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Sample records for independently predict survival

  1. SHOX2 is a Potent Independent Biomarker to Predict Survival of WHO Grade II–III Diffuse Gliomas

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    Yu-An Zhang

    2016-11-01

    Interpretation: We have identified that SHOX2 expression or methylation are potent independent prognostic indicators for predicting LGG patient survival, and have potential to identify an important subset of LGG patients with IDHwt status with significantly better overall survival. The combination of IDH or other relevant markers with SHOX2 identified LGG subsets with significantly different survival outcomes, and further understanding of these subsets may benefit therapeutic target identification and therapy selections for glioma patients.

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

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    Brian W. Cross

    2012-01-01

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

  3. Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival

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    Scalerta Romano

    2009-12-01

    Full Text Available Abstract Background The detection of circulating tumor cells (CTC is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma. Methods Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR for the expression of four CTC related genes: carcinoembryonic antigen (CEA, cytokeratin-19 (CK19, vascular endothelial growth factor (VEGF and Survivin (BIRC5. Results Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome. Conclusions Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients.

  4. {sup 18}F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with {sup 90}Y microspheres

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    Haug, Alexander R. [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany); Klinikum Grosshadern, Department of Nuclear Medicine, Munich (Germany); Heinemann, Volker [Ludwig-Maximilians-University, Department of Internal Medicine III, Munich (Germany); Bruns, Christiane J. [Ludwig-Maximilians-University, Department of Surgery, Munich (Germany); Hoffmann, Ralf; Jakobs, Tobias [Ludwig-Maximilians-University, Institute of Clinical Radiology, Munich (Germany); Bartenstein, Peter; Hacker, Marcus [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany)

    2011-06-15

    .04). FDG PET/CT was able to predict patient outcome after radioembolization treatment, with the change in metabolically active tumour volume at 3 months being the best independent predictor. High tumour vascularization, as indicated by MAA scintigraphy, was not a prerequisite for successful radioembolization and was even associated with a tendency towards shorter survival. (orig.)

  5. Urine Monocyte Chemoattractant Protein-1 Is an Independent Predictive Factor of Hospital Readmission and Survival in Cirrhosis.

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    Isabel Graupera

    Full Text Available MCP-1 (monocyte chemoattractant protein-1 is a proinflammatory cytokine involved in chemotaxis of monocytes. In several diseases, such as acute coronary syndromes and heart failure, elevated MCP-1 levels have been associated with poor outcomes. Little is known about MCP-1 in cirrhosis.To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis.Prospective study of 218 patients discharged from hospital after an admission for complications of cirrhosis. Urine and plasma levels of MCP-1 and other urine proinflammatroy biomarkers: osteopontin(OPN, trefoil-factor3 and liver-fatty-acid-binding protein were measured at admission. Urine non-inflammatory mediators cystatin-C, β2microglobulin and albumin were measured as control biomarkers. The relationship between these biomarkers and the 3-month hospital readmission, complications of cirrhosis, and mortality were assessed.69 patients(32% had at least one readmission during the 3-month period of follow-up and 30 patients died(14%. Urine MCP-1 and OPN levels, were associated with 3-month probability of readmission (0.85 (0.27-2.1 and 2003 (705-4586 ug/g creat vs 0.47 (0.2-1.1 and 1188 (512-2958 ug/g creat, in patients with and without readmission, respectively; p<0.05; median (IQR. Furthermore, urine levels of MCP-1 were significantly associated with mortality (1.01 (1-3.6 vs 0.5 (0.2-1.1 μg/g creat, in dead and alive patients at 3 months; p<0.05. Patients with higher levels of urine MCP-1 (above percentile 75th had higher probability of development of hepatic encephalopathy, bacterial infections or AKI. Urine MCP-1 was an independent predictive factor of hospital readmission and combined end-point of readmission or dead at 3 months. Plasma levels of MCP-1 did not correlated with outcomes.Urine, but not plasma, MCP-1 levels are associated with hospital readmission, development of complications of cirrhosis, and mortality. These results suggest that in cirrhosis there is an

  6. Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma

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    Kristensen, Lasse Sommer; Asmar, Fazila; Dimopoulos, Konstantinos

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Improvements in overall survival have been observed with the introduction of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), however, prognostic markers are ...

  7. Independent external validation of radiotherapy and its impact on the accuracy of a nomogram for predicting survival of women with endometrial cancer.

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    Koskas, Martin; Bendifallah, Sofiane; Luton, Dominique; Darai, Emile; Rouzier, Roman

    2011-11-01

    To externally validate and assess the impact of radiotherapy on the accuracy of a nomogram for predicting overall survival of women with endometrial cancer. Using data from the Surveillance, Epidemiology, and End Results (SEER), we assessed the concordance indexes, the discrimination and the calibration provided by a nomogram for predicting overall survival. Patients were grouped into deciles based on their survival predictions, and the three-year overall survival in each group was compared with the mean predicted probability. Between 1988 and 2006, 64,023 patients were analyzed and divided into two groups: 14,323 patients with adjuvant radiotherapy and 49,700 patients without adjuvant radiotherapy. Among the whole population, predicted and observed three-year overall survivals were 85.2% and 85.6% (+/-0.1%) respectively. In patients with adjuvant radiotherapy, overall survivals were 81.0% and 83.1% (+/-0.3%) and in patients without adjuvant radiotherapy, they were 86.5% and 86.3% (+/-0.2%) respectively. The concordance indexes for the whole population, in patients with radiotherapy and in patients without radiotherapy were 0.811 (+/-0.004), 0.751 (+/-0.009) and 0.803 (+/-0.006) respectively. The mean and maximal errors in patients with radiotherapy were 2.1% and 4.0% and in patients without radiotherapy 2.3% and 8.1%. The nomogram can accurately predict three-year overall survival, whether patients undergo adjuvant radiotherapy or not. The nomogram has an improved individual discrimination when compared with the 1988 and the 2009 staging systems for endometrial cancer. It may be useful in the information processed for patients and in building surveillance timing. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. PTK6 regulates IGF-1-induced anchorage-independent survival.

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    Hanna Y Irie

    Full Text Available BACKGROUND: Proteins that are required for anchorage-independent survival of tumor cells represent attractive targets for therapeutic intervention since this property is believed to be critical for survival of tumor cells displaced from their natural niches. Anchorage-independent survival is induced by growth factor receptor hyperactivation in many cell types. We aimed to identify molecules that critically regulate IGF-1-induced anchorage-independent survival. METHODS AND RESULTS: We conducted a high-throughput siRNA screen and identified PTK6 as a critical component of IGF-1 receptor (IGF-1R-induced anchorage-independent survival of mammary epithelial cells. PTK6 downregulation induces apoptosis of breast and ovarian cancer cells deprived of matrix attachment, whereas its overexpression enhances survival. Reverse-phase protein arrays and subsequent analyses revealed that PTK6 forms a complex with IGF-1R and the adaptor protein IRS-1, and modulates anchorage-independent survival by regulating IGF-1R expression and phosphorylation. PTK6 is highly expressed not only in the previously reported Her2(+ breast cancer subtype, but also in high grade ER(+, Luminal B tumors and high expression is associated with adverse outcomes. CONCLUSIONS: These findings highlight PTK6 as a critical regulator of anchorage-independent survival of breast and ovarian tumor cells via modulation of IGF-1 receptor signaling, thus supporting PTK6 as a potential therapeutic target for multiple tumor types. The combined genomic and proteomic approaches in this report provide an effective strategy for identifying oncogenes and their mechanism of action.

  9. PREDICT : model for prediction of survival in localized prostate cancer

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    Kerkmeijer, Linda G W; Monninkhof, Evelyn M.; van Oort, Inge M.; van der Poel, Henk G.; de Meerleer, Gert; van Vulpen, Marco

    2016-01-01

    Purpose: Current models for prediction of prostate cancer-specific survival do not incorporate all present-day interventions. In the present study, a pre-treatment prediction model for patients with localized prostate cancer was developed.Methods: From 1989 to 2008, 3383 patients were treated with I

  10. Combining gene signatures improves prediction of breast cancer survival.

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    Xi Zhao

    Full Text Available BACKGROUND: Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123 and test set (n = 81, respectively. Gene sets from eleven previously published gene signatures are included in the study. PRINCIPAL FINDINGS: To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014. Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001. The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. CONCLUSION: Combining the predictive strength of multiple gene signatures improves

  11. Ebola Blood Test May Help Predict Survival Chances

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    ... page: https://medlineplus.gov/news/fullstory_163165.html Ebola Blood Test May Help Predict Survival Chances Findings ... help determine a person's chance of surviving an Ebola infection, researchers say. "It is not just defining ...

  12. Preoperative White Matter Lesions Are Independent Predictors of Long-Term Survival after Internal Carotid Endarterectomy

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    Niku Oksala

    2014-06-01

    Full Text Available Background: Cerebral white matter lesions (WMLs predict long-term survival of conservatively treated acute stroke patients with etiology other than carotid stenosis. In carotid endarterectomy patients, WMLs are associated with severe carotid stenosis and unstable plaques, with the risk of perioperative complications and with increased 30-day perioperative risk of death. However, no data exist on their effect on postoperative long-term survival, a factor important when considering the net benefit from carotid endarterectomy. Whether this effect is independent of classical risk factors and indications for surgery is not known either. We hypothesized that WMLs could be evaluated from preoperative routine computed tomography (CT scans and are predictors of postoperative survival, independent of classical cardiovascular risk factors, indication category and degree of carotid stenosis. Methods: A total of 353 of 481 (73.4% consecutive patients subjected to carotid endarterectomy due to different indications, i.e. asymptomatic stenosis (n = 28, 7.9%, amaurosis fugax (n = 52, 14.7%, transient ischemic attack (n = 135, 38.2% or ischemic stroke (n = 138, 39.1%, from prospective vascular registries during the years 2001-2010 with digital preoperative CT scans, were included in the study. WMLs were rated by a radiologist (Wahlund criteria in a blinded fashion. Internal carotid artery (ICA stenoses were angiographically graded (Results: WML severity could be assessed with a substantial intraobserver agreement (Spearman's rho 0.843, p Conclusions: WMLs in a preoperative CT scan provide a substantially reliable estimate of postoperative long-term survival of carotid endarterectomy patients independent of currently used criteria, i.e. cardiovascular risk factors, indication category and degree of ipsilateral ICA stenosis.

  13. Asbestos Burden Predicts Survival in Pleural Mesothelioma

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    Christensen, Brock C; Roelofs, Cora R.; Longacker, Jennifer L.; Marsit, Carmen J; Nelson, Heather H.; Kelsey, Karl T.; Godleski, John Joseph; Bueno, Raphael; Sugarbaker, David John

    2008-01-01

    Background: Malignant pleural mesothelioma (MPM) is a rapidly fatal asbestos-associated malignancy with a median survival time of < 1 year following diagnosis. Treatment strategy is determined in part using known prognostic factors. Objective: The aim of this study was to examine the relationship between asbestos exposure and survival outcome in MPM in an effort to advance the understanding of the contribution of asbestos exposure to MPM prognosis. Methods: We studied incident cases of MPM...

  14. Assessment of performance of survival prediction models for cancer prognosis

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    Chen Hung-Chia

    2012-07-01

    Full Text Available Abstract Background Cancer survival studies are commonly analyzed using survival-time prediction models for cancer prognosis. A number of different performance metrics are used to ascertain the concordance between the predicted risk score of each patient and the actual survival time, but these metrics can sometimes conflict. Alternatively, patients are sometimes divided into two classes according to a survival-time threshold, and binary classifiers are applied to predict each patient’s class. Although this approach has several drawbacks, it does provide natural performance metrics such as positive and negative predictive values to enable unambiguous assessments. Methods We compare the survival-time prediction and survival-time threshold approaches to analyzing cancer survival studies. We review and compare common performance metrics for the two approaches. We present new randomization tests and cross-validation methods to enable unambiguous statistical inferences for several performance metrics used with the survival-time prediction approach. We consider five survival prediction models consisting of one clinical model, two gene expression models, and two models from combinations of clinical and gene expression models. Results A public breast cancer dataset was used to compare several performance metrics using five prediction models. 1 For some prediction models, the hazard ratio from fitting a Cox proportional hazards model was significant, but the two-group comparison was insignificant, and vice versa. 2 The randomization test and cross-validation were generally consistent with the p-values obtained from the standard performance metrics. 3 Binary classifiers highly depended on how the risk groups were defined; a slight change of the survival threshold for assignment of classes led to very different prediction results. Conclusions 1 Different performance metrics for evaluation of a survival prediction model may give different conclusions in

  15. Prediction of survival with alternative modeling techniques using pseudo values

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    T. van der Ploeg (Tjeerd); F.R. Datema (Frank); R.J. Baatenburg de Jong (Robert Jan); E.W. Steyerberg (Ewout)

    2014-01-01

    textabstractBackground: The use of alternative modeling techniques for predicting patient survival is complicated by the fact that some alternative techniques cannot readily deal with censoring, which is essential for analyzing survival data. In the current study, we aimed to demonstrate that pseudo

  16. Prediction of survival with alternative modeling techniques using pseudo values.

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    Tjeerd van der Ploeg

    Full Text Available BACKGROUND: The use of alternative modeling techniques for predicting patient survival is complicated by the fact that some alternative techniques cannot readily deal with censoring, which is essential for analyzing survival data. In the current study, we aimed to demonstrate that pseudo values enable statistically appropriate analyses of survival outcomes when used in seven alternative modeling techniques. METHODS: In this case study, we analyzed survival of 1282 Dutch patients with newly diagnosed Head and Neck Squamous Cell Carcinoma (HNSCC with conventional Kaplan-Meier and Cox regression analysis. We subsequently calculated pseudo values to reflect the individual survival patterns. We used these pseudo values to compare recursive partitioning (RPART, neural nets (NNET, logistic regression (LR general linear models (GLM and three variants of support vector machines (SVM with respect to dichotomous 60-month survival, and continuous pseudo values at 60 months or estimated survival time. We used the area under the ROC curve (AUC and the root of the mean squared error (RMSE to compare the performance of these models using bootstrap validation. RESULTS: Of a total of 1282 patients, 986 patients died during a median follow-up of 66 months (60-month survival: 52% [95% CI: 50%-55%]. The LR model had the highest optimism corrected AUC (0.791 to predict 60-month survival, followed by the SVM model with a linear kernel (AUC 0.787. The GLM model had the smallest optimism corrected RMSE when continuous pseudo values were considered for 60-month survival or the estimated survival time followed by SVM models with a linear kernel. The estimated importance of predictors varied substantially by the specific aspect of survival studied and modeling technique used. CONCLUSIONS: The use of pseudo values makes it readily possible to apply alternative modeling techniques to survival problems, to compare their performance and to search further for promising

  17. Prediction of breast cancer survival through knowledge discovery in databases.

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    Lotfnezhad Afshar, Hadi; Ahmadi, Maryam; Roudbari, Masoud; Sadoughi, Farahnaz

    2015-01-26

    The collection of large volumes of medical data has offered an opportunity to develop prediction models for survival by the medical research community. Medical researchers who seek to discover and extract hidden patterns and relationships among large number of variables use knowledge discovery in databases (KDD) to predict the outcome of a disease. The study was conducted to develop predictive models and discover relationships between certain predictor variables and survival in the context of breast cancer. This study is Cross sectional. After data preparation, data of 22,763 female patients, mean age 59.4 years, stored in the Surveillance Epidemiology and End Results (SEER) breast cancer dataset were analyzed anonymously. IBM SPSS Statistics 16, Access 2003 and Excel 2003 were used in the data preparation and IBM SPSS Modeler 14.2 was used in the model design. Support Vector Machine (SVM) model outperformed other models in the prediction of breast cancer survival. Analysis showed SVM model detected ten important predictor variables contributing mostly to prediction of breast cancer survival. Among important variables, behavior of tumor as the most important variable and stage of malignancy as the least important variable were identified. In current study, applying of the knowledge discovery method in the breast cancer dataset predicted the survival condition of breast cancer patients with high confidence and identified the most important variables participating in breast cancer survival.

  18. Cardiopulmonary exercise factors predict survival in patients with advanced interstitial lung disease referred for lung transplantation.

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    Layton, Aimee M; Armstrong, Hilary F; Kim, Hanyoung P; Meza, Kimbery S; D'Ovidio, Frank; Arcasoy, Selim M

    2017-05-01

    The purpose of this work was to determine if parameters assessed during Cardiopulmonary Exercise Testing (CPET) while using supplemental oxygen can independently predict one-year transplant-free survival in patients with Interstitial Lung Disease (ILD) referred for lung transplant evaluation. We performed a chart review of patients with ILD who completed CPET with 30% FiO2 and gathered spirometry, pulmonary hemodynamic, six-minute walk, and CPET data. The primary end-point was death or lung transplantation within one-year of CPET. The final data set included 192 patients. 79 patients died/underwent transplant, 113 survived transplant-free. Multivariable Cox regression revealed peak workload % predicted, nadir CPET SpO2, and FVC% predicted as independent predictors of one-year transplant-free survival. Of the independent predictors of survival, receiver operating characteristics analysis revealed peak workload %predicted cutoff of 35% to be highly discriminatory, more so than nadir CPET SpO2 or FVC % predicted in identifying patients at risk for one-year mortality or transplant (peak workload % predicted < 35% HR = 4.71, 95% CI = 2.64-8.38 and area under the curve (AUC) = 0.740, nadir CPET SpO2 < 86% HR = 2.27, 95%CI = 1.41-3.68, AUC = 0.645, FVC %predicted <45% HR = 1.82, 95% CI = 1.15-2.87, AUC = 0.624). Peak workload % predicted, nadir CPET SpO2, and FVC% predicted in ILD patients referred for lung transplant evaluation are independently predictive of one-year mortality or need for transplant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer

    Science.gov (United States)

    Zhuang, Cheng-Le; Huang, Dong-Dong; Pang, Wen-Yang; Zhou, Chong-Jun; Wang, Su-Lin; Lou, Neng; Ma, Liang-Liang; Yu, Zhen; Shen, Xian

    2016-01-01

    Abstract Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm2/m2 for women and 40.8 cm2/m2 for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia is independently associated with overall and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. PMID:27043677

  20. Predicting Mean Survival Time from Reported Median Survival Time for Cancer Patients

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    Lousdal, Mette L; Kristiansen, Ivar S; Møller, Bjørn;

    2016-01-01

    BACKGROUND: Mean duration of survival following treatment is a prerequisite for cost-effectiveness analyses used for assessing new and costly life-extending therapies for cancer patients. Mean survival time is rarely reported due to censoring imposed by limited follow-up time, whereas the median...... survival time often is. The empirical relationship between mean and median survival time for cancer patients is not known. AIM: To derive the empirical associations between mean and median survival time across cancer types and to validate this empirical prediction approach and compare it with the standard...... approach of fitting a Weibull distribution. METHODS: We included all patients in Norway diagnosed from 1960 to 1999 with one of the 13 most common solid tumor cancers until emigration, death, or 31 December 2011, whichever came first. Observed median, restricted mean, and mean survival times were obtained...

  1. Clinical prediction of 5-year survival in systemic sclerosis

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    Fransen, Julie Munk; Popa-Diaconu, D; Hesselstrand, R

    2011-01-01

    Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate...

  2. Physician predictions of graft survival following liver transplantation

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    Feurer, Irene D.; Austin, Mary T.; Porayko, Michael K.; Wright, J. Kelly; Lorenzi, Nancy M.; Pinson, C. Wright; Aronsky, Dominik

    2007-01-01

    Introduction. Due to the scarcity of cadaveric livers, clinical judgment must be used to avoid futile transplants. However, the accuracy of human judgment for predicting outcomes following liver transplantation is unknown. The study aim was to assess expert clinicians’ ability to predict graft survival and to compare their performance to published survival models. Materials and methods. Pre-transplant case summaries were prepared based on 16 actual, randomly selected liver transplants. Clinicians specializing in the care of liver transplant patients were invited to assess the likelihood of 90-day graft survival for each case using (1) a 4-point Likert scale ranging from poor to excellent, and (2) a visual analog scale denoting the probability of survival. Four published models were also used to predict survival for the 16 cases. Results. Completed instruments were received from 50 clinicians. Prognostic estimates on the two scales were highly correlated (median r=0.88). Individual clinicians’ predictive ability was 0.61±0.13, by area under the receiver operating characteristic curve. The performance of published models was MELD 0.59, Desai 0.66, Ghobrial 0.61, and Thuluvath 0.45. For three cases, clinicians consistently overestimated the probability of survival (87±10%, 89±9%, 86±9%); these patients had early graft failures caused by postoperative complications. Discussion. Clinicians varied in their ability to predict survival for a set of pre-transplant scenarios, but performed similarly to published models. When clinicians overestimated the chance of transplant success, either sepsis or hepatic artery thrombosis was involved; such events may be hard to predict before surgery. PMID:18345303

  3. Prediction of patient survival in cases of acute paraquat poisoning.

    Science.gov (United States)

    Hong, Sae-Yong; Lee, Ji-Sung; Sun, In O; Lee, Kwang-Young; Gil, Hyo-Wook

    2014-01-01

    Paraquat concentration-time data have been used to predict the clinical outcome following ingestion. However, these studies have included only small populations, although paraquat poisoning has a very high mortality rate. The purpose of this study was to develop a simple and reliable model to predict survival according to the time interval post-ingestion in patients with acute paraquat poisoning. Data were retrospectively collected for patients who were admitted with paraquat poisoning to Soonchunhyang University Choenan Hospital between January 2005 and December 2012. Plasma paraquat levels were measured using high-performance liquid chromatography. To validate the model we developed, we used external data from 788 subjects admitted to the Presbyterian Medical Center, Jeonju, Korea, between January 2007 and December 2012. Two thousand one hundred thirty six patients were included in this study. The overall survival rate was 44% (939/2136). The probability of survival for any specified time and concentration could be predicted as (exp(logit))/(1+exp(logit)), where logit = 1.3544+[-3.4688 × log10(plasma paraquat μg/M[Formula: see text])]+[-2.3169 × log10(hours since ingestion)]. The external validation study showed that our model was highly accurate for the prediction of survival (C statics 0.964; 95% CI [0.952-0.975]). We have developed a model that is effective for predicting survival after paraquat intoxication.

  4. Does Metastatic Lymph Node SUVmax Predict Survival in Patients with Esophageal Cancer?

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    Betül Vatankulu

    2015-10-01

    Full Text Available Objective: We aimed to investigate the SUVmax of primary tumor and metastatic lymph node in predicting survival in patients with esophageal cancer. Methods: We retrospectively analyzed patients with esophageal cancer between 2009 and 2011 who had FDG positronemission tomography (PET/computed tomography (CT. All patients were followed-up to 2013. Clinical staging, SUVmax of primary tumor and metastatic lymph node were evaluated. Results: One hundred seven patients were included in the study. All patients were followed-up between 2 and 49 months. The mean SUVmax of primary tumor and metastatic lymph node were 19.3±8.8 and 10.4±9.1, respectively. Metastatic lymph node SUVmax had an effect in predicting survival whereas primary tumor SUVmax did not have an effect (p=0.014 and p=0.262, respectively. Multivariate Cox regression analysis showed that clinical stage of the disease was the only independent factor predicting survival (p=0.001. Conclusion: Among patients with esophageal cancer, the value of primary tumor SUVmax did not have an effect on survival. Clinical stage assessed with FDG PET/CT imaging was found to predict survival in esophageal carcinoma. Additionally, lymph node SUVmax was identified as a new parameter in predicting survival in the present study

  5. Cyclosporin A enhances neural precursor cell survival in mice through a calcineurin-independent pathway.

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    Sachewsky, Nadia; Hunt, Jessica; Cooke, Michael J; Azimi, Ashkan; Zarin, Taraneh; Miu, Carween; Shoichet, Molly S; Morshead, Cindi M

    2014-08-01

    Cyclosporin A (CsA) has direct effects on neural stem and progenitor cells (together termed neural precursor cells; NPCs) in the adult central nervous system. Administration of CsA in vitro or in vivo promotes the survival of NPCs and expands the pools of NPCs in mice. Moreover, CsA administration is effective in promoting NPC activation, tissue repair and functional recovery in a mouse model of cortical stroke. The mechanism(s) by which CsA mediates this cell survival effect remains unknown. Herein, we examined both calcineurin-dependent and calcineurin-independent pathways through which CsA might mediate NPC survival. To examine calcineurin-dependent pathways, we utilized FK506 (Tacrolimus), an immunosuppressive molecule that inhibits calcineurin, as well as drugs that inhibit cyclophilin A-mediated activation of calcineurin. To evaluate the calcineurin-independent pathway, we utilized NIM811, a non-immunosuppressive CsA analog that functions independently of calcineurin by blocking mitochondrial permeability transition pore formation. We found that only NIM811 can entirely account for the pro-survival effects of CsA on NPCs. Indeed, blocking signaling pathways downstream of calcineurin activation using nNOS mice did not inhibit CsA-mediated cell survival, which supports the proposal that the effects are calcinuerin-independent. In vivo studies revealed that NIM811 administration mimics the pro-survival effects of CsA on NPCs and promotes functional recovery in a model of cortical stroke, identical to the effects seen with CsA administration. We conclude that CsA mediates its effect on NPC survival through calcineurin-independent inhibition of mitochondrial permeability transition pore formation and suggest that this pathway has potential therapeutic benefits for developing NPC-mediated cell replacement strategies. © 2014. Published by The Company of Biologists Ltd.

  6. Comparing Three Data Mining Methods to Predict Kidney Transplant Survival

    Science.gov (United States)

    Shahmoradi, Leila; Langarizadeh, Mostafa; Pourmand, Gholamreza; fard, Ziba Aghsaei; Borhani, Alireza

    2016-01-01

    Introduction: One of the most important complications of post-transplant is rejection. Analyzing survival is one of the areas of medical prognosis and data mining, as an effective approach, has the capacity of analyzing and estimating outcomes in advance through discovering appropriate models among data. The present study aims at comparing the effectiveness of C5.0 algorithms, neural network and C&RTree to predict kidney transplant survival before transplant. Method: To detect factors effective in predicting transplant survival, information needs analysis was performed via a researcher-made questionnaire. A checklist was prepared and data of 513 kidney disease patient files were extracted from Sina Urology Research Center. Following CRISP methodology for data mining, IBM SPSS Modeler 14.2, C5.0, C&RTree algorithms and neural network were used. Results: Body Mass Index (BMI), cause of renal dysfunction and duration of dialysis were evaluated in all three models as the most effective factors in transplant survival. C5.0 algorithm with the highest validity (96.77%) was the first in estimating kidney transplant survival in patients followed by C&RTree (83.7%) and neural network (79.5%) models. Conclusion: Among the three models, C5.0 algorithm was the top model with high validity that confirms its strength in predicting survival. The most effective kidney transplant survival factors were detected in this study; therefore, duration of transplant survival (year) can be determined considering the regulations set for a new sample with specific characteristics. PMID:28163356

  7. Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score.

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    Clive, Amelia O; Kahan, Brennan C; Hooper, Clare E; Bhatnagar, Rahul; Morley, Anna J; Zahan-Evans, Natalie; Bintcliffe, Oliver J; Boshuizen, Rogier C; Fysh, Edward T H; Tobin, Claire L; Medford, Andrew R L; Harvey, John E; van den Heuvel, Michel M; Lee, Y C Gary; Maskell, Nick A

    2014-12-01

    Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system. Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated. Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228-549; n=43), 130 days (47-467; n=129) and 44 days (22-77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, pLENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Preoperative thrombocytosis predicts poor survival in patients with glioblastoma

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    Brockmann, Marc A.; Giese, Alf; Mueller, Kathrin; Kaba, Finjap Janvier; Lohr, Frank; Weiss, Christel; Gottschalk, Stefan; Nolte, Ingo; Leppert, Jan; Tuettenberg, Jochen; Groden, Christoph

    2007-01-01

    Thrombocytosis, which is defined as a platelet count greater than 400 platelets/nl, has been found to be an independent predictor of shorter survival in various tumors. Release of growth factors from tumors has been proposed to increase platelet counts. Preoperative platelet counts and other clinical and hematological parameters were reviewed from the records of 153 patients diagnosed between 1999 and 2004 with histologically confirmed glioblastoma in order to evaluate the prognostic significance of preoperative thrombocytosis in these patients. The relationship between thrombocytosis and survival was initially analyzed in all patients regardless of further therapy. Univariate log-rank tests showed that the median survival time of 29 patients with preoperative thrombocytosis (19%) was significantly shorter (4 months; 95% confidence interval [95% CI], 3–6 months) compared to 124 patients with normal platelet counts (11 months; 95% CI, 8–13 months; p = 0.0006). Multivariate analysis (Cox proportional hazards model) confirmed preoperative platelet count, age, prothrombin time, and activated partial thromboplastin time to be prognostic factors of survival (all p thrombocytosis was diagnosed (6 months; 95% CI, 4–12 months) compared to patients with normal platelet count (13 months; 95% CI, 11–15 months; p = 0.0359). In multivariate analysis, age, platelet count, preoperative prothrombin time, and degree of tumor resection retained significance as prognostic factors of survival (all p thrombocytosis to be a prognostic factor associated with shorter survival time in patients with glioblastoma. PMID:17504931

  9. Serum YKL-40 independently predicts outcome after transcatheter arterial chemoembolization of hepatocellular carcinoma.

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    Cheng-Bao Zhu

    Full Text Available BACKGROUND: Transcatheter arterial chemoembolization (TACE is the most widely used treatment option for unresectable hepatocellular carcinoma (HCC. Elevated serum YKL-40 level has been shown to predict poor prognosis in HCC patients undergoing resection. This study was designed to validate the prognostic significance of serum YKL-40 in patients with HCC undergoing TACE treatment. METHODS: Serum YKL-40 level was determined by enzyme-linked immunosorbent assay. Overall survival (OS was evaluated with the Kaplan-Meier method and compared by the log-rank test. Multivariate study with Cox proportional hazard model was used to evaluate independent prognostic variables of OS. RESULTS: The median pretreatment serum YKL-40 in HCC patients with was significantly higher than that in healthy controls (P<0.001. The YKL-40 could predict survival precisely either in a dichotomized or continuous fashion (P<0.001 and P = 0.001, respectively. Multivariate Cox regression analysis indicated that serum YKL-40 was an independent prognostic factor for OS in HCC patients (P = 0.001. In further stratified analyses, YKL-40 could discriminate the outcomes of patients with low and high alpha-fetoprotein (AFP level (P = 0.006 and 0.016, respectively. Furthermore, the combination of serum YKL-40 and AFP had more capacity to predict patients' outcomes. CONCLUSIONS: Serum YKL-40 was demonstrated to be an independent prognostic biomarker in HCC patients treated with TACE. Our results need confirmation in an independent study.

  10. Predicting ICU survival: A meta-level approach

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    Stamoulis Konstantinos

    2008-07-01

    Full Text Available Abstract Background The performance of separate Intensive Care Unit (ICU status scoring systems vis-à-vis prediction of outcome is not satisfactory. Computer-based predictive modeling techniques may yield good results but their performance has seldom been extensively compared to that of other mature or emerging predictive models. The objective of the present study was twofold: to propose a prototype meta-level predicting approach concerning Intensive Care Unit (ICU survival and to evaluate the effectiveness of typical mining models in this context. Methods Data on 158 men and 46 women, were used retrospectively (75% of the patients survived. We used Glasgow Coma Scale (GCS, Acute Physiology And Chronic Health Evaluation II (APACHE II, Sequential Organ Failure Assessment (SOFA and Injury Severity Score (ISS values to structure a decision tree (DTM, a neural network (NNM and a logistic regression (LRM model and we evaluated the assessment indicators implementing Receiver Operating Characteristics (ROC plot analysis. Results Our findings indicate that regarding the assessment of indicators' capacity there are specific discrete limits that should be taken into account. The Az score ± SE was 0.8773± 0.0376 for the DTM, 0.8061± 0.0427 for the NNM and 0.8204± 0.0376 for the LRM, suggesting that the proposed DTM achieved a near optimal Az score. Conclusion The predicting processes of ICU survival may go "one step forward", by using classic composite assessment indicators as variables.

  11. Predicting the survival of diabetes using neural network

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    Mamuda, Mamman; Sathasivam, Saratha

    2017-08-01

    Data mining techniques at the present time are used in predicting diseases of health care industries. Neural Network is one among the prevailing method in data mining techniques of an intelligent field for predicting diseases in health care industries. This paper presents a study on the prediction of the survival of diabetes diseases using different learning algorithms from the supervised learning algorithms of neural network. Three learning algorithms are considered in this study: (i) The levenberg-marquardt learning algorithm (ii) The Bayesian regulation learning algorithm and (iii) The scaled conjugate gradient learning algorithm. The network is trained using the Pima Indian Diabetes Dataset with the help of MATLAB R2014(a) software. The performance of each algorithm is further discussed through regression analysis. The prediction accuracy of the best algorithm is further computed to validate the accurate prediction

  12. Evaluating Random Forests for Survival Analysis Using Prediction Error Curves

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    Ulla B. Mogensen

    2012-09-01

    Full Text Available Prediction error curves are increasingly used to assess and compare predictions in survival analysis. This article surveys the R package pec which provides a set of functions for efficient computation of prediction error curves. The software implements inverse probability of censoring weights to deal with right censored data and several variants of cross-validation to deal with the apparent error problem. In principle, all kinds of prediction models can be assessed, and the package readily supports most traditional regression modeling strategies, like Cox regression or additive hazard regression, as well as state of the art machine learning methods such as random forests, a nonparametric method which provides promising alternatives to traditional strategies in low and high-dimensional settings. We show how the functionality of pec can be extended to yet unsupported prediction models. As an example, we implement support for random forest prediction models based on the R packages randomSurvivalForest and party. Using data of the Copenhagen Stroke Study we use pec to compare random forests to a Cox regression model derived from stepwise variable selection.

  13. Nomogram including pretherapeutic parameters for prediction of survival after SIRT of hepatic metastases from colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fendler, Wolfgang Peter [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Klinik und Poliklinik fuer Nuklearmedizin, Munich (Germany); Ilhan, Harun [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Paprottka, Philipp M. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, Munich (Germany); Jakobs, Tobias F. [Hospital Barmherzige Brueder, Department of Diagnostic and Interventional Radiology, Munich (Germany); Heinemann, Volker [Ludwig-Maximilians-University of Munich, Department of Internal Medicine III, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Bartenstein, Peter; Haug, Alexander R. [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Khalaf, Feras [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Ezziddin, Samer [Saarland University Medical Center, Department of Nuclear Medicine, Homburg (Germany); Hacker, Marcus [Vienna General Hospital, Department of Nuclear Medicine, Vienna (Austria)

    2015-09-15

    Pre-therapeutic prediction of outcome is important for clinicians and patients in determining whether selective internal radiation therapy (SIRT) is indicated for hepatic metastases of colorectal cancer (CRC). Pre-therapeutic characteristics of 100 patients with colorectal liver metastases (CRLM) treated by radioembolization were analyzed to develop a nomogram for predicting survival. Prognostic factors were selected by univariate Cox regression analysis and subsequent tested by multivariate analysis for predicting patient survival. The nomogram was validated with reference to an external patient cohort (n = 25) from the Bonn University Department of Nuclear Medicine. Of the 13 parameters tested, four were independently associated with reduced patient survival in multivariate analysis. These parameters included no liver surgery before SIRT (HR:1.81, p = 0.014), CEA serum level ≥ 150 ng/ml (HR:2.08, p = 0.001), transaminase toxicity level ≥2.5 x upper limit of normal (HR:2.82, p = 0.001), and summed computed tomography (CT) size of the largest two liver lesions ≥10 cm (HR:2.31, p < 0.001). The area under the receiver-operating characteristic curve for our prediction model was 0.83 for the external patient cohort, indicating superior performance of our multivariate model compared to a model ignoring covariates. The nomogram developed in our study entailing four pre-therapeutic parameters gives good prediction of patient survival post SIRT. (orig.)

  14. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis.

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    van der Burgh, Hannelore K; Schmidt, Ruben; Westeneng, Henk-Jan; de Reus, Marcel A; van den Berg, Leonard H; van den Heuvel, Martijn P

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data to predict survival of ALS patients using deep learning, a machine learning technique highly effective in a broad range of big-data analyses. A group of 135 ALS patients was included from whom high-resolution diffusion-weighted and T1-weighted images were acquired at the first visit to the outpatient clinic. Next, each of the patients was monitored carefully and survival time to death was recorded. Patients were labeled as short, medium or long survivors, based on their recorded time to death as measured from the time of disease onset. In the deep learning procedure, the total group of 135 patients was split into a training set for deep learning (n = 83 patients), a validation set (n = 20) and an independent evaluation set (n = 32) to evaluate the performance of the obtained deep learning networks. Deep learning based on clinical characteristics predicted survival category correctly in 68.8% of the cases. Deep learning based on MRI predicted 62.5% correctly using structural connectivity and 62.5% using brain morphology data. Notably, when we combined the three sources of information, deep learning prediction accuracy increased to 84.4%. Taken together, our findings show the added value of MRI with respect to predicting survival in ALS, demonstrating the advantage of deep learning in disease prognostication.

  15. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Hannelore K. van der Burgh

    2017-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data to predict survival of ALS patients using deep learning, a machine learning technique highly effective in a broad range of big-data analyses. A group of 135 ALS patients was included from whom high-resolution diffusion-weighted and T1-weighted images were acquired at the first visit to the outpatient clinic. Next, each of the patients was monitored carefully and survival time to death was recorded. Patients were labeled as short, medium or long survivors, based on their recorded time to death as measured from the time of disease onset. In the deep learning procedure, the total group of 135 patients was split into a training set for deep learning (n = 83 patients, a validation set (n = 20 and an independent evaluation set (n = 32 to evaluate the performance of the obtained deep learning networks. Deep learning based on clinical characteristics predicted survival category correctly in 68.8% of the cases. Deep learning based on MRI predicted 62.5% correctly using structural connectivity and 62.5% using brain morphology data. Notably, when we combined the three sources of information, deep learning prediction accuracy increased to 84.4%. Taken together, our findings show the added value of MRI with respect to predicting survival in ALS, demonstrating the advantage of deep learning in disease prognostication.

  16. Predicting functional decline and survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ong, Mei-Lyn; Tan, Pei Fang; Holbrook, Joanna D

    2017-01-01

    Better predictors of amyotrophic lateral sclerosis disease course could enable smaller and more targeted clinical trials. Partially to address this aim, the Prize for Life foundation collected de-identified records from amyotrophic lateral sclerosis sufferers who participated in clinical trials of investigational drugs and made them available to researchers in the PRO-ACT database. In this study, time series data from PRO-ACT subjects were fitted to exponential models. Binary classes for decline in the total score of amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R) (fast/slow progression) and survival (high/low death risk) were derived. Data was segregated into training and test sets via cross validation. Learning algorithms were applied to the demographic, clinical and laboratory parameters in the training set to predict ALSFRS-R decline and the derived fast/slow progression and high/low death risk categories. The performance of predictive models was assessed by cross-validation in the test set using Receiver Operator Curves and root mean squared errors. A model created using a boosting algorithm containing the decline in four parameters (weight, alkaline phosphatase, albumin and creatine kinase) post baseline, was able to predict functional decline class (fast or slow) with fair accuracy (AUC = 0.82). However similar approaches to build a predictive model for decline class by baseline subject characteristics were not successful. In contrast, baseline values of total bilirubin, gamma glutamyltransferase, urine specific gravity and ALSFRS-R item score-climbing stairs were sufficient to predict survival class. Using combinations of small numbers of variables it was possible to predict classes of functional decline and survival across the 1-2 year timeframe available in PRO-ACT. These findings may have utility for design of future ALS clinical trials.

  17. Prediction of patient survival in cases of acute paraquat poisoning.

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    Sae-Yong Hong

    Full Text Available Paraquat concentration-time data have been used to predict the clinical outcome following ingestion. However, these studies have included only small populations, although paraquat poisoning has a very high mortality rate. The purpose of this study was to develop a simple and reliable model to predict survival according to the time interval post-ingestion in patients with acute paraquat poisoning. Data were retrospectively collected for patients who were admitted with paraquat poisoning to Soonchunhyang University Choenan Hospital between January 2005 and December 2012. Plasma paraquat levels were measured using high-performance liquid chromatography. To validate the model we developed, we used external data from 788 subjects admitted to the Presbyterian Medical Center, Jeonju, Korea, between January 2007 and December 2012. Two thousand one hundred thirty six patients were included in this study. The overall survival rate was 44% (939/2136. The probability of survival for any specified time and concentration could be predicted as (exp(logit/(1+exp(logit, where logit = 1.3544+[-3.4688 × log10(plasma paraquat μg/M[Formula: see text

  18. Factors Predicting Survival after Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma

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    Farina M. Hanif

    2014-10-01

    Full Text Available Background: Transarterial chemoembolization is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma. Survival after transarterial chemoembolization can be highly variable. The purpose of this study is to identify the factors that predict overall survival of patients with unresectable hepatocellular carcinoma who undergo transarterial chemoembolization as the initial therapy. Methods:We included patients who underwent transarterial chemoembolization from 2007 to 2012 in this study. Patient’s age, gender, cause of cirrhosis, Child-Turcotte-Pugh score, model of end-stage liver disease score, Cancer of the Liver Italian Program score, Okuda stage, alpha- fetoprotein level, site, size and number of tumors were recorded. Radiological response to transarterial chemoembolization was assessed by computerized tomography scan at 1 and 3 months after the procedure. Repeat sessions of transarterial chemoembolization were performed according to the response. We performed survival assessment and all patients were assessed for survival at the last follow-up. Results: Included in this study were 71 patients of whom there were 57 (80.3 % males, with a mean age of 51.9±12.1 years (range: 18-76 years. The mean follow-up period was 12.5±10.7 months. A total of 31 (43.7% patients had only one session of transarterial chemoembolization, 17 (23.9% underwent 2 and 11 (15.5% had 3 or more sessions. On univariate analysis, significant factors that predicted survival included serum bilirubin (P=0.02, esophageal varices (P=0.002, Cancer of the Liver Italian Program score (P=0.003, tumor size (P=0.005, >3 sessions of transarterial chemoembolization (P=0.006 and patient's age (P=0.001. Cox regression analysis showed that tumor size of 1 transarterial chemoembolization session (P=0.004 were associated with better survival. Conclusion: Our study demonstrates that survival after transarterial chemoem- bolization is predicted by tumor size

  19. Procalcitonin Clearance for Early Prediction of Survival in Critically Ill Patients with Severe Sepsis

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    Mohd Basri Mat Nor

    2014-01-01

    Full Text Available Introduction. Serum procalcitonin (PCT diagnosed sepsis in critically ill patients; however, its prediction for survival is not well established. We evaluated the prognostic value of dynamic changes of PCT in sepsis patients. Methods. A prospective observational study was conducted in adult ICU. Patients with systemic inflammatory response syndrome (SIRS were recruited. Daily PCT were measured for 3 days. 48 h PCT clearance (PCTc-48 was defined as percentage of baseline PCT minus 48 h PCT over baseline PCT. Results. 95 SIRS patients were enrolled (67 sepsis and 28 noninfectious SIRS. 40% patients in the sepsis group died in hospital. Day 1-PCT was associated with diagnosis of sepsis (AUC 0.65 (95% CI, 0.55 to 0.76 but was not predictive of mortality. In sepsis patients, PCTc-48 was associated with prediction of survival (AUC 0.69 (95% CI, 0.53 to 0.84. Patients with PCTc-48 > 30% were independently associated with survival (HR 2.90 (95% CI 1.22 to 6.90. Conclusions. PCTc-48 is associated with prediction of survival in critically ill patients with sepsis. This could assist clinicians in risk stratification; however, the small sample size, and a single-centre study, may limit the generalisability of the finding. This would benefit from replication in future multicentre study.

  20. Survival Predictions of Ceramic Crowns Using Statistical Fracture Mechanics.

    Science.gov (United States)

    Nasrin, S; Katsube, N; Seghi, R R; Rokhlin, S I

    2017-01-01

    This work establishes a survival probability methodology for interface-initiated fatigue failures of monolithic ceramic crowns under simulated masticatory loading. A complete 3-dimensional (3D) finite element analysis model of a minimally reduced molar crown was developed using commercially available hardware and software. Estimates of material surface flaw distributions and fatigue parameters for 3 reinforced glass-ceramics (fluormica [FM], leucite [LR], and lithium disilicate [LD]) and a dense sintered yttrium-stabilized zirconia (YZ) were obtained from the literature and incorporated into the model. Utilizing the proposed fracture mechanics-based model, crown survival probability as a function of loading cycles was obtained from simulations performed on the 4 ceramic materials utilizing identical crown geometries and loading conditions. The weaker ceramic materials (FM and LR) resulted in lower survival rates than the more recently developed higher-strength ceramic materials (LD and YZ). The simulated 10-y survival rate of crowns fabricated from YZ was only slightly better than those fabricated from LD. In addition, 2 of the model crown systems (FM and LD) were expanded to determine regional-dependent failure probabilities. This analysis predicted that the LD-based crowns were more likely to fail from fractures initiating from margin areas, whereas the FM-based crowns showed a slightly higher probability of failure from fractures initiating from the occlusal table below the contact areas. These 2 predicted fracture initiation locations have some agreement with reported fractographic analyses of failed crowns. In this model, we considered the maximum tensile stress tangential to the interfacial surface, as opposed to the more universally reported maximum principal stress, because it more directly impacts crack propagation. While the accuracy of these predictions needs to be experimentally verified, the model can provide a fundamental understanding of the

  1. Predicting functional capacity during treadmill testing independent of exercise protocol.

    Science.gov (United States)

    Foster, C; Crowe, A J; Daines, E; Dumit, M; Green, M A; Lettau, S; Thompson, N N; Weymier, J

    1996-06-01

    Clinically useful estimates of VO2max from treadmill tests (GXT) may be made using protocol-specific equations. In many cases, GXT may proceed more effectively if the clinician is free to adjust speed and grade independent of a specific protocol. We sought to determine whether VO2max could be predicted from the estimated steady-state VO2 of the terminal exercise stage. Seventy clinically stable individuals performed GXT with direct measurement of VO2. Exercise was incremented each minute to optimize clinical examination. Measured VO2max was compared to the estimated steady-state VO2 of the terminal stage based on ACSM equations. Equations for walking or running were used based on the patient's observed method of ambulation. The measured VO2max was always less than the ACSM estimate, with a regular relationship between measured and estimated VO2max. No handrail support: VO2max = 0.869.ACSM -0.07; R2 = 0.955, SEE = 4.8 ml.min-1.kg-1 (N = 30). With handrail support: VO2max = 0.694.ACSM + 3.33; R2 = 0.833, SEE = 4.4 ml.min-1.kg-1 (N = 40). The equations were cross-validated with 20 patients. The correlation between predicted and observed values was r = 0.98 and 0.97 without and with handrail support, respectively. The mean absolute prediction error (3.1 and 4.1 ml.min-1.kg-1) were similar to protocol-specific equations. We conclude that VO2max can be predicted independent of treadmill protocol with approximately the same error as protocol-specific equations.

  2. Dynamic model for predicting survival of mature larvae of Tribolium confusum during facility heat treatments.

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    Boina, Dhana Raj; Subramanyam, Bhadriraju; Alavi, Sajid

    2008-06-01

    Structural heat treatment, a viable alternative to methyl bromide fumigation, involves raising the ambient temperature of food-processing facilities between 50 and 60 degrees C by using gas, electric, or steam heaters, and holding these elevated temperatures for 24 h or longer to kill stored-product insects. A dynamic model was developed to predict survival of mature larvae, which is the most heat-tolerant stage of the confused flour beetle, Tribolium confusum (Jacquelin du Val), at elevated temperatures between 46 and 60 degrees C. The model is based on two nonlinear relationships: 1) logarithmic survival of T. confusum mature larvae as a function of time, and 2) logarithmic reduction in larval survival as a function of temperature. The dynamic model was validated with nine independent data sets collected during actual facility heat treatments conducted on two separate occasions at the Kansas State University pilot flour and feed mills. The rate of increase of temperature over time varied among the nine locations where mature larvae of T. confusum were exposed, and the approximate heating rates during the entire heat treatment ranged from 1.1 to 13.2 degrees C/h. The absolute deviation in the predicted number of larvae surviving the heat treatment was within 3-7% of the actual observed data. Comparison of the absolute deviation in the time taken for equivalent larval survival showed that the model predictions were within 2-6% of the observed data. The dynamic model can be used to predict survival of mature larvae of T. confusum during heat treatments of food-processing facilities based on time-dependent temperature profiles obtained at any given location.

  3. Early social networks predict survival in wild bottlenose dolphins.

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    Margaret A Stanton

    Full Text Available A fundamental question concerning group-living species is what factors influence the evolution of sociality. Although several studies link adult social bonds to fitness, social patterns and relationships are often formed early in life and are also likely to have fitness consequences, particularly in species with lengthy developmental periods, extensive social learning, and early social bond-formation. In a longitudinal study of bottlenose dolphins (Tursiops sp., calf social network structure, specifically the metric eigenvector centrality, predicted juvenile survival in males. Additionally, male calves that died post-weaning had stronger ties to juvenile males than surviving male calves, suggesting that juvenile males impose fitness costs on their younger counterparts. Our study indicates that selection is acting on social traits early in life and highlights the need to examine the costs and benefits of social bonds during formative life history stages.

  4. The meaning of weaning in wild Phayre's leaf monkeys: last nipple contact, survival, and independence.

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    Borries, Carola; Lu, Amy; Ossi-Lupo, Kerry; Larney, Eileen; Koenig, Andreas

    2014-06-01

    In primates and other mammals, weaning is an equivocal concept, as is reflected in the numerous ways it is measured: a) first intake of solid food, b) conflict over access to the nipple, c) ability to survive without mother, d) maternal resumption of cycling, or e) the cessation of nipple contact. The lack of a consistent definition means that weaning age, although it falls between gestation (fetal growth) and age at first reproduction (most energy diverted from growth), is currently not a reliable life history variable capturing offspring independence. Using data for wild Phayre's leaf monkeys (Trachypithecus phayrei crepusculus) at Phu Khieo Wildlife Sanctuary, Thailand (51 offspring, four groups), we asked whether the end of nipple contact indicates offspring independence as measured by survival to 3 years. To establish a baseline for the onset of independence, we assessed the youngest age at which individuals were orphaned (15-17 months) but then survived to 3 years. Next we determined that offspring age at last nipple contact (19.0 months) was comparable to two other independently calculated measures: offspring age at mother's first postpartum ovulation (11.5 months), and age at mother's re-conception (15.6 months). Using these separate "starting points," we arrived at similar ages for nipple contact cessation (18.4 and 19.2 months, respectively). Overall, in wild (but not in provisioned) Asian colobines, age at last nipple contact was allometrically related to adult female body mass, supporting its designation as a life history variable. Future comparisons need to show if this holds for other taxa. Copyright © 2014 Wiley Periodicals, Inc.

  5. Baseline Quality of Life Factors Predict Long Term Survival after Elective Resection for Colorectal Cancer

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    Abhiram Sharma

    2013-01-01

    Full Text Available Background. Studies have shown an association between baseline quality of life (Qol and survival in advanced cancers. The aim of this study was to investigate their predictive value in long term survival after elective colorectal cancer resection. Methods. A consecutive series of patients undergoing elective colorectal cancer surgery for nonmetastatic disease were recruited in 2003/04. Patients completed standardized quality of life questionnaires (HADS, FACTC, MRS, and PANAS prior to and 6 weeks after surgery. Univariate (log-rank test and multivariate analyses (Cox proportional hazards were performed to predict long term survival. Results. Ninety-seven patients met the inclusion criteria. Sixty-five (67% were male and the median age of the group was 70 years. Forty-six (47.5% patients had died and the mean survival was 1,741 days (median 2159, range 9–2923 days. Preoperative mood rating scale and functional assessment of cancer therapy-colorectal FACT C emotional well-being and postoperative FACT C additional concerns were independent predictors of long term survival. Conclusion. Incorporating psychosocial measures in preoperative assessment of cancer patients could help to identify patients who require assessment with a view to implementing psychosocial interventions. These active interventions to maximize mood and well-being should form an integral part of multidisciplinary treatment in these patients.

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

    Science.gov (United States)

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

    2017-08-26

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

  7. Machine learning models in breast cancer survival prediction.

    Science.gov (United States)

    Montazeri, Mitra; Montazeri, Mohadeseh; Montazeri, Mahdieh; Beigzadeh, Amin

    2016-01-01

    Breast cancer is one of the most common cancers with a high mortality rate among women. With the early diagnosis of breast cancer survival will increase from 56% to more than 86%. Therefore, an accurate and reliable system is necessary for the early diagnosis of this cancer. The proposed model is the combination of rules and different machine learning techniques. Machine learning models can help physicians to reduce the number of false decisions. They try to exploit patterns and relationships among a large number of cases and predict the outcome of a disease using historical cases stored in datasets. The objective of this study is to propose a rule-based classification method with machine learning techniques for the prediction of different types of Breast cancer survival. We use a dataset with eight attributes that include the records of 900 patients in which 876 patients (97.3%) and 24 (2.7%) patients were females and males respectively. Naive Bayes (NB), Trees Random Forest (TRF), 1-Nearest Neighbor (1NN), AdaBoost (AD), Support Vector Machine (SVM), RBF Network (RBFN), and Multilayer Perceptron (MLP) machine learning techniques with 10-cross fold technique were used with the proposed model for the prediction of breast cancer survival. The performance of machine learning techniques were evaluated with accuracy, precision, sensitivity, specificity, and area under ROC curve. Out of 900 patients, 803 patients and 97 patients were alive and dead, respectively. In this study, Trees Random Forest (TRF) technique showed better results in comparison to other techniques (NB, 1NN, AD, SVM and RBFN, MLP). The accuracy, sensitivity and the area under ROC curve of TRF are 96%, 96%, 93%, respectively. However, 1NN machine learning technique provided poor performance (accuracy 91%, sensitivity 91% and area under ROC curve 78%). This study demonstrates that Trees Random Forest model (TRF) which is a rule-based classification model was the best model with the highest level of

  8. Predicting and Modelling of Survival Data when Cox's Regression Model does not hold

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2002-01-01

    Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects......Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects...

  9. Post-exercise heart rate recovery independently predicts mortality risk in patients with chronic heart failure.

    Science.gov (United States)

    Tang, Yi-Da; Dewland, Thomas A; Wencker, Detlef; Katz, Stuart D

    2009-12-01

    Post-exercise heart rate recovery (HRR) is an index of parasympathetic function associated with clinical outcomes in populations with and without documented coronary heart disease. Decreased parasympathetic activity is thought to be associated with disease progression in chronic heart failure (HF), but an independent association between post-exercise HRR and clinical outcomes among such patients has not been established. We measured HRR (calculated as the difference between heart rate at peak exercise and after 1 minute of recovery) in 202 HF subjects and recorded 17 mortality and 15 urgent transplantation outcome events over 624 days of follow-up. Reduced post-exercise HRR was independently associated with increased event risk after adjusting for other exercise-derived variables (peak oxygen uptake and change in minute ventilation per change in carbon dioxide production slope), for the Heart Failure Survival Score (adjusted HR 1.09 for 1 beat/min reduction, 95% CI 1.05-1.13, P Heart Failure Model score (adjusted HR 1.08 for one beat/min reduction, 95% CI 1.05-1.12, P exercise HRR (>or=30 beats/min) had low risk of events irrespective of the risk predicted by the survival scores. In a subgroup of 15 subjects, reduced post-exercise HRR was associated with increased serum markers of inflammation (interleukin-6, r = 0.58, P = .024; high-sensitivity C-reactive protein, r = 0.66, P = .007). Post-exercise HRR predicts mortality risk in patients with HF and provides prognostic information independent of previously described survival models. Pathophysiologic links between autonomic function and inflammation may be mediators of this association.

  10. Reasoning Support for Risk Prediction and Prevention in Independent Living

    CERN Document Server

    Mileo, A; Bisiani, R

    2010-01-01

    In recent years there has been growing interest in solutions for the delivery of clinical care for the elderly, due to the large increase in aging population. Monitoring a patient in his home environment is necessary to ensure continuity of care in home settings, but, to be useful, this activity must not be too invasive for patients and a burden for caregivers. We prototyped a system called SINDI (Secure and INDependent lIving), focused on i) collecting a limited amount of data about the person and the environment through Wireless Sensor Networks (WSN), and ii) inferring from these data enough information to support caregivers in understanding patients' well being and in predicting possible evolutions of their health. Our hierarchical logic-based model of health combines data from different sources, sensor data, tests results, common-sense knowledge and patient's clinical profile at the lower level, and correlation rules between health conditions across upper levels. The logical formalization and the reasonin...

  11. Prognostic nomograms for predicting survival and distant metastases in locally advanced rectal cancers.

    Directory of Open Access Journals (Sweden)

    Junjie Peng

    Full Text Available To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment.A total of 883 patients with stage II-III rectal cancers were retrospectively collected from a single institution. Survival analyses were performed to assess each variable for overall survival (OS, local recurrence (LR and distant metastases (DM. Cox models were performed to develop a predictive model for each endpoint. The performance of model prediction was validated by cross validation and on an independent group of patients.The 5-year LR, DM and OS rates were 22.3%, 32.7% and 63.8%, respectively. Two prognostic nomograms were successfully developed to predict 5-year OS and DM-free survival rates, with c-index of 0.70 (95% CI = [0.66, 0.73] and 0.68 (95% CI = [0.64, 0.72] on the original dataset, and 0.76 (95% CI = [0.67, 0.86] and 0.73 (95% CI = [0.63, 0.83] on the validation dataset, respectively. Factors in our models included age, gender, carcinoembryonic antigen value, tumor location, T stage, N stage, metastatic lymph nodes ratio, adjuvant chemotherapy and chemoradiotherapy. Predicted by our nomogram, substantial variability in terms of 5-year OS and DM-free survival was observed within each TNM stage category.The prognostic nomograms integrated demographic and clinicopathological factors to account for tumor and patient heterogeneity, and thereby provided a more individualized outcome prognostication. Our individualized prediction nomograms could help patients with preoperatively under-staged rectal cancer about their postoperative treatment strategies and follow-up protocols.

  12. Survival model construction guided by fit and predictive strength.

    Science.gov (United States)

    Chauvel, Cécile; O'Quigley, John

    2016-10-05

    Survival model construction can be guided by goodness-of-fit techniques as well as measures of predictive strength. Here, we aim to bring together these distinct techniques within the context of a single framework. The goal is how to best characterize and code the effects of the variables, in particular time dependencies, when taken either singly or in combination with other related covariates. Simple graphical techniques can provide an immediate visual indication as to the goodness-of-fit but, in cases of departure from model assumptions, will point in the direction of a more involved and richer alternative model. These techniques appear to be intuitive. This intuition is backed up by formal theorems that underlie the process of building richer models from simpler ones. Measures of predictive strength are used in conjunction with these goodness-of-fit techniques and, again, formal theorems show that these measures can be used to help identify models closest to the unknown non-proportional hazards mechanism that we can suppose generates the observations. Illustrations from studies in breast cancer show how these tools can be of help in guiding the practical problem of efficient model construction for survival data.

  13. PDCD6 is an independent predictor of progression free survival in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Su Dan

    2012-02-01

    Full Text Available Abstract Background Programmed cell death 6 (PDCD6 beside its known proapoptotic functions may be a player in survival pathways in cancer. The purpose of this study is to further explore the roles of PDCD6 in epithelial ovarian cancer. Methods Lentiviral vector with shRNA for PDCD6 was used to investigate the effects of PDCD6 knockdown on cell growth, cell cycle, apoptosis and motility in ovarian cancer cells. Two hundred twelve epithelial ovarian cancer tissues were analyzed for mRNA expression of PDCD6 using RT-PCR. Associations of its expression with clinical pathological factors, progression free and overall survival were evaluated. Results PDCD6 is highly expressed in metastatic ovarian cancer cells and positively regulates cell migration and invasion. Significantly, the level of PDCD6 expression in epithelial ovarian cancer correlates with clinical progression. Patients with medium or high levels of PDCD6 mRNA were at higher risk for disease progression, compared to those with low levels (HR, 1.29; P = 0.024 for medium levels; and HR, 1.57; P = 0.045 for high levels after adjusting for age, disease stage, tumor grade, histologic type and residual tumor size. Kaplan-Meier survival analysis demonstrated similar results. However, no association was found between PDCD6 expression and overall survival. Conclusions PDCD6 seems to play an important role in ovarian cancer progression and it may be an independent predictor of progression free survival in epithelial ovarian cancer. Further studies are needed to more completely elucidate the molecular mechanisms of PDCD6 involve in ovarian cancer progression.

  14. Health-related quality of life predicts long-term survival in patients with peripheral artery disease

    DEFF Research Database (Denmark)

    Issa, Samson M; Hoeks, Sanne E; Scholte op Reimer, Wilma J M;

    2010-01-01

    We examined whether health-related quality of life (HRQoL) predicts long-term survival in patients with peripheral artery disease (PAD) independent of established prognostic risk factors. In 2004, data on 711 consecutive patients with PAD undergoing vascular surgery were collected from 11 hospita...

  15. Prediction of survival in patients with Stage IV kidney cancer

    Directory of Open Access Journals (Sweden)

    L. V. Mirilenko

    2015-01-01

    Full Text Available The efficiency of treatment was evaluated and the predictors of adjusted survival (AS were identified in patients with disseminated kidney cancer treated at the Republican Research and Practical Center for Oncology and Medical Radiology in 1999 to 2011 (A.E. Okeanov, P.I. Moiseev, L.F. Levin. Malignant tumors in Belarus, 2001–2012. Edited by O.G. Sukonko. Seven factors (regional lymph node metastases; distant bone metastases; a high-grade tumor; sarcomatous tumor differentiation; hemoglobin levels of < 125 g/l in women and < 150 g/l in men; an erythrocyte sedimentation rate of 40 mm/h; palliative surgery were found to have an independent, unfavorable impact on AS. A multidimensional model was built to define what risk group low (no more than 2 poor factors, moderate (3–4 poor factors, and high (more than 4 poor factors the patients with Stage IV kidney cancer belonged to. In these groups, the median survival was 34.7, 17.2, and 4.0 months and 3-year AS rates were 48.6, 24.6, and 3.2 %, respectively. 

  16. Survival prediction in patients undergoing radionuclide therapy based on intratumoral somatostatin-receptor heterogeneity

    Science.gov (United States)

    Ilhan, Harun; Higuchi, Takahiro; Buck, Andreas K.; Lehner, Sebastian; Bartenstein, Peter; Bengel, Frank; Schatka, Imke; Muegge, Dirk O.; Papp, László; Zsótér, Norbert; Große-Ophoff, Tobias; Essler, Markus; Bundschuh, Ralph A.

    2017-01-01

    The NETTER-1 trial demonstrated significantly improved progression-free survival (PFS) for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) emphasizing the high demand for response prediction in appropriate candidates. In this multicenter study, we aimed to elucidate the prognostic value of tumor heterogeneity as assessed by somatostatin receptor (SSTR)-PET/CT. 141 patients with SSTR-expressing tumors were analyzed obtaining SSTR-PET/CT before PRRT (1-6 cycles, 177Lu somatostatin analog). Using the Interview Fusion Workstation (Mediso), a total of 872 metastases were manually segmented. Conventional PET parameters as well as textural features representing intratumoral heterogeneity were computed. The prognostic ability for PFS and overall survival (OS) were examined. After performing Cox regression, independent parameters were determined by ROC analysis to obtain cut-off values to be used for Kaplan-Meier analysis. Within follow-up (median, 43.1 months), 75 patients showed disease progression (median, 22.2 m) and 54 patients died (median, 27.6 m). Cox analysis identified 8 statistically independent heterogeneity parameters for time-to-progression and time-to-death. Among them, the textural feature Entropy predicted both PFS and OS. Conventional PET parameters failed in response prediction. Imaging-based heterogeneity assessment provides prognostic information in PRRT candidates and outperformed conventional PET parameters. Its implementation in clinical practice can pave the way for individualized patient management. PMID:27705948

  17. Six-Minute-Walk Distance Predicts Waiting List Survival in Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Lederer, David J.; Arcasoy, Selim M.; Wilt, Jessie S.; D'Ovidio, Frank; Sonett, Joshua R.; Kawut, Steven M.

    2006-01-01

    Rationale: Functional studies may be useful to predict survival in idiopathic pulmonary fibrosis (IPF). Various cutoffs of 6-min-walk distance (6MWD) have been suggested to identify patients at a high risk of death. Objectives: To examine the association between 6MWD and survival in patients with IPF listed for lung transplantation, and to identify sensitive and specific cutoffs for predicting death at 6 mo. Methods: We performed a retrospective cohort study of 454 patients classified as having IPF listed for lung transplantation with the United Network for Organ Sharing between June 30, 2004 and July 22, 2005. Measurements and Main Results: Lower 6MWD was associated with an increased mortality rate (p value for linear trend < 0.0001). Patients with a walk distance less than 207 m had a more than fourfold greater mortality rate than those with a walk distance of 207 m or more, despite adjustment for demographics, anthropomorphics, FVC % predicted, pulmonary hypertension, and medical comorbidities (adjusted rate ratio, 4.7; 95% confidence interval, 2.5–8.9; p < 0.0001). 6MWD was a significantly better predictor of 6-mo mortality than was FVC % predicted (c-statistic = 0.73 vs. 0.59, respectively; p = 0.02). Conclusions: Lower 6MWD was strongly and independently associated with an increased mortality rate for wait-listed patients classified as having IPF. 6MWD was a better predictor of death at 6 mo than was FVC % predicted. PMID:16778159

  18. CAML mediates survival of Myc-induced lymphoma cells independent of tail-anchored protein insertion.

    Science.gov (United States)

    Shing, Jennifer C; Lindquist, Lonn D; Borgese, Nica; Bram, Richard J

    2017-01-01

    Calcium-modulating cyclophilin ligand (CAML) is an endoplasmic reticulum (ER) protein that functions, along with WRB and TRC40, to mediate tail-anchored (TA) protein insertion into the ER membrane. Physiologic roles for CAML include endocytic trafficking, intracellular calcium signaling, and the survival and proliferation of specialized immune cells, recently attributed to its requirement for TA protein insertion. To identify a possible role for CAML in cancer cells, we generated Eμ-Myc transgenic mice that carry a tamoxifen-inducible deletion allele of Caml. In multiple B-cell lymphoma cell lines derived from these mice, homozygous loss of Caml activated apoptosis. Cell death was blocked by Bcl-2/Bcl-xL overexpression; however, rescue from apoptosis was insufficient to restore proliferation. Tumors established from an Eμ-Myc lymphoma cell line completely regressed after tamoxifen administration, suggesting that CAML is also required for these cancer cells to survive and grow in vivo. Cell cycle analyses of Caml-deleted lymphoma cells revealed an arrest in G2/M, accompanied by low expression of the mitotic marker, phospho-histone H3 (Ser10). Surprisingly, lymphoma cell viability did not depend on the domain of CAML required for its interaction with TRC40. Furthermore, a small protein fragment consisting of the C-terminal 111 amino acid residues of CAML, encompassing the WRB-binding domain, was sufficient to rescue growth and survival of Caml-deleted lymphoma cells. Critically, this minimal region of CAML did not restore TA protein insertion in knockout cells. Taken together, these data reveal an essential role for CAML in supporting survival and mitotic progression in Myc-driven lymphomas that is independent of its TA protein insertion function.

  19. A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer.

    Science.gov (United States)

    Vollan, Hans Kristian Moen; Rueda, Oscar M; Chin, Suet-Feung; Curtis, Christina; Turashvili, Gulisa; Shah, Sohrab; Lingjærde, Ole Christian; Yuan, Yinyin; Ng, Charlotte K; Dunning, Mark J; Dicks, Ed; Provenzano, Elena; Sammut, Stephen; McKinney, Steven; Ellis, Ian O; Pinder, Sarah; Purushotham, Arnie; Murphy, Leigh C; Kristensen, Vessela N; Brenton, James D; Pharoah, Paul D P; Børresen-Dale, Anne-Lise; Aparicio, Samuel; Caldas, Carlos

    2015-01-01

    prognostication tool PREDICT significantly improved its performance. CAAI positive ovarian cancers (52%) also had worse prognosis: HRs of 1.3 (95%CI, 1.1-1.7) for PFS and 1.3 (95%CI, 1.1-1.6) for OS. This study validates CAAI as an independent predictor of survival in both ER+ and ER- breast cancer and reveals a significant prognostic value for CAAI in high-grade serous ovarian cancer.

  20. Antioxidant defenses predict long-term survival in a passerine bird.

    Directory of Open Access Journals (Sweden)

    Nicola Saino

    Full Text Available BACKGROUND: Normal and pathological processes entail the production of oxidative substances that can damage biological molecules and harm physiological functions. Organisms have evolved complex mechanisms of antioxidant defense, and any imbalance between oxidative challenge and antioxidant protection can depress fitness components and accelerate senescence. While the role of oxidative stress in pathogenesis and aging has been studied intensively in humans and model animal species under laboratory conditions, there is a dearth of knowledge on its role in shaping life-histories of animals under natural selection regimes. Yet, given the pervasive nature and likely fitness consequences of oxidative damage, it can be expected that the need to secure efficient antioxidant protection is powerful in molding the evolutionary ecology of animals. Here, we test whether overall antioxidant defense varies with age and predicts long-term survival, using a wild population of a migratory passerine bird, the barn swallow (Hirundo rustica, as a model. METHODOLOGY/PRINCIPAL FINDINGS: Plasma antioxidant capacity (AOC of breeding individuals was measured using standard protocols and annual survival was monitored over five years (2006-2010 on a large sample of selection episodes. AOC did not covary with age in longitudinal analyses after discounting the effect of selection. AOC positively predicted annual survival independently of sex. Individuals were highly consistent in their relative levels of AOC, implying the existence of additive genetic variance and/or environmental (including early maternal components consistently acting through their lives. CONCLUSIONS: Using longitudinal data we showed that high levels of antioxidant protection positively predict long-term survival in a wild animal population. Present results are therefore novel in disclosing a role for antioxidant protection in determining survival under natural conditions, strongly demanding for more

  1. Business Bankruptcy Prediction Based on Survival Analysis Approach

    Directory of Open Access Journals (Sweden)

    Ming - Chang Lee

    2014-04-01

    Full Text Available This study sampled companies listed on Taiwan Stock Exchange that examined financial distress between 200 3 and 20 09 . It uses the survival analysis to find the main indicators which can explain the business bankruptcy in Taiwan. This paper use s the Cox P roportional H azard M odel to assess the usefulness of traditional financial ratios and market variables as predictors of the probability of business failure to a given time. This paper presents empirical results of a study regarding 12 financial ratios as predictors of business failure in Taiwan. It showed that it does not need many ratios to be able to anticipate potential business bankruptcy. T he financial distress probability model is constructed using Profitability, Leverage, Efficiency and Valuation ratio variables. In the proposed steps of business failure prediction model , it used detail SAS procedure. The study proves that t he accuracies of classification of the mode in o verall accuracy of classification are 87.93%

  2. Interoceptive Ability Predicts Survival on a London Trading Floor.

    Science.gov (United States)

    Kandasamy, Narayanan; Garfinkel, Sarah N; Page, Lionel; Hardy, Ben; Critchley, Hugo D; Gurnell, Mark; Coates, John M

    2016-09-19

    Interoception is the sensing of physiological signals originating inside the body, such as hunger, pain and heart rate. People with greater sensitivity to interoceptive signals, as measured by, for example, tests of heart beat detection, perform better in laboratory studies of risky decision-making. However, there has been little field work to determine if interoceptive sensitivity contributes to success in real-world, high-stakes risk taking. Here, we report on a study in which we quantified heartbeat detection skills in a group of financial traders working on a London trading floor. We found that traders are better able to perceive their own heartbeats than matched controls from the non-trading population. Moreover, the interoceptive ability of traders predicted their relative profitability, and strikingly, how long they survived in the financial markets. Our results suggest that signals from the body - the gut feelings of financial lore - contribute to success in the markets.

  3. Ion channel gene expression predicts survival in glioma patients.

    Science.gov (United States)

    Wang, Rong; Gurguis, Christopher I; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

    2015-08-03

    Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients.

  4. Hemoglobin Screening Independently Predicts All-Cause Mortality.

    Science.gov (United States)

    Fulks, Michael; Dolan, Vera F; Stout, Robert L

    2015-01-01

    Objective .- Determine if the addition of hemoglobin testing improves risk prediction for life insurance applicants. Method .- Hemoglobin results for insurance applicants tested from 1993 to 2007, with vital status determined by Social Security Death Master File follow-up in 2011, were analyzed by age and sex with and without accounting for the contribution of other test results. Results .- Hemoglobin values ≤12.0 g/dL (and possibly ≤13.0 g/dL) in females age 50+ (but not age 15.0 g/dL (and possibly >14.0 g/dL) for all females and for hemoglobin values >16.0 g/dL for males. Conclusion .- Hemoglobin testing can add additional independent risk assessment to that obtained from other laboratory testing, BP and build in this relatively healthy insurance applicant population. Multiple studies support this finding at older ages, but data (and the prevalence of diseases impacting hemoglobin levels) are limited at younger ages.

  5. EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer

    Science.gov (United States)

    Husa, Anna-Maria; Magić, Željana; Larsson, Malin; Fornander, Tommy; Pérez-Tenorio, Gizeh

    2016-01-01

    The EPH and ephrins function as both receptor and ligands and the output on their complex signaling is currently investigated in cancer. Previous work shows that some EPH family members have clinical value in breast cancer, suggesting that this family could be a source of novel clinical targets. Here we quantified the mRNA expression levels of EPH receptors and their ligands, ephrins, in 65 node positive breast cancer samples by RT-PCR with TaqMan® Micro Fluidics Cards Microarray. Upon hierarchical clustering of the mRNA expression levels, we identified a subgroup of patients with high expression, and poor clinical outcome. EPHA2, EPHA4, EFNB1, EFNB2, EPHB2 and EPHB6 were significantly correlated with the cluster groups and particularly EPHB2 was an independent prognostic factor in multivariate analysis and in four public databases. The EPHB2 protein expression was also analyzed by immunohistochemistry in paraffin embedded material (cohort 2). EPHB2 was detected in the membrane and cytoplasmic cell compartments and there was an inverse correlation between membranous and cytoplasmic EPHB2. Membranous EPHB2 predicted longer breast cancer survival in both univariate and multivariate analysis while cytoplasmic EPHB2 indicated shorter breast cancer survival in univariate analysis. Concluding: the EPH/EFN cluster analysis revealed that high EPH/EFN mRNA expression is an independent prognostic factor for poor survival. Especially EPHB2 predicted poor breast cancer survival in several materials and EPHB2 protein expression has also prognostic value depending on cell localization. PMID:26870995

  6. Factors predicting survival in patients with proximal gastric carcinoma involving the esophagus

    Institute of Scientific and Technical Information of China (English)

    Yi-Fen Zhang; Jiong Shi; Hui-Ping Yu; An-Ning Feng; Xiang-Shan Fan; Gregory Y Lauwers; Hiroshi Mashimo

    2012-01-01

    AIM:To investigate the clinicopathologic features which predict surgical overall survival in patients with proximal gastric carcinoma involving the esophagus (PGCE).METHODS:Electronic pathology database established in the Department of Pathology of the Nanjing Drum Tower Hospital was searched for consecutive resection cases of proximal gastric carcinoma over the period from May 2004 through July 2009.Each retrieved pathology report was reviewed and the cases with tumors crossing the gastroesophageal junction line were selected as PGCE.Each tumor was re-staged,following the guidelines on esophageal adenocarcinoma,according to the 7th edition of the American Joint Commission on Cancer Staging Manual.All histology slides were studied along with the pathology report for a retrospective analysis of 13 clinicopathologic features,i.e.,age,gender,Helicobacter pylori (H.pylori) infection,surgical modality,Siewert type,tumor Bormann's type,size,differentiation,histology type,surgical margin,lymphovascular and perineural invasion,and pathologic stage in relation to survival after surgical resection.Prognostic factors for overall survival were assessed with uniand multi-variate analyses.RESULTS:Patients' mean age was 65 years (range:47-90 years).The male:female ratio was 3.3.The 1-,3-and 5-year overall survival rates were 87%,61% and 32%,respectively.By univariate analysis,age,male gender,H,pylori,tumor Bormann's type,size,histology type,surgical modality,positive surgical margin,lymphovascular invasion,and pT stage were not predictivefor overall survival; in contrast,perineural invasion (P =0.003),poor differentiation (P =0.0003),> 15 total lymph nodes retrieved (P =0.008),positive lymphnodes (P =0.001),and distant metastasis (P =0.005)predicted poor post-operative overall survival.Celiac axis nodal metastasis was associated with significantly worse overall survival (P =0.007).By multivariate analysis,≥ 16 positive nodes (P =0.018),lymph node ratio > 0.2 (P =0

  7. Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer: Analysis from a Large-Scale Cohort.

    Science.gov (United States)

    Zhuang, Cheng-Le; Huang, Dong-Dong; Pang, Wen-Yang; Zhou, Chong-Jun; Wang, Su-Lin; Lou, Neng; Ma, Liang-Liang; Yu, Zhen; Shen, Xian

    2016-03-01

    Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm²/m² for women and 40.8 cm²/m² for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia is independently associated with overall and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I.

  8. Calcium-independent phospholipase A₂, group VIA, is critical for RPE cell survival

    DEFF Research Database (Denmark)

    Kolko, Miriam; Vohra, Rupali; Westlund, Barbro S.;

    2014-01-01

    PURPOSE: To investigate the significance of calcium-independent phospholipase A₂, group VIA (iPLA2-VIA), in RPE cell survival following responses to sodium iodate (SI) in cell cultures. METHODS: The human retinal pigment epithelium (RPE) cell line (ARPE-19) cells and primary mouse-RPE cultures were...... of iPLA₂-VIA after SI exposure. Inhibitors of iPLA₂-VIA were used to explore a potential protective role in cells exposed to SI. Primary RPE cell cultures were grown from iPLA₂-VIA knockout mice and wild-type mice. The cultures were exposed to SI to investigate a possible increased protection against......-VIA-specific inhibitors in ARPE-19 cell cultures. RPE cultures from iPLA₂-VIA knockout mice were less vulnerable to SI-induced cell death compared to RPE cultures from wild-type mice. CONCLUSIONS: SI -induced RPE cell death involves iPLA₂-VIA upregulation and activation, and amelioration of SI...

  9. Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)

    2016-06-15

    To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

  10. Vitamin D Affects Survival Independently of Vascular Calcification in Chronic Kidney Disease

    Science.gov (United States)

    Barreto, Daniela Veit; Barreto, Fellype Carvalho; Liabeuf, Sophie; Temmar, Mohammed; Boitte, Francis; Choukroun, Gabriel; Fournier, Albert; Massy, Ziad A.

    2009-01-01

    Background and objectives: Cardiovascular disease is the main cause of mortality in chronic kidney disease (CKD) patients. Vitamin D might have beneficial effects on vascular health. The aim of this study was to determine the prevalence of vitamin D deficiency (25-hydroxyvitamin D [25D] ≤ 15 ng/ml) and insufficiency (25D levels between 16 and 30 ng/ml) in a cohort of patients at different CKD stages and the relationships between vitamin D serum levels, vascular calcification and stiffness, and the mortality risk. Design, setting, participants & measurements: One hundred forty CKD patients (85 men, mean age 67 ± 12 yr; CKD stages 2 [8%], 3 [26%], 4 [26%], 5 [7%], and 5D [(33%]) were allocated for a prospective study. Serum levels of 25D and 1,25-dihydroxyvitamin D, aortic calcification score, and pulse wave velocity (PWV) were evaluated. Results: There was a high prevalence of vitamin D deficiency (42%) and insufficiency (34%). Patients with 25D ≤ 16.7 ng/ml (median) had a significantly lower survival rate than patients with 25D >16.7 ng/ml (mean follow-up, 605 ± 217 d; range, 10 to 889; P = 0.05). Multivariate adjustments (included age, gender, diabetes, arterial pressure, CKD stage, phosphate, albumin, hemoglobin, aortic calcification score and PWV) confirmed 25D level as an independent predictor of all-cause mortality. Conclusions: Vitamin D deficiency and insufficiency were highly prevalent in this CKD cohort. Low 25D levels affected mortality independently of vascular calcification and stiffness, suggesting that 25D may influence survival in CKD patients via additional pathways that need to be further explored. PMID:19443628

  11. Soluble L-selectin levels predict survival in sepsis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

    2002-01-01

    To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis.......To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis....

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

    Directory of Open Access Journals (Sweden)

    Maria Göbel

    Full Text Available 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.

  13. Fractal dimension of chromatin is an independent prognostic factor for survival in melanoma

    Directory of Open Access Journals (Sweden)

    Landman Gilles

    2010-06-01

    Full Text Available Abstract Background Prognostic factors in malignant melanoma are currently based on clinical data and morphologic examination. Other prognostic features, however, which are not yet used in daily practice, might add important information and thus improve prognosis, treatment, and survival. Therefore a search for new markers is desirable. Previous studies have demonstrated that fractal characteristics of nuclear chromatin are of prognostic importance in neoplasias. We have therefore investigated whether the fractal dimension of nuclear chromatin measured in routine histological preparations of malignant melanomas could be a prognostic factor for survival. Methods We examined 71 primary superficial spreading cutaneous melanoma specimens (thickness ≥ 1 mm from patients with a minimum follow up of 5 years. Nuclear area, form factor and fractal dimension of chromatin texture were obtained from digitalized images of hematoxylin-eosin stained tissue micro array sections. Clark's level, tumor thickness and mitotic rate were also determined. Results The median follow-up was 104 months. Tumor thickness, Clark's level, mitotic rate, nuclear area and fractal dimension were significant risk factors in univariate Cox regressions. In the multivariate Cox regression, stratified for the presence or absence of metastases at diagnosis, only the Clark level and fractal dimension of the nuclear chromatin were included as independent prognostic factors in the final regression model. Conclusion In general, a more aggressive behaviour is usually found in genetically unstable neoplasias with a higher number of genetic or epigenetic changes, which on the other hand, provoke a more complex chromatin rearrangement. The increased nuclear fractal dimension found in the more aggressive melanomas is the mathematical equivalent of a higher complexity of the chromatin architecture. So, there is strong evidence that the fractal dimension of the nuclear chromatin texture is a new

  14. Stomach position in prediction of survival in left-sided congenital diaphragmatic hernia with or without fetoscopic endoluminal tracheal occlusion.

    Science.gov (United States)

    Cordier, A-G; Jani, J C; Cannie, M M; Rodó, C; Fabietti, I; Persico, N; Saada, J; Carreras, E; Senat, M-V; Benachi, A

    2015-08-01

    To investigate the value of fetal stomach position in predicting postnatal outcome in left-sided congenital diaphragmatic hernia (CDH) with and without fetoscopic endoluminal tracheal occlusion (FETO). This was a retrospective review of CDH cases that were expectantly managed or treated with FETO, assessed from May 2008 to October 2013, in which we graded, on a scale of 1-4, stomach position on the four-chamber view of the heart with respect to thoracic structures. Logistic regression analysis was used to investigate the effect of management center (Paris, Brussels, Barcelona, Milan), stomach grading, observed-to-expected lung area-to-head circumference ratio (O/E-LHR), gestational age at delivery, birth weight in expectantly managed CDH, gestational ages at FETO and at removal and period of tracheal occlusion, on postnatal survival in CDH cases treated with FETO. We identified 67 expectantly managed CDH cases and 47 CDH cases that were treated with FETO. In expectantly managed CDH, stomach position and O/E-LHR predicted postnatal survival independently. In CDH treated with FETO, stomach position and gestational age at delivery predicted postnatal survival independently. In left-sided CDH with or without FETO, stomach position is predictive of postnatal survival. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  15. Prognostic factors to predict survival in non-small-cell lung cancer with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Tiantian Li; Xuezhen Ma; Yuan Yao

    2014-01-01

    Objective:The purpose of the study was to assess prognostic factors to predict overal survival (OS) and progres-sion-free survival (PFS) in non-smal-celllung cancer (NSCLC) with brain metastasis (BM). Methods:From November 2011 to March 2013, the clinical data of 31 NSCLC cases with BM treated with multiple modalities including brain radiotherapy alone, systemic chemotherapy, whole brain radiotherapy (WBRT) combined with tyrosine kinase inhibitor (TKIs). The ef icacy and adverse reaction were evaluated after treatment. Results:In terms of intracranial lesions, the objective response rate (ORR) and the disease control rate (DCR) were 22.6%and 90.3%, respectively. As for systemic disease, ORR and DCR were 32.3%and 93.5%, respectively. The median time to progression-free survival (PFS) was 298 days (95%CI:258.624-337.376 days), whereas in the epidermal growth factor receptor (EGFR) mutation patients was 331 days. Patients who received EGFR-TKIs combined with brain radiation had better response rate (RR) than those only brain radiation. Univariate analysis showed that the EGFR-mutations could predictive factors for PFS, and not to other clinical pathological features. The most common toxici-ties were rash and diarrhea, but al were wel-tolerated. Conclusion:EGFR-mutations is the independent prognostic factors af ecting the survival rates of NSCLC patients with BM. Through the clinical observation, icotinib combined with WBRT may be ef ective on brain metastases in NSCLC patients, and toxicities are tolerable, which worth further study.

  16. Polymorphism at 19q13.41 predicts breast cancer survival specifically after endocrine therapy

    Science.gov (United States)

    Khan, Sofia; Fagerholm, Rainer; Rafiq, Sajjad; Tapper, William; Aittomäki, Kristiina; Liu, Jianjun

    2015-01-01

    Purpose Although most estrogen receptor (ER)-positive breast cancer patients benefit from endocrine therapies, a significant proportion do not. Our aim was to identify inherited genetic variations that might predict survival among patients receiving adjuvant endocrine therapies. Experimental Design We performed a meta-analysis of two genome-wide studies; Helsinki Breast Cancer Study, 805 patients, with 240 receiving endocrine therapy and Prospective study of Outcomes in Sporadic versus Hereditary breast cancer, 536 patients, with 155 endocrine therapy-patients, evaluating 486,478 single nucleotide polymorphisms (SNPs). The top four associations from the endocrine treatment subgroup were further investigated in two independent datasets totalling 5011 patients, with 3485 receiving endocrine therapy. Results A meta-analysis identified a common SNP rs8113308, mapped to 19q13.41, associating with reduced survival among endocrine treated patients (hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.37-2.07, P = 6.34 ×10−7) and improved survival among ER-negative patients, with a similar trend in ER-positive cases not receiving endocrine therapy. In a multivariate analysis adjusted for conventional prognostic factors, we found a significant interaction between the rs8113308 and endocrine treatment indicating a predictive, treatment-specific effect of the SNP rs8113308 on breast cancer survival, with the per-allele HR for interaction 2.16 (95% CI 1.30 – 3.60, Pinteraction = 0.003) and HR=7.77 (95% CI 0.93 – 64.71) for the homozygous genotype carriers. A biological rationale is suggested by in silico functional analyses. Conclusions Our findings suggest carrying the rs8113308 rare allele may identify patients who will not benefit from adjuvant endocrine treatment. PMID:25964295

  17. Conditional survival predictions after nephrectomy for renal cell carcinoma.

    NARCIS (Netherlands)

    Karakiewicz, P.I.; Suardi, N.; Capitanio, U.; Isbarn, H.; Jeldres, C.; Perrotte, P.; Sun, M.; Ficarra, V.; Zigeuner, R.; Tostain, J.; Mejean, A.; Cindolo, L.; Pantuck, A.J.; Belldegrun, A.S.; Zini, L.; Taille, A. De La; Chautard, D.; Descotes, J.L.; Shariat, S.F.; Valeri, A.; Mulders, P.F.A.; Lang, H.; Lechevallier, E.; Patard, J.J.

    2009-01-01

    PURPOSE: Conditional survival implies that on average long-term cancer survivors have a better prognosis than do newly diagnosed individuals. We explored the effect of conditional survival in renal cell carcinoma. MATERIALS AND METHODS: We studied 3,560 patients with renal cell carcinoma of all stag

  18. The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

    Science.gov (United States)

    Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

    2015-01-01

    Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

  19. Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Bertini, Ivano; Cacciatore, Stefano; Jensen, Benny V;

    2012-01-01

    survival (HR, 3.4; 95% confidence interval, 2.06-5.50; P = 1.33 × 10(-6)). A number of metabolites concurred with the (1)H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that (1)H-NMR profiling of patient serum can provide a strong metabolomic signature of m......Earlier detection of patients with metastatic colorectal cancer (mCRC) might improve their treatment and survival outcomes. In this study, we used proton nuclear magnetic resonance ((1)H-NMR) to profile the serum metabolome in patients with mCRC and determine whether a disease signature may exist...... that is strong enough to predict overall survival (OS). In 153 patients with mCRC and 139 healthy subjects from three Danish hospitals, we profiled two independent sets of serum samples in a prospective phase II study. In the training set, (1)H-NMR metabolomic profiling could discriminate patients with mCRC from...

  20. Network-based survival analysis reveals subnetwork signatures for predicting outcomes of ovarian cancer treatment.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Cox regression is commonly used to predict the outcome by the time to an event of interest and in addition, identify relevant features for survival analysis in cancer genomics. Due to the high-dimensionality of high-throughput genomic data, existing Cox models trained on any particular dataset usually generalize poorly to other independent datasets. In this paper, we propose a network-based Cox regression model called Net-Cox and applied Net-Cox for a large-scale survival analysis across multiple ovarian cancer datasets. Net-Cox integrates gene network information into the Cox's proportional hazard model to explore the co-expression or functional relation among high-dimensional gene expression features in the gene network. Net-Cox was applied to analyze three independent gene expression datasets including the TCGA ovarian cancer dataset and two other public ovarian cancer datasets. Net-Cox with the network information from gene co-expression or functional relations identified highly consistent signature genes across the three datasets, and because of the better generalization across the datasets, Net-Cox also consistently improved the accuracy of survival prediction over the Cox models regularized by L(2 or L(1. This study focused on analyzing the death and recurrence outcomes in the treatment of ovarian carcinoma to identify signature genes that can more reliably predict the events. The signature genes comprise dense protein-protein interaction subnetworks, enriched by extracellular matrix receptors and modulators or by nuclear signaling components downstream of extracellular signal-regulated kinases. In the laboratory validation of the signature genes, a tumor array experiment by protein staining on an independent patient cohort from Mayo Clinic showed that the protein expression of the signature gene FBN1 is a biomarker significantly associated with the early recurrence after 12 months of the treatment in the ovarian cancer patients who are

  1. Network-based survival analysis reveals subnetwork signatures for predicting outcomes of ovarian cancer treatment.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Cox regression is commonly used to predict the outcome by the time to an event of interest and in addition, identify relevant features for survival analysis in cancer genomics. Due to the high-dimensionality of high-throughput genomic data, existing Cox models trained on any particular dataset usually generalize poorly to other independent datasets. In this paper, we propose a network-based Cox regression model called Net-Cox and applied Net-Cox for a large-scale survival analysis across multiple ovarian cancer datasets. Net-Cox integrates gene network information into the Cox's proportional hazard model to explore the co-expression or functional relation among high-dimensional gene expression features in the gene network. Net-Cox was applied to analyze three independent gene expression datasets including the TCGA ovarian cancer dataset and two other public ovarian cancer datasets. Net-Cox with the network information from gene co-expression or functional relations identified highly consistent signature genes across the three datasets, and because of the better generalization across the datasets, Net-Cox also consistently improved the accuracy of survival prediction over the Cox models regularized by L(2 or L(1. This study focused on analyzing the death and recurrence outcomes in the treatment of ovarian carcinoma to identify signature genes that can more reliably predict the events. The signature genes comprise dense protein-protein interaction subnetworks, enriched by extracellular matrix receptors and modulators or by nuclear signaling components downstream of extracellular signal-regulated kinases. In the laboratory validation of the signature genes, a tumor array experiment by protein staining on an independent patient cohort from Mayo Clinic showed that the protein expression of the signature gene FBN1 is a biomarker significantly associated with the early recurrence after 12 months of the treatment in the ovarian cancer patients who are

  2. ECOG is as independent predictor of the response to chemotherapy, overall survival and progression-free survival in carcinoma of unknown primary site

    Science.gov (United States)

    Grajales-Álvarez, Rocío; Martin-Aguilar, Ana; Silva, Juan A.; De La Garza-Salazar, Jaime G.; Ruiz-García, Erika; López-Camarillo, César; Marchat, Laurence A.; La Vega, Horacio Astudillo-De

    2017-01-01

    The aim of the present study was to determine whether age, gender, functional status, histology, tumor location, number of metastases, and levels of the tumor markers, lactate dehydrogenase (LDH) and albumin, are poor prognostic factors for the response to chemotherapy in patients with carcinoma of unknown primary site. A total of 149 patients diagnosed with carcinoma of unknown primary site that was histologically confirmed, and treated with chemotherapy in the Oncology Hospital, National Medical Center, ‘Century XXI’ IMSS, Mexico City, Mexico during the period between January 2002 to December 2009, were carefully selected for the present study. The analysis of 149 patients diagnosed with carcinoma of unknown primary site revealed that the liver was the organ with the highest frequency of metastases (33.5%). The objective response rates to chemotherapy were ~30.2%. Notably, ECOG was an important predictor of response to chemotherapy (P=0.008). The median progression-free survival was 7.1 months. Upon multivariate analysis, the Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status was observed as an independent predictor of progression (P<0.0001). The median overall survival was 14.2 months. The ECOG was also an independent predictor of mortality (P<0.0001). In conclusion, the data from the present study have demonstrated that ECOG is an independent predictor of a poor response to chemotherapy, lower overall survival and progression-free survival in carcinoma of unknown primary site. PMID:28515916

  3. Predicting survival and morbidity-free survival to very old age

    NARCIS (Netherlands)

    R.S. Newson (Rachel); J.C.M. Witteman (Jacqueline); O.H. Franco (Oscar); B.H.Ch. Stricker (Bruno); M.M.B. Breteler (Monique); A. Hofman (Albert); H.W. Tiemeier (Henning)

    2010-01-01

    textabstractAs life expectancy continually increases, it is imperative to identify determinants of survival to the extreme end of the lifespan and more importantly to identify factors that increase the chance of survival free of major morbidities. As such, the current study assessed 45 common diseas

  4. Human and Autologous Adipose-derived Stromal Cells Increase Flap Survival in Rats Independently of Host Immune Response

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Andersen, Ditte Caroline

    2017-01-01

    evaluated after 7 days. RESULTS: The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human...... and rat SVF and human ASC but not for SVF lysate. Human cells were not detected in the flaps after 7 days. CONCLUSIONS: Flap survival increased with SVF treatment regardless of human or autologous origin, suggesting that increased flap survival is independent of the host immune response. All cell...... injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC....

  5. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis

    OpenAIRE

    Hannelore K. van der Burgh; Schmidt, Ruben; Westeneng, Henk-Jan; de Reus, Marcel A.; van den Berg, Leonard H; Van Den Heuvel, Martijn P.

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data to predict survival of ALS patients using deep learning, a machine learning technique highly effective in a broad range of big-data analyses. A group of 135 ALS patients was included from whom high...

  6. ADAMTS8 and ADAMTS15 expression predicts survival in human breast carcinoma

    DEFF Research Database (Denmark)

    Porter, Sarah; Span, Paul N; Sweep, Fred C G J;

    2006-01-01

    We recently undertook expression profiling of all 19 human ADAMTS metalloproteinases (a disintegrin and metalloproteinase with thrombospondin motifs) in malignant and non-neoplastic breast tissue and showed that 11 of the ADAMTS genes are dysregulated in breast carcinoma. We identified a subgroup......% C.I. = 2.16-13.5, p prediction of poor prognosis by ADAMTS8 and ADAMTS15 expression was found to be independent of other classical clinicopathological factors. Results observed in FVB-PyMT mice, a robust transgenic model of highly metastatic...... breast carcinoma, fitted the expectation that relatively high expression levels of ADAMTS8 together with low expression levels of ADAMTS15 seen in human breast carcinoma are associated with a poor clinical outcome. In summary, ADAMTS8 and ADAMTS15 have emerged as novel predictors of survival in patients...

  7. Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients

    Energy Technology Data Exchange (ETDEWEB)

    Paprottka, K.J.; Schoeppe, F.; Ingrisch, M.; Ruebenthaler, J.; Sommer, N.N.; Paprottka, P.M. [LMU - University of Munich, Department of Clinical Radiology, Munich (Germany); Toni, E. de [LMU - University of Munich, Department of Hepatology, Munich (Germany); Ilhan, H.; Zacherl, M.; Todica, A. [LMU - University of Munich, Department of Nuclear Medicine, Munich (Germany)

    2017-07-15

    To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors. (orig.)

  8. Donor chimerism early after reduced-intensity conditioning hematopoietic stem cell transplantation predicts relapse and survival.

    Science.gov (United States)

    Koreth, John; Kim, Haesook T; Nikiforow, Sarah; Milford, Edgar L; Armand, Philippe; Cutler, Corey; Glotzbecker, Brett; Ho, Vincent T; Antin, Joseph H; Soiffer, Robert J; Ritz, Jerome; Alyea, Edwin P

    2014-10-01

    The impact of early donor cell chimerism on outcomes of T cell-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T cell chimerism was also assessed. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse, and nonrelapse mortality (NRM). We evaluated 688 patients with hematologic malignancies (48% myeloid and 52% lymphoid) and a median age of 57 years (range, 18 to 74) undergoing RIC HSCT with T cell-replete donor grafts (97% peripheral blood; 92% HLA-matched), with a median follow-up of 58.2 months (range, 12.6 to 120.7). In multivariable analysis, total donor cell and T cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most predictive. D100 total donor cell chimerism D100 total donor cell chimerism or T cell chimerism. Low donor chimerism early after RIC HSCT is an independent risk factor for relapse and impaired survival. Donor chimerism assessment early after RIC HSCT can prognosticate for long-term outcomes and help identify high-risk patient cohorts who may benefit from additional therapeutic interventions. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Gene expression-based classification of non-small cell lung carcinomas and survival prediction.

    Directory of Open Access Journals (Sweden)

    Jun Hou

    Full Text Available BACKGROUND: Current clinical therapy of non-small cell lung cancer depends on histo-pathological classification. This approach poorly predicts clinical outcome for individual patients. Gene expression profiling holds promise to improve clinical stratification, thus paving the way for individualized therapy. METHODOLOGY AND PRINCIPAL FINDINGS: A genome-wide gene expression analysis was performed on a cohort of 91 patients. We used 91 tumor- and 65 adjacent normal lung tissue samples. We defined sets of predictor genes (probe sets with the expression profiles. The power of predictor genes was evaluated using an independent cohort of 96 non-small cell lung cancer- and 6 normal lung samples. We identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of non-small cell lung cancer. Correlation analysis identified 17 genes which showed the best association with post-surgery survival time. This signature was used for stratification of all patients in two risk groups. Kaplan-Meier survival curves show that the two groups display a significant difference in post-surgery survival time (p = 5.6E-6. The performance of the signatures was validated using a patient cohort of similar size (Duke University, n = 96. Compared to previously published prognostic signatures for NSCLC, the 17 gene signature performed well on these two cohorts. CONCLUSIONS: The gene signatures identified are promising tools for histo-pathological classification of non-small cell lung cancer, and may improve the prediction of clinical outcome.

  10. Do depressive symptoms predict the incidence of myocardial infarction independent of hopelessness?

    Science.gov (United States)

    Pössel, Patrick; Mitchell, Amanda M; Ronkainen, Kimmo; Kaplan, George A; Kauhanen, Jussi; Valtonen, Maarit

    2015-01-01

    Depression and hopelessness predict myocardial infarction, but it is unclear whether depression and hopelessness are independent predictors of myocardial infarction incidents. Hopelessness, depression, and myocardial infarction incidence rate 18 years later were measured in 2005 men. Cox regressions were conducted with hopelessness and depression serving as individual predictors of myocardial infarction. Another Cox model examined whether the two predictors predict myocardial infarction when adjusting for each other. Depression and hopelessness predicted myocardial infarction in independent regressions, but when adjusting for each other, hopelessness, but not depression, predicted myocardial infarction incidents. Thus, these results suggest that depression and hopelessness are not independent predictors of myocardial infarction. © The Author(s) 2013.

  11. Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib

    Directory of Open Access Journals (Sweden)

    Lee SH

    2015-04-01

    Full Text Available Sangheun Lee,1,* Beom Kyung Kim,2–5,* Seung Up Kim,2–5 Jun Yong Park,2–5 Do Young Kim,2–5 Sang Hoon Ahn,2–6 Kwang-Hyub Han2–6 1Department of Internal Medicine, International St Mary’s Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea; 2Department of Internal Medicine, 3Institute of Gastroenterology, 4Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea; 6Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea.   *These authors contributed equally to this work Background: It is not clear whether tumor marker responses can predict survival during sorafenib treatment in hepatocellular carcinoma (HCC. We investigated whether the α-fetoprotein (AFP response is associated with survival in patients with advanced HCC treated with sorafenib. Methods: We retrospectively reviewed the records of 126 patients with advanced HCC treated with sorafenib between 2007 and 2012. An AFP response was defined as >20% decrease from baseline. At 6–8 weeks after commencing sorafenib, AFP and radiological responses were assessed by modified Response Evaluation Criteria in Solid Tumors. Results: The median overall survival (OS and progression-free survival (PFS were 6.2 and 3.5 months, respectively. Of the study population, a partial response (PR was identified in 5 patients (4.0%, stable disease (SD in 65 patients (51.6%, and progressive disease (PD in 57 patients (44.4%, respectively. AFP non-response was an independent prognostic factor for poor OS (median 10.9 months for AFP response vs 5.2 months for AFP non-response, together with Child-Pugh B, tumor diameter ≥10 cm, and portal vein invasion (all P<0.05, and PFS (median 5.3 months for AFP response vs 2.9 months for AFP non-response, together with tumor diameter ≥10 cm and portal vein invasion (all P<0.05. SD or PR was more frequently found

  12. Disseminated tumor cells in pancreatic cancer-an independent prognosticator of disease progression and survival

    NARCIS (Netherlands)

    Effenberger, Katharina E.; Schroeder, Cornelia; Eulenburg, Christine; Reeh, Matthias; Tachezy, Michael; Riethdorf, Sabine; Vashist, Yogesh K.; Izbicki, Jakob R.; Pantel, Klaus; Bockhorn, Maximilian

    2012-01-01

    Pancreatic cancer is one of the most devastating cancers with a 6-month median survival and a 5-year survival rate of 35%. Still important aspects of its aggressive biology remain elusive and advanced therapeutic regimens have not been substantially successful. We investigated the prognostic role of

  13. Immune phenotypes predict survival in patients with glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Haouraa Mostafa

    2016-09-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM, a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. Methods Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively. Results Using descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival. Conclusions Defined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.

  14. Mesh-independent prediction of skin burns injury.

    Science.gov (United States)

    Ng, E Y; Chua, L T

    2000-01-01

    This paper presents a robust finite element model (FEM) with multiple-layers of varying properties for investigation of burn effects on human skin during a burning process resulting from exposure of skin surface to a contact heat source and a hot moving fluid. Henriques' theory of skin burns is used in conjunction with two-dimensional Pennes bioheat transfer equation for determining the spatial and temporal extent of burn injury. The model developed is a two-dimensional axisymmetric model in cylindrical coordinates. The various tissue layers account for changing thermal properties with respect to skin anatomy. A finite element scheme that uses the backward Euler method is used to solve the problem. The injury processes of skin subsequent to the removal of the heat source (post-burn) will also be inspected. The mesh employed in this model consists of a high density of nodes and elements in which a thorough mesh convergence study was done. A comparison of the transient temperature field computed by this model against Diller's results using the FE technique with a comparatively coarse mesh of 125 elements and experimental data by Orgill et al. has been done in the present study. It concluded that improved accurate solutions have been performed using the robust model developed due to the achievement of a mesh-independent solution.

  15. Comparative study of joint analysis of microarray gene expression data in survival prediction and risk assessment of breast cancer patients.

    Science.gov (United States)

    Yasrebi, Haleh

    2016-09-01

    Microarray gene expression data sets are jointly analyzed to increase statistical power. They could either be merged together or analyzed by meta-analysis. For a given ensemble of data sets, it cannot be foreseen which of these paradigms, merging or meta-analysis, works better. In this article, three joint analysis methods, Z-score normalization, ComBat and the inverse normal method (meta-analysis) were selected for survival prognosis and risk assessment of breast cancer patients. The methods were applied to eight microarray gene expression data sets, totaling 1324 patients with two clinical endpoints, overall survival and relapse-free survival. The performance derived from the joint analysis methods was evaluated using Cox regression for survival analysis and independent validation used as bias estimation. Overall, Z-score normalization had a better performance than ComBat and meta-analysis. Higher Area Under the Receiver Operating Characteristic curve and hazard ratio were also obtained when independent validation was used as bias estimation. With a lower time and memory complexity, Z-score normalization is a simple method for joint analysis of microarray gene expression data sets. The derived findings suggest further assessment of this method in future survival prediction and cancer classification applications.

  16. VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels.

    Science.gov (United States)

    Cariboni, Anna; Davidson, Kathryn; Dozio, Elena; Memi, Fani; Schwarz, Quenten; Stossi, Fabio; Parnavelas, John G; Ruhrberg, Christiana

    2011-09-01

    Gonadotropin-releasing hormone (GnRH) neurons are neuroendocrine cells that are born in the nasal placode during embryonic development and migrate through the nose and forebrain to the hypothalamus, where they regulate reproduction. Many molecular pathways that guide their migration have been identified, but little is known about the factors that control the survival of the migrating GnRH neurons as they negotiate different environments. We previously reported that the class 3 semaphorin SEMA3A signals through its neuropilin receptors, NRP1 and NRP2, to organise the axons that guide migrating GnRH neurons from their birthplace into the brain. By combining analysis of genetically altered mice with in vitro models, we show here that the alternative neuropilin ligand VEGF164 promotes the survival of migrating GnRH neurons by co-activating the ERK and AKT signalling pathways through NRP1. We also demonstrate that survival signalling relies on neuronal, but not endothelial, NRP1 expression and that it occurs independently of KDR, the main VEGF receptor in blood vessels. Therefore, VEGF164 provides survival signals directly to developing GnRH neurons, independently of its role in blood vessels. Finally, we show that the VEGF164-mediated neuronal survival and SEMA3A-mediated axon guidance cooperate to ensure that migrating GnRH neurons reach the brain. Thus, the loss of both neuropilin ligands leads to an almost complete failure to establish the GnRH neuron system.

  17. Predicted Water Immersion Survival Times for Anti-Exposure Ensembles

    Science.gov (United States)

    2005-10-01

    which to determine what garments need to be worn and when. Therefore, the goal of this study was to develop a family of risk curves based on the...females who are known to lose more body heat than men3, and also does not account for wave effects, fatigue, last mealtime , injuries, attitude, etc...garments. These heat stress data combined with the immersion survivability estimates can be used to generate a family of curves to provide comprehensive

  18. Telomerase-independent paths to immortality in predictable cancer subtypes.

    Science.gov (United States)

    Durant, Stephen T

    2012-01-01

    The vast majority of cancers commandeer the activity of telomerase - the remarkable enzyme responsible for prolonging cellular lifespan by maintaining the length of telomeres at the ends of chromosomes. Telomerase is only normally active in embryonic and highly proliferative somatic cells. Thus, targeting telomerase is an attractive anti-cancer therapeutic rationale currently under investigation in various phases of clinical development. However, previous reports suggest that an average of 10-15% of all cancers lose the functional activity of telomerase and most of these turn to an Alternative Lengthening of Telomeres pathway (ALT). ALT-positive tumours will therefore not respond to anti-telomerase therapies and there is a real possibility that such drugs would be toxic to normal telomerase-utilising cells and ultimately select for resistant cells that activate an ALT mechanism. ALT exploits certain DNA damage response (DDR) components to counteract telomere shortening and rapid trimming. ALT has been reported in many cancer subtypes including sarcoma, gastric carcinoma, central nervous system malignancies, subtypes of kidney (Wilm's Tumour) and bladder carcinoma, mesothelioma, malignant melanoma and germ cell testicular cancers to name but a few. A recent heroic study that analysed ALT in over six thousand tumour samples supports this historical spread, although only reporting an approximate 4% prevalence. This review highlights the various methods of ALT detection, unravels several molecular ALT models thought to promote telomere maintenance and elongation, spotlights the DDR components known to facilitate these and explores why certain tissues are more likely to subvert DDR away from its usually protective functions, resulting in a predictive pattern of prevalence in specific cancer subsets.

  19. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

    Science.gov (United States)

    Patel, Uday B; Taylor, Fiona; Blomqvist, Lennart; George, Christopher; Evans, Hywel; Tekkis, Paris; Quirke, Philip; Sebag-Montefiore, David; Moran, Brendan; Heald, Richard; Guthrie, Ashley; Bees, Nicola; Swift, Ian; Pennert, Kjell; Brown, Gina

    2011-10-01

    To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

  20. Quality of life predicts overall survival in women with platinum-resistant ovarian cancer: an AURELIA substudy.

    Science.gov (United States)

    Roncolato, F T; Gibbs, E; Lee, C K; Asher, R; Davies, L C; Gebski, V J; Friedlander, M; Hilpert, F; Wenzel, L; Stockler, M R; King, M; Pujade-Lauraine, E

    2017-08-01

    Women with platinum-resistant ovarian cancer are a heterogeneous group whose median overall survival is 12 months. We hypothesized that their quality of life (QoL) scores would be prognostic. Data from AURELIA (n = 326), a randomized trial of chemotherapy with or without bevacizumab, were used to identify baseline QoL domains [EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 and OV28] that were significantly associated with overall survival in multivariable Cox regression analyses. Patients were classified as having good, medium, or poor risk. Cutpoints were validated in an independent dataset, CARTAXHY (n = 136). Multivariable analyses of significant QoL domains on survival were adjusted for clinicopathological prognostic factors. The additional QoL information was assessed using C statistic. In AURELIA, all domains, except cognitive function, predicted overall survival in univariable analyses. Physical function (P 93) risk categories for physical function, median overall survival was 11.0, 14.7, and 19.3 months, respectively (P 44), medium- (13-44), and low- (AURELIA (P < 0.001) and 10.5, 19.6, and 24.1 months in CARTAXHY (P = 0.02). Physical function (P = 0.02) and abdominal/gastrointestinal symptoms (P = 0.03) remained independent prognostic factors after adjustment for clinicopathological factors. The C statistic of the full model was 0.71. For QoL factors alone, patient factors alone and disease factors alone, the C statistics were 0.61, 0.61, and 0.67 respectively. Physical function and abdominal/gastrointestinal symptom scores improved predictions of overall survival over clinicopathological factors alone in platinum-resistant ovarian cancer. This additional prognostic information could improve trial stratification, patient-doctor communication about prognosis, and clinical decision-making. NCT00976911.

  1. Ex Vivo Perfusion Characteristics of Donation After Cardiac Death Kidneys Predict Long-Term Graft Survival.

    Science.gov (United States)

    Sevinc, M; Stamp, S; Ling, J; Carter, N; Talbot, D; Sheerin, N

    2016-12-01

    Ex vivo perfusion is used in our unit for kidneys donated after cardiac death (DCD). Perfusion flow index (PFI), resistance, and perfusate glutathione S-transferase (GST) can be measured to assess graft viability. We assessed whether measurements taken during perfusion could predict long-term outcome after transplantation. All DCD kidney transplants performed from 2002 to 2014 were included in this study. The exclusion criteria were: incomplete data, kidneys not machine perfused, kidneys perfused in continuous mode, and dual transplantation. There were 155 kidney transplantations included in the final analysis. Demographic data, ischemia times, donor hypertension, graft function, survival and machine perfusion parameters after 3 hours were analyzed. Each perfusion parameter was divided into 3 groups as high, medium, and low. Estimated glomerular filtration rate was calculated at 12 months and then yearly after transplantation. There was a significant association between graft survival and PFI and GST (P values, .020 and .022, respectively). PFI was the only independent parameter to predict graft survival. A low PFI during ex vivo hypothermic perfusion is associated with inferior graft survival after DCD kidney transplantation. We propose that PFI is a measure of the health of the graft vasculature and that a low PFI indicates vascular disease and therefore predicts a worse long-term outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Pre-transplant quality of life does not predict survival after lung transplantation

    NARCIS (Netherlands)

    Vermeulen, Karin M.; TenVergert, Elisabeth M.; Verschuuren, Erik A. M.; Erasmus, Michiel E.; van der Bij, Wim

    2008-01-01

    Background: Currently, the goal of lung transplantation is not only to improve survival but also includes' improvement of health-related quality of life (HRQL). Limited knowledge is available about the value of HRQL before lung transplantation with regard to predicting survival after lung transplant

  3. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van der Burgh, Hannelore K; Schmidt, Ruben; Westeneng, Henk-Jan; de Reus, Marcel A; van den Berg, Leonard H; van den Heuvel, Martijn P

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data

  4. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van der Burgh, Hannelore K; Schmidt, Ruben; Westeneng, Henk-Jan; de Reus, Marcel A; van den Berg, Leonard H; van den Heuvel, Martijn P

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data

  5. Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers.

    Directory of Open Access Journals (Sweden)

    Elena Pereira

    critical inflection point in precision medicine. This study suggests that the use of personalized ctDNA biomarkers in gynecologic cancers can identify the presence of residual tumor while also more dynamically predicting response to treatment relative to currently used serum and imaging studies. Of particular interest, ctDNA was an independent predictor of survival in patients with ovarian and endometrial cancers. Earlier recognition of disease persistence and/or recurrence and the ability to stratify into better and worse outcome groups through ctDNA surveillance may open the window for improved survival and quality and life in these cancers.

  6. Predicting survival of Salmonella in low-water activity foods: an analysis of literature data.

    Science.gov (United States)

    Santillana Farakos, Sofia M; Schaffner, Donald W; Frank, Joseph F

    2014-09-01

    Factors such as temperature, water activity (aw), substrate, culture media, serotype, and strain influence the survival of Salmonella in low-aw foods. Predictive models for Salmonella survival in low-aw foods at temperatures ranging from 21 to 80(u) C and water activities below 0.6 were previously developed. Literature data on survival of Salmonella in low-aw foods were analyzed in the present study to validate these predictive models and to determine global influencing factors. The results showed the Weibull model provided suitable fits to the data in 75% of the curves as compared with the log-linear model. The secondary models predicting the time required for log-decimal reduction (log δ) and shape factor (log β) values were useful in predicting the survival of Salmonella in low-aw foods. Statistical analysis indicated overall fail-safe secondary models, with 88% of the residuals in the acceptable and safe zones (foods and its influencing factors.

  7. Predicting survival of pancreatic cancer patients treated with gemcitabine using longitudinal tumour size data.

    Science.gov (United States)

    Wendling, Thierry; Mistry, Hitesh; Ogungbenro, Kayode; Aarons, Leon

    2016-05-01

    Measures derived from longitudinal tumour size data have been increasingly utilised to predict survival of patients with solid tumours. The aim of this study was to examine the prognostic value of such measures for patients with metastatic pancreatic cancer undergoing gemcitabine therapy. The control data from two Phase III studies were retrospectively used to develop (271 patients) and validate (398 patients) survival models. Firstly, 31 baseline variables were screened from the training set using penalised Cox regression. Secondly, tumour shrinkage metrics were interpolated for each patient by hierarchical modelling of the tumour size time-series. Subsequently, survival models were built by applying two approaches: the first aimed at incorporating model-derived tumour size metrics in a parametric model, and the second simply aimed at identifying empirical factors using Cox regression. Finally, the performance of the models in predicting patient survival was evaluated on the validation set. Depending on the modelling approach applied, albumin, body surface area, neutrophil, baseline tumour size and tumour shrinkage measures were identified as potential prognostic factors. The distributional assumption on survival times appeared to affect the identification of risk factors but not the ability to describe the training data. The two survival modelling approaches performed similarly in predicting the validation data. A parametric model that incorporates model-derived tumour shrinkage metrics in addition to other baseline variables could predict reasonably well survival of patients with metastatic pancreatic cancer. However, the predictive performance was not significantly better than a simple Cox model that incorporates only baseline characteristics.

  8. A Transcriptional Fingerprint of Estrogen in Human Breast Cancer Predicts Patient Survival

    Directory of Open Access Journals (Sweden)

    Jianjun Yu

    2008-01-01

    Full Text Available Estrogen signaling plays an essential role in breast cancer progression, and estrogen receptor (ER status has long been a marker of hormone responsiveness. However, ER status alone has been an incomplete predictor of endocrine therapy, as some ER+ tumors, nevertheless, have poor prognosis. Here we sought to use expression profiling of ER+ breast cancer cells to screen for a robust estrogen-regulated gene signature that may serve as a better indicator of cancer outcome. We identified 532 estrogen-induced genes and further developed a 73-gene signature that best separated a training set of 286 primary breast carcinomas into prognostic subtypes by stepwise cross-validation. Notably, this signature predicts clinical outcome in over 10 patient cohorts as well as their respective ER+ subcohorts. Further, this signature separates patients who have received endocrine therapy into two prognostic subgroups, suggesting its specificity as a measure of estrogen signaling, and thus hormone sensitivity. The 73-gene signature also provides additional predictive value for patient survival, independent of other clinical parameters, and outperforms other previously reported molecular outcome signatures. Taken together, these data demonstrate the power of using cell culture systems to screen for robust gene signatures of clinical relevance.

  9. Endobronchial mucosa invasion predicts survival in patients with small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Pai-Chien Chou

    Full Text Available BACKGROUND: Current staging system for small cell lung cancer (SCLC categorizes patients into limited- or extensive-stage disease groups according to anatomical localizations. Even so, a wide-range of survival times has been observed among patients in the same staging system. This study aimed to identify whether endobronchial mucosa invasion is an independent predictor for poor survival in patients with SCLC, and to compare the survival time between patients with and without endobronchial mucosa invasion. METHODS: We studied 432 consecutive patients with SCLC based on histological examination of biopsy specimens or on fine-needle aspiration cytology, and received computed tomography and bone scan for staging. All the enrolled patients were assessed for endobronchial mucosa invasion by bronchoscopic and histological examination. Survival days were compared between patients with or without endobronchial mucosa invasion and the predictors of decreased survival days were investigated. RESULTS: 84% (364/432 of SCLC patients had endobronchial mucosal invasion by cancer cells at initial diagnosis. Endobronchial mucosal involvement (Hazard ratio [HR], 2.01; 95% Confidence Interval [CI], 1.30-3.10, age (HR, 1.04; 95% CI, 1.03-1.06, and extensive stage (HR, 1.39; 95% CI, 1.06-1.84 were independent contributing factors for shorter survival time, while received chemotherapy (HR, 0.32; 95% CI, 0.25-0.42 was an independent contributing factor better outcome. The survival days of SCLC patients with endobronchial involvement were markedly decreased compared with patients without (median 145 vs. 290, p<0.0001. Among SCLC patients of either limited (median 180 vs. 460, p<0.0001 or extensive (median 125 vs. 207, p<0.0001 stages, the median survival duration for patients with endobronchial mucosal invasion was shorter than those with intact endobronchial mucosa, respectively. CONCLUSION: Endobronchial mucosal involvement is an independent prognostic factor for SCLC

  10. Application of Artificial Neural Network in Predicting the Survival Rate of Gastric Cancer Patients

    OpenAIRE

    Biglarian, A; E. Hajizadeh; Kazemnejad, A; Zali, MR

    2011-01-01

    "nBackground: The aim of this study was to predict the survival rate of Iranian gastric cancer patients using the Cox proportional hazard and artificial neural network models as well as comparing the ability of these approaches in predicting the survival of these patients."nMethods: In this historical cohort study, the data gathered from 436 registered gastric cancer patients who have had surgery between 2002 and 2007 at the Taleghani Hospital (a referral center for gastrointestinal...

  11. The Factor of Culture in Modernization fnd Predicting the Commonwealth of Independent States Future

    Directory of Open Access Journals (Sweden)

    K P Kurylev

    2012-03-01

    Full Text Available The article considers the integration processes features within the Commonwealth of Independent States, defines the role and place of cooperation in the humanitarian sphere. The authors make an attempt to predict the future of the CIS.

  12. Subjective fear, interference by threat, and fear associations independently predict fear-related behavior in children

    NARCIS (Netherlands)

    Klein, A.M.; Kleinherenbrink, A.V.; Simons, C.; de Gier, E.; Klein, S.; Allart, E.; Bögels, S.M.; Becker, E.S.; Rinck, M.

    2012-01-01

    Background and objectives: Several information-processing models highlight the independent roles of controlled and automatic processes in explaining fearful behavior. Therefore, we investigated whether direct measures of controlled processes and indirect measures of automatic processes predict uniqu

  13. Soluble L-selectin levels predict survival in sepsis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

    2002-01-01

    OBJECTIVE: To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis. DESIGN: A prospective study of mortality in patients with sepsis whose serum levels of sL-selectin were measured on admission to an intensive care unit (ICU) and 4 days later. Follow-up data...... organs, and 14 control subjects. MEASUREMENTS AND RESULTS: On admission to the ICU the Simplified Acute Physiology Score (SAPS) II was calculated, and relevant microbial cultures were performed. Mortality was registered at various follow-up points: 7 days after admission, at discharge from hospital......, and 3 and 12 months after admission. Serum sL-selectin levels were significantly lower in the patients than in the controls. Sepsis nonsurvivors had significantly lower levels than survivors. Efficiency analysis and receiver operation characteristics showed that the ideal cutoff point for s...

  14. Survival and settlement success of coral planulae: Independent and synergistic effects of macroalgae and microbes

    NARCIS (Netherlands)

    Vermeij, M.J.A.; Smith, J.E.; Smith, C.M.; Vega Thurber, R.; Sandin, S.A.

    2009-01-01

    Restoration of degraded coral reef communities is dependent on successful recruitment and survival of new coral planulae. Degraded reefs are often characterized by high cover of fleshy algae and high microbial densities, complemented by low abundance of coral and coral recruits. Here, we

  15. Gene expression of PMP22 is an independent prognostic factor for disease-free and overall survival in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Schiebel Ingrid

    2010-12-01

    Full Text Available Abstract Background Gene expression of peripheral myelin protein 22 (PMP22 and the epithelial membrane proteins (EMPs was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer. Methods In a retrospective multicenter study, gene expression of PMP22 and the EMPs was measured in 249 primary breast tumors by real-time PCR. Results were statistically analyzed together with clinical data. Results In univariable Cox regression analyses PMP22 and the EMPs were not associated with disease-free survival or tumor-related mortality. However, multivariable Cox regression revealed that patients with higher than median PMP22 gene expression have a 3.47 times higher risk to die of cancer compared to patients with equal values on clinical covariables but lower PMP22 expression. They also have a 1.77 times higher risk to relapse than those with lower PMP22 expression. The proportion of explained variation in overall survival due to PMP22 gene expression was 6.5% and thus PMP22 contributes equally to prognosis of overall survival as nodal status and estrogen receptor status. Cross validation demonstrates that 5-years survival rates can be refined by incorporating PMP22 into the prediction model. Conclusions PMP22 gene expression is a novel independent prognostic factor for disease-free survival and overall survival for breast cancer patients. Including it into a model with established prognostic factors will increase the accuracy of prognosis.

  16. Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.

    Directory of Open Access Journals (Sweden)

    Patrick N Harter

    Full Text Available The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.

  17. Advanced Online Survival Analysis Tool for Predictive Modelling in Clinical Data Science.

    Science.gov (United States)

    Montes-Torres, Julio; Subirats, José Luis; Ribelles, Nuria; Urda, Daniel; Franco, Leonardo; Alba, Emilio; Jerez, José Manuel

    2016-01-01

    One of the prevailing applications of machine learning is the use of predictive modelling in clinical survival analysis. In this work, we present our view of the current situation of computer tools for survival analysis, stressing the need of transferring the latest results in the field of machine learning to biomedical researchers. We propose a web based software for survival analysis called OSA (Online Survival Analysis), which has been developed as an open access and user friendly option to obtain discrete time, predictive survival models at individual level using machine learning techniques, and to perform standard survival analysis. OSA employs an Artificial Neural Network (ANN) based method to produce the predictive survival models. Additionally, the software can easily generate survival and hazard curves with multiple options to personalise the plots, obtain contingency tables from the uploaded data to perform different tests, and fit a Cox regression model from a number of predictor variables. In the Materials and Methods section, we depict the general architecture of the application and introduce the mathematical background of each of the implemented methods. The study concludes with examples of use showing the results obtained with public datasets.

  18. Respiratory Muscle Strength as a Predictive Biomarker for Survival in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Polkey, Michael I; Lyall, Rebecca A; Yang, Ke; Johnson, Erin; Leigh, P Nigel; Moxham, John

    2017-01-01

    Biomarkers for survival in amyotrophic lateral sclerosis (ALS) would facilitate the development of novel drugs. Although respiratory muscle weakness is a known predictor of poor prognosis, a comprehensive comparison of different tests is lacking. To compare the predictive power of invasive and noninvasive respiratory muscle strength assessments for survival or ventilator-free survival, up to 3 years. From a previously published report respiratory muscle strength measurements were available for 78 patients with ALS. Time to death and/or ventilation were ascertained. Receiver operating characteristic analysis was used to determine the cutoff point of each parameter. Each respiratory muscle strength assessment individually achieved statistical significance for prediction of survival or ventilator-free survival. In multivariate analysis sniff trans-diaphragmatic and esophageal pressure, twitch trans-diaphragmatic pressure (Tw Pdi), age, and maximal static expiratory mouth pressure were significant predictors of ventilation-free survival and Tw Pdi and maximal static expiratory mouth pressure for absolute survival. Although all measures had good specificity, there were differing sensitivities. All cutoff points for the VC were greater than 80% of normal, except for prediction of 3-month outcomes. Sequential data showed a linear decline for direct measures of respiratory muscle strength, whereas VC showed little to no decline until 12 months before death/ventilation. The most powerful biomarker for mortality stratification was Tw Pdi, but the predictive power of sniff nasal inspiratory pressure was also excellent. A VC within normal range suggested a good prognosis at 3 months but was of little other value.

  19. A simple protein-energy wasting score predicts survival in maintenance hemodialysis patients.

    Science.gov (United States)

    Moreau-Gaudry, Xavier; Jean, Guillaume; Genet, Leslie; Lataillade, Dominique; Legrand, Eric; Kuentz, François; Fouque, Denis

    2014-11-01

    Nutritional status is a powerful predictor of survival in maintenance hemodialysis patients but remains challenging to assess. We defined a new Protein Energy Wasting (PEW) score based on the nomenclature proposed by the International Society of Renal Nutrition and Metabolism in 2008. This score, graded from 0 (worse) to 4 (best) was derived from 4 body nutrition compartments: serum albumin, body mass index, a normalized serum creatinine value, and protein intake as assessed by nPNA. We applied this score to 1443 patients from the ARNOS prospective dialysis cohort and provide survival data from 2005 until 2008. Patients survival at 3.5 year. Survival ranged from 84%-69% according to the protein-energy wasting score. There was a clear-cut reduction in survival (5%-7%; P < 0.01) for each unit decrement in the score grade. There was a 99% survival at 1 year for patients with the score of 4. In addition, the 6-month variation of this PEW score also strongly predicted patients' survival (P < 0.01). A new simple and easy-to-get PEW score predicts survival in maintenance hemodialysis patients. Furthermore, increase of this nutritional score over time also indicates survival improvement, and may help to better identify subgroups of patients with a high mortality rate, in which nutrition support should be enforced. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  20. Single sample expression-anchored mechanisms predict survival in head and neck cancer.

    Directory of Open Access Journals (Sweden)

    Xinan Yang

    2012-01-01

    Full Text Available Gene expression signatures that are predictive of therapeutic response or prognosis are increasingly useful in clinical care; however, mechanistic (and intuitive interpretation of expression arrays remains an unmet challenge. Additionally, there is surprisingly little gene overlap among distinct clinically validated expression signatures. These "causality challenges" hinder the adoption of signatures as compared to functionally well-characterized single gene biomarkers. To increase the utility of multi-gene signatures in survival studies, we developed a novel approach to generate "personal mechanism signatures" of molecular pathways and functions from gene expression arrays. FAIME, the Functional Analysis of Individual Microarray Expression, computes mechanism scores using rank-weighted gene expression of an individual sample. By comparing head and neck squamous cell carcinoma (HNSCC samples with non-tumor control tissues, the precision and recall of deregulated FAIME-derived mechanisms of pathways and molecular functions are comparable to those produced by conventional cohort-wide methods (e.g. GSEA. The overlap of "Oncogenic FAIME Features of HNSCC" (statistically significant and differentially regulated FAIME-derived genesets representing GO functions or KEGG pathways derived from HNSCC tissue among three distinct HNSCC datasets (pathways:46%, p<0.001 is more significant than the gene overlap (genes:4%. These Oncogenic FAIME Features of HNSCC can accurately discriminate tumors from control tissues in two additional HNSCC datasets (n = 35 and 91, F-accuracy = 100% and 97%, empirical p<0.001, area under the receiver operating characteristic curves = 99% and 92%, and stratify recurrence-free survival in patients from two independent studies (p = 0.0018 and p = 0.032, log-rank. Previous approaches depending on group assignment of individual samples before selecting features or learning a classifier are limited by design to

  1. Does adding risk-trends to survival models improve in-hospital mortality predictions? A cohort study

    Directory of Open Access Journals (Sweden)

    Forster Alan J

    2011-07-01

    Full Text Available Abstract Background Clinicians informally assess changes in patients' status over time to prognosticate their outcomes. The incorporation of trends in patient status into regression models could improve their ability to predict outcomes. In this study, we used a unique approach to measure trends in patient hospital death risk and determined whether the incorporation of these trend measures into a survival model improved the accuracy of its risk predictions. Methods We included all adult inpatient hospitalizations between 1 April 2004 and 31 March 2009 at our institution. We used the daily mortality risk scores from an existing time-dependent survival model to create five trend indicators: absolute and relative percent change in the risk score from the previous day; absolute and relative percent change in the risk score from the start of the trend; and number of days with a trend in the risk score. In the derivation set, we determined which trend indicators were associated with time to death in hospital, independent of the existing covariates. In the validation set, we compared the predictive performance of the existing model with and without the trend indicators. Results Three trend indicators were independently associated with time to hospital mortality: the absolute change in the risk score from the previous day; the absolute change in the risk score from the start of the trend; and the number of consecutive days with a trend in the risk score. However, adding these trend indicators to the existing model resulted in only small improvements in model discrimination and calibration. Conclusions We produced several indicators of trend in patient risk that were significantly associated with time to hospital death independent of the model used to create them. In other survival models, our approach of incorporating risk trends could be explored to improve their performance without the collection of additional data.

  2. TRPM1 (melastatin) expression is an independent predictor of overall survival in clinical AJCC stage I and II melanoma patients.

    Science.gov (United States)

    Brożyna, Anna A; Guo, Huazhang; Yang, Sun-Eun; Cornelius, Lynn; Linette, Gerald; Murphy, Michael; Sheehan, Christine; Ross, Jeffrey; Slominski, Andrzej; Carlson, J Andrew

    2017-04-01

    The expression of TRPM1 (melastatin) mRNA is an independent marker, as measured by radioactive in situ hybridization (RISH), of disease-free survival in primary cutaneous melanoma (PM). The aim of the study was to determine if chromogenic in situ hybridization (CISH) can reproduce results examining diagnostic and prognostic utility of TRPM1 mRNA expression in melanocytic proliferations as measured by RISH. The expression of TRPM1 mRNA was detected by CISH in melanocytic nevi (MN, n = 61), PM (n = 145) and metastatic melanomas (MMs, n = 15). A progressive loss of TRPM1 was found moving from MN to PM to MM. The histologic stepwise model of melanoma progression revealed that loss of TRPM1 occurred at the transition of RGP PM to VGP PM. As a diagnostic marker, TRPM1 gradient loss showed 93.8% sensitivity and 52.4% specificity for PM. Loss of TRPM1 mRNA correlated with melanoma aggressiveness markers and was independent predictor of disease-free and overall survival. The corresponding survival curves for degree of melanoma pigmentation matched those for degree of loss of TPRM1 mRNA. Loss of TRPM1 mRNA expression appears to be a crucial event in the progression of melanoma to a more malignant, metastatic phenotype. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Unbiased Prediction and Feature Selection in High-Dimensional Survival Regression

    Science.gov (United States)

    Laimighofer, Michael; Krumsiek, Jan; Theis, Fabian J.

    2016-01-01

    Abstract With widespread availability of omics profiling techniques, the analysis and interpretation of high-dimensional omics data, for example, for biomarkers, is becoming an increasingly important part of clinical medicine because such datasets constitute a promising resource for predicting survival outcomes. However, early experience has shown that biomarkers often generalize poorly. Thus, it is crucial that models are not overfitted and give accurate results with new data. In addition, reliable detection of multivariate biomarkers with high predictive power (feature selection) is of particular interest in clinical settings. We present an approach that addresses both aspects in high-dimensional survival models. Within a nested cross-validation (CV), we fit a survival model, evaluate a dataset in an unbiased fashion, and select features with the best predictive power by applying a weighted combination of CV runs. We evaluate our approach using simulated toy data, as well as three breast cancer datasets, to predict the survival of breast cancer patients after treatment. In all datasets, we achieve more reliable estimation of predictive power for unseen cases and better predictive performance compared to the standard CoxLasso model. Taken together, we present a comprehensive and flexible framework for survival models, including performance estimation, final feature selection, and final model construction. The proposed algorithm is implemented in an open source R package (SurvRank) available on CRAN. PMID:26894327

  4. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  5. Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT promoter methylation as independent favourable prognostic factor

    Directory of Open Access Journals (Sweden)

    Smrdel Uros

    2016-12-01

    Full Text Available In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma.

  6. Human and Autologous Adipose-derived Stromal Cells Increase Flap Survival in Rats Independently of Host Immune Response.

    Science.gov (United States)

    Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Andersen, Ditte Caroline; Sheikh, Søren Paludan; Sørensen, Jens Ahm

    2017-07-22

    There is a rising interest in adipose-derived stromal cells for clinical use; however, it is unknown whether freshly isolated stromal cells (SVF) or culture-expanded cells (ASCs) are more efficacious. We therefore aimed to compare the 2 cellular therapies in an in vivo model of angiogenesis, the ischemic flap in rats, which induces acute ischemia. We also aimed to determine the importance of cell presence and the host immune response. A total of 96 rats (n = 12 in each group) were used, and in each rat, a caudally based random flap measuring 2 × 7 cm was made. The study was conducted in 3 phases. First, each rat was treated with human SVF cells, human ASCs, or vehicle. Second, each rat was treated with human SVF, human SVF lysate, or vehicle. Finally, each rat was treated with rat (autologous) SVF cells or vehicle. Flap survival, vessel density, and stromal cell retention were evaluated after 7 days. The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human and rat SVF and human ASC but not for SVF lysate. Human cells were not detected in the flaps after 7 days. Flap survival increased with SVF treatment regardless of human or autologous origin, suggesting that increased flap survival is independent of the host immune response. All cell injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC.

  7. Significance of bioindicators to predict survival in irradiated minipigs.

    Science.gov (United States)

    Moroni, Maria; Port, Matthias; Koch, Amory; Gulani, Jatinder; Meineke, Viktor; Abend, Michael

    2014-06-01

    The minipig is emerging as a potential alternative non-rodent animal model. Several biological markers (e.g., blood counts, laboratory parameters, and clinical signs) have been proposed for rapid triage of radiation victims. Here, the authors focus on the significance of bio-indicators for prediction of survivors after irradiation and compare it with human data; the relationship between these biomarkers and radiation dose is not part of this study. Male Göttingen minipigs (age 4-5 mo, weight 9-10 kg) were irradiated (or sham-irradiated) bilaterally with gamma-photons (⁶⁰Co, 0.5-0.6 Gy min⁻¹) in the dose range of 1.6-12 Gy. Peripheral blood cell counts, laboratory parameters, and clinical symptoms were collected up to 10 d after irradiation and analyzed using logistic regression analysis and calculating ROC curves. In moribund pigs, parameters such as decreased lymphocyte/granulocyte counts, increased C-reactive protein, alkaline phosphatase values, as well as increased citrulline values and body temperature, significantly (p 0.8). However, most predictive within the first 3 d after exposure was a combination of decreased lymphocyte counts and increased body temperature observed as early as 3 h after radiation exposure (ROC: 0.93-0.96, p < 0.0001). Sham-irradiated animals (corresponding to "worried wells") could be easily discriminated from dying pigs, thus pointing to the diagnostic significance of this analysis. These data corroborate with earlier findings performed on human radiation victims suffering from severe hematological syndrome and provide further evidence for the suitability of the minipig model as a potential alternative non-rodent animal model.

  8. Application of a biochemical and clinical model to predict individual survival in patients with end-stage liver disease

    Institute of Scientific and Technical Information of China (English)

    Eduardo Vilar Gomez; Luis Calzadilla Bertot; Bienvenido Gra Oramas; Enrique Arus Soler; Raimundo Llanio Navarro; Javier Diaz Elias; Oscar Villa Jiménez; Maria del Rosario Abreu Vazquez

    2009-01-01

    AIM:To investigate the capability of a biochemical and clinical model,BioCliM,in predicting the survival of cirrhotic patients.METHODS:We prospectively evaluated the survival of 172 cirrhotic patients.The model was constructed using clinical (ascites,encephalopathy and variceal bleeding) and biochemical (serum creatinine and serum total bilirubin) variables that were selected from a Cox proportional hazards model.It was applied to estimate 12-,52- and 104-wk survival.The model's calibration using the Hosmer-Lemeshow statistic was computed at 104 wk in a validation dataset.Finally,the model's validity was tested among an independent set of 85 patients who were stratified into 2 risk groups (low risk ≤8 and high risk>8).RESULTS:In the validation cohort,all measures of fit,discrimination and calibration were improved when the biochemical and clinical model was used.The proposed model had better predictive values (c-statistic:0.90,0.91,0.91) than the Model for End-stage Liver Disease (MELD) and Child-Pugh (CP) scores for 12-,52- and 104-wk mortality,respectively.In addition,the Hosmer-Lemeshow (H-L) statistic revealed that the biochemical and clinical model (H-L,4.69) is better calibrated than MELD (H-L,17.06) and CP (H-L,14.23).There were no significant differences between the observed and expected survival curves in the stratified risk groups (low risk,P=0.61;high risk,P=0.77).CONCLUSION:Our data suggest that the proposed model is able to accurately predict survival in cirrhotic patients.

  9. Elevated serum level of YKL-40 is an independent prognostic factor for poor survival in patients with metastatic melanoma

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Johansen, Julia Sidenius; Gehl, Julie;

    2006-01-01

    that serum YKL-40 (hazard ratio       [HR] = 1.9; 95% confidence interval [CI], 1.2-2.8; P = 0.004) and serum       lactate dehydrogenase (LDH) (HR = 1.9; 95% CI, 1.2-2.9; P = 0.004) were       independent prognostic factors for survival. A combination variable of       elevated serum YKL-40 and LDH...... quadrupled the risk of early death (HR =       4.4; 95% CI, 2.5-7.7; P LDH had a stronger prognostic impact       than the American Joint Committee on Cancer (AJCC) Stage IV       classification. Furthermore, serum...... was an independent prognostic factor for poor       survival in patients with metastatic melanoma. When combining serum YKL-40       and LDH, patients could be separated into three prognostic groups based on       the number of elevated biomarkers. The findings should be validated in an       independent study...

  10. Addition of MR imaging features and genetic biomarkers strengthens glioblastoma survival prediction in TCGA patients.

    Science.gov (United States)

    Nicolasjilwan, Manal; Hu, Ying; Yan, Chunhua; Meerzaman, Daoud; Holder, Chad A; Gutman, David; Jain, Rajan; Colen, Rivka; Rubin, Daniel L; Zinn, Pascal O; Hwang, Scott N; Raghavan, Prashant; Hammoud, Dima A; Scarpace, Lisa M; Mikkelsen, Tom; Chen, James; Gevaert, Olivier; Buetow, Kenneth; Freymann, John; Kirby, Justin; Flanders, Adam E; Wintermark, Max

    2015-07-01

    The purpose of our study was to assess whether a model combining clinical factors, MR imaging features, and genomics would better predict overall survival of patients with glioblastoma (GBM) than either individual data type. The study was conducted leveraging The Cancer Genome Atlas (TCGA) effort supported by the National Institutes of Health. Six neuroradiologists reviewed MRI images from The Cancer Imaging Archive (http://cancerimagingarchive.net) of 102 GBM patients using the VASARI scoring system. The patients' clinical and genetic data were obtained from the TCGA website (http://www.cancergenome.nih.gov/). Patient outcome was measured in terms of overall survival time. The association between different categories of biomarkers and survival was evaluated using Cox analysis. The features that were significantly associated with survival were: (1) clinical factors: chemotherapy; (2) imaging: proportion of tumor contrast enhancement on MRI; and (3) genomics: HRAS copy number variation. The combination of these three biomarkers resulted in an incremental increase in the strength of prediction of survival, with the model that included clinical, imaging, and genetic variables having the highest predictive accuracy (area under the curve 0.679±0.068, Akaike's information criterion 566.7, P<0.001). A combination of clinical factors, imaging features, and HRAS copy number variation best predicts survival of patients with GBM. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Addition of MR Imaging Features and Genetic Biomarkers Strengthen Glioblastoma Survival Prediction in TCGA Patients

    Science.gov (United States)

    Nicolasjilwan, Manal; Hu, Ying; Yan, Chunhua; Meerzaman, Daoud; Holder, Chad A.; Gutman, David; Jain, Rajan; Colen, Rivka; Rubin, Daniel L.; Zinn, Pascal O.; Hwang, Scott N.; Raghavan, Prashant; Hammoud, Dima A; Scarpace, Lisa M; Mikkelsen, Tom; Chen, James; Gevaert, Olivier; Buetow, Kenneth; Freymann, John; Kirby, Justin; Flanders, Adam E.; Wintermark, Max

    2017-01-01

    PURPOSE The purpose of our study was to assess whether a model combining clinical factors, MR imaging features, and genomics would better predict overall survival of patients with glioblastoma (GBM) than either individual data type. METHODS The study was conducted leveraging the Cancer Genome Atlas (TCGA) effort supported by the National Institutes of Health. Six neuroradiologists reviewed MRI images from The Cancer Imaging Archive (http://cancerimagingarchive.net) of 102 GBM patients using the VASARI scoring system. The patients’ clinical and genetic data were obtained from the TCGA website (http://www.cancergenome.nih.gov/). Patient outcome was measured in terms of overall survival time. The association between different categories of biomarkers and survival was evaluated using Cox analysis. RESULTS The features that were significantly associated with survival were: 1) clinical factors: chemotherapy; 2) imaging: proportion of tumor contrast enhancement on MRI, and 3) genomics: HRAS copy number variation. The combination of these three biomarkers resulted in an incremental increase in the strength of prediction of survival, with the model that included clinical, imaging, and genetic variables having the highest predictive accuracy (area under the curve 0.679 ± 0.068, Akaike’s information criterion 566.7, p < 0.001). CONCLUSION A combination of clinical factors, imaging features, and HRAS copy number variation best predicts survival of patients with GBM. PMID:24997477

  12. Hand-Rearing, Release and Survival of African Penguin Chicks Abandoned Before Independence by Moulting Parents

    Science.gov (United States)

    Sherley, Richard B.; Waller, Lauren J.; Strauss, Venessa; Geldenhuys, Deon; Underhill, Les G.; Parsons, Nola J.

    2014-01-01

    The African penguin Spheniscus demersus has an ‘Endangered’ conservation status and a decreasing population. Following abandonment, 841 African penguin chicks in 2006 and 481 in 2007 were admitted to SANCCOB (Southern African Foundation for the Conservation of Coastal Birds) for hand-rearing from colonies in the Western Cape, South Africa, after large numbers of breeding adults commenced moult with chicks still in the nest. Of those admitted, 91% and 73% respectively were released into the wild. There were veterinary concerns about avian malaria, airsacculitis and pneumonia, feather-loss and pododermatitis (bumblefoot). Post-release juvenile (0.32, s.e.  = 0.08) and adult (0.76, s.e.  = 0.10) survival rates were similar to African penguin chicks reared after oil spills and to recent survival rates recorded for naturally-reared birds. By December 2012, 12 birds had bred, six at their colony of origin, and the apparent recruitment rate was 0.11 (s.e.  = 0.03). Hand-rearing of abandoned penguin chicks is recommended as a conservation tool to limit mortality and to bolster the population at specific colonies. The feasibility of conservation translocations for the creation of new colonies for this species using hand-reared chicks warrants investigation. Any such programme would be predicated on adequate disease surveillance programmes established to minimise the risk of disease introduction to wild birds. PMID:25337698

  13. Hand-rearing, release and survival of African penguin chicks abandoned before independence by moulting parents.

    Science.gov (United States)

    Sherley, Richard B; Waller, Lauren J; Strauss, Venessa; Geldenhuys, Deon; Underhill, Les G; Parsons, Nola J

    2014-01-01

    The African penguin Spheniscus demersus has an 'Endangered' conservation status and a decreasing population. Following abandonment, 841 African penguin chicks in 2006 and 481 in 2007 were admitted to SANCCOB (Southern African Foundation for the Conservation of Coastal Birds) for hand-rearing from colonies in the Western Cape, South Africa, after large numbers of breeding adults commenced moult with chicks still in the nest. Of those admitted, 91% and 73% respectively were released into the wild. There were veterinary concerns about avian malaria, airsacculitis and pneumonia, feather-loss and pododermatitis (bumblefoot). Post-release juvenile (0.32, s.e.  = 0.08) and adult (0.76, s.e.  = 0.10) survival rates were similar to African penguin chicks reared after oil spills and to recent survival rates recorded for naturally-reared birds. By December 2012, 12 birds had bred, six at their colony of origin, and the apparent recruitment rate was 0.11 (s.e.  = 0.03). Hand-rearing of abandoned penguin chicks is recommended as a conservation tool to limit mortality and to bolster the population at specific colonies. The feasibility of conservation translocations for the creation of new colonies for this species using hand-reared chicks warrants investigation. Any such programme would be predicated on adequate disease surveillance programmes established to minimise the risk of disease introduction to wild birds.

  14. Hand-rearing, release and survival of African penguin chicks abandoned before independence by moulting parents.

    Directory of Open Access Journals (Sweden)

    Richard B Sherley

    Full Text Available The African penguin Spheniscus demersus has an 'Endangered' conservation status and a decreasing population. Following abandonment, 841 African penguin chicks in 2006 and 481 in 2007 were admitted to SANCCOB (Southern African Foundation for the Conservation of Coastal Birds for hand-rearing from colonies in the Western Cape, South Africa, after large numbers of breeding adults commenced moult with chicks still in the nest. Of those admitted, 91% and 73% respectively were released into the wild. There were veterinary concerns about avian malaria, airsacculitis and pneumonia, feather-loss and pododermatitis (bumblefoot. Post-release juvenile (0.32, s.e.  = 0.08 and adult (0.76, s.e.  = 0.10 survival rates were similar to African penguin chicks reared after oil spills and to recent survival rates recorded for naturally-reared birds. By December 2012, 12 birds had bred, six at their colony of origin, and the apparent recruitment rate was 0.11 (s.e.  = 0.03. Hand-rearing of abandoned penguin chicks is recommended as a conservation tool to limit mortality and to bolster the population at specific colonies. The feasibility of conservation translocations for the creation of new colonies for this species using hand-reared chicks warrants investigation. Any such programme would be predicated on adequate disease surveillance programmes established to minimise the risk of disease introduction to wild birds.

  15. {sup 18}F-FDG PET/CT predicts survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Carkaci, Selin [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); The Ohio State University, Department of Radiology, Columbus, OH (United States); Sherman, Christopher T.; Ozkan, Efe; Adrada, Beatriz E.; Yang, Wei T. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Wei, Wei [The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States); Rohren, Eric M. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Mawlawi, Osama R. [The University of Texas MD Anderson Cancer Center, Department of Imaging Physics, Houston, TX (United States); Ueno, Naoto T. [The University of Texas MD Anderson Cancer Center, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology, Houston, TX (United States); Buchholz, Thomas A. [The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX (United States)

    2013-12-15

    The objective of this study was to evaluate the role of {sup 18}F-FDG PET/CT in predicting overall survival in inflammatory breast cancer patients undergoing neoadjuvant chemotherapy. Included in this retrospective study were 53 patients with inflammatory breast cancer who had at least two PET/CT studies including a baseline study before the start of neoadjuvant chemotherapy. Univariate and multivariate analyses were performed to assess the effects on survival of the following factors: tumor maximum standardized uptake value (SUVmax) at baseline, preoperatively and at follow-up, decrease in tumor SUVmax, histological tumor type, grade, estrogen, progesterone, HER2/neu receptor status, and extent of disease at presentation including axillary nodal and distant metastases. By univariate analysis, survival was significantly associated with decrease in tumor SUVmax and tumor receptor status. Patients with decrease in tumor SUVmax had better survival (P = 0.02). Patients with a triple-negative tumor (P = 0.0006), a Her2/neu-negative tumor (P = 0.038) or an ER-negative tumor (P = 0.039) had worse survival. Multivariate analysis confirmed decrease in tumor SUVmax and triple-negative receptor status as significant predictors of survival. Every 10 % decrease in tumor SUVmax from baseline translated to a 15 % lower probability of death, and complete resolution of tumor FDG uptake translated to 80 % lower probability of death (P = 0.014). Patients with a triple-negative tumor had 4.11 times higher probability of death (P = 0.004). Decrease in tumor SUVmax is an independent predictor of survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy. Further investigation with prospective studies is warranted to clarify its role in assessing response and altering therapy. (orig.)

  16. Epstein-Barr virus infection serves as an independent predictor of survival in patients with lymphoepithelioma-like gastric carcinoma.

    Science.gov (United States)

    Min, Byung-Hoon; Tae, Chung Hyun; Ahn, Soo Min; Kang, So Young; Woo, Sook-Young; Kim, Seonwoo; Kim, Kyoung-Mee

    2016-07-01

    The pathogenesis and clinicopathologic characteristics of Epstein-Barr virus (EBV)-negative lymphoepithelioma-like gastric carcinoma (LELC) are still unclear. In addition, it remains controversial whether EBV infection itself affects the prognosis of LELC. Between 1995 and 2011, 145 LELC patients (124 patients with EBV infection and 21 patients without EBV infection) underwent radical gastrectomy with D2 lymph node dissection. The clinicopathologic features and prognosis of EBV-negative LELC cases were compared with those of EBV-positive LELC cases. The median duration of follow-up after surgery was 55 months. Microsatellite instability (MSI) analysis was performed on 20 EBV-negative LELC cases. EBV-negative LELC accounted for 14.5 % of the total LELC cases. EBV-negative LELC was significantly associated with older age, female sex, advanced T stage, and advanced American Joint Committee on Cancer (AJCC) tumor stage compared with EBV-positive LELC. In univariate analysis, patients with EBV-negative LELC had significantly shorter overall, disease-specific, and recurrence-free survival than those with EBV-positive LELC. The 5-year overall survival rates were 81.0 % for patients with EBV-negative LELC and 96.2 % for patients with EBV-positive LELC. In a Cox proportional hazards model, EBV infection, age, and AJCC tumor stage were identified as independent predictors of overall survival. MSI-high, MSI-low, and microsatellite-stable tumors accounted for 25, 10, and 65 % of EBV-negative LELC cases, respectively. MSI status did not affect the prognosis of EBV-negative LELC cases. EBV infection serves as an independent predictor of survival in patients with LELC. EBV-negative LELC exhibited clinicopathologic features and prognosis distinct from those of EBV-positive LELC.

  17. Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Steedman Tracey

    2008-08-01

    Full Text Available Abstract Background Increased arterial stiffness is associated with mortality in patients with chronic kidney disease. Cardiovascular magnetic resonance (CMR permits assessment of the central arteries to measure aortic function. Methods We studied the relationship between central haemodynamics and outcome using CMR in 144 chronic kidney disease patients with estimated glomerular filtration rate Results Median follow up after the scan was 24 months. There were no significant differences in aortic distensibilty or aortic volumetric arterial strain between pre-dialysis and dialysis patients. Aortic distensibilty and volumetric arterial strain negatively correlated with age. Aortic distensibilty and volumetric arterial strain were lower in diabetics, patients with ischaemic heart disease and peripheral vascular disease. During follow up there were 20 deaths. Patients who died had lower aortic distensibilty than survivors. In a survival analysis, diabetes, systolic blood pressure and aortic distensibilty were independent predictors of mortality. There were 12 non-fatal cardiovascular events during follow up. Analysing the combined end point of death or a vascular event, diabetes, aortic distensibilty and volumetric arterial strain were predictors of events. Conclusion Deranged vascular function measured with CMR correlates with cardiovascular risk factors and predicts outcome. CMR measures of vascular function are potential targets for interventions to reduce cardiovascular risk.

  18. Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho; Kim, So Yeon [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Ramaiya, Nikhil H.; Tirumani, Sree Harsha [Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, MA (United States); Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    To evaluate the prognostic value of CT to predict recurrence-free and overall survival in patients with pancreatic neuroendocrine neoplasms (PanNENs). Between January 2004 and December 2012, 161 consecutive patients who underwent preoperative triphasic CT and surgical resection with curative intent for PanNENs were identified. The tumour consistency, margin, presence of calcification, pancreatic duct dilatation, bile duct dilatation, vascular invasion, and hepatic metastases were evaluated. The tumour size, arterial enhancement ratio, and portal enhancement ratio were measured. The Cox proportional hazard model was used to determine the association between CT features and recurrence-free survival and overall survival. By multivariate analysis, tumour size (>3 cm) (hazard ratio, 3.314; p = 0.006), portal enhancement ratio (≤1.1) (hazard ratio, 2.718; p = 0.006), and hepatic metastases (hazard ratio, 4.374; p = 0.003) were independent significant variables for worse recurrence-free survival. Portal enhancement ratio (≤1.1) (hazard ratio, 5.951; p = 0.001) and hepatic metastases (hazard ratio, 4.122; p = 0.021) were independent significant variables for worse overall survival. Portal enhancement ratio (≤1.1) and hepatic metastases assessed on CT were common independent prognostic factors for worse recurrence-free survival and overall survival in patients with PanNENs. (orig.)

  19. For prediction of elder survival by a Gompertz model, number dead is preferable to number alive.

    Science.gov (United States)

    Easton, Dexter M; Hirsch, Henry R

    2008-12-01

    The standard Gompertz equation for human survival fits very poorly the survival data of the very old (age 85 and above), who appear to survive better than predicted. An alternative Gompertz model based on the number of individuals who have died, rather than the number that are alive, at each age, tracks the data more accurately. The alternative model is based on the same differential equation as in the usual Gompertz model. The standard model describes the accelerated exponential decay of the number alive, whereas the alternative, heretofore unutilized model describes the decelerated exponential growth of the number dead. The alternative model is complementary to the standard and, together, the two Gompertz formulations allow accurate prediction of survival of the older as well as the younger mature members of the population.

  20. Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival

    DEFF Research Database (Denmark)

    Aaberg-Jessen, Charlotte; Christensen, Karina; Offenberg, Hanne Kjær

    2009-01-01

    In colorectal cancer and breast cancer a high TIMP-1 level has been shown to correlate with a shorter overall patient survival and it has been suggested that TIMP-1 is involved in tumour invasion, proliferation and apoptosis in different types of cancers. TIMP-1 is known to be expressed in gliomas...... with the lowest TIMP-1 expression had a significantly longer overall survival (HR (95% CI) = 3.2 (1.5-6.7), P = 0.004) when compared to the patients with higher TIMP-1 protein expression. In conclusion, this study showed that low TIMP-1 immunohistochemical expression predicts longer overall survival...

  1. Introduction of a prediction model to assigning periodontal prognosis based on survival rates.

    Science.gov (United States)

    Martinez-Canut, Pedro; Alcaraz, Jaime; Alcaraz, Jaime; Alvarez-Novoa, Pablo; Alvarez-Novoa, Carmen; Marcos, Ana; Noguerol, Blas; Noguerol, Fernando; Zabalegui, Ion

    2017-09-04

    To develop a prediction model for tooth loss due to periodontal disease (TLPD) in patients following periodontal maintenance (PM), and assess its performance using a multicentre approach. A multilevel analysis of eleven predictors of TLPD in 500 patients following PM was carried out to calculate the probability of TLPD. This algorithm was applied to three different TLPD samples (369 teeth) gathered retrospectively by nine periodontist, associating several intervals of probability with the corresponding survival rates, based on significant differences in the mean survival rates. The reproducibility of these associations was assessed in each sample (One-way ANOVA and pair-wise comparison with Bonferroni corrections). The model presented high specificity and moderate sensitivity, with optimal calibration and discrimination measurements. Seven intervals of probability were associated with seven survival rates and these associations contained close to 80% of the cases: the probability predicted the survival rate at this percentage. The model performed well in the three samples, since the mean survival rates of each association were significantly different within each sample, while no significant differences between the samples were found in pair-wise comparisons of means. This model might be useful for predicting survival rates in different TLPD samples This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound

    Science.gov (United States)

    Tadayyon, Hadi; Sannachi, Lakshmanan; Gangeh, Mehrdad J.; Kim, Christina; Ghandi, Sonal; Trudeau, Maureen; Pritchard, Kathleen; Tran, William T.; Slodkowska, Elzbieta; Sadeghi-Naini, Ali; Czarnota, Gregory J.

    2017-04-01

    Quantitative ultrasound (QUS) can probe tissue structure and analyze tumour characteristics. Using a 6-MHz ultrasound system, radiofrequency data were acquired from 56 locally advanced breast cancer patients prior to their neoadjuvant chemotherapy (NAC) and QUS texture features were computed from regions of interest in tumour cores and their margins as potential predictive and prognostic indicators. Breast tumour molecular features were also collected and used for analysis. A multiparametric QUS model was constructed, which demonstrated a response prediction accuracy of 88% and ability to predict patient 5-year survival rates (p = 0.01). QUS features demonstrated superior performance in comparison to molecular markers and the combination of QUS and molecular markers did not improve response prediction. This study demonstrates, for the first time, that non-invasive QUS features in the core and margin of breast tumours can indicate breast cancer response to neoadjuvant chemotherapy (NAC) and predict five-year recurrence-free survival.

  3. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    Energy Technology Data Exchange (ETDEWEB)

    Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  4. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    Science.gov (United States)

    Fleischmann, Achim; Thalmann, George N; Perren, Aurel; Seiler, Roland

    2014-03-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumors and corresponding lymph nodes. The prognostic impact of these 2 TRGs, the highest (dominant) TRG per patient, and competing tumor features reflecting tumor regression (ypT/ypN stage, maximum diameter of the residual tumor) were determined. Tumor characteristics in initial transurethral resection of the bladder specimens were tested for response prediction. The frequency of TRGs 1, 2, and 3 in the primary tumors were n=16, n=19, and n=21; corresponding data from the lymph nodes were n=31, n=9, and n=16. Interobserver agreement in determination of the TRG was strong (κ=0.8). Univariately, all evaluated parameters were significantly (P ≤ 0.001) related to overall survival; however, the segregation of the Kaplan-Meier curves was best for the dominant TRG. In multivariate analysis, only dominant TRG predicted overall survival independently (P=0.035). In transurethral resection specimens of the chemotherapy-naive bladder cancer, the only tumor feature with significant (Ptumor regression, the dominant TRG was the only independent risk factor. A favorable chemotherapy response is associated with a high proliferation rate in the initial chemotherapy-naive bladder cancer. This feature might help personalize neoadjuvant chemotherapy.

  5. Impact of MELD score in predicting short-term survival after primary liver transplantation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To study the efficacy of model for end-stage liver disease (MEL D) in predicting short-term outcomes in patients undergoing liver transplantation (LT). Methods: The consecutive 62 patients who had received primary LT in our hospital from November 2000 to January 2005 were retrospectively analyzed. The pretransplantation MELD and Child-Turcotte-Pugh (CTP) scores of these patients were calculated. Concordance c-statistic was used to assess the efficacies of MELD and CTP scores in predicting the first posttransplantation 3-month survival rate. Results: Among the 62 patients receiving primary LT, 12 died during the first 3-month period and the posttransplantation 3-month survival rate was 80.65%. The 3-month survival rate predicted by using CTP score and MELD score was0.685 and 0.873, respectively. Unlike CTP calssification, MELD score indentified two subgroups of patients with CTP C with different overall survival (0.8824 vs 0.4545, χ2 = 7.00, P = 0.0081). Conclusion: Our present study shows that MELD score could offer more accurate prediction for short-term survival in patients who undergo primary LT than CTP score.

  6. Body Composition Predicts Survival in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

    Science.gov (United States)

    Parikh, Neehar D; Zhang, Peng; Singal, Amit G; Derstine, Brian A; Krishnamurthy, Venkat; Barman, Pranab; Waljee, Akbar K; Su, Grace L

    2017-06-01

    The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is often uncertain. We aimed to utilize analytic morphomics, a high-throughput imaging analysis, to assess if body composition is predictive of post-TACE survival. We included patients from a single center (Ann Arbor VA) who had TACE as the primary treatment for HCC and had a pre-treatment CT scans. Univariate analysis and multivariate conditional inference tree analysis were utilized to identify the morphomic characteristics predictive of one-year survival. were validated in an external cohort (University of Michigan Health System) of HCC patients who underwent TACE as their primary treatment. In the 75 patients in the derivation cohort, median survival was 439 (IQR: 377-685) days from receipt of TACE, with 1-year survival of 61%. Visceral fat density (VFD) was the only morphomic factor predictive of overall and 1-year survival (phepatic decompensation after TACE (phepatic decompensation. VFD may serve as a radiographic biomarker in predicting TACE outcomes.

  7. Meta-Analysis of Microarray Data Identifies GAS6 Expression as an Independent Predictor of Poor Survival in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Michelle Buehler

    2013-01-01

    Full Text Available Seeking new biomarkers for epithelial ovarian cancer, the fifth most common cause of death from all cancers in women and the leading cause of death from gynaecological malignancies, we performed a meta-analysis of three independent studies and compared the results in regard to clinicopathological parameters. This analysis revealed that GAS6 was highly expressed in ovarian cancer and therefore was selected as our candidate of choice. GAS6 encodes a secreted protein involved in physiological processes including cell proliferation, chemotaxis, and cell survival. We performed immunohistochemistry on various ovarian cancer tissues and found that GAS6 expression was elevated in tumour tissue samples compared to healthy control samples (. In addition, GAS6 expression was also higher in tumours from patients with residual disease compared to those without. Our data propose GAS6 as an independent predictor of poor survival, suggesting GAS6, both on the mRNA and on the protein level, as a potential biomarker for ovarian cancer. In clinical practice, the staining of a tumour biopsy for GAS6 may be useful to assess cancer prognosis and/or to monitor disease progression.

  8. Improved survival prediction from lung function data in a large population sample

    DEFF Research Database (Denmark)

    Miller, M.R.; Pedersen, O.F.; Lange, P.

    2008-01-01

    mortality in the Copenhagen City Heart Study data. Cox regression models were derived for survival over 25 years in 13,900 subjects. Age on entry, sex, smoking status, body mass index, previous myocardial infarction and diabetes were putative predictors together with FEV1 either as raw data, standardised....... In univariate predictions of all cause mortality the HR for FEV1/ht(2) categories was 2-4 times higher than those for FEV1PP and 3-10 times higher for airway related tung disease mortality. We conclude that FEV1/ht(2) is superior to FEV1PP for predicting survival. in a general population and this method...

  9. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.; Fournier, Marcia V.

    2008-10-20

    One of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively. Our results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome. The 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic

  10. Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factor

    Science.gov (United States)

    Smrdel, Uros; Zwitter, Matjaz; Bostjancic, Emanuela; Zupan, Andrej; Kovac, Viljem; Glavac, Damjan; Bokal, Drago; Jerebic, Janja

    2016-01-01

    Abstract Background In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. Patients and methods Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent in situ hybridization). Results Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p = 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups. Conclusions Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored. PMID:27904447

  11. MITF-independent pro-survival role of BRG1-containing SWI/SNF complex in melanoma cells.

    Directory of Open Access Journals (Sweden)

    Lubica Ondrušová

    Full Text Available Metastasized malignant melanoma has a poor prognosis because of its intrinsic resistance to chemotherapy and radiotherapy. The central role in the melanoma transcriptional network has the transcription factor MITF (microphthalmia-associated transcription factor. It has been shown recently that the expression of MITF and some of its target genes require the SWI/SNF chromatin remodeling complex. Here we demonstrate that survival of melanoma cells requires functional SWI/SNF complex not only by supporting expression of MITF and its targets and but also by activating expression of prosurvival proteins not directly regulated by MITF. Microarray analysis revealed that besides the MITF-driven genes, expression of proteins like osteopontin, IGF1, TGFß2 and survivin, the factors known to be generally associated with progression of tumors and the antiapoptotic properties, were reduced in acute BRG1-depleted 501mel cells. Western blots and RT-PCR confirmed the microarray findings. These proteins have been verified to be expressed independently of MITF, because MITF depletion did not impair their expression. Because these genes are not regulated by MITF, the data suggests that loss of BRG1-based SWI/SNF complexes negatively affects survival pathways beyond the MITF cascade. Immunohistochemistry showed high expression of both BRM and BRG1 in primary melanomas. Exogenous CDK2, osteopontin, or IGF1 each alone partly relieved the block of proliferation imposed by BRG1 depletion, implicating that more factors, besides the MITF target genes, are involved in melanoma cell survival. Together these results demonstrate an essential role of SWI/SNF for the expression of MITF-dependent and MITF-independent prosurvival factors in melanoma cells and suggest that SWI/SNF may be a potential and effective target in melanoma therapy.

  12. Seven-CpG-based prognostic signature coupled with gene expression predicts survival of oral squamous cell carcinoma.

    Science.gov (United States)

    Shen, Sipeng; Wang, Guanrong; Shi, Qianwen; Zhang, Ruyang; Zhao, Yang; Wei, Yongyue; Chen, Feng; Christiani, David C

    2017-01-01

    DNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma. A multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas (TCGA) data as training set which were validated in two independent datasets from Gene Expression Omnibus (GEO). The correlation between DNA methylation and corresponding gene expression and the prognostic value of the gene expression were explored as well. The seven DNA methylation CpG sites were identified which were significantly associated with OSCC overall survival. Prognostic signature, a weighted linear combination of the seven CpG sites, successfully distinguished the overall survival of OSCC patients and had a moderate predictive ability for survival [training set: hazard ratio (HR) = 3.23, P = 5.52 × 10(-10), area under the curve (AUC) = 0.76; validation set 1: HR = 2.79, P = 0.010, AUC = 0.67; validation set 2: HR = 3.69, P = 0.011, AUC = 0.66]. Stratification analysis by human papillomavirus status, clinical stage, age, gender, smoking status, and grade retained statistical significance. Expression of genes corresponding to candidate CpG sites (AJAP1, SHANK2, FOXA2, MT1A, ZNF570, HOXC4, and HOXB4) was also significantly associated with patient's survival. Signature integrating of DNA methylation, gene expression, and clinical information showed a superior ability for prognostic prediction (AUC = 0.78). Prognostic signature integrated of DNA methylation, gene expression, and clinical information provides a better prognostic prediction value for OSCC patients than that with clinical information only.

  13. SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment.

    Science.gov (United States)

    Shi, Mingguang; He, Jianmin

    2016-04-01

    Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non-responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials.

  14. Independent or synergistic relationship of proteinuria and glomerular filtration rate on patient and renal survival in patients with glomerulonephritis?

    Science.gov (United States)

    Haider, Dominik G; Masghati, Salome; Goliasch, Georg; Fuhrmann, Valentin; Soleiman, Afschin; Wolzt, Michael; Baierl, Andreas; Druml, Wilfred; Hörl, Walter H

    2014-12-01

    Glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD) identifies patients at risk for death or end-stage renal disease (ESRD). CKD staging by GFR should incorporate proteinuria to augment risk stratification. We therefore tested the predictive power of the combination of GFR with proteinuria in patients with different histologically-diagnosed types of glomerulonephritis (GN). In a retrospective analysis, 2,687 patients with different forms of GN from 123 Austrian centres were investigated. Full data sets were available from 1,892 subjects. Classes of CKD on the basis of estimated GFR (eGFR) and of proteinuria grouped as 3.5 g/24 h were tested for their association with all-cause mortality and ESRD. During a median follow-up of 130 months [interquartile range (IQR) 90; 178] 478 patients (25.3 %) died. Median eGFR was 49 ml/min/1.73 m(2) (IQR 24; 81) and proteinuria 3.8 g/24 h (IQR 1.7; 8.0). Adjusted multivariate Cox regression indicated that renal survival but not overall survival is related to proteinuria >3.5 g/24 h [as opposed to proteinuria >3.5 g/24 h exists only in patients with immunoglobulin (Ig)A GN (HR 4.93), miscellaneous GN (HR 1.74), and CKD stage 5 (HR 2.50). Additionally, proteinuria is a risk factor for renal survival in males more than in females with GN and proteinuria >3.5 g/24 h (HR 1.91). Proteinuria is a strong risk factor for renal survival particularly in patients with proteinuria >3.5 g/24 but not for all types of GN, nor for all CKD stages. Proteinuria is not a risk factor for overall survival in patients with GN.

  15. How well does pathologic stage predict survival for esophageal adenocarcinoma after neoadjuvant therapy?

    Science.gov (United States)

    Nelson, Rebecca A.; Kim, Joseph; Raz, Dan

    2015-01-01

    Background Cancer staging systems are designed to predict survival and stratify patients. The 7th edition of the American Joint Commission on Cancer (AJCC7) staging system for esophageal cancer was modeled using survival data on patients who underwent esophagectomy without induction or adjuvant therapy. In the United States, the standard of care for patients with locally advanced tumors often includes neoadjuvant therapy. The prognostic value of the pathologic stage for these patients is unknown. Methods Data from the Surveillance Epidemiology and End Results (SEER) were used to identify 1,243 patients with adenocarcinoma of the esophagus who underwent surgery after neoadjuvant therapy from 1988-2009. Included in the analysis were pathologically-staged, non-metastatic patients who had radiation as part of their neoadjuvant therapy. The AJCC7 staging system and an alternate system were modeled using Kaplan-Meier survival methods. The two systems were compared using log-rank chi-squared statistics, with large chi-squared values indicating accuracy in survival prediction. Results The AJCC staging system was able to predict survival for patients who had neoadjuvant therapy (P<0.001, chi-squared =81.8); however, there was little distinction between stage subgroups. Patients with neoadjuvant radiotherapy had improved survival for pathologic stage II and III disease. An alternative, simpler staging system was better able to stratify patients with neoadjuvant therapy (P<0.001, chi-squared =100.5). Conclusions The current AJCC staging system is able to predict survival in esophageal adenocarcinoma patients undergoing neoadjuvant therapy, however, there is less distinction among stage subgroups. An alternative, simpler stage grouping may better stratify patients receiving neoadjuvant therapy. PMID:25973240

  16. Predicting the survival rate of mouse embryonic stem cells cryopreserved in alginate beads.

    Science.gov (United States)

    Sambu, S; Xu, X; Ye, H; Cui, Z F

    2011-11-01

    Stem cell cryopreservation in three-dimensional (3D) scaffolds may offer better protection to cells leading to higher survival rates. However, it introduces heterogeneity in cryoprotective agent (CPA) concentrations, durations of exposure to CPA, and freezing and thawing rate within constructs. This paper applies a mathematical model which couples the mass transport of dimethyl sulphoxide (DMSO) in a cell-seeded spherical construct and cell membrane transport into mouse embryonic stem cells (mESCs) to predict overall cell survival rate (CSR) based on CPA equilibrium exposure times (t(E)) and concentrations. The effect of freeze-concentration is also considered. To enable such a prediction, a contour plot was constructed using experimental data obtained in cryopreservation of cell suspensions with DMSO at a cooling rate of 1 degrees C/min. Thereafter, the diffusion in the alginate bead and the membrane transport of CPA was numerically simulated. Results were mapped onto the survival rate contours yielding 'predicted' CSR. The effects of loading time, hindrance, construct radius, and CPA concentration on predicted CSR were examined. From these results, an operation window with upper and lower t(E) of 12-19 min (for 0.6 mm radius beads and 1.4 M DMSO) yielded an overall viability of 60 per cent. The model predictions and the best experimental cryopreservation results with encapsulated mESCs were in agreement. Hence, optimization based on post-thaw CSR can accelerate the identification of cryopreservation protocols and parameters for maximizing cell survival.

  17.  Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis.

    Science.gov (United States)

    Begini, Paola; Gigante, Elia; Antonelli, Giulio; Carbonetti, Francesco; Iannicelli, Elsa; Anania, Giulia; Imperatrice, Barbara; Pellicelli, Adriano Maria; Fave, Gianfranco Delle; Marignani, Massimo

     Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.

  18. Imaging descriptors improve the predictive power of survival models for glioblastoma patients.

    Science.gov (United States)

    Mazurowski, Maciej Andrzej; Desjardins, Annick; Malof, Jordan Milton

    2013-10-01

    Because effective prediction of survival time can be highly beneficial for the treatment of glioblastoma patients, the relationship between survival time and multiple patient characteristics has been investigated. In this paper, we investigate whether the predictive power of a survival model based on clinical patient features improves when MRI features are also included in the model. The subjects in this study were 82 glioblastoma patients for whom clinical features as well as MR imaging exams were made available by The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA). Twenty-six imaging features in the available MR scans were assessed by radiologists from the TCGA Glioma Phenotype Research Group. We used multivariate Cox proportional hazards regression to construct 2 survival models: one that used 3 clinical features (age, gender, and KPS) as the covariates and 1 that used both the imaging features and the clinical features as the covariates. Then, we used 2 measures to compare the predictive performance of these 2 models: area under the receiver operating characteristic curve for the 1-year survival threshold and overall concordance index. To eliminate any positive performance estimation bias, we used leave-one-out cross-validation. The performance of the model based on both clinical and imaging features was higher than the performance of the model based on only the clinical features, in terms of both area under the receiver operating characteristic curve (P < .01) and the overall concordance index (P < .01). Imaging features assessed using a controlled lexicon have additional predictive value compared with clinical features when predicting survival time in glioblastoma patients.

  19. p53 expression is of independent predictive value in lymph node-negative breast carcinoma.

    Science.gov (United States)

    Fresno, M; Molina, R; Pérez del Río, M J; Alvarez, S; Díaz-Iglesias, J M; García, I; Herrero, A

    1997-07-01

    The aim of this study was to evaluate p53 expression, determined by immunohistochemistry, in 151 infiltrating ductal breast carcinomas with negative axillary lymph nodes, and to determine whether p53 can be considered as an independent prognostic value for overall and disease-free survival. A monoclonal antibody (DO-7) that reacts with an epitope on the N terminal portion of the human protein p53 was used to detect p53 in paraffin-embedded sections, utilising a standard avidin-biotin-peroxidase complex (ABC) technique with a microwave oven antigen retrieval. Overexpression of p53 (more than 50% of stained cells) was found in 45 cases (30%). Forty-five cases were negative and occasionally or moderately stained cells were present in 61 cases. p53 protein overexpression was significantly associated with high histological grade and tumour necrosis, high MIB-1 value (MIB-1 > 30%) and negative oestrogen receptor status. Univariate analysis (log-rank) showed a shorter overall survival (P = 0.003) in patients with high tumour p53 positivity. This statistical significance was also seen on multivariate analysis (Cox's logistic regression, P = 0.004). p53 protein overexpression is an independent prognostic marker in node-negative breast carcinoma for overall survival and should be used with other prognostic factors.

  20. Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival.

    Science.gov (United States)

    Visco, Carlo; Falisi, Erika; Young, Ken H; Pascarella, Michela; Perbellini, Omar; Carli, Giuseppe; Novella, Elisabetta; Rossi, Davide; Giaretta, Ilaria; Cavallini, Chiara; Scupoli, Maria Teresa; De Rossi, Anita; D'Amore, Emanuele Stefano Giovanni; Rassu, Mario; Gaidano, Gianluca; Pizzolo, Giovanni; Ambrosetti, Achille; Rodeghiero, Francesco

    2015-07-30

    The relation between Epstein-Barr virus (EBV) DNA load and clinical course of patients with chronic lymphocytic leukemia (CLL) is unknown. We assessed EBV DNA load by quantitative PCR at CLL presentation in mononuclear cells (MNC) of 220 prospective patients that were enrolled and followed-up in two major Institutions. In 20 patients EBV DNA load was also assessed on plasma samples. Forty-one age-matched healthy subjects were tested for EBV DNA load on MNC. Findings were validated in an independent retrospective cohort of 112 patients with CLL. EBV DNA load was detectable in 59%, and high (≥2000 copies/µg DNA) in 19% of patients, but it was negative in plasma samples. EBV DNA load was significantly higher in CLL patients than in healthy subjects (P EBV load and clinical stage or biological variables, except for 11q deletion (P = .004), CD38 expression (P = .003), and NOTCH1 mutations (P = .05). High EBV load led to a 3.14-fold increase in the hazard ratio of death and to a shorter overall survival (OS; P = .001). Poor OS was attributable, at least in part, to shorter time-to-first-treatment (P = .0008), with no higher risk of Richter's transformation or second cancer. Multivariate analysis selected high levels of EBV load as independent predictor of OS after controlling for confounding clinical and biological variables. EBV DNA load at presentation is an independent predictor of OS in patients with CLL.

  1. DWCox: A density-weighted Cox model for outlier-robust prediction of prostate cancer survival

    OpenAIRE

    Jinfeng Xiao; Sheng Wang; Jingbo Shang; Henry Lin; Doris Xin; Xiang Ren; Jiawei Han; Jian Peng

    2016-01-01

    Reliable predictions on the risk and survival time of prostate cancer patients based on their clinical records can help guide their treatment and provide hints about the disease mechanism. The Cox regression is currently a commonly accepted approach for such tasks in clinical applications. More complex methods, like ensemble approaches, have the potential of reaching better prediction accuracy at the cost of increased training difficulty and worse result interpretability. Better performance o...

  2. Identification of a Survival-independent Metastasis-enhancing Role of Hypoxia-inducible Factor-1  with a Hypoxia-tolerant Tumor Cell Line

    OpenAIRE

    2010-01-01

    During tumor progression, malignant cells must repeatedly survive microenvironmental stress. Hypoxia-inducible factor-1 (HIF-1) signaling has emerged as one major pathway allowing cellular adaptation to stress. Recent findings led to the hypothesis that HIF-1α may enhance the metastatic potential of tumor cells by a survival-independent mechanism. So far it has not been shown that HIF-1α also directly regulates invasive processes during metastasis in addition to conferring a survival advantag...

  3. Predicting survival of endoscopic gastrostomy candidates using the underlying disease, serum cholesterol, albumin and transferrin levels

    Directory of Open Access Journals (Sweden)

    Jorge Fonseca

    2013-08-01

    Full Text Available Background: Endoscopic gastrostomy (PEG is the gold standard for long-term enteral feeding. An adequate PEG candidate must have life expectancy longer than a few weeks. Patients surviving less than three weeks should have a nasogastric tube, and gastrostomy should be avoid. There are few studies looking to prognostic factors and fewer attempts of creating a predictor model for PEG patient's survival. Aim: The aim of this study was creating a predictive survival model for PEG candidates, using underlying disease, cholesterol, albumin and transferrin. Methods: Data was obtained from records of adult patients that underwent PEG between 1999 and 2011. Patients surviving 3 weeks were considered adequate survivors. A full logistic regression model was used to classify future cases into one of the two groups of survival. Results: An equation for the probability of future cases was generated, in order to obtain a P value. In the future, patients with a P > 0,88 will have a 64,7% probability of adequate surviving; patients with a P < 0,88 will have a 70.3% probability of short surviving. Conclusions: When clinical evaluation alone does not display a clear prognosis, this equation should be included in the evaluation of gastrostomy candidates, avoiding useless gastrostomy.

  4. Comparison of Elixhauser and Charlson Methods for Predicting Oral Cancer Survival.

    Science.gov (United States)

    Chang, Heng-Jui; Chen, Po-Chun; Yang, Ching-Chieh; Su, Yu-Chieh; Lee, Ching-Chih

    2016-02-01

    Cancer survival correlates not only with the features of primary malignancy but also with the degree of underlying comorbidities. Of the multiple methods used for evaluating the impact of comorbidities on survival, the Charlson and Elixhauser methods are most common. This study compared these 2 comorbidity measures for predicting survival in oral cancer patients. Using the Taiwan National Health Insurance claims data (2008-2011), we acquired data regarding patients' characteristics, comorbidities, and survival from 3583 oral cancer patients. Comorbidity was classified according to both the Charlson comorbidity and Elixhauser comorbidity based on the International Classification of Diseases, 9th Revision. The Elixhauser comorbidity score and Charlson comorbidity score were also calculated. The prediction of survival was determined using measures of discrimination, including the Akaike information criterion and Harrell C (C-statistic). The mean age of the study cohort was 52 ± 10 years, and 94.9% of the patients were male. The median follow-up time was 30.1 months, and the 3-year overall survival was 61.6%. Elixhauser comorbidity method added higher discrimination, compared with the Charlson comorbidity method (Harrell C, 0.677 vs 0.651). Furthermore, the Elixhauser comorbidity score outperformed the Charlson comorbidity score in continuous variable (Harrell C, 0.654 vs 0.646) and category (Harrell C, 0.658 vs 0.645). The Elixhauser method is a superior comorbidity risk-adjustment model for oral cancer survival prediction. Utilization of the Elixhauser comorbidity method may be encouraged for risk adjustment in oral cancer study.

  5. Chest computed tomography scores are predictive of survival in patients with cystic fibrosis awaiting lung transplantation

    NARCIS (Netherlands)

    M. Loeve (Martine); W.C.J. Hop (Wim); M. de Bruijne (Marleen); P.Th.W. van Hal (Peter); P. Robinson; A. Aitken; J.D. Dodd (Jonathan); H.A.W.M. Tiddens (Harm)

    2012-01-01

    textabstractRationale: Up to one-third of patients with cystic fibrosis (CF) awaiting lung transplantation (LTX) die while waiting. Inclusion of computed tomography (CT) scores may improve survival prediction models such as the lung allocation score (LAS). Objectives: This study investigated the

  6. Risk Prediction of One-Year Mortality in Patients with Cardiac Arrhythmias Using Random Survival Forest.

    Science.gov (United States)

    Miao, Fen; Cai, Yun-Peng; Zhang, Yu-Xiao; Li, Ye; Zhang, Yuan-Ting

    2015-01-01

    Existing models for predicting mortality based on traditional Cox proportional hazard approach (CPH) often have low prediction accuracy. This paper aims to develop a clinical risk model with good accuracy for predicting 1-year mortality in cardiac arrhythmias patients using random survival forest (RSF), a robust approach for survival analysis. 10,488 cardiac arrhythmias patients available in the public MIMIC II clinical database were investigated, with 3,452 deaths occurring within 1-year followups. Forty risk factors including demographics and clinical and laboratory information and antiarrhythmic agents were analyzed as potential predictors of all-cause mortality. RSF was adopted to build a comprehensive survival model and a simplified risk model composed of 14 top risk factors. The built comprehensive model achieved a prediction accuracy of 0.81 measured by c-statistic with 10-fold cross validation. The simplified risk model also achieved a good accuracy of 0.799. Both results outperformed traditional CPH (which achieved a c-statistic of 0.733 for the comprehensive model and 0.718 for the simplified model). Moreover, various factors are observed to have nonlinear impact on cardiac arrhythmias prognosis. As a result, RSF based model which took nonlinearity into account significantly outperformed traditional Cox proportional hazard model and has great potential to be a more effective approach for survival analysis.

  7. Amyloid Load in Fat Tissue Reflects Disease Severity and Predicts Survival in Amyloidosis

    NARCIS (Netherlands)

    Van Gameren, Ingrid I.; Hazenberg, Bouke P. C.; Bijzet, Johan; Haagsma, Elizabeth B.; Vellenga, Edo; Posthumus, Marcel D.; Jager, Pieter L.; Van Rijswijk, Martin H.

    2010-01-01

    Objective. The severity of systemic amyloidosis is thought to be related to the extent of amyloid deposition. We studied whether amyloid load in fat tissue reflects disease severity and predicts survival. Methods. We studied all consecutive patients with systemic amyloidosis seen between January 199

  8. Native cardiac reserve predicts survival in acute post infarction heart failure in mice

    Science.gov (United States)

    Täng, Margareta Scharin; Råmunddal, Truls; Lindbom, Malin; Omerovic, Elmir

    2007-01-01

    Cardiac reserve can be used to predict survival and outcome in patients with heart failure. The aim of this study was to investigate if native cardiac reserve could predict survival after myocardial infarction (MI) in mice. Method We investigated 27 healthy C57Bl6 mice (♂10–12 weeks old) with echocardiography using a high-frequency 15-MHz linear transducer. Investigations were performed both at rest and after pharmacological stress induced by dobutamine (1 μg/g body weight i.p.). The day after the echocardiography examination, a large MI was induced by ligation of the left anterior descending (LAD) coronary artery for evaluation of mortality rate. Results Two weeks after induction of MI, 7 mice were alive (26%). Evaluation of the difference between the surviving and deceased animals showed that the survivors had a better native ability to increase systolic performance (ΔLVESd -1.86 vs -1.28mm p = 0.02) upon dobutamine challenge, resulting in a better cardiac reserve (ΔFS 37 vs 25% p = 0.02 and ΔCO 0.27 vs -0.10 ml/min p = 0.02) and a better chronotropic reserve (ΔR-R interval -68 vs -19 ms p < 0.01). A positive relationship was found between ability to survive and both cardiac (p < 0.05) and chronotropic reserve (p < 0.05) when the mice were divided into three groups: survivors, surviving < 7 days, and surviving < 1 day. Conclusion We conclude that before MI induction the surviving animals had a better cardiac function compared with the deceased. This indicates that native cardiac and chronotropic reserve may be an important determinant and predictor of survival in the setting of large MI and post-infarction heart failure. PMID:18053159

  9. High CD10 expression in lymph node metastases from surgically treated prostate cancer independently predicts early death.

    Science.gov (United States)

    Fleischmann, Achim; Rocha, Carla; Saxer-Sekulic, Nikolina; Zlobec, Inti; Sauter, Guido; Thalmann, George N

    2011-06-01

    Patients with nodal positive prostate cancers are an important cohort with poorly defined risk factors. CD10 is a cell surface metallopeptidase that has been suggested to play a role in prostate cancer progression. CD10 expression was evaluated in 119 nodal positive prostate cancer patients using tissue microarrays constructed from primary tumors and lymph node metastases. All patients underwent radical prostatectomy and standardized extended lymphadenectomy. They had no neoadjuvant therapy and received deferred androgen deprivation. In the primary tumor, high CD10 expression was significantly associated with earlier death from disease when compared with low CD10 expression (5-year survival 73.7% vs. 91.8%; p = 0.043). In the metastases, a high CD10 expression was significantly associated with larger total size of metastases (median 11.4 vs. 6.5 mm; p = 0.015), earlier death of disease (5-year survival 71.5% vs. 87.3%; p = 0.017), and death of any cause (5-year survival 70.0% vs. 87.2%; p = 0.001) when compared with low CD10 expression. CD10 expression in the metastases added independent prognostic information for overall survival (p = 0.029) after adjustment for Gleason score of the primary tumor, nodal tumor burden, and resection margins. In conclusion, a high CD10 expression in prostate cancer predicts early death. This information is inherent in the primary tumors and in the lymph node metastases and might help to personalize patient management.

  10. Addressing issues associated with evaluating prediction models for survival endpoints based on the concordance statistic.

    Science.gov (United States)

    Wang, Ming; Long, Qi

    2016-09-01

    Prediction models for disease risk and prognosis play an important role in biomedical research, and evaluating their predictive accuracy in the presence of censored data is of substantial interest. The standard concordance (c) statistic has been extended to provide a summary measure of predictive accuracy for survival models. Motivated by a prostate cancer study, we address several issues associated with evaluating survival prediction models based on c-statistic with a focus on estimators using the technique of inverse probability of censoring weighting (IPCW). Compared to the existing work, we provide complete results on the asymptotic properties of the IPCW estimators under the assumption of coarsening at random (CAR), and propose a sensitivity analysis under the mechanism of noncoarsening at random (NCAR). In addition, we extend the IPCW approach as well as the sensitivity analysis to high-dimensional settings. The predictive accuracy of prediction models for cancer recurrence after prostatectomy is assessed by applying the proposed approaches. We find that the estimated predictive accuracy for the models in consideration is sensitive to NCAR assumption, and thus identify the best predictive model. Finally, we further evaluate the performance of the proposed methods in both settings of low-dimensional and high-dimensional data under CAR and NCAR through simulations.

  11. Predicting survival outcomes using subsets of significant genes in prognostic marker studies with microarrays

    Directory of Open Access Journals (Sweden)

    Matsui Shigeyuki

    2006-03-01

    Full Text Available Abstract Background Genetic markers hold great promise for refining our ability to establish precise prognostic prediction for diseases. The development of comprehensive gene expression microarray technology has allowed the selection of relevant marker genes from a large pool of candidate genes in early-phased, developmental prognostic marker studies. The primary analytical task in such studies is to select a small fraction of relevant genes, typically from a list of significant genes, for further investigation in subsequent studies. Results We develop a methodology for predicting survival outcomes using subsets of significant genes in prognostic marker studies with microarrays. Key components in this methodology include building prediction models, assessing predictive performance of prediction models, and assessing significance of prediction results. As particular specifications, we assume Cox proportional hazard models with a compound covariate. For assessing predictive accuracy, we propose to use the cross-validated log partial likelihood. To assess significance of prediction results, we apply permutation procedures in cross-validated prediction. As an additional key component peculiar to prognostic prediction, we also consider incorporation of standard prognostic factors. The methodology is evaluated using both simulated and real data. Conclusion The developed methodology for prognostic prediction using a subset of significant genes can provide new insights based on predictive capability, possibly incorporating standard prognostic factors, in selecting a fraction of relevant genes for subsequent studies.

  12. Obesity as an independent risk factor for decreased survival in node-positive high-risk breast cancer.

    Science.gov (United States)

    Scholz, Christoph; Andergassen, U; Hepp, P; Schindlbeck, C; Friedl, Thomas W P; Harbeck, N; Kiechle, M; Sommer, H; Hauner, H; Friese, K; Rack, B; Janni, W

    2015-06-01

    Obese breast cancer patients have a higher risk of lymph node metastasis and a poorer prognosis compared to patients with normal weight. For obese women with node-positive breast cancer, an association between body weight and prognosis remains unclear. In this retrospective study, we analyzed patient data from the Phase-III ADEBAR trial, in which high-risk breast cancer patients (pT1-4, pN2-3, pM0) were randomized into a docetaxel-based versus epirubicin-based chemotherapy regimen. Patients were grouped according to their BMI value as underweight/normal weight (BMI obese (BMI ≥ 30 kg/m(2); n = 285). Overweight and obese patients were older, had larger tumors and were more likely to be postmenopausal at the time of diagnosis compared to underweight/normal-weight patients (all p obese patients had a significantly shorter disease-free survival (DFS; HR 1.43; 95 % CI 1.11-1.86; p = 0.006) and overall survival (OS; HR 1.56; 95 % CI 1.14-2.14; p = 0.006) than non-obese patients. Subgroup analyses revealed that the differences in DFS and OS were significant for postmenopausal but not for premenopausal patients, and that the survival benefit of non-obese patients was more pronounced in women with hormone-receptor-positive disease. Obesity constitutes an independent, adverse prognostic factor in high-risk node-positive breast cancer patients, in particular for postmenopausal women and women with hormone-receptor-positive disease.

  13. Supraclavicular node disease is not an independent prognostic factor for survival of esophageal cancer patients treated with definitive chemoradiation.

    Science.gov (United States)

    Jeene, Paul M; Versteijne, Eva; van Berge Henegouwen, Mark I; Bergmann, Jacques J G H M; Geijsen, Elisabeth D; van Laarhoven, Hanneke W M; Hulshof, Maarten C C M

    2017-01-01

    The prognostic value of supraclavicular lymph node (SCN) metastases in esophageal cancer is not well established. We analyzed the prognostic value of SCN disease in patients after definitive chemoradiation (dCRT) for esophageal cancer. We retrospectively analyzed 207 patients treated between 2003 and 2013 to identify the prognostic value of metastasis in the SCN on treatment failure and survival. All patients were treated with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel 50 mg/m(2) and carboplatin AUC2. Median follow-up for patients alive was 43.3 months. The median overall survival (OS) for all patients was 17.5 months. OS at one, three and five years was 67%, 36% and 21%, respectively. For patients with metastasis in a SCN, OS was 23.6 months compared to 17.1 months for patients without metastasis in the SCN (p = .51). In multivariate analyses, higher cT status, cN status and adenocarcinoma were found to be prognostically unfavorable, but a positive SCN was not (p = .67). Median OS and median disease-free survival for tumors with SCN involvement and N0/1 disease was 49.0 months and 51.6 months, respectively, compared to 14.2 months and 8.2 months, respectively, in patients with N2/3 disease. In esophageal cancer treated with dCRT, the number of affected lymph nodes is an important independent prognostic factor, whereas involvement of a SCN is not. Supraclavicular lymph nodes should be considered as regional lymph nodes and treated with curative intent if the total number of involved lymph nodes is limited.

  14. Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival

    Directory of Open Access Journals (Sweden)

    Fujimoto Kiyohide

    2011-05-01

    Full Text Available Abstract Background Survival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated in vitro and in vivo. Methods COX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown in vivo. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells. Results Treatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA, resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes. Conclusions COX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.

  15. Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer

    Science.gov (United States)

    Egloff, Shanna A. Arnold; Du, Liping; Loomans, Holli A.; Starchenko, Alina; Su, Pei-Fang; Ketova, Tatiana; Knoll, Paul B.; Wang, Jifeng; Haddad, Ahmed Q.; Fadare, Oluwole; Cates, Justin M.; Lotan, Yair; Shyr, Yu; Clark, Peter E.; Zijlstra, Andries

    2017-01-01

    Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03–2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02–1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators. PMID:27894096

  16. Prediction of moisture content of alfalfa using density-independent functions of microwave dielectric properties

    Science.gov (United States)

    Shrestha, Bijay L.; Wood, Hugh C.; Sokhansanj, Shahab

    2005-05-01

    The use of density-independent functions of the dielectric properties of chopped alfalfa, calculated from microwave reflection coefficients from 300 MHz to 18 GHz, was studied for determining moisture content in the range from 12% to 73%, wet basis, at bulk densities from 0.139 to 0.716 g cm-3 at 20 °C. Prediction of moisture content with worst-case relative errors of about 3% or less over the range from 20% to 73% confirmed promising prospects for use of such density-independent functions for reliable moisture measurement for important plant materials.

  17. Expression of IL-4 and IL-13 predicts recurrence and survival in localized clear-cell renal cell carcinoma.

    Science.gov (United States)

    Chang, Yuan; Xu, Le; An, Huimin; Fu, Qiang; Chen, Lian; Lin, Zongming; Xu, Jiejie

    2015-01-01

    Interleukin-4 (IL-4) and IL-13 are anti-inflammatory and immunoregulatory cytokines that can influence cancer-directed immunosurveillance. However, they are not evaluated as biomarkers for ccRCC outcomes. The aim of this study was to investigate the prognostic value of tumor-derived IL-4 and IL-13 in patients with localized ccRCC after surgery. Our study comprised 194 consecutive patients with localized ccRCC undergoing nephrectomy in a single center. Clinical characteristics, recurrence-free survival (RFS) and overall survival (OS) were recorded. We assessed IL-4 and IL-13 expression as continuous variables and dichotomized as low versus high by immunohistochemistry. For associations with RFS and OS, we used the Kaplan-Meier method and Cox regression models. Concordance index was calculated for predictive accuracy. We found that high expression levels of IL-4 and IL-13 were associated with increased recurrence (P IL-13 expression (IL-4/IL-13 signature) was an independent prognostic factor for RFS and OS (P = 0.009 and P = 0.016, respectively). When applied to UISS score, IL-4/IL-13 signature improved the predictive accuracy. Notably, this improvement in prediction was mainly observed in patients with low-risk disease. To conclude, IL-4/IL-13 signature is an independent predictor of outcomes in patients with localized ccRCC, and the prognostic value is more prominent among patients with low-risk disease. Evaluation of IL-4 and IL-13 expression provides the opportunity to optimize postsurgical management and develop novel targeted therapies for ccRCC patients.

  18. Measure of functional independence dominates discharge outcome prediction after inpatient rehabilitation for stroke.

    Science.gov (United States)

    Brown, Allen W; Therneau, Terry M; Schultz, Billie A; Niewczyk, Paulette M; Granger, Carl V

    2015-04-01

    Identifying clinical data acquired at inpatient rehabilitation admission for stroke that accurately predict key outcomes at discharge could inform the development of customized plans of care to achieve favorable outcomes. The purpose of this analysis was to use a large comprehensive national data set to consider a wide range of clinical elements known at admission to identify those that predict key outcomes at rehabilitation discharge. Sample data were obtained from the Uniform Data System for Medical Rehabilitation data set with the diagnosis of stroke for the years 2005 through 2007. This data set includes demographic, administrative, and medical variables collected at admission and discharge and uses the FIM (functional independence measure) instrument to assess functional independence. Primary outcomes of interest were functional independence measure gain, length of stay, and discharge to home. The sample included 148,367 people (75% white; mean age, 70.6±13.1 years; 97% with ischemic stroke) admitted to inpatient rehabilitation a mean of 8.2±12 days after symptom onset. The total functional independence measure score, the functional independence measure motor subscore, and the case-mix group were equally the strongest predictors for any of the primary outcomes. The most clinically relevant 3-variable model used the functional independence measure motor subscore, age, and walking distance at admission (r(2)=0.107). No important additional effect for any other variable was detected when added to this model. This analysis shows that a measure of functional independence in motor performance and age at rehabilitation hospital admission for stroke are predominant predictors of outcome at discharge in a uniquely large US national data set. © 2015 American Heart Association, Inc.

  19. A simple model for predicting survival of angler-caught and released largemouth bass

    Science.gov (United States)

    Wilde, G.R.; Pope, K.L.

    2008-01-01

    We conducted a controlled experiment in the laboratory to assess the influence of anatomical hooking location and water temperature on survival of angler-caught and released largemouth bass Micropterus salmoides. Survival was 98% (58 of 59 fish) among fish that were hand-hooked within the oral cavity (including the gills), whereas survival was 66% (33 of 50 fish) among fish that were hand-hooked in the esophagus. Survival of hooked fish was not significantly influenced by water temperature (7-27??C) or the hooking location X water temperature interaction. We combined our results with prior research to develop a predictive model of largemouth bass survival, which was 98.3% (SD = 1.87%) for fish hooked in the oral cavity and 55.0% (SD = 9.70%) for fish hooked in the esophagus. The model is valid for water temperatures ranging from 7??C to 27??C and allows one to estimate, with known precision, the survival of angler-caught and released largemouth bass without the need for controlled studies or for holding fish in pens or cages to assess delayed mortality. ?? Copyright by the American Fisheries Society 2008.

  20. Development of a Summarized Health Index (SHI for use in predicting survival in sea turtles.

    Directory of Open Access Journals (Sweden)

    Tsung-Hsien Li

    Full Text Available Veterinary care plays an influential role in sea turtle rehabilitation, especially in endangered species. Physiological characteristics, hematological and plasma biochemistry profiles, are useful references for clinical management in animals, especially when animals are during the convalescence period. In this study, these factors associated with sea turtle surviving were analyzed. The blood samples were collected when sea turtles remained alive, and then animals were followed up for surviving status. The results indicated that significantly negative correlation was found between buoyancy disorders (BD and sea turtle surviving (p < 0.05. Furthermore, non-surviving sea turtles had significantly higher levels of aspartate aminotranspherase (AST, creatinine kinase (CK, creatinine and uric acid (UA than surviving sea turtles (all p < 0.05. After further analysis by multiple logistic regression model, only factors of BD, creatinine and UA were included in the equation for calculating summarized health index (SHI for each individual. Through evaluation by receiver operating characteristic (ROC curve, the result indicated that the area under curve was 0.920 ± 0.037, and a cut-off SHI value of 2.5244 showed 80.0% sensitivity and 86.7% specificity in predicting survival. Therefore, the developed SHI could be a useful index to evaluate health status of sea turtles and to improve veterinary care at rehabilitation facilities.

  1. Can {sup 18}F-FDOPA PET/CT predict survival in patients with suspected recurrent glioma? A prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Karunanithi, Sellam, E-mail: drsellam84@yahoo.co.in [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India); Sharma, Punit; Kumar, Abhishek [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India); Gupta, Deepak Kumar [Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi (India); Khangembam, Bangkim Chandra; Ballal, Sanjana; Kumar, Rakesh; Kumar, Rajeev [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India); Bal, Chandrasekhar, E-mail: csbal@hotmail.com [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India)

    2014-01-15

    Purpose of the present study was to evaluate the role of {sup 18}F-FDOPA PET/CT for predicting survival in patients with suspected recurrent glioma. Methods: A total of 33 previously treated, histopathologically proven glioma patients with clinical and contrast enhanced MRI findings suspicious for recurrence were enrolled in this prospective study. All patients underwent {sup 18}F-FDOPA PET/CT. Ratios of tumor uptake to normal tissue uptake were generated by dividing the tumor SUVmax with SUVmax of the contralateral normal brain tissue (T/N), normal striatum (T/S), normal white matter (T/W) and normal cerebellum (T/C). Patients were followed up clinically and by repeated imaging. Data was censored, if the patient died of disease or at the end of the study. Survival analysis was performed for the distributions of each variable and by multivariate analysis. Results: {sup 18}F-FDOPA PET/CT was positive for recurrence in 25 patients and negative in 8. Death occurred in nineteen patients. Median follow up period was 20.2 months. Median survival in this study was 39.2 months. In univariate analysis significant association of survival was noted with results of {sup 18}F-FDOPA PET/CT (P = 0.007) and {sup 18}F-FDOPA PET/CT quantitative parameters namely SUVmax (P = 0.001), T/S (P = 0.005), T/W (P = 0.0004), T/N (P = 0.001) and T/C (P = 0.003) were found to be significant. On multivariate analysis, only MRI size of the recurrent tumor (P = 0.002) and T/N ratio of {sup 18}F-FDOPA PET/CT (P = 0.005) were found to be independent predictors of survival. Conclusion: T/N ratio on {sup 18}F-FDOPA PET/CT is an independent predictor of survival in patients with suspected recurrent glioma, along with size of recurrent tumor on MRI.

  2. Genomic prediction of survival time in a population of brown laying hens showing cannibalistic behavior.

    Science.gov (United States)

    Alemu, Setegn W; Calus, Mario P L; Muir, William M; Peeters, Katrijn; Vereijken, Addie; Bijma, Piter

    2016-09-13

    Mortality due to cannibalism causes both economic and welfare problems in laying hens. To limit mortality due to cannibalism, laying hens are often beak-trimmed, which is undesirable for animal welfare reasons. Genetic selection is an alternative strategy to increase survival and is more efficient by taking heritable variation that originates from social interactions into account, which are modelled as the so-called indirect genetic effects (IGE). Despite the considerable heritable variation in survival time due to IGE, genetic improvement of survival time in laying hens is still challenging because the detected heritable variation of the trait with IGE is still limited, ranging from 0.06 to 0.26, and individuals that are still alive at the end of the recording period are censored. Furthermore, survival time records are available late in life and only on females. To cope with these challenges, we tested the hypothesis that genomic prediction increases the accuracy of estimated breeding values (EBV) compared to parental average EBV, and increases response to selection for survival time compared to a traditional breeding scheme. We tested this hypothesis in two lines of brown layers with intact beaks, which show cannibalism, and also the hypothesis that the rate of inbreeding per year is lower for genomic selection than for the traditional breeding scheme. The standard deviation of genomic prediction EBV for survival time was around 22 days for both lines, indicating good prospects for selection against mortality in laying hens with intact beaks. Genomic prediction increased the accuracy of the EBV by 35 and 32 % compared to the parent average EBV for the two lines. At the current reference population size, predicted response to selection was 91 % higher when using genomic selection than with the traditional breeding scheme, as a result of a shorter generation interval in males and greater accuracy of selection in females. The predicted rate of inbreeding per

  3. Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Agerbaek, M; Alsner, J; Marcussen, N

    2003-01-01

    The objective of the study was to investigate the predictive value of various clinical, biochemical, and histopathological parameters, with special emphasis on the expression of the retinoblastoma protein (pRB), on the radiation response in bladder cancer. In order to obtain a truly objective....... Expression of pRB was assessed by immunohistochemical staining as present or absent. Complete response to radiotherapy was obtained in 42 of 106 evaluable patients (40%). Predictive for CR to radiotherapy, in univariate analysis, was transurethral resection (as opposed to biopsy), B-haemoglobin, no upper...... urinary retention, and loss of pRB staining. Loss of pRB staining was the strongest independent predictor of radiation response in multivariate logistic regression analysis and absence of upper urinary retention was the only other significant factor. Loss of pRB was the only parameter showing...

  4. HSP70 mediates survival in apoptotic cells-Boolean network prediction and experimental validation.

    Science.gov (United States)

    Vasaikar, Suhas V; Ghosh, Sourish; Narain, Priyam; Basu, Anirban; Gomes, James

    2015-01-01

    Neuronal stress or injury results in the activation of proteins, which regulate the balance between survival and apoptosis. However, the complex mechanism of cell signaling involving cell death and survival, activated in response to cellular stress is not yet completely understood. To bring more clarity about these mechanisms, a Boolean network was constructed that represented the apoptotic pathway in neuronal cells. FasL and neurotrophic growth factor (NGF) were considered as inputs in the absence and presence of heat shock proteins known to shift the balance toward survival by rescuing pro-apoptotic cells. The probabilities of survival, DNA repair and apoptosis as cellular fates, in the presence of either the growth factor or FasL, revealed a survival bias encoded in the network. Boolean predictions tested by measuring the mRNA level of caspase-3, caspase-8, and BAX in neuronal Neuro2a (N2a) cell line with NGF and FasL as external input, showed positive correlation with the observed experimental results for survival and apoptotic states. It was observed that HSP70 contributed more toward rescuing cells from apoptosis in comparison to HSP27, HSP40, and HSP90. Overexpression of HSP70 in N2a transfected cells showed reversal of cellular fate from FasL-induced apoptosis to survival. Further, the pro-survival role of the proteins BCL2, IAP, cFLIP, and NFκB determined by vertex perturbation analysis was experimentally validated through protein inhibition experiments using EM20-25, Embelin and Wedelolactone, which resulted in 1.27-, 1.26-, and 1.46-fold increase in apoptosis of N2a cells. The existence of a one-to-one correspondence between cellular fates and attractor states shows that Boolean networks may be employed with confidence in qualitative analytical studies of biological networks.

  5. Predictive factors of survival in patients treated with definitive chemoradiotherapy for squamous cell esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Frédéric Di Fiore; Stéphane Lecleire; Olivier Rigal; Marie-Pierre Galais; Emmanuel Ben Soussan; Isabelle David; Bernard Paillot; Jacques-Henri Jacob; Pierre Michel

    2006-01-01

    AIM: The aim of the study was to evaluate the predictive factors of survival in patients with locally advanced squamous cell esophageal carcinoma (LASCOC) treated with definitive chemoradiotherapy (CRT)regimen based on the 5FU/CDDP combination.METHODS: All patients with LASCOC treated with a definitive CRT using the 5FU/CDDP combination between 1994 and 2000 were retrospectively included.Clinical complete response (CCR) to CRT was assessed by esophageal endoscopy and CT-scan 2 mo after CRT completion. Prognostic factors of survival were assessed using univariate and multivariate analysis by the Cox regression model.RESULTS: A total of 116 patients were included in the study. A CCR to CRT was observed in 86/116 (74.1%).The median survival was 20 mo (range 2-114) and the 5-year survival was 9.4%. Median survival of responder patients to CRT was 25 mo (range 3-114) as compared to 9 mo (range 2-81) in non-responder patients (P <0.001). In univariate analysis, survival was associated with CCR (P < 0.001), WHO performance status < 2 (P= 0.01), tumour length < 6 cm (P = 0.045) and weight loss < 10% was in limit of significance (P = 0.053). In multivariate analysis, survival was dependant to CCR (P< 0.0001), weight loss < 10% (P = 0.034) and WHO performance < 2 (P = 0.046).CONCLUSION: Our results suggest that survival in patients with LASCOC treated with definitive CRT was correlated to CCR, weight loss and WHO performance status.

  6. A Stock Market Prediction Method Based on Support Vector Machines (SVM and Independent Component Analysis (ICA

    Directory of Open Access Journals (Sweden)

    Hakob GRIGORYAN

    2016-08-01

    Full Text Available The research presented in this work focuses on financial time series prediction problem. The integrated prediction model based on support vector machines (SVM with independent component analysis (ICA (called SVM-ICA is proposed for stock market prediction. The presented approach first uses ICA technique to extract important features from the research data, and then applies SVM technique to perform time series prediction. The results obtained from the SVM-ICA technique are compared with the results of SVM-based model without using any pre-processing step. In order to show the effectiveness of the proposed methodology, two different research data are used as illustrative examples. In experiments, the root mean square error (RMSE measure is used to evaluate the performance of proposed models. The comparative analysis leads to the conclusion that the proposed SVM-ICA model outperforms the simple SVM-based model in forecasting task of nonstationary time series.

  7. Ventral striatum encodes past and predicted value independent of motor contingencies.

    Science.gov (United States)

    Goldstein, Brandon L; Barnett, Brian R; Vasquez, Gloria; Tobia, Steven C; Kashtelyan, Vadim; Burton, Amanda C; Bryden, Daniel W; Roesch, Matthew R

    2012-02-08

    The ventral striatum (VS) is thought to signal the predicted value of expected outcomes. However, it is still unclear whether VS can encode value independently from variables often yoked to value such as response direction and latency. Expectations of high value reward are often associated with a particular action and faster latencies. To address this issue we trained rats to perform a task in which the size of the predicted reward was signaled before the instrumental response was instructed. Instrumental directional cues were presented briefly at a variable onset to reduce accuracy and increase reaction time. Rats were more accurate and slower when a large versus small reward was at stake. We found that activity in VS was high during odors that predicted large reward even though reaction times were slower under these conditions. In addition to these effects, we found that activity before the reward predicting cue reflected past and predicted reward. These results demonstrate that VS can encode value independent of motor contingencies and that the role of VS in goal-directed behavior is not just to increase vigor of specific actions when more is at stake.

  8. Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma

    Directory of Open Access Journals (Sweden)

    Bignotti Eliana

    2012-11-01

    Full Text Available Abstract Background Endometrial cancer is the most common gynecologic malignancy in developed countries. Trop-2 is a glycoprotein involved in cellular signal transduction and is differentially overexpressed relative to normal tissue in a variety of human adenocarcinomas, including endometrioid endometrial carcinomas (EEC. Trop-2 overexpression has been proposed as a marker for biologically aggressive tumor phenotypes. Methods Trop-2 protein expression was quantified using tissue microarrays consisting of formalin-fixed paraffin-embedded specimens from 118 patients who underwent surgical staging from 2001–9 by laparotomy for EEC. Clinicopathologic characteristics including age, stage, grade, lymphovascular space invasion, and medical comorbidities were correlated with immunostaining score. Univariate and multivariate analyses were performed for overall survival, disease-free survival, and progression-free survival in relation to clinical parameters and Trop-2 protein expression. Results Clinical outcome data were available for 103 patients. Strong Trop-2 immunostaining was significantly associated with higher tumor grade (p=0.02 and cervical involvement (p Conclusions Trop-2 protein overexpression is significantly associated with higher tumor grade and serves as an independent prognostic factor for DFS in endometrioid endometrial cancer.

  9. The regrowth kinetic of the surviving population is independent of acute and chronic responses to temozolomide in glioblastoma cell lines.

    Science.gov (United States)

    Silva, Andrew Oliveira; Dalsin, Eloisa; Onzi, Giovana Ravizzoni; Filippi-Chiela, Eduardo Cremonese; Lenz, Guido

    2016-11-01

    Chemotherapy acts on cancer cells by producing multiple effects on a cell population including cell cycle arrest, necrosis, apoptosis and senescence. However, often a subpopulation of cells survives and the behavior of this subpopulation, which is responsible for cancer recurrence, remains obscure. Here we investigated the in vitro short- and long-term responses of six glioblastoma cell lines to clinically relevant doses of temozolomide for 5 days followed by 23 days of recovery, mimicking the standard schedule used in glioblastoma patient for this drug. These cells presented different profiles of sensitivity to temozolomide with varying levels of cell cycle arrest, autophagy and senescence, followed by a regrowth of the surviving cells. The initial reduction in cell number and the subsequent regrowth was analyzed with four new parameters applied to Cumulative Population Doubling (CPD) curves that describe the overall sensitivity of the population and the characteristic of the regrowth: the relative end point CPD (RendCPD); the relative Area Under Curve (rAUC); the Relative Time to Cross a Threshold (RTCT); and the Relative Proliferation Rate (RPR). Surprisingly, the kinetics of regrowth were not predicted by the mechanisms activated after treatment nor by the acute or overall sensitivity. With this study we added new parameters that describe key responses of glioblastoma cell populations to temozolomide treatment. These parameters can also be applied to other cell types and treatments and will help to understand the behavior of the surviving cancer cells after treatment and shed light on studies of cancer resistance and recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. DISIS: prediction of drug response through an iterative sure independence screening.

    Directory of Open Access Journals (Sweden)

    Yun Fang

    Full Text Available Prediction of drug response based on genomic alterations is an important task in the research of personalized medicine. Current elastic net model utilized a sure independence screening to select relevant genomic features with drug response, but it may neglect the combination effect of some marginally weak features. In this work, we applied an iterative sure independence screening scheme to select drug response relevant features from the Cancer Cell Line Encyclopedia (CCLE dataset. For each drug in CCLE, we selected up to 40 features including gene expressions, mutation and copy number alterations of cancer-related genes, and some of them are significantly strong features but showing weak marginal correlation with drug response vector. Lasso regression based on the selected features showed that our prediction accuracies are higher than those by elastic net regression for most drugs.

  11. NT-ProBNP Independently Predicts Long-Term Mortality in Patients Admitted for Coronary Angiography

    DEFF Research Database (Denmark)

    Ruwald, Martin Huth; Goetze, Jens Peter; Bech, Jan

    2014-01-01

    angiography (CAG). A total of 337 patients with suspected CAD who underwent elective or acute CAG were followed up for a mean period of 6.7 years. Primary end points were all-cause mortality (ACM) and the combined end point of ACM, nonfatal myocardial infarction, and revascularization. In all, 53 (16......%) patients died and 88 (26%) patients reached the combined end point. Preprocedural NT-proBNP above 32 pmol/L independently predicted ACM (hazard ratio [HR] 3.11; confidence interval [CI]: 1.60-6.07; P = .001) and the combined end point (HR 2.44 [CI: 1.50-3.97]; P ...-proBNP is an independent predictor of ACM on long-term follow-up. N-terminal-proBNP is a reliable predictive marker of mortality in the setting of stable or unstable angina....

  12. Gross genomic damage measured by DNA image cytometry independently predicts gastric cancer patient survival

    NARCIS (Netherlands)

    Belien, J.A.M.; Buffart, T.E.; Gill, A.; Broeckaert, M.A.M.; Quirke, P.; Meijer, G.A.; Grabsch, H.

    2009-01-01

    BACKGROUND: DNA aneuploidy reflects gross genomic changes. It can be measured by flow cytometry (FCM-DNA) or image cytometry (ICM-DNA). In gastric cancer, the prevalence of DNA aneuploidy has been reported to range from 27 to 100%, with conflicting associations with clinicopathological variables. Th

  13. Distribution of lymph node metastases is an independent predictor of survival for sigmoid colon and rectal cancer.

    Science.gov (United States)

    Huh, Jung Wook; Kim, Young Jin; Kim, Hyeong Rok

    2012-01-01

    This study evaluated the prognostic significance of the distribution of lymph node metastases (LND) in patients with colorectal cancer. The impact of the LND on survival in colorectal cancer is unknown. A total of 1205 consecutive patients who underwent potentially curative surgery for sigmoid colon or rectal cancer with high ligation of the inferior mesenteric artery (IMA) from January 1997 to February 2008 were assigned to 4 groups based on LND: LND0, no lymph node metastases-615 patients (51.0%); LND1, metastases in the pericolic nodes-324 patients (26.9%); LND2, metastases in the intermediate nodes-172 patients (14.3%); and LND3, node metastases at the origin of the IMA-94 patients (7.8%). The 5-year overall survival rates of patients with LND0, LND1, LND2, and LND3 were 83%, 63%, 52%, and 28%, respectively (P cancer patients, but it does not predict local recurrence. The N categorization including LND may enhance the prognostic value of the TNM staging system for patients with node-positive sigmoid colon or rectal cancer.

  14. Sarcopenia predicts survival outcomes among patients with urothelial carcinoma of the upper urinary tract undergoing radical nephroureterectomy: a retrospective multi-institution study.

    Science.gov (United States)

    Ishihara, Hiroki; Kondo, Tsunenori; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Kobayashi, Hirohito; Hashimoto, Yasunobu; Tanabe, Kazunari

    2017-02-01

    We aimed to evaluate the effect of sarcopenia, a condition of low muscle mass, on the survival among patients who were undergoing radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUT). We retrospectively reviewed consecutive patients with UCUT (cT[any]N0M0) who underwent RNU between 2003 and 2013 at our department and its affiliated institutions. Preoperative computed tomography images were used to calculate each patient's skeletal muscle index, an indicator of whole-body muscle mass. Sarcopenia was defined according to the sex-specific consensus definitions, based on the patient's skeletal muscle and body mass indexes. We analyzed the relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU to identify factors that predicted patient survival. A total of 137 patients were included, and 90 patients (65.7 %) were diagnosed with sarcopenia. Compared to the non-sarcopenic patients, the sarcopenic patients had a significant inferior 5-year RFS (48.8 vs. 79.6 %, p = 0.0002), CSS (57.1 vs. 92.6 %, p sarcopenia was an independent predictor of shorter RFS, CSS, and OS (all, p Sarcopenia was an independent predictor of survival among patients with UCUT who were undergoing RNU.

  15. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-06-25

    Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

  16. Cell survival in carbon beams - comparison of amorphous track model predictions

    DEFF Research Database (Denmark)

    Grzanka, L.; Greilich, S.; Korcyl, M.

    distribution models, and gamma response models was developed. This software can be used for direct numerical comparison between the models, submodels and their parameters and experimental data. In the present paper, we look at 10%-survival data from cell lines irradiated in vitro with carbon and proton beams......Introduction: Predictions of the radiobiological effectiveness (RBE) play an essential role in treatment planning with heavy charged particles. Amorphous track models ( [1] , [2] , also referred to as track structure models) provide currently the most suitable description of cell survival under ion...... by Tsuruoka et al. [4] . Results and conclusion: Preliminary results show a good agreement of models predictions and the experimental data for clinical doses. When investigating the influence of radial dose distributions on inactivation cross section in the Katz model, we found that one of the most important...

  17. A hemocyte gene expression signature correlated with predictive capacity of oysters to survive Vibrio infections

    Directory of Open Access Journals (Sweden)

    Rosa Rafael

    2012-06-01

    Full Text Available Abstract Background The complex balance between environmental and host factors is an important determinant of susceptibility to infection. Disturbances of this equilibrium may result in multifactorial diseases as illustrated by the summer mortality syndrome, a worldwide and complex phenomenon that affects the oysters, Crassostrea gigas. The summer mortality syndrome reveals a physiological intolerance making this oyster species susceptible to diseases. Exploration of genetic basis governing the oyster resistance or susceptibility to infections is thus a major goal for understanding field mortality events. In this context, we used high-throughput genomic approaches to identify genetic traits that may characterize inherent survival capacities in C. gigas. Results Using digital gene expression (DGE, we analyzed the transcriptomes of hemocytes (immunocompetent cells of oysters able or not able to survive infections by Vibrio species shown to be involved in summer mortalities. Hemocytes were nonlethally collected from oysters before Vibrio experimental infection, and two DGE libraries were generated from individuals that survived or did not survive. Exploration of DGE data and microfluidic qPCR analyses at individual level showed an extraordinary polymorphism in gene expressions, but also a set of hemocyte-expressed genes whose basal mRNA levels discriminate oyster capacity to survive infections by the pathogenic V. splendidus LGP32. Finally, we identified a signature of 14 genes that predicted oyster survival capacity. Their expressions are likely driven by distinct transcriptional regulation processes associated or not associated to gene copy number variation (CNV. Conclusions We provide here for the first time in oyster a gene expression survival signature that represents a useful tool for understanding mortality events and for assessing genetic traits of interest for disease resistance selection programs.

  18. MRI and thallium-201 SPECT in the prediction of survival in glioma

    Energy Technology Data Exchange (ETDEWEB)

    Vos, Maaike J. [VU University Medical Center, Department of Neurology, Amsterdam (Netherlands); Medical Center Haaglanden, Department of Neurology, PO Box 432, The Hague (Netherlands); Berkhof, Johannes [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Hoekstra, Otto S. [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Bosma, Ingeborg; Sizoo, Eefje M.; Heimans, Jan J.; Reijneveld, Jaap C.; Postma, Tjeerd J. [VU University Medical Center, Department of Neurology, Amsterdam (Netherlands); Sanchez, Esther [VU University Medical Center, Department of Radiology, Amsterdam (Netherlands); Lagerwaard, Frank J. [VU University Medical Center, Department of Radiation Oncology, Amsterdam (Netherlands); Buter, Jan [VU University Medical Center, Department of Medical Oncology, Amsterdam (Netherlands); Noske, David P. [VU University Medical Center, Department of Neurosurgery and Neuro-Oncology Research Group, Amsterdam (Netherlands)

    2012-06-15

    This paper aims to study the value of MRI and Thallium 201 ({sup 201}Tl) single-photon emission computed tomography (SPECT) in the prediction of overall survival (OS) in glioma patients treated with temozolomide (TMZ) and to evaluate timing of radiological follow-up. We included patients treated with TMZ chemoradiotherapy for newly diagnosed glioblastoma multiforme (GBM) and with TMZ for recurrent glioma. MRIs and {sup 201}Tl SPECTs were obtained at regular intervals. The value of both imaging modalities in predicting OS was examined using Cox regression analyses. Altogether, 138 MRIs and 113 {sup 201}Tl SPECTs in 46 patients were performed. Both imaging modalities were strongly related to OS (P {<=} 0.02). In newly diagnosed GBM patients, the last follow-up MRI (i.e., after six adjuvant TMZ courses) and SPECT (i.e., after three adjuvant TMZ courses) were the strongest predictors of OS (P = 0.01). In recurrent glioma patients, baseline measurements appeared to be the most predictive of OS (P < 0.01). The addition of one imaging modality to the other did not contribute to the prediction of OS. Both MRI and {sup 201}Tl SPECT are valuable in the prediction of OS. It is adequate to restrict to one of both modalities in the radiological follow-up during treatment. In the primary GBM setting, MRI after six adjuvant TMZ courses contributes significantly to the prediction of survival. In the recurrent glioma setting, baseline MRI appears to be a powerful predictor of survival, whereas follow-up MRIs during TMZ seem to be of little additional value. (orig.)

  19. Sarcopenia and inflammation are independent predictors of survival in male patients newly diagnosed with small cell lung cancer.

    Science.gov (United States)

    Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kang, Myoung Hee; Park, Hee Jung; Jeon, Kyung Nyeo; Kim, Seok-Hyun; Kim, Moon Jin; Kang, Jung-Hun; Lee, Gyeong-Won

    2016-05-01

    Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the neutrophil-to-lymphocyte ratio (NLR). A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non-sarcopenia/high NLR, and non-sarcopenia/low NLR. Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months, p = 0.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months, p = 0.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively, p sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (p < 0.001). In SCLC, sarcopenic male patients with high NLR have a poor prognosis and do not tolerate standard treatment. Intensive supportive care is needed in these patients.

  20. Staging systems for predicting survival of patients with hepatocellular carcinoma after surgery

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To compare the staging systems for stratifying and predicting the prognosis of patients with hepatocel-lular carcinoma (HCC) after partial hepatectomy (PH). METHODS: Clinical data about 438 HCC patients who underwent PH from January 1991 to December 2004 at our hospital were retrospectively analyzed. Tumor stage was evaluated following the Chinese tumor node me-tastasis (TNM) and barcelona clinic liver cancer (BCLC) staging systems, respectively. Survival curves for the HCC patients were plotted using ...

  1. Enhancing the Lasso Approach for Developing a Survival Prediction Model Based on Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Shuhei Kaneko

    2015-01-01

    Full Text Available In the past decade, researchers in oncology have sought to develop survival prediction models using gene expression data. The least absolute shrinkage and selection operator (lasso has been widely used to select genes that truly correlated with a patient’s survival. The lasso selects genes for prediction by shrinking a large number of coefficients of the candidate genes towards zero based on a tuning parameter that is often determined by a cross-validation (CV. However, this method can pass over (or fail to identify true positive genes (i.e., it identifies false negatives in certain instances, because the lasso tends to favor the development of a simple prediction model. Here, we attempt to monitor the identification of false negatives by developing a method for estimating the number of true positive (TP genes for a series of values of a tuning parameter that assumes a mixture distribution for the lasso estimates. Using our developed method, we performed a simulation study to examine its precision in estimating the number of TP genes. Additionally, we applied our method to a real gene expression dataset and found that it was able to identify genes correlated with survival that a CV method was unable to detect.

  2. Does field independence predict visuo-spatial abilities underpinning human navigation? Behavioural evidence.

    Science.gov (United States)

    Boccia, Maddalena; Piccardi, Laura; Di Marco, Mariangela; Pizzamiglio, Luigi; Guariglia, Cecilia

    2016-10-01

    Field independence (FI) has been defined as the extent to which the individual perceives part of a field as discrete from the surrounding field, rather than embedded in the field. It has been proposed to represent a relatively stable pattern in individuals' predisposition towards information processing. In the present study, we assessed the effect of FI on skills underpinning human navigation. Fifty Healthy individuals took part in this study. FI has been assessed by using the group embedded figures test (GEFT). Participants were also asked to perform several visuo-spatial orientation tasks, including the perspective taking/spatial orientation test (PTSOT), the mental rotation task (MRT) and the vividness task, as well as the Santa Barbara Sense of Direction Scale, a self-reported questionnaire, which has been found to predict environmental spatial orientation ability. We found that performances on the GEFT significantly predicted performances on the PTSOT and the MRT. This result supports the idea that FI predicts human navigation.

  3. Child-Pugh-Turcott versus Meld score for predicting survival in a retrospective cohort of black African cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    KA Attia; KC Ackoundou-N'guessan; AT N'dri-yoman; AK Mahassadi; E Messou; YF Bathaix; YH Kissi

    2008-01-01

    AIM: To compare the performance of the Child-Pugh-Turcott (CPT) score to that of the model for end-stage liver disease (MELD) score in predicting survival of a retrospective cohort of 172 Black African patients with cirrhosis on a short and mid-term basis.METHODS: Univariate and multivariate (Cox model)analyses were used to identify factors related to mortality. Relationship between the two scores was appreciated by calculating the correlation coefficient.The Kaplan Meier method and the log rank test were used to elaborate and compare survival respectively.The Areas Under the Curves were used to compare the performance between scores at 3, 6 and 12 mo.RESULTS: The study population comprised 172 patients, of which 68.9% were male. The mean age of the patient was 47.5 ± 13 years. Hepatitis B virus infection was the cause of cirrhosis in 70% of the cases.The overall mortality was 31.4% over 11 years of follow up. Independent factors significantly associated with mortality were: CPT score (HR = 3.3, 95% CI [1.7-6.2])(P 1.5 mg/dL versus serum creatine 21 vs MELD < 21). The area under the curves (AUC)that predict survival was 0.72 and 0.75 at 3 mo (P = 0.68),0.64 and 0.62 at 6 mo (P = 0.67), 0.69 and 0.64 at 12 mo (P = 0.38) respectively for the CPT score and the MELD score.CONCLUSION: The CPT score displays the same prognostic significance as does the MELD score in black African patients with cirrhosis. Moreover, its handling appears less cumbersome in clinical practice as compared to the latter.

  4. HIF1-Alpha Expression Predicts Survival of Patients with Squamous Cell Carcinoma of the Oral Cavity

    Science.gov (United States)

    dos Santos, Marcelo; Mercante, Ana Maria da Cunha; Louro, Iúri Drumond; Gonçalves, Antônio José; de Carvalho, Marcos Brasilino; da Silva, Eloiza Helena Tajara; da Silva, Adriana Madeira Álvares

    2012-01-01

    Background Oral squamous cell carcinoma is an important cause of death and morbidity wordwide and effective prognostic markers are still to be discovered. HIF1α protein is associated with hypoxia response and neovascularization, essential conditions for solid tumors survival. The relationship between HIF1α expression, tumor progression and treatment response in head and neck cancer is still poorly understood. Patients and Methods In this study, we investigated HIF1α expression by immunohistochemistry in tissue microarrays and its relationship with clinical findings, histopathological results and survival of 66 patients with squamous cell carcinoma of the lower mouth. Results Our results demonstrated that high HIF1α expression is associated with local disease-free survival, independently from the choice of treatment. Furthermore, high expression of HIF1α in patients treated with postoperative radiotherapy was associated with survival, therefore being a novel prognostic marker in squamous cell carcinoma of the mouth. Additionally, our results showed that MVD was associated with HIF1α expression and local disease relapse. Conclusion These findings suggest that HIF1α expression can be used as a prognostic marker and predictor of postoperative radiotherapy response, helping the oncologist choose the best treatment for each patient. PMID:23028863

  5. Two-parameter Failure Model Improves Time-independent and Time-dependent Failure Predictions

    Energy Technology Data Exchange (ETDEWEB)

    Huddleston, R L

    2004-01-27

    A new analytical model for predicting failure under a generalized, triaxial stress state was developed by the author and initially reported in 1984. The model was validated for predicting failure under elevated-temperature creep-rupture conditions. Biaxial data for three alloy steels, Types 304 and 316 stainless steels and Inconel 600, demonstrated two to three orders of magnitude reduction in the scatter of predicted versus observed creep-rupture times as compared to the classical failure models of Mises, Tresca, and Rankine. In 1990, the new model was incorporated into American Society of Mechanical Engineers (ASME) Code Case N47-29 for design of components operating under creep-rupture conditions. The current report provides additional validation of the model for predicting failure under time-independent conditions and also outlines a methodology for predicting failure under cyclic, time-dependent, creep-fatigue conditions. The later extension of the methodology may have the potential to improve failure predictions there as well. These results are relevant to most design applications, but they have special relevance to high-performance design applications such as components for high-pressure equipment, nuclear reactors, and jet engines.

  6. Two-parameter Failure Model Improves Time-independent and Time-dependent Failure Predictions

    Energy Technology Data Exchange (ETDEWEB)

    Huddleston, R L

    2004-01-27

    A new analytical model for predicting failure under a generalized, triaxial stress state was developed by the author and initially reported in 1984. The model was validated for predicting failure under elevated-temperature creep-rupture conditions. Biaxial data for three alloy steels, Types 304 and 316 stainless steels and Inconel 600, demonstrated two to three orders of magnitude reduction in the scatter of predicted versus observed creep-rupture times as compared to the classical failure models of Mises, Tresca, and Rankine. In 1990, the new model was incorporated into American Society of Mechanical Engineers (ASME) Code Case N47-29 for design of components operating under creep-rupture conditions. The current report provides additional validation of the model for predicting failure under time-independent conditions and also outlines a methodology for predicting failure under cyclic, time-dependent, creep-fatigue conditions. The later extension of the methodology may have the potential to improve failure predictions there as well. These results are relevant to most design applications, but they have special relevance to high-performance design applications such as components for high-pressure equipment, nuclear reactors, and jet engines.

  7. SIRT1 and c-Myc Promote Liver Tumor Cell Survival and Predict Poor Survival of Human Hepatocellular Carcinomas

    Science.gov (United States)

    Jang, Kyu Yun; Noh, Sang Jae; Lehwald, Nadja; Tao, Guo-Zhong; Bellovin, David I.; Park, Ho Sung; Moon, Woo Sung; Felsher, Dean W.; Sylvester, Karl G.

    2012-01-01

    The increased expression of SIRT1 has recently been identified in numerous human tumors and a possible correlation with c-Myc oncogene has been proposed. However, it remains unclear whether SIRT1 functions as an oncogene or tumor suppressor. We sought to elucidate the role of SIRT1 in liver cancer under the influence of c-Myc and to determine the prognostic significance of SIRT1 and c-Myc expression in human hepatocellular carcinoma. The effect of either over-expression or knock down of SIRT1 on cell proliferation and survival was evaluated in both mouse and human liver cancer cells. Nicotinamide, an inhibitor of SIRT1, was also evaluated for its effects on liver tumorigenesis. The prognostic significance of the immunohistochemical detection of SIRT1 and c-Myc was evaluated in 154 hepatocellular carcinoma patients. SIRT1 and c-Myc regulate each other via a positive feedback loop and act synergistically to promote hepatocellular proliferation in both mice and human liver tumor cells. Tumor growth was significantly inhibited by nicotinamide in vivo and in vitro. In human hepatocellular carcinoma, SIRT1 expression positively correlated with c-Myc, Ki67 and p53 expression, as well as high á-fetoprotein level. Moreover, the expression of SIRT1, c-Myc and p53 were independent prognostic indicators of hepatocellular carcinoma. In conclusion, this study demonstrates that SIRT1 expression supports liver tumorigenesis and is closely correlated with oncogenic c-MYC expression. In addition, both SIRT1 and c-Myc may be useful prognostic indicators of hepatocellular carcinoma and SIRT1 targeted therapy may be beneficial in the treatment of hepatocellular carcinoma. PMID:23024800

  8. Prediction of Independent Walking Ability for Severely Hemiplegic Stroke Patients at Discharge from a Rehabilitation Hospital.

    Science.gov (United States)

    Hirano, Yoshitake; Hayashi, Takeshi; Nitta, Osamu; Takahashi, Hidetoshi; Nishio, Daisuke; Minakawa, Tomoya; Kigawa, Hiroshi

    2016-08-01

    It is important to predict walking ability for stroke patients, because rehabilitation programs are planned on such predictions. We therefore examined predictive factors that are available before discharge from a rehabilitation hospital. Seventy-two consecutive patients with a first attack of stroke with severe hemiplegia were included in this study. We retrospectively evaluated background factors (age, gender, time from stroke onset, paresis side, and stroke type). Other neurological and physical parameters were collected by means of the modified National Institutes of Health Stroke Scale, the Mini-Mental State Examination, the Trunk Control Test (TCT), and the knee extension strength/body weight ratio on the unaffected side (KES/BW-US) at the time of admission. We divided the patients into 2 groups, the independent group (n = 49) and the dependent group (n = 23), on the basis of the Barthel Index of mobility at the time of discharge. We then compared the 2 groups with respect to the aforementioned parameters. We also performed stepwise discriminant analyses to ascertain which parameters are the best predictors of walking ability at the time of discharge. Age, TCT score, and the KES/BW-US ratio were significantly different between the groups. Discriminant analysis revealed that younger age and a higher KES/BW-US ratio were significantly associated with walking ability at discharge, which could be precisely predicted using the following formula: Y = .093 × (age) - 4.316 × (KES/BW-US) - 4.984. At the time of admission, age and the KES/BW-US ratio permit the prediction of independent walking ability at the time of discharge. Our formula predicts walking ability with an accuracy of more than 91%. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. Country, sex, EDSS change and therapy choice independently predict treatment discontinuation in multiple sclerosis and clinically isolated syndrome.

    Directory of Open Access Journals (Sweden)

    Claire Meyniel

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

  11. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2010-01-01

    BACKGROUND: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. METHODS: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). RESULTS: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. CONCLUSION: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

  12. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Gallagher William M

    2010-04-01

    Full Text Available Abstract Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC on tissue microarrays (TMA consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS. Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46 of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012. Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93; p = 0.03 when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

  13. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2010-04-01

    Abstract Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

  14. An Easy Tool to Predict Survival in Patients Receiving Radiation Therapy for Painful Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Monninkhof, Evelyn M. [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht (Netherlands); Bollen, Laurens; Dijkstra, Sander P. [Department of Orthopedic Surgery, Leiden University Medical Center (Netherlands); Steen-Banasik, Elzbieta M. van der [ARTI Institute for Radiation Oncology Arnhem, Arnhem (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, University Medical Center Nijmegen, Nijmegen (Netherlands); Marijnen, Corrie A.; Linden, Yvette M. van der [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2014-11-15

    Purpose: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. Methods and Materials: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. Results: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. Conclusion: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is

  15. Country, sex, EDSS change and therapy choice independently predict treatment discontinuation in multiple sclerosis and clinically isolated syndrome.

    Science.gov (United States)

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

    2012-01-01

    We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS). The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation. A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, pEDSS change and IMD choice independently predicted time to first IMD cessation.

  16. MRI features predict survival and molecular markers in diffuse lower-grade gliomas.

    Science.gov (United States)

    Zhou, Hao; Vallières, Martin; Bai, Harrison X; Su, Chang; Tang, Haiyun; Oldridge, Derek; Zhang, Zishu; Xiao, Bo; Liao, Weihua; Tao, Yongguang; Zhou, Jianhua; Zhang, Paul; Yang, Li

    2017-06-01

    Previous studies have shown that MR imaging features can be used to predict survival and molecular profile of glioblastoma. However, no study of a similar type has been performed on lower-grade gliomas (LGGs). Presurgical MRIs of 165 patients with diffuse low- and intermediate-grade gliomas (histological grades II and III) were scored according to the Visually Accessible Rembrandt Images (VASARI) annotations. Radiomic models using automated texture analysis and VASARI features were built to predict isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q codeletion status, histological grade, and tumor progression. Interrater analysis showed significant agreement in all imaging features scored (k = 0.703-1.000). On multivariate Cox regression analysis, no enhancement and a smooth non-enhancing margin were associated with longer progression-free survival (PFS), while a smooth non-enhancing margin was associated with longer overall survival (OS) after taking into account age, grade, tumor location, histology, extent of resection, and IDH1 1p/19q subtype. Using logistic regression and bootstrap testing evaluations, texture models were found to possess higher prediction potential for IDH1 mutation, 1p/19q codeletion status, histological grade, and progression of LGGs than VASARI features, with areas under the receiver-operating characteristic curves of 0.86 ± 0.01, 0.96 ± 0.01, 0.86 ± 0.01, and 0.80 ± 0.01, respectively. No enhancement and a smooth non-enhancing margin on MRI were predictive of longer PFS, while a smooth non-enhancing margin was a significant predictor of longer OS in LGGs. Textural analyses of MR imaging data predicted IDH1 mutation, 1p/19q codeletion, histological grade, and tumor progression with high accuracy.

  17. Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.

    Science.gov (United States)

    Buda-Nowak, Anna; Kucharz, Jakub; Dumnicka, Paulina; Kuzniewski, Marek; Herman, Roman Maria; Zygulska, Aneta L; Kusnierz-Cabala, Beata

    2017-04-01

    Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly.

  18. Depression of p53-independent Akt survival signals after high-LET radiation in mutated p53 cells

    Science.gov (United States)

    Ohnishi, Takeo; Takahashi, Akihisa; Nakagawa, Yosuke

    Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses the activities of serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signals were analyzed with Western blotting analysis 1 h, 2 h, 3 h and 6 h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis.Akt-related protein levels were decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G _{2}/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and depresses cell growth by suppressing Akt-related signals, even in the mp53 cells.

  19. Elevated serum level of YKL-40 is an independent prognostic factor for poor survival in patients with metastatic melanoma

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Johansen, Julia Sidenius; Gehl, Julie

    2006-01-01

    BACKGROUND: YKL-40 is a growth factor for connective tissue cells and       stimulates migration of endothelial cells. Cancer cells, macrophages, and       neutrophils secrete YKL-40. Its function in cancer is unknown. High serum       YKL-40 levels have been associated with a poor prognosis...... that serum YKL-40 (hazard ratio       [HR] = 1.9; 95% confidence interval [CI], 1.2-2.8; P = 0.004) and serum       lactate dehydrogenase (LDH) (HR = 1.9; 95% CI, 1.2-2.9; P = 0.004) were       independent prognostic factors for survival. A combination variable of       elevated serum YKL-40 and LDH...... quadrupled the risk of early death (HR =       4.4; 95% CI, 2.5-7.7; P Cancer (AJCC) Stage IV       classification. Furthermore, serum...

  20. Autophagy induction is a Tor- and Tp53-independent cell survival response in a zebrafish model of disrupted ribosome biogenesis.

    Directory of Open Access Journals (Sweden)

    Yeliz Boglev

    Full Text Available Ribosome biogenesis underpins cell growth and division. Disruptions in ribosome biogenesis and translation initiation are deleterious to development and underlie a spectrum of diseases known collectively as ribosomopathies. Here, we describe a novel zebrafish mutant, titania (tti(s450, which harbours a recessive lethal mutation in pwp2h, a gene encoding a protein component of the small subunit processome. The biochemical impacts of this lesion are decreased production of mature 18S rRNA molecules, activation of Tp53, and impaired ribosome biogenesis. In tti(s450, the growth of the endodermal organs, eyes, brain, and craniofacial structures is severely arrested and autophagy is up-regulated, allowing intestinal epithelial cells to evade cell death. Inhibiting autophagy in tti(s450 larvae markedly reduces their lifespan. Somewhat surprisingly, autophagy induction in tti(s450 larvae is independent of the state of the Tor pathway and proceeds unabated in Tp53-mutant larvae. These data demonstrate that autophagy is a survival mechanism invoked in response to ribosomal stress. This response may be of relevance to therapeutic strategies aimed at killing cancer cells by targeting ribosome biogenesis. In certain contexts, these treatments may promote autophagy and contribute to cancer cells evading cell death.

  1. Prediction of survival in patients with cardiogenic shock and multiorgan failure treated with biventricular assist device.

    Science.gov (United States)

    Potapov, Evgenij V; Stepanenko, Alexander; Kukucka, Marian; Ba Fadhl, Faiz H; Qedra, Naser; Weng, Yuguo; Pasic, Miralem; Lehmkuhl, Hans B; Krabatsch, Thomas; Hetzer, Roland

    2010-01-01

    Mechanical circulatory support (MCS) is valuable in saving the lives of patients with severe cardiogenic shock. However, their survival is limited if multiorgan failure (MOF) proves to be irreversible. Although ventricular assist devices (VADs) have been shown to reverse end-organ failure in some patients, the pathophysiological mechanisms of end-organ failure and its regression are not fully understood, and clinical markers and thresholds for the "point of no return" are lacking. We investigated predictors of 30-day survival in patients supported with a biventricular assist device (BVAD). We studied 157 patients implanted with a Berlin Heart EXCOR BVAD between 1987 and 2006. Children younger than 10 years and cases with postcardiotomy syndrome and transplant failure were excluded from the analysis as well as patients with technical or bleeding problems requiring rethoracotomy. In total, 69 clinical, hemodynamic, echocardiographic, and laboratory parameters were evaluated. Most of the patients suffered from ischemic cardiomyopathy or acute myocardial infarction. In addition, the preoperative multiple organ dysfunction syndrome (MODS) and the sequential organ failure assessment (SOFA) scores were calculated. The patients were divided into two groups regarding procedural success: group I-survival >30 days or heart transplantation or weaning from device (n = 105) and group II-death on system shock and MOF do not predict survival on BVAD. As expected, older patients are at higher risk for death on BVAD. Acidosis and high MODS score predict unfavorable outcome. However, the prediction of clinical outcome in patients in severe cardiogenic shock supported by BVAD is possible in extreme situations only.

  2. A signature inferred from Drosophila mitotic genes predicts survival of breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Christian Damasco

    Full Text Available INTRODUCTION: The classification of breast cancer patients into risk groups provides a powerful tool for the identification of patients who will benefit from aggressive systemic therapy. The analysis of microarray data has generated several gene expression signatures that improve diagnosis and allow risk assessment. There is also evidence that cell proliferation-related genes have a high predictive power within these signatures. METHODS: We thus constructed a gene expression signature (the DM signature using the human orthologues of 108 Drosophila melanogaster genes required for either the maintenance of chromosome integrity (36 genes or mitotic division (72 genes. RESULTS: The DM signature has minimal overlap with the extant signatures and is highly predictive of survival in 5 large breast cancer datasets. In addition, we show that the DM signature outperforms many widely used breast cancer signatures in predictive power, and performs comparably to other proliferation-based signatures. For most genes of the DM signature, an increased expression is negatively correlated with patient survival. The genes that provide the highest contribution to the predictive power of the DM signature are those involved in cytokinesis. CONCLUSION: This finding highlights cytokinesis as an important marker in breast cancer prognosis and as a possible target for antimitotic therapies.

  3. Modelling circulating tumour cells for personalised survival prediction in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Gianluca Ascolani

    2015-05-01

    Full Text Available Ductal carcinoma is one of the most common cancers among women, and the main cause of death is the formation of metastases. The development of metastases is caused by cancer cells that migrate from the primary tumour site (the mammary duct through the blood vessels and extravasating they initiate metastasis. Here, we propose a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone. Through a branching process model, we describe the relation between the survival times and the four markers mainly involved in metastatic breast cancer (EPCAM, CD47, CD44 and MET. In particular, the model takes into account the gene expression profile of circulating tumour cells to predict personalised survival probability. We also include the administration of drugs as bisphosphonates, which reduce the formation of circulating tumour cells and their survival in the blood vessels, in order to analyse the dynamic changes induced by the therapy. We analyse the effects of circulating tumour cells on the progression of the disease providing a quantitative measure of the cell driver mutations needed for invading the bone tissue. Our model allows to design intervention scenarios that alter the patient-specific survival probability by modifying the populations of circulating tumour cells and it could be extended to other cancer metastasis dynamics.

  4. Predictive parameters of survival in hemodialysis patients with restless leg syndrome

    Directory of Open Access Journals (Sweden)

    Radojica V Stolic

    2014-01-01

    Full Text Available Restless leg syndrome (RLS affects the quality of life and survival in patients on hemodialysis (HD. The aim of this study was to determine the characteristics and survival parameters in patients on HD with RLS. This study was a non-randomized clinical study involving 204 patients on HD, of whom 71 were female and 133 were male. Symptoms of RLS were defined as positive responses to four questions comprising the criteria of RLS. We recorded the outcome of treatment, biochemical analyses, demographic, sexual, anthropometric and clinical characteristics in all study patients. Patients with RLS who completed the study had a significantly higher body mass index and lower intima-media thickness and flow through the arteriovenous fistula. Among patients with RLS who died, there were more smokers as well as higher incidences of cardiovascular disease and diabetes mellitus. Among patients with RLS who survived, there were a greater number of patients with preserved diuresis and receiving erythropoietin therapy. Patients who completed the study had significantly higher levels of hemoglobin, creatinine, serum iron and transferrin satura-tion. Diabetes mellitus (B = 1.802; P = 0.002 and low Kt/V (B = -5.218; P = 0.001 were major predictive parameters for survival.

  5. ROCK I Has More Accurate Prognostic Value than MET in Predicting Patient Survival in Colorectal Cancer.

    Science.gov (United States)

    Li, Jian; Bharadwaj, Shruthi S; Guzman, Grace; Vishnubhotla, Ramana; Glover, Sarah C

    2015-06-01

    Colorectal cancer remains the second leading cause of death in the United States despite improvements in incidence rates and advancements in screening. The present study evaluated the prognostic value of two tumor markers, MET and ROCK I, which have been noted in other cancers to provide more accurate prognoses of patient outcomes than tumor staging alone. We constructed a tissue microarray from surgical specimens of adenocarcinomas from 108 colorectal cancer patients. Using immunohistochemistry, we examined the expression levels of tumor markers MET and ROCK I, with a pathologist blinded to patient identities and clinical outcomes providing the scoring of MET and ROCK I expression. We then used retrospective analysis of patients' survival data to provide correlations with expression levels of MET and ROCK I. Both MET and ROCK I were significantly over-expressed in colorectal cancer tissues, relative to the unaffected adjacent mucosa. Kaplan-Meier survival analysis revealed that patients' 5-year survival was inversely correlated with levels of expression of ROCK I. In contrast, MET was less strongly correlated with five-year survival. ROCK I provides better efficacy in predicting patient outcomes, compared to either tumor staging or MET expression. As a result, ROCK I may provide a less invasive method of assessing patient prognoses and directing therapeutic interventions. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Reduced CDX2 expression predicts poor overall survival in patients with colorectal cancer.

    Science.gov (United States)

    Hong, Kwang Dae; Lee, Dooseok; Lee, Youngseok; Lee, Sun Il; Moon, Hong Young

    2013-04-01

    The homeodomain transcription factor CDX2 directs development and maintenance of normal intestinal epithelium. However, the role of CDX2 in colorectal carcinogenesis is poorly understood. Hence, we investigated the CDX2 expression in patients with colorectal cancer and its relationship to tumor cell proliferation and differentiation and evaluated the role of this molecule as a biologic marker for the prediction of poor patient survival. We retrospectively reviewed 207 patients with colorectal cancer, with an available paraffin block, who underwent surgical resection between January 2002 and December 2004 at Korea University Guro Hospital. CDX2 expression was compared between tumor tissue and the adjacent normal mucosa using immunohistochemistry and Western blot analysis. Immunohistochemical staining for CDX2, Ki-67, and CK20 was performed in each tumor tissue. Immunohistochemistry revealed that CDX2 protein is overexpressed by colorectal cancer compared with adjacent normal mucosa (P < 0.001). In the Western blot analysis, tumor tissue showed a trend toward overexpression of CDX2 protein compared with normal mucosa (P = 0.09). CDX2 expression showed a significant direct correlation with the expression of Ki-67 and CK20 in tumor tissue (P = 0.028 and P = 0.042, respectively). Survival analysis showed that reduced CDX2 expression was statistically and significantly related to poor overall survival. Reduced CDX2 expression is associated with poor overall survival in patients with colorectal cancer and may be clinically useful as a marker for poor prognosis.

  7. Probability Prediction in Multistate Survival Models for Patients with Chronic Myeloid Leukaemia

    Institute of Scientific and Technical Information of China (English)

    FANG Ya; Hein Putter

    2005-01-01

    In order to find an appropriate model suitable for a multistate survival experiment, 634 patients with chronic myeloid leukaemia (CML) were selected to illustrate the method of analysis.After transplantation, there were 4 possible situations for a patient: disease free, relapse but still alive, death before relapse, and death after relapse. The last 3 events were considered as treatment failure. The results showed that the risk of death before relapse was higher than that of the relapse,especially in the first year after transplantation with competing-risk method. The result of patients with relapse time less than 12 months was much poor by the Kaplan-Meier method. And the multistate survival models were developed, which were detailed and informative based on the analysis of competing risks and Kaplan-Meier analysis. With the multistate survival models, a further analysis on conditional probability was made for patients who were disease free and still alive at month 12 after transplantation. It was concluded that it was possible for an individual patient to predict the 4 possible probabilities at any time. Also the prognoses for relapse either death or not and death either before or afterrelapse may be given. Furthermore, the conditional probabilities for patients who were disease free and still alive in a given time after transplantation can be predicted.

  8. Survival Prediction and Feature Selection in Patients with Breast Cancer Using Support Vector Regression

    Directory of Open Access Journals (Sweden)

    Shahrbanoo Goli

    2016-01-01

    Full Text Available The Support Vector Regression (SVR model has been broadly used for response prediction. However, few researchers have used SVR for survival analysis. In this study, a new SVR model is proposed and SVR with different kernels and the traditional Cox model are trained. The models are compared based on different performance measures. We also select the best subset of features using three feature selection methods: combination of SVR and statistical tests, univariate feature selection based on concordance index, and recursive feature elimination. The evaluations are performed using available medical datasets and also a Breast Cancer (BC dataset consisting of 573 patients who visited the Oncology Clinic of Hamadan province in Iran. Results show that, for the BC dataset, survival time can be predicted more accurately by linear SVR than nonlinear SVR. Based on the three feature selection methods, metastasis status, progesterone receptor status, and human epidermal growth factor receptor 2 status are the best features associated to survival. Also, according to the obtained results, performance of linear and nonlinear kernels is comparable. The proposed SVR model performs similar to or slightly better than other models. Also, SVR performs similar to or better than Cox when all features are included in model.

  9. An Integrative Pathway-based Clinical-genomic Model for Cancer Survival Prediction.

    Science.gov (United States)

    Chen, Xi; Wang, Lily; Ishwaran, Hemant

    2010-09-01

    Prediction models that use gene expression levels are now being proposed for personalized treatment of cancer, but building accurate models that are easy to interpret remains a challenge. In this paper, we describe an integrative clinical-genomic approach that combines both genomic pathway and clinical information. First, we summarize information from genes in each pathway using Supervised Principal Components (SPCA) to obtain pathway-based genomic predictors. Next, we build a prediction model based on clinical variables and pathway-based genomic predictors using Random Survival Forests (RSF). Our rationale for this two-stage procedure is that the underlying disease process may be influenced by environmental exposure (measured by clinical variables) and perturbations in different pathways (measured by pathway-based genomic variables), as well as their interactions. Using two cancer microarray datasets, we show that the pathway-based clinical-genomic model outperforms gene-based clinical-genomic models, with improved prediction accuracy and interpretability.

  10. General Inattentiveness Is a Long-Term Reliable Trait Independently Predictive of Psychological Health

    DEFF Research Database (Denmark)

    Jensen, Christian Gaden; Niclasen, Janni; Vangkilde, Signe

    2016-01-01

    The Mindful Attention Awareness Scale (MAAS) measures perceived degree of inattentiveness in different contexts and is often used as a reversed indicator of mindfulness. MAAS is hypothesized to reflect a psychological trait or disposition when used outside attentional training contexts, but the l......The Mindful Attention Awareness Scale (MAAS) measures perceived degree of inattentiveness in different contexts and is often used as a reversed indicator of mindfulness. MAAS is hypothesized to reflect a psychological trait or disposition when used outside attentional training contexts......, but the long-term test-retest reliability of MAAS scores is virtually untested. It is unknown whether MAAS predicts psychological health after controlling for standardized socioeconomic status classifications. First, MAAS translated to Danish was validated psychometrically within a randomly invited healthy...... adult community sample (N = 490). Factor analysis confirmed that MAAS scores quantified a unifactorial construct of excellent composite reliability and consistent convergent validity. Structural equation modeling revealed that MAAS scores contributed independently to predicting psychological distress...

  11. Empathy and nonattachment independently predict peer nominations of prosocial behaviour of adolescents

    Directory of Open Access Journals (Sweden)

    Baljinder K Sahdra

    2015-03-01

    Full Text Available There is a plethora of research showing that empathy promotes prosocial behaviour among young people. We examined a relatively new construct in the mindfulness literature, nonattachment, defined as a flexible way of relating to one’s experiences without clinging to or suppressing them. We tested whether nonattachment could predict prosociality above and beyond empathy. Nonattachment implies high cognitive flexibility and sufficient mental resources to step out of excessive self-cherishing to be there for others in need. Multilevel Poisson models using a sample of 15-year olds (N=1831 showed that empathy and nonattachment independently predicted prosocial behaviours of helpfulness and kindness, as judged by same-sex and opposite-sex peers, except for when boys nominated girls. The effects of nonattachment remained substantial in more conservative models including self-esteem and peer nominations of liking.

  12. Cervical cancer survival prediction using hybrid of SMOTE, CART and smooth support vector machine

    Science.gov (United States)

    Purnami, S. W.; Khasanah, P. M.; Sumartini, S. H.; Chosuvivatwong, V.; Sriplung, H.

    2016-04-01

    According to the WHO, every two minutes there is one patient who died from cervical cancer. The high mortality rate is due to the lack of awareness of women for early detection. There are several factors that supposedly influence the survival of cervical cancer patients, including age, anemia status, stage, type of treatment, complications and secondary disease. This study wants to classify/predict cervical cancer survival based on those factors. Various classifications methods: classification and regression tree (CART), smooth support vector machine (SSVM), three order spline SSVM (TSSVM) were used. Since the data of cervical cancer are imbalanced, synthetic minority oversampling technique (SMOTE) is used for handling imbalanced dataset. Performances of these methods are evaluated using accuracy, sensitivity and specificity. Results of this study show that balancing data using SMOTE as preprocessing can improve performance of classification. The SMOTE-SSVM method provided better result than SMOTE-TSSVM and SMOTE-CART.

  13. Prediction of survival after surgery due to skeletal metastases in the extremities

    DEFF Research Database (Denmark)

    Sørensen, M S; Gerds, T A; Hindsø, K

    2016-01-01

    AIMS: The purpose of this study was to develop a prognostic model for predicting survival of patients undergoing surgery owing to metastatic bone disease (MBD) in the appendicular skeleton. METHODS: We included a historical cohort of 130 consecutive patients (mean age 64 years, 30 to 85; 76 females....../54 males) who underwent joint arthroplasty surgery (140 procedures) owing to MBD in the appendicular skeleton during the period between January 2003 and December 2008. Primary cancer, pre-operative haemoglobin, fracture versus impending fracture, Karnofsky score, visceral metastases, multiple bony...... metastases and American Society of Anaesthesiologist's score were included into a series of logistic regression models. The outcome was the survival status at three, six and 12 months respectively. Results were internally validated based on 1000 cross-validations and reported as time-dependent area under...

  14. Gene Expression-Based Survival Prediction in Lung Adenocarcinoma: A Multi-Site, Blinded Validation Study

    Science.gov (United States)

    Shedden, Kerby; Taylor, Jeremy M.G.; Enkemann, Steve A.; Tsao, Ming S.; Yeatman, Timothy J.; Gerald, William L.; Eschrich, Steve; Jurisica, Igor; Venkatraman, Seshan E.; Meyerson, Matthew; Kuick, Rork; Dobbin, Kevin K.; Lively, Tracy; Jacobson, James W.; Beer, David G.; Giordano, Thomas J.; Misek, David E.; Chang, Andrew C.; Zhu, Chang Qi; Strumpf, Dan; Hanash, Samir; Shepherd, Francis A.; Ding, Kuyue; Seymour, Lesley; Naoki, Katsuhiko; Pennell, Nathan; Weir, Barbara; Verhaak, Roel; Ladd-Acosta, Christine; Golub, Todd; Gruidl, Mike; Szoke, Janos; Zakowski, Maureen; Rusch, Valerie; Kris, Mark; Viale, Agnes; Motoi, Noriko; Travis, William; Sharma, Anupama

    2009-01-01

    Although prognostic gene expression signatures for survival in early stage lung cancer have been proposed, for clinical application it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) can be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas. PMID:18641660

  15. Loss of expression of BAP1 predicts longer survival in mesothelioma.

    Science.gov (United States)

    Farzin, Mahtab; Toon, Christopher W; Clarkson, Adele; Sioson, Loretta; Watson, Nicole; Andrici, Juliana; Gill, Anthony J

    2015-06-01

    BRCA1-associated protein 1 (BAP1) is a tumour suppressor gene frequently inactivated in mesothelioma, rarely also in association with germline mutation. BAP1 mutations have been associated with improved prognosis and distinct clinicopathological features. We sought to determine the clinicopathological significance of BAP1 immunohistochemistry (IHC) in mesothelioma.We performed IHC on a tissue microarray (TMA) cohort comprising all available thoracic mesotheliomas encountered during the period 1991-2014 at our institution (n = 229). All cases were independently reviewed to confirm the diagnosis and subclassify as epithelioid, sarcomatoid or biphasic. The median age at diagnosis was 72 years; 188 (82.1%) were male; 120 (52.4%) were epithelioid (median survival 13.0 months), 67 (29.3%) sarcomatoid (median survival 5.6 months) and 42 (18.3%) biphasic (median survival 10.6 months). Negative staining for BAP1 (defined as completely absent nuclear staining in the presence of positive internal controls in non-neoplastic cells) occurred in 106 (46.3%) mesotheliomas. There was complete interobserver concordance for BAP1 IHC status. BAP1 loss was strongly associated with younger age at onset (p mesothelioma.

  16. The Independent Living Scales in civil competency evaluations: initial findings and prediction of competency adjudication.

    Science.gov (United States)

    Quickel, Emalee J W; Demakis, George J

    2013-06-01

    We address a gap in the literature on civil competency by examining characteristics of those who undergo civil competency evaluations and how well Managing Money and Health and Safety subscales of the Independent Living Scales (ILS) predict legal competency adjudications. We were also interested whether these subscales are more accurate in making such predictions than the Mini-Mental State Examination and Trail-Making Test, Parts A and B, well-known measures of neuropsychological functioning. Actual legal competency decisions were obtained from public court records on 71 individuals with either mental retardation/borderline intellectual functioning (MR/BIF) or psychiatric, neurological, or combined psychiatric or neurological diagnoses. We found that those with neurological diagnoses performed significantly better on the Trail-Making Test, Part A, than the MR/BIF and combined neurological and psychiatric groups, and they demonstrated trends in the same direction for other measures. Both ILS subscales performed better than the cognitive measures, in terms of both hit rate and predictive value, in predicting ultimate judicial decision-making about competency. These findings are particularly relevant for clinicians who must decide what measures to include in an assessment battery in civil competency evaluations.

  17. Radiation therapy for nasopharyngeal carcinoma: the predictive value of interim survival assessment.

    Science.gov (United States)

    Toya, Ryo; Murakami, Ryuji; Saito, Tetsuo; Murakami, Daizo; Matsuyama, Tomohiko; Baba, Yuji; Nishimura, Ryuichi; Hirai, Toshinori; Semba, Akiko; Yumoto, Eiji; Yamashita, Yasuyuki; Oya, Natsuo

    2016-09-01

    Pretreatment characteristics are suggested as predictive and/or prognostic factors for nasopharyngeal carcinoma (NPC); however, individual tumor radiosensitivities have previously not been considered. As boost planning is recommended for NPC, we performed interim assessments of magnetic resonance (MR) images for boost planning and retrospectively evaluated their predictive value for the survival of NPC patients. Radiation therapy via elective nodal irradiation (median dose: 39.6 Gy) with/without chemotherapy was used to treat 63 NPC patients. Boost irradiation (median total dose: 70 Gy) was performed based on the interim assessment. The largest lymph node (LN) was measured on MR images acquired at the time of interim assessment. The site of first failure was local in 8 (12.7%), regional in 7 (11.1%), and distant in 12 patients (19.0%). All 7 patients with regional failure harbored LNs ≥15 mm at interim assessment. We divided the 63 patients into two groups based on LN size [large (≥15 mm), n = 10 and small (interim assessment could predict survival in NPC patients.

  18. Survival prediction based on compound covariate under Cox proportional hazard models.

    Directory of Open Access Journals (Sweden)

    Takeshi Emura

    Full Text Available Survival prediction from a large number of covariates is a current focus of statistical and medical research. In this paper, we study a methodology known as the compound covariate prediction performed under univariate Cox proportional hazard models. We demonstrate via simulations and real data analysis that the compound covariate method generally competes well with ridge regression and Lasso methods, both already well-studied methods for predicting survival outcomes with a large number of covariates. Furthermore, we develop a refinement of the compound covariate method by incorporating likelihood information from multivariate Cox models. The new proposal is an adaptive method that borrows information contained in both the univariate and multivariate Cox regression estimators. We show that the new proposal has a theoretical justification from a statistical large sample theory and is naturally interpreted as a shrinkage-type estimator, a popular class of estimators in statistical literature. Two datasets, the primary biliary cirrhosis of the liver data and the non-small-cell lung cancer data, are used for illustration. The proposed method is implemented in R package "compound.Cox" available in CRAN at http://cran.r-project.org/.

  19. Osteoprotegerin independently predicts mortality in patients with stable coronary artery disease: the CLARICOR trial.

    Science.gov (United States)

    Bjerre, Mette; Hilden, Jørgen; Kastrup, Jens; Skoog, Maria; Hansen, Jørgen F; Kolmos, Hans J; Jensen, Gorm B; Kjøller, Erik; Winkel, Per; Flyvbjerg, Allan; Gluud, Christian

    2014-11-01

    To elucidate the prognostic power of serum osteoprotegerin (OPG) in patients with stable coronary artery disease (CAD). Serum OPG levels were measured in the CLARICOR trial cohort of 4063 patients with stable CAD on blood samples drawn at randomization. The follow-up was 2.6 years for detailed cardiovascular events and 6 years for all-cause mortality. OPG levels were significantly increased in non-survivors (21%) compared to survivors (median [quartiles] 2092 ng/L [1636; 2800] compared to 1695 ng/L [1322; 2193, p < 0.0001]). The 2.6-year follow-up showed that OPG adds to the prediction of both cardiovascular and all-cause mortality in combination with clinical risk factors (HR [one log10 unit increase] 6.1 [95% CI 2.4-15.6, p = 0.0001]) and HR 6.5 [95% CI 3.4-12.5, p < 0.0001], respectively). Similar, in the 6-year follow-up, OPG was found to be a strong predictor for all-cause mortality. Importantly, OPG remained an independent predictor of mortality even after adjustment for both clinical and conventional cardiovascular risk markers (HR 2.5 [95% CI 1.6-3.9, p < 0.0001]). Serum OPG has a long-lasting independent predictive power as to all-cause mortality and cardiovascular death in patients with stable CAD.

  20. Gut Microbiota Alterations can predict Hospitalizations in Cirrhosis Independent of Diabetes Mellitus.

    Science.gov (United States)

    Bajaj, Jasmohan S; Betrapally, Naga S; Hylemon, Phillip B; Thacker, Leroy R; Daita, Kalyani; Kang, Dae Joong; White, Melanie B; Unser, Ariel B; Fagan, Andrew; Gavis, Edith A; Sikaroodi, Masoumeh; Dalmet, Swati; Heuman, Douglas M; Gillevet, Patrick M

    2015-12-22

    Diabetes (DM) is prevalent in cirrhosis and may modulate the risk of hospitalization through gut dysbiosis. We aimed to define the role of gut microbiota on 90-day hospitalizations and of concomitant DM on microbiota. Cirrhotic outpatients with/without DM underwent stool and sigmoid mucosal microbial analysis and were followed for 90 days. Microbial composition was compared between those with/without DM, and those who were hospitalized/not. Regression/ROC analyses for hospitalizations were performed using clinical and microbial features. 278 cirrhotics [39% hepatic encephalopathy (HE), 31%DM] underwent stool while 72 underwent mucosal analyses. Ultimately, 94 were hospitalized and they had higher MELD, proton pump inhibitor (PPI) use and HE without difference in DM. Stool/mucosal microbiota were significantly altered in those who were hospitalized (UNIFRAC p microbiota UNIFRAC (stool, p = 0.003, mucosa, p = 0.04) with higher stool Bacteroidaceae and lower Ruminococcaeae. Stool Bacteroidaceaeae and Clostridiales XIV predicted 90-day hospitalizations independent of clinical predictors (MELD, HE, PPI). Stool and colonic mucosal microbiome are altered in cirrhotics who get hospitalized with independent prediction using stool Bacteroidaceae and Clostridiales XIV. Concomitant DM distinctly impacts gut microbiota without affecting hospitalizations.

  1. Salivary gland carcinoma : Independent prognostic factors for locoregional control, distant metastases, and overall survival: Results of the Dutch Head and Neck Oncology Cooperative Group

    NARCIS (Netherlands)

    Terhaard, CHJ; Lubsen, H; Van der Tweel, [No Value; Hilgers, FJM; Eijkenboom, WMH; Marres, HAM; Tjho-Heslinga, RE; de Jong, JMA; Roodenburg, JLN

    2004-01-01

    Background. We analyzed the records of patients with malignant salivary gland tumors, as diagnosed in centers of the Dutch Head and Neck Oncology Cooperative Group, in search of independent prognostic factors for locoregional control, distant metastases, and overall survival. Methods. In 565 patient

  2. Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma

    Science.gov (United States)

    Maurer, Matthew J.; Jais, Jean-Philippe; Ghesquières, Hervé; Witzig, Thomas E.; Hong, Fangxin; Haioun, Corinne; Thompson, Carrie A.; Thieblemont, Catherine; Micallef, Ivana N.; Porrata, Luis F.; Ribrag, Vincent; Nowakowski, Gregorz S.; Casanovas, Olivier; Bologna, Serge; Morschhauser, Franck; Morrison, Vicki A.; Peterson, Bruce A.; Macon, William R.; Copie-Bergman, Christiane; Feldman, Andrew L.; Syrbu, Sergei I.; Kurtin, Paul J.; Gascoyne, Randy D.; Li, Hailun; Allmer, Cristine; Kahl, Brad S.; Ansell, Stephen M.; Slager, Susan L.; Link, Brian K.; Salles, Gilles; Habermann, Thomas M.; Tilly, Hervé; Cerhan, James R.

    2016-01-01

    We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline-based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c-statistic = 0.671) in the validation dataset compared to the IPI (c-statistic = 0.649) or the NCCN-IPI (c-statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12–88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps. PMID:26492520

  3. [Clinical application value of prognostic nutritional index for predicting survival in patients with advanced non-small cell lung cancer].

    Science.gov (United States)

    Xu, W J; Kang, Y M; Zhou, L; Chen, F F; Song, Y H; Zhang, C Q

    2017-02-23

    Objective: To explore the clinical application value of prognostic nutritional index(PNI) for predicting overall survival(OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods: 123 patients with histologically confirmed non-small cell lung cancer were enrolled in this study, and their clinical and laboratory data were reviewed. The PNI was calculated as 10×serum albumin value+ 5×total lymphocyte countin peripheral blood.Univariate and multivariate analyses were used to identify the potential prognostic factors for advanced NSCLC. Results: PNI of the 123 NSCLC patients was 46.24±6.56. PNI was significantly associated with age, weight loss and pleural effusion (P0.05). The median OS of the 123 patients was 19.5 months. The median OS in the higher PNI group (PNI≥46.24) and lower PNI group(PNI<46.24) were 25.2 months and 16.4 months, respectively.The 1-year survival rates were 80.6% and 63.9%, and 2-year survival rates were 54.8% and 19.6%, respectively (P<0.01). Univariate analysis showed that PNI, age, dyspnea, and weight loss were related to the OS of the advanced NSCLC patients (P<0.05). Multivariate analysis identified PNI as an independent prognostic factor for OS of advanced NSCLC (P<0.001). Conclusion: PNI can be easily calculated, and may be used as a relatively new prognostic indicator for advanced NSCLC in clinical practice.

  4. Late Release of Circulating Endothelial Cells and Endothelial Progenitor Cells after Chemotherapy Predicts Response and Survival in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Jeanine M. Roodhart

    2010-01-01

    Full Text Available We and others have previously demonstrated that the acute release of progenitor cells in response to chemotherapy actually reduces the efficacy of the chemotherapy. Here, we take these data further and investigate the clinical relevance of circulating endothelial (progenitor cells (CE(PCs and modulatory cytokines in patients after chemotherapy with relation to progression-free and overall survival (PFS/OS. Patients treated with various chemotherapeutics were included. Blood sampling was performed at baseline, 4 hours, and 7 and 21 days after chemotherapy. The mononuclear cell fraction was analyzed for CE(PC by FACS analysis. Plasma was analyzed for cytokines by ELISA or Luminex technique. CE(PCs were correlated with response and PFS/OS using Cox proportional hazard regression analysis. We measured CE(PCs and cytokines in 71 patients. Only patients treated with paclitaxel showed an immediate increase in endothelial progenitor cell 4 hours after start of treatment. These immediate changes did not correlate with response or survival. After 7 and 21 days of chemotherapy, a large and consistent increase in CE(PC was found (P < .01, independent of the type of chemotherapy. Changes in CE(PC levels at day 7 correlated with an increase in tumor volume after three cycles of chemotherapy and predicted PFS/OS, regardless of the tumor type or chemotherapy. These findings indicate that the late release of CE(PC is a common phenomenon after chemotherapeutic treatment. The correlation with a clinical response and survival provides further support for the biologic relevance of these cells in patients' prognosis and stresses their possible use as a therapeutic target.

  5. Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer.

    Science.gov (United States)

    Wang, Baohua; Song, Ning; Yu, Tong; Zhou, Lianya; Zhang, Helin; Duan, Lin; He, Wenshu; Zhu, Yihua; Bai, Yunfei; Zhu, Miao

    2014-01-01

    In this study, we conducted a meta-analysis on high-throughput gene expression data to identify TNF-α-mediated genes implicated in lung cancer. We first investigated the gene expression profiles of two independent TNF-α/TNFR KO murine models. The EGF receptor signaling pathway was the top pathway associated with genes mediated by TNF-α. After matching the TNF-α-mediated mouse genes to their human orthologs, we compared the expression patterns of the TNF-α-mediated genes in normal and tumor lung tissues obtained from humans. Based on the TNF-α-mediated genes that were dysregulated in lung tumors, we developed a prognostic gene signature that effectively predicted recurrence-free survival in lung cancer in two validation cohorts. Resampling tests suggested that the prognostic power of the gene signature was not by chance, and multivariate analysis suggested that this gene signature was independent of the traditional clinical factors and enhanced the identification of lung cancer patients at greater risk for recurrence.

  6. Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer.

    Directory of Open Access Journals (Sweden)

    Baohua Wang

    Full Text Available In this study, we conducted a meta-analysis on high-throughput gene expression data to identify TNF-α-mediated genes implicated in lung cancer. We first investigated the gene expression profiles of two independent TNF-α/TNFR KO murine models. The EGF receptor signaling pathway was the top pathway associated with genes mediated by TNF-α. After matching the TNF-α-mediated mouse genes to their human orthologs, we compared the expression patterns of the TNF-α-mediated genes in normal and tumor lung tissues obtained from humans. Based on the TNF-α-mediated genes that were dysregulated in lung tumors, we developed a prognostic gene signature that effectively predicted recurrence-free survival in lung cancer in two validation cohorts. Resampling tests suggested that the prognostic power of the gene signature was not by chance, and multivariate analysis suggested that this gene signature was independent of the traditional clinical factors and enhanced the identification of lung cancer patients at greater risk for recurrence.

  7. Nestin is an independent predictor of cancer-specific survival after radical cystectomy in patients with urothelial carcinoma of the bladder.

    Directory of Open Access Journals (Sweden)

    Ken-ichi Tabata

    Full Text Available OBJECTIVES: To investigate the association between the expression of nestin, a class VI intermediate filament protein, and pathologic features or survival in patients with urothelial carcinoma of the bladder (UCB. METHODS: Nestin expression in tumor cells was immunohistochemically studied in 93 patients with UCB who underwent radical cystectomy with pelvic lymphadenectomy. The associations with clinicopathologic parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of nestin expression on survival. RESULTS: Nestin expression in cystectomy specimens was observed in 13 of 93 patients (14.0%. Nestin expression was associated with pathologic tumor stage (p = 0.006. Nestin-negative patients had better overall survival compared with nestin-positive patients (log-rank p = 0.0148. Univariable analysis indicated that nestin expression, lymphovascular invasion, and lymph node status were significantly associated with cancer-specific survival (hazard ratios, 2.78, 2.15, and 2.80, respectively. On multivariable analysis, nestin expression and lymph node status were independent prognostic factors in cancer-specific survival (hazard ratios, 2.45 and 2.65, respectively. CONCLUSIONS: The results suggest that nestin expression is a novel independent prognostic indicator for patients with UCB and a potentially useful marker to select patients who may be candidates for adjuvant chemotherapy.

  8. The MITOS system predicts long-term survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Tramacere, Irene; Dalla Bella, Eleonora; Chiò, Adriano; Mora, Gabriele; Filippini, Graziella; Lauria, Giuseppe

    2015-11-01

    The choice of adequate proxy for long-term survival, the ultimate outcome in randomised clinical trials (RCT) assessing disease-modifying treatments for amyotrophic lateral sclerosis (ALS), is a key issue. The intrinsic limitations of the ALS Functional Rating Scale-Revised (ALSFRS-R), including non-linearity, multidimensionality and floor-effect, have emerged and its usefulness argued. The ALS Milano-Torino staging (ALS-MITOS) system was proposed as a novel tool to measure the progression of ALS and overcome these limitations. This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months. Analyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes. The ALS-MITOS system is composed of four key domains included in the ALSFRS-R scale (walking/self-care, swallowing, communicating and breathing), each with a threshold reflecting the loss of function in the specific ALSFRS-R subscores. Sensitivity, specificity and the area under the curve of the receiver operating characteristic curves of the ALS-MITOS system stages and ALSFRS-R decline at 6 months were calculated and compared with the primary outcome (survival, tracheotomy or >23-hour non-invasive ventilation) at 12 and 18 months Predicted probabilities of the ALS-MITO system at 6 months for any event at 12 and 18 months were computed through logistic regression models. Disease progression from baseline to 6 months as defined by the ALS-MITOS system predicted death, tracheotomy or >23-hour non-invasive ventilation at 12 months with 82% sensitivity (95% CI 71% to 93%, n=37/45) and 63% specificity (95% CI 55% to 71%, n=92/146), and at 18 months with 71% sensitivity (95% CI 61% to 82%, n=50/70) and 68% specificity (95% CI 60% to 77%, n=76/111). The analysis of ALS-MITOS and ALSFRS-R progression at 6-month follow-up showed that the best cut-off to

  9. Management of hepatocellular carcinoma: Predictive valueof immunohistochemical markers for postoperative survival

    Institute of Scientific and Technical Information of China (English)

    Zhao-Shan Niu; Xiao-Jun Niu; Mei Wang

    2015-01-01

    Hepatocellular carcinoma (HCC) accounts for over 90%of all primary liver cancers. With an ever increasingincidence trend year by year, it has become the thirdmost common cause of death from cancer worldwide.Hepatic resection is generally considered to be one ofthe most effective therapies for HCC patients, however,there is a high risk of recurrence in postoperativeHCC. In clinical practice, there exists an urgent needfor valid prognostic markers to identify patientswith prognosis, hence the importance of studies onprognostic markers in improving the prediction of HCCprognosis. This review focuses on the most promisingimmunohistochemical prognostic markers in predictingthe postoperative survival of HCC patients.

  10. Developing and Validating a Survival Prediction Model for NSCLC Patients Through Distributed Learning Across 3 Countries.

    Science.gov (United States)

    Jochems, Arthur; Deist, Timo M; El Naqa, Issam; Kessler, Marc; Mayo, Chuck; Reeves, Jackson; Jolly, Shruti; Matuszak, Martha; Ten Haken, Randall; van Soest, Johan; Oberije, Cary; Faivre-Finn, Corinne; Price, Gareth; de Ruysscher, Dirk; Lambin, Philippe; Dekker, Andre

    2017-10-01

    Tools for survival prediction for non-small cell lung cancer (NSCLC) patients treated with chemoradiation or radiation therapy are of limited quality. In this work, we developed a predictive model of survival at 2 years. The model is based on a large volume of historical patient data and serves as a proof of concept to demonstrate the distributed learning approach. Clinical data from 698 lung cancer patients, treated with curative intent with chemoradiation or radiation therapy alone, were collected and stored at 2 different cancer institutes (559 patients at Maastro clinic (Netherlands) and 139 at Michigan university [United States]). The model was further validated on 196 patients originating from The Christie (United Kingdon). A Bayesian network model was adapted for distributed learning (the animation can be viewed at https://www.youtube.com/watch?v=ZDJFOxpwqEA). Two-year posttreatment survival was chosen as the endpoint. The Maastro clinic cohort data are publicly available at https://www.cancerdata.org/publication/developing-and-validating-survival-prediction-model-nsclc-patients-through-distributed, and the developed models can be found at www.predictcancer.org. Variables included in the final model were T and N category, age, performance status, and total tumor dose. The model has an area under the curve (AUC) of 0.66 on the external validation set and an AUC of 0.62 on a 5-fold cross validation. A model based on the T and N category performed with an AUC of 0.47 on the validation set, significantly worse than our model (P<.001). Learning the model in a centralized or distributed fashion yields a minor difference on the probabilities of the conditional probability tables (0.6%); the discriminative performance of the models on the validation set is similar (P=.26). Distributed learning from federated databases allows learning of predictive models on data originating from multiple institutions while avoiding many of the data-sharing barriers. We believe

  11. Genetic polymorphism in a VEGF-independent angiogenesis gene ANGPT1 and overall survival of colorectal cancer patients after surgical resection.

    Directory of Open Access Journals (Sweden)

    Jingyao Dai

    Full Text Available BACKGROUND: The VEGF-independent angiogenic signaling plays an important role in the development of colorectal cancer (CRC. However, its implication in the clinical outcome of CRC has not been reported. This study aimed to investigate the association between genetic variations in several major VEGF-independent signaling pathway genes and the overall survival of CRC patients. METHODS: Seven single nucleotide polymorphisms (SNPs in four important VEGF-independent angiogenic genes (ANGPT1, AMOT, DLL4 and ENG were genotyped in a Chinese population with 408 CRC patients. RESULTS: One SNP, rs1954727 in ANGPT1, was significantly associated with CRC overall survival. Compared to patients with the homozygous wild-type genotype of rs1954727, those with heterozygous and homozygous variant genotypes exhibited a favorable overall survival with a hazard ratio (HR of 0.89 (95% confidence interval [CI] 0.55-1.43, P = 0.623, and 0.32 (95% CI 0.15-0.71, P = 0.005, respectively (P trend = 0.008. In stratified analysis, this association remained significant in patients receiving chemotherapy (P trend = 0.012, but not in those without chemotherapy. We further evaluated the effects of chemotherapy on CRC survival that was stratified by rs1954727 genotypes. We found that chemotherapy resulted in a significantly better overall survival in the CRC patients (HR = 0.44, 95% CI 0.26-0.75, P = 0.002, which was especially prominent in those patients with the heterozygous genotype of rs1954727 (HR = 0.45, 95%CI 0.22-0.92, P = 0.028. CONCLUSION: Our data suggest that rs1954727 in ANGPT1 gene might be a prognostic biomarker for the overall survival of CRC patients, especially in those receiving chemotherapy, a finding that warrants validation in larger independent populations.

  12. Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.

    Science.gov (United States)

    Dienstmann, R; Mason, M J; Sinicrope, F A; Phipps, A I; Tejpar, S; Nesbakken, A; Danielsen, S A; Sveen, A; Buchanan, D D; Clendenning, M; Rosty, C; Bot, B; Alberts, S R; Milburn Jessup, J; Lothe, R A; Delorenzi, M; Newcomb, P A; Sargent, D; Guinney, J

    2017-05-01

    TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61-0.68 in the TNM alone model to 0.63-0.71 in models with added molecular markers, 0.65-0.73 with clinicopathological features and 0.66-0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases prediction accuracy in multivariable models that include

  13. Polygenic Scores Predict Alcohol Problems in an Independent Sample and Show Moderation by the Environment

    Directory of Open Access Journals (Sweden)

    Jessica E. Salvatore

    2014-04-01

    Full Text Available Alcohol problems represent a classic example of a complex behavioral outcome that is likely influenced by many genes of small effect. A polygenic approach, which examines aggregate measured genetic effects, can have predictive power in cases where individual genes or genetic variants do not. In the current study, we first tested whether polygenic risk for alcohol problems—derived from genome-wide association estimates of an alcohol problems factor score from the age 18 assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4304 individuals of European descent; 57% female—predicted alcohol problems earlier in development (age 14 in an independent sample (FinnTwin12; n = 1162; 53% female. We then tested whether environmental factors (parental knowledge and peer deviance moderated polygenic risk to predict alcohol problems in the FinnTwin12 sample. We found evidence for both polygenic association and for additive polygene-environment interaction. Higher polygenic scores predicted a greater number of alcohol problems (range of Pearson partial correlations 0.07–0.08, all p-values ≤ 0.01. Moreover, genetic influences were significantly more pronounced under conditions of low parental knowledge or high peer deviance (unstandardized regression coefficients (b, p-values (p, and percent of variance (R2 accounted for by interaction terms: b = 1.54, p = 0.02, R2 = 0.33%; b = 0.94, p = 0.04, R2 = 0.30%, respectively. Supplementary set-based analyses indicated that the individual top single nucleotide polymorphisms (SNPs contributing to the polygenic scores were not individually enriched for gene-environment interaction. Although the magnitude of the observed effects are small, this study illustrates the usefulness of polygenic approaches for understanding the pathways by which measured genetic predispositions come together with environmental factors to predict complex behavioral outcomes.

  14. Polygenic Scores Predict Alcohol Problems in an Independent Sample and Show Moderation by the Environment

    Science.gov (United States)

    Salvatore, Jessica E.; Aliev, Fazil; Edwards, Alexis C.; Evans, David M.; Macleod, John; Hickman, Matthew; Lewis, Glyn; Kendler, Kenneth S.; Loukola, Anu; Korhonen, Tellervo; Latvala, Antti; Rose, Richard J.; Kaprio, Jaakko; Dick, Danielle M.

    2014-01-01

    Alcohol problems represent a classic example of a complex behavioral outcome that is likely influenced by many genes of small effect. A polygenic approach, which examines aggregate measured genetic effects, can have predictive power in cases where individual genes or genetic variants do not. In the current study, we first tested whether polygenic risk for alcohol problems—derived from genome-wide association estimates of an alcohol problems factor score from the age 18 assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4304 individuals of European descent; 57% female)—predicted alcohol problems earlier in development (age 14) in an independent sample (FinnTwin12; n = 1162; 53% female). We then tested whether environmental factors (parental knowledge and peer deviance) moderated polygenic risk to predict alcohol problems in the FinnTwin12 sample. We found evidence for both polygenic association and for additive polygene-environment interaction. Higher polygenic scores predicted a greater number of alcohol problems (range of Pearson partial correlations 0.07–0.08, all p-values ≤ 0.01). Moreover, genetic influences were significantly more pronounced under conditions of low parental knowledge or high peer deviance (unstandardized regression coefficients (b), p-values (p), and percent of variance (R2) accounted for by interaction terms: b = 1.54, p = 0.02, R2 = 0.33%; b = 0.94, p = 0.04, R2 = 0.30%, respectively). Supplementary set-based analyses indicated that the individual top single nucleotide polymorphisms (SNPs) contributing to the polygenic scores were not individually enriched for gene-environment interaction. Although the magnitude of the observed effects are small, this study illustrates the usefulness of polygenic approaches for understanding the pathways by which measured genetic predispositions come together with environmental factors to predict complex behavioral outcomes. PMID:24727307

  15. Islet Oxygen Consumption Rate (OCR Dose Predicts Insulin Independence in Clinical Islet Autotransplantation.

    Directory of Open Access Journals (Sweden)

    Klearchos K Papas

    Full Text Available Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR in predicting clinical islet autotransplant (IAT insulin independence (II. IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity.Membrane integrity staining (FDA/PI, OCR normalized to DNA (OCR/DNA, islet equivalent (IE and OCR (viable IE normalized to recipient body weight (IE dose and OCR dose, and OCR/DNA normalized to islet size index (ISI were used to characterize autoislet preparations (n = 35. Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis.Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001. These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC = 0.94 for IE dose and 0.96 for OCR dose. FDA/PI (AUC = 0.49 and OCR/DNA (AUC = 0.58 did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72.Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.

  16. Cell survival in carbon beams - comparison of amorphous track model predictions

    DEFF Research Database (Denmark)

    Grzanka, L.; Greilich, S.; Korcyl, M.

    . [2] . In addition, a new approach based on microdosimetric distributions is presented and investigated [3] . Material and methods: A suitable software library embrasing the mentioned amorphous track models including numerous submodels with respect to delta-electron range models, radial dose......Introduction: Predictions of the radiobiological effectiveness (RBE) play an essential role in treatment planning with heavy charged particles. Amorphous track models ( [1] , [2] , also referred to as track structure models) provide currently the most suitable description of cell survival under ion...... irradiation. The aim of this paper is to compare the predictions from different amorphous approaches found in the literature - more specifically the phenomenological, analytical model by Katz and co-workers [1] and a Monte-Carlo based full as implemented for example in the local effect model by Scholz et al...

  17. Self-determined motivation predicts independent, home-based exercise following cardiac rehabilitation.

    Science.gov (United States)

    Russell, Kelly L; Bray, Steven R

    2009-05-01

    To investigate self-determined motivation as a predictor of exercise behavior 3 and 6 weeks following completion of cardiac rehabilitation (CR) as well as the relationship between psychological need satisfaction and self-determined motivation to exercise. CR outpatients (n = 68; M(age) = 64.90 +/- 8.86 years). The design was correlational (cross-sectional and prospective), with psychological need satisfaction predicting self-determined motivation at the completion of CR and self-determined motivation predicting exercise behavior at 3- and 6-week follow-ups. Psychological need satisfaction for competence predicted self-determined motivation to exercise (beta = .32, p motivation at the end of CR was correlated with exercise behavior at 3-week follow-up (r(68) = .22, p motivation. Greater self-determined motivation to exercise, in turn, relates to higher levels of subsequent independent exercise behavior. Nurturing psychological needs and self-determined motivation during CR may assist participants in maintaining exercise following CR. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

  18. p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q)

    Science.gov (United States)

    Saft, Leonie; Karimi, Mohsen; Ghaderi, Mehran; Matolcsy, András; Mufti, Ghulam J.; Kulasekararaj, Austin; Göhring, Gudrun; Giagounidis, Aristoteles; Selleslag, Dominik; Muus, Petra; Sanz, Guillermo; Mittelman, Moshe; Bowen, David; Porwit, Anna; Fu, Tommy; Backstrom, Jay; Fenaux, Pierre; MacBeth, Kyle J.; Hellström-Lindberg, Eva

    2014-01-01

    Del(5q) myelodysplastic syndromes defined by the International Prognostic Scoring System as low- or intermediate-1-risk (lower-risk) are considered to have an indolent course; however, recent data have identified a subgroup of these patients with more aggressive disease and poorer outcomes. Using deep sequencing technology, we previously demonstrated that 18% of patients with lower-risk del(5q) myelodysplastic syndromes carry TP53 mutated subclones rendering them at higher risk of progression. In this study, bone marrow biopsies from 85 patients treated with lenalidomide in the MDS-004 clinical trial were retrospectively assessed for p53 expression by immunohistochemistry in association with outcome. Strong p53 expression in ≥1% of bone marrow progenitor cells, observed in 35% (30 of 85) of patients, was significantly associated with higher acute myeloid leukemia risk (P=0.0006), shorter overall survival (P=0.0175), and a lower cytogenetic response rate (P=0.009), but not with achievement or duration of 26-week transfusion independence response. In a multivariate analysis, p53-positive immunohistochemistry was the strongest independent predictor of transformation to acute myeloid leukemia (P=0.0035). Pyrosequencing analysis of laser-microdissected cells with strong p53 expression confirmed the TP53 mutation, whereas cells with moderate expression predominantly had wild-type p53. This study validates p53 immunohistochemistry as a strong and clinically useful predictive tool in patients with lower-risk del(5q) myelodysplastic syndromes. This study was based on data from the MDS 004 trial (clinicaltrials.gov identifier: NCT00179621). PMID:24682512

  19. The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

    Science.gov (United States)

    Cornec-Le Gall, Emilie; Audrézet, Marie-Pierre; Rousseau, Annick; Hourmant, Maryvonne; Renaudineau, Eric; Charasse, Christophe; Morin, Marie-Pascale; Moal, Marie-Christine; Dantal, Jacques; Wehbe, Bassem; Perrichot, Régine; Frouget, Thierry; Vigneau, Cécile; Potier, Jérôme; Jousset, Philippe; Guillodo, Marie-Paule; Siohan, Pascale; Terki, Nazim; Sawadogo, Théophile; Legrand, Didier; Menoyo-Calonge, Victorio; Benarbia, Seddik; Besnier, Dominique; Longuet, Hélène; Férec, Claude

    2016-01-01

    The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD. PMID:26150605

  20. Prenatal prediction of neonatal survival in cases diagnosed with congenital diaphragmatic hernia using abdomen-to-thorax ratio determined by ultrasonography.

    Science.gov (United States)

    Lee, Ji Yeon; Jun, Jong Kwan; Lee, JoonHo

    2014-09-01

    The aim of this study was to evaluate the usefulness of abdomen-to-thorax ratio (ATR) measured by antenatal ultrasonography for predicting neonatal survival of fetuses with congenital diaphragmatic hernia (CDH). We identified 75 fetuses who were prenatally diagnosed with CDH and delivered in Seoul National University Hospital from 1998 to 2012, retrospectively. Of these, 40 cases who met the following criteria were included: (i) singleton pregnancy; (ii) a case that had available ultrasonographic images; and (iii) a neonate in whom follow-up until discharge from the hospital was available. ATR was measured as follows: each anteroposterior distance (APD) in the abdominal and thoracic cavity was measured in the same midsagittal plane with the fetal neutral position. A thoracic APD was measured from the back to the distal end of the sternum and an abdominal APD from the back to the most protruding abdominal surface. ATR is the ratio of the abdominal APD versus the thoracic APD. Survival rates were 57.5%. There were significant differences in ATR, lung-head ratio (LHR), observed/expected-LHR, quantitative lung index and intrathoracic liver between survivors and non-survivors. Regression analysis demonstrated that only ATR and intrathoracic position of the liver were independent predictors of survival. ATR by multivariate analysis had the most influence on survival rate (P = 0.002). The area under the receiver-operator curve for prediction of survival from ATR was 0.770 (P = 0.004). The diagnostic cut-off value for ATR was 0.96. Because ATR is effective to predict neonatal survival in CDH fetuses and is easy to measure, it can be used as another powerful parameter for managing CDH fetuses. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  1. Molecular classification and survival prediction in human gliomas based on proteome analysis.

    Science.gov (United States)

    Iwadate, Yasuo; Sakaida, Tsukasa; Hiwasa, Takaki; Nagai, Yuichiro; Ishikura, Hiroshi; Takiguchi, Masaki; Yamaura, Akira

    2004-04-01

    The biological features of gliomas, which are characterized by highly heterogeneous biological aggressiveness even in the same histological category, would be precisely described by global gene expression data at the protein level. We investigated whether proteome analysis based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry can identify differences in protein expression between high- and low-grade glioma tissues. Proteome profiling patterns were compared in 85 tissue samples: 52 glioblastoma multiforme, 13 anaplastic astrocytomas, 10 atrocytomas, and 10 normal brain tissues. We could completely distinguish the normal brain tissues from glioma tissues by cluster analysis based on the proteome profiling patterns. Proteome-based clustering significantly correlated with the patient survival, and we could identify a biologically distinct subset of astrocytomas with aggressive nature. Discriminant analysis extracted a set of 37 proteins differentially expressed based on histological grading. Among them, many of the proteins that were increased in high-grade gliomas were categorized as signal transduction proteins, including small G-proteins. Immunohistochemical analysis confirmed the expression of identified proteins in glioma tissues. The present study shows that proteome analysis is useful to develop a novel system for the prediction of biological aggressiveness of gliomas. The proteins identified here could be novel biomarkers for survival prediction and rational targets for antiglioma therapy.

  2. EGFR expression level predicts response and overall survival in gastric cancer PDTX model treated with cetuximab

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective:hTe aim of this study was to determine whether the EGFR statuscould significantly predict some benefit in overall survival and response to cetuximab in advanced GC xenografts.Methods: Two hundred xenografts derived from 20 GC patients were established. Then they were divided into cetuximab treated group and control group randomly.Results:Among the cetuximab treated group, 4 GC cases were identified responded to cetuximab.hTose cetuximab treated PDX models had longer OS than non-treated. High EGFR mRNA expression and immunohistochemistry score are more prone to response to cetuximab. EGFR amplification, mRNA and protein overexpression were associated with the OS in cetuximab treated PDX models. Moreover, in the PDX models derived from EGFR ampliifcation, mRNA or protein overexpression cases, the OS is signiifcantly different between the cetuximab treated and control group, while the OS in not statistically different in other cases.Conclusion:EGFR status predicts sensitivity to therapy and survival in GC treated with cetuximab, especially the mRNA and protein expression level.

  3. A survival prediction model of rats in hemorrhagic shock using the random forest classifier.

    Science.gov (United States)

    Choi, Joon Yul; Kim, Sung Kean; Lee, Wan Hyung; Yoo, Tae Keun; Kim, Deok Won

    2012-01-01

    Hemorrhagic shock is the cause of one third of deaths resulting from injury in the world. Although many studies have tried to diagnose hemorrhagic shock early and accurately, such attempts were inconclusive due to compensatory mechanisms of humans. The objective of this study was to construct a survival prediction model of rats in hemorrhagic shock using a random forest (RF) model, which is a newly emerged classifier acknowledged for its performance. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), lactate concentration (LC), and perfusion (PF) measured in rats were used as input variables for the RF model and its performance was compared with that of a logistic regression (LR) model. Before constructing the models, we performed a 5-fold cross validation for RF variable selection and forward stepwise variable selection for the LR model to see which variables are important for the models. For the LR model, sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (ROC-AUC) were 1, 0.89, 0.94, and 0.98, respectively. For the RF models, sensitivity, specificity, accuracy, and AUC were 0.96, 1, 0.98, and 0.99, respectively. In conclusion, the RF model was superior to the LR model for survival prediction in the rat model.

  4. Do conflict resolution and recovery predict the survival of adolescents' romantic relationships?

    Directory of Open Access Journals (Sweden)

    Thao Ha

    Full Text Available Numerous studies have shown that being able to resolve and recover from conflicts is of key importance for relationship satisfaction and stability in adults. Less is known about the importance of these relationship dynamics in adolescent romantic relationships. Therefore, this study investigated whether conflict resolution and recovery predict breakups in middle adolescent couples. Couples who are able to resolve and recover from conflict were expected to demonstrate a lower probability of breaking up. In total, 80 adolescent couples (M age = 15.48, SD = 1.16 participated in a 4-wave prospective questionnaire and observational study, with one year between measurements. In addition to self-report measures, adolescents were observed in real-time during conflicts with their partners. Multilevel Proportional Hazard analyses revealed that, contrary to the hypothesis, conflict resolution and conflict recovery did not predict the likelihood of breakup. Survival differences were not attributable to conflict resolution or conflict recovery. More research is needed to consider the unique relationship factors of adolescent romantic relationships to determine why some relationships survive while others do not.

  5. Utilization of Data Mining Techniques for Prediction and Diagnosis of Tuberculosis Disease Survivability

    Directory of Open Access Journals (Sweden)

    K.R.Lakshmi

    2013-10-01

    Full Text Available The prediction and diagnosis of Tuberculosis survivability has been a challenging research problem for many researchers. Since the early dates of the related research, much advancement has been recorded in several related fields. For instance, thanks to innovative biomedical technologies, better explanatory prognostic factors are being measured and recorded; thanks to low cost computer hardware and software technologies, high volume better quality data is being collected and stored automatically; and finally thanks to better analytical methods, those voluminous data is being processed effectively and efficiently. Tuberculosis is one of the leading diseases for all people in developed countries including India. It is the most common cause of death in human being. The high incidence of Tuberculosis in all people has increased significantly in the last years. In this paper we have discussed various data mining approaches that have been utilized for Tuberculosis diagnosis and prognosis. This study paper summarizes various review and technical articles on Tuberculosis diagnosis and prognosis also we focus on current research being carried out using the data mining techniques to enhance the Tuberculosis diagnosis and prognosis. Here, we took advantage of those available technological advancements to develop the best prediction model for Tuberculosis survivability.

  6. Organism activity levels predict marine invertebrate survival during ancient global change extinctions.

    Science.gov (United States)

    Clapham, Matthew E

    2017-04-01

    Multistressor global change, the combined influence of ocean warming, acidification, and deoxygenation, poses a serious threat to marine organisms. Experimental studies imply that organisms with higher levels of activity should be more resilient, but testing this prediction and understanding organism vulnerability at a global scale, over evolutionary timescales, and in natural ecosystems remain challenging. The fossil record, which contains multiple extinctions triggered by multistressor global change, is ideally suited for testing hypotheses at broad geographic, taxonomic, and temporal scales. Here, I assess the importance of activity level for survival of well-skeletonized benthic marine invertebrates over a 100-million-year-long interval (Permian to Jurassic periods) containing four global change extinctions, including the end-Permian and end-Triassic mass extinctions. More active organisms, based on a semiquantitative score incorporating feeding and motility, were significantly more likely to survive during three of the four extinction events (Guadalupian, end-Permian, and end-Triassic). In contrast, activity was not an important control on survival during nonextinction intervals. Both the end-Permian and end-Triassic mass extinctions also triggered abrupt shifts to increased dominance by more active organisms. Although mean activity gradually returned toward pre-extinction values, the net result was a permanent ratcheting of ecosystem-wide activity to higher levels. Selectivity patterns during ancient global change extinctions confirm the hypothesis that higher activity, a proxy for respiratory physiology, is a fundamental control on survival, although the roles of specific physiological traits (such as extracellular pCO2 or aerobic scope) cannot be distinguished. Modern marine ecosystems are dominated by more active organisms, in part because of selectivity ratcheting during these ancient extinctions, so on average may be less vulnerable to global change

  7. Prediction of the survival and functional ability of severe stroke patients after ICU therapeutic intervention

    Directory of Open Access Journals (Sweden)

    Aoun-Bacha Zeina

    2008-06-01

    Full Text Available Abstract Background This study evaluated the benefits and impact of ICU therapeutic interventions on the survival and functional ability of severe cerebrovascular accident (CVA patients. Methods Sixty-two ICU patients suffering from severe ischemic/haemorrhagic stroke were evaluated for CVA severity using APACHE II and the Glasgow coma scale (GCS. Survival was determined using Kaplan-Meier survival tables and survival prediction factors were determined by Cox multivariate analysis. Functional ability was assessed using the stroke impact scale (SIS-16 and Karnofsky score. Risk factors, life support techniques and neurosurgical interventions were recorded. One year post-CVA dependency was investigated using multivariate analysis based on linear regression. Results The study cohort constituted 6% of all CVA (37.8% haemorrhagic/62.2% ischemic admissions. Patient mean(SD age was 65.8(12.3 years with a 1:1 male: female ratio. During the study period 16 patients had died within the ICU and seven in the year following hospital release. The mean(SD APACHE II score at hospital admission was 14.9(6.0 and ICU mean duration of stay was 11.2(15.4 days. Mechanical ventilation was required in 37.1% of cases. Risk ratios were; GCS at admission 0.8(0.14, (p = 0.024, APACHE II 1.11(0.11, (p = 0.05 and duration of mechanical ventilation 1.07(0.07, (p = 0.046. Linear coefficients were: type of CVA – haemorrhagic versus ischemic: -18.95(4.58 (p = 0.007, GCS at hospital admission: -6.83(1.08, (p = 0.001, and duration of hospital stay -0.38(0.14, (p = 0.40. Conclusion To ensure a better prognosis CVA patients require ICU therapeutic interventions. However, as we have shown, where tests can determine the worst affected patients with a poor vital and functional outcome should treatment be withheld?

  8. DNA fragmentation in brighter sperm predicts male fertility independently from age and semen parameters.

    Science.gov (United States)

    Muratori, Monica; Marchiani, Sara; Tamburrino, Lara; Cambi, Marta; Lotti, Francesco; Natali, Ilaria; Filimberti, Erminio; Noci, Ivo; Forti, Gianni; Maggi, Mario; Baldi, Elisabetta

    2015-09-01

    To evaluate whether sperm DNA fragmentation (sDF), measured in brighter, dimmer, and total populations, predicts natural conception, and to evaluate the intra-individual variability of sDF. Prospective study. Outpatient clinic and diagnostic laboratory. A total of 348 unselected patients and 86 proven fertile men. None. sDF was revealed with the use of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)/propidium iodide (PI). Receiver operating characteristic (ROC) curves were built before and after matching fertile men to patients for age (76:152) or semen parameters (68:136) or both (49:98). Intra-individual variability of sDF was assessed over 2 years. Brighter (area under ROC curve [AUC] 0.718 ± 0.54), dimmer (AUC 0.655 ± 0.63), and total (AUC 0.757 ± 0.54) sDF predict male fertility in unmatched and age- or semen parameters-matched subjects. After matching for both age and semen parameters, only brighter (AUC 0.711 ± 0.83) and total (AUC 0.675 ± 0.92) sDF predict male fertility. At high values of total sDF, brighter predicts natural conception better than total sDF. Intra-individual coefficients of variation of sDF were 9.2 ± 8.6% (n = 25), 12.9 ± 12.7% (n = 53), and 14.0 ± 12.6% (n = 70) over, respectively, 100-day and 1- and 2-year periods, appearing to be the most stable of the evaluated semen parameters. The predictive power of total sDF partially depends on age and semen parameters, whereas brighter sDF independently predicts natural conception. Therefore, brighter sDF is a fraction of sDF that adds new information to the routine semen analysis. At high levels of sDF, distinguishing the two sperm populations improves the predictive power of sDF. Overall, our results support the idea that TUNEL/PI can be of clinical usefulness in the male fertility workup. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer.

    Science.gov (United States)

    Lu, Yan; Govindan, Ramaswamy; Wang, Liang; Liu, Peng-yuan; Goodgame, Boone; Wen, Weidong; Sezhiyan, Ananth; Pfeifer, John; Li, Ya-fei; Hua, Xing; Wang, Yian; Yang, Ping; You, Ming

    2012-05-01

    About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19-25 nt and play important roles in gene regulation in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis of stage I NSCLC. MiRNAs extracted from 527 stage I NSCLC patients were profiled on the human miRNA expression profiling v2 panel (Illumina). The expression profiles were analyzed for their association with cancer subtypes, lung cancer brain metastasis and recurrence/relapse free survival (RFS). MiRNA expression patterns between lung adenocarcinoma and squamous cell carcinoma differed significantly with 171 miRNAs, including Let-7 family members and miR-205. Ten miRNAs associated with brain metastasis were identified including miR-145*, which inhibit cell invasion and metastasis. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 34 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype, whereas the second containing 27 miRNAs was adenocarcinoma specific. Both signatures were validated using formalin-fixed paraffin embedded and/or fresh frozen tissues in independent data set with 170 stage I patients. Our findings have important prognostic or therapeutic implications for the management of stage I lung cancer patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease.

  10. Factors predicting long-term survival in low-risk diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael B; Pedersen, Niels T; Christensen, Bjarne E

    2003-01-01

    population-based data from the Danish Lymphoma Group, we analyzed if prognostic clinical pretreatment factors could be identified in patients with low-risk DLBCL. One hundred seventy-seven patients, all with a prognostic profile as favorable as possible according to the IPI and treated with anthracycline-based...... combination chemotherapy (92%) or loco-regional radiotherapy/surgery (8%) with curative intent were included. The median age was 50 years and 170 achieved complete remission. The median follow-up time was 11 years. Twenty-six patients relapsed, with a median time to relapse of 12.1 months. Overall survival...... at 5 years and 10 years was 85% and 75%, respectively. Stage II was associated with poor response to treatment (P=0.044). In a multivariate analysis, Stage II (P=0.001) and age >50 years (P=0.043) were independently associated with poor outcome. Patients without these adverse factors had an excellent...

  11. [Aortic valve replacement as an independent predictive factor for later development of aortic dissection].

    Science.gov (United States)

    von Kodolitsch, Y; Simic, O; Bregenzer, T; Dresler, C; Haverich, A; Nienaber, C A

    1998-08-01

    Dissection of the ascending aorta (type A) following later after aortic valve replacement has been described with increasing frequency. This study analyzes the role of aortic valve replacement for the evolution of late dissection. In a series of 80 consecutive patients with type A dissection, a previous aortic valve replacement had been performed in 12 cases (15%). In addition to arterial hypertension (p syndrome (p factor for type A dissection. Dissection occurred 3 +/- 4 years after aortic valve replacement with a clinical and anatomical profile similar to classic dissection as proven by comparison to a group of 62 patients with classic dissection associated with arterial hypertension or Marfan syndrome. With 75% and 66%, respectively, 30 day and 1 year survival of patients with dissection following later after aortic valve replacement was similar to patients with classic type A dissection. Extensive thinning and/or fragility (p associated with a high risk for late dissection; this finding was substantiated by comparison to a control group of 10 consecutive patients with a similarly dilated aortic root but no dissection. Type and diameter of valve prostheses, cross-clamp time, NYHA functional class, and left ventricular ejection fraction were unrelated to late dissection. Previous aortic valve replacement is an independent predisposing factor for a dissection of the ascending aorta later. At the time of aortic valve replacement, prophylactic replacement or wrapping of the ascending aorta should be considered in patients with a thinned/fragile aortic wall even without a markedly dilated aortic root.

  12. Determination of HER2 phosphorylation at tyrosine 1221/1222 improves prediction of poor survival for breast cancer patients with hormone receptor-positive tumors

    DEFF Research Database (Denmark)

    Frogne, Thomas; Laenkholm, Anne-Vibeke; Lyng, Maria B

    2009-01-01

    as with overall survival. Expression of pAkt and pErk was not correlated with survival. In multivariate analysis, pHER2 expression was clearly an independent marker for poor disease-free survival and overall survival when tested against tumor size, tumor grade, nodal status and HER2. Lastly, comparison of HER...

  13. 25-Hydroxyvitamin D3 Deficiency Independently Predicts Cognitive Impairment in Patients with Systemic Lupus Erythematosus.

    Directory of Open Access Journals (Sweden)

    Sen Hee Tay

    Full Text Available Cognitive dysfunction has been reported in 20-80% of SLE patients. Converging evidence has indicated the importance of vitamin D as a neuroimmunomodulator for cognitive function. In this study, we evaluated the relationship between vitamin D and cognitive dysfunction.Consecutive age- and gender-matched SLE patients and healthy controls (HCs were administered Automated Neuropsychological Assessment Metrics in this cross-sectional study. The primary outcome was the total throughput score (TTS. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS. Levels of 25-hydroxyvitamin D [25(OHD3 and total 25(OHD] were measured using Liquid Chromatography-Tandem Mass Spectrometry.In total, 61 SLE patients and 61 HCs were studied. SLE patients scored significantly lower than HCs in the TTS (p = 0.004. There were no statistically significant differences in 25(OHD3 levels, total 25(OHD levels and total 25(OHD deficiency between SLE patients and HCs. However, more SLE patients had 25(OHD3 deficiency compared to HCs [12 (19.7% versus 2 (3.3%, p = 0.003]. Deficiency of 25(OHD3 (β = -63.667, SE = 27.456, p = 0.025, but not other vitamin D variables, independently predicted worse TTS after adjusting for age, education, gender, ethnicity, HADS-Total, duration of SLE, SELENA-SLEDAI, SLICC/ACR Damage Index and cumulative steroid dose in SLE patients. Age (β = -4.261, SE = 0.866, p < 0.001 was the only predictor of TTS after adjusting for education, gender, ethnicity, HADS-Total, vitamin D levels or status in HCs.Deficiency of 25(OHD3, a potentially modifiable risk factor, independently predicted cognitive impairment in SLE patients.

  14. Restructuring the navigational field: individual predisposition towards field independence predicts preferred navigational strategy.

    Science.gov (United States)

    Boccia, Maddalena; Piccardi, Laura; D'Alessandro, Adele; Nori, Raffaella; Guariglia, Cecilia

    2017-06-01

    To successfully navigate within an environment, individuals have to organize the spatial information in terms of salient landmarks, paths and general layout of the navigational environment. They may differ in the strategy they adopt to orientate themselves, with some individuals preferring to use salient landmarks (landmark spatial style, L-SS), others preferring to plan routes or paths through an egocentric strategy in which landmarks are connected with each other (route spatial style, R-SS) and others still create a global map-like configuration of the environment regardless of their own position in the environment (survey spatial style, S-SS). Here, we assessed whether Field independence (FI), that is the extent to which the individual perceives part of a field as discrete from the surrounding field rather than embedded in the field, predicted the individual's spatial style. We assessed the individual's spatial style using the spatial cognitive style test (SCST) and measured FI using the group embedded figure test (GEFT). We found that FI predicted general spatial ability, with a higher level of FI being associated with better performances on the SCST. Also, Field-independent individuals showed a marked preference for an S-SS. These results suggest that a higher level of FI is associated with better performance on higher level spatial tasks (i.e. R-SS and S-SS) that is tasks requiring individuals to restructure the "navigational field" according to the navigational goal. The results also suggest that a higher level of FI makes individuals more prone to use a global and complex map-like representation of the environment.

  15. TIMP-3 expression associates with malignant behaviors and predicts favorable survival in HCC.

    Directory of Open Access Journals (Sweden)

    Xuefeng Gu

    Full Text Available The tissue inhibitors of metalloproteinases (TIMPs are proteins that specifically inhibit the proteolytic activity of the matrix metalloproteinases (MMPs. TIMP-3, the only member of the TIMPs that can tightly bind to the extracellular matrix, has been identified as a unique tumor suppressor that demonstrates the ability to inhibit tumor angiogenesis, invasion, and metastasis. This study aimed to detect the expression of TIMP-3 in hepatocellular carcinoma (HCC and investigate the association between TIMP-3 expression and its clinicopathological significance in HCC patients. In the current study, reverse transcription-polymerase chain reaction (RT-PCR and Western blotting of HCC cell lines and one-step quantitative reverse transcription PCR (qPCR and immunohistochemistry (IHC analyses in HCC tissues were performed, to characterize the TIMP-3 expression. Kaplan-Meier survival and Cox regression analyses were utilized to evaluate the prognosis of 101 HCC patients. The results showed that the expression of TIMP-3 in HCC was significantly decreased relative to that of non-cancerous cells and tissues. Furthermore, the TIMP-3 expression was statistically associated with malignant behaviors of HCC, including portal vein invasion (p = 0.036 and lymph node metastasis (p = 0.030. Cox regression analysis revealed that TIMP-3 expression was an independent prognostic factor for disease-free survival (p = 0.039 and overall survival (p = 0.049. These data indicate that TIMP-3 expression is a valuable prognostic biomarker for HCC and that TIMP-3 expression suggests a favorable prognosis for HCC patients.

  16. Sociosexual attitudes and dyadic sexual desire independently predict women's preferences for male vocal masculinity.

    Science.gov (United States)

    O'Connor, Jillian J M; Jones, Benedict C; Fraccaro, Paul J; Tigue, Cara C; Pisanski, Katarzyna; Feinberg, David R

    2014-10-01

    Research suggests that the desire to behave sexually with a partner (dyadic sexual desire) may reflect desire for intimacy whereas solitary sexual desire may reflect pleasure seeking motivations more generally. Because direct reproductive success can only be increased with a sexual partner, we tested whether dyadic sexual desire was a better predictor of women's preferences for lower pitched men's voices (a marker of relatively high reproductive success) than was solitary sexual desire. In Study 1, women (N = 95) with higher dyadic sexual desire scores on the Sexual Desire Inventory-2 preferred masculinized male voices more than did women with lower dyadic sexual desire scores. We did not find a significant relationship between women's vocal masculinity preferences and their solitary sexual desire scores. In Study 2, we tested whether the relationship between voice preferences and dyadic sexual desire scores was related to differences in sociosexual orientation. Women (N = 80) with more positive attitudes towards uncommitted sex had stronger vocal masculinity preferences regardless of whether men's attractiveness was judged for short-term or long-term relationships. Independent of the effect of sociosexual attitudes, dyadic sexual desire positively predicted women's masculinity preferences when assessing men's attractiveness for short-term but not long-term relationships. These effects were independent of women's own relationship status and hormonal contraceptive use. Our results provide further evidence that women's mate preferences may independently reflect individual differences in both sexual desire and openness to short-term relationships, potentially with the ultimate function of maximizing the fitness benefits of women's mate choices.

  17. The Severity of Fatty Liver Disease Relating to Metabolic Abnormalities Independently Predicts Coronary Calcification

    Directory of Open Access Journals (Sweden)

    Ying-Hsiang Lee

    2011-01-01

    Full Text Available Background. Nonalcoholic fatty liver disease (NAFLD is one of the metabolic disorders presented in liver. The relationship between severity of NAFLD and coronary atherosclerotic burden remains largely unknown. Methods and Materials. We analyzed subjects undergoing coronary calcium score evaluation by computed tomography (MDCT and fatty liver assessment using abdominal ultrasonography. Framingham risk score (FRS and metabolic risk score (MRS were obtained in all subjects. A graded, semiquantitative score was established to quantify the severity of NAFLD. Multivariate logistic regression analysis was used to depict the association between NAFLD and calcium score. Results. Of all, 342 participants (female: 22.5%, mean age: 48.7±7.0 years met the sufficient information rendering detailed analysis. The severity of NAFLD was positively associated with MRS (X2=6.12, trend P<0.001 and FRS (X2=5.88, trend P<0.001. After multivariable adjustment for clinical variables and life styles, the existence of moderate to severe NAFLD was independently associated with abnormal calcium score (P<0.05. Conclusion. The severity of NAFLD correlated well with metabolic abnormality and was independently predict coronary calcification beyond clinical factors. Our data suggests that NAFLD based on ultrasonogram could positively reflect the burden of coronary calcification.

  18. Predicting Survival from Telomere Length versus Conventional Predictors: A Multinational Population-Based Cohort Study.

    Science.gov (United States)

    Glei, Dana A; Goldman, Noreen; Risques, Rosa Ana; Rehkopf, David H; Dow, William H; Rosero-Bixby, Luis; Weinstein, Maxine

    2016-01-01

    Telomere length has generated substantial interest as a potential predictor of aging-related diseases and mortality. Some studies have reported significant associations, but few have tested its ability to discriminate between decedents and survivors compared with a broad range of well-established predictors that include both biomarkers and commonly collected self-reported data. Our aim here was to quantify the prognostic value of leukocyte telomere length relative to age, sex, and 19 other variables for predicting five-year mortality among older persons in three countries. We used data from nationally representative surveys in Costa Rica (N = 923, aged 61+), Taiwan (N = 976, aged 54+), and the U.S. (N = 2672, aged 60+). Our study used a prospective cohort design with all-cause mortality during five years post-exam as the outcome. We fit Cox hazards models separately by country, and assessed the discriminatory ability of each predictor. Age was, by far, the single best predictor of all-cause mortality, whereas leukocyte telomere length was only somewhat better than random chance in terms of discriminating between decedents and survivors. After adjustment for age and sex, telomere length ranked between 15th and 17th (out of 20), and its incremental contribution was small; nine self-reported variables (e.g., mobility, global self-assessed health status, limitations with activities of daily living, smoking status), a cognitive assessment, and three biological markers (C-reactive protein, serum creatinine, and glycosylated hemoglobin) were more powerful predictors of mortality in all three countries. Results were similar for cause-specific models (i.e., mortality from cardiovascular disease, cancer, and all other causes combined). Leukocyte telomere length had a statistically discernible, but weak, association with mortality, but it did not predict survival as well as age or many other self-reported variables. Although telomere length may eventually help scientists

  19. Distance in cancer gene expression from stem cells predicts patient survival.

    Science.gov (United States)

    Riester, Markus; Wu, Hua-Jun; Zehir, Ahmet; Gönen, Mithat; Moreira, Andre L; Downey, Robert J; Michor, Franziska

    2017-01-01

    The degree of histologic cellular differentiation of a cancer has been associated with prognosis but is subjectively assessed. We hypothesized that information about tumor differentiation of individual cancers could be derived objectively from cancer gene expression data, and would allow creation of a cancer phylogenetic framework that would correlate with clinical, histologic and molecular characteristics of the cancers, as well as predict prognosis. Here we utilized mRNA expression data from 4,413 patient samples with 7 diverse cancer histologies to explore the utility of ordering samples by their distance in gene expression from that of stem cells. A differentiation baseline was obtained by including expression data of human embryonic stem cells (hESC) and human mesenchymal stem cells (hMSC) for solid tumors, and of hESC and CD34+ cells for liquid tumors. We found that the correlation distance (the degree of similarity) between the gene expression profile of a tumor sample and that of stem cells orients cancers in a clinically coherent fashion. For all histologies analyzed (including carcinomas, sarcomas, and hematologic malignancies), patients with cancers with gene expression patterns most similar to that of stem cells had poorer overall survival. We also found that the genes in all undifferentiated cancers of diverse histologies that were most differentially expressed were associated with up-regulation of specific oncogenes and down-regulation of specific tumor suppressor genes. Thus, a stem cell-oriented phylogeny of cancers allows for the derivation of a novel cancer gene expression signature found in all undifferentiated forms of diverse cancer histologies, that is competitive in predicting overall survival in cancer patients compared to previously published prediction models, and is coherent in that gene expression was associated with up-regulation of specific oncogenes and down-regulation of specific tumor suppressor genes associated with regulation of

  20. Is obesity predictive of cardiovascular dysfunction independent of cardiovascular risk factors?

    Science.gov (United States)

    DeVallance, E; Fournier, S B; Donley, D A; Bonner, D E; Lee, K; Frisbee, J C; Chantler, P D

    2015-02-01

    Obesity is thought to exert detrimental effects on the cardiovascular (CV) system. However, this relationship is impacted by the co-occurrence of CV risk factors, type 2 diabetes (T2DM) and overt disease. We examined the relationships between obesity, assessed by body mass index (BMI) and waist circumference (WC), and CV function in 102 subjects without overt CV disease. We hypothesized that obesity would be independently predictive of CV remodeling and functional differences, especially at peak exercise. Brachial (bSBP) and central (cSBP) systolic pressure, carotid-to-femoral pulse wave velocity (PWVcf) augmentation index (AGI; by SphygmoCor), and carotid remodeling (B-mode ultrasound) were examined at rest. Further, peak exercise cardiac imaging (Doppler ultrasound) was performed to measure the coupling between the heart and arterial system. In backward elimination regression models, accounting for CV risk factors, neither BMI nor WC were predictors of carotid thickness or PWVcf; rather age, triglycerides and hypertension were the main determinants. However, BMI and WC predicted carotid cross-sectional area and lumen diameter. When examining the relationship between body size and SBP, BMI (β=0.32) and WC (β=0.25) were predictors of bSBP (Pdisease, and after accounting for CV risk factors, is susceptible to pathophysiological adaptations that may predispose individuals to an increased risk of CV events.

  1. Predictive value of assessing diastolic strain rate on survival in cardiac amyloidosis patients with preserved ejection fraction.

    Directory of Open Access Journals (Sweden)

    Dan Liu

    Full Text Available Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA, we hypothesized that speckle-tracking-imaging (STI derived longitudinal early diastolic strain rate (LSRdias could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50%.Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients.Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years. Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views.Nineteen (46% out of 41 CA patients died during a median of 16 months (quartiles 5-35 months follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6 ± 2 vs. 8 ± 3 mm, global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p < 0.05. NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.17-3.26, P = 0.010, global LSRdias (HR = 7.30, 95% CI 2.08-25.65, P = 0.002, and E/LSRdias (HR = 2.98, 95% CI 1.54-5.79, P = 0.001 remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S-1 (sensitivity 68%, specificity 67%. Global LSRdias < 0.85 S-1 predicted a 4-fold increased mortality in CA patients with preserved LVEF.STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF.

  2. Can survival prediction be improved by merging gene expression data sets?

    Directory of Open Access Journals (Sweden)

    Haleh Yasrebi

    Full Text Available BACKGROUND: High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite (a The diversity of microarray platforms used. (b The heterogeneity of patients cohorts. (c The heterogeneity of breast cancer disease. (d Substantial variation of time to death or relapse. (e The reduced number of genes in the merged data

  3. Infused autograft lymphocyte to monocyte ratio predicts survival in classical Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Porrata LF

    2015-02-01

    Full Text Available Luis F Porrata, David J Inwards, Stephen M Ansell, Ivana N Micallef, Patrick B Johnston, William J Hogan, Svetomir N Markovic Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA Abstract: The infused autograft lymphocyte to monocyte ratio (A-LMR as a surrogate marker of host immunity (ie, absolute lymphocyte count and CD14+ HLA-DRlow/neg immunosuppressive monocytes (ie, absolute monocyte count is a prognostic factor for patients with diffuse large B-cell lymphoma after autologous peripheral hematopoietic stem cell transplantation (APHSCT. Thus, we set out to investigate if A-LMR can also affect survival post-APHSCT in classical Hodgkin lymphoma. From 1994 to 2012, 183 patients with classical Hodgkin lymphoma who underwent APHSCT were studied. The patients were randomly divided into a training set (n=122 and a validation set (n=61. The receiver operating characteristic and area under the curve identified an A-LMR ≥1 as the best cut-off value and validated by the k-fold cross-validation in the training set. Multivariate analysis showed A-LMR to be an independent prognostic factor for survival in the training set. Patients with an A-LMR ≥1.0 experienced a superior overall survival (OS versus patients with an A-LMR <1.0 (median OS not reached versus 40.4 months, 5-year OS rates of 86% [95% CI 72–93] versus 43% [95% CI 28–58], P<0.0001, respectively in the training set. In the validation set, an A-LMR ≥1 showed a median OS of not reached versus 41.4 months for an A-LMR ,1, 5-year OS rates of 90% (95% CI 73–97 versus 48% (95% CI 28–68; P<0.0001. A-LMR provides a platform to engineer an autograft versus tumor effect to improve clinical outcomes in patients with classical Hodgkin lymphoma undergoing APHSCT. Keywords: autograft absolute lymphocyte to monocyte count ratio, survival, autologous peripheral hematopoietic stem cell transplantation, classical Hodgkin lymphoma

  4. Can subjective global assessment of nutritional status predict survival in ovarian cancer?

    Directory of Open Access Journals (Sweden)

    Gupta Digant

    2008-10-01

    Full Text Available Abstract Background Malnutrition is a significant problem in patients with ovarian cancer. The goal of this study was to investigate the prognostic role of Subjective Global Assessment (SGA in patients with ovarian cancer treated in an integrative cancer treatment setting. Methods We evaluated a case series of 132 ovarian cancer patients treated at Cancer Treatment Centers of America® from Jan 2001 to May 2006. SGA was used to assess nutritional status at baseline. Using SGA, patients were classified as well nourished (SGA A, moderately malnourished (SGA B or severely malnourished (SGA C. Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of SGA independent of other factors. Results Of 132 patients, 24 were newly diagnosed while 108 had received prior treatment. 15 had stage I disease at diagnosis, 8 stage II, 85 stage III and 17 stage IV. The median age at presentation was 54.4 years (range 25.5 – 82.5 years. 66 patients were well-nourished (SGA A, 35 moderately malnourished (SGA B and 31 severely malnourished (SGA C. Well nourished patients had a median survival of 19.3 months (95% CI: 14.1 to 24.5, moderately malnourished 15.5 months (95% CI: 5.8 to 25.1, and severely malnourished 6.7 months (95% CI: 4.1 to 9.3; the difference being statistically significant (p = 0.0003. Multivariate Cox modeling, after adjusting for stage at diagnosis and prior treatment history found that moderately malnourished and severely malnourished status were associated with a relative risk of 2.1 (95% CI: 1.2 to 3.6, p = 0.008 and 3.4 (95% CI: 1.9 to 5.8, p Conclusion Univariate and multivariate survival analyses found that low SGA scores (i.e. well-nourished status are associated with better survival outcomes. This study lends support to the role of aggressive nutritional intervention in improving patient outcomes in cancer care.

  5. PREDICTIVE MODEL FOR SURVIVAL AND GROWTH OF SALMONELLA TYPHIMURIUM DT104 ON CHICKEN SKIN DURING TEMPERATURE ABUSE

    Science.gov (United States)

    To better predict risk of Salmonella infection from chicken subjected to temperature abuse, a study was undertaken to develop a predictive model for survival and growth of Salmonella Typhimurium DT104 on chicken skin with native micro flora. For model development, chicken skin portions were inocula...

  6. Prediction models for risk of developing type 2 diabetes : systematic literature search and independent external validation study

    NARCIS (Netherlands)

    Abbasi, Ali; Peelen, Linda M.; Corpeleijn, Eva; van der Schouw, Yvonne T.; Stolk, Ronald P.; Spijkerman, Annemieke M. W.; van der A, Daphne L.; Moons, Karel G. M.; Navis, Gerjan; Bakker, Stephan J. L.; Beulens, Joline W. J.

    2012-01-01

    Objective To identify existing prediction models for the risk of development of type 2 diabetes and to externally validate them in a large independent cohort. Data sources Systematic search of English, German, and Dutch literature in PubMed until February 2011 to identify prediction models for diabe

  7. Neisseria gonorrhoeae survive intraleukocytic oxygen-independent antimicrobial capacities of anaerobic and aerobic granulocytes in the presence of pyocin lethal for extracellular gonococci.

    Science.gov (United States)

    Casey, S G; Shafer, W M; Spitznagel, J K

    1986-05-01

    The resistance of a piliated, transparent variant of Neisseria gonorrhoeae FA19 to intraleukocytic killing by human polymorphonuclear neutrophils (PMN) was examined. In both aerobic and anaerobic PMN monolayers, approximately 2% of the intracellular gonococci survived for as long as 165 min. Anaerobic PMN were as effective as aerobic PMN in the intracellular killing of gonococci. Hence, O2-independent antimicrobial systems of PMN performed a significant role in the intraleukocytic killing of gonococci were intracellular was supported by the elimination of extracellular bacteria by the addition of pyocin 103 and confirmed by the fluorescent antibody staining of intact gonococci after the PMN were permeabilized to antibody with a Formalin-acetone treatment of PMN monolayers. Our data indicate that while the majority of ingested gonococci are killed by O2-independent antimicrobial systems, a small number (about 2%), survive even when care is taken to eliminate extracellular bacteria.

  8. LncRNA Expression Discriminates Karyotype and Predicts Survival in B-lymphoblastic Leukemia

    Science.gov (United States)

    Fernando, Thilini R.; Rodriguez-Malave, Norma I.; Waters, Ella V.; Yan, Weihong; Casero, David; Basso, Giuseppe; Pigazzi, Martina; Rao, Dinesh S.

    2015-01-01

    Long non-coding RNAs (lncRNAs) have been found to play a role in gene regulation with dysregulated expression in various cancers. The precise role that lncRNA expression plays in the pathogenesis of B-acute lymphoblastic leukemia (B-ALL) is unknown. Therefore, unbiased microarray profiling was performed on human B-ALL specimens and it was determined that lncRNA expression correlates with cytogenetic abnormalities, which was confirmed by RT-qPCR in a large set of B-ALL cases. Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B-cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development. Implications lncRNA expression has the potential to segregate the common subtypes of B-ALL, predict the cytogenetic subtype, and indicate prognosis. PMID:25681502

  9. Consciousness levels one week after admission to a palliative care unit improve survival prediction in advanced cancer patients.

    Science.gov (United States)

    Tsai, Jaw-Shiun; Chen, Chao-Hsien; Wu, Chih-Hsun; Chiu, Tai-Yuan; Morita, Tatsuya; Chang, Chin-Hao; Hung, Shou-Hung; Lee, Ya-Ping; Chen, Ching-Yu

    2015-02-01

    Consciousness is an important factor of survival prediction in advanced cancer patients. However, effects on survival of changes over time in consciousness in advanced cancer patients have not been fully explored. This study evaluated changes in consciousness after admission to a palliative care unit and their correlation with prognosis in terminal cancer patients. This is a prospective observational study. From a palliative care unit in Taiwan, 531 cancer patients (51.8% male) were recruited. Consciousness status was assessed at admission and one week afterwards and recorded as normal or impaired. The mean age was 65.28±13.59 years, and the average survival time was 23.41±37.69 days. Patients with normal consciousness at admission (n=317) had better survival than those with impaired consciousness at admission (n=214): (17.0 days versus 6.0 days, pconsciousness at admission had a higher percentage of survival than the impaired (78.9% versus 44.3%, pconsciousness levels: (1) normal at admission and one week afterwards, (2) impaired at admission but normal one week afterwards, (3) normal at admission but impaired one week afterwards, and (4) impaired both at admission and one week afterwards. The former two groups had significantly better survival than the latter two groups: (median survival counted from day 7 after admission), 25.5, 27.0, 7.0, and 7.0 days, respectively. Consciousness levels one week after admission should be integrated into survival prediction in advanced cancer patients.

  10. Drug release from extruded solid lipid matrices: theoretical predictions and independent experiments.

    Science.gov (United States)

    Güres, Sinan; Siepmann, Florence; Siepmann, Juergen; Kleinebudde, Peter

    2012-01-01

    The aim of this study was to use a mechanistically realistic mathematical model based on Fick's second law to quantitatively predict the release profiles from solid lipid extrudates consisting of a ternary matrix. Diprophylline was studied as a freely water-soluble model drug, glycerol tristearate as a matrix former and polyethylene glycol or crospovidone as a pore former (blend ratio: 50:45:5%w/w/w). The choice of these ratios is based on former studies. Strains with a diameter of 0.6, 1, 1.5, 2.7 and 3.5mm were prepared using a twin-screw extruder at 65 °C and cut into cylinders of varying lengths. Drug release in demineralised water was measured using the USP 32 basket apparatus. Based on SEM pictures of extrudates before and after exposure to the release medium as well as on DSC measurements and visual observations, an analytical solution of Fick's second law of diffusion was identified in order to quantify the resulting diprophylline release kinetics from the systems. Fitting the model to one set of experimentally determined diprophylline release kinetics from PEG containing extrudates allowed determining the apparent diffusion coefficient of this drug (or water) in this lipid matrix. Knowing this value, the impact of the dimensions of the cylinders on drug release could be quantitatively predicted. Importantly, these theoretical predictions could be confirmed by independent experimental results. Thus, diffusion is the dominant mass transport mechanism controlling drug release in this type of advanced drug delivery systems. In contrast, theoretical predictions of the impact of the device dimensions in the case of crospovidone containing extrudates significantly underestimated the real diprophylline release rates. This could be attributed to the disintegration of this type of dosage forms when exceeding a specific minimal device diameter. Thus, mathematical modelling can potentially significantly speed up the development of solid lipid extrudates, but care has

  11. Systemic Inflammatory Response Syndrome (SIRS) Score Independently Predicts Poor Outcome in Isolated Traumatic Brain Injury.

    Science.gov (United States)

    Jacome, Tomas; Tatum, Danielle

    2017-05-25

    Systemic inflammatory response syndrome (SIRS) is frequently observed after various types of acute cerebral injury and has been linked to clinical deterioration in non-traumatic brain injury (TBI). SIRS scores have also been shown to be predictive of length of stay and mortality in trauma patients. We aimed to determine the prognostic utility of SIRS present at admission in trauma patients with isolated TBI. This was a 5-year retrospective cohort study of adults (≥18 years) with isolated TBI admitted to a Level II trauma center. The prognostic value of SIRS, total SIRS scores, and each SIRS criterion was examined by Χ (2) and logistic regression analyses. Of the 330 patients identified, 50 (15.2%) met SIRS criteria. SIRS was significantly associated with poor outcome (P SIRS score of 2 on admission (P = 0.007) and increased significantly to 6.5 times in patients with a SIRS score of 3 (P = 0.002). Logistic regression demonstrated SIRS and each criterion to be significant independent prognostic factors (SIRS, P = 0.030; body temperature, P = 0.006; tachypnea, P = 0.022, tachycardia P = 0.023). SIRS at admission is an independent predictor of poor outcome in isolated TBI patients. These data demonstrate SIRS to be an important clinical tool that may be used in facilitating prognostication, particularly in elderly trauma patients. Future prospective studies aimed at therapeutic interventions to mitigate SIRS in TBI patients are warranted. Prognostic, Level III.

  12. Predicting dissolved inorganic nitrogen leaching in European forests using two independent databases.

    Science.gov (United States)

    Dise, N B; Rothwell, J J; Gauci, V; van der Salm, C; de Vries, W

    2009-02-15

    Regional-scale databases can be particularly useful for identifying relationships between dissolved inorganic nitrogen (N) leaching in forests and environmental drivers, which in turn allow an assessment of the risk of ecosystem damage, such as forest acidification and eutrophication of downstream water bodies. However, detecting the 'signal' of a significant correlate to N leaching against a background of wide variability in other factors requires a large number of sites, and the validation of models developed requires a similarly large number of independent sites. Here we use two large and fully independent databases of forest ecosystems across Europe to develop and validate indicators of N saturation and leaching. One database was used for model development and the other for validating these models. Among 35 variables considered, the most significant indicators of N leaching in the model development database were: the flux of dissolved inorganic N in deposition, mean annual temperature, mean altitude, the site drainage (plot vs catchment), needle- and litter-N concentration, organic horizon C:N ratio, and subsoil pH. Altitude was not a consistent predictor (it was significant in the development database but not in the validation database), and needle and litter N concentration, plot vs catchment, and subsoil pH all showed high intercorrelation with N deposition and so were not significant in models already including N deposition. The most consistent and useful indicators of N leaching were throughfall N deposition, organic horizon C:N ratio and mean annual temperature. Sites receiving low levels of N deposition (<8 kg N ha(-1) y(-1)) showed very low output fluxes of N and were simulated separately from more polluted forests. In general, the models successfully predicted N leaching (mean of +/-5 kg N ha(-1) y(-1) between observed and predicted) from forests at early to intermediate stages of nitrogen saturation but not from nitrogen-saturated sites. Thus, simple

  13. Baseline CSF p-tau levels independently predict progression of hippocampal atrophy in Alzheimer disease

    Science.gov (United States)

    Henneman, W J.P.; Vrenken, H; Barnes, J; Sluimer, I C.; Verwey, N A.; Blankenstein, M A.; Klein, M; Fox, N C.; Scheltens, P; Barkhof, F; van der Flier, W M.

    2009-01-01

    Objective: To investigate whether baseline CSF biomarkers are associated with hippocampal atrophy rate as a measure of disease progression in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls, controlling for baseline neuropsychological and MRI findings. Methods: We assessed data from 31 patients with AD, 25 patients with MCI, and 19 controls (mean age 68 ± 8 years; 39 [52%] female) who visited our memory clinic and had received serial MRI scanning (scan interval 1.7 ± 0.7 years). At baseline, CSF biomarkers (amyloid β 1-42, tau, and tau phosphorylated at threonine 181 [p-tau]) were obtained, as well as neuropsychological data. Baseline MRI scans were assessed using visual rating scales for medial temporal lobe atrophy (MTA), global cortical atrophy, and white matter hyperintensities. Hippocampal atrophy rates were estimated using regional nonlinear “fluid” registration of follow-up scan to baseline scan. Results: Stepwise multiple linear regression, adjusted for age and sex, showed that increased CSF p-tau levels (β [standard error]: −0.79 [0.35]) at baseline was independently associated with higher subsequent hippocampal atrophy rates (p < 0.05), together with poorer memory performance (0.09 [0.04]) and more severe MTA (−0.60 [0.21]). The association of memory function with hippocampal atrophy rate was explained by the link with diagnosis, because it disappeared from the model after we additionally corrected for diagnosis. Conclusions: Baseline CSF levels of tau phosphorylated at threonine 181 are independently associated with subsequent disease progression, as reflected by hippocampal atrophy rate. This effect is independent of baseline neuropsychological and MRI predictors. Our results imply that predicting disease progression can best be achieved by combining information from different modalities. GLOSSARY Aβ1-42 = amyloid β 1-42; AD = Alzheimer disease; FOV = field of view; GCA = global cortical

  14. Thrombocytosis at secondary cytoreduction for recurrent ovarian cancer predicts suboptimal resection and poor survival.

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    Cohen, Joshua G; Tran, Arthur-Quan; Rimel, B J; Cass, Ilana; Walsh, Christine S; Karlan, Beth Y; Li, Andrew J

    2014-03-01

    A growing body of evidence supports a role for thrombocytosis in the promotion of epithelial ovarian cancer biology. However, studies have only linked preoperative platelet count at time of initial cytoreductive surgery to clinical outcome. Here, we sought to determine the impact of elevated platelet count at time of secondary cytoreductive surgery (SCS) for recurrent disease. Under an IRB-approved protocol, we identified 107 women with invasive epithelial ovarian cancer who underwent SCS between January 1997 and June 2012. We reviewed clinical, laboratory, and pathologic records from this retrospective cohort. The data was analyzed using the chi-squared, Fisher's exact, Cox proportional hazards, and Kaplan-Meier tests. We defined thrombocytosis as a platelet count ≥ 350 × 10(9)/L and optimal resection at SCS as microscopic residual disease. Thirteen of 107 women (12%) with recurrent ovarian cancer had thrombocytosis prior to SCS. Preoperative thrombocytosis at SCS was associated with failure to undergo optimal resection (p=0.0001). Women with preoperative thrombocytosis at time of SCS demonstrated shorter overall survival (33 months) compared to those with normal platelet counts (46 months, p=0.004). On multivariate analysis, only preoperative platelet count retained significance as an independent prognostic factor (p=0.025) after controlling for age at SCS (p=0.90), disease free interval from primary treatment (0.06), and initial stage of disease (0.66). Elevated platelet count at time of SCS is associated with suboptimal resection and shortened overall survival. These data provide further evidence supporting a plausible role for thrombocytosis in aggressive ovarian tumor biology. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. High expression of HMGA2 predicts poor survival in patients with clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Na N

    2016-11-01

    Full Text Available Ning Na,1,* Tujie Si,2,* Zhengyu Huang,1,* Bin Miao,1 Liangqing Hong,1 Heng Li,1 Jiang Qiu,2 Jianguang Qiu3 1Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, 2Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, 3Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: High-mobility group AT-hook 2 (HMGA2 is involved in a wide spectrum of biological processes and is upregulated in several tumors, but its role in renal carcinoma remains unclear. The aim of this study was to examine the expression of HMGA2 and its relationship to the overall survival (OS of patients with non-metastatic clear cell renal cell carcinoma (ccRCC following surgery. The expression of HMGA2 was evaluated retrospectively by immunohistochemistry (IHC in 162 patients with ccRCC who underwent nephrectomy in 2003 and 2004. An IHC analysis revealed that HMGA2 was expressed in the nuclei of tumor cells in 146 (90.1% patients with ccRCC. The level of HMGA2 was positively correlated with tumor size, lymph node metastasis, and Fuhrman Grade. A Kaplan–Meier analysis with log-rank test found that patients with high HMGA2 expression had a poor outcome and that patients with low HMGA2 expression had better survival. Cox regression analysis showed that HMGA2 expression could serve as an independent prognostic factor for ccRCC patients. The efficacy of the following prognostic models was improved when HMGA2 expression was added: tumor node metastasis stage, UCLA Integrated Scoring System, Mayo Clinic stage, size, grade, and necrosis score. In summary, this study showed that HMGA2 expression is an independent prognostic factor for OS in patients with ccRCC. HMGA2 was found to be a valuable biomarker for ccRCC progression. Keywords: renal carcinoma, high-mobility group protein A

  16. Pretreatment Evaluation of Microcirculation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Survival in Primary Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    DeVries, Alexander Friedrich [Department of Radio-Oncology, Academic Teaching Hospital Feldkirch, Feldkirch (Austria); Piringer, Gudrun, E-mail: gudrun.piringer@hotmail.com [Department of Oncology, Wels-Grieskirchen Medical Hospital, Wels (Austria); Kremser, Christian; Judmaier, Werner [Department of Radiology, Innsbruck Medical University, Innsbruck (Austria); Saely, Christoph Hubert [Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch (Austria); Lukas, Peter [Department of Radio-Oncology, Innsbruck Medical University, Innsbruck (Austria); Öfner, Dietmar [Department of Surgery, Paracelsus Medical University, Salzburg (Austria)

    2014-12-01

    Purpose: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. Methods and Materials: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T{sub 1} mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration–time curve divided by the maximum of the arterial input function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. Results: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). Conclusions: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.

  17. Developing and comparing two different prognostic indexes for predicting disease-free survival of nonmetastatic breast cancer patients

    OpenAIRE

    TOKATLI, Zehra Füsun; Türe, Mevlüt; Ömürlü, İmran Kurt; ALAS, Ruşen Çoşar; Uzal, Mustafa Cem

    2011-01-01

    To determine 2 different prognostic indexes (PI) for the differentiation of subgroups of nonmetastatic breast cancer patients with the Cox regression analysis and survival tree (ST) methods and the additional usage of the Kaplan-Meier estimates to investigate the predictive power of these methods. Materials and methods: Prognostic factors data were collected for 410 patients. The Cox regression analysis examines the relationship of the survival distribution and covariates. The ST method is ...

  18. Factors predicting survival for HIV-infected patients with respiratory failure.

    Science.gov (United States)

    van Leeuwen, H J; Boereboom, F T; Pols, M A; Hoepelman, A I; Savelkoul, J T

    2000-09-01

    Despite improved treatment modalities, the mortality of HIV infected patients admitted to the intensive care unit with respiratory failure remains high. To help ICU physicians in advising HIV infected patients whether to undergo mechanical ventilation, we retrospectively investigated prognostic factors predicting hospital outcome for HIV-infected patients, admitted to a medical intensive care unit with respiratory failure before the era of highly-active anti-retroviral therapy. A retrospective chart review was carried out of all HIV-infected patients with respiratory failure admitted to the medical ICU of a Dutch University Hospital between 1991 and 1997. In the six year period, 29 HIV-infected patients were admitted to the ICU for respiratory failure. Mechanical ventilation, CD4 cell count, APACHE II score, APACHE III score, ARDS and length of ICU stay all differed significantly between survivors and non-survivors. However, a multivariate analysis only showed the need for mechanical ventilation as an independent risk factor for mortality. The only combination of factors able to accurately predict mortality for the individual patient was the development of ARDS and the requirement of mechanical ventilation. The combination of mechanical ventilation and ARDS accurately predicts hospital outcome in HIV-infected patients presenting with respiratory failure before the HAART era.

  19. High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

    Science.gov (United States)

    Seppälä, Miia; Pohjola, Konsta; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Renkonen, Risto; Lemström, Karl; Paavonen, Timo; Toppila-Salmi, Sanna

    2016-12-01

    Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.

  20. Functional T cells targeting NY-ESO-1 or Melan-A are predictive for survival of patients with distant melanoma metastasis.

    Science.gov (United States)

    Weide, Benjamin; Zelba, Henning; Derhovanessian, Evelyna; Pflugfelder, Annette; Eigentler, Thomas K; Di Giacomo, Anna Maria; Maio, Michele; Aarntzen, Erik H J G; de Vries, I Jolanda M; Sucker, Antje; Schadendorf, Dirk; Büttner, Petra; Garbe, Claus; Pawelec, Graham

    2012-05-20

    To analyze the prognostic relevance of circulating T cells responding to NY-ESO-1, Melan-A, MAGE-3, and survivin in patients with melanoma with distant metastasis. We examined 84 patients with follow-up after analysis (cohort A), 18 long-term survivors with an extraordinarily favorable course of disease before analysis (> 24 months survival after first occurrence of distant metastases; cohort B), and 14 healthy controls. Circulating antigen-reactive T cells were characterized by intracellular cytokine staining after in vitro stimulation. In cohort A patients, the presence of T cells responding to peptides from NY-ESO-1, Melan-A, or MAGE-3 and the M category according to the American Joint Committee on Cancer classification were significantly associated with survival. T cells responding to NY-ESO-1 and Melan-A (hazard ratios, 0.29 and 0.18, respectively) remained independent prognostic factors in Cox regression analysis and were superior to the M category in predicting outcome. Median survival of patients possessing T cells responding to NY-ESO-1, Melan-A, or both was 21 months, compared with 6 months for all others. NY-ESO-1-responsive T cells were detected in 70% of cohort A patients surviving > 18 months and in 50% of cohort B patients. Melan-A responses were found in 42% and 47% of patients in cohorts A and B, respectively. In contrast, the proportion was only 22% for NY-ESO-1 and 23% for Melan-A in those who died within 6 months. The presence of circulating T cells responding to Melan-A or NY-ESO-1 had strong independent prognostic impact on survival in advanced melanoma. Our findings support the therapeutic relevance of Melan-A and NY-ESO-1 as targets for immunotherapy.

  1. The serum concentrations of leptin and MCP-1 independently predict low back pain duration.

    Science.gov (United States)

    Lippi, Giuseppe; Dagostino, Concetta; Buonocore, Ruggero; Aloe, Rosalia; Bonaguri, Chiara; Fanelli, Guido; Allegri, Massimo

    2017-08-28

    Low back pain (LBP) is a very frequent condition, affecting most people at some point throughout their life. This cross-sectional study was aimed to investigate a selected panel of cytokines and inflammatory biomarkers in patients with or without LBP. The study population consisted of 104 patients diagnosed with LBP (52 non-persistent and 52 persistent) and 52 healthy subjects with no LBP. Blood samples were collected for assessment of adiponectin, leptin, monocyte chemoattractant protein-1 (MCP-1) and C reactive protein (CRP). The duration of LBP was categorized as "no pain", "non-persistent LBP" and "persistent LBP". Higher values of CRP and lower concentrations of both leptin and MCP-1 were found in LBP patients compared to controls, whereas adiponectin did not differ among groups. MCP-1 was also lower in patients with non-persistent than in those with persistent LBP. Age, leptin (relative risk, 11.8; 95% CI, 3.9-35.8) and MCP-1 (relative risk, 2.7; 95% CI, 1.7-4.4) were independently associated with presence and duration of LBP. The combination of age, leptin and MCP-1 predicted 61% of the risk of LBP duration. The area under the curve of MCP-1 for distinguishing persistent from non-persistent LBP was 0.65 (95% CI, 0.54-0.76). Then results of our study suggest that leptin and MCP-1 may be promising biomarkers for diagnosis of acute LBP and its risk to become chronic.

  2. Comparison of the RTS and ISS scores on prediction of survival chances in multiple trauma patients.

    Science.gov (United States)

    Akhavan Akbari, G; Mohammadian, A

    2012-01-01

    Trauma represents the third cause of death after cardio vascular disease and tumors. Also in Iran, road accidents are one of the leading causes of death. Rapid evaluation of trauma severity and prediction of prognosis and mortality rate and probability of survival and rapid treatment of patients is necessary. One of the useful instruments for this is ISS and RTS scoring systems. This study evaluated 70 multi trauma patients in Fatemi trauma center affiliated to Ardabil University of medical science. This study was prospective study populations were 70 trauma patients admitted in Fatemi trauma center. During the II month, and patients data was collected by clinical evaluating of patients and follow up them and arranged as a questionnaire then related findings were evaluated by SPSS software. The average age of patients was 37.6±23.5 years and minimum and maximum age was 1 and 85 years. The most common involved group was 10-19 years (13 men and 1 woman). 81.4% of patients (57 cases were male) and 18.6% were female (13 cases). The most common causes of trauma was car accident with 64.2% frequency (43 cases) and then motorcycle accident with 16.4% frequency (11 cases) and all injured patient due to motorcycle accident compose the age group less than 40 years old. Also car accident had the highest frequency in both gender. Other causes of trauma were fall down with 13.5% frequency (9 cases) and under debris 5.9% (4 cases). Also from 70 studied patients, 67 cases (95.7%) had blunt trauma and 3 cases (4.3%) had penetrating trauma. The most penetrating trauma occurs in ages less than 50 years and was in the range of 30-50 years. The average RTS and ISS was 10.67±1.45 and 18.11±8.64, high and low scores of ISS existed in all age groups but a low score of RTS was highest in the children age group. The average length of ICU stay was 12.14±11.11 days. Overall mortality was 15.7 (11 cases). In this study, by the ISS increasing, the mortality rate also increased. But there

  3. Target inhibition networks: predicting selective combinations of druggable targets to block cancer survival pathways.

    Directory of Open Access Journals (Sweden)

    Jing Tang

    Full Text Available A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks. Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and synthetic lethal interactions. However, due to the exponentially increasing number of potential drug and target combinations, systematic approaches are needed for prioritizing the most potent multi-target alternatives on a global network level. We took a functional systems pharmacology approach toward the identification of selective target combinations for specific cancer cells by combining large-scale screening data on drug treatment efficacies and drug-target binding affinities. Our model-based prediction approach, named TIMMA, takes advantage of the polypharmacological effects of drugs and infers combinatorial drug efficacies through system-level target inhibition networks. Case studies in MCF-7 and MDA-MB-231 breast cancer and BxPC-3 pancreatic cancer cells demonstrated how the target inhibition modeling allows systematic exploration of functional interactions between drugs and their targets to maximally inhibit multiple survival pathways in a given cancer type. The TIMMA prediction results were experimentally validated by means of systematic siRNA-mediated silencing of the selected targets and their pairwise combinations, showing increased ability to identify not only such druggable kinase targets that are essential for cancer survival either individually or in combination, but also synergistic interactions indicative of non-additive drug efficacies. These system-level analyses were enabled by a novel model construction method utilizing maximization and minimization rules, as well as a model selection algorithm based on sequential forward floating search. Compared with an existing computational solution, TIMMA showed both enhanced

  4. Gene signatures derived from a c-MET-driven liver cancer mouse model predict survival of patients with hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Irena Ivanovska

    Full Text Available Biomarkers derived from gene expression profiling data may have a high false-positive rate and must be rigorously validated using independent clinical data sets, which are not always available. Although animal model systems could provide alternative data sets to formulate hypotheses and limit the number of signatures to be tested in clinical samples, the predictive power of such an approach is not yet proven. The present study aims to analyze the molecular signatures of liver cancer in a c-MET-transgenic mouse model and investigate its prognostic relevance to human hepatocellular carcinoma (HCC. Tissue samples were obtained from tumor (TU, adjacent non-tumor (AN and distant normal (DN liver in Tet-operator regulated (TRE human c-MET transgenic mice (n = 21 as well as from a Chinese cohort of 272 HBV- and 9 HCV-associated HCC patients. Whole genome microarray expression profiling was conducted in Affymetrix gene expression chips, and prognostic significances of gene expression signatures were evaluated across the two species. Our data revealed parallels between mouse and human liver tumors, including down-regulation of metabolic pathways and up-regulation of cell cycle processes. The mouse tumors were most similar to a subset of patient samples characterized by activation of the Wnt pathway, but distinctive in the p53 pathway signals. Of potential clinical utility, we identified a set of genes that were down regulated in both mouse tumors and human HCC having significant predictive power on overall and disease-free survival, which were highly enriched for metabolic functions. In conclusions, this study provides evidence that a disease model can serve as a possible platform for generating hypotheses to be tested in human tissues and highlights an efficient method for generating biomarker signatures before extensive clinical trials have been initiated.

  5. Gene expression variation to predict 10-year survival in lymph-node-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Karlsson Per

    2008-09-01

    Full Text Available Abstract Background It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated. Methods 46 tumours from node-negative breast cancer patients were studied with gene expression microarrays. A t-test was carried out in order to find a set of genes where the expression might predict clinical outcome. Two classifiers were used for evaluation of the gene lists, a correlation-based classifier and a Voting Features Interval (VFI classifier. We then evaluated the predictive accuracy of this expression signature on tumour sets from two similar studies on lymph-node negative patients. They had both developed gene expression signatures superior to current methods in classifying node-negative breast tumours. These two signatures were also tested on our material. Results A list of 51 genes whose expression profiles could predict clinical outcome with high accuracy in our material (96% or 89% accuracy in cross-validation, depending on type of classifier was developed. When tested on two independent data sets, the expression signature based on the 51 identified genes had good predictive qualities in one of the data sets (74% accuracy, whereas their predictive value on the other data set were poor, presumably due to the fact that only 23 of the 51 genes were found in that material. We also found that previously developed expression signatures could predict clinical outcome well to moderately well in our material (72% and 61%, respectively. Conclusion The list of 51 genes derived in this study might have potential for clinical utility as a prognostic gene set, and may include candidate genes of potential relevance for clinical outcome in breast cancer. According to the predictions by this expression signature, 30 of the 46 patients may have benefited from different adjuvant treatment than they recieved. Trial

  6. The proneural molecular signature is enriched in oligodendrogliomas and predicts improved survival among diffuse gliomas.

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    Lee A D Cooper

    Full Text Available The Cancer Genome Atlas Project (TCGA has produced an extensive collection of '-omic' data on glioblastoma (GBM, resulting in several key insights on expression signatures. Despite the richness of TCGA GBM data, the absence of lower grade gliomas in this data set prevents analysis genes related to progression and the uncovering of predictive signatures. A complementary dataset exists in the form of the NCI Repository for Molecular Brain Neoplasia Data (Rembrandt, which contains molecular and clinical data for diffuse gliomas across the full spectrum of histologic class and grade. Here we present an investigation of the significance of the TCGA consortium's expression classification when applied to Rembrandt gliomas. We demonstrate that the proneural signature predicts improved clinical outcome among 176 Rembrandt gliomas that includes all histologies and grades, including GBMs (log rank test p = 1.16e-6, but also among 75 grade II and grade III samples (p  =  2.65e-4. This gene expression signature was enriched in tumors with oligodendroglioma histology and also predicted improved survival in this tumor type (n =  43, p  =  1.25e-4. Thus, expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for lower grade oligodendrogliomas, and likely represent important differences in tumor biology with implications for treatment and therapy. Integrated DNA and RNA analysis of low-grade and high-grade proneural gliomas identified increased expression and gene amplification of several genes including GLIS3, TGFB2, TNC, AURKA, and VEGFA in proneural GBMs, with corresponding loss of DLL3 and HEY2. Pathway analysis highlights the importance of the Notch and Hedgehog pathways in the proneural subtype. This demonstrates that the expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for low-grade oligodendrogliomas, and likely represent important differences in tumor

  7. Severe Spastic Contractures and Diabetes Mellitus Independently Predict Subsequent Minimal Trauma Fractures Among Long-Term Care Residents.

    Science.gov (United States)

    Lam, Kuen; Leung, Man Fuk; Kwan, Chi Wai; Kwan, Joseph

    2016-11-01

    The study aimed to examine the epidemiology of hypertonic contractures and its relationship with minimal trauma fracture (MTF), and to determine the incidence and predictors of (MTF) in long-term care residents. This was a longitudinal cohort study of prospectively collected data. Participants were followed from March 2007 to March 2016 or until death. A 300-bed long-term care hospital in Hong Kong. All long-term care residents who were in need of continuous medical and nursing care for their activities of daily living. Information on patients' demographic data, severe contracture defined as a decrease of 50% or more of the normal passive range of joint movement of the joint, and severe limb spasticity defined by the Modified Ashworth Scale higher than grade 3, medical comorbidities, functional status, cognitive status, nutritional status including body mass index and serum albumin, past history of fractures, were evaluated as potential risk factors for subsequent MTF. Three hundred ninety-six residents [148 males, mean ± standard deviation (SD), age = 79 ± 16 years] were included for analysis. The presence of severe contracture was highly prevalent among the study population: 91% of residents had at least 1 severe contracture, and 41% of residents had severe contractures involving all 4 limbs. Moreover, there were a significant proportion of residents who had severe limb spasticity with the elbow flexors (32.4%) and knee flexors (33.9%) being the most commonly involved muscles. Twelve residents (3%) suffered from subsequent MTF over a median follow-up of 33 (SD = 30) months. Seven out of these 12 residents died during the follow-up period, with a mean survival of 17.8 months (SD = 12.6) after the fracture event. The following 2 factors were found to independently predict subsequent MTF in a multivariate Cox regression: bilateral severe spastic knee contractures (hazard ratio = 16.5, P contractures are common morbidities in long-term care residents

  8. {sup 18}F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Salaun, Pierre-Yves; Robin, Philippe [University Hospital, Nuclear Medicine Department, Brest (France); Campion, Loic [ICO-Gauducheau Cancer Institute, Statistical Department, Nantes (France); Ansquer, Catherine; Mathieu, Cedric [University Hospital, Nuclear Medicine Department, Nantes (France); Frampas, Eric [University Hospital, Radiology Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); Bournaud, Claire [University Hospital, Nuclear Medicine Department, Lyon (France); Vuillez, Jean-Philippe [University Hospital, Nuclear Medicine Department, Grenoble (France); Taieb, David [University Hospital, Nuclear Medicine Department, Marseille (France); Rousseau, Caroline [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Drui, Delphine [University Hospital, Endocrinology Department, Nantes (France); Mirallie, Eric [University Hospital, Surgery Department, Nantes (France); Borson-Chazot, Francoise [University Hospital, Endocrinology Department, Lyon (France); Goldenberg, David M. [IBC Pharmaceuticals, Inc., and Immunomedics, Inc., Morris Plains, NJ (United States); Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, NJ (United States); Chatal, Jean-Francois [GIP ARRONAX, Saint-Herblain (France); Barbet, Jacques [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); GIP ARRONAX, Saint-Herblain (France); Kraeber-Bodere, Francoise [University Hospital, Nuclear Medicine Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Hotel Dieu University Hospital, Nuclear Medicine Department, Nantes (France)

    2014-08-15

    analysis of OS from MTC diagnosis. {sup 18}F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment. (orig.)

  9. Analyses of potential predictive markers and survival data for a response to sunitinib in patients with metastatic renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Juana Dornbusch

    Full Text Available BACKGROUND: Patients with metastatic clear cell renal cell carcinoma (ccRCC are frequently treated with tyrosine kinase inhibitors (TKI such as sunitinib. It inhibits angiogenic pathways by mainly targeting the receptors of VEGF and PDGF. In ccRCC, angiogenesis is characterized by the inactivation of the von Hippel-Lindau gene (VHL which in turn leads to the induction of HIF1α target genes such as CA9 and VEGF. Furthermore, the angiogenic phenotype of ccRCC is also reflected by endothelial markers (CD31, CD34 or other tumor-promoting factors like Ki67 or survivin. METHODS: Tissue microarrays from primary tumor specimens of 42 patients with metastatic ccRCC under sunitinib therapy were immunohistochemically stained for selected markers related to angiogenesis. The prognostic and predictive potential of theses markers was assessed on the basis of the objective response rate which was evaluated according to the RECIST criteria after 3, 6, 9 months and after last report (12-54 months of sunitinib treatment. Additionally, VHL copy number and mutation analyses were performed on DNA from cryo-preserved tumor tissues of 20 ccRCC patients. RESULTS: Immunostaining of HIF-1α, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2, pPDGFRα and -β was significantly associated with the sunitinib response after 6 and 9 months as well as last report under therapy. Furthermore, HIF-1α, CA9, CD34, VEGFR1 and -3 and PDGRFα showed significant associations with progression-free survival (PFS and overall survival (OS. In multivariate Cox proportional hazards regression analyses high CA9 membrane staining and a response after 9 months were independent prognostic factors for longer OS. Frequently observed copy number loss and mutation of VHL gene lead to altered expression of VHL, HIF-1α, CA9, and VEGF. CONCLUSIONS: Immunoexpression of HIF-1α, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2, pPDGFRα and -β in the primary tumors of metastatic ccRCC patients might support the

  10. Independent Walking as a Major Skill for the Development of Anticipatory Postural Control: Evidence from Adjustments to Predictable Perturbations

    OpenAIRE

    Fabien Cignetti; Milan Zedka; Marianne Vaugoyeau; Christine Assaiante

    2013-01-01

    Although there is suggestive evidence that a link exists between independent walking and the ability to establish anticipatory strategy to stabilize posture, the extent to which this skill facilitates the development of anticipatory postural control remains largely unknown. Here, we examined the role of independent walking on the infants' ability to anticipate predictable external perturbations. Non-walking infants, walking infants and adults were sitting on a platform that produced continuou...

  11. MET gene copy number predicts worse overall survival in patients with non-small cell lung cancer (NSCLC; a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Anastasios Dimou

    Full Text Available OBJECTIVES: MET is a receptor present in the membrane of NSCLC cells and is known to promote cell proliferation, survival and migration. MET gene copy number is a common genetic alteration and inhibition o MET emerges as a promising targeted therapy in NSCLC. Here we aim to combine in a meta-analysis, data on the effect of high MET gene copy number on the overall survival of patients with resected NSCLC. METHODS: Two independent investigators applied parallel search strategies with the terms "MET AND lung cancer", "MET AND NSCLC", "MET gene copy number AND prognosis" in PubMed through January 2014. We selected the studies that investigated the association of MET gene copy number with survival, in patients who received surgery. RESULTS: Among 1096 titles that were identified in the initial search, we retrieved 9 studies on retrospective cohorts with adequate retrievable data regarding the prognostic impact of MET gene copy number on the survival of patients with NSCLC. Out of those, 6 used FISH and the remaining 3 used RT PCR to assess the MET gene copy number in the primary tumor. We calculated the I2 statistic to assess heterogeneity (I2 = 72%. MET gene copy number predicted worse overall survival when all studies were combined in a random effects model (HR = 1.78, 95% CI 1.22-2.60. When only the studies that had at least 50% of adenocarcinoma patients in their populations were included, the effect was significant (five studies, HR 1.55, 95% CI 1.23-1.94. This was not true when we included only the studies with no more than 50% of the patients having adenocarcinoma histology (four studies HR 2.18, 95% CI 0.97-4.90. CONCLUSIONS: Higher MET gene copy number in the primary tumor at the time of diagnosis predicts worse outcome in patients with NSCLC. This prognostic impact may be adenocarcinoma histology specific.

  12. A Mycobacterium avium subsp. paratuberculosis predicted serine protease is associated with acid stress and intraphagosomal survival

    Directory of Open Access Journals (Sweden)

    Abirami Kugadas

    2016-08-01

    Full Text Available AbstractThe ability to maintain intra-cellular pH is crucial for bacteria and other microbes to survive in diverse environments, particularly those that undergo fluctuations in pH. Mechanisms of acid resistance remain poorly understood in mycobacteria. Although studies investigating acid stress in M. tuberculosis are gaining traction, few center on Mycobacterium avium subsp. paratuberculosis (MAP, the etiological agent of chronic enteritis in ruminants. We identified a MAP acid stress response network involved in macrophage infection. The central node of this network was MAP0403, a predicted serine protease that shared an 86% amino acid identity with MarP in M. tuberculosis. Previous studies confirmed MarP as a serine protease integral to maintaining intra-bacterial pH and survival in acid in vitro and in vivo. We show that MAP0403 is upregulated in infected macrophage and MAC-T cells and coincided with phagosome acidification. Treatment of mammalian cells with bafilomcyin A1, a potent inhibitor of phagosomal vATPases, diminished MAP0403 transcription. MAP0403 expression was also noted in acidic medium. A surrogate host, M. smegmatis mc2 155, was designed to express MAP0403 and when exposed to either macrophages or in vitro acid stress had increase bacterial cell viability, which corresponds to maintenance of intra-bacterial pH in acidic (pH = 5 conditions. These data suggest that MAP0403 may be the equivalent of MarP in MAP. Future studies confirming MAP0403 as a serine protease and exploring its structure and possible substrates are warranted.

  13. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    Science.gov (United States)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  14. NanOx, a new model to predict cell survival in the context of particle therapy

    Science.gov (United States)

    Cunha, M.; Monini, C.; Testa, E.; Beuve, M.

    2017-02-01

    Particle therapy is increasingly attractive for the treatment of tumors and the number of facilities offering it is rising worldwide. Due to the well-known enhanced effectiveness of ions, it is of utmost importance to plan treatments with great care to ensure tumor killing and healthy tissues sparing. Hence, the accurate quantification of the relative biological effectiveness (RBE) of ions, used in the calculation of the biological dose, is critical. Nevertheless, the RBE is a complex function of many parameters and its determination requires modeling. The approaches currently used have allowed particle therapy to thrive, but still show some shortcomings. We present herein a short description of a new theoretical framework, NanOx, to calculate cell survival in the context of particle therapy. It gathers principles from existing approaches, while addressing some of their weaknesses. NanOx is a multiscale model that takes the stochastic nature of radiation at nanometric and micrometric scales fully into account, integrating also the chemical aspects of radiation-matter interaction. The latter are included in the model by means of a chemical specific energy, determined from the production of reactive chemical species induced by irradiation. Such a production represents the accumulation of oxidative stress and sublethal damage in the cell, potentially generating non-local lethal events in NanOx. The complementary local lethal events occur in a very localized region and can, alone, lead to cell death. Both these classes of events contribute to cell death. The comparison between experimental data and model predictions for the V79 cell line show a good agreement. In particular, the dependence of the typical shoulders of cell survival curves on linear energy transfer are well described, but also the effectiveness of different ions, including the overkill effect. These results required the adjustment of a number of parameters compatible with the application of the model in

  15. {sup 18}F-FDG PET/CT predicts survival after {sup 90}Y transarterial radioembolization in unresectable hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jreige, Mario; Mitsakis, Periklis; Gucht, Axel van der; Pomoni, Anastasia; Silva-Monteiro, Marina; Boubaker, Ariane; Nicod-Lalonde, Marie; Prior, John O.; Schaefer, Niklaus [Lausanne University Hospital, Department of Nuclear Medicine and Molecular Imaging, Lausanne (Switzerland); Gnesin, Silvano [Lausanne University Hospital, Institute of Radiation Physics, Lausanne (Switzerland); Duran, Rafael; Denys, Alban [Lausanne University Hospital, Department of Radiodiagnostic and Interventional Radiology, Lausanne (Switzerland)

    2017-07-15

    To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 ({sup 90}Y-TARE) for unresectable hepatocellular carcinoma (uHCC). We analysed data from 48 patients in our prospective database undergoing {sup 90}Y-TARE treatment for uHCC (31 resin, 17 glass). All patients underwent {sup 18}F-FDG PET/CT and morphological imaging (CT and MRI scans) as part of a pretherapeutic work-up. Patients did not receive any treatment between these imaging procedures and {sup 90}Y-TARE. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were used to assess the prognostic value of {sup 18}F-FDG PET/CT metabolic parameters, including SUV{sub max}, tumour-to-liver (T/L) uptake ratio and SUV{sub mean} of healthy liver, and morphological data, including number and size of lesions, portal-venous infiltration (PVI). Relevant prognostic factors for HCC including Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumour size, PVI and serum AFP level were compared with metabolic parameters in univariate and multivariate analyses. The median follow-up in living patients was 16.2 months (range 11.4-50.1 months). Relapse occurred in 34 patients (70.8%) at a median of 7.4 months (range 1.4-27.9 months) after {sup 90}Y-TARE, and relapse occurred in 24 of 34 patients (70.8%) who died from their disease at a median of 8.1 months (range 2.2-35.2 months). Significant prognostic markers for PFS were the mean and median lesion SUV{sub max} (both P = 0.01; median PFS 10.2 vs. 7.4 months), and significant prognostic markers for OS were the first quarter (Q1) cut-off values for lesion SUV{sub max} and T/L uptake ratio (both P = 0.02; median OS 30.9 vs. 9 months). The multivariate analysis confirmed that lesion SUV{sub max} and T/L uptake ratio were independent negative predictors of PFS (hazard ratio, HR, 2.7, 95% CI 1.2-6.1, P = 0.02, for mean

  16. Diffusion-weighted magnetic resonance imaging predicts survival in patients with liver-predominant metastatic colorectal cancer shortly after selective internal radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Schmeel, Frederic Carsten; Simon, Birgit; Luetkens, Julian Alexander; Traeber, Frank; Schmeel, Leonard Christopher; Schild, Hans Heinz; Hadizadeh, Dariusch Reza [University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universitaet Bonn, Department of Radiology, Bonn (Germany); Sabet, Amir [University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universitaet Bonn, Department of Nuclear Medicine, Bonn (Germany); University Hospital Essen, Universitaet Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany); Ezziddin, Samer [University Hospital Bonn, Rheinische-Friedrich-Wilhelms-Universitaet Bonn, Department of Nuclear Medicine, Bonn (Germany); University Hospital Saarland, Universitaet des Saarlandes, Department of Nuclear Medicine, Homburg (Germany)

    2017-03-15

    To investigate whether quantifications of apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) can predict overall survival (OS) in patients with liver-predominant metastatic colorectal cancer (CRC) following selective internal radiation therapy with {sup 90}Yttrium-microspheres (SIRT). Forty-four patients underwent DWI 19 ± 16 days before and 36 ± 10 days after SIRT. Tumour-size and intratumoral minimal ADC (minADC) values were measured for 132 liver metastases on baseline and follow-up DWI. Optimal functional imaging response to treatment was determined by receiver operating characteristics and defined as ≥22 % increase in post-therapeutic minADC. Survival analysis was performed with the Kaplan-Meier method and Cox-regression comparing various variables with potential impact on OS. Median OS was 8 months. The following parameters were significantly associated with median OS: optimal functional imaging response (18 vs. 5 months; p < 0.001), hepatic tumour burden <50 % (8 vs. 5 months; p = 0.018), Eastern Cooperative Oncology Group performance scale <1 (10 vs. 4 months; p = 0.012) and progressive disease according to Response and Evaluation Criteria in Solid Tumours (8 vs. 3 months; p = 0.001). On multivariate analysis, optimal functional imaging response and hepatic tumour burden remained independent predictors of OS. Functional imaging response assessment using minADC changes on DWI may predict survival in CRC shortly after SIRT. (orig.)

  17. Preimplantation biopsy predicts delayed graft function, glomerular filtration rate and long-term graft survival of transplanted kidneys

    Directory of Open Access Journals (Sweden)

    José A. Pedroso

    2016-01-01

    Full Text Available The predictive value of preimplantation biopsies for long-term graft function is often limited by conflicting results. The aim of this study was to evaluate the influence of time-zero graft biopsy histological scores on early and late graft function, graft survival and patient survival, at different time points. We retrospectively analyzed 284 preimplantation biopsies at a single center, in a cohort of recipients with grafts from live and deceased donors (standard and nonstandard, and their impact in posttransplant renal function after a mean follow-up of 7 years (range 1-16. Implantation biopsy score (IBS, a combination score derived from 4 histopathological aspects, was determined from each sample. The correlation with incidence of delayed graft function (DGF, creatinine clearance (1st, 3rd and 5th posttransplant year and graft and patient survival at 1 and 5 years were evaluated. Preimplantation biopsies provided somewhat of a prognostic index of early function and outcome of the transplanted kidney in the short and long term. In the immediate posttransplantation period, the degree of arteriolosclerosis and interstitial fibrosis correlated better with the presence of DGF. IBS values between 4 and 6 were predictive of worst renal function at 1st and 3rd years posttransplant and 5-year graft survival. The most important histological finding, in effectively transplanted grafts, was the grade of interstitial fibrosis. Patient survival was not influenced by IBS. Higher preimplantation biopsy scores predicted an increased risk of early graft losses, especially primary nonfunction. Graft survival (at 1st and 5th years after transplant but not patient survival was predicted by IBS.

  18. Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study

    Science.gov (United States)

    Ganly, Ian; Amit, Moran; Kou, Lei; Palmer, Frank L.; Migliacci, Jocelyn; Katabi, Nora; Yu, Changhong; Kattan, Michael W.; Binenbaum, Yoav; Sharma, Kanika; Naomi, Ramer; Abib, Agbetoba; Miles, Brett; Yang, Xinjie; Lei, Delin; Bjoerndal, Kristine; Godballe, Christian; Mücke, Thomas; Wolff, Klaus-Dietrich; Fliss, Dan; Eckardt, André M.; Chiara, Copelli; Sesenna, Enrico; Ali, Safina; Czerwonka, Lukas; Goldstein, David P.; Gil, Ziv; Patel, Snehal G.

    2016-01-01

    Background Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. Methods ACC patients managed at 10 international centers were identified. Patient, tumor, and treatment characteristics were recorded and an international collaborative dataset created. Multivariable competing risk models were then built to predict the 10 year recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and cancer specific mortality (CSM). All predictors of interest were added in the starting full models before selection, including age, gender, tumor site, clinical T stage, perineural invasion, margin status, pathologic N-status, and M-status. Stepdown method was used in model selection to choose predictive variables. An external dataset of 99 patients from 2 other institutions was used to validate the nomograms. Findings Of 438 ACC patients, 27.2% (119/438) died from ACC and 38.8% (170/438) died of other causes. Median follow-up was 56 months (range 1–306). The nomogram for OS had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N-status and M-status) with a concordance index (CI) of 0.71. The nomogram for CSM had the same variables, except margin status, with a concordance index (CI) of 0.70. The nomogram for RFP had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N status and perineural invasion) (CI 0.66). The nomogram for DRFP had 6 variables (gender, clinical T stage, tumor site, pathologic N-status, perineural invasion and margin status) (CI 0.64). Concordance index for the external validation set were 0.76, 0.72, 0.67 and 0.70 respectively. Interpretation Using an international collaborative database we have created the first nomograms which

  19. Predicting censored survival data based on the interactions between meta-dimensional omics data in breast cancer.

    Science.gov (United States)

    Kim, Dokyoon; Li, Ruowang; Dudek, Scott M; Ritchie, Marylyn D

    2015-08-01

    Evaluation of survival models to predict cancer patient prognosis is one of the most important areas of emphasis in cancer research. A binary classification approach has difficulty directly predicting survival due to the characteristics of censored observations and the fact that the predictive power depends on the threshold used to set two classes. In contrast, the traditional Cox regression approach has some drawbacks in the sense that it does not allow for the identification of interactions between genomic features, which could have key roles associated with cancer prognosis. In addition, data integration is regarded as one of the important issues in improving the predictive power of survival models since cancer could be caused by multiple alterations through meta-dimensional genomic data including genome, epigenome, transcriptome, and proteome. Here we have proposed a new integrative framework designed to perform these three functions simultaneously: (1) predicting censored survival data; (2) integrating meta-dimensional omics data; (3) identifying interactions within/between meta-dimensional genomic features associated with survival. In order to predict censored survival time, martingale residuals were calculated as a new continuous outcome and a new fitness function used by the grammatical evolution neural network (GENN) based on mean absolute difference of martingale residuals was implemented. To test the utility of the proposed framework, a simulation study was conducted, followed by an analysis of meta-dimensional omics data including copy number, gene expression, DNA methylation, and protein expression data in breast cancer retrieved from The Cancer Genome Atlas (TCGA). On the basis of the results from breast cancer dataset, we were able to identify interactions not only within a single dimension of genomic data but also between meta-dimensional omics data that are associated with survival. Notably, the predictive power of our best meta-dimensional model

  20. p16 expression independent of human papillomavirus is associated with lower stage and longer disease-free survival in oral cavity squamous cell carcinoma.

    Science.gov (United States)

    Satgunaseelan, Laveniya; Virk, Sohaib A; Lum, Trina; Gao, Kan; Clark, Jonathan R; Gupta, Ruta

    2016-08-01

    There is limited information regarding the incidence of p16 expression, its association with human papillomavirus (HPV) and prognosis in oral cavity squamous cell carcinoma (OSCC). The role of p16 in OSCC is evaluated in 215 cases using tissue microarrays (TMAs). p16 immunohistochemistry and HPV in situ hybridisation were performed on TMAs following histopathology review of 215 patients with OSCC in the Sydney Head and Neck Cancer Institute database. Thirty-seven (17.2%) cases showed p16 expression without association with HPV. p16 expression significantly decreased with increasing pT category (p=0.002). p16 expression was associated with longer disease-specific survival on univariable analysis (p=0.044) but not on multivariable analysis adjusting for depth of invasion. Amongst patients receiving adjuvant radiotherapy, patients with p16 expression had significantly longer disease-free and overall survival. p16 expression was seen in early stage OSCCs and was associated with better survival following surgery and radiotherapy. While not an independent predictor of survival, p16 may mediate its effects by contributing to reduced proliferative capacity, leading to smaller tumour size and lower invasive potential.

  1. The platelet-to-lymphocyte ratio predicts poor survival in patients with huge hepatocellular carcinoma that received transarterial chemoembolization.

    Science.gov (United States)

    Xue, Tong-Chun; Jia, Qing-An; Ge, Ning-Ling; Zhang, Bo-Heng; Wang, Yan-Hong; Ren, Zheng-Gang; Ye, Sheng-Long

    2015-08-01

    Inflammation is particularly strong in huge hepatocellular carcinoma (HCC). However, it is unclear whether the platelet-to-lymphocyte ratio (PLR), as an inflammatory-related marker, can predict survival of patients with huge HCC. In this study, we enrolled 291 patients with huge HCC (diameter over 10 cm) who were undergoing repeated transarterial chemoembolization (TACE) at our institute. The baseline PLR was calculated from complete serum blood counts before the first chemoembolization. We found that a baseline PLR cutoff value over 150 best predicted huge HCC survival. The 12, 24, and 36 months survival rates in the high PLR group (22.6, 8.1, and 4.1 %, respectively) were significantly lower than in the low PLR group (35.6, 22.4, and 14 %, respectively). Thus, a significant difference was found in overall survival (log-rank test, p huge HCC, a high baseline PLR is a useful predictor of poor survival in patients undergoing chemoembolization. Additional anti-inflammatory or anti-platelet treatments, in combination with TACE, may improve survival in HCC patients with high PLR.

  2. Observational attachment theory-based parenting measures predict children's attachment narratives independently from social learning theory-based measures.

    Science.gov (United States)

    Matias, Carla; O'Connor, Thomas G; Futh, Annabel; Scott, Stephen

    2014-01-01

    Conceptually and methodologically distinct models exist for assessing quality of parent-child relationships, but few studies contrast competing models or assess their overlap in predicting developmental outcomes. Using observational methodology, the current study examined the distinctiveness of attachment theory-based and social learning theory-based measures of parenting in predicting two key measures of child adjustment: security of attachment narratives and social acceptance in peer nominations. A total of 113 5-6-year-old children from ethnically diverse families participated. Parent-child relationships were rated using standard paradigms. Measures derived from attachment theory included sensitive responding and mutuality; measures derived from social learning theory included positive attending, directives, and criticism. Child outcomes were independently-rated attachment narrative representations and peer nominations. Results indicated that Attachment theory-based and Social Learning theory-based measures were modestly correlated; nonetheless, parent-child mutuality predicted secure child attachment narratives independently of social learning theory-based measures; in contrast, criticism predicted peer-nominated fighting independently of attachment theory-based measures. In young children, there is some evidence that attachment theory-based measures may be particularly predictive of attachment narratives; however, no single model of measuring parent-child relationships is likely to best predict multiple developmental outcomes. Assessment in research and applied settings may benefit from integration of different theoretical and methodological paradigms.

  3. Early brain loss in circuits affected by Alzheimer’s disease is predicted by fornix microstructure but may be independent of gray matter

    Directory of Open Access Journals (Sweden)

    Evan eFletcher

    2014-05-01

    Full Text Available In a cohort of community-recruited elderly subjects with normal cognition at initial evaluation, we found that baseline fornix white matter microstructure was significantly correlated with early volumetric longitudinal tissue change across a region of interest (called fSROI, which overlaps circuits known to be selectively vulnerable to AD pathology. Other white matter and gray matter regions had much weaker or non-existent associations with longitudinal tissue change. Tissue loss in fSROI was in turn a significant factor in a survival model of cognitive decline, as was baseline fornix microstructure. These findings suggest that WM deterioration in the fornix and tissue loss in fSROI may be the early beginnings of posterior limbic circuit and default mode network degeneration. We also found that gray matter baseline volumes in the entorhinal cortex and hippocampus predicted cognitive decline in survival models. But since GM regions did not also significantly predict brain tissue loss, our results may imply a view in which early, prodromal deterioration appears as two quasi independent processes in white and gray matter regions of the limbic circuit crucial to memory.

  4. Higher Levels of GATA3 Predict Better Survival in Women with Breast Cancer

    Science.gov (United States)

    Yoon, Nam K.; Maresh, Erin L.; Shen, Dejun; Elshimali, Yahya; Apple, Sophia; Horvath, Steve; Mah, Vei; Bose, Shikha; Chia, David; Chang, Helena R.; Goodglick, Lee

    2010-01-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. GATA3 in particular is necessary for mammary gland maturation, and its loss has been implicated in breast cancer development. Our goal was to validate the ability of GATA3 expression to predict survival in breast cancer patients. Protein expression of GATA3 was analyzed on a high density tissue microarray consisting of 242 cases of breast cancer. We associated GATA3 expression with patient outcomes and clinicopathological variables. Expression of GATA3 was significantly increased in breast cancer, in situ lesions, and hyperplastic tissue compared to normal breast tissue. GATA3 expression decreased with increasing tumor grade. Low GATA3 expression was a significant predictor of disease-related death in all patients, as well as in subgroups of estrogen receptor positive or low grade patients. Additionally, low GATA3 expression correlated with increased tumor size and estrogen and progesterone receptor negativity. GATA3 is an important predictor of disease outcome in breast cancer patients. This finding has been validated in a diverse set of populations. Thus, GATA3 expression has utility as a prognostic indicator in breast cancer. PMID:21078439

  5. Prognostic Nomograms for Pre- and Postoperative Predictions of Long-Term Survival for Patients Who Underwent Liver Resection for Huge Hepatocellular Carcinoma.

    Science.gov (United States)

    Li, Yuntong; Xia, Yong; Li, Jun; Wu, Dong; Wan, Xuying; Wang, Kui; Wu, Mengchao; Liu, Jingfeng; Lau, Wan Yee; Shen, Feng

    2015-11-01

    Liver resection is an effective treatment in select patients with huge hepatocellular carcinoma (HCC, diameter ≥10 cm). This study aimed to develop nomograms for pre- and postoperative predictions of overall survival (OS) for these patients. There were 464 consecutive patients who underwent liver resection for huge HCC at the Eastern Hepatobiliary Surgery Hospital (EHBH) between January 2008 and December 2009. They were collected and divided into a training cohort (n = 310) and an internal validation cohort (n = 154). Another 90 patients who were operated on at the Fujian Medical University (FMU) between January 2008 and April 2010 served as an external validation cohort. The surgical morbidity, mortality, time to recurrence, and OS were observed. Two prognostic nomograms were developed based separately on the data obtained before and after surgery. Discrimination and predictive accuracy of the models were measured using concordance index (C-index), calibration curves, and validation study. The postoperative 4-year tumor recurrence and OS rates were, respectively, 79.0% and 41.2% in the patients from the EHBH and 78.8% and 37.6% in those from the FMU. Independent predictors of OS on multivariable analysis using pre- and postoperative data were respectively incorporated into the 2 nomograms. In the training cohort, calibration curves for the probability of 4-year postoperative survival fitted well. The C-indexes of the pre- and postoperative nomograms in predicting OS were 0.75 (95% CI 0.72 to 0.78) and 0.78 (95% CI 0.75 to 0.81), respectively. The internal and external validation studies optimally supported these results. The 2 nomograms achieved accurate pre- or postoperative predictions of long-term survival for patients with huge HCC after liver resection. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Predicting survival after curative colectomy for cancer: individualizing colon cancer staging.

    Science.gov (United States)

    Weiser, Martin R; Gönen, Mithat; Chou, Joanne F; Kattan, Michael W; Schrag, Deborah

    2011-12-20

    Cancer staging determines extent of disease, facilitating prognostication and treatment decision making. The American Joint Committee on Cancer (AJCC) TNM classification system is the most commonly used staging algorithm for colon cancer, categorizing patients on the basis of only these three variables (tumor, node, and metastasis). The purpose of this study was to extend the seventh edition of the AJCC staging system for colon cancer to incorporate additional information available from tumor registries, thereby improving prognostic accuracy. Records from 128,853 patients with primary colon cancer reported to the Surveillance, Epidemiology and End Results Program from 1994 to 2005 were used to construct and validate three survival models for patients with primary curative-intent surgery. Independent training/test data sets were used to develop and test alternative models. The seventh edition TNM staging system was compared with models supplementing TNM staging with additional demographic and tumor variables available from the registry by calculating a concordance index, performing calibration, and identifying the area under receiver operating characteristic (ROC) curves. Inclusion of additional registry covariates improved prognostic estimates. The concordance index rose from 0.60 (95% CI, 0.59 to 0.61) for the AJCC model, with T- and N-stage variables, to 0.68 (95% CI, 0.67 to 0.68) for the model including tumor grade, number of collected metastatic lymph nodes, age, and sex. ROC curves for the extended model had higher sensitivity, at all values of specificity, than the TNM system; calibration curves indicated no deviation from the reference line. Prognostic models incorporating readily available data elements outperform the current AJCC system. These models can assist in personalizing treatment and follow-up for patients with colon cancer.

  7. Longitudinal robustness of variables predicting independent gait following severe middle cerebral artery stroke: a prospective cohort study.

    NARCIS (Netherlands)

    Kollen, B.; Kwakkel, G.; Lindeman, E.

    2006-01-01

    OBJECTIVE: To determine within the first 10 weeks post onset the most robust variables in the prediction of recovery of independent gait at six months post stroke. DESIGN: A prospective cohort study. SUBJECTS: One hundred and one first ever ischaemic middle cerebral artery stroke patients. None of

  8. Longitudinal robustness of variables predicting independent gait following severe middle cerebral artery stroke: a prospective cohort study.

    NARCIS (Netherlands)

    Kollen, B.; Kwakkel, G.; Lindeman, E.

    2006-01-01

    OBJECTIVE: To determine within the first 10 weeks post onset the most robust variables in the prediction of recovery of independent gait at six months post stroke. DESIGN: A prospective cohort study. SUBJECTS: One hundred and one first ever ischaemic middle cerebral artery stroke patients. None of t

  9. Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity.

    Directory of Open Access Journals (Sweden)

    Jason A Pfister

    Full Text Available BACKGROUND: Growing evidence suggests that sirtuins, a family of seven distinct NAD-dependent enzymes, are involved in the regulation of neuronal survival. Indeed, SIRT1 has been reported to protect against neuronal death, while SIRT2 promotes neurodegeneration. The effect of SIRTs 3-7 on the regulation of neuronal survival, if any, has yet to be reported. METHODOLOGY AND PRINCIPAL FINDINGS: We examined the effect of expressing each of the seven SIRT proteins in healthy cerebellar granule neurons (CGNs or in neurons induced to die by low potassium (LK treatment. We report that SIRT1 protects neurons from LK-induced apoptosis, while SIRT2, SIRT3 and SIRT6 induce apoptosis in otherwise healthy neurons. SIRT5 is generally localized to both the nucleus and cytoplasm of CGNs and exerts a protective effect. In a subset of neurons, however, SIRT5 localizes to the mitochondria and in this case it promotes neuronal death. Interestingly, the protective effect of SIRT1 in neurons is not reduced by treatments with nicotinamide or sirtinol, two pharmacological inhibitors of SIRT1. Neuroprotection was also observed with two separate mutant forms of SIRT1, H363Y and H355A, both of which lack deacetylase activity. Furthermore, LK-induced neuronal death was not prevented by resveratrol, a pharmacological activator of SIRT1, at concentrations at which it activates SIRT1. We extended our analysis to HT-22 neuroblastoma cells which can be induced to die by homocysteic acid treatment. While the effects of most of the SIRT proteins were similar to that observed in CGNs, SIRT6 was modestly protective against homocysteic acid toxicity in HT-22 cells. SIRT5 was generally localized in the mitochondria of HT-22 cells and was apoptotic. CONCLUSIONS/SIGNIFICANCE: Overall, our study makes three contributions - (a it represents the first analysis of SIRT3-7 in the regulation of neuronal survival, (b it shows that neuroprotection by SIRT1 can be mediated by a novel, non

  10. Predicting long-term independency in activities of daily living after middle cerebral artery stroke: does information from MRI have added predictive value compared with clinical information?

    NARCIS (Netherlands)

    Schiemanck, S.K.; Kwakkel, G.; Post, M.W.; Kappelle, L.J.; Prevo, A.J.

    2006-01-01

    BACKGROUND AND PURPOSE: To investigate whether neuroimaging information has added predictive value compared with clinical information for independency in activities of daily living (ADL) 1 year after stroke. METHODS: Seventy-five first-ever middle cerebral artery stroke survivors were evaluated in l

  11. Co-expression of parathyroid hormone related protein and TGF-beta in breast cancer predicts poor survival outcome.

    Science.gov (United States)

    Xu, Cheng; Wang, Zhengyuan; Cui, Rongrong; He, Hongyu; Lin, Xiaoyan; Sheng, Yuan; Zhang, Hongwei

    2015-11-23

    Better methods to predict prognosis can play a supplementary role in administering individualized treatment for breast cancer patients. Altered expressions of PTHrP and TGF-β have been observed in various types of human cancers. The objective of the current study was to evaluate the association of PTHrP and TGF-β level with the clinicopathological features of the breast cancer patients. Immunohistochemistry was used to examine PTHrP and TGF-β protein expression in 497 cases of early breast cancer, and Kaplan-Meier method and COX's Proportional Hazard Model were applied to the prognostic value of PTHrP and TGF-β expression. Both over-expressed TGF-β and PTHrP were correlated with the tumor in larger size, higher proportion of axillary lymph node metastasis and later clinical stage. Additionally, the tumors with a high TGF-β level developed poor differentiation, and only TGF-β expression was associated with disease-free survival (DFS) of the breast cancer patients. Followed up for a median of 48 months, it was found that only the patients with negative TGF-β expression had longer DFS (P PTHrP expression tended to show a higher rate of bone metastasis (67.6 % vs. 45.8 %, P = 0.019). In ER negative subgroup, those who developed PTHrP positive expression presented poor prognosis (P PTHrP expression were significantly associated with the high risk of metastases. As indicated by Cox's regression analysis, TGF-β expression and the high proportion of axillary lymph node metastasis served as significant independent predictors for breast cancer recurrence. TGF-β and PTHrP were confirmed to be involved in regulating the malignant progression in breast cancer, and PTHrP expression, to be associated with bone metastasis as a potential prognostic marker in ER negative breast cancer.

  12. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne B; Dyrskjøt, Lars; von der Maase, Hans;

    2007-01-01

    in an independent material of 124 patients receiving cisplatin-containing therapy. RESULTS: Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin......PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...... and survival. EXPERIMENTAL DESIGN: Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry...

  13. Emmprin and Survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Andersen, Lars Dyrskjøt; Maase, Hans von der;

    2007-01-01

    in an independent material of 124 patients receiving cisplatin-containing therapy. RESULTS: Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin......PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...... and survival. EXPERIMENTAL DESIGN: Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry...

  14. Hypoadiponectinemia predicts impaired endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients: an 8-year prospective study

    Institute of Scientific and Technical Information of China (English)

    LI Hui; XIAO Yang; LIU Hui; CHEN Xiao-yan; LI Xin-ying; TANG Wei-li; LIU Shi-ping; XU Ai-min; ZHOU Zhi-guang

    2011-01-01

    Background Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties.The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function in newly diagnosed type 2 diabetic patients in an 8-year prospective study.Methods In the prospective study,we enrolled 133 newly diagnosed type 2 diabetic patients without subclinical atherosclerosis and gave them intensive therapy; the mean treatment period was 8 years.Intensive treatment was a stepwise implementation of behavior modification and pharmacological therapy targeting hyperglycaemia,hypertension,dyslipidaemia and obesity.We measured baseline circulating adiponectin with an enzyme-linked immunosorbent assay,endothelium-dependent and -independent vasodilation by high-resolution vascular ultrasound.At year 8,102 patients were reexamined for endothelium-dependent and -independent vasodilation.Results Sex-adjusted adiponectin level was positively correlated with endothelium-independent vasodilation both at baseline (r=0.150,P=0.043) and at year 8 (r=0.339,P=0.001),whereas no association was found between adiponectin and endothelium-dependent vasodilation.In a stepwise multivariate linear regression model,adiponectin was an independent predictor for impaired endothelium-independent vasodilation at year 8 (P=0.001).Conclusions Plasma adiponectin concentration was associated with endothelium-independent vasodilation and hypoadiponectinemia predicted the impairment of endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients under multifactorial intervention.These data support the causative link of impairment of endothelium-independent vasodilation with hypoadiponectinemia.

  15. Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: Analysis of survival and prognostic markers

    Directory of Open Access Journals (Sweden)

    Wickramarachchi RE

    2010-09-01

    Full Text Available Abstract Objectives This study compares clinico-pathological features in young (50 years with colorectal cancer, survival in the young and the influence of pre-operative clinical and histological factors on survival. Materials and methods A twelve year prospective database of colorectal cancer was analysed. Fifty-three young patients were compared with forty seven consecutive older patients over fifty years old. An analysis of survival was undertaken in young patients using Kaplan Meier graphs, non parametric methods, Cox's Proportional Hazard Ratios and Weibull Hazard models. Results Young patients comprised 13.4 percent of 397 with colorectal cancer. Duration of symptoms and presentation in the young was similar to older patients (median, range; young patients; 6 months, 2 weeks to 2 years, older patients; 4 months, 4 weeks to 3 years, p > 0.05. In both groups, the majority presented without bowel obstruction (young - 81%, older - 94%. Cancer proximal to the splenic flexure was present more in young than in older patients. Synchronous cancers were found exclusively in the young. Mucinous tumours were seen in 16% of young and 4% of older patients (p Conclusion If patients, who are less than 40 years old with colorectal cancer, survive twenty months after operation, the prognosis improves and their survival becomes predictable.

  16. A prognostic model to predict survival in 867 World Health Organization-defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment.

    Science.gov (United States)

    Passamonti, Francesco; Thiele, Jürgen; Girodon, Francois; Rumi, Elisa; Carobbio, Alessandra; Gisslinger, Heinz; Kvasnicka, Hans Michael; Ruggeri, Marco; Randi, Maria Luigia; Gangat, Naseema; Vannucchi, Alessandro Maria; Gianatti, Andrea; Gisslinger, Bettina; Müllauer, Leonhard; Rodeghiero, Francesco; d'Amore, Emanuele S G; Bertozzi, Irene; Hanson, Curtis A; Boveri, Emanuela; Marino, Filippo; Maffioli, Margherita; Caramazza, Domenica; Antonioli, Elisabetta; Carrai, Valentina; Buxhofer-Ausch, Veronika; Pascutto, Cristiana; Cazzola, Mario; Barbui, Tiziano; Tefferi, Ayalew

    2012-08-01

    Diagnosis of essential thrombocythemia (ET) has been updated in the last World Health Organization (WHO) classification. We developed a prognostic model to predict survival at diagnosis, named IPSET (International Prognostic Score for ET), studying patients with WHO-defined ET. Age 60 years or older, leukocyte count ≥ 11 × 10(9)/L, and prior thrombosis significantly affected survival, by multivariable Cox regression. On the basis of the hazard ratio, we assigned 2 points to age and 1 each to leukocyte count and thrombosis. So, the IPSET model allocated 867 patients into 3 risk categories with significantly different survival: low (sum of points = 0; median survival not reached), intermediate (sum = 1-2; median survival 24.5 years), and high (sum = 3-4, median survival 13.8 years). The IPSET model was further validated in 2 independent cohorts including 132 WHO-defined ET and 234 Polycythemia Vera Study Group-defined ET patients. The IPSET model was able to predict the occurrence of thrombosis, and not to predict post-ET myelofibrosis. In conclusion, IPSET, based on age ≥ 60 years, leukocyte count ≥ 11 × 10(9)/L, and history of thrombosis allows prognostic assessment of WHO-defined ET and the validation process makes IPSET applicable in all patients phenotypically appearing as ET.

  17. Prognostic value of 13C-phenylalanine breath test on predicting survival in patients with chronic liver failure

    Institute of Scientific and Technical Information of China (English)

    I Gallardo-Wong; S Morán; G Rodríguez-Leal; B Casta(n)eda-Romero; R Mera; J Poo; M Uribe; M Dehesa

    2007-01-01

    AIM: To evaluate the prognostic value of percentage of 13C-phenylalanine oxidation (13C-PheOx) obtained by 13C-phenylalanine breath test (13C-PheBT) on the survival of patients with chronic liver failure.METHODS: The hepatic function was determined by standard liver blood tests and the percentage of 13C-PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox.RESULTS: Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78,0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child-Pugh classes, age, creatinine and the percentage of 13C-PheOx (HR 0.338, 95% CI:0.150-0.762, P = 0.009) were independent predictors of survival. When Child-Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin,creatinine, age and the percentage of 13C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival.CONCLUSION: Percentage of 13C-PheOx obtained by 13C-PheBT is a strong predictor of survival in patients with chronic liver disease.

  18. Occult and Overt HBV Co-Infections Independently Predict Postoperative Prognosis in HCV-Associated Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Ming-Ling Chang

    Full Text Available The roles of chronic hepatitis B virus (HBV co-infection (CI in carcinogenesis of hepatitis C virus (HCV-associated hepatocellular carcinoma (HCC remained controversial. To gain new insights into this issue, we investigated the postoperative prognostic value of HBVCI in HCV-associated HCC.A study cohort of 115 liver tissues obtained from the noncancerous parts of surgically removed HCV-associated HCCs were subjected to virological analysis in a tertiary care setting. Assayed factors included clinicopathological variables, tissue amounts of viral genomes, genotypic characterization of viruses, as well as the presence of overt (serum HBsAg positive or occult (serum HBsAg negative but tissue HBV-DNA positive HBVCI. Cox proportional hazard model was used to estimate postoperative survivals.Of the 115 patients, overt and occult HBVCIs were detected in 35 and 16 patients, respectively. Multivariate analysis revealed that tumor size >3 cm (adjusted hazard ratio (AHR, 2.079 [95% confidence interval, 1.149∼3.761], alpha-fetoprotein >8 ng/mL (AHR, 5.976 [2.007∼17.794] albumin 50 U/L (AHR,1.086 [1.006∼1.172], presence of occult HBVCI (AHR, 2.708 [1.317∼5.566], and absence of overt HBVCI (AHR, 2.216 [1.15∼4.269] were independently associated with unfavorable disease-free survival. Patients with occult HBVCI had a shorter disease-free (P = 0.002, a shorter overall survival (P = 0.026, a higher bilirubin level (P = 0.003 and a higher prevalence of precore G1896A mutation (P = 0.006 compared with those with overt HBVCI.Occult and overt HBVCI served as independent predictors for postoperative survival in HCV-associated HCC.

  19. Plasma levels of soluble CD14 independently predict mortality in HIV infection

    DEFF Research Database (Denmark)

    Sandler, Netanya G; Wand, Handan; Roque, Annelys

    2011-01-01

    Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an independent predictor of HIV disease progression. The association of microbial translocation with clinical outcom...

  20. Mesh Independent Probabilistic Residual Life Prediction of Metallic Airframe Structures Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Engineering and Materials, Inc. (GEM) along with its team members, Clarkson University and LM Aero, propose to develop a mesh independent probabilistic...

  1. Cell contact as an independent factor modulating cardiac myocyte hypertrophy and survival in long-term primary culture

    Science.gov (United States)

    Clark, W. A.; Decker, M. L.; Behnke-Barclay, M.; Janes, D. M.; Decker, R. S.

    1998-01-01

    Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. In this study, we show that the myocyte plating density affects not only the hypertrophic response and features of the differentiated phenotype of isolated adult myocytes, but also plays a significant role influencing myocyte survival in vitro. The native rod-shaped phenotype of freshly isolated adult myocytes persists in an environment which minimizes myocyte attachment and spreading on the substratum. However, these conditions are not optimal for long-term maintenance of cultured adult cardiac myocytes. Conditions which promote myocyte attachment and spreading on the substratum, on the other hand, also promote the re-establishment of new intercellular contacts between myocytes. These contacts appear to play a significant role in the development of spontaneous activity, which enhances the redevelopment of highly differentiated contractile, junctional, and sarcoplasmic reticulum structures in the cultured adult cardiomyocyte. Although it has previously been shown that adult cardiac myocytes are typically quiescent in culture, the addition of beta-adrenergic agonists stimulates beating and myocyte hypertrophy, and thereby serves to increase the level of intercellular contact as well. However, in densely-plated cultures with intrinsically high levels of intercellular contact, spontaneous contractile activity develops without the addition of beta-adrenergic agonists. In this study, we compare the function, morphology, and natural history of adult feline cardiomyocytes which have been maintained in cultures with different levels of intercellular contact, with and without the addition of beta-adrenergic agonists

  2. Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes

    DEFF Research Database (Denmark)

    Verdelho, Ana; Madureira, Sofia; Moleiro, Carla

    2013-01-01

    Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC).......Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC)....

  3. Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Robert E. Page

    2007-01-01

    Full Text Available Background: Proprotein convertases (PCs are serine proteases that after restricted proteolysis activate many proteins that play a crucial role in cancer such as metalloproteinases, growth factors and growth factor receptors, adhesion molecules, and angiogenic factors. Although the expression of several PCs is increased in many tumors, their expression in primary ovarian tumors has not been studied in detail. We sought to determine if there was an association between the expression of the ubiquitously expressed PCs, furin, PACE-4, PC-5 and PC-7, and ovarian tumor progression. Methods: We assessed their expression by RT-PCR, Real-time PCR, Western blot, and immunohistochemistry using cells derived from normal human ovarian surface epithelium (HOSE and cancer cell lines as well as ovarian epithelial cancer specimens (45 RT-PCR/Real-time PCR, and 120 archival specimens for Immunohistochemistry. Results: We found that furin expression was restricted to the cancer cell lines. In contrast, PACE-4 and PC-7 showed expression only in normal HOSE cells lines. Furthermore, furin was predominantly expressed in primary tumors from patients who survived for less than five years. The other PCs are either expressed in the group of survivors (PC-7 and PACE4 or expressed in low amounts (PC-5. Conclusions: Our studies point to a clear relationship between furin and ovarian cancer. In addition, these results show that furin exhibits the closest association with ovarian cancer among the ubiquitously expressed PCs, arguing against the redundancy of these proteases. In summary, furin may constitute a marker for ovarian tumor progression and could contribute to predict the outcome of this disease.

  4. IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide.

    NARCIS (Netherlands)

    Dubbink, H.J.; Taal, W.; Marion, R. van; Kros, J.M.; Heuvel, I. van; Bromberg, J.E.; Zonnenberg, B.A.; Zonnenberg, C.B.; Postma, T.J.; Gijtenbeek, J.M.M.; Boogerd, W.; Groenendijk, F.H.; Smitt, P.A.; Dinjens, W.N.; Bent, M.J. van den

    2009-01-01

    BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade

  5. IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide

    NARCIS (Netherlands)

    Dubbink, H. J.; Taal, W.; van Marion, R.; Kros, J. M.; van Heuvel, I.; Bromberg, J. E.; Zonnenberg, B. A.; Zonnenberg, C. B. L.; Postma, T. J.; Gijtenbeek, J. M. M.; Boogerd, W.; Groenendijk, F. H.; Smitt, P. A. E. Sillevis; Dinjens, W. N. M.; van den Bent, M. J.

    2009-01-01

    Background: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade

  6. An easy tool to predict survival in patients receiving radiation therapy for painful bone metastases

    NARCIS (Netherlands)

    Westhoff, P.G.; Graeff, A. de; Monninkhof, E.M.; Bollen, L.; Dijkstra, S.P.; Steen-Banasik, E.M. van der; Vulpen, M. van; Leer, J.W.H.; Marijnen, C.A.; Linden, Y.M. van der; Study, G.

    2014-01-01

    PURPOSE: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and p

  7. Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in resected non-small cell lung cancer patients.

    Science.gov (United States)

    Li, Yunsong; Cheng, Xu; Chen, Zhong; Liu, Yi; Liu, Zhidong; Xu, Shaofa

    2017-07-10

    We tested the hypothesis that circulating tumor cells (CTCs) in preoperative peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long-term survival in resected non-small cell lung cancer (NSCLC) patients. CTCs were separated from blood using magnetic beads coated with antibodies against epithelial-cell adhesion molecule (EpCAM) via magnetic-activated cell sorting (MACS). CTCs were quantified with fluorescence-labeled antibodies against pan-cytokeratin through flow cytometry. CTCs were quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with resected NSCLC. The association between CTCs and prognosis in these patients was evaluated after a 5-year follow-up. In NSCLC patients, outcomes were assessed according to CTC levels at surgery. NSCLC patients identified as high-risk groups exhibited >5 CTCs/15 mL in PPB and >50 CTCs/15 mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that the CTC count in PPB or IPVB was an independent risk factor for tumor-free surivival (TFS) and overall survival (OS). The high-risk group of patients had a shorter median TFS (22 months vs. >60.0 months, p 60 months, p PPB and IPVB was an independent risk factor for TFS and OS in resected NSCLC patients.

  8. The tumor-to-breast volume ratio (TBR) predicts cancer-specific survival in breast cancer patients who underwent modified radical mastectomy.

    Science.gov (United States)

    Wen, Jiahuai; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Yang, Lu; Xiao, Xiangsheng; Xie, Xiaoming

    2016-06-01

    Breast cancer is the most common cancer in women globally, and tumor size measured as the largest diameter of the tumor focus is currently used in tumor-lymph node-metastasis (TNM) staging for prognosis and treatment decisions. The present study utilized the tumor-to-breast volume ratio (TBR) to evaluate the relative tumor size and determined the prognostic impact of TBR on survival in patients with breast cancer. Two thousand twenty-five consecutive breast cancer patients who underwent modified radical mastectomy between January 2002 and December 2008 at Sun Yat-Sen University Cancer Center were enrolled in this retrospective study. Kaplan-Meier analysis was used to assess the prognostic effect of TBR on cancer-specific survival (CSS), and univariate log-rank test and multivariate Cox proportional hazards regression model were performed to identify independent prognostic factors. The optimal cutoff value of TBR was determined to be 1.70 %, and 1473 and 552 patients were categorized to low-TBR and high-TBR groups, respectively. In the whole patient cohort, CSS was significantly shorter in the high-TBR group (110.2 vs 128.5 months, P breast cancer patients (hazard ratio (HR) 1.489, 95 % CI 1.130-1.961, P = 0.005). High TBR was independently associated with poor prognosis in breast cancer patients. This variable may serve as a valuable parameter to predict the outcomes of breast cancer.

  9. Fibroblast growth factor receptor 4 gene (FGFR4) 388Arg allele predicts prolonged survival and platinum sensitivity in advanced ovarian cancer.

    Science.gov (United States)

    Marmé, Frederik; Hielscher, Thomas; Hug, Sarah; Bondong, Sandra; Zeillinger, Robert; Castillo-Tong, Dan Cacsire; Sehouli, Jalid; Braicu, Ioana; Vergote, Ignace; Isabella, Cadron; Mahner, Sven; Ferschke, Irmgard; Rom, Joachim; Sohn, Christof; Schneeweiss, Andreas; Altevogt, Peter

    2012-08-15

    FGFR4 has been shown to play an important role in the etiology and progression of solid tumors. A single nucleotide polymorphism (SNP) within the FGFR4 gene has previously been linked to prognosis and response to chemotherapy in breast cancer and other malignancies. This study evaluates the relevance of this SNP in advanced ovarian cancer. FGFR4-genotype was analyzed in 236 patients recruited as part of the OVCAD project. Genotyping was performed on germ-line DNA using a TaqMan based genotyping assay. Results were correlated with clinicopathological variables and survival. The FGFR4 388Arg genotype was significantly associated with prolonged progression-free and overall survival (univariate: HR 0.68, p = 0.017; HR 0.49, p = 0.005; multivariate: HR 0.69, p = 0.025; HR 0.49, p = 0.006) though the positive prognostic value was restricted to patients without postoperative residual tumor. Indeed, there was a significant interaction between FGFR4 genotype and residual tumor for overall survival. Furthermore, the FGFR4 388Arg genotype significantly correlated with platinum sensitivity in the same subgroup (multivariate OR 3.81 p = 0.004). FGFR4 Arg388Gly genotype is an independent and strong context specific prognostic factor in patients with advanced ovarian cancer and could be used to predict platinum-sensitivity.

  10. Validation of the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) pulmonary hypertension prediction model in a unique population and utility in the prediction of long-term survival.

    Science.gov (United States)

    Cogswell, Rebecca; Kobashigawa, Erin; McGlothlin, Dana; Shaw, Robin; De Marco, Teresa

    2012-11-01

    The Registry to Evaluate Early and Long-Term Pulmonary Arterial (PAH) Hypertension Disease Management (REVEAL) model was designed to predict 1-year survival in patients with PAH. Multivariate prediction models need to be evaluated in cohorts distinct from the derivation set to determine external validity. In addition, limited data exist on the utility of this model in the prediction of long-term survival. REVEAL model performance was assessed to predict 1-year and 5-year outcomes, defined as survival or composite survival or freedom from lung transplant, in 140 patients with PAH. The validation cohort had a higher proportion of human immunodeficiency virus (7.9% vs 1.9%, p model to predict survival was 0.765 at 1 year and 0.712 at 5 years of follow-up. The C-index of the model to predict composite survival or freedom from lung transplant was 0.805 and 0.724 at 1 and 5 years of follow-up, respectively. Prediction by the model, however, was weakest among patients with intermediate-risk predicted survival. The REVEAL model had adequate discrimination to predict 1-year survival in this small but clinically distinct validation cohort. Although the model also had predictive ability out to 5 years, prediction was limited among patients of intermediate risk, suggesting our prediction methods can still be improved. Copyright © 2012. Published by Elsevier Inc.

  11. Combining Gait Speed and Recall Memory to Predict Survival in Late Life: Population-Based Study.

    Science.gov (United States)

    Marengoni, Alessandra; Bandinelli, Stefania; Maietti, Elisa; Guralnik, Jack; Zuliani, Giovanni; Ferrucci, Luigi; Volpato, Stefano

    2017-03-01

    To evaluate the relationship between gait speed, recall memory, and mortality. A cohort study (last follow-up December 2009). Tuscany, Italy. Individual data from 1,014 community-dwelling older adults aged 60 years or older with baseline gait speed and recall memory measurements and follow-up for a median time of 9.10 (IQR 7.1;9.3) years. Participants were a mean (SD) age of 73.9 (7.3) years, and 55.8% women. Participants walking faster than 0.8 m/s were defined as fast walkers; good recall memory was defined as a score of 2 or 3 in the 3-word delayed recall section of the Mini-Mental State Examination. All-cause mortality. There were 302 deaths and the overall 100 person-year death rate was 3.77 (95% CI: 3.37-4.22). Both low gait speed and poor recall memory were associated with mortality when analysed separately (HR = 2.47; 95% CI: 1.87-3.27 and HR = 1.47; 95% CI: 1.16-1.87, respectively). When we grouped participants according to both recall and gait speed, death rates (100 person-years) progressively increased from those with both good gait speed and memory (2.0; 95% CI: 1.6-2.5), to those with fast walk but poor memory (3.4; 95% CI: 2.8-4.2), to those with slow walk and good memory (8.8; 95% CI: 6.4-12.1), to those with both slow walk and poor memory (13.0; 95% CI: 10.6-16.1). In multivariate analysis, poor memory significantly increases mortality risk among persons with fast gait speed (HR = 1.40; 95% CI: 1.04-1.89). In older persons, gait speed and recall memory are independent predictors of expected survival. Information on memory function might better stratify mortality risk among persons with fast gait speed. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  12. Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation.

    Science.gov (United States)

    Ting, Stephen M S; Iqbal, Hasan; Kanji, Hemali; Hamborg, Thomas; Aldridge, Nicolas; Krishnan, Nithya; Imray, Chris H E; Banerjee, Prithwish; Bland, Rosemary; Higgins, Robert; Zehnder, Daniel

    2014-01-01

    Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for ≤5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan-Meier estimates, patients with AT ratio, 4.48; 95% confidence interval, 1.78 to 11.38; P=0.002). Survival did not differ significantly among patients with AT ≥40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant.

  13. Celecoxib and LLW-3-6 Reduce Survival of Human Glioma Cells Independently and Synergistically with Sulfasalazine.

    Science.gov (United States)

    Yerokun, Tokunbo; Winfield, Leyte L

    2015-12-01

    Gliomas are among the most commonly diagnosed central nervous system tumors. Celecoxib has been utilized with success in the treatment of several types of cancer, including gliomas. The present study examined the antiproliferative effects of celecoxib and its benzimidazole-based analog, LLW-3-6, when used as co-treatment with sulfasalazine against human glioma LN18 cells. At 48-h treatment, the glioma cells maintained 60% viability in the presence of celecoxib or LLW-3-6 at the maximum concentration tested (40 μM). Co-treatment of glioma cells under a non-lethal dose (50 μM) of sulfasalazine and either celecoxib or LLW-3-6 (administered at different concentrations) resulted in improved inhibition of cell viability. The concentration of the molecules required to reduce cell growth in the combined treatment was significantly less than that needed when either molecule was administered independently. Based on computational values, LLW-3-6 has physiochemical characteristics that should allow for improved bioavailability in comparison to that of celecoxib.

  14. Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer

    Science.gov (United States)

    Feng, Ming-Xuan; Wang, Ya-Hui; Yang, Xiao-Mei; He, Ping; Tian, Guang-Ang; Zhang, Xiao-Xin; Li, Qing; Cao, Xiao-Yan; Huo, Yan-Miao; Yang, Min-Wei; Fu, Xue-Liang; Li, Jiao; Liu, De-Jun; Dai, Miao; Wen, Shan-Yun; Gu, Jian-Ren; Hong, Jie; Hua, Rong; Zhang, Zhi-Gang; Sun, Yong-Wei

    2016-01-01

    Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3), an extracellular matrix (ECM) protein associated with vascular morphogenesis and remodeling, is commonly upregulated in multiple types of human cancers and correlates with tumor progression. However, its expression pattern and underlying cellular functions in pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. In current study, we observed that expression of EDIL3 was significantly up-regulated in PDAC compared with normal controls in both cell lines and clinical specimens. In addition, elevated EDIL3 expression was positively correlated with patients’ TNM stage and T classification. Kaplan-Meier analysis indicated that high EDIL3 expression was significantly associated with shorter overall survival times in PDAC patients. Multivariate Cox regression analysis confirmed EDIL3 expression, age, lymph node metastasis and histological differentiation as independent prognostic factors in PDAC. Knockdown of EDIL3 showed no significant influence on cell viability, migration, invasion and starvation-induced apoptosis, but compromised anoikis resistance and anchorage independent tumor growth of PDAC cells. Meanwhile, treatment with recombinant EDIL3 protein markedly promoted anoikis resistance and anchorage independent tumor growth. Mechanistically, we demonstrated that altered protein expression of Bcl-2 family might contribute to the oncogenic activities of EDIL3. In conclusion, this study provides evidences that EDIL3 is a potential predictor and plays an important role in anchorage independent tumor growth of PDAC and EDIL3-related pathways might represent a novel therapeutic strategy for treatment of pancreatic cancer. PMID:26735172

  15. Role functioning before start of adjuvant treatment was an independent prognostic factor for survival and time to failure. A report from the Nordic adjuvant interferon trial for patients with high-risk melanoma

    DEFF Research Database (Denmark)

    Brandberg, Yvonne; Johansson, Hemming; Aamdal, Steinar

    2013-01-01

    To investigate the role of health-related quality of life (HRQoL) at randomization as independent prognostic factors for survival and time to failure, and to explore associations between HRQoL and treatment effects.......To investigate the role of health-related quality of life (HRQoL) at randomization as independent prognostic factors for survival and time to failure, and to explore associations between HRQoL and treatment effects....

  16. Predicting short-term survival after liver transplantation on eight score systems: a national report from China Liver Transplant Registry.

    Science.gov (United States)

    Ling, Qi; Dai, Haojiang; Zhuang, Runzhou; Shen, Tian; Wang, Weilin; Xu, Xiao; Zheng, Shusen

    2017-02-13

    To compare the performance of eight score systems (MELD, uMELD, MELD-Na. iMELD, UKELD, MELD-AS, CTP, and mCTP) in predicting the post-transplant mortality, we analyzed the data of 6,014 adult cirrhotic patients who underwent liver transplantation between January 2003 and December 2010 from the China Liver Transplant Registry database. In hepatitis B virus (HBV) group, MELD, uMELD and MELD-AS showed good predictive accuracies at 3-month mortality after liver transplantation; by comparison with other five models, MELD presented the best ability in predicting 3-month, 6-month and 1-year mortality, showing a significantly better predictive ability than UKELD and iMELD. In hepatitis C virus and Alcohol groups, the predictive ability did not differ significantly between MELD and other models. Patient survivals in different MELD categories were of statistically significant difference. Among patients with MELD score >35, a new prognostic model based on serum creatinine, need for hemodialysis and moderate ascites could identify the sickest one. In conclusion, MELD is superior to other score systems in predicting short-term post-transplant survival in patients with HBV-related liver disease. Among patients with MELD score >35, a new prognostic model can identify the sickest patients who should be excluded from waiting list to prevent wasteful transplantation.

  17. Elevated preoperative neutrophil-to-lymphocyte ratio predicts poor disease-free survival in Chinese women with breast cancer.

    Science.gov (United States)

    Hong, Jin; Mao, Yan; Chen, Xiaosong; Zhu, Li; He, Jianrong; Chen, Weiguo; Li, Yafen; Lin, Lin; Fei, Xiaochun; Shen, Kunwei

    2016-03-01

    Inflammation and tumor immune microenviroment are critical factors for prognosis in numerous cancers. The aim of this study was to determine the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) in breast cancer. We performed a retrospective analysis of 487 patients diagnosed with primary breast cancer at Shanghai Ruijin hospital from January 2009 to December 2010. Hematological parameters before surgery, clinicopathological data, and survival status were obtained. Survival analysis was used to evaluate the prognostic value of NLR. The optimal cutoff value was determined as 1.93 for NLR and the median follow-up time was 55.0 months. On univariate analysis, patients with high NLR (>1.93) had worse 5-year disease-free survival (DFS) compared to those with low NLR (77.9 vs 88.0 %, p = 0.002). Regarding overall survival, there was no significant difference between patients with high NLR and low NLR, with 5-year overall survival of 90.8 and 91.7 % (p = 0.707). In triple-negative breast cancer, patients with high NLR was associated with worse 5-year DFS compared with patients with low NLR (63.4 vs 84.9 %, p = 0.040). Mutivariate analysis revealed that NLR was an independent prognostic factor for DFS in breast cancer (HR = 1.867, 95 % confidence interval; (95%CI) = 1.155-3.017, p = 0.011). Preoperative NLR is an independent predictor of DFS in breast cancer patients, especially in triple-negative subtype. Further studies are required to validate the prognostic value of NLR before clinical application.

  18. The use of multiple hierarchically independent gene ontology terms in gene function prediction and genome annotation

    NARCIS (Netherlands)

    Kourmpetis, Y.I.A.; Burgt, van der A.; Bink, M.C.A.M.; Braak, ter C.J.F.; Ham, van R.C.H.J.

    2007-01-01

    The Gene Ontology (GO) is a widely used controlled vocabulary for the description of gene function. In this study we quantify the usage of multiple and hierarchically independent GO terms in the curated genome annotations of seven well-studied species. In most genomes, significant proportions (6 -

  19. An early-biomarker algorithm predicts lethal graft-versus-host disease and survival

    Science.gov (United States)

    Hartwell, Matthew J.; Özbek, Umut; Holler, Ernst; Major-Monfried, Hannah; Reddy, Pavan; Aziz, Mina; Hogan, William J.; Ayuk, Francis; Efebera, Yvonne A.; Hexner, Elizabeth O.; Bunworasate, Udomsak; Qayed, Muna; Ordemann, Rainer; Wölfl, Matthias; Mielke, Stephan; Chen, Yi-Bin; Devine, Steven; Jagasia, Madan; Kitko, Carrie L.; Litzow, Mark R.; Kröger, Nicolaus; Locatelli, Franco; Morales, George; Nakamura, Ryotaro; Reshef, Ran; Rösler, Wolf; Weber, Daniela; Yanik, Gregory A.; Levine, John E.; Ferrara, James L.M.

    2017-01-01

    BACKGROUND. No laboratory test can predict the risk of nonrelapse mortality (NRM) or severe graft-versus-host disease (GVHD) after hematopoietic cellular transplantation (HCT) prior to the onset of GVHD symptoms. METHODS. Patient blood samples on day 7 after HCT were obtained from a multicenter set of 1,287 patients, and 620 samples were assigned to a training set. We measured the concentrations of 4 GVHD biomarkers (ST2, REG3α, TNFR1, and IL-2Rα) and used them to model 6-month NRM using rigorous cross-validation strategies to identify the best algorithm that defined 2 distinct risk groups. We then applied the final algorithm in an independent test set (n = 309) and validation set (n = 358). RESULTS. A 2-biomarker model using ST2 and REG3α concentrations identified patients with a cumulative incidence of 6-month NRM of 28% in the high-risk group and 7% in the low-risk group (P < 0.001). The algorithm performed equally well in the test set (33% vs. 7%, P < 0.001) and the multicenter validation set (26% vs. 10%, P < 0.001). Sixteen percent, 17%, and 20% of patients were at high risk in the training, test, and validation sets, respectively. GVHD-related mortality was greater in high-risk patients (18% vs. 4%, P < 0.001), as was severe gastrointestinal GVHD (17% vs. 8%, P < 0.001). The same algorithm can be successfully adapted to define 3 distinct risk groups at GVHD onset. CONCLUSION. A biomarker algorithm based on a blood sample taken 7 days after HCT can consistently identify a group of patients at high risk for lethal GVHD and NRM. FUNDING. The National Cancer Institute, American Cancer Society, and the Doris Duke Charitable Foundation. PMID:28194439

  20. Impact of tumour volume on prediction of progression-free survival in sinonasal cancer

    Directory of Open Access Journals (Sweden)

    Hennersdorf Florian

    2015-09-01

    Full Text Available Background. The present study aimed to analyse potential prognostic factors, with emphasis on tumour volume, in determining progression free survival (PFS for malignancies of the nasal cavity and the paranasal sinuses.

  1. The cardio-renal-anaemia syndrome predicts survival in peritoneally dialyzed patients

    National Research Council Canada - National Science Library

    Malyszko, Jolanta; Zbroch, Edyta; Malyszko, Jacek; Mysliwiec, Michal; Iaina, Adrian

    2010-01-01

    .... The correction of anaemia was effective in the amelioration of both cardiac and renal failure. We studied the relationship between the severity of CRA syndrome in peritoneally dialyzed patients and their survival probability...

  2. Development of a Summarized Health Index (SHI) for use in predicting survival in sea turtles.

    Science.gov (United States)

    Li, Tsung-Hsien; Chang, Chao-Chin; Cheng, I-Jiunn; Lin, Suen-Chuain

    2015-01-01

    Veterinary care plays an influential role in sea turtle rehabilitation, especially in endangered species. Physiological characteristics, hematological and plasma biochemistry profiles, are useful references for clinical management in animals, especially when animals are during the convalescence period. In this study, these factors associated with sea turtle surviving were analyzed. The blood samples were collected when sea turtles remained alive, and then animals were followed up for surviving status. The results indicated that significantly negative correlation was found between buoyancy disorders (BD) and sea turtle surviving (p sea turtles had significantly higher levels of aspartate aminotranspherase (AST), creatinine kinase (CK), creatinine and uric acid (UA) than surviving sea turtles (all p sea turtles and to improve veterinary care at rehabilitation facilities.

  3. A critical analysis of the combined usage of protein localization prediction methods: Increasing the number of independent data sets can reduce the accuracy of predicted mitochondrial localization

    Science.gov (United States)

    Lythgow, Kieren T.; Hudson, Gavin; Andras, Peter; Chinnery, Patrick F.

    2011-01-01

    In the absence of a comprehensive experimentally derived mitochondrial proteome, several bioinformatic approaches have been developed to aid the identification of novel mitochondrial disease genes within mapped nuclear genetic loci. Often, many classifiers are combined to increase the sensitivity and specificity of the predictions. Here we show that the greatest sensitivity and specificity are obtained by using a combination of seven carefully selected classifiers. We also show that increasing the number of independent prediction methods can paradoxically decrease the accuracy of predicting mitochondrial localization. This approach will help to accelerate the identification of new mitochondrial disease genes by providing a principled way for the selection for combination of appropriate prediction methods of mitochondrial localization of proteins. PMID:21195798

  4. Pretransplant prediction of posttransplant survival for liver recipients with benign end-stage liver diseases: a nonlinear model.

    Directory of Open Access Journals (Sweden)

    Ming Zhang

    Full Text Available BACKGROUND: The scarcity of grafts available necessitates a system that considers expected posttransplant survival, in addition to pretransplant mortality as estimated by the MELD. So far, however, conventional linear techniques have failed to achieve sufficient accuracy in posttransplant outcome prediction. In this study, we aim to develop a pretransplant predictive model for liver recipients' survival with benign end-stage liver diseases (BESLD by a nonlinear method based on pretransplant characteristics, and compare its performance with a BESLD-specific prognostic model (MELD and a general-illness severity model (the sequential organ failure assessment score, or SOFA score. METHODOLOGY/PRINCIPAL FINDINGS: With retrospectively collected data on 360 recipients receiving deceased-donor transplantation for BESLD between February 1999 and August 2009 in the west China hospital of Sichuan university, we developed a multi-layer perceptron (MLP network to predict one-year and two-year survival probability after transplantation. The performances of the MLP, SOFA, and MELD were assessed by measuring both calibration ability and discriminative power, with Hosmer-Lemeshow test and receiver operating characteristic analysis, respectively. By the forward stepwise selection, donor age and BMI; serum concentration of HB, Crea, ALB, TB, ALT, INR, Na(+; presence of pretransplant diabetes; dialysis prior to transplantation, and microbiologically proven sepsis were identified to be the optimal input features. The MLP, employing 18 input neurons and 12 hidden neurons, yielded high predictive accuracy, with c-statistic of 0.91 (P<0.001 in one-year and 0.88 (P<0.001 in two-year prediction. The performances of SOFA and MELD were fairly poor in prognostic assessment, with c-statistics of 0.70 and 0.66, respectively, in one-year prediction, and 0.67 and 0.65 in two-year prediction. CONCLUSIONS/SIGNIFICANCE: The posttransplant prognosis is a multidimensional nonlinear

  5. Polymorphisms in MicroRNA Binding Sites Predict Colorectal Cancer Survival

    Science.gov (United States)

    Yang, Ying-Pi; Ting, Wen-Chien; Chen, Lu-Min; Lu, Te-Ling; Bao, Bo-Ying

    2017-01-01

    Background: MicroRNAs (miRNAs) mediate negative regulation of target genes through base pairing, and aberrant miRNA expression has been described in cancers. We hypothesized that single nucleotide polymorphisms (SNPs) within miRNA target sites might influence clinical outcomes in patients with colorectal cancer. Methods: Sixteen common SNPs within miRNA target sites were identified, and the association between these SNPs and overall survival was assessed in colorectal cancer patients using Kaplan-Meier analysis, Cox regression model, and survival tree analysis. Results: Survival tree analysis identified a higher-order genetic interaction profile consisting of the RPS6KB1 rs1051424 and ZNF839 rs11704 that was significantly associated with overall survival. The 5-year survival rates were 74.6%, 62.7%, and 57.1% for the low-, medium-, and high-risk genetic profiles, respectively (P = 0.006). The genetic interaction profile remained significant even after adjusting for potential risk factors. Additional in silico analysis provided evidence that rs1051424 and rs11704 affect RPS6KB1 and ZNF839 expressions, which in turn is significantly correlated with prognosis in colorectal cancer. Conclusion: Our results suggest that the genetic interaction profiles among SNPs within miRNA target sites might be prognostic markers for colorectal cancer survival. PMID:28138309

  6. Multi-objective evolutionary algorithms for fuzzy classification in survival prediction.

    Science.gov (United States)

    Jiménez, Fernando; Sánchez, Gracia; Juárez, José M

    2014-03-01

    This paper presents a novel rule-based fuzzy classification methodology for survival/mortality prediction in severe burnt patients. Due to the ethical aspects involved in this medical scenario, physicians tend not to accept a computer-based evaluation unless they understand why and how such a recommendation is given. Therefore, any fuzzy classifier model must be both accurate and interpretable. The proposed methodology is a three-step process: (1) multi-objective constrained optimization of a patient's data set, using Pareto-based elitist multi-objective evolutionary algorithms to maximize accuracy and minimize the complexity (number of rules) of classifiers, subject to interpretability constraints; this step produces a set of alternative (Pareto) classifiers; (2) linguistic labeling, which assigns a linguistic label to each fuzzy set of the classifiers; this step is essential to the interpretability of the classifiers; (3) decision making, whereby a classifier is chosen, if it is satisfactory, according to the preferences of the decision maker. If no classifier is satisfactory for the decision maker, the process starts again in step (1) with a different input parameter set. The performance of three multi-objective evolutionary algorithms, niched pre-selection multi-objective algorithm, elitist Pareto-based multi-objective evolutionary algorithm for diversity reinforcement (ENORA) and the non-dominated sorting genetic algorithm (NSGA-II), was tested using a patient's data set from an intensive care burn unit and a standard machine learning data set from an standard machine learning repository. The results are compared using the hypervolume multi-objective metric. Besides, the results have been compared with other non-evolutionary techniques and validated with a multi-objective cross-validation technique. Our proposal improves the classification rate obtained by other non-evolutionary techniques (decision trees, artificial neural networks, Naive Bayes, and case

  7. The Carcinoma–Stromal Ratio of Colon Carcinoma Is an Independent Factor for Survival Compared to Lymph Node Status and Tumor Stage

    Directory of Open Access Journals (Sweden)

    Wilma E. Mesker

    2007-01-01

    Full Text Available Background: Tumor staging insufficiently discriminates between colon cancer patients with poor and better prognosis. We have evaluated, for the primary tumor, if the carcinoma-percentage (CP, as a derivative from the carcinoma-stromal ratio, can be applied as a candidate marker to identify patients for adjuvant therapy. Methods: In a retrospective study of 63 patients with colon cancer (stage I–III, 1990–2001 the carcinoma-percentage of the primary tumor was estimated on routine H&E stained histological sections. Additionally these findings were validated in a second independent study of 59 patients (stage I–III, 1980–1992. (None of the patients had received preoperative chemo- or radiation therapy nor adjuvant chemotherapy. Results: Of 122 analyzed patients 33 (27.0% had a low CP and 89 (73.0% a high CP. The analysis of mean survival revealed: overall-survival (OS 2.13 years, disease-free- survival (DFS 1.51 years for CP-low and OS 7.36 years, DFS 6.89 years for CP-high. Five-year survival rates for CP-low versus CP-high were respectively for OS: 15.2% and 73.0% and for DFS: 12.1% and 67.4%. High levels of significance were found (OS p < 0.0001, DFS p < 0.0001 with hazard ratio’s of 3.73 and 4.18. In a multivariate Cox regression analysis, CP remained an independent variable when adjusted for either stage or for tumor status and lymph-node status (OSp < 0.001, OSp < 0.001. Conclusions: The carcinoma-percentage in primary colon cancer is a factor to discriminate between patients with a poor and a better outcome of disease. This parameter is already available upon routine histological investigation and can, in addition to the TNM classification, be a candidate marker to further stratify into more individual risk groups.

  8. Ability of Functional Independence Measure to accurately predict functional outcome of stroke-specific population: Systematic review

    OpenAIRE

    Madeleine Spencer, DPT, PT; Karen Skop, DPT, PT; Kristina Shesko, DPT, PT; Kristen Nollinger, DPT, PT; Douglas Chumney, DPT, PT; Roberta A. Newton, PT, PhD

    2010-01-01

    Stroke is a leading cause of functional impairments. The ability to quantify the functional ability of poststroke patients engaged in a rehabilitation program may assist in prediction of their functional outcome. The Functional Independence Measure (FIM) is widely used and accepted as a functional-level assessment tool that evaluates the functional status of patients throughout the rehabilitation process. From February to March 2009, we searched MEDLINE, Ovid, CINAHL, and EBSCO for full-text ...

  9. Social affiliation matters: both same-sex and opposite-sex relationships predict survival in wild female baboons.

    Science.gov (United States)

    Archie, Elizabeth A; Tung, Jenny; Clark, Michael; Altmann, Jeanne; Alberts, Susan C

    2014-10-22

    Social integration and support can have profound effects on human survival. The extent of this phenomenon in non-human animals is largely unknown, but such knowledge is important to understanding the evolution of both lifespan and sociality. Here, we report evidence that levels of affiliative social behaviour (i.e. 'social connectedness') with both same-sex and opposite-sex conspecifics predict adult survival in wild female baboons. In the Amboseli ecosystem in Kenya, adult female baboons that were socially connected to either adult males or adult females lived longer than females who were socially isolated from both sexes--females with strong connectedness to individuals of both sexes lived the longest. Female social connectedness to males was predicted by high dominance rank, indicating that males are a limited resource for females, and females compete for access to male social partners. To date, only a handful of animal studies have found that social relationships may affect survival. This study extends those findings by examining relationships to both sexes in by far the largest dataset yet examined for any animal. Our results support the idea that social effects on survival are evolutionarily conserved in social mammals.

  10. Technical Note: Assessing predictive capacity and conditional independence of landslide predisposing factors for shallow landslide susceptibility models

    Directory of Open Access Journals (Sweden)

    S. Pereira

    2012-04-01

    Full Text Available The aim of this study is to identify the landslide predisposing factors' combination using a bivariate statistical model that best predicts landslide susceptibility. The best model is one that has simultaneously good performance in terms of suitability and predictive power and has been developed using variables that are conditionally independent. The study area is the Santa Marta de Penaguião council (70 km2 located in the Northern Portugal.

    In order to identify the best combination of landslide predisposing factors, all possible combinations using up to seven predisposing factors were performed, which resulted in 120 predictions that were assessed with a landside inventory containing 767 shallow translational slides. The best landslide susceptibility model was selected according to the model degree of fitness and on the basis of a conditional independence criterion. The best model was developed with only three landslide predisposing factors (slope angle, inverse wetness index, and land use and was compared with a model developed using all seven landslide predisposing factors.

    Results showed that it is possible to produce a reliable landslide susceptibility model using fewer landslide predisposing factors, which contributes towards higher conditional independence.

  11. Predicting the activity coefficients of free-solvent for concentrated globular protein solutions using independently determined physical parameters.

    Directory of Open Access Journals (Sweden)

    Devin W McBride

    Full Text Available The activity coefficient is largely considered an empirical parameter that was traditionally introduced to correct the non-ideality observed in thermodynamic systems such as osmotic pressure. Here, the activity coefficient of free-solvent is related to physically realistic parameters and a mathematical expression is developed to directly predict the activity coefficients of free-solvent, for aqueous protein solutions up to near-saturation concentrations. The model is based on the free-solvent model, which has previously been shown to provide excellent prediction of the osmotic pressure of concentrated and crowded globular proteins in aqueous solutions up to near-saturation concentrations. Thus, this model uses only the independently determined, physically realizable quantities: mole fraction, solvent accessible surface area, and ion binding, in its prediction. Predictions are presented for the activity coefficients of free-solvent for near-saturated protein solutions containing either bovine serum albumin or hemoglobin. As a verification step, the predictability of the model for the activity coefficient of sucrose solutions was evaluated. The predicted activity coefficients of free-solvent are compared to the calculated activity coefficients of free-solvent based on osmotic pressure data. It is observed that the predicted activity coefficients are increasingly dependent on the solute-solvent parameters as the protein concentration increases to near-saturation concentrations.

  12. Predicting the activity coefficients of free-solvent for concentrated globular protein solutions using independently determined physical parameters.

    Science.gov (United States)

    McBride, Devin W; Rodgers, Victor G J

    2013-01-01

    The activity coefficient is largely considered an empirical parameter that was traditionally introduced to correct the non-ideality observed in thermodynamic systems such as osmotic pressure. Here, the activity coefficient of free-solvent is related to physically realistic parameters and a mathematical expression is developed to directly predict the activity coefficients of free-solvent, for aqueous protein solutions up to near-saturation concentrations. The model is based on the free-solvent model, which has previously been shown to provide excellent prediction of the osmotic pressure of concentrated and crowded globular proteins in aqueous solutions up to near-saturation concentrations. Thus, this model uses only the independently determined, physically realizable quantities: mole fraction, solvent accessible surface area, and ion binding, in its prediction. Predictions are presented for the activity coefficients of free-solvent for near-saturated protein solutions containing either bovine serum albumin or hemoglobin. As a verification step, the predictability of the model for the activity coefficient of sucrose solutions was evaluated. The predicted activity coefficients of free-solvent are compared to the calculated activity coefficients of free-solvent based on osmotic pressure data. It is observed that the predicted activity coefficients are increasingly dependent on the solute-solvent parameters as the protein concentration increases to near-saturation concentrations.

  13. High-sensitivity C-reactive protein levels predict survival and are related to haemodynamics in alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Mortensen, Christian; Andersen, Ove; Krag, Aleksander;

    2012-01-01

    Inflammation may be implicated in the haemodynamic deterioration and in the development of complications in patients with cirrhosis. High-sensitivity C-reactive protein (hsCRP) is a marker of low-grade inflammation, and predicts outcomes in patients at risk of ischaemic heart disease....... Proinflammatory cytokines reflect immune activation and have been found to be elevated in cirrhosis. We investigated a possible association between markers of inflammation and splanchnic and systemic haemodynamics, complications and survival in patients with cirrhosis....

  14. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    OpenAIRE

    Fleischmann, Achim; Thalmann, George; Perren, Aurel; Seiler,Roland

    2014-01-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumor...

  15. A graded prognostic assessment scale to predict overall survival in patients diagnosed with brain metastases undergoing Gamma-knife radiosurgery

    OpenAIRE

    Shahzadi, Sohrab; Azimi, Parisa; Bitaraf, Mohammad Ali; Azar, Maziar; Alikhani, Mazdak; Zali, Alireza; Sadeghi, Sohrab; Salmanian, Soraya

    2012-01-01

    Abstract: Background: The present study aims to evaluate the Graded Prognostic Assessment (GPA) score for predicting overall survival in patients diagnosed with brain metastases undergoing Gamma-knife radiosurgery. Methods: This was a cross sectional study conducted on the patients diagnosed with brain metastases undergoing Gamma-knife radiosurgery during 2003 to 2011. Clinical and radiological parameters were evaluated, and the GPA score were determined. Kaplan–Meier and log-rank tests were ...

  16. Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer.

    Science.gov (United States)

    Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

    2017-07-01

    This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.

  17. Obstructive sleep apnea predicts risk of metabolic syndrome independently of obesity: a meta-analysis

    Science.gov (United States)

    Qian, Yingjun; Xu, Huajun; Wang, Yuyu; Yi, Hongliang; Yin, Shankai

    2016-01-01

    Introduction Obstructive sleep apnea (OSA) has been suggested to be associated with a high risk of metabolic syndrome (MS). However, results on whether the association between OSA and risk of MS is independent of obesity, and the effect of nocturnal intermittent hypoxia (IH) on MS, are conflicting. Our purpose was to estimate the magnitude of the independent association between OSA and risk of MS and further explore whether nocturnal IH in OSA plays a role in MS risk. Material and methods The PubMed and EMBASE databases were systematically searched (until January 21, 2015) for available observational evidence. Unadjusted and body mass index (BMI)-adjusted pooled odds ratios (ORs) for MS in OSA or higher nocturnal IH were calculated using fixed or random models. Tests of homogeneity, publication bias, and robustness of the results were performed. Results A total of 13 independent studies (involving 857 participants in 3 case-control studies and 7077 participants in 10 cross-sectional studies) were included. The OSA was significantly associated with an increased risk of MS in a meta-analysis of 10 studies (pooled OR = 1.72, 95% CI: 1.31–2.26, p < 0.001), with a BMI-adjusted pooled OR of 1.97 (95% CI: 1.34–2.88, p < 0.001). Pooled results from 3 studies on the oxygen desaturation index (ODI) and MS risk (OR = 1.96, 95% CI: 1.73–2.22, p < 0.001) and 3 studies on the cumulative percentage of sleep time with SpO2 below 90% (CT90) and MS risk (OR = 1.05, 95% CI: 1.02–1.07, p < 0.001) were also significant. Conclusions Our findings demonstrated a significant association between OSA and increased MS risk independent of BMI, and further indicated a role of nocturnal IH in this association.

  18. Zone-size nonuniformity of {sup 18}F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Nai-Ming [Chang Gung Memorial Hospital and Chang Gung University, Departments of Nuclear Medicine, Taiyuan (China); Chang Gung Memorial Hospital, Department of Nuclear Medicine, Keelung (China); National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Fang, Yu-Hua Dean [Chang Gung University, Department of Electrical Engineering, Taiyuan (China); Lee, Li-yu [Chang Gung University College of Medicine, Department of Pathology, Chang Gung Memorial Hospital, Taoyuan (China); Chang, Joseph Tung-Chieh; Tsan, Din-Li [Chang Gung University College of Medicine, Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan (China); Ng, Shu-Hang [Chang Gung University College of Medicine, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Taoyuan (China); Wang, Hung-Ming [Chang Gung University College of Medicine, Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan (China); Liao, Chun-Ta [Chang Gung University College of Medicine, Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan (China); Yang, Lan-Yan [Chang Gung Memorial Hospital, Biostatistics Unit, Clinical Trial Center, Taoyuan (China); Hsu, Ching-Han [National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Yen, Tzu-Chen [Chang Gung Memorial Hospital and Chang Gung University, Departments of Nuclear Medicine, Taiyuan (China); Chang Gung University College of Medicine, Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taipei (China)

    2014-10-23

    The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUV{sub max} 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment {sup 18}F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUV{sub max} 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification. (orig.)

  19. Predictive factors for survival for out-born infants born between 23 and 24 weeks of gestation in the post-surfactant era: fourteen years' experience in a single neonatal care unit, 1987-2000.

    Science.gov (United States)

    Hosono, Shigeharu; Ohno, Tsutomu; Kimoto, Hirofumi; Shimizu, Masaki; Takahashi, Shigeru; Harada, Kensuke

    2008-10-01

    The purpose of the present paper was to identify the predictive factors for survival for out-born infants born between 23 and 24 weeks of gestation. Ninety-two infants born between 23 and 24 weeks' gestation who were admitted to a level III neonatal intensive care unit from 1987 to 2000, were retrospectively studied. Survival was defined as discharge from the neonatal intensive care unit. Logistic regression was done to determine which clinical factors were most predictive of survival. The independent variables that were entered into the models were determined by preliminary univariate analysis. Ninety-two infants were enrolled in the present study, 49 of whom survived in the surfactant era. The four variables that were found to be most predictive for survival on logistic regression were systolic blood pressure at 6 h (odds ratio [OR], 1.3; 95% confidence interval [CI]: 1.11-1.44 1 mmHg), ventilatory index born at 23-24 weeks of gestation.

  20. Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Yosuke [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Takahashi, Akihisa [Advanced Scientific Research Leader Development Unit, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Kajihara, Atsuhisa; Yamakawa, Nobuhiro; Imai, Yuichiro [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ota, Ichiro; Okamoto, Noritomo [Department of Otorhinolaryngology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Mori, Eiichiro [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Noda, Taichi [Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Furusawa, Yoshiya [Heavy-ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kirita, Tadaaki [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ohnishi, Takeo, E-mail: tohnishi@naramed-u.ac.jp [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer High-LET radiation induces efficiently apoptosis regardless of p53 gene status. Black-Right-Pointing-Pointer We examined whether high-LET radiation depresses the Akt-survival signals. Black-Right-Pointing-Pointer High-LET radiation depresses of survival signals even in the mp53 cancer cells. Black-Right-Pointing-Pointer High-LET radiation activates Caspase-9 through depression of survival signals. Black-Right-Pointing-Pointer High-LET radiation suppresses cell growth through depression of survival signals. -- Abstract: Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6 h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G{sub 2}/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp

  1. Early post-treatment FDG PET predicts survival after {sup 90}Y microsphere radioembolization in liver-dominant metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Aouf, Anas; Sabet, Amin; Ghamari, Shahab; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Meyer, Carsten; Pieper, Claus C. [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2014-10-29

    The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with {sup 90}Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent {sup 18}F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUV{sub max}) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p < 0.001) with a median OS of 10 months (95 % CI 3-16) versus 4 months (95 % CI 2-6). Hepatic tumour burden also had significant impact on treatment outcome (p < 0.001) with a median OS of 5 months (95 % CI, 3-7) for patients with >25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using {sup 18}F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

  2. Elevated Pretreatment Serum Concentration of YKL-40-An Independent Prognostic Biomarker for Poor Survival in Patients With Metastatic Nonsmall Cell Lung Cancer

    DEFF Research Database (Denmark)

    Thom, I.; Andritzky, B.; Schuch, G.

    2010-01-01

    BACKGROUND: The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role...... of YKL-40 has not been established in non-small cell lung cancer (NSCLC). METHODS: Pretreatment serum levels of YKL-40 were determined in 189 patients with NSCLC (143 men and 46 women; median age, 62 years;, age range, 41-76 years). Twelve percent of patients had stage IIIB disease, and 88% had stage IV...... below the median (median survival, 32 weeks vs 41 weeks; P = .007). In multivariate analysis, the serum YKL-40 level, the presence of bone lesions, and the serum lactate dehydrogenase level were independent, statistically significant prognostic factors. CONCLUSIONS: The pretreatment serum YKL-40 level...

  3. Using weather indices to predict survival of winter wheat in a cool temperate environment

    Science.gov (United States)

    Hayhoe, H. N.; Lapen, D. R.; Andrews, C. J.

    2002-10-01

    Seven years of winter survival data for winter wheat (Triticum aestivum L.) were collected on a loam soil located on the Central Experimental Farm at Ottawa, Ontario (45°23'N, 75°43'W). The site was low-lying and subject to frequent winter flooding and ice-sheet formation. Two cultivars, a soft white and a hard red winter wheat, were planted in September. Crop establishment was measured in late fall and the percentage survival was measured in April of the following year. Meteorological data, which were available from the nearby weather site, were used to develop a large set of monthly weather indices that were felt to be important for winter survival. The objective of the study was to use genetic selection algorithms and artificial neural networks to select a subset of critical weather factors and topographic features and to model winter survival. The six weather indices selected were the total rain depth for December (mm), the total rain depth for February (mm), the number of days of the month with snow on the ground for January, the extreme minimum observed daily air temperature for March (°C), the number of days of the month with snow on the ground for March, and the number of days of April with a daily maximum air temperature greater than 0 °C. It was found 89% of the variation in winter survival could be explained by these six weather indices, the cultivar, elevation and plot location.

  4. Cognitive performance and functional status are the major factors predicting survival of centenarians in Poland.

    Science.gov (United States)

    Mossakowska, Malgorzata; Broczek, Katarzyna; Wieczorowska-Tobis, Katarzyna; Klich-Rączka, Alicja; Jonas, Marta; Pawlik-Pachucka, Eliza; Safranow, Krzysztof; Kuznicki, Jacek; Puzianowska-Kuznicka, Monika

    2014-10-01

    Clinical and biochemical predictors of extreme longevity would be useful in geriatric practice but have still not been clearly defined. To identify the best nongenetic predictors of survival in centenarians, we examined 340 individuals aged 100+ years. A detailed questionnaire was completed, and comprehensive geriatric assessment and blood analyses were performed. Survival of study participants was checked annually over the period of 10 years. In the univariate Cox proportional hazards model, a longer survival of centenarians was correlated with a higher adjusted Mini-Mental State Examination (MMSE(adj)) score (p HR = 0.978 per each MMSE(adj) point, 95% CI: 0.964-0.993, p = .004; HR = 0.900 per each ADL point, 95% CI: 0.842-0.962, p = .002, respectively). In multivariate analysis with the ADL score substituted by the IADL(adj) score, the only predictor of survival was MMSE(adj) (HR = 0.973 per each MMSE(adj) point, 95% CI: 0.958-0.988, p = .0006). Cognitive and functional performances are predictors of survival in centenarians. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Protein kinase A (PknA) of Mycobacterium tuberculosis is independently activated and is critical for growth in vitro and survival of the pathogen in the host.

    Science.gov (United States)

    Nagarajan, Sathya Narayanan; Upadhyay, Sandeep; Chawla, Yogesh; Khan, Shazia; Naz, Saba; Subramanian, Jayashree; Gandotra, Sheetal; Nandicoori, Vinay Kumar

    2015-04-10

    The essential mycobacterial protein kinases PknA and PknB play crucial roles in modulating cell shape and division. However, the precise in vivo functional aspects of PknA have not been investigated. This study aims to dissect the role of PknA in mediating cell survival in vitro as well as in vivo. We observed aberrant cell shape and severe growth defects when PknA was depleted. Using the mouse infection model, we observe that PknA is essential for survival of the pathogen in the host. Complementation studies affirm the importance of the kinase, juxtamembrane, and transmembrane domains of PknA. Surprisingly, the extracytoplasmic domain is dispensable for cell growth and survival in vitro. We find that phosphorylation of the activation loop at Thr(172) of PknA is critical for bacterial growth. PknB has been previously suggested to be the receptor kinase, which activates multiple kinases, including PknA, by trans-phosphorylating their activation loop residues. Using phospho-specific PknA antibodies and conditional pknB mutant, we find that PknA autophosphorylates its activation loop independent of PknB. Fluorescently tagged PknA and PknB show distinctive distribution patterns within the cell, suggesting that although both kinases are known to modulate cell shape and division, their modes of action are likely to be different. This is supported by our findings that expression of kinase-dead PknA versus kinase-dead PknB in mycobacterial cells leads to different cellular phenotypes. Data indicate that although PknA and PknB are expressed as part of the same operon, they appear to be regulating cellular processes through divergent signaling pathways.

  6. CCR9 interactions support ovarian cancer cell survival and resistance to cisplatin-induced apoptosis in a PI3K-dependent and FAK-independent fashion

    Directory of Open Access Journals (Sweden)

    Johnson Erica L

    2010-06-01

    Full Text Available Abstract Background Cisplatin is more often used to treat ovarian cancer (OvCa, which provides modest survival advantage primarily due to chemo-resistance and up regulated anti-apoptotic machineries in OvCa cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in OvCa cell may improve therapeutic outcomes. We have shown that ovarian cancer cells express CC chemokine receptor-9 (CCR9. Others have also shown that CCL25, the only natural ligand for CCR9, up regulates anti-apoptotic proteins in immature T lymphocytes. Hence, it is plausible that CCR9-mediated cell signals might be involved in OvCa cell survival and inhibition of cisplatin-induced apoptosis. In this study, we investigated the potential role and molecular mechanisms of CCR9-mediated inhibition of cisplatin-induced apoptosis in OvCa cells. Methods Cell proliferation, vibrant apoptosis, and TUNEL assays were performed with or without cisplatin treatment in presence or absence of CCL25 to determine the role of the CCR9-CCL25 axis in cisplatin resistance. In situ Fast Activated cell-based ELISA (FACE assays were performed to determine anti-apoptotic signaling molecules responsible for CCL25-CCR9 mediated survival. Results Our results show interactions between CCR9 and CCL25 increased anti-apoptotic signaling cascades in OvCa cells, which rescued cells from cisplatin-induced cell death. Specifically, CCL25-CCR9 interactions mediated Akt, activation as well as GSK-3β and FKHR phosphorylation in a PI3K-dependent and FAK-independent fashion. Conclusions Our results suggest the CCR9-CCL25 axis plays an important role in reducing cisplatin-induced apoptosis of OvCa cells.

  7. Artificial neural network modeling using clinical and knowledge independent variables predicts salt intake reduction behavior.

    Science.gov (United States)

    Isma'eel, Hussain A; Sakr, George E; Almedawar, Mohamad M; Fathallah, Jihan; Garabedian, Torkom; Eddine, Savo Bou Zein; Nasreddine, Lara; Elhajj, Imad H

    2015-06-01

    High dietary salt intake is directly linked to hypertension and cardiovascular diseases (CVDs). Predicting behaviors regarding salt intake habits is vital to guide interventions and increase their effectiveness. We aim to compare the accuracy of an artificial neural network (ANN) based tool that predicts behavior from key knowledge questions along with clinical data in a high cardiovascular risk cohort relative to the least square models (LSM) method. We collected knowledge, attitude and behavior data on 115 patients. A behavior score was calculated to classify patients' behavior towards reducing salt intake. Accuracy comparison between ANN and regression analysis was calculated using the bootstrap technique with 200 iterations. Starting from a 69-item questionnaire, a reduced model was developed and included eight knowledge items found to result in the highest accuracy of 62% CI (58-67%). The best prediction accuracy in the full and reduced models was attained by ANN at 66% and 62%, respectively, compared to full and reduced LSM at 40% and 34%, respectively. The average relative increase in accuracy over all in the full and reduced models is 82% and 102%, respectively. Using ANN modeling, we can predict salt reduction behaviors with 66% accuracy. The statistical model has been implemented in an online calculator and can be used in clinics to estimate the patient's behavior. This will help implementation in future research to further prove clinical utility of this tool to guide therapeutic salt reduction interventions in high cardiovascular risk individuals.

  8. Intra-operative amylase in peri-pancreatic fluid independently predicts for pancreatic fistula post pancreaticoduodectomy

    NARCIS (Netherlands)

    Reuver, P.R.; Gundara, J.; Hugh, T.J.; Samra, J.S.; Mittal, A.

    2016-01-01

    BACKGROUND: Post-operative pancreatic fistula (POPF) is a common and potentially life-threatening complication following pancreaticoduodectomy. The aim of this study was to assess the predictive value of intra-operative amylase concentration (IOAC) in peri-pancreatic fluid after resection for the di

  9. Rapid brain responses independently predict gain maximization and loss minimization during economic decision making.

    Science.gov (United States)

    San Martín, René; Appelbaum, Lawrence G; Pearson, John M; Huettel, Scott A; Woldorff, Marty G

    2013-04-17

    Success in many decision-making scenarios depends on the ability to maximize gains and minimize losses. Even if an agent knows which cues lead to gains and which lead to losses, that agent could still make choices yielding suboptimal rewards. Here, by analyzing event-related potentials (ERPs) recorded in humans during a probabilistic gambling task, we show that individuals' behavioral tendencies to maximize gains and to minimize losses are associated with their ERP responses to the receipt of those gains and losses, respectively. We focused our analyses on ERP signals that predict behavioral adjustment: the frontocentral feedback-related negativity (FRN) and two P300 (P3) subcomponents, the frontocentral P3a and the parietal P3b. We found that, across participants, gain maximization was predicted by differences in amplitude of the P3b for suboptimal versus optimal gains (i.e., P3b amplitude difference between the least good and the best gains). Conversely, loss minimization was predicted by differences in the P3b amplitude to suboptimal versus optimal losses (i.e., difference between the worst and the least bad losses). Finally, we observed that the P3a and P3b, but not the FRN, predicted behavioral adjustment on subsequent trials, suggesting a specific adaptive mechanism by which prior experience may alter ensuing behavior. These findings indicate that individual differences in gain maximization and loss minimization are linked to individual differences in rapid neural responses to monetary outcomes.

  10. Postoperative neutrophil-to-lymphocyte ratio change predicts survival of patients with small hepatocellular carcinoma undergoing radiofrequency ablation.

    Directory of Open Access Journals (Sweden)

    Jiaqiang Dan

    Full Text Available BACKGROUND: An elevated preoperative neutrophil-to-lymphocyte ratio (NLR has been reported to be a prognostic factor for hepatocellular carcinoma (HCC patients after treatment. However, the clinical implication of postoperative NLR change remains unclear. MATERIALS AND METHODS: From May 2005 to Aug 2008, a cohort of consecutive 178 small HCC patients treated with radiofrequency ablation (RFA was retrospectively reviewed. The NLR was recorded within 3 days before and 1 month after RFA. Baseline characteristics, overall survival (OS and recurrence free survival (RFS were compared according to preoperative NLR and/or postoperative NLR change. Prognostic factors were assessed by multivariate analysis. RESULTS: Compared with preoperative NLR level, postoperative NLR decreased in 87 patients and increased in 91 patients after RFA. No significant differences were identified between two groups in commonly used clinic-pathologic features. The 1, 3, 5 years OS was 98.8%, 78.6%, 67.1% for NLR decreased group, and 92.2%, 55.5%, 35.4% for NLR increased group respectively (P<0.001; the corresponding RFS was 94.2%, 65.2%, 33.8% and 81.7%, 46.1%, 12.4% respectively (P<0.001. In subgroup analysis, the survival of patients with lower or higher preoperative NLR can be distinguished more accurate by postoperative NLR change. Multivariate analysis showed that postoperative NLR change, but not preoperative NLR, was an independent prognostic factor for both OS (P<0.001, HR = 2.39, 95%CI 1.53-3.72 and RFS (P = 0.003, HR = 1.69, 95%CI 1.87-8.24. CONCLUSION: The postoperative NLR change was an independent prognostic factor for small HCC patient undergoing RFA, and patients with decreased NLR indicated better survival than those with increased NLR.

  11. An ENSO-Forecast Independent Statistical Model for the Prediction of Annual Atlantic Tropical Cyclone Frequency in April

    Directory of Open Access Journals (Sweden)

    Kenny Xie

    2014-01-01

    Full Text Available Statistical models for preseason prediction of annual Atlantic tropical cyclone (TC and hurricane counts generally include El Niño/Southern Oscillation (ENSO forecasts as a predictor. As a result, the predictions from such models are often contaminated by the errors in ENSO forecasts. In this study, it is found that the latent heat flux (LHF over Eastern Tropical Pacific (ETP, defined as the region 0°–5°N, 115°–125°W in spring is negatively correlated with the annual Atlantic TC and hurricane counts. By using stepwise backward elimination regression, it is further shown that the March value of ETP LHF is a better predictor than the spring or summer ENSO index for Atlantic TC counts. Leave-one-out cross validation indicates that the annual Atlantic TC counts predicted by this ENSO-independent statistical model show a remarkable correlation with the actual TC counts (R=0.72; P value <0.01. For Atlantic hurricanes, the predictions using March ETP LHF and summer (July–September ENSO indices show only minor differences except in moderate to strong El Niño years. Thus, March ETP LHF is an excellent predictor for seasonal Atlantic TC prediction and a viable alternative to using ENSO index for Atlantic hurricane prediction.

  12. Predicting the Survival Time for Bladder Cancer Using an Addi-tive Hazards Model in Microarray Data

    Directory of Open Access Journals (Sweden)

    Leili TAPAK

    2016-02-01

    Full Text Available Background: One substantial part of microarray studies is to predict patients’ survival based on their gene expression profile. Variable selection techniques are powerful tools to handle high dimensionality in analysis of microarray data. However, these techniques have not been investigated in competing risks setting. This study aimed to investigate the performance of four sparse variable selection methods in estimating the survival time.Methods: The data included 1381 gene expression measurements and clinical information from 301 patients with bladder cancer operated in the years 1987 to 2000 in hospitals in Denmark, Sweden, Spain, France, and England. Four methods of the least absolute shrinkage and selection operator, smoothly clipped absolute deviation, the smooth integration of counting and absolute deviation and elastic net were utilized for simultaneous variable selection and estimation under an additive hazards model. The criteria of area under ROC curve, Brier score and c-index were used to compare the methods.Results: The median follow-up time for all patients was 47 months. The elastic net approach was indicated to outperform other methods. The elastic net had the lowest integrated Brier score (0.137±0.07 and the greatest median of the over-time AUC and C-index (0.803±0.06 and 0.779±0.13, respectively. Five out of 19 selected genes by the elastic net were significant (P<0.05 under an additive hazards model. It was indicated that the expression of RTN4, SON, IGF1R and CDC20 decrease the survival time, while the expression of SMARCAD1 increase it.Conclusion: The elastic net had higher capability than the other methods for the prediction of survival time in patients with bladder cancer in the presence of competing risks base on additive hazards model.Keywords: Survival analysis, Microarray data, Additive hazards model, Variable selection, Bladder cancer 

  13. Bcl-2/Bax protein ratio predicts 5-fluorouracil sensitivity independently of p53 status

    OpenAIRE

    Mirjolet, J-F; Barberi-Heyob, M; Didelot, C; Peyrat, J-P; Abecassis, J; Millon, R.; Merlin, J-L

    2000-01-01

    p53 tumour-suppressor gene is involved in cell growth control, arrest and apoptosis. Nevertheless cell cycle arrest and apoptosis induction can be observed in p53-defective cells after exposure to DNA-damaging agents such as 5-fluorouracil (5-FU) suggesting the importance of alternative pathways via p53-independent mechanisms. In order to establish relationship between p53 status, cell cycle arrest, Bcl-2/Bax regulation and 5-FU sensitivity, we examined p53 mRNA and protein expression and p53...

  14. Strange quark polarization of the nucleon: a parameter-independent prediction of the chiral potential model.

    Science.gov (United States)

    Chen, X B; Chen, X S; Wang, F

    2001-07-02

    We perform a one-loop calculation of the strange quark polarization (Deltas) of the nucleon in an SU(3) chiral potential model. We find that if the intermediate quark excited states are summed over in a proper way, i.e., summed up to a given energy instead of given radial and orbital quantum numbers, Deltas turns out to be almost independent of all the model parameters: quark masses and potential strengths. The contribution from the quark-antiquark pair creation and annihilation " Z" diagrams is found to be significant. Our numerical results agree quite reasonably with experiments and lattice QCD calculations.

  15. Number of rib fractures thresholds independently predict worse outcomes in older patients with blunt trauma.

    Science.gov (United States)

    Shulzhenko, Nikita O; Zens, Tiffany J; Beems, Megan V; Jung, Hee Soo; O'Rourke, Ann P; Liepert, Amy E; Scarborough, John E; Agarwal, Suresh K

    2017-04-01

    There have been conflicting reports regarding whether the number of rib fractures sustained in blunt trauma is associated independently with worse patient outcomes. We sought to investigate this risk-adjusted relationship among the lesser-studied population of older adults. A retrospective review of the National Trauma Data Bank was performed for patients with blunt trauma who were ≥65 years old and had rib fractures between 2009 and 2012 (N = 67,695). Control data were collected for age, sex, injury severity score, injury mechanism, 24 comorbidities, and number of rib fractures. Outcome data included hospital mortality, hospital and intensive care unit durations of stay, duration of mechanical ventilation, and the occurrence of pneumonia. Multiple logistic and linear regression analyses were performed. Sustaining ≥5 rib fractures was associated with increased intensive care unit admission (odds ratio: 1.14, P rib fractures was associated with an increased incidence of pneumonia (odds ratio: 1.32, P rib fractures was associated with increased mortality (odds ratio: 1.51, P rib fractures is a significant predictor of worse outcomes independent of patient characteristics, comorbidities, and trauma burden. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis☆

    Science.gov (United States)

    Ripoll, Cristina; Groszmann, Roberto J.; Garcia-Tsao, Guadalupe; Bosch, Jaime; Grace, Norman; Burroughs, Andrew; Planas, Ramon; Escorsell, Angels; Garcia-Pagan, Juan Carlos; Makuch, Robert; Patch, David; Matloff, Daniel S.

    2013-01-01

    Background/Aims A total of 213 patients with compensated cirrhosis, portal hypertension and no varices were included in a trial evaluating beta-blockers in preventing varices. Predictors of the development of hepatocellular carcinoma (HCC), including hepatic venous pressure gradient (HVPG) were analyzed. Methods Baseline laboratory tests, ultrasound and HVPG measurements were performed. Patients were followed prospectively every three months until development of varices or variceal bleeding or end of the study in 09/02. The endpoint was HCC development according to standard diagnostic criteria. Univariate and multivariate Cox regression models were developed to identify predictors of HCC. Results In a median follow-up of 58 months 26/213 (12.2%) patients developed HCC. Eight patients were transplanted and 28 patients died without HCC. Twenty-one (84%) HCC developed in patients with HCV. On multivariate analysis HVPG (HR 1.18; 95%CI 1.08–1.29), albumin (HR 0.34; 95%CI 0.14–0.83) and viral etiology (HR 4.59; 95%CI 1.51–13.92) were independent predictors of HCC development. ROC curves identified 10 mmHg of HVPG as the best cutoff; those who had an HVPG above this value had a 6-fold increase in the HCC incidence. Conclusions Portal hypertension is an independent predictor of HCC development. An HVPG >10 mmHg is associated with a 6-fold increase of HCC risk. PMID:19303163

  17. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chun-Chieh [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China); Lai, Chyong-Huey [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Huang, Yi-Ting [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Chao, Angel; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China)

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  18. The G Protein-Coupled Receptor RAI3 Is an Independent Prognostic Factor for Pancreatic Cancer Survival and Regulates Proliferation via STAT3 Phosphorylation

    Science.gov (United States)

    Jahny, Elisabeth; Yang, Hai; Liu, Bin; Jahnke, Beatrix; Lademann, Franziska; Knösel, Thomas; Rümmele, Petra; Grützmann, Robert; Aust, Daniela E.; Denz, Axel

    2017-01-01

    Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest tumors worldwide. Understanding the function of gene expression alterations is a prerequisite for developing new strategies in diagnostic and therapy. GPRC5A (RAI3), coding for a seven transmembrane G protein-coupled receptor is known to be overexpressed in pancreatic cancer and might be an interesting candidate for therapeutic intervention. Expression levels of RAI3 were compared using a tissue microarray of 435 resected patients with pancreatic cancer as well as 209 samples from chronic pancreatitis (CP), intra-ductal papillary mucinous neoplasm (IPMN) and normal pancreatic tissue. To elucidate the function of RAI3 overexpression, siRNA based knock-down was used and transfected cells were analyzed using proliferation and migration assays. Pancreatic cancer patients showed a statistically significant overexpression of RAI3 in comparison to normal and chronic pancreatitis tissue. Especially the loss of apical RAI3 expression represents an independent prognostic parameter for overall survival of patients with pancreatic cancer. Suppression of GPRC5a results in decreased cell growth, proliferation and migration in pancreatic cancer cell lines via a STAT3 modulated pathway, independent from ERK activation. PMID:28114355

  19. Chest computed tomography scores are predictive of survival in patients with cystic fibrosis awaiting lung transplantation

    DEFF Research Database (Denmark)

    Loeve, Martine; Hop, Wim C. J.; de Bruijne, Marleen

    2012-01-01

    /inflammation" (INF), air trapping/hypoperfusion (AT), normal/hyperperfusion (NOR) and bulla/cysts (BUL). The volume of each component was computed using semi-automated software. Survival analysis included Kaplan-Meier curves, and Cox-regression models. Measurements and main results: 366 (186 males) out of 411...

  20. Retransplantation of the liver in adults : outcome and predictive factors for survival

    NARCIS (Netherlands)

    Postma, R; Haagsma, EB; Peeters, PMJG; van den Berg, AP; Slooff, MJH

    2004-01-01

    Hepatic retransplantation is considered to carry a higher risk than primary transplantation. Survival might improve with more experience and better immunosuppression. We studied all 55 patients who were adults at the time of their first retransplantation and who underwent retransplantation between 1

  1. Prediction of Survival for Preterm Births by Weight and Gestational Age: Retrospective Population Based Study

    National Research Council Canada - National Science Library

    Elizabeth S. Draper; Bradley Manktelow; David J. Field; David James

    1999-01-01

    ... (a) known to be alive at the onset of labour, and (b) admitted for neonatal care. Results 738 deaths occurred in 3760 infants born between 22 and 32 weeks' gestation during the study period, giving an overall survival rate of 80.4...

  2. Are Breast Cancer Molecular Classes Predictive of Survival in Patients with Long Follow-Up?

    Directory of Open Access Journals (Sweden)

    Danae Pracella

    2013-01-01

    Full Text Available In this study we investigate the clinical outcomes of 305 breast cancer (BC patients, aged 55 years or younger, with long follow-up and according to intrinsic subtypes. The cohort included 151 lymph node negative (LN− and 154 lymph node positive (LN+ patients. Luminal A tumors were mainly LN−, well differentiated, and of stage I; among them AR was an indicator of good prognosis. Luminal B and HER2 positive nonluminal cancers showed higher tumor grade and nodal metastases as well as higher proliferation status and stage. Among luminal tumors, those PR positive and vimentin negative showed a longer survival. HER2-positive nonluminal and TN patients showed a poorer outcome, with BC-specific death mostly occurring within 5 and 10 years. Only luminal tumor patients underwent BC death over 10 years. When patients were divided in to LN− and LN+ no differences in survival were observed in the luminal subgroups. LN− patients have good survival even after 20 years of follow-up (about 75%, while for LN+ patients survival at 20 years (around 40% was comparable to HER2-positive nonluminal and TN groups. In conclusion, in our experience ER-positive breast tumors are better divided by classical clinical stage than molecular classification, and they need longer clinical follow-up especially in cases with lymph node involvement.

  3. Predicting Secondary School Dropout among South African Adolescents: A Survival Analysis Approach

    Science.gov (United States)

    Weybright, Elizabeth H.; Caldwell, Linda L.; Xie, Hui; Wegner, Lisa; Smith, Edward A.

    2017-01-01

    Education is one of the strongest predictors of health worldwide. In South Africa, school dropout is a crisis where by Grade 12, only 52% of the age appropriate population remain enrolled. Survival analysis was used to identify the risk of dropping out of secondary school for male and female adolescents and examine the influence of substance use…

  4. 139 Clinically Applicable and Biologically Validated MRI Radiomic Test Method Predicts Glioblastoma Genomic Landscape and Survival.

    Science.gov (United States)

    Zinn, Pascal O; Singh, Sanjay K; Kotrotsou, Aikaterini; Zandi, Faramak; Thomas, Ginu; Hatami, Masumeh; Luedi, Markus M; Elakkad, Ahmed; Hassan, Islam; Gumin, Joy; Sulman, Erik P; Lang, Frederick F; Colen, Rivka R

    2016-08-01

    Imaging is the modality of choice for noninvasive characterization of biological tissue and organ systems; imaging serves as early diagnostic tool for most disease processes and is rapidly evolving, thus transforming the way we diagnose and follow patients over time. A vast number of cancer imaging characteristics have been correlated to underlying genomics; however, none have established causality. Therefore, our objectives were to test if there is a causal relationship between imaging and genomic information; and to develop a clinically relevant radiomic pipeline for glioblastoma molecular characterization. Functional validation was performed using a prototypic in vivo RNA-interference-based orthotopic xenograft mouse model. The automated pipeline collects 4800 MRI-derived texture features per tumor. Using univariate feature selection and boosted tree predictive modeling, a patient-specific genomic probability map was derived and patient survival predicted (The Cancer Genome Atlas/MD Anderson data sets). Data demonstrated a significant xenograft to human association (area under the curve [AUC] 84%, P applicable analytical imaging method termed Radiome Sequencing to allow for automated image analysis, prediction of key genomic events, and survival. This method is scalable and applicable to any type of medical imaging. Further, it allows for human-mouse matched coclinical trials, in-depth end point analysis, and upfront noninvasive high-resolution radiomics-based diagnostic, prognostic, and predictive biomarker development.

  5. Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma.

    Science.gov (United States)

    Svendsen, Agnete; Verhoeff, Joost J C; Immervoll, Heike; Brøgger, Jan C; Kmiecik, Justyna; Poli, Aurelie; Netland, Inger A; Prestegarden, Lars; Planagumà, Jesús; Torsvik, Anja; Kjersem, Anneli Bohne; Sakariassen, Per Ø; Heggdal, Jan I; Van Furth, Wouter R; Bjerkvig, Rolf; Lund-Johansen, Morten; Enger, Per Ø; Felsberg, Joerg; Brons, Nicolaas H C; Tronstad, Karl J; Waha, Andreas; Chekenya, Martha

    2011-10-01

    Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experimental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This effect was independent of age at diagnosis, treatment received and hypermethylation of the O(6)-methylguanine methyltransferase (MGMT) DNA repair gene promoter. NG2 was frequently co-expressed with nestin and vimentin but rarely with CD133 and the NG2 positive tumour cells harboured genetic aberrations typical for GBM. 2D proteomics of 11 randomly selected biopsies revealed upregulation of an antioxidant, peroxiredoxin-1 (PRDX-1), in the shortest surviving patients. Expression of PRDX-1 was associated with significantly reduced products of oxidative stress. Furthermore, NG2 expressing GBM cells showed resistance to ionising radiation (IR), rapidly recognised DNA damage and effectuated cell cycle checkpoint signalling. PRDX-1 knockdown transiently slowed tumour growth rates and sensitised them to IR in vivo. Our data establish NG2 as an important prognostic factor for GBM patient survival, by mediating resistance to radiotherapy through induction of ROS scavenging enzymes and preferential DNA damage signalling.

  6. Predicting Individualized Postoperative Survival for Stage II/III Colon Cancer Using a Mobile Application Derived from the National Cancer Data Base

    Science.gov (United States)

    Gabriel, Emmanuel; Attwood, Kristopher; Thirunavukarasu, Pragatheeshwar; Al-Sukhni, Eisar; Boland, Patrick; Nurkin, Steven

    2017-01-01

    BACKGROUND Prediction calculators estimate postoperative survival and assist the decision-making process for adjuvant treatment. The objective of this study was to create a postoperative overall survival (OS) calculator for patients with stage II/III colon cancer. Factors that influence OS, including comorbidity and postoperative variables, were included. STUDY DESIGN The National Cancer Data Base was queried for patients with stage II/III colon cancer, diagnosed between 2004 and 2006, who had surgical resection. Patients were randomly divided to a testing (nt) cohort comprising 80% of the dataset and a validation (nv) cohort comprising 20%. Multivariable Cox proportional hazards regression of nt was performed to identify factors associated with 5-year OS. These were used to build a prediction model. The performance was assessed using the nv cohort and translated into mobile software. RESULTS A total of 129,040 patients had surgery. After exclusion of patients with carcinoma in situ, non-adenocarcinoma histology, more than 1 malignancy, stage I or IV disease, or missing data, 34,176 patients were used in the development of the calculator. Independent predictors of OS included patient-specific characteristics, pathologic factors, and treatment options, including type of surgery and adjuvant therapy. Length of postoperative stay and unplanned readmission rates were also incorporated as surrogates for postoperative complications (1-day increase in postoperative stay, hazard ratio [HR] 1.019, 95% CI 1.018 to 1.021, p cancer. This prediction model uses nationwide data, culminating in a highly comprehensive, clinically useful tool. PMID:26922599

  7. SU-E-T-131: Artificial Neural Networks Applied to Overall Survival Prediction for Patients with Periampullary Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Y; Yu, J; Yeung, V; Palmer, J; Yu, Y; Lu, B; Babinsky, L; Burkhart, R; Leiby, B; Siow, V; Lavu, H; Rosato, E; Winter, J; Lewis, N; Sama, A; Mitchell, E; Anne, P; Hurwitz, M; Yeo, C; Bar-Ad, V [Thomas Jefferson University Hospital, Philadelphia, PA (United States); and others

    2015-06-15

    Purpose: Artificial neural networks (ANN) can be used to discover complex relations within datasets to help with medical decision making. This study aimed to develop an ANN method to predict two-year overall survival of patients with peri-ampullary cancer (PAC) following resection. Methods: Data were collected from 334 patients with PAC following resection treated in our institutional pancreatic tumor registry between 2006 and 2012. The dataset contains 14 variables including age, gender, T-stage, tumor differentiation, positive-lymph-node ratio, positive resection margins, chemotherapy, radiation therapy, and tumor histology.After censoring for two-year survival analysis, 309 patients were left, of which 44 patients (∼15%) were randomly selected to form testing set. The remaining 265 cases were randomly divided into training set (211 cases, ∼80% of 265) and validation set (54 cases, ∼20% of 265) for 20 times to build 20 ANN models. Each ANN has one hidden layer with 5 units. The 20 ANN models were ranked according to their concordance index (c-index) of prediction on validation sets. To further improve prediction, the top 10% of ANN models were selected, and their outputs averaged for prediction on testing set. Results: By random division, 44 cases in testing set and the remaining 265 cases have approximately equal two-year survival rates, 36.4% and 35.5% respectively. The 20 ANN models, which were trained and validated on the 265 cases, yielded mean c-indexes as 0.59 and 0.63 on validation sets and the testing set, respectively. C-index was 0.72 when the two best ANN models (top 10%) were used in prediction on testing set. The c-index of Cox regression analysis was 0.63. Conclusion: ANN improved survival prediction for patients with PAC. More patient data and further analysis of additional factors may be needed for a more robust model, which will help guide physicians in providing optimal post-operative care. This project was supported by PA CURE Grant.

  8. Prediction models for the mortality risk in chronic dialysis patients: a systematic review and independent external validation study.

    Science.gov (United States)

    Ramspek, Chava L; Voskamp, Pauline Wm; van Ittersum, Frans J; Krediet, Raymond T; Dekker, Friedo W; van Diepen, Merel

    2017-01-01

    In medicine, many more prediction models have been developed than are implemented or used in clinical practice. These models cannot be recommended for clinical use before external validity is established. Though various models to predict mortality in dialysis patients have been published, very few have been validated and none are used in routine clinical practice. The aim of the current study was to identify existing models for predicting mortality in dialysis patients through a review and subsequently to externally validate these models in the same large independent patient cohort, in order to assess and compare their predictive capacities. A systematic review was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. To account for missing data, multiple imputation was performed. The original prediction formulae were extracted from selected studies. The probability of death per model was calculated for each individual within the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD). The predictive performance of the models was assessed based on their discrimination and calibration. In total, 16 articles were included in the systematic review. External validation was performed in 1,943 dialysis patients from NECOSAD for a total of seven models. The models performed moderately to well in terms of discrimination, with C-statistics ranging from 0.710 (interquartile range 0.708-0.711) to 0.752 (interquartile range 0.750-0.753) for a time frame of 1 year. According to the calibration, most models overestimated the probability of death. Overall, the performance of the models was poorer in the external validation than in the original population, affirming the importance of external validation. Floege et al's models showed the highest predictive performance. The present study is a step forward in the use of a prediction model as a useful tool for nephrologists, using evidence-based medicine that

  9. DEAR1 is a dominant regulator of acinar morphogenesis and an independent predictor of local recurrence-free survival in early-onset breast cancer.

    Directory of Open Access Journals (Sweden)

    Steven T Lott

    2009-05-01

    Full Text Available BACKGROUND: Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium-associated RING Chromosome 1, a novel gene encoding a member of the TRIM (tripartite motif subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer. METHODS AND FINDINGS: Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS, an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue

  10. Integration of Multi-Modal Biomedical Data to Predict Cancer Grade and Patient Survival.

    Science.gov (United States)

    Phan, John H; Hoffman, Ryan; Kothari, Sonal; Wu, Po-Yen; Wang, May D

    2016-02-01

    The Big Data era in Biomedical research has resulted in large-cohort data repositories such as The Cancer Genome Atlas (TCGA). These repositories routinely contain hundreds of matched patient samples for genomic, proteomic, imaging, and clinical data modalities, enabling holistic and multi-modal integrative analysis of human disease. Using TCGA renal and ovarian cancer data, we conducted a novel investigation of multi-modal data integration by combining histopathological image and RNA-seq data. We compared the performances of two integrative prediction methods: majority vote and stacked generalization. Results indicate that integration of multiple data modalities improves prediction of cancer grade and outcome. Specifically, stacked generalization, a method that integrates multiple data modalities to produce a single prediction result, outperforms both single-data-modality prediction and majority vote. Moreover, stacked generalization reveals the contribution of each data modality (and specific features within each data modality) to the final prediction result and may provide biological insights to explain prediction performance.

  11. Does feedback-related brain response during reinforcement learning predict socio-motivational (in-dependence in adolescence?

    Directory of Open Access Journals (Sweden)

    Diana eRaufelder

    2016-05-01

    Full Text Available This multi-methodological study applied functional magnetic resonance imaging (fMRI to investigate neural activation in a group of adolescent students (N = 88 during a probabilistic reinforcement learning task. We related patterns of emerging brain activity and individual learning rates to socio-motivational (in-dependence manifested in four different motivation types (MT: (1 peer-dependent MT, (2 teacher-dependent MT, (3 peer-and-teacher-dependent MT, (4 peer-and-teacher-independent MT. A multinomial regression analysis revealed that the individual learning rate predicts students’ membership to the independent MT, or the peer-and-teacher-dependent MT. Additionally, the striatum, a brain region associated with behavioral adaptation and flexibility, showed increased learning-related activation in students with motivational independence. Moreover, the prefrontal cortex, which is involved in behavioral control, was more active in students of the peer-and-teacher-dependent MT. Overall, this study offers new insights into the interplay of motivation and learning with (1 a focus on inter-individual differences in the role of peers and teachers as source of students’ individual motivation and (2 its potential neurobiological basis.

  12. Does Feedback-Related Brain Response during Reinforcement Learning Predict Socio-motivational (In-)dependence in Adolescence?

    Science.gov (United States)

    Raufelder, Diana; Boehme, Rebecca; Romund, Lydia; Golde, Sabrina; Lorenz, Robert C.; Gleich, Tobias; Beck, Anne

    2016-01-01

    This multi-methodological study applied functional magnetic resonance imaging to investigate neural activation in a group of adolescent students (N = 88) during a probabilistic reinforcement learning task. We related patterns of emerging brain activity and individual learning rates to socio-motivational (in-)dependence manifested in four different motivation types (MTs): (1) peer-dependent MT, (2) teacher-dependent MT, (3) peer-and-teacher-dependent MT, (4) peer-and-teacher-independent MT. A multinomial regression analysis revealed that the individual learning rate predicts students’ membership to the independent MT, or the peer-and-teacher-dependent MT. Additionally, the striatum, a brain region associated with behavioral adaptation and flexibility, showed increased learning-related activation in students with motivational independence. Moreover, the prefrontal cortex, which is involved in behavioral control, was more active in students of the peer-and-teacher-dependent MT. Overall, this study offers new insights into the interplay of motivation and learning with (1) a focus on inter-individual differences in the role of peers and teachers as source of students’ individual motivation and (2) its potential neurobiological basis. PMID:27199873

  13. Independent value added by diffusion MRI for prediction of cognitive function in older adults

    Directory of Open Access Journals (Sweden)

    Julia A Scott

    2017-01-01

    Full Text Available The purpose of this study was to determine whether white matter microstructure measured by diffusion magnetic resonance imaging (dMRI provides independent information about baseline level or change in executive function (EF or memory (MEM in older adults with and without cognitive impairment. Longitudinal data was acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI study from phases GO and 2 (2009–2015. ADNI participants included were diagnosed as cognitively normal (n = 46, early mild cognitive impairment (MCI (n = 48, late MCI (n = 29, and dementia (n = 39 at baseline. We modeled the association between dMRI-based global white matter mean diffusivity (MD and baseline level and change in EF and MEM composite scores, in models controlling for baseline bilateral hippocampal volume, regional cerebral FDG PET metabolism and global cerebral AV45 PET uptake. EF and MEM composite scores were measured at baseline, 6, 12, 24 and 36 months. In the baseline late MCI and dementia groups, greater global MD was associated with lesser baseline EF, but not EF change nor MEM baseline or change. As expected, lesser hippocampal volume and lesser FDG PET metabolism was associated with greater rates of EF and MEM decline. In ADNI-GO/2 participants, white matter integrity provided independent information about current executive function, but was not sensitive to future cognitive change. Since individuals experiencing executive function declines progress to dementia more rapidly than those with only memory impairment, better biomarkers of future executive function decline are needed.

  14. SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma.

    Science.gov (United States)

    Dhanda, J; Triantafyllou, A; Liloglou, T; Kalirai, H; Lloyd, B; Hanlon, R; Shaw, R J; Sibson, D R; Risk, J M

    2014-11-25

    Extracapsular spread (ECS) in cervical lymph nodes is the single-most prognostic clinical variable in oral squamous cell carcinoma (OSCC), but diagnosis is possible only after histopathological examination. A promising biomarker in the primary tumour, alpha smooth muscle actin (SMA) has been shown to be highly prognostic, however, validated biomarkers to predict ECS prior to primary treatment are not yet available. In 102 OSCC cases, conventional imaging was compared with pTNM staging. SERPINE1, identified from expression microarray of primary tumours as a potential biomarker for ECS, was validated through mRNA expression, and by immunohistochemistry (IHC) on a tissue microarray from the same cohort. Similarly, expression of SMA was also compared with its association with ECS and survival. Expression was analysed separately in the tumour centre and advancing front; and prognostic capability determined using Kaplan-Meier survival analysis. Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (PSMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (PSMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95%; SMA: 82%; combination: 81%). A combination of SMA and SERPINE1 IHC offer potential as prognostic biomarkers in OSCC. Our findings suggest that biomarkers at the invasive front are likely to be necessary in prediction of ECS or in therapeutic stratification.

  15. Correlation of Amine Swingbed On-Orbit CO2 Performance with a Hardware Independent Predictive Model

    Science.gov (United States)

    Papale, William; Sweterlitsch, Jeffery

    2015-01-01

    The Amine Swingbed Payload is an experimental system deployed on the International Space Station (ISS) that includes a two-bed, vacuum regenerated, amine-based carbon dioxide (CO2) removal subsystem as the principal item under investigation. The aminebased subsystem, also described previously in various publications as CAMRAS 3, was originally designed, fabricated and tested by Hamilton Sundstrand Space Systems International, Inc. (HSSSI) and delivered to NASA in November 2008. The CAMRAS 3 unit was subsequently designed into a flight payload experiment in 2010 and 2011, with flight test integration activities accomplished on-orbit between January 2012 and March 2013. Payload activation was accomplished in May 2013 followed by a 1000 hour experimental period. The experimental nature of the Payload and the interaction with the dynamic ISS environment present unique scientific and engineering challenges, in particular to the verification and validation of the expected Payload CO2 removal performance. A modeling and simulation approach that incorporates principles of chemical reaction engineering has been developed for the amine-based system to predict the dynamic cabin CO2 partial pressure with given inputs of sorbent bed size, process air flow, operating temperature, half-cycle time, CO2 generation rate, cabin volume and the magnitude of vacuum available. Simulation runs using the model to predict ambient CO2 concentrations show good correlation to on-orbit performance measurements and ISS dynamic concentrations for the assumed operating conditions. The dynamic predictive modelling could benefit operational planning to help ensure ISS CO2 concentrations are maintained below prescribed limits and for the Orion vehicle to simulate various operating conditions, scenarios and transients.

  16. Prediction of kidney survival in children with primary focal segmental glomerulosclerosis (a two-center study.

    Directory of Open Access Journals (Sweden)

    Alaleh Gheissari

    2007-07-01

    Full Text Available BACKGROUND: Focal segmental glomerulosclerosis (FSGS is one of the most common glomerulopathies in children leading to end stage renal disease (ESRD. Different values of median renal survival have been reported among different ethnicities and races. Many factors are assumed to be responsible for ESRD in these patients. In this study, we tried to determine median renal survival (MRS and also some clinical and histopathological features predisposing FSGS
    patients to ESRD in two referral hospitals in Tehran.
    METHODS: The study involved 103 FSGS patients (61 males and 42 females with a mean age of 7.08 ± 0.68 years. The diagnosis was made based on kidney biopsies. All kidney biopsies were studied by light and immunofluorescent microscopes. Ocular grids (counting squares were used as the standard method to calculate the percentage of cortical interstitial fibrosis (CIF. The percentage of glomerular sclerosis was presented as renal injury score. Glomerular filtration rate (GFR950 ml/min was considered as renal death or the end point. Patients were followed for 1 to 15 years, until occurrence of renal death.
    RESULTS: The MRS was 9.04 ± 1.8 yrs. The renal survival reached 72%, 47% and 17% after 5, 10 and 15 years, respectively. Univariate analysis showed significant reverse correlation (P<0.05 between renal survival and the following variables: hypertension, anemia, GFR at the time of first admission and also renal injury score >50%, peritubular fibrosis, periglomerular fibrosis, tubular atrophy and CIFC20%. However, multivariate analysis revealed only a reverse correlation between renal survival with CIFC20% and also hypertension (P<0.0001 and P<0.05, respectively.
    CONCLUSIONS: In our patients, FSGS showed a rapid course towards ESRD compared with patients of western countries. Perhaps some ethnic and genetic factors such as angiotensin converting enzyme genotypes

  17. Independent Monitoring for Network Survivability

    Science.gov (United States)

    2002-10-01

    controllable from web page (with password protection) archsvr felix.htmlweb browser (e.g. Netscape) GUI (web page) web server gnuplot cmd file postgres gnuplot ...operational. 2.2 Correlation / Matroid method simulation tool chain tiers Output ( gnuplot cmd file) imm matcorr reduce topomap fixedfxsim Path-link List...tiers Output ( gnuplot cmd file) realize weak reduce

  18. Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP

    Science.gov (United States)

    LeBlanc, Michael L.; Unger, Joseph M.; Miller, Thomas P.; Grogan, Thomas M.; Persky, Daniel O.; Martel, Ralph R.; Sabalos, Constantine M.; Seligmann, Bruce; Braziel, Rita M.; Campo, Elias; Rosenwald, Andreas; Connors, Joseph M.; Sehn, Laurie H.; Johnson, Nathalie; Gascoyne, Randy D.

    2008-01-01

    Gene expression profiling (GEP) on frozen tissues has identified genes predicting outcome in patients with diffuse large B-cell lymphoma (DLBCL). Confirmation of results in current patients is limited by availability of frozen samples and addition of monoclonal antibodies to treatment regimens. We used a quantitative nuclease protection assay (qNPA) to analyze formalin-fixed, paraffin-embedded tissue blocks for 36 previously identified genes (N = 209, 93 chemotherapy; 116 rituximab + chemotherapy). By qNPA, 208 cases were successfully analyzed (99.5%). In addition, 15 of 36 and 11 of 36 genes, representing each functional group previously identified by GEP, were associated with survival (P 80%) as independent indicators of survival, together distinguishing cases with the worst prognosis. Our results solve a clinical research problem by demonstrating that prognostic genes can be meaningfully quantified using qNPA technology on formalin-fixed, paraffin-embedded tissues; previous GEP findings in DLBCL are relevant with current treatments; and 2 genes, representing immune escape and proliferation, are the common features of the most aggressive DLBCL. PMID:18544678

  19. Combined Prediction Model of Death Toll for Road Traffic Accidents Based on Independent and Dependent Variables

    Science.gov (United States)

    Zhong-xiang, Feng; Shi-sheng, Lu; Wei-hua, Zhang; Nan-nan, Zhang

    2014-01-01

    In order to build a combined model which can meet the variation rule of death toll data for road traffic accidents and can reflect the influence of multiple factors on traffic accidents and improve prediction accuracy for accidents, the Verhulst model was built based on the number of death tolls for road traffic accidents in China from 2002 to 2011; and car ownership, population, GDP, highway freight volume, highway passenger transportation volume, and highway mileage were chosen as the factors to build the death toll multivariate linear regression model. Then the two models were combined to be a combined prediction model which has weight coefficient. Shapley value method was applied to calculate the weight coefficient by assessing contributions. Finally, the combined model was used to recalculate the number of death tolls from 2002 to 2011, and the combined model was compared with the Verhulst and multivariate linear regression models. The results showed that the new model could not only characterize the death toll data characteristics but also quantify the degree of influence to the death toll by each influencing factor and had high accuracy as well as strong practicability. PMID:25610454

  20. Financial strain and stressful events predict newlyweds' negative communication independent of relationship satisfaction.

    Science.gov (United States)

    Williamson, Hannah C; Karney, Benjamin R; Bradbury, Thomas N

    2013-02-01

    Social-learning perspectives explicitly recognize the role of partners' personal histories and contexts as possible causes of couple communication behavior, but these assumptions are rarely tested directly, and operationalizations of context in behavioral research on couples rarely extend beyond the interacting dyad. To broaden our understanding of why couples differ in communication, the current study examined whether observed behaviors in marital interactions covary with individual experiences and contextual factors. Behaviors coded from in-home conversations of 414 ethnically diverse newlywed couples were examined simultaneously in relation to childhood and family-of-origin experiences, financial strain and stressful life events, depressive symptoms, and relationship satisfaction. A latent factor representing financial strain and stressful life events was the strongest correlate of negative communication, with higher levels of stress predicting more negativity. Relationship satisfaction was the strongest correlate of observed positivity, with higher levels of satisfaction predicting more positivity. Childhood and family experiences were unrelated to behaviors, whereas results for depressive symptoms were complex and counterintuitive. Because the negative behaviors highlighted in social-learning models of relationship functioning, and often targeted in educational interventions, covary reliably with the stresses and financial strains that couples experience, contextual factors merit greater emphasis in models designed to explain and prevent marital deterioration.

  1. Combined Prediction Model of Death Toll for Road Traffic Accidents Based on Independent and Dependent Variables

    Directory of Open Access Journals (Sweden)

    Feng Zhong-xiang

    2014-01-01

    Full Text Available In order to build a combined model which can meet the variation rule of death toll data for road traffic accidents and can reflect the influence of multiple factors on traffic accidents and improve prediction accuracy for accidents, the Verhulst model was built based on the number of death tolls for road traffic accidents in China from 2002 to 2011; and car ownership, population, GDP, highway freight volume, highway passenger transportation volume, and highway mileage were chosen as the factors to build the death toll multivariate linear regression model. Then the two models were combined to be a combined prediction model which has weight coefficient. Shapley value method was applied to calculate the weight coefficient by assessing contributions. Finally, the combined model was used to recalculate the number of death tolls from 2002 to 2011, and the combined model was compared with the Verhulst and multivariate linear regression models. The results showed that the new model could not only characterize the death toll data characteristics but also quantify the degree of influence to the death toll by each influencing factor and had high accuracy as well as strong practicability.

  2. Salinity independent volume fraction prediction in water-gas-oil multiphase flows using artificial neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Salgado, C.M.; Pereira, Claudio M.N.A.; Brandao, Luis E.B., E-mail: otero@ien.gov.b, E-mail: cmnap@ien.gov.b, E-mail: brandao@ien.gov.b [Instituto de Engenharia Nuclear (DIRA/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Div. de Radiofarmacos

    2011-07-01

    This work investigates the response of a volume fraction prediction system for water-gas-oil multiphase flows considering variations on water salinity. The approach is based on gamma-ray pulse height distributions pattern recognition by means the artificial neural networks (ANNs). The detection system uses appropriate fan beam geometry, comprised of a dual-energy gamma-ray source and two NaI(Tl) detectors adequately positioned outside the pipe in order measure transmitted and scattered beams. An ideal and static theoretical model for annular flow regime have been developed using MCNP-X code, which was used to provide training, test and validation data for the ANN. More than 500 simulations have been done, in which water salinity have been ranged from 0 to 16% in order to cover a most practical situations. Validation tests have included values of volume fractions and water salinity different from those used in ANN training phase. The results presented here show that the proposed approach may be successfully applied to material volume fraction prediction on watergas- oil multiphase flows considering practical (real) levels of variations in water salinity. (author)

  3. Pretreatment metabolic tumour volume is predictive of disease-free survival and overall survival in patients with oesophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lemarignier, Charles; Gouel, Pierrick [Centre Henri Becquerel and Rouen University Hospital, Department of Nuclear Medicine, Rouen (France); Di Fiore, Frederic [Rouen University Hospital, Department of Gastroenterology, Rouen (France); Centre Henri Becquerel, Department of Medical oncology, Rouen (France); Marre, Charline; Michel, Pierre [Rouen University Hospital, Department of Gastroenterology, Rouen (France); Hapdey, Sebastien; Modzelewski, Romain; Vera, Pierre [Centre Henri Becquerel and Rouen University Hospital, Department of Nuclear Medicine, Rouen (France); University of Rouen, QuantIF (Litis EA 4108 - FR CNRS 3638), Rouen (France); Dubray, Bernard [University of Rouen, QuantIF (Litis EA 4108 - FR CNRS 3638), Rouen (France); Centre Henri Becquerel and Rouen University Hospital, Department of Radiotherapy and Medical Physics, Rouen (France)

    2014-11-15

    It has been suggested that FDG PET has predictive value for the prognosis of treated oesophageal carcinoma. However, the studies reported in the literature have shown discordant results. The aim of this study was to determine whether pretherapy quantitative metabolic parameters correlate with patient outcomes. Included in the study were 67 patients with a histological diagnosis of oesophageal squamous cell carcinoma. Each patient underwent {sup 18}F-FDG PET (4.5 MBq/kg) before chemoradiotherapy. Quantitative analysis was performed using the following parameters: age, weight loss, location, N stage, OMS performance status, MTV{sub p} and MTV{sub p'} (metabolic tumour volume determined by two different physicians), MTV{sub 40%} (volume for a threshold of 40 % of SUVmax), MTV{sub a} (volume automatically determined with a contrast-based adaptive threshold method), SUVmax, SUVmean and TLG (total lesion glycolysis). MTV{sub p} and MTV{sub 40%} were highly correlated (Pearson's index 0.92). SUVmean{sub p} and SUVmean{sub 40%} were also correlated (Pearson's index 0.86), as were TLG{sub p} and TLG{sub 40%} (Pearson's index 0.98). Similarly, the parameters obtained with the adaptive threshold method (MTV{sub a}, SUVmean{sub a} and TLG{sub a}) were correlated with those obtained manually (MTV{sub p}, SUVmean{sub p} and TLG{sub p}). The manual metabolic tumour volume determination (MTV{sub p} and MTV{sub p'}) was reproducible. Multivariate analysis for disease-free survival (DFS) showed that a larger MTV{sub p} was associated with a shorter DFS (p = 0.004) and that a higher SUVmax was associated with a longer DFS (p = 0.02). Multivariate analysis for overall survival (OS) showed that a larger MTV{sub p} was associated with a shorter OS (p = 0.01) and that a tumour in the distal oesophagus was associated with a longer OS (p = 0.005). The associations among the other parameters were not statistically significant. Metabolic tumour volume is a major

  4. Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma.

    Science.gov (United States)

    Inagaki, Atsushi; Tajima, Emi; Uranishi, Miyuki; Totani, Haruhito; Asao, Yu; Ogura, Hiroka; Masaki, Ayako; Yoshida, Tatsuya; Mori, Fumiko; Ito, Asahi; Yano, Hiroki; Ri, Masaki; Kayukawa, Satoshi; Kataoka, Takae; Kusumoto, Shigeru; Ishida, Takashi; Hayami, Yoshihito; Hanamura, Ichiro; Komatsu, Hirokazu; Inagaki, Hiroshi; Matsuda, Yasufumi; Ueda, Ryuzo; Iida, Shinsuke

    2013-12-01

    CCND1, FGFR3 and c-MAF mRNA expression of tumor samples from 123 multiple myeloma patients were analyzed by global RQ/RT-PCR. CCND1, FGFR3 and c-MAF were positive in 44 (36%), 28 (23%) and 16 (13%) of patients, respectively. In 7 patients, both FGFR3 and c-MAF were positive. The expression of c-MAF was independent unfavorable prognostic factors for overall survival (OS). Autologous stem cell transplantation improved progression-free survival of CCND1-positive patients. Bortezomib, thalidomide or lenalidomide extended OS of FGFR3 and/or c-MAF-positive patients. Thus, CCND1, FGFR3 and c-MAF mRNA expression can predict survival and is useful for planning stratified treatment strategies for myeloma patients.

  5. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites

    DEFF Research Database (Denmark)

    Krag, A; Bendtsen, F; Henriksen, J H;

    2010-01-01

    OBJECTIVES: Recent studies suggest that cardiac dysfunction precedes development of the hepatorenal syndrome. In this follow-up study, we aimed to investigate the relation between cardiac and renal function in patients with cirrhosis and ascites and the impact of cardiac systolic function...... on survival. Patients and DESIGN: Twenty-four patients with cirrhosis and ascites were included. Cardiac function was investigated by gated myocardial perfusion imaging (MPI) for assessment of cardiac index (CI) and cardiac volumes. The renal function was assessed by determination of glomerular filtration...... (130 (SD 46) vs 78 (SD 29) mumol/l, pdeveloped hepatorenal syndrome type 1 within 3 months was higher in the group with low CI than in the high CI group (43% vs 5%, p = 0.04). Patients with the lowest CI (N = 8) had significantly poorer survival at 3, 9, and 12 months...

  6. Metabolic syndrome independently predicts future diabetes in women with a history of gestational diabetes mellitus

    Science.gov (United States)

    Cho, Nam H.; Ahn, Chang Ho; Moon, Joon Ho; Kwak, Soo Heon; Choi, Sung Hee; Lim, Soo; Park, Kyong Soo; Metzger, Boyd E.; Jang, Hak C.

    2016-01-01

    Abstract Metabolic syndrome (MetS) is an established predisposing condition for type 2 diabetes mellitus (T2DM). However, it is not thoroughly evaluated whether MetS increases the risk of T2DM in women with a previous history of gestational diabetes mellitus (GDM) who already at high risk of T2DM compared with the general population. We investigated the impact of MetS on the development of postpartum diabetes in women with a history of GDM. This was a multicenter, prospective cohort study of women diagnosed with GDM. The follow-up evaluations, including the oral glucose tolerance test, were completed at 6 weeks postpartum and annually thereafter. MetS was diagnosed at the initial postpartum evaluation according to the revised criteria of the National Cholesterol Education Program-Adult Treatment Panel III. The risk of developing type 2 diabetes (T2DM) in the follow-up period was analyzed based on the presence of MetS, and the adjusted risk was calculated using a Cox proportional hazards model. A total of 412 women without diabetes at the initial postpartum evaluation participated in the annual follow-up for median 3.8 years. MetS was prevalent in 66 (19.2%) women at the initial postpartum evaluation. The incidences of diabetes in women with and without MetS were 825 and 227 per 10,000 person-years, respectively (P < 0.001). The presence of MetS was an independent risk factor for T2DM, with a hazard ratio (HR) of 2.23 (95% confidence interval 1.04–5.08) in multivariate analysis after adjustment for clinical and metabolic parameters. When we considered MetS and impaired fasting glucose (IFG) separately, women with MetS, IFG, or both had an increased risk of T2DM, with HRs of 4.17, 4.36, and 6.98, respectively. The presence of MetS during the early postpartum period is an independent risk factor for the development of T2DM in women with a previous history of GDM. PMID:27583868

  7. Visceral Obesity Predicts Fewer Lymph Node Metastases and Better Overall Survival in Colon Cancer

    OpenAIRE

    Park, Se Woo; Lee, Hang Lak; Doo, Eun Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Oh Young; Han, Dong Soo; Yoon, Byung Chul; Choi, Ho Soon; Lee, Kang Hong

    2015-01-01

    Background The relationship between visceral obesity and colon cancer outcome has not been well studied. The goal of this study was to determine the impact of visceral obesity on lymph node (LN) metastasis and overall survival (OS) in colon cancer. Materials and Methods Metastatic LN ratio (MLR) was defined as the number of involved nodes by tumor divided by the total number of resected LNs. Visceral (VFA) and subcutaneous fat areas (SFA) were determined by measuring abdominal fat volume dist...

  8. Reduction in plasma cell proliferation after initial therapy in newly diagnosed multiple myeloma measures treatment response and predicts improved survival.

    Science.gov (United States)

    Larsen, Jeremy T; Chee, Cheng E; Lust, John A; Greipp, Philip R; Rajkumar, S Vincent

    2011-09-08

    Standard myeloma treatment response criteria are determined principally by changes in the monoclonal protein. Reduction in the size of the proliferative component of malignant plasma cells may be an additional metric of assessing response to therapy. We retrospectively analyzed 176 patients with newly diagnosed myeloma with a measurable plasma cell labeling index (PCLI) at diagnosis and repeat measurement 4 months after initiation of therapy. PCLI response was defined as a ≥ 60% reduction. Baseline PCLI is an independent prognostic factor; therefore, we categorized patients into 3 groups: PCLI ≥ 3% (high), ≥ 1% (intermediate), and compared with 29 months in nonresponders (P = .02). Improved median overall survival with PCLI response occurred in the high initial PCLI group (28 vs 7 months; P = .003) and intermediate group (64 vs 24 months; P = .002). The application of PCLI response and serum M-spike response together provided further prognostic information. On multivariate analysis, the prognostic value of PCLI response was independent of β(2)-microglobulin, elevated creatinine, serum M-spike response, and baseline PCLI. We conclude that a significant reduction in plasma cell proliferation in patients with newly diagnosed myeloma is an important predictor of survival.

  9. Childhood Hodgkin International Prognostic Score (CHIPS) Predicts event-free survival in Hodgkin Lymphoma: A Report from the Children's Oncology Group.

    Science.gov (United States)

    Schwartz, Cindy L; Chen, Lu; McCarten, Kathleen; Wolden, Suzanne; Constine, Louis S; Hutchison, Robert E; de Alarcon, Pedro A; Keller, Frank G; Kelly, Kara M; Trippet, Tanya A; Voss, Stephan D; Friedman, Debra L

    2017-04-01

    Early response to initial chemotherapy in Hodgkin lymphoma (HL) measured by computed tomography (CT) and/or positron emission tomography (PET) after two to three cycles of chemotherapy may inform therapeutic decisions. Risk stratification at diagnosis could, however, allow earlier and potentially more efficacious treatment modifications. We developed a predictive model for event-free survival (EFS) in pediatric/adolescent HL using clinical data known at diagnosis from 1103 intermediate-risk HL patients treated on Children's Oncology Group protocol AHOD0031 with doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy and radiation. Independent predictors of EFS were identified and used to develop and validate a prognostic score (Childhood Hodgkin International Prognostic Score [CHIPS]). A training cohort was randomly selected to include approximately half of the overall cohort, with the remainder forming the validation cohort. Stage 4 disease, large mediastinal mass, albumin (<3.5), and fever were independent predictors of EFS that were each assigned one point in the CHIPS.  Four-year EFS was 93.1% for patients with CHIPS = 0, 88.5% for patients with CHIPS = 1, 77.6% for patients with CHIPS = 2, and 69.2% for patients with CHIPS = 3. CHIPS was highly predictive of EFS, identifying a subset (with CHIPS 2 or 3) that comprises 27% of intermediate-risk patients who have a 4-year EFS of <80% and who may benefit from early therapeutic augmentation.  Furthermore, CHIPS identified higher risk patients who were not identified by early PET or CT response. CHIPS is a robust and inexpensive approach to predicting risk in patients with intermediate-risk HL that may improve ability to tailor therapy to risk factors known at diagnosis. © 2016 Wiley Periodicals, Inc.

  10. Composition of symbiotic bacteria predicts survival in Panamanian golden frogs infected with a lethal fungus.

    Science.gov (United States)

    Becker, Matthew H; Walke, Jenifer B; Cikanek, Shawna; Savage, Anna E; Mattheus, Nichole; Santiago, Celina N; Minbiole, Kevin P C; Harris, Reid N; Belden, Lisa K; Gratwicke, Brian

    2015-04-22

    Symbiotic microbes can dramatically impact host health and fitness, and recent research in a diversity of systems suggests that different symbiont community structures may result in distinct outcomes for the host. In amphibians, some symbiotic skin bacteria produce metabolites that inhibit the growth of Batrachochytrium dendrobatidis (Bd), a cutaneous fungal pathogen that has caused many amphibian population declines and extinctions. Treatment with beneficial bacteria (probiotics) prevents Bd infection in some amphibian species and creates optimism for conservation of species that are highly susceptible to chytridiomycosis, the disease caused by Bd. In a laboratory experiment, we used Bd-inhibitory bacteria from Bd-tolerant Panamanian amphibians in a probiotic development trial with Panamanian golden frogs, Atelopus zeteki, a species currently surviving only in captive assurance colonies. Approximately 30% of infected golden frogs survived Bd exposure by either clearing infection or maintaining low Bd loads, but this was not associated with probiotic treatment. Survival was instead related to initial composition of the skin bacterial community and metabolites present on the skin. These results suggest a strong link between the structure of these symbiotic microbial communities and amphibian host health in the face of Bd exposure and also suggest a new approach for developing amphibian probiotics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  11. Morphologic complexity of epithelial architecture for predicting invasive breast cancer survival

    Directory of Open Access Journals (Sweden)

    Tambasco Mauro

    2010-12-01

    Full Text Available Abstract Background Precise criteria for optimal patient selection for adjuvant chemotherapy remain controversial and include subjective components such as tumour morphometry (pathological grade. There is a need to replace subjective criteria with objective measurements to improve risk assessment and therapeutic decisions. We assessed the prognostic value of fractal dimension (an objective measure of morphologic complexity for invasive ductal carcinoma of the breast. Methods We applied fractal analysis to pan-cytokeratin stained tissue microarray (TMA cores derived from 379 patients. Patients were categorized according to low (1.75, N = 90 fractal dimension. Cox proportional-hazards regression was used to assess the relationship between disease-specific and overall survival and fractal dimension, tumour size, grade, nodal status, estrogen receptor status, and HER-2/neu status. Results Patients with higher fractal score had significantly lower disease-specific 10-year survival (25.0%, 56.4%, and 69.4% for high, intermediate, and low fractal dimension, respectively, p Conclusion Except for nodal status, morphologic complexity of breast epithelium as measured quantitatively by fractal dimension was more strongly and significantly associated with disease-specific and overall survival than standard prognosticators.

  12. Can gene expression profiling predict survival for patients with squamous cell carcinoma of the lung?

    Directory of Open Access Journals (Sweden)

    Endo Chiaki

    2004-12-01

    Full Text Available Abstract Background Lung cancer remains to be the leading cause of cancer death worldwide. Patients with similar lung cancer may experience quite different clinical outcomes. Reliable molecular prognostic markers are needed to characterize the disparity. In order to identify the genes responsible for the aggressiveness of squamous cell carcinoma of the lung, we applied DNA microarray technology to a case control study. Fifteen patients with surgically treated stage I squamous cell lung cancer were selected. Ten were one-to-one matched on tumour size and grade, age, gender, and smoking status; five died of lung cancer recurrence within 24 months (high-aggressive group, and five survived more than 54 months after surgery (low-aggressive group. Five additional tissues were included as test samples. Unsupervised and supervised approaches were used to explore the relationship among samples and identify differentially expressed genes. We also evaluated the gene markers' accuracy in segregating samples to their respective group. Functional gene networks for the significant genes were retrieved, and their association with survival was tested. Results Unsupervised clustering did not group tumours based on survival experience. At p Conclusion The overall gene expression pattern between the high and low aggressive squamous cell carcinomas of the lung did not differ significantly with the control of confounding factors. A small subset of genes or genes in specific pathways may be responsible for the aggressive nature of a tumour and could potentially serve as panels of prognostic markers for stage I squamous cell lung cancer.

  13. Vascular and Alzheimer's disease markers independently predict brain atrophy rate in Alzheimer's Disease Neuroimaging Initiative controls.

    Science.gov (United States)

    Barnes, Josephine; Carmichael, Owen T; Leung, Kelvin K; Schwarz, Christopher; Ridgway, Gerard R; Bartlett, Jonathan W; Malone, Ian B; Schott, Jonathan M; Rossor, Martin N; Biessels, Geert Jan; DeCarli, Charlie; Fox, Nick C

    2013-08-01

    This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Aβ1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and Aβ1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and Aβ1-42 (p = 0.001) were independently associated with BSI in controls; in MCI Aβ1-42 (p brain atrophy in the context of AD pathology in pre-dementia stages.

  14. Melanoma long non-coding RNA signature predicts prognostic survival and directs clinical risk-specific treatments.

    Science.gov (United States)

    Chen, Xijia; Guo, Wenna; Xu, Xin-Jian; Su, Fangchu; Wang, Yi; Zhang, Yingzheng; Wang, Qiang; Zhu, Liucun

    2017-03-01

    Various studies have demonstrated that the Breslow thickness, tumor ulceration and mitotic index could serve as prognostic markers in patients with cutaneous melanoma. Recently, however, as these clinicopathological biomarkers lack efficient interpretation of endogenous mechanism of melanoma, the emphasis on the prognosis of melanoma has transformed to molecular tumor markers. This study was designed to identify survival-related long non-coding RNAs (lncRNAs), and based on the different expressions of these lncRNAs, clinical risk-specific diagnosis and adjuvant therapy could be employed on melanoma patients, especially patients in the early course of disease or patients with a Breslow thickness no more than 2mm. The clinical information and corresponding RNA expression data were obtained from The Cancer Genome Atlas dataset and Gene Expression Omnibus dataset (GSE65904). All samples were categorized into one training dataset and two validation datasets. Cox proportional hazard regression analysis was then used to identify survival-related lncRNAs and risk assessment signature was constructed in training dataset. Kaplan-Meier method was used to estimate the utility of this signature in predicting the duration of survival of patients both in the training dataset and two validation datasets. Meanwhile receiver operating characteristic analyses were used to evaluate the predictive effectiveness of this signature in two validation datasets. It was found that the signature was effective while used for risk stratification, and Kaplan-Meier analyses indicated that the duration of survival of patients in high-risk groups were significantly shorter than that of low-risk groups. Moreover, areas under the receiver operating characteristic curve were 0.711 (95% confidence interval: 0.618-0.804) and 0.698 (95% confidence interval: 0.614-0.782) when this signature was used to predict the patients' duration of survival in two validation datasets respectively, indicating the

  15. Cumulative scores based onplasma D-dimer andserum albumin levels predict survival inesophageal squamous cell carcinoma patients treated withtransthoracic esophagectomy

    Institute of Scientific and Technical Information of China (English)

    DeQingLiu; FangFangLi; WeiHuaJia

    2016-01-01

    Background:Recently, studies have shown that plasma D‑dimer and serum albumin are prognostic markers for esophageal cancer. The purpose of this study was to evaluate a novel prognostic scoring system—DA score (combi‑nation of preoperative plasma D‑dimer and serum albumin levels)—and analyze the association between survival of patients with esophageal squamous cell carcinoma (ESCC) and their Glasgow prognostic score. Methods:In this retrospective study, preoperative biochemical markers and clinicopathologic factors in 260 ESCC patients treated with transthoracic esophagectomy were reviewed. According to receiver operating characteristic analysis, the cutoff values of D‑dimer and albumin were deifned as 0.5μg/mL and 43.8g/L, respectively. Patients with high D‑dimer levels (≥0.5μg/mL) and low albumin levels (<43.8g/L) were assigned a score of 2, those with only one of the two abnormalities were assigned a score of 1, and those with neither of the two abnormalities were assigned a score of 0. Results:ESCC patients with a DA score of 0, 1, and 2 numbered 55, 116, and 89, respectively. Survival analysis showed that patients with a DA score of 2 had lower overall survival (OS) rates than those with DA scores of 1 and 0 (37.1% vs. 52.6% and 76.4%,P<0.001); similar ifndings were observed for disease‑free survival (DFS) rates (32.6% vs. 44.8% and 67.3%,P<0.001). In addition, the predictive value of the DA score was also signiifcant in patients with stages I–IIA and stages IIB–IV ESCC. Multivariate Cox regression analyses indicated that hazard ratios (HRs) for predicting OS of patients with DA scores 1 and 2 were 2.25 (P=0.010) and 3.14 (P<0.001), respectively, compared with those with a DA score of 0, and HRs for predicting DFS of patients with DA scores of 1 and 2 were 1.86 (P=0.023) and 2.68 (P<0.001), respectively, compared with those with a DA scores of 0. Conclusions:Our study suggests that preoperative DA scores are notably associated with

  16. CK2α phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients.

    Science.gov (United States)

    Bae, Jun Sang; Park, See-Hyoung; Kim, Kyoung Min; Kwon, Keun Sang; Kim, Chan Young; Lee, Hun Ku; Park, Byung-Hyun; Park, Ho Sung; Lee, Ho; Moon, Woo Sung; Chung, Myoung Ja; Sylvester, Karl G; Jang, Kyu Yun

    2015-02-15