively. TN phenotype was associated with worse survival times than non-TN phenotype after radiotherapy (6.9 months vs. 17 months) (P < 0.01). On multivariate analysis, good prognosis was associated with non-TN status, lower graded prognosis assessment class, and nonexistence of active extracranial metastases. After whole brain irradiation followed by IMRT or 3DCRT treatment, TN phenotype breast cancer patients with intracranial metastasis had high objective response rates but shorter survival time. With respect to survival in breast cancer patients with intracranial metastasis, the TN phenotype represents a significant adverse prognostic factor.

Bell's palsy. A prospective, longitudinal, descriptive, and observational analysis of prognosis factors for recovery in Mexican patients.

PubMed

Sánchez-Chapul, Laura; Reyes-Cadena, Susana; Andrade-Cabrera, José Luis; Carrillo-Soto, Irma A; León-Hernández, Saúl R; Paniagua-Pérez, Rogelio; Olivera-Díaz, Hiram; Baños-Mendoza, Teresa; Flores-Mondragón, Gabriela; Hernández-Campos, Norma A

2011-01-01

To determine the prognosis factors in Mexican patients with Bell's palsy. We designed a prospective, longitudinal, descriptive, and observational analysis. Two hundred and fifty one patients diagnosed with Bell's palsy at the National Institute of Rehabilitation were included. We studied the sociodemographic characteristics, seasonal occurrence, sidedness, symptoms, and therapeutic options to determine the prognostic factors for their recovery. Thirty-nine percent of patients had a complete recovery and 41.5% had an incomplete recovery. Marital status, gender, etiology, symptoms, sidedness, House-Brackmann grade, and treatments did not represent significant prognostic factors for recovery. Age > 40 years (OR = 2.4, IC 95% 1.3-4.3, p = 0.002) and lack of physical therapy (OR = 6.4, IC 95% 1.4-29.6, p = 0.006) were significant prognostic factors for incomplete recovery. Familial palsy resulted to be a protective prognostic factor against an incomplete recovery (OR = 0.54, IC 95% 0.28-1.01, p = 0.039). This protection factor was only significant in female patients (OR = 0.41, p = 0.22) but not in male patients (OR = 1.0, p = 0.61). The proportion of cases with incomplete recovery was high. The age > 40 years and lack of physical therapy were the only significant prognostic factors for an incomplete recovery.

Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors.

PubMed

Cho, Gene Young; Moy, Linda; Kim, Sungheon G; Baete, Steven H; Moccaldi, Melanie; Babb, James S; Sodickson, Daniel K; Sigmund, Eric E

2016-08-01

To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 ± 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. • Novel IVIM biomarkers characterize heterogeneous breast cancer. • Histogram analysis enables quantification of tumour heterogeneity. • IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

Prognostic Factors for Predicting Outcomes After Intramedullary Nailing of the Tibia

PubMed Central

Schemitsch, Emil H.; Bhandari, Mohit; Guyatt, Gordon; Sanders, David W.; Swiontkowski, Marc; Tornetta, Paul; Walter, Stephen D.; Zdero, Rad; Goslings, J.C.; Teague, David; Jeray, Kyle; McKee, Michael D.; Schemitsch, Emil H.; Bhandari, Mohit; Guyatt, Gordon; Sanders, David W.; Swiontkowski, Marc; Tornetta, Paul; Walter, Stephen D.; Zdero, Rad; Goslings, J.C.; Teague, David; Jeray, Kyle; McKee, Michael D.

2012-01-01

Background: Prediction of negative postoperative outcomes after long-bone fracture treatment may help to optimize patient care. We recently completed the Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT), a large, multicenter trial of reamed and unreamed intramedullary nailing of tibial shaft fractures in 1226 patients. Using the SPRINT data, we conducted an investigation of baseline and surgical factors to determine any associations with an increased risk of adverse events within one year of intramedullary nailing. Methods: Using multivariable logistic regression analysis, we investigated fifteen baseline and surgical factors for any associations with an increased risk of negative outcomes. Results: There was an increased risk of negative events in patients with a high-energy mechanism of injury (odds ratio [OR] = 1.57; 95% confidence interval [CI], 1.05 to 2.35), a stainless steel compared with a titanium nail (OR = 1.52; 95% CI, 1.10 to 2.13), a fracture gap (OR = 2.40; 95% CI, 1.47 to 3.94), and full weight-bearing status after surgery (OR = 1.63; 95% CI, 1.00 to 2.64). There was no increased risk with the use of nonsteroidal anti-inflammatory agents, late or early time to surgery, or smoking status. Open fractures had a higher risk of events among patients treated with reamed nailing (OR = 3.26; 95% CI, 2.01 to 5.28) but not in patients treated with unreamed nailing (OR = 1.50; 95% CI, 0.92 to 2.47). Patients with open fractures who had wound management either without any additional procedures or with delayed primary closure had a decreased risk of events compared with patients who required subsequent, more complex reconstruction (OR = 0.18 [95% CI, 0.09 to 0.35] and 0.29 [95% CI, 0.14 to 0.62], respectively). Conclusions: We identified several baseline fracture and surgical characteristics that may increase the risk of adverse events in patients with tibial shaft fractures. Surgeons should consider the predictors identified in our analysis to inform patients treated for tibial shaft fractures. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID:23032589

Risk stratification personalised model for prediction of life-threatening ventricular tachyarrhythmias in patients with chronic heart failure.

PubMed

Frolov, Alexander Vladimirovich; Vaikhanskaya, Tatjana Gennadjevna; Melnikova, Olga Petrovna; Vorobiev, Anatoly Pavlovich; Guel, Ludmila Michajlovna

2017-01-01

The development of prognostic factors of life-threatening ventricular tachyarrhythmias (VTA) and sudden cardiac death (SCD) continues to maintain its priority and relevance in cardiology. The development of a method of personalised prognosis based on multifactorial analysis of the risk factors associated with life-threatening heart rhythm disturbances is considered a key research and clinical task. To design a prognostic and mathematical model to define personalised risk for life-threatening VTA in patients with chronic heart failure (CHF). The study included 240 patients with CHF (mean-age of 50.5 ± 12.1 years; left ventricular ejection fraction 32.8 ± 10.9%; follow-up period 36.8 ± 5.7 months). The participants received basic therapy for heart failure. The elec-trocardiogram (ECG) markers of myocardial electrical instability were assessed including microvolt T-wave alternans, heart rate turbulence, heart rate deceleration, and QT dispersion. Additionally, echocardiography and Holter monitoring (HM) were performed. The cardiovascular events were considered as primary endpoints, including SCD, paroxysmal ventricular tachycardia/ventricular fibrillation (VT/VF) based on HM-ECG data, and data obtained from implantable device interrogation (CRT-D, ICD) as well as appropriated shocks. During the follow-up period, 66 (27.5%) subjects with CHF showed adverse arrhythmic events, including nine SCD events and 57 VTAs. Data from a stepwise discriminant analysis of cumulative ECG-markers of myocardial electrical instability were used to make a mathematical model of preliminary VTA risk stratification. Uni- and multivariate Cox logistic regression analysis were performed to define an individualised risk stratification model of SCD/VTA. A binary logistic regression model demonstrated a high prognostic significance of discriminant function with a classification sensitivity of 80.8% and specificity of 99.1% (F = 31.2; c2 = 143.2; p < 0.0001). The method of personalised risk stratification using Cox logistic regression allows correct classification of more than 93.9% of CHF cases. A robust body of evidence concerning logistic regression prognostic significance to define VTA risk allows inclusion of this method into the algorithm of subsequent control and selection of the optimal treatment modality to treat patients with CHF.

The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia

PubMed Central

Nahajevszky, Sarolta; Andrikovics, Hajnalka; Batai, Arpad; Adam, Emma; Bors, Andras; Csomor, Judit; Gopcsa, Laszlo; Koszarska, Magdalena; Kozma, Andras; Lovas, Nora; Lueff, Sandor; Matrai, Zoltan; Meggyesi, Nora; Sinko, Janos; Sipos, Andrea; Varkonyi, Andrea; Fekete, Sandor; Tordai, Attila; Masszi, Tamas

2011-01-01

Background Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia. Design and Methods Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent. Results The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P=0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P=0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P=0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P=0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P=0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P=0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P=0.024) and overall survival (P=0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype. Conclusions Janus kinase 2 46/1 haplotype influences morphological distribution, increasing the predisposition towards an acute myelomonocytoid form. It may be a novel, independent unfavorable risk factor in acute myeloid leukemia with a normal karyotype. PMID:21791467

Maximum Diameter and Number of Tumors as a New Prognostic Indicator of Colorectal Liver Metastases.

PubMed

Yoshimoto, Toshiaki; Morine, Yuji; Imura, Satoru; Ikemoto, Tetsuya; Iwahashi, Syuichi; Saito, Y U; Yamada, Sinichiro; Ishikawa, Daichi; Teraoku, Hiroki; Yoshikawa, Masato; Higashijima, Jun; Takasu, Chie; Shimada, Mitsuo

2017-01-01

Surgical resection is currently considered the only potentially curative option as a treatment strategy of colorectal liver metastases (CRLM). However, the criteria for selection of resectable CRLM are not clear. The aim of this study was to confirm a new prognostic indicator of CRLM after hepatic resection. One hundred thirty nine patients who underwent initial surgical resection from 1994 to 2015 were investigated retrospectively. Prognostic factors of overall survival including the product of maximum diameter and number of metastases (MDN) were analyzed. Primary tumor differentiation, vessel invasion, lymph node (LN) metastasis, non-optimally resectable metastases, H score, grade of liver metastases, resection with non-curative intent and MDN were found to be prognostic factors of overall survival (OS). In multivariate analyses of clinicopathological features associated with OS, MDN and non-curative intent were independent prognostic factors. Patients with MDN ≥30 had shown significantly poorer prognosis than patients with MDN <30 in OS and relapse-free survival (RFS). MDN ≥30 is an independent prognostic factor of survival in patients with CRLM and optimal surgical criterion of hepatectomy for CRLM. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Outcomes of interfacility critical care adult patient transport: a systematic review

PubMed Central

Fan, Eddy; MacDonald, Russell D; Adhikari, Neill KJ; Scales, Damon C; Wax, Randy S; Stewart, Thomas E; Ferguson, Niall D

2006-01-01

Introduction We aimed to determine the adverse events and important prognostic factors associated with interfacility transport of intubated and mechanically ventilated adult patients. Methods We performed a systematic review of MEDLINE, CENTRAL, EMBASE, CINAHL, HEALTHSTAR, and Web of Science (from inception until 10 January 2005) for all clinical studies describing the incidence and predictors of adverse events in intubated and mechanically ventilated adult patients undergoing interfacility transport. The bibliographies of selected articles were also examined. Results Five studies (245 patients) met the inclusion criteria. All were case-series and two were prospective in design. Due to the paucity of studies and significant heterogeneity in study population, outcome events, and results, we synthesized data in a qualitative manner. Pre-transport severity of illness was reported in only one study. The most common indication for transport was a need for investigations and/or specialist care (three studies, 220 patients). Transport modalities included air (fixed or rotor wing; 66% of patients) and ground (31%) ambulance, and commercial aircraft (3%). Transport teams included a physician in three studies (220 patients). Death during transfer was rare (n = 1). No other adverse events or significant therapeutic interventions during transport were reported. One study reported a 19% (28/145) incidence of respiratory alkalosis on arrival and another study documented a 30% overall intensive care unit mortality, while no adverse events or outcomes were reported after arrival in the three other studies. Conclusion Insufficient data exist to draw firm conclusions regarding the mortality, morbidity, or risk factors associated with the interfacility transport of intubated and mechanically ventilated adult patients. Further study is required to define the risks and benefits of interfacility transfer in this patient population. Such information is important for the planning and allocation of resources related to transporting critically ill adults. PMID:16356212

Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

PubMed

Cainap, Calin; Nagy, Viorica; Seicean, Andrada; Gherman, Alexandra; Laszlo, Istvan; Lisencu, Cosmin; Nadim, Al Hajar; Constantin, Anne-Marie; Cainap, Simona

2016-01-01

The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

Prognostic factors of non-functioning pancreatic neuroendocrine tumor revisited: The value of WHO 2010 classification.

PubMed

Bu, Jiyoung; Youn, Sangmin; Kwon, Wooil; Jang, Kee Taek; Han, Sanghyup; Han, Sunjong; You, Younghun; Heo, Jin Seok; Choi, Seong Ho; Choi, Dong Wook

2018-02-01

Various factors have been reported as prognostic factors of non-functional pancreatic neuroendocrine tumors (NF-pNETs). There remains some controversy as to the factors which might actually serve to successfully prognosticate future manifestation and diagnosis of NF-pNETs. As well, consensus regarding management strategy has never been achieved. The aim of this study is to further investigate potential prognostic factors using a large single-center cohort to help determine the management strategy of NF-pNETs. During the time period 1995 through 2013, 166 patients with NF-pNETs who underwent surgery in Samsung Medical Center were entered in a prospective database, and those factors thought to represent predictors of prognosis were tested in uni- and multivariate models. The median follow-up time was 46.5 months; there was a maximum follow-up period of 217 months. The five-year overall survival and disease-free survival rates were 88.5% and 77.0%, respectively. The 2010 WHO classification was found to be the only prognostic factor which affects overall survival and disease-free survival in multivariate analysis. Also, pathologic tumor size and preoperative image tumor size correlated strongly with the WHO grades ( p <0.001, and p <0.001). Our study demonstrates that 2010 WHO classification represents a valuable prognostic factor of NF-pNETs and tumor size on preoperative image correlated with WHO grade. In view of the foregoing, the preoperative image size is thought to represent a reasonable reference with regard to determination and development of treatment strategy of NF-pNETs.

Prognostic significance of anaplasia and angiogenesis in childhood medulloblastoma: a pediatric oncology group study.

PubMed

Ozer, Erdener; Sarialioglu, Faik; Cetingoz, Riza; Yüceer, Nurullah; Cakmakci, Handan; Ozkal, Sermin; Olgun, Nur; Uysal, Kamer; Corapcioglu, Funda; Canda, Serefettin

2004-01-01

The purpose of this study was to investigate whether quantitative assessment of cytologic anaplasia and angiogenesis may predict the clinical prognosis in medulloblastoma and stratify the patients to avoid both undertreatment and overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric Oncology Group were evaluated with respect to some prognostic variables, including histologic assessment of nodularity and desmoplasia, grading of anaplasia, measurement of nuclear size, mitotic cell count, quantification of angiogenesis, including vascular surface density (VSD) and microvessel number (NVES), and immunohistochemical scoring of vascular endothelial growth factor (VEGF) expression. Univariate and multivariate analyses for prognostic indicators for survival were performed. Univariate analysis revealed that extensive nodularity was a significant favorable prognostic factor, whereas the presence of anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant unfavorable prognostic factors. Using multivariate analysis, increased nuclear size was found to be an independent unfavorable prognostic factor for survival. Neither the presence of desmoplasia nor VEGF expression was significantly related to patient survival. Although care must be taken not to overstate the importance of the results of this single-institution preliminary report, pathologic grading of medulloblastomas with respect to grading of anaplasia and quantification of nodularity, nuclear size, and microvessel profiles may be clinically useful for the treatment of medulloblastomas. Further validation of the independent prognostic significance of nuclear size in stratifying patients is required.

Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

PubMed

Karatas, Fatih; Erdem, Gokmen Umut; Sahin, Suleyman; Aytekin, Aydin; Yuce, Deniz; Sever, Ali R; Babacan, Taner; Ates, Ozturk; Ozisik, Yavuz; Altundag, Kadri

2017-04-01

The relation between higher body mass index (BMI) and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a controversial issue according to the data of Western and Asian patients. The aim of this study is to evaluate BMI and pCR to NAC and discuss the importance of pCR outcomes in Turkish BC patients as a bridging country between Europe and Asia. Of the 4423 BC patients diagnosed between the years 1994 and 2015 in Hacettepe University Cancer Institute, 295 female patients with stage II and III BC were enrolled in the study. Three different group divisions were done according to patients' BMI as normal or underweight (N/U) patients (BMI <25 kg/m 2 ), overweight (OW) patients (BMI = 25-29.9 kg/m 2 ) and obese (OB) patients (BMI ≥30 kg/m 2 ). BC subtypes were defined as luminal-like (ER/PR-positive and HER2-negative), HER2/luminal (ER/PR-positive and HER2-positive), HER2-type (ER/PR-negative and HER2-positive), and triple-negative (TNBC; ER/PR- and HER2-negative). The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed according to Kaplan-Meier method. The Log-rank test was used to compare the subgroup analysis and logistic regression analysis to determine the independent prognostic factors. In this study, a total number of 93 (31.5%) patients were N/U, 107 (36.3%) patients were OW and 95 (32.2%) patients were OB. Among groups, except for the age, no baseline clinicopathological differences were found. In 70 (23.7%) patients, pCR was achieved. pCR rates in N/U, OW and OB were 31.2%, 22.4%, and 17.9% respectively, showing a considerable trend towards significance (P = 0.09 in chi-square test). In the multivariate logistic regression analysis, obesity was an independent adverse prognostic feature on pCR to NAC compared to N/U patients (OR, 0.34; 95% CI, 0.13 to 0.85, P = 0.02). The recurrence rates were slightly increased with the increase of BMI (N/U = 24.7%, OW = 29.0% and OB = 40%; P = 0.06 respectively). Median RFS was significantly higher in N/U group compared to OB patients (150 vs. 76 months respectively, P = 0.03) and was also higher in pCR group compared to non-pCR patients (151 vs. 77 months P = 0.004). Median OS was significantly higher in N/U patients compared to OB patients (N/U = not reached, OW = 211 and OB = 114 months; P = 0.01) and was also higher in pCR group compared to non-pCR patients (not reached vs. 211 months P = 0.04). In Cox regression analysis; pCR, histopathological grade and TNBC were found as independent prognostic factors on OS (HR, 0.29; 95% CI, 0.11 to 0.79, P = 0.015, HR, 2.09; 95% CI, 1.14 to 3.83, P = 0.017, HR, 1.95; 95% CI, 1.01 to 3.77, P = 0.046, respectively). It was observed that obesity was an important independent prognostic factor which has an adverse effect on pCR. Moreover it causes decreasing RFS and OS in BC patients who had received NAC. The probability of inefficient treatment in obese patients should be considered. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prognostic factors for return-to-work following surgery for carpal tunnel syndrome: a systematic review.

PubMed

Peters, Susan; Johnston, Venerina; Hines, Sonia; Ross, Mark; Coppieters, Michel

2016-09-01

Carpal tunnel syndrome (CTS) is a common problem, that can be effectively managed by surgery. Screening for prognostic factors is important to identify workers who are at a greater risk of a poor work outcome in order to implement tailored interventions to facilitate their return-to-work. To synthesize the best available evidence on the association of preoperative prognostic factors with work-related outcomes in people who have undergone carpal tunnel surgery. Participants included those who were employed at the time of surgery, underwent carpal tunnel surgery and planned to return-to-work. The primary outcome was return-to-work. Quantitative studies investigating at least one prognostic factor for a work-related outcome in studies of workers who had carpal tunnel surgery were considered. Eleven electronic databases were searched from their respective inception date up to July 2015. A total of 3893 publications were reviewed. The quality of the included studies was assessed by two reviewers using a modified version of an appraisal tool (Joanna Briggs Institute Meta-analysis of Statistical Assessment and Review Instrument [JBI-MAStARI]). The following criteria were evaluated: study population representativeness, clearly defined prognostic factors and outcomes, potential confounding variables and appropriate statistical analysis. Data extraction was performed using a modified version of the standardized extraction tool from JBI-MAStARI. Statistical pooling was not possible. Findings are presented in tables and narrative format. Eleven studies (13 publications) investigating 93 prognostic factors for delayed return-to-work or prolonged work disability outcomes and 27 prognostic factors for work role functioning in 4187 participants were identified.Prognostic factors associated with workers' increased likelihood of an earlier return-to-work in a moderate-to-high-quality study included worker expected or desired fewer days off work, occupation, lower pain anxiety and if CTS had not altered their work role.Prognostic factors for a poorer work-related outcome included older age, lower household income, greater upper extremity functional limitation, greater than two musculoskeletal pain sites, lower recovery expectations, worse mental health status, job accommodation availability, high job strain, high job demands with high job control, poor co-worker relationships, poor baseline work role functioning, less-supportive workplace policies, preoperative work absence due to CTS or work disability of any cause, workers' compensation status, attorney involvement, and post-diagnosis surgical wait time. For workers who have had carpal tunnel surgery, there are a number of factors which may be modified in order to improve return-to-work times.

Acute Kidney Injury Predicts Major Adverse Outcomes in Diabetes: Synergic Impact With Low Glomerular Filtration Rate and Albuminuria.

PubMed

Monseu, Mathilde; Gand, Elise; Saulnier, Pierre-Jean; Ragot, Stéphanie; Piguel, Xavier; Zaoui, Philippe; Rigalleau, Vincent; Marechaud, Richard; Roussel, Ronan; Hadjadj, Samy; Halimi, Jean-Michel

2015-12-01

Subjects with diabetes are prone to the development of cardiovascular and noncardiovascular complications. In separate studies, acute kidney injury (AKI), albuminuria, and low estimated glomerular filtration rate (eGFR) were shown to predict adverse outcomes, but, when considered together, their respective prognostic value is unknown. Patients with type 2 diabetes consecutively recruited in the SURDIAGENE cohort were prospectively followed up for major diabetes-related events, as adjudicated by an independent committee: death (with cause), major cardiovascular events (myocardial infarction, stroke, congestive heart failure, amputation, and arterial revascularization), and renal failure (i.e., sustained doubling of serum creatinine level or end-stage renal disease). Intrahospital AKI occurred in 411 of 1,371 patients during the median follow-up period of 69 months. In multivariate analyses, AKI was significantly associated with cardiovascular and noncardiovascular death, including cancer-related death. In multivariate analyses, AKI was a powerful predictor of major adverse cardiovascular events, heart failure requiring hospitalization, myocardial infarction, stroke, lower-limb amputation or revascularization, and carotid artery revascularization. AKI, eGFR, and albuminuria, even when simultaneously considered in multivariate models, predicted all-cause and cardiovascular deaths. All three renal biomarkers were also prognostic of most adverse outcomes and of the risk of renal failure. AKI, low eGFR, and elevated albuminuria, separately or together, are compelling biomarkers of major adverse outcomes and death in diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Integration of Wall Motion, Coronary Flow Velocity, and Left Ventricular Contractile Reserve in a Single Test: Prognostic Value of Vasodilator Stress Echocardiography in Patients with Diabetes.

PubMed

Cortigiani, Lauro; Huqi, Alda; Ciampi, Quirino; Bombardini, Tonino; Bovenzi, Francesco; Picano, Eugenio

2018-06-01

Coronary flow velocity reserve (CFVR) and left ventricular contractile reserve (LVCR) have demonstrated prognostic importance in patients with diabetes. The aim of this study was to investigate the prognostic contribution of combined evaluation of CFVR and LVCR in patients with diabetes with nonischemic stress echocardiography. Three hundred seventy-five patients with diabetes (mean age, 68 ± 9 years) with nonischemic dipyridamole stress echocardiography underwent assessment of CFVR of the left anterior descending coronary artery (prospectively) and LVCR with left ventricular force (retrospectively) in a multicenter study. On receiver operating characteristic analysis, LVCR ≤ 1.1 was the best prognostic predictor and was considered an abnormal value. CFVR was abnormal (≤2) in 139 patients (37%), LVCR in 156 (42%), neither in 157 (42%), and both in 77 (21%). During a median follow-up period of 16 months, 86 major adverse cardiac events occurred: 16 deaths, 13 myocardial infarctions, and 57 revascularizations. Multivariate prognostic indicators were CFVR ≤ 2 (P < .0001), age (P = .03), and LVCR ≤ 1.1 (P = .04). The 3-year rate of major adverse cardiac events was 63% in patients with both abnormal CFVR and LVCR, 42% in those with abnormal CFVR only, 19% in those with abnormal LVCR only, and 10% in patients with both normal CFVR and LVCR. The 3-year hard event rate was 3% in patients with both normal CFVR and LVCR, fivefold higher in patients with abnormal CFVR or LVCR only, and ninefold higher in patients with both abnormal CFVR and LVCR. Patients with diabetes with nonischemic dipyridamole stress echocardiography may still have significant risk in presence of abnormal CFVR and/or LVCR, which assess the underlying, largely unrelated, microvascular and myocardial components of coronary circulation. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

An elevated neutrophil-lymphocyte ratio is associated with adverse outcomes following single time-point paracetamol (acetaminophen) overdose: a time-course analysis.

PubMed

Craig, Darren G; Kitto, Laura; Zafar, Sara; Reid, Thomas W D J; Martin, Kirsty G; Davidson, Janice S; Hayes, Peter C; Simpson, Kenneth J

2014-09-01

The innate immune system is profoundly dysregulated in paracetamol (acetaminophen)-induced liver injury. The neutrophil-lymphocyte ratio (NLR) is a simple bedside index with prognostic value in a number of inflammatory conditions. To evaluate the prognostic accuracy of the NLR in patients with significant liver injury following single time-point and staggered paracetamol overdoses. Time-course analysis of 100 single time-point and 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Timed laboratory samples were correlated with time elapsed after overdose or admission, respectively, and the NLR was calculated. A total of 49/100 single time-point patients developed hepatic encephalopathy (HE). Median NLRs were higher at both 72 (P=0.0047) and 96 h after overdose (P=0.0041) in single time-point patients who died or were transplanted. Maximum NLR values by 96 h were associated with increasing HE grade (P=0.0005). An NLR of more than 16.7 during the first 96 h following overdose was independently associated with the development of HE [odds ratio 5.65 (95% confidence interval 1.67-19.13), P=0.005]. Maximum NLR values by 96 h were strongly associated with the requirement for intracranial pressure monitoring (P<0.0001), renal replacement therapy (P=0.0002) and inotropic support (P=0.0005). In contrast, in the staggered overdose cohort, the NLR was not associated with adverse outcomes or death/transplantation either at admission or subsequently. The NLR is a simple test which is strongly associated with adverse outcomes following single time-point, but not staggered, paracetamol overdoses. Future studies should assess the value of incorporating the NLR into existing prognostic and triage indices of single time-point paracetamol overdose.

Long-term outcome of patients with triphasic mitral flow with a mid-diastolic L wave: prognostic role of left atrial volume and N-terminal pro-brain natriuretic peptide.

PubMed

Kim, Sung-Ai; Son, Jungwoo; Shim, Chi-Young; Choi, Eui-Young; Ha, Jong-Won

2017-09-01

A mid-diastolic L wave has been recognized as a marker of advanced left ventricular (LV) diastolic dysfunction. However, its prognostic implication is unclear. This study assessed long-term prognosis and independent predictors of adverse outcomes in patients with a mid-diastolic L wave. A total of 144 consecutive patients (mean age 63 ± 12 years, 88 female) with a mid-diastolic L wave of ≥0.2 m/s and in sinus rhythm were identified. Patients with significant valvular heart disease, low LV ejection fraction and arrhythmias were excluded. Subjects were followed up for cardiovascular (CV) mortality and hospitalization for heart failure (HF). During follow-up for a median of 44 months (1-76), CV deaths and hospitalization for HF occurred in 41 (28%) patients. In multivariate Cox analysis, age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.001), log N-terminal pro-brain natriuretic peptide (NT-proBNP)(HR 3.81; 95% CI 1.78-8.15; p = 0.001), and left atrial volume index (HR 1.02; 95% CI 1.01-1.04; p = 0.019) were independent predictors of adverse outcomes in patients with a mid-diastolic L wave. In a stepwise model, NT-proBNP showed an incremental prognostic value for prediction of adverse outcomes when added to the clinical and echocardiographic parameters (Chi square from 30.1 to 41.1, p < 0.001). Patients with a mid-diastolic L wave and clinical, biochemical, and echocardiographic evidence of advanced diastolic dysfunction showed poor long-term clinical outcome.

Left ventricular energy model predicts adverse events in women with suspected myocardial ischemia: results from the NHLBI-sponsored women’s ischemia syndrome evaluation (WISE) study

PubMed Central

Weinberg, Nicole; Pohost, Gerald M.; Bairey Merz, C. Noel; Shaw, Leslee J.; Sopko, George; Fuisz, Anthon; Rogers, William J.; Walsh, Edward G.; Johnson, B. Delia; Sharaf, Barry L.; Pepine, Carl J.; Mankad, Sunil; Reis, Steven E.; Rayarao, Geetha; Vido, Diane A.; Bittner, Vera; Tauxe, Lindsey; Olson, Marian B.; Kelsey, Sheryl F.; Biederman, Robert WW

2013-01-01

Objectives To assess the prognostic value of a left ventricular energy-model in women with suspected myocardial ischemia. Background The prognostic value of internal energy utilization (IEU) of the left ventricle in women with suspected myocardial ischemia is unknown. Methods Women [n=227, mean age 59±12 years (range, 31-86 years)], with symptoms of myocardial ischemia, underwent myocardial perfusion imaging (MPI) assessment for regional perfusion defects along with measurement of ventricular volumes separately by gated Single Photon Emission Computed Tomography (SPECT) (n=207) and magnetic resonance imaging (MRI) (n=203). During follow-up (40±17 months), time to first major adverse cardiovascular event (MACE, death, myocardial infarction or hospitalization for congestive heart failure) was analyzed using MRI and gated SPECT variables. Results Adverse events occurred in 31 (14%). Multivariable Cox models were formed for each modality: IEU and wall thickness by MRI (Chi-squared 34, P<0.005) and IEU and systolic blood pressure by gated SEPCT (Chi-squared 34, P<0.005). The models remained predictive after adjustment for age, disease history and Framingham risk score. For each Cox model, patients were categorized as high-risk if the model hazard was positive and not high-risk otherwise. Kaplan-Meier analysis of time to MACE was performed for high-risk vs. not high-risk for MR (log rank 25.3, P<0.001) and gated SEPCT (log rank 18.2, P<0.001) models. Conclusions Among women with suspected myocardial ischemia a high internal energy utilization has higher prognostic value than either a low EF or the presence of a myocardial perfusion defect assessed using two independent modalities of MR or gated SPECT. PMID:24015377

Time to treatment and acute coronary syndromes: bridging the gap in rapid decision making.

PubMed

Peacock, W Frank

2010-01-01

The role of cardiac biomarkers in the diagnosis, risk stratification, and treatment of patients with chest pain and suspected acute coronary syndromes (ACS) has continued to evolve. Although it is clear that troponin (Tn) measurement provides independent prognostic information in patients with suspected ACS, it is less well established that early B-type natriuretic peptide (BNP) measurement provides additional incremental prognostic information above and beyond electrocardiography and Tn measurement. It is useful to identify patients at high risk for adverse events through measurement of Tn and BNP levels so that timely treatment decisions can be made.

Cytologic anaplasia is a prognostic factor in osteosarcoma biopsies, but mitotic rate or extent of spontaneous tumor necrosis are not: a critique of the College of American Pathologists Bone Biopsy template.

PubMed

Cates, Justin Mm; Dupont, William D

2017-01-01

The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well-established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (≥90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high-grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated.

Health-related quality-of-life parameters as independent prognostic factors in advanced or metastatic bladder cancer.

PubMed

Roychowdhury, D F; Hayden, A; Liepa, A M

2003-02-15

This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer. Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox's proportional hazards model. Factors with individual prognostic value (P <.05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model. HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.

Prognostic stratification model for patients with stage I non-small cell lung cancer adenocarcinoma treated with surgical resection without adjuvant therapies using metabolic features measured on F-18 FDG PET and postoperative pathologic factors.

PubMed

Kang, Yeon-Koo; Song, Yoo Sung; Cho, Sukki; Jheon, Sanghoon; Lee, Won Woo; Kim, Kwhanmien; Kim, Sang Eun

2018-05-01

In the management of non-small cell lung cancer (NSCLC), the prognostic stratification of stage I tumors without indication of adjuvant therapy, remains to be elucidated in order to better select patients who can benefit from additional therapies. We aimed to stratify the prognosis of patients with stage I NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. We retrospectively enrolled 128 patients with stage I NSCLC without any high-risk factors, who underwent curative surgical resection without adjuvant therapies. Preoperative clinical and postoperative pathologic factors were evaluated by medical record review. Standardized uptake value corrected with lean body mass (SUL max ) was measured on F-18 FDG PET. Among the factors, independent predictors for recurrence-free survival (RFS) were selected using univariate and stepwise multivariate survival analyses. A prognostic stratification model for RFS was designed using the selected factors. Tumors recurred in nineteen patients (14.8%). Among the investigated clinicopathologic and FDG PET factors, SUL max on PET and spread through air spaces (STAS) on pathologic review were determined to be independent prognostic factors for RFS. A prognostic model was designed using these two factors in the following manner: (1) Low-risk: SUL max  ≤ 1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high-risk: SUL max> 1.9 and observed STAS. This model exhibited significant predictive power for RFS. We showed that FDG uptake and STAS are significant prognostic markers in stage I NSCLC adenocarcinoma treated with surgical resection without adjuvant therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Refining prognosis in lung cancer: A report on the quality and relevance of clinical prognostic tools

PubMed Central

Mahar, Alyson L.; Compton, Carolyn; McShane, Lisa M.; Halabi, Susan; Asamura, Hisao; Rami-Porta, Ramon; Groome, Patti A.

2015-01-01

Introduction Accurate, individualized prognostication for lung cancer patients requires the integration of standard patient and pathologic factors, biologic, genetic, and other molecular characteristics of the tumor. Clinical prognostic tools aim to aggregate information on an individual patient to predict disease outcomes such as overall survival, but little is known about their clinical utility and accuracy in lung cancer. Methods A systematic search of the scientific literature for clinical prognostic tools in lung cancer published Jan 1, 1996-Jan 27, 2015 was performed. In addition, web-based resources were searched. A priori criteria determined by the Molecular Modellers Working Group of the American Joint Committee on Cancer were used to investigate the quality and usefulness of tools. Criteria included clinical presentation, model development approaches, validation strategies, and performance metrics. Results Thirty-two prognostic tools were identified. Patients with metastases were the most frequently considered population in non-small cell lung cancer. All tools for small cell lung cancer covered that entire patient population. Included prognostic factors varied considerably across tools. Internal validity was not formally evaluated for most tools and only eleven were evaluated for external validity. Two key considerations were highlighted for tool development: identification of an explicit purpose related to a relevant clinical population and clear decision-points, and prioritized inclusion of established prognostic factors over emerging factors. Conclusions Prognostic tools will contribute more meaningfully to the practice of personalized medicine if better study design and analysis approaches are used in their development and validation. PMID:26313682

Phosphohistone-H3 (PHH3) is prognostic relevant in Merkel cell carcinomas but Merkel cell polyomavirus is a more powerful prognostic factor than AJCC clinical stage, PHH3, Ki-67 or mitotic indices.

PubMed

Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kato, Masako; Nagata, Keiko; Murakami, Ichiro; Hayashi, Kazuhiko

2015-08-01

Merkel cell carcinomas (MCCs) associated with Merkel cell polyomavirus (MCPyV) have better prognosis than those without MCPyV. The relationship between mitotic index (MI) and MCC outcome has remained elusive because of the difficulty in differentiating mitotic cells from apoptotic ones. We evaluated the role of phosphohistone-H3 (PHH3) (Ser10), a new mitotic count biomarker, in MCPyV-positive or -negative MCC patients, and assessed its prognostic value in comparison to Ki-67 labeling index or MI using hematoxylin and eosin (HE) staining. We compared the prognostic value of PHH3 mitotic index with that of MI by HE in 19 MCPyV-positive and 9 MCPyV-negative MCC patients. PHH3-positive immunoreactivity was mostly observed in mitotic figures. Multivariate analysis significantly showed that MCPyV status (HR, 0.004; 95% CI 0.0003-0.058) and the American Joint Committee of Cancer (AJCC) stage (HR, 5.02; 95% CI 1.23-20.51) were observed as significantly independent prognostic factors for OS. PHH3-positive cell counts/10 HPF was a slightly significant independent prognostic factor for OS (HR, 4.96; 95% CI 0.93-26.55). PHH3-positive MI and MCPyV status in MCC patients are useful in prognostication, although MCPyV-infection is a more powerful prognostic factor in MCCs than the AJCC scheme on proliferation or mitotic indices. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability.

PubMed

Intragumtornchai, Tanin; Bunworasate, Udomsak; Siritanaratkul, Noppadol; Khuhapinant, Archrob; Nawarawong, Weerasak; Norasetthada, Lalita; Lekhakula, Arnuparp; Rujirojindakul, Pairaya; Sirijerachai, Chittima; Chansung, Kanjana; Suwanban, Tawatchai; Chuncharunee, Suporn; Niparuck, Pimjai; Wongkhantee, Somchai; Mongkonsritragoon, Wichean; Numbenjapon, Tontanai

2013-01-01

The impact of health insurance with inequitable rituximab coverage on the survival of patients with diffuse large B-cell lymphoma (DLBCL) has never been reported. We conducted a nationwide multicenter analysis on the outcome of 553 adult patients consecutively diagnosed with DLBCL between July 2003 and June 2006, in whom treatment cost was reimbursed under the Civil Servant Medical Benefit Scheme (CSMBS) (n =201) or the Universal Coverage Scheme (UCS) (n =352). The international prognostic index was comparable between the two payment groups. Rituximab-based therapy was administered in 45.3% and 3.1% of CSMBS and UCS patients, respectively (p <0.001). With a median follow-up of 24.6 months, the 6-year progression-free survival (PFS) was superior for CSMBS patients (34.2 vs. 23.2%, p =0.005). "Not treated with rituximab-based therapy" was the strongest adverse prognostic feature indicating a short PFS (hazard ratio 2.1, p <0.001). It is concluded that lack of access to rituximab is the principal factor accounting for the inferior PFS observed in Thai patients with DLBCL who are treated under the UCS.

Expression and functional role of inhibitor-of-apoptosis protein livin (BIRC7) in neuroblastoma.

PubMed

Dasgupta, Anindya; Alvarado, Carlos S; Xu, Zhiheng; Findley, Harry W

2010-09-10

We evaluated the expression of the inhibitor-of-apoptosis protein (IAP)livin (BIRC7)in 59 cases ofneuroblastoma (NBL) by quantitative RT-PCR. We also examined the role of livin in protecting tumor cells from chemotherapy drugs. Livin expression varied significantly amongtumors. High levels of expression were observed in 17 of 39 patients with advanced stages (stages 3 and 4) and 6 of 20 patients with localized stages (stages 1 and 2). Livin-transfected, MYCN-amplified NBL cells showed increased resistance to doxorubicin and etoposide. Conversely, livin knockdown with siRNA enhanced spontaneous and drug-induced apoptosis in NBL cells. Multivariate analysis of prognostic factors showed that high livin expression worsened prognosis for patients with MYCN-amplified tumors. Our data suggest that (i) livin is frequently expressed in NBL and protects tumor cells with amplified MYCN oncogene from genotoxic agents; (ii) the antiapoptotic effect of livin in NBL is blocked by siRNA; (iii) in the sample studied, high livin expression enhanced the adverse prognostic impact of MYCN amplification. These findings suggest that livin may contribute to drug resistance in NBL. Copyright © 2010 Elsevier Inc. All rights reserved.

Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

PubMed

Radujkovic, Aleksandar; Guglielmi, Cesare; Bergantini, Stefania; Iacobelli, Simona; van Biezen, Anja; Milojkovic, Dragana; Gratwohl, Alois; Schattenberg, Antonius V M B; Verdonck, Leo F; Niederwieser, Dietger W; de Witte, Theo; Kröger, Nicolaus; Olavarria, Eduardo

2015-07-01

Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3(+) cells ≥ 50 × 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Sex and interleukin-6 are prognostic factors for autoimmune toxicity following treatment with anti-CTLA4 blockade.

PubMed

Valpione, Sara; Pasquali, Sandro; Campana, Luca Giovanni; Piccin, Luisa; Mocellin, Simone; Pigozzo, Jacopo; Chiarion-Sileni, Vanna

2018-04-11

Ipilimumab is a licensed immunotherapy for metastatic melanoma patients and, in the US, as adjuvant treatment for high risk melanoma radically resected. The use of ipilimumab is associated with a typical but unpredictable pattern of side effects. The purpose of this study was to identify clinical features and blood biomarkers capable of predicting ipilimumab related toxicity. We performed a prospective study aimed at analyzing potential clinical and biological markers associated with immune-related toxicity in patients treated with ipilimumab (3 mg/kg, q3w). We enrolled 140 consecutive melanoma patients treated with ipilimumab for metastatic disease. The following prospectively collected data were utilized: patient characteristics, previous therapies, level of circulating biomarkers associated with tumour burden or immune-inflammation status (lactic dehydrogenase, C-reactive protein, β2-microglobulin, vascular endothelial growth factor, interleukin-2, interleukin-6, S-100, alkaline phosphatase, transaminases) and blood cells subsets (leukocyte and lymphocyte subpopulations). Logistic regression was used for multivariate analysis of data. Out of 140 patients, 36 (26%) experienced a severe adverse event, 33 (24%) discontinued treatment for severe toxicity. Among the immune-profile biomarkers analyzed, only interleukin-6 was associated with the risk of toxicity. Female patients had a further increase of immune-related adverse events. Low baseline interleukin-6 serum levels (OR = 2.84, 95% CI 1.34-6.03, P = 0.007) and sex female (OR = 1.5, 95% CI 1.06-2.16 P = 0.022) and were significant and independent risk factors for immune related adverse events. Baseline IL6 serum levels and female sex were significantly and independently associated with higher risk of severe toxicity and could be exploited in clinical practice to personalize toxicity surveillance in patients treated with ipilimumab.

Platelet-lymphocyte ratio is an independent prognostic factor in patients with ALK-positive non-small-cell lung cancer.

PubMed

Han, Ying; Wang, Jing; Hong, Liping; Sun, Leina; Zhuang, Hongqing; Sun, Bingsheng; Wang, Hua; Zhang, Xinwei; Ren, Xiubao

2017-01-01

As the prognostic value of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear in patients with ALK-positive non-small-cell lung cancer (NSCLC), this study assessed the importance of these factors was in this patient subset. In 173 patients with primary ALK-positive NSCLC at pathological stages I-IV, neutrophil, platelet, lymphocyte, D-dimer and eosinophil levels were recorded before starting treatment. The patients' median NLR and PLR values were 2.10 and 127.69, respectively. Univariate analyses showed that NLR and PLR values, the D-dimer level and the eosinophil count were all associated with survival. Although multivariate analysis showed PLR to be an independent prognostic factor for overall survival (p = 0.018), NLR was not. PLR is an independent prognostic factor in ALK-positive NSCLC.

Evaluation of prognostic factors in liver-limited metastatic colorectal cancer: a preplanned analysis of the FIRE-1 trial

PubMed Central

Giessen, C; Fischer von Weikersthal, L; Laubender, R P; Stintzing, S; Modest, D P; Schalhorn, A; Schulz, C; Heinemann, V

2013-01-01

Background: Liver-limited disease (LLD) denotes a specific subgroup of metastatic colorectal cancer (mCRC) patients. Patients and Methods: A total of 479 patients with unresectable mCRC from an irinotecan-based randomised phase III trial were evaluated. Patients with LLD and non-LLD and hepatic resection were differentiated. Based on baseline patient characteristic, prognostic factors for hepatic resection were evaluated. Furthermore, prognostic factors for median overall survival (OS) were estimated via Cox regression in LLD patients. Results: Secondary liver resection was performed in 38 out of 479 patients (resection rate: 7.9%). Prognostic factors for hepatic resection were LLD, lactate dehydrogenase (LDH), node-negative primary, alkaline phosphatase (AP) and Karnofsky performance status (PS). Median OS was significantly increased after hepatic resection (48 months), whereas OS in LLD (17 months) and non-LLD (19 months) was comparable in non-resected patients. With the inapplicability of Koehne's risk classification in LLD patients, a new score based on only the independent prognostic factors LDH and white blood cell (WBC) provided markedly improved information on the outcome. Conclusion: Patients undergoing hepatic resection showed favourable long-term survival, whereas non-resected LLD patients and non-LLD patients did not differ with regard to progression-free survival and OS. The LDH levels and WBC count were confirmed as prognostic factors and provide a useful and simple score for OS-related risk stratification also in LLD. PMID:23963138

Sex-based Prognostic Implications of Nonobstructive Coronary Artery Disease: Results from the International Multicenter CONFIRM Study

PubMed Central

Taylor, Carolyn M.; Gransar, Heidi; Shaw, Leslee J.; Ahmadi, Amir; Thompson, Angus; Humphries, Karin; Berman, Daniel S.; Hausleiter, Jörg; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Fillippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Chow, Benjamin J. W.; Cury, Ricardo C.; Delago, Augustin J.; Dunning, Allison L.; Feuchtner, Gudrun M.; Hadamitzky, Martin; Kaufmann, Philipp A.; Lin, Fay Y.; Chinnaiyan, Kavitha M.; Maffei, Erica; Raff, Gilbert L.; Villines, Todd C.; Gomez, Millie J.; Min, James K.

2014-01-01

Purpose To determine the clinical outcomes of women and men with nonobstructive coronary artery disease (CADcoronary artery disease) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CADcoronary artery disease risk factors, angina typicality, and CADcoronary artery disease extent and distribution. Materials and Methods Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CADcoronary artery disease or nonobstructive (<50% stenosis) CADcoronary artery disease were examined. Men and women were propensity matched for age, CADcoronary artery disease risk factors, angina typicality, and CADcoronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CADcoronary artery disease presence and extent were related to incident major adverse cardiovascular events (MACEmajor adverse cardiovascular events), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. Results At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACEmajor adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACEmajor adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CADcoronary artery disease was associated with similarly increased MACEmajor adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval {CIconfidence interval}: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CIconfidence interval: 1.07, 2.93], P = .03). Conclusion When matched for age, CADcoronary artery disease risk factors, angina typicality, and nonobstructive CADcoronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction. © RSNA, 2014 Online supplemental material is available for this article. PMID:25028784

Sex-based prognostic implications of nonobstructive coronary artery disease: results from the international multicenter CONFIRM study.

PubMed

Leipsic, Jonathon; Taylor, Carolyn M; Gransar, Heidi; Shaw, Leslee J; Ahmadi, Amir; Thompson, Angus; Humphries, Karin; Berman, Daniel S; Hausleiter, Jörg; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J; Cademartiri, Fillippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chow, Benjamin J W; Cury, Ricardo C; Delago, Augustin J; Dunning, Allison L; Feuchtner, Gudrun M; Hadamitzky, Martin; Kaufmann, Philipp A; Lin, Fay Y; Chinnaiyan, Kavitha M; Maffei, Erica; Raff, Gilbert L; Villines, Todd C; Gomez, Millie J; Min, James K

2014-11-01

To determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution. Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (<50% stenosis) CAD coronary artery disease were examined. Men and women were propensity matched for age, CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CAD coronary artery disease presence and extent were related to incident major adverse cardiovascular events ( MACE major adverse cardiovascular events ), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACE major adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACE major adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CAD coronary artery disease was associated with similarly increased MACE major adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval { CI confidence interval }: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI confidence interval : 1.07, 2.93], P = .03). When matched for age, CAD coronary artery disease risk factors, angina typicality, and nonobstructive CAD coronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction.

Job insecurity and prognosis after myocardial infarction: the SHEEP Study.

PubMed

László, Krisztina D; Engström, Karin; Hallqvist, Johan; Ahlbom, Anders; Janszky, Imre

2013-09-10

The prognostic role of job insecurity in coronary heart disease is unknown. We aimed to analyze whether job insecurity predicts mortality and recurrent events after a first acute myocardial infarction (AMI). We studied non-fatal AMI cases involved in the Stockholm Heart Epidemiology Program who were in paid employment and younger than 65 years (n=676). Shortly after their AMI, patients completed a questionnaire about job insecurity, demographic, work-related, clinical and lifestyle factors and participated in a clinical examination three months after discharge from the hospital. They were followed for 8.5 years for mortality and cardiovascular events. After adjusting for previous morbidity, demographic and work-related factors, job insecurity was associated with an increased risk of the combined endpoint of cardiac death and non-fatal AMI, of total mortality and of heart failure; the hazard ratios (HR) and the 95% confidence intervals (CI) were 1.50 (1.02-2.22), 1.69 (1.04-2.75) and 1.62 (1.07-2.44), respectively. Similar associations, but with less statistical power were observed between job insecurity and cardiac death (HR (95% CI): 1.57 (0.80-3.09)) and stroke (HR (95% CI): 1.46 (0.71-3.02)), respectively. Adjustment for potential mediators, i.e. sleep problems, health behaviour, hypertension, blood lipids, glucose, inflammatory and coagulation factors did not alter considerably the relationship between job insecurity and the combination of cardiac mortality and non-fatal AMI. Our results suggest that job insecurity is an adverse prognostic factor in patients with a first AMI. Future studies are needed to confirm this finding and to determine the mechanisms underlying the observed relationship. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Low skeletal muscle mass is a predictive factor for chemotherapy dose-limiting toxicity in patients with locally advanced head and neck cancer.

PubMed

Wendrich, Anne W; Swartz, Justin E; Bril, Sandra I; Wegner, Inge; de Graeff, Alexander; Smid, Ernst J; de Bree, Remco; Pothen, Ajit J

2017-08-01

Low skeletal muscle mass (SMM) or sarcopenia is emerging as an adverse prognostic factor for chemotherapy dose-limiting toxicity (CLDT) and survival in cancer patients. Our aim was to determine the impact of low SMM on CDLT in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) treated with primary radiochemotherapy (RCT). Consecutive patients diagnosed with LA-HNSCC and treated with primary RCT between 2007 and 2011 in our center were included. Clinical variables were retrospectively retrieved and SMM was measured at the level of the third cervical vertebra using pre-treatment head and neck CT-scans. After determining a cut-off value for low SMM, multivariate analysis was performed to identify prognostic factors for CDLT. Of 112 patients included, 30.4% experienced CDLT. The optimal cut-off value for low SMM as a predictor of CDLT was ≤43.2cm 2 /m 2 . Using this cut-off, 54.5% patients had low SMM. Patients with low SMM experienced CDLT more frequently than patients with normal SMM (44.3% vs. 13.7%, p<0.001) and received a higher dose of chemotherapy/kg lean body mass (estimated from SMM, p=0.044). At multivariate analysis, low SMM was independently inversely associated with CDLT (OR 0.93, 95%CI: 0.88-0.98). Patients experiencing CDLT had a lower overall survival than patients who did not (mean 36.6vs. 54.2months, p=0.038). Low SMM is an independent risk factor for CDLT in LA-HNSCC patients treated with primary RCT. Pre-therapeutic estimation of SMM using routine CT-scans of the head and neck region may identify patients at risk of CDLT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Expression of CD33 is a predictive factor for effect of gemtuzumab ozogamicin at different doses in adult acute myeloid leukaemia.

PubMed

Khan, N; Hills, R K; Virgo, P; Couzens, S; Clark, N; Gilkes, A; Richardson, P; Knapper, S; Grimwade, D; Russell, N H; Burnett, A K; Freeman, S D

2017-05-01

It remains unclear in adult acute myeloid leukaemia (AML) whether leukaemic expression of CD33, the target antigen for gemtuzumab ozogamicin (GO), adds prognostic information on GO effectiveness at different doses. CD33 expression quantified in 1583 patients recruited to UK-NCRI-AML17 (younger adults) and UK-NCRI-AML16 (older adults) trials was correlated with clinical outcomes and benefit from GO including a dose randomisation. CD33 expression associated with genetic subgroups, including lower levels in both adverse karyotype and core-binding factor (CBF)-AML, but was not independently prognostic. When comparing GO versus no GO (n=393, CBF-AMLs excluded) by stratified subgroup-adjusted analysis, patients with lowest quartile (Q1) %CD33-positivity had no benefit from GO (relapse risk, HR 2.41 (1.27-4.56), P=0.009 for trend; overall survival, HR 1.52 (0.92-2.52)). However, from the dose randomisation (NCRI-AML17, n=464, CBF-AMLs included), 6 mg/m 2 GO only had a relapse benefit without increased early mortality in CD33-low (Q1) patients (relapse risk HR 0.64 (0.36-1.12) versus 1.70 (0.99-2.92) for CD33-high, P=0.007 for trend). Thus CD33 expression is a predictive factor for GO effect in adult AML; although GO does not appear to benefit the non-CBF AML patients with lowest CD33 expression a higher GO dose may be more effective for CD33-low but not CD33-high younger adults.

Endoscopic duodenal stent versus surgical gastrojejunostomy for gastric outlet obstruction in patients with advanced pancreatic cancer.

PubMed

Uemura, Shinya; Iwashita, Takuji; Iwata, Keisuke; Mukai, Tsuyoshi; Osada, Shinji; Sekino, Takafumi; Adachi, Takahito; Kawai, Masahiko; Yasuda, Ichiro; Shimizu, Masahito

2018-05-03

Malignant gastric outlet obstruction (GOO) often develops in patients with advanced pancreatic cancer (APC). It is not clear whether endoscopic duodenal stenting (DS) or surgical gastrojejunostomy (GJJ) is preferable as palliative treatment. To compare the efficacy and safety of GJJ and DS for GOO with APC. Consecutive 99 patients who underwent DS or GJJ for GOO with APC were evaluated. We compared the technical and clinical success rates, the incidence of adverse event (AE), the time to start chemotherapy and discharge and survival durations between DS and GJJ. Prognostic factors for overall survival (OS) were investigated on the multivariate analysis. GOO was managed with GJJ in 35 and DS in 64. The technical and clinical success rates were comparable. DS was associated with shorter time to start oral intake and earlier chemotherapy start and discharge. No difference was seen in the early and late AE rates. Multivariate analyses of prognostic factors for OS showed that performance status ≧2, administration of chemotherapy, and presence of obstructive jaundice to be significant factors. There were no significant differences in survival durations between the groups, regardless of the PS. There were no significant differences in the technical and clinical success and AE rates and survival duration between DS and GJJ in management of GOO by APC. DS may be a preferable option over GJJ given that it will lead to an earlier return to oral intake, a shortened length of hospital stay, and finally an earlier referral for chemotherapy. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer

PubMed Central

Hiroshige, Tasuku; Eguchi, Yoshiro; Yoshizumi, Osamu; Chikui, Katsuaki; Kumagai, Hisaji; Kawaguchi, Yoshihiro; Onishi, Rei; Hayashi, Tokumasa; Watanabe, Kouta; Mitani, Tomotaro; Saito, Koujiro; Igawa, Tsukasa

2018-01-01

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC. PMID:29725416

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer.

PubMed

Hiroshige, Tasuku; Eguchi, Yoshiro; Yoshizumi, Osamu; Chikui, Katsuaki; Kumagai, Hisaji; Kawaguchi, Yoshihiro; Onishi, Rei; Hayashi, Tokumasa; Watanabe, Kouta; Mitani, Tomotaro; Saito, Koujiro; Igawa, Tsukasa

2018-05-01

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC.

Quantifying the advantages and disadvantages of pre-placement genetic screening

PubMed Central

Palmer, K; Poole, J; Rawbone, R; Coggon, D

2004-01-01

Background: Tests of genotype may enable workers at unusual risk of future ill-health to be identified. Using them to select for employment, however, entails gains and losses to employers and employees. Ensuring a fair balance between the rights and obligations of each group requires a value judgement, but the advantages and disadvantages to interested parties must first be quantified in a meaningful way. Method and Results: The purposes of pre-employment screening are reviewed, and several simple measures relevant to the separate interests of employers and job applicants proposed—number screened to prevent a single adverse outcome; number excluded to prevent a case; expected incidence of the adverse outcome in those excluded; and preventable fraction. The derivation of these measures is illustrated, and the factors that influence them (the prevalence of the prognostic trait, the relative risk that it carries for an adverse outcome, and the overall incidence of disease) are related algebraically and graphically, to aid judgement on the utility of screening under different circumstances. Conclusions: In sensitive areas such as genetic testing the onus should be on the employer to justify plans for pre-placement screening. Several quantitative measures can be used to inform the ethical and economic debate about screening and to evaluate alternative strategies for prevention. PMID:15090667

Quantifying the advantages and disadvantages of pre-placement genetic screening.

PubMed

Palmer, K T; Poole, J; Rawbone, R G; Coggon, D

2004-05-01

Tests of genotype may enable workers at unusual risk of future ill-health to be identified. Using them to select for employment, however, entails gains and losses to employers and employees. Ensuring a fair balance between the rights and obligations of each group requires a value judgement, but the advantages and disadvantages to interested parties must first be quantified in a meaningful way. The purposes of pre-employment screening are reviewed, and several simple measures relevant to the separate interests of employers and job applicants proposed-number screened to prevent a single adverse outcome; number excluded to prevent a case; expected incidence of the adverse outcome in those excluded; and preventable fraction. The derivation of these measures is illustrated, and the factors that influence them (the prevalence of the prognostic trait, the relative risk that it carries for an adverse outcome, and the overall incidence of disease) are related algebraically and graphically, to aid judgement on the utility of screening under different circumstances. In sensitive areas such as genetic testing the onus should be on the employer to justify plans for pre-placement screening. Several quantitative measures can be used to inform the ethical and economic debate about screening and to evaluate alternative strategies for prevention.

Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.

PubMed

Fox, P; Hudson, M; Brown, C; Lord, S; Gebski, V; De Souza, P; Lee, C K

2013-07-09

The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC). Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers. Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil-lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification. Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

[Pathogenetic and Prognostic Role of Growth Factors in the Development of Chronic Heart Failure].

PubMed

Teplyakov, A T; Berezikova, E N; Shilov, S N; Efremova, A V; Pustovetova, M G; Popova, A A; Grakova, E V; Torim, Y Y; Safronov, I D; Andriyanova, A V

2017-10-01

To study the role of growth factors ((vascular endothelial growth factor (VEGF), platelet derived growth factor AB (PDGF-AB) and basic fibroblast growth factor (FGF-basic)) in the development and progression of chronic heart failure (CHF) in patients with ishcemic heart disease (IHD). We included in this study 94 patients with CHF. The control group comprised 32 persons. Blood serum levels of growth factors were determined at baseline and after 12 months of observation by enzyme-linked immunosorbent assay. VEGF, PDGF-AB and FGF-basic play an important role in the pathogenesis and progression of heart failure in patients with IHD, determining the increased risk of adverse cardiovascular events in this pathology. Serum activity of growth factors characterizes the severity and course of CHF: with disease progression levels of VEGF and FGF-basic decrease and PDGF-AB concentration increases. Initial low level of VEGF expression regardless of the sex of the patient's sex, significantly low level of FGF-basic and significantly high PDGF-AB in men characterizes unfavorable course of CHF. A correlation has been established between blood serum levels of VEGF, PDGF-AB and FGF-basic and severity and course of CHF.

Low CLL-1 Expression Is a Novel Adverse Predictor in 123 Patients with De Novo CD34+ Acute Myeloid Leukemia.

PubMed

Wang, Yan-Yu; Chen, Wen-Lian; Weng, Xiang-Qin; Sheng, Yan; Wu, Jing; Hao, Jie; Liu, Zhan-Yun; Zhu, Yong-Mei; Chen, Bing; Xiong, Shu-Min; Chen, Yu; Chen, Qiu-Sheng; Sun, Hui-Ping; Li, Jun-Min; Wang, Jin

2017-10-15

Recent reports state that C-type lectin-like molecule-1 (CLL-1) in acute myeloid leukemia (AML) is expressed primarily on myeloid cells, but there is still no investigation about its prognostic significance on leukemic blast compartment. Hence, this study aimed to evaluate the prognostic value of CLL-1 in 123 patients with de novo CD34 + Non-M3 AML. Multiparameter flow cytometry was used to assess the expression of CLL-1 on immature compartment in AML and control groups. We found that CLL-1 expression level on blast compartment was closely linked to clinical characteristics, treatment response, and survival outcome of patients. Decreased expression of CLL-1 was observed on immature compartment from AML patients as compared with controls (62.6% vs. 86.5%, P < 0.05). Logistic model exhibited that CLL-1 low independently predicted low complete remission rate with an odds ratio of 4.57 (2.53-6.61, P < 0.05). Additionally, CLL-1 expression level at diagnosis was inversely correlated to the residual blast cells (residual leukemia cell) after induction chemotherapy (r = -0.423, P < 0.05). Furthermore, multivariate Cox regression model demonstrated that CLL-1 low was still an independent adverse predictor (P < 0.05 for event-free survival, P < 0.05 for overall survival). Notably, CLL-1 low was able to discriminate poor survival patients from intermediate- and favorable-risk groups. Taken together, CLL-1 is a novel prognostic predictor that could be exploited to supplement the current AML prognostic risk stratification system, and potentially optimize the clinical management of AML.

Circulating FABP4 is a prognostic biomarker in patients with acute coronary syndrome but not in asymptomatic individuals.

PubMed

Reiser, Hans; Klingenberg, Roland; Hof, Danielle; Cooksley-Decasper, Seraina; Fuchs, Nina; Akhmedov, Alexander; Zoller, Stefan; Marques-Vidal, Pedro; Marti Soler, Helena; Heg, Dik; Landmesser, Ulf; Rodondi, Nicolas; Mach, Francois; Windecker, Stephan; Vollenweider, Peter; Matter, Christian M; Lüscher, Thomas F; von Eckardstein, Arnold; Gawinecka, Joanna

2015-08-01

Blood-borne biomarkers reflecting atherosclerotic plaque burden have great potential to improve clinical management of atherosclerotic coronary artery disease and acute coronary syndrome (ACS). Using data integration from gene expression profiling of coronary thrombi versus peripheral blood mononuclear cells and proteomic analysis of atherosclerotic plaque-derived secretomes versus healthy tissue secretomes, we identified fatty acid-binding protein 4 (FABP4) as a biomarker candidate for coronary artery disease. Its diagnostic and prognostic performance was validated in 3 different clinical settings: (1) in a cross-sectional cohort of patients with stable coronary artery disease, ACS, and healthy individuals (n=820), (2) in a nested case-control cohort of patients with ACS with 30-day follow-up (n=200), and (3) in a population-based nested case-control cohort of asymptomatic individuals with 5-year follow-up (n=414). Circulating FABP4 was marginally higher in patients with ST-segment-elevation myocardial infarction (24.9 ng/mL) compared with controls (23.4 ng/mL; P=0.01). However, elevated FABP4 was associated with adverse secondary cerebrovascular or cardiovascular events during 30-day follow-up after index ACS, independent of age, sex, renal function, and body mass index (odds ratio, 1.7; 95% confidence interval, 1.1-2.5; P=0.02). Circulating FABP4 predicted adverse events with similar prognostic performance as the GRACE in-hospital risk score or N-terminal pro-brain natriuretic peptide. Finally, no significant difference between baseline FABP4 was found in asymptomatic individuals with or without coronary events during 5-year follow-up. Circulating FABP4 may prove useful as a prognostic biomarker in risk stratification of patients with ACS. © 2015 American Heart Association, Inc.

The Glasgow Prognostic Score as a significant predictor of diffuse large B cell lymphoma treated with R-CHOP in China.

PubMed

Li, Xiaoyang; Zhang, Yunxiang; Zhao, Weili; Liu, Zhao; Shen, Yang; Li, Junmin; Shen, Zhixiang

2015-01-01

The Glasgow Prognostic Score (GPS) incorporates C-reactive protein and albumin as clinically useful markers of tumor behavior and shows significant prognostic value in several types of solid tumors. The accuracy of the GPS in predicting outcomes in diffuse large B cell lymphoma (DLBCL) remains unknown. We performed this study to evaluate the prognostic significance of the GPS in DLBCL in China. We retrospectively analyzed 160 patients with newly diagnosed DLBCL at the Shanghai Ruijin Hospital (China). The prognostic value of the GPS was evaluated and compared with that of the International Prognostic Index (IPI) and immunohistochemical subtyping. The GPS was defined as follows: GPS-0, C-reactive protein (CRP) ≤10 mg/L and albumin ≥35 g/L; GPS-1, CRP >10 mg/L or albumin <35 g/L; and GPS-2, CRP >10 mg/L and albumin <35 g/L. Patients with lower GPS tended to have better outcomes including progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS and high IPI score were independent adverse predictors of OS. Similar to several other tumors, GPS is a reliable predictor of survival outcomes in DLBCL patients treated with R-CHOP therapy. Inflammatory responses are implicated in the progression and survival of patients with DLBCL.

The Shifting Paradigm of Prognostic Factors of Colorectal Liver Metastases: From Tumor-Centered to Host Immune-Centered Factors

PubMed Central

Donadon, Matteo; Lleo, Ana; Di Tommaso, Luca; Soldani, Cristiana; Franceschini, Barbara; Roncalli, Massimo; Torzilli, Guido

2018-01-01

The determinants of prognosis in patients with colorectal liver metastases (CLM) have been traditionally searched among the tumoral factors, either of the primary colorectal tumor or of the CLM. While many different scoring systems have been developed based on those clinic-pathological factors with disparate results, there has been the introduction of genetic biological markers that added a theranostic perspective. More recently, other important elements, such as those factors related to the host immune system, have been proposed as determinants of prognosis of CLM patients. In the present work, we review the current prognostic factors of CLM patients as well as the burgeoning shifting paradigm of prognostication that relies on the host immune system. PMID:29892573

Factors Affecting Physicians' Intentions to Communicate Personalized Prognostic Information to Cancer Patients at the End of Life: An Experimental Vignette Study.

PubMed

Han, Paul K J; Dieckmann, Nathan F; Holt, Christina; Gutheil, Caitlin; Peters, Ellen

2016-08-01

To explore the effects of personalized prognostic information on physicians' intentions to communicate prognosis to cancer patients at the end of life, and to identify factors that moderate these effects. A factorial experiment was conducted in which 93 family medicine physicians were presented with a hypothetical vignette depicting an end-stage gastric cancer patient seeking prognostic information. Physicians' intentions to communicate prognosis were assessed before and after provision of personalized prognostic information, while emotional distress of the patient and ambiguity (imprecision) of the prognostic estimate were varied between subjects. General linear models were used to test the effects of personalized prognostic information, patient distress, and ambiguity on prognostic communication intentions, and potential moderating effects of 1) perceived patient distress, 2) perceived credibility of prognostic models, 3) physician numeracy (objective and subjective), and 4) physician aversion to risk and ambiguity. Provision of personalized prognostic information increased prognostic communication intentions (P < 0.001, η(2) = 0.38), although experimentally manipulated patient distress and prognostic ambiguity had no effects. Greater change in communication intentions was positively associated with higher perceived credibility of prognostic models (P = 0.007, η(2) = 0.10), higher objective numeracy (P = 0.01, η(2) = 0.09), female sex (P = 0.01, η(2) = 0.08), and lower perceived patient distress (P = 0.02, η(2) = 0.07). Intentions to communicate available personalized prognostic information were positively associated with higher perceived credibility of prognostic models (P = 0.02, η(2) = 0.09), higher subjective numeracy (P = 0.02, η(2) = 0.08), and lower ambiguity aversion (P = 0.06, η(2) = 0.04). Provision of personalized prognostic information increases physicians' prognostic communication intentions to a hypothetical end-stage cancer patient, and situational and physician characteristics moderate this effect. More research is needed to confirm these findings and elucidate the determinants of prognostic communication at the end of life. © The Author(s) 2016.

Contribution of artificial intelligence to the knowledge of prognostic factors in Hodgkin's lymphoma.

PubMed

Buciński, Adam; Marszałł, Michał Piotr; Krysiński, Jerzy; Lemieszek, Andrzej; Załuski, Jerzy

2010-07-01

Hodgkin's lymphoma is one of the most curable malignancies and most patients achieve a lasting complete remission. In this study, artificial neural network (ANN) analysis was shown to provide significant factors with regard to 5-year recurrence after lymphoma treatment. Data from 114 patients treated for Hodgkin's disease were available for evaluation and comparison. A total of 31 variables were subjected to ANN analysis. The ANN approach as an advanced multivariate data processing method was shown to provide objective prognostic data. Some of these prognostic factors are consistent or even identical to the factors evaluated earlier by other statistical methods.

Branched-chain amino acids to tyrosine ratio (BTR) predicts intrahepatic distant recurrence and survival for early hepatocellular carcinoma.

PubMed

Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

2013-01-01

The Child-Pugh classification system is the most widely used system for assessing hepatic functional reserve in HCC treatment. In the Child-Pugh classification system, serum albumin levels are used to accurately assess the status of protein metabolism and nutrition. To date, a lack of attention has been given to amino acid metabolism. In the present study, we investigated whether the branched-chain amino acids to tyrosine ratio (BTR) as an indicator of amino acid metabolism can serve as both a prognostic factor for early HCC and a predictive factor for recurrence. We conducted a cohort study of 50 patients with stage I/II HCC enrolled between May 2002 and December 2010. It was investigated whether BTR can serve as both a prognostic factor and a predictive factor for HCC recurrence. Overall survival rates were significantly higher in patients with high baseline BTR than in those with low BTR. Multivariate analysis showed that both BTR and serum albumin were prognostic factors, and that BTR was the best predictive factor for recurrence. BTR was a prognostic factor for early HCC and the most predictive factor for intrahepatic distant recurrence and contributing factors for survival.

Contribution of vascular endothelial growth factor to the Nottingham prognostic index in node-negative breast cancer

PubMed Central

Coradini, D; Boracchi, P; Daidone, M Grazia; Pellizzaro, C; Miodini, P; Ammatuna, M; Tomasic, G; Biganzoli, E

2001-01-01

The prognostic contribution of intratumour VEGF, the most important factor in tumour-induced angiogenesis, to NPI was evaluated by using flexible modelling in a series of 226 N-primary breast cancer patients in which steroid receptors and cell proliferation were also accounted for. VEGF provided an additional prognostic contribution to NPI mainly within ER-poor tumours. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11556826

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

PubMed

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

2016-11-01

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

[PROGNOSTIC MODELS IN MODERN MANAGEMENT OF VULVAR CANCER].

PubMed

Tsvetkov, Ch; Gorchev, G; Tomov, S; Nikolova, M; Genchev, G

2016-01-01

The aim of the research was to evaluate and analyse prognosis and prognostic factors in patients with squamous cell vulvar carcinoma after primary surgery with individual approach applied during the course of treatment. In the period between January 2000 and July 2010, 113 patients with squamous cell carcinoma of the vulva were diagnosed and operated on at Gynecologic Oncology Clinic of Medical University, Pleven. All the patients were monitored at the same clinic. Individual approach was applied to each patient and whenever it was possible, more conservative operative techniques were applied. The probable clinicopathological characteristics influencing the overall survival and recurrence free survival were analyzed. Univariate statistical analysis and Cox regression analysis were made in order to evaluate the characteristics, which were statistically significant for overall survival and survival without recurrence. A multivariate logistic regression analysis (Forward Wald procedure) was applied to evaluate the combined influence of the significant factors. While performing the multivariate analysis, the synergic effect of the independent prognostic factors of both kinds of survivals was also evaluated. Approaching individually each patient, we applied the following operative techniques: 1. Deep total radical vulvectomy with separate incisions for lymph dissection (LD) or without dissection--68 (60.18 %) patients. 2. En-bloc vulvectomy with bilateral LD without vulva reconstruction--10 (8.85%) 3. Modified radical vulvactomy (hemivulvectomy, patial vulvactomy)--25 (22.02%). 4. wide-local excision--3 (2.65%). 5. Simple (total /partial) vulvectomy--5 (4.43%) patients. 6. En-bloc resection with reconstruction--2 (1.77%) After a thorough analysis of the overall survival and recurrence free survival, we made the conclusion that the relapse occurrence and clinical stage of FIGO were independent prognostic factors for overall survival and the independent prognostic factors for recurrence free survival were: metastatic inguinal nodes (unilateral or bilateral), tumor size (above or below 3 cm) and lymphovascular space invasion. On the basis of these results we created two prognostic models: 1. A prognostic model of overall survival 2. A prognostic model for survival without recurrence. Following the surgical staging of the disease, were able to gather and analyse important clinicopathological indexes, which gave us the opportunity to form prognostic groups for overall survival and recurrence-free survival.

Young adult breast cancer patients have a poor prognosis independent of prognostic clinicopathological factors: a study from the Japanese Breast Cancer Registry.

PubMed

Kataoka, Akemi; Iwamoto, Takayuki; Tokunaga, Eriko; Tomotaki, Ai; Kumamaru, Hiraku; Miyata, Hiroaki; Niikura, Naoki; Kawai, Masaaki; Anan, Keisei; Hayashi, Naoki; Masuda, Shinobu; Tsugawa, Koichiro; Aogi, Kenjiro; Ishida, Takanori; Masuoka, Hideji; Iijima, Kotaro; Kinoshita, Takayuki; Nakamura, Seigo; Tokuda, Yutaka

2016-11-01

The aim of this study was to investigate whether young age at onset of breast cancer is an independent prognostic factor in patients from the Japanese Breast Cancer Registry, after adjustment of known clinicopathological prognostic factors. Of the 53,670 patients registered between 2004 and 2006 and surveyed after a 5-year follow-up prognosis, 25,898 breast cancer patients (48.3 %), who were obtained prognostic data, were examined. Clinicopathological factors were compared between young adult (YA; <35 years), middle-aged adult (MA; 35-50 years), and older adult (OA; >50 years) patients. Five-year disease-free survival (DFS) and overall survival (OS) rates were studied. YA patients were associated with an advanced TNM stage and aggressive characteristics (e.g. human epidermal growth factor receptor 2 (HER2)-positive or oestrogen receptor (ER)-negative breast cancers) compared to MA and OA patients (P < 0.001). The 5-year DFS and OS rates were 79.4 % and 90.8, 88.5 and 95.0 %, and 87.8 % and 91.6 % for YA, MA, and OA patients, respectively. From the multivariable regression analysis, young age at onset was confirmed as an independent prognostic factor for both DFS (hazard ratio 1.73, 95 % confidence interval 1.42-2.10; P < 0.001) and OS (hazard ratio 1.58, 95 % confidence interval 1.16-2.15; P = 0.004). Young age at onset is an independent negative prognostic factor in breast cancer. Further studies are required to develop new therapeutic strategies for YA breast cancer patients.

Clinical Significance of Soluble Intercellular Adhesion Molecule-1 and Interleukin-6 in Patients with Extrahepatic Cholangiocarcinoma.

PubMed

Shimura, Tatsuo; Shibata, Masahiko; Gonda, Kenji; Kofunato, Yasuhide; Okada, Ryo; Ishigame, Teruhide; Kimura, Takashi; Kenjo, Akira; Marubashi, Shigeru; Kono, Koji; Takenoshita, Seiichi

2017-09-19

Purpose/Aim: Although several prognostic factors for extrahepatic cholangiocarcinoma (EHC) have been reported, preoperative prognostic factors have yet to be established. We investigated the serum concentration of angiogenic, inflammatory, and nutritional parameters. Twenty-five patients with EHC were enrolled before starting treatment. Preoperative prognostic factors were identified using multivariate analyses. The serum soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in the patients with EHC (436.0 ± 43.2 ng/ml) than in the healthy volunteers (228.6 ± 22.0 ng/ml) (p <.001). In addition, the serum IL-6 levels were significantly higher in the patients (18.0 ± 5.6 pg/ml) than in the healthy volunteers (5.7 ± 0.8 pg/ml) (p <.05). The serum IL-6 and sICAM-1 showed a strong correlation (r = 0.559) in the patients with EHC (p <.01). The serum IL-6 (area under the curve = 0.764, p =.030, cut-off level = 11.6) and sICAM-1 (area under the curve = 0.818, p =.007, cutoff level = 322.6) were revealed to be useful as prognostic factors by the receiver operating characteristic curves. The high IL-6 group and the high sICAM-1 group showed poorer DSS than those of the respective low groups. In the multivariate analysis, IL-6 (hazard ratio: 1.050, 95% confidence interval: 1.002-1.100, p =.043) and sICAM-1 (hazard ratio: 1.009, 95% confidence interval: 1.002-1.015, p =.009) were independent prognostic factors for DSS. IL-6 and sICAM-1 were independent preoperative prognostic factors in EHC patients, causing continuous inflammation and malnutrition in collaboration with other pro-angiogenic factors.

The Prognostic Significance of Biomarkers in Predicting Outcome in Patients With Coronary Artery Disease and Left Ventricular Dysfunction: Results of the Biomarker Sub-Study of the Surgical Treatment for Ischemic Heart Failure (STICH) Trials

PubMed Central

Feldman, Arthur M.; Mann, Douglas L.; She, Lilin; Bristow, Michael R.; Maisel, Alan S.; McNamara, Dennis M.; Walsh, Ryan; Lee, Dorellyn L.; Wos, Stanislaw; Lang, Irene; Wells, Gretchen; Drazner, Mark H.; Schmedtje, John F.; Pauly, Daniel F.; Sueta, Carla A.; Di Maio, Michael; Kron, Irving L.; Velazquez, Eric J.; Lee, Kerry L.

2013-01-01

Background Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting (CABG) but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the Biomarker Sub-studies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or CABG whereas those in STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Methods and Results In sub-study patients assigned to STICH Hypothesis 1 (n=606), plasma levels of sTNFR-1 and BNP were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP χ2=40.6; p<0.0001: sTNFR-1 χ2=38,9; p<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ2=30.3) and sTNFR-1 (χ2=45.5) were highly predictive in univariate analysis (p<0.0001) as well as in multivariable analysis for the primary endpoint of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ2=6.0; p=0.049) and sTNFR-1 (χ2=8.8; p=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤ 0.1), Net Reclassification Improvement (NRI) for the primary endpoints was 0.29 for BNP and 0.21 for sTNFR-1in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in two large and independent studies, thus providing important cross-validation for the prognostic importance of these two biomarkers. PMID:23584092

Predictive and Prognostic Factors in Ovarian and Uterine Carcinosarcomas

PubMed Central

Cicin, İrfan; Özatlı, Tahsin; Türkmen, Esma; Özturk, Türkan; Özçelik, Melike; Çabuk, Devrim; Gökdurnalı, Ayşe; Balvan, Özlem; Yıldız, Yaşar; Şeker, Metin; Özdemir, Nuriye; Yapar, Burcu; Tanrıverdi, Özgür; Günaydin, Yusuf; Menekşe, Serkan; Öksüzoğlu, Berna; Aksoy, Asude; Erdogan, Bülent; Bekir Hacıoglu, M.; Arpaci, Erkan; Sevinç, Alper

2016-01-01

Background: Prognostic factors and the standard treatment approach for gynaecological carcinosarcomas have not yet been clearly defined. Although carcinosarcomas are more aggressive than pure epithelial tumours, they are treated similarly. Serous/clear cell and endometrioid components may be predictive factors for the efficacy of adjuvant chemotherapy (CT) or radiotherapy (RT) or RT in patients with uterine and ovarian carcinosarcomas. Heterologous carcinosarcomas may benefit more from adjuvant CT. Aims: We aimed to define the prognostic and predictive factors associated with treatment options in ovarian (OCS) and uterine carcinosarcoma (UCS). Study Design: Retrospective cross-sectional study Methods: We retrospectively reviewed the medical records of patients with ovarian and uterine carcinosarcoma from 2000 to 2013, and 127 women were included in this study (24 ovarian and 103 uterine). Patients admitted to seventeen oncology centres in Turkey between 2000 and December 2013 with a histologically proven diagnosis of uterine carcinosarcoma with FIGO 2009 stage I–III and patients with sufficient data obtained from well-kept medical records were included in this study. Stage IV tumours were excluded. The patient records were retrospectively reviewed. Data from 104 patients were evaluated for this study. Results: Age (≥70 years) was a poor prognostic factor for UCS (p=0.036). Pelvic±para aortic lymph node dissection did not affect overall survival (OS) (p=0.35). Macroscopic residual disease was related with OS (p<0.01). The median OS was significantly longer in stage I–II patients than stage III patients (p=0.03). Adjuvant treatment improved OS (p=0.013). Adjuvant radiotherapy tended to increase the median OS (p=0.075). However, this tendency was observed in UCS (p=0.08) rather than OCS (p=0.6).Adjuvant chemotherapy had no effect on OS (p=0.15).Adjuvant radiotherapy significantly prolonged the median OS in patients with endometrioid component (p=0.034). A serous/clear cell component was a negative prognostic factor (p=0.035). Patients with serous/clear cell histology for whom adjuvant chemotherapy was applied had significantly longer OS (p=0.019), and there was no beneficial effect of adjuvant radiotherapy (p=0.4). Adjuvant chemotherapy was effective in heterologous tumours (p=0.026). In multivariate analysis, the stage and chemotherapy were prognostic factors for all patients. Age was an independent prognostic factor for UCS. However, serous/clear cell histology and radiotherapy tended to be significant prognostic factors. Conclusion: The primary location, the histological type of sarcomatous and the epithelial component may be predictive factors for the efficacy of chemotherapy or radiotherapy in UCS and OCS. PMID:27761279

Molecular profiling of tumour budding implicates TGFβ-mediated epithelial-mesenchymal transition as a therapeutic target in oral squamous cell carcinoma.

PubMed

Jensen, D H; Dabelsteen, E; Specht, L; Fiehn, A M K; Therkildsen, M H; Jønson, L; Vikesaa, J; Nielsen, F C; von Buchwald, C

2015-08-01

Although tumour budding is an adverse prognostic factor for many cancer types, the molecular mechanisms governing this phenomenon are incompletely understood. Therefore, understanding the molecular basis of tumour budding may provide new therapeutic and diagnostic options. We employ digital image analysis to demonstrate that the number of tumour buds in cytokeratin-stained sections correlates with patients having lymph node metastases at diagnosis. The tumour bud count was also a predictor of overall survival, independent of TNM stage. Tumour buds and paired central tumour areas were subsequently collected from oral squamous cell carcinoma (OSCC) specimens, using laser capture microdissection, and examined with RNA sequencing and miRNA-qPCR arrays. Compared with cells from the central parts of the tumours, budding cells exhibited a particular gene expression signature, comprising factors involved in epithelial-mesenchymal transition (EMT) and activated TGFβ signalling. Transcription factors ZEB1 and PRRX1 were up-regulated concomitantly with the decreased expression of mesenchymal-epithelial (MET) transcription factors (eg OVOL1) in addition to Krüppel-like factors and Grainyhead-like factors. Moreover, miR-200 family members were down-regulated in budding tumour cells. We used immunohistochemistry to validate five markers of the EMT/MET process in 199 OSCC tumours, as well as in situ hybridization in 20 OSCC samples. Given the strong relationship between tumour budding and the development of lymph node metastases and an adverse prognosis, therapeutics based on inhibiting the activation of TGFβ signalling may prove useful in the treatment of OSCC. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol.

PubMed

Buldini, Barbara; Rizzati, Frida; Masetti, Riccardo; Fagioli, Franca; Menna, Giuseppe; Micalizzi, Concetta; Putti, Maria Caterina; Rizzari, Carmelo; Santoro, Nicola; Zecca, Marco; Disarò, Silvia; Rondelli, Roberto; Merli, Pietro; Pigazzi, Martina; Pession, Andrea; Locatelli, Franco; Basso, Giuseppe

2017-04-01

In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD), by multicolour flow-cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica-AML 2002/01 trial. At the end of the first induction course, MRD was <0·1% in 69, 0·1-1% in 16 and >1% in 51 patients. The 8-year disease-free survival (DFS) of 125 children in morphological complete remission and with MRD <0·1%, 0·1-1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS. Our results show that MRD detected by flow-cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post-remission treatment. © 2017 John Wiley & Sons Ltd.

[Relevance of Vascular Trauma in Trauma Care - Impact on Clinical Course and Mortality].

PubMed

Lech, L; Jerkku, T; Kanz, K-G; Wierer, M; Mutschler, W; Koeppel, T A; Lefering, R; Banafsche, R

2016-10-01

There is a lack of evidence as to the relevance of vascular trauma (VT) in patients with severe injuries. Therefore, we reviewed registry data in the present study in order to systematically objectify the effect of VT in these patients. This study aimed to provide an adequate picture of the relevance of vascular trauma and to identify adverse prognostic factors. In a retrospective analysis of records from the TraumaRegister DGU® (TR-DGU) in two subgroups with moderate and severe VT, we examined the records for differences in terms of morbidity, mortality, follow-up and prognostic parameters compared to patients without VT with the same ISS. From a total of 42,326 patients, 2,961 (7 %) had a VT, and in 2,437 cases a severe VT (AIS ≥ 3) was diagnosed (5.8 %). In addition to a higher incidence of shock and a 2 to 3-fold increase in fluid replacement and erythrocyte transfusion, patients with severe VT had a 60 % higher rate of multiple organ failure, and in-hospital mortality was twice as high (33.8 %). The massively increased early mortality (8.0 vs. 25.2 %) clearly illustrates how severely injured patients are placed at risk by the presence of a relevant VT with a comparable ISS. In our opinion, due to an unexpected poor prognosis in the TR-DGU data for vascular injuries, increased attention is required in the care of severely injured patients. Based on our comprehensive analysis of negative prognostic factors, a further adjustment to the standards of vascular medicine could be advisable. The influence of the level of care provided by the admitting hospital and the relevance of a further hospital transfer to prognosis and clinical outcome is currently being analysed. Georg Thieme Verlag KG Stuttgart · New York.

Prognostic value of dynamic electrocardiographic T wave changes in non-ST elevation acute coronary syndrome.

PubMed

Sarak, Bradley; Goodman, Shaun G; Yan, Raymond T; Tan, Mary K; Steg, Ph Gabriel; Tan, Nigel S; Fox, Keith A A; Udell, Jacob A; Brieger, David; Welsh, Robert C; Gale, Chris P; Yan, Andrew T

2016-09-01

To assess the relationship between the evolution of T wave inversion (TWI) on the 24-48 h postadmission ECG and the patient characteristics, management and clinical outcomes among those with non-ST elevation acute coronary syndrome (NSTE-ACS). We evaluated admission and 24-48 h follow-up ECGs of 7201 patients with NSTE-ACS from the prospective, multicentre Global Registry of Acute Coronary Events (GRACE) and Canadian ACS Registry I. We performed multivariable analyses to determine the association between new TWI (on follow-up ECG only), resolved TWI (on admission ECG only) and persistent TWI (on both admission and follow-up ECG) and inhospital and cumulative 6-month all-cause mortality. Patients with TWI were older, more likely to have cardiovascular risk factors, higher Killip class and GRACE risk scores. After adjustment for known prognostic factors, compared with patients presenting without TWI, new TWI was associated with significantly lower inhospital mortality (OR=0.60, 95% CI 0.38 to 0.95, p=0.029), whereas resolved (OR=1.06, 95% CI 0.65 to 1.75, p=0.81) and persistent (OR=0.73, 95% CI 0.48 to 1.11, p=0.14) TWI did not predict inhospital mortality. No TWI pattern independently predicted inhospital adverse cardiovascular events or cumulative 6-month mortality. In contrast, ST depression on the admission and follow-up ECG were independent predictors of inhospital and 6-month mortality. Across the spectrum of NSTE-ACS, TWI within 48 h of presentation was associated with high-risk clinical features, but its presence or dynamic change did not provide additional prognostic value beyond other established clinical predictors. 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/

Determinants and prognostic implications of Cardiac Troponin T measured by a sensitive assay in Type 2 Diabetes Mellitus

PubMed Central

2010-01-01

Background The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. Methods cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if availabe (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). Results One-hundred thirteen (90 %) had detectable cTnT at baseline and of those, 22 (18 % of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r = 0.92, p > 0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p = 0.058). Conclusions Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found. PMID:20843304

Determinants and prognostic implications of cardiac troponin T measured by a sensitive assay in type 2 diabetes mellitus.

PubMed

Hallén, Jonas; Johansen, Odd Erik; Birkeland, Kåre I; Gullestad, Lars; Aakhus, Svend; Endresen, Knut; Tjora, Solve; Jaffe, Allan S; Atar, Dan

2010-09-15

The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if available (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). One-hundred thirteen (90%) had detectable cTnT at baseline and of those, 22 (18% of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r=0.92, p>0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p=0.058). Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found.

Utility of Inflammatory Marker- and Nutritional Status-based Prognostic Factors for Predicting the Prognosis of Stage IV Gastric Cancer Patients Undergoing Non-curative Surgery.

PubMed

Mimatsu, Kenji; Fukino, Nobutada; Ogasawara, Yasuo; Saino, Yoko; Oida, Takatsugu

2017-08-01

The present study aimed to compare the utility of various inflammatory marker- and nutritional status-based prognostic factors, including many previous established prognostic factors, for predicting the prognosis of stage IV gastric cancer patients undergoing non-curative surgery. A total of 33 patients with stage IV gastric cancer who had undergone palliative gastrectomy and gastrojejunostomy were included in the study. Univariate and multivariate analyses were performed to evaluate the relationships between the mGPS, PNI, NLR, PLR, the CONUT, various clinicopathological factors and cancer-specific survival (CS). Among patients who received non-curative surgery, univariate analysis of CS identified the following significant risk factors: chemotherapy, mGPS and NLR, and multivariate analysis revealed that the mGPS was independently associated with CS. The mGPS was a more useful prognostic factor than the PNI, NLR, PLR and CONUT in patients undergoing non-curative surgery for stage IV gastric cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Serum tumor markers in breast cancer: are they of clinical value?

PubMed

Duffy, Michael J

2006-03-01

Although multiple serum-based tumor markers have been described for breast cancer, such as CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen (CEA), tissue polypeptide antigen, tissue polypeptide specific antigen, and HER-2 (the extracellular domain), the most widely used are CA 15-3 and CEA. The literature relevant to serum tumor markers in breast cancer was reviewed. Particular attention was given to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. Because of a lack of sensitivity for early disease and lack of specificity, none of the available markers is of value for the detection of early breast cancer. High preoperative concentrations of CA 15-3 are, however, associated with adverse patient outcome. Although serial determinations of tumor markers after primary treatment for breast cancer can preclinically detect recurrent/metastatic disease with lead times of approximately 2-9 months, the clinical value of this lead time remains to be determined. Serum markers, however, are the only validated approach for monitoring treatment in patients with advanced disease that cannot be evaluated by use of conventional criteria. CA 15-3 is one of the first circulating prognostic factors for breast cancer. Preoperative concentrations thus might be combined with existing prognostic factors for predicting outcome in patients with newly diagnosed breast cancer. At present, the most important clinical application of CA 15-3 is in monitoring therapy in patients with advanced breast cancer that is not assessable by existing clinical or radiologic procedures.

Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy.

PubMed

Österlund, P; Soveri, L-M; Isoniemi, H; Poussa, T; Alanko, T; Bono, P

2011-02-15

Hypertension (HTN) is a common toxicity of anti-VEGF (vascular endothelial growth factor) antibody treatment. It may be a marker of VEGF signalling pathway inhibition and therefore represent a cancer biomarker in metastatic colorectal cancer (mCRC) patients treated with chemotherapy and bevacizumab. A total of 101 consecutive patients with mCRC were treated with standard chemotherapy combined with bevacizumab at dose of 2.5 mg kg(-1) per week in a single centre. The median follow-up time of the patients alive was 64 months. Blood pressure was measured before each bevacizumab infusion, and HTN was graded according to common toxicity criteria for adverse events version 3.0. Overall, 57 patients (56%) developed ≥grade 1 HTN (median blood pressure 168/97 mm Hg), whereas 44 (44%) remained normotensive when treated with bevacizumab-containing chemotherapy regimen. Overall response rate was higher among patients with HTN (30 vs 20%; P=0.025). Hypertension was associated with improved progression-free survival (10.5 vs 5.3 months; P=0.008) and overall survival (25.8 vs 11.7 months; P<0.001), and development of HTN within 3 months had an independent, prognostic influence in a multivariate landmark survival analysis together with other known mCRC prognostic factors (P=0.007). There was no association between HTN and development of thromboembolic complications. Hypertension may predict outcome of bevacizumab-containing chemotherapy in mCRC. These data require confirmation in prospective studies including pharmacodynamic and pharmacokinetic analyses.

Pulmonary complications in patients with haematological malignancies treated at a respiratory ICU.

PubMed

Ewig, S; Torres, A; Riquelme, R; El-Ebiary, M; Rovira, M; Carreras, E; Raño, A; Xaubet, A

1998-07-01

Patients with haematological malignancies developing severe pulmonary complications have a poor outcome, especially after bone-marrow transplantation (BMT). We studied the aetiology, the yield of different diagnostic tools, as well as the outcome and prognostic factors in the corresponding population admitted to our respiratory intensive care unit (RICU). Overall, 89 patients with haematological malignancies and pulmonary complications treated within a 10 yr period were included. The underlying malignancies were predominantly acute leukaemia and chronic myeloid leukaemia (66/89, 74%). Fifty-two of 89 (58%) patients were bone marrow recipients. An aetiological diagnosis could be obtained in 61/89 (69%) of cases. The aetiology was infectious in 37/89 (42%) and noninfectious in 24/89 (27%). Blood cultures and cytological examinations of bronchoalveolar lavage fluid were the diagnostic tools with the highest yield (13/43 (30%) and 13/45 (29%) positive results, respectively). Necropsy results were coincident with results obtained during the lifetime in 43% of cases with infectious and 60% with noninfectious aetiologies. Overall mortality was 70/89 (79%), and 47/52 (90%) in transplant recipients. The requirement of mechanical ventilation, BMT, and an interval <90 days of BMT prior to ICU admission were independent adverse prognostic factors. The outcome in this patient population was uniformly poor. It was worst in bone marrow recipients developing pulmonary complications <90 days after transplantation and requiring mechanical ventilation. Decisions about intensive care unit admission and mech-anical ventilation should seriously consider the dismal prognosis of these patients.

Lung Radiofrequency Ablation for the Treatment of Unresectable Recurrent Non-Small-Cell Lung Cancer After Surgical Intervention

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

Kodama, Hiroshi, E-mail: h-kodama@clin.medic.mie-u.ac.jp; Yamakado, Koichiro; Takaki, Haruyuki

Purpose: A retrospective evaluation was done of clinical utility of lung radiofrequency (RF) ablation in recurrent non-small-cell lung cancer (NSCLC) after surgical intervention. Methods: During May 2003 to October 2010, 44 consecutive patients (26 male and 18 female) received curative lung RF ablation for 51 recurrent NSCLC (mean diameter 1.7 {+-} 0.9 cm, range 0.6 to 4.0) after surgical intervention. Safety, tumor progression rate, overall survival, and recurrence-free survival were evaluated. Prognostic factors were evaluated in multivariate analysis. Results: A total of 55 lung RF sessions were performed. Pneumothorax requiring pluerosclerosis (n = 2) and surgical suture (n = 1)more » were the only grade 3 or 4 adverse events (5.5%, 3 of 55). During mean follow-up of 28.6 {+-} 20.3 months (range 1 to 98), local tumor progression was found in 5 patients (11.4%, 5 of 44). The 1-, 3-, and 5-year overall survival rates were 97.7, 72.9, and 55.7%, respectively. The 1- and 3-year recurrence-free survival rates were 76.7 and 41.1%, respectively. Tumor size and sex were independent significant prognostic factors in multivariate analysis. The 5-year survival rates were 73.3% in 18 women and 60.5% in 38 patients who had small tumors measuring {<=}3 cm. Conclusion: Our results suggest that lung RF ablation is a safe and useful therapeutic option for obtaining long-term survival in treated patients.« less

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

PubMed

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

2016-02-01

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

Relation of N-terminal pro-brain natriuretic peptide levels and their prognostic power in chronic stable heart failure to obesity status.

PubMed

Frankenstein, Lutz; Remppis, Andrew; Nelles, Manfred; Schaelling, Bernd; Schellberg, Dieter; Katus, Hugo; Zugck, Christian

2008-11-01

To investigate the relationship between body mass index (BMI) and N-terminal pro-brain natriuretic peptide (NTproBNP) level and resultant prognostic capacity in chronic heart failure (CHF) controlled for known confounders. We formed 206 triplets of patients (n = 618) with stable systolic CHF matched with respect to age, sex, renal function (MDRD, modification of diet in renal disease formula), and NYHA class, each with a BMI >30 kg/m(2) (group 3), 20-24.9 kg/m(2) (group 1), and 25-29.9 kg/m(2) (group 2). BMI conveys a 4% drop in NTproBNP per unit increase. This influence remained significant after correction for age, sex, MDRD, NYHA, heart rate, rhythm, and ejection fraction. NTproBNP remained an independent predictor of adverse outcome after correction for age, sex, BMI, NYHA, MDRD, and ejection fraction. Despite numerical differences, prognostic power was comparable between BMI groups (log-transformed NTproBNP; group 1: hazard ratio (HR) 1.435, 95% CI 1.046-1.967, chi(2) 5.02, P = 0.03; group 2: HR 1.604, 95% CI 1.203-2.138, chi(2) 10.36, P = 0.001; group 3: HR 1.735, 95% CI 1.302-2.313, chi(2) 14.12, P = 0.0002) (P = NS, all). An NTproBNP correction factor was calculated. Even matched for NYHA, age, sex, and renal function, BMI exerts a significant and independent inverse influence on NTproBNP in patients with stable CHF. NTproBNP retained equal statistical power in all three BMI groups.

Droplet digital PCR analysis of NOTCH1 gene mutations in chronic lymphocytic leukemia.

PubMed

Minervini, Angela; Francesco Minervini, Crescenzio; Anelli, Luisa; Zagaria, Antonella; Casieri, Paola; Coccaro, Nicoletta; Cumbo, Cosimo; Tota, Giuseppina; Impera, Luciana; Orsini, Paola; Brunetti, Claudia; Giordano, Annamaria; Specchia, Giorgina; Albano, Francesco

2016-12-27

In chronic lymphocytic leukemia (CLL), NOTCH1 gene mutations (NOTCH1mut) have been associated with adverse prognostic features but the independence of these as a prognostic factor is still controversial. In our study we validated a c.7541-7542delCT NOTCH1 mutation assay based on droplet digital PCR (ddPCR); we also analyzed the NOTCH1mut allelic burden, expressed as fractional abundance (FA), in 88 CLL patients at diagnosis to assess its prognostic role and made a longitudinal ddPCR analysis in 10 cases harboring NOTCH1mut to verify the FA variation over time. Our data revealed that with the ddPCR approach the incidence of NOTCH1mut in CLL was much higher (53.4%) than expected. However, longitudinal ddPCR analysis of CLL cases showed a statistically significant reduction of the NOTCH1mut FA detected at diagnosis after treatment (median FA 11.67 % vs 0.09 %, respectively, p = 0.01); the same difference, in terms of NOTCH1mut FA, was observed in the relapsed cases compared to the NOTCH1mut allelic fraction observed in patients in complete or partial remission (median FA 4.75% vs 0.43%, respectively, p = 0.007). Our study demonstrated a much higher incidence of NOTCH1mut in CLL than has previously been reported, and showed that the NOTCH1mut allelic burden evaluation by ddPCR might identify patients in need of a closer clinical follow-up during the "watch and wait" interval and after standard chemotherapy.

MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

PubMed Central

Xu-Monette, Zijun Y.; Møller, Michael B.; Tzankov, Alexander; Montes-Moreno, Santiago; Hu, Wenwei; Manyam, Ganiraju C.; Kristensen, Louise; Fan, Lei; Visco, Carlo; Dybkær, Karen; Chiu, April; Tam, Wayne; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W. L.; van Krieken, J. Han; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J. M.; Wu, Lin; Zhao, Xiaoying; Bueso-Ramos, Carlos E.; Wang, Sa A.; Go, Ronald S.; Li, Yong; Winter, Jane N.; Medeiros, L. Jeffrey

2013-01-01

MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically–defined large cohort of de novo DLBCL patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, we assessed MDM2 and p53 expression by immunohistochemistry (n = 478), MDM2 gene amplification by fluorescence in situ hybridization (n = 364), and a single nucleotide polymorphism in the MDM2 promoter, SNP309, by SNP genotyping assay (n = 108). Our results show that MDM2 overexpression, unlike p53 overexpression, is not a significant prognostic factor in overall DLBCL. Both MDM2 and p53 overexpression do not predict for an adverse clinical outcome in patients with wild-type p53 but predicts for significantly poorer survival in patients with mutated p53. Variable p53 activities may ultimately determine the survival differences, as suggested by the gene expression profiling analysis. MDM2 amplification was observed in 3 of 364 (0.8%) patients with high MDM2 expression. The presence of SNP309 did not correlate with MDM2 expression and survival. This study indicates that evaluation of MDM2 and p53 expression correlating with TP53 genetic status is essential to assess their prognostic significance and is important for designing therapeutic strategies that target the MDM2-p53 interaction. PMID:23982177

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial.

PubMed

Marx, Wolfgang; McCarthy, Alexandra L; Ried, Karin; Vitetta, Luis; McKavanagh, Daniel; Thomson, Damien; Sali, Avni; Isenring, Liz

2014-04-09

Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. In a double-blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms experienced by oncology patients; this trial will address the significant limitations within the current literature and in doing so, will investigate the effect of ginger supplementation as an adjuvant treatment in modulating nausea and vomiting symptoms. ANZCTR.org.au Identifier: ACTRN12613000120774.

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial

PubMed Central

2014-01-01

Background Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. Methods/Design In a double–blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. Discussion Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms experienced by oncology patients; this trial will address the significant limitations within the current literature and in doing so, will investigate the effect of ginger supplementation as an adjuvant treatment in modulating nausea and vomiting symptoms. Trial registration ANZCTR.org.au Identifier: ACTRN12613000120774. PMID:24712653

[Myometrial invasion as a prognostic factor in endometrial adenocarcinoma].

PubMed

Mihalcea, D; Aursulesei, D

2009-01-01

Myometrial invasion is one of the most important prognostic factors in endometrial cancer. We have studied a cohort of 62 patients with endometrial cancer who underwent surgery in 4-th Gynecology Clinic of "Cuza Vodă" Hospital, Iaşi between 1997-2008. Myometrial invasion was determined intraoperatory by gross visual inspection and frozen section exam and by histopathological exam after surgery. We have investigated the relationship between myometrial invasion and other prognostic factors: histological type, grading and lymph node metastasis. In 36 cases the invasion was absent or minimal, and only in a cases the myometrum was completely invaded.

Mode of detection: an independent prognostic factor for women with breast cancer.

PubMed

Hofvind, Solveig; Holen, Åsne; Román, Marta; Sebuødegård, Sofie; Puig-Vives, Montse; Akslen, Lars

2016-06-01

To investigate breast cancer survival and risk of breast cancer death by detection mode (screen-detected, interval, and detected outside the screening programme), adjusting for prognostic and predictive tumour characteristics. Information about detection mode, prognostic (age, tumour size, histologic grade, lymph node status) and predictive factors (molecular subtypes based on immunohistochemical analyses of hormone receptor status (estrogen and progesterone) and Her2 status) were available for 8344 women in Norway aged 50-69 at diagnosis of breast cancer, 2005-2011. A total of 255 breast cancer deaths were registered by the end of 2011. Kaplan-Meier method was used to estimate six years breast cancer specific survival and Cox proportional hazard model to estimate hazard ratio (HR) for breast cancer death by detection mode, adjusting for prognostic and predictive factors. Women with screen-detected cancer had favourable prognostic and predictive tumour characteristics compared with interval cancers and those detected outside the screening programme. The favourable characteristics were present for screen-detected cancers, also within the subtypes. Adjusted HR of dying from breast cancer was two times higher for women with symptomatic breast cancer (interval or outside the screening), using screen-detected tumours as the reference. Detection mode is an independent prognostic factor for women diagnosed with breast cancer. Information on detection mode might be relevant for patient management to avoid overtreatment. © The Author(s) 2015.

Time from prior chemotherapy enhances prognostic risk grouping in the second-line setting of advanced urothelial carcinoma: a retrospective analysis of pooled, prospective phase 2 trials.

PubMed

Sonpavde, Guru; Pond, Gregory R; Fougeray, Ronan; Choueiri, Toni K; Qu, Angela Q; Vaughn, David J; Niegisch, Guenter; Albers, Peter; James, Nicholas D; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S; Galsky, Matthew D; Petrylak, Daniel P; Vaishampayan, Ulka N; Khan, Awais; Vogelzang, Nicholas J; Beer, Tomasz M; Stadler, Walter M; O'Donnell, Peter H; Sternberg, Cora N; Rosenberg, Jonathan E; Bellmunt, Joaquim

2013-04-01

Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM). The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors. Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n=570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n=352). Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures. ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic=0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb <10 g/dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Time from Prior Chemotherapy Enhances Prognostic Risk Grouping in the Second-line Setting of Advanced Urothelial Carcinoma: A Retrospective Analysis of Pooled, Prospective Phase 2 Trials

PubMed Central

Sonpavde, Guru; Pond, Gregory R.; Fougeray, Ronan; Choueiri, Toni K.; Qu, Angela Q.; Vaughn, David J.; Niegisch, Guenter; Albers, Peter; James, Nicholas D.; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S.; Galsky, Matthew D.; Petrylak, Daniel P.; Vaishampayan, Ulka N.; Khan, Awais; Vogelzang, Nicholas J.; Beer, Tomasz M.; Stadler, Walter M.; O’Donnell, Peter H.; Sternberg, Cora N.; Rosenberg, Jonathan E.; Bellmunt, Joaquim

2014-01-01

Background Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM). Objectives The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors. Design, setting, and participants: Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n = 570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n = 352). Outcome measurements and statistical analysis Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures. Results and limitations ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic = 0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Conclusions Shorter TFPC enhances prognostic classification independent of ECOG-PS>0, Hb<10 g/ dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials. PMID:23206856

Prognostic significance of pleural lavage cytology after thoracotomy and before closure of the chest in lung cancer.

PubMed

Taniguchi, Yuji; Nakamura, Hiroshige; Miwa, Ken; Adachi, Yoshin; Fujioka, Shinji; Haruki, Tomohiro; Horie, Yasushi

2009-07-01

Some reports have described pleural lavage cytology (PLC) to be a prognostic factor for non-small cell lung cancer (NSCLC) patients. However, there have only been a few reports describing the findings both immediately after thoracotomy (PLC after thoracotomy) and before the closure of the chest (PLC before closure). From April 2002 to April 2008, both PLC after thoracotomy and PLC before closure were performed in 296 consecutive patients who underwent resections for NSCLC. PLC after thoracotomy was positive in 14 patients. The survival rate in the PLC after thoracotomy positive cases was significantly poorer than in PLC after thoracotomy negative cases (P=0.047). In contrast, there were 26 PLC before closure positive cases. The survival rate in the PLC before closure positive cases was significantly poorer than in the PLC before closure negative cases (P<0.0001). Multivariate analyses revealed that PLC after thoracotomy is not an independent prognostic factor in our study. However, PLC before closure was an independent prognostic factor based on multivariate analyses. We conclude that PLC before closure was found to be a better prognostic factor than PLC after thoracotomy for NSCLC patients.

Systematic review of renal carcinoma prognostic factors.

PubMed

Lorente, D; Trilla, E; Meseguer, A; Planas, J; Placer, J; Celma, A; Salvador, C; Regis, L; Morote, J

2017-05-01

The natural history of renal cell carcinoma is heterogeneous. Some scenarios can be found in terms of clinical presentation, clinical evolution or type of recurrence (local/metastatic). The aim of this publication is to analyze the most important prognostic factors published in the literature. A literature review ob published papers was performed using the Pubmed, from first Motzer's classification published in 1999 to 2015, according to PRISMA declaration. Search was done using the following keywords: kidney neoplasm, kidney cancer, renal cell carcinoma, prognostic factors, mortality, survival and disease progression. Papers were classified according to level of evidence, the number of patients included and the type of study performed. The evolution in the knowledge of molecular pathways related to renal oncogenesis and the new targeted therapies has left to remain obsolete the old prognostic models. It's necessary to perform a continuous review to actualize nomograms and to adapt them to the new scenarios. Is necessary to perform a proper external validation of existing prognostic factors using prospective and multicentric studies to add them into the daily urologist clinical practice. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

Prognostic Significance of Interleukin-34 (IL-34) in Patients With Chronic Heart Failure With or Without Renal Insufficiency.

PubMed

Tao, Rong; Fan, Qin; Zhang, Hang; Xie, Hongyang; Lu, Lin; Gu, Gang; Wang, Fang; Xi, Rui; Hu, Jian; Chen, Qiujing; Niu, Wenquan; Shen, Weifeng; Zhang, Ruiyan; Yan, Xiaoxiang

2017-04-01

Renal dysfunction, commonly associated with cardiac dysfunction, has predictive value for adverse long-term outcomes in heart failure (HF). We previously identified a novel renal biomarker, interleukin-34 (IL-34), elevated in HF patients and associated with kidney dysfunction and coronary artery disease during HF. However, the prognostic value of IL-34 in HF remains unclear, so that the present study aimed to determine it. This prospective, observational study included 510 consecutive HF patients with their serum IL-34 as well as other variables measured at baseline, and they were followed up for 2 years. The primary end point was a composite of cardiovascular death or a first HF hospitalization, with cardiovascular death, HF hospitalization, and all-cause mortality as secondary outcomes. There was a significant and gradual increase in risk as IL-34 increased, determined by log-rank tests with Kaplan-Meier curves. Serum IL-34 was also a significant prognostic predictor of the primary end point (1.301 [1.115-1.518]; P =0.001), cardiovascular death (1.347 [1.096-1.655]; P =0.005), HF hospitalization (1.234 [1.018-1.494]; P =0.032), and all-cause mortality (1.343 [1.115-1.618]; P =0.002) in HF as per SD increase in the log IL-34 level after adjusting for age, sex, traditional risk factors, and N-terminal pro-brain natriuretic peptide. Especially, IL-34 had a more-significant prognostic value in HF patients with kidney impairment than those without. IL-34 is a significant predictor of cardiovascular death, HF hospitalization, and all-cause mortality in chronic HF, especially when concomitant with renal dysfunction. Serum IL-34 measurement may provide new insights linking kidney impairment to poor HF outcomes beyond other renal markers. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma.

PubMed

Lee, Yi-Ying; Chao, Tung-Bo; Sheu, Ming-Jen; Tian, Yu-Feng; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Lin, Ching-Yih; Li, Chien-Feng

2016-01-01

Background : Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC. Methods : We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates. Results : GAD1 overexpression was significantly associated with an increase in the primary tumor status ( p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV ( p = 0.002) and was a univariate predictor of adverse outcomes of DSS ( p = 0.002), DMeFS ( p < 0.0001), and LRFS ( p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS ( p = 0.004, hazard ratio = 2.234), DMeFS ( p < 0.001, hazard ratio = 4.218), and LRFS ( p = 0.013, hazard ratio = 2.441) rates. Conclusions : Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities.

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

PubMed Central

Atilla, Erden; Toprak, Selami K.; Demirer, Taner

2017-01-01

Iron overload is an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation (HSCT). In the HSCT setting, pretransplant and early posttransplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload was shown to be related to infections, hepatic sinusoidal obstruction syndrome, mucositis, liver dysfunction, and acute graft-versus-host disease. Hyperferritinemia causes decreased survival rates in both pre- and posttransplant settings. Serum ferritin levels, magnetic resonance imaging, and liver biopsy are diagnostic tools for iron overload. Organ dysfunction due to iron overload may cause high mortality rates and therefore sufficient iron chelation therapy is recommended in this setting. In this review the management of iron overload in adult HSCT is discussed. PMID:27956374

Prognostic Factors for Persistent Leg-Pain in Patients Hospitalized With Acute Sciatica.

PubMed

Fjeld, Olaf; Grotle, Margreth; Siewers, Vibeke; Pedersen, Linda M; Nilsen, Kristian Bernhard; Zwart, John-Anker

2017-03-01

Prospective cohort study. To identify potential prognostic factors for persistent leg-pain at 12 months among patients hospitalized with acute severe sciatica. The long-term outcome for patients admitted to hospital with sciatica is generally unfavorable. Results concerning prognostic factors for persistent sciatica are limited and conflicting. A total of 210 patients acutely admitted to hospital for either surgical or nonsurgical treatment of sciatica were consecutively recruited and received a thorough clinical and radiographic examination in addition to responding to a comprehensive questionnaire. Follow-up assessments were done at 6 weeks, 6 months, and 12 months. Potential prognostic factors were measured at baseline and at 6 weeks. The impact of these factors on leg-pain was analyzed by multiple linear regression modeling. A total of 151 patients completed the entire study, 93 receiving nonrandomized surgical treatment. The final multivariate models showed that the following factors were significantly associated with leg-pain at 12 months: high psychosocial risk according to the Örebro Musculosceletal Pain Questionnaire (unstandardized beta coefficient 1.55, 95% confidence interval [CI] 0.72-2.38, P < 0.001), not receiving surgical treatment (1.11, 95% CI 0.29-1.93, P = 0.01), not actively employed upon admission (1.47, 95% CI 0.63-2.31, P < 0.01), and self-reported leg-pain recorded 6 weeks posthospital admission (0.49, 95% CI 0.34-0.63, P < 0.001). Interaction analysis showed that the Örebro Musculosceletal Pain Questionnaire had significant prognostic value only on the nonsurgically treated patients (3.26, 95% CI 1.89-4.63, P < 0.001). The results suggest that a psychosocial screening tool and the implementation of a 6-week postadmission follow-up has prognostic value in the hospital management of severe sciatica. 2.

Prognostic factors in prostate cancer.

PubMed

Braeckman, Johan; Michielsen, Dirk

2007-01-01

In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before assessing screening.

A contemporary review of management and prognostic factors of upper tract urothelial carcinoma.

PubMed

Leow, Jeffrey J; Orsola, Anna; Chang, Steven L; Bellmunt, Joaquim

2015-04-01

Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. Although the main treatment is radical nephroureterectomy (NU), oncologic outcomes are not comparable to lower tract urothelial cancers. Identifying prognostic factors can help guide management and potentially improve outcomes. This article systematically reviews current literature on prognostic factors and management options for UTUC. A comprehensive literature search was performed to identify all studies examining prognostic factors and management options for UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to November 2014. An updated systematic review was performed. Preoperative prognostic factors for UTUC patients include age, race, performance status, obesity, smoking status, elevated fibrinogen levels, hydronephrosis, tumor size, multi-focality, location, clinical grade and previous/synchronous bladder cancer. Postoperative variables include tumor stage/grade, multifocality, nodal involvement, lympho-vascular invasion, initial ureteral location, necrosis, sessile architecture, variant histologies and presence of tissue ALDH1 and SOX2. Curative treatment of choice is NU, with lymphadenectomy conferring survival benefits. Minimally invasive surgery has equivalent oncologic and better peri-operative outcomes compared to open surgery. Conservative therapy includes adjuvant BCG and intravesical mitomycin C. Two randomized trials investigating postoperative instillation of mitomycin C suggest bladder recurrence benefits. Adjuvant chemo-radiotherapy may be useful for patients with advanced T3/4 and/or N+ disease. Gold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery. Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vemurafenib in BRAF-mutant metastatic melanoma patients in real-world clinical practice: prognostic factors associated with clinical outcomes.

PubMed

Schouwenburg, Maartje G; Jochems, Anouk; Leeneman, Brenda; Franken, Margreet G; van den Eertwegh, Alfons J M; Haanen, John B A G; van Zeijl, Michiel C T; Aarts, Maureen J; van Akkooi, Alexander C J; van den Berkmortel, Franchette W P J; Blokx, Willeke A M; de Groot, Jan Willem B; Hospers, Geke A P; Kapiteijn, Ellen; Koornstra, Rutger H; Kruit, Wim H; Louwman, Marieke W J; Piersma, Djura; van Rijn, Rozemarijn S; Suijkerbuijk, Karijn P M; Ten Tije, Albert J; Vreugdenhil, Gerard; Wouters, Michel W J M; van der Hoeven, Jacobus J M

2018-08-01

The aim of this population-based study was to identify the factors associated with clinical outcomes in vemurafenib-treated patients and to evaluate outcomes across subgroups of patients with different risk profiles. Data were retrieved from the Dutch Melanoma Treatment Registry. Time to next treatment (TTNT) and overall survival (OS) of all metastatic melanoma patients who received vemurafenib between 2012 and 2015 were assessed using Kaplan-Meier estimates. A risk score was developed on the basis of all prognostic factors associated with TTNT and OS derived from multivariable Cox regression analyses. Patients were stratified according to the presence of prognostic risk factors by counting the number of factors, ranging from 0 to 6. A total of 626 patients received vemurafenib with a median follow-up of 35.8 months. The median TTNT and OS were 4.7 months [95% confidence intervals (CI): 4.4-5.1] and 7.3 months (95% CI: 6.6-8.0). The strongest prognostic factors were serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group performance score, number of organ sites involved and brain metastases. Patients with a favourable risk profile (no risk factors) had a median TTNT and OS of 7.1 (95% CI: 5.8-8.5) and 15.4 months (95% CI: 10.0-20.9). The median OS more than halved for patients with greater than or equal to 2 risk factors compared with patients with no risk factors. The clinical outcomes of vemurafenib in metastatic melanoma patients with a favourable risk profile are comparable with the results of the trials. Combining prognostic factors into a risk score could be valuable to stratify patients into favourable and poor-prognosis groups.

The Prognostic Value of Signet-Ring Cell Histology in Resected Gastric Adenocarcinoma.

PubMed

Postlewait, Lauren M; Squires, Malcolm H; Kooby, David A; Poultsides, George A; Weber, Sharon M; Bloomston, Mark; Fields, Ryan C; Pawlik, Timothy M; Votanopoulos, Konstantinos I; Schmidt, Carl R; Ejaz, Aslam; Acher, Alexandra W; Worhunsky, David J; Saunders, Neil; Swords, Douglas; Jin, Linda X; Cho, Clifford S; Winslow, Emily R; Cardona, Kenneth; Staley, Charles A; Maithel, Shishir K

2015-12-01

Conflicting data exist on the prognostic implication of signet-ring cell (SRC) histology in gastric adenocarcinoma (GAC). All patients who underwent curative-intent resection of GAC from the seven institutions of the U.S. Gastric Cancer Collaborative between 2000 and 2012 were included. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Stage-specific analyses were performed. A total of 768 patients met the inclusion criteria. SRC was present in 40.6 % of patients and was associated with female sex (52.9 vs. 38.6 %; p < 0.001), younger age (61 vs. 67 years; p < 0.001), poor differentiation (94.8 vs. 50.3 %; p < 0.001), perineural invasion (PNI) (41.4 vs. 23 %; p < 0.001), microscopically positive resection margins (R1, 24.7 vs. 8.6 %; p < 0.001), distal location (82.2 vs. 70.1 %; p < 0.001), receipt of adjuvant therapy (63 vs. 51.2 %; p = 0.002), and more advanced stage (stage 3: 55.2 vs. 36.5 %; p < 0.001). SRC was associated with earlier recurrence (56.7 months vs. median not reached; p = 0.009) and decreased OS (33.7 vs. 46.6 months; p = 0.011). When accounting for other adverse pathologic features, PNI (hazard ratio [HR] 1.57; p = 0.016) and higher stage (HR 2.64; p < 0.001) were associated with decreased RFS, but SRC was not. Although PNI (HR 1.52; p = 0.007), higher stage (HR 2.11; p < 0.001), greater size (HR 1.05; p = 0.016), and adjuvant therapy (HR 0.50; p < 0.001) were associated with OS, SRC was not. Similarly, when accounting for adverse pathologic factors on multivariate analysis, stage-specific analyses showed no association between SRC and RFS or OS. SRC histology is associated with adverse pathologic features including poor differentiation, higher stage, and microscopically positive resection margins but is not independently associated with reduced RFS or OS. Identification of signet-ring histology during preoperative evaluation should not, in isolation, dictate treatment strategy.

Predictors and Prognostic Value of Worsening Renal Function During Admission in HFpEF Versus HFrEF: Data From the KorAHF (Korean Acute Heart Failure) Registry.

PubMed

Kang, Jeehoon; Park, Jin Joo; Cho, Young-Jin; Oh, Il-Young; Park, Hyun-Ah; Lee, Sang Eun; Kim, Min-Seok; Cho, Hyun-Jai; Lee, Hae-Young; Choi, Jin Oh; Hwang, Kyung-Kuk; Kim, Kye Hun; Yoo, Byung-Su; Kang, Seok-Min; Baek, Sang Hong; Jeon, Eun-Seok; Kim, Jae-Joong; Cho, Myeong-Chan; Chae, Shung Chull; Oh, Byung-Hee; Choi, Dong-Ju

2018-03-13

Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF). A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P <0.001 in HFrEF and HFpEF). Prevalence of WRF increased as creatinine clearance decreased in both heart failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P =0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P =0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P =0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P =0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF. In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication.

PubMed

Paschka, Peter; Schlenk, Richard F; Gaidzik, Verena I; Habdank, Marianne; Krönke, Jan; Bullinger, Lars; Späth, Daniela; Kayser, Sabine; Zucknick, Manuela; Götze, Katharina; Horst, Heinz-A; Germing, Ulrich; Döhner, Hartmut; Döhner, Konstanze

2010-08-01

To analyze the frequency and prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations in acute myeloid leukemia (AML). We studied 805 adults (age range, 16 to 60 years) with AML enrolled on German-Austrian AML Study Group (AMLSG) treatment trials AML HD98A and APL HD95 for mutations in exon 4 of IDH1 and IDH2. Patients were also studied for NPM1, FLT3, MLL, and CEBPA mutations. The median follow-up for survival was 6.3 years. IDH mutations were found in 129 patients (16.0%) -IDH1 in 61 patients (7.6%), and IDH2 in 70 patients (8.7%). Two patients had both IDH1 and IDH2 mutations. All but one IDH1 mutation caused substitutions of residue R132; IDH2 mutations caused changes of R140 (n = 48) or R172 (n = 22). IDH mutations were associated with older age (P < .001; effect conferred by IDH2 only); lower WBC (P = .04); higher platelets (P < .001); cytogenetically normal (CN) -AML (P< .001); and NPM1 mutations, in particular with the genotype of mutated NPM1 without FLT3 internal tandem duplication (ITD; P < .001). In patients with CN-AML with the latter genotype, IDH mutations adversely impacted relapse-free survival (RFS; P = .02) and overall survival (P = .03), whereas outcome was not affected in patients with CN-AML who lacked this genotype. In CN-AML, multivariable analyses revealed a significant interaction between IDH mutation and the genotype of mutated NPM1 without FLT3-ITD (ie, the adverse impact of IDH mutation [RFS]; P = .046 was restricted to this patient subset). IDH1 and IDH2 mutations are recurring genetic changes in AML. They constitute a poor prognostic factor in CN-AML with mutated NPM1 without FLT3-ITD, which allows refined risk stratification of this AML subset.

Parotid metastasis--an independent prognostic factor for head and neck cutaneous squamous cell carcinoma.

PubMed

Ch'ng, S; Maitra, A; Lea, R; Brasch, H; Tan, S T

2006-01-01

Metastatic parotid cutaneous squamous cell carcinoma (SCC) is the most common parotid gland malignancy in New Zealand and Australia. The current AJCC TNM staging system does not account for the extent of nodal metastasis. A staging system that separates parotid (P stage) from neck disease (N stage) has been proposed recently. To review the outcome of patients with metastatic head and neck cutaneous SCC treated at our multidisciplinary Head and Neck Service using the proposed staging system. Consecutive patients were culled from our Head and Neck/Skull Base Database, 1990-2004. These patients were restaged according to the proposed staging system: P stage: P0 = no disease in the parotid (i.e., neck disease only); P1 = metastatic node < or = 3 cm; P2=metastatic node > 3 cm and < or =6 cm, or multiple nodes; and P3 = metastatic node > 6 cm, or disease involving the facial nerve or skull base. N stage: N0=no disease in the neck (i.e., parotid disease only); N1 = single ipsilateral metastatic node < or = 3 cm; and N2 = multiple metastatic nodes, or any node > 3 cm, or contralateral neck involvement. Loco-regional recurrence and disease-specific survival were calculated using the Kaplan-Meier method and comparison of graphs made with the log-rank test. Multivariate analysis using the Cox regression model was carried out to assess the impact of various parameters. Sixty-seven patients with metastatic head and neck cutaneous SCC were identified. Thirty-seven patients had parotid metastasis (of whom 13 also had neck disease) while 21 had neck metastasis alone. Nine patients had dermal or soft tissue metastasis. These nine patients were excluded from this series, and data analysis was carried out on the remaining 58 (46 men, 12 women, mean age 71 years) patients. Sixty-seven percent of the patients underwent post-operative adjuvant radiotherapy. The five-year disease-specific survival rate was 54%. Among 56 patients followed up to disease recurrence or for a minimum period of 18 months, the loco-regional recurrence rate was 52%. The presence of parotid disease was an independent prognostic factor on survival (p < 0.01), and P3 fared significantly worse than P1 and P2. Those patients who had both parotid and neck disease fared worse than those who had parotid or neck disease alone (p = 0.01). N2 had a significantly poorer outcome compared with N1 (p < 0.01). Immunosuppression (p = 0.01) and a positive surgical margin (p < 0.01) were significant adverse prognostic factors for survival. Adjuvant radiotherapy, extracapsular spread, and perineural and vascular invasion did not influence survival. Our study demonstrates that the extent of parotid disease is an independent prognostic factor for metastatic head and neck cutaneous SCC.

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.

Prolonged survival after diagnosis of brain metastasis from breast cancer: contributing factors and treatment implications.

PubMed

Honda, Yayoi; Aruga, Tomoyuki; Yamashita, Toshinari; Miyamoto, Hiromi; Horiguchi, Kazumi; Kitagawa, Dai; Idera, Nami; Goto, Risa; Kuroi, Katsumasa

2015-08-01

The prognosis of breast cancer-derived brain metastasis is poor, but new drugs and recent therapeutic strategies have helped extend survival in patients. Prediction of therapeutic responses and outcomes is not yet possible, however. In a retrospective study, we examined prognostic factors in patients with breast cancer-derived brain metastasis, and we tested the prognostic utility of a breast cancer-specific Graded Prognostic Assessment in these patients. Sixty-three patients diagnosed with brain metastasis from breast cancer treated surgically and adjuvantly were included. We examined clinical variables per primary tumor subtype: ER+/HER2- (luminal), HER2+ (human epidermal growth factor receptor type 2-enriched) or ER-/PR-/HER2- (triple negative). We also categorized patients' breast cancer-specific Graded Prognostic Assessment scores and analyzed post-brain metastasis survival time in relation to these categories. The breast cancers comprised the following subtypes: luminal, n = 18; human epidermal growth factor receptor type 2-enriched, n = 27 and triple-negative, n = 18; median survival per subtype was 11, 37 and 3 months, respectively. Survival of human epidermal growth factor receptor type 2-enriched patients was longer, though not significantly (P = 0.188), than that of luminal patients. Survival of triple-negative patients was significantly short (vs. human epidermal growth factor receptor type 2-enriched patients, P < 0.001). Karnofsky performance status, HER2 status and the disease-free interval (from initial treatment to first recurrence) were shown to be significant prognostic factors (Karnofsky performance status < 70: relative risk 2.08, P = 0.028; HER2+: relative risk 2.911, P = 0.004; disease-free interval < 24 months: relative risk 1.933, P = 0.011). Breast cancer-specific Graded Prognostic Assessment scores reflected disease-free intervals and survival times. Our data indicate that breast cancer-specific Graded Prognostic Assessment-based prediction will be helpful in determining appropriate therapeutic strategies for patients with brain metastasis from breast cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

PubMed Central

Fabregat-Andrés, Óscar; Estornell-Erill, Jordi; Ridocci-Soriano, Francisco; Pérez-Boscá, José Leandro; García-González, Pilar; Payá-Serrano, Rafael; Morell, Salvador; Cortijo, Julio

2016-01-01

Background Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. Results 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). Conclusions In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF. PMID:26840055

Symptoms of an Intrauterine Hematoma Associated with Pregnancy Complications: A Systematic Review

PubMed Central

Xiang, Lan; Wei, Zhaolian; Cao, Yunxia

2014-01-01

Objective To evaluate the predictive value of the symptoms of an intrauterine hematoma (IUH) for adverse pregnancy outcomes. Methods A literature review was performed with the search terms, including intrauterine/subchorionic/retroplacental/subplacental hematoma/hemorrhage/bleeding/collection/fluid, covering the period from January, 1981 to January, 2014. We just focused on the pregnancy outcomes associated with different symptoms of an IUH. Results It is generally agreed that a retroplacental, posterior or subchorionic in the fundus of uterus, and/or persistent IUH is associated with adverse outcomes in the ongoing pregnancy. However, the prognosis value of both volume and gestational age at diagnosis of IUH still remains controversial. Some researchers argue that a large IUH is associated with an increased risk of adverse events during pregnancy while others refuted. It is believed by some that the earlier an IUH was detected, the higher the risk for adverse outcomes would be, while no or weak association were reported by other studies. The prognostic value of the simultaneous presence of vaginal bleeding on pregnancy outcome is also controversial. Conclusions Both the position relative to the placenta or uterus and duration of IUH have strong predictive value on the prognosis in the ongoing pregnancy. However, the prognostic values of the IUH volume, gestational age at diagnosis and the simultaneous presence of vaginal bleeding remain controversial up to now. Moreover, most of previous reports are small, uncontrolled studies with incomplete information. Prospective, large sample, cohorts studies which take all detailed symptoms of an IUH into consideration are needed when we evaluate its clinical significance in the prognosis of pregnancy. PMID:25369062

[Cryptogenic West syndrome: Clinical profile, response to treatment and prognostic factors].

PubMed

Calderón Romero, María; Arce Portillo, Elena; López Lobato, Mercedes; Muñoz Cabello, Beatriz; Blanco Martínez, Bárbara; Madruga Garrido, Marcos; Alonso Luego, Olga

2017-12-06

West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors. The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6 years, with a minimum of 2 years. The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical-clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis. The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis.

PubMed

Zampeli, Evanthia; Gizis, Michalis; Siakavellas, Spyros I; Bamias, Giorgos

2014-08-15

Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve (primary non-response) or lose response after a period of improvement (secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters that may predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular (immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

Exploring factors related to metastasis free survival in breast cancer patients using Bayesian cure models.

PubMed

Jafari-Koshki, Tohid; Mansourian, Marjan; Mokarian, Fariborz

2014-01-01

Breast cancer is a fatal disease and the most frequently diagnosed cancer in women with an increasing pattern worldwide. The burden is mostly attributed to metastatic cancers that occur in one-third of patients and the treatments are palliative. It is of great interest to determine factors affecting time from cancer diagnosis to secondary metastasis. Cure rate models assume a Poisson distribution for the number of unobservable metastatic-component cells that are completely deleted from the non-metastasis patient body but some may remain and result in metastasis. Time to metastasis is defined as a function of the number of these cells and the time for each cell to develop a detectable sign of metastasis. Covariates are introduced to the model via the rate of metastatic-component cells. We used non-mixture cure rate models with Weibull and log-logistic distributions in a Bayesian setting to assess the relationship between metastasis free survival and covariates. The median of metastasis free survival was 76.9 months. Various models showed that from covariates in the study, lymph node involvement ratio and being progesterone receptor positive were significant, with an adverse and a beneficial effect on metastasis free survival, respectively. The estimated fraction of patients cured from metastasis was almost 48%. The Weibull model had a slightly better performance than log-logistic. Cure rate models are popular in survival studies and outperform other models under certain conditions. We explored the prognostic factors of metastatic breast cancer from a different viewpoint. In this study, metastasis sites were analyzed all together. Conducting similar studies in a larger sample of cancer patients as well as evaluating the prognostic value of covariates in metastasis to each site separately are recommended.

Symptomatic spinal metastasis: A systematic literature review of the preoperative prognostic factors for survival, neurological, functional and quality of life in surgically treated patients and methodological recommendations for prognostic studies

PubMed Central

Nater, Anick; Martin, Allan R.; Sahgal, Arjun; Choi, David

2017-01-01

Purpose While several clinical prediction rules (CPRs) of survival exist for patients with symptomatic spinal metastasis (SSM), these have variable prognostic ability and there is no recognized CPR for health related quality of life (HRQoL). We undertook a critical appraisal of the literature to identify key preoperative prognostic factors of clinical outcomes in patients with SSM who were treated surgically. The results of this study could be used to modify existing or develop new CPRs. Methods Seven electronic databases were searched (1990–2015), without language restriction, to identify studies that performed multivariate analysis of preoperative predictors of survival, neurological, functional and HRQoL outcomes in surgical patients with SSM. Individual studies were assessed for class of evidence. The strength of the overall body of evidence was evaluated using GRADE for each predictor. Results Among 4,818 unique citations, 17 were included; all were in English, rated Class III and focused on survival, revealing a total of 46 predictors. The strength of the overall body of evidence was very low for 39 and low for 7 predictors. Due to considerable heterogeneity in patient samples and prognostic factors investigated as well as several methodological issues, our results had a moderately high risk of bias and were difficult to interpret. Conclusions The quality of evidence for predictors of survival was, at best, low. We failed to identify studies that evaluated preoperative prognostic factors for neurological, functional, or HRQoL outcomes in surgical patients with SSM. We formulated methodological recommendations for prognostic studies to promote acquiring high-quality evidence to better estimate predictor effect sizes to improve patient education, surgical decision-making and development of CPRs. PMID:28225772

The importance of histopathological and clinical variables in predicting the evolution of colon cancer.

PubMed

Diculescu, Mircea; Iacob, Răzvan; Iacob, Speranţa; Croitoru, Adina; Becheanu, Gabriel; Popeneciu, Valentin

2002-09-01

It has been a consensus that prognostic factors should always be taken into account before planning treatment in colorectal cancer. A 5 year prospective study was conducted, in order to assess the importance of several histopathological and clinical prognostic variables in the prediction of evolution in colon cancer. Some of the factors included in the analysis are still subject to dispute by different authors. 46 of 53 screened patients qualified to enter the study and underwent a potentially curative resection of the tumor, followed, when necessary, by adjuvant chemotherapy. Univariate and multivariate analyses were carried out in order to identify independent prognostic indicators. The endpoint of the study was considered the recurrence of the tumor or the detection of metastases. 65.2% of the patients had a good evolution during the follow up period. Multivariate survival analysis performed by Cox proportional hazard model identified 3 independent prognostic factors: Dukes stage (p = 0.00002), the grade of differentiation (p = 0.0009) and the weight loss index, representing the weight loss of the patient divided by the number of months when it was actually lost (p = 0.02). Age under 40 years, sex, microscopic aspect of the tumor, tumor location, anemia degree were not identified by our analysis as having prognostic importance. Histopathological factors continue to be the most valuable source of information regarding the possible evolution of patients with colorectal cancer. Individual clinical symptoms or biological parameters such as erytrocyte sedimentation rate or hemoglobin level are of little or no prognostic value. More research is required relating to the impact of a performance status index (which could include also weight loss index) as another reliable prognostic variable.

Number of negative lymph nodes should be considered for incorporation into staging for breast cancer

PubMed Central

Wu, San-Gang; Wang, Yan; Zhou, Juan; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; He, Zhen-Yu

2015-01-01

This study aimed to investigate the prognostic value of the number of involved lymph nodes (pN), number of removed lymph nodes (RLNs), lymph node ratio (LNR), number of negative lymph nodes (NLNs), and log odds of positive lymph nodes (LODDS) in breast cancer patients. The records of 2,515 breast cancer patients who received a mastectomy or breast-conserving surgery were retrospectively reviewed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors. The median follow-up time was 64.2 months, and the 8-year disease-free survival (DFS) and overall survival (OS) were 74.6% and 82.3%, respectively. Univariate analysis showed that pN stage, LNR, number of RLNs, and number of NLNs were significant prognostic factors for DFS and OS (all, P < 0.05). LODDS was a significant prognostic factor for OS (P = 0.021). Multivariate analysis indicated that pN stage and the number of NLNs were independent prognostic factors for DFS and OS. A higher number of NLNs was associated with higher DFS and OS, and a higher number of involved lymph nodes were associated with poorer DFS and OS. Patients with a NLNs count > 9 had better survival (P < 0.001). Subgroup analysis showed that the NLNs count had a prognostic value in patients with different pT stages and different lymph node status (log-rank P < 0.05). For breast cancer, pN stage and NLNs count have a better prognostic value compared to the RLNs count, LNR, and LODDS. Number of negative lymph nodes should be considered for incorporation into staging for breast cancer. PMID:25973321

[Studies of prognostic factor and chemotherapeutic effect of epithelial ovarian cancer using Cox's proportional hazard model].

PubMed

Umesaki, N; Sugawa, T; Yajima, A; Satoh, S; Terashima, Y; Ochiai, K; Tomoda, Y; Kanoh, T; Noda, K; Yakushiji, M

1993-12-01

To make clear the prognostic factor and chemotherapeutic effect of epithelial ovarian cancer, a multiple-center study involving 22 hospitals in Japan was conducted using Cox's proportional hazard model. A total of 1,181 cases were reviewed. Clinical stage, histologic type, and residual tumor diameter were significant prognostic factors, but the degree of tissue differentiation was not. The effect of remission induction chemotherapy was assessed with or without CDDP, and a distinct prognostic difference was noted. Among the patients receiving CDDP + ADM + other chemotherapeutic agents (PA group), CDDP + other chemotherapeutic agents (PO group) and CDDP only (P group), the prognosis of the PO group was better than for the P group. The long-term prognosis improving effect of chemotherapy was assessed. Neither maintenance chemotherapy based on oral administration of pyrimidine fluoride nor immunotherapy had any long-term prognosis improving effect, while intermittent chemotherapy based on CDDP resulted in improved prognosis.

A primary tumor of mixed histological type is a novel poor prognostic factor for patients undergoing resection of liver metastasis from gastric cancer.

PubMed

Ikari, Naoki; Taniguchi, Kiyoaki; Serizawa, Akiko; Yamada, Takuji; Yamamoto, Masakazu; Furukawa, Toru

2017-05-01

Surgical resection can be an option for the treatment of metastatic liver tumors originating from gastric cancer; however, its prognostic impact is controversial. The aim of this study was to identify prognostic factors in patients with surgical resection of liver metastasis from gastric cancer. We retrospectively analyzed the clinicopathological features of 38 consecutive patients undergoing hepatectomy for metastatic tumors from gastric cancer in our institution between 1990 and 2014. The median overall survival of the patients was 28 months. The 5-year survival rate was 33.9%. Primary tumors of a mixed histological type, and residual tumors during the course of treatment were identified as significant independent poor prognostic factors. Histological evaluation of primary tumors may aid to identify patients suitable for undergoing surgical resection of liver metastasis from gastric cancer. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Prognostic role of heart-type fatty acid binding protein in pulmonary embolism: a meta-analysis.

PubMed

Liu, Mingjie; Yuan, Xia; Qiu, Xianming; Shan, Xiaoxi; Lin, Dianjie; Zhu, Ling

2015-01-01

Pulmonary embolism (PE) has a high morbidity and mortality. Hence it is important to recognize factors associated with higher risk of adverse outcomes in hemodynamically stable patients. Heart-type fatty acid binding protein (H-FABP) is a novel marker evaluated in recent years for prognosis in acute PE. Our aim was to evaluate the available evidence on the accuracy of H-FABP for predicting the prognosis of adverse clinical outcomes (defined as the occurrence of any of the following: death, cardiopulmonary resuscitation, endotracheal intubation, use of vasopressors, thrombolysis, surgical embolectomy, or admission to the intensive care unit) or mortality in patients with acute PE. Unrestricted searches of PubMed, the Cochrane Library, Web of Science and Science Direct were performed using the terms of "H-FABP" or "heart-type fatty acid binding protein" and ("pulmonary embolism" or "pulmonary thromboembolism"). A random-effect model was used to pool study results; χ(2) and I(2) testing was used to test for heterogeneity. Data of six studies were included in this analysis. 34 of 119(28.57%; 95%CI, 20.42%-36.72%) patients with elevated H-FABP levels had adverse events during follow-up compared with 24 of 475 (5.05%; 95%CI, 3.08%-7.02%) patients with normal levels. High H-FABP levels were associated with a high risk of occurrence of adverse clinical outcome (pooled OR, 10.81; 95%CI, 3.92-29.83). The results of this meta-analysis indicate that H-FABP is a good predictor for adverse outcomes in patients with acute PE. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemotherapy-induced neutropenia is associated with prolonged remission duration and survival time in canine lymphoma.

PubMed

Wang, S L; Lee, J J; Liao, A T

2015-07-01

Myelosuppression is one of the most common side effects of chemotherapy. The aim of this study was to determine whether chemotherapy-induced neutropenia is a positive prognostic indicator for remission and survival time in dogs with lymphoma. Fifty dogs with multicentric lymphoma received CHOP-based (C-cyclophosphamide; H-hydroxydaunorubicin; O-vincristine; P-prednisolone) chemotherapy using conventional dosages. Complete blood counts were recorded to determine the presence or absence of neutropenia after treatment. Toxicity, remission, and survival times were recorded and analysed. Thirteen dogs had chemotherapy-induced neutropenia and 37 had no neutropenia during the study period. No statistical difference was found between the groups for signalment or the presence of historical negative prognostic factors, except for bodyweight (P = 0.02). The median first remission times in the neutropenia and no neutropenia groups were 812 and 219 days, respectively (P <0.01). The median survival times of dogs in the neutropenia and no neutropenia groups were 952 and 282 days, respectively (P <0.01). Dogs with lymphoma that had chemotherapy-induced neutropenia exhibited significantly increased remission and survival times compared with dogs without neutropenia. Chemotherapeutic dosages may be adjusted individually to induce neutropenia without severe adverse effects in order to achieve longer remission and survival times. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

PubMed Central

Lu, Jing; Lu, Jin; Liu, Aijun; Fu, Weijun; Du, Juan; Huang, Xiaojun; Chen, Wenming; Hou, Jian

2015-01-01

The International Staging System (ISS) is the most important prognostic system for multiple myeloma (MM). It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS) of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p < 0.001), and the median progression-free survival (PFS) was 30/29.5/25 months (p = 0.072), respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system. PMID:26640799

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project.

PubMed

Weisenburger, Dennis D; Savage, Kerry J; Harris, Nancy Lee; Gascoyne, Randy D; Jaffe, Elaine S; MacLennan, Kenneth A; Rüdiger, Thomas; Pileri, Stefano; Nakamura, Shigeo; Nathwani, Bharat; Campo, Elias; Berger, Francoise; Coiffier, Bertrand; Kim, Won-Seog; Holte, Harald; Federico, Massimo; Au, Wing Y; Tobinai, Kensei; Armitage, James O; Vose, Julie M

2011-03-24

The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.

[Prognostic factors of early breast cancer].

PubMed

Almagro, Elena; González, Cynthia S; Espinosa, Enrique

2016-02-19

Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Marital status is an independent prognostic factor for pancreatic neuroendocrine tumors patients: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

PubMed

Zhou, Huaqiang; Zhang, Yuanzhe; Song, Yiyan; Tan, Wulin; Qiu, Zeting; Li, Si; Chen, Qinchang; Gao, Shaowei

2017-09-01

Marital status's prognostic impact on pancreatic neuroendocrine tumors (PNET) has not been rigorously studied. We aimed to explore the relationship between marital status and outcomes of PNET. We retrospectively investigated 2060 PNET cases between 2004 and 2010 from Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by Chi 2 test, t-test as appropriate. Kaplan-Meier methods and COX proportional hazard models were used to ascertain independent prognostic factors. Married patients had better 5-year overall survival (OS) (53.37% vs. 42.27%, P<0.001) and 5-year pancreatic neuroendocrine tumor specific survival (PNSS) (67.76% vs. 59.82%, P=0.001) comparing with unmarried patients. Multivariate analysis revealed marital status is an independent prognostic factor, with married patients showing better OS (HR=0.74; 95% CI: 0.65-0.84; P<0.001) and PNSS (HR=0.78; 95% CI: 0.66-0.92; P=0.004). Subgroup analysis suggested marital status plays a more important role in the PNET patients with distant stage rather than regional or localized disease. Marital status is an independent prognostic factor for survival in PNET patients. Poor prognosis in unmarried patients may be associated with a delayed diagnosis with advanced tumor stage, psychosocial and socioeconomic factors. Further studies are needed. Copyright © 2017. Published by Elsevier Masson SAS.

Prognostic factors in non-surgically treated sciatica: a systematic review.

PubMed

Ashworth, Julie; Konstantinou, Kika; Dunn, Kate M

2011-09-25

When present sciatica is considered an obstacle to recovery in low back pain patients, yet evidence is limited regarding prognostic factors for persistent disability in this patient group. The aim of this study is to describe and summarise the evidence regarding prognostic factors for sciatica in non-surgically treated cohorts. Understanding the prognostic factors in sciatica and their relative importance may allow the identification of patients with particular risk factors who might benefit from early or specific types of treatment in order to optimise outcome. A systematic literature search was conducted using Medline, EMBASE and CINAHL electronic databases. Prospective cohort studies describing subjects with sciatica and measuring pain, disability or recovery outcomes were included. Studies of cohorts comprised entirely of surgically treated patients were excluded and mixed surgically and conservatively treated cohorts were included only if the results were analysed separately by treatment group or if the analysis was adjusted for treatment. Seven adequate or high quality eligible studies were identified. There were conflicting but mainly negative results regarding the influence of baseline pain severity, neurological deficit, nerve root tension signs, duration of symptoms and radiological findings on outcome. A number of factors including age, gender, smoking, previous history of sciatica and heaviness of work do not appear to influence outcome. In contrast to studies of low back pain and purely surgically treated sciatica cohorts, psychological factors were rarely investigated. At present, the heterogeneity of the available studies makes it difficult to draw firm conclusions about sciatica prognosis, and highlights the need for further research for this group of patients. Large scale prospective studies of high methodological quality, using a well-defined, consistent definition of sciatica and investigating psychosocial factors alongside clinical and radiological findings are recommended to identify prognostic factors in this population.

Prognostic factors in non-surgically treated sciatica: A systematic review

PubMed Central

2011-01-01

Background When present sciatica is considered an obstacle to recovery in low back pain patients, yet evidence is limited regarding prognostic factors for persistent disability in this patient group. The aim of this study is to describe and summarise the evidence regarding prognostic factors for sciatica in non-surgically treated cohorts. Understanding the prognostic factors in sciatica and their relative importance may allow the identification of patients with particular risk factors who might benefit from early or specific types of treatment in order to optimise outcome. Methods A systematic literature search was conducted using Medline, EMBASE and CINAHL electronic databases. Prospective cohort studies describing subjects with sciatica and measuring pain, disability or recovery outcomes were included. Studies of cohorts comprised entirely of surgically treated patients were excluded and mixed surgically and conservatively treated cohorts were included only if the results were analysed separately by treatment group or if the analysis was adjusted for treatment. Results Seven adequate or high quality eligible studies were identified. There were conflicting but mainly negative results regarding the influence of baseline pain severity, neurological deficit, nerve root tension signs, duration of symptoms and radiological findings on outcome. A number of factors including age, gender, smoking, previous history of sciatica and heaviness of work do not appear to influence outcome. In contrast to studies of low back pain and purely surgically treated sciatica cohorts, psychological factors were rarely investigated. Conclusions At present, the heterogeneity of the available studies makes it difficult to draw firm conclusions about sciatica prognosis, and highlights the need for further research for this group of patients. Large scale prospective studies of high methodological quality, using a well-defined, consistent definition of sciatica and investigating psychosocial factors alongside clinical and radiological findings are recommended to identify prognostic factors in this population. PMID:21943339

Predictors of postoperative outcomes of cubital tunnel syndrome treatments using multiple logistic regression analysis.

PubMed

Suzuki, Taku; Iwamoto, Takuji; Shizu, Kanae; Suzuki, Katsuji; Yamada, Harumoto; Sato, Kazuki

2017-05-01

This retrospective study was designed to investigate prognostic factors for postoperative outcomes for cubital tunnel syndrome (CubTS) using multiple logistic regression analysis with a large number of patients. Eighty-three patients with CubTS who underwent surgeries were enrolled. The following potential prognostic factors for disease severity were selected according to previous reports: sex, age, type of surgery, disease duration, body mass index, cervical lesion, presence of diabetes mellitus, Workers' Compensation status, preoperative severity, and preoperative electrodiagnostic testing. Postoperative severity of disease was assessed 2 years after surgery by Messina's criteria which is an outcome measure specifically for CubTS. Bivariate analysis was performed to select candidate prognostic factors for multiple linear regression analyses. Multiple logistic regression analysis was conducted to identify the association between postoperative severity and selected prognostic factors. Both bivariate and multiple linear regression analysis revealed only preoperative severity as an independent risk factor for poor prognosis, while other factors did not show any significant association. Although conflicting results exist regarding prognosis of CubTS, this study supports evidence from previous studies and concludes early surgical intervention portends the most favorable prognosis. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Prognosis of Pain and Physical Functioning in Patients With Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

PubMed

de Rooij, Mariëtte; van der Leeden, Marike; Heymans, Martijn W; Holla, Jasmijn F M; Häkkinen, Arja; Lems, Willem F; Roorda, Leo D; Veenhof, Cindy; Sanchez-Ramirez, Diana C; de Vet, Henrica C W; Dekker, Joost

2016-04-01

To systematically summarize the literature on the course of pain in patients with knee osteoarthritis (OA), prognostic factors that predict deterioration of pain, the course of physical functioning, and prognostic factors that predict deterioration of physical functioning in persons with knee OA. A search was conducted in PubMed, CINAHL, Embase, Psych-INFO, and SPORTDiscus up to January 2014. A meta-analysis and a qualitative data synthesis were performed. Of the 58 studies included, 39 were of high quality. High heterogeneity across studies (I(2)  >90%) and within study populations (reflected by large SDs of change scores) was found. Therefore, the course of pain and physical functioning was interpreted to be indistinct. We found strong evidence for a number of prognostic factors predicting deterioration in pain (e.g., higher knee pain at baseline, bilateral knee symptoms, and depressive symptoms). We also found strong evidence for a number of prognostic factors predicting deterioration in physical functioning (e.g., worsening in radiographic OA, worsening of knee pain, lower knee extension muscle strength, lower walking speed, and higher comorbidity count). Because of high heterogeneity across studies and within study populations, no conclusions can be drawn with regard to the course of pain and physical functioning. These findings support current research efforts to define subgroups or phenotypes within knee OA populations. Strong evidence was found for knee characteristics, clinical factors, and psychosocial factors as prognostics of deterioration of pain and physical functioning. © 2016, American College of Rheumatology.

Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a case cohort study.

PubMed

Carr, Brian I; Buch, Shama C; Kondragunta, Venkateswarlu; Pancoska, Petr; Branch, Robert A

2008-08-01

A total of 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end-point for all analyses. We found in our overall analysis, that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated alpha-fetoprotein (AFP) or bilirubin or alkaline phosphatases were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient subgroups based on poor liver function and aggressive tumor characteristics. In subgroup analysis based on these subsets, there was clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant, independent but modest risk factors. The results of this large dataset show that amongst nonsurgical HCC patients, there are clear subsets with longer survival than other subsets. This data also supports the concept of heterogeneity of HCC.

Transcription factor activating protein 4 is synthetically lethal and a master regulator of MYCN-amplified neuroblastoma.

PubMed

Boboila, Shuobo; Lopez, Gonzalo; Yu, Jiyang; Banerjee, Debarshi; Kadenhe-Chiweshe, Angela; Connolly, Eileen P; Kandel, Jessica J; Rajbhandari, Presha; Silva, Jose M; Califano, Andrea; Yamashiro, Darrell J

2018-06-07

Despite the identification of MYCN amplification as an adverse prognostic marker in neuroblastoma, MYCN inhibitors have yet to be developed. Here, by integrating evidence from a whole-genome shRNA library screen and the computational inference of master regulator proteins, we identify transcription factor activating protein 4 (TFAP4) as a critical effector of MYCN amplification in neuroblastoma, providing a novel synthetic lethal target. We demonstrate that TFAP4 is a direct target of MYCN in neuroblastoma cells, and that its expression and activity strongly negatively correlate with neuroblastoma patient survival. Silencing TFAP4 selectively inhibits MYCN-amplified neuroblastoma cell growth both in vitro and in vivo, in xenograft mouse models. Mechanistically, silencing TFAP4 induces neuroblastoma differentiation, as evidenced by increased neurite outgrowth and upregulation of neuronal markers. Taken together, our results demonstrate that TFAP4 is a key regulator of MYCN-amplified neuroblastoma and may represent a valuable novel therapeutic target.

Healthcare Professionals' Knowledge of Influenza and Influenza Vaccination: Results of a National Survey in Poland.

PubMed

Kuchar, Ernest; Ludwikowska, Kamila; Antczak, Adam; Nitsch-Osuch, Aneta

2018-01-01

In Poland, the seasonal influenza vaccination rate is just barely 3% which may be related to the unsatisfactory knowledge of influenza among healthcare professionals, poor recognition of the benefits of influenza immunization and the fear of side effects. To address these issues, we surveyed healthcare professionals through an online questionnaire consisting of 18 closed-ended items. The questionnaire was completed by 495 healthcare professionals, mostly physicians (83%). The results revealed gaps in the knowledge concerning influenza diagnosis, complications, risk groups, and prognostic factors. On average, respondents only answered 4.8 of the 18 questions correctly (27%). Only 10% of respondents passed the threshold of 50% correct answers. The knowledge of contraindications to vaccination far outweighed the knowledge of indications for vaccination. Poor knowledge with a focus on the adverse effects of immunization may be a significant factor responsible for the low vaccination rate in Poland. To increase vaccination rate, healthcare professionals need to be educated about influenza-related risks and benefits of vaccination.

Baduanjin Exercise Prevents post-Myocardial Infarction Left Ventricular Remodeling (BE-PREMIER trial): Design and Rationale of a Pragmatic Randomized Controlled Trial.

PubMed

Mao, Shuai; Zhang, Xiaoxuan; Shao, Biying; Hu, Xiyan; Hu, Yanan; Li, Winny; Guo, Liheng; Zhang, Minzhou

2016-06-01

Left ventricular (LV) remodeling following myocardial infarction (MI) is an established prognostic factor for adverse cardiovascular events and the leading cause of heart failure. Empirical observations have suggested that Baduanjin exercise, an important component of traditional Chinese Qigong, may exert potential benefits on cardiopulmonary function. However, the impact of a Baduanjin exercise-based cardiac rehabilitation program for patients recovering from a recent MI has yet to be assessed. The aim of this trial is to evaluate the potential role of Baduanjin exercise in preventing the maladaptive progression to adverse LV remodeling in patients post-MI. A total of 110 clinically stable patients following an MI after undergoing successful infarct-related artery reperfusion will be randomly assigned to the Baduanjin exercise group or usual exercise control group. In addition to usual physical activity, participants in the Baduanjin exercise group will participate in a 45 min Baduanjin exercise training session twice a week, for a total of 12 weeks. The primary endpoint will be the percentage change in LV end-diastolic volume index (LVEDVi) assessed using echocardiography from baseline to 6 months. The results of this study may provide novel evidence on the efficacy of Baduanjin exercise therapy in post-MI patients in reversing adverse LV remodeling and improving clinical outcome. Clinical Trials.gov: NCT02693795.

Prognostic significance of dilated inferior vena cava in advanced decompensated heart failure.

PubMed

Lee, Hsin-Fu; Hsu, Lung-An; Chang, Chi-Jen; Chan, Yi-Hsin; Wang, Chun-Li; Ho, Wan-Jing; Chu, Pao-Hsien

2014-10-01

Dilated inferior vena cava (IVC) is prevalent among patients with heart failure (HF), but whether its presence predicts worsening renal function (WRF) or adverse outcomes is unclear. This cohort study analyzed patients with left ventricular ejection fraction <40 % and repeated hospitalizations (≥2 times) for HF between August 2009 and August 2011. The study endpoints were death and HF re-hospitalization. Among baseline parameters, IVC diameter was the most powerful predictor for the development of WRF (area under the curve = 0.795, cut-off value = 20.5 mm). During the 2-year follow-up, 36 patients (49 %) were re-hospitalized for HF and 14 patients (19 %) died. The event rates were significantly greater in the WRF group than in the non-WRF group (71 vs. 30 %, P < 0.001 for HF re-hospitalization; 29 vs. 10 %, P = 0.03 for death). In Cox regression model, the risk of combined end-points was increased in patients with aging, elevated blood urine nitrogen, IVC >21 mm, and WRF. When adjusted for confounding factors, IVC >21 mm [hazard ratio (HR) 3.73, 95 % confidence interval (CI) 1.66-8.34] and WRF (HR 2.68, 95 % CI 1.07-6.75) were significant predictors for adverse outcomes. In patients with advanced decompensated HF, dilated IVC (>21 mm) predicted the development of WRF and could be a predictor for adverse outcomes.

Increased body mass index is associated with improved overall survival in extranodal natural killer/T-cell lymphoma, nasal type.

PubMed

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Liu, Xi-Yu; Zhou, Fang; OuYang, Zhou; Sun, Zhong-Yi; Huang, Li-Jun; He, Jun-Qiao; Yao, Yuan; Fan, Zhou; Tang, Tian; Jiang, Wen-Qi

2017-01-17

The role of body mass index (BMI) in lymphoma survival outcomes is controversial. The prognostic significance of BMI in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is unclear. We evaluated the prognostic role of BMI in patients with ENKTL. We retrospectively analyzed 742 patients with newly diagnosed ENKTL. The prognostic value of BMI was compared between patients with low BMIs (< 20.0 kg/m2) and patients with high BMIs (≥ 20.0 kg/m2). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) was also evaluated and compared with that of the BMI classification. Patients with low BMIs tended to exhibit higher Eastern Cooperative Oncology Group performance status (ECOG PS) scores (≥ 2) (P = 0.001), more frequent B symptoms (P < 0.001), lower albumin levels (P < 0.001), higher KPI scores (P = 0.03), and lower rates of complete remission (P < 0.001) than patients with high BMIs, as well as inferior progression-free survival (PFS, P = 0.003), and inferior overall survival (OS, P = 0.001). Multivariate analysis demonstrated that age > 60 years, mass > 5 cm, stage III/IV, elevated LDH levels, albumin levels < 35 g/L and low BMIs were independent adverse predictors of OS. The BMI classification was found to be superior to the IPI with respect to predicting patient outcomes among low-risk patients and the KPI with respect to distinguishing between intermediate-low- and high-intermediate-risk patients. Higher BMI at the time of diagnosis is associated with improved overall survival in ENKTL. Using the BMI classification may improve the IPI and KPI prognostic models.

Increased body mass index is associated with improved overall survival in extranodal natural killer/T-cell lymphoma, nasal type

PubMed Central

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Liu, Xi-Yu; Zhou, Fang; OuYang, Zhou; Sun, Zhong-Yi; Huang, Li-Jun; He, Jun-Qiao; Yao, Yuan; Fan, Zhou; Tang, Tian; Jiang, Wen-Qi

2017-01-01

Objectives: The role of body mass index (BMI) in lymphoma survival outcomes is controversial. The prognostic significance of BMI in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is unclear. We evaluated the prognostic role of BMI in patients with ENKTL. Methods: We retrospectively analyzed 742 patients with newly diagnosed ENKTL. The prognostic value of BMI was compared between patients with low BMIs (< 20.0 kg/m2) and patients with high BMIs (≥ 20.0 kg/m2). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) was also evaluated and compared with that of the BMI classification. Results: Patients with low BMIs tended to exhibit higher Eastern Cooperative Oncology Group performance status (ECOG PS) scores (≥ 2) (P = 0.001), more frequent B symptoms (P < 0.001), lower albumin levels (P < 0.001), higher KPI scores (P = 0.03), and lower rates of complete remission (P < 0.001) than patients with high BMIs, as well as inferior progression-free survival (PFS, P = 0.003), and inferior overall survival (OS, P = 0.001). Multivariate analysis demonstrated that age > 60 years, mass > 5 cm, stage III/IV, elevated LDH levels, albumin levels < 35 g/L and low BMIs were independent adverse predictors of OS. The BMI classification was found to be superior to the IPI with respect to predicting patient outcomes among low-risk patients and the KPI with respect to distinguishing between intermediate-low- and high-intermediate-risk patients. Conclusions: Higher BMI at the time of diagnosis is associated with improved overall survival in ENKTL. Using the BMI classification may improve the IPI and KPI prognostic models. PMID:28002803

Prognostic role of ABO blood type in patients with extranodal natural killer/T cell lymphoma, nasal type: a triple-center study.

PubMed

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Tang, Tian; Zhang, Pei-Ying; Jiang, Wen-Qi

2017-07-31

The prognostic significance of ABO blood type for lymphoma is largely unknown. We evaluated the prognostic role of ABO blood type in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed clinical data of 697 patients with newly diagnosed ENKTL from three cancer centers. The prognostic value of ABO blood type was evaluated using Kaplan-Meier curves and Cox proportional hazard models. The prognostic values of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were also evaluated. Compared with patients with blood type O, those with blood type non-O tended to display elevated baseline serum C-reactive protein levels (P = 0.038), lower rate of complete remission (P = 0.005), shorter progression-free survival (PFS, P < 0.001), and shorter overall survival (OS, P = 0.001). Patients with blood type O/AB had longer PFS (P < 0.001) and OS (P = 0.001) compared with those with blood type A/B. Multivariate analysis demonstrated that age >60 years (P < 0.001), mass ≥5 cm (P = 0.001), stage III/IV (P < 0.001), elevated serum lactate dehydrogenase (LDH) levels (P = 0.001), and blood type non-O were independent adverse predictors of OS (P = 0.001). ABO blood type was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the intermediate-to-low- and high-to-intermediate-risk groups. ABO blood type was an independent predictor of clinical outcome for patients with ENKTL.

The National Hospital Discharge Survey and Nationwide Inpatient Sample: the databases used affect results in THA research.

PubMed

Bekkers, Stijn; Bot, Arjan G J; Makarawung, Dennis; Neuhaus, Valentin; Ring, David

2014-11-01

The National Hospital Discharge Survey (NHDS) and the Nationwide Inpatient Sample (NIS) collect sample data and publish annual estimates of inpatient care in the United States, and both are commonly used in orthopaedic research. However, there are important differences between the databases, and because of these differences, asking these two databases the same question may result in different answers. The degree to which this is true for arthroplasty-related research has, to our knowledge, not been characterized. We tested the following null hypotheses: (1) there are no differences between the NHDS and NIS in patient characteristics, comorbidities, and adverse events in patients with hip osteoarthritis treated with THA, and (2) there are no differences between databases in factors associated with inpatient mortality, adverse events, and length of hospital stay after THA. The NHDS and NIS databases use different methods of data collection and weighting to provide data representative of all nonfederal hospital discharges in the United States. In 2006 the NHDS database contained 203,149 patients with hip arthritis treated with hip arthroplasty, and the NIS database included 193,879 patients. Multivariable analyses for factors associated with inpatient mortality, adverse events, and days of care were constructed for each database. We found that 26 of 42 of the factors in demographics, comorbidities, and adverse events after THA in the NIS and NHDS databases differed more than 10%. Age and days of care were associated with inpatient mortality with the NHDS and the NIS although the effect rates differ more than 10%. The NIS identified seven other factors not identified by the NHDS: wound complications, congestive heart failure, new mental disorder, chronic pulmonary disease, dementia, geographic region Northeast, acute postoperative anemia, and sex, that were associated with inpatient mortality even after controlling for potentially confounding variables. For inpatient adverse events, atrial fibrillation, osteoporosis, and female sex were associated with the NHDS and the NIS although the effect rates differ more than 10%. There were different directions for sources of payment, dementia, congestive heart failure, and geographic region. For longer length of stay, common factors differing more than 10% in effect rate included chronic pulmonary disease, atrial fibrillation, complication not elsewhere classified, congestive heart failure, transfusion, discharge nonroutine compared with routine, acute postoperative anemia, hypertension, wound adverse events, and diabetes mellitus, whereas discrepant factors included geographic region, payment method, dementia, sex, and iatrogenic hypotension. Studies that use large databases intended to be representative of the entire United States population can produce different results, likely related to differences in the databases, such as the number of comorbidities and procedures that can be entered in the database. In other words, analyses of large databases can have limited reliability and should be interpreted with caution. Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

Improving the Prognostic Ability through Better Use of Standard Clinical Data - The Nottingham Prognostic Index as an Example

PubMed Central

Winzer, Klaus-Jürgen; Buchholz, Anika; Schumacher, Martin; Sauerbrei, Willi

2016-01-01

Background Prognostic factors and prognostic models play a key role in medical research and patient management. The Nottingham Prognostic Index (NPI) is a well-established prognostic classification scheme for patients with breast cancer. In a very simple way, it combines the information from tumor size, lymph node stage and tumor grade. For the resulting index cutpoints are proposed to classify it into three to six groups with different prognosis. As not all prognostic information from the three and other standard factors is used, we will consider improvement of the prognostic ability using suitable analysis approaches. Methods and Findings Reanalyzing overall survival data of 1560 patients from a clinical database by using multivariable fractional polynomials and further modern statistical methods we illustrate suitable multivariable modelling and methods to derive and assess the prognostic ability of an index. Using a REMARK type profile we summarize relevant steps of the analysis. Adding the information from hormonal receptor status and using the full information from the three NPI components, specifically concerning the number of positive lymph nodes, an extended NPI with improved prognostic ability is derived. Conclusions The prognostic ability of even one of the best established prognostic index in medicine can be improved by using suitable statistical methodology to extract the full information from standard clinical data. This extended version of the NPI can serve as a benchmark to assess the added value of new information, ranging from a new single clinical marker to a derived index from omics data. An established benchmark would also help to harmonize the statistical analyses of such studies and protect against the propagation of many false promises concerning the prognostic value of new measurements. Statistical methods used are generally available and can be used for similar analyses in other diseases. PMID:26938061

A consensus prognostic gene expression classifier for ER positive breast cancer

PubMed Central

Teschendorff, Andrew E; Naderi, Ali; Barbosa-Morais, Nuno L; Pinder, Sarah E; Ellis, Ian O; Aparicio, Sam; Brenton, James D; Caldas, Carlos

2006-01-01

Background A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. Results Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation. Conclusion The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors. PMID:17076897

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia.

PubMed

Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

2013-04-01

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics.

Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma

PubMed Central

Fu, Hangcheng; Liu, Yidong; Xu, Le; Chang, Yuan; Zhou, Lin; Zhang, Weijuan; Yang, Yuanfeng; Xu, Jiejie

2016-01-01

Abstract Mucin-4 (MUC4), a member of membrane-bound mucins, has been reported to exert a large variety of distinctive roles in tumorigenesis of different cancers. MUC4 is aberrantly expressed in clear-cell renal cell carcinoma (ccRCC) but its prognostic value is still unveiled. This study aims to assess the clinical significance of MUC4 expression in patients with ccRCC. The expression of MUC4 was assessed by immunohistochemistry in 198 patients with ccRCC who underwent nephrectomy retrospectively in 2003 and 2004. Sixty-seven patients died before the last follow-up in the cohort. Kaplan–Meier method with log-rank test was applied to compare survival curves. Univariate and multivariate Cox regression models were applied to evaluate the prognostic value of MUC4 expression in overall survival (OS). The predictive nomogram was constructed based on the independent prognostic factors. The calibration was built to evaluate the predictive accuracy of nomogram. In patients with ccRCC, MUC4 expression, which was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 3.891; P < 0.001), was negatively associated with tumor size (P = 0.036), Fuhrman grade (P = 0.044), and OS (P < 0.001). The prognostic accuracy of TNM stage, UCLA Integrated Scoring System (UISS), and Mayo clinic stage, size, grade, and necrosis score (SSIGN) prognostic models was improved when MUC4 expression was added. The independent prognostic factors, pT stage, distant metastases, Fuhrman grade, sarcomatoid, and MUC4 expression were integrated to establish a predictive nomogram with high predictive accuracy. MUC4 expression is an independent prognostic factor for OS in patients with ccRCC. PMID:27124015

A nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma

PubMed Central

Liu, Jin-Shi; Huang, Ying; Yang, Xun; Feng, Ji-Feng

2015-01-01

Background: Inflammation plays an important role in cancer progression and prognosis. However, the prognostic values of inflammatory biomarkers in esophageal cancer (EC) were not established. In the present study, therefore, we initially used a nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 326 ESCC patients were included in this retrospective study. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) were analyzed in the current study. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). Cox regression analysis was also performed to evaluate the prognostic factors. A nomogram was established to predict the prognosis for CSS. Results: Patients were divided into 3 groups according to GPS (GPS 0, 1 and 2) and 2 groups according to NLR (≤3.45 and >3.45), PLR (≤166.5 and >166.5) and LMR (≤2.30 and >2.30). The 5-year CSS in patients with GPS 0, 1 and 2 were 49.2%, 26.8% and 11.9%, respectively (P<0.001). In addition, patients with NLR (>3.45), PLR (>166.5) and LMR (≤2.30) were significantly associated with decreased CSS, respectively (P<0.001). Multivariate analysis revealed that GPS (P<0.001), PLR (P=0.002) and LMR (P=0.002) were independent prognostic factors in patients with ESCC. In addition, a nomogram was established according to all significantly independent factors for CSS. The Harrell’s c-index for CSS prediction was 0.72. Conclusion: GPS, PLR and LMR were potential prognostic biomarkers in patients with ESCC. The nomogram based on CSS could be used as an accurately prognostic prediction for patients with ESCC. PMID:26328248

Increased Trimethylamine N-oxide (TMAO) Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus

PubMed Central

Wilson Tang, W. H.; Wang, Zeneng; Li, Xinmin S.; Fan, Yiying; Li, Daniel S.; Wu, Yuping; Hazen, Stanley L.

2017-01-01

Background Recent studies show a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine and coronary artery disease pathogenesis. Concentrations of a pro-atherogenic gut microbe-generated metabolite, trimethylamine N-oxide (TMAO), predict increased incident cardiovascular disease risks in multiple cohorts. TMAO concentrations are increased in patients with type 2 diabetes mellitus (T2DM), but their prognostic value and relation to glycemic control are unclear. Methods We examined the relationship between fasting TMAO and two of its nutrient precursors, choline and betaine, versus 3-year major adverse cardiac events and 5-year mortality in 1,216 stable patients with T2DM who underwent elective diagnostic coronary angiography. Results TMAO (4.4 µmol/L [interquartile range 2.8–7.7µmol/L] vs. 3.6[2.3–5.7µmol/L]; P<0.001) and choline concentrations were higher in individuals with T2DM versus healthy controls. Within T2DM patients, higher plasma TMAO was associated with a significant 3.0-fold increased 3-year major adverse cardiac events risk (P<0.001) and a 3.6-fold increased 5-year mortality risk (P<0.001). Following adjustments for traditional risk factors and high sensitivity C-reactive protein, glycated hemoglobin and estimated glomerular filtration rate, increased TMAO concentrations remained predictive of both major adverse cardiac events and mortality risks in T2DM patients (e.g. Quartiles 4 vs. 1, hazard ratio 2.05[95%CI 1.31–3.20], P<0.001; and 2.07[95%CI 1.37–3.14], P<0.001, respectively). Conclusion Fasting plasma concentrations of the pro-atherogenic gut microbe-generated metabolite TMAO are higher in diabetic patients and portend higher major adverse cardiac events and mortality risks independent of traditional risk factors, renal function, and relationship to glycemic control. PMID:27864387

Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus.

PubMed

Tang, W H Wilson; Wang, Zeneng; Li, Xinmin S; Fan, Yiying; Li, Daniel S; Wu, Yuping; Hazen, Stanley L

2017-01-01

Recent studies show a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine and coronary artery disease pathogenesis. Concentrations of a proatherogenic gut microbe-generated metabolite, trimethylamine N-oxide (TMAO), predict increased incident cardiovascular disease risks in multiple cohorts. TMAO concentrations are increased in patients with type 2 diabetes mellitus (T2DM), but their prognostic value and relation to glycemic control are unclear. We examined the relationship between fasting TMAO and 2 of its nutrient precursors, choline and betaine, vs 3-year major adverse cardiac events and 5-year mortality in 1216 stable patients with T2DM who underwent elective diagnostic coronary angiography. TMAO [4.4 μmol/L (interquartile range 2.8-7.7 μmol/L) vs 3.6 (2.3-5.7 μmol/L); P < 0.001] and choline concentrations were higher in individuals with T2DM vs healthy controls. Within T2DM patients, higher plasma TMAO was associated with a significant 3.0-fold increased 3-year major adverse cardiac event risk (P < 0.001) and a 3.6-fold increased 5-year mortality risk (P < 0.001). Following adjustments for traditional risk factors and high-sensitivity C-reactive protein, glycohemoglobin, and estimated glomerular filtration rate, increased TMAO concentrations remained predictive of both major adverse cardiac events and mortality risks in T2DM patients [e.g., quartiles 4 vs 1, hazard ratio 2.05 (95% CI, 1.31-3.20), P < 0.001; and 2.07 (95% CI, 1.37-3.14), P < 0.001, respectively]. Fasting plasma concentrations of the proatherogenic gut microbe-generated metabolite TMAO are higher in diabetic patients and portend higher major adverse cardiac events and mortality risks independent of traditional risk factors, renal function, and relationship to glycemic control. © 2016 American Association for Clinical Chemistry.

The clinical safety of high-dose piracetam--its use in the treatment of acute stroke.

PubMed

De Reuck, J; Van Vleymen, B

1999-03-01

Recent post-marketing surveillance reports have confirmed the benign safety profile and lack of organ toxicity shown by piracetam during its 25 years of clinical usage. Tolerance has proved equally good with the more recent use of larger doses (up to 24 g/day) for the long-term control of cortical myoclonus and when given intravenously to patients with acute stroke. This paper provides a brief review of these findings and records the safety of piracetam as found in the Piracetam in Acute Stroke Study (PASS), a randomized multicenter placebo-controlled study in 927 patients with acute ischemic stroke. Patients receive one intravenous bolus injection of placebo or 12 g piracetam, piracetam 12 g daily for 4 weeks and maintenance treatment for 8 weeks. The major results have been reported (De Deyn et al., Stroke 28 [1997] 2347-2352). Safety was assessed taking into account adverse events including abnormal laboratory test results and mortality. Death within 12 weeks occurred more frequently in the piracetam group but the difference from placebo was not significant. Of many potential risk, prognostic and treatment-related factors examined by logistic regression, 6 contributed significantly to death of which the most important were initial severity of stroke and age. Neither treatment nor any treatment-related factor contributed significantly to death. Adverse events were similar in frequency, type and severity in piracetam and placebo groups. Events of cerebral, non-cerebral and uncertain origin likewise occurred with similar frequency. Few patients discontinued because of adverse events. There was no difference between treatments in the frequency of events associated with bleeding, including hemorrhagic transformation of infarction. An important finding was that, of 31 patients with primary hemorrhagic stroke enrolled, 3 piracetam-treated patients died compared with 6 on placebo. The results suggest that piracetam in high dosage may be given to patients with acute stroke without significant adverse effects.

Mortality-related Factors in Patients with Malignant Obstructive Jaundice.

PubMed

Kurniawan, Juferdy; Hasan, Irsan; Gani, Rino Alvani; Simadibrata, Marcellus

2016-10-01

to obtain survival rate and mortality-related factors of malignant obstructive jaundice patients. all medical records of obstructive jaundice inpatient at Cipto Mangunkusumo Hospital, Jakarta from January 2010 to December 2013 were reviewed retrospectively. The following factors were analyzed in terms of mortality: age, gender, sepsis, hypoalbumin, serum bilirubin level, serum CA 19-9 level, billiary drainage, non-ampulla Vateri carcinoma, and comorbid factors. total 181 out of 402 patients were enrolled in this study with male proportion was 58.6%, and patients aged 50 years or above was 57.5%. Multivariate analysis showed that only sepsis, unsuccessful or no prior biliary drainage and Charlson comorbid score ≥4 were independent predictors of mortality. Patients with significant prognostic factors had median survival 14 days compared with overall median survival 26 days. Score ≥2 identified as the highest prognostic score threshold with sensitivity 68%, specificity 75%, and AUC on ROC curve 0.769. sepsis, unsuccessful or no prior bilirary drainage, and Charlson comorbid score ≥4 are factors significantly associated with shortened survival in malignant obstructive jaundice patients. Prognostic score  ≥2 was determined to classify patients into high risk mortality group. Mortality of patients with those significant prognostic factors can be predicted in 76.9%.

State of the art and taxonomy of prognostics approaches, trends of prognostics applications and open issues towards maturity at different technology readiness levels

NASA Astrophysics Data System (ADS)

Javed, Kamran; Gouriveau, Rafael; Zerhouni, Noureddine

2017-09-01

Integrating prognostics to a real application requires a certain maturity level and for this reason there is a lack of success stories about development of a complete Prognostics and Health Management system. In fact, the maturity of prognostics is closely linked to data and domain specific entities like modeling. Basically, prognostics task aims at predicting the degradation of engineering assets. However, practically it is not possible to precisely predict the impending failure, which requires a thorough understanding to encounter different sources of uncertainty that affect prognostics. Therefore, different aspects crucial to the prognostics framework, i.e., from monitoring data to remaining useful life of equipment need to be addressed. To this aim, the paper contributes to state of the art and taxonomy of prognostics approaches and their application perspectives. In addition, factors for prognostics approach selection are identified, and new case studies from component-system level are discussed. Moreover, open challenges toward maturity of the prognostics under uncertainty are highlighted and scheme for an efficient prognostics approach is presented. Finally, the existing challenges for verification and validation of prognostics at different technology readiness levels are discussed with respect to open challenges.

[Clinical characteristics and prognostic factors of pulmonary tuberculosis with concurrent lung cancer].

PubMed

Gu, Yingchun; Song, Yelin; Liu, Yufeng

2014-09-30

To explore the clinical characteristics and prognostic factors of pulmonary tuberculosis with concurrent lung cancer. Comprehensive analyses were conducted for 58 cases of pulmonary tuberculosis patients with lung cancer. Their clinical symptoms, signs and imaging results were analyzed between January 1998 and January 2005 at Qingdao Chest Hospital. Kaplan-Meier method was utilized to calculate their survival rates. Nine prognostic characteristics were analyzed. Single factor analysis was performed with Logrank test and multi-factor analysis with Cox regression model. The initial symptoms were cough, chest tightness, fever and hemoptysis. Chest radiology showed the coexistence of two diseases was 36 in the same lobe and 22 in different lobes. And there were pulmonary nodules (n = 24), cavities (n = 19), infiltration (n = 8) and atelectasis (n = 7). According to the pathological characteristics, there were squamous carcinoma (n = 33), adenocarcinoma (n = 17), small cell carcinoma (n = 4) and unidentified (n = 4) respectively. The TNM stages were I (n = 13), II(n = 22), III (n = 16) and IV (n = 7) respectively. The median survival period was 24 months. And the 1, 3, 5-year survival rates were 65.5%, 65.5% and 29.0% respectively. Single factor analysis showed that lung cancer TNM staging (P = 0.000) and tuberculosis activity (P = 0.024) were significantly associated with patient prognosis. And multi-factor analysis showed that lung cancer TNM staging (RR = 2.629, 95%CI: 1.759-3.928, P = 0.000) and tuberculosis activity (RR = 1.885, 95%CI: 1.023-3.471, P = 0.042) were relatively independent prognostic factors. The clinical and radiological characteristics contribute jointly to early diagnosis and therapy of tuberculosis with concurrent lung cancer. And TNM staging of lung cancer and activity of tuberculosis are major prognostic factors.

A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis.

PubMed

Kim, Seok Jin; Yoon, Dok Hyun; Jaccard, Arnaud; Chng, Wee Joo; Lim, Soon Thye; Hong, Huangming; Park, Yong; Chang, Kian Meng; Maeda, Yoshinobu; Ishida, Fumihiro; Shin, Dong-Yeop; Kim, Jin Seok; Jeong, Seong Hyun; Yang, Deok-Hwan; Jo, Jae-Cheol; Lee, Gyeong-Won; Choi, Chul Won; Lee, Won-Sik; Chen, Tsai-Yun; Kim, Kiyeun; Jung, Sin-Ho; Murayama, Tohru; Oki, Yasuhiro; Advani, Ranjana; d'Amore, Francesco; Schmitz, Norbert; Suh, Cheolwon; Suzuki, Ritsuro; Kwong, Yok Lam; Lin, Tong-Yu; Kim, Won Seog

2016-03-01

The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted. We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort. We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group. PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy. Samsung Biomedical Research Institute. Copyright © 2016 Elsevier Ltd. All rights reserved.

TNM: evolution and relation to other prognostic factors.

PubMed

Sobin, Leslie H

2003-01-01

The TNM Classification describes the anatomic extent of cancer. TNM's ability to separately classify the individual tumor (T), node (N), and metastasis (M) elements and then group them into stages differs from other cancer staging classifications (e.g., Dukes), which are only concerned with summarized groups. The objectives of the TNM Classification are to aid the clinician in the planning of treatment, give some indication of prognosis, assist in the evaluation of the results of treatment, and facilitate the exchange of information. During the past 50 years, the TNM system has evolved under the influence of advances in diagnosis and treatment. Radiographic imaging (e.g., endoscopic ultrasound for the depth of invasion of esophageal and rectal tumors) has improved the accuracy of the clinical T, N, and M classifications. Advances in treatment have necessitated more detail in some T4 categories. Developments in multimodality therapy have increased the importance of the "y" symbol and the R (residual tumor) classification. New surgical techniques have resulted in the elaboration of the sentinel node (sn) symbol. The use of immunohistochemistry has resulted in the classification of isolated tumor cells and their distinction from micrometastasis. The most important challenge facing users of the TNM Classification is how it should interface with the large number of non-anatomic prognostic factors that are currently in use or under study. As non-anatomic prognostic factors become widely used, the TNM system provides an inviting foundation upon which to build a prognostic classification; however, this carries a risk that the system will be overwhelmed by a variety of prognostic data. An anatomic extent-of-disease classification is needed to aid practitioners in selecting the initial therapeutic approach, stratifying patients for therapeutic studies, evaluating non-anatomic prognostic factors at specific anatomic stages, comparing the weight of non-anatomic factors with extent of disease, and communicating the extent of disease data in a uniform manner. Methods are needed to express the overall prognosis without losing the vital anatomic content of TNM. These methods should be able to integrate multiple prognostic factors, including TNM, while permitting the TNM system to remain intact and distinct. This article discusses examples of such approaches.

Neuroimaging and Neurodevelopmental Outcome in Extremely Preterm Infants

PubMed Central

Barnes, Patrick D.; Bulas, Dorothy; Slovis, Thomas L.; Finer, Neil N.; Wrage, Lisa A.; Das, Abhik; Tyson, Jon E.; Stevenson, David K.; Carlo, Waldemar A.; Walsh, Michele C.; Laptook, Abbot R.; Yoder, Bradley A.; Van Meurs, Krisa P.; Faix, Roger G.; Rich, Wade; Newman, Nancy S.; Cheng, Helen; Heyne, Roy J.; Vohr, Betty R.; Acarregui, Michael J.; Vaucher, Yvonne E.; Pappas, Athina; Peralta-Carcelen, Myriam; Wilson-Costello, Deanne E.; Evans, Patricia W.; Goldstein, Ricki F.; Myers, Gary J.; Poindexter, Brenda B.; McGowan, Elisabeth C.; Adams-Chapman, Ira; Fuller, Janell; Higgins, Rosemary D.

2015-01-01

BACKGROUND: Extremely preterm infants are at risk for neurodevelopmental impairment (NDI). Early cranial ultrasound (CUS) is usual practice, but near-term brain MRI has been reported to better predict outcomes. We prospectively evaluated MRI white matter abnormality (WMA) and cerebellar lesions, and serial CUS adverse findings as predictors of outcomes at 18 to 22 months’ corrected age. METHODS: Early and late CUS, and brain MRI were read by masked central readers, in a large cohort (n = 480) of infants <28 weeks’ gestation surviving to near term in the Neonatal Research Network. Outcomes included NDI or death after neuroimaging, and significant gross motor impairment or death, with NDI defined as cognitive composite score <70, significant gross motor impairment, and severe hearing or visual impairment. Multivariable models evaluated the relative predictive value of neuroimaging while controlling for other factors. RESULTS: Of 480 infants, 15 died and 20 were lost. Increasing severity of WMA and significant cerebellar lesions on MRI were associated with adverse outcomes. Cerebellar lesions were rarely identified by CUS. In full multivariable models, both late CUS and MRI, but not early CUS, remained independently associated with NDI or death (MRI cerebellar lesions: odds ratio, 3.0 [95% confidence interval: 1.3–6.8]; late CUS: odds ratio, 9.8 [95% confidence interval: 2.8–35]), and significant gross motor impairment or death. In models that did not include late CUS, MRI moderate-severe WMA was independently associated with adverse outcomes. CONCLUSIONS: Both late CUS and near-term MRI abnormalities were associated with outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of near-term neuroimaging. PMID:25554820

High frequency of CD34+CD38-/low immature leukemia cells is correlated with unfavorable prognosis in acute myeloid leukemia.

PubMed

Plesa, Adriana; Dumontet, Charles; Mattei, Eve; Tagoug, Ines; Hayette, Sandrine; Sujobert, Pierre; Tigaud, Isabelle; Pages, Marie Pierre; Chelghoum, Youcef; Baracco, Fiorenza; Labussierre, Helene; Ducastelle, Sophie; Paubelle, Etienne; Nicolini, Franck Emmanuel; Elhamri, Mohamed; Campos, Lydia; Plesa, Claudiu; Morisset, Stéphane; Salles, Gilles; Bertrand, Yves; Michallet, Mauricette; Thomas, Xavier

2017-12-26

To evaluate the importance of the CD34+CD38- cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival. Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia (AML) were studied between September 2008 and December 2010 at our Institution (Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8C panels and FACS CANTO and Diva software (BD Bioscience). We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38- population. Using a cut-off value of 1% of CD34+CD38- from total "bulk leukemic cells" we found that a high (> 1%) level of CD34+CD38- blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38- leukemic cells > 1% was an independent predictor of DFS [HR = 2.8 (1.02-7.73), P = 0.04] and OS [HR = 2.65 (1.09-6.43), P = 0.03]. Taken together, these results show that a CD34/CD38 "backbone" for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.

The evolution of clinical trials for infant acute lymphoblastic leukemia

PubMed Central

Kotecha, R S; Gottardo, N G; Kees, U R; Cole, C H

2014-01-01

Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior outcome in comparison with older children. Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has plateaued in recent years. Historically, infants were treated on risk-adapted childhood ALL protocols. These studies were pivotal in identifying the need for infant-specific protocols, delineating prognostic categories and the requirement for a more unified approach between study groups to overcome limitations in accrual because of low incidence. This subsequently led to the development of collaborative infant-specific studies. Landmark outcomes have included the elimination of cranial radiotherapy following the discovery of intrathecal and high-dose systemic therapy as a superior and effective treatment strategy for central nervous system disease prophylaxis, with improved neurodevelopmental outcome. Universal prospective identification of independent adverse prognostic factors, including presence of a mixed lineage leukemia rearrangement and young age, has established the basis for risk stratification within current trials. The infant-specific trials have defined limits to which conventional chemotherapeutic agents can be intensified to optimize the balance between treatment efficacy and toxicity. Despite variations in therapeutic intensity, there has been no recent improvement in survival due to the equilibrium between relapse and toxicity. Ultimately, to improve the outcome for infants with ALL, key areas still to be addressed include identification and adaptation of novel prognostic markers and innovative therapies, establishing the role of hematopoietic stem cell transplantation in first complete remission, treatment strategies for relapsed/refractory disease and monitoring and timely intervention of late effects in survivors. This would be best achieved through a single unified international trial. PMID:24727996

Detection of circulating Bmi-1 mRNA in plasma and its potential diagnostic and prognostic value for uterine cervical cancer.

PubMed

Zhang, Xin; Wang, Chuanxin; Wang, Lili; Du, Lutao; Wang, Shun; Zheng, Guixi; Li, Wei; Zhuang, Xuewei; Zhang, Xuhua; Dong, Zhaogang

2012-07-01

Bmi-1 is overexpressed in uterine cervical cancer (UCC) and is found to be associated with adverse clinical characteristics and poor prognosis. However, little information is available on the status of circulating Bmi-1 mRNA in UCC. Because circulating cell-free nucleic acids have emerged as a novel class of markers for cancer detection, our research aims to address this question by detecting the circulating Bmi-1 mRNA and to assess its diagnostic and prognostic potential in UCC. Reverse transcription quantitative real-time PCR method was established to detect the circulating Bmi-1 mRNA in plasma of 109 patients with UCC, 138 patients with cervical intraepithelial neoplasia (CIN) and 80 healthy volunteers, and found that it was significantly increased in UCC compared with CINs and healthy controls (all at p < 0.001). Moreover, its high level was significantly correlated with advanced clinical stage (p < 0.001) and positive lymph nodes metastasis (p = 0.002). The area under the receiver operating characteristic curve (AUC) was 0.881, and the optimal cut-off value was 0.057, providing a sensitivity of 69.7% and a specificity of 95.9%. The AUC for circulating Bmi-1 mRNA showed higher diagnosis capability than that for SCC-Ag (p = 0.035) or CA125 (p < 0.001) currently utilized. Kaplan-Meier analysis demonstrated a correlation between increased circulating Bmi-1 mRNA level and reduced disease-free survival (DFS) (p = 0.001) and overall survival (OS) (p = 0.015). And, Cox analysis indicated that it was an independent prognostic factor for DFS and OS. We conclude that circulating Bmi-1 mRNA may be a potential noninvasive molecular marker for diagnosis and prognosis of UCC. Copyright © 2011 UICC.

A retrospective analysis of survival factors of high intensity focused ultrasound (HIFU) treatment for unresectable pancreatic cancer.

PubMed

Ning, Zhou-Yu; Cheng, Chien-Shan; Xie, Jing; Chen, Qi-Wen; Xu, Li-Tao; Zhuang, Li-Ping; Zhang, Chen-Yue; Song, Li-Bin; Shi, Wei-Dong; Zhu, Xiao-Yan; Wang, Peng; Wang, Kun; Meng, Zhi-Qiang

2016-06-01

To retrospectively evaluate possible impact factors of HIFU treatment outcome for unresectable pancreatic cancer patients. A total of 689 patients with unresectable pancreatic cancer were recruited in our center from December 30, 2007 to January 30, 2015. 436 patients with unresectable pancreatic cancers received HIFU treatment; the other 253 patients received non-HIFU treatment. Among these 436 patients, 345 patients received a one-time HIFU treatment, 91 patients received HIFU treatment from 2 to 5 times in the same pancreatic mass; 89 patients received HIFU treatment alone; 347 patients received HIFU-based combined therapies. Complications and overall survivals (OS) data in each group were collected. The median overall survivals (mOS) in HIFU group and non-HIFU group were 7.1 vs. 5 months (P=0.005): 9.3 vs. 7.3 months (P=0.202) for patients with stage II disease, 8.3 vs. 7.3 months (P=0.783) for patients with stage III disease, and 6.4 vs. 4.2 months (P<0.0001) for patients with stage IV disease, respectively. Furthermore, there was a significant difference between repeated HIFU and one-time HIFU (mOS: 8.6 vs. 6.8 months, P=0.011). Time of HIFU treatment (P=0.0027), chemotherapy (P<0.0001), radiotherapy (P=0.0006), regional intra-arterial chemotherapy (RIAC) (P<0.0001), and stage (P<0.0001) were independent prognostic factors for the patients who received HIFU treatment. Cox analysis on the relative risk of prognostic factors showed that repeated HIFU vs. one-time HIFU (HR=0.729: 95% CI=0.576-0.924), chemotherapy vs. non-chemotherapy (HR=0.664: 95% CI=0.576-0.766), radiotherapy vs. non-radiotherapy (HR=0.580: 95% CI=0.427-0.789), RIAC vs. non-RIAC (HR=0.737: 95% CI=0.648-0.837), and stage (HR=1.386, 95% CI=1.187-1.619) were associated with significantly inferior survival. Overall, adverse events occurred in 23.2% (101/436) in the HIFU group, which included increase of serum or urinary amylase levels, incomplete intestinal obstruction, mild fever, etc. There were no severe adverse events such as skin burns or GI perforation related to HIFU therapy in any of the patients treated. This retrospective analysis revealed that the use of a multimodal treatment approach (the combined therapy of HIFU, RIAC, and chemotherapy, with or without radiotherapy) could improve survival of patients with unresectable pancreatic cancer, and repeated HIFU presented a survival benefit and did not increase risk.

Re-evaluation of DNA Index as a Prognostic Factor in Children with Precursor B Cell Acute Lymphoblastic Leukemia.

PubMed

Noh, O Kyu; Park, Se Jin; Park, Hyeon Jin; Ju, HeeYoung; Han, Seung Hyon; Jung, Hyun Joo; Park, Jun Eun

2017-09-01

We aimed to investigate the prognostic value of DNA index (DI) in children with precursor B cell acute lymphoblastic lymphoma (pre-B ALL). From January 2003 to December 2014, 72 children diagnosed with pre-B ALL were analyzed. We analyzed the prognostic value of DI and its relations with other prognostic factors. The DI cut-point of 1.16 did not discriminate significantly the groups between high and low survivals (DI≥1.16 versus <1.16; 5-year OS, 90.5% vs. 82.8%, p =0.665). We explored the survivals according to the level of DI (<1.00, 1.00, 1.01-1.30, 1.31-1.60, 1.61-1.90, and >1.90), and the survival of children with a DI between 1.00-1.90 were significantly higher than that of children with DI of <1.00 or >1.90 (5-year OS, 90.6% vs. 50.0%, p <0.001). The DI of 1.16 was not a significant cut-point discriminating the risk group in children with pre-B ALL. However, the DI divided by specific ranges of values remained an independent prognostic factor. Further studies are warranted to re-evaluate the prognostic value and cut-point of DI in children treated with recent treatment protocols. © 2017 by the Association of Clinical Scientists, Inc.

Serum total hCGβ level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract.

PubMed

Douglas, J; Sharp, A; Chau, C; Head, J; Drake, T; Wheater, M; Geldart, T; Mead, G; Crabb, S J

2014-04-02

Serum total human chorionic gonadotrophin β subunit (hCGβ) level might have prognostic value in urothelial transitional cell carcinoma (TCC) but has not been investigated for independence from other prognostic variables. We utilised a clinical database of patients receiving chemotherapy between 2005 and 2011 for urothelial TCC and an independent cohort of radical cystectomy patients for validation purposes. Prognostic variables were tested by univariate Kaplan-Meier analyses and log-rank tests. Statistically significant variables were then assessed by multivariate Cox regression. Total hCGβ level was dichotomised at < vs ≥2 IU l(-1). A total of 235 chemotherapy patients were eligible. For neoadjuvant chemotherapy, established prognostic factors including low ECOG performance status, normal haemoglobin, lower T stage and suitability for cisplatin-based chemotherapy were associated with favourable survival in univariate analyses. In addition, low hCGβ level was favourable when assessed either before (median survival not reached vs 1.86 years, P=0.001) or on completion of chemotherapy (4.27 vs 0.42 years, P=0.000002). This was confirmed in multivariate analyses and in patients receiving first- and second-line palliative chemotherapy, and in a radical cystectomy validation set. Serum total hCGβ level is an independent prognostic factor in patients receiving chemotherapy for urothelial TCC in both curative and palliative settings.

[Neuroendocrine neoplasm of digestive system with different grades: a clinicopathologic and prognostic study].

PubMed

Zhang, Ming-hui; Liu, Yan-hui; Luo, Xin-lan; Lin, Xing-tao; Zhuang, Heng-guo

2012-07-01

To study the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. The clinicopathologic features of 139 cases of neuroendocrine neoplasm occurring in digestive system were retrospectively reviewed and graded according to the 2010 World Health Organization classification of tumours of the digestive system. Immunohistochemical study for synaptophysin, chromogranin A and Ki-67 was carried out. The follow-up and survival data were analysed using Kaplan-Meier method. Prognostic factors were tested by Log-rank testing and independent risk factors were analysed using Cox regression model. Amongst the 139 cases studied, there were 88 cases (63.3%) of grade 1 tumors, 9 cases (6.5%) of grade 2 tumors and 42 cases (30.2%) of grade 3 tumors. There was diffusely positive staining for synaptophysin and chromogranin A in most of the grade 1 and grade 2 tumors. The staining in grade 3 tumors however was focal (P < 0.05). The differences in tumor size, depth of invasion, presence of tumor emboli, perineural permeation, nodal involvement, distant metastasis and survival rate amongst the three groups was statistically significant (P < 0.05). There is significant difference in the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. It is considered as an independent prognostic factor and represents a useful tool for prognostic evaluation of such tumors, both in clinical practice and research.

Recurrent ischemia across the spectrum of acute coronary syndromes: prevalence and prognostic significance of (re-)infarction and ST-segment changes in a large contemporary registry.

PubMed

Yan, Andrew T; Steg, Philippe Gabriel; Fitzgerald, Gordon; Feldman, Laurent J; Eagle, Kim A; Gore, Joel M; Anderson, Frederick A; López-Sendón, Jose; Gurfinkel, Enrique P; Brieger, David; Goodman, Shaun G

2010-11-05

There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era. The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS. Data were collected on standardized case report forms. Of the 29,400 ACS patients enrolled in May 2000-March 2007, 21% developed RI; 2.4%, 4.9%, and 16% had myocardial (re-)infarction [(re-)MI], RI with ST-segment changes, and RI without ST-segment changes (not mutually exclusive), respectively. Rates of in-hospital mortality and complications, and 6-month mortality were significantly higher among patients with RI compared to those without; the rates were highest for patients who developed (re-)MI, followed by those with RI and ST-segment changes. After adjusting for other validated prognosticators in the GRACE risk score, all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality. Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI (P for interaction=0.003). Despite the current use of intensive medical therapies, RI remains a common and serious consequence across the spectrum of ACS. Different types of RI confer a variable adverse prognostic impact. Re-MI is associated with the worst outcome, which appears to be mitigated by early revascularization. Our findings underscore the persistent need to improve the treatment of ACS. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Prognostic significance of infarct core pathology revealed by quantitative non-contrast in comparison with contrast cardiac magnetic resonance imaging in reperfused ST-elevation myocardial infarction survivors.

PubMed

Carrick, David; Haig, Caroline; Rauhalammi, Sam; Ahmed, Nadeem; Mordi, Ify; McEntegart, Margaret; Petrie, Mark C; Eteiba, Hany; Hood, Stuart; Watkins, Stuart; Lindsay, Mitchell; Mahrous, Ahmed; Ford, Ian; Tzemos, Niko; Sattar, Naveed; Welsh, Paul; Radjenovic, Aleksandra; Oldroyd, Keith G; Berry, Colin

2016-04-01

To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean ± SD age 59 ± 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume ≥20% at 6 months. All-cause death or first heart failure hospitalization was a pre-specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all-cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar. Infarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted. CLINICALTRIALS. NCT02072850. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

[Prognosis in pediatric traumatic brain injury. A dynamic cohort study].

PubMed

Vázquez-Solís, María G; Villa-Manzano, Alberto I; Sánchez-Mosco, Dalia I; Vargas-Lares, José de Jesús; Plascencia-Fernández, Irma

2013-01-01

traumatic brain injury is a main cause of hospital admission and death in children. Our objective was to identify prognostic factors of pediatric traumatic brain injury. this was a dynamic cohort study of traumatic brain injury with 6 months follow-up. The exposition was: mild or moderate/severe traumatic brain injury, searching for prognosis (morbidity-mortality and decreased Glasgow scale). Relative risk and logistic regression was estimated for prognostic factors. we evaluated 440 patients with mild traumatic brain injury and 98 with moderate/severe traumatic brain injury. Morbidity for mild traumatic brain injury was 1 %; for moderate/severe traumatic brain injury, 5 %. There were no deaths. Prognostic factors for moderate/severe traumatic brain injury were associated injuries (RR = 133), fractures (RR = 60), street accidents (RR = 17), night time accidents (RR = 2.3) and weekend accidents (RR = 2). Decreased Glasgow scale was found in 9 %, having as prognostic factors: visible injuries (RR = 3), grown-up supervision (RR = 2.5) and time of progress (RR = 1.6). there should be a prognosis established based on kinetic energy of the injury and not only with Glasgow Scale.

Audiophonological results after cochlear implantation in 40 congenitally deaf patients: preliminary results.

PubMed

Loundon, N; Busquet, D; Roger, G; Moatti, L; Garabedian, E N

2000-11-30

The aim of this study is to evaluate the prognostic factors of audiophonological results in cochlear implant in congenitally deaf patients. Between 1991 and 1996. 40 congenitally deaf children underwent cochlear implantation in our department, at an average age of 7 years (median: 5 years). The results of speech therapy were evaluated with a mean follow-up of 2 years and were classified according to four criteria: perception of sound, speech perception, speech production and the level of oral language. For each criterion, a score was established ranging from zero to four. These scores were weighted according to age such that the results before and after implantation only reflected the changes related to the implantation. The prognostic factors for good results were: a good level of oral communication before implantation, residual hearing, progressive deafness and implantation at a young age. On the other hand, poor prognostic factors were: the presence of behavioral disorders and poor communication skills prior to implantation. Overall, the major prognostic factor for a good outcome appeared to be the preoperative level of oral language, even if this was rudimentary.

Prognostic factors for patients undergoing vitrified-warmed human embryo transfer cycles: a retrospective cohort study.

PubMed

Takahashi, Toshifumi; Hasegawa, Ayumi; Igarashi, Hideki; Amita, Mitsuyoshi; Matsukawa, Jun; Takehara, Isao; Suzuki, Satoko; Nagase, Satoru

2017-06-01

We examined the prognostic factors for pregnancy in 210 vitrified-warmed embryo transfer (ET) cycles in 121 patients. The univariate analysis showed that age, gravida, the number of cycles associated with infertility caused by endometriosis, the number of previous assisted reproductive technology (ART) treatment cycles, and the number of ICSI procedures were significantly lower in pregnant cycles compared with non-pregnant cycles. The percentages of ET using at least one intact embryo and of ET using at least one embryo that had developed further after warming were significantly higher in pregnant cycles compared with non-pregnant cycles. Multivariate logistic regression analysis showed that previous ART treatment cycles, ET with at least one intact embryo, and ET using at least one embryo that had developed further were independent prognostic factors for pregnancy in vitrified-warmed ET cycles. We conclude that fewer previous ART treatment cycles, ET using at least one intact embryo, and ET with embryos that have developed further after warming might be favourable prognostic factors for pregnancy in vitrified-warmed ET cycles.

Predicting stabilizing treatment outcomes for complex posttraumatic stress disorder and dissociative identity disorder: an expertise-based prognostic model.

PubMed

Baars, Erik W; van der Hart, Onno; Nijenhuis, Ellert R S; Chu, James A; Glas, Gerrit; Draijer, Nel

2011-01-01

The purpose of this study was to develop an expertise-based prognostic model for the treatment of complex posttraumatic stress disorder (PTSD) and dissociative identity disorder (DID). We developed a survey in 2 rounds: In the first round we surveyed 42 experienced therapists (22 DID and 20 complex PTSD therapists), and in the second round we surveyed a subset of 22 of the 42 therapists (13 DID and 9 complex PTSD therapists). First, we drew on therapists' knowledge of prognostic factors for stabilization-oriented treatment of complex PTSD and DID. Second, therapists prioritized a list of prognostic factors by estimating the size of each variable's prognostic effect; we clustered these factors according to content and named the clusters. Next, concept mapping methodology and statistical analyses (including principal components analyses) were used to transform individual judgments into weighted group judgments for clusters of items. A prognostic model, based on consensually determined estimates of effect sizes, of 8 clusters containing 51 factors for both complex PTSD and DID was formed. It includes the clusters lack of motivation, lack of healthy relationships, lack of healthy therapeutic relationships, lack of other internal and external resources, serious Axis I comorbidity, serious Axis II comorbidity, poor attachment, and self-destruction. In addition, a set of 5 DID-specific items was constructed. The model is supportive of the current phase-oriented treatment model, emphasizing the strengthening of the therapeutic relationship and the patient's resources in the initial stabilization phase. Further research is needed to test the model's statistical and clinical validity.

Treatment and prognostic factors of radiation-associated angiosarcoma (RAAS) after primary breast cancer: a systematic review.

PubMed

Depla, A L; Scharloo-Karels, C H; de Jong, M A A; Oldenborg, S; Kolff, M W; Oei, S B; van Coevorden, F; van Rhoon, G C; Baartman, E A; Scholten, R J; Crezee, J; van Tienhoven, G

2014-07-01

Radiation-associated angiosarcoma (RAAS) of the breast is a rare, aggressive disease. The incidence is increasing with the prolonged survival of women irradiated for primary breast cancer. Surgery is the current treatment of choice. Prognosis is poor. This review aims to evaluate all publications on primary treatment of RAAS to identify prognostic factors and evaluate treatment modalities. Databases were searched for articles with published individual patient data on prognostic factors, treatment and follow-up of patients with RAAS. A regression analysis was performed to test the prognostic values of age, interval between primary treatment and RAAS, tumour size and grade on the local recurrence-free interval (LRFI) and overall survival (OS). The effects of treatment modalities surgery, radiation (with or without hyperthermia) and chemotherapy or combinations were evaluated. 74 articles were included, representing data on 222 patients. In these patients, the 5-year OS was 43% and 5-year LRFI was 32%. Tumour size and age were significant prognostic factors on LRFI and OS. Of all patients, 68% received surgery alone, 17% surgery and reirradiation and 6% surgery with chemotherapy. The remaining 9% received primary treatments without surgery. Surgery with radiotherapy had a better 5-year LRFI of 57% compared to 34% for surgery alone (p=0.008). The value of other treatment modalities could not be assessed. This systematic review confirms the poor prognosis of RAAS. Tumour size and age were of prognostic value. The addition of reirradiation to surgery in the treatment of RAAS appears to enhance local control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Difference in Postsurgical Prognostic Factors between Lung Adenocarcinoma and Squamous Cell Carcinoma

PubMed Central

Sakai, Hiroki; Kimura, Hiroyuki; Miyazawa, Tomoyuki; Marushima, Hideki; Saji, Hisashi

2017-01-01

Purpose: The aim of this study was to compare the clinicopathologic prognostic factors between patients who underwent lung resection for adenocarcinoma (AD) and those with squamous cell carcinoma (SQ). Methods: A database of patients with lung AD or SQ who underwent surgery with curative intent in our department from January 2008 to December 2014 was reviewed. Associations between various clinicopathologic factors, postsurgical recurrence-free survival (RFS), and overall survival (OS) were analyzed to find significant prognostic factors. Results: A total of 537 lung cancer patients (AD, 434; SQ, 103) were included in this study. Although RFS was similar in patients with AD and SQ, OS was significantly poorer in those with SQ. Multivariate analysis in patients with AD revealed that age (≥69 vs. <69), lymphatic invasion, and histologic pleural invasion (p0 vs. p1–3) were associated with RFS, while gender and pleural invasion were associated with OS. In SQ, however, smoking, clinical stage, and pulmonary metastasis were associated with RFS in the multivariate analysis. Conclusion: Since significant postoperative prognostic factors are quite different between lung AD and SQ, these two histologic types should be differently analyzed in a clinical study. PMID:28966230

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

Body mass index is a prognostic factor in adult patients with acute myeloid leukemia.

PubMed

Ando, Taiki; Yamazaki, Etsuko; Ogusa, Eriko; Ishii, Yoshimi; Yamamoto, Wataru; Motohashi, Kenji; Tachibana, Takayoshi; Hagihara, Maki; Matsumoto, Kenji; Tanaka, Masatsugu; Hashimoto, Chizuko; Koharazawa, Hideyuki; Fujimaki, Katsumichi; Taguchi, Jun; Fujita, Hiroyuki; Kanamori, Heiwa; Fujisawa, Shin; Nakajima, Hideaki

2017-05-01

Body mass index (BMI), which represents the proportion of weight to height, is a controversial prognostic factor for acute myeloid leukemia (AML). We evaluated prognostic value of BMI in Japanese AML. The study included 369 adult patients with newly diagnosed AML who were administered either daunorubicin or idarubicin with cytarabine as induction chemotherapy. The patients were categorized into two groups according to their BMI: the NW group (BMI < 25.0 kg/m 2 ; normal and underweight) and OW group (BMI ≥ 25.0 kg/m 2 ; overweight and obese). We analyzed treatment efficacy and toxicity of induction chemotherapy, and survival outcomes in each group. Patients in the OW group showed a better complete remission rate than the NW group (86.1 versus 76.5%, P = 0.045), no early death (0.0 versus 4.1%, P = 0.042), and better overall survival (OS) at 3 years (62.2 versus 50.1%, P = 0.012). Multivariate analysis showed BMI is an independent prognostic factor for OS (hazard ratio 0.62, 95% confidence interval 0.42-0.92, P = 0.017). These results indicate the prognostic value of BMI in adult AML patients.

Chronic Kidney Disease in Pregnancy.

PubMed

Koratala, Abhilash; Bhattacharya, Deepti; Kazory, Amir

2017-09-01

With the increasing prevalence of chronic kidney disease (CKD) worldwide, the number of pregnant women with various degrees of renal dysfunction is expected to increase. There is a bidirectional relation between CKD and pregnancy in which renal dysfunction negatively affects pregnancy outcomes, and the pregnancy can have a deleterious impact on various aspects of kidney disease. It has been shown that even mild renal dysfunction can increase considerably the risk of adverse maternal and fetal outcomes. Moreover, data suggest that a history of recovery from acute kidney injury is associated with adverse pregnancy outcomes. In addition to kidney dysfunction, maternal hypertension and proteinuria predispose women to negative outcomes and are important factors to consider in preconception counseling and the process of risk stratification. In this review, we provide an overview of the physiologic renal changes during pregnancy as well as available data regarding CKD and pregnancy outcomes. We also highlight the important management strategies in women with certain selected renal conditions that are seen commonly during the childbearing years. We call for future research on underexplored areas such as the concept of renal functional reserve to develop a potential clinical tool for prognostication and risk stratification of women at higher risk for complications during pregnancy.

Endothelial dysfunction in metabolic and vascular disorders.

PubMed

Polovina, Marija M; Potpara, Tatjana S

2014-03-01

Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS

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

Shultz, David B.; Modlin, Leslie A.; Jayachandran, Priya

Purpose: To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS). Patients and Methods: We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS. Results: Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the timemore » of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites. Conclusion: Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.« less

Current concepts in penetrating and blast injury to the central nervous system.

PubMed

Rosenfeld, Jeffrey V; Bell, Randy S; Armonda, Rocco

2015-06-01

To review the current management, prognostic factors and outcomes of penetrating and blast injuries to the central nervous system and highlight the differences between gunshot wound, blast injury and stabbing. A review of the current literature was performed. Of patients with craniocerebral GSW, 66-90% die before reaching hospital. Of those who are admitted to hospital, up to 51% survive. The patient age, GCS, pupil size and reaction, ballistics and CT features are important factors in the decision to operate and in prognostication. Blast injury to the brain is a component of multisystem polytrauma and has become a common injury encountered in war zones and following urban terrorist events. GSW to the spine account for 13-17% of all gunshot injuries. Urgent resuscitation, correction of coagulopathy and early surgery with wide cranial decompression may improve the outcome in selected patients with severe craniocerebral GSW. More limited surgery is undertaken for focal brain injury due to GSW. A non-operative approach may be taken if the clinical status is very poor (GCS 3, fixed dilated pupils) or GCS 4-5 with adverse CT findings or where there is a high likelihood of death or poor outcome. Civilian spinal GSWs are usually stable neurologically and biomechanically and do not require exploration. The indications for exploration are as follows: (1) compressive lesions with partial spinal cord or cauda equina injury, (2) mechanical instability and (3) complications. The principles of management of blast injury to the head and spine are the same as for GSW. Multidisciplinary specialist management is required for these complex injuries.

Determination of Prognostic Factors for Vaginal Mucosal Toxicity Associated With Intravaginal High-Dose Rate Brachytherapy in Patients With Endometrial Cancer

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

Bahng, Agnes Y.; Dagan, Avner; Bruner, Deborah W.

2012-02-01

Purpose: The objective of this study was to determine the patient- and treatment-related prognostic factors associated with vaginal toxicity in patients who received intravaginal high dose rate (HDR) brachytherapy alone as adjuvant treatment for endometrial cancer. Secondary goals of this study included a quantitative assessment of optimal dilator use frequency and a crude assessment of clinical predictors for compliant dilator use. Methods and Materials: We retrospectively reviewed the charts of 100 patients with histologically confirmed endometrial cancer who underwent total hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection and adjuvant intravaginal brachytherapy between 1995 and 2009 at themore » Hospital of University of Pennsylvania. The most common treatment regimen used was 21 Gy in three fractions (71 patients). Symptoms of vaginal mucosal toxicity were taken from the history and physical exams noted in the patients' charts and were graded according to the Common Toxicity Criteria for Adverse Events v. 4.02. Results: The incidence of Grade 1 or asymptomatic vaginal toxicity was 33% and Grade 2-3 or symptomatic vaginal toxicity was 14%. Multivariate analysis of age, active length, and dilator use two to three times a week revealed odds ratios of 0.93 (p = 0.013), 3.96 (p = 0.008), and 0.17 (p = 0.032) respectively. Conclusion: Increasing age, vaginal dilator use of at least two to three times a week, and shorter active length were found to be significantly associated with a decreased risk of vaginal stenosis. Future prospective studies are necessary to validate our findings.« less

DGKI methylation status modulates the prognostic value of MGMT in glioblastoma patients treated with combined radio-chemotherapy with temozolomide.

PubMed

Etcheverry, Amandine; Aubry, Marc; Idbaih, Ahmed; Vauleon, Elodie; Marie, Yannick; Menei, Philippe; Boniface, Rachel; Figarella-Branger, Dominique; Karayan-Tapon, Lucie; Quillien, Veronique; Sanson, Marc; de Tayrac, Marie; Delattre, Jean-Yves; Mosser, Jean

2014-01-01

Consistently reported prognostic factors for glioblastoma (GBM) are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status. 399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1) and MGMT-methylated patients (population 2). Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2. The nomogram-based stratification of the cohort identified two risk groups (high/low) with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram. Our results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future.

Multicollinearity in prognostic factor analyses using the EORTC QLQ-C30: identification and impact on model selection.

PubMed

Van Steen, Kristel; Curran, Desmond; Kramer, Jocelyn; Molenberghs, Geert; Van Vreckem, Ann; Bottomley, Andrew; Sylvester, Richard

2002-12-30

Clinical and quality of life (QL) variables from an EORTC clinical trial of first line chemotherapy in advanced breast cancer were used in a prognostic factor analysis of survival and response to chemotherapy. For response, different final multivariate models were obtained from forward and backward selection methods, suggesting a disconcerting instability. Quality of life was measured using the EORTC QLQ-C30 questionnaire completed by patients. Subscales on the questionnaire are known to be highly correlated, and therefore it was hypothesized that multicollinearity contributed to model instability. A correlation matrix indicated that global QL was highly correlated with 7 out of 11 variables. In a first attempt to explore multicollinearity, we used global QL as dependent variable in a regression model with other QL subscales as predictors. Afterwards, standard diagnostic tests for multicollinearity were performed. An exploratory principal components analysis and factor analysis of the QL subscales identified at most three important components and indicated that inclusion of global QL made minimal difference to the loadings on each component, suggesting that it is redundant in the model. In a second approach, we advocate a bootstrap technique to assess the stability of the models. Based on these analyses and since global QL exacerbates problems of multicollinearity, we therefore recommend that global QL be excluded from prognostic factor analyses using the QLQ-C30. The prognostic factor analysis was rerun without global QL in the model, and selected the same significant prognostic factors as before. Copyright 2002 John Wiley & Sons, Ltd.

Prognostic factors in sensory recovery after digital nerve repair.

PubMed

Bulut, Tuğrul; Akgün, Ulaş; Çıtlak, Atilla; Aslan, Cihan; Şener, Ufuk; Şener, Muhittin

2016-01-01

The prognostic factors that affect sensory nerve recovery after digital nerve repair are variable because of nonhomogeneous data, subjective tests, and different assessment/scoring methods. The aim of this study was to evaluate the success of sensory nerve recovery after digital nerve repair and to investigate the prognostic factors in sensorial healing. Ninety-six digital nerve repairs of 63 patients were retrospectively evaluated. All nerves were repaired with end-to-end neurorraphy. The static two-point discrimination (s2PD) and Semmes Weinstein monofilament (SWM) tests were performed to evaluate sensory recovery. The association between prognostic factors such as gender, age, involved digit, time from injury to repair, length of follow-up, smoking, concomitant injuries, type of injury, and sensory recovery results were assessed. The s2PD test demonstrated excellent results in 26 nerves (27%), good results in 61 nerves (64%), and poor results in 9 nerves (9%). The results of the SWM test according to Imai classification showed that 31 nerves (32%) were normal, light touch was diminished in 38 nerves (40%), protective sensation was diminished in 17 nerves (18%), loss of protective sensation occurred in 5 nerves (5%), and 5 nerves (5%) were anesthetic. There was a negative relationship between age, smoking, concomitant injuries, and sensory recovery. Our results demonstrate that concomitant tendon, bone and vascular injuries, older age, and smoking were associated with worse sensory nerve recovery results. However, all digital nerve injuries should be repaired, regardless of these prognostic factors.

Prognostic factors in patients with metastatic spinal cord compression secondary to melanoma: a systematic review.

PubMed

Hadden, Nicholas J; McIntosh, Jerome R D; Jay, Samuel; Whittaker, Paula J

2018-02-01

Melanoma is one of the most common primary tumours associated with metastatic spinal cord compression (MSCC). The aim of this review is to identify prognostic factors specifically for MSCC secondary to melanoma. A systematic search of literature was performed in MEDLINE, Embase and the Cochrane Library to identify studies reporting prognostic factors for patients with MSCC secondary to melanoma. Two studies, involving a total of 39 patients, fulfilled the inclusion criteria. The variables associated with increased survival were receiving postoperative radiotherapy, receiving chemotherapy, perioperative lactate dehydrogenase level less than or equal to 8.0 µkat/l, preoperative haemoglobin level more than 11.5 mg/dl, an interval of 4 or more years between melanoma diagnosis and skeletal metastasis, absence of further skeletal metastases, absence of visceral metastases, Eastern Cooperative Oncology Group Performance Status of 2 or less, two or fewer involved vertebrae, being ambulatory preradiotherapy and an interval of more than 7 days between developing motor deficits and radiotherapy. The variables associated with good functional outcome were slow development of motor dysfunction, good performance status and being ambulatory before radiotherapy. The most important prognostic factors for survival are Eastern Cooperative Oncology Group Performance Status of 2 or less and absence of visceral metastases. There is a lack of studies looking specifically at prognostic factors for patients with MSCC secondary to melanoma, and the number of patients involved in the existing studies is small.

Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

PubMed Central

Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

2015-01-01

Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white blood cell count were independent prognostic factors. PMID:26190424

Impact of sex on prognostic host factors in surgical patients with lung cancer.

PubMed

Wainer, Zoe; Wright, Gavin M; Gough, Karla; Daniels, Marissa G; Choong, Peter; Conron, Matthew; Russell, Prudence A; Alam, Naveed Z; Ball, David; Solomon, Benjamin

2017-12-01

Lung cancer has markedly poorer survival in men. Recognized important prognostic factors are divided into host, tumour and environmental factors. Traditional staging systems that use only tumour factors to predict prognosis are of limited accuracy. By examining sex-based patterns of disease-specific survival in non-small cell lung cancer patients, we determined the effect of sex on the prognostic value of additional host factors. Two cohorts of patients treated surgically with curative intent between 2000 and 2009 were utilized. The primary cohort was from Melbourne, Australia, with an independent validation set from the American Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate analyses of validated host-related prognostic factors were performed in both cohorts to investigate the differences in survival between men and women. The Melbourne cohort had 605 patients (61% men) and SEER cohort comprised 55 681 patients (51% men). Disease-specific 5-year survival showed men had statistically significant poorer survival in both cohorts (P < 0.001); Melbourne men at 53.2% compared with women at 68.3%, and SEER 53.3% men and 62.0% women were alive at 5 years. Being male was independently prognostic for disease-specific mortality in the Melbourne cohort after adjustment for ethnicity, smoking history, performance status, age, pathological stage and histology (hazard ratio = 1.54, 95% confidence interval: 1.10-2.16, P = 0.012). Sex differences in non-small cell lung cancer are important irrespective of age, ethnicity, smoking, performance status and tumour, node and metastasis stage. Epidemiological findings such as these should be translated into research and clinical paradigms to determine the factors that influence the survival disadvantage experienced by men. © 2016 Royal Australasian College of Surgeons.

Prognostic factors in Acanthamoeba keratitis.

PubMed

Kaiserman, Igor; Bahar, Irit; McAllum, Penny; Srinivasan, Sathish; Elbaz, Uri; Slomovic, Allan R; Rootman, David S

2012-06-01

To assess the prognostic factors influencing visual prognosis and length of treatment after acanthamoeba keratitis (AK). Forty-two AK eyes of 41 patients treated between 1999 and 2006 were included. A diagnosis of AK was made on the basis of culture results with a corresponding clinical presentation. We calculated the prognostic effect of the various factors on final visual acuity and the length of treatment. Multivariate regression analysis was used to adjust for the simultaneous effects of the various prognostic factors. Mean follow-up was 19.7 ± 21.0 months. Sixty-four percent of cases had > 1 identified risk factor for AK, the most common risk factor being contact lens wear (92.9% of eyes). At presentation, median best spectacle corrected visual acuity (BCVA) was 20/200 (20/30 to Hand Motion [HM]) that improved after treatment to 20/50 (20/20 to Counting Fingers [CF]). Infection acquired by swimming or related to contact lenses had significantly better final BCVA (p = 0.03 and p = 0.007, respectively). Neuritis and pseudodendrites were also associated with better final BCVA (p = 0.04 and p = 0.05, respectively). Having had an epithelial defect on presentation and having been treated with topical steroid were associated with worse final best spectacle corrected visual acuity (BSCVA) (p = 0.0006 and p = 0.04). Multivariate regression analysis found a good initial visual acuity (p = 0.002), infections related to swimming (p = 0.01), the absence of an epithelial defect (p = 0.03), having been treated with chlorhexidine (p = 0.05), and not having receive steroids (p = 0.003) to significantly forecast a good final BCVA. We identified several prognostic factors that can help clinicians evaluate the expected visual damage of the AK infection and thus tailor treatment accordingly. Copyright © 2012 Canadian Ophthalmological Society. All rights reserved.

Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

PubMed Central

Giraldi, L; Leoncini, E; Pastorino, R; Wünsch-Filho, V; de Carvalho, M; Lopez, R; Cadoni, G; Arzani, D; Petrelli, L; Bosetti, C; La Vecchia, C; Garavello, W; Polesel, J; Serraino, D; Simonato, L; Canova, C; Richiardi, L; Boffetta, P; Hashibe, M; Lee, Y C A; Boccia, S

2017-01-01

Abstract Background This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. Patients and methods We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. Results Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01–6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16–2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22–3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03–1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. Conclusions OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients. PMID:28945835

FDG-PET/CT and diffusion-weighted imaging for resected lung cancer: correlation of maximum standardized uptake value and apparent diffusion coefficient value with prognostic factors.

PubMed

Usuda, Katsuo; Funasaki, Aika; Sekimura, Atsushi; Motono, Nozomu; Matoba, Munetaka; Doai, Mariko; Yamada, Sohsuke; Ueda, Yoshimichi; Uramoto, Hidetaka

2018-04-09

Diffusion-weighted magnetic resonance imaging (DWI) is useful for detecting malignant tumors and the assessment of lymph nodes, as FDG-PET/CT is. But it is not clear how DWI influences the prognosis of lung cancer patients. The focus of this study is to evaluate the correlations between maximum standardized uptake value (SUVmax) of FDG-PET/CT and apparent diffusion coefficient (ADC) value of DWI with known prognostic factors in resected lung cancer. A total of 227 patients with resected lung cancers were enrolled in this study. FEG-PET/CT and DWI were performed in each patient before surgery. There were 168 patients with adenocarcinoma, 44 patients with squamous cell carcinoma, and 15 patients with other cell types. SUVmax was a factor that was correlated to T factor, N factor, or cell differentiation. ADC of lung cancer was a factor that was not correlated to T factor, or N factor. There was a significantly weak inverse relationship between SUVmax and ADC (Correlation coefficient r = - 0.227). In analysis of survival, there were significant differences between the categories of sex, age, pT factor, pN factor, cell differentiation, cell type, and SUVmax. Univariate analysis revealed that SUVmax, pN factor, age, cell differentiation, cell type, sex, and pT factor were significant factors. Multivariate analysis revealed that SUVmax and pN factor were independent significant prognostic factors. SUVmax was a significant prognostic factor that is correlated to T factor, N factor, or cell differentiation, but ADC was not. SUVmax may be more useful for predicting the prognosis of lung cancer than ADC values.

Human fetal cardiovascular profile score and neonatal outcome in intrauterine growth restriction.

PubMed

Mäkikallio, K; Räsänen, J; Mäkikallio, T; Vuolteenaho, O; Huhta, J C

2008-01-01

To determine whether low cardiovascular profile (CVP) score has prognostic value for predicting neonatal mortality and severe morbidity in human fetuses with growth restriction. Seventy-five consecutive growth-restricted fetuses with Doppler examination of cardiovascular hemodynamics within a week prior to delivery comprised the study population. Hydrops, heart size, cardiac function and venous and arterial hemodynamics were evaluated for CVP score. The primary outcome measures were neonatal mortality and cerebral palsy. During the neonatal period, six of 75 neonates died and two had cerebral palsy (Group 1, n = 8). Compared with the fetuses discharged home from hospital (Group 2, n = 67), those in Group 1 were delivered at an earlier gestational age (28 (range, 24-35) weeks vs. 35 (range, 26-40) weeks, P < 0.01) and had lower CVP scores (4 (range, 2-6) vs. 9 (range, 5-10), P < 0.0001). All CVP subscale scores were lower (P < 0.01) in Group 1 than in Group 2 fetuses. Gestational age-adjusted hazard ratios (95% CIs) for adverse neonatal outcome were highest for cardiomegaly (13.9 (1.7-114.3), P = 0.014), monophasic atrioventricular filling pattern or holosystolic tricuspid regurgitation (9.5 (2.3-38.4), P = 0.002) and atrial pulsations in the umbilical vein 7.7 (1.4-41.2), P = 0.017). Growth-restricted fetuses with adverse neonatal outcome have lower CVP scores than do fetuses with favorable neonatal outcome. The strongest predictors for adverse neonatal outcome in the CVP score were cardiomegaly, abnormal cardiac function with monophasic atrioventricular filling or holosystolic tricuspid regurgitation and increased systemic venous pressure. These assessments have independent prognostic power for adverse neonatal outcome even after adjustment for gestational age. Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.

P21, COX-2, and E-cadherin are potential prognostic factors for esophageal squamous cell carcinoma.

PubMed

Lin, Yao; Shen, Lu-Yan; Fu, Hao; Dong, Bin; Yang, He-Li; Yan, Wan-Pu; Kang, Xiao-Zheng; Dai, Liang; Zhou, Hai-Tao; Yang, Yong-Bo; Liang, Zhen; Chen, Ke-Neng

2017-02-01

Much research effort has been devoted to identifying prognostic factors for esophageal squamous cell carcinoma (ESCC) by immunohistochemistry; however, no conclusive findings have been reached thus far. We hypothesized that certain molecules identified in previous studies might serve as useful prognostic markers for ESCC. Therefore, the aim of the current study was to validate the most relevant markers showing potential for ESCC prognosis in our prospective esophageal cancer database. A literature search was performed using the PubMed database for papers published between 1980 and 2015 using the following key words: 'esophageal cancer,' 'prognosis,' and 'immunohistochemistry.' Literature selection criteria were established to identify the most widely studied markers, and we further validated the selected markers in a cohort from our single-surgeon team, including 153 esophageal cancer patients treated from 2000 to 2010. A total of 1799 articles were identified, 82 of which met the selection criteria. Twelve markers were found to be the most widely studied, and the validation results indicated that only P21, COX-2, and E-cadherin were independent prognostic factors for ESCC patients in this series. The systemic review and cohort validation suggest that P21, COX-2, and E-cadherin are potential prognostic factors for ESCC, paving the way for more targeted prospective validation in the future. © 2016 International Society for Diseases of the Esophagus.

Clinical Features and Prognostic Factors of Hodgkin's Lymphoma: A Single Center Experience.

PubMed

Kılıçkap, Saadettin; Barışta, Ibrahim; Ulger, Sükran; Celik, Ismail; Selek, Uğur; Yıldız, Ferah; Kars, Ayşe; Ozışık, Yavuz; Tekuzman, Gülten

2013-06-01

Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Retrospective study. Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of "B" symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country.

Metastatic Spinal Cord Compression from Non-Small-Cell Lung Cancer Treated with Surgery and Adjuvant Therapies: A Retrospective Analysis of Outcomes and Prognostic Factors in 116 Patients.

PubMed

Tang, Yu; Qu, Jintao; Wu, Juan; Li, Song; Zhou, Yue; Xiao, Jianru

2015-09-02

Metastatic spinal cord compression is a disastrous consequence of non-small-cell lung cancer (NSCLC). There have been few studies of the outcomes or prognostic factors in patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies. From 2002 to 2013, 116 patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies were enrolled in this retrospective analysis. Kaplan-Meier methods and Cox regression analysis were used to estimate overall survival and identify prognostic factors for survival. Multivariate analysis suggested that the Eastern Cooperative Oncology Group performance status (ECOG-PS), preoperative and postoperative Frankel scores, postoperative adjuvant radiation therapy, and target therapy were independent prognostic factors. Ninety patients died at a median of twelve months (range, three to forty-seven months) postoperatively, and twenty-six patients were still alive at the time of final follow-up (at a median of fifteen months [range, five to fifty-four months]). The complete disappearance of deficits in spinal cord function after surgery was the most robust predictor of survival. Adjuvant radiation therapy and target therapy were also associated with a better prognosis. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Prognostic Value of Negative Coronary CT Angiography in Severely Obese Patients Prior to Bariatric Surgery: a Follow-Up After 6 Years.

PubMed

Messerli, Michael; Maywald, Céline; Wälti, Stephan; Warschkow, René; Wildermuth, Simon; Alkadhi, Hatem; Leschka, Sebastian; Schiesser, Marc

2017-08-01

This study aims to determine the long-term prognostic value of coronary CT angiography (CCTA) prior to bariatric surgery in severely obese patients with a body mass index (BMI) ≥35 kg/m 2 . Seventy consecutive patients undergoing cardiac CT for coronary assessment prior to bariatric surgery were prospectively included. Images were analysed for the presence of coronary calcification and for non-obstructive (<50%) or obstructive (>50% stenosis) coronary artery disease (CAD). A median clinical follow-up of 6.1 years in 54 patients was obtained for major adverse cardiovascular events (MACEs), defined as death, non-fatal myocardial infarction or coronary revascularisation. Weight loss and BMI decrease following bariatric surgery were recorded. The median BMI prior to surgery was 46.9 kg/m 2 . The median percentage of excess BMI loss after surgery was 75%. CT showed coronary calcification in 26 (48%) patients, whereas 28 (52%) patients had no calcification. CCTA revealed normal coronaries in 47 (87%) and non-obstructive CAD in 7 (13%) patients. No obstructive CAD was found. All patients successfully underwent bariatric surgery, and no MACE occurred neither perioperatively nor in the follow-up period. The negative predictive value of CCTA was 100% (95% confidence interval of 90.1-100.0%). In severely obese patients, the absence of obstructive CAD in cardiac CT prior to bariatric surgery with subsequently marked weight reduction has strong long-term prognostic implications for ruling out major adverse cardiac events in the postoperative period.

Change in Quality of Life after Rehabilitation: Prognostic Factors for Visually Impaired Adults

ERIC Educational Resources Information Center

Langelaan, Maaike; de Boer, Michiel R.; van Nispen, Ruth M. A.; Wouters, Bill; Moll, Annette C.; van Rens, Ger H. M. B.

2009-01-01

The overall aim of rehabilitation for visually impaired adults is to improve the quality of life and (societal) participation. The objectives of this study were to obtain the short-term and long-term outcome of a comprehensive rehabilitation programme on quality of life for visually impaired adults, and prognostic baseline factors responsible for…

Osteosarcoma: Diagnostic dilemmas in histopathology and prognostic factors

PubMed Central

Wadhwa, Neelam

2014-01-01

Osteosarcoma (OS), the commonest malignancy of osteoarticular origin, is a very aggressive neoplasm. Divergent histologic differentiation is common in OS; hence triple diagnostic approach is essential in all cases. 20% cases are atypical owing to lack of concurrence among clinicoradiologic and pathologic features necessitating resampling. Recognition of specific anatomic and histologic variants is essential in view of better outcome. Traditional prognostic factors of OS do stratify patients for short term outcome, but often fail to predict their long term outcome. Considering the negligible improvement in the patient outcome during the last 20 years, search for novel prognostic factors is in progress like ezrin vascular endothelial growth factor, chemokine receptors, dysregulation of various micro ribonucleic acid are potentially promising. Their utility needs to be validated by long term followup studies before they are incorporated in routine clinical practice. PMID:24932029

Gastric lymphomas in Turkey. Analysis of prognostic factors with special emphasis on flow cytometric DNA content.

PubMed

Aydin, Z D; Barista, I; Canpinar, H; Sungur, A; Tekuzman, G

2000-07-01

In contrast to DNA ploidy, to the authors' knowledge the prognostic significance of S-phase fraction (SPF) in gastric lymphomas has not been determined. In the current study, the prognostic significance of various parameters including SPF and DNA aneuploidy were analyzed and some distinct epidemiologic and biologic features of gastric lymphomas in Turkey were found. A series of 78 gastric lymphoma patients followed at Hacettepe University is reported. DNA flow cytometry was performed for 34 patients. The influence of various parameters on survival was investigated with the log rank test. The Cox proportional hazards model was fitted to identify independent prognostic factors. The median age of the patients was 50 years. There was no correlation between patient age and tumor grade. DNA content analysis revealed 4 of the 34 cases to be aneuploid with DNA index values < 1.0. The mean SPF was 33.5%. In the univariate analysis, surgical resection of the tumor, modified Ann Arbor stage, performance status, response to first-line chemotherapy, lactate dehydrogenase (LDH) level, and SPF were important prognostic factors for disease free survival (DFS). The same parameters, excluding LDH level, were important for determining overall survival (OS). In the multivariate analysis, surgical resection of the tumor, disease stage, performance status, and age were found to be important prognostic factors for OS. To the authors' knowledge the current study is the first to demonstrate the prognostic significance of SPF in gastric lymphomas. The distinguishing features of Turkish gastric lymphoma patients are 1) DNA indices of aneuploid cases that all are < 1.0, which is a unique feature; 2) a lower percentage of aneuploid cases; 3) a higher SPF; 4) a younger age distribution; and 5) lack of an age-grade correlation. The authors conclude that gastric lymphomas in Turkey have distinct biologic and epidemiologic characteristics. Copyright 2000 American Cancer Society.

Prognostic value of interleukin-6 and interleukin-6 receptor in organ-confined clear-cell renal cell carcinoma: a 5-year conditional cancer-specific survival analysis.

PubMed

Fu, Qiang; Chang, Yuan; An, Huimin; Fu, Hangcheng; Zhu, Yu; Xu, Le; Zhang, Weijuan; Xu, Jiejie

2015-12-01

Interleukin-6 (IL-6) is the major cytokine that induces transcriptional acute and chronic inflammation responses, and was recently incorporated as a recurrence prognostication signature for localised clear-cell renal cell carcinoma (ccRCC). As the prognostic efficacy of initial risk factors may ebb during long-term practice, we aim to report conditional cancer-specific survival (CCSS) of RCC patients and evaluate the impact of IL-6 as well as its receptor (IL-6R) to offer more relevant prognostic information accounting for elapsing time. We enrolled 180 histologically proven localised ccRCC patients who underwent nephrectomy between 2001 and 2004 with available pathologic information. Five-year CCSS was determined and stratified by future prognostic factors. Constant Cox regression analysis and Harrell's concordance index were used to indicate the predictive accuracy of established models. The 5-year CCSS of organ-confined ccRCC patients with both IL-6- and IL-6R-positive expression was 52% at year 2 after surgery, which was close to locally advanced patients (48%, P=0.564) and was significantly poorer than organ-confined patients with IL-6- or IL-6R-negative expression (89%, P<0.001). Multivariate analyses proved IL-6 and IL-6R as independent predictors after adjusting for demographic factors. Concordance index of pT-IL-6-IL-6R risk stratification was markedly higher compared with the stage, size, grade and necrosis prognostic model (0.724 vs 0.669, P=0.002) or UCLA Integrated Staging System (0.724 vs 0.642, P=0.007) in organ-confined ccRCC population during the first 5 years. Combined IL-6 and IL-6R coexpression emerges as an independent early-stage immunologic prognostic factor for organ-confined ccRCC patients.

A novel literature-based approach to identify genetic and molecular predictors of survival in glioblastoma multiforme: Analysis of 14,678 patients using systematic review and meta-analytical tools.

PubMed

Thuy, Matthew N T; Kam, Jeremy K T; Lee, Geoffrey C Y; Tao, Peter L; Ling, Dorothy Q; Cheng, Melissa; Goh, Su Kah; Papachristos, Alexander J; Shukla, Lipi; Wall, Krystal-Leigh; Smoll, Nicolas R; Jones, Jordan J; Gikenye, Njeri; Soh, Bob; Moffat, Brad; Johnson, Nick; Drummond, Katharine J

2015-05-01

Glioblastoma multiforme (GBM) has a poor prognosis despite maximal multimodal therapy. Biomarkers of relevance to prognosis which may also identify treatment targets are needed. A few hundred genetic and molecular predictors have been implicated in the literature, however with the exception of IDH1 and O6-MGMT, there is uncertainty regarding their true prognostic relevance. This study analyses reported genetic and molecular predictors of prognosis in GBM. For each, its relationship with univariate overall survival in adults with GBM is described. A systematic search of MEDLINE (1998-July 2010) was performed. Eligible papers studied the effect of any genetic or molecular marker on univariate overall survival in adult patients with histologically diagnosed GBM. Primary outcomes were median survival difference in months and univariate hazard ratios. Analyses included converting 126 Kaplan-Meier curves and 27 raw data sets into primary outcomes. Seventy-four random effects meta-analyses were performed on 39 unique genetic or molecular factors. Objective criteria were designed to classify factors into the categories of clearly prognostic, weakly prognostic, non-prognostic and promising. Included were 304 publications and 174 studies involving 14,678 unique patients from 33 countries. We identified 422 reported genetic and molecular predictors, of which 52 had ⩾2 studies. IDH1 mutation and O6-MGMT were classified as clearly prognostic, validating the methodology. High Ki-67/MIB-1 and loss of heterozygosity of chromosome 10/10q were classified as weakly prognostic. Four factors were classified as non-prognostic and 13 factors were classified as promising and worthy of additional investigation. Funnel plot analysis did not identify any evidence of publication bias. This study demonstrates a novel literature and meta-analytical based approach to maximise the value that can be derived from the plethora of literature reports of molecular and genetic factors in GBM. Caution is advised in over-interpreting the results due to study limitations. Further research to develop this methodology and improvements in study reporting are suggested. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer.

PubMed

Nobashi, Tomomi; Koyasu, Sho; Nakamoto, Yuji; Kubo, Takeshi; Ishimori, Takayoshi; Kim, Young H; Yoshizawa, Akihiko; Togashi, Kaori

2016-01-01

To investigate the prognostic value of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET) parameters for small-cell lung cancer (SCLC), according to the primary tumour location, adjusted by conventional prognostic factors. From 2008 to 2013, we enrolled consecutive patients with histologically proven SCLC, who had undergone FDG-PET/CT prior to initial therapy. The primary tumour location was categorized into central or peripheral types. PET parameters and clinical variables were evaluated using univariate and multivariate analysis. A total of 69 patients were enrolled in this study; 28 of these patients were categorized as having the central type and 41 patients as having the peripheral type. In univariate analysis, stage, serum neuron-specific enolase, whole-body metabolic tumour volume (WB-MTV) and whole-body total lesion glycolysis (WB-TLG) were found to be significant in both types of patients. In multivariate analysis, the independent prognostic factor was found to be stage in the central type, but WB-MTV and WB-TLG in the peripheral type. Kaplan-Meier analysis demonstrated that patients with peripheral type with limited disease and low WB-MTV or WB-TLG showed significantly better overall survival than all of the other groups (p < 0.0083). The FDG-PET volumetric parameters were demonstrated to be significant and independent prognostic factors in patients with peripheral type of SCLC, while stage was the only independent prognostic factor in patients with central type of SCLC. FDG-PET is a non-invasive method that could potentially be used to estimate the prognosis of patients, especially those with peripheral-type SCLC.

Macroscopic appearance of Type IV and giant Type III is a high risk for a poor prognosis in pathological stage II/III advanced gastric cancer with postoperative adjuvant chemotherapy

PubMed Central

Yamashita, Keishi; Ema, Akira; Hosoda, Kei; Mieno, Hiroaki; Moriya, Hiromitsu; Katada, Natsuya; Watanabe, Masahiko

2017-01-01

AIM To evaluate whether a high risk macroscopic appearance (Type IV and giant Type III) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage II/III (pStage II/III) gastric cancer. METHODS One hundred and seventy-two advanced gastric cancer (defined as pT2 or beyond) patients with pStage II/III who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival (RFS) (35.7%) and overall survival (OS) (34%) than an average risk appearance (P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13th Japanese Gastric Cancer Association (JGCA) pT (P = 0.01), but not with the 13th JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13th JGCA pStage (P < 0.0001) and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified high-risk macroscopic appearance (P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13th JGCA stage in pStage II/III advanced gastric cancer. PMID:28451064

Prediction of overall survival for metastatic pancreatic cancer: Development and validation of a prognostic nomogram with data from open clinical trial and real-world study.

PubMed

Hang, Junjie; Wu, Lixia; Zhu, Lina; Sun, Zhiqiang; Wang, Ge; Pan, Jingjing; Zheng, Suhua; Xu, Kequn; Du, Jiadi; Jiang, Hua

2018-06-01

It is necessary to develop prognostic tools of metastatic pancreatic cancer (MPC) for optimizing therapeutic strategies. Thus, we tried to develop and validate a prognostic nomogram of MPC. Data from 3 clinical trials (NCT00844649, NCT01124786, and NCT00574275) and 133 Chinese MPC patients were used for analysis. The former 2 trials were taken as the training cohort while NCT00574275 was used as the validation cohort. In addition, 133 MPC patients treated in China were taken as the testing cohort. Cox regression model was used to investigate prognostic factors in the training cohort. With these factors, we established a nomogram and verified it by Harrell's concordance index (C-index) and calibration plots. Furthermore, the nomogram was externally validated in the validation cohort and testing cohort. In the training cohort (n = 445), performance status, liver metastasis, Carbohydrate antigen 19-9 (CA19-9) log-value, absolute neutrophil count (ANC), and albumin were independent prognostic factors for overall survival (OS). A nomogram was established with these factors to predict OS and survival probabilities. The nomogram showed an acceptable discrimination ability (C-index: .683) and good calibration, and was further externally validated in the validation cohort (n = 273, C-index: .699) and testing cohort (n = 133, C-index: .653).The nomogram total points (NTP) had the potential to stratify patients into 3-risk groups with median OS of 11.7, 7.0 and 3.7 months (P < .001), respectively. In conclusion, the prognostic nomogram with NTP can predict OS for patients with MPC with considerable accuracy. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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.

Prognostic significance of chemotherapy-induced necrosis in osteosarcoma patients receiving pasteurized autografts

PubMed Central

Joo, Min Wook; Kang, Yong Koo; Yoo, Chang-Young; Cha, Sung Ho

2017-01-01

Background Among various reconstruction methods after wide excision for osteosarcoma, pasteurized autograft is often preferred. While the whole area of the tumor can be assessed for chemotherapy-induced necrosis, one of the important prognostic factors, in other reconstructive techniques, only a portion removed from a wide-resection specimen is available when using pasteurized autograft method. The assessment, therefore, may be unreliable. We analyzed the prognostic significance of the chemotherapy-induced necrosis in osteosarcoma patients who underwent reconstruction with pasteurized autografts. Patients and methods We reviewed the records of osteosarcoma patients who underwent treatment in our institution from 1998 to 2013. Cases of reconstruction with pasteurized autografts were defined as the patient group, and the same number of patients who underwent other reconstruction methods served as controls. Chemotherapy-induced necrosis was evaluated for removed extra-osseous and curetted intramedullary tumor tissues. Results A total of 22 patients were identified; the median age was 15.5 years, and there were 12 males. The most common tumor location was the distal femur. The most common histological subtype was osteoblastic. Median size was 8.1 cm. Disease status was stage IIB in 13 patients and IIA in 9. Median follow-up was 76 months. No differences between the patient and control groups were observed in potential prognostic factors, overall survival, metastasis-free survival, or recurrence-free survival. Univariate analyses demonstrated that histological response was a significant prognostic factor for metastasis-free survival and also significant for recurrence-free survival. Conclusion Chemotherapy-induced necrosis grading, using only available tumor tissues, could be a prognostic factor for osteosarcoma patients receiving pasteurized autografts for reconstructive surgery. PMID:28196121

Prognostic Role of Carcinoembryonic Antigen Level after Preoperative Chemoradiotherapy in Patients with Rectal Cancer.

PubMed

Huh, Jung Wook; Yun, Seong Hyeon; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Kim, Hee Cheol; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

2018-05-29

The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT. We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (< 5 ng/mL) and high CEA (≥ 5 ng/mL). Median post-CRT CEA level was 1.7 ng/mL (range, 0.1-207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4-176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P < 0.001 and P = 0.001, respectively). Post-CRT CEA level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival. The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer.

Nonsentinel lymph node status in patients with cutaneous melanoma: results from a multi-institution prognostic study.

PubMed

Pasquali, Sandro; Mocellin, Simone; Mozzillo, Nicola; Maurichi, Andrea; Quaglino, Pietro; Borgognoni, Lorenzo; Solari, Nicola; Piazzalunga, Dario; Mascheroni, Luigi; Giudice, Giuseppe; Patuzzo, Roberto; Caracò, Corrado; Ribero, Simone; Marone, Ugo; Santinami, Mario; Rossi, Carlo Riccardo

2014-03-20

We investigated whether the nonsentinel lymph node (NSLN) status in patients with melanoma improves the prognostic accuracy of common staging features; then we formulated a proposal for including the NSLN status in the current melanoma staging system. We retrospectively collected the clinicopathologic data of 1,538 patients with positive SLN status who underwent completion lymph node dissection (CLND) at nine Italian centers. Multivariable Cox regression survival analysis was used to identify independent prognostic factors. Literature meta-analysis was used to summarize the available evidence on the prognostic value of the NSLN status in patients with positive SLN. NSLN metastasis was observed in 353 patients (23%). After a median follow-up of 45 months, NSLN status was an independent prognostic factor for melanoma-specific survival (hazard ratio [HR] = 1.34; 95% CI, 1.18 to 1.52; P < .001). NSLN status efficiently stratified the prognosis of patients with two to three positive lymph nodes (n = 387; HR = 1.39; 95% CI, 1.07 to 1.81; P = .013), independently of other staging features. Searching the literature, this patient subgroup was investigated in other two studies. Pooling the results (n = 620 patients; 284 NSLN negative and 336 NSLN positive), we found that NSLN status is a highly significant prognostic factor (summary HR = 1.59; 95% CI, 1.27 to 1.98; P < .001) in patients with two to three positive lymph nodes. These findings support the independent prognostic value of the NSLN status in patients with two to three positive lymph nodes, suggesting that this information should be considered for the routine staging in patients with melanoma.

Prognosis in advanced lung cancer--A prospective study examining key clinicopathological factors.

PubMed

Simmons, Claribel P; Koinis, Filippos; Fallon, Marie T; Fearon, Kenneth C; Bowden, Jo; Solheim, Tora S; Gronberg, Bjorn Henning; McMillan, Donald C; Gioulbasanis, Ioannis; Laird, Barry J

2015-06-01

In patients with advanced incurable lung cancer deciding as to the most appropriate treatment (e.g., chemotherapy or supportive care only) is challenging. In such patients the TNM classification system has reached its ceiling therefore other factors are used to assess prognosis and as such, guide treatment. Performance status (PS), weight loss and inflammatory biomarkers (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer however these have not been compared. This study compares key prognostic factors in advanced lung cancer. Patients with newly diagnosed advanced lung cancer were recruited and demographics, weight loss, other prognostic factors (mGPS, PS) were collected. Kaplan-Meier and Cox regression methods were used to compare these prognostic factors. 390 patients with advanced incurable lung cancer were recruited; 341 were male, median age was 66 years (IQR 59-73) and patients had stage IV non-small cell (n=288) (73.8%) or extensive stage small cell lung cancer (n=102) (26.2%). The median survival was 7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50-2.02) and mGPS (HR 1.67, CI 1.40-2.00) predicted survival (p<0.001). Survival at 3 months ranged from 99% (ECOG 0-1) to 74% (ECOG 2) and using mGPS, from 99% (mGPS0) to 71% (mGPS2). In combination, survival ranged from 99% (mGPS 0, ECOG 0-1) to 33% (mGPS2, ECOG 3). Performance status and the mGPS are superior prognostic factors in advanced lung cancer. In combination, these improved survival prediction compared with either alone. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Development Of A Multivariate Prognostic Model For Pain And Activity Limitation In People With Low Back Disorders Receiving Physiotherapy.

PubMed

Ford, Jon J; Richards BPhysio, Matt C; Surkitt BPhysio, Luke D; Chan BPhysio, Alexander Yp; Slater, Sarah L; Taylor, Nicholas F; Hahne, Andrew J

2018-05-28

To identify predictors for back pain, leg pain and activity limitation in patients with early persistent low back disorders. Prospective inception cohort study; Setting: primary care private physiotherapy clinics in Melbourne, Australia. 300 adults aged 18-65 years with low back and/or referred leg pain of ≥6-weeks and ≤6-months duration. Not applicable. Numerical rating scales for back pain and leg pain as well as the Oswestry Disability Scale. Prognostic factors included sociodemographics, treatment related factors, subjective/physical examination, subgrouping factors and standardized questionnaires. Univariate analysis followed by generalized estimating equations were used to develop a multivariate prognostic model for back pain, leg pain and activity limitation. Fifty-eight prognostic factors progressed to the multivariate stage where 15 showed significant (p<0.05) associations with at least one of the three outcomes. There were five indicators of positive outcome (two types of low back disorder subgroups, paresthesia below waist, walking as an easing factor and low transversus abdominis tone) and 10 indicators of negative outcome (both parents born overseas, deep leg symptoms, longer sick leave duration, high multifidus tone, clinically determined inflammation, higher back and leg pain severity, lower lifting capacity, lower work capacity and higher pain drawing percentage coverage). The preliminary model identifying predictors of low back disorders explained up to 37% of the variance in outcome. This study evaluated a comprehensive range of prognostic factors reflective of both the biomedical and psychosocial domains of low back disorders. The preliminary multivariate model requires further validation before being considered for clinical use. Copyright © 2018. Published by Elsevier Inc.

Prognostic factors in operable breast cancer treated with neoadjuvant chemotherapy: towards a quantification of residual disease.

PubMed

Mombelli, Sarah; Kwiatkowski, Fabrice; Abrial, Catherine; Wang-Lopez, Qian; de Boissieu, Paul; Garbar, Christian; Bensussan, Armand; Curé, Hervé

2015-01-01

Neoadjuvant chemotherapy (NACT) allows for a more frequent use of breast-conservative surgery; it is also an in vivo model of individual tumor sensitivity which permits to determine new prognostic factors to personalize the therapeutic approach. Between 2000 and 2012, 318 patients with primary invasive breast cancer were treated with a median of 6 cycles of NACT; they received either an anthracycline-based FEC 100 protocol (31.1%), or anthracyclines + taxanes (53.5%), with trastuzumab if indicated (15.4%). After a median follow-up of 44.2 months, the pathological complete response rate according to the classification of Chevallier et al. [Am J Clin Oncol 1993;16:223-228] was 19.3%, and overall (OS) and disease-free survival (DFS) at 10 years were 60.2 and 69.6%, respectively. Univariate analyses demonstrated that the Residual Disease in Breast and Nodes (RDBN) index was the most significant prognostic factor for OS (p = 0.0082) and DFS (p = 0.0022), and multivariate analyses mainly revealed that the residual tumor size, residual involved node number and post-chemotherapy Scarff-Bloom-Richardson (SBR) grading were the most significant prognostic factors. In a cohort of patients who were all homogeneously treated with some of the most common drugs for breast cancer, we demonstrate that NACT may provide additional prognostic factors and confirm the RDBN index. As this index allows for the prediction of survival with different breast cancer subtypes, we suggest that it should be calculated routinely to help clinicians to select patients who need adjuvant treatments. 2015 S. Karger AG, Basel

Predictive factors of tumor control and survival after radiosurgery for local failures of nasopharyngeal carcinoma.

PubMed

Chua, Daniel T T; Sham, Jonathan S T; Hung, Kwan-Ngai; Leung, Lucullus H T; Au, Gordon K H

2006-12-01

Stereotactic radiosurgery has been employed as a salvage treatment of local failures of nasopharyngeal carcinoma (NPC). To identify patients that would benefit from radiosurgery, we reviewed our data with emphasis on factors that predicted treatment outcome. A total of 48 patients with local failures of NPC were treated by stereotactic radiosurgery between March 1996 and February 2005. Radiosurgery was administered using a modified linear accelerator with single or multiple isocenters to deliver a median dose of 12.5 Gy to the target periphery. Median follow-up was 54 months. Five-year local failure-free probability after radiosurgery was 47.2% and 5-year overall survival rate was 46.9%. Neuroendocrine complications occurred in 27% of patients but there were no treatment-related deaths. Time interval from primary radiotherapy, retreatment T stage, prior local failures and tumor volume were significant predictive factors of local control and/or survival whereas age was of marginal significance in predicting survival. A radiosurgery prognostic scoring system was designed based on these predictive factors. Five-year local failure-free probabilities in patients with good, intermediate and poor prognostic scores were 100%, 42.5%, and 9.6%. The corresponding five-year overall survival rates were 100%, 51.1%, and 0%. Important factors that predicted tumor control and survival after radiosurgery were identified. Patients with good prognostic score should be treated by radiosurgery in view of the excellent results. Patients with intermediate prognostic score may also be treated by radiosurgery but those with poor prognostic score should receive other salvage treatments.

Survival rate and prognostic factors of conventional osteosarcoma in Northern Thailand: A series from Chiang Mai University Hospital.

PubMed

Pruksakorn, Dumnoensun; Phanphaisarn, Areerak; Arpornchayanon, Olarn; Uttamo, Nantawat; Leerapun, Taninnit; Settakorn, Jongkolnee

2015-12-01

Osteosarcoma is a common and aggressive primary malignant bone tumor occurring in children and adolescents. It is one of the most aggressive human cancers and the most common cause of cancer-associated limb loss. As treatment in Thailand has produced a lower survival rate than in developed countries; therefore, this study identified survival rate and the poor prognostic factors of osteosarcoma in Northern Thailand. The retrospective cases of osteosarcoma, diagnosis between 1 January 1996 and 31 December 2013, were evaluated. Five and ten year overall survival rates were analyzed using time-to-event analysis. Potential prognostic factors were identified by multivariate regression analysis. There were 208 newly diagnosed osteosarcomas during that period, and 144 cases met the criteria for analysis. The majority of the osteosarcoma cases (78.5%) were aged 0-24 years. The overall 5- and 10-year survival rates were 37.9% and 33.6%, respectively. Presence of metastasis at initial examination, delayed and against treatment co-operation, and axial skeletal location were identified as independent prognostic factors for survival, with hazard ratios of 4.3, 2.5 and 3.8, and 3.1, respectively. This osteosarcoma cohort had a relatively poor overall survival rate. The prognostic factors identified would play a critical role in modifying survival rates of osteosarcoma patients; as rapid disease recognition, a better treatment counselling, as well as improving of chemotherapeutic regimens were found to be important in improving the overall survival rate in Thailand. Copyright © 2015 Elsevier Ltd. All rights reserved.

Do the conventional clinicopathologic parameters predict for response and survival in head and neck cancer patients undergoing neoadjuvant chemotherapy?

PubMed

Fonseca, E; Cruz, J J; Dueñas, A; Gómez, A; Sánchez, P; Martín, G; Nieto, A; Soria, P; Muñoz, A; Gómez, J L; Pardal, J L

1996-01-01

Neoadjuvant chemotherapy for head and neck carcinoma is still an important treatment modality. The prognostic value of patient and tumor parameters has been extensively evaluated in several trials, yielding mixed results. We report the prognostic factors emerging from a group of patients undergoing neoadjuvant chemotherapy. From April 1986 to June 1992, 149 consecutive patients received cisplatin-5-fluorouracil-based neoadjuvant chemotherapy. After four courses of chemotherapy, patients underwent local-regional treatment with surgery, radiation or both. A variety of patient and tumor characteristics were evaluated as predictors for response to chemotherapy and survival. The complete response, partial response and no response rates to NAC were 52%, 33% and 15%, respectively. No parameters predicted response to chemotherapy. At a maximum follow-up of 87 months, overall survival was 39% and disease-free survival was 49%. Variables shown to be predictors of survival in univariate analyses were age, performance status, histology, site, T, N, stage, and response to chemotherapy. Using the Cox regression analysis, only complete response to induction chemotherapy (P = 0.0006), performance status (P = 0.03), stage (P = 0.01), age (P = 0.03) and primary tumor site (P = 0.04) emerged as independent prognostic factors for survival. Complete response to chemotherapy was confirmed as the strongest prognostic factor influencing survival. However, conventional clinicopathologic factors did not predict response, hence, potential prognostic biologic and molecular factors for response must be sought. At present, much effort must be made for the improvement of the complete response rate, which seems to be a requisite to prolong survival.

Incidence and prognostic factors for postoperative frozen shoulder after shoulder surgery: a prospective cohort study.

PubMed

Koorevaar, Rinco C T; Van't Riet, Esther; Ipskamp, Marcel; Bulstra, Sjoerd K

2017-03-01

Frozen shoulder is a potential complication after shoulder surgery. It is a clinical condition that is often associated with marked disability and can have a profound effect on the patient's quality of life. The incidence, etiology, pathology and prognostic factors of postoperative frozen shoulder after shoulder surgery are not known. The purpose of this explorative study was to determine the incidence of postoperative frozen shoulder after various operative shoulder procedures. A second aim was to identify prognostic factors for postoperative frozen shoulder after shoulder surgery. 505 consecutive patients undergoing elective shoulder surgery were included in this prospective cohort study. Follow-up was 6 months after surgery. A prediction model was developed to identify prognostic factors for postoperative frozen shoulder after shoulder surgery using the TRIPOD guidelines. We nominated five potential predictors: gender, diabetes mellitus, type of physiotherapy, arthroscopic surgery and DASH score. Frozen shoulder was identified in 11% of the patients after shoulder surgery and was more common in females (15%) than in males (8%). Frozen shoulder was encountered after all types of operative procedures. A prediction model based on four variables (diabetes mellitus, specialized shoulder physiotherapy, arthroscopic surgery and DASH score) discriminated reasonably well with an AUC of 0.712. Postoperative frozen shoulder is a serious complication after shoulder surgery, with an incidence of 11%. Four prognostic factors were identified for postoperative frozen shoulder: diabetes mellitus, arthroscopic surgery, specialized shoulder physiotherapy and DASH score. The combination of these four variables provided a prediction rule for postoperative frozen shoulder with reasonable fit. Level II, prospective cohort study.

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia

PubMed Central

Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

2013-01-01

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. This trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374. PMID:23065509

EMMPRIN expression in oral squamous cell carcinomas: correlation with tumor proliferation and patient survival.

PubMed

Monteiro, Luís Silva; Delgado, Maria Leonor; Ricardo, Sara; Garcez, Fernanda; do Amaral, Barbas; Pacheco, José Júlio; Lopes, Carlos; Bousbaa, Hassan

2014-01-01

The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) expression in oral squamous cell carcinomas (OSCC), and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases with OSCC. Statistical analysis was conducted to examine their clinicopathological and prognostic significance in OSCC. EMMPRIN membrane expression was observed in all cases, with both membrane and cytoplasmic tumor expression in 61 cases (82.4%). EMMPRIN overexpression was observed in 56 cases (75.7%). Moderately or poorly differentiated tumors showed EMMPRIN overexpression more frequently than well-differentiated tumors (P = 0.002). Overexpression of EMMPRIN was correlated with high Ki-67 expression (P = 0.004). In the multivariate analysis, EMMPRIN overexpression reveals an adverse independent prognostic value for cancer-specific survival (CSS) (P = 0.034). Our results reveal that EMMPRIN protein is overexpressed in more than two-thirds of OSCC cases, especially in high proliferative and less differentiated tumors. The independent value of EMMPRIN overexpression in CSS suggests that this protein could be used as an important biological prognostic marker for patients with OSCC. Moreover, the high expression of EMMPRIN makes it a possible therapeutic target in OSCC patients.

Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

PubMed

Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

2017-06-01

Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular profiling identifies prognostic markers of stage IA lung adenocarcinoma.

PubMed

Zhang, Jie; Shao, Jinchen; Zhu, Lei; Zhao, Ruiying; Xing, Jie; Wang, Jun; Guo, Xiaohui; Tu, Shichun; Han, Baohui; Yu, Keke

2017-09-26

We previously showed that different pathologic subtypes were associated with different prognostic values in patients with stage IA lung adenocarcinoma (AC). We hypothesize that differential gene expression profiles of different subtypes may be valuable factors for prognosis in stage IA lung adenocarcinoma. We performed microarray gene expression profiling on tumor tissues micro-dissected from patients with acinar and solid predominant subtypes of stage IA lung adenocarcinoma. These patients had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China in 2012. No patient had preoperative treatment. We performed the Gene Set Enrichment Analysis (GSEA) analysis to look for gene expression signatures associated with tumor subtypes. The histologic subtypes of all patients were classified according to the 2015 WHO lung Adenocarcinoma classification. We found that patients with the solid predominant subtype are enriched for genes involved in RNA polymerase activity as well as inactivation of the p53 pathway. Further, we identified a list of genes that may serve as prognostic markers for stage IA lung adenocarcinoma. Validation in the TCGA database shows that these genes are correlated with survival, suggesting that they are novel prognostic factors for stage IA lung adenocarcinoma. In conclusion, we have uncovered novel prognostic factors for stage IA lung adenocarcinoma using gene expression profiling in combination with histopathology subtyping.

Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children's Oncology Group.

PubMed

Pollack, Ian F; Hamilton, Ronald L; Burger, Peter C; Brat, Daniel J; Rosenblum, Marc K; Murdoch, Geoffrey H; Nikiforova, Marina N; Holmes, Emiko J; Zhou, Tianni; Cohen, Kenneth J; Jakacki, Regina I

2010-09-01

Aberrant activation of Akt is a common finding in adult malignant gliomas, resulting in most cases from mutations or deletions involving PTEN, which allows constitutive Akt phosphorylation. In contrast, we have previously reported that pediatric malignant gliomas, which are morphologically similar to lesions arising in adults, have a substantially lower incidence of genomic alterations of PTEN. The objective of this study was to determine whether Akt activation was also an uncommon finding in childhood malignant gliomas and whether this feature was associated with survival. To address this issue, we examined the frequency of Akt activation, determined by overexpression of the activated phosphorylated form of Akt (Se(473)) on immunohistochemical analysis, in a series of 53 childhood malignant gliomas obtained from newly diagnosed patients treated on the Children's Oncology Group ACNS0126 and 0423 studies. The relationship between Akt activation and p53 overexpression, MIB1 labeling, and tumor histology was evaluated. The association between Akt activation and survival was also assessed. Overexpression of activated Akt was observed in 42 of 53 tumors, far in excess of the frequency of PTEN mutations we have previously observed. There was no association between Akt activation and either histology, p53 overexpression, or MIB1 proliferation indices. Although tumors that lacked Akt overexpression had a trend toward more favorable event-free survival and overall survival (p = 0.06), this association reflected that non-overexpressing tumors were significantly more likely to have undergone extensive tumor removal, which was independently associated with outcome. Activation of Akt is a common finding in pediatric malignant gliomas, although it remains uncertain whether this is an independent adverse prognostic factor. In view of the frequency of Akt activation, the evaluation of molecularly targeted therapies that inhibit this pathway warrants consideration for these tumors.

Evaluation of relative dose intensity during the early phase of first-line sunitinib treatment using a 2-week-on/1-week-off regimen for metastatic renal cell carcinoma.

PubMed

Iwamoto, Kana; Ishihara, Hiroki; Takagi, Toshio; Kondo, Tsunenori; Yoshida, Kazuhiko; Iizuka, Junpei; Tanabe, Kazunari

2018-04-23

Sunitinib treatment with a 2-week-on/1-week-off schedule (Schedule 2/1) is a common alternative regimen with high relative dose intensity (RDI) and superior tolerability for patients with metastatic renal cell carcinoma (mRCC). The prognostic impact of RDI is reported only in 4-week-on/2-week-off or mixed regimens. Herein, we evaluated the prognostic impact of RDI during early-phase sunitinib treatment using Schedule 2/1. Seventy-four patients who received first-line sunitinib treatment using Schedule 2/1 were evaluated. Endpoints were progression-free survival (PFS) and overall survival (OS). We assessed RDI within the initial two cycles (2c-RDI), and its prognostic impact. Predictive factors for 2c-RDI deterioration were also evaluated. The cut-off value of 2c-RDI was set at 65%. Based on this cut-off, 31 patients (42.0%) were classified into the low 2c-RDI group (< 65%). PFS and OS were significantly shorter in the low-2c-RDI patients, compared with the high 2c-RDI patients (median PFS: 6.15 vs. 18.4 months, p = 0.0005; OS 11.0 vs. 39.3 months, p = 0.0002). Furthermore, multivariate analyses showed that the development of dose-limiting toxicities (DLTs) within the initial two cycles, as well as low initial dose, were independent factors for low 2c-RDI (DLTs: OR 18.6, 95% CI 3.27-105.30, p = 0.0010; initial dose: OR 9.26, 95% CI 1.42-60.40, p = 0.020). The most common adverse event was thrombocytopenia (any grade: 24.3%; grade ≥ 3: 8.1%). More than 65% of 2c-RDI should be maintained for optimal therapeutic effect of sunitinib treatment using Schedule 2/1. To achieve the appropriate 2c-RDI, careful follow-up for patient tolerability is needed to avoid early DLT development.

Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.

PubMed

Sangro, Bruno; Carpanese, Livio; Cianni, Roberto; Golfieri, Rita; Gasparini, Daniele; Ezziddin, Samer; Paprottka, Philipp M; Fiore, Francesco; Van Buskirk, Mark; Bilbao, Jose Ignacio; Ettorre, Giuseppe Maria; Salvatori, Rita; Giampalma, Emanuela; Geatti, Onelio; Wilhelm, Kai; Hoffmann, Ralf Thorsten; Izzo, Francesco; Iñarrairaegui, Mercedes; Maini, Carlo Ludovico; Urigo, Carlo; Cappelli, Alberta; Vit, Alessandro; Ahmadzadehfar, Hojjat; Jakobs, Tobias Franz; Lastoria, Secondo

2011-09-02

A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium-90-labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole-liver (45.2%) or right-lobe (38.5%) infusions. Typically, patients were Child-Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one-quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9-15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6-38.1 months]; BCLC B, 16.9 months [95% CI, 12.8-22.8 months]; BCLC C, 10.0 months [95% CI, 7.7-10.9 months]). Consistent with this finding , survival varied significantly by ECOG status, hepatic function (Child-Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha-fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All-cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively. This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options. Copyright © 2011 American Association for the Study of Liver Diseases.

Primary Gastrointestinal Lymphoma

PubMed Central

Chen, Yinting; Chen, Yanzhu; Chen, Shaojie; Wu, Lili; Xu, Lishu; Lian, Guoda; Yang, Kege; Li, Yaqing; Zeng, Linjuan; Huang, Kaihong

2015-01-01

Abstract Primary gastrointestinal lymphoma (PGIL) is a rare malignant tumor without standard diagnosis and treatment methods. This study is aimed to systematically analyze its clinical characteristics and draw out an appropriate flow chart of diagnosis and treatment process for PGIL in China. This study retrospectively analyzed the clinicopathological characteristics, diagnostic approaches, prognostic factors, and therapeutic modalities in 415 cases of PGIL in Chinese province of Guangdong. A systematic review was conducted in 118 studies containing 5075 patients to further identify clinical manifestations and mortalities of therapeutic modalities. The most common clinical presentations were abdominal pain and bloody stools. Endoscopic biopsy was an important diagnostic means, and usually more than once to make a definite diagnosis. Retrospective multicenter clinical study showed that younger onset age (<60 years), female, one region involved, one lesion, early stage, International Prognostic Index (IPI ≤1), normal lactate dehydrogenase (LDH), normal albumin, and nonemergency operation were significant prognostic factors for B-cell lymphoma; non-B symptom, tumor restricted to gastric or ileocecal region, one lesion, performance status (PS ≤1), normal LDH, and nonsurgery alone were significant prognostic factors for T-cell lymphoma. Site of origin and IPI were independent prognostic factors for B-cell lymphoma; PS was the independent prognostic factor for T-cell lymphoma. And T-cell lymphoma had worse overall survival (OS) and progression-free survival (PFS) than B-cell lymphoma. Among different therapeutic modalities, chemotherapy alone or combined with surgery showed better OS and PFS than surgery alone for diffuse large B-cell lymphoma (DLBCL) of stage I/II E and T-cell lymphoma. For DLBCL of stage III E/IV and mucosa-associated lymphoid tissue lymphoma, OS and PFS did not differ among different therapeutic groups. In meta-analysis, surgery plus chemotherapy showed lowest mortality. Chemotherapy alone or combined with surgery may be the first-line treatment for DLBCL of stage I/II E and T-cell lymphoma. A flow chart of diagnosis and treatment process for PGIL was approximately drew out. PMID:26632732

Prognostic factors of primary gastrointestinal stromal tumors: a cohort study based on high-volume centers.

PubMed

Liu, Xuechao; Qiu, Haibo; Zhang, Peng; Feng, Xingyu; Chen, Tao; Li, Yong; Tao, Kaixiong; Li, Guoxin; Sun, Xiaowei; Zhou, Zhiwei

2018-02-01

We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors (GISTs). Data from 2,570 consecutive GIST patients from four medical centers in China (January 2001-December 2015) were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors. Of the included patients, 1,375 (53.5%) were male, and the patient age range was 18 to 95 (median, 58) years. The tumors were mostly found in the stomach (64.5%), small intestine (25.1%) and colorectal region (5.1%). At the time of diagnosis, the median tumor size was 4.0 (range: 0.1-55.0) cm, and the median mitotic index per 50 high power fields (HPFs) was 3 (range: 0-254). Of the 2,168 resected patients, 2,009 (92.7%) received curative resection. According to the modified National Institutes of Health (NIH) classification, 21.9%, 28.9%, 14.1% and 35.1% were very low-, low-, intermediate- and high-risk tumors, respectively. The rate of positivity was 96.4% for c-Kit, 87.1% for CD34, 96.9% for delay of germination 1 (DOG-1), 8.0% for S-100, 31.0% for smooth muscle actin (SMA) and 5.1% for desmin. However, the prognostic value of each was limited. Multivariate analysis showed that age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors. Furthermore, we found that high-risk patients benefited significantly from postoperative imatinib (P<0.001), whereas intermediate-risk patients did not (P=0.954). Age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors in patients with GISTs. Moreover, determining whether intermediate-risk patients can benefit from adjuvant imatinib would be of considerable interest in future studies.

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer.

PubMed

Kimbung, Siker; Johansson, Ida; Danielsson, Anna; Veerla, Srinivas; Egyhazi Brage, Suzanne; Frostvik Stolt, Marianne; Skoog, Lambert; Carlsson, Lena; Einbeigi, Zakaria; Lidbrink, Elisabet; Linderholm, Barbro; Loman, Niklas; Malmström, Per-Olof; Söderberg, Martin; Walz, Thomas M; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2016-01-01

The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. ©2015 American Association for Cancer Research.

Prognostic Impact of the 6th and 7th American Joint Committee on Cancer TNM Staging Systems on Esophageal Cancer Patients Treated With Chemoradiotherapy

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

Nomura, Motoo, E-mail: excell@hkg.odn.ne.jp; Department of Radiation Oncology, Aichi Cancer Center Hospital; Shitara, Kohei

2012-02-01

Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of themore » 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.« less

Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.

PubMed

Wang, Dong-Yu; Done, Susan J; Mc Cready, David R; Leong, Wey L

2014-07-04

Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). The original training cohort reached a statistically significant difference (p < 0.05) in disease-free survivals between the three CMTC groups after an additional two years of follow-up (median = 55 months). The prognostic value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments.

Predictive models and prognostic factors for upper tract urothelial carcinoma: a comprehensive review of the literature.

PubMed

Mbeutcha, Aurélie; Mathieu, Romain; Rouprêt, Morgan; Gust, Kilian M; Briganti, Alberto; Karakiewicz, Pierre I; Shariat, Shahrokh F

2016-10-01

In the context of customized patient care for upper tract urothelial carcinoma (UTUC), decision-making could be facilitated by risk assessment and prediction tools. The aim of this study was to provide a critical overview of existing predictive models and to review emerging promising prognostic factors for UTUC. A literature search of articles published in English from January 2000 to June 2016 was performed using PubMed. Studies on risk group stratification models and predictive tools in UTUC were selected, together with studies on predictive factors and biomarkers associated with advanced-stage UTUC and oncological outcomes after surgery. Various predictive tools have been described for advanced-stage UTUC assessment, disease recurrence and cancer-specific survival (CSS). Most of these models are based on well-established prognostic factors such as tumor stage, grade and lymph node (LN) metastasis, but some also integrate newly described prognostic factors and biomarkers. These new prediction tools seem to reach a high level of accuracy, but they lack external validation and decision-making analysis. The combinations of patient-, pathology- and surgery-related factors together with novel biomarkers have led to promising predictive tools for oncological outcomes in UTUC. However, external validation of these predictive models is a prerequisite before their introduction into daily practice. New models predicting response to therapy are urgently needed to allow accurate and safe individualized management in this heterogeneous disease.

Peculiarities of transformation of adaptation level of the astronaut in conditions of long-lasting flight

NASA Astrophysics Data System (ADS)

Padashulya, H.; Prisnyakova, L.; Prisnyakov, V.

Prognostication of the development of adverse factors of psychological processes in the personality of the astronaut who time and again feels transformation of internal structure of his personality is one of cardinal problems of the long-lasting flight Adaptation to changing conditions of long-lasting flight is of particular importance because it has an effect on the efficiency of discharged functions and mutual relations in the team The fact of standard psychological changes emerging in the personality being in the state of structural transformations is the precondition for the possibility of prognostication Age-specific gender and temperamental differences in the personality enable to standardize these changes Examination of the process of transformation of adaptation level of the personality in the varied environment depending on the type of temperament and constituents age and gender is chief object of the report In the report it is shown that in the process of transformation of adaptation parameters - attitude to guillemotleft work guillemotright guillemotleft family guillemotright guillemotleft environment guillemotright and guillemotleft ego guillemotright - the changes can go in two directions - in the direction of increase and decline of indexes The trend of increase enables to accumulate them and form potentiality to reduce or increase the level of personality adaptation There is a hypothesis that the dynamics of the process of transformation of adaptation parameter is shown up in the orientation of increase of

[Prognosis of survival in advanced cancer].

PubMed

de Arriba Méndez, J J

2007-01-01

Accurate prognoses are important in the care of patients with advanced cancer to assist clinicians in their decision making, and to help patients set their goals and priorities. Several studies have demonstrated that doctors are inaccurate and overly optimistic when predicting the survival of patients with advanced and terminal cancer. To improve prognostic accuracy, clinicians can use a number of factors that have proven to be associated with life expectancy: performance status, some signs and symptoms and some laboratory markers. Prognostic scores including most of the factors are also developed. Patients and their families can benefit from realistic prognostic information in a simple and empathetic manner.

[Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer].

PubMed

Yao, Shuyang; Qian, Kun; Wang, Ruotian; Li, Yuanbo; Zhang, Yi

2015-06-01

This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed) in previously treated advanced non-small cell lung cancer (NSCLC). Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS) was evaluated by Kaplan-Meier method. Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR) (28.1% vs 18.2%, P=0.341), disease control rate (DFS)(43.8% vs 45.5%, P=0.890), and PFS (4.3 months vs 3.8 months, P=0.506). In the icotinib group, the ORR of epidermal growth factor receptor (EGFR) mutant was significantly higher than that of EGFR unknown or wild type (P=0.017). In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001). Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

Clinical Features and Prognostic Factors of Hodgkin’s Lymphoma: A Single Center Experience

PubMed Central

Kılıçkap, Saadettin; Barışta, İbrahim; Ülger, Şükran; Çelik, İsmail; Selek, Uğur; Yıldız, Ferah; Kars, Ayşe; Özışık, Yavuz; Tekuzman, Gülten

2013-01-01

Background: Hodgkin’s lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. Aims: We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Study Design: Retrospective study. Methods: Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. Results: We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of “B” symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. Conclusion: This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country. PMID:25207097

Implications of prognostic factors and risk groups in the management of differentiated thyroid cancer.

PubMed

Shaha, Ashok R

2004-03-01

The outcome in differentiated thyroid cancer generally depends on the stage of the disease at the time of presentation; prognostic factors such as age, grade, size, extension, or distant metastasis; and risk groups (eg, low or high risk). The author has reviewed a large number of patients with differentiated thyroid cancer to analyze their hypothesis and to confirm that various risk groups have a major implication in relation to extent of the treatment and outcome. Differentiated thyroid cancers make up 90% of all thyroid tumors. The prognostic factors are well defined, such as age, size of the tumor, extrathyroidal extension, presence of distant metastasis, histological appearance, and grade of the tumor. The author has previously divided the risk groups into low-, intermediate-, and high-risk categories based on prognostic factors. The study describes the author's treatment approach related to the extent of thyroidectomy and adjuvant therapy based on various risk groups and the long-term survival. Retrospective. In a retrospective review of 1038 patients with differentiated thyroid carcinoma, various prognostic factors were studied by univariate and multivariate analysis. The significant prognostic factors were studied in detail and, based on these prognostic factors, the patients were divided into low-, intermediate- and high-risk groups. The survival curves were plotted by Kaplan-Meier method. The long-term survivals in low-, intermediate- and high-risk groups were 99%, 87%, and 57% respectively. Based on these risk groups, a decision tree was made regarding extent of thyroidectomy and adjuvant treatment. In the high-risk group and selected patients in the intermediate-risk group, aggressive surgery including removal of all gross disease and extrathyroidal extension with postoperative radioactive iodine ablation is recommended. In the low-risk group and selected patients in the intermediate-risk group, lobectomy appears to be satisfactory with excellent long-term outcome. The surgical treatment offers the best long-term results in low-risk patients, and the role of adjuvant treatment in this group is questionable. The decisions in the management of well-differentiated thyroid cancer should be based on various prognostic factors and risk groups. The long-term survival in the low-risk group is excellent, and consideration should be given to conservative surgical resection depending on the extent of the disease. In the high-risk group and selected patients in the intermediate-risk group, total thyroidectomy with radioactive ablation is warranted. A consideration may be given to external-beam radiation therapy in selected high-risk patients. It is apparent, based on the author's clinical experience and critical retrospective analysis, that the author's hypothesis that risk groups are extremely important in the long-term outcome of patients with differentiated thyroid cancer is correct. Based on various risk groups, the author currently is able to guide the treatment policies for thyroid cancer.

No association between anxiety and depression and adverse clinical outcome among patients with cardiovascular disease: findings from the DANREHAB trial.

PubMed

Kornerup, Henriette; Zwisler, Ann-Dorthe Olsen; Prescott, Eva

2011-10-01

Anxiety and depression have been linked to adverse prognostic outcome in patients with cardiovascular disease (CVD) with mixed results. The timing of anxiety and depression measurement has received little attention so far. The study sample consisted of 536 patients admitted to hospital for CVD and followed in a rehabilitation trial. Symptoms were assessed using the Hospital Anxiety and Depression Scale at baseline and after 1 year. Cox proportional hazards model was used to describe the association between anxiety and depression and adverse outcome (myocardial infarction (MI), heart failure (HF), stroke, death and a combined endpoint) after 5 years. Prevalence of anxiety and depression at baseline was 32% and 13%, respectively. There were 303 combined events; 140 deaths, 60 patients had MI, 177 patients were admitted to hospital with HF and 60 patients had a stroke. Neither anxiety nor depression at any time was associated with mortality or the combined endpoint. Anxiety in IHD patients at baseline and at 1 year was associated with increased risk of MI (HR 2.74; 95% CI: 1.10-6.83) but was attenuated after adjusting for other risk factors (HR 1.18; 95% CI: 0.39-3.55). Both anxiety and depression at 1 year were associated with increased risk of stroke: HR 2.25 (95% CI: 1.05-4.82) and 2.34 (95% CI: 0.99-5.50), respectively, but risk associated with anxiety was attenuated after adjustment. There were no gender differences. Contrary to conclusions from recent meta-analyses, anxiety and depression measured at baseline and after 1 year were not associated with adverse outcome in CVD patients after multivariable adjustment. Copyright © 2011 Elsevier Inc. All rights reserved.

Use of tailored loading-dose clopidogrel in patients undergoing selected percutaneous coronary intervention based on adenosine diphosphate-mediated platelet aggregation.

PubMed

Meng, Kang; Lü, Shu-Zheng; Zhu, Hua-Gang; Chen, Xin; Ge, Chang-Jiang; Song, Xian-Tao

2010-12-01

Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention. A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n = 104) served as the Talcom (Taijia) group; others (n = 101) received Plavix, the Plavix group. Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months. Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a > 50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P = 0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P > 0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of > 50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P = 5.43). No acute or subacute stent thrombosis events occurred. An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

Advances in therapy for Philadelphia-positive acute lymphoblastic leukaemia of childhood and adolescence.

PubMed

Bleckmann, Kirsten; Schrappe, Martin

2016-03-01

The presence of the BCR/ABL1 fusion gene in childhood acute lymphoblastic leukaemia (ALL) is a rare finding and has been an adverse prognostic factor associated with a high risk of therapeutic failure. The current key components of treatment are intensive polychemotherapy and a BCR/ABL1 kinase domain inhibitor. This treatment approach has been applied in a few clinical trials by paediatric leukaemia study groups. Thus, this subtype of ALL serves as the first model system for truly targeted treatment. The role of haematopoietic stem cell transplantation (HSCT) is increasingly called into question, at least in a favourable, though not yet clearly defined, subset of patients. Currently, the choice of the most effective tyrosine kinase inhibitor is not yet settled, in particular, in view of potential reduction of overall treatment intensity. © 2016 John Wiley & Sons Ltd.

Measuring Biological Age via Metabonomics: The Metabolic Age Score.

PubMed

Hertel, Johannes; Friedrich, Nele; Wittfeld, Katharina; Pietzner, Maik; Budde, Kathrin; Van der Auwera, Sandra; Lohmann, Tobias; Teumer, Alexander; Völzke, Henry; Nauck, Matthias; Grabe, Hans Jörgen

2016-02-05

Chronological age is one of the most important risk factors for adverse clinical outcome. Still, two individuals at the same chronological age could have different biological aging states, leading to different individual risk profiles. Capturing this individual variance could constitute an even more powerful predictor enhancing prediction in age-related morbidity. Applying a nonlinear regression technique, we constructed a metabonomic measurement for biological age, the metabolic age score, based on urine data measured via (1)H NMR spectroscopy. We validated the score in two large independent population-based samples by revealing its significant associations with chronological age and age-related clinical phenotypes as well as its independent predictive value for survival over approximately 13 years of follow-up. Furthermore, the metabolic age score was prognostic for weight loss in a sample of individuals who underwent bariatric surgery. We conclude that the metabolic age score is an informative measurement of biological age with possible applications in personalized medicine.

Social experiential deprivation in autism spectrum disorders: A possible prognostic factor?

PubMed

Kaku, Sowmyashree Mayur; Basheer, Salah; Venkatasubramanian, Ganesan; Bharath, Rose Dawn; Girimaji, Satish Chandra; Srinath, Shoba

2017-04-01

Autism spectrum disorders (ASD) are well known to be influenced by various environmental factors. Among these influencers, social experiential deprivation (SED) in infancy is one of them which is not well reported. We explored factors contributing to SED in 11 young children diagnosed to have ASD and compared them to 24 children without SED also having ASD. Intervention mainly addressing factors causing SED for 6 months demonstrated that children with SED had a better outcome at follow up. Could SED be a possible prognostic factor in children with ASD? Copyright © 2017 Elsevier B.V. All rights reserved.

Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide.

PubMed

Hou, Jinxiao; Wang, Shuye; Zhang, Yingmei; Fan, Dachuan; Li, Haitao; Yang, Yiju; Ge, Fei; Hou, Wenyi; Fu, Jinyue; Wang, Ping; Zhao, Hongli; Sun, Jiayue; Yang, Kunpeng; Zhou, Jin; Li, Xiaoxia

2017-12-01

Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days. In total, 35 EDs (16.2%) occurred that were caused by hemorrhage, differentiation syndrome (DS), infection, and other causes, in order of prevalence. The independent prognostic factors for overall ED and death within 8-30 days were the same and included serum creatinine level, Eastern Cooperative Oncology Group (ECOG) score, sex, and fibrinogen level. The risk factors for hemorrhagic ED and death within 7 days were similar and included serum creatinine level, ECOG score, and white blood cell count, while hemorrhagic ED was also associated with D-dimer. Our findings revealed a high rate of ED, and the causes of ED were similar to those among patients who received ATRA-based therapy. Increased creatinine level was the most powerful predictor, and an ECOG score greater than 2 was another strong prognostic factor for all four types of ED.

Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

PubMed

Jary, Marine; Lecomte, Thierry; Bouché, Olivier; Kim, Stefano; Dobi, Erion; Queiroz, Lise; Ghiringhelli, Francois; Etienne, Hélène; Léger, Julie; Godet, Yann; Balland, Jérémy; Lakkis, Zaher; Adotevi, Olivier; Bonnetain, Franck; Borg, Christophe; Vernerey, Dewi

2016-11-15

In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p < 0.0001). This score had a good discrimination ability (C-index = 0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values. © 2016 UICC.

Prognostic model based on nailfold capillaroscopy for identifying Raynaud's phenomenon patients at high risk for the development of a scleroderma spectrum disorder: PRINCE (prognostic index for nailfold capillaroscopic examination).

PubMed

Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta; Lubatti, Chiara; Meani, Laura; Zahalkova, Lenka; Zeni, Silvana; Fantini, Flavio

2008-07-01

To construct a prognostic index based on nailfold capillaroscopic examinations that is capable of predicting the 5-year transition from isolated Raynaud's phenomenon (RP) to RP secondary to scleroderma spectrum disorders (SSDs). The study involved 104 consecutive adult patients with a clinical history of isolated RP, and the index was externally validated in another cohort of 100 patients with the same characteristics. Both groups were followed up for 1-8 years. Six variables were examined because of their potential prognostic relevance (branching, enlarged and giant loops, capillary disorganization, microhemorrhages, and the number of capillaries). The only factors that played a significant prognostic role were the presence of giant loops (hazard ratio [HR] 2.64, P = 0.008) and microhemorrhages (HR 2.33, P = 0.01), and the number of capillaries (analyzed as a continuous variable). The adjusted prognostic role of these factors was evaluated by means of multivariate regression analysis, and the results were used to construct an algorithm-based prognostic index. The model was internally and externally validated. Our prognostic capillaroscopic index identifies RP patients in whom the risk of developing SSDs is high. This model is a weighted combination of different capillaroscopy parameters that allows physicians to stratify RP patients easily, using a relatively simple diagram to deduce the prognosis. Our results suggest that this index could be used in clinical practice, and its further inclusion in prospective studies will undoubtedly help in exploring its potential in predicting treatment response.

Insulin-like growth factor II messenger RNA-binding protein-3 is an independent prognostic factor in uterine leiomyosarcoma.

PubMed

Yasutake, Nobuko; Ohishi, Yoshihiro; Taguchi, Kenichi; Hiraki, Yuka; Oya, Masafumi; Oshiro, Yumi; Mine, Mari; Iwasaki, Takeshi; Yamamoto, Hidetaka; Kohashi, Kenichi; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

2018-04-01

The aim of this study was to identify the prognostic factors of uterine leiomyosarcoma (ULMS). We reviewed 60 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expression of insulin-like growth factor II messenger RNA-binding protein-3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. Mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (P < 0.0001), older age (P = 0.0244) and IMP3 expression (P = 0.0011) were significant predictors of a poor outcome. Multivariate analysis revealed advanced stage (P < 0.0001) and IMP3 (P = 0.0373) as independent predictors of a poor prognosis. Expressions of cell cycle markers and hormone receptors, and MED12 mutations (12% in ULMSs) were not identified as prognostic markers in this study. IMP3 expression in ULMS could be a marker of a poor prognosis. © 2017 John Wiley & Sons Ltd.

Influence of marital status on the survival of adults with extrahepatic/intrahepatic cholangiocarcinoma.

PubMed

Chen, Zhiqiang; Pu, Liyong; Gao, Wen; Zhang, Long; Han, Guoyong; Zhu, Qin; Li, Xiangcheng; Wu, Jindao; Wang, Xuehao

2017-04-25

Although the prognostic value of marital status has been implicated in many cancers, its prognostic impact on cholangiocarcinoma has not yet been determined. The aim of this study was to examine the association between marital status and cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from the Surveillance, Epidemiology, and End Results database. We found widowed patients were more likely to be female, aged more than 70, and from low income areas. Multivariate analysis indicated that marital status was an independent prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis suggested the widowed status independently predicted poor survival at regional stage and in older patients with intrahepatic cholangiocarcinoma. To conclude, marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed patients are at greater risk of death than others.

Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.

PubMed

De Paz, Dante; Kao, Huang-Kai; Huang, Yenlin; Chang, Kai-Ping

2017-08-10

Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients. In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy. Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

Clinicopathologic and prognostic factors in adenoid cystic carcinoma of head and neck minor salivary glands: A clinical analysis of 130 cases.

PubMed

He, Shizhi; Li, Pingdong; Zhong, Qi; Hou, Lizhen; Yu, Zhenkun; Huang, Zhigang; Chen, Xuejun; Fang, Jugao; Chen, Xiaohong

This study was to investigate clinicopathologic characteristics and prognostic factors in adenoid cystic carcinoma of head and neck minor salivary glands. We conducted a retrospective review of 130 patients with adenoid cystic carcinoma of head and neck minor salivary glands that were evaluated between 2000 and 2013 in Beijng Tongren Hospital. Five-year overall survival and disease-free survival rates were 80.8% and 55.6%. Local recurrence rate was 40%, regional recurrence 3.8%, and distant metastasis was 28.5%. On univariate analysis, solid histological subtype, perineural invasion, positive surgical margins and advanced stages were found to be poor prognostic indicators. On multivariate analysis, solid histological subtype and positive surgical margins were significant prognostic factors of worse overall survival. Solid histological subtype and positive surgical margins were the most important predictors of poor outcome in adenoid cystic carcinoma of minor salivary glands. Surgery with postoperative radiation were recommended treatment and offered durable local control. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies.

PubMed

Bruix, Jordi; Cheng, Ann-Lii; Meinhardt, Gerold; Nakajima, Keiko; De Sanctis, Yoriko; Llovet, Josep

2017-11-01

Sorafenib, an oral multikinase inhibitor, significantly prolonged overall survival (OS) vs. placebo in patients with unresectable hepatocellular carcinoma (HCC) in two phase III studies, SHARP (Sorafenib HCC Assessment Randomized Protocol) and Asia Pacific (AP). To assess prognostic factors for HCC and predictive factors of sorafenib benefit, we conducted a pooled exploratory analysis from these placebo-controlled phase III studies. To identify potential prognostic factors for OS, univariate and multivariate (MV) analyses were performed for baseline variables by Cox proportional hazards model. Hazard ratios (HRs) and median OS were evaluated across pooled subgroups. To assess factors predictive of sorafenib benefit, the interaction term between treatment for each subgroup was evaluated by Cox proportional hazard model. In 827 patients (448 sorafenib; 379 placebo) analyzed, strong prognostic factors for poorer OS identified from MV analysis in both treatment arms were presence of macroscopic vascular invasion (MVI), high alpha-fetoprotein (AFP), and high neutrophil-to-lymphocyte ratio (NLR; ⩽ vs. >median [3.1]). Sorafenib OS benefit was consistently observed across all subgroups. Significantly greater OS sorafenib benefit vs. placebo was observed in patients without extrahepatic spread (EHS; HR, 0.55 vs. 0.84), with hepatitis C virus (HCV) (HR, 0.47 vs. 0.81), and a low NLR (HR, 0.59 vs. 0.84). In this exploratory analysis, presence of MVI, high AFP, and high NLR were prognostic factors of poorer OS. Sorafenib benefit was consistently observed irrespective of prognostic factors. Lack of EHS, HCV, and lower NLR were predictive of a greater OS benefit with sorafenib. This exploratory pooled analysis showed that treatment with sorafenib provides a survival benefit in all subgroups of patients with HCC; however, the magnitude of benefit is greater in patients with disease confined to the liver (without extrahepatic spread), or in those with hepatitis C virus, or a lower neutrophil-to-lymphocyte ratio, an indicator of inflammation status. These results help inform the prognosis of patients receiving sorafenib therapy and provide further refinements for the design of trials testing new agents vs. sorafenib. Clinical Trial Numbers: NCT00105443 and NCT00492752. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Using Cox's proportional hazards model for prognostication in carcinoma of the upper aero-digestive tract.

PubMed

Wolfensberger, M

1992-01-01

One of the major short comings of the traditional TNM system is its limited potential for prognostication. With the development of multifactorial analysis techniques, such as Cox's proportional hazards model, it has become possible to simultaneously evaluate a large number of prognostic variables. Cox's model allows both the identification of prognostically relevant variables and the quantification of their prognostic influence. These characteristics make it a helpful tool for analysis as well as for prognostication. The goal of the present study was to develop a prognostic index for patients with carcinoma of the upper aero-digestive tract which makes use of all prognostically relevant variables. To accomplish this, the survival data of 800 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx were analyzed. Sixty-one variables were screened for prognostic significance; of these only 19 variables (including age, tumor location, T, N and M stages, resection margins, capsular invasion of nodal metastases, and treatment modality) were found to significantly correlate with prognosis. With the help of Cox's equation, a prognostic index (PI) was computed for every combination of prognostic factors. To test the proposed model, the prognostic index was applied to 120 patients with carcinoma of the oral cavity or oropharynx. A comparison of predicted and observed survival showed good overall correlation, although actual survival tended to be better than predicted.

Visual outcomes and prognostic factors in open-globe injuries.

PubMed

Fujikawa, Azusa; Mohamed, Yasser Helmy; Kinoshita, Hirofumi; Matsumoto, Makiko; Uematsu, Masafumi; Tsuiki, Eiko; Suzuma, Kiyoshi; Kitaoka, Takashi

2018-06-08

Ocular trauma is an important cause of visual loss worldwide. Improvements in our knowledge of the pathophysiology and management of ocular trauma during the past 30 years, in conjunction with advances in the instrumentation and techniques of ocular surgery, have improved the efficacy of vitreoretinal surgery in injured eyes. The aim of the current study was to determine the visual outcomes and prognostic factors of open-globe injuries in the Japanese population. Retrospective study of 59 eyes of 59 patients presented with open globe injuries between September 2008 and March 2014 at Nagasaki University Hospital was conducted. Demographic factors including age, gender, and clinical data such as cause of injury, presenting visual acuity (VA), location of injury, type of injury, lens status, presence of intraocular foreign body, types of required surgeries, and final VA were recorded. According to the classification of Ocular Trauma Classification Group, wound location was classified into three zones. Chi-square test was used to compare presented data. Out of the 59 patients, 46 were placed in the Light Perception (LP) group, and 13 were placed in the No Light Perception (NLP) group. Work-related trauma was the most common cause (27 eyes) followed by falls (19eyes). Work-related trauma was common in males (P = 0.004), while falls was significantly common in females (P = 0.00001). Zone III injuries had statistically significantly poor prognostic factor compared to other zones (P = 0.04). All cases of NLP group (100%) presented with rupture globe. Poor VA at first visit (P = 0.00001), rupture globe (P = 0.026), history of penetrating keratoplasty (PK) (P = 0.017), retinal detachment (RD) (P = 0.0001), vitreous hemorrhage (VH) (P = 0.044), and dislocation of crystalline lens (P = 0.0003) were considered as poor prognostic factors. Poor VA at first visit, rupture globe, zone III injuries, history of penetrating keratoplasty, RD, VH, and dislocation of crystalline lens were found to be poor prognostic factors. PPV had a good prognostic value in open globe injuries associated with posterior segment involvement.

Using Multivariate Regression Model with Least Absolute Shrinkage and Selection Operator (LASSO) to Predict the Incidence of Xerostomia after Intensity-Modulated Radiotherapy for Head and Neck Cancer

PubMed Central

Ting, Hui-Min; Chang, Liyun; Huang, Yu-Jie; Wu, Jia-Ming; Wang, Hung-Yu; Horng, Mong-Fong; Chang, Chun-Ming; Lan, Jen-Hong; Huang, Ya-Yu; Fang, Fu-Min; Leung, Stephen Wan

2014-01-01

Purpose The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO) to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC) patients treated with IMRT. Methods and Materials Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3+ xerostomia) was defined as moderate-to-severe xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT. Normal tissue complication probability (NTCP) models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R2, chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. Results Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R2 was satisfactory and corresponded well with the expected values. Conclusions Multivariate NTCP models with LASSO can be used to predict patient-rated xerostomia after IMRT. PMID:24586971

Using multivariate regression model with least absolute shrinkage and selection operator (LASSO) to predict the incidence of Xerostomia after intensity-modulated radiotherapy for head and neck cancer.

PubMed

Lee, Tsair-Fwu; Chao, Pei-Ju; Ting, Hui-Min; Chang, Liyun; Huang, Yu-Jie; Wu, Jia-Ming; Wang, Hung-Yu; Horng, Mong-Fong; Chang, Chun-Ming; Lan, Jen-Hong; Huang, Ya-Yu; Fang, Fu-Min; Leung, Stephen Wan

2014-01-01

The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO) to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC) patients treated with IMRT. Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3(+) xerostomia) was defined as moderate-to-severe xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT. Normal tissue complication probability (NTCP) models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R(2), chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R(2) was satisfactory and corresponded well with the expected values. Multivariate NTCP models with LASSO can be used to predict patient-rated xerostomia after IMRT.

Novel recurrent chromosomal aberrations detected in clonal plasma cells of light chain amyloidosis patients show potential adverse prognostic effect: first results from a genome-wide copy number array analysis

PubMed Central

Granzow, Martin; Hegenbart, Ute; Hinderhofer, Katrin; Hose, Dirk; Seckinger, Anja; Bochtler, Tilmann; Hemminki, Kari; Goldschmidt, Hartmut; Schönland, Stefan O.; Jauch, Anna

2017-01-01

Immunoglobulin light chain (AL) amyloidosis is a rare plasma cell dyscrasia characterized by the deposition of abnormal amyloid fibrils in multiple organs, thus impairing their function. In the largest cohort studied up to now of 118 CD138-purified plasma cell samples from previously untreated immunoglobulin light chain amyloidosis patients, we assessed in parallel copy number alterations using high-density copy number arrays and interphase fluorescence in situ hybridization (iFISH). We used fluorescence in situ hybridization probes for the IgH translocations t(11;14), t(4;14), and t(14;16) or any other IgH rearrangement as well as numerical aberrations of the chromosome loci 1q21, 8p21, 5p15/5q35, 11q22.3 or 11q23, 13q14, 15q22, 17p13, and 19q13. Recurrent gains included chromosomes 1q (36%), 9 (24%), 11q (24%), as well as 19 (15%). Recurrent losses affected chromosome 13 (29% monosomy) and partial losses of 14q (19%), 16q (14%) and 13q (12%), respectively. In 88% of patients with translocation t(11;14), the hallmark chromosomal aberration in AL amyloidosis, a concomitant gain of 11q22.3/11q23 detected by iFISH was part of the unbalanced translocation der(14)t(11;14)(q13;q32) with the breakpoint in the CCND1/MYEOV gene region. Partial loss of chromosome regions 14q and 16q were significantly associated to gain 1q. Gain 1q21 detected by iFISH almost always resulted from a gain of the long arm of chromosome 1 and not from trisomy 1, whereas deletions on chromosome 1p were rarely found. Overall and event-free survival analysis found a potential adverse prognostic effect of concomitant gain 1q and deletion 14q as well as of deletion 1p. In conclusion, in the first whole genome report of clonal plasma cells in AL amyloidosis, novel aberrations and hitherto unknown potential adverse prognostic effects were uncovered. PMID:28341732

Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiologic parameters.

PubMed

Rigolin, Gian Matteo; Cibien, Francesca; Martinelli, Sara; Formigaro, Luca; Rizzotto, Lara; Tammiso, Elisa; Saccenti, Elena; Bardi, Antonella; Cavazzini, Francesco; Ciccone, Maria; Nichele, Ilaria; Pizzolo, Giovanni; Zaja, Francesco; Fanin, Renato; Galieni, Piero; Dalsass, Alessia; Mestichelli, Francesca; Testa, Nicoletta; Negrini, Massimo; Cuneo, Antonio

2012-03-08

It is unclear whether karyotype aberrations that occur in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC; n = 64) and a validation cohort (VC; n = 84) of patients with chronic lymphocytic leukemia with "normal" FISH. An abnormal karyotype was found in 21.5% and 35.7% of cases in the LC and VC, respectively, and was associated with a lower immunophenotypic score (P = .030 in the LC, P = .035 in the VC), advanced stage (P = .040 in the VC), and need for treatment (P = .002 in the LC, P = < .0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In patients with chronic lymphocytic leukemia with normal FISH, karyotypic aberrations by conventional cytogenetics with novel mitogens identify a subset of cases with adverse prognostic features.

Prognostic impact of CXCL16 and CXCR6 in non-small cell lung cancer: combined high CXCL16 expression in tumor stroma and cancer cells yields improved survival.

PubMed

Hald, Sigurd M; Kiselev, Yury; Al-Saad, Samer; Richardsen, Elin; Johannessen, Charles; Eilertsen, Marte; Kilvaer, Thomas K; Al-Shibli, Khalid; Andersen, Sigve; Busund, Lill-Tove; Bremnes, Roy M; Donnem, Tom

2015-05-29

The chemokine CXCL16 and its receptor CXCR6 are expressed by a variety of immune cells and have been shown to influence angiogenesis. The expression of CXCR6 and CXCL16 has been examined in numerous human cancers; however no studies have yet investigated their influence on prognosis in non-small cell lung cancer (NSCLC). We aimed to explore their prognostic significance in NSCLC, in addition to examining associations with previously investigated markers. Resected tumor tissue from 335 consecutive unselected stage I-IIIA NSCLC patients (1990-2005) were collected. Immunohistochemistry was used to evaluate the expression of CXCR6 and CXCL16 on tissue microarrays. In vitro, NSCLC cells (NCI-H460, A549 cells) were transfected with CXCL16 siRNA to examine effects on proliferation. In univariate analysis, ↑ stromal cell CXCL16 expression was a significant positive prognostic factor (P = 0.016). CXCR6 was expressed in cancer cells, but did not show any prognostic impact. In the multivariate analysis, combined ↑cancer, and ↑stromal cell CXCL16 expression was an independent positive prognostic factor when compared to ↓stromal and ↓cancer cell expression (HR: 0.42; 95 % CI: 0.20-0.88; P = 0.022). Knockdown of CXCL16 by siRNA resulted in accelerated proliferation of NSCLC cell lines. We have shown that combined ↑cancer and ↑stromal cell CXCL16 expression is an independent positive prognostic factor in NSCLC. Further studies are warranted to elucidate the biological mechanism underlying this finding.

Anatomical location of metastatic lymph nodes: an indispensable prognostic factor for gastric cancer patients who underwent curative resection.

PubMed

Zhao, Bochao; Zhang, Jingting; Zhang, Jiale; Chen, Xiuxiu; Chen, Junqing; Wang, Zhenning; Xu, Huimian; Huang, Baojun

2018-02-01

Although the numeric-based lymph node (LN) staging was widely used in the worldwide, it did not represent the anatomical location of metastatic lymph nodes (MLNs) and not reflect extent of LN dissection. Therefore, in the present study, we investigated whether the anatomical location of MLNs was still necessary to evaluate the prognosis of node-positive gastric cancer (GC) patients. We reviewed 1451 GC patients who underwent radical gastrectomy in our institution between January 1986 and January 2008. All patients were reclassified into several groups according to the anatomical location of MLNs and the number of MLNs. The prognostic differences between different patient groups were compared and clinicopathologic features were analyzed. In the present study, both anatomical location of MLNs and the number of MLNs were identified as the independent prognostic factors (p < .01). The patients with extraperigastric LN involvement showed a poorer prognosis compared with the perigastric-only group (p < .001). For the N1-N2 stage patients, the prognostic discrepancy was still observed among them when the anatomical location of MLNs was considered (p < .05). For the N3-stage patients, although the anatomical location of MLNs had no significant effect on the prognosis of these patients, the higher number of MLNs in the extraperigastric area was correlated with the unfavorable prognosis (p < .05). The anatomical location of MLNs was an important factor influencing the prognostic outcome of GC patients. To provide more accurate prognostic information for GC patients, the anatomical location of MLNs should not be ignored.

Diffuse large B-cell lymphoma, not otherwise specified of the palate: A case report

PubMed Central

Pereira, Thaís SF.; Castro, Alexandre F.; Mesquita, Ricardo A.

2013-01-01

Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin´s lymphoma found in oral and maxillofacial regions. A large number of cases may be biologically heterogeneous, which are commonly defined as DLBCL, not otherwise specified (NOS) by the World Health Organization (WHO-2008). The present case reports on an ulcer of raised and irregular edges, found on the border between the hard and soft palate, as the first and only manifestation of an extranodal non-Hodgkin lymphoma in an 85-year-old patient. Incisional biopsy was carried out, and the specimen revealed a proliferation of large lymphoid cells suggestive of diffuse large cell lymphoma. An immunohistochemical analysis was performed. EBV-RNA was assessed by in situ hybridization that also proved to be negative. Immunohistochemical and EBV analyses are important to avoid delays and inappropriate treatment strategies. Although advanced age is considered an adverse prognostic factor, early diagnosis did prove to be a key contributory factor in the cure of non-Hodgkin lymphoma. Key words:Diffuse large B-cell lymphoma, elderly, EBV. PMID:24455096

[Pediatric medulloblastoma: Retrospective series of 52 patients].

PubMed

Vigneron, C; Antoni, D; Coca, A; Entz-Werlé, N; Lutz, P; Spiegel, A; Jannier, S; Niederst, C; Jarnet, D; Meyer, P; Kehrli, P; Noël, G

2016-04-01

Retrospective analysis of the results of 52 children irradiated for a medulloblastoma. Between 1974 and 2012, 52 children with an average age of 6 years and a half (11 months-17 years and a half) were treated with surgery then with radiotherapy at the Comprehensive Cancer Centre of Strasbourg (France). For 44 children, the treatment consisted of a chemotherapy. After a mean follow-up of 106.6 months (7-446 months), 13 relapses and 24 deaths were observed. Overall survival at 5 years and 10 years were 62% and 57%, respectively. Disease-free survival at 5 years and 10 years were 80% and 63%, respectively. Univariate analysis found the following adverse prognostic factors: the existence of a postoperative residue, the positivity of the cerebrospinal fluid, the metastatic status and medulloblastoma of high-risk. Positivity of the cerebrospinal fluid remains a negative factor in multivariate analysis. These results confirm the survival rate obtained by a conventional approach (surgery then irradiation). Insufficiency of results and rarity of medulloblastoma require the establishment of international protocols. Copyright © 2016. Published by Elsevier SAS.

Tumour biomarkers: homeostasis as a novel prognostic indicator

PubMed Central

Falco, Michela; Palma, Giuseppe; Rea, Domenica; De Biase, Davide; Scala, Stefania; D'Aiuto, Massimiliano; Facchini, Gaetano; Perdonà, Sisto; Barbieri, Antonio

2016-01-01

The term ‘personalized medicine’ refers to a medical procedure that consists in the grouping of patients based on their predicted individual response to therapy or risk of disease. In oncologic patients, a ‘tailored’ therapeutic approach may potentially improve their survival and well-being by not only reducing the tumour, but also enhancing therapeutic response and minimizing the adverse effects. Diagnostic tests are often used to select appropriate and optimal therapies that rely both on patient genome and other molecular/cellular analysis. Several studies have shown that lifestyle and environmental factors can influence the epigenome and that epigenetic events may be involved in carcinogenesis. Thus, in addition to traditional biomarkers, epigenetic factors are raising considerable interest, because they could potentially be used as an excellent tool for cancer diagnosis and prognosis. In this review, we summarize the role of conventional cancer genetic biomarkers and their association with epigenomics. Furthermore, we will focus on the so-called ‘homeostatic biomarkers’ that result from the physiological response to cancer, emphasizing the concept that an altered ‘new’ homeostasis influence not only tumour environment, but also the whole organism. PMID:27927793

Prognostic value of mutational characteristics in gastrointestinal stromal tumors: a single-center experience in 275 cases.

PubMed

Wang, Ming; Xu, Jia; Zhao, Wenyi; Tu, Lin; Qiu, Weiqing; Wang, Chaojie; Shen, Yangyin; Liu, Qiang; Cao, Hui

2014-01-01

The objective of this study was to investigate the impact of KIT/PDGFRA mutations on the prognosis of gastrointestinal stromal tumors (GISTs). In the present study, genotype analyses were performed based on GIST samples from 275 patients. The relationship between mutation and clinicopathological characteristics were explored. All factors were evaluated for their impacts on relapse-free survival (RFS). Briefly, the results of genotype analyses showed that mutations were identified in 258 (93.8 %) patients, and deletion was the most frequent type of mutation accounting for 47.3 % (122/258) of all mutation cases, followed by substitution (87/258, 33.7 %) and duplication (49/258, 19.0 %). Moreover, for KIT exon 11 mutation, the most frequently involved area was from codon 557 to 560. Deep analyses showed that the mutation types were correlated with tumor location (P = 0.005), tumor size (P = 0.022), mitosis rate (P < 0.001), risk grade (P < 0.001), and relapse (P = 0.004). Furthermore, delW557-K558 correlated with mitosis rate (P = 0.042) and relapse (P = 0.036), and delTyr568/570 correlated with tumor origin (P = 0.018). Most importantly, mitotic rate [HR = 2.901 (95 % CI 1.094-7.695), P = 0.032] and risk grade [HR = 9.629 (95 % CI 1.997-46.416), P = 0.005] would be the representative traditional prognostic factors, and deletion with >3 codons would be an novel independent predictor of poor outcome for RFS in GIST patients with deletion mutation of KIT exon 11 [HR = 7.970 (95 % CI 1.774-35.803), P = 0.007]. All results indicated that mutation determined clinicopathological features and prognosis of GISTs, and more than three codons involvement may be a novel adverse indicator.

Survivin as prognostic and predictive factor in patients treated with gemcitabine, dexamethasone, and cisplatin for relapsed or refractory aggressive NHL.

PubMed

el Aziz, Lamiss Mohamed Abd

2014-11-01

The prognosis of relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) after front-line therapy remains poor. The development of more effective and less toxic salvage regimens remains a major challenge. Survivin is a member of the family of inhibitors of apoptosis, and survivin was associated with short survival and bad prognosis. This study was to evaluate the efficacy of GDP regimen (gemcitabine, dexamethasone and cisplatin) on relapsed or refractory aggressive NHL and various prognostic factors with special emphasis on survivin and observe the . Forty-six patients with relapsed and refractory NHL, intermediate or high-grade NHL (Revised European American Lymphoma Classification), who at least one regimen were enrolled into this study, which was carried out at Department, , Tanta University from July 2012 to July 2014. The patients were treated with GDP regimen (gemcitabine 1,000 mg/m(2) on days one and eight, dexamethasone 40 mg on days 1-3, and cisplatin 25 mg/m(2) on days 1-3) every 3 weeks. The efficacy and adverse events were evaluated according to the WHO criteria. All patients were assessed for efficacy and toxicity. The overall response rate was 58.7 %. Fourteen patients showed a complete response, thirteen partial responses, twelve stable diseases, and seven progressive disease. The 24-month overall survival was 50.8 %. Survivin is associated with low overall response and shorter overall survival. Grade 3 anemia was observed in four patients, grade 3 leucopenia in six patients, grade 3 neutropenia in six patients, and grade 3 thrombocytopenia in four patients. Non-hematologic toxicity included grade 3 infection in four patients. The present schedule of GDP showed modest efficacy and mild toxicity in patients with relapsed or refractory aggressive NHL.

The incidence of ophthalmopathy after radioiodine therapy for Graves` disease: Prognostic factors and the role of methimazole

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

Kung, A.W.C.; Cheng, A.

1994-08-01

Radioactive iodine-131 (RAI) has been reported to be associated with a high incidence of development or exacerbation of Graves` ophthalmopathy (GO). This is thought to be associated with a surge of autoantibodies after RAI therapy. The role of methimazole (MMI), which possesses immunomodulatory action, in the prevention of GO was explored by studying 114 patients with Graves` disease. They were assigned randomly to receive either RAI alone or adjunctive antithyroid drugs, which consisted of MMI and L-T{sub 4} as a block-replacement therapy for 12 months and were followed for 2 yr. Thirty-five patients (30.7%) had GO at presentation. Twenty-one (18%)more » patients developed new GO, and six had worsening of preexisting GO. The development of hypothyroidism (P < 0.01) and an elevation of TSH (P < 0.05) were associated with increased risk of development or exacerbation of GO. The chance of development or exacerbation of GO is higher in those with no ophthalmopathy than in those with preexisting GO at presentation (P = 0.002). The incidence of development or exacerbation of GO was similar in the two treatment groups (RAI, 22.8%; adjunctive antithyroid drugs, 23.7%; P = NS). MMI was able to suppress the surge of TSH receptor antibody (TRAB) after RAI, but a surge in TRAB was not of prognostic significance for the development of GO after RAI. Patients who developed or had exacerbation of GO actually had lower TRAB at presentation (P = 0.02). The authors conclude that hypothyroidism with elevated TSH is an important adverse factor for the development or exacerbation of GO, and MMI was unable to prevent the development or exacerbation of GO after RAI. 35 refs., 4 tabs.« less

Clinical Outcomes and Prognostic Factors of High-Dose Proton Beam Therapy for Peripheral Stage I Non-Small-Cell Lung Cancer.

PubMed

Hatayama, Yoshiomi; Nakamura, Tatsuya; Suzuki, Motohisa; Azami, Yusuke; Ono, Takashi; Yabuuchi, Tomonori; Hayashi, Yuichiro; Kimura, Kanako; Hirose, Katsumi; Wada, Hitoshi; Hareyama, Masato; Kikuchi, Yasuhiro; Takai, Yoshihiro

2016-09-01

The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Conventional chemotherapy or hypomethylating agents for older patients with acute myeloid leukaemia?

PubMed

Ferrara, Felicetto

2014-03-01

Acute myeloid leukaemia (AML) is the second more frequent hematologic malignancy in developed countries and primarily affects older adults with a median age at diagnosis of 69 years. Given the progressive ageing of the general population, the incidence of the disease in elderly people is expected to further increase in the years to come. Along with cytogenetics at diagnosis, age represents the most relevant prognostic factor in AML, in that the outcome steadily declines with increasing age. Reasons for poor prognosis include more frequent unfavourable karyotype and other adverse biologic characteristics, such as high rates of expression of genes drug resistance related and high prevalence of secondary AML. Noticeably, as compared with young adults, poorer results in elderly patients have been reported within any cytogenetic and molecular prognostic subgroup, because of frequent comorbid diseases, which render many patients ineligible to intensive chemotherapy. Therefore, predictive models have been developed with the aim of achieving best therapeutic results avoiding unnecessary toxicity. Following conventional induction therapy, older AML patients have complete remission rates in the range of 45-65%, and fewer than 10% of them survive for a minimum of 5 years. On the other hand, hypomethylating agents, such as azacytidine and decitabine offer the possibility of long-term disease control without necessarily achieving complete remission and can represent a reasonable alternative to intensive chemotherapy. Either intensive chemotherapy or hypomethylating agents have lights and shadows, and the therapeutic selection is often influenced by physician's and patient's attitude rather than definite criteria. Research is progress in order to assess predictive biologic factors, which would help clinicians in the selection of patients who can take actual benefit from different therapeutic options. Copyright © 2013 John Wiley & Sons, Ltd.

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

Fukumitsu, Nobuyoshi, E-mail: fukumitsun@yahoo.co.jp; Okumura, Toshiyuki; Mizumoto, Masashi

Purpose: To investigate the clinical features, prognostic factors, and toxicity of treatment for unresectable carcinomas of the nasal cavity and paranasal sinus (NCPS) treated with proton beam therapy (PBT). Methods and Materials: Seventeen patients (13 men, 4 women) with unresectable carcinomas of the NCPS who underwent PBT at University of Tsukuba between 2001 and 2007 were analyzed. The patients' median age was 62 years (range, 30-83 years). The tumors were located in the nasal cavity in 3 patients, the frontal sinus in 1, the ethmoid sinus in 9, and the maxillary sinus in 4. The clinical stage was Stage IVAmore » in 5 cases, IVB in 10, and recurrent in 2. The tumors were deemed unresectable for medical reasons in 16 patients and because of refusal at a previous hospital 4 months earlier in 1 patient. All the patients received PBT irradiation dose of 22-82.5 GyE and a total of 72.4-89.6 GyE over 30-64 fractions (median 78 GyE over 36 fractions) with X-ray, with attention not exceeding the delivery of 50 GyE to the optic chiasm and brainstem. Results: The overall survival rate was 47.1% at 2 years and 15.7% at 5 years, and the local control rate was 35.0% at 2 years and 17.5% at 5 years. Invasion of the frontal or sphenoid sinus was a prognostic factor for overall survival or local control. Late toxicity of more than Grade 3 was found in 2 patients (brain necrosis in 1 and ipsilateral blindness in 1); however, no mortal adverse effects were observed. Conclusion: Proton beam therapy enabled a reduced irradiation dose to the optic chiasm and brainstem, enabling the safe treatment of unresectable carcinomas in the NCPS. Superior or posterior extension of the tumor influenced patient outcome.« less

Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.

PubMed

Mignogna, Chiara; Staropoli, Nicoletta; Botta, Cirino; De Marco, Carmela; Rizzuto, Antonia; Morelli, Michele; Di Cello, Annalisa; Franco, Renato; Camastra, Caterina; Presta, Ivan; Malara, Natalia; Salvino, Angela; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Barni, Tullio; Donato, Giuseppe; Di Vito, Anna

2016-05-21

High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment.

Predictors of Gleason Score (GS) upgrading on subsequent prostatectomy: a single Institution study in a cohort of patients with GS 6

PubMed Central

Mehta, Vikas; Rycyna, Kevin; Baesens, Bart MM; Barkan, Güliz A; Paner, Gladell P; Flanigan, Robert C; Wojcik, Eva M; Venkataraman, Girish

2012-01-01

Background Biopsy Gleason score (bGS) remains an important prognostic indicator for adverse outcomes in Prostate Cancer (PCA). In the light of recent studies purporting difference in prognostic outcomes for the subgroups of GS7 group (primary Gleason pattern 4 vs. 3), upgrading of a bGS of 6 to a GS≥7 has serious implications. We sought to identify pre-operative factors associated with upgrading in a cohort of GS6 patients who underwent prostatectomy. Design We identified 281 cases of GS6 PCA on biopsy with subsequent prostatectomies. Using data on pre-operative variables (age, PSA, biopsy pathology parameters), logistic regression models (LRM) were developed to identify factors that could be used to predict upgrading to GS≥7 on subsequent prostatectomy. A decision tree (DT) was constructed. Results 92 of 281 cases (32.7%) were upgraded on subsequent prostatectomy. LRM identified a model with two variables with statistically significant ability to predict upgrading, including pre-biopsy PSA (Odds Ratio 8.66; 2.03-37.49, 95% CI) and highest percentage of cancer at any single biopsy site (Odds Ratio 1.03, 1.01-1.05, 95% CI). This two-parameter model yielded an area under curve of 0.67. The decision tree was constructed using only 3 leave nodes; with a test set classification accuracy of 70%. Conclusions A simplistic model using clinical and biopsy data is able to predict the likelihood of upgrading of GS with an acceptable level of certainty. External validation of these findings along with development of a nomogram will aid in better stratifying the cohort of low risk patients as based on the GS. PMID:22949931

Stereotactic radiotherapy following surgery for brain metastasis: Predictive factors for local control and radionecrosis.

PubMed

Doré, M; Martin, S; Delpon, G; Clément, K; Campion, L; Thillays, F

2017-02-01

To evaluate local control and adverse effects after postoperative hypofractionated stereotactic radiosurgery in patients with brain metastasis. We reviewed patients who had hypofractionated stereotactic radiosurgery (7.7Gy×3 prescribed to the 70% isodose line, with 2mm planning target volume margin) following resection from March 2008 to January 2014. The primary endpoint was local failure defined as recurrence within the surgical cavity. Secondary endpoints were distant failure rates and the occurrence of radionecrosis. Out of 95 patients, 39.2% had metastatic lesions from a non-small cell lung cancer primary tumour. The median Graded Prognostic Assessment score was 3 (48% of patients). One-year local control rates were 84%. Factors associated with improved local control were no cavity enhancement on pre-radiation MRI (P<0.00001), planning target volume less than 12cm 3 (P=0.005), Graded Prognostic Assessment score 2 or above (P=0.009). One-year distant cerebral control rates were 56%. Thirty-three percent of patients received whole brain radiation therapy. Histologically proven radionecrosis of brain tissue occurred in 7.2% of cases. The size of the preoperative lesion and the volume of healthy brain tissue receiving 21Gy (V 21 ) were both predictive of the incidence of radionecrosis (P=0.010 and 0.036, respectively). Adjuvant hypofractionated stereotactic radiosurgery to the postoperative cavity in patients with brain metastases results in excellent local control in selected patients, helps delay the use of whole brain radiation, and is associated with a relatively low risk of radionecrosis. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

[Triple-negative breast carcinoma--rewiev of current literature].

PubMed

Rubovszky, Gábor; Udvarhelyi, Nóra; Horváth, Zsolt; Láng, István; Kásler, Miklós

2010-12-01

Breast cancer is one of the most common malignancies in women. Approximately 15% of cases belong to the triple-negative breast cancer (TNBC) group, in which no estrogen/progesterone receptors, or HER2 expression is detected. The unfavorable prognosis of this group of patients, as well as the lack of effective targeted therapy makes TNBC the subject of intensive research. In the present study, we searched PubMed for publications from January 2007 to June 2009 with the following key-words in addition to "breast cancer" and "triple negative": "epidemiology" or "gene-profile" or "predictive" or "prognostic" or "therapy" or "review". A total of 513 publications were identified. Relevant references were also reviewed. Beyond the well-known facts that TNBC affects younger patients, and is more common among Afro- or Hispano-Americans with lower socioeconomic status, hormonal environment and obesity emerged as potential etiologic factors. TNBC is not a homogenous disease. It can be further sub-classified based on histomorphologic features and immunohistochemistry. Hereditary BRCA1 mutations as well as acquired BRCA1 disfunction are described to be common in TNBC. Previously, many investigators considered TNBC to be identical to a subgroup called basal-like breast cancer defined by gene expression micro-array technology, but in the light of more recent findings, this view is no longer accepted by most investigators. Several large studies provide evidence that triple negativity, per se, is an independent adverse prognostic factor, in spite of the fact that approximately 10% of TNBC patients have a good prognosis. The therapy of choice for TNBC is systemic chemotherapy. Promising novel targeted chemotherapeutic agents include PARP1 inhibitors, a new group of compounds exploiting the defective DNA repair machinery. Rubovszky G, Udvarhelyi N, Horváth Z, Láng I, Kásler M. Triple negative breast carcinoma - rewiev of current literature.

Postoperative Infectious Complications are Associated with Adverse Oncologic Outcomes in Esophageal Cancer Patients Undergoing Preoperative Chemotherapy.

PubMed

Yamashita, Kotaro; Makino, Tomoki; Miyata, Hiroshi; Miyazaki, Yasuhiro; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Yamasaki, Makoto; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2016-06-01

For some types of cancer, postoperative complications can negatively influence survival, but the association between these complications and oncological outcomes is unclear for patients with esophageal cancer who receive preoperative treatments. Data were retrospectively analyzed for patients who underwent curative resection following preoperative chemotherapy for esophageal squamous cell carcinoma from 2001 to 2011. Clinicopathological parameters and cancer-specific survival (CSS) were compared between patients with and without severe postoperative complications, grade III or higher, using the Clavien-Dindo classification. Of 255 patients identified, 104 (40.8 %) postoperatively developed severe complications. The most common complication was atelectasis in 61 (23.9 %), followed by pulmonary infection in 22 (8.6 %). Three-field lymphadenectomy, longer operation time, and more blood loss were significantly associated with a higher incidence of severe complications. Multivariate analysis of CSS revealed severe complications [hazard ratio (HR) = 1.642, 95 % confidence interval (95 % CI) 1.095-2.460, p = 0.016] as a significant prognostic factor along with pT stage [HR = 2.081, 95 % CI 1.351-3.266, p < 0.001] and pN stage [HR = 3.724, 95 % CI 2.111-7.126, p < 0.001], whereas postoperative serum C-reactive protein value was not statistically significant. Among all complications, severe pulmonary infection was the only independent prognostic factor [HR = 2.504, 95 % CI 1.308-4.427, p = 0.007]. The incidence of postoperative infectious complications, in particular pulmonary infection, is associated with unfavorable prognosis in patients with esophageal cancer undergoing preoperative chemotherapy.

Clinical Characteristics and Prognosis of End-stage Hypertrophic Cardiomyopathy.

PubMed

Xiao, Yan; Yang, Kun-Qi; Yang, Yan-Kun; Liu, Ya-Xin; Tian, Tao; Song, Lei; Jiang, Xiong-Jing; Zhou, Xian-Liang

2015-06-05

End-stage hypertrophic cardiomyopathy (HCM) is complicated by substantial adverse events. However, few studies have focused on electrocardiographic features and their prognostic values in HCM. This study aimed to evaluate the clinical manifestations and prognostic value of electrocardiography in patients with end-stage HCM. End-stage HCM patients were enrolled from a total of 1844 consecutive HCM patients from April 2002 to November 2013 at Fuwai Hospital. Clinical data, including medical history, electrocardiography, and echocardiography, were analyzed. Cox hazards regression analysis was used to assess the risk factors for cardiovascular mortality. End-stage HCM was identified in 99 (5.4%) patients, averaged at 52 ± 16 years old at entry. Atrial fibrillation was observed in 53 patients and mural thrombus in 19 patients. During 3.9 ± 3.0 years of follow-up, embolic stroke, refractory heart failure, and death or transplantation were observed in 20, 39, and 51 patients, respectively. The incidence of annual mortality was 13.2%. Multivariate Cox hazards regression analysis identified New York Heart Association Class (NYHA) III/IV at entry (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.05-3.80; P = 0.036), left bundle branch block (LBBB) (HR: 2.80; 95% CI: 1.47-5.31; P = 0.002), and an abnormal Q wave (HR: 2.21; 95% CI: 1.16-4.23; P = 0.016) as independent predictors of cardiovascular death, in accordance with all-cause death and heart failure-related death. LBBB and an abnormal Q wave are risk factors of cardiovascular mortality in end-stage HCM and provide new evidence for early intervention. Susceptibility of end-stage HCM patients to mural thrombus and embolic events warrants further attention.

Clear cell carcinomas of the ovary have poorer outcomes compared with serous carcinomas: Results from a single-center Taiwanese study.

PubMed

Ku, Fei-Chun; Wu, Ren-Chin; Yang, Lan-Yan; Tang, Yun-Hsin; Chang, Wei-Yang; Yang, Jung-Erh; Wang, Chun-Chieh; Jung, Shih-Ming; Lin, Cheng-Tao; Chang, Ting-Chang; Chao, Angel; Lai, Chyong-Huey

2018-02-01

To compare the clinical outcomes of Taiwanese patients with ovarian clear cell carcinomas (CCCs) and serous carcinomas (SCs). We retrieved the clinical records of women with epithelial ovarian cancer (Stage I-IV) who received primary surgeries between 2000 and 2013. Cancer-specific survival (CSS), progression-free survival, and survival after recurrence (SAR) of CCC and SC patients were retrospectively compared. Multivariate analysis was used to identify the independent predictors of survival. Of 891 women diagnosed with epithelial ovarian cancer, 169 CCCs and 351 high-grade SCs were analyzed. The 5-year CSS rates of CCC patients were significantly lower than those of SC for both Stage III (22.3% vs. 47.3%, p = 0.001) and Stage IV (0% vs. 24.4%, p = 0.001) disease. In the absence of gross residual malignancies, the 5-year CSS rate was better for CCC (82.3%) than SC (75.2%, p = 0.010). The 5-year SAR rate was significantly lower for CCC than SC (14.3% vs. 24.4%, p = 0.002). Old age and residual malignancies were independent prognostic factors for CSS in the entire cohort of CCC patients. In the subgroup of Stage I CCC, positive cytology was identified as the only adverse prognostic factor for CSS. The clinical outcomes of CCC are generally poorer than SC. Complete cytoreduction to no gross residual disease should be ideally achieved in CCC patients. A greater understanding of the molecular pathogenesis of CCC may lead to tailored therapies, ultimately optimizing outcomes. Copyright © 2017. Published by Elsevier B.V.

[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.

Adjuvant Chemotherapy Improves the Probability of Freedom From Recurrence in Patients With Resected Stage IB Lung Adenocarcinoma.

PubMed

Hung, Jung-Jyh; Wu, Yu-Chung; Chou, Teh-Ying; Jeng, Wen-Juei; Yeh, Yi-Chen; Hsu, Wen-Hu

2016-04-01

The benefit of adjuvant chemotherapy remains controversial for patients with stage IB non-small-cell lung cancer (NSCLC). This study investigated the effect of adjuvant chemotherapy and the predictors of benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. A total of 243 patients with completely resected pathologic stage IB lung adenocarcinoma were included in the study. Predictors of the benefits of improved overall survival (OS) or probability of freedom from recurrence (FFR) from platinum-based adjuvant chemotherapy in patients with resected stage IB lung adenocarcinoma were investigated. Among the 243 patients, 70 (28.8%) had received platinum-based doublet adjuvant chemotherapy. A micropapillary/solid-predominant pattern (versus an acinar/papillary-predominant pattern) was a significantly worse prognostic factor for probability of FFR (p = 0.033). Although adjuvant chemotherapy (versus surgical intervention alone) was not a significant prognostic factor for OS (p = 0.303), it was a significant prognostic factor for a better probability of FFR (p = 0.029) on multivariate analysis. In propensity-score-matched pairs, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not (p = 0.386). Patients who received adjuvant chemotherapy had a significantly better probability of FFR than those who did not (p = 0.043). For patients with a predominantly micropapillary/solid pattern, adjuvant chemotherapy (p = 0.033) was a significant prognostic factor for a better probability of FFR on multivariate analysis. Adjuvant chemotherapy is a favorable prognostic factor for the probability of FFR in patients with stage IB lung adenocarcinoma, particularly in those with a micropapillary/solid-predominant pattern. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Current management and prognostic factors in physiotherapy practice for patients with shoulder pain: design of a prospective cohort study.

PubMed

Karel, Yasmaine H J M; Scholten-Peeters, Wendy G M; Thoomes-de Graaf, Marloes; Duijn, Edwin; Ottenheijm, Ramon P G; van den Borne, Maaike P J; Koes, Bart W; Verhagen, Arianne P; Dinant, Geert-Jan; Tetteroo, Eric; Beumer, Annechien; van Broekhoven, Joost B; Heijmans, Marcel

2013-02-11

Shoulder pain is disabling and has a considerable socio-economic impact. Over 50% of patients presenting in primary care still have symptoms after 6 months; moreover, prognostic factors such as pain intensity, age, disability level and duration of complaints are associated with poor outcome. Most shoulder complaints in this group are categorized as non-specific. Musculoskeletal ultrasound might be a useful imaging method to detect subgroups of patients with subacromial disorders.This article describes the design of a prospective cohort study evaluating the influence of known prognostic and possible prognostic factors, such as findings from musculoskeletal ultrasound outcome and working alliance, on the recovery of shoulder pain. Also, to assess the usual physiotherapy care for shoulder pain and examine the inter-rater reliability of musculoskeletal ultrasound between radiologists and physiotherapists for patients with shoulder pain. A prospective cohort study including an inter-rater reliability study. Patients presenting in primary care physiotherapy practice with shoulder pain are enrolled. At baseline validated questionnaires are used to measure patient characteristics, disease-specific characteristics and social factors. Physical examination is performed according to the expertise of the physiotherapists. Follow-up measurements will be performed 6, 12 and 26 weeks after inclusion. Primary outcome measure is perceived recovery, measured on a 7-point Likert scale. Logistic regression analysis will be used to evaluate the association between prognostic factors and recovery. The ShoCoDiP (Shoulder Complaints and using Diagnostic ultrasound in Physiotherapy practice) cohort study will provide information on current management of patients with shoulder pain in primary care, provide data to develop a prediction model for shoulder pain in primary care and to evaluate whether musculoskeletal ultrasound can improve prognosis.

New prognostic factors and scoring system for patients with skeletal metastasis.

PubMed

Katagiri, Hirohisa; Okada, Rieko; Takagi, Tatsuya; Takahashi, Mitsuru; Murata, Hideki; Harada, Hideyuki; Nishimura, Tetsuo; Asakura, Hirofumi; Ogawa, Hirofumi

2014-10-01

The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ≤3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

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

Yeo, Seung-Gu; Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan; Kim, Dae Yong, E-mail: radiopiakim@hanmail.net

2012-02-01

Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints weremore » disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.« less

Prognostic Factors of Uterine Serous Carcinoma-A Multicenter Study.

PubMed

Zhong, Xiaozhu; Wang, Jianliu; Kaku, Tengen; Wang, Zhiqi; Li, Xiaoping; Wei, Lihui

2018-04-04

The prognostic factors of uterine serous carcinoma (USC) vary among studies, and there is no report of Chinese USC patients. The aim of this study was to investigate the clinicopathological characteristics and prognostic factors in Chinese patients with USC. Patients with USC from 13 authoritative university hospitals in China and treated between 2004 and 2014 were retrospectively reviewed. Three-year disease-free survival rate (DFSR), cumulative recurrence, and cumulative mortality were estimated by Kaplan-Meier analyses and log-rank tests. Multivariate Cox regression analysis was used to model the association of potential prognostic factors with clinical outcomes. Data of a total of 241 patients were reviewed. The median follow-up was 26 months (range, 1-128 months). Median age was 60 years (range, 39-84 years), and 58.0% had stages I-II disease. The 3-year DFSR and cumulative recurrence were 46.8% and 27.7%. Advanced stage (III and IV) (P = 0.004), myometrial invasion (P = 0.001), adnexal involvement (P < 0.001), lymph node metastasis (P = 0.025), and positive peritoneal cytology (P = 0.007) were independently associated with 3-year DFSR. Advanced stage (P = 0.017), myometrial invasion (P = 0.008), adnexal involvement (odds ratio, 2.987; P = 0.001), lymph node metastasis (P = 0.031), and positive peritoneal cytology (P = 0.001) were independently associated with the cumulative recurrence. Myometrial invasion (P = 0.004) and positive peritoneal cytology (P = 0.025) were independently associated with 3-year cumulative mortality. Peritoneal cytology and myometrial invasion could be independent prognostic factors for 3-year DFSR, cumulative recurrence, and cumulative mortality of patients with USC. Prospective studies are needed to confirm these results.

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms.

PubMed

Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2017-06-01

The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs. © 2017 Society for Endocrinology.

A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients

PubMed Central

Luedi, Markus M.; Singh, Sanjay K.; Mosley, Jennifer C.; Hatami, Masumeh; Gumin, Joy; Sulman, Erik P.; Lang, Frederick F.; Stueber, Frank; Zinn, Pascal O.; Colen, Rivka R.

2016-01-01

Background Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods We utilized three independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in TCGA and REMBRANDT databases. In silico connectivity Map analysis identified camptothecin as antagonist to dexamethasone induced negative effects. Results Pathway analyses predicted an activation of dexamethasone network (z-score:2.908). Top activated canonical pathways included ‘role of BRCA1 in DNA damage response’ (p=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when co-incubated with dexamethasone. Altered cellular functions included cell-movement, cell-survival, and apoptosis with z-scores of 2.815, 5.137, and −3.122 respectively. CEBPB was activated in a dose dependent manner specifically in slow-dividing ‘stem-like’ cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk score had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone effects. Conclusions Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects. PMID:27653222

TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis.

PubMed

Kulasekararaj, Austin G; Smith, Alexander E; Mian, Syed A; Mohamedali, Azim M; Krishnamurthy, Pramila; Lea, Nicholas C; Gäken, Joop; Pennaneach, Coralie; Ireland, Robin; Czepulkowski, Barbara; Pomplun, Sabine; Marsh, Judith C; Mufti, Ghulam J

2013-03-01

This study aimed to determine the incidence/prognostic impact of TP53 mutation in 318 myelodysplastic syndrome (MDS) patients, and to correlate the changes to cytogenetics, single nucleotide polymorphism array karyotyping and clinical outcome. The median age was 65 years (17-89 years) and median follow-up was 45 months [95% confidence interval (CI) 27-62 months]. TP53 mutations occurred in 30 (9.4%) patients, exclusively in isolated del5q (19%) and complex karyotype (CK) with -5/5q-(72%), correlated with International Prognostic Scoring System intermediate-2/high, TP53 protein expression, higher blast count and leukaemic progression. Patients with mutant TP53 had a paucity of mutations in other genes implicated in myeloid malignancies. Median overall survival of patients with TP53 mutation was shorter than wild-type (9 versus 66 months, P < 0.001) and it retained significance in multivariable model (Hazard Ratio 3.8, 95%CI 2.3-6.3,P < 0.001). None of the sequentially analysed samples showed a disappearance of the mutant clone or emergence of new clones, suggesting an early occurrence of TP53 mutations. A reduction in mutant clone correlated with response to 5-azacitidine, however clones increased in non-responders and persisted at relapse. The adverse impact of TP53 persists after adjustment for cytogenetic risk and is of practical importance in evaluating prognosis. The relatively common occurrence of these mutations in two different prognostic spectrums of MDS, i.e. isolated 5q- and CK with -5/5q-, possibly implies two different mechanistic roles for TP53 protein. © 2013 Crown copyright. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia

PubMed Central

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

2015-01-01

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

Profiles of neurological outcome prediction among intensivists.

PubMed

Racine, Eric; Dion, Marie-Josée; Wijman, Christine A C; Illes, Judy; Lansberg, Maarten G

2009-12-01

Advances in intensive care medicine have increased survival rates of patients with critical neurological conditions. The focus of prognostication for such patients is therefore shifting from predicting chances of survival to meaningful neurological recovery. This study assessed the variability in long-term outcome predictions among physicians and aimed to identify factors that may account for this variability. Based on a clinical vignette describing a comatose patient suffering from post-anoxic brain injury intensivists were asked in a semi-structured interview about the patient's specific neurological prognosis and about prognostication in general. Qualitative research methods were used to identify areas of variability in prognostication and to classify physicians according to specific prognostication profiles. Quantitative statistics were used to assess for associations between prognostication profiles and physicians' demographic and practice characteristics. Eighteen intensivists participated. Functional outcome predictions varied along an evaluative dimension (fair/good-poor) and a confidence dimension (certain-uncertain). More experienced physicians tended to be more pessimistic about the patient's functional outcome and more certain of their prognosis. Attitudes toward quality of life varied along an evaluative dimension (good-poor) and a "style" dimension (objective-subjective). Older and more experienced physicians were more likely to express objective judgments of quality of life and to predict a worse quality of life for the patient than their younger and less experienced counterparts. Various prognostication profiles exist among intensivists. These may be dictated by factors such as physicians' age and clinical experience. Awareness of these associations may be a first step to more uniform prognostication.

Primary Neuroendocrine Carcinoma of the Breast: Histopathological Criteria, Prognostic Factors, and Review of the Literature

PubMed Central

Marinova, Lena; Vicheva, Snezhinka

2016-01-01

We present here a case of a 42-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). We discuss the importance of histological criteria for primary neuroendocrine mammary carcinoma, established by WHO in 2003 and 2012. After an overview of different cases of primary neuroendocrine carcinoma of the breast published in the literature, we present information about differential diagnosis, prognostic factors, and surgical and adjuvant treatment. Prognosis of NECB is not different from that of other invasive breast carcinomas and the most important prognostic factor is tumor grade (G). There is no standard treatment and patients should be treated similarly to patients with invasive ductal carcinoma, NOS (not otherwise specified), whose choice of therapy depends on tumor's size, degree of differentiation, clinical stage, and hormonal status. PMID:27840759

Prognostic factors versus markers of response to treatment versus surrogate endpoints: Three different concepts.

PubMed

Sormani, Maria Pia

2017-03-01

Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments.

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.

[Prognostic value of three different staging schemes based on pN, MLR and LODDS in patients with T3 esophageal cancer].

PubMed

Wang, L; Cai, L; Chen, Q; Jiang, Y H

2017-10-23

Objective: To evaluate the prognostic value of three different staging schemes based on positive lymph nodes (pN), metastatic lymph nodes ratio (MLR) and log odds of positive lymph nodes (LODDS) in patients with T3 esophageal cancer. Methods: From 2007 to 2014, clinicopathological characteristics of 905 patients who were pathologically diagnosed as T3 esophageal cancer and underwent radical esophagectomy in Zhejiang Cancer Hospital were retrospectively analyzed. Kaplan-Meier curves and Multivariate Cox proportional hazards models were used to evaluate the independent prognostic factors. The values of three lymph node staging schemes for predicting 5-year survival were analyzed by using receiver operating characteristic (ROC) curves. Results: The 1-, 3- and 5-year overall survival rates of patients with T3 esophageal cancer were 80.9%, 50.0% and 38.4%, respectively. Multivariate analysis showed that MLR stage, LODDS stage and differentiation were independent prognostic survival factors ( P <0.05 for all). ROC curves showed that the area under the curve of pN stage, MLR stage, LODDS stage was 0.607, 0.613 and 0.618, respectively. However, the differences were not statistically significant ( P >0.05). Conclusions: LODDS is an independent prognostic factor for patients with T3 esophageal cancer. The value of LODDS staging system may be superior to pN staging system for evaluating the prognosis of these patients.

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

PubMed Central

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

2015-01-01

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

Construction of a new, objective prognostic score for terminally ill cancer patients: a multicenter study.

PubMed

Suh, Sang-Yeon; Choi, Youn Seon; Shim, Jae Yong; Kim, Young Sung; Yeom, Chang Hwan; Kim, Daeyoung; Park, Shin Ae; Kim, Sooa; Seo, Ji Yeon; Kim, Su Hyun; Kim, Daegyeun; Choi, Sung-Eun; Ahn, Hong-Yup

2010-02-01

The goal of this study was to develop a new, objective prognostic score (OPS) for terminally ill cancer patients based on an integrated model that includes novel objective prognostic factors. A multicenter study of 209 terminally ill cancer patients from six training hospitals in Korea were prospectively followed until death. The Cox proportional hazard model was used to adjust for the influence of clinical and laboratory variables on survival time. The OPS was calculated from the sum of partial scores obtained from seven significant predictors determined by the final model. The partial score was based on the hazard ratio of each predictor. The accuracy of the OPS was evaluated. The overall median survival was 26 days. On the multivariate analysis, reduced oral intake, resting dyspnea, low performance status, leukocytosis, elevated bilirubin, elevated creatinine, and elevated lactate dehydrogenase (LDH) were identified as poor prognostic factors. The range of OPS was from 0.0 to 7.0. For the above cutoff point of 3.0, the 3-week prediction sensitivity was 74.7%, the specificity was 76.5%, and the overall accuracy was 75.5%. We developed the new OPS, without clinician's survival estimates but including a new prognostic factor (LDH). This new instrument demonstrated accurate prediction of the 3-week survival. The OPS had acceptable accuracy in this study population (training set). Further validation is required on an independent population (testing set).

CDX2 prognostic value in stage II/III resected colon cancer is related to CMS classification.

PubMed

Pilati, C; Taieb, J; Balogoun, R; Marisa, L; de Reyniès, A; Laurent-Puig, P

2017-05-01

Caudal-type homeobox transcription factor 2 (CDX2) is involved in colon cancer (CC) oncogenesis and has been proposed as a prognostic biomarker in patients with stage II or III CC. We analyzed CDX2 expression in a series of 469 CC typed for the new international consensus molecular subtype (CMS) classification, and we confirmed results in a series of 90 CC. Here, we show that lack of CDX2 expression is only present in the mesenchymal subgroup (CMS4) and in MSI-immune tumors (CMS1) and not in CMS2 and CMS3 colon cancer. Although CDX2 expression was a globally independent prognostic factor, loss of CDX2 expression is not associated with a worse prognosis in the CMS1 group, but is highly prognostic in CMS4 patients for both relapse free and overall survival. Similarly, lack of CDX2 expression was a bad prognostic factor in MSS patients, but not in MSI. Our work suggests that combination of the consensual CMS classification and lack of CDX2 expression could be a useful marker to identify CMS4/CDX2-negative patients with a very poor prognosis. © The Author 2017. 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.

Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years.

PubMed

Park, Soochul; Lee, Dong Hyun; Kim, Seung Woo; Roh, Yun Ho

2017-01-01

We performed a retrospective, prognostic analysis of a cohort of patients with epilepsy according to time of relapse after four seizure-free years. Planned withdrawal of antiepileptic drugs (AEDs) and at least 3 years of follow-up after AED discontinuation were performed. The following two groups were assessed: (1) an early relapse (ER) group of patients who experienced recurrence during AED withdrawal and (2) a late relapse (LR) group of patients who experienced recurrence after completion of the AED discontinuation process. After dichotomization, the relapse rate, prognostic factors, and their impacts for each group were compared with those of a group of patients who continued to be seizure-free after AED withdrawal (SF group) using multiple logistic regression analysis. The AED intake mode was also analyzed. Two hundred seventeen (64.6%) of the 336 total patients experienced relapse. One hundred thirty-nine patients (41.4%) and 78 patients (23.2%) were included in the LR and ER groups, respectively. Symptom duration >120 months showed the strongest negative prognostic impact as demonstrated by the 4.7-fold higher risk of recurrence in the ER group compared with the SF group. Additional factors with a negative prognostic impact included an age at epilepsy onset of ≤20 years and the presence of localization-related epilepsy. No reliable predictor between the SF and LR groups was revealed. After exclusion of the SF group, post hoc analysis according to age at epilepsy onset and symptom duration showed that the above-mentioned negative prognostic factors significantly affected the relapse patterns of the LR and ER groups. The results suggest that longer symptom duration, which could be associated with intrinsic reactivation of epilepsy, is the strongest negative prognostic factor for relapse. Relapse after AED withdrawal in prolonged follow-up of seizure-free patients is one aspect of the natural history of epilepsy. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Using prognostic models in CLL to personalize approach to clinical care: Are we there yet?

PubMed

Mina, Alain; Sandoval Sus, Jose; Sleiman, Elsa; Pinilla-Ibarz, Javier; Awan, Farrukh T; Kharfan-Dabaja, Mohamed A

2018-03-01

Four decades ago, two staging systems were developed to help stratify CLL into different prognostic categories. These systems, the Rai and the Binet staging, depended entirely on abnormal exam findings and evidence of anemia and thrombocytopenia. Better understanding of biologic, genetic, and molecular characteristics of CLL have contributed to better appreciating its clinical heterogeneity. New prognostic models, the GCLLSG prognostic index and the CLL-IPI, emerged. They incorporate biologic and genetic information related to CLL and are capable of predicting survival outcomes and cases anticipated to need therapy earlier in the disease course. Accordingly, these newer models are helping develop better informed surveillance strategies and ultimately tailor treatment intensity according to presence (or lack thereof) of certain prognostic markers. This represents a step towards personalizing care of CLL patients. We anticipate that as more prognostic factors continue to be identified, the GCLLSG prognostic index and CLL-IPI models will undergo further revisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lipoprotein(a) levels predict adverse vascular events after acute myocardial infarction.

PubMed

Mitsuda, Takayuki; Uemura, Yusuke; Ishii, Hideki; Takemoto, Kenji; Uchikawa, Tomohiro; Koyasu, Masayoshi; Ishikawa, Shinji; Miura, Ayako; Imai, Ryo; Iwamiya, Satoshi; Ozaki, Yuta; Kato, Tomohiro; Shibata, Rei; Watarai, Masato; Murohara, Toyoaki

2016-12-01

Lipoprotein(a) [Lp(a)], which is genetically determined, has been reported as an independent risk factor for atherosclerotic vascular disease. However, the prognostic value of Lp(a) for secondary vascular events in patients after coronary artery disease has not been fully elucidated. This 3-year observational study included a total of 176 patients with ST-elevated myocardial infarction (STEMI), whose Lp(a) levels were measured within 24 h after primary percutaneous coronary intervention. We divided enrolled patients into two groups according to Lp(a) level and investigated the association between Lp(a) and the incidence of major adverse cardiac and cerebrovascular events (MACCE). A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of MACCE than those with lower Lp(a) levels (log-rank P = 0.034). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the occurrence of MACCE after adjusting for other classical risk factors of atherosclerotic vascular diseases (hazard ratio 1.030, 95 % confidence interval: 1.011-1.048, P = 0.002). In receiver-operating curve analysis, the cutoff value to maximize the predictive power of Lp(a) was 19.0 mg/dl (area under the curve = 0.674, sensitivity 69.2 %, specificity 62.0 %). Evaluation of Lp(a) in addition to the established coronary risk factors improved their predictive value for the occurrence of MACCE. In conclusion, Lp(a) levels at admission independently predict secondary vascular events in patients with STEMI. Lp(a) might provide useful information for the development of secondary prevention strategies in patients with myocardial infarction.

Prediabetes and diabetes are both risk factors for adverse outcomes in infective endocarditis.

PubMed

Wei, X-B; Liu, Y-H; Huang, J-L; Chen, X-L; Yu, D-Q; Tan, N; Chen, J-Y; He, P-C

2018-06-16

Diabetes is a risk factor in infective endocarditis. However, few studies have focused on the prognostic value of prediabetes in infective endocarditis. This analysis aimed to explore the relationship between prediabetes and outcomes for people with infective endocarditis. Diabetes and prediabetes definitions were based on the American Diabetes Association 2014 criteria. A total of 866 people who had been consecutively diagnosed with infective endocarditis between January 2009 and July 2015 were included in the analysis. They were divided into three groups: normoglycaemia (n = 469), prediabetes (n = 246) and diabetes (n = 151). Univariate and multivariate analyses were used to identify risk factors for adverse outcomes. Overall in-hospital mortality was 8.5% (74 of 866), and differed significantly among the normoglycaemia, prediabetes and diabetes groups (3.4%, 12.6% and 17.9%, respectively; P < 0.001). Compared with the normoglycaemia group, the adjusted odds ratio for in-hospital death was 2.42 [95% confidence interval (CI) 1.11-5.31; P = 0.027) for prediabetes and 3.39 (95% CI 1.48-7.80; P = 0.004) for diabetes. The cumulative long-term death rate was significantly higher in the prediabetes or diabetes groups than in the normoglycaemia group (log-rank = 34.82; P < 0.001). In addition to diabetes, prediabetes was also associated with a higher risk of in-hospital and long-term mortality among people with infective endocarditis. Therefore, attention should be paid to this population. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

PubMed

Nakai, Yousuke; Yamamoto, Ryuichi; Matsuyama, Masato; Sakai, Yuji; Takayama, Yukiko; Ushio, Jun; Ito, Yukiko; Kitamura, Katsuya; Ryozawa, Shomei; Imamura, Tsunao; Tsuchida, Kouhei; Hayama, Jo; Itoi, Takao; Kawaguchi, Yoshiaki; Yoshida, Yu; Sugimori, Kazuya; Shimura, Kenji; Mizuide, Masafumi; Iwai, Tomohisa; Nishikawa, Ko; Yagioka, Hiroshi; Nagahama, Masatsugu; Toda, Nobuo; Saito, Tomotaka; Yasuda, Ichiro; Hirano, Kenji; Togawa, Osamu; Nakamura, Kenji; Maetani, Iruru; Sasahira, Naoki; Isayama, Hiroyuki

2018-05-01

Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

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

Schoenfeld, Jonathan D., E-mail: jdschoenfeld@partners.org; Sher, David J.; Norris, Charles M.

Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinomamore » in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions: Treatment of salivary gland malignancies with postoperative IMRT was well tolerated with a high rate of local control. Chemoradiotherapy resulted in excellent local control in a subgroup of patients with adverse prognostic factors and might be warranted in select patients.« less

Gender and ethnic differences in chronic myelogenous leukemia prognosis and treatment response: a single-institution retrospective study

PubMed Central

Lee, Justin P; Birnstein, Elliott; Masiello, David; Yang, Dongyun; Yang, Allen S

2009-01-01

Background In the last decade the importance of ethnicity, socio-economic and gender differences in relation to disease incidence, diagnosis, and prognosis has been realized. Differences in these areas have become a major health policy focus in the United States. Our study was undertaken to examine the demographic and clinical features of chronic myelogenous leukemia (CML) patients presenting initially at the LAC+USC Medical Center, which serves an ethnically diverse population. Results Patients were evenly split by gender, overwhelmingly Hispanic (60.9%), and quite young (median age 39, range 17–65) compared with previously reported CML patient populations. Previous CML studies identified significant anemia (Hgb <12 g/dl), significant thrombocytosis (platelets >450 × 109/l), and significant leukocytosis (WBC >50 × 109/l) as significant adverse pretreatment prognostic factors. Using these indicators, in addition to the validated Hasford and Sokal scores, patients were stratified and analyzed via gender and ethnicity. A significantly greater proportion of women presented with significant anemia (p = 0.019, Fisher's exact test) and significant thrombocytosis (p = 0.041, Fisher's exact test) compared to men, although no differences were found in risk stratification or treatment response. MCV values for women were significantly (p = 0.02, 2-sample t-test) lower than those for men, suggesting iron deficiency anemia. Focusing on ethnicity, Hispanics as a whole had significantly lower Hasford risk stratification (p = 0.046, Fisher's exact test), and significantly greater likelihood (p = 0.016, Fisher's exact test) of achieving 3-month complete haematological remission (CHR) compared with non-Hispanics at LAC+USC Medical Center, though differences in treatment outcome were no longer significant with analysis limited to patients treated with first-line imatinib. Conclusion Female CML patients at LAC+USC Medical Center present with more significant adverse pre-treatment prognostic factors compared to men, but achieve comparable outcomes. Hispanic patients present with lower risk profile CML and achieve better treatment responses compared to non-Hispanic patients as a whole; these ethnic differences are no longer significant when statistical analysis is limited to patients given imatinib as first-line therapy. Our patients achieve response rates inferior to those of large-scale national studies. This constellation of findings has not been reported in previous studies, and is likely reflective of a unique patient population. PMID:19630970