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Sample records for predicts inferior survival

  1. Baseline low immunoglobulin A predicts inferior disease-free survival in pediatric acute myeloid leukemia and serial evaluation suggests role of immunoglobulin A in leukemogenesis.

    PubMed

    Bansal, Anuj Kumar; Vishnubhatla, Sreenivas; Kumar, Uma; Bakhshi, Sameer

    2014-05-01

    Abstract Data on serial evaluation of immunoglobulins (Ig) in pediatric AML is lacking. From April 2010 to May 2011, 45 consecutive patients with AML aged 1-18 years were prospectively enrolled along with nine healthy controls. Ig were assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow-up and relapse. At diagnosis, Ig levels were significantly higher in patients than in healthy controls. Patienths with gum hypertrophy had low Ig levels (IgG, p = 0.007; IgA, p = 0.003; IgM, p = 0.06). Baseline Ig did not correlate with complete remission (CR). Patients who relapsed had a lower baseline IgA level than those in continuous CR (169 ± 94 g/dL vs. 310 ± 177 g/dL, p = 0.019). Patients with a low baseline IgA level (less than median) had inferior disease-free-survival (DFS) on multivariate analysis (p = 0.048). Post-induction, IgM (p < 0.001) and IgA (p = 0.048) were significantly reduced as compared to their baseline values. On serial follow-up in patients who were in continuous CR, there was a significant decrease in IgA from post-induction until 6 months after treatment completion. This is the first study to evaluate the trend of humoral immunity in sequential pediatric patients with AML. Our study demonstrates that in pediatric AML, baseline Ig were higher than in controls. Gum hypertrophy was observed in patients with low Ig (IgA and IgG) levels. Relatively lower baseline IgA predicted disease relapse and inferior DFS. On serial follow-up, IgA significantly decreased in those who continued to stay in CR but not in patients who relapsed, suggesting an association of IgA with leukemogenesis. PMID:23865831

  2. Determinants of survival after inferior vena cava trauma.

    PubMed

    Kuehne, J; Frankhouse, J; Modrall, G; Golshani, S; Aziz, I; Demetriades, D; Yellin, A E

    1999-10-01

    Inferior vena cava (IVC) injuries continue to be associated with mortality rates of 21 to 66 per cent despite advances in prehospital, surgical, and critical care. The purpose of this study was to evaluate outcome of patients with IVC injury after treatment at a major urban trauma center and to identify factors predictive of survival. Between 1989 and 1995, 158 patients presented to the Los Angeles County + University of Southern California Medical Center with IVC injuries. One hundred thirty-six patient records were available for review, and 69 data points were collected and analyzed. Mean age was 26 years (range, 6-54), and 122 (90%) patients were male. Mechanism of injury included gunshot in 88 (65%) patients, stab in 23 (17%) patients, shotgun in 7 (5%) patients, and blunt trauma in 18 (13%) patients. The mean Injury Severity Score was 25. Seventy (52%) patients were hypotensive. Eleven (8%) patients died before surgical intervention, and 25 (18%) patients died before operative repair. Repair (79), ligation (20), or observation (1) was accomplished in 100 (74%) patients. Overall survival was 48 per cent and 65 per cent in the 100 patients surviving to operative repair, including 5 of 20 patients requiring IVC ligation. Significant differences (P<0.001) between survivors and nonsurvivors included Injury Severity Score, Glasgow Coma Score, hematocrit, hypotension, emergent thoracotomy, blood loss, level of injury, tamponade, and associated aortic injury. Logistic regression analysis identified hypotension, anatomic level of injury, and associated aortic injury as significant predictors of outcome (P = 0.001). Survival is predominantly determined by severity and anatomic accessibility of the IVC injury and by the absence of associated major vascular injuries. Ligation may control otherwise exsanguinating injuries and should be considered early in the management of complex injuries. PMID:10515547

  3. Predicting Survival in ARDS.

    PubMed

    Karnik, Niteen D; Gupta, Anish V

    2015-11-01

    Acute respiratory distress syndrome (ARDS) is a fulminant clinical disorder of varied etiology, characterized by diffuse lung injury and severe hypoxemia. It is a leading cause of ICU admission and the associated high mortality has sparked a lot of research on etiology, outcome, scoring systems, mortality predictors, biomarkers including inflammatory cytokines and even genomics in ARDS. The previously used AECC (American European Consensus Conference) definition (1994) of ARDS was replaced by the recent Berlin definition (2012) so as to improve its validity and reliability.1,2 This would not only standardize patient enrollment into clinical trials but also help implement the results of these trials into clinical practice. Although various studies have shown a reduction in mortality due to ARDS, it has been largely attributed to the general improvement in critical care and the use of lung protection ventilation strategies.3-6 Hence focus on the etiology, co-morbidities, risk factors, complications and mortality predictors, is the need of the hour so as to improve survival. ARDS can occur secondary to multiple causes i.e. either due to direct lung involvement (pneumonia, lung contusion etc) or indirect alveolar damage by inflammatory cytokines (sepsis, trauma, burns, pancreatitis etc.). The causes of ARDS in tropical countries are varied with seasonal variation. Acute febrile illnesses (AFI) like malaria, leptospirosis and dengue usually predominate in the monsoons while H1N1 infection and pneumonias typically peak in the colder winter months. However, malaria, dengue and H1N1 have a potential to be perennial. PMID:27608777

  4. Early allograft dysfunction in liver transplantation with donation after cardiac death donors results in inferior survival.

    PubMed

    Lee, David D; Singh, Amandeep; Burns, Justin M; Perry, Dana K; Nguyen, Justin H; Taner, C Burcin

    2014-12-01

    Donation after cardiac death (DCD) liver allografts have been associated with increased morbidity from primary nonfunction, biliary complications, early allograft failure, cost, and mortality. Early allograft dysfunction (EAD) after liver transplantation has been found to be associated with inferior patient and graft survival. In a cohort of 205 consecutive liver-only transplant patients with allografts from DCD donors at a single center, the incidence of EAD was found to be 39.5%. The patient survival rates for those with no EAD and those with EAD at 1, 3, and 5 years were 97% and 89%, 79% and 79%, and 61% and 54%, respectively (P = 0.009). Allograft survival rates for recipients with no EAD and those with EAD at 1, 3, and 5 years were 90% and 75%, 72% and 64%, and 53% and 43%, respectively (P = 0.003). A multivariate analysis demonstrated a significant association between the development of EAD and the cold ischemia time [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.01-1.56, P = 0.037] and hepatocellular cancer as a secondary diagnosis in recipients (OR = 2.26, 95% CI = 1.11-4.58, P = 0.025). There was no correlation between EAD and the development of ischemic cholangiopathy. In conclusion, EAD results in inferior patient and graft survival in recipients of DCD liver allografts. Understanding the events that cause EAD and developing preventive or early therapeutic approaches should be the focus of future investigations. PMID:25179581

  5. Eisenmenger syndrome: a case of survival after ventricular tachycardia due to inferior myocardial infarction in a 48-year-old patient with congenital large ventricular septal defect.

    PubMed

    Passarani, Simonetta; Vignati, Gabriele; Einaudi, Arturo

    2004-06-01

    Eisenmenger syndrome is the most common consequence of congenital cyanotic heart disease seen in adults; survival to the fifth decade of life is rare. Death is very difficult to predict: it is related to sudden cardiac ventricular arrhythmia, massive hemoptysis and right heart failure. In this paper, a patient with ventricular septal defect and Eisenmenger reaction is described. The patient was relatively well until 48 years of age, when she underwent surgery because of a cerebral abscess without cerebral complications but with some deterioration of her cardiac function. After discharge, the patient was readmitted to the hospital because the electrocardiogram showed persistent ST inferior elevation. Echocardiography demonstrated poor contractility and inferior akinesia. Sudden ventricular tachycardia occurred and the patient became unconscious. She was successfully resuscitated and, following a period of ventilation, the hemodynamics stabilized and she was discharged 17 days later. She remained well two years later. PMID:15229766

  6. Factors predictive of survival in ampullary carcinoma.

    PubMed Central

    Howe, J R; Klimstra, D S; Moccia, R D; Conlon, K C; Brennan, M F

    1998-01-01

    OBJECTIVE: To review the recent Memorial Sloan-Kettering Cancer Center experience with adenocarcinoma of the ampulla of Vater and to identify clinicopathologic factors that have an impact on patient survival. SUMMARY BACKGROUND DATA: The prognosis for patients with tumors of the ampulla of Vater is improved relative to other periampullary neoplasms. Identification of independent prognostic factors in ampullary tumors has been limited by small numbers of tumors and a lack of pathologic review. METHODS: Data were collected prospectively for patients presenting with periampullary carcinomas to the Memorial Sloan-Kettering Cancer Center between October 15, 1983 and June 30, 1995. The correlation between clinicopathologic variables and survival of ampullary carcinoma was tested by the Kaplan-Meier method and log-rank test, and Cox proportional hazards regression. Survival of patients with periampullary adenocarcinomas was compared by the Kaplan-Meier method. RESULTS: In 123 patients presenting with ampullary carcinoma, 101 tumors (82.1%) were resected. Factors significantly correlated with improved survival were resection (p < 0.01), and in resected tumors, negative nodes (p = 0.04) and margins (p = 0.02) independently predicted for improved survival. In periampullary tumors, the highest rates of resection and overall survival (median, 43.6 months) were found in ampullary carcinomas. CONCLUSIONS: Factors predictive of improved survival in ampullary carcinoma include resection, negative margins, and negative nodes. Improved overall survival in ampullary relative to periampullary adenocarcinoma is due in part to a significantly higher rate of resection. Images Figure 1. PMID:9671071

  7. Protein Markers Predict Survival in Glioma Patients.

    PubMed

    Stetson, Lindsay C; Dazard, Jean-Eudes; Barnholtz-Sloan, Jill S

    2016-07-01

    Glioblastoma multiforme (GBM) is a genomically complex and aggressive primary adult brain tumor, with a median survival time of 12-14 months. The heterogeneous nature of this disease has made the identification and validation of prognostic biomarkers difficult. Using reverse phase protein array data from 203 primary untreated GBM patients, we have identified a set of 13 proteins with prognostic significance. Our protein signature predictive of glioblastoma (PROTGLIO) patient survival model was constructed and validated on independent data sets and was shown to significantly predict survival in GBM patients (log-rank test: p = 0.0009). Using a multivariate Cox proportional hazards, we have shown that our PROTGLIO model is distinct from other known GBM prognostic factors (age at diagnosis, extent of surgical resection, postoperative Karnofsky performance score (KPS), treatment with temozolomide (TMZ) chemoradiation, and methylation of the MGMT gene). Tenfold cross-validation repetition of our model generation procedure confirmed validation of PROTGLIO. The model was further validated on an independent set of isocitrate dehydrogenase wild-type (IDHwt) lower grade gliomas (LGG)-a portion of these tumors progress rapidly to GBM. The PROTGLIO model contains proteins, such as Cox-2 and Annexin 1, involved in inflammatory response, pointing to potential therapeutic interventions. The PROTGLIO model is a simple and effective predictor of overall survival in glioblastoma patients, making it potentially useful in clinical practice of glioblastoma multiforme. PMID:27143410

  8. Predicting survival time for cold exposure

    NASA Astrophysics Data System (ADS)

    Tikuisis, Peter

    1995-06-01

    The prediction of survival time (ST) for cold exposure is speculative as reliable controlled data of deep hypothermia are unavailable. At best, guidance can be obtained from case histories of accidental exposure. This study describes the development of a mathematical model for the prediction of ST under sedentary conditions in the cold. The model is based on steady-state heat conduction in a single cylinder comprised of a core and two concentric annular shells representing the fat plus skin and the clothing plus still boundary layer, respectively. The ambient condition can be either air or water; the distinction is made by assigning different values of insulation to the still boundary layer. Metabolic heat production ( M) is comprised of resting and shivering components with the latter predicted by temperature signals from the core and skin. Where the cold exposure is too severe for M to balance heat loss, ST is largely determined by the rate of heat loss from the body. Where a balance occurs, ST is governed by the endurance time for shivering. End of survival is marked by the deep core temperature reaching a value of 30° C. The model was calibrated against survival data of cold water (0 to 20° C) immersion and then applied to cold air exposure. A sampling of ST predictions for the nude exposure of an average healthy male in relatively calm air (1 km/h wind speed) are the following: 1.8, 2.5, 4.1, 9.0, and >24 h for -30, -20, -10, 0, and 10° C, respectively. With two layers of loose clothing (average thickness of 1 mm each) in a 5 km/h wind, STs are 4.0, 5.6, 8.6, 15.4, and >24 h for -50, -40, -30, -20, and -10° C. The predicted STs must be weighted against the extrapolative nature of the model. At present, it would be prudent to use the predictions in a relative sense, that is, to compare or rank-order predicted STs for various combinations of ambient conditions and clothing protection.

  9. Malondialdehyde can predict survival in hemodialysis patients

    PubMed Central

    RUSU, CRINA CLAUDIA; RACASAN, SIMONA; KACSO, INA MARIA; MOLDOVAN, DIANA; POTRA, ALINA; PATIU, IOAN MIHAI; VLADUTIU, DAN; CAPRIOARA, MIRELA GHERMAN

    2016-01-01

    Background and aims Cardiovascular (CV) disease is the leading cause of morbidity and mortality in hemodialysis (HD) patients. Kidney disease is associated with increased oxidative stress (OS), a nontraditional CV risk factor. Few studies evaluate the effect of OS markers on CV events (CVE) and survival in HD patients. The aim of this study is to examine potential determinants of OS markers and their predictive role on survival and CV morbidity and mortality in HD patients during a long-term follow-up (108 months). Methods We conducted an analytical cross-sectional prospective observational study, carried on a cohort of randomly selected HD patients. We registered in 44 HD patients baseline characteristics, OS markers, mortality and CVE over a period of 108 months and we used statistical analysis (descriptive, Kaplan-Meier, univariate and multivariate Cox model) for interpretation. Results Bound malondialdehyde (bMDA) was positively correlated with serum calcium, protein carbonyls (PC) were inversely correlated with diastolic blood pressure (DBP) and directly correlated with ferritin, NOx was directly correlated with ceruloplasmin) and serum albumin. Of the measured OS markers only bMDA was related to survival (HR=3.29 95% CI (1.28–8.44), p=0.01), and approached statistical significance in the effect on CV mortality (HR=2.85 95% CI (0.88–9.22), p=0.07). None of the measured OS markers was associated with CVE. Conclusions bMDA has a strong predictive value on survival in HD patients in a long-term follow-up (9 years). Its value is correlated with CV mortality but is not a predictor of CV events. Regular assessment of MDA in HD patients and the development of strategies aimed at reducing oxidative stress in these patients might be beneficial. PMID:27152077

  10. Low NK cell counts in peripheral blood are associated with inferior overall survival in patients with follicular lymphoma

    PubMed Central

    Shafer, Danielle; Smith, Mitchell R.; Borghaei, Hossein; Millenson, Michael M.; Li, Tianyu; Litwin, Samuel; Anad, Rachna; Al-Saleem, Tahseen

    2013-01-01

    Host immune responses influence follicular lymphoma (FL) outcomes. To test our hypothesis that immune cells in blood reflect that response, we assessed by peripheral blood flow cytometry in 75 untreated FL patients the absolute counts of: lymphocytes (ALC), CD4+T (ACD4C), CD8+T (ACD8C) and natural killer (ANKC) cells. Low ANKC was the only parameter associated with inferior overall survival by univariate analysis (p= 0.02), and trended to significance in multivariable analysis with ACD4C (p= 0.08). Five (24%) patients with low initial ANKC died, while none with normal/high ANKC have died Conclusions: Evaluation of blood ANKC may be a useful indicator of outcome in previously untreated FL patients. PMID:23968916

  11. The left inferior parietal lobe represents stored hand-postures for object use and action prediction

    PubMed Central

    van Elk, Michiel

    2014-01-01

    Action semantics enables us to plan actions with objects and to predict others' object-directed actions as well. Previous studies have suggested that action semantics are represented in a fronto-parietal action network that has also been implicated to play a role in action observation. In the present fMRI study it was investigated how activity within this network changes as a function of the predictability of an action involving multiple objects and requiring the use of action semantics. Participants performed an action prediction task in which they were required to anticipate the use of a centrally presented object that could be moved to an associated target object (e.g., hammer—nail). The availability of actor information (i.e., presenting a hand grasping the central object) and the number of possible target objects (i.e., 0, 1, or 2 target objects) were independently manipulated, resulting in different levels of predictability. It was found that making an action prediction based on actor information resulted in an increased activation in the extrastriate body area (EBA) and the fronto-parietal action observation network (AON). Predicting actions involving a target object resulted in increased activation in the bilateral IPL and frontal motor areas. Within the AON, activity in the left inferior parietal lobe (IPL) and the left premotor cortex (PMC) increased as a function of the level of action predictability. Together these findings suggest that the left IPL represents stored hand-postures that can be used for planning object-directed actions and for predicting other's actions as well. PMID:24795681

  12. High Ligation of Inferior Mesenteric Artery in Left Colonic and Rectal Cancers: Lymph Node Yield and Survival Benefit.

    PubMed

    Charan, Ishwar; Kapoor, Akhil; Singhal, Mukesh Kumar; Jagawat, Namrata; Bhavsar, Deepak; Jain, Vikas; Kumar, Vanita; Kumar, Harvindra Singh

    2015-12-01

    During surgery for colorectal cancer, the inferior mesenteric artery (IMA) may be ligated either directly at the origin of the IMA from the aorta (high ligation) or at a point just below the origin of the left colic artery (low ligation). Sixty patients of left colonic and rectal cancer undergoing elective curative surgery in 2007 and 2008 were selected for this observational study. The resected lymph nodes were grouped into three levels: along the bowel wall (D1), along IMA below left colic (D2), and along the IMA and its root (D3). Statistical analysis was performed with SPSS version 20.0. D2 level was involved pathologically in 20 (33.3 %) and D3 in six out of 44 (13.6 %) patients. The median nodal yield with high and low ligation were 33 and 25, respectively (p = 0.048). Median overall survival for high ligation was 62 months versus 42 months for low ligation (p = 0.190). High ligation of the IMA for rectal and left colonic cancers can improve lymph node yield, thus facilitating accurate tumor staging and thus better disease prognostication, but the survival benefit is not significant. PMID:27011519

  13. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established. PMID:26805098

  14. Interrogating the Aged Striatum: Robust Survival of Grafted Dopamine Neurons in Aging Rats Produces Inferior Behavioral Recovery and Evidence of Impaired Integration

    PubMed Central

    Collier, Timothy J.; O’Malley, Jennifer; Rademacher, David J.; Stancati, Jennifer A.; Sisson, Kellie A.; Sortwell, Caryl E.; Paumier, Katrina L.; Gebremedhin, Kibrom G.; Steece-Collier, Kathy

    2015-01-01

    Advanced age is the primary risk factor for Parkinson disease (PD). In PD patients and rodent models of PD, advanced age is associated with inferior symptomatic benefit following intrastriatal grafting of embryonic dopamine (DA) neurons, a pattern believed to result from decreased survival and reinnervation provided by grafted neurons in the aged host. To help understand the capacity of the aged, parkinsonian striatum to be remodeled with new DA terminals, we used a grafting model and examined whether increasing the number of grafted DA neurons in aged rats would translate to enhanced behavioral recovery. Young (3 mo), middle-aged (15 mo), and aged (22 mo) parkinsonian rats were grafted with proportionately increasing numbers of embryonic ventral mesencephalic (VM) cells to evaluate whether the limitations of the graft environment in subjects of advancing age can be offset by increased numbers of transplanted neurons. Despite robust survival of grafted neurons in aged rats, reinnervation of striatal neurons remained inferior and amelioration of levodopa-induced dyskinesias (LID) was delayed or absent. This study demonstrates that: 1) counter to previous evidence, under certain conditions the aged striatum can support robust survival of grafted DA neurons; and 2) unknown factors associated with the aged striatum result in inferior integration of graft and host, and continue to present obstacles to full therapeutic efficacy of DA cell-based therapy in this model of aging. PMID:25771169

  15. Metastatic Sites Predict Prostate Cancer Survival.

    PubMed

    2016-05-01

    A new meta-analysis of clinical trial data from patients with metastatic castration-resistant prostate cancer indicates that overall survival is strongly influenced by where the disease spreads. Men with visceral disease-liver or lung metastases-fare worse than those with bone or lymph node involvement. PMID:27001152

  16. A K-nearest neighbors survival probability prediction method.

    PubMed

    Lowsky, D J; Ding, Y; Lee, D K K; McCulloch, C E; Ross, L F; Thistlethwaite, J R; Zenios, S A

    2013-05-30

    We introduce a nonparametric survival prediction method for right-censored data. The method generates a survival curve prediction by constructing a (weighted) Kaplan-Meier estimator using the outcomes of the K most similar training observations. Each observation has an associated set of covariates, and a metric on the covariate space is used to measure similarity between observations. We apply our method to a kidney transplantation data set to generate patient-specific distributions of graft survival and to a simulated data set in which the proportional hazards assumption is explicitly violated. We compare the performance of our method with the standard Cox model and the random survival forests method. PMID:23653217

  17. Bacterial survival in turfgrass as predicted from the UV environment

    NASA Astrophysics Data System (ADS)

    Walter-Shea, Elizabeth; Yuen, Gary; Hubbard, Kenneth; Horst, Garald

    2002-01-01

    Phylloplane microorganism survival is presumably affected by ultraviolet radiation (UV) penetrating into plant canopies, but little field data exist relating microorganism population dynamics to canopy UV level. Recent advances in field measurements involving the use of biological dosimeters and miniature radiometers make possible data sets for use in assessing the impact of UV on phylloplane microbe survival. The objective of this study was to compare field survival of a bacterial species, applied to turfgrass as a biological disease control agent, with predicted survival based on the prevailing UV-B environment under natural and attenuated UV conditions. Derived survival curves and radiation penetration equations (based on radiometer and biodosimeter field measurements of UV-B transmittance) were applied to predict bacterial survival within a turfgrass canopy at different leaf area indices. Due to the range in UV levels within a canopy, as indicated by the maximum (sunfleck areas) and minimum (shaded areas) transmitted irradiance values, bacterial survival can vary; predicted bacterial survival based only on average light penetration tended to underestimate survival. Further study should address contributions due to microenvironmental effects (e.g., canopy temperature, leaf wetness, and canopy structure), the spatial distribution of bacterium leaf microsites and bacterium survival on leaf surfaces.

  18. Prediction of Breast Cancer Survival Through Knowledge Discovery in Databases

    PubMed Central

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

    2015-01-01

    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. PMID:25946945

  19. Predicting Clustered Dental Implant Survival Using Frailty Methods

    PubMed Central

    Chuang, S.-K.; Cai, T.

    2008-01-01

    The purpose of this study was to predict future implant survival using information on risk factors and on the survival status of an individual’s existing implant(s). We considered a retrospective cohort study with 677 individuals having 2349 implants placed. We proposed to predict the survival probabilities using the Cox proportional hazards frailty model, with three important risk factors: smoking status, timing of placement, and implant staging. For a non-smoking individual with 2 implants placed, an immediate implant and in one stage, the marginal probability that 1 implant would survive 12 months was 85.8% (95%CI: 77%, 91.7%), and the predicted joint probability of surviving for 12 months was 75.1% (95%CI: 62.1%, 84.7%). If 1 implant was placed earlier and had survived for 12 months, then the second implant had an 87.5% (95%CI: 80.3%, 92.4%) chance of surviving 12 months. Such conditional and joint predictions can assist in clinical decision-making for individuals. PMID:17122171

  20. Genetic mutational profiling analysis of T cell acute lymphoblastic leukemia reveal mutant FBXW7 as a prognostic indicator for inferior survival.

    PubMed

    Yuan, Lan; Lu, Ling; Yang, Yongchen; Sun, Hengjuan; Chen, Xi; Huang, Yi; Wang, Xingjuan; Zou, Lin; Bao, Liming

    2015-11-01

    T cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplasm for which there are currently no adequate biomarkers for developing risk-adapted therapeutic regimens to improve the treatment outcome. In this prospective study of 83 Chinese patients (54 children and 29 adults) with de novo T-ALL, we analyzed mutations in 11 T-ALL genes: NOTCH1, FBXW7, PHF6, PTEN, N-RAS, K-RAS, WT1, IL7R, PIK3CA, PIK3RA, and AKT1. NOTCH1 mutations were identified in 51.9 and 37.9 % of pediatric and adult patients, respectively, and these patients showed improved overall survival (OS) and event-free survival (EFS). The FBXW7 mutant was present in 25.9 and 6.9 % of pediatric and adult patients, respectively, and was associated with inferior OS and EFS in pediatric T-ALL. Multivariate analysis revealed that mutant FBXW7 was an independent prognostic indicator for inferior EFS (hazard ratio [HR] 4.38; 95 % confidence interval [CI] 1.15-16.71; p = 0.03) and tended to be associated with reduced OS (HR 2.81; 95 % CI 0.91-8.69; p = 0.074) in pediatric T-ALL. Mutant PHF6 was present in 13 and 20.7 % of our childhood and adult cohorts, respectively, while PTEN mutations were noted in 11.1 % of the pediatric patients. PTEN and NOTCH1 mutations were almost mutually exclusive, while IL7R and WT1 mutations were rare in pediatric T-ALL and PTPN11 and AKT1 mutations were infrequent in adult T-ALL. This study revealed differences in the mutational profiles of pediatric and adult T-ALL and suggests mutant FBXW7 as an independent prognostic indicator for inferior survival in pediatric T-ALL. PMID:26341754

  1. Predicting venous insufficiency in flaps raised on the deep inferior epigastric system using computed tomography (CT) angiography.

    PubMed

    Wagels, M; Pillay, R; Saylor, A; Vrtik, L; Senewiratne, S

    2015-12-01

    Computed Tomography Angiogram (CTA) has become a routine part of pre-operative assessment of vascular anatomy and design in perforator flaps. We conducted a retrospective cohort study of flap raised on the deep inferior epigastric system (DIES) at our institution in order to identify CTA signs that might predict venous congestion in these flaps. 98 consecutive patients who had 124 DIES flaps raised from 2008 to 2012 were studied. Of these 124 flaps, four (3.2%) developed venous congestion. Our results showed that a Superficial Inferior Epigastric Vein (SIEV) that is larger than the DIEV at origin is highly predictive of congestion (5.2 vs 3.5 mm, p = 0.007). The findings of an axial non-arborising superficial system (96.7% vs 0, p < 0.001), without connection to deep system perforators (38.1 vs 88.8%, p < 0.001) and a type I pedicle were also predictive (75 vs 64.2%, p = 0.22). These results show the importance of CTAs as a pre-operative study for the identification of risk factors for venous compromise, and their use should prompt a robust discussion of the risk of flap failure with patients, and contingency planning to augment venous drainage with the superficial system if required. PMID:26375461

  2. Higher expression levels of the HOXA9 gene, closely associated with MLL-PTD and EZH2 mutations, predict inferior outcome in acute myeloid leukemia

    PubMed Central

    Gao, Li; Sun, Junzhong; Liu, Fang; Zhang, Hui; Ma, Yigai

    2016-01-01

    Background Although the biological insight of acute myeloid leukemia (AML) has increased in the past few years, the discovery of novel discriminative biomarkers remains of utmost value for improving outcome predictions. Systematical studies concerning the clinical implications and genetic correlations of HOXA9 aberrations in patients with AML are relatively promising. Materials and methods Here, we investigated mutational status and the mRNA levels of the HOXA9 gene in 258 patients with AML. Furthermore, hematological characteristics, chromosome abnormalities, and genetic mutations associated with AML were analyzed, followed by the assessment of clinical survival. Besides, the expression level and mutational status of MEIS1, a cofactor of HOXA9, were also detected in patients with AML with the aim of a deeper understanding about the homeodomain-containing transcription factors associated with hematological characteristics. Results HOXA9 and MEIS1 mutations were detected in 4.26% and 3.49% AML cases, respectively. No correlations were detected between mutation status and clinical characteristics, cytogenetic and genetic aberrations, and clinical survival. Higher HOXA9 expression levels were correlated with white blood cell count and closely associated with unfavorable karyotype as well as MLL-PTD and EZH2 mutations, whereas, there was an inverse correlation with the French–American–British M3 subtype. Compared with patients with lower HOXA9 expression levels, those with higher HOXA9 expression levels had a lower complete remission rate and inferior survivals in both AML and cytogenetically normal AML. Conclusion HOXA9 expression may serve as a promising biomarker to ameliorate a prognostic model for predicting clinical outcome and consummating individualized treatment in patients with AML. PMID:26929642

  3. Development of a Score Predicting Survival after Palliative Reirradiation

    PubMed Central

    Haukland, Ellinor; Grosu, Anca L.

    2014-01-01

    Purpose. To develop a prognostic model for predicting survival after palliative reirradiation (PR). Methods and Materials. We analyzed all 87 PR courses administered at a dedicated palliative radiotherapy facility between 20.06.2007 (opening) and 31.12.2009. Uni- and multivariate survival analyses were performed, the previously published survival prediction score (SPS) was evaluated, and a PR-specific prognostic score was calculated. Results. In multivariate analysis, four parameters significantly influenced survival: performance status, use of steroids, presence of liver metastases, and pleural effusion. Based on these parameters, a 4-tiered score was developed. Median survival was 24.5 months for the favorable group, 9.7 and 2.8 months for the two intermediate groups, and 1.1 months for the unfavorable group (P = 0.019 for comparison between the two favorable groups and P ≤ 0.002 for all other pair-wise comparisons). All patients in the unfavorable group died within 2 months. Conclusion. The performance of PR-specific score was promising and might facilitate identification of patients who survive long enough to benefit from PR. It should be validated in independent patient groups, ideally from several institutions and countries. PMID:25332718

  4. Repetition Suppression in the Left Inferior Frontal Gyrus Predicts Tone Learning Performance.

    PubMed

    Asaridou, Salomi S; Takashima, Atsuko; Dediu, Dan; Hagoort, Peter; McQueen, James M

    2016-06-01

    Do individuals differ in how efficiently they process non-native sounds? To what extent do these differences relate to individual variability in sound-learning aptitude? We addressed these questions by assessing the sound-learning abilities of Dutch native speakers as they were trained on non-native tone contrasts. We used fMRI repetition suppression to the non-native tones to measure participants' neuronal processing efficiency before and after training. Although all participants improved in tone identification with training, there was large individual variability in learning performance. A repetition suppression effect to tone was found in the bilateral inferior frontal gyri (IFGs) before training. No whole-brain effect was found after training; a region-of-interest analysis, however, showed that, after training, repetition suppression to tone in the left IFG correlated positively with learning. That is, individuals who were better in learning the non-native tones showed larger repetition suppression in this area. Crucially, this was true even before training. These findings add to existing evidence that the left IFG plays an important role in sound learning and indicate that individual differences in learning aptitude stem from differences in the neuronal efficiency with which non-native sounds are processed. PMID:26113631

  5. Subliminal enhancement of predictive effects during syntactic processing in the left inferior frontal gyrus: an MEG study

    PubMed Central

    Iijima, Kazuki; Sakai, Kuniyoshi L.

    2014-01-01

    Predictive syntactic processing plays an essential role in language comprehension. In our previous study using Japanese object-verb (OV) sentences, we showed that the left inferior frontal gyrus (IFG) responses to a verb increased at 120–140 ms after the verb onset, indicating predictive effects caused by a preceding object. To further elucidate the automaticity of the predictive effects in the present magnetoencephalography study, we examined whether a subliminally presented verb (“subliminal verb”) enhanced the predictive effects on the sentence-final verb (“target verb”) unconsciously, i.e., without awareness. By presenting a subliminal verb after the object, enhanced predictive effects on the target verb would be detected in the OV sentences when the transitivity of the target verb matched with that of the subliminal verb (“congruent condition”), because the subliminal verb just after the object could determine the grammaticality of the sentence. For the OV sentences under the congruent condition, we observed significantly increased left IFG responses at 140–160 ms after the target verb onset. In contrast, responses in the precuneus and midcingulate cortex (MCC) were significantly reduced for the OV sentences under the congruent condition at 110–140 and 280–300 ms, respectively. By using partial Granger causality analyses for the OV sentences under the congruent condition, we revealed a bidirectional interaction between the left IFG and MCC at 60–160 ms, as well as a significant influence from the MCC to the precuneus. These results indicate that a top-down influence from the left IFG to the MCC, and then to the precuneus, is critical in syntactic decisions, whereas the MCC shares its task-set information with the left IFG to achieve automatic and predictive processes of syntax. PMID:25404899

  6. Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates Accurately Predict Human Core Object Recognition Performance.

    PubMed

    Majaj, Najib J; Hong, Ha; Solomon, Ethan A; DiCarlo, James J

    2015-09-30

    To go beyond qualitative models of the biological substrate of object recognition, we ask: can a single ventral stream neuronal linking hypothesis quantitatively account for core object recognition performance over a broad range of tasks? We measured human performance in 64 object recognition tests using thousands of challenging images that explore shape similarity and identity preserving object variation. We then used multielectrode arrays to measure neuronal population responses to those same images in visual areas V4 and inferior temporal (IT) cortex of monkeys and simulated V1 population responses. We tested leading candidate linking hypotheses and control hypotheses, each postulating how ventral stream neuronal responses underlie object recognition behavior. Specifically, for each hypothesis, we computed the predicted performance on the 64 tests and compared it with the measured pattern of human performance. All tested hypotheses based on low- and mid-level visually evoked activity (pixels, V1, and V4) were very poor predictors of the human behavioral pattern. However, simple learned weighted sums of distributed average IT firing rates exactly predicted the behavioral pattern. More elaborate linking hypotheses relying on IT trial-by-trial correlational structure, finer IT temporal codes, or ones that strictly respect the known spatial substructures of IT ("face patches") did not improve predictive power. Although these results do not reject those more elaborate hypotheses, they suggest a simple, sufficient quantitative model: each object recognition task is learned from the spatially distributed mean firing rates (100 ms) of ∼60,000 IT neurons and is executed as a simple weighted sum of those firing rates. Significance statement: We sought to go beyond qualitative models of visual object recognition and determine whether a single neuronal linking hypothesis can quantitatively account for core object recognition behavior. To achieve this, we designed a

  7. Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates Accurately Predict Human Core Object Recognition Performance

    PubMed Central

    Hong, Ha; Solomon, Ethan A.; DiCarlo, James J.

    2015-01-01

    To go beyond qualitative models of the biological substrate of object recognition, we ask: can a single ventral stream neuronal linking hypothesis quantitatively account for core object recognition performance over a broad range of tasks? We measured human performance in 64 object recognition tests using thousands of challenging images that explore shape similarity and identity preserving object variation. We then used multielectrode arrays to measure neuronal population responses to those same images in visual areas V4 and inferior temporal (IT) cortex of monkeys and simulated V1 population responses. We tested leading candidate linking hypotheses and control hypotheses, each postulating how ventral stream neuronal responses underlie object recognition behavior. Specifically, for each hypothesis, we computed the predicted performance on the 64 tests and compared it with the measured pattern of human performance. All tested hypotheses based on low- and mid-level visually evoked activity (pixels, V1, and V4) were very poor predictors of the human behavioral pattern. However, simple learned weighted sums of distributed average IT firing rates exactly predicted the behavioral pattern. More elaborate linking hypotheses relying on IT trial-by-trial correlational structure, finer IT temporal codes, or ones that strictly respect the known spatial substructures of IT (“face patches”) did not improve predictive power. Although these results do not reject those more elaborate hypotheses, they suggest a simple, sufficient quantitative model: each object recognition task is learned from the spatially distributed mean firing rates (100 ms) of ∼60,000 IT neurons and is executed as a simple weighted sum of those firing rates. SIGNIFICANCE STATEMENT We sought to go beyond qualitative models of visual object recognition and determine whether a single neuronal linking hypothesis can quantitatively account for core object recognition behavior. To achieve this, we designed a

  8. Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome

    PubMed Central

    Radujkovic, Aleksandar; Becker, Natalia; Benner, Axel; Penack, Olaf; Platzbecker, Uwe; Stölzel, Friedrich; Bornhäuser, Martin; Hegenbart, Ute; Ho, Anthony D.; Dreger, Peter; Luft, Thomas

    2015-01-01

    Allogeneic stem cell transplantation (alloSCT) represents a curative therapeutic option for patients with myelodysplastic syndrome (MDS), but relapse and non-relapse mortality (NRM) limit treatment efficacy. Based on our previous observation in acute myeloid leukemia we investigated the impact of pre-transplant weight loss on post-transplant outcome in MDS patients. A total of 111 patients diagnosed with MDS according to WHO criteria transplanted between 2000 and 2012 in three different transplant centers were included into the analysis. Data on weight loss were collected from medical records prior to conditioning therapy and 3–6 months earlier. Patient, disease and transplant characteristics did not differ between patients with weight loss (2–5%, n = 17; > 5%, n = 17) and those without (n = 77). In a mixed effect model, weight loss was associated with higher risk MDS (p = 0.046). In multivariable analyses, pre-transplant weight loss exceeding 5% was associated with a higher incidence of relapse (p < 0.001) and NRM (p = 0.007). Pre-transplant weight loss of 2–5% and > 5% were independent predictors of worse disease-free (p = 0.023 and p < 0.001, respectively) and overall survival (p = 0.043 and p < 0.001, respectively). Our retrospective study suggests that MDS patients losing weight prior to alloSCT have an inferior outcome after transplantation. Prospective studies addressing pre-transplant nutritional interventions are highly warranted. PMID:26360778

  9. Prediction of 5-Year Survival with Data Mining Algorithms.

    PubMed

    Sailer, Fabian; Pobiruchin, Monika; Bochum, Sylvia; Martens, Uwe M; Schramm, Wendelin

    2015-01-01

    Survival time prediction at the time of diagnosis is of great importance to make decisions about treatment and long-term follow-up care. However, predicting the outcome of cancer on the basis of clinical information is a challenging task. We now examined the ability of ten different data mining algorithms (Perceptron, Rule Induction, Support Vector Machine, Linear Regression, Naïve Bayes, Decision Tree, k-nearest Neighbor, Logistic Regression, Neural Network, Random Forest) to predict the dichotomous attribute "5-year-survival" based on seven attributes (sex, UICC-stage, etc.) which are available at the time of diagnosis. For this study we made use of the nationwide German research data set on colon cancer provided by the Robert Koch Institute. To assess the results a comparison between data mining algorithms and physicians' opinions was performed. Therefore, physicians guessed the survival time by leveraging the same seven attributes. The average accuracy of the physicians' opinion was 59%, the average accuracy of the machine learning algorithms was 67.7%. PMID:26152957

  10. Melanoma microRNA signature predicts post-recurrence survival

    PubMed Central

    Segura, Miguel F.; Belitskaya-Lévy, Ilana; Rose, Amy E.; Zakrzewski, Jan; Gaziel, Avital; Hanniford, Douglas; Darvishian, Farbod; Berman, Russell; Shapiro, Richard; Pavlick, Anna; Osman, Iman; Hernando, Eva

    2015-01-01

    Purpose To identify a melanoma miRNA expression signature that is predictive of outcome and then evaluate its potential to improve risk stratification when added to the standard of care staging criteria. Experimental design Total RNA was extracted from 59 formalin-fixed paraffin embedded (FFPE) melanoma metastases and hybridized to miRNA arrays containing 911 probes. We then correlated miRNA expression with post-recurrence survival and other clinicopathological criteria. Results We identified a signature of 18 miRNAs whose overexpression was significantly correlated with longer survival, defined as more than 18 months post-recurrence survival. Subsequent cross-validation showed that a small subset of these miRNAs can predict post-recurrence survival in metastatic melanoma with an estimated accuracy of 80.2% [95% CI: 79.8%, 80.6%]. In contrast to standard of care staging criteria, this six-miRNA signature significantly stratified stage III patients into “better” and “worse” prognostic categories, and a multivariate Cox regression analysis revealed the signature to be an independent predictor of survival. Furthermore, we demonstrated that most miRNAs from the signature also showed differential expression between patients with “better” and “worse prognosis” in the corresponding paired primary melanoma. Conclusion MiRNA signatures have potential as clinically relevant biomarkers of prognosis in metastatic melanoma. Our data suggest that molecularly-based models of risk assessment can improve the standard staging criteria and support the incorporation of miRNAs into such models. PMID:20179230

  11. Hematopoietic cell transplant comorbidity index is predictive of survival after autologous hematopoietic cell transplantation in multiple myeloma.

    PubMed

    Saad, Ayman; Mahindra, Anuj; Zhang, Mei-Jie; Zhong, Xiaobo; Costa, Luciano J; Dispenzieri, Angela; Drobyski, William R; Freytes, Cesar O; Gale, Robert Peter; Gasparetto, Cristina J; Holmberg, Leona A; Kamble, Rammurti T; Krishnan, Amrita Y; Kyle, Robert A; Marks, David; Nishihori, Taiga; Pasquini, Marcelo C; Ramanathan, Muthalagu; Lonial, Sagar; Savani, Bipin N; Saber, Wael; Sharma, Manish; Sorror, Mohamed L; Wirk, Baldeep M; Hari, Parameswaran N

    2014-03-01

    Autologous hematopoietic stem cell transplantation (AHCT) improves survival in patients with multiple myeloma (MM) but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and survival in patients with MM undergoing AHCT. We analyzed outcomes of 1156 patients of AHCT after high-dose melphalan reported to the Center for International Blood and Marrow Transplant Research. Individual comorbidities were prospectively collected at the time of AHCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. HCT-CI score was 0, 1, 2, 3, and >3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score > 2 (26%). Higher HCT-CI was associated with lower KPS < 90 (33% of subjects score of 0 versus 50% in HCT-CI score > 2). HCT-CI score > 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohort). One-year NRM was low at 2% (95% confidence interval, 1% to 4%) and did not correlate with HCT-CI score (P = .9). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score > 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Overall survival was also inferior with KPS < 90 (P < .001), IgA subtype (P ≤ .001), those receiving >1 pretransplant induction regimen (P = .007), and those with resistant disease at the time of AHCT (P < .001). AHCT for MM is associated with low NRM, and death is predominantly related to disease progression. Although a higher HCT-CI score did not

  12. Immunohistochemistry for myc predicts survival in colorectal cancer.

    PubMed

    Toon, Christopher W; Chou, Angela; Clarkson, Adele; DeSilva, Keshani; Houang, Michelle; Chan, Joseph C Y; Sioson, Loretta L; Jankova, Lucy; Gill, Anthony J

    2014-01-01

    MYC over-expression as determined by molecular means has been reported as a favorable prognostic biomarker in colorectal carcinoma (CRC). However MYC expression analysis is not available in the routine clinical setting. We investigated whether immunohistochemistry (IHC) for the myc protein using a novel commercially available rabbit monoclonal antibody [clone Y69] which is currently in widespread clinical use for lymphoma diagnosis could be used to predict outcome in resected CRC. Myc IHC was performed on a tissue microarray (TMA) comprising a retrospective cohort of 1421 CRC patients and scored blinded as to all clinical and pathological data. IHC was also performed on a subcohort of whole section CRCs to assess staining characteristics and concordance with TMA expression. MYC over-expression was found in 980 (69%) of CRCs and was associated with tumor stage and DNA mismatch repair/BRAF status. There was substantial agreement between TMA and whole section myc IHC (kappa = 0.742, p<0.01). CRCs with MYC over-expression demonstrated improved 5-year survival (93.2% vs. 57.3%), with the effect significantly modulated by the dominant effect of tumor stage, age at diagnosis and lymphovascular space invasion status on survival. We conclude that myc status as determined by IHC alone can be used to predict overall survival in patients with CRC undergoing surgical resection. PMID:24503701

  13. Predicting patient survival before and after hospice enrollment.

    PubMed

    Christakis, N A

    1998-01-01

    Despite the apparent advantages of hospice care, several barriers exist in terms of patient referral. Physicians' prognoses play a large role in determining when hospice care should begin. Predicting patient survival is a subjective decision dependent on several factors that vary before and after hospice enrollment. Currently, the stay of patients in hospice is very short; this can be attributed to late referral by physicians. Additional research on physician behavior and prognostication could help optimize the use of hospice as a valuable health care resource, thereby improving end of life care for terminally ill patients. PMID:9644394

  14. Polymorphisms of nucleotide excision repair genes predict melanoma survival.

    PubMed

    Li, Chunying; Yin, Ming; Wang, Li-E; Amos, Christopher I; Zhu, Dakai; Lee, Jeffrey E; Gershenwald, Jeffrey E; Grimm, Elizabeth A; Wei, Qingyi

    2013-07-01

    Melanoma is the most highly malignant skin cancer, and nucleotide excision repair (NER) is involved in melanoma susceptibility. In this analysis of 1,042 melanoma patients, we evaluated whether genetic variants of NER genes may predict survival outcome of melanoma patients. We used genotyping data of 74 tagging single-nucleotide polymorphisms (tagSNPs) in eight core NER genes from our genome-wide association study (including two in XPA, 14 in XPC, three in XPE, four in ERCC1, 10 in ERCC2, eight in ERCC3, 14 in ERCC4, and 19 in ERCC5) and evaluated their associations with prognosis of melanoma patients. Using the Cox proportional hazards model and Kaplan-Meier analysis, we found a predictive role of XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871 SNPs in the prognosis of melanoma patients (rs28720291: AG vs. GG, adjusted hazard ratio (adjHR)=11.2, 95% confidence interval (CI) 3.04-40.9, P=0.0003; rs4150314: AG vs. GG, adjHR=4.76, 95% CI 1.09-20.8, P=0.038; rs2470458: AA vs. AG/GG, adjHR=2.11, 95% CI 1.03-4.33, P=0.040; and rs50871: AA vs. AC/CC adjHR=2.27, 95% CI 1.18-4.35, P=0.015). Patients with an increasing number of unfavorable genotypes had markedly increased death risk. Genetic variants of NER genes, particularly XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871, may independently or jointly modulate survival outcome of melanoma patients. Because our results were based on a median follow-up of 3 years without multiple test corrections, additional large prospective studies are needed to confirm our findings. PMID:23407396

  15. Loss of H3K27 tri-methylation is a diagnostic marker for malignant peripheral nerve sheath tumors and an indicator for an inferior survival.

    PubMed

    Cleven, Arjen H G; Sannaa, Ghadah A Al; Briaire-de Bruijn, Inge; Ingram, Davis R; van de Rijn, Matt; Rubin, Brian P; de Vries, Maurits W; Watson, Kelsey L; Torres, Kelia E; Wang, Wei-Lien; van Duinen, Sjoerd G; Hogendoorn, Pancras C W; Lazar, Alexander J; Bovée, Judith V M G

    2016-06-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that can show overlapping features with benign neurofibromas as well as high-grade sarcomas. Additional diagnostic markers are needed to aid in this often challenging differential diagnosis. Recently mutations in two critical components of the polycomb repressor 2 (PRC2) complex, SUZ12 and EED, were reported to occur specifically in MPNSTs while such mutations are absent in neurofibromas, both in the setting of neurofibromatosis (NF) and sporadic cases. Furthermore, both SUZ12 and EED mutations in MPNSTs were associated with loss of H3K27 tri-methylation, a downstream target of PRC2. Therefore, we tested whether H3K27me3 immunohistochemistry is useful as a diagnostic and prognostic marker for MPNSTs. We performed H3K27me3 immunohistochemistry in 162 primary MPNSTs, 97 neurofibromas and 341 other tumors using tissue microarray. We observed loss of H3K27me3 in 34% (55/162) of all MPNSTs while expression was retained in all neurofibromas including atypical (n=8) and plexiform subtypes (n=24). Within other tumors we detected loss of H3K27me3 in only 7% (24/341). Surprisingly, 60% (9/15) of synovial sarcomas and 38% (3/8) of fibrosarcomatous dermatofibrosarcoma protuberans (DFSP) showed loss of H3K27 trimethylation. Only 1 out of 44 schwannomas showed loss of H3K27me3 and all 4 perineuriomas showed intact H3K27me3. Furthermore, MPNSTs with loss of H3K27 tri-methylation showed inferior survival compared with MPNSTs with intact H3K27 tri-methylation, which was validated in two independent cohorts. Our results indicate that H3K27me3 immunohistochemistry is useful as a diagnostic marker, in which loss of H3K27me3 favors MPNST above neurofibroma. However, H3K27me3 immunohistochemistry is not suitable to distinguish MPNST from its morphological mimicker synovial sarcoma or fibrosarcomatous DFSP. Since loss of H3K27 tri-methylation was related to poorer survival in MPNST, chromatin modification mediated

  16. Loss of H3K27 tri-methylation is a diagnostic marker for Malignant Peripheral Nerve Sheath Tumors and an indicator for an inferior survival

    PubMed Central

    Cleven, Arjen H.G.; Al Sannaa, Ghadah A.; Bruijn, Inge Briaire-de; Ingram, Davis R.; van de Rijn, Matt; Rubin, Brian P.; de Vries, Maurits; Watson, Kelsey; Torres, Keila E.; Wang, Wei-Lien; van Duinen, Sjoerd; Hogendoorn, Pancras C. W.; Lazar, Alexander J.; Bovée, Judith V.M.G.

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that can show overlapping features with benign neurofibromas as well as high-grade sarcomas. Additional diagnostic markers are needed to aid in this often challenging differential diagnosis. Recently mutations in two critical components of the polycomb repressor 2 (PRC2) complex, SUZ12 and EED, were reported to occur specifically in MPNSTs while such mutations are absent in neurofibromas, both in the setting of neurofibromatosis (NF) and sporadic cases. Furthermore, both SUZ12 and EED mutations in MPNSTs were associated with loss of H3K27 tri-methylation, a downstream target of PRC2. Therefore we tested whether H3K27me3 immunohistochemistry is useful as a diagnostic and prognostic marker for MPNSTs. We performed H3K27me3 immunohistochemistry in 162 primary MPNSTs, 97 neurofibromas and 341 other tumors using tissue microarray. We observed loss of H3K27me3 in 34% (55/162) of all MPNSTs while expression was retained in all neurofibromas including atypical (n=8) and plexiform subtypes (n=24). Within other tumors we detected loss of H3K27me3 in only 7% (24/341). Surprisingly, 60% (9/15) of synovial sarcomas and 38% (3/8) of fibrosarcomatous dermatofibrosarcoma protuberans (DFSP) showed loss of H3K27 trimethylation. Only 1 out of 44 schwannomas showed loss of H3K27me3 and all 4 perineuriomas showed intact H3K27me3. Furthermore, MPNSTs with loss of H3K27 tri-methylation showed inferior survival compared to MPNSTs with intact H3K27 tri-methylation, which was validated in two independent cohorts. Our results indicate that H3K27me3 immunohistochemistry is useful as a diagnostic marker in which loss of H3K27me3 favours MPNST above neurofibroma. However H3K27me3 immunohistochemistry is not suitable to distinguish MPNST from its morphological mimicker synovial sarcoma or fibrosarcomatous DFSP. Since loss of H3K27 tri-methylation was related to poorer survival in MPNST, chromatin modification mediated by

  17. Survival outcomes scores (SOFT, BAR, and Pedi-SOFT) are accurate in predicting post-liver transplant survival in adolescents.

    PubMed

    Conjeevaram Selvakumar, Praveen Kumar; Maksimak, Brian; Hanouneh, Ibrahim; Youssef, Dalia H; Lopez, Rocio; Alkhouri, Naim

    2016-09-01

    SOFT and BAR scores utilize recipient, donor, and graft factors to predict the 3-month survival after LT in adults (≥18 years). Recently, Pedi-SOFT score was developed to predict 3-month survival after LT in young children (≤12 years). These scoring systems have not been studied in adolescent patients (13-17 years). We evaluated the accuracy of these scoring systems in predicting the 3-month post-LT survival in adolescents through a retrospective analysis of data from UNOS of patients aged 13-17 years who received LT between 03/01/2002 and 12/31/2012. Recipients of combined organ transplants, donation after cardiac death, or living donor graft were excluded. A total of 711 adolescent LT recipients were included with a mean age of 15.2±1.4 years. A total of 100 patients died post-LT including 33 within 3 months. SOFT, BAR, and Pedi-SOFT scores were all found to be good predictors of 3-month post-transplant survival outcome with areas under the ROC curve of 0.81, 0.80, and 0.81, respectively. All three scores provided good accuracy for predicting 3-month survival post-LT in adolescents and may help clinical decision making to optimize survival rate and organ utilization. PMID:27478012

  18. Camouflage predicts survival in ground-nesting birds.

    PubMed

    Troscianko, Jolyon; Wilson-Aggarwal, Jared; Stevens, Martin; Spottiswoode, Claire N

    2016-01-01

    Evading detection by predators is crucial for survival. Camouflage is therefore a widespread adaptation, but despite substantial research effort our understanding of different camouflage strategies has relied predominantly on artificial systems and on experiments disregarding how camouflage is perceived by predators. Here we show for the first time in a natural system, that survival probability of wild animals is directly related to their level of camouflage as perceived by the visual systems of their main predators. Ground-nesting plovers and coursers flee as threats approach, and their clutches were more likely to survive when their egg contrast matched their surrounds. In nightjars - which remain motionless as threats approach - clutch survival depended on plumage pattern matching between the incubating bird and its surrounds. Our findings highlight the importance of pattern and luminance based camouflage properties, and the effectiveness of modern techniques in capturing the adaptive properties of visual phenotypes. PMID:26822039

  19. Camouflage predicts survival in ground-nesting birds

    PubMed Central

    Troscianko, Jolyon; Wilson-Aggarwal, Jared; Stevens, Martin; Spottiswoode, Claire N.

    2016-01-01

    Evading detection by predators is crucial for survival. Camouflage is therefore a widespread adaptation, but despite substantial research effort our understanding of different camouflage strategies has relied predominantly on artificial systems and on experiments disregarding how camouflage is perceived by predators. Here we show for the first time in a natural system, that survival probability of wild animals is directly related to their level of camouflage as perceived by the visual systems of their main predators. Ground-nesting plovers and coursers flee as threats approach, and their clutches were more likely to survive when their egg contrast matched their surrounds. In nightjars – which remain motionless as threats approach – clutch survival depended on plumage pattern matching between the incubating bird and its surrounds. Our findings highlight the importance of pattern and luminance based camouflage properties, and the effectiveness of modern techniques in capturing the adaptive properties of visual phenotypes. PMID:26822039

  20. Tumor-infiltrating lymphocytes predict cutaneous melanoma survival.

    PubMed

    Fortes, Cristina; Mastroeni, Simona; Mannooranparampil, Thomas J; Passarelli, Francesca; Zappalà, Alba; Annessi, Giorgio; Marino, Claudia; Caggiati, Alessio; Russo, Nicoletta; Michelozzi, Paola

    2015-08-01

    Understanding differences in survival across distinct subgroups of melanoma patients may help with the choice of types of therapy. Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the role of TILs in melanoma mortality is controversial. The aim of this study was to investigate independent prognostic factors for melanoma mortality. We carried out a 10-year cohort study on 4133 melanoma patients from the same geographic area (Lazio) with primary cutaneous melanoma diagnosed between January 1998 and December 2008. The probability of survival was estimated using Kaplan-Meier methods and prognostic factors were evaluated by multivariate analysis (Cox proportional hazards model). The 10-year survival rate for melanoma decreased with increasing Breslow thickness (Pfor trend<0.0001) and with age (Pfor trend<0.0001) whereas survival increased with increasing levels of TILs (Pfor trend=0.0001). The 10-year survival rate for melanoma divided into TILs intensity as scanty, moderate, and marked was 88.0, 92.2, and 97.0%, respectively. In the multivariate Cox model, the presence of high levels of TILs in primary invasive melanomas was associated with a lower risk of melanoma death (hazard ratio 0.32; 95% confidence interval 0.13-0.82) after controlling for sex, age, Breslow thickness, histological type, mitotic rate, and ulceration. After including lymph node status in the multivariate analysis, the protective effect of marked TILs on melanoma mortality remained (hazard ratio 0.37; 95% confidence interval 0.15-0.94). The results of this study suggest that the immune microenvironment affects melanoma survival. PMID:25933208

  1. Socioeconomic status and prediction of ventricular fibrillation survival.

    PubMed Central

    Hallstrom, A; Boutin, P; Cobb, L; Johnson, E

    1993-01-01

    OBJECTIVES. The association between socioeconomic status and cardiac arrest is less well known than some other associations with cardiac arrest. We used property tax assessments as a measure of socioeconomic status in a study of victims of out-of-hospital cardiac arrest found in ventricular fibrillation. METHODS. We studied patients attended by the Seattle Fire Department's emergency medical services system between May 1986 and August 1988. During the period studied, 356 episodes met the study criteria; 114 (32%) of these patients survived without major neurologic deficit. Residential property tax assessments were available for 253 of the patients. RESULTS. After adjustments were made for age, witnessed collapse, bystander-initiated cardiopulmonary resuscitation, time from call to paramedic arrival, activity, location of collapse, and chronic morbidity, an association of survival with greater assessed value per living unit was observed. An increase of $50,000 in value per unit was associated with a 1.6-fold increase in survival rate. CONCLUSIONS. Not only are persons in the lower socioeconomic strata at greater risk for cardiac mortality, but they are also less likely to survive an episode of out-of-hospital cardiac arrest. PMID:8427331

  2. HOXB7 Promotes Invasion and Predicts Survival in Pancreatic Adenocarcinoma

    PubMed Central

    Kovochich, Anne Nguyen; Arensman, Michael; Lay, Anna R.; Rao, Nagesh P.; Donahue, Timothy; Li, Xinmin; French, Samuel W.; Dawson, David W.

    2013-01-01

    BACKGROUND The homeobox gene HOXB7 is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, invasion, and angiogenesis. Although published microarray data suggest HOXB7 is overexpressed in pancreatic ductal adenocarcinoma (PDAC), its function in pancreatic cancer has not been studied. METHODS HOXB7 message and protein levels were examined in PDAC cell lines and patient samples, as well as in normal pancreas. HOXB7 protein expression in patient tumors was determined by immunohistochemistry and correlated with clinicopathologic factors and survival. The impact of HOXB7 on cell proliferation, growth, and invasion was assessed by knockdown and overexpression in PDAC cell lines. Candidate genes whose expression levels were altered following HOXB7 knockdown were determined by microarray analysis. RESULTS HOXB7 message and protein levels were significantly elevated in PDAC cell lines and patient tumor samples relative to normal pancreas. Evaluation of a tissue microarray of 145 resected PDACs found high HOXB7 protein expression was correlated with lymph node metastasis (P = .034) and an independent predictor of worse overall survival in multivariate analysis (hazard ratio = 1.56, 95% confidence interval = 1.02–2.39). HOXB7 knockdown or overexpression in PDAC cell lines resulted in decreased or increased invasion, respectively, without influencing proliferation or cell viability. CONCLUSIONS HOXB7 is frequently overexpressed in PDAC, specifically promotes invasive phenotype, and is associated with lymph node metastasis and worse survival outcome. HOXB7 and its downstream targets may represent novel clinical biomarkers or targets of therapy for inhibiting the invasive and metastatic capacity of PDAC. PMID:22914903

  3. Can oncologists predict survival for patients with progressive disease after standard chemotherapies?

    PubMed Central

    Taniyama, T.K.; Hashimoto, K.; Katsumata, N.; Hirakawa, A.; Yonemori, K.; Yunokawa, M.; Shimizu, C.; Tamura, K.; Ando, M.; Fujiwara, Y.

    2014-01-01

    Background Prediction of prognosis is important for patients so that they can make the most of the rest of their lives. Oncologists could predict survival, but the accuracy of such predictions is unclear. Methods In this observational prospective cohort study, 14 oncologists treating 9 major adult solid malignancies were asked to complete questionnaires predicting survival based on performance status, oral intake, and other clinical factors when patients experienced progressive disease after standard chemotherapies. Clinically predicted survival (cps) was calculated by the oncologists from the date of progressive disease to the predicted date of death. Actual survival (as) was compared with cps using Kaplan–Meier survival curves, and factors affecting inaccurate prediction were determined by logistic regression analysis. The prediction of survival time was considered accurate when the cps/as ratio was between 0.67 and 1.33. Results The study cohort consisted of 75 patients. Median cps was 120 days (interquartile range: 60–180 days), and median as was 121 days (interquartile range: 40–234 days). The participating oncologists accurately predicted as within a 33% range 36% of the time; the survival time was overestimated 36% of time and underestimated 28% of the time. The factors affecting the accuracy of the survival estimate were the experience of the oncologist, patient age, and information given about the palliative care unit. Conclusions Prediction of cps was accurate for just slightly more than one third of all patients in this study. Additional investigation of putative prognostic factors with a larger sample size is warranted. PMID:24764697

  4. Trajectories of Serum Albumin Predict Survival of Peritoneal Dialysis Patients

    PubMed Central

    Chiu, Ping-Fang; Tsai, Chun-Chieh; Wu, Chia-Lin; Yang, Tse-Yen; Liou, Hung-Hsiang; Chen, Hung-Lin; Kor, Chew-Teng; Chang, Chia-Chu; Chang, Horng-Rong

    2016-01-01

    Abstract Although initial serum albumin level is highly associated with overall and cardiovascular mortality in peritoneal dialysis (PD) patients, we consider that the dynamic change and trend of albumin after initiation of PD are also essential. We enrolled patients who received PD for more than 3 months from January 1999 to March 2014. We categorized these patients into 2 groups by the difference in serum albumin level (Δalbumin = difference between peak with initial albumin level = peak albumin level − initial albumin level) after PD. The patients with Δalbumin < 0.2 g/dL (median level) were considered as group A (n, number = 238) and those with Δalbumin ≥ 0.2 g/dL were considered as group B (n = 278). Further, we stratified these patients into quartiles: Q1 Δalbumin < −0.2 g/dL; Q2, −0.2 ≦∼ <0.2 g/dL; Q3, 0.2 ≦∼ <0.6 g/dL; and Q4, ≥0.6 g/dL. Regression analysis was performed to determine the correlation of initial albumin and Δalbumin. Group A patients presented with higher levels of serum albumin (3.71 ± 0.54 vs 3.04 ± 0.55 g/dL; P < 0.001) and hematocrit as well as better initial residual renal function. However, those in group A had lower serum albumin increment and downward-sloped trends after dialysis. In contrast, the albumin trend was upward sloped and the increment of albumin was remarkable in group B, despite the high prevalence of cardiovascular diseases and diabetes. Overtime, group A patients had poorer survival and experienced more frequent and longer hospitalizations. Group Q1 patients with least albumin increment had worst survival. Group Q4 patients with lowest initial albumin also had poor survival. Age, diabetes, cardiovascular diseases, BMI, initial albumin, and Δalbumin could affect patient outcomes independently. Regression analysis showed a better outcome can be obtained if the initial albumin level is at least above 3.15 g/dL. (Initial albumin level

  5. Prognostication of Survival in Patients With Advanced Cancer: Predicting the Unpredictable?

    PubMed Central

    Hui, David

    2016-01-01

    Background Prognosis is a key driver of clinical decision-making. However, available prognostication tools have limited accuracy and variable levels of validation. Methods Principles of survival prediction and literature on clinician prediction of survival, prognostic factors, and prognostic models were reviewed, with a focus on patients with advanced cancer and a survival rate of a few months or less. Results The 4 principles of survival prediction are (a) prognostication is a process instead of an event, (b) prognostic factors may evolve over the course of the disease, (c) prognostic accuracy for a given prognostic factor/tool varies by the definition of accuracy, the patient population, and the time frame of prediction, and (d) the exact timing of death cannot be predicted with certainty. Clinician prediction of survival rate is the most commonly used approach to formulate prognosis. However, clinicians often overestimate survival rates with the temporal question. Other clinician prediction of survival approaches, such as surprise and probabilistic questions, have higher rates of accuracy. Established prognostic factors in the advanced cancer setting include decreased performance status, delirium, dysphagia, cancer anorexia–cachexia, dyspnea, inflammation, and malnutrition. Novel prognostic factors, such as phase angle, may improve rates of accuracy. Many prognostic models are available, including the Palliative Prognostic Score, the Palliative Prognostic Index, and the Glasgow Prognostic Score. Conclusions Despite the uncertainty in survival prediction, existing prognostic tools can facilitate clinical decision-making by providing approximated time frames (months, weeks, or days). Future research should focus on clarifying and comparing the rates of accuracy for existing prognostic tools, identifying and validating novel prognostic factors, and linking prognostication to decision-making. PMID:26678976

  6. Paradoxical Herniation After Unilateral Decompressive Craniectomy Predicts Better Patient Survival

    PubMed Central

    Chen, Weiqiang; Guo, Jingfang; Wu, Jin; Peng, Guoyi; Huang, Mindong; Cai, Chuwei; Yang, Yingming; Wang, Shousen

    2016-01-01

    Abstract Paradoxical herniation (PH) is a life-threatening emergency after decompressive craniectomy. In the current study, we examined patient survival in patients who developed PH after decompressive craniectomy versus those who did not. Risk factors for, and management of, PH were also analyzed. This retrospective analysis included 429 consecutive patients receiving decompressive craniectomy during a period from January 2007 to December 2012. Mortality rate and Glasgow Outcome Scale (GOS) were compared between those who developed PH (n = 13) versus those who did not (n = 416). A stepwise multivariate logistic regression analysis was carried out to examine the risk factors for PH. The overall mortality in the entire sample was 22.8%, with a median follow-up of 6 months. Oddly enough, all 13 patients who developed PH survived beyond 6 months. Glasgow Coma Scale did not differ between the 2 groups upon admission, but GOS was significantly higher in subjects who developed PH. Both the disease type and coma degree were comparable between the 13 PH patients and the remaining 416 patients. In all PH episodes, patients responded to emergency treatments that included intravenous hydration, cerebral spinal fluid drainage discontinuation, and Trendelenburg position. A regression analysis indicated the following independent risk factors for PH: external ventriculostomy, lumbar puncture, and continuous external lumbar drainage. The rate of PH is approximately 3% after decompressive craniectomy. The most intriguing findings of the current study were the 0% mortality in those who developed PH versus 23.6% mortality in those who did not develop PH and significant difference of GOS score at 6-month follow-up between the 2 groups, suggesting that PH after decompressive craniectomy should be managed aggressively. The risk factors for PH include external ventriculostomy, ventriculoperitoneal shunt, lumbar puncture, and continuous external lumbar drainage. PMID:26945365

  7. Cardiopulmonary bypass (CPB) has no significant impact on survival in patients undergoing nephrectomy and level III-IV inferior vena cava thrombectomy; a multi-institutional analysis

    PubMed Central

    Dall'Era, Marc A.; Durbin-Johnson, Blythe; Carballido, Joaquín A.; Chandrasekar, Thenappan; Chromecki, Thomas; Ciancio, Gaetano; Daneshmand, Siamak; Gontero, Paolo; Gonzalez, Javier; Haferkamp, Axel; Hohenfellner, Markus; Huang, William C.; Espinós, Estefania Linares; Mandel, Philipp; Martinez-Salamanca, Juan I.; Master, Viraj A.; McKiernan, James M.; Montorsi, Francesco; Novara, Giacomo; Pahernik, Sascha; Palou, Juan; Pruthi, Raj S.; Rodriguez-Faba, Oscar; Russo, Paul; Scherr, Douglas S.; Shariat, Shahrokh F.; Spahn, Martin; Terrone, Carlo; Vergho, Daniel; Wallen, Eric M.; Xylinas, Evanguelos; Zigeuner, Richard; Libertino, John A.; Evans, Christopher P.

    2016-01-01

    Purpose The impact of cardiopulmonary bypass (CPB) usage in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We sought to determine the impact of cardiopulmonary bypass (CPB) on overall and cancer specific survival, as well as surgical complication rates, and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without CPB. Patients and Methods We retrospectively analyzed 362 patients with RCC and with level III or IV tumor thrombus from 1992 to 2012 in 22 US and European centers. Cox proportional hazards models were used to compare overall and cancer-specific survival between patients with and without CPB. Perioperative mortality and complications rates were assessed using logistic regression analyses. Results The median overall survival was 24.6 months in non-CPB patients and 26.6 months in CPB patients. Overall survival and cancer-specific survival (CSS) did not differ significantly in both groups, neither in univariate analysis nor when adjusting for known risk factors. In multivariate analysis, no significant differences were seen in hospital LOS, Clavien 1-4 complication rate, intraoperative or 30 day mortality, and CSS between both groups. Limitations include the retrospective nature of the study. Conclusions In our multi-institutional analysis, the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality in the multivariate analysis. Higher surgical complications were not independently associated with the use of CPB. PMID:25797392

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

    PubMed

    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. PMID:27532883

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

    PubMed Central

    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. PMID:27532883

  10. Predicted Gains from Inbred-Progeny Selection Is Inferior to Half-sib Selection for Two Maize Populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Historically, inbred progeny selection has been promoted as an effective means of improving both inbred and outbred performance, and in some cases superior to other methods. The predicted effectiveness of inbred-progeny selection was based on several factors, the most common being the proportion of ...

  11. Integration of multimodal RNA-seq data for prediction of kidney cancer survival

    PubMed Central

    Schwartzi, Matt; Parkl, Martin; Phanl, John H.; Wang., May D.

    2016-01-01

    Kidney cancer is of prominent concern in modern medicine. Predicting patient survival is critical to patient awareness and developing a proper treatment regimens. Previous prediction models built upon molecular feature analysis are limited to just gene expression data. In this study we investigate the difference in predicting five year survival between unimodal and multimodal analysis of RNA-seq data from gene, exon, junction, and isoform modalities. Our preliminary findings report higher predictive accuracy-as measured by area under the ROC curve (AUC)-for multimodal learning when compared to unimodal learning with both support vector machine (SVM) and k-nearest neighbor (KNN) methods. The results of this study justify further research on the use of multimodal RNA-seq data to predict survival for other cancer types using a larger sample size and additional machine learning methods. PMID:27532026

  12. An interactive Bayesian model for prediction of lymph node ratio and survival in pancreatic cancer patients

    PubMed Central

    Smith, Brian J; Mezhir, James J

    2014-01-01

    Background Regional lymph node status has long been used as a dichotomous predictor of clinical outcomes in cancer patients. More recently, interest has turned to the prognostic utility of lymph node ratio (LNR), quantified as the proportion of positive nodes examined. However, statistical tools for the joint modeling of LNR and its effect on cancer survival are lacking. Methods Data were obtained from the NCI SEER cancer registry on 6400 patients diagnosed with pancreatic ductal adenocarcinoma from 2004 to 2010 and who underwent radical oncologic resection. A novel Bayesian statistical approach was developed and applied to model simultaneously patients’ true, but unobservable, LNR statuses and overall survival. New web development tools were then employed to create an interactive web application for individualized patient prediction. Results Histologic grade and T and M stages were important predictors of LNR status. Significant predictors of survival included age, gender, marital status, grade, histology, T and M stages, tumor size, and radiation therapy. LNR was found to have a highly significant, non-linear effect on survival. Furthermore, predictive performance of the survival model compared favorably to those from studies with more homogeneous patients and individualized predictors. Conclusions We provide a new approach and tool set for the prediction of LNR and survival that are generally applicable to a host of cancer types, including breast, colon, melanoma, and stomach. Our methods are illustrated with the development of a validated model and web applications for the prediction of survival in a large set of pancreatic cancer patients. PMID:24444460

  13. Predicting response and survival in chemotherapy-treated triple-negative breast cancer

    PubMed Central

    Prat, A; Lluch, A; Albanell, J; Barry, W T; Fan, C; Chacón, J I; Parker, J S; Calvo, L; Plazaola, A; Arcusa, A; Seguí-Palmer, M A; Burgues, O; Ribelles, N; Rodriguez-Lescure, A; Guerrero, A; Ruiz-Borrego, M; Munarriz, B; López, J A; Adamo, B; Cheang, M C U; Li, Y; Hu, Z; Gulley, M L; Vidal, M J; Pitcher, B N; Liu, M C; Citron, M L; Ellis, M J; Mardis, E; Vickery, T; Hudis, C A; Winer, E P; Carey, L A; Caballero, R; Carrasco, E; Martín, M; Perou, C M; Alba, E

    2014-01-01

    Background: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). Methods: Gene expression and clinical–pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. Results: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55–81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. Conclusions: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not. PMID:25101563

  14. The radiosensitivity index predicts for overall survival in glioblastoma

    PubMed Central

    Ahmed, Kamran A.; Chinnaiyan, Prakash; Fulp, William J.; Eschrich, Steven; Torres-Roca, Javier F.; Caudell, Jimmy J.

    2015-01-01

    We have previously developed a multigene expression model of tumor radiosensitivity (RSI) with clinical validation in multiple cohorts and disease sites. We hypothesized RSI would identify glioblastoma patients who would respond to radiation and predict treatment outcomes. Clinical and array based gene expression (Affymetrix HT Human Genome U133 Array Plate Set) level 2 data was downloaded from the cancer genome atlas (TCGA). A total of 270 patients were identified for the analysis: 214 who underwent radiotherapy and temozolomide and 56 who did not undergo radiotherapy. Median follow-up for the entire cohort was 9.1 months (range: 0.04–92.2 months). Patients who did not receive radiotherapy were more likely to be older (p < 0.001) and of poorer performance status (p < 0.001). On multivariate analysis, RSI is an independent predictor of OS (HR = 1.64, 95% CI 1.08–2.5; p = 0.02). Furthermore, on subset analysis, radiosensitive patients had significantly improved OS in the patients with high MGMT expression (unmethylated MGMT), 1 year OS 84.1% vs. 53.7% (p = 0.005). This observation held on MVA (HR = 1.94, 95% CI 1.19–3.31; p = 0.008), suggesting that RT has a larger therapeutic impact in these patients. In conclusion, RSI predicts for OS in glioblastoma. These data further confirm the value of RSI as a disease-site independent biomarker. PMID:26451615

  15. Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use

    PubMed Central

    2012-01-01

    Introduction To investigate whether respiratory variation of inferior vena cava diameter (cIVC) predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure (ACF). Methods Forty patients with ACF and spontaneous breathing were included. Response to fluid challenge was defined as a 15% increase of subaortic velocity time index (VTI) measured by transthoracic echocardiography. Inferior vena cava diameters were recorded by a subcostal view using M Mode. The cIVC was calculated as follows: (Dmax - Dmin/Dmax) × 100 and then receiver operating characteristic (ROC) curves were generated for cIVC, baseline VTI, E wave velocity, E/A and E/Ea ratios. Results Among 40 included patients, 20 (50%) were responders (R). The causes of ACF were sepsis (n = 24), haemorrhage (n = 11), and dehydration (n = 5). The area under the ROC curve for cIVC was 0.77 (95% CI: 0.60-0.88). The best cutoff value was 40% (Se = 70%, Sp = 80%). The AUC of the ROC curves for baseline E wave velocity, VTI, E/A ratio, E/Ea ratio were 0.83 (95% CI: 0.68-0.93), 0.78 (95% CI: 0.61-0.88), 0.76 (95% CI: 0.59-0.89), 0.58 (95% CI: 0.41-0.75), respectively. The differences between AUC the ROC curves for cIVC and baseline E wave velocity, baseline VTI, baseline E/A ratio, and baseline E/Ea ratio were not statistically different (p = 0.46, p = 0.99, p = 1.00, p = 0.26, respectively). Conclusion In spontaneously breathing patients with ACF, high cIVC values (>40%) are usually associated with fluid responsiveness while low values (< 40%) do not exclude fluid responsiveness. PMID:23043910

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

    PubMed Central

    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

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

    PubMed

    Laimighofer, Michael; Krumsiek, Jan; Buettner, Florian; Theis, Fabian J

    2016-04-01

    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

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

    PubMed Central

    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

    2014-01-01

    Background 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. Methods 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. Results 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, p<0.01), 3 months (0.84 vs 0.75, p<0.01) and 6 months (0.85 vs 0.76, p<0.01). Conclusions The LENT 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. PMID:25100651

  19. Accuracy of Inferior Vena Cava Ultrasound for Predicting Dehydration in Children with Acute Diarrhea in Resource-Limited Settings

    PubMed Central

    Modi, Payal; Glavis-Bloom, Justin; Nasrin, Sabiha; Guy, Allysia; Rege, Soham; Noble, Vicki E.; Alam, Nur H.; Levine, Adam C.

    2016-01-01

    Introduction Although dehydration from diarrhea is a leading cause of morbidity and mortality in children under five, existing methods of assessing dehydration status in children have limited accuracy. Objective To assess the accuracy of point-of-care ultrasound measurement of the aorta-to-IVC ratio as a predictor of dehydration in children. Methods A prospective cohort study of children under five years with acute diarrhea was conducted in the rehydration unit of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Ultrasound measurements of aorta-to-IVC ratio and dehydrated weight were obtained on patient arrival. Percent weight change was monitored during rehydration to classify children as having “some dehydration” with weight change 3–9% or “severe dehydration” with weight change > 9%. Logistic regression analysis and Receiver-Operator Characteristic (ROC) curves were used to evaluate the accuracy of aorta-to-IVC ratio as a predictor of dehydration severity. Results 850 children were enrolled, of which 771 were included in the final analysis. Aorta to IVC ratio was a significant predictor of the percent dehydration in children with acute diarrhea, with each 1-point increase in the aorta to IVC ratio predicting a 1.1% increase in the percent dehydration of the child. However, the area under the ROC curve (0.60), sensitivity (67%), and specificity (49%), for predicting severe dehydration were all poor. Conclusions Point-of-care ultrasound of the aorta-to-IVC ratio was statistically associated with volume status, but was not accurate enough to be used as an independent screening tool for dehydration in children under five years presenting with acute diarrhea in a resource-limited setting. PMID:26766306

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

    PubMed Central

    Hirsch, Henry R.

    2008-01-01

    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. PMID:19424855

  1. Vasoreactivity to inhaled nitric oxide with oxygen predicts long-term survival in pulmonary arterial hypertension.

    PubMed

    Malhotra, Rajeev; Hess, Dean; Lewis, Gregory D; Bloch, Kenneth D; Waxman, Aaron B; Semigran, Marc J

    2011-04-01

    Pulmonary vasodilator testing is currently used to guide management of patients with pulmonary arterial hypertension (PAH). However, the utility of the pulmonary vascular response to inhaled nitric oxide (NO) and oxygen in predicting survival has not been established. Eighty patients with WHO Group I PAH underwent vasodilator testing with inhaled NO (80 ppm with 90% O(2) for 10 minutes) at the time of diagnosis. Changes in right atrial (RA) pressure, mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure, Fick cardiac output, and pulmonary vascular resistance (PVR) were tested for associations to long-term survival (median follow-up 2.4 years). Five-year survival was 56%. Baseline PVR (mean±SD 850±580 dyne-sec/cm(5)) and mPAP (49±14 mmHg) did not predict survival, whereas the change in either PVR or mPAP while breathing NO and O(2) was predictive. Patients with a ≥30% reduction in PVR with inhaled NO and O(2) had a 53% relative reduction in mortality (Cox hazard ratio 0.47, 95% confidence interval (CI) 0.23-0.99, P=0.047), and those with a ≥12% reduction in mPAP with inhaled NO and O(2) had a 55% relative reduction in mortality (hazard ratio 0.45, 95% CI 0.22-0.96, P=0.038). The same vasoreactive thresholds predicted survival in the subset of patients who never were treated with calcium channel antagonists (n=66). Multivariate analysis showed that decreases in PVR and mPAP with inhaled NO and O(2) were independent predictors of survival. Reduction in PVR or mPAP during short-term administration of inhaled NO and O(2) predicts survival in PAH patients. PMID:22020367

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

    SciTech Connect

    Oberije, Cary; De Ruysscher, Dirk; Houben, Ruud; Heuvel, Michel van de; Uyterlinde, Wilma; Deasy, Joseph O.; Belderbos, Jose; Dingemans, Anne-Marie C.; Rimner, Andreas; Din, Shaun; Lambin, Philippe

    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.

  3. Survival Prediction Score: A Simple but Age-Dependent Method Predicting Prognosis in Patients Undergoing Palliative Radiotherapy

    PubMed Central

    Dalhaug, Astrid; Pawinski, Adam; Haukland, Ellinor

    2014-01-01

    Purpose. Validation of a Canadian three-tiered prognostic model (survival prediction score, SPS) in Norwegian cancer patients referred for palliative radiotherapy (PRT), and evaluation of age-dependent performance of the model. Patients and Methods. We analyzed all 579 PRT courses administered at a dedicated PRT facility between 20.06.07 and 31.12.2009. SPS was assigned as originally described, That is, by taking into consideration three variables: primary cancer type, site of metastases, and performance status. Results. Patients with poor prognosis (non-breast cancer, metastases other than bone, and Karnofsky performance status (KPS) ≤ 60) had median survival of 13 weeks. Those with intermediate prognosis (two of these parameters) survived for a median of 29 weeks, and patients with good prognosis for a median of 114 weeks, P < 0.001. While this model performed well in patients who were 60 years or older, it was less satisfactory in younger patients (no significant difference between the good and intermediate prognosis groups). Conclusion. SPS should mainly be used to predict survival of elderly cancer patients. However, even in this group accuracy is limited because the good prognosis group contained patients with short survival, while the poor prognosis group contained long-term survivors. Thus, improved models should be developed. PMID:25006508

  4. Radiographic Response to Locoregional Therapy in Hepatocellular Carcinoma Predicts Patient Survival Times

    PubMed Central

    Memon, Khairuddin; Kulik, Laura; Lewandowski, Robert J; Wang, Edward; Riaz, Ahsun; Ryu, Robert K; Sato, Kent T; Marshall, Karen; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Senthilnathan, Seanthan; Baker, Talia; Gates, Vanessa L; Abecassis, Michael; Benson, Al B; Mulcahy, Mary F; Omary, Reed A; Salem, Riad

    2011-01-01

    Background & Aims It is not clear whether survival times of patients with hepatocellular carcinoma (HCC) are associated with their response to therapy. We analyzed the association between tumor response and survival times of patients with HCC who were treated with locoregional therapies (LRTs; chemoembolization and radioembolization). Methods Patients received LRTs over a 9-year period (n=463). Patients with metastases, portal venous thrombosis, or who had received transplants were excluded; 159 patients with Child-Pugh≤B7 were analyzed. Response (based on European Association for Study of the Liver [EASL] or World Health Organization [WHO] criteria) was associated with survival times using the landmark, risk-of-death, and Mantel-Byar methodologies. In a subanalysis, survival times of responders were compared to those of patients with stable disease (SD) and progressive disease (PD). Results Based on 6-month data, in landmark analysis, responders survived longer than nonresponders (based on EASL but not WHO criteria: P=0.002 and 0.0694). The risk of death was also lower for responders (based on EASL but not WHO criteria: P=0.0463 and 0.707). Landmark analysis of 12-month data showed that responders survived longer than nonresponders (P=<0.0001 and 0.004, based on EASL and WHO criteria, respectively). The risk of death was lower for responders (P=0.0132 and 0.010, based on EASL and WHO criteria, respectively). By the Mantel-Byar method, responders had longer survival than nonresponders, based on EASL criteria (P<0.0001; P=0.596 with WHO criteria). In the subanalysis, responders lived longer than patients with SD or PD. Conclusion Radiographic response to LRTs predicts survival time. EASL criteria for response more consistently predicted survival times than WHO criteria. The goal of LRT should be to achieve a radiologic response, rather than to stabilize disease. PMID:21664356

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

    SciTech Connect

    Seo, YoungSeok; Yoo, Seong Yul; Kim, Mi-Sook; Yang, Kwang Mo; Yoo, Hyung Jun; Kim, Jin Ho; Shin, Young-Joo; Kang, Jin Kyu; Lee, Kyung Hee; Lee, Eui Don; Rhu, Sang Young; Choi, Suck Chul; Kim, Moon Hong; Kim, Beob Jong; Kim, Min-Suk; Cho, Chul-Koo

    2011-03-01

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

  6. Reactive oxygen species–associated molecular signature predicts survival in patients with sepsis

    PubMed Central

    Zhou, Tong; Wang, Ting; Slepian, Marvin J.; Garcia, Joe G. N.; Hecker, Louise

    2016-01-01

    Abstract Sepsis-related multiple organ dysfunction syndrome is a leading cause of death in intensive care units. There is overwhelming evidence that oxidative stress plays a significant role in the pathogenesis of sepsis-associated multiple organ failure; however, reactive oxygen species (ROS)–associated biomarkers and/or diagnostics that define mortality or predict survival in sepsis are lacking. Lung or peripheral blood gene expression analysis has gained increasing recognition as a potential prognostic and/or diagnostic tool. The objective of this study was to identify ROS-associated biomarkers predictive of survival in patients with sepsis. In-silico analyses of expression profiles allowed the identification of a 21-gene ROS-associated molecular signature that predicts survival in sepsis patients. Importantly, this signature performed well in a validation cohort consisting of sepsis patients aggregated from distinct patient populations recruited from different sites. Our signature outperforms randomly generated signatures of the same signature gene size. Our findings further validate the critical role of ROSs in the pathogenesis of sepsis and provide a novel gene signature that predicts survival in sepsis patients. These results also highlight the utility of peripheral blood molecular signatures as biomarkers for predicting mortality risk in patients with sepsis, which could facilitate the development of personalized therapies. PMID:27252846

  7. The value of surrogate endpoints for predicting real-world survival across five cancer types.

    PubMed

    Shafrin, Jason; Brookmeyer, Ron; Peneva, Desi; Park, Jinhee; Zhang, Jie; Figlin, Robert A; Lakdawalla, Darius N

    2016-04-01

    Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints - progression-free survival (PFS) and time to progression (TTP) - to predict real-world OS across five cancers. Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan-Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991-2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R(2) from linear regressions. Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P = 0.026). Among all real-world patients using sample treatments (N = 309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P = 0.194). Results were qualitatively similar using median absolute prediction error and R(2) metrics. Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone. PMID:26743800

  8. Successful validation of a survival prediction model in patients with metastases in the spinal column

    SciTech Connect

    Chow, Edward . E-mail: Edward.Chow@sw.ca; Harris, Kristin; Fung, Kinwah

    2006-08-01

    Purpose: The Dutch Bone Metastases Study Group developed a survival prediction model in patients with symptomatic spinal bone metastases to guide the treating physician. The objective of this study was to validate the Dutch model and compare with our previously developed survival model at the Rapid Response Radiotherapy Program (RRRP model). Methods and Materials: The following prognostic factors were extracted from a prospective database in an outpatient palliative radiotherapy clinic: Karnofsky Performance Scores (KPS), primary cancer site, and visceral involvement for the Dutch model; primary cancer site, site of metastases, KPS, fatigue, appetite, and shortness of breath scores in the Edmonton Symptom Assessment Scale for the RRRP model. Patients were assigned scores according to each model. The survival probabilities were generated and calibration was performed for each model. Results: A total of 231 patients with spinal bone metastases from 1999 and 2002 were included in the analysis. The survival probabilities were similar to those in the original models. The calibration comparing actual survival with predicted survival from the Dutch and RRRP models gave R{sup 2} values of 0.90 and 0.86, respectively. Conclusion: The two models were successfully validated. The Dutch model using three clinical prognostic factors was easier to administer.

  9. Clinical Nomogram for Predicting Survival of Esophageal Cancer Patients after Esophagectomy

    PubMed Central

    Cao, Jinlin; Yuan, Ping; Wang, Luming; Wang, Yiqing; Ma, Honghai; Yuan, Xiaoshuai; Lv, Wang; Hu, Jian

    2016-01-01

    The aim of this study was to construct an effective clinical nomogram for predicting the survival of esophageal cancer patients after esophagectomy. We identified esophageal cancer patients (n = 4,281) who underwent esophagectomy between 1988 and 2007 from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Clinically significant parameters for survival were used to construct a nomogram based on Cox regression analyses. The model was validated using bootstrap resampling and a Chinese cohort (n = 145). A total of 4,109 patients from the SEER database were included for analysis. The multivariate analyses showed that the factors of age, race, histology, tumor site, tumor size, grade and depth of invasion, and the numbers of metastases and retrieved nodes were independent prognostic factors. All of these factors were selected into the nomogram. The nomogram showed a clear prognostic superiority over the seventh AJCC-TNM classification (C-index: SEER cohort, 0.716 vs 0.693, respectively; P < 0.01; Chinese cohort, 0.699 vs 0.680, respectively; P < 0.01). Calibration of the nomogram predicted the probabilities of 3- and 5-year survival, which corresponded closely with the actual survival rates. This novel prognostic model may improve clinicians’ abilities to predict individualized survival and to make treatment recommendations. PMID:27215834

  10. Does right ventricular function predict survival in patients with chronic obstructive lung disease?

    PubMed Central

    France, A J; Prescott, R J; Biernacki, W; Muir, A L; MacNee, W

    1988-01-01

    Non-invasive measurements of the right ventricular ejection fraction by radionuclide ventriculography were made in 115 patients with chronic obstructive lung disease. Survival was assessed over a mean period of 918 days. The right ventricular ejection fraction was reasonably normal in most patients (mean 0.42, range 0.10-0.66) but was lower in those with peripheral oedema, indicating cor pulmonale (mean 0.31 (SD 0.07); p less than 0.0001). Right ventricular ejection fraction was related to survival, but the relationship was weak (p = 0.03) by comparison with the association between the arterial oxygen and carbon dioxide tensions and survival (both p less than 0.0001). It is concluded that, although right ventricular function is predictive of survival in patients with chronic obstructive lung disease, it is probably a reflection of severity of disease and does not directly affect the prognosis. PMID:3175974

  11. Application of neural networks and sensitivity analysis to improved prediction of trauma survival.

    PubMed

    Hunter, A; Kennedy, L; Henry, J; Ferguson, I

    2000-05-01

    The performance of trauma departments is widely audited by applying predictive models that assess probability of survival, and examining the rate of unexpected survivals and deaths. Although the TRISS methodology, a logistic regression modelling technique, is still the de facto standard, it is known that neural network models perform better. A key issue when applying neural network models is the selection of input variables. This paper proposes a novel form of sensitivity analysis, which is simpler to apply than existing techniques, and can be used for both numeric and nominal input variables. The technique is applied to the audit survival problem, and used to analyse the TRISS variables. The conclusions discuss the implications for the design of further improved scoring schemes and predictive models. PMID:10699681

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

    PubMed Central

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

    2016-01-01

    Abstract 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. PMID:26886653

  13. Model to predict survival after surgical resection of intrahepatic cholangiocarcinoma: the Mayo Clinic experience

    PubMed Central

    Ali, Shahzad M; Clark, Clancy J; Mounajjed, Taofic; Wu, Tsung-Teh; Harmsen, William S; Reid-Lombardo, KMarie; Truty, Mark J; Kendrick, Michael L; Farnell, Michael B; Nagorney, David M; Que, Florencia G

    2015-01-01

    Background The 7th edition of the American Joint Committee on Cancer (AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma (ICC). The present study attempted to investigate the validity of these findings. Methods A single-centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan–Meier estimates and log-rank tests. Results A total of 150 patients underwent surgery, 126 (84%) of whom met the present study's inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow-up was 4.5 years. The median patient age was 58 years (range: 24–79 years). Median body mass index was 27 kg/m2 (range: 17–46 kg/m2). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes (P < 0.001). A negative resection margin was associated with improved survival (P < 0.001). Conclusions The AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC. PMID:25410716

  14. Extent of Resection of Glioblastoma Revisited: Personalized Survival Modeling Facilitates More Accurate Survival Prediction and Supports a Maximum-Safe-Resection Approach to Surgery

    PubMed Central

    Marko, Nicholas F.; Weil, Robert J.; Schroeder, Jason L.; Lang, Frederick F.; Suki, Dima; Sawaya, Raymond E.

    2014-01-01

    Purpose Approximately 12,000 glioblastomas are diagnosed annually in the United States. The median survival rate for this disease is 12 months, but individual survival rates can vary with patient-specific factors, including extent of surgical resection (EOR). The goal of our investigation is to develop a reliable strategy for personalized survival prediction and for quantifying the relationship between survival, EOR, and adjuvant chemoradiotherapy. Patients and Methods We used accelerated failure time (AFT) modeling using data from 721 newly diagnosed patients with glioblastoma (from 1993 to 2010) to model the factors affecting individualized survival after surgical resection, and we used the model to construct probabilistic, patient-specific tools for survival prediction. We validated this model with independent data from 109 patients from a second institution. Results AFT modeling using age, Karnofsky performance score, EOR, and adjuvant chemoradiotherapy produced a continuous, nonlinear, multivariable survival model for glioblastoma. The median personalized predictive error was 4.37 months, representing a more than 20% improvement over current methods. Subsequent model-based calculations yield patient-specific predictions of the incremental effects of EOR and adjuvant therapy on survival. Conclusion Nonlinear, multivariable AFT modeling outperforms current methods for estimating individual survival after glioblastoma resection. The model produces personalized survival curves and quantifies the relationship between variables modulating patient-specific survival. This approach provides comprehensive, personalized, probabilistic, and clinically relevant information regarding the anticipated course of disease, the overall prognosis, and the patient-specific influence of EOR and adjuvant chemoradiotherapy. The continuous, nonlinear relationship identified between expected median survival and EOR argues against a surgical management strategy based on rigid EOR

  15. Predicting post-treatment survivability of patients with breast cancer using Artificial Neural Network methods.

    PubMed

    Wang, Tan-Nai; Cheng, Chung-Hao; Chiu, Hung-Wen

    2013-01-01

    In the last decade, the use of data mining techniques has become widely accepted in medical applications, especially in predicting cancer patients' survival. In this study, we attempted to train an Artificial Neural Network (ANN) to predict the patients' five-year survivability. Breast cancer patients who were diagnosed and received standard treatment in one hospital during 2000 to 2003 in Taiwan were collected for train and test the ANN. There were 604 patients in this dataset excluding died not in breast cancer. Among them 140 patients died within five years after their first radiotherapy treatment. The artificial neural networks were created by STATISTICA(®) software. Five variables (age, surgery and radiotherapy type, tumor size, regional lymph nodes, distant metastasis) were selected as the input features for ANN to predict the five-year survivability of breast cancer patients. We trained 100 artificial neural networks and chose the best one to analyze. The accuracy rate is 85% and area under the receiver operating characteristic (ROC) curve is 0.79. It shows that artificial neural network is a good tool to predict the five-year survivability of breast cancer patients. PMID:24109931

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

    PubMed Central

    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. PMID:26379761

  17. High Pretreatment D-Dimer Levels Correlate with Adverse Clinical Features and Predict Poor Survival in Patients with Natural Killer/T-Cell Lymphoma

    PubMed Central

    Sun, Peng; Yan, Shu-mei; Liu, Pan-pan; Li, Zhi-ming; Jiang, Wen-qi

    2016-01-01

    Pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The aim of this study was to evaluate the prognostic value of D-dimer levels in patients with newly diagnosed natural killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival was set as 1.2 μg/mL based on the receiver operating curve analysis. Patients with a D-dimer level ≥ 1.2 μg/mL had significantly more adverse clinical features, including poor performance status, advanced stage diseases, B symptoms, elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes, more extranodal diseases, and higher International Prognostic Index and natural killer/T-cell lymphoma prognostic index scores. A D-dimer level ≥ 1.2 μg/mL was significantly associated with inferior 3-year overall survival (OS, 13.0 vs. 68.5%, P < 0.001). In the multivariate analysis, a D-dimer level ≥ 1.2 μg/mL remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47–6.68, P = 0.003) after adjusting for other confounding prognostic factors. Among patients with Ann Arbor stage I-II diseases, those with a D-dimer level ≥ 1.2 μg/mL had a significantly worse survival than those with a D-dimer level < 1.2 μg/mL (3 year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high D-dimer level was similar to that of the advanced-stage patients. In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in patients with NKTCL. PMID:27032016

  18. Socioeconomic and Other Demographic Disparities Predicting Survival among Head and Neck Cancer Patients

    PubMed Central

    Choi, Seung Hee; Terrell, Jeffrey E.; Fowler, Karen E.; McLean, Scott A.; Ghanem, Tamer; Wolf, Gregory T.; Bradford, Carol R.; Taylor, Jeremy; Duffy, Sonia A.

    2016-01-01

    Background The Institute of Medicine (IOM) report, “Unequal Treatment,” which defines disparities as racially based, indicates that disparities in cancer diagnosis and treatment are less clear. While a number of studies have acknowledged cancer disparities, they have limitations of retrospective nature, small sample sizes, inability to control for covariates, and measurement errors. Objective The purpose of this study was to examine disparities as predictors of survival among newly diagnosed head and neck cancer patients recruited from 3 hospitals in Michigan, USA, while controlling for a number of covariates (health behaviors, medical comorbidities, and treatment modality). Methods Longitudinal data were collected from newly diagnosed head and neck cancer patients (N = 634). The independent variables were median household income, education, race, age, sex, and marital status. The outcome variables were overall, cancer-specific, and disease-free survival censored at 5 years. Kaplan-Meier curves and univariate and multivariate Cox proportional hazards models were performed to examine demographic disparities in relation to survival. Results Five-year overall, cancer-specific, and disease-free survival were 65.4% (407/622), 76.4% (487/622), and 67.0% (427/622), respectively. Lower income (HR, 1.5; 95% CI, 1.1–2.0 for overall survival; HR, 1.4; 95% CI, 1.0–1.9 for cancer-specific survival), high school education or less (HR, 1.4; 95% CI, 1.1–1.9 for overall survival; HR, 1.4; 95% CI, 1.1–1.9 for cancer-specific survival), and older age in decades (HR, 1.4; 95% CI, 1.2–1.7 for overall survival; HR, 1.2; 95% CI, 1.1–1.4 for cancer-specific survival) decreased both overall and disease-free survival rates. A high school education or less (HR, 1.4; 95% CI, 1.0–2.1) and advanced age (HR, 1.3; 95% CI, 1.1–1.6) were significant independent predictors of poor cancer-specific survival. Conclusion Low income, low education, and advanced age predicted poor

  19. Bilateral inferior turbinate osteoma.

    PubMed

    Sahemey, R; Warfield, A T; Ahmed, S

    2016-01-01

    Osteomas are the most common benign osteoclastic tumours of the paranasal sinuses. However, nasal cavity and turbinate osteomas are extremely rare. Only nine middle turbinate, three inferior turbinate and one inferior turbinate osteoma cases have been reported to date. The present case report describes the management and follow-up of symptomatic bilateral inferior turbinate osteoma.A 60-year-old female presented with symptoms of bilateral nasal obstruction and right-sided epiphora. Radiological investigation found hypertrophic bony changes involving both inferior turbinates. The patient was managed successfully by endoscopic inferior turbinectomies in order to achieve a patent airway, with no further recurrence of tumour after 3 months postoperatively.To the best of our knowledge, this is the first reported case of bilateral inferior turbinate osteoma. We describe a safe and minimally invasive method of tumour resection, which has a better cosmetic outcome compared with other approaches. PMID:27534890

  20. Lung Cancer Survival Prediction using Ensemble Data Mining on Seer Data

    DOE PAGESBeta

    Agrawal, Ankit; Misra, Sanchit; Narayanan, Ramanathan; Polepeddi, Lalith; Choudhary, Alok

    2012-01-01

    We analyze the lung cancer data available from the SEER program with the aim of developing accurate survival prediction models for lung cancer. Carefully designed preprocessing steps resulted in removal/modification/splitting of several attributes, and 2 of the 11 derived attributes were found to have significant predictive power. Several supervised classification methods were used on the preprocessed data along with various data mining optimizations and validations. In our experiments, ensemble voting of five decision tree based classifiers and meta-classifiers was found to result in the best prediction performance in terms of accuracy and area under the ROC curve. We have developedmore » an on-line lung cancer outcome calculator for estimating the risk of mortality after 6 months, 9 months, 1 year, 2 year and 5 years of diagnosis, for which a smaller non-redundant subset of 13 attributes was carefully selected using attribute selection techniques, while trying to retain the predictive power of the original set of attributes. Further, ensemble voting models were also created for predicting conditional survival outcome for lung cancer (estimating risk of mortality after 5 years of diagnosis, given that the patient has already survived for a period of time), and included in the calculator. The on-line lung cancer outcome calculator developed as a result of this study is available at http://info.eecs.northwestern.edu:8080/LungCancerOutcomeCalculator/.« less

  1. Epithelial–mesenchymal transition-associated secretory phenotype predicts survival in lung cancer patients

    PubMed Central

    Reka, Ajaya Kumar; Chen, Guoan; Keshamouni, Venkateshwar G.

    2014-01-01

    In cancer cells, the process of epithelial–mesenchymal transition (EMT) confers migratory and invasive capacity, resistance to apoptosis, drug resistance, evasion of host immune surveillance and tumor stem cell traits. Cells undergoing EMT may represent tumor cells with metastatic potential. Characterizing the EMT secretome may identify biomarkers to monitor EMT in tumor progression and provide a prognostic signature to predict patient survival. Utilizing a transforming growth factor-β-induced cell culture model of EMT, we quantitatively profiled differentially secreted proteins, by GeLC-tandem mass spectrometry. Integrating with the corresponding transcriptome, we derived an EMT-associated secretory phenotype (EASP) comprising of proteins that were differentially upregulated both at protein and mRNA levels. Four independent primary tumor-derived gene expression data sets of lung cancers were used for survival analysis by the random survival forests (RSF) method. Analysis of 97-gene EASP expression in human lung adenocarcinoma tumors revealed strong positive correlations with lymph node metastasis, advanced tumor stage and histological grade. RSF analysis built on a training set (n = 442), including age, sex and stage as variables, stratified three independent lung cancer data sets into low-, medium- and high-risk groups with significant differences in overall survival. We further refined EASP to a 20 gene signature (rEASP) based on variable importance scores from RSF analysis. Similar to EASP, rEASP predicted survival of both adenocarcinoma and squamous carcinoma patients. More importantly, it predicted survival in the early-stage cancers. These results demonstrate that integrative analysis of the critical biological process of EMT provides mechanism-based and clinically relevant biomarkers with significant prognostic value. PMID:24510113

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

    USGS Publications Warehouse

    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.

  3. Development of a Summarized Health Index (SHI) for Use in Predicting Survival in Sea Turtles

    PubMed Central

    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 < 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. PMID:25803431

  4. Body Condition Indices Predict Reproductive Success but Not Survival in a Sedentary, Tropical Bird

    PubMed Central

    Milenkaya, Olga; Catlin, Daniel H.; Legge, Sarah; Walters, Jeffrey R.

    2015-01-01

    Body condition may predict individual fitness because those in better condition have more resources to allocate towards improving their fitness. However, the hypothesis that condition indices are meaningful proxies for fitness has been questioned. Here, we ask if intraspecific variation in condition indices predicts annual reproductive success and survival. We monitored a population of Neochmia phaeton (crimson finch), a sedentary, tropical passerine, for reproductive success and survival over four breeding seasons, and sampled them for commonly used condition indices: mass adjusted for body size, muscle and fat scores, packed cell volume, hemoglobin concentration, total plasma protein, and heterophil to lymphocyte ratio. Our study population is well suited for this research because individuals forage in common areas and do not hold territories such that variation in condition between individuals is not confounded by differences in habitat quality. Furthermore, we controlled for factors that are known to impact condition indices in our study population (e.g., breeding stage) such that we assessed individual condition relative to others in the same context. Condition indices that reflect energy reserves predicted both the probability of an individual fledging young and the number of young produced that survived to independence, but only during some years. Those that were relatively heavy for their body size produced about three times more independent young compared to light individuals. That energy reserves are a meaningful predictor of reproductive success in a sedentary passerine supports the idea that energy reserves are at least sometimes predictors of fitness. However, hematological indices failed to predict reproductive success and none of the indices predicted survival. Therefore, some but not all condition indices may be informative, but because we found that most indices did not predict any component of fitness, we question the ubiquitous interpretation of

  5. Immunoprofile-based subgrouping of urothelial bladder carcinomas for survival prediction.

    PubMed

    Kim, Kyungeun; Sung, Chang Ohk; Park, Bong-Hee; Ku, Ja Yoon; Go, Heounjeong; Ro, Jae Y; Kim, Jiyoon; Cho, Yong Mee

    2015-10-01

    One of the major challenges in bladder cancer management is in distinguishing aggressive from indolent tumors with similar clinicopathological factors, especially in cases of high-grade T1 stage tumors. To define a set of prognostic factors that can be easily assessed in clinical practice with a high cost-effectiveness, the expressions of 11 proteins were examined immunohistochemically in 403 cases of transurethral resection of bladder tumors, then correlated to clinical outcomes. Based on the protein immunoprofiles, urothelial carcinomas were divided into 4 intrinsic molecular subgroups with different clinical outcomes: subgroups 1 and 4 with the poorest survival, subgroup 2 with the best survival, and subgroup 3 with the intermediate survival outcome. The protein expression patterns of the 4 subgroups were mutually exclusive: overexpression of p53, EZH2, E2F1, and IMP3 and high Ki-67 proliferation index in subgroup 1; overexpression of cytoplasmic survivin in subgroup 4; overexpression of membranous TSP1 and cytoplasmic p27 in subgroup 2; and no representative protein overexpression in subgroup 3. Using these protein immunoprofiles, 3 risk groups were generated, which predicted disease-specific survival not only in total bladder carcinoma cases with 0.737 of predictive accuracy but also in high-grade stage T1 tumors with 0.658 of predictive accuracy. These results showed that urothelial carcinomas were composed of 4 clinically relevant molecular subgroups based on protein expression and that overall survival of those patients could be predicted using a set of a small number of protein expressions not only in total cases but also in high-grade stage T1 tumors. PMID:26232864

  6. HSP70 mediates survival in apoptotic cells—Boolean network prediction and experimental validation

    PubMed Central

    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. PMID:26379495

  7. Surprise Questions for Survival Prediction in Patients With Advanced Cancer: A Multicenter Prospective Cohort Study

    PubMed Central

    Hamano, Jun; Morita, Tatsuya; Inoue, Satoshi; Ikenaga, Masayuki; Matsumoto, Yoshihisa; Sekine, Ryuichi; Yamaguchi, Takashi; Hirohashi, Takeshi; Tajima, Tsukasa; Tatara, Ryohei; Watanabe, Hiroaki; Otani, Hiroyuki; Takigawa, Chizuko; Matsuda, Yoshinobu; Nagaoka, Hiroka; Mori, Masanori; Yamamoto, Naoki; Shimizu, Mie; Sasara, Takeshi

    2015-01-01

    Background. Predicting the short-term survival in cancer patients is an important issue for patients, family, and oncologists. Although the prognostic accuracy of the surprise question has value in 1-year mortality for cancer patients, the prognostic value for short-term survival has not been formally assessed. The primary aim of the present study was to assess the prognostic value of the surprise question for 7-day and 30-day survival in patients with advanced cancer. Patients and Methods. The present multicenter prospective cohort study was conducted in Japan from September 2012 through April 2014, involving 16 palliative care units, 19 hospital-based palliative care teams, and 23 home-based palliative care services. Results. We recruited 2,425 patients and included 2,361 for analysis: 912 from hospital-based palliative care teams, 895 from hospital palliative care units, and 554 from home-based palliative care services. The sensitivity, specificity, positive predictive value, and negative predictive value of the 7-day survival surprise question were 84.7% (95% confidence interval [CI], 80.7%–88.0%), 68.0% (95% CI, 67.3%–68.5%), 30.3% (95% CI, 28.9%–31.5%), and 96.4% (95% CI, 95.5%–97.2%), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the 30-day surprise question were 95.6% (95% CI, 94.4%–96.6%), 37.0% (95% CI, 35.9%–37.9%), 57.6% (95% CI, 56.8%–58.2%), and 90.4% (95% CI, 87.7%–92.6%), respectively. Conclusion. Surprise questions are useful for screening patients for short survival. However, the high false-positive rates do not allow clinicians to provide definitive prognosis prediction. Implications for Practice: The findings of this study indicate that clinicians can screen patients for 7- or 30-day survival using surprise questions with 90% or more sensitivity. Clinicians cannot provide accurate prognosis estimation, and all patients will not always die within the defined periods. The

  8. Imbalanced learning for clinical survival group prediction of brain tumor patients

    NASA Astrophysics Data System (ADS)

    Zhou, Mu; Hall, Lawrence O.; Goldgof, Dmitry B.; Gillies, Robert J.; Gatenby, Robert A.

    2015-03-01

    Accurate computer-aided prediction of survival time for brain tumor patients requires a thorough understanding of clinical data, since it provides useful prior knowledge for learning models. However, to simplify the learning process, traditional settings often assume datasets with equally distributed classes, which clearly does not reflect a typical distribution. In this paper, we investigate the problem of mining knowledge from an imbalanced dataset (i.e., a skewed distribution) to predict survival time. In particular, we propose an algorithmic framework to predict survival groups of brain tumor patients using multi-modality MRI data. Both an imbalanced distribution and classifier design are jointly considered: 1) We used the Synthetic Minority Over-sampling Technique to compensate for the imbalanced distribution; 2) A predictive linear regression model was adopted to learn a pair of class-specific dictionaries, which were derived from reformulated balanced data. We tested the proposed framework using a dataset of 42 patients with Glioblastoma Multiforme (GBM) tumors whose scans were obtained from the cancer genome atlas (TCGA). Experimental results showed that the proposed method achieved 95.24% accuracy.

  9. Network regularised Cox regression and multiplex network models to predict disease comorbidities and survival of cancer.

    PubMed

    Xu, Haoming; Moni, Mohammad Ali; Liò, Pietro

    2015-12-01

    In cancer genomics, gene expression levels provide important molecular signatures for all types of cancer, and this could be very useful for predicting the survival of cancer patients. However, the main challenge of gene expression data analysis is high dimensionality, and microarray is characterised by few number of samples with large number of genes. To overcome this problem, a variety of penalised Cox proportional hazard models have been proposed. We introduce a novel network regularised Cox proportional hazard model and a novel multiplex network model to measure the disease comorbidities and to predict survival of the cancer patient. Our methods are applied to analyse seven microarray cancer gene expression datasets: breast cancer, ovarian cancer, lung cancer, liver cancer, renal cancer and osteosarcoma. Firstly, we applied a principal component analysis to reduce the dimensionality of original gene expression data. Secondly, we applied a network regularised Cox regression model on the reduced gene expression datasets. By using normalised mutual information method and multiplex network model, we predict the comorbidities for the liver cancer based on the integration of diverse set of omics and clinical data, and we find the diseasome associations (disease-gene association) among different cancers based on the identified common significant genes. Finally, we evaluated the precision of the approach with respect to the accuracy of survival prediction using ROC curves. We report that colon cancer, liver cancer and renal cancer share the CXCL5 gene, and breast cancer, ovarian cancer and renal cancer share the CCND2 gene. Our methods are useful to predict survival of the patient and disease comorbidities more accurately and helpful for improvement of the care of patients with comorbidity. Software in Matlab and R is available on our GitHub page: https://github.com/ssnhcom/NetworkRegularisedCox.git. PMID:26611766

  10. Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients With Primary Ovarian Serous Carcinoma

    PubMed Central

    Gillet, Jean-Pierre; Calcagno, Anna Maria; Varma, Sudhir; Davidson, Ben; Bunkholt Elstrand, Mari; Ganapathi, Ram; Kamat, Aparna A.; Sood, Anil K.; Ambudkar, Suresh V.; Seiden, Michael V.; Rueda, Bo R.; Gottesman, Michael M.

    2012-01-01

    Purpose This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. Experimental Design We applied a customized TaqMan Low Density Array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes. Results Leave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (P=0.06), four covariates (age, stage, CA125 level and surgical debulking) do (P=0.03). When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in overall survival prediction (log-rank statistic P<0.003). The predictive power of this 11-gene signature was confirmed by dividing high and low risk patient groups, as defined by their clinical covariates, into four specific risk groups based on expression levels. Conclusion This study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin- and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer. PMID:22492981

  11. Prediction of survival in glioma patients by means of positron emission tomography

    SciTech Connect

    Patronas, N.J.; Di Chiro, G.; Kufta, C.; Bairamian, D.; Kornblith, P.L.; Simon, R.; Larson, S.M.

    1985-06-01

    The aim of this study was to determine whether positron emission tomography (PET) with fluorine-18 (18F)-2-deoxyglucose (FDG) can be used as a prognostic test in patients with high-grade cerebral gliomas, regardless of the treatment given. Forty-five patients with astrocytoma Grade III or IV were included in this analysis. The mean survival time of patients with tumors exhibiting high glucose utilization as determined by PET-FDG was 5 months, whereas patients with gliomas showing lower glucose utilization had a mean survival period of 19 months. It is postulated that PET-FDG scans reflect the biological behavior of high-grade astrocytomas and may be used to predict the survival time of patients harboring such neoplasms.

  12. Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients

    PubMed Central

    Muffly, Lori S.; Kocherginsky, Masha; Stock, Wendy; Chu, Quynh; Bishop, Michael R.; Godley, Lucy A.; Kline, Justin; Liu, Hongtao; Odenike, Olatoyosi M.; Larson, Richard A.; van Besien, Koen; Artz, Andrew S.

    2014-01-01

    Allogeneic hematopoietic cell transplantation is increasingly utilized in older adults. This study prospectively evaluated the prognostic utility of geriatric assessment domains prior to allogeneic transplantation in recipients aged 50 years and over. Geriatric assessment was performed prior to transplant, and included validated measures across domains of function and disability, comorbidity, frailty, mental health, nutritional status, and systemic inflammation. A total of 203 patients completed geriatric assessment and underwent transplant. Median age was 58 years (range 50–73). After adjusting for established prognostic factors, limitations in instrumental activities of daily living (HR 2.38, 95%CI: 1.59–3.56; P<0.001), slow walk speed (HR 1.80, 95%CI: 1.14–2.83; P=0.01), high comorbidity by hematopoietic cell transplantation-specific comorbidity index (HR 1.56, 95%CI: 1.07–2.28; P=0.02), low mental health by short-form-36 mental component summary (HR 1.67, 95%CI: 1.13–2.48; P=0.01), and elevated serum C-reactive protein (HR 2.51, 95%CI: 1.54–4.09; P<0.001) were significantly associated with inferior overall survival. These associations were more pronounced in the cohort 60 years and over. Geriatric assessment measures confer independent prognostic utility in older allogeneic transplant recipients. Implementation of geriatric assessment prior to allogeneic transplantation may aid appropriate selection of older adults. PMID:24816237

  13. DNA methyltransferase 3a rs1550117 genetic polymorphism predicts poor survival in gastric cancer patients

    PubMed Central

    Wang, Chuan; Jia, Zhifang; Ma, Hongxi; Cao, Donghui; Wu, Xing; Wen, Simin; You, Lili; Cao, Xueyuan; Jiang, Jing

    2015-01-01

    DNA methyltransferase 3a (DNMT3a) have been suggested to play a crucial role in human cancer prognosis. Single nucleotide polymorphisms (SNPs) in DNMT3a genes may have an impact on the prognosis of cancers. This study aimed to investigate the association between SNPs of DNMT3a gene and prognosis of gastric cancer (GC). Two sites of DNMT3a SNPs, rs1550117 and rs13420827 were selected and genotyped using TaqMan assay in 447 GC patients who received gastrectomy. Effects of genotypes on clinical outcomes of GC were calculated by Kaplan-Meier survival analysis and Cox regression model. We found that the AG or AA genotype of rs1550117 was associated with significantly poorer survival and increased death risk of GC compared with GG genotype (dominant model: HR=1.35, 95% CI=1.01-1.80, P=0.043). Further multivariate Cox regression analysis revealed that in addition to the known factors including male, larger tumor sizes and high clinical stage, rs1550117 variant was an independently predictive factor for survival in GC patients. No significant association was found between rs13420827 genetic variants and GC prognosis. Our findings first demonstrated that DNMT3a rs1550117 polymorphism may be a potential biomarker in predicting overall survival of GC patients. PMID:26823816

  14. Nestling telomere shortening, but not telomere length, reflects developmental stress and predicts survival in wild birds

    PubMed Central

    Boonekamp, Jelle J.; Mulder, G. A.; Salomons, H. Martijn; Dijkstra, Cor; Verhulst, Simon

    2014-01-01

    Developmental stressors often have long-term fitness consequences, but linking offspring traits to fitness prospects has remained a challenge. Telomere length predicts mortality in adult birds, and may provide a link between developmental conditions and fitness prospects. Here, we examine the effects of manipulated brood size on growth, telomere dynamics and post-fledging survival in free-living jackdaws. Nestlings in enlarged broods achieved lower mass and lost 21% more telomere repeats relative to nestlings in reduced broods, showing that developmental stress accelerates telomere shortening. Adult telomere length was positively correlated with their telomere length as nestling (r = 0.83). Thus, an advantage of long telomeres in nestlings is carried through to adulthood. Nestling telomere shortening predicted post-fledging survival and recruitment independent of manipulation and fledgling mass. This effect was strong, with a threefold difference in recruitment probability over the telomere shortening range. By contrast, absolute telomere length was neither affected by brood size manipulation nor related to survival. We conclude that telomere loss, but not absolute telomere length, links developmental conditions to subsequent survival and suggest that telomere shortening may provide a key to unravelling the physiological causes of developmental effects on fitness. PMID:24789893

  15. The Geriatric Nutritional Risk Index Predicts Survival in Elderly Esophageal Squamous Cell Carcinoma Patients with Radiotherapy

    PubMed Central

    Wang, Kunlun; Liu, Yang; You, Jie; Cui, Han; Zhu, Yiwei; Yuan, Ling

    2016-01-01

    The impact of nutritional status on survival among elderly esophageal squamous cell carcinoma (ESCC) patients undergoing radiotherapy is unclear. In this study, we aimed at validating the performance of the geriatric nutritional risk index (GNRI) in predicting overall survival time in elderly ESCC patients with radiotherapy. A retrospective cohort study was conducted on 239 ESCC patients aged 60 and over admitted consecutively from January 2008 to November 2014 in the Department of Radiotherapy, Henan Tumor Hospital (Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan, China. All patients were subjected to nutritional screening using GNRI, and were followed for the occurrence of lymphatic node metastasis, radiation complication and mortality. The Kaplan–Meier method with Log-rank test was used to estimate survival curves. Univariable Cox regression analysis was used to identify variables associated with overall survival time. Among the 239 patients, 184 patients (76.9%) took no nutritional risk, 32 patients (13.4%) took moderate risk of malnutrition, and 23 patients (9.7%) took a high risk of malnutrition. Univariable Cox regression showed that both high nutritional risk group and moderate nutritional risk group were significantly less likely to survive than no nutritional risk patients (hazard ratio (HR) = 1.688, 95% confidence interval (CI) = 1.019–2.798 for moderate risk group, and HR = 2.699, 95% CI = 1.512–4.819 for high risk group, respectively). The GNRI is an independent prognostic factor for overall survival time in elderly ESCC patients with radiotherapy. A GNRI ≤98 can be suggested as an indicator of surviving less. PMID:27196126

  16. Glycated Albumin Predicts Long-term Survival in Patients Undergoing Hemodialysis

    PubMed Central

    Lu, Chien-Lin; Ma, Wen-Ya; Lin, Yuh-Feng; Shyu, Jia-Fwu; Wang, Yuan-Hung; Liu, Yueh-Min; Wu, Chia-Chao; Lu, Kuo-Cheng

    2016-01-01

    Background: In patients with advanced renal dysfunction undergoing maintenance hemodialysis, glycated albumin (GA) levels may be more representative of blood glucose levels than hemoglobin A1C levels. The aim of this study was to determine the predictive power of GA levels on long-term survival in hemodialysis patients. Methods: A total of 176 patients with a mean age of 68.2 years were enrolled. The median duration of follow-up was 51.0 months. Receiver-operating characteristic curve analysis was utilized to determine the optimal cutoff value. We examined the cumulative survival rate by Kaplan-Meier estimates and the influence of known survival factors with the multivariate Cox proportional-hazard regression model. Results: In the whole patient group, cumulative survival in the low GA group was better than in the high GA group (p=0.030), with more prominence in those aged <70 years (p=0.029). In subgroup analysis, both diabetic (DM) and non-DM patients with low GA had a better cumulative survival compared with those with high GA. The risk of mortality increased by 3.0% for each 1% increase in serum GA level in all patients undergoing hemodialysis. Conclusions: In addition to serving as a glycemic control marker, GA levels may be useful for evaluating the risk of death in both DM and non-DM patients on hemodialysis. PMID:27226780

  17. Artificial neural networks for diagnosis and survival prediction in colon cancer

    PubMed Central

    Ahmed, Farid E

    2005-01-01

    ANNs are nonlinear regression computational devices that have been used for over 45 years in classification and survival prediction in several biomedical systems, including colon cancer. Described in this article is the theory behind the three-layer free forward artificial neural networks with backpropagation error, which is widely used in biomedical fields, and a methodological approach to its application for cancer research, as exemplified by colon cancer. Review of the literature shows that applications of these networks have improved the accuracy of colon cancer classification and survival prediction when compared to other statistical or clinicopathological methods. Accuracy, however, must be exercised when designing, using and publishing biomedical results employing machine-learning devices such as ANNs in worldwide literature in order to enhance confidence in the quality and reliability of reported data. PMID:16083507

  18. Reduction in predicted survival times in cold water due to wind and waves.

    PubMed

    Power, Jonathan; Simões Ré, António; Barwood, Martin; Tikuisis, Peter; Tipton, Michael

    2015-07-01

    Recent marine accidents have called into question the level of protection provided by immersion suits in real (harsh) life situations. Two immersion suit studies, one dry and the other with 500 mL of water underneath the suit, were conducted in cold water with 10-12 males in each to test body heat loss under three environmental conditions: calm, as mandated for immersion suit certification, and two combinations of wind plus waves to simulate conditions typically found offshore. In both studies mean skin heat loss was higher in wind and waves vs. calm; deep body temperature and oxygen consumption were not different. Mean survival time predictions exceeded 36 h for all conditions in the first study but were markedly less in the second in both calm and wind and waves. Immersion suit protection and consequential predicted survival times under realistic environmental conditions and with leakage are reduced relative to calm conditions. PMID:25766418

  19. Predicting the clonogenic survival of A549 cells after modulated x-ray irradiation using the linear quadratic model

    NASA Astrophysics Data System (ADS)

    Bromley, Regina; Oliver, Lyn; Davey, Ross; Harvie, Rozelle; Baldock, Clive

    2009-01-01

    In this study we present two prediction methods, mean dose and summed dose, for predicting the number of A549 cells that will survive after modulated x-ray irradiation. The prediction methods incorporate the dose profile from the modulated x-ray fluence map applied across the cell sample and the linear quadratic (LQ) model. We investigated the clonogenic survival of A549 cells when irradiated using two different modulated x-ray fluence maps. Differences between the measured and predicted surviving fraction were observed for modulated x-ray irradiation. When the x-ray fluence map produced a steep dose gradient across the sample, fewer cells survived in the unirradiated region than expected. When the x-ray fluence map produced a less steep dose gradient across the sample, more cells survived in the unirradiated region than expected. Regardless of the steepness of the dose gradient, more cells survived in the irradiated region than expected for the reference dose range of 1-10 Gy. The change in the cell survival for the unirradiated regions of the two different dose gradients may be an important factor to consider when predicting the number of cells that will survive at the edge of modulated x-ray fields. This investigation provides an improved method of predicting cell survival for modulated x-ray radiation treatment. It highlights the limitations of the LQ model, particularly in its ability to describe the biological response of cells irradiated under these conditions.

  20. Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival

    PubMed Central

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

    2015-01-01

    Hepatocellular carcinoma (HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year, it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients, however, there is a high risk of recurrence in postoperative HCC. In clinical practice, there exists an urgent need for valid prognostic markers to identify patients with prognosis, hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients. PMID:25624992

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

    PubMed

    Kaneko, Shuhei; Hirakawa, Akihiro; Hamada, Chikuma

    2015-01-01

    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. PMID:26146513

  2. Transcriptome sequencing uncovers a three-long noncoding RNA signature in predicting breast cancer survival.

    PubMed

    Guo, Wenna; Wang, Qiang; Zhan, Yueping; Chen, Xijia; Yu, Qi; Zhang, Jiawei; Wang, Yi; Xu, Xin-Jian; Zhu, Liucun

    2016-01-01

    Long noncoding RNAs (lncRNAs) play a crucial role in tumorigenesis. The aim of this study is to identify lncRNA signature that can predict breast cancer patient survival. RNA expression data from 1064 patients were downloaded from The Cancer Genome Atlas project. Cox regression, Kaplan-Meier, and receiver operating characteristic (ROC) analyses were performed to construct a model for predicting the overall survival (OS) of patients and evaluate it. A model consisting of three lncRNA genes (CAT104, LINC01234, and STXBP5-AS1) was identified. The Kaplan-Meier analysis and ROC curves proved that the model could predict the prognostic survival with good sensitivity and specificity in both the validation set (AUC = 0.752, 95% confidence intervals (CI): 0.651-0.854) and the microarray dataset (AUC = 0.714, 95%CI: 0.615-0.814). Further study showed the three-lncRNA signature was not only pervasive in different breast cancer stages, subtypes and age groups, but also provides more accurate prognostic information than some widely known biomarkers. The results suggested that RNA-seq transcriptome profiling provides that the three-lncRNA signature is an independent prognostic biomarker, and have clinical significance. In addition, lncRNA, miRNA, and mRNA interaction network indicated lncRNAs may intervene in breast cancer pathogenesis by binding to miR-190b, acting as competing endogenous RNAs. PMID:27338266

  3. Transcriptome sequencing uncovers a three–long noncoding RNA signature in predicting breast cancer survival

    PubMed Central

    Guo, Wenna; Wang, Qiang; Zhan, Yueping; Chen, Xijia; Yu, Qi; Zhang, Jiawei; Wang, Yi; Xu, Xin-jian; Zhu, Liucun

    2016-01-01

    Long noncoding RNAs (lncRNAs) play a crucial role in tumorigenesis. The aim of this study is to identify lncRNA signature that can predict breast cancer patient survival. RNA expression data from 1064 patients were downloaded from The Cancer Genome Atlas project. Cox regression, Kaplan–Meier, and receiver operating characteristic (ROC) analyses were performed to construct a model for predicting the overall survival (OS) of patients and evaluate it. A model consisting of three lncRNA genes (CAT104, LINC01234, and STXBP5-AS1) was identified. The Kaplan–Meier analysis and ROC curves proved that the model could predict the prognostic survival with good sensitivity and specificity in both the validation set (AUC = 0.752, 95% confidence intervals (CI): 0.651–0.854) and the microarray dataset (AUC = 0.714, 95%CI: 0.615–0.814). Further study showed the three-lncRNA signature was not only pervasive in different breast cancer stages, subtypes and age groups, but also provides more accurate prognostic information than some widely known biomarkers. The results suggested that RNA-seq transcriptome profiling provides that the three-lncRNA signature is an independent prognostic biomarker, and have clinical significance. In addition, lncRNA, miRNA, and mRNA interaction network indicated lncRNAs may intervene in breast cancer pathogenesis by binding to miR-190b, acting as competing endogenous RNAs. PMID:27338266

  4. A new approach: role of data mining in prediction of survival of burn patients.

    PubMed

    Patil, Bankat Madhavrao; Joshi, Ramesh C; Toshniwal, Durga; Biradar, Siddeshwar

    2011-12-01

    The prediction of burn patient survivability is a difficult problem to investigate till present times. In present study a prediction Model for patients with burns was built, and its capability to accurately predict the survivability was assessed. We have compared different data mining techniques to asses the performance of various algorithms based on the different measures used in the analysis of information pertaining to medical domain. Obtained results were evaluated for correctness with the help of registered medical practitioners. The dataset was collected from SRT (Swami Ramanand Tirth) Hospital in India, which is one of the Asia's largest rural hospitals. Dataset contains records of 180 patients mainly suffering from burn injuries collected during period from the year 2002 to 2006. Features contain patients' age, sex and percentage of burn received for eight different parts of the body. Prediction models have been developed through rigorous comparative study of important and relevant data mining classification techniques namely, navie bayes, decision tree, support vector machine and back propagation. Performance comparison was also carried out for measuring unbiased estimate of the prediction models using 10-fold cross-validation method. Using the analysis of obtained results, we show that Navie bayes is the best predictor with an accuracy of 97.78% on the holdout samples, further, both the decision tree and support vector machine (SVM) techniques demonstrated an accuracy of 96.12%, and back propagation technique resulted in achieving accuracy of 95%. PMID:20703764

  5. The Value of Serum NR2 Antibody in Prediction of Post-Cardiopulmonary Resuscitation Survival

    PubMed Central

    Bidari, Ali; Vaziri, Samira; Moazen Zadeh, Ehsan; Farahmand, Sahar; Talachian, Elham

    2015-01-01

    Introduction: N-methyl-D-aspartate receptor subunits antibody (NR2-ab) is a sensitive marker of ischemic brain damage in clinical circumstances, such as cerebrovascular accidents. We aimed to assess the value of serum NR2-ab in predicting the post-cardiopulmonary resuscitation (CPR) survival. Methods: In this cohort study, we examined serum NR2-ab levels 1 hour after the return of spontaneous circulation (ROSC) in 49 successfully resuscitated patients. Patients with traumatic or asphyxic arrests, prior neurological insults, or major medical illnesses were excluded. Participants were followed until death or hospital discharge. Demographic data, coronary artery disease risk factors, time before initiation of CPR, and CPR duration were documented. In addition, Glasgow coma scale (GCS), blood pressure, and survival status of patients were recorded at 1, 6, 24, and 72 hour(s) after ROSC. Descriptive analyses were performed, and the Cox proportional hazard model was applied to assess if NR2-ab level is an independent predictive factor of survival. Results: 49 successfully resuscitated patients were evaluated; 27 (55%) survived to hospital discharge, 4 (8.1%) were in vegetative state, 10 (20.4%) were physically disabled, and 13 (26.5%) were physically functional. Within 72 hours of ROSC all of the 12 NR2-ab positive patients died. In contrast, 31 (84%) of the NR2-ab negative patients survived. Sensitivity, specificity, positive and negative likelihood ratios of NR2-ab in prediction of survival were 54.5% (95%CI=32.7%-74.9%), 100% (95%CI=84.5%-100%), infinite, and 45.5% (95%CI=28.8%-71.8%), respectively. Subsequent analysis showed that both NR2-ab status and GCS were independent risk factors of death. Conclusions: A positive NR2-ab serum test 1 hour after ROSC correlated with lower 72-hour survival. Further studies are required to validate this finding and demonstrate the value of a quantitative NR2-ab assay and its optimal time of measurement. PMID:26495391

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

    SciTech Connect

    Westhoff, Paulien G.; Graeff, Alexander de; Monninkhof, Evelyn M.; Bollen, Laurens; Dijkstra, Sander P.; Steen-Banasik, Elzbieta M. van der; Vulpen, Marco van; Leer, Jan Willem H.; Marijnen, Corrie A.; Linden, Yvette M. van der

    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 provided.

  7. The BMP inhibitor DAND5 in serum predicts poor survival in breast cancer

    PubMed Central

    Huang, Sheng; Huang, Naisi; Li, Shan; Shao, Zhiming; Wu, Jiong

    2016-01-01

    Background & Aims Breast cancer (BC) is prevalent worldwide malignant cancer. Improvements in timely and effective diagnosis and prediction are needed. As reported, secreted DAND5 is contributed to BC metastasis. We aim to assess whether DAND5 in peripheral blood serum could determine BC-specific mortality. Methods We used immunohistochemistry staining to detect DAND5 expression in our BC tissue array including 250 samples. Angiogenesis assay and xenograft mice model were used to examine the secreted DAND5 function in BC progression. Serum concentration of DAND5 was examined by ELISA in 1730 BC patients. Kaplan-Meier and adjusted Cox proportional hazards models were utilized to analyze the prognosis and survival of BC patients. Results Tissue array results showed that positive DAND5 staining cases displayed a higher likelihood of occurrence of disease events (HR=5.494; 95% CI: 1.008-2.353; P=0.048) in univariate analysis and remained the same trend in multivariate analysis (HR=2.537; 95% CI: 1.056-6.096; P=0.037). DAND5 positive patients exerted generally poor DFS (P=0.041) in the Kaplan-Meier survival analysis. Furthermore, secreted DAND5 promoted tumor growth and angiogenesis in vitro and in vivo. In addition, positive DAND5 in BC patients serum was associated with increased risk of disease events occurrence (univariate: HR=1.58; 95% CI: 1.206-2.070; P=0.001; multivariate: HR=1.4; 95% CI: 1.003-1.954; P=0.048) in univariate and multivariate survival analysis. In the Kaplan-Meier analysis, serum DAND5 positively correlated with poor DFS (P=0.001) and DDFS (P=0.002). Conclusions DAND5 was correlated with poor survival and could serve as an easily detectable serum biomarker to predict the survival of breast cancer. PMID:26908452

  8. Preoperative Body Mass Index, Blood Albumin and Triglycerides Predict Survival for Patients with Gastric Cancer

    PubMed Central

    Liu, Bin Zheng; Tao, Lin; Chen, Yun Zhao; Li, Xu Zhe; Dong, Yu Ling; Ma, Ya Jing; Li, Shu Gang; Li, Feng; Zhang, Wen Jie

    2016-01-01

    Background Gastric cancer (GC) is common and its prognosis is often poor due to difficulties in early diagnosis and optimal treatment strategies. TNM staging system is useful in predicting prognosis but only possible after surgery. Therefore, it is desirable to investigate prognostic factors/markers that may predict prognosis before surgery by which helps appropriate management decisions preoperatively. Methods A total of 320 GC patients were consecutively recruited from 2004 to 2013 and followed up for 127 months (10.6 years) after surgery. These patients’ were examined for body mass index (BMI) and blood levels of albumin, triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C). Kaplan-Meier method and log rank test were used to analyze long-term survival using the above potential risk markers. We first employed medians of these variables to reveal maximal potentials of the above prognostic predictors. Results Three major findings were obtained: (1) Preoperative BMI was positively correlated with albumin (r = 0.144, P<0.05) and triglyceride (r = 0.365, P<0.01), but negatively correlated with TNM staging (r = -0.265, P<0.05). Preoperative albumin levels were positively correlated with triglyceride (r = 0.173, P<0.05) but again, negatively correlated with TNM staging (r = -0.137, P<0.05); (2) Poor survival was observed in GC patients with lower levels of BMI (P = 0.028), albumin (P = 0.004), and triglyceride (P = 0.043), respectively. Receiver operating characteristic (ROC) curve analyses suggested BMI, albumin and triglyceride to have survival-predictor powers similar to TNM system; and (3) Cox multi-factorial analyses demonstrated that age (P = 0.049), BMI (P = 0.016), cell differentiation (P = 0.001), and TNM staging (P = 0.011) were independent overall survival-predictors for GC patients. Conclusions Preoperative BMI, albumin, and triglyceride levels are capable of predicting survival for

  9. Nuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival

    PubMed Central

    Qian, Zhongqing; Zhou, Tong; Gurguis, Christopher I.; Xu, Xiaoyan; Wen, Qing; Lv, Jingzhu; Fang, Fang; Hecker, Louise; Cress, Anne E.; Natarajan, Viswanathan; Jacobson, Jeffrey R.; Zhang, Donna D.; Garcia, Joe G. N.; Wang, Ting

    2015-01-01

    Nuclear factor, erythroid 2-like 2 (NFE2L2), a transcription factor also known as NF-E2-related factor 2 (Nrf2), is a key cytoprotective gene that regulates critical antioxidant and stress-responsive genes. Nrf2 has been demonstrated to be a promising therapeutic target and useful biomarker in malignant disease. We hypothesized that NFE2L2-mediated gene expression would reflect cancer severity and progression. We conducted a meta-analysis of microarray data for 240 NFE2L2-mediated genes that were enriched in tumor tissues. We then developed a risk scoring system based on NFE2L2 gene expression profiling and designated 50 tumor-associated genes as the NFE2L2-associated molecular signature (NAMS). We tested the relationship between this gene expression signature and both recurrence-free survival and overall survival in lung cancer patients. We find that NAMS predicts clinical outcome in the training cohort and in 12 out of 20 validation cohorts. Cox proportional hazard regressions indicate that NAMS is a robust prognostic gene signature, independent of other clinical and pathological factors including patient age, gender, smoking, gene alteration, MYC level, and cancer stage. NAMS is an excellent predictor of recurrence-free survival and overall survival in human lung cancer. This gene signature represents a promising prognostic biomarker in human lung cancer. PMID:26596768

  10. Nuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival.

    PubMed

    Qian, Zhongqing; Zhou, Tong; Gurguis, Christopher I; Xu, Xiaoyan; Wen, Qing; Lv, Jingzhu; Fang, Fang; Hecker, Louise; Cress, Anne E; Natarajan, Viswanathan; Jacobson, Jeffrey R; Zhang, Donna D; Garcia, Joe G N; Wang, Ting

    2015-01-01

    Nuclear factor, erythroid 2-like 2 (NFE2L2), a transcription factor also known as NF-E2-related factor 2 (Nrf2), is a key cytoprotective gene that regulates critical antioxidant and stress-responsive genes. Nrf2 has been demonstrated to be a promising therapeutic target and useful biomarker in malignant disease. We hypothesized that NFE2L2-mediated gene expression would reflect cancer severity and progression. We conducted a meta-analysis of microarray data for 240 NFE2L2-mediated genes that were enriched in tumor tissues. We then developed a risk scoring system based on NFE2L2 gene expression profiling and designated 50 tumor-associated genes as the NFE2L2-associated molecular signature (NAMS). We tested the relationship between this gene expression signature and both recurrence-free survival and overall survival in lung cancer patients. We find that NAMS predicts clinical outcome in the training cohort and in 12 out of 20 validation cohorts. Cox proportional hazard regressions indicate that NAMS is a robust prognostic gene signature, independent of other clinical and pathological factors including patient age, gender, smoking, gene alteration, MYC level, and cancer stage. NAMS is an excellent predictor of recurrence-free survival and overall survival in human lung cancer. This gene signature represents a promising prognostic biomarker in human lung cancer. PMID:26596768

  11. Modelling Circulating Tumour Cells for Personalised Survival Prediction in Metastatic Breast Cancer

    PubMed Central

    2015-01-01

    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. PMID:25978366

  12. The Power of Renal Function Estimation Equations for Predicting Long-Term Kidney Graft Survival

    PubMed Central

    Choi, Hoon Young; Joo, Dong Jin; Song, Mi Kyung; Kim, Myoung Soo; Park, Hyeong Cheon; Kim, Yu Seun; Kim, Beom Seok

    2016-01-01

    Abstract Evaluation of renal function using an accurate estimation equation is important for predicting long-term graft survival. We designed this retrospective cohort study to evaluate the predictive power of renal function estimation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) study equations for graft survival. We reviewed data of 3290 adult kidney transplant recipients who underwent transplantation at a single center between April 1979 and September 2012. The reliability and agreement of chronic kidney disease (CKD) stages based on the estimated glomerular filtration rate (eGFR) as calculated by the CKD-EPI and MDRD equations were evaluated using Bland–Altman plots and Cohen weighted kappa analyses. The predictive power of CKD stages as classified by each equation for graft survival was investigated using Cox regression models. Additionally, Pearson and Spearman correlation coefficients were used to reveal the relationship between graft survival and eGFR equations. Of 3290 kidney transplant recipients, 3040 were included in the analysis. The mean follow-up duration was 128.08 ± 83.54 months, and 29.8% of participants were reclassified to higher eGFR categories by the CKD-EPI equation compared to the category classification by the MDRD equation. eGFR calculated using the MDRD equation was underestimated compared to that calculated using the CKD-EPI equation, based on the Bland–Altman plot. In Cohen weighted kappa analysis, agreement across CKD stages classified using the 2 equations was reliable, but all CKD stages classified using the MDRD equation appeared to be in lower eGFR categories than those classified using the CKD-EPI equation. Pearson and Spearman correlation analyses indicated that the CKD stage as classified by the CKD-EPI equation, but not the MDRD equation, was significantly correlated with the risk of graft failure. In multivariable Cox regression analysis for

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Predictive modelling of Lactobacillus casei KN291 survival in fermented soy beverage.

    PubMed

    Zielińska, Dorota; Dorota, Zielińska; Kołożyn-Krajewska, Danuta; Danuta, Kołożyn-Krajewska; Goryl, Antoni; Antoni, Goryl; Motyl, Ilona

    2014-02-01

    The aim of the study was to construct and verify predictive growth and survival models of a potentially probiotic bacteria in fermented soy beverage. The research material included natural soy beverage (Polgrunt, Poland) and the strain of lactic acid bacteria (LAB) - Lactobacillus casei KN291. To construct predictive models for the growth and survival of L. casei KN291 bacteria in the fermented soy beverage we design an experiment which allowed the collection of CFU data. Fermented soy beverage samples were stored at various temperature conditions (5, 10, 15, and 20°C) for 28 days. On the basis of obtained data concerning the survival of L. casei KN291 bacteria in soy beverage at different temperature and time conditions, two non-linear models (r(2)= 0.68-0.93) and two surface models (r(2)=0.76-0.79) were constructed; these models described the behaviour of the bacteria in the product to a satisfactory extent. Verification of the surface models was carried out utilizing the validation data - at 7°C during 28 days. It was found that applied models were well fitted and charged with small systematic errors, which is evidenced by accuracy factor - Af, bias factor - Bf and mean squared error - MSE. The constructed microbiological growth and survival models of L. casei KN291 in fermented soy beverage enable the estimation of products shelf life period, which in this case is defined by the requirement for the level of the bacteria to be above 10(6) CFU/cm(3). The constructed models may be useful as a tool for the manufacture of probiotic foods to estimate of their shelf life period. PMID:24500482

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

    PubMed Central

    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

  16. Predicting the Survival Time for Bladder Cancer Using an Additive Hazards Model in Microarray Data

    PubMed Central

    TAPAK, Leili; MAHJUB, Hossein; SADEGHIFAR, Majid; SAIDIJAM, Massoud; POOROLAJAL, Jalal

    2016-01-01

    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. PMID:27114989

  17. First-year PSA kinetics and minima after prostate cancer radiotherapy are predictive of overall survival

    SciTech Connect

    Cheung, Rex . E-mail: mrcheung@mdanderson.org; Tucker, Susan L.; Kuban, Deborah A.

    2006-09-01

    Purpose: We analyzed whether first-year prostate-specific antigen (PSA) kinetics and minima are predictive of overall survival (OS). Methods and Materials: The data set contained 1,174 patients treated with external beam radiotherapy (RT) from 1987 to 2001. The relative rate of change ({lambda}) in post-RT PSA values during the first year (13.5 months) was computed using regression analysis of ln(PSA) vs. time. We also computed the PSA minimum (mPSA) reached during the same period. Recursive partitioning analysis was used to identify the relevant cutpoints for the factors being investigated for its association with survival: age, pretreatment PSA, radiation dose, relative rate of change in PSA post-RT, and 1-year PSA minimum. For each of the other factors stage, Gleason score and risk group, all possible cutpoints were considered in the multivariate analyses. Significant factors were considered in the multivariate analyses to identify independent predictors for overall survival. Results: The median value of {lambda} was -1.0 years{sup -1} (range, -11.0-5.1 years{sup -1}). The 1-year minimum had a median of 0.8 ng/mL (range, 0.01-30.9 ng/mL). Recursive partitioning analysis and Cox proportional hazards analyses identified the following pretreatment or treatment factors adversely related to OS: age, Gleason score, stage, and dose. First-year mPSA {>=} 4 ng/mL and {lambda} > 0 were post-RT independent prognostic factors for worse OS. Conclusion: First-year post-RT PSA kinetics and minima are early response parameters predictive of overall survival for prostate cancer patients. These factors may be useful in selecting patients for early salvage therapy.

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

    PubMed Central

    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

  19. A Simple Scoring System Predicting the Survival Time of Patients with Bone Metastases after RT

    PubMed Central

    Zhang, Wen-Yi; Li, Hui-Fang; Su, Meng; Lin, Rui-Fang; Chen, Xing-Xing; Zhang, Ping; Zou, Chang-Lin

    2016-01-01

    Objectives This study aimed to develop a scoring system to predict the survival time of patients with bone metastases after radiation therapy (RT). The scoring system can guide physicians to a better selection of appropriate treatment regimens. Materials and Methods The medical records of 125 patients with bone metastases treated with RT between January 2007 and September 2010 were reviewed retrospectively. Fifteen potential prognostic factors were investigated: sex, age, Karnofsky performance score (KPS), type of primary tumor, resection of tumor before bone metastases, interval between primary tumor diagnosis and diagnosis of bone metastases, Carcinoembryonic Antigen(CEA), lung metastases before bone metastases, liver metastases before bone metastases, brain metastases before bone metastases, stage, T, N, M, and degree of cellular differentiation. Results In an univariate analysis, 10 factors were significantly associated with survival time after bone metastasis: sex, KPS, breast cancer, esophageal cancer, colorectal cancer, interval between tumor diagnosis and diagnosis of bone metastases, CEA, lung metastases before bone metastases, T-staging, and differentiation. In a multivariate analysis, 7 factors were found to be significant: sex, KPS, esophageal cancer, colorectal cancer, interval between tumor diagnosis and diagnosis of bone metastases, T-staging, and differentiation. The median survival of all patients with bone metastases after RT was 14.1 months. There were significant differences in the median survival of patients with bone metastases after RT of 4.9 months, 10.5 months, and 29.7 months in groups 1, 2, and 3, respectively (P<0.001). Conclusion According to this scoring system, the survival time of patients after bone metastasis can be estimated. PMID:27438606

  20. Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

    SciTech Connect

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Myerson, Robert J.; Fleshman, James W.; Grigsby, Perry W.

    2008-05-01

    Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer.

  1. Fascin expression predicts survival after potentially curative resection of node-positive colon cancer.

    PubMed

    Chan, Charles; Jankova, Lucy; Fung, Caroline L S; Clarke, Candice; Robertson, Graham; Chapuis, Pierre H; Bokey, Les; Lin, Betty P C; Dent, Owen F; Clarke, Stephen

    2010-05-01

    Fascin, an actin-bundling protein, is expressed in many neoplasms including colorectal cancer. It is considered to be a mediator of tumor cell invasion and an indicator of aggressive phenotype; however, there are few reports on the association between fascin and prognosis in colorectal cancer. The aims of this study were to: (a) investigate the expression of fascin in the central part of the tumor and at the invasive front in patients who had a potentially curative resection for node-positive colonic carcinoma; (b) examine the method of scoring fascin expression; and (c) investigate the association between fascin expression and overall survival and other clinicopathologic features. Fascin expression was assessed by immunostaining of microarrays from archived tissue of 470 patients who were followed for a minimum of 5 years after resection. Other clinicopathologic data had been recorded prospectively according to a standardized protocol. Analysis of overall survival was by the Kaplan-Meier method and Cox regression. For both central tumor tissue and the invasive front, it was found that the percentage of stained cells was a sufficient measure of fascin expression in relation to survival, with staining intensity providing no significant additional information. At both levels, there was a significant independent association between high fascin expression and diminished survival, although this association was much stronger in the central region (adjusted hazard ratio 1.6, P<0.001) than at the invasive front (adjusted hazard ratio 1.1, P=0.044). Fascin expression predicted overall survival but did not displace other routinely collected clinicopathologic predictors. PMID:20410808

  2. Predictive factors for survival and score application in liver retransplantation for hepatitis C recurrence

    PubMed Central

    Song, Alice Tung Wan; Sobesky, Rodolphe; Vinaixa, Carmen; Dumortier, Jérôme; Radenne, Sylvie; Durand, François; Calmus, Yvon; Rousseau, Géraldine; Latournerie, Marianne; Feray, Cyrille; Delvart, Valérie; Roche, Bruno; Haim-Boukobza, Stéphanie; Roque-Afonso, Anne-Marie; Castaing, Denis; Abdala, Edson; D’Albuquerque, Luiz Augusto Carneiro; Duclos-Vallée, Jean-Charles; Berenguer, Marina; Samuel, Didier

    2016-01-01

    AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus (HCV) recurrence and to apply a survival score to this population. METHODS: We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers (seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis (FCH) post-first graft presenting with hepatic decompensation. RESULTS: Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease (MELD) score < 25 when replaced on the waiting list, and a retransplantation donor age < 60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patients who underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andrés score was applied to 102 patients for whom all score variables were

  3. Lymph Node Micrometastases in Early-Stage Cervical Cancer are Not Predictive of Survival.

    PubMed

    Stany, Michael P; Stone, Pamela J B; Felix, Juan C; Amezcua, Charles A; Groshen, Susan; Ye, Wei; Kyser, Kathy L; Howard, Robin S; Zahn, Chris M; Muderspach, Laila I; Lentz, Scott E; Chernofsky, Mildred R

    2015-07-01

    Although patients with early-stage cervical cancer have in general a favorable prognosis, 10% to 40% patients still recur depending on pathologic risk factors. The objective of this study was to evaluate if the presence of lymph node micrometastasis (LNmM) had an impact on patient's survival. We performed a multi-institutional retrospective review on patients with early-stage cervical cancer, with histologically negative lymph nodes, treated with radical hysterectomy and pelvic lymphadenectomy for the study period 1994 to 2004. Tissue blocks of lymph nodes from the patient's original surgery were recut and then evaluated for the presence of micrometastases. One hundred twenty-nine patients were identified who met inclusion criteria. LNmM were found in 26 patients (20%). In an average follow-up time of 70 mo, there were 11 recurrences (8.5%). Of the 11 recurrences, 2 (18%) patients had LNmM. Patients with LNmM were more likely to have received adjuvant radiation and chemotherapy. In stratified log-rank analysis, LNmM were not associated with any other high-risk clinical or pathologic variables. Survival data analysis did not demonstrate an association between the presence of LNmM and recurrence or overall survival. The presence of LNmM was not associated with an unfavorable prognosis nor was it associated with other high-risk clinical or pathologic variables predicting recurrence. Further study is warranted to understand the role of micrometastases in cervical cancer. PMID:26061072

  4. Baseline burnout symptoms predict visuospatial executive function during survival school training in special operations military personnel.

    PubMed

    Morgan, Charles A; Russell, Bartlett; McNeil, Jeff; Maxwell, Jeff; Snyder, Peter J; Southwick, Steven M; Pietrzak, Robert H

    2011-05-01

    Burnout symptoms, which are characterized by exhaustion, cynicism, and a reduced sense of professional efficacy, may deleteriously affect cognitive function in military personnel. A total of 32 U.S. Military Special Operations personnel enrolled in Survival School completed measures of trauma history, dissociation, and burnout before training. They then completed the Groton Maze Learning Test (GMLT), a neuropsychological measure of integrative visuospatial executive function during three field-based phases of Survival School-enemy evasion, captivity/interrogation, and escape/release from captivity. Lower pre-training perceptions of professional efficacy were associated with reduced executive function during all of the field-based phases of Survival School, even after adjustment for years of education, cynicism, and baseline GMLT scores. Magnitudes of decrements in executive function in Marines with low efficacy relative to those with high efficacy increased as training progressed and ranged from .58 during enemy evasion to .99 during escape/release from captivity. Pre-training perceptions of burnout may predict visuospatial executive function during naturalistic training-related stress in military personnel. Assessment of burnout symptoms, particularly perceptions of professional efficacy, may help identify military personnel at risk for stress-related executive dysfunction. PMID:21466738

  5. Postchemoradiotherapy Positron Emission Tomography Predicts Pathologic Response and Survival in Patients With Esophageal Cancer

    SciTech Connect

    Jayachandran, Priya; Pai, Reetesh K.; Quon, Andrew; Graves, Edward; Krakow, Trevor E.; La, Trang; Loo, Billy W.; Koong, Albert C.; Chang, Daniel T.

    2012-10-01

    Purpose: To correlate the prechemoradiotherapy (CRT) and post-CRT metabolic tumor volume (MTV) on positron emission tomography (PET) scanning with the pathologic response and survival in patients receiving preoperative CRT for esophageal cancer. Materials and Methods: The medical records of 37 patients with histologically confirmed Stage I-IVA esophageal cancer treated with CRT with or without surgical resection were reviewed. Of the 37 patients, 21 received preoperative CRT (57%) and 16 received definitive CRT (43%). All patients had a pre-CRT and 32 had a post-CRT PET scan. The MTV was measured on the pre-CRT PET and post-CRT PET scan, respectively, using a minimum standardized uptake value (SUV) threshold x, where x = 2, 2.5, 3, or the SUV maximum Multiplication-Sign 50%. The total glycolytic activity (TGA{sub x}) was defined as the mean SUV Multiplication-Sign MTV{sub x}. The MTV ratio was defined as the pre-CRT PET MTV/post-CRT MTV. The SUV ratio was defined similarly. A single pathologist scored the pathologic response using a tumor regression grade (TRG) scale. Results: The median follow-up was 1.5 years (range, 0.4-4.9). No significant correlation was found between any parameters on the pre-CRT PET scan and the TRG or overall survival (OS). Multiple post-CRT MTV values and post-TGA values correlated with the TRG and OS; however, the MTV{sub 2.5Post} and TGA{sub 2.5Post} had the greatest correlation. The MTV{sub 2} ratio correlated with OS. The maximum SUV on either the pre-CRT and post-CRT PET scans or the maximum SUV ratio did not correlate with the TRG or OS. Patients treated preoperatively had survival similar compared with those treated definitively with a good PET response (p = 0.97) and significantly better than that of patients treated definitively with a poor PET response (p < 0.0001). Conclusion: The maximum SUV was not a predictive or prognostic parameter. The MTV{sub 2.5} and TGA{sub 2.5} were useful markers for predicting the response and

  6. A nomogram for predicting survival of nasopharyngeal carcinoma patients with metachronous metastasis.

    PubMed

    Zeng, Zixun; Shen, Lujun; Wang, Yue; Shi, Feng; Chen, Chen; Wu, Ming; Bai, Yutong; Pan, Changchuan; Xia, Yunfei; Wu, Peihong; Li, Wang

    2016-07-01

    Patients with metachronous metastatic nasopharyngeal carcinoma (NPC) differ significantly in survival outcomes. The aim of this study is to build a clinically practical nomogram incorporating known tumor prognostic factors to predict survival for metastatic NPC patients in epidemic areas.A total of 860 patients with metachronous metastatic nasopharyngeal carcinoma were analyzed retrospectively. Variables assessed were age, gender, body mass index, Karnofsky Performance Status (KPS), Union for International Cancer Control (UICC) T and N stages, World Health Organization (WHO) histology type, serum lactate dehydrogenase (sLDH) level, serum Epstein-Barr virus (EBV) level, treatment modality, specific metastatic location (lung/liver/bone), number of metastatic location(s) (isolated vs multiple), and number of metastatic lesion(s) in metastatic location(s) (single vs multiple). The independent prognostic factors for overall survival (OS) by Cox-regression model were utilized to build the nomogram.Independent prognostic factors for OS of metastatic NPC patients included age, UICC N stage, KPS, sLDH, number of metastatic locations, number of metastatic lesions, involvement of liver metastasis, and involvement of bone metastasis. Calibration of the final model suggested a c-index of 0.68 (95% confidence interval [CI], 0.65-0.69). Based on the total point (TP) by nomogram, we further subdivided the study cohort into 4 groups. Group 1 (TP < 320, 208 patients) had the lowest risk of dying. Discrimination was visualized by the differences in survival between these 4 groups (group 2/group 1: hazard ratio [HR] = 1.61, 95%CI: 1.24-2.09; group 3/group 1: HR = 2.20, 95%CI: 1.69-2.86; and group 4/group 1: HR = 3.66, 95%CI: 2.82-4.75).The developed nomogram can help guide the prognostication of patients with metachronous metastatic NPC in epidemic areas. PMID:27399084

  7. Interleukin-10 Haplotype May Predict Survival and Relapse in Resected Non-Small Cell Lung Cancer

    PubMed Central

    Wu, Tzu-Chin; Wang, Lee; Chien, Wen-Pin; Cheng, Ya-Wen; Chen, Chih-Yi; Shieh, Shwn-Huey; Lee, Huei

    2012-01-01

    IL-10 is associated with tumor malignancy via immune escape. We hypothesized that IL-10 haplotypes categorized by IL-10 promoter polymorphisms at –1082A>G, –819C>T, and –592C>A might influence IL-10 expression and give rise to non-small cell lung cancer (NSCLC) patients with poor outcomes and relapse. We collected adjacent normal tissues from 385 NSCLC patients to determine IL-10 haplotypes by direct sequencing and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Of the 385 tumors, 241 were available to evaluate IL-10 mRNA expression levels by real-time RT-PCR. The influence of IL-10 haplotypes on overall survival (OS) and relapse free survival (RFS) were determined by Kaplan-Meier and multivariate Cox regression analysis. The results showed that IL-10 mRNA levels were significantly higher in tumors with the non-ATA haplotype than with the ATA haplotype (P = 0.004). Patients with the non-ATA haplotype had shorter OS and RFS periods than did patients with the ATA haplotype. This may be associated with the observation that the number of tumor-infiltrating lymphocytes was decreased in the tumors with higher levels of IL-10. Consistently, T cells from the peripheral blood of the patients with non-ATA haplotype were more susceptible to apoptosis and less cytotoxic to tumor cells, compared to those from the patients with ATA haplotype. The results suggest that IL-10 can promote tumor malignancy via promoting T cell apoptosis and tumor cell survival, and IL-10 haplotype evaluated by PCR-RFLP or direct sequencing may be used to predict survival and relapse in resected NSCLC, helping clinicians to make appropriate decisions on treatment of the patients. PMID:22848356

  8. Patient and tumour biology predict survival beyond the Milan criteria in liver transplantation for hepatocellular carcinoma

    PubMed Central

    Andreou, Andreas; Gül, Safak; Pascher, Andreas; Schöning, Wenzel; Al-Abadi, Hussein; Bahra, Marcus; Klein, Fritz; Denecke, Timm; Strücker, Benjamin; Puhl, Gero; Pratschke, Johann; Seehofer, Daniel

    2015-01-01

    Background Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are not considered for liver transplantation (LT) in many centres; however, LT may be the only treatment able to achieve long-term survival in patients with unresectable HCC. The aim of this study was to assess the role of recipient age and tumour biology expressed by the DNA index in the selection of HCC patients for LT. Patients Clinicopathological data of 364 patients with HCC who underwent LT between 1989 and 2010 were evaluated. Overall survival (OS) was analysed by patient age, tumour burden based on Milan criteria and the DNA index. Results After a median follow-up time of 78 months, the median survival was 100 months. Factors associated with OS on univariate analysis included Milan criteria, patient age, hepatitis C infection, alpha-fetoprotein (AFP) level, the DNA index, number of HCC, diameter of HCC, bilobar HCC, microvascular tumour invasion and tumour grading. On multivariate analysis, HCC beyond Milan criteria and the DNA index >1.5 independently predicted a worse OS. When stratifying patients by both age and Milan criteria, patients ≤60 years with HCC beyond Milan criteria had an OS comparable to that of patients >60 years within Milan criteria (10-year OS: 33% versus 37%, P = 0.08). Patients ≤60 years with HCC beyond Milan criteria but a favourable DNA index ≤1.5 achieved excellent long-term outcomes, comparable with those of patients within Milan criteria. Conclusions Patients ≤60 years may undergo LT for HCC with favourable outcomes independently of their tumour burden. Additional assessment of tumour biology, e.g. using the DNA index, especially in this subgroup of patients can support the selection of LT candidates who may derive the most long-term survival benefit, even if Milan criteria are not fulfilled. PMID:25263399

  9. The Lymphocyte-Monocyte Ratio Predicts Patient Survival and Aggressiveness of Ovarian Cancer

    PubMed Central

    Eo, Wan Kyu; Chang, Hye Jung; Kwon, Sang Hoon; Koh, Suk Bong; Kim, Young Ok; Ji, Yong Il; Kim, Hong-Bae; Lee, Ji Young; Suh, Dong Soo; Kim, Ki Hyung; Chang, Ik Jin; Kim, Heung Yeol; Chang, Suk Choo

    2016-01-01

    Objective: To measure the prognostic value of the lymphocyte-monocyte ratio (LMR) in patients with epithelial ovarian cancer (EOC). Methods: We retrospectively examined the LMR as a prognosticator in a cohort of 234 patients with EOC who underwent surgical resection. Patients were categorized into two different groups based on the LMR (LMR-low and LMR-high) using cut-off values determined by receiver operating characteristic (ROC) curve analysis. The objective of the study was to assess the effect of the LMR on progression-free survival (PFS) and overall survival (OS), and to validate the LMR as an independent predictor of survival. Results: Using the data collected from the whole cohort, the optimized LMR cut-off value selected on the ROC curve was 2.07 for both PFS and OS. The LMR-low and LMR-high groups included 48 (20.5%) and 186 patients (79.5%), respectively. The 5-year PFS rates in the LMR-low and LMR-high groups were 40.0 and 62.5% (P < 0.0001), respectively, and the 5-year OS rates in these two groups were 42.2 and 67.2% (P < 0.0001), respectively. On multivariate analysis, we identified age, International Federation of Gynecology and Obstetrics (FIGO) stage, and cancer antigen 125 levels to be the strongest valuable prognostic factors affecting PFS (P = 0.0421, P = 0.0012, and P = 0.0313, respectively) and age, FIGO stage, and the LMR as the most valuable prognostic factors predicting OS (P = 0.0064, P = 0.0029, and P = 0.0293, respectively). Conclusion: The LMR is an independent prognostic factor affecting the survival of patients with EOC. PMID:26918042

  10. Do Conflict Resolution and Recovery Predict the Survival of Adolescents' Romantic Relationships?

    PubMed Central

    Ha, Thao; Overbeek, Geertjan; Lichtwarck-Aschoff, Anna; Engels, Rutger C. M. E.

    2013-01-01

    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. PMID:23613960

  11. Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction

    PubMed Central

    Rawstron, Andy C.; Gregory, Walter M.; de Tute, Ruth M.; Davies, Faith E.; Bell, Sue E.; Drayson, Mark T.; Cook, Gordon; Jackson, Graham H.; Morgan, Gareth J.; Child, J. Anthony

    2015-01-01

    The detection of minimal residual disease (MRD) in myeloma using a 0.01% threshold (10−4) after treatment is an independent predictor of progression-free survival (PFS), but not always of overall survival (OS). However, MRD level is a continuous variable, and the predictive value of the depth of tumor depletion was evaluated in 397 patients treated intensively in the Medical Research Council Myeloma IX study. There was a significant improvement in OS for each log depletion in MRD level (median OS was 1 year for ≥10%, 4 years for 1% to <10%, 5.9 years for 0.1% to <1%, 6.8 years for 0.01% to <0.1%, and more than 7.5 years for <0.01% MRD). MRD level as a continuous variable determined by flow cytometry independently predicts both PFS and OS, with approximately 1 year median OS benefit per log depletion. The trial was registered at www.isrctn.com as #68454111. PMID:25645353

  12. Survival in rectal cancer is predicted by T cell infiltration of tumour-associated lymphoid nodules

    PubMed Central

    McMullen, T P W; Lai, R; Dabbagh, L; Wallace, T M; de Gara, C J

    2010-01-01

    Lymphoid nodules are a normal component of the mucosa of the rectum, but little is known about their function and whether they contribute to the host immune response in malignancy. In rectal cancer specimens from patients with local (n = 18), regional (n = 12) and distant (n = 10) disease, we quantified T cell (CD3, CD25) and dendritic cell (CD1a, CD83) levels at the tumour margin as well as within tumour-associated lymphoid nodules. In normal tissue CD3+, but not CD25+, T cells are concentrated at high levels within lymphoid nodules, with significantly fewer cells found in surrounding normal mucosa (P = 0·001). Mature (CD83), but not immature (CD1a), dendritic cells in normal tissue are also found clustered almost exclusively within lymphoid nodules (P = < 0·0001). In rectal tumours, both CD3+ T cells (P = 0·004) and CD83+ dendritic cells (P = 0·0001) are also localized preferentially within tumour-associated lymphoid nodules. However, when comparing tumour specimens to normal rectal tissue, the average density of CD3+ T cells (P = 0·0005) and CD83+ dendritic cells (P = 0·0006) in tumour-associated lymphoid nodules was significantly less than that seen in lymphoid nodules in normal mucosa. Interestingly, regardless of where quantified, T cell and dendritic cell levels did not depend upon the stage of disease. Increased CD3+ T cell infiltration of tumour-associated lymphoid nodules predicted improved survival, independent of stage (P = 0·05). Other T cell (CD25) markers and different levels of CD1a+ or CD83+ dendritic cells did not predict survival. Tumour-associated lymphoid nodules, enriched in dendritic cells and T cells, may be an important site for antigen presentation and increased T cell infiltration may be a marker for improved survival. PMID:20408858

  13. Factors Predicting Graft-versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Hematopoietic Cell Transplantation: Multivariable Analysis from a Single Center.

    PubMed

    Solh, Melhem; Zhang, Xu; Connor, Katelin; Brown, Stacey; Solomon, Scott R; Morris, Lawrence E; Holland, H Kent; Bashey, Asad

    2016-08-01

    The ideal outcome of allogeneic hematopoietic cell transplantation (allo-HCT) is based on survival that is free of morbidity. The most common causes of treatment failure and morbidity after HCT are relapse, graft-versus-host disease (GVHD), and nonrelapse death. A composite endpoint that measures survival free of clinically significant negative events may be a useful way to determine the success of allo-HCT. We assessed GVHD and relapse-free survival (GRFS) where the events were acute GVHD grades III to IV, chronic GVHD requiring immunosuppression, relapse, or death in 531 consecutive adult patients who received an allo-HCT between 2006 and 2014 at our center. Median follow-up of living patients was 46 months (range, 12 to 123). HLA matched related donor (MRD, n = 198, 37%), matched unrelated donor (MUD, n = 205, 39%), and haploidentical donor with post-transplant cyclophosphamide (HID, n = 128, 24%) were used. Thirty-six percent of patients had a high/very-high Dana Farber disease risk index (DRI). Estimated rates of GRFS at 1 and 2 years after MRD, MUD, and HID transplantations were 34% and 26%, 26% and 17%, and 33% and 31%, respectively, with MRD recipients having a better GRFS than MUD (P < .05). On multivariable analysis, peripheral blood stem cell source (HR, 1.34; P = .04), MUD (HR, 1.41; P = .003), and high/very high DRI (HR, 1.66; P = .001) were all associated with a worse GFRS post-HCT. These data suggest that GRFS can be predicted by patient disease risk, stem cell source, and donor type. Importantly, MUDs produce inferior GRFS to MRDs, whereas HIDs do not. PMID:27095692

  14. A new cluster-based oversampling method for improving survival prediction of hepatocellular carcinoma patients.

    PubMed

    Santos, Miriam Seoane; Abreu, Pedro Henriques; García-Laencina, Pedro J; Simão, Adélia; Carvalho, Armando

    2015-12-01

    Liver cancer is the sixth most frequently diagnosed cancer and, particularly, Hepatocellular Carcinoma (HCC) represents more than 90% of primary liver cancers. Clinicians assess each patient's treatment on the basis of evidence-based medicine, which may not always apply to a specific patient, given the biological variability among individuals. Over the years, and for the particular case of Hepatocellular Carcinoma, some research studies have been developing strategies for assisting clinicians in decision making, using computational methods (e.g. machine learning techniques) to extract knowledge from the clinical data. However, these studies have some limitations that have not yet been addressed: some do not focus entirely on Hepatocellular Carcinoma patients, others have strict application boundaries, and none considers the heterogeneity between patients nor the presence of missing data, a common drawback in healthcare contexts. In this work, a real complex Hepatocellular Carcinoma database composed of heterogeneous clinical features is studied. We propose a new cluster-based oversampling approach robust to small and imbalanced datasets, which accounts for the heterogeneity of patients with Hepatocellular Carcinoma. The preprocessing procedures of this work are based on data imputation considering appropriate distance metrics for both heterogeneous and missing data (HEOM) and clustering studies to assess the underlying patient groups in the studied dataset (K-means). The final approach is applied in order to diminish the impact of underlying patient profiles with reduced sizes on survival prediction. It is based on K-means clustering and the SMOTE algorithm to build a representative dataset and use it as training example for different machine learning procedures (logistic regression and neural networks). The results are evaluated in terms of survival prediction and compared across baseline approaches that do not consider clustering and/or oversampling using the

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed Central

    Anand, Sanya; Sebra, Robert; Catalina Camacho, Sandra; Garnar-Wortzel, Leopold; Nair, Navya; Moshier, Erin; Wooten, Melissa; Uzilov, Andrew; Chen, Rong; Prasad-Hayes, Monica; Zakashansky, Konstantin; Beddoe, Ann Marie; Schadt, Eric; Dottino, Peter; Martignetti, John A.

    2015-01-01

    Background High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools. Methods and Findings Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival. Conclusions Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic

  18. Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma

    PubMed Central

    Kim, Yuhree; Margonis, Georgios A.; Prescott, Jason D.; Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Wang, Tracy S.; Evans, Douglas B.; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Jin, Linda X.; Weber, Sharon M.; Salem, Ahmed I.; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Poultsides, George A.; Pawlik, Timothy M.

    2016-01-01

    IMPORTANCE Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. OBJECTIVES To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction. DESIGN, SETTING, AND PARTICIPANTS Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015. MAIN OUTCOMES AND MEASURES The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63–5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47–15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95–3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27–4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02–3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00–3.17; P = .05), positive

  19. Predicting long-term risk for relationship dissolution using nonparametric conditional survival trees.

    PubMed

    Kliem, Sören; Weusthoff, Sarah; Hahlweg, Kurt; Baucom, Katherine J W; Baucom, Brian R

    2015-12-01

    Identifying risk factors for divorce or separation is an important step in the prevention of negative individual outcomes and societal costs associated with relationship dissolution. Programs that aim to prevent relationship distress and dissolution typically focus on changing processes that occur during couple conflict, although the predictive ability of conflict-specific variables has not been examined in the context of other factors related to relationship dissolution. The authors examine whether emotional responding and communication during couple conflict predict relationship dissolution after controlling for overall relationship quality and individual well-being. Using nonparametric conditional survival trees, the study at hand simultaneously examined the predictive abilities of physiological (systolic and diastolic blood pressure, heart rate, cortisol) and behavioral (fundamental frequency; f0) indices of emotional responding, as well as observationally coded positive and negative communication behavior, on long-term relationship stability after controlling for relationship satisfaction and symptoms of depression. One hundred thirty-six spouses were assessed after participating in a randomized clinical trial of a relationship distress prevention program as well as 11 years thereafter; 32.5% of the couples' relationships had dissolved by follow up. For men, the only significant predictor of relationship dissolution was cortisol change score (p = .012). For women, only f0 range was a significant predictor of relationship dissolution (p = .034). These findings highlight the importance of emotional responding during couple conflict for long-term relationship stability. PMID:26192131

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  1. Small increases in enhancement on MRI may predict survival post radiotherapy in patients with glioblastoma.

    PubMed

    Gzell, Cecelia Elizabeth; Wheeler, Helen R; McCloud, Philip; Kastelan, Marina; Back, Michael

    2016-05-01

    To assess impact of volumetric changes in tumour volume post chemoradiotherapy in glioblastoma. Patients managed with chemoradiotherapy between 2008 and 2011 were included. Patients with incomplete MRI sets were excluded. Analyses were performed on post-operative MRI, and MRIs at 1 month (M+1), 3 months (M+3), 5 months (M+5), 7 months (M+7), and 12 months (M+12) post completion of RT. RANO definitions of response were used for all techniques. Modified RANO criteria and two volumetric analysis techniques were used. The two volumetric analysis techniques involved utility of the Eclipse treatment planning software to calculate the volume of delineated tissue: surgical cavity plus all surrounding enhancement (Volumetric) versus surrounding enhancement only (Rim). Retrospective analysis of 49 patients with median survival of 18.4 months. Using Volumetric analysis the difference in MS for patients who had a <5 % increase versus ≥5 % at M+3 was 23.1 versus 15.1 months (p = 0.006), and M+5 was 26.3 versus 15.1 months (p = 0.006). For patients who were classified as progressive disease using modified RANO criteria at M+1 and M+3 there was a difference in MS compared with those who were not (M+1: 13.1 vs. 19.4 months, p = 0.017, M+3: 13.2 vs. 20.1 months, p = 0.096). An increase in the volume of cavity and enhancement of ≥5 % at M+3 and M+5 post RT was associated with reduced survival, suggesting that increases in radiological abnormality of <25 % may predict survival. PMID:26879084

  2. HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas.

    PubMed

    Kostareli, Efterpi; Holzinger, Dana; Bogatyrova, Olga; Hielscher, Thomas; Wichmann, Gunnar; Keck, Michaela; Lahrmann, Bernd; Grabe, Niels; Flechtenmacher, Christa; Schmidt, Christopher R; Seiwert, Tanguy; Dyckhoff, Gerhard; Dietz, Andreas; Höfler, Daniela; Pawlita, Michael; Benner, Axel; Bosch, Franz X; Plinkert, Peter; Plass, Christoph; Weichenhan, Dieter; Hess, Jochen

    2013-06-01

    High-risk types of human papilloma virus (HPV) are increasingly associated with oropharyngeal squamous cell carcinoma (OPSCC). Strikingly, patients with HPV-positive OPSCC are highly curable with ionizing radiation and have better survival compared with HPV-negative patients, but the underlying molecular mechanisms remain poorly understood. We applied an array-based approach to monitor global changes in CpG island hypermethylation between HPV-negative and HPV-positive OPSCCs and identified a specific pattern of differentially methylated regions that critically depends on the presence of viral transcripts. HPV-related alterations were confirmed for the majority of candidate gene promoters by mass spectrometric, quantitative methylation analysis. There was a significant inverse correlation between promoter hypermethylation of ALDH1A2, OSR2, GATA4, GRIA4, and IRX4 and transcript levels. Interestingly, Kaplan-Meier analysis revealed that a combined promoter methylation pattern of low methylation levels in ALDH1A2 and OSR2 promoters and high methylation levels in GATA4, GRIA4, and IRX4 promoters was significantly correlated with improved survival in 3 independent patient cohorts. ALDH1A2 protein levels, determined by immunohistochemistry on tissue microarrays, confirmed the association with clinical outcome. In summary, our study highlights specific alterations in global gene promoter methylation in HPV-driven OPSCCs and identifies a signature that predicts the clinical outcome in OPSCCs. PMID:23635773

  3. Leukocyte telomere length predicts overall survival in hepatocellular carcinoma treated with transarterial chemoembolization.

    PubMed

    Liu, Han-Qiang; An, Jia-Ze; Liu, Juan; Yang, Ye-Fa; Zhang, Hong-Xin; Zhao, Bin-Yu; Li, Ji-Bin; Yang, Hu-Shan; Chen, Zhi-Nan; Xing, Jin-Liang

    2012-05-01

    Previous studies have reported that telomere length in peripheral blood leukocytes can predict the clinical outcome of several cancers. However, whether leukocyte telomere length is associated with the prognosis of hepatocellular carcinoma (HCC) remains to be determined. In this study, relative telomere length (RTL) in peripheral blood leukocytes was measured using a real-time PCR-based method for 269 HCC patients treated with transarterial chemoembolization (TACE) from two independent hospitals. The association between RTL and the overall survival (OS) of HCC was analyzed. The immunological function of the HCC patients with different leukocyte RTLs was evaluated. Multivariate analyses indicated that long leukocyte RTL was significantly associated with poor OS of HCC patients, with a hazard ratio of 2.04 (95% confidence interval, 1.46-2.86; P < 0.001). Kaplan-Meier analyses showed a significant difference of median survival time between patients with long and short RTL (log rank P < 0.001). Fluorescence-activated cell sorting analyses showed that the long RTL group had a significantly increased percentage of CD4(+)CD25(+)FOXP3(+) Treg in CD4(+) T cells compared with short RTL group (P = 0.002). In conclusion, our results suggest that leukocyte RTL may serve as an independent prognostic marker for HCC patients treated with TACE. PMID:22318909

  4. Prediction of survival of diffuse large B-cell lymphoma patients via the expression of three inflammatory genes.

    PubMed

    Zhao, Shuangtao; Bai, Nan; Cui, Jianlin; Xiang, Rong; Li, Na

    2016-08-01

    Currently, several gene-expression signatures that were used to predict survival of diffuse large B-cell lymphoma (DLBCL) patients, showed a restriction on the practical work for lack of convenient operation. In this study, we screened inflammatory genes whose expression correlated with survival of DLBCL and established a predictive model including IL6, IL1A and CSF3 through multivariate Cox regression based on the expression of these three genes. We validated the model at protein level in our clinical serum cohort composed of 101 patients of DLBCL and 50 healthy controls and 534 DLBCL patients at mRNA level from three independent Gene Expression Omnibus (GEO) data sets. We found our model to be independent of the International Prognostic Index (IPI), moreover, it can augment the predictive power of IPI. In summary, our three-gene model is sufficient to predict survival of DLBCL patients via measuring the concentration of three inflammatory cytokines in peripheral blood. PMID:27394196

  5. Body Composition Features Predict Overall Survival in Patients With Hepatocellular Carcinoma

    PubMed Central

    Singal, Amit G; Zhang, Peng; Waljee, Akbar K; Ananthakrishnan, Lakshmi; Parikh, Neehar D; Sharma, Pratima; Barman, Pranab; Krishnamurthy, Venkataramu; Wang, Lu; Wang, Stewart C; Su, Grace L

    2016-01-01

    Objectives: Existing prognostic models for patients with hepatocellular carcinoma (HCC) have limitations. Analytic morphomics, a novel process to measure body composition using computational image-processing algorithms, may offer further prognostic information. The aim of this study was to develop and validate a prognostic model for HCC patients using body composition features and objective clinical information. Methods: Using computed tomography scans from a cohort of HCC patients at the VA Ann Arbor Healthcare System between January 2006 and December 2013, we developed a prognostic model using analytic morphomics and routine clinical data based on multivariate Cox regression and regularization methods. We assessed model performance using C-statistics and validated predicted survival probabilities. We validated model performance in an external cohort of HCC patients from Parkland Hospital, a safety-net health system in Dallas County. Results: The derivation cohort consisted of 204 HCC patients (20.1% Barcelona Clinic Liver Cancer classification (BCLC) 0/A), and the validation cohort had 225 patients (22.2% BCLC 0/A). The analytic morphomics model had good prognostic accuracy in the derivation cohort (C-statistic 0.80, 95% confidence interval (CI) 0.71–0.89) and external validation cohort (C-statistic 0.75, 95% CI 0.68–0.82). The accuracy of the analytic morphomics model was significantly higher than that of TNM and BCLC staging systems in derivation (P<0.001 for both) and validation (P<0.001 for both) cohorts. For calibration, mean absolute errors in predicted 1-year survival probabilities were 5.3% (90% quantile of 7.5%) and 7.6% (90% quantile of 12.5%) in the derivation and validation cohorts, respectively. Conclusion: Body composition features, combined with readily available clinical data, can provide valuable prognostic information for patients with newly diagnosed HCC. PMID:27228403

  6. Albumin concentrations plus neutrophil lymphocyte ratios for predicting overall survival after curative resection for gastric cancer

    PubMed Central

    Sun, Xiaowei; Wang, Juncheng; Liu, Jianjun; Chen, Shangxiang; Liu, Xuechao

    2016-01-01

    Background In patients with gastric cancer (GC), survival is poor, given the late diagnosis. Risk-stratifying these patients earlier could help improve care. We determined whether combining preoperative albumin concentration and the neutrophil lymphocyte ratio (COA-NLR) could predict overall survival (OS) better than other prognostic indexes. Methods We calculated the COA-NLR and other prognostic indexes with data obtained within 1 week before surgery in a retrospective analysis of patients with GC undergoing curative resection between September 2000 and November 2012. Patients with concentrations of hypoalbuminemia above 35 g/L and an NLR value of 2.3 or higher were given a score of 2. Patients with one of these conditions or neither were allocated scores of 1 or 0, respectively. Patients were monitored until July 2014. Results OS in the 873 eligible patients was 44.9% in patients with a COA-NLR score of 0, 29.8% in patients with a score of 1, and 20.3% in patients with a score of 2 (P<0.001). The COA-NLR score was independently associated with OS (hazard ratio, 1.35; 95% confidence interval, 1.12 to 1.63; P=0.002). Moreover, the area under the receiver operating characteristics curve was 0.62 for the COA-NLR, which was significantly higher (<0.001) than that of the NLR ratio (0.60), the Glasgow prognostic score (0.58), and the platelet lymphocyte ratio (0.54). The COA-NLR was especially accurate for patients with stage I–II GC and the three values (0, 1, and 2) divided patients into subgroups more accurately than did the other indexes (area under the curve value: 0.66, P<0.001). Conclusion The preoperative COA-NLR index is useful for predicting postoperative OS in patients with GC and can be used to guide targeted therapy. PMID:27536130

  7. Predictive Capability of Near-Infrared Fluorescence Angiography in Submental Perforator Flap Survival

    PubMed Central

    Matsui, Aya; Lee, Bernard T.; Winer, Joshua H.; Laurence, Rita G.; Frangioni, John V.

    2010-01-01

    Background Perforator flaps have become increasingly popular in reconstructive surgery as patients experience less donor-site morbidity than with conventional musculocutaneous flaps. Previously, our laboratory described the intraoperative use of near-infrared (NIR) fluorescence angiography for patient-specific perforator-flap design. This study evaluates the predictive capability of NIR fluorescence angiography for flap survival in submental flap reconstruction. Methods NIR angiography was performed using indocyanine green at 0, 0.5, 24, 48, and 72 h post-surgery after flap creation in 12 pigs. A single perforator artery was preserved during flap creation based on location (central or non-central) and dominance (dominant or non-dominant). Venous drainage, arterial perfusion, and perfused area as percentage of total flap were analyzed. Clinical assessments of perfusion were compared with those made using NIR imaging and histology. Results Use of NIR fluorescence angiography immediately after flap creation accurately predicted areas of perfusion at 72 h (p = 0.0013), compared to the initial clinical assessment (p = 0.3085). Identification of necrosis by histology at 72 h correlated with NIR findings of insufficient arterial perfusion immediately after flap creation. No statistically significant differences in perfusion metrics were detected based on location or dominance of the preserved perforator; however, flaps containing central perforators had a higher percent perfused area than those with non-central perforators. Conclusions The use of NIR angiography immediately after flap creation can predict areas of perfusion at 72 h. This predictive capability may permit intraoperative revision of compromised flaps that have a high likelihood of failure. PMID:21042109

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

    SciTech Connect

    DeVries, Alexander Friedrich; Piringer, Gudrun; Kremser, Christian; Judmaier, Werner; Saely, Christoph Hubert; Lukas, Peter; Öfner, Dietmar

    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.

  9. Transcriptomic analysis predicts survival and sensitivity to anticancer drugs of patients with a pancreatic adenocarcinoma.

    PubMed

    Duconseil, Pauline; Gilabert, Marine; Gayet, Odile; Loncle, Celine; Moutardier, Vincent; Turrini, Olivier; Calvo, Ezequiel; Ewald, Jacques; Giovannini, Marc; Gasmi, Mohamed; Bories, Erwan; Barthet, Marc; Ouaissi, Mehdi; Goncalves, Anthony; Poizat, Flora; Raoul, Jean Luc; Secq, Veronique; Garcia, Stephane; Viens, Patrice; Iovanna, Juan; Dusetti, Nelson

    2015-04-01

    A major impediment to the effective treatment of patients with pancreatic ductal adenocarcinoma (PDAC) is the molecular heterogeneity of this disease, which is reflected in an equally diverse pattern of clinical outcome and in responses to therapies. We developed an efficient strategy in which PDAC samples from 17 consecutive patients were collected by endoscopic ultrasound-guided fine-needle aspiration or surgery and were preserved as breathing tumors by xenografting and as a primary culture of epithelial cells. Transcriptomic analysis was performed from breathing tumors by an Affymetrix approach. We observed significant heterogeneity in the RNA expression profile of tumors. However, the bioinformatic analysis of these data was able to discriminate between patients with long- and short-term survival corresponding to patients with moderately or poorly differentiated PDAC tumors, respectively. Primary culture of cells allowed us to analyze their relative sensitivity to anticancer drugs in vitro using a chemogram, similar to the antibiogram for microorganisms, establishing an individual profile of drug sensitivity. As expected, the response was patient dependent. We also found that transcriptomic analysis predicts the sensitivity of cells to the five anticancer drugs most frequently used to treat patients with PDAC. In conclusion, using this approach, we found that transcriptomic analysis could predict the sensitivity to anticancer drugs and the clinical outcome of patients with PDAC. PMID:25765988

  10. Upregulation of spondin-2 predicts poor survival of colorectal carcinoma patients

    PubMed Central

    Wang, Jie; Cui, Shu-Jian; Lou, Xiao-Min; Yan, Bing; Qiao, Jie; Jiang, Ying-Hua; Zhang, Li-Jun; Yang, Peng-Yuan; Liu, Feng

    2015-01-01

    Colorectal cancer (CRC) is the third and second most common cancer in males and females worldwide, respectively. Spondin-2 is a conserved secreted extracellular matrix protein and a candidate cancer biomarker. Here we found that Spondin-2 mRNA was upregulated in CRC tissues using quantitative RT-PCR and data-mining of public Oncomine microarray datasets. Spondin-2 protein was increased in CRC tissues, as revealed by immunohistochemistry analyses of two tissue microarrays containing 180 cases. Spondin-2 gene expression was significantly associated with CRC stage, T stage, M stage and Dukes stage, while its protein was associated with age and M stage. Kaplan-Meier analysis revealed that the upregulated Spondin-2 mRNA and protein predicted poor prognosis of CRC patients. Univariate and multivariate Cox regression analyses indicated that grade, recurrence, N stage and high Spondin-2 were independent predictors of overall survival of CRC patients. ELISA revealed that plasma Spondin-2 was upregulated in CRC and dropped after surgery. Receiver operating characteristic curve analysis demonstrated that plasma Spondin-2 has superior predictive performance for CRC with an area under the curve of 0.959 and the best sensitivity/specificity of 100%/90%. Furthermore, ectopic expression of Spondin-2 enhanced colon cancer cell proliferation. Spondin-2 could be an independent diagnostic and prognostic biomarker of colon cancer. PMID:25945835

  11. Upregulation of spondin-2 predicts poor survival of colorectal carcinoma patients.

    PubMed

    Zhang, Qian; Wang, Xiao-Qing; Wang, Jie; Cui, Shu-Jian; Lou, Xiao-Min; Yan, Bing; Qiao, Jie; Jiang, Ying-Hua; Zhang, Li-Jun; Yang, Peng-Yuan; Liu, Feng

    2015-06-20

    Colorectal cancer (CRC) is the third and second most common cancer in males and females worldwide, respectively. Spondin-2 is a conserved secreted extracellular matrix protein and a candidate cancer biomarker. Here we found that Spondin-2 mRNA was upregulated in CRC tissues using quantitative RT-PCR and data-mining of public Oncomine microarray datasets. Spondin-2 protein was increased in CRC tissues, as revealed by immunohistochemistry analyses of two tissue microarrays containing 180 cases. Spondin-2 gene expression was significantly associated with CRC stage, T stage, M stage and Dukes stage, while its protein was associated with age and M stage. Kaplan-Meier analysis revealed that the upregulated Spondin-2 mRNA and protein predicted poor prognosis of CRC patients. Univariate and multivariate Cox regression analyses indicated that grade, recurrence, N stage and high Spondin-2 were independent predictors of overall survival of CRC patients. ELISA revealed that plasma Spondin-2 was upregulated in CRC and dropped after surgery. Receiver operating characteristic curve analysis demonstrated that plasma Spondin-2 has superior predictive performance for CRC with an area under the curve of 0.959 and the best sensitivity/specificity of 100%/90%. Furthermore, ectopic expression of Spondin-2 enhanced colon cancer cell proliferation. Spondin-2 could be an independent diagnostic and prognostic biomarker of colon cancer. PMID:25945835

  12. Inferior alveolar nerve repositioning.

    PubMed

    Louis, P J

    2001-09-01

    Nerve repositioning is a viable alternative for patients with an atrophic edentulous posterior mandible. Patients, however, should be informed of the potential risks of neurosensory disturbance. Documentation of the patient's baseline neurosensory function should be performed with a two-point discrimination test or directional brush stroke test preoperatively and postoperatively. Recovery of nerve function should be expected in 3 to 6 months. The potential for mandibular fracture when combining nerve repositioning with implant placement also should be discussed with the patient. This can be avoided by minimizing the amount of buccal cortical plate removal during localization of the nerve and maintaining the integrity of the inferior cortex of the mandible. Additionally, avoid overseating the implant, thus avoiding stress along the inferior border of the mandible. The procedure does allow for the placement of longer implants, which should improve implant longevity. Patients undergoing this procedure have expressed overall satisfaction with the results. Nerve repositioning also can be used to preserve the inferior alveolar nerve during resection of benign tumors or cysts of the mandible. This procedure allows the surgeon to maintain nerve function in situations in which the nerve would otherwise have to be resected. PMID:11665379

  13. PIAS3 expression in squamous cell lung cancer is low and predicts overall survival

    PubMed Central

    Abbas, Rime; McColl, Karen S; Kresak, Adam; Yang, Michael; Chen, Yanwen; Fu, Pingfu; Wildey, Gary; Dowlati, Afshin

    2015-01-01

    Unlike lung adenocarcinoma, little progress has been made in the treatment of squamous cell lung carcinoma (SCC). The Cancer Genome Atlas (TCGA) has recently reported that receptor tyrosine kinase signaling pathways are altered in 26% of SCC tumors, validating the importance of downstream Signal Transducers and Activators of Transcription 3 (STAT3) activity as a prime therapeutic target in this cancer. In the present report we examine the status of an endogenous inhibitor of STAT3, called Protein Inhibitor of Activated STAT3 (PIAS3), in SCC and its potential role in this disease. We examine PIAS3 expression in SCC tumors and cell lines by immunohistochemistry of a tissue microarray and western blotting. PIAS3 mRNA expression and survival data are analyzed in the TCGA data set. SCC cell lines are treated with curcumin to regulate PIAS3 expression and cell growth. PIAS3 protein expression is decreased in a majority of lung SCC tumors and cell lines. Analysis of PIAS3 mRNA transcript levels demonstrated that low PIAS3 levels predicted poor survival; Cox regression analysis revealed a hazard ratio of 0.57 (95% CI: 0.37–0.87), indicating a decrease in the risk of death by 43% for every unit elevation in PIAS3 gene expression. Curcumin treatment increased endogenous PIAS3 expression and decreased cell growth and viability in Calu-1 cells, a model of SCC. Our results implicate PIAS3 loss in the pathology of lung SCC and raise the therapeutic possibility of upregulating PIAS3 expression as a single target that can suppress signaling from the multiple receptor tyrosine kinase receptors found to be amplified in SCC. PMID:25573684

  14. Fitness predicts long-term survival after a cardiovascular event: a prospective cohort study

    PubMed Central

    Barons, Martine J; Turner, Sally; Parsons, Nicholas; Griffiths, Frances; Bethell, Hugh; Weich, Scott; Thorogood, Margaret

    2015-01-01

    Objectives To identify the role of fitness, fitness change, body mass index and other factors in predicting long-term (>5 years) survival in patients with coronary heart disease. Design Cohort study of patients with coronary heart disease recruited from 1 January 1993 to 31 December 2002, followed up to March 2011 (1 day to 18 years 3 months, mean 10.7 years). Setting A community-based National Health Service (NHS) cardiac rehabilitation programme serving the Basingstoke and Alton area in Hampshire, UK. Participants An unselected cohort of NHS patients, 2167 men and 547 women aged 28–88 years, who attended the rehabilitation programme following acute myocardial infarction, an episode of angina or revascularisation, and had a baseline fitness test. Main outcome measures Cardiovascular mortality and all-cause mortality. Results A high level of fitness (VO2≥22 mL/kg/min for men, VO2≥19 mL/kg/min for women) at completion of the programme was associated with decreased all-cause death, as was a prescription for statins or aspirin, and female gender. Increase in all-cause mortality was associated with higher age and ACE inhibitors prescription. Higher risk of cardiovascular mortality was associated with increasing age, prescriptions for ACE inhibitor, and diagnosis of myocardial infarction or angina as compared with the other diagnoses. Conclusions Prior fitness and fitness improvement are strong predictors of long-term survival in patients who have experienced a cardiac event or procedure. Some secondary prevention medications make a significant contribution to reducing all-cause mortality and cardiovascular mortality in these patients. This study supports public health messages promoting fitness for life. PMID:26493455

  15. Plasma matrix metalloproteinase 1 improves the detection and survival prediction of esophageal squamous cell carcinoma

    PubMed Central

    Chen, Yu-Kuei; Tung, Chun-Wei; Lee, Jui-Ying; Hung, Yi-Chun; Lee, Chien-Hung; Chou, Shah-Hwa; Lin, Hung-Shun; Wu, Ming-Tsang; Wu, I-Chen

    2016-01-01

    This study aimed to identify noninvasive protein markers capable of detecting the presence and prognosis of esophageal squamous-cell carcinoma (ESCC). Analyzing microarray expression data collected from 17-pair ESCC specimens, we identified one protein, matrix metalloproteinase-1 (MMP1), as a possibly useful marker. Plasma MMP1 was then measured by enzyme-linked immunosorbent assay (ELISA) in 210 ESCC patients and 197 healthy controls. ESCC patients had higher mean levels of MMP1 than controls (8.7 ± 7.5 vs. 6.7 ± 4.9 ng/mL, p < 0.0001). Using the highest quartile level (9.67 ng/mL) as cut-off, we found a 9.0-fold risk of ESCC in those with higher plasma MMP1 after adjusting for covariates (95% confidence interval = 2.2, 36.0). Heavy smokers and heavy drinkers with higher plasma MMP1 had 61.4- and 31.0 times the risk, respectively, than non-users with lower MMP1. In the survival analysis, compared to those with MMP1 ≤ 9.67 ng/mL, ESCC patients with MMP1 > 9.67 ng/mL had a 48% increase in the risk of ESCC death (adjusted hazard ratio = 1.48; 95% CI = 1.04–2.10). In conclusion, plasma MMP1 may serve as a noninvasive marker of detecting the presence and predicting the survival of ESCC. PMID:27436512

  16. A Mycobacterium avium subsp. paratuberculosis Predicted Serine Protease Is Associated with Acid Stress and Intraphagosomal Survival.

    PubMed

    Kugadas, Abirami; Lamont, Elise A; Bannantine, John P; Shoyama, Fernanda M; Brenner, Evan; Janagama, Harish K; Sreevatsan, Srinand

    2016-01-01

    The 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 macrophages and MAC-T cells that 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 mc(2) 155, was designed to express MAP0403 and when exposed to either macrophages or in vitro acid stress had increased bacterial cell viability, which corresponds to maintenance of intra-bacterial pH in acidic (pH = 5) conditions, compared to the parent strain. 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. PMID:27597934

  17. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    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.

  18. Overweight and obesity predict better overall survival rates in cancer patients with distant metastases.

    PubMed

    Tsang, Ngan Ming; Pai, Ping Ching; Chuang, Chi Cheng; Chuang, Wen Ching; Tseng, Chen Kan; Chang, Kai Ping; Yen, Tzu Chen; Lin, Jen Der; Chang, Joseph Tung Chieh

    2016-04-01

    Recent studies conducted in patients with chronic diseases have reported an inverse association between body mass index (BMI) and mortality. However, the question as to whether BMI may predict prognosis in patients with metastatic cancer remains open. We therefore designed the current retrospective study to investigate the potential association between BMI and overall survival (OS) in patients with distant metastases (DM) and a favorable performance status. Between 2000 and 2012, a total of 4010 cancer patients with DM who required radiotherapy (RT) and had their BMI measured at the initiation of RT were identified. The relation between BMI and OS was examined by univariate and multivariable analysis. The median OS time was 3.23 months (range: 0.1-122.17) for underweight patients, 6.08 months (range: 0.03-149.46) for normal-weight patients, 7.99 months (range: 0.07-158.01) for overweight patients, and 12.49 months (range, 0.2-164.1) for obese patients (log-rank: P < 0.001). Compared with normal-weight patients, both obese (HR = 0.676; 95% P < 0.001) and overweight individuals (HR = 0.84; P < 0.001) had a reduced risk of all-cause mortality in multivariable analysis. Conversely, underweight patients had a significantly higher risk of death from all causes (HR = 1.41; P < 0.001). Overweight and obesity are independent predictors of better OS in metastatic patients with a good performance status. Increased BMI may play a role to identify metastatic patients with superior survival outcome and exhibit a potential to encourage aggressive management in those patients even with metastases. PMID:26811258

  19. A Mycobacterium avium subsp. paratuberculosis Predicted Serine Protease Is Associated with Acid Stress and Intraphagosomal Survival

    PubMed Central

    Kugadas, Abirami; Lamont, Elise A.; Bannantine, John P.; Shoyama, Fernanda M.; Brenner, Evan; Janagama, Harish K.; Sreevatsan, Srinand

    2016-01-01

    The 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 macrophages and MAC-T cells that 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 increased bacterial cell viability, which corresponds to maintenance of intra-bacterial pH in acidic (pH = 5) conditions, compared to the parent strain. 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. PMID:27597934

  20. Clinical variables and primary tumor characteristics predictive of the development of melanoma brain metastasis and post-brain metastasis survival

    PubMed Central

    Zakrzewski, Jan; Geraghty, Laurel N.; Rose, Amy E.; Christos, Paul J.; Mazumdar, Madhu; Polsky, David; Shapiro, Richard; Berman, Russell; Darvishian, Farbod; Hernando, Eva; Pavlick, Anna; Osman, Iman

    2010-01-01

    Background Melanoma patients who develop brain metastases (B-Met) have limited survival and are excluded from most clinical trials. In this study, we sought to identify primary tumor characteristics and clinical features predictive of B-Met development and post-B-Met survival. Methods We studied a prospectively accrued cohort of 900 melanoma patients to identify clinicopathologic features of primary melanoma (e.g. thickness, ulceration, mitotic index, lymphovascular invasion) that are predictive of B-Met development and post-B-Met survival. Associations between clinical variables present at the time of B-Met diagnosis (e.g. extracranial metastases, B-Met location, presence of neurological symptoms) and post-B-Met survival were also assessed. Univariate associations were analyzed using Kaplan-Meier survival analysis, and the effect of independent predictors assessed using a multivariate Cox proportional hazards regression. Results 89 (10%) of the 900 patients developed B-Met. Ulceration and site of primary on the head and neck were independent predictors of B-Met development on multivariate analysis (p=0.001 and p=0.003, respectively). Clinical variables predictive of post-B-Met survival on multivariate analysis included the presence of neurological symptoms (p=0.008) and extracranial metastases (p=0.04). Ulceration was the only primary tumor characteristic that remained a significant predictor of post-B-Met survival on multivariate analysis (p=0.04). Conclusions Primary tumor ulceration was the strongest predictor of B-Met development and remained an independent predictor of decreased post-B-Met survival in a multivariate analysis inclusive of primary tumor characteristics and clinical variables. Our results suggest that patients with ulcerated primaries should be prospectively studied to determine if heightened surveillance for B-Met can improve clinical outcome. PMID:21472718

  1. Go/No Go task performance predicts cortical thickness in the caudal inferior frontal gyrus in young adults with and without ADHD.

    PubMed

    Newman, Erik; Jernigan, Terry L; Lisdahl, Krista M; Tamm, Leanne; Tapert, Susan F; Potkin, Steven G; Mathalon, Daniel; Molina, Brooke; Bjork, James; Castellanos, F Xavier; Swanson, James; Kuperman, Joshua M; Bartsch, Hauke; Chen, Chi-Hua; Dale, Anders M; Epstein, Jeffery N; Group, Mta Neuroimaging

    2016-09-01

    Response inhibition deficits are widely believed to be at the core of Attention-Deficit Hyperactivity Disorder (ADHD). Several studies have examined neural architectural correlates of ADHD, but research directly examining structural correlates of response inhibition is lacking. Here we examine the relationship between response inhibition as measured by a Go/No Go task, and cortical surface area and thickness of the caudal inferior frontal gyrus (cIFG), a region implicated in functional imaging studies of response inhibition, in a sample of 114 young adults with and without ADHD diagnosed initially during childhood. We used multiple linear regression models to test the hypothesis that Go/No Go performance would be associated with cIFG surface area or thickness. Results showed that poorer Go/No Go performance was associated with thicker cIFG cortex, and this effect was not mediated by ADHD status or history of substance use. However, independent of Go/No Go performance, persistence of ADHD symptoms and more frequent cannabis use were associated with thinner cIFG. Go/No Go performance was not associated with cortical surface area. The association between poor inhibitory functioning and thicker cIFG suggests that maturation of this region may differ in low performing participants. An independent association of persistent ADHD symptoms and frequent cannabis use with thinner cIFG cortex suggests that distinct neural mechanisms within this region may play a role in inhibitory function, broader ADHD symptomatology, and cannabis use. These results contribute to Research Domain Criteria (RDoC) by revealing novel associations between neural architectural phenotypes and basic neurobehavioral processes measured dimensionally. PMID:26404018

  2. Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study

    PubMed Central

    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

  3. What Matters Most for Predicting Survival? A Multinational Population-Based Cohort Study.

    PubMed

    Goldman, Noreen; Glei, Dana A; Weinstein, Maxine

    2016-01-01

    Despite myriad efforts among social scientists, epidemiologists, and clinicians to identify variables with strong linkages to mortality, few researchers have evaluated statistically the relative strength of a comprehensive set of predictors of survival. Here, we determine the strongest predictors of five-year mortality in four national, prospective studies of older adults. We analyze nationally representative surveys of older adults in four countries with similar levels of life expectancy: England (n = 6113, ages 52+), the US (n = 2023, ages 50+), Costa Rica (n = 2694, ages 60+), and Taiwan (n = 1032, ages 53+). Each survey includes a broad set of demographic, social, health, and biological variables that have been shown previously to predict mortality. We rank 57 predictors, 25 of which are available in all four countries, net of age and sex. We use the area under the receiver operating characteristic curve and assess robustness with additional discrimination measures. We demonstrate consistent findings across four countries with different cultural traditions, levels of economic development, and epidemiological transitions. Self-reported measures of instrumental activities of daily living limitations, mobility limitations, and overall self-assessed health are among the top predictors in all four samples. C-reactive protein, additional inflammatory markers, homocysteine, serum albumin, three performance assessments (gait speed, grip strength, and chair stands), and exercise frequency also discriminate well between decedents and survivors when these measures are available. We identify several promising candidates that could improve mortality prediction for both population-based and clinical populations. Better prognostic tools are likely to provide researchers with new insights into the behavioral and biological pathways that underlie social stratification in health and may allow physicians to have more informed discussions with patients about end-of-life treatment

  4. What Matters Most for Predicting Survival? A Multinational Population-Based Cohort Study

    PubMed Central

    Goldman, Noreen; Glei, Dana A; Weinstein, Maxine

    2016-01-01

    Despite myriad efforts among social scientists, epidemiologists, and clinicians to identify variables with strong linkages to mortality, few researchers have evaluated statistically the relative strength of a comprehensive set of predictors of survival. Here, we determine the strongest predictors of five-year mortality in four national, prospective studies of older adults. We analyze nationally representative surveys of older adults in four countries with similar levels of life expectancy: England (n = 6113, ages 52+), the US (n = 2023, ages 50+), Costa Rica (n = 2694, ages 60+), and Taiwan (n = 1032, ages 53+). Each survey includes a broad set of demographic, social, health, and biological variables that have been shown previously to predict mortality. We rank 57 predictors, 25 of which are available in all four countries, net of age and sex. We use the area under the receiver operating characteristic curve and assess robustness with additional discrimination measures. We demonstrate consistent findings across four countries with different cultural traditions, levels of economic development, and epidemiological transitions. Self-reported measures of instrumental activities of daily living limitations, mobility limitations, and overall self-assessed health are among the top predictors in all four samples. C-reactive protein, additional inflammatory markers, homocysteine, serum albumin, three performance assessments (gait speed, grip strength, and chair stands), and exercise frequency also discriminate well between decedents and survivors when these measures are available. We identify several promising candidates that could improve mortality prediction for both population-based and clinical populations. Better prognostic tools are likely to provide researchers with new insights into the behavioral and biological pathways that underlie social stratification in health and may allow physicians to have more informed discussions with patients about end-of-life treatment

  5. CD4+ follicular helper T cell infiltration predicts breast cancer survival

    PubMed Central

    Gu-Trantien, Chunyan; Loi, Sherene; Garaud, Soizic; Equeter, Carole; Libin, Myriam; de Wind, Alexandre; Ravoet, Marie; Le Buanec, Hélène; Sibille, Catherine; Manfouo-Foutsop, Germain; Veys, Isabelle; Haibe-Kains, Benjamin; Singhal, Sandeep K.; Michiels, Stefan; Rothé, Françoise; Salgado, Roberto; Duvillier, Hugues; Ignatiadis, Michail; Desmedt, Christine; Bron, Dominique; Larsimont, Denis; Piccart, Martine; Sotiriou, Christos; Willard-Gallo, Karen

    2013-01-01

    CD4+ T cells are critical regulators of immune responses, but their functional role in human breast cancer is relatively unknown. The goal of this study was to produce an image of CD4+ T cells infiltrating breast tumors using limited ex vivo manipulation to better understand the in vivo differences associated with patient prognosis. We performed comprehensive molecular profiling of infiltrating CD4+ T cells isolated from untreated invasive primary tumors and found that the infiltrating T cell subpopulations included follicular helper T (Tfh) cells, which have not previously been found in solid tumors, as well as Th1, Th2, and Th17 effector memory cells and Tregs. T cell signaling pathway alterations included a mixture of activation and suppression characterized by restricted cytokine/chemokine production, which inversely paralleled lymphoid infiltration levels and could be reproduced in activated donor CD4+ T cells treated with primary tumor supernatant. A comparison of extensively versus minimally infiltrated tumors showed that CXCL13-producing CD4+ Tfh cells distinguish extensive immune infiltrates, principally located in tertiary lymphoid structure germinal centers. An 8-gene Tfh signature, signifying organized antitumor immunity, robustly predicted survival or preoperative response to chemotherapy. Our identification of CD4+ Tfh cells in breast cancer suggests that they are an important immune element whose presence in the tumor is a prognostic factor. PMID:23778140

  6. A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma

    PubMed Central

    Wei, Jin-Huan; Haddad, Ahmed; Wu, Kai-Jie; Zhao, Hong-Wei; Kapur, Payal; Zhang, Zhi-Ling; Zhao, Liang-Yun; Chen, Zhen-Hua; Zhou, Yun-Yun; Zhou, Jian-Cheng; Wang, Bin; Yu, Yan-Hong; Cai, Mu-Yan; Xie, Dan; Liao, Bing; Li, Cai-Xia; Li, Pei-Xing; Wang, Zong-Ren; Zhou, Fang-Jian; Shi, Lei; Liu, Qing-Zuo; Gao, Zhen-Li; He, Da-Lin; Chen, Wei; Hsieh, Jer-Tsong; Li, Quan-Zhen; Margulis, Vitaly; Luo, Jun-Hang

    2015-01-01

    Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96−4.82; P=3.9 × 10−6−2.2 × 10−9), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual ‘stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system. PMID:26515236

  7. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report.

    PubMed

    Palumbo, Antonio; Bringhen, Sara; Mateos, Maria-Victoria; Larocca, Alessandra; Facon, Thierry; Kumar, Shaji K; Offidani, Massimo; McCarthy, Philip; Evangelista, Andrea; Lonial, Sagar; Zweegman, Sonja; Musto, Pellegrino; Terpos, Evangelos; Belch, Andrew; Hajek, Roman; Ludwig, Heinz; Stewart, A Keith; Moreau, Philippe; Anderson, Kenneth; Einsele, Hermann; Durie, Brian G M; Dimopoulos, Meletios A; Landgren, Ola; San Miguel, Jesus F; Richardson, Paul; Sonneveld, Pieter; Rajkumar, S Vincent

    2015-03-26

    We conducted a pooled analysis of 869 individual newly diagnosed elderly patient data from 3 prospective trials. At diagnosis, a geriatric assessment had been performed. An additive scoring system (range 0-5), based on age, comorbidities, and cognitive and physical conditions, was developed to identify 3 groups: fit (score = 0, 39%), intermediate fitness (score = 1, 31%), and frail (score ≥2, 30%). The 3-year overall survival was 84% in fit, 76% in intermediate-fitness (hazard ratio [HR], 1.61; P = .042), and 57% in frail (HR, 3.57; P < .001) patients. The cumulative incidence of grade ≥3 nonhematologic adverse events at 12 months was 22.2% in fit, 26.4% in intermediate-fitness (HR, 1.23; P = .217), and 34.0% in frail (HR, 1.74; P < .001) patients. The cumulative incidence of treatment discontinuation at 12 months was 16.5% in fit, 20.8% in intermediate-fitness (HR, 1.41; P = .052), and 31.2% in frail (HR, 2.21; P < .001) patients. Our frailty score predicts mortality and the risk of toxicity in elderly myeloma patients. The International Myeloma Working group proposes this score for the measurement of frailty in designing future clinical trials. These trials are registered at www.clinicaltrials.gov as #NCT01093136 (EMN01), #NCT01190787 (26866138MMY2069), and #NCT01346787 (IST-CAR-506). PMID:25628469

  8. Immune response genes and pathogen presence predict migration survival in wild salmon smolts.

    PubMed

    Jeffries, Ken M; Hinch, Scott G; Gale, Marika Kirstin; Clark, Timothy D; Lotto, Andrew G; Casselman, Matthew T; Li, Shaorong; Rechisky, Erin L; Porter, Aswea D; Welch, David W; Miller, Kristina M

    2014-12-01

    We present the first data to link physiological responses and pathogen presence with subsequent fate during migration of wild salmonid smolts. We tagged and non-lethally sampled gill tissue from sockeye salmon (Oncorhynchus nerka) smolts as they left their nursery lake (Chilko Lake, BC, Canada) to compare gene expression profiles and freshwater pathogen loads with migration success over the first ~1150 km of their migration to the North Pacific Ocean using acoustic telemetry. Fifteen per cent of smolts were never detected again after release, and these fish had gene expression profiles consistent with an immune response to one or more viral pathogens compared with fish that survived their freshwater migration. Among the significantly upregulated genes of the fish that were never detected postrelease were MX (interferon-induced GTP-binding protein Mx) and STAT1 (signal transducer and activator of transcription 1-alpha/beta), which are characteristic of a type I interferon response to viral pathogens. The most commonly detected pathogen in the smolts leaving the nursery lake was infectious haematopoietic necrosis virus (IHNV). Collectively, these data show that some of the fish assumed to have died after leaving the nursery lake appeared to be responding to one or more viral pathogens and had elevated stress levels that could have contributed to some of the mortality shortly after release. We present the first evidence that changes in gene expression may be predictive of some of the freshwater migration mortality in wild salmonid smolts. PMID:25354752

  9. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report

    PubMed Central

    Bringhen, Sara; Mateos, Maria-Victoria; Larocca, Alessandra; Facon, Thierry; Kumar, Shaji K.; Offidani, Massimo; McCarthy, Philip; Evangelista, Andrea; Lonial, Sagar; Zweegman, Sonja; Musto, Pellegrino; Terpos, Evangelos; Belch, Andrew; Hajek, Roman; Ludwig, Heinz; Stewart, A. Keith; Moreau, Philippe; Anderson, Kenneth; Einsele, Hermann; Durie, Brian G. M.; Dimopoulos, Meletios A.; Landgren, Ola; San Miguel, Jesus F.; Richardson, Paul; Sonneveld, Pieter; Rajkumar, S. Vincent

    2015-01-01

    We conducted a pooled analysis of 869 individual newly diagnosed elderly patient data from 3 prospective trials. At diagnosis, a geriatric assessment had been performed. An additive scoring system (range 0-5), based on age, comorbidities, and cognitive and physical conditions, was developed to identify 3 groups: fit (score = 0, 39%), intermediate fitness (score = 1, 31%), and frail (score ≥2, 30%). The 3-year overall survival was 84% in fit, 76% in intermediate-fitness (hazard ratio [HR], 1.61; P = .042), and 57% in frail (HR, 3.57; P < .001) patients. The cumulative incidence of grade ≥3 nonhematologic adverse events at 12 months was 22.2% in fit, 26.4% in intermediate-fitness (HR, 1.23; P = .217), and 34.0% in frail (HR, 1.74; P < .001) patients. The cumulative incidence of treatment discontinuation at 12 months was 16.5% in fit, 20.8% in intermediate-fitness (HR, 1.41; P = .052), and 31.2% in frail (HR, 2.21; P < .001) patients. Our frailty score predicts mortality and the risk of toxicity in elderly myeloma patients. The International Myeloma Working group proposes this score for the measurement of frailty in designing future clinical trials. These trials are registered at www.clinicaltrials.gov as #NCT01093136 (EMN01), #NCT01190787 (26866138MMY2069), and #NCT01346787 (IST-CAR-506). PMID:25628469

  10. Prediction of recurrence-free survival using a protein expression-based risk classifier for head and neck cancer

    PubMed Central

    Chauhan, S S; Kaur, J; Kumar, M; Matta, A; Srivastava, G; Alyass, A; Assi, J; Leong, I; MacMillan, C; Witterick, I; Colgan, T J; Shukla, N K; Thakar, A; Sharma, M C; Siu, K W M; Walfish, P G; Ralhan, R

    2015-01-01

    Loco-regional recurrence in 50% of oral squamous cell carcinoma (OSCC) patients poses major challenge for oncologists. Lack of biomarkers that can predict disease aggressiveness and recurrence risk makes the scenario more dismal. On the basis of our earlier global proteomic analyses we identified five differentially expressed proteins in OSCC. This study aimed to develop protein biomarkers-based prognostic risk prediction model for OSCC. Sub-cellular expression of five proteins, S100A7, heterogeneous nuclear ribonucleoproteinK (hnRNPK), prothymosin α (PTMA), 14-3-3ζ and 14-3-3σ was analyzed by immunohistochemistry in test set (282 Indian OSCCs and 209 normal tissues), correlated with clinic–pathological parameters and clinical outcome over 12 years to develop a risk model for prediction of recurrence-free survival. This risk classifier was externally validated in 135 Canadian OSCC and 96 normal tissues. Biomarker signature score based on PTMA, S100A7 and hnRNPK was associated with recurrence free survival of OSCC patients (hazard ratio=1.11; 95% confidence interval 1.08, 1.13, P<0.001, optimism-corrected c-statistic=0.69) independent of clinical parameters. Biomarker signature score stratified OSCC patients into high- and low-risk groups with significant difference for disease recurrence. The high-risk group had median survival 14 months, and 3-year survival rate of 30%, whereas low-risk group survival probability did not reach 50%, and had 3-year survival rate of 71%. As a powerful predictor of 3-year recurrence-free survival in OSCC patients, the newly developed biomarkers panel risk classifier will facilitate patient counseling for personalized treatment. PMID:25893634

  11. Expression and Immune Responses to MAGE Antigens Predict Survival in Epithelial Ovarian Cancer

    PubMed Central

    Daudi, Sayeema; Eng, Kevin H.; Mhawech-Fauceglia, Paulette; Morrison, Carl; Miliotto, Anthony; Beck, Amy; Matsuzaki, Junko; Tsuji, Takemasa; Groman, Adrienne; Gnjatic, Sacha; Spagnoli, Guillo; Lele, Shashikant; Odunsi, Kunle

    2014-01-01

    The MAGE cancer-testis antigens (CTA) are attractive candidates for immunotherapy. The aim of this study was to determine the frequency of expression, humoral immunity and prognostic significance of MAGE CTA in human epithelial ovarian cancer (EOC). mRNA or protein expression frequencies were determined for MAGE-A1, -A3, -A4, -A10 and -C1 (CT7) in tissue samples obtained from 400 patients with EOC. The presence of autologous antibodies against the MAGE antigens was determined from 285 serum samples. The relationships between MAGE expression, humoral immunity to MAGE antigens, and clinico-pathologic characteristics were studied. The individual frequencies of expression were as follows: A1: 15% (42/281), A3: 36% (131/390), A4: 47% (186/399), A10: 52% (204/395), C1: 16% (42/267). Strong concordant expression was noted with MAGE-A1:–A4, MAGE-A1:–C1 and MAGE-A4:–A10 (p<0.0005). Expression of MAGE-A1 or -A10 antigens resulted in poor progression free survival (PFS) (OR 1.44, CI 1.01–2.04, p = 0.044 and OR 1.3, CI 1.03–1.64, p = 0.03, respectively); whereas, MAGE-C1 expression was associated with improved PFS (OR 0.62, CI 0.42–0.92, p = 0.016). The improved PFS observed for MAGE-C1 expression, was diminished by co-expression of MAGE-A1 or -A10. Spontaneous humoral immunity to the MAGE antigens was present in 9% (27/285) of patients, and this predicted poor overall survival (log-rank test p = 0.0137). These findings indicate that MAGE-A1, MAGE-A4, MAGE-A3, and MAGE-A10 are priority attractive targets for polyvalent immunotherapy in ovarian cancer patients. PMID:25101620

  12. An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia

    PubMed Central

    Metzeler, Klaus H.; Hummel, Manuela; Bloomfield, Clara D.; Spiekermann, Karsten; Braess, Jan; Sauerland, Maria-Cristina; Heinecke, Achim; Radmacher, Michael; Marcucci, Guido; Whitman, Susan P.; Maharry, Kati; Paschka, Peter; Larson, Richard A.; Berdel, Wolfgang E.; Büchner, Thomas; Wörmann, Bernhard; Mansmann, Ulrich; Hiddemann, Wolfgang

    2008-01-01

    Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P = .002), event-free survival (HR = 1.73; P = .001), and relapse-free survival (HR = 1.76; P = .025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR = 4.11; P < .001), event-free survival (HR = 2.90; P < .001), and relapse-free survival (HR = 3.14, P < .001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene-expression signature that offers additional prognostic information for patients with CN-AML. PMID:18716133

  13. A Hybrid Approach of Gene Sets and Single Genes for the Prediction of Survival Risks with Gene Expression Data

    PubMed Central

    Seok, Junhee; Davis, Ronald W.; Xiao, Wenzhong

    2015-01-01

    Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn’t been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge. PMID:25933378

  14. Advanced MRI may complement histological diagnosis of lower grade gliomas and help in predicting survival.

    PubMed

    Cuccarini, Valeria; Erbetta, A; Farinotti, M; Cuppini, L; Ghielmetti, F; Pollo, B; Di Meco, F; Grisoli, M; Filippini, G; Finocchiaro, G; Bruzzone, M G; Eoli, M

    2016-01-01

    MRI grading of grade II and III gliomas may have an important impact on treatment decisions. Occasionally,both conventional MRI (cMRI) and histology fail to clearly establish the tumour grade. Three cMRI features(no necrosis; no relevant oedema; absent or faint contrast enhancement) previously validated in 196 patients with supratentorial gliomas directed our selection of 68 suspected low-grade gliomas (LGG) that were also investigated by advanced MRI (aMRI), including perfusion weighted imaging (PWI), diffusion weighted imaging(DWI) and spectroscopy. All the gliomas had histopathological diagnoses. Sensitivity and specificity of cMRI preoperative diagnosis were 78.5 and 38.5 %, respectively, and 85.7 and 53.8 % when a MRI was included, respectively. ROC analysis showed that cut-off values of 1.29 for maximum rCBV, 1.69 for minimum rADC, 2.1 for rCho/Cr ratio could differentiate between LGG and HGG with a sensitivity of 61.5, 53.8, and 53.8 % and a specificity of 54.7, 43 and 64.3 %, respectively. A significantly longer OS was observed in patients with a maximum rCBV<1.46 and minimum rADC>1.69 (80 vs 55 months, p = 0.01; 80 vs 51 months, p = 0.002, respectively). This result was also confirmed when cases were stratified according to pathology (LGG vs HGG). The ability of a MRI to differentiate between LGG and HGG and to predict survival improved as the number of a MRI techniques considered increased. In a selected population of suspected LGG,classification by cMRI underestimated the actual fraction of HGG. aMRI slightly increased the diagnostic accuracy compared to histopathology. However, DWI and PWI were prognostic markers independent of histological grade. PMID:26468137

  15. Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma.

    PubMed

    Kucharz, Jakub; Giza, Agnieszka; Dumnicka, Paulina; Kuzniewski, Marek; Kusnierz-Cabala, Beata; Bryniarski, Pawel; Herman, Roma; Zygulska, Aneta Lidia; Krzemieniecki, Krzysztof

    2016-10-01

    Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in 'low' and 'intermediate' Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81-0.99) and 0.76 (0.65-0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib's inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential. PMID:27573381

  16. Prognostic Value of Preoperatively Obtained Clinical and Laboratory Data in Predicting Survival Following Orthotopic Liver Transplantation

    PubMed Central

    Cuervas-Mons, Valentin; Millan, Isabel; Gavaler, Judith S.; Starzl, Thomas E.; Van Thiel, David H.

    2010-01-01

    Twenty-seven clinical and laboratory data and the subsequent clinical course of 93 consecutive adult patients who underwent orthotopic liver transplantation for various chronic advanced liver diseases were analyzed retrospectively to assess the risk factors of early major bacterial infection and death after the procedure. Forty-one patients (44%) had early major bacterial infection during hospitalization for orthotopic liver transplantation. The mortality rate was 70.7% in patients with early major bacterial infection and was 7.7% in patients without early major bacterial infection (p < 0.001). Total serum bilirubin, total white blood cell count and polymorphonuclear cell count, IgG (all p < 0.05) and plasma creatinine level (p < 0.001) were higher in patients that developed early major bacterial infection than in those who did not. By step-wise discriminant analysis, the strongest risk factor for early major bacterial infection was the serum creatinine level, which achieved an accuracy of 69% for a creatinine level greater than 1.58 mg per dl. Seven variables (ascites, hepatic encephalopathy, elevated white blood and polymorphonuclear cell count, decreased helper to suppressor T cell ratio and elevated plasma creatinine and bilirubin levels) were associated with a significant increased risk for death. A step-wise discriminant analysis of these seven factors resulted in the demonstration of serum creatinine as the greatest risk factor for mortality. A preoperative serum creatinine either less than or greater than 1.72 mg per dl accurately predicts survival or death, respectively, in 79% of cases. These data suggest that the baseline preoperative serum creatinine level provides the best indication of the short-term prognosis after liver transplantation than does any other preoperatively obtained index of the patient’s status. PMID:3530947

  17. The cardio-renal-anaemia syndrome predicts survival in peritoneally dialyzed patients

    PubMed Central

    Zbroch, Edyta; Malyszko, Jacek; Mysliwiec, Michal; Iaina, Adrian

    2010-01-01

    Introduction Anaemia is one of the arms of the cardio-renal-anaemia syndrome (CRA) in chronic kidney disease (CKD) patients. 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. Material and methods Fifty-six patients on peritoneal dialysis were followed for 1 year. Definition of the severity of the CRA in dialysis patients: cardiac arm – NYHA class I-IV = 1-4 points, renal arm – non-diabetic patients age < 65 =1 point, non-diabetic patients age>65 = 2 points, diabetic patients age < 65 = 3 points, diabetic patients age>65 = 4 points, anaemia arm – Hb 11-13 g/dl (male), 11-12 g/dl (female) = 1 point, Hb 10-11 g/dl = 2 points, Hb 9-10 g/dl = 3 points, Hb < 9 g/dl = 4 points. The severity score = cardiac + renal + anaemia arms score divided by 3 (maximum 4 points). Results A total of 10/56 patients (18%) died during the study. The median value for the severity score of the whole group was 1.69. In Kaplan-Meier analysis CRA severity score was strongly associated with mortality (p < 0.001). It also correlated with albumin, CRP, erythropoietin treatment, Hb and fasting glucose. In the multivariate regression analysis age, Hb, albumin, and presence of diabetes remained significant predictors of death. Conclusions The severity score of CRA syndrome in peritoneally dialyzed patients is an independent and very significant predictor of death. The patients with a high severity score had more hypoalbuminaemia, higher inflammation markers and higher prevalence of diabetes and chronic heart failure. Cardio-renal-anaemia syndrome severity scoring as defined by us could be an easy tool to predict outcome of dialysis patients. PMID:22371797

  18. A model to predict survival following pancreaticoduodenectomy for malignancy based on tumour site, stage and lymph node ratio☆

    PubMed Central

    Dasari, Bobby V.M.; Roberts, Keith J.; Hodson, James; Stevens, Lewis; Smith, Andrew M.; Hubscher, Stefan G.; Isaac, John; Muiesan, Paolo; Sutcliffe, Robert P.; Marudanayagam, Ravi; Mirza, Darius F.

    2016-01-01

    Background Site of tumour origin, lymph node metastases and lymph node ratio (LNR) are identified as important factors determining prognosis in patients undergoing pancreaticoduodenectomy (PD). This study hypothesised that a prognostic index to predict survival could be developed through statistical modelling based on these pathological variables. Methods Patients who underwent PD between 2004 and 2013 were included. Univariable and multivariable (Cox regression) analyses were performed to identify predictors of survival, and a prognostic index was derived. The prognostic index was then validated using an external patient cohort. Results A total of 567 patients who underwent PD were used as a derivation cohort. Tumour site (p < 0.001), tumour size (p = 0.002), T-stage (p < 0.001), vascular involvement (p = 0.002), number of positive nodes (p < 0.001) and LNR (p < 0.001) were significantly associated with survival in univariable analysis. LNR (p < 0.001), tumour site (p < 0.001), T-stage (p = 0.007) remained significant predictors of survival in multivariable analysis, and were combined to derive a prognostic index. The accuracy of the prognostic index was assessed both on the original cohort, and a validation set of 194 patients from another institutional prospective database. The AUROC scores for predicting the overall survival at 3 years were 0.77 in the derivation cohort and 0.74 in the validation cohort. Conclusion The Pancreaticoduodenectomy Prognostic Index is a validated clinico-pathological model based on tumour site, T-stage and LNR to predict long-term survival following PD. PMID:27037202

  19. Inferior Vena Cava Thrombosis.

    PubMed

    Alkhouli, Mohamad; Morad, Mohammad; Narins, Craig R; Raza, Farhan; Bashir, Riyaz

    2016-04-11

    Thrombosis of the inferior vena cava (IVC) is an under-recognized entity that is associated with significant short- and long-term morbidity and mortality. In absence of a congenital anomaly, the most common cause of IVC thrombosis is the presence of an unretrieved IVC filter. Due to the substantial increase in the number of IVC filters placed in the United States and the very low filter retrieval rates, clinicians are faced with a very large population of patients at risk for developing IVC thrombosis. Nevertheless, there is a paucity of data and societal guidelines with regards to the diagnosis and management of IVC thrombosis. This paper aims to enhance the awareness of this uncommon, but morbid, condition by providing a concise, yet comprehensive, review of the etiology, diagnostic approaches, and treatment strategies in patients with IVC thrombosis. PMID:26952909

  20. Missing data imputation on the 5-year survival prediction of breast cancer patients with unknown discrete values.

    PubMed

    García-Laencina, Pedro J; Abreu, Pedro Henriques; Abreu, Miguel Henriques; Afonoso, Noémia

    2015-04-01

    Breast cancer is the most frequently diagnosed cancer in women. Using historical patient information stored in clinical datasets, data mining and machine learning approaches can be applied to predict the survival of breast cancer patients. A common drawback is the absence of information, i.e., missing data, in certain clinical trials. However, most standard prediction methods are not able to handle incomplete samples and, then, missing data imputation is a widely applied approach for solving this inconvenience. Therefore, and taking into account the characteristics of each breast cancer dataset, it is required to perform a detailed analysis to determine the most appropriate imputation and prediction methods in each clinical environment. This research work analyzes a real breast cancer dataset from Institute Portuguese of Oncology of Porto with a high percentage of unknown categorical information (most clinical data of the patients are incomplete), which is a challenge in terms of complexity. Four scenarios are evaluated: (I) 5-year survival prediction without imputation and 5-year survival prediction from cleaned dataset with (II) Mode imputation, (III) Expectation-Maximization imputation and (IV) K-Nearest Neighbors imputation. Prediction models for breast cancer survivability are constructed using four different methods: K-Nearest Neighbors, Classification Trees, Logistic Regression and Support Vector Machines. Experiments are performed in a nested ten-fold cross-validation procedure and, according to the obtained results, the best results are provided by the K-Nearest Neighbors algorithm: more than 81% of accuracy and more than 0.78 of area under the Receiver Operator Characteristic curve, which constitutes very good results in this complex scenario. PMID:25725446

  1. A Novel and Validated Inflammation-Based Score (IBS) Predicts Survival in Patients With Hepatocellular Carcinoma Following Curative Surgical Resection

    PubMed Central

    Fu, Yi-Peng; Ni, Xiao-Chun; Yi, Yong; Cai, Xiao-Yan; He, Hong-Wei; Wang, Jia-Xing; Lu, Zhu-Feng; Han, Xu; Cao, Ya; Zhou, Jian; Fan, Jia; Qiu, Shuang-Jian

    2016-01-01

    Abstract As chronic inflammation is involved in the pathogenesis and progression of hepatocellular carcinoma (HCC), we investigated the prognostic accuracy of a cluster of inflammatory scores, including the Glasgow Prognostic Score, modified Glasgow Prognostic Score, platelet to lymphocyte ratio, Prognostic Nutritional Index, Prognostic Index, and a novel Inflammation-Based Score (IBS) integrated preoperative and postoperative neutrophil to lymphocyte ratio in 2 independent cohorts. Further, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy. Prognostic value of inflammatory scores and Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training cohort of 772 patients with HCC underwent hepatectomy. Independent predictors of survival identified in multivariate analysis were validated in an independent set of 349 patients with an overall similar clinical feature. In both training and validation cohorts, IBS, microscopic vascular invasion, and BCLC stage emerged as independent factors of overall survival (OS) and recurrence-free survival (RFS). The predictive capacity of the IBS in both OS and RFS appeared superior to that of the other inflammatory scores in terms of C-index. Additionally, the formulated nomogram comprised IBS resulted in more accurate prognostic prediction compared with BCLC stage alone. IBS is a novel and validated prognostic indicator of HCC after curative resection, and a robust HCC nomogram including IBS was developed to predict survival for patients after hepatectomy. PMID:26886627

  2. The Predicted Impact of Ipilimumab Usage on Survival in Previously Treated Advanced or Metastatic Melanoma in the UK

    PubMed Central

    Larkin, James; Hatswell, Anthony J.; Nathan, Paul; Lebmeier, Maximilian; Lee, Dawn

    2015-01-01

    Background Evaluating long-term prognosis is important for physicians, patients and payers. This study reports the results of a model developed to predict long-term survival for UK patients receiving second-line ipilimumab. Methods MDX010-20 trial data were used to predict survival for ipilimumab versus UK best supportive care. Two aspects of this analysis required novel approaches: 1) The overall survival Kaplan–Meier data shape is unusual: an initial steep decline is observed before a ‘plateau’. 2) The need to extrapolate beyond the trial end (4.6 years). Based upon UK clinician advice, a three-part curve fit was used: from 0–1.5 years, Kaplan–Meier data from the trial; from 1.5–5 years, standard parametric curve fits; after 5 years, long-term data from the American Joint Committee on Cancer registry. Results This approach provided good internal validity: low mean absolute error and good match to median and mean trial data. Lifetime predicted means were 2.77 years for ipilimumab and 1.07 for best supportive care, driven by increased long-term survival with ipilimumab. Conclusion To understand the full benefit of treatment and to meet reimbursement requirements, accurate estimation of treatment benefit is key. Models, such as the one presented, can be used to extrapolate beyond trials. PMID:26700304

  3. Pretreatment Health Behaviors Predict Survival Among Patients With Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Duffy, Sonia A.; Ronis, David L.; McLean, Scott; Fowler, Karen E.; Gruber, Stephen B.; Wolf, Gregory T.; Terrell, Jeffrey E.

    2009-01-01

    Purpose Our prior work has shown that the health behaviors of head and neck cancer patients are interrelated and are associated with quality of life; however, other than smoking, the relationship between health behaviors and survival is unclear. Patients and Methods A prospective cohort study was conducted to determine the relationship between five pretreatment health behaviors (smoking, alcohol, diet, physical activity, and sleep) and all-cause survival among 504 head and neck cancer patients. Results Smoking status was the strongest predictor of survival, with both current smokers (hazard ratio [HR] = 2.4; 95% CI, 1.3 to 4.4) and former smokers (HR = 2.0; 95% CI, 1.2 to 3.5) showing significant associations with poor survival. Problem drinking was associated with survival in the univariate analysis (HR = 1.4; 95% CI, 1.0 to 2.0) but lost significance when controlling for other factors. Low fruit intake was negatively associated with survival in the univariate analysis only (HR = 1.6; 95% CI, 1.1 to 2.1), whereas vegetable intake was not significant in either univariate or multivariate analyses. Although physical activity was associated with survival in the univariate analysis (HR = 0.95; 95% CI, 0.93 to 0.97), it was not significant in the multivariate model. Sleep was not significantly associated with survival in either univariate or multivariate analysis. Control variables that were also independently associated with survival in the multivariate analysis were age, education, tumor site, cancer stage, and surgical treatment. Conclusion Variation in selected pretreatment health behaviors (eg, smoking, fruit intake, and physical activity) in this population is associated with variation in survival. PMID:19289626

  4. Methylation status at HYAL2 predicts overall and progression-free survival of colon cancer patients under 5-FU chemotherapy.

    PubMed

    Pfütze, Katrin; Benner, Axel; Hoffmeister, Michael; Jansen, Lina; Yang, Rongxi; Bläker, Hendrik; Herpel, Esther; Ulrich, Alexis; Ulrich, Cornelia M; Chang-Claude, Jenny; Brenner, Hermann; Burwinkel, Barbara

    2015-12-01

    DNA methylation variations in gene promoter regions are well documented tumor-specific alterations in human malignancies including colon cancer, which may influence tumor behavior and clinical outcome. As a subset of colon cancer patients does not benefit from adjuvant chemotherapy, predictive biomarkers are desirable. Here, we describe that DNA methylation levels at CpG loci of hyaluronoglucosaminidase 2 (HYLA2) could be used to identify stage II and III colon cancer patients who are most likely to benefit from 5-flourouracil (5-FU) chemotherapy with respect to overall survival and progression-free survival. PMID:26453961

  5. Simple models based on gamma-glutamyl transpeptidase and platelets for predicting survival in hepatitis B-associated hepatocellular carcinoma

    PubMed Central

    Pang, Qing; Bi, Jian-Bin; Wang, Zhi-Xin; Xu, Xin-Sen; Qu, Kai; Miao, Run-Chen; Chen, Wei; Zhou, Yan-Yan; Liu, Chang

    2016-01-01

    Background Several hepatic cirrhosis-derived noninvasive models have been developed to predict the incidence and outcomes of hepatocellular carcinoma (HCC). We aimed to investigate the prognostic significance of the two novel established cirrhosis-associated models based on gamma-glutamyl transpeptidase (GGT) and platelets in hepatitis B-associated HCC. Methods We retrospectively evaluated 182 HCC patients with positive hepatitis B surface antigen who received radical therapy at a single institution between 2002 and 2012. Laboratory data prior to operation were collected to calculate the GGT to platelets ratio (GPR) and the S-index. Predictive factors associated with overall survival and recurrence-free survival were assessed using log-rank test and multivariate Cox analysis. Additional analyses were performed after patients were stratified based on cirrhosis status, tumor size, therapy methods, and so forth, to investigate the prognostic significance in different subgroups. Results During a median follow-up time of 45.0 months, a total of 88 (48.4%) patients died and 79 (43.4%) patients recurred. The cut-off points for GPR and S-index in predicting death were determined to be 0.76 and 0.56, respectively. Compared with patients with a lower GPR, those with GPR ≥0.76 had a higher probability of cirrhosis and a larger tumor (both P<0.05). GPR and S-index were both found to be significantly associated with survival by univariate log-rank test. Multivariate analysis identified tumor size ≥5 and high level of GPR, but not high Barcelona Clinic Liver Cancer stage or S-index, as independent factors for predicting poor overall survival and recurrence-free survival. Conclusion The GPR is an effective preoperative predictor for outcomes in hepatitis B-associated HCC. PMID:27110127

  6. A Preoperative Nutritional Index for Predicting Cancer-Specific and Overall Survival in Chinese Patients With Laryngeal Cancer

    PubMed Central

    Fu, Yan; Chen, Shu-Wei; Chen, Shi-Qi; Ou-Yang, Dian; Liu, Wei-Wei; Song, Ming; Yang, An-Kui; Zhang, Quan

    2016-01-01

    Abstract Pinato prognostic nutritional index (PNI) adequately predicts long-term outcomes of various malignancies. However, its value in predicting outcomes in laryngeal squamous cell carcinoma (LSCC) is unknown. All patients newly diagnosed with LSCC presenting to the Department of Head and Neck Oncology at Sun Yat-sen University Cancer Center between January 1, 1990 and July 31, 2010 were eligible. The PNI was calculated as serum albumin (g/L) + 5 × total lymphocyte count/L. The Cutoff Finder software program was used to classify the patients into 3 groups for which the PNI score was at least 70% sensitive, at least 70% specific, or equivocal. Cancer-specific survival was estimated using the Kaplan–Meier method, and predictors were assessed with Cox regression analysis. Median time between surgery and PNI administration for the 975 eligible patients was 83 months. Index score groups were significantly associated with age, T stage, TNM stage, and type of surgery. Five-year CSS and OS were 57.3% and 56.6% in patients with PNI scores below 48.65 (low-probability of survival), 72.8% and 71.3% with scores between 48.65 and 56.93 (moderate-probability of survival), and 77.6% and 75.3% with scores above 56.93 (high-probability of survival); 10-year CSS and OS were 44.2% and 42.7%, 61.6% and 55.6%, 68.3% and 63.5%, respectively. The PNI score groups significantly predicted CSS and OS (P < 0.001). The PNI is an inexpensive and readily available score that predicted survival in patients with LSCC after curative laryngectomy. PMID:26986105

  7. Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

    PubMed

    Rowe, Casey J; Tang, Fiona; Hughes, Maria Celia B; Rodero, Mathieu P; Malt, Maryrose; Lambie, Duncan; Barbour, Andrew; Hayward, Nicholas K; Smithers, B Mark; Green, Adele C; Khosrotehrani, Kiarash

    2016-08-01

    Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed. PMID:26990817

  8. Usefulness of High-Density Lipoprotein Cholesterol to Predict Survival in Pulmonary Arterial Hypertension.

    PubMed

    Larsen, Carolyn M; McCully, Robert B; Murphy, Joseph G; Kushwaha, Sudhir S; Frantz, Robert P; Kane, Garvan C

    2016-07-15

    It has been suggested that lipoprotein abnormalities may contribute to the pulmonary arteriolar dysfunction observed in pulmonary arterial hypertension (PAH). High-density lipoprotein cholesterol (HDL) has vasodilatory, anti-inflammatory, and endothelial protective properties. We hypothesized that a higher serum HDL level may be advantageous for survival in PAH and that the serum HDL level at diagnosis would be an independent predictor of survival in PAH and be additive to previously validated predictors of survival. This study included all patients with PAH seen at the Mayo Clinic Pulmonary Hypertension Clinic from January 1, 1995, to December 31, 2009, who had a baseline HDL measurement. Mortality was analyzed over 5 years using the Kaplan-Meier method. Univariate and multivariable Cox proportional hazards ratios were calculated to evaluate the relation between baseline HDL level and survival. HDL levels were available for 227 patients. Higher HDL levels were associated with significantly lower mortality. Patients with an HDL >54 mg/dl at diagnosis had a 5-year survival of 59%. By comparison those with an HDL <34 mg/dl had a 5-year survival of 30%. On multivariate analysis, higher HDL was associated with an age-adjusted risk ratio for death of 0.78 (CI 0.67 to 0.91; p <0.01) per 10 mg/dl increase. In conclusion, HDL was an independent predictor of survival in PAH. PMID:27291969

  9. Bilateral inferior petrosal sinus sampling.

    PubMed

    Zampetti, Benedetta; Grossrubatscher, Erika; Dalino Ciaramella, Paolo; Boccardi, Edoardo; Loli, Paola

    2016-07-01

    Simultaneous bilateral inferior petrosal sinus sampling (BIPSS) plays a crucial role in the diagnostic work-up of Cushing's syndrome. It is the most accurate procedure in the differential diagnosis of hypercortisolism of pituitary or ectopic origin, as compared with clinical, biochemical and imaging analyses, with a sensitivity and specificity of 88-100% and 67-100%, respectively. In the setting of hypercortisolemia, ACTH levels obtained from venous drainage of the pituitary are expected to be higher than the levels of peripheral blood, thus suggesting pituitary ACTH excess as the cause of hypercortisolism. Direct stimulation of the pituitary corticotroph with corticotrophin-releasing hormone enhances the sensitivity of the procedure. The procedure must be undertaken in the presence of hypercortisolemia, which suppresses both the basal and stimulated secretory activity of normal corticotrophic cells: ACTH measured in the sinus is, therefore, the result of the secretory activity of the tumor tissue. The poor accuracy in lateralization of BIPSS (positive predictive value of 50-70%) makes interpetrosal ACTH gradient alone not sufficient for the localization of the tumor. An accurate exploration of the gland is recommended if a tumor is not found in the predicted area. Despite the fact that BIPSS is an invasive procedure, the occurrence of adverse events is extremely rare, particularly if it is performed by experienced operators in referral centres. PMID:27352844

  10. Bilateral inferior petrosal sinus sampling

    PubMed Central

    Grossrubatscher, Erika; Dalino Ciaramella, Paolo; Boccardi, Edoardo

    2016-01-01

    Simultaneous bilateral inferior petrosal sinus sampling (BIPSS) plays a crucial role in the diagnostic work-up of Cushing’s syndrome. It is the most accurate procedure in the differential diagnosis of hypercortisolism of pituitary or ectopic origin, as compared with clinical, biochemical and imaging analyses, with a sensitivity and specificity of 88–100% and 67–100%, respectively. In the setting of hypercortisolemia, ACTH levels obtained from venous drainage of the pituitary are expected to be higher than the levels of peripheral blood, thus suggesting pituitary ACTH excess as the cause of hypercortisolism. Direct stimulation of the pituitary corticotroph with corticotrophin-releasing hormone enhances the sensitivity of the procedure. The procedure must be undertaken in the presence of hypercortisolemia, which suppresses both the basal and stimulated secretory activity of normal corticotrophic cells: ACTH measured in the sinus is, therefore, the result of the secretory activity of the tumor tissue. The poor accuracy in lateralization of BIPSS (positive predictive value of 50–70%) makes interpetrosal ACTH gradient alone not sufficient for the localization of the tumor. An accurate exploration of the gland is recommended if a tumor is not found in the predicted area. Despite the fact that BIPSS is an invasive procedure, the occurrence of adverse events is extremely rare, particularly if it is performed by experienced operators in referral centres. PMID:27352844

  11. The Time to Clearance of Peripheral Blood Blasts Predicts Complete Remission and Survival in Chinese Adults with Acute Myeloid Leukemia.

    PubMed

    Li, Xiaoyang; Zhu, Hongming; Zhang, Yunxiang; Zhao, Weili; Mi, Jianqing; Hu, Jiong; Li, Junmin

    2016-01-01

    The value of clearance of peripheral blood blasts (PBB) as a predictor of outcomes in acute myeloid leukemia (AML) is controversial. To investigate the prognostic significance of the time to clearance of PBB after induction in Chinese patients with AML, a retrospective analysis of 146 patients with newly diagnosed AML at Shanghai Ruijin Hospital was performed. Patients were categorized into early blast clearance (EBC; ≤5 days) and delayed blast clearance (DBC; >5 days) groups based on a receiver operating characteristic analysis. Complete remission (CR) after induction chemotherapy was related to the time to clearance of PBB (p < 0.001). Relapse-free survival (RFS; p = 0.003) and overall survival (p < 0.001) were longer in the EBC group. Multivariate analysis demonstrated that the time to clearance of PBB and cytogenetic risk independently predicted CR and RFS. Early clearance of PBB after induction chemotherapy can be a significant predictor of survival outcomes in AML patients. PMID:26967450

  12. Optimism and survival: does an optimistic outlook predict better survival at advanced ages? A twelve-year follow-up of Danish nonagenarians

    PubMed Central

    Jeune, Bernard; Andersen-Ranberg, Karen; Martinussen, Torben; Vaupel, James W.; Christensen, Kaare

    2013-01-01

    Background and aims Studies examining predictors of survival among the oldest-old have primarily focused on objective measures, such as physical function and health status. Only a few studies have examined the effect of personality traits on survival, such as optimism. The aim of this study was to examine whether an optimistic outlook predicts survival among the oldest-old. Methods The Danish 1905 Cohort Survey is a nationwide, longitudinal survey comprising all individuals born in Denmark in 1905. At baseline in 1998, a total of 2,262 persons aged 92 or 93 agreed to participate in the intake survey. The baseline in-person interview consisted of a comprehensive questionnaire including physical functioning and health, and a question about whether the respondent had an optimistic, neutral or pessimistic outlook on his or her own future. Results During the follow-up period of 12 years (1998–2010) there were 2,239 deaths (99 %) in the 1905 Cohort Survey. Univariable analyses revealed that optimistic women and men were at lower risk of death compared to their neutral counterparts [HR 0.82, 95 % CI (0.73–0.93) and 0.81, 95 % CI (0.66–0.99), respectively]. When confounding factors such as baseline physical and cognitive functioning and disease were taken into account the association between optimism and survival weakened in both sexes, but the general pattern persisted. Optimistic women were still at lower risk of death compared to neutral women [HR 0.85, 95 % CI (0.74–0.97)]. The risk of death was also decreased for optimistic men compared to their neutral counterparts, but the effect was non-significant [HR 0.91, 95 % CI (0.73–1.13)]. Conclusion An optimistic outlook appears to be a significant predictor of survival among the oldest-old women. It may also be a significant predictor for men but the sample size is small. PMID:24014276

  13. Validation of a predictive model for survival and growth of Salmonella Typhimurium DT104 on chicken skin for extrapolation to a previous history of frozen storage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A predictive model for survival and growth of Salmonella Typhimurium DT104 on chicken skin was evaluated for its ability to predict survival and growth of the same organism after frozen storage for 6 days at -20 C. Experimental methods used to collect data for model development were the same as tho...

  14. Social affiliation matters: both same-sex and opposite-sex relationships predict survival in wild female baboons

    PubMed Central

    Archie, Elizabeth A.; Tung, Jenny; Clark, Michael; Altmann, Jeanne; Alberts, Susan C.

    2014-01-01

    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. PMID:25209936

  15. Validation of a modified clinical risk score to predict cancer-specific survival for stage II colon cancer

    PubMed Central

    Oliphant, Raymond; Horgan, Paul G; Morrison, David S; McMillan, Donald C

    2015-01-01

    Many patients with stage II colon cancer will die of their disease despite curative surgery. Therefore, identification of patients at high risk of poor outcome after surgery for stage II colon cancer is desirable. This study aims to validate a clinical risk score to predict cancer-specific survival in patients undergoing surgery for stage II colon cancer. Patients undergoing surgery for stage II colon cancer in 16 hospitals in the West of Scotland between 2001 and 2004 were identified from a prospectively maintained regional clinical audit database. Overall and cancer-specific survival rates up to 5 years were calculated. A total of 871 patients were included. At 5 years, cancer-specific survival was 81.9% and overall survival was 65.6%. On multivariate analysis, age ≥75 years (hazard ratio (HR) 2.11, 95% confidence intervals (CI) 1.57–2.85; P<0.001) and emergency presentation (HR 1.97, 95% CI 1.43–2.70; P<0.001) were independently associated with cancer-specific survival. Age and mode of presentation HRs were added to form a clinical risk score of 0–2. The cancer-specific survival at 5 years for patients with a cumulative score 0 was 88.7%, 1 was 78.2% and 2 was 65.9%. These results validate a modified simple clinical risk score for patients undergoing surgery for stage II colon cancer. The combination of these two universally documented clinical factors provides a solid foundation for the examination of the impact of additional clinicopathological and treatment factors on overall and cancer-specific survival. PMID:25487740

  16. External validation of a web-based prognostic tool for predicting survival for patients in hospice care.

    PubMed

    Miladinovic, Branko; Mhaskar, Rahul; Kumar, Ambuj; Kim, Sehwan; Schonwetter, Ronald; Djulbegovic, Benjamin

    2013-01-01

    Prognostat is an interactive Web-based prognostic tool for estimating hospice patient survival based on a patient's Palliative Performance Scale (PPS) score, age, gender, and cancer status. The tool was developed using data from 5,893 palliative care patients, which was collected at the Victoria Hospice in Victoria, British Columbia, Canada, beginning in 1994. This study externally validates Prognostat with a retrospective cohort of 590 hospice patients at LifePath Hospice and Palliative Care in Florida, USA. The criteria used to evaluate the prognostic performance were the Brier score, area under the receiver operating curve, discrimination slope, and Hosmer-Lemeshow goodness-of-fit test. Though the Kaplan-Meier curves show each PPS level to be distinct and significantly different, the findings reveal low agreement between observed survival in our cohort of patients and survival predicted by the prognostic tool. Before developing a new prognostic model, researchers are encouraged to update survival estimates obtained using Prognostat with the information from their cohort of patients. If it is to be useful to patients and clinicians, Prognostat needs to explicitly report patient risk scores and estimates of baseline survival. PMID:24380212

  17. Blood neutrophil-lymphocyte ratio predicts survival after hepatectomy for hepatocellular carcinoma: A propensity score-based analysis

    PubMed Central

    Yang, Hao-Jie; Guo, Zhe; Yang, Yu-Ting; Jiang, Jing-Hang; Qi, Ya-Peng; Li, Ji-Jia; Li, Le-Qun; Xiang, Bang-De

    2016-01-01

    AIM: To investigate whether an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) can predict poor survival in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed 526 patients with HCC who underwent surgery between 2004 and 2011. RESULTS: Preoperative NLR ≥ 2.81 was an independent predictor of poor disease-free survival (DFS, P < 0.001) and overall survival (OS, P = 0.044). Compared with patients who showed a preoperative NLR < 2.81 and postoperative increase, patients who showed preoperative NLR ≥ 2.81 and postoperative decrease had worse survival (DFS, P < 0.001; OS, P < 0.001). Among patients with preoperative NLR ≥ 2.81, survival was significantly higher among those showing a postoperative decrease in NLR than among those showing an increase (DFS, P < 0.001; OS, P < 0.001). When elevated, alpha-fetoprotein (AFP) provided no prognostic information, and so preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS whenever AFP levels are low or high. CONCLUSION: Preoperative NLR ≥ 2.81 may be an indicator of poor DFS and OS in patients with HCC undergoing surgery. Preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS when elevated AFP levels provide no prognostic information. PMID:27275101

  18. Preoperative cognitive function predicts survival in patients with resectable pancreatic ductal adenocarcinoma

    PubMed Central

    Baekelandt, Bart M.G.; Hjermstad, Marianne J.; Nordby, Tom; Fagerland, Morten W.; Kure, Elin H.; Heiberg, Turid; Buanes, Trond; Labori, Knut J.

    2015-01-01

    Background The purpose of this prospective study was to evaluate whether pre-surgery health-related quality of life (HRQoL) and subjectively rated symptom scores are prognostic factors for survival in patients with resectable pancreatic ductal adenocarcinoma (PDAC). Methods Patients undergoing pancreatic resection for PDAC completed the Edmonton Symptom Assessment System (ESAS) and the EORTC QLQ-C30 and QLQ-PAN26 questionnaires preoperatively. Patient, tumor and treatment characteristics, recurrence and survival were registered. Results Sixty-six consecutive patients underwent R0/R1 resection for PDAC. Baseline ESAS and EORTC questionnaire compliance was 44/66 (67%) with no statistically significant differences between compliers (n = 44) and non-compliers (n = 22) when comparing clinicopathological parameters and survival. Univariable analyses showed that three symptoms (nausea, dry mouth, cognitive function) and two clinicopathological factors (CA 19-9 > 400 U/ml, lymph node ratio > 0.1) were significantly associated with shorter survival (p < 0.05). In multivariable analysis, cognitive function was the only independent predictor for survival: hazard ratio = 0.35 (95%CI 0.13–0.93) for high vs low cognitive function. Median survival times for patients with high and low cognitive function were 21 and 10 months, respectively (p < 0.001). Conclusion Presurgery cognitive function is a significant independent predictor of survival in patients with resectable PDAC. Thus, presurgery patient reported outcomes may provide as strong prognostic information as clinicopathological factors. PMID:27017164

  19. Survival predictability of lean and fat mass in men and women undergoing maintenance hemodialysis123

    PubMed Central

    Noori, Nazanin; Kovesdy, Csaba P; Dukkipati, Ramanath; Kim, Youngmee; Duong, Uyen; Bross, Rachelle; Oreopoulos, Antigone; Luna, Amanda; Benner, Debbie; Kopple, Joel D

    2010-01-01

    Background: Larger body size is associated with greater survival in maintenance hemodialysis (MHD) patients. It is not clear how lean body mass (LBM) and fat mass (FM) compare in their associations with survival across sex in these patients. Objective: We examined the hypothesis that higher FM and LBM are associated with greater survival in MHD patents irrespective of sex. Design: In 742 MHD patients, including 31% African Americans with a mean (±SD) age of 54 ± 15 y, we categorized men (n = 391) and women (n = 351) separately into 4 quartiles of near-infrared interactance–measured LBM and FM. Cox proportional hazards models estimated death hazard ratios (HRs) (and 95% CIs), and cubic spline models were used to examine associations with mortality over 5 y (2001–2006). Results: After adjustment for case-mix and inflammatory markers, the highest quartiles of FM and LBM were associated with greater survival in women: HRs of 0.38 (95% CI: 0.20, 0.71) and 0.34 (95% CI: 0.17, 0.67), respectively (reference: first quartile). In men, the highest quartiles of FM and percentage FM (FM%) but not of LBM were associated with greater survival: HRs of 0.51 (95% CI: 0.27, 0.96), 0.45 (95% CI: 0.23, 0.88), and 1.17 (95% CI: 0.60, 2.27), respectively. Cubic spline analyses showed greater survival with higher FM% and higher “FM minus LBM percentiles” in both sexes, whereas a higher LBM was protective in women. Conclusions: In MHD patients, higher FM in both sexes and higher LBM in women appear to be protective. The survival advantage of FM appears to be superior to that of LBM. Clinical trials to examine the outcomes of interventions that modify body composition in MHD patients are indicated. PMID:20844076

  20. Inferior epigastric artery pseudoaneurysms

    PubMed Central

    Avula, SK

    2015-01-01

    Introduction Inferior epigastric artery (IEA) pseudoaneurysms are recognised complications of abdominal wall procedures, and a variety of approaches including surgical excision and ligation, percutaneous procedures and conservative management have been employed in treating this rare complication. Methods We describe a case of an IEA pseudoaneurysm diagnosed on computed tomography (CT) angiography, 14 days following a laparoscopic assisted low anterior resection, which was managed successfully with surgical excision and ligation. A review of the literature identified 32 reports of this complication since 1973 with 69% of cases occurring since 2000. Findings The main aetiology of IEA pseudoaneurysm was abdominal surgery (n=20); 65% of cases were attributable to abdominal wound closure or laparoscopic surgery. Two-thirds (66%) of patients presented between 11 and 63 days, and all except 1 case presented with discomfort, abdominal mass or haemodynamic instability. Colour Doppler ultrasonography was the imaging modality of choice (n=18), either alone or in combination with computed tomography and/or angiography. Surgical ligation and excision and percutaneous coil embolisation formed the mainstay of attempted treatments (69%), particularly following treatment failure using an alternative technique. Conclusions The incidence of iatrogenic IEA pseudoaneurysms appears to be increasing. Awareness of this rare complication is of clinical importance to avoid excessive morbidity for affected individuals. PMID:26263930

  1. Using weather indices to predict survival of winter wheat in a cool temperate environment

    NASA Astrophysics Data System (ADS)

    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.

  2. Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy

    PubMed Central

    Jia, Zhifang; Wu, Xing; Cao, Donghui; Wang, Chuan; You, Lili; Jin, Meishan; Wen, Simin; Cao, Xueyuan; Jiang, Jing

    2016-01-01

    DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms of DNMT1 may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms of DNMT1 gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of the DNMT1 gene were genotyped by TaqMan assays. Kaplan-Meier survival plots and Cox proportional hazard regression were used to analyze the associations between SNPs of DNMT1 and survival of GC. Patients carrying rs2228611 GA/AA genotype tended to live longer than those bearing the GG genotype (HR 0.68, 95% CI: 0.51–0.91, P = 0.007). Further multivariate Cox regression analysis showed that rs2228611 was an independent prognostic factor (GA/AA versus GG: OR 0.67, 95% CI 0.49–0.91, P = 0.010). Nevertheless, other SNPs did not show any significant associations with survival of GC. Polymorphisms of the DNMT1 gene may affect overall survival of GC. The SNP rs2228611 has the potentiality to serve as an independent prognostic marker for GC patients. PMID:27087738

  3. Pancreatectomy Predicts Improved Survival for Pancreatic Adenocarcinoma: Results of an Instrumental Variable Analysis

    PubMed Central

    McDowell, Bradley D.; Chapman, Cole G.; Smith, Brian J.; Button, Anna M.; Chrischilles, Elizabeth A.; Mezhir, James J.

    2014-01-01

    Background and Objective Pancreatic resection is the standard therapy for patients with stage I/II pancreatic ductal adenocarcinoma (PDA), yet many studies demonstrate low rates of resection. The objective of this study is to evaluate whether increasing resection rates would result in an increase in average survival in patients with stage I/II PDA. Methods SEER data were analyzed for patients with stage I/II pancreatic head cancers treated from 2004–2009. Pancreatectomy rates were examined within Health Service Areas (HSA) across 18 SEER regions. An instrumental variables (IV) analysis was performed, using HSA rates as an instrument, to determine the impact of increasing resection rates on survival. Results Pancreatectomy was performed in 4,322 of the 8,323 patients evaluated with stage I/II PDA (overall resection rate=51.9%). The resection rate across HSAs ranged from an average of 38.6% in the lowest quintile to 67.3% in the highest quintile. Median survival was improved in HSAs with higher resection rates. IV analysis revealed that, for patients whose treatment choices were influenced by the rates of resection in their geographic region, pancreatectomy was associated with a statistically significant increase in overall survival. Conclusions When controlling for confounders using IV analysis, pancreatectomy is associated with a statistically significant increase in survival for patients with resectable PDA. Based on these results, if resection rates were to increase in select patients, then average survival would also be expected to increase. It is important that this information be provided to physicians and patients so they can properly weigh the risks and advantages of pancreatectomy as treatment for PDA. PMID:24979599

  4. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

    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.

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

    PubMed

    Shi, Mingguang; He, Jianmin

    2016-04-22

    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. PMID:26864276

  6. Downstaging of TURBT-Based Muscle-Invasive Bladder Cancer by Radical Cystectomy Predicts Better Survival

    PubMed Central

    van Dijk, P. R.; Ploeg, M.; Aben, K. K. H.; Weijerman, P. C.; Karthaus, H. F. M.; van Berkel, J. Th. H.; Viddeleer, A. C.; Geboers, A.; van Boven, E.; Witjes, J. A.; Kiemeney, L. A. L. M.

    2011-01-01

    Differences between clinical (cT) and pathological tumor (pT) stage occur often after radical cystectomy (RC) for muscle-invasive bladder cancer. In order to evaluate the impact of downstaging on recurrence and survival, we selected patients from a large, contemporary, population-based series of 1,409 patients with MIBC. We included all patients who underwent RC (N=643) and excluded patients who received (neo)adjuvant therapy, those with known metastasis at time of diagnosis, and those with nonurothelial cell tumors. Disease outcomes were defined as recurrence-free survival (RFS) and relative survival (RS), as a good approximation of bladder cancer-specific survival. After applying the exclusion criteria, 375 patients were eligible for analysis. Tumor downstaging was found to be common after RC; in 99 patients (26.4%), tumor downstaging to non-muscle-invasive stages at RC occurred. Hydronephrosis at baseline and positive lymph nodes at RC occurred significantly less often in these patients. In 62 patients, no tumor was left in the cystectomy specimen. pT stage was pT1 in 20 patients and pTis in 17 patients. Patients with tumor downstaging have about a 30% higher RFS and RS compared to those without. Consequently, tumor downstaging is a favorable marker for prognosis after RC. PMID:22084800

  7. Do thallium myocardial perfusion scan abnormalities predict survival in sarcoid patients without cardiac symptoms

    SciTech Connect

    Kinney, E.L.; Caldwell, J.W. )

    1990-07-01

    Whereas the total mortality rate for sarcoidosis is 0.2 per 100,000, the prognosis, when the heart is involved, is very much worse. The authors used the difference in mortality rate to infer whether thallium 201 myocardial perfusion scan abnormalities correspond to myocardial sarcoid by making the simplifying assumption that if they do, then patients with abnormal scans will be found to have a death rate similar to patients with sarcoid heart disease. The authors therefore analyzed complete survival data on 52 sarcoid patients without cardiac symptoms an average of eighty-nine months after they had been scanned as part of a protocol. By use of survival analysis (the Cox proportional hazards model), the only variable that was significantly associated with survival was age. The patients' scan pattern, treatment status, gender, and race were not significantly related to survival. The authors conclude that thallium myocardial perfusion scans cannot reliably be used to diagnose sarcoid heart disease in sarcoid patients without cardiac symptoms.

  8. Anatomical Involvement of the Subventricular Zone Predicts Poor Survival Outcome in Low-Grade Astrocytomas

    PubMed Central

    Liu, Shuai; Wang, Yinyan; Fan, Xing; Ma, Jun; Ma, Wenbin; Wang, Renzhi; Jiang, Tao

    2016-01-01

    The subventricular zone (SVZ) has been implicated in the origination, development, and biological behavior of gliomas. Tumor-SVZ contact is also postulated to be a poor prognostic factor in glioblastomas. We aimed to evaluate the prognostic consequence of the anatomical involvement of low-grade gliomas with the SVZ. To that end, we reviewed 143 patients with diffuse astrocytomas, and tumor lesions were manually delineated on magnetic resonance images. We initially investigated the prognostic role of SVZ contact in all patients. Additionally, we investigated the influence of the anatomical proximity of the tumor lesion centroids to the SVZ in the SVZ-involved patient cohorts, as well as location within the SVZ. We found SVZ contact with tumors to be a significant prognostic factor of overall survival in all patients with diffuse astrocytomas (p = 0.027). In the SVZ-involved cohort, a shorter distance from the tumor centroid to the SVZ (≤30 mm) correlated with shorter overall survival (p = 0.022) on univariate analysis. However, there was no significant difference in overall survival with respect to the SVZ region involved with the tumor (p = 0.930). Multivariate analysis showed that a shorter distance between the tumor centroid and the SVZ (p = 0.039) was significantly associated with poor overall survival in SVZ-involved patients. Hence, this study helps establish the prognostic role of the anatomical interaction of tumors with the SVZ in low-grade astrocytomas. PMID:27120204

  9. Tumor CTLA-4 overexpression predicts poor survival in patients with nasopharyngeal carcinoma

    PubMed Central

    Lu, Jia-Bin; Chen, Qiu-Yan; Tang, Lin-Quan; Zhang, Lu; Liu, Li-Ting; Zhang, Li; Mai, Hai-Qiang

    2016-01-01

    The expression levels of CTLA-4 and CD28 were analyzed in 191 nasopharyngeal carcinoma (NPC) patients diagnosed and treated at our hospital between January 2010 and November 2011. The 3-year overall survival (OS) rate (91.4% vs. 81.2%,p = 0.043), failure-free survival (FFS) rate (82.8% vs. 68.0%, p = 0.009) and distant failure-free survival (D-FFS) rate (85.8% vs. 72.3%, p = 0.006) in the low tumor CTLA-4 expression group was higher than in the high tumor CTLA-4 group. There were no differences between the locoregional failure-free survival (LR-FFS) rates in the high and low tumor CTLA-4 expression groups. Moreover, no differences in the OS, FFS, D-FFS, or LR-FFS were observed between the groups with high and low lymphocyte CTLA-4 levels, high and low tumor CD28 levels, or high and low lymphocyte CD28 levels. Cox regression analysis confirmed the prognostic value of tumor CTLA-4 expression, particularly for D-FFS, in NPC patients (p = 0.044). NPC patients with high tumor CTLA-4 expression had a poorer prognosis than those with low expression. PMID:26918337

  10. Radiofrequency Ablation of Colorectal Liver Metastases: Small Size Favorably Predicts Technique Effectiveness and Survival

    SciTech Connect

    Veltri, Andrea Sacchetto, Paola; Tosetti, Irene; Pagano, Eva; Fava, Cesare; Gandini, Giovanni

    2008-09-15

    The objective of this study was to analyze long-term results of radiofrequency thermal ablation (RFA) for colorectal metastases (MTS), in order to evaluate predictors for adverse events, technique effectiveness, and survival. One hundred ninety-nine nonresectable MTS (0.5-8 cm; mean, 2.9 cm) in 122 patients underwent a total of 166 RFA sessions, percutaneously or during surgery. The technique was 'simple' or 'combined' with vascular occlusion. The mean follow-up time was 24.2 months. Complications, technique effectiveness, and survival rates were statistically analyzed. Adverse events occurred in 8.1% of lesions (major complication rate: 1.1%), 7.1% with simple and 16.7% with combined technique (p = 0.15). Early complete response was obtained in 151 lesions (81.2%), but 49 lesions (26.3%) recurred locally after a mean of 10.4 months. Sustained complete ablation was achieved in 66.7% of lesions {<=}3 cm versus 33.3% of lesions >3 cm (p < 0.0001). Survival rates at 1, 3, and 5 years were 91%, 54%, and 33%, respectively, from the diagnosis of MTS and 79%, 38%, and 22%, respectively, from RFA. Mean survival time from RFA was 31.5 months, 36.2 in patients with main MTS {<=}3 cm and 23.2 in those with at least one lesion >3 cm (p = 0.006). We conclude that 'simple' RFA is safe and successful for MTS {<=}3 cm, contributing to prolong survival when patients can be completely treated.

  11. Combined P16 and human papillomavirus testing predicts head and neck cancer survival.

    PubMed

    Salazar, Christian R; Anayannis, Nicole; Smith, Richard V; Wang, Yanhua; Haigentz, Missak; Garg, Madhur; Schiff, Bradley A; Kawachi, Nicole; Elman, Jordan; Belbin, Thomas J; Prystowsky, Michael B; Burk, Robert D; Schlecht, Nicolas F

    2014-11-15

    While its prognostic significance remains unclear, p16(INK4a) protein expression is increasingly being used as a surrogate marker for oncogenic human papillomavirus (HPV) infection in head and neck squamous cell carcinomas (HNSCC). To evaluate the prognostic utility of p16 expression in HNSCC, we prospectively collected 163 primary tumor specimens from histologically confirmed HNSCC patients who were followed for up to 9.4 years. Formalin fixed tumor specimens were tested for p16 protein expression by immunohistochemistry (IHC). HPV type-16 DNA and RNA was detected by MY09/11-PCR and E6/E7 RT-PCR on matched frozen tissue, respectively. P16 protein expression was detected more often in oropharyngeal tumors (53%) as compared with laryngeal (24%), hypopharyngeal (8%) or oral cavity tumors (4%; p<0.0001). With respect to prognosis, p16-positive oropharyngeal tumors exhibited significantly better overall survival than p16-negative tumors (log-rank test p=0.04), whereas no survival benefit was observed for nonoropharyngeal tumors. However, when both p16 and HPV DNA test results were considered, concordantly positive nonoropharyngeal tumors had significantly better disease-specific survival than concordantly negative nonoropharyngeal tumors after controlling for sex, nodal stage, tumor size, tumor subsite, primary tumor site number, smoking and drinking [adjusted hazard ratio (HR)=0.04, 0.01-0.54]. Compared with concordantly negative nonoropharyngeal HNSCC, p16(+)/HPV16(-) nonoropharyngeal HNSCC (n=13, 7%) demonstrated no significant improvement in disease-specific survival when HPV16 was detected by RNA (adjusted HR=0.83, 0.22-3.17). Our findings show that p16 IHC alone has potential as a prognostic test for oropharyngeal cancer survival, but combined p16/HPV testing is necessary to identify HPV-associated nonoropharyngeal HNSCC with better prognosis. PMID:24706381

  12. Cerebral performance category at hospital discharge predicts long-term survival of cardiac arrest survivors receiving targeted temperature management

    PubMed Central

    Hsu, Cindy H.; Li, Jiaqi; Cinousis, Marisa J.; Sheak, Kelsey R.; Gaieski, David F.; Abella, Benjamin S.; Leary, Marion

    2014-01-01

    Objective Despite recent advancements in post-cardiac arrest resuscitation, the optimal measurement of post-arrest outcome remains unclear. We hypothesized that cerebral performance category (CPC) score can predict the long-term outcome of post- arrest survivors who received targeted temperature management (TTM) during their post-arrest hospital care. Design Retrospective chart review. Setting Two academic medical centers from May, 2005 to December, 2012. Patients The medical records of 2,417 out-of-hospital and in-hospital post-cardiac arrest patients were reviewed to identify 140 out of 582 survivors who received TTM. Interventions None. Measurements and Main Results The CPC scores at hospital discharge were determined by three independent abstractors. The 1-month, 6-month, and 12-month survival of these patients were determined by reviewing hospital records, querying the Social Security Death Index, and follow-up telephone calls. The unadjusted long-term survival and adjusted survival association with CPC were calculated. Of the 2,417 identified cardiac arrest patients, 24.1% (582/2417) were successfully resuscitated, of whom 24.1% (140/582) received post-arrest TTM. Overall, 42.9% (60/140) were discharged with CPC 1, 27.1% (38/140) with CPC 2, 18.6% (26/140) with CPC 3, and 11.4% (16/140) with CPC 4. CPC 1 survivors had the highest long-term survival followed by CPC 2 and 3, with CPC 4 having the lowest long-term survival (p < 0.001, log-rank test). We found that CPC 3 (hazard ratio = 3.62, p < 0.05) and CPC 4 (hazard ratio = 12.73, p <0.001) remained associated with worse survival after adjusting for age, gender, race, shockable rhythm, time to TTM initiation, total duration of resuscitation, withdrawal of care, and location of arrest. Conclusion Patients with different CPC scores at discharge have significantly different survival trajectories. Favorable CPC at hospital discharge predicts better long-term outcomes of cardiac arrest survivors who received TTM

  13. The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

    PubMed Central

    Kamieniak, Marta M.; Muñoz-Repeto, Ivan; Borrego, Salud; Hernando, Susana; Hernández-Agudo, Elena; Heredia Soto, Victoria; Márquez-Rodas, Ivan; Echarri, María José; Lacambra-Calvet, Carmen; Sáez, Raquel; Redondo, Andrés; Benítez, Javier

    2016-01-01

    Objective We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. Methods In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients’ survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Results Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. Conclusion Low

  14. Do prostatic biopsies 12 months or more after external irradiation for adenocarcinoma, stage III, predict long-term survival

    SciTech Connect

    Cox, J.D.; Kline, R.W.

    1983-03-01

    Serial biopsies of the prostate after high dose external irradiation for adenocarcinoma show a gradual disappearance of the neoplastic cells. With such treatment, results of the biopsies do not have any short term prognostic significance. However, positive biopsies 12 months or more after treatment are reputed to be an unfavorable sign for long-term survival. From August, 1970 through February, 1974, 45 consecutive patients with locally advanced adenocarcinoma of the prostate underwent external irradiation with 2 MV X rays or cobalt-60 teletherapy. The center of the prostate received a total dose of 70 Gy in 30-37 fractions in 43 to 56 days. With a median follow-up of 8 years, the actuarial survival rates, uncorrected for death from intercurrent disease, are 69% at 5 years and 49% at 10 years. Biopsies of the prostate 12 months or more after treatment were available from 31 patients; 19 had one or more positive biopsies. Prostatic biopsies obtained 24 months or more after treatment were available from 21 patients: 10 had positive and 11 had negative biopsies; the survival curves are identical for those with and without residual cancer cells. Following adequate irradiation of patients with locally advanced adenocarcinoma of the prostate, the results of biopsies obtained one or two years after treatment do not predict long-term survival.

  15. Gene Expression Profile for Predicting Survival in Advanced-Stage Serous Ovarian Cancer Across Two Independent Datasets

    PubMed Central

    Yoshihara, Kosuke; Tajima, Atsushi; Yahata, Tetsuro; Kodama, Shoji; Fujiwara, Hiroyuki; Suzuki, Mitsuaki; Onishi, Yoshitaka; Hatae, Masayuki; Sueyoshi, Kazunobu; Fujiwara, Hisaya; Kudo, Yoshiki; Kotera, Kohei; Masuzaki, Hideaki; Tashiro, Hironori; Katabuchi, Hidetaka; Inoue, Ituro; Tanaka, Kenichi

    2010-01-01

    Background Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer. Methodology/Principal Findings Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). Conclusions/Significance The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer. PMID:20300634

  16. Extraversion predicts longer survival in gorillas: an 18-year longitudinal study

    PubMed Central

    Weiss, Alexander; Gartner, Marieke C.; Gold, Kenneth C.; Stoinski, Tara S.

    2013-01-01

    Personality plays an important role in determining human health and risk of earlier death. However, the mechanisms underlying those associations remain unknown. We moved away from testing hypotheses rooted in the activities of modern humans, by testing whether these associations are ancestral and one side of a trade-off between fitness costs and benefits. We examined personality predictors of survival in 283 captive western lowland gorillas (Gorilla gorilla gorilla) followed for 18 years. We found that of four gorilla personality dimensions—dominance, extraversion, neuroticism and agreeableness—extraversion was associated with longer survival. This effect could not be explained by demographic information or husbandry practices. These findings suggest that understanding how extraversion and other personality domains influence longevity requires investigating the evolutionary bases of this association in nonhuman primates and other species. PMID:23222443

  17. Extraversion predicts longer survival in gorillas: an 18-year longitudinal study.

    PubMed

    Weiss, Alexander; Gartner, Marieke C; Gold, Kenneth C; Stoinski, Tara S

    2013-02-01

    Personality plays an important role in determining human health and risk of earlier death. However, the mechanisms underlying those associations remain unknown. We moved away from testing hypotheses rooted in the activities of modern humans, by testing whether these associations are ancestral and one side of a trade-off between fitness costs and benefits. We examined personality predictors of survival in 283 captive western lowland gorillas (Gorilla gorilla gorilla) followed for 18 years. We found that of four gorilla personality dimensions--dominance, extraversion, neuroticism and agreeableness--extraversion was associated with longer survival. This effect could not be explained by demographic information or husbandry practices. These findings suggest that understanding how extraversion and other personality domains influence longevity requires investigating the evolutionary bases of this association in nonhuman primates and other species. PMID:23222443

  18. Down-regulation of Barx2 predicts poor survival in colorectal cancer.

    PubMed

    Mi, Yushuai; Zhao, Senlin; Zhang, Weihao; Zhang, Dongyuan; Weng, Junyong; Huang, Kejian; Sun, Huimin; Tang, Huamei; Zhang, Xin; Sun, Xiaofeng; Peng, Zhihai; Wen, Yugang

    2016-09-01

    Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar family, has an important role in controlling the expression of cell adhesion molecules and has been reported in an increasing array of tumor types except colorectal cancer (CRC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in CRC. First, we analyzed the expression of Barx2 in two independent public datasets from Oncomine. Subsequently, we evaluated Barx2 mRNA and protein expression by quantitative real-time PCR and western blotting, respectively. It was determined that Barx2 expression was lower in tumor tissues than in adjacent non-tumorous colorectal tissues of CRC patients, consistent with results from the public datasets. Subsequently, a tissue microarray containing 196 CRC specimens was evaluated for Barx2 expression by immunohistochemical staining. It was found that low expression of Barx2 significantly correlated with TNM stage, AJCC stage, differentiation, and relapse in patients with CRC. Patients with lower levels of Barx2 expression showed reduced disease-free survival and overall survival. Furthermore, a trend toward shorter overall survival in the patient group with Barx2-negative tumors independent of advanced AJCC stage and poor differentiation was determined by Kaplan-Meier survival analysis. Based on univariate and multivariate analyses, Barx2 expression was an independent prognostic factor for determining CRC prognosis. Taken together, low Barx2 expression was associated with the progression of CRC and could serve as a potential independent prognostic biomarker for patients with CRC. PMID:27453340

  19. Shunting branch of portal vein and stent position predict survival after transjugular intrahepatic portosystemic shunt

    PubMed Central

    Bai, Ming; He, Chuang-Ye; Qi, Xing-Shun; Yin, Zhan-Xin; Wang, Jian-Hong; Guo, Wen-Gang; Niu, Jing; Xia, Jie-Lai; Zhang, Zhuo-Li; Larson, Andrew C; Wu, Kai-Chun; Fan, Dai-Ming; Han, Guo-Hong

    2014-01-01

    AIM: To evaluate the effect of the shunting branch of the portal vein (PV) (left or right) and the initial stent position (optimal or suboptimal) of a transjugular intrahepatic portosystemic shunt (TIPS). METHODS: We retrospectively reviewed 307 consecutive cirrhotic patients who underwent TIPS placement for variceal bleeding from March 2001 to July 2010 at our center. The left PV was used in 221 patients and the right PV in the remaining 86 patients. And, 224 and 83 patients have optimal stent position and sub-optimal stent positions, respectively. The patients were followed until October 2011 or their death. Hepatic encephalopathy, shunt dysfunction, and survival were evaluated as outcomes. The difference between the groups was compared by Kaplan-Meier analysis. A Cox regression model was employed to evaluate the predictors. RESULTS: Among the patients who underwent TIPS to the left PV, the risk of hepatic encephalopathy (P = 0.002) and mortality were lower (P < 0.001) compared to those to the right PV. Patients who underwent TIPS with optimal initial stent position had a higher primary patency (P < 0.001) and better survival (P = 0.006) than those with suboptimal initial stent position. The shunting branch of the portal vein and the initial stent position were independent predictors of hepatic encephalopathy and shunt dysfunction after TIPS, respectively. And, both were independent predictors of survival. CONCLUSION: TIPS placed to the left portal vein with optimal stent position may reduce the risk of hepatic encephalopathy and improve the primary patency rates, thereby prolonging survival. PMID:24574750

  20. A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype.

    PubMed

    Valente, Kari; Blackham, Aaron U; Levine, Edward; Russell, Greg; Votanopoulos, Konstantinos I; Stewart, John H; Shen, Perry; Geisinger, Kim R; Sirintrapun, Sahussapont J

    2016-09-01

    Diffuse malignant peritoneal mesothelioma (MPeM) is rare and arises from peritoneal serosal surfaces. Although it shares similar histomorphology with its counterpart, malignant pleural mesothelioma, etiologies, clinical courses, and therapies differ. Nuclear grading and level of mitoses have been correlated with prognosis in malignant pleural mesothelioma with epithelioid subtype. Whether nuclear grading and level of mitoses correlate with prognosis in MPeM is still unknown. Our study utilizes a 2 tier system incorporating nuclear features and level of the mitoses to stratify cases of MPeM with epithelioid subtype. Fifty-one cases of MPeM with clinical follow-up underwent retrospective microscopic review. From that subset, 46 cases were of epithelioid subtype, which were then stratified into a low-grade or high-grade tier. Survival times were calculated on the basis of Kaplan-Meier analysis. The low-grade tier had higher overall survival with a median of 11.9 years and 57% at 5 years when compared with the high-grade tier with a median of 3.3 years and 21% at 5 years (P=0.002). Although not statistically significant, the low-grade tier had higher progression-free survival with a median of 4.7 years and 65% at 5 years when compared with the high-grade tier with a median of 1.9 years and 35% at 5 years (P=0.089). Our study is first to specifically evaluate and correlate nuclear features and level of mitoses with overall survival in MPeM with epithelioid subtype. PMID:27438989

  1. Hepatocellular carcinoma treated by conventional transarterial chemoembolization in field-practice: Serum sodium predicts survival

    PubMed Central

    Biolato, Marco; Miele, Luca; Vero, Vittoria; Racco, Simona; Di Stasi, Carmine; Iezzi, Roberto; Zanché, Andrea; Pompili, Maurizio; Rapaccini, Gian Ludovico; La Torre, Giuseppe; Gasbarrini, Antonio; Grieco, Antonio

    2014-01-01

    AIM: To assess the prognostic role of baseline clinical, biochemical and radiological characteristics of patients with hepatocellular carcinoma (HCC) treated with the first transarterial chemoembolization (TACE) procedure. METHODS: Patients with HCC treated with conventional TACE in a tertiary care setting from 1997 to 2008 were retrospectively reviewed. Predictors of survival were identified using the Cox proportional regression model. RESULTS: Two hundred and seventy patients were included. Median age was 66 years, 81% were male, 58% were HCV-positive, 18% hepatitis B surface antigen-positive, 64% had a Child A status, 40% patients had a largest nodule diameter ≥ 5 cm and 32% had more than 3 tumor nodules. Median overall survival of the whole cohort was 25 mo (95%CI: 21.8-28.2) and the 1-, 2- and 3-year probability of survival was 80%, 50% and 31%, respectively. Non-tumor segmental portal vein thrombosis (HR = 1.76, 95%CI: 1.22-2.54), serum sodium (HR = 1.65, 95%CI: 1.25-2.18), diameter of largest nodule (HR = 1.59, 95%CI: 1.22-2.091), number of nodules (HR = 1.41, 95%CI: 1.06-1.88), alpha-fetoprotein (HR = 1.35, 95%CI: 1.03-1.76) and alkaline phosphatase (HR = 1.33, 95%CI: 1.01-1.74) were independent prognostic factors for overall survival on multivariate analysis. CONCLUSION: The inclusion of serum sodium alongside the already known prognostic factors may allow a better prognostic definition of patients with HCC as candidates for conventional TACE. PMID:25009388

  2. Composition of symbiotic bacteria predicts survival in Panamanian golden frogs infected with a lethal fungus

    PubMed Central

    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

    2015-01-01

    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. PMID:25788591

  3. Composition of symbiotic bacteria predicts survival in Panamanian golden frogs infected with a lethal fungus.

    PubMed

    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. PMID:25788591

  4. Peritumoral Small EphrinA5 Isoform Level Predicts the Postoperative Survival in Hepatocellular Carcinoma

    PubMed Central

    Yeh, Ta-Sen; Wang, Yu-Ling; Liang, Kung-Hao; Yeh, Chau-Ting; Chen, Tse-Ching

    2012-01-01

    Background EphrinA5, a member of Eph/Ephrin family, possesses two alternative isoforms, large ephrinA5 isoform (ephrinA5L) and small ephrinA5 isoform (ephrinA5S). EphrinA5L is a putative tumor suppressor in several types of human cancers. However, the role of ephrinA5S in hepato-carcinogenesis remains unclear. In this study, we evaluate the role of ephrinA5 isoforms in human hepatocellular carcinomas (HCC). Methodology/Principal Findings A total of 142 paired HCCs and peritumoral liver tissue was examined for relative expression of ephrinA5L and ephrinA5S by using quantitative real-time polymerase chain reaction. We analyzed their expression in relation to clinical parameters, disease-free survival and overall survival. Functional assays were performed to dissect the possible underlying mechanisms. Both ephrinA5L and ephrinA5S were significantly downregulated in HCCs, as compared to those in peritumoral tissue (p = 0.013 and 0.001). Univariate analysis demonstrated that ephrinA5S was positively correlated with old age and histological grade. In multivariate analysis, high ephrinA5S expression in peritumoral tissue had better disease-free survival (p = 0.002) and overall survival (p = 0.045) in patients with HCC after surgical resection. Functional analysis in HCC cell lines revealed that ephrinA5S had a more potent suppressive effect than ephrinA5L on cell proliferation (p<0.05) and migration (p<0.01). Furthermore, forced expression of both ephrinA5 isoforms in HCC cell lines significantly down-regulated epidermal growth factor receptor (EGFR) expression by promoting c-Cbl-mediated EGFR degradation. Conclusions/Significance EphrinA5S might be a useful prognostic biomarker for HCCs after surgical resection. EphrinA5, especially ephrinA5S, acts as a tumor suppressor in hepatocarcinogenesis. Peritumoral small ephrinA5 isoform level could determine the postoperative survival in hepatocellular carcinoma. PMID:22860012

  5. An integrated model of clinical information and gene expression for prediction of survival in ovarian cancer patients.

    PubMed

    Yang, Rendong; Xiong, Jie; Deng, Defeng; Wang, Yiren; Liu, Hequn; Jiang, Guli; Peng, Yangqin; Peng, Xiaoning; Zeng, Xiaomin

    2016-06-01

    Accumulating evidence shows that clinical factors alone are not adequate for predicting the survival of patients with ovarian cancer (OvCa), and many genes have been found to be associated with OvCa prognosis. The objective of this study was to develop a model that integrates clinical information and a gene signature to predict the survival durations of patients diagnosed with OvCa. We constructed mRNA and microRNA expression profiles and gathered the corresponding clinical data of 552 OvCa patients and 8 normal controls from The Cancer Genome Atlas. Using univariate Cox regression followed by a permutation test, elastic net-regulated Cox regression, and ridge regression, we generated a prognosis index consisting of 2 clinical variables, 7 protective mRNAs, 12 risky mRNAs, and 1 protective microRNA. The area under the curve of the receiver operating characteristic of the integrated clinical-and-gene model was 0.756, larger than that of the clinical-alone model (0.686) or the gene-alone model (0.703). OvCa patients in the high-risk group had a significantly shorter overall survival time compared with patients in the low-risk group (hazard ratio = 8.374, 95% confidence interval = 4.444-15.780, P = 4.90 × 10(-11), by the Wald test). The reliability of the gene signature was confirmed by a public external data set from the Gene Expression Omnibus. Our conclusions that we have identified an integrated clinical-and-gene model superior to the traditional clinical-alone model in ascertaining the survival prognosis of patients with OvCa. Our findings may prove valuable for improving the clinical management of OvCa. PMID:27059002

  6. Survival Prediction for Terminally Ill Cancer Patients: Revision of the Palliative Prognostic Score with Incorporation of Delirium

    PubMed Central

    Maltoni, Marco; Miceli, Rosalba; Mariani, Luigi; Caraceni, Augusto; Amadori, Dino; Nanni, Oriana

    2011-01-01

    Purpose. An existing and validated palliative prognostic (PaP) score predicts survival in terminally ill cancer patients based on dyspnea, anorexia, Karnofsky performance status score, clinical prediction of survival, total WBC, and lymphocyte percentage. The PaP score assigns patients to three different risk groups according to a 30-day survival probability—group A, >70%; group B, 30%–70%; group C, <30%. The impact of delirium is known but was not incorporated into the PaP score. Materials and Methods. Our aim was to incorporate information on delirium into the PaP score based on a retrospective series of 361 terminally ill cancer patients. We followed the approach of “validation by calibration,” proposed by van Houwelingen and later adapted by Miceli for achieving score revision with inclusion of a new variable. The discriminating performance of the scores was estimated using the K statistic. Results. The prognostic contribution of delirium was confirmed as statistically significant (p < .001) and the variable was accordingly incorporated into the PaP score (D-PaP score). Following this revision, 30-day survival estimates in groups A, B, and C were 83%, 50%, and 9% for the D-PaP score and 87%, 51%, and 16% for the PaP score, respectively. The overall performance of the D-PaP score was better than that of the PaP score. Conclusion. The revision of the PaP score was carried out by modifying the cutoff values used for prognostic grouping without, however, affecting the partial scores of the original tool. The performance of the D-PaP score was better than that of the PaP score and its key feature of simplicity was maintained. PMID:22042788

  7. Clinical and Biologic Features Predictive of Survival After Relapse of Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project

    PubMed Central

    London, Wendy B.; Castel, Victoria; Monclair, Tom; Ambros, Peter F.; Pearson, Andrew D.J.; Cohn, Susan L.; Berthold, Frank; Nakagawara, Akira; Ladenstein, Ruth L.; Iehara, Tomoko; Matthay, Katherine K.

    2011-01-01

    Purpose Survival after neuroblastoma relapse is poor. Understanding the relationship between clinical and biologic features and outcome after relapse may help in selection of optimal therapy. Our aim was to determine which factors were significantly predictive of postrelapse overall survival (OS) in patients with recurrent neuroblastoma—particularly whether time from diagnosis to first relapse (TTFR) was a significant predictor of OS. Patients and Methods Patients with first relapse/progression were identified in the International Neuroblastoma Risk Group (INRG) database. Time from study enrollment until first event and OS time starting from first event were calculated. Cox regression models were used to calculate the hazard ratio of increased death risk and perform survival tree regression. TTFR was tested in a multivariable Cox model with other factors. Results In the INRG database (N = 8,800), 2,266 patients experienced first progression/relapse. Median time to relapse was 13.2 months (range, 1 day to 11.4 years). Five-year OS from time of first event was 20% (SE, ± 1%). TTFR was statistically significantly associated with OS time in a nonlinear relationship; patients with TTFR of 36 months or longer had the lowest risk of death, followed by patients who relapsed in the period of 0 to less than 6 months or 18 to 36 months. Patients who relapsed between 6 and 18 months after diagnosis had the highest risk of death. TTFR, age, International Neuroblastoma Staging System stage, and MYCN copy number status were independently predictive of postrelapse OS in multivariable analysis. Conclusion Age, stage, MYCN status, and TTFR are significant prognostic factors for postrelapse survival and may help in the design of clinical trials evaluating novel agents. PMID:21768459

  8. Bigger is not always better: offspring size does not predict growth or survival for seven ascidian species.

    PubMed

    Jacobs, Molly W; Sherrard, Kristin M

    2010-12-01

    The presumed trade-off between offspring size and quality predicted by life history theory is often invoked to explain the wide range of propagule sizes observed in animals and plants. This trade-off is broadly supported by intraspecific studies but has been difficult to test in an interspecific context, particularly in animals. We tested the fitness consequences of offspring size both intra- and interspecifically for seven species of ascidians (sessile, suspension-feeding, marine invertebrates) whose offspring volumes varied over three orders of magnitude. We measured two major components of fitness, juvenile growth rates and survival, in laboratory and field experiments encompassing several food conditions. Contrary to the predictions of life history theory, larger offspring size did not result in higher rates of growth or survival, and large offspring did not perform better under nutritional stress, either intraspecifically or interspecifically. In fact, two of the four species with small offspring grew rapidly enough to catch up in size to the species with large offspring in as little as eight weeks, under wild-type food conditions. Trade-offs between growth potential and defense may overwhelm and obscure any trade-offs between offspring size and survival or growth rate. While large initial size may still confer a competitive advantage, we failed to detect any consequences of interspecific variation in initial size. This implies that larger offspring in these species, far from being inherently superior in growth or survival, require compensation in other aspects of life history if reproductive effort is to be efficient. Our results suggest that the importance of initial offspring size is context dependent and often overestimated relative to other life history traits. PMID:21302831

  9. Prediction of time dependent survival in HF patients after VAD implantation using pre- and post-operative data.

    PubMed

    Kourou, Konstantina; Rigas, George; Exarchos, Konstantinos P; Goletsis, Yorgos; Exarchos, Themis P; Jacobs, Steven; Meyns, Bart; Trivella, Maria-Giovanna; Fotiadis, Dimitrios I

    2016-03-01

    Heart failure is one of the most common diseases worldwide. In recent years, Ventricular Assist Devices (VADs) have become a valuable option for patients with advanced HF. Although it has been shown that VADs improve patient survival rates, several complications persist during left VAD (LVAD) support. The stratification scores currently employed are mostly generic, i.e. not specifically built for LVAD patients, and are based on pre-implantation patient data. In this work we apply data mining approaches for the prediction of time dependent survival in patients after LVAD implantation. Moreover, the predictions acquired with the use of pre-implantation data are enriched by employing post-implantation data, i.e. follow-up data. Different clinical scenarios have been depicted and the subsequent conditions are tested in order to identify the optimal set of pre- and post-implant features, as well as the most suitable algorithms for feature selection and prediction. The proposed approach is applied to a real dataset of 71 patients, reporting an accuracy of 84.5%, sensitivity of 87% and specificity of 82%. Based on the reported results, expert cardio-surgeons can be supported in planning the treatment of VAD patients. PMID:26820445

  10. Prognostic Model to Predict Survival Outcome for Curatively Resected Liposarcoma: A Multi-Institutional Experience

    PubMed Central

    Oh, Yoon Jung; Yi, Seong Yoon; Kim, Ki Hyang; Cho, Yong Jin; Beum, Seung Hoon; Lee, Young Han; Suh, Jin-Suck; Hur, Hyuk; Kim, Kyung Sik; Kim, Sung Hoon; Choi, Young Deuk; Shin, Kyoo-Ho; Jun, Hyun Jung; Kim, Sung Joo; Lee, Jeeyun; Park, Se Hoon; Noh, Sung Hoon; Rha, Sun Young; Kim, Hyo Song

    2016-01-01

    Purpose: We performed this study to analyze the clinical features and prognosis of Korean patients with liposarcoma. Patients & Methods: Between October 1986 and April 2013, 231 patients who were diagnosed with liposarcoma by histologic examination were enrolled in this study. Results: The distribution of histologic subtypes was well-differentiated (n = 97, 42%), myxoid (n = 74, 32%), dedifferentiated (n = 32, 13.9%), pleomorphic (n = 15, 6.5%), and round-cell liposarcoma (n = 13, 5.6%). The majority of liposarcomas were located in the lower extremities (35.5%) and retroperitoneum (34.2%). Prognosis was worse for the trunk group compared with the extremity group (median disease-free survival [DFS] 3.3 vs. 9.9 years, respectively, P <0.001). Median DFS was significantly worse in patients with high grade histology compared to those with low grade histology (16.9% vs. 65.7%, P <0.001). The independent prognostic factors associated with survival were histology (hazard ratio [HR] 3.01; 95% confidence interval [CI], 1.82-4.97; P <0.001) and primary site (HR 1.80; 95% CI, 1.12-2.89; P = 0.015). Three risk groups with different survival outcomes were identified: group 1 (n = 98), no risk factors; group 2 (n = 92), one risk factor; and group 3 (n = 41), two risk factors. Conclusions: Histologic subtype and primary site were independent prognostic factors for curatively resected liposarcoma. A prognostic model for patients with liposarcoma clarified distinct groups of patients with good prognostic discrimination. PMID:27326262

  11. Predictive role of vascular endothelial growth factor polymorphisms in the survival of renal cell carcinoma patients.

    PubMed

    Yang, Y-Q; Chen, J

    2014-01-01

    We conducted a study to investigate the possible role of the vascular endothelial growth factor (VEGF) polymorphisms -2578C/A, -1154G/A and -634C/G and clinical factors in renal cell carcinoma (RCC) prognosis in a cohort of 336 RCC cases. A total of 336 patients with RCC were recruited from PLA General Hospital between January 2004 and December 2005. All patients were followed up until December 2010, and no patient was lost to follow-up. The follow-up time of this study was 60 months. At the time of analysis, a total of 210 died during the follow-up. The median overall survival for patients was 29.1 months (95%CI = 17.1 to 41.3 months), and the 5-year survival rate for the patients was 37.5%. Our study showed that Karnofsky performance status ≥60 could delay death from RCC, with HR (95%CI) of 0.57 (0.39-0.84). Patients with anemia, platelet count >400 x 10(9)/L, neutrophilia and lymphocytes >160 g/L had increased risk of death from RCC, with HR (95%CI) of 1.84 (1.18-2.96), 2.01 (1.27-3.25), 1.65 (1.03-2.56) and 1.49 (0.99-2.71), respectively. The VEGF -2578AA and -1154AA genotypes were significantly associated with a poor overall survival of RCC patients, with HR (95%CI) of 2.41 (1.32-5.13) and 3.77 (1.42-15.67), respectively. In conclusion, our study presented the factors regarding the prognosis of RCC patients, and high platelet and neutrophil counts, low lymphocytes, and VEGF -2578C/A and -1154G/A polymorphisms were shown to be independent factors for a lower prognosis of RCC patients. PMID:25062489

  12. Intraoperative Blood Loss Independently Predicts Survival and Recurrence after Resection of Colorectal Cancer Liver Metastasis

    PubMed Central

    Wu, Xiao-Jun; Wang, Fu-Long; Lu, Zhen-Hai; Zhang, Rong-Xin; Ding, Pei-Rong; Fan, Wen-Hua; Pan, Zhi-Zhong; De-Sen Wan

    2013-01-01

    Background Although numerous prognostic factors have been reported for colorectal cancer liver metastasis (CRLM), few studies have reported intraoperative blood loss (IBL) effects on clinical outcome after CRLM resection. Methods We retrospectively evaluated the clinical and histopathological characteristics of 139 patients who underwent liver resection for CRLM. The IBL cutoff volume was calculated using receiver operating characteristic curves. Overall survival (OS) and recurrence free survival (RFS) were assessed using the Kaplan–Meier and Cox regression methods. Results All patients underwent curative resection. The median follow up period was 25.0 months (range, 2.1–88.8). Body mass index (BMI) and CRLM number and tumor size were associated with increased IBL. BMI (P=0.01; 95% CI = 1.3–8.5) and IBL (P<0.01; 95% CI = 1.6–12.5) were independent OSOs predictors. Five factors, including IBL (P=0.02; 95% CI = 1.1–4.1), were significantly related to RFS via multivariate Cox regression analysis. In addition, OSOs and RFS significantly decreased with increasing IBL volumes. The 5-year OSOs of patients with IBL≤250, 250–500, and >500mL were 71%, 33%, and 0%, respectively (P<0.01). RFS of patients within three IBL volumes at the end of the first year were 67%, 38%, and 18%, respectively (P<0.01). Conclusions IBL during CRLM resection is an independent predictor of long term survival and tumor recurrence, and its prognostic value was confirmed by a dose–response relationship. PMID:24098431

  13. High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT

    PubMed Central

    Danby, R D; Zhang, W; Medd, P; Littlewood, T J; Peniket, A; Rocha, V; Roberts, D J

    2016-01-01

    Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3+CD4+CD25+FOXP3+CD127dim/−) dose transplanted was 4.7 × 106/kg, with Tregs accounting for a median of 2.96% of CD4+ T cells. Patients transplanted with grafts containing a Treg/CD4+ T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4+ T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4+ T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P<0.001) and lymphocyte (HR, 0.54; P=0.009) recovery. These data support the hypothesis that the proportion of Tregs in allogeneic HSC grafts influences clinical outcome and suggest that Treg therapies could improve allogeneic HSC transplantation. PMID:26389831

  14. SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients

    SciTech Connect

    Kotti, Angeliki Holmqvist, Annica; Albertsson, Maria; Sun, Xiao-Feng

    2014-04-01

    Purpose: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT. Methods and Materials: The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry. Results: Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569). Conclusions: SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.

  15. Dynamic of bone marrow fibrosis regression predicts survival after allogeneic stem cell transplantation for myelofibrosis.

    PubMed

    Kröger, Nicolaus; Zabelina, Tatjana; Alchalby, Haefaa; Stübig, Thomas; Wolschke, Christine; Ayuk, Francis; von Hünerbein, Natascha; Kvasnicka, Hans-Michael; Thiele, Jürgen; Kreipe, Hans-Heinrich; Büsche, Guntram

    2014-06-01

    We correlate regression of bone marrow fibrosis (BMF) on day 30 and 100 after dose- reduced allogeneic stem cell transplantation (allo-SCT) in 57 patients with primary or post-essential thrombocythemia/polycythemia vera myelofibrosis with graft function and survival. The distribution of International Prognostic Scoring System (IPSS) risk score categories was 1 patient with low risk, 5 patients with intermediate-1 risk, 18 patients with intermediate-2 risk, and 33 patients with high risk. Before allo-SCT, 41 patients (72%) were classified as XXX [myclofibrosis (MF)]-3 and 16 (28%) were classified as MF-2 according to the World Health Organization criteria. At postengraftment day +30 (±10 days), 21% of the patients had near-complete or complete regression of BMF (MF-0/-1), and on day +100 (±20 days), 54% were MF-0/-1. The 5-year overall survival rate at day +100 was 96% in patients with MF-0/-1 and 57% for those with MF-2/-3 (P = .04). There was no difference in BMF regression at day +100 between IPSS high-risk and low/intermediate-risk patients. Complete donor cell chimerism at day +100 was seen in 81% of patients with MF-0/-1 and in 31% of those with MF-2/-3. Patients with MF-2/-3 at day +100 were more likely to be transfusion-dependent for either RBCs (P = .014) or platelets (P = .018). Rapid BMF regression after reduced-intensity conditioning allo-SCT resulted in a favorable survival independent of IPSS risk score at transplantation. PMID:24589549

  16. Lymphocyte-to-monocyte ratio predicts survival after radiofrequency ablation for colorectal liver metastases

    PubMed Central

    Facciorusso, Antonio; Del Prete, Valentina; Crucinio, Nicola; Serviddio, Gaetano; Vendemiale, Gianluigi; Muscatiello, Nicola

    2016-01-01

    AIM: To test the correlation between lymphocyte-to-monocyte ratio (LMR) and survival after radiofrequency ablation (RFA) for colorectal liver metastasis (CLMs). METHODS: From July 2003 to Feb 2012, 127 consecutive patients with 193 histologically-proven unresectable CLMs were treated with percutaneous RFA at the University of Foggia. All patients had undergone primary colorectal tumor resection before RFA and received systemic chemotherapy. LMR was calculated by dividing lymphocyte count by monocyte count assessed at baseline. Treatment-related toxicity was defined as any adverse events occurred within 4 wk after the procedure. Overall survival (OS) and time to recurrence (TTR) were estimated from the date of RFA by Kaplan-Meier with plots and median (95%CI). The inferential analysis for time to event data was conducted using the Cox univariate and multivariate regression model to estimate hazard ratios (HR) and 95%CI. Statistically significant variables from the univariate Cox analysis were considered for the multivariate models. RESULTS: Median age was 66 years (range 38-88) and patients were prevalently male (69.2%). Median LMR was 4.38% (0.79-88) whereas median number of nodules was 2 (1-3) with a median maximum diameter of 27 mm (10-45). Median OS was 38 mo (34-53) and survival rate (SR) was 89.4%, 40.4% and 33.3% at 1, 4 and 5 years respectively in the whole cohort. Running log-rank test analysis found 3.96% as the most significant prognostic cut-off point for LMR and stratifying the study population by this LMR value median OS resulted 55 mo (37-69) in patients with LMR > 3.96% and 34 (26-39) mo in patients with LMR ≤ 3.96% (HR = 0.53, 0.34-0.85, P = 0.007). Nodule size and LMR were the only significant predictors for OS in multivariate analysis. Median TTR was 29 mo (22-35) with a recurrence-free survival (RFS) rate of 72.6%, 32.1% and 21.8% at 1, 4 and 5 years, respectively in the whole study group. Nodule size and LMR were confirmed as significant

  17. New Symptom-Based Predictive Tool for Survival at Seven and Thirty Days Developed by Palliative Home Care Teams

    PubMed Central

    Bescos, Mar; Barcons, Miquel; Torrubia, Pilar; Trujillano, Javier; Requena, Antonio

    2014-01-01

    Abstract Aim: This study sought to develop models to predict survival at 7 and 30 days based on symptoms detected by palliative home care teams (PHCTs). Materials and methods: This prospective analytic study included a 6-month recruitment period with patient monitoring until death or 180 days after recruitment. The inclusion criteria consisted of age greater than 18 years, advanced cancer, and treatment provided by participating PHCTs between April and July 2009. The study variables included death at 7 or 30 days, survival time, age, gender, place of residence, type of tumor and extension, presence of 11 signs and symptoms measured with a 0–3 Likert scale, functional and cognitive status, and use of a subcutaneous butterfly needle. The statistics applied included a descriptive analysis according to the percentage or mean±standard deviation. For symptom comparison between surviving and nonsurviving patients, the χ2 test was used. Classification and regression tree (CART) methodology was used for model development. An internal validation system (cross-validation with 10 partitions) was used to ensure generalization of the models. The area under the receiver operating characteristics (ROC) curve was calculated (with a 95% confidence interval) to assess the validation of the models. Results: A total of 698 patients were included. The mean age of the patients was 73.7±12 years, and 60.3% were male. The most frequent type of neoplasm was digestive (37.6%). The mean Karnofsky score was 51.8±14, the patients' cognitive status according to the Pfeiffer test was 2.6±4 errors, and 8.3% of patients required a subcutaneous butterfly needle. Each model provided 8 decision rules with a probability assignment range between 2.2% and 99.1%. The model used to predict the probability of death at 7 days included the presence of anorexia and dysphagia and the level of consciousness, and this model produced areas under the curve (AUCs) of 0.88 (0.86–0.90) and 0.81 (0.79–0

  18. Survival time prediction of patients with glioblastoma multiforme tumors using spatial distance measurement

    NASA Astrophysics Data System (ADS)

    Zhou, Mu; Hall, Lawrence O.; Goldgof, Dmitry B.; Gillies, Robert J.; Gatenby, Robert A.

    2013-02-01

    Regional variations in tumor blood flow and necrosis are commonly observed in cross sectional imaging of clinical cancers. We hypothesize that radiologically-defined regional variations in tumor characteristics can be used to define distinct "habitats" that reflect the underlying evolutionary dynamics. Here we present an experimental framework to extract spatially-explicit variations in tumor features (habitats) from multiple MRI sequences performed on patients with Glioblastoma Multiforme (GBM). The MRI sequences consist of post gadolinium T1-weighted, FLAIR, and T2-weighted images from The Cancer Genome Atlas (TCGA). Our strategy is to identify spatially distinct, radiologically-defined intratumoral habitats by characterizing each small tumor regions based on their combined properties in 3 different MRI sequences. Initial tumor identification was performed by manually drawing a mask on a T1-weighted post contrast image slice. The extracted tumor was segmented into an enhancing and non-enhancing region by the Otsu segmentation algorithm, followed by a mask mapping procedure onto the corresponding FLAIR and T2-weighted images. Then Otsu was applied on the FLAIR and T2 images separately. We find that tumor heterogeneity measured through Distance Features (DF) can be used as a strong predictor of survival time. In an initial cohort of 16 cases slow progressing tumors have lower DF values (are less heterogeneous) compared to those with fast progression and short survival times.

  19. Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients.

    PubMed

    Harutyunyan, Nika M; Vardanyan, Suzie; Ghermezi, Michael; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R

    2016-07-01

    Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma. PMID:27017948

  20. Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy

    PubMed Central

    DeNardo, David G.; Brennan, Donal J.; Rexhepaj, Elton; Ruffell, Brian; Shiao, Stephen L.; Madden, Stephen F.; Gallagher, William M.; Wadhwani, Nikhil; Keil, Scott D.; Junaid, Sharfaa A.; Rugo, Hope S.; Hwang, E. Shelley; Jirström, Karin; West, Brian L.; Coussens, Lisa M.

    2011-01-01

    Immune-regulated pathways influence multiple aspects of cancer development. In this article we demonstrate that both macrophage abundance and T-cell abundance in breast cancer represent prognostic indicators for recurrence-free and overall survival. We provide evidence that response to chemotherapy is in part regulated by these leukocytes; cytotoxic therapies induce mammary epithelial cells to produce monocyte/macrophage recruitment factors, including colony stimulating factor 1 (CSF1) and interleukin-34, which together enhance CSF1 receptor (CSF1R)–dependent macrophage infiltration. Blockade of macrophage recruitment with CSF1R-signaling antagonists, in combination with paclitaxel, improved survival of mammary tumor–bearing mice by slowing primary tumor development and reducing pulmonary metastasis. These improved aspects of mammary carcinogenesis were accompanied by decreased vessel density and appearance of antitumor immune programs fostering tumor suppression in a CD8+ T-cell–dependent manner. These data provide a rationale for targeting macrophage recruitment/ response pathways, notably CSF1R, in combination with cytotoxic therapy, and identification of a breast cancer population likely to benefit from this novel therapeutic approach. PMID:22039576

  1. Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value

    PubMed Central

    Walker, Michael J.; Zhou, Cong; Backen, Alison; Pernemalm, Maria; Williamson, Andrew J.K.; Priest, Lynsey J.C.; Koh, Pek; Faivre-Finn, Corinne; Blackhall, Fiona H.; Dive, Caroline; Whetton, Anthony D.

    2015-01-01

    Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived > 18 mo were compared to the same time points from patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform. Over 650 proteins were detected and relatively quantified. Proteins which showed a change during radiotherapy were selected for validation using an orthogonal antibody-based approach. Two of these proteins were verified in a separate patient cohort: values of CRP and LRG1 combined gave a highly significant indication of extended survival post one week of radiotherapy treatment. PMID:26425690

  2. Machine-learning prediction of cancer survival: a retrospective study using electronic administrative records and a cancer registry

    PubMed Central

    Gupta, Sunil; Tran, Truyen; Luo, Wei; Phung, Dinh; Kennedy, Richard Lee; Broad, Adam; Campbell, David; Kipp, David; Singh, Madhu; Khasraw, Mustafa; Matheson, Leigh; Ashley, David M; Venkatesh, Svetha

    2014-01-01

    Objectives Using the prediction of cancer outcome as a model, we have tested the hypothesis that through analysing routinely collected digital data contained in an electronic administrative record (EAR), using machine-learning techniques, we could enhance conventional methods in predicting clinical outcomes. Setting A regional cancer centre in Australia. Participants Disease-specific data from a purpose-built cancer registry (Evaluation of Cancer Outcomes (ECO)) from 869 patients were used to predict survival at 6, 12 and 24 months. The model was validated with data from a further 94 patients, and results compared to the assessment of five specialist oncologists. Machine-learning prediction using ECO data was compared with that using EAR and a model combining ECO and EAR data. Primary and secondary outcome measures Survival prediction accuracy in terms of the area under the receiver operating characteristic curve (AUC). Results The ECO model yielded AUCs of 0.87 (95% CI 0.848 to 0.890) at 6 months, 0.796 (95% CI 0.774 to 0.823) at 12 months and 0.764 (95% CI 0.737 to 0.789) at 24 months. Each was slightly better than the performance of the clinician panel. The model performed consistently across a range of cancers, including rare cancers. Combining ECO and EAR data yielded better prediction than the ECO-based model (AUCs ranging from 0.757 to 0.997 for 6 months, AUCs from 0.689 to 0.988 for 12 months and AUCs from 0.713 to 0.973 for 24 months). The best prediction was for genitourinary, head and neck, lung, skin, and upper gastrointestinal tumours. Conclusions Machine learning applied to information from a disease-specific (cancer) database and the EAR can be used to predict clinical outcomes. Importantly, the approach described made use of digital data that is already routinely collected but underexploited by clinical health systems. PMID:24643167

  3. A Lymph Node Ratio of 10% Is Predictive of Survival in Stage III Colon Cancer: A French Regional Study

    PubMed Central

    Sabbagh, Charles; Mauvais, François; Cosse, Cyril; Rebibo, Lionel; Joly, Jean-Paul; Dromer, Didier; Aubert, Christine; Carton, Sophie; Dron, Bernard; Dadamessi, Innocenti; Maes, Bernard; Perrier, Guillaume; Manaouil, David; Fontaine, Jean-François; Gozy, Michel; Panis, Xavier; Foncelle, Pierre Henri; de Fresnoy, Hugues; Leroux, Fabien; Vaneslander, Pierre; Ghighi, Caroline; Regimbeau, Jean-Marc

    2014-01-01

    Lymph node ratio (LNR) (positive lymph nodes/sampled lymph nodes) is predictive of survival in colon cancer. The aim of the present study was to validate the LNR as a prognostic factor and to determine the optimum LNR cutoff for distinguishing between “good prognosis” and “poor prognosis” colon cancer patients. From January 2003 to December 2007, patients with TNM stage III colon cancer operated on with at least of 3 years of follow-up and not lost to follow-up were included in this retrospective study. The two primary endpoints were 3-year overall survival (OS) and disease-free survival (DFS) as a function of the LNR groups and the cutoff. One hundred seventy-eight patients were included. There was no correlation between the LNR group and 3-year OS (P = 0.06) and a significant correlation between the LNR group and 3-year DFS (P = 0.03). The optimal LNR cutoff of 10% was significantly correlated with 3-year OS (P = 0.02) and DFS (P = 0.02). The LNR was not an accurate prognostic factor when fewer than 12 lymph nodes were sampled. Clarification and simplification of the LNR classification are prerequisites for use of this system in randomized control trials. An LNR of 10% appears to be the optimal cutoff. PMID:25058763

  4. A lymph node ratio of 10% is predictive of survival in stage III colon cancer: a French regional study.

    PubMed

    Sabbagh, Charles; Mauvais, François; Cosse, Cyril; Rebibo, Lionel; Joly, Jean-Paul; Dromer, Didier; Aubert, Christine; Carton, Sophie; Dron, Bernard; Dadamessi, Innocenti; Maes, Bernard; Perrier, Guillaume; Manaouil, David; Fontaine, Jean-François; Gozy, Michel; Panis, Xavier; Foncelle, Pierre Henri; de Fresnoy, Hugues; Leroux, Fabien; Vaneslander, Pierre; Ghighi, Caroline; Regimbeau, Jean-Marc

    2014-01-01

    Lymph node ratio (LNR) (positive lymph nodes/sampled lymph nodes) is predictive of survival in colon cancer. The aim of the present study was to validate the LNR as a prognostic factor and to determine the optimum LNR cutoff for distinguishing between "good prognosis" and "poor prognosis" colon cancer patients. From January 2003 to December 2007, patients with TNM stage III colon cancer operated on with at least of 3 years of follow-up and not lost to follow-up were included in this retrospective study. The two primary endpoints were 3-year overall survival (OS) and disease-free survival (DFS) as a function of the LNR groups and the cutoff. One hundred seventy-eight patients were included. There was no correlation between the LNR group and 3-year OS (P=0.06) and a significant correlation between the LNR group and 3-year DFS (P=0.03). The optimal LNR cutoff of 10% was significantly correlated with 3-year OS (P=0.02) and DFS (P=0.02). The LNR was not an accurate prognostic factor when fewer than 12 lymph nodes were sampled. Clarification and simplification of the LNR classification are prerequisites for use of this system in randomized control trials. An LNR of 10% appears to be the optimal cutoff. PMID:25058763

  5. Long‐Term Post‐CABG Survival: Performance of Clinical Risk Models Versus Actuarial Predictions

    PubMed Central

    Carr, Brendan M.; Romeiser, Jamie; Ruan, Joyce; Gupta, Sandeep; Seifert, Frank C.; Zhu, Wei

    2015-01-01

    Abstract Background/aim Clinical risk models are commonly used to predict short‐term coronary artery bypass grafting (CABG) mortality but are less commonly used to predict long‐term mortality. The added value of long‐term mortality clinical risk models over traditional actuarial models has not been evaluated. To address this, the predictive performance of a long‐term clinical risk model was compared with that of an actuarial model to identify the clinical variable(s) most responsible for any differences observed. Methods Long‐term mortality for 1028 CABG patients was estimated using the Hannan New York State clinical risk model and an actuarial model (based on age, gender, and race/ethnicity). Vital status was assessed using the Social Security Death Index. Observed/expected (O/E) ratios were calculated, and the models' predictive performances were compared using a nested c‐index approach. Linear regression analyses identified the subgroup of risk factors driving the differences observed. Results Mortality rates were 3%, 9%, and 17% at one‐, three‐, and five years, respectively (median follow‐up: five years). The clinical risk model provided more accurate predictions. Greater divergence between model estimates occurred with increasing long‐term mortality risk, with baseline renal dysfunction identified as a particularly important driver of these differences. Conclusions Long‐term mortality clinical risk models provide enhanced predictive power compared to actuarial models. Using the Hannan risk model, a patient's long‐term mortality risk can be accurately assessed and subgroups of higher‐risk patients can be identified for enhanced follow‐up care. More research appears warranted to refine long‐term CABG clinical risk models. doi: 10.1111/jocs.12665 (J Card Surg 2016;31:23–30) PMID:26543019

  6. TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas

    PubMed Central

    Qu, Yiping; Wang, Maode; Cui, Bo; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2016-01-01

    Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P < 0.001), and demonstrated that the RTL was strongly correlated with tumor recurrence. Importantly, TERT promoter mutations or long RTL caused a significantly poorer survival than TERT wild-type or short RTL. Coexisting TERT promoter mutations and long RTL were more commonly associated with poor patient survival than they were individually. Notably, the patients with TERT promoter mutations particularly C228T or long RTL were resistant to radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas. PMID:26556853

  7. Gene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients.

    PubMed

    Kostareli, Efterpi; Hielscher, Thomas; Zucknick, Manuela; Baboci, Lorena; Wichmann, Gunnar; Holzinger, Dana; Mücke, Oliver; Pawlita, Michael; Del Mistro, Annarosa; Boscolo-Rizzo, Paolo; Da Mosto, Maria Cristina; Tirelli, Giancarlo; Plinkert, Peter; Dietz, Andreas; Plass, Christoph; Weichenhan, Dieter; Hess, Jochen

    2016-01-01

    Infection with high-risk types of human papilloma virus (HPV) is currently the best-established prognostic marker for head and neck squamous cell carcinoma (HNSCC), one of the most common and lethal human malignancies worldwide. Clinical trials have been launched to address the concept of treatment de-escalation for HPV-positive HNSCC with the final aim to reduce treatment related toxicity and debilitating long-term impacts on the quality of life. However, HPV-related tumors are mainly restricted to oropharyngeal SCC (OPSCC) and there is an urgent need to establish reliable biomarkers for all patients at high risk for treatment failure. A patient cohort (n = 295) with mainly non-OPSCC (72.9%) and a low prevalence of HPV16-related tumors (8.8%) was analyzed by MassARRAY to determine a previously established prognostic methylation score (MS). Kaplan-Meier revealed a highly significant correlation between a high MS and a favorable survival for OPSCC (P = 0.0004) and for non-OPSCC (P<0.0001), which was confirmed for all HNSCC by multivariate Cox regression models (HR: 9.67, 95% CI [4.61-20.30], P<0.0001). Next, we established a minimal methylation signature score (MMSS), which consists of ten most informative of the originally 62 CpG units used for the MS. The prognostic value of the MMSS was confirmed by Kaplan-Meier analysis for all HNSCC (P<0.0001) and non-OPSCC (P = 0.0002), and was supported by multivariate Cox regression models for all HNSCC (HR: 2.15, 95% CI [1.36-3.41], P = 0.001). In summary, the MS and the MMSS exhibit an excellent performance as prognosticators for survival, which is not limited by the anatomical site, and both could be implemented in future clinical trials. PMID:26786582

  8. Quantification of mutant alleles in circulating tumor DNA can predict survival in lung cancer

    PubMed Central

    Ye, Xin; Bai, Hua; Wang, Zhijie; Sun, Yun; Zhao, Jun; An, Tongtong; Duan, Jianchun; Wu, Meina; Wang, Jie

    2016-01-01

    Purpose We aimed to investigate the feasibility of droplet digital PCR (ddPCR) for the quantitative and dynamic detection of EGFR mutations and next generation sequencing (NGS) for screening EGFR-tyrosine kinase inhibitors (EGFR-TKIs) resistance-relevant mutations in circulating tumor DNA (ctDNA) from advanced lung adenocarcinoma (ADC) patients. Results Detection limit of EGFR mutation in ctDNA by ddPCR was 0.04%. Taking the EGFR mutation in tumor tissue as the golden standard, the concordance of EGFR mutations detected in ctDNA was 74% (54/73). Patients with EGFR mutation in ctDNA (n = 54) superior progression-free survival (PFS, median, 12.6 vs. 6.7 months, P < 0.001) and overall survival (OS, median, 35.6 vs. 23.8 months, P = 0.028) compared to those with EGFR wild type in ctDNA (n = 19). Patients with high EGFR-mutated abundance in ctDNA (> 5.15%) showed better PFS compared to those with low EGFR mutated abundance (≤ 5.15%) (PFS, median, 15.4 vs. 11.1 months, P = 0.021). NGS results showed that 66.6% (8/12) total mutational copy number were elevated and 76.5% (26/34) mutual mutation frequency increased after disease progression. Methods Seventy-three advanced ADC patients with tumor tissues carrying EGFR mutations and their matched pre- and post-EGFR-TKIs plasma samples were enrolled in this study. Absolute quantities of plasma EGFR mutant and wild-type alleles were measured by ddPCR. Multi-genes testing was performed using NGS in 12 patients. Conclusions Dynamic and quantitative analysis of EGFR mutation in ctDNA could guide personalized therapy for advanced ADC. NGS shows good performance in multiple genes testing especially novel and uncommon genes. PMID:26989078

  9. Paradoxical Herniation After Unilateral Decompressive Craniectomy Predicts Better Patient Survival: A Retrospective Analysis of 429 Cases.

    PubMed

    Chen, Weiqiang; Guo, Jingfang; Wu, Jin; Peng, Guoyi; Huang, Mindong; Cai, Chuwei; Yang, Yingming; Wang, Shousen

    2016-03-01

    Paradoxical herniation (PH) is a life-threatening emergency after decompressive craniectomy. In the current study, we examined patient survival in patients who developed PH after decompressive craniectomy versus those who did not. Risk factors for, and management of, PH were also analyzed. This retrospective analysis included 429 consecutive patients receiving decompressive craniectomy during a period from January 2007 to December 2012. Mortality rate and Glasgow Outcome Scale (GOS) were compared between those who developed PH (n = 13) versus those who did not (n = 416). A stepwise multivariate logistic regression analysis was carried out to examine the risk factors for PH. The overall mortality in the entire sample was 22.8%, with a median follow-up of 6 months. Oddly enough, all 13 patients who developed PH survived beyond 6 months. Glasgow Coma Scale did not differ between the 2 groups upon admission, but GOS was significantly higher in subjects who developed PH. Both the disease type and coma degree were comparable between the 13 PH patients and the remaining 416 patients. In all PH episodes, patients responded to emergency treatments that included intravenous hydration, cerebral spinal fluid drainage discontinuation, and Trendelenburg position. A regression analysis indicated the following independent risk factors for PH: external ventriculostomy, lumbar puncture, and continuous external lumbar drainage. The rate of PH is approximately 3% after decompressive craniectomy. The most intriguing findings of the current study were the 0% mortality in those who developed PH versus 23.6% mortality in those who did not develop PH and significant difference of GOS score at 6-month follow-up between the 2 groups, suggesting that PH after decompressive craniectomy should be managed aggressively. The risk factors for PH include external ventriculostomy, ventriculoperitoneal shunt, lumbar puncture, and continuous external lumbar drainage. PMID:26945365

  10. Early-phase circulating miRNAs predict tumor recurrence and survival of hepatocellular carcinoma patients after liver transplantation

    PubMed Central

    NG, Kevin Tak-Pan; Lo, Chung Mau; Wong, Nathalie; Li, Chang Xian; Qi, Xiang; Liu, Xiao Bing; Geng, Wei; Yeung, Oscar Wai-Ho; Ma, Yuen Yuen; Chan, See Ching; Man, Kwan

    2016-01-01

    Post-liver transplantation tumor recurrence is a major challenge for hepatocellular carcinoma (HCC) recipients. We aimed to identify early-phase circulating microRNAs after liver transplantation for predicting tumor recurrence and survival of HCC recipients. Circulating microRNA profiles at early-phase (2-hour after portal vein reperfusion) after liver transplantation were compared between HCC recipients with (n=4) and without tumor recurrence (n=8) by microarray analyses. Candidate microRNAs were validated in 62 HCC recipients by quantitative RT-PCR. The prognostic values of microRNAs for tumor recurrence and survival were examined. Simulated in vitro ischemia-reperfusion injury models were employed to characterize the possible mechanism of up-regulation of circulating microRNAs. Our results showed that up-regulation of circulating miR-148a, miR-1246 or miR-1290 at early-phase was significantly associated with HCC recurrence after liver transplantation. Among them, miR-148a (p=0.030) and miR-1246 (p=0.009) were significant predictors of HCC recurrence. MiR-1246 was an independent predictor of overall (p=0.023) and disease-free survival (p=0.020) of HCC recipients. The level of early-phase circulating miR-1246 was positively correlated with serum AST and ALT levels in HCC recipients after liver transplantation. The expression of hepatic miR-1246 was positively correlated with TNFα mRNA. In vitro experiments indicated that injury-induced activation and differentiation of macrophages significantly elevated the expression and secretion of miR-1246. In conclusion, early-phase circulating miR-1246 is an indicator of hepatic injury and a novel prognostic biomarker for tumor recurrence and survival of HCC recipients after liver transplantation. PMID:26918346

  11. miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS.

    PubMed

    Fiore, Danilo; Donnarumma, Elvira; Roscigno, Giuseppina; Iaboni, Margherita; Russo, Valentina; Affinito, Alessandra; Adamo, Assunta; De Martino, Fabio; Quintavalle, Cristina; Romano, Giulia; Greco, Adelaide; Soini, Ylermi; Brunetti, Arturo; Croce, Carlo M; Condorelli, Gerolama

    2016-04-12

    Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12-14 months. There is thus increasing interest in the identification of molecular signatures predicting glioblastoma prognosis and in how to improve the therapeutic approach. Here, we report miR-340 as prognostic tumor-suppressor microRNA for glioblastoma. We analyzed microRNA expression in > 500 glioblastoma patients and found that although miR-340 is strongly down-regulated in glioblastoma overall, it is up-regulated in LTS patients compared to short-term survivors (STS). Indeed, miR-340 expression predicted better prognosis in glioblastoma patients. Coherently, overexpression of miR-340 in glioblastoma cells was found to produce a tumor-suppressive activity. We identified NRAS mRNA as a critical, direct target of miR-340: in fact, miR-340 negatively influenced multiple aspects of glioblastoma tumorigenesis by down-regulating NRAS and downstream AKT and ERK pathways. Thus, we demonstrate that expression of miR-340 in glioblastoma is responsible for a strong tumor-suppressive effect in LTS patients by down-regulating NRAS. miR-340 may thus represent a novel marker for glioblastoma diagnosis and prognosis, and may be developed into a tool to improve treatment of glioblastoma. PMID:26799668

  12. miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS

    PubMed Central

    Fiore, Danilo; Donnarumma, Elvira; Roscigno, Giuseppina; Iaboni, Margherita; Russo, Valentina; Affinito, Alessandra; Adamo, Assunta; De Martino, Fabio; Quintavalle, Cristina; Romano, Giulia; Greco, Adelaide; Soini, Ylermi; Brunetti, Arturo; Croce, Carlo M.; Condorelli, Gerolama

    2016-01-01

    Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12–14 months. There is thus increasing interest in the identification of molecular signatures predicting glioblastoma prognosis and in how to improve the therapeutic approach. Here, we report miR-340 as prognostic tumor-suppressor microRNA for glioblastoma. We analyzed microRNA expression in > 500 glioblastoma patients and found that although miR-340 is strongly down-regulated in glioblastoma overall, it is up-regulated in LTS patients compared to short-term survivors (STS). Indeed, miR-340 expression predicted better prognosis in glioblastoma patients. Coherently, overexpression of miR-340 in glioblastoma cells was found to produce a tumor-suppressive activity. We identified NRAS mRNA as a critical, direct target of miR-340: in fact, miR-340 negatively influenced multiple aspects of glioblastoma tumorigenesis by down-regulating NRAS and downstream AKT and ERK pathways. Thus, we demonstrate that expression of miR-340 in glioblastoma is responsible for a strong tumor-suppressive effect in LTS patients by down-regulating NRAS. miR-340 may thus represent a novel marker for glioblastoma diagnosis and prognosis, and may be developed into a tool to improve treatment of glioblastoma. PMID:26799668

  13. SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma

    PubMed Central

    Dhanda, J; Triantafyllou, A; Liloglou, T; Kalirai, H; Lloyd, B; Hanlon, R; Shaw, R J; Sibson, D R; Risk, J M

    2014-01-01

    Background: 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. Methods: 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. Results: Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (P<0.001). ECS was associated with expression of either or both proteins in all cases. SMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (P<0.001). MRI showed poor sensitivity for detection of nodal metastasis (56%) and ECS (7%). Both separately, and in combination, SERPINE1 and SMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95% SMA: 82% combination: 81%). Conclusion: 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. PMID:25268377

  14. Evaluation of MR markers that predict survival in patients with newly diagnosed GBM prior to adjuvant therapy.

    PubMed

    Saraswathy, Suja; Crawford, Forrest W; Lamborn, Kathleen R; Pirzkall, Andrea; Chang, Susan; Cha, Soonmee; Nelson, Sarah J

    2009-01-01

    Purpose Glioblastoma Multiforme (GBM) is the most common and lethal primary brain tumor in adults. The goal of this study was to test the predictive value of MR parameters in relation to the survival of patients with newly diagnosed GBM who were scanned prior to receiving adjuvant radiation and chemotherapy. Methods The study population comprised 68 patients who had surgical resection and were to be treated with fractionated external beam radiation therapy and chemotherapy. Imaging scans included anatomical MRI, diffusion and perfusion weighted imaging and (1)H MRSI. The MR data were acquired 3-5 weeks after surgery and approximately 1 week before treatment with radiation therapy. The diffusion, perfusion and spectroscopic parameter values were quantified and subjected to proportional hazards analysis that was adjusted for age and scanner field strength. Results The patients with larger lesion burden based upon volumes of anatomic lesions, volume of CNI2 (number of voxels within the T2 lesion having choline to NAA index >2), volume of CBV3 (number of pixels within the T2 lesion having relative cerebral blood volume >3), and volume of nADC1.5 (number of pixels within the T2 lesion having normalized apparent diffusion coefficient <1.5) had a higher risk for poor outcome. High intensities of combined measures of lactate and lipid in the T2 and CNI2 regions were also associated with poor survival. Conclusions Our study indicated that several pre-treatment anatomic, physiological and metabolic MR parameters are predictive of survival. This information may be important for stratifying patients to specific treatment protocols and for planning focal therapy. PMID:18810326

  15. Evaluation of MR markers that predict survival in patients with newly diagnosed GBM prior to adjuvant therapy

    PubMed Central

    Saraswathy, Suja; Crawford, Forrest W.; Lamborn, Kathleen R.; Pirzkal, Andrea; Chang, Susan; Cha, Soonmee

    2010-01-01

    Purpose Glioblastoma Multiforme (GBM) is the most common and lethal primary brain tumor in adults. The goal of this study was to test the predictive value of MR parameters in relation to the survival of patients with newly diagnosed GBM who were scanned prior to receiving adjuvant radiation and chemotherapy. Methods The study population comprised 68 patients who had surgical resection and were to be treated with fractionated external beam radiation therapy and chemotherapy. Imaging scans included anatomical MRI, diffusion and perfusion weighted imaging and 1H MRSI. The MR data were acquired 3–5 weeks after surgery and approximately 1 week before treatment with radiation therapy. The diffusion, perfusion and spectroscopic parameter values were quantified and subjected to proportional hazards analysis that was adjusted for age and scanner field strength. Results The patients with larger lesion burden based upon volumes of anatomic lesions, volume of CNI2 (number of voxels within the T2 lesion having choline to NAA index >2), volume of CBV3 (number of pixels within the T2 lesion having relative cerebral blood volume >3), and volume of nADC1.5 (number of pixels within the T2 lesion having normalized apparent diffusion coefficient <1.5) had a higher risk for poor outcome. High intensities of combined measures of lactate and lipid in the T2 and CNI2 regions were also associated with poor survival. Conclusions Our study indicated that several pre-treatment anatomic, physiological and metabolic MR parameters are predictive of survival. This information may be important for stratifying patients to specific treatment protocols and for planning focal therapy. PMID:18810326

  16. The Neutrophil-Platelet Score (NPS) Predicts Survival in Primary Operable Colorectal Cancer and a Variety of Common Cancers

    PubMed Central

    Watt, David G.; Proctor, Michael J.; Park, James H.; Horgan, Paul G.; McMillan, Donald C.

    2015-01-01

    Introduction Recent in-vitro studies have suggested that a critical checkpoint early in the inflammatory process involves the interaction between neutrophils and platelets. This confirms the importance of the innate immune system in the elaboration of the systemic inflammatory response. The aim of the present study was to examine whether a combination of the neutrophil and platelet counts were predictive of survival in patients with cancer. Methods Patients with histologically proven colorectal cancer who underwent potentially curative resection at a single centre between March 1999 and May 2013 (n = 796) and patients with cancer from the Glasgow Inflammation Outcome Study, who had a blood sample taken between January 2000 and December 2007 (n = 9649) were included in the analysis. Results In the colorectal cancer cohort, there were 173 cancer and 135 non-cancer deaths. In patients undergoing elective surgery, cancer-specific survival (CSS) at 5 years ranged from 97% in patients with TNM I disease and NPS = 0 to 57% in patients with TNM III disease and NPS = 2 (p = 0.019) and in patients undergoing elective surgery for node-negative colon cancer from 98% (TNM I, NPS = 0) to 65% (TNM II, NPS = 2) (p = 0.004). In those with a variety of common cancers there were 5218 cancer and 929 non-cancer deaths. On multivariate analysis, adjusting for age and sex and stratified by tumour site, incremental increase in the NPS was significantly associated with poorer CSS (p<0.001). Conclusion The neutrophil-platelet score predicted survival in a variety of common cancers and highlights the importance of the innate immune system in patients with cancer. PMID:26544968

  17. Simulation of the Inferior Mirage

    NASA Astrophysics Data System (ADS)

    Branca, Mario

    2010-09-01

    A mirage can occur when a continuous variation in the refractive index of the air causes light rays to follow a curved path. As a result, the image we see is displaced from the location of the object. If the image appears higher in the air than the object, it is called a "superior" mirage, while if it appears lower it is called an "inferior" mirage.2 The most common example of an inferior mirage is when, on a hot day, a stretch of dry road off in the distance appears to be wet (see Fig. 1). Many lab activities have been described that simulate the formation of superior mirages. In these demonstrations light beams curve downward as they pass through a nonuni-form fluid.3-6 Much less common are laboratory demonstrations of upward-curving light rays of the kind responsible for inferior mirages. This paper describes a simple version of such a demonstration.

  18. Prognostic nomogram to predict progression-free survival in patients with platinum-sensitive recurrent ovarian cancer

    PubMed Central

    Lee, C K; Simes, R J; Brown, C; Lord, S; Wagner, U; Plante, M; Vergote, I; Pisano, C; Parma, G; Burges, A; Bourgeois, H; Högberg, T; Bentley, J; Angleitner-Boubenizek, L; Ferrero, A; Richter, B; Hirte, H; Gebski, V; Pfisterer, J; Pujade-Lauraine, E; Friedlander, M

    2011-01-01

    Background: Patients with platinum-sensitive recurrent ovarian cancer are a heterogeneous group, and it is not possible to accurately predict the progression-free survival (PFS) in these patients. We developed and validated a nomogram to help improve prediction of PFS in patients treated with platinum-based chemotherapy. Methods: The nomogram was developed in a training cohort (n=955) from the CALYPSO trial and validated in the AGO-OVAR 2.5 Study (n=340). The proportional-hazards model (nomogram) was based on pre-treatment characteristics. Results: The nomogram had a concordance index (C-index) of 0.645. Significant predictors were tumour size platinum-chemotherapy-free interval, CA-125, number of organ metastatic sites and white blood count. When the nomogram was applied without CA-125 (CA-125 was not available in validation cohort), the C-indices were 0.624 (training) and 0.594 (validation). When classification was based only on the platinum-chemotherapy-free interval, the indices were 0.571 (training) and 0.560 (validation). The calibration plot in the validation cohort based on four predictors (without CA-125) suggested good agreement between actual and nomogram-predicted 12-month PFS probabilities. Conclusion: This nomogram, using five pre-treatment characteristics, improves prediction of PFS in patients with platinum-sensitive ovarian cancer having platinum-based chemotherapy. It will be useful for the design and stratification of patients in clinical trials and also for counselling patients. PMID:21915127

  19. Does the Hospital Predict Readmission? A Multi-level Survival Analysis Approach.

    PubMed

    Leon, Scott C; Stoner, Alison M; Dickson, Daniel A

    2016-07-01

    Time to psychiatric rehospitalization was predicted for a sample of 1473 Medicaid-insured youth in Illinois in 2005 and 2006. A multi-level model statistical strategy was employed to account for the fact that youth days to rehospitalization were nested within hospital and to test the hypothesis that hospitals would vary significantly in return rates, controlling for individual-level (e.g., symptom, demographic) variables. Hospitals did not vary significantly in days to rehospitalization. At the individual-level, level of externalizing behavior and residential treatment placement predicted a faster return to the hospital. These results support the perspective that hospital outcomes are best operationalized using variables tied more directly to the inpatient episode (e.g., LOS, reductions in acuity). PMID:25925793

  20. Individualized Prediction of Overall Survival After Postoperative Radiation Therapy in Patients With Early-Stage Cervical Cancer: A Korean Radiation Oncology Group Study (KROG 13-03)

    SciTech Connect

    Lee, Hyun Jin; Han, Seungbong; Kim, Young Seok; Nam, Joo-Hyun; Kim, Hak Jae; Kim, Jae Weon; Park, Won; Kim, Byoung-Gie; Kim, Jin Hee; Cha, Soon Do; Kim, Juree; Lee, Ki-Heon; Yoon, Mee Sun; and others

    2013-11-15

    Purpose: A nomogram is a predictive statistical model that generates the continuous probability of a clinical event such as death or recurrence. The aim of the study was to construct a nomogram to predict 5-year overall survival after postoperative radiation therapy for stage IB to IIA cervical cancer. Methods and Materials: The clinical data from 1702 patients with early-stage cervical cancer, treated at 10 participating hospitals from 1990 to 2011, were reviewed to develop a prediction nomogram based on the Cox proportional hazards model. Demographic, clinical, and pathologic variables were included and analyzed to formulate the nomogram. The discrimination and calibration power of the model was measured using a concordance index (c-index) and calibration curve. Results: The median follow-up period for surviving patients was 75.6 months, and the 5-year overall survival probability was 87.1%. The final model was constructed using the following variables: age, number of positive pelvic lymph nodes, parametrial invasion, lymphovascular invasion, and the use of concurrent chemotherapy. The nomogram predicted the 5-year overall survival with a c-index of 0.69, which was superior to the predictive power of the International Federation of Gynecology and Obstetrics (FIGO) staging system (c-index of 0.54). Conclusions: A survival-predicting nomogram that offers an accurate level of prediction and discrimination was developed based on a large multi-center study. The model may be more useful than the FIGO staging system for counseling individual patients regarding prognosis.

  1. Solar activity at birth predicted infant survival and women's fertility in historical Norway

    PubMed Central

    Skjærvø, Gine Roll; Fossøy, Frode; Røskaft, Eivin

    2015-01-01

    Ultraviolet radiation (UVR) can suppress essential molecular and cellular mechanisms during early development in living organisms and variations in solar activity during early development may thus influence their health and reproduction. Although the ultimate consequences of UVR on aquatic organisms in early life are well known, similar studies on terrestrial vertebrates, including humans, have remained limited. Using data on temporal variation in sunspot numbers and individual-based demographic data (N = 8662 births) from Norway between 1676 and 1878, while controlling for maternal effects, socioeconomic status, cohort and ecology, we show that solar activity (total solar irradiance) at birth decreased the probability of survival to adulthood for both men and women. On average, the lifespans of individuals born in a solar maximum period were 5.2 years shorter than those born in a solar minimum period. In addition, fertility and lifetime reproductive success (LRS) were reduced among low-status women born in years with high solar activity. The proximate explanation for the relationship between solar activity and infant mortality may be an effect of folate degradation during pregnancy caused by UVR. Our results suggest that solar activity at birth may have consequences for human lifetime performance both within and between generations. PMID:25567646

  2. Solar activity at birth predicted infant survival and women's fertility in historical Norway.

    PubMed

    Skjærvø, Gine Roll; Fossøy, Frode; Røskaft, Eivin

    2015-02-22

    Ultraviolet radiation (UVR) can suppress essential molecular and cellular mechanisms during early development in living organisms and variations in solar activity during early development may thus influence their health and reproduction. Although the ultimate consequences of UVR on aquatic organisms in early life are well known, similar studies on terrestrial vertebrates, including humans, have remained limited. Using data on temporal variation in sunspot numbers and individual-based demographic data (N = 8662 births) from Norway between 1676 and 1878, while controlling for maternal effects, socioeconomic status, cohort and ecology, we show that solar activity (total solar irradiance) at birth decreased the probability of survival to adulthood for both men and women. On average, the lifespans of individuals born in a solar maximum period were 5.2 years shorter than those born in a solar minimum period. In addition, fertility and lifetime reproductive success (LRS) were reduced among low-status women born in years with high solar activity. The proximate explanation for the relationship between solar activity and infant mortality may be an effect of folate degradation during pregnancy caused by UVR. Our results suggest that solar activity at birth may have consequences for human lifetime performance both within and between generations. PMID:25567646

  3. Can we predict very short term survival in small cell lung cancer?

    PubMed

    Quoix, E; Hedelin, G; Popin, E; Charloux, A; Dietemann, A; Seibert, R; Roeslin, N; Pauli, G

    1993-12-01

    We retrospectively reviewed the charts of 151 consecutive patients diagnosed as small cell lung cancer in our department and who had at least one course of chemotherapy. Nineteen patients died during the first 2 months, of the probability were reported to construct a receiver operating characteristic curve i.e. 13% of the population. The probability of dying within 2 months was investigated through a stepwise logistic regression. A performance status < or = 70 (Karnofsky index), an age > 60, a platelet count < or = 150,000/mm3, elevated alkaline phosphatase and a sodium < or = 135 mmol/l were independent predictors of a very short term survival and contributed to the equation for the probability of dying within a 2-month period. Sensitivity and specificity for various cutoff points characteristic curve allowing one to determine for a given patient his risk of being a very short term survivor. Such an approach could prevent inclusion of patients with high risk of early death in clinical trials and help to choose appropriate treatments for such poor risk patients. PMID:8075968

  4. Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients.

    PubMed

    Kamieniak, Marta M; Rico, Daniel; Milne, Roger L; Muñoz-Repeto, Ivan; Ibáñez, Kristina; Grillo, Miguel A; Domingo, Samuel; Borrego, Salud; Cazorla, Alicia; García-Bueno, José M; Hernando, Susana; García-Donas, Jesús; Hernández-Agudo, Elena; Y Cajal, Teresa Ramón; Robles-Díaz, Luis; Márquez-Rodas, Ivan; Cusidó, Maite; Sáez, Raquel; Lacambra-Calvet, Carmen; Osorio, Ana; Urioste, Miguel; Cigudosa, Juan C; Paz-Ares, Luis; Palacios, José; Benítez, Javier; García, María J

    2015-02-01

    Standard treatments for advanced high-grade serous ovarian carcinomas (HGSOCs) show significant side-effects and provide only short-term survival benefits due to disease recurrence. Thus, identification of novel prognostic and predictive biomarkers is urgently needed. We have used 42 paraffin-embedded HGSOCs, to evaluate the utility of DNA copy number alterations, as potential predictors of clinical outcome. Copy number-based unsupervised clustering stratified HGSOCs into two clusters of different immunohistopathological features and survival outcome (HR = 0.15, 95%CI = 0.03-0.81; Padj = 0.03). We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life. PMID:25454820

  5. Measurements of tumor cell autophagy predict invasiveness, resistance to chemotherapy, and survival in melanoma

    PubMed Central

    Ma, Xiaohong; Piao, Shengfu; Wang, Dan; Mcafee, Quentin; Nathanson, Katherine L.; Lum, Julian J.; Li, Lin Z.; Amaravadi, Ravi K.

    2011-01-01

    Purpose Autophagy consists of lysosome-dependent degradation of cytoplasmic contents sequestered by autophagic vesicles (AV). The role of autophagy in determining tumor aggressiveness and response to therapy in melanoma was investigated in this study. Experimental Design Autophagy was measured in tumor biopsies obtained from metastatic melanoma patients enrolled on a phase II trial of temozolomide and sorafenib and correlated to clinical outcome. These results were compared to autophagy measurements in aggressive and indolent melanoma cells grown in two and three dimensional culture and as xenograft tumors. The effects of autophagy inhibition with either hydroxychloroquine or inducible shRNA against the autophagy gene ATG5 were assessed in three dimensional spheroids. Results Patients whose tumors had a high autophagic index were less likely to respond to treatment and had a shorter survival compared to those with a low autophagic index. Differences in autophagy were less evident in aggressive and indolent melanoma cells grown in monolayer culture. In contrast, autophagy was increased in aggressive compared to indolent melanoma xenograft tumors. This difference was recapitulated when aggressive and indolent melanoma cells were grown as spheroids. Autophagy inhibition with either hydroxychloroquine or inducible shRNA against ATG5 resulted in cell death in aggressive melanoma spheroids, and significantly augmented temozolomide-induced cell death. Conclusions Autophagy is a potential prognostic factor and therapeutic target in melanoma. Three dimensional culture mimics the tumor microenvironment better than monolayer culture and is an appropriate model for studying therapeutic combinations involving autophagy modulators autophagy inhibition should be tested clinically in patients with melanoma. PMID:21325076

  6. Carboplatin–paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer

    PubMed Central

    Lee, C K; Gurney, H; Brown, C; Sorio, R; Donadello, N; Tulunay, G; Meier, W; Bacon, M; Maenpaa, J; Petru, E; Reed, N; Gebski, V; Pujade-Lauraine, E; Lord, S; Simes, R J; Friedlander, M

    2011-01-01

    Background: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin–paclitaxel (CP) or carboplatin–liposomal doxorubicin (CPLD). Methods: We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 109 per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS. Results: Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin–liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008). Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin–liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15). Conclusion: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity. PMID:21750553

  7. Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients.

    PubMed

    Sharma, Pratima; Parikh, Neehar D; Yu, Jessica; Barman, Pranab; Derstine, Brian A; Sonnenday, Christopher J; Wang, Stewart C; Su, Grace L

    2016-08-01

    Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). Recent data suggest that body composition features strongly affect post-LT mortality. We examined the impact of body composition on post-LT mortality in patients with HCC. Data on adult LT recipients who received Model for End-Stage Liver Disease exception for HCC between February 29, 2002, and December 31, 2013, and who had a computed tomography (CT) scan any time 6 months prior to LT were reviewed (n = 118). All available CT scan Digital Imaging and Communication in Medicine files were analyzed using a semiautomated high throughput methodology with algorithms programmed in MATLAB. Analytic morphomics measurements including dorsal muscle group (DMG) area, visceral and subcutaneous fat, and bone mineral density (BMD) were taken at the bottom of the eleventh thoracic vertebral level. Thirty-two (27%) patients died during the median follow-up of 4.4 years. The number of HCC lesions (hazard ratio [HR], 2.81; P < 0.001), BMD (HR = 0.90/Hounsfield units [HU]; P = 0.03), pre-LT locoregional therapy (HR = 0.14; P < 0.001), and donor age (HR = 1.05; P < 0.001) were the independent predictors of post-LT mortality. DMG area did not affect post-LT survival. In conclusion, in addition to number of HCC lesions and pre-LT locoregional therapy, low BMD, a surrogate for bone loss rather than DMG area, was independently associated with post-LT mortality in HCC patients. Bone loss may be an early marker of deconditioning that precedes sarcopenia and may affect transplant outcomes. Liver Transplantation 22 1092-1098 2016 AASLD. PMID:27064263

  8. Predicting Response to Hormonal Therapy and Survival in Men with Hormone Sensitive Metastatic Prostate Cancer

    PubMed Central

    Grivas, Petros D.; Robins, Diane M.; Hussain, Maha

    2014-01-01

    Androgen deprivation is the cornerstone of the management of metastatic prostate cancer. Despite several decades of clinical experience with this therapy there are no standard predictive biomarkers for response. Although several candidate genetic, hormonal, inflammatory, biochemical, metabolic biomarkers have been suggested as potential predictors of response and outcome, none has been prospectively validated nor has proven clinical utility to date. There is significant heterogeneity in the depth and duration of hormonal response and in the natural history of advanced disease; therefore to better optimize/individualize therapy and for future development, identification of biomarkers is critical. This review summarizes the current data on the role of several candidate biomarkers that have been evaluated in the advanced/metastatic disease setting. PMID:22705096

  9. Ki-67 Expression in CRC Lymph Node Metastasis Does Not Predict Survival

    PubMed Central

    Martins, Sandra F.; Amorim, Ricardo; Mota, Sílvia Coelho; Costa, Luís; Pardal, Fernando; Rodrigues, Mesquita; Longatto-Filho, Adhemar

    2015-01-01

    Colorectal cancer is one of the most common malignancies and a leading cause of cancer death worldwide. Molecular markers may improve clinicopathologic staging and provide a basis to guide novel therapeutic strategies which target specific tumour-associated molecules according to individual tumour biology; however, so far, no ideal molecular marker has been found to predict disease progression. We tested Ki-67 proliferation marker in primary and lymph node metastasis of CRC. We observed a statistical significant difference between the positive rates of neoplastic cells positively stained by Ki-67 in both sites, with remarkable increased number of Ki-67 positive cells in primary tumor cells compared to cancer cells that invaded lymph nodes. We can speculate that the metastatic CRC in lymph node can be more resistant to the drugs that target cellular division. PMID:26448927

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

    PubMed

    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; Casasnovas, 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

    2016-02-01

    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

  11. DNA-PK – a candidate driver of hepatocarcinogenesis and tissue biomarker that predicts response to treatment and survival

    PubMed Central

    Cornell, Liam; Munck, Joanne; Alsinet, Clara; Villanueva, Augusto; Ogle, Laura; Willoughby, Catherine; Televantou, Despina; Thomas, Huw; Jackson, Jennifer; Burt, Alastair; Newell, David; Rose, John; Manas, Derek M; Shapiro, Geoffrey; Curtin, Nicola; Reeves, Helen L

    2014-01-01

    Purpose Therapy resistance and associated liver disease make hepatocellular cancers (HCC) difficult to treat with traditional cytotoxic therapies, while newer targeted approaches offer only modest survival benefit. We focused on DNA-dependent protein kinase, DNA-PKcs, encoded by PRKDC and central to DNA damage repair by non-homologous end joining. Our aim was to explore its roles in hepatocarcinogenesis and as a novel therapeutic candidate. Experimental Design PRKDC was characterised in liver tissues from of 132 patients (normal liver (n=10), cirrhotic liver (n=13), dysplastic nodules (n=18), HCC (n=91)) using Affymetrix U133 Plus 2.0 and 500K Human Mapping SNP arrays (cohort 1). In addition, we studied a case series of 45 patients with HCC undergoing diagnostic biopsy (cohort 2). Histological grading, response to treatment and survival were correlated with DNA-PKcs quantified immunohistochemically. Parallel in vitro studies determined the impact of DNA-PK on DNA repair and response to cytotoxic therapy. Results Increased PRKDC expression in HCC was associated with amplification of its genetic locus in cohort 1. In cohort 2, elevated DNA-PKcs identified patients with treatment-resistant HCC, progressing at a median of 4.5 months compared to 16.9 months, while elevation of activated pDNA-PK independently predicted poorer survival. DNA-PKcs was high in HCC cell lines, where its inhibition with NU7441 potentiated irradiation and doxorubicin-induced cytoxicity, while the combination suppressed HCC growth in vitro and in vivo. Conclusions These data identify PRKDC/DNA-PKcs as a candidate driver of hepatocarcinogenesis, whose biopsy characterisation at diagnosis may impact stratification of current therapies, and whose specific future targeting may overcome resistance. PMID:25480831

  12. High incidence of MYC and BCL2 abnormalities in mantle cell lymphoma, although only MYC abnormality predicts poor survival

    PubMed Central

    Li, Chengwen; Zhong, Shizhen; Chen, Weiwei; Li, Zengjun; Xiong, Wenjie; Liu, Wei; Liu, Enbin; Cui, Rui; Ru, Kun; Zhang, Peihong; Xu, Yan; An, Gang; Lv, Rui; Qi, Junyuan; Wang, Jianxiang; Cheng, Tao; Qiu, Lugui

    2015-01-01

    The incidence and prognostic role of MYC and BCL2 rearrangements in mature B-cell lymphomas have been extensively studied, except the infrequent mantle cell lymphoma (MCL). Here, we analyzed the MYC and BCL2 abnormalities and other cytogenetic aberrations by fluorescence in situ hybridization (FISH) in 50 MCL patients with bone marrow involvement. Eighteen patients (36.0%) had MYC gains and/or amplifications, and twelve patients (24.0%) had BCL2 gains and/or amplifications. Among the 18 patients with MYC abnormality, four had simultaneous MYC translocations, but no BCL2 translocation was detected among patients with BCL2 abnormality. Only two patients (4.0%) had both MYC and BCL2 abnormalities. The patients with a MYC abnormality had a significantly higher tumor burden, a higher percentage of medium/high risk MIPI group and genomic instability compared to those without this abnormality. However, no significant difference was observed between patients with or without a BCL2 abnormality in terms of clinical and cytogenetic factors. Patients with a MYC abnormality had poorer progress-free survival (PFS) (9.0 vs. 48.0 months, p = .000) and overall survival (OS) (12.0 vs. 94.5 months, p = .000), but the presence of a BCL2 abnormality did not significantly influence either PFS or OS. In multivariate analysis, the MYC abnormality was the independent adverse factor for both PFS and OS, and intensive chemotherapy did not improve the outcome of these patients. Thus, the presence of a MYC but not BCL2 abnormality predicted the poor survival of MCL patients, and a new treatment strategy should be developed for these patients. PMID:26517511

  13. Context-dependent survival, fecundity and predicted population-level consequences of brucellosis in African buffalo.

    PubMed

    Gorsich, Erin E; Ezenwa, Vanessa O; Cross, Paul C; Bengis, Roy G; Jolles, Anna E

    2015-07-01

    Chronic infections may have negative impacts on wildlife populations, yet their effects are difficult to detect in the absence of long-term population monitoring. Brucella abortus, the bacteria responsible for bovine brucellosis, causes chronic infections and abortions in wild and domestic ungulates, but its impact on population dynamics is not well understood. We report infection patterns and fitness correlates of bovine brucellosis in African buffalo based on (1) 7 years of cross-sectional disease surveys and (2) a 4-year longitudinal study in Kruger National Park (KNP), South Africa. We then used a matrix population model to translate these observed patterns into predicted population-level effects. Annual brucellosis seroprevalence ranged from 8·7% (95% CI = 1·8-15·6) to 47·6% (95% CI = 35·1-60·1) increased with age until adulthood (>6) and varied by location within KNP. Animals were on average in worse condition after testing positive for brucellosis (F = -5·074, P < 0·0001), and infection was associated with a 2·0 (95% CI = 1·1-3·7) fold increase in mortality (χ(2)  = 2·039, P = 0·036). Buffalo in low body condition were associated with lower reproductive success (F = 2·683, P = 0·034), but there was no association between brucellosis and pregnancy or being observed with a calf. For the range of body condition scores observed in the population, the model-predicted growth rate was λ = 1·11 (95% CI = 1·02-1·21) in herds without brucellosis and λ = 1·00 (95% CI = 0·85-1·16) when brucellosis seroprevalence was 30%. Our results suggest that brucellosis infection can potentially result in reduced population growth rates, but because these effects varied with demographic and environmental conditions, they may remain unseen without intensive, longitudinal monitoring. PMID:25714466

  14. Phospho-T356RB1 predicts survival in HPV-negative squamous cell carcinoma of the head and neck

    PubMed Central

    Handorf, Elizabeth; Nikonova, Anna; Dubyk, Cara; Peri, Suraj; Lango, Miriam; Ridge, John A.; Serebriiskii, Ilya G.; Burtness, Barbara; Golemis, Erica A.; Mehra, Ranee

    2015-01-01

    Locally advanced squamous cell carcinoma of the head and neck (SCCHN) that is not associated with human papillomavirus (HPV) has a poor prognosis in contrast to HPV-positive disease. To better understand the importance of RB1 activity in HPV-negative SCCHN, we investigated the prognostic value of inhibitory CDK4/6 phosphorylation of RB1 on threonine 356 (T356) in archival HPV-negative tumor specimens from patients who underwent surgical resection and adjuvant radiation. We benchmarked pT356RB1 to total RB1, Ki67, pT202/Y204ERK1/2, and TP53, as quantified by automatic quantitative analysis (AQUA), and correlated protein expression with tumor stage and grade. High expression of pT356RB1 but not total RB1 predicted reduced overall survival (OS; P = 0.0295), indicating the potential relevance of post-translational phosphorylation. Paired analysis of The Cancer Genome Atlas (TCGA) data for regulators of this RB1 phosphorylation identified loss or truncating mutation of negative regulator CDKN2A (p16) and elevated expression of the CDK4/6 activator CCND1 (cyclin D) as also predicting poor survival. Given that CDK4/6 inhibitors have been most effective in the context of functional RB1 and low expression or deletion of p16 in other tumor types, these data suggest such agents may merit evaluation in HPV-negative SCCHN, specifically in cases associated with high pT356RB1. PMID:26265441

  15. Simple Measures of Function and Symptoms in Hospitalized Heart Failure Patients Predict Short-Term Cardiac Event-Free Survival

    PubMed Central

    Cataldo, Janine; Mackin, Lynda

    2014-01-01

    Background. Heart failure (HF) is a prevalent chronic condition where patients experience numerous uncomfortable symptoms, low functional status, and high mortality rates. Objective. To determine whether function and/or symptoms predict cardiac event-free survival in hospitalized HF patients within 90 days of hospital discharge. Methods. Inpatients (N = 32) had HF symptoms assessed with 4 yes/no questions. Function was determined with NYHA Classification, Katz Index of Activities of Daily Living (ADLs), and directly with the short physical performance battery (SPPB). Survival was analyzed with time to the first postdischarge cardiac event with events defined as cardiac rehospitalization, heart transplantation, or death. Results. Mean age was 58.2 ± 13.6 years. Patient reported ADL function was nearly independent (5.6 ± 1.1) while direct measure (SPPB) showed moderate functional limitation (6.4 ± 3.1). Within 90 days, 40.6% patients had a cardiac event. At discharge, each increase in NYHA Classification was associated with a 3.4-fold higher risk of cardiac events (95% CI 1.4–8.5). Patients reporting symptoms of dyspnea, fatigue, and orthopnea before discharge had a 4.0-fold, 9.7-fold, and 12.8-fold, respectively, greater risk of cardiac events (95% CI 1.2–13.2; 1.2–75.1; 1.7–99.7). Conclusions. Simple assessments of function and symptoms easily performed at discharge may predict short-term cardiac outcomes in hospitalized HF patients. PMID:24672717

  16. Burst predicting neurons survive an in vitro glutamate injury model of cerebral ischemia.

    PubMed

    Kuebler, Eric S; Tauskela, Joseph S; Aylsworth, Amy; Zhao, Xigeng; Thivierge, Jean-Philippe

    2015-01-01

    Neuronal activity in vitro exhibits network bursts characterized by brief periods of increased spike rates. Recent work shows that a subpopulation of neurons reliably predicts the occurrence of network bursts. Here, we examined the role of burst predictors in cultures undergoing an in vitro model of cerebral ischemia. Dissociated primary cortical neurons were plated on multielectrode arrays and spontaneous activity was recorded at 17 days in vitro (DIV). This activity was characterized by neuronal avalanches where burst statistics followed a power law. We identified burst predictors as channels that consistently fired immediately prior to network bursts. The timing of these predictors relative to bursts followed a skewed distribution that differed sharply from a null model based on branching ratio. A portion of cultures were subjected to an excitotoxic insult (DIV 18). Propidium iodine and fluorescence imaging confirmed cell death in these cultures. While the insult did not alter the distribution of avalanches, it resulted in alterations in overall spike rates. Burst predictors, however, maintained baseline levels of activity. The resilience of burst predictors following excitotoxic insult suggests a key role of these units in maintaining network activity following injury, with implications for the selective effects of ischemia in the brain. PMID:26648112

  17. Burst predicting neurons survive an in vitro glutamate injury model of cerebral ischemia

    PubMed Central

    Kuebler, Eric S.; Tauskela, Joseph S.; Aylsworth, Amy; Zhao, Xigeng; Thivierge, Jean-Philippe

    2015-01-01

    Neuronal activity in vitro exhibits network bursts characterized by brief periods of increased spike rates. Recent work shows that a subpopulation of neurons reliably predicts the occurrence of network bursts. Here, we examined the role of burst predictors in cultures undergoing an in vitro model of cerebral ischemia. Dissociated primary cortical neurons were plated on multielectrode arrays and spontaneous activity was recorded at 17 days in vitro (DIV). This activity was characterized by neuronal avalanches where burst statistics followed a power law. We identified burst predictors as channels that consistently fired immediately prior to network bursts. The timing of these predictors relative to bursts followed a skewed distribution that differed sharply from a null model based on branching ratio. A portion of cultures were subjected to an excitotoxic insult (DIV 18). Propidium iodine and fluorescence imaging confirmed cell death in these cultures. While the insult did not alter the distribution of avalanches, it resulted in alterations in overall spike rates. Burst predictors, however, maintained baseline levels of activity. The resilience of burst predictors following excitotoxic insult suggests a key role of these units in maintaining network activity following injury, with implications for the selective effects of ischemia in the brain. PMID:26648112

  18. Sex-biased survival predicts adult sex ratio variation in wild birds

    PubMed Central

    Székely, Tamás; Liker, András; Freckleton, Robert P.; Fichtel, Claudia; Kappeler, Peter M.

    2014-01-01

    Adult sex ratio (ASR) is a central concept in population demography and breeding system evolution, and has implications for population viability and biodiversity conservation. ASR exhibits immense interspecific variation in wild populations, although the causes of this variation have remained elusive. Using phylogenetic analyses of 187 avian species from 59 families, we show that neither hatching sex ratios nor fledging sex ratios correlate with ASR. However, sex-biased adult mortality is a significant predictor of ASR, and this relationship is robust to 100 alternative phylogenetic hypotheses, and potential ecological and life-history confounds. A significant component of adult mortality bias is sexual selection acting on males, whereas increased reproductive output predicts higher mortality in females. These results provide the most comprehensive insights into ASR variation to date, and suggest that ASR is an outcome of selective processes operating differentially on adult males and females. Therefore, revealing the causes of ASR variation in wild populations is essential for understanding breeding systems and population dynamics. PMID:24966308

  19. Sex-biased survival predicts adult sex ratio variation in wild birds.

    PubMed

    Székely, Tamás; Liker, András; Freckleton, Robert P; Fichtel, Claudia; Kappeler, Peter M

    2014-08-01

    Adult sex ratio (ASR) is a central concept in population demography and breeding system evolution, and has implications for population viability and biodiversity conservation. ASR exhibits immense interspecific variation in wild populations, although the causes of this variation have remained elusive. Using phylogenetic analyses of 187 avian species from 59 families, we show that neither hatching sex ratios nor fledging sex ratios correlate with ASR. However, sex-biased adult mortality is a significant predictor of ASR, and this relationship is robust to 100 alternative phylogenetic hypotheses, and potential ecological and life-history confounds. A significant component of adult mortality bias is sexual selection acting on males, whereas increased reproductive output predicts higher mortality in females. These results provide the most comprehensive insights into ASR variation to date, and suggest that ASR is an outcome of selective processes operating differentially on adult males and females. Therefore, revealing the causes of ASR variation in wild populations is essential for understanding breeding systems and population dynamics. PMID:24966308

  20. A Systematic Review of Predictions of Survival in Palliative Care: How Accurate Are Clinicians and Who Are the Experts?

    PubMed Central

    Harris, Adam; Harries, Priscilla

    2016-01-01

    Background Prognostic accuracy in palliative care is valued by patients, carers, and healthcare professionals. Previous reviews suggest clinicians are inaccurate at survival estimates, but have only reported the accuracy of estimates on patients with a cancer diagnosis. Objectives To examine the accuracy of clinicians’ estimates of survival and to determine if any clinical profession is better at doing so than another. Data Sources MEDLINE, Embase, CINAHL, and the Cochrane Database of Systematic Reviews and Trials. All databases were searched from the start of the database up to June 2015. Reference lists of eligible articles were also checked. Eligibility Criteria Inclusion criteria: patients over 18, palliative population and setting, quantifiable estimate based on real patients, full publication written in English. Exclusion criteria: if the estimate was following an intervention, such as surgery, or the patient was artificially ventilated or in intensive care. Study Appraisal and Synthesis Methods A quality assessment was completed with the QUIPS tool. Data on the reported accuracy of estimates and information about the clinicians were extracted. Studies were grouped by type of estimate: categorical (the clinician had a predetermined list of outcomes to choose from), continuous (open-ended estimate), or probabilistic (likelihood of surviving a particular time frame). Results 4,642 records were identified; 42 studies fully met the review criteria. Wide variation was shown with categorical estimates (range 23% to 78%) and continuous estimates ranged between an underestimate of 86 days to an overestimate of 93 days. The four papers which used probabilistic estimates tended to show greater accuracy (c-statistics of 0.74–0.78). Information available about the clinicians providing the estimates was limited. Overall, there was no clear “expert” subgroup of clinicians identified. Limitations High heterogeneity limited the analyses possible and prevented an

  1. Evaluation of the 2008 Predictions of Run-Timing and Survival of Wild Migrant Yearling Chinook and Steelhead on the Columbia and Snake Rivers.

    SciTech Connect

    Beer, W. Nicholas; Iltis, Susannah; Anderson, James J.

    2009-01-01

    Columbia Basin Research uses the COMPASS model on a daily basis during the outmigration of Snake River Chinook and steelhead smolts to predict downstream passage and survival. Fish arrival predictions and observations from program RealTime along with predicted and observed environmental conditions are used to make in-season predictions of arrival and survival to various dams in the Columbia and Snake Rivers. For 2008, calibrations of travel and survival parameters for two stocks of fish-Snake River yearling PIT-tagged wild chinook salmon (chin1pit) and Snake River PIT-tagged steelhead (lgrStlhd)-were used to model travel and survival of steelhead and chinook stocks from Lower Granite Dam (LWG) or McNary Dam (MCN) to Bonneville Dam (BON). This report summarizes the success of the COMPASS/RealTime process to model these migrations as they occur. We compared model results on timing and survival to data from two sources: stock specific counts at dams and end-of-season control survival estimates (Jim Faulkner, NOAA, pers. comm. Dec. 16, 2008). The difference between the predicted and observed day of median passage and the Mean Absolute Deviation (MAD) between predicted and observed arrival cumulative distributions are measures of timing accuracy. MAD is essentially the average percentage error over the season. The difference between the predicted and observed survivals is a measure of survival accuracy. Model results and timing data were in good agreement from LWG to John Day Dam (JDA). Predictions of median passage days for the chin1pit and lgrStlhd stocks were 0 and 2 days (respectively) later than observed. MAD for chin1pit and lgrStlhd stocks at JDA were 2.3% and 5.9% (respectively). Between JDA and BON modeling and timing data were not as well matched. At BON, median passage predictions were 6 and 10 days later than observed and MAD values were 7.8% and 16.0% respectively. Model results and survival data were in good agreement from LWG to MCN. COMPASS predicted

  2. Predicting Short-term Mortality and Long-term Survival of Hospitalized U.S. Patients with Alcoholic Hepatitis

    PubMed Central

    Cuthbert, Jennifer A.; Arslanlar, Sami; Yepuri, Jay; Montrose, Marc; Ahn, Chul W.; Shah, Jessica P.

    2014-01-01

    Background No study has evaluated current scoring systems for their accuracy in predicting short- and long-term outcome of alcoholic hepatitis in a U.S. population. Methods We reviewed electronic records for patients with ALD admitted to Parkland Memorial Hospital between January 2002 and August 2005. Data and outcomes for 148 of 1761 admissions meeting pre-defined criteria were collected. The discriminant function (DF) was revised (INRdf) to account for changes in prothrombin time reagents that could potentially affect identification of risk using the prior DF threshold of > 32. Admission and theoretical peak scores using the Model for End-stage Liver Disease (MELD) were calculated. Analysis models compared 5 different scoring systems. Results INRdf was closely correlated with the old DF (r2 = 0.95). Multivariate analysis of data showed that survival at 28 days was significantly associated with admission values for white blood cell count (p = 0.006), a scoring system using a combination of age, bilirubin, coagulation status and creatinine (p < 0.001) as well as an elevated ammonia result within 2 days of admission (p = 0.006). When peak values for MELD were included, they were the most significant predictor of short-term mortality (p < 0.001) followed by INRdf (p = 0.006 Conclusion On admission, 2 scoring systems that identify a subset of patients with severe alcoholic liver disease are able to predict > 50% mortality at 4 weeks as well as > 80% mortality at 6 months without specific treatment. PMID:24445730

  3. Serotonin in the inferior colliculus.

    PubMed

    Hurley, Laura M; Thompson, Ann M; Pollak, George D

    2002-06-01

    It has been recognized for some time that serotonin fibers originating in raphe nuclei are present in the inferior colliculi of all mammalian species studied. More recently, serotonin has been found to modulate the responses of single inferior colliculus neurons to many types of auditory stimuli, ranging from simple tone bursts to complex species-specific vocalizations. The effects of serotonin are often quite strong, and for some neurons are also highly specific. A dramatic illustration of this is that serotonin can change the selectivity of some neurons for sounds, including species-specific vocalizations. These results are discussed in light of several theories on the function of serotonin in the IC, and of outstanding issues that remain to be addressed. PMID:12117504

  4. Simulation of the Inferior Mirage

    ERIC Educational Resources Information Center

    Branca, Mario

    2010-01-01

    A mirage can occur when a continuous variation in the refractive index of the air causes light rays to follow a curved path. As a result, the image we see is displaced from the location of the object. If the image appears higher in the air than the object, it is called a "superior" mirage, while if it appears lower it is called an "inferior"…

  5. Patients with Congenital Systemic-to-Pulmonary Shunts and Increased Pulmonary Vascular Resistance: What Predicts Postoperative Survival?

    PubMed Central

    Gan, Hui-Li; Zhang, Jian-Qun; Zhou, Qi-Wen; Feng, Lei; Chen, Fei; Yang, Yi

    2014-01-01

    Background We carried out a retrospective data review of patients with systemic to pulmonary shunts that underwent surgical repair between February 1990 and February 2012 in order to assess preoperative pulmonary vascular dynamic risk factors for predicting early and late deaths due presumably to pulmonary vascular disease. Methods and Results A total of 1024 cases of congenital systemic-to-pulmonary shunt and advanced pulmonary vascular disease beyond infancy and early childhood were closed surgically. The mean follow up duration was 8.5±5.5 (range 0.7 to 20) years. Sixty-one in-hospital deaths (5.96%, 61/1024) occurred after the shunt closure procedure and there were 46 late deaths, yielding 107 total deaths. We analyzed preoperative pulmonary vascular resistance index (PVRI), pulmonary vascular resistance index on pure oxygen challenge (PVRIO), difference between PVRI and PVRIO (PVRID), Qp∶Qs, and Rp∶Rs as individual risk predictors. The results showed that these individual factors all predicted in-hospital death and total death with PVRIO showing better performance than other risk factors. A multivariable Cox regression model was built,and suggested that PVRID and Qp∶Qs were informative factors for predicting survival time from late death and closure of congenital septal defects was safe with a PVRIO<10.3 WU.m2 and PVRID>7.3 WU.m2 on 100% oxygen. Conclusions All 4 variables, PVRI, PVRIO, PVRID and Qp∶Qs, should be considered in deciding surgical closure of congenital septal defects and a PVRIO<10.3 WU.m2 and PVRID>7.3 WU.m2 on 100% oxygen are associated with a favorable risk benefit profile for the procedure. PMID:24416187

  6. A model to predict survival at one month, one year, and five years after liver transplantation based on pretransplant clinical characteristics.

    PubMed

    Thuluvath, Paul J; Yoo, Hwan Y; Thompson, Richard E

    2003-05-01

    Reliable models that could predict outcome of liver transplantation (LT) may guide physicians to advise their patients of immediate and late survival chances and may help them to optimize organ use. The objective of this study was to develop user-friendly models to predict short and long-term mortality after LT in adults based on pre-LT recipient characteristics. The United Network for Organ Sharing (UNOS) transplant registry (n = 38,876) from 1987 to 2001 was used to develop and validate the model. Two thirds of patients were randomized to develop the model (the modeling group), and the remaining third was randomized to cross-validate (the cross-validation group) it. Three separate models, using multivariate logistic regression analysis, were created and validated to predict survival at 1 month, 1 year, and 5 years. Using the total severity scores of patients in the modeling group, a predictive model then was created, and the predicted probability of death as a function of total score then was compared in the cross-validation group. The independent variables that were found to be very significant for 1 month and 1 year survival were age, body mass index (BMI), UNOS status 1, etiology, serum bilirubin (for 1 month and 1 year only), creatinine, and race (only for 5 years). The actual deaths in the cross-validation group followed very closely the predicted survival graph. The chi-squared goodness-of-fit test confirmed that the model could predict mortality reliably at 1 month, 1 year, and 5 years. We have developed and validated user-friendly models that could reliably predict short-term and long-term survival after LT. PMID:12740799

  7. Recursive Partitioning Analysis Index Is Predictive for Overall Survival in Patients Undergoing Spine Stereotactic Body Radiation Therapy for Spinal Metastases

    SciTech Connect

    Chao, Samuel T.; Koyfman, Shlomo A.; Woody, Neil; Angelov, Lilyana; Soeder, Sherry L.; Reddy, Chandana A.; Rybicki, Lisa A.; Djemil, Toufik; Suh, John H.

    2012-04-01

    Purpose: To generate a prognostic index using recursive partitioning analysis (RPA) for patients undergoing spine stereotactic body radiation therapy (sSBRT) for spinal metastases (sMet). Methods and Materials: From an institutional review board-approved database, 174 patients were treated for sMet with sSBRT between February 2006 and August 2009. Median dose was 14 Gy (range, 8-24 Gy), typically in a single fraction (range, 1-5). Kaplan-Meier analysis was performed to detect any correlation between survival and histology. Histologies were divided into favorable (breast and prostate), radioresistant (renal cell, melanoma and sarcoma), and other (all other histologies). RPA was performed to identify any association of the following variables with overall survival (OS) following sSBRT: histology, gender, age, Karnofsky performance status (KPS), control of primary, extraosseous metastases, time from primary diagnosis (TPD), dose of sSBRT ({<=}14 Gy vs. >14 Gy), extent of spine disease (epidural only, bone and epidural, bone only), upfront or salvage treatment, presence of paraspinal extension, and previous surgery. Results: Median follow-up was 8.9 months. Median OS time from sSBRT was 10.7 months. Median OS intervals for favorable histologies were 14 months, 11.2 months for radioresistant histologies, and 7.3 months for other histologies (p = 0.02). RPA analysis resulted in three classes (p < 0.0001). Class 1 was defined as TPD of >30 months and KPS of >70; Class 2 was TPD of >30 months and KPS of {<=}70 or a TPD of {<=}30 months and age <70 years old; Class 3 was TPD of {<=}30 months and age {>=}70 years old. Median OS was 21.1 months for Class 1 (n = 59), 8.7 months for Class 2 (n = 104), and 2.4 months for Class 3 (n = 11). Conclusion: sSBRT patients treated for sMet have a wide variability in OS. We developed an RPA classification system that is predictive of OS. While many patients are treated for palliation of pain or to avoid symptomatic progression, this

  8. WE-E-17A-03: FDG-PET-Based Radiomics to Predict Local Control and Survival Following Radiotherapy

    SciTech Connect

    Oh, J; Apte, A; Folkerts, M; Kohutek, Z; Wu, A; Rimmer, A; Lee, N; Deasy, J

    2014-06-15

    Purpose: An exploding field in cancer research is “radiomics,” based on the hypothesis that there is statistical (hidden) information in medical images that is prognostic or predictive of outcomes. Our group has developed an efficient pipeline to extract and analyze quantitative image features from medical images as related to outcomes or diagnosis. In this work, we summarize our previous studies with positron emission tomography (PET) images and show the potential of the use of radiomics for outcomes research. Methods: We analyzed two cancer datasets, each consisting of pre-radiotherapy-treatment PET scans: 163 T1-2N0M0 non-small cell lung cancer (NSCLC) patients and 174 head and neck (H and N) cancer patients with stage III–IV. The PET scans were converted to Computational Environment for Radiological Research (CERR) format, and CERR was used to generate 24 shape, texture, and intensity-histogram based image features. Data-mining and logistic regression methods were then used to model local failure (LF) and overall survival (OS). Unbiased estimates of performance were generated using leave-one-out cross-validation (LOOCV). Results: For predicting LF, the models with biologically equivalent dose (BED) and TLG (metabolic tumor volume (MTV) x SUVmean) in NSCLC, and skewness and MTV in H and N, achieved the best performance with AUC=0.818 (p<0.0001) and AUC=0.826 (p=0.0002), respectively. For predicting OS, the models with kurtosis and volume in NSCLC and SUVmax and homogeneity in H and N achieved the best performance with AUC=0.706 (p<0.0001) and AUC=0.656 (p=0.0003), respectively. On LOOCV, all these models retained significant predictive power. Interestingly, MTV was highly correlated with LF in both sites. Conclusion: PET-based imaged features are promising tools for improving treatment management decision making. Much more research is needed to identify optimal radiomics metrics and to correlate imaging phenotype with other clinical or genomic information.

  9. Aspartate aminotransferase-lymphocyte ratio index and systemic immune-inflammation index predict overall survival in HBV-related hepatocellular carcinoma patients after transcatheter arterial chemoembolization

    PubMed Central

    Yang, Zongguo; Zhang, Jianliang; Lu, Yunfei; Xu, Qingnian; Tang, Bozong; Wang, Qiang; Zhang, Wensi; Chen, Shishi; Lu, Lingqing; Chen, Xiaorong

    2015-01-01

    It has been suggested that lymphocytes play central roles in host antitumor immune responses and control cancer outcome. We reviewed the clinical parameters of 189 hepatocellular carcinoma (HCC) patients and investigated the prognostic significance of lymphocyte-related scores in HCC patients following transcatheter arterial chemoembolization (TACE). Survival analysis revealed that an elevated aspartate aminotransferase-lymphocyte ratio index (ALRI) > 57 and a systemic immune-inflammation index (SII) > 300 were negatively associated with overall survival in HBV-related HCC (HR = 2.181, P = 0.003 and HR = 2.453, P = 0.003; respectively). Spearman chi-square analysis showed that ALRI had a specificity of 82.4% and that SII index had a sensitivity of 71.9% for HCC overall survival. ALRI and SII had negative predictive values of 74.6% and 80%, respectively for HCC overall survival. Additionally, Barcelona Clinic Liver Cancer (BCLC) stage C patients had significantly higher ALRI and SII scores (both P < 0.0001) and poorer overall survival (HR = 3.618, P < 0.001). Additionally, HCC patients with portal vein tumor thrombosis (PVTT) had higher ALRI and SII scores (P < 0.0001 and P = 0.0059, respectively). In conclusion, as noninvasive, low cost, easily assessable and reproducible parameters, elevated ALRI and SII should be used as negative predictive factors for overall survival in HBV-related HCC in clinical practice. PMID:26506519

  10. Tyrosine kinase inhibitor sunitinib therapy is effective in the treatment of bone metastasis from cancer of unknown primary: Identification of clinical and immunohistochemical biomarkers predicting survival.

    PubMed

    Ma, Yifei; Zhou, Wang; He, Shaohui; Xu, Wei; Xiao, Jianru

    2016-09-15

    Bone metastasis from cancer of unknown primary (BMCUP) brings poor survival prognosis and its management remains controversial. Sunitinib (SUTENT) proved effective in many sorts of solid tumors but has never been applied for patients with occult primary cancers, and there is no study to identify sensitive or resistant biomarkers for sunitinib therapy in CUP patients. An analysis was carried out to investigate the efficacy of sunitinib by multivariate survival analysis of 286 patients with BMCUP. We further carried out multivariate analysis to identify histological and clinical biomarkers that could predict sensitivity or resistance for sunitinib therapy. Of the 286 patients included from January 2011 to March 2016, sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive and resistant biomarkers were identified in histological specimen of patients receiving sunitinib therapy. Clinical factors were also identified that predict poor survival prognosis for sunitinib therapy. Sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive markers for sunitinib therapy include KDR positivity and early-developed treatment-induced hypertension. Resistance factors for sunitinib include VEGF positivity, CAIX positivity and squamous cell carcinoma pathology type. Prolonged symptom time and severe weight loss before therapy seemed to be associated with poor survival prognosis for sunitinib therapy. PMID:27164264

  11. Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia

    PubMed Central

    Klein, Hans-Ulrich; Hascher, Antje; Isken, Fabienne; Tickenbrock, Lara; Thoennissen, Nils; Agrawal-Singh, Shuchi; Tschanter, Petra; Disselhoff, Christine; Wang, Yipeng; Becker, Anke; Thiede, Christian; Ehninger, Gerhard; zur Stadt, Udo; Koschmieder, Steffen; Seidl, Matthias; Müller, Frank U.; Schmitz, Wilhelm; Schlenke, Peter; McClelland, Michael; Berdel, Wolfgang E.; Dugas, Martin; Serve, Hubert

    2010-01-01

    Acute myeloid leukemia (AML) is commonly associated with alterations in transcription factors because of altered expression or gene mutations. These changes might induce leukemia-specific patterns of histone modifications. We used chromatin-immunoprecipitation on microarray to analyze histone 3 lysine 9 trimethylation (H3K9me3) patterns in primary AML (n = 108), acute lymphoid leukemia (n = 28), CD34+ cells (n = 21) and white blood cells (n = 15) specimens. Hundreds of promoter regions in AML showed significant alterations in H3K9me3 levels. H3K9me3 deregulation in AML occurred preferentially as a decrease in H3K9me3 levels at core promoter regions. The altered genomic regions showed an overrepresentation of cis-binding sites for ETS and cyclic adenosine monophosphate response elements (CREs) for transcription factors of the CREB/CREM/ATF1 family. The decrease in H3K9me3 levels at CREs was associated with increased CRE-driven promoter activity in AML blasts in vivo. AML-specific H3K9me3 patterns were not associated with known cytogenetic abnormalities. But a signature derived from H3K9me3 patterns predicted event-free survival in AML patients. When the H3K9me3 signature was combined with established clinical prognostic markers, it outperformed prognosis prediction based on clinical parameters alone. These findings demonstrate widespread changes of H3K9me3 levels at gene promoters in AML. Signatures of histone modification patterns are associated with patient prognosis in AML. PMID:20498303

  12. High-sensitive Troponin T measurements early after heart transplantation predict short- and long-term survival.

    PubMed

    Erbel, Christian; Taskin, Rukiye; Doesch, Andreas; Dengler, Thomas J; Wangler, Susanne; Akhavanpoor, Mohammadreza; Ruhparwar, Arjang; Giannitsis, Evangelos; Katus, Hugo A; Gleissner, Christian A

    2013-03-01

    Following heart transplantation, cardiac biomarkers remain elevated for several weeks eventually as a result of membrane leakage of the donor organ. We now test the predictive power of blood levels of troponin T (TNT) measured by the new hsTNT assay (Roche Diagnostics, Roche Diagnostics, Mannheim, Germany) early after heart transplantation. TNT was determined in 141 cardiac allograft recipients and 40 controls. Our findings demonstrate that patients who died within the first year after transplantation had significantly higher median hsTNT serum levels 6 weeks after transplantation (156 ng/l ± 203 vs. 29 ng/l ± 21, P = 0.0002). Using ROC analysis, a serum hsTNT concentration of 33.55 ng/l 6 weeks after transplantation was found to be the best cutoff to predict death at 1 year (HR 0.16, 95%CI:0.05-0.46, P = 0.001) with a sensitivity of 90.91% and a specificity of 70.97%. In addition, survival at 5 years (HR 0.15, 95% CI 0.06-0.35, P < 0.0001) was significantly better among patients below that cutoff value. In multivariate analysis, hsTNT serum level 6 weeks after transplantation emerged as an independent predictor for first-year mortality (hsTNT-HR 0.90, 95% CI: 0.81-1.00, P = 0.03). Cardiac troponin T concentrations early after transplantation as measured with a highly sensitive assay represent a strong and independent risk predictor of death after heart transplantation. PMID:23252662

  13. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    PubMed Central

    Chapiro, Julius; Duran, Rafael; Lin, MingDe; Schernthaner, Rüdiger; Lesage, David; Wang, Zhijun; Savic, Lynn Jeanette; Geschwind, Jean-François

    2015-01-01

    Objectives This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). Methods This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan–Meier analysis and compared using Cox proportional hazard ratios (HR). Results Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). Conclusion The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. PMID:25636420

  14. TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy.

    PubMed

    Munch-Petersen, Helga D; Asmar, Fazila; Dimopoulos, Konstantinos; Areškevičiūtė, Aušrinė; Brown, Peter; Girkov, Mia Seremet; Pedersen, Anja; Sjö, Lene D; Heegaard, Steffen; Broholm, Helle; Kristensen, Lasse S; Ralfkiaer, Elisabeth; Grønbæk, Kirsten

    2016-01-01

    Primary central nervous system lymphoma (PCNSL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) confined to the CNS. TP53 mutations (MUT-TP53) were investigated in the context of MIR34A/B/C- and DAPK promoter methylation status, and associated with clinical outcomes in PCNSL patients. In a total of 107 PCNSL patients clinical data were recorded, histopathology reassessed, and genetic and epigenetic aberrations of the p53-miR34-DAPK network studied. TP53 mutational status (exon 5-8), with structural classification of single nucleotide variations according to the IARC-TP53-Database, methylation status of MIR34A/B/C and DAPK, and p53-protein expression were assessed. The 57/107 (53.2 %) patients that were treated with combination chemotherapy +/- rituximab (CCT-treated) had a significantly better median overall survival (OS) (31.3 months) than patients treated with other regimens (high-dose methotrexate/whole brain radiation therapy, 6.0 months, or no therapy, 0.83 months), P < 0.0001. TP53 mutations were identified in 32/86 (37.2 %), among which 12 patients had hotspot/direct DNA contact mutations. CCT-treated patients with PCNSL harboring a hotspot/direct DNA contact MUT-TP53 (n = 9) had a significantly worse OS and progression free survival (PFS) compared to patients with non-hotspot/non-direct DNA contact MUT-TP53 or wild-type TP53 (median PFS 4.6 versus 18.2 or 45.7 months), P = 0.041 and P = 0.00076, respectively. Multivariate Cox regression analysis confirmed that hotspot/direct DNA contact MUT-TP53 was predictive of poor outcome in CCT-treated PCNSL patients, P = 0.012 and P = 0.008; HR: 1.86 and 1.95, for OS and PFS, respectively. MIR34A, MIR34B/C, and DAPK promoter methylation were detected in 53/93 (57.0 %), 80/84 (95.2 %), and 70/75 (93.3 %) of the PCNSL patients with no influence on survival. Combined MUT-TP53 and MIR34A methylation was associated with poor PFS (median 6.4 versus 38.0 months), P = 0

  15. PFKL/miR-128 axis regulates glycolysis by inhibiting AKT phosphorylation and predicts poor survival in lung cancer.

    PubMed

    Yang, Jie; Li, Jingqiu; Le, Yanping; Zhou, Chengwei; Zhang, Shun; Gong, Zhaohui

    2016-01-01

    MicroRNAs (miRNAs) affect cancer cell glucose metabolism by targeting mRNAs of diverse enzymes that have been implicated in oxidative phosphorylation (OXPHOS) and glycolytic pathways. However, the mechanisms that underlie miRNA-mediated regulation of phosphofructokinase (PFK), a key rate-limiting enzyme in glycolysis, remain largely unknown. Here, we show that miR-128 directly targets PFK liver type (PFKL) in lung cancer cells and regulates endogenous expression of PFKL at both the mRNA and protein levels. In line with this, overexpression of miR-128 decreased glucose uptake and lactate production, as well as increased cellular ATP content. Interestingly, knockdown of miR-128 was shown to promote lung cancer cell growth and colony formation. Moreover, we observed that miR-128 expression inversely correlated with PFKL mRNA levels in clinic lung cancer samples and that increased PFKL expression predicted poor overall survival in lung cancer patients. Mechanistically, we showed that miR-128 regulates PFKL via a feedback loop that involves inhibition of the AKT signaling pathway. Together, our results suggest that miR-128 acts as a metabolic regulator in lung cancer cells that may be therapeutically exploited. PMID:27186417

  16. PFKL/miR-128 axis regulates glycolysis by inhibiting AKT phosphorylation and predicts poor survival in lung cancer

    PubMed Central

    Yang, Jie; Li, Jingqiu; Le, Yanping; Zhou, Chengwei; Zhang, Shun; Gong, Zhaohui

    2016-01-01

    MicroRNAs (miRNAs) affect cancer cell glucose metabolism by targeting mRNAs of diverse enzymes that have been implicated in oxidative phosphorylation (OXPHOS) and glycolytic pathways. However, the mechanisms that underlie miRNA-mediated regulation of phosphofructokinase (PFK), a key rate-limiting enzyme in glycolysis, remain largely unknown. Here, we show that miR-128 directly targets PFK liver type (PFKL) in lung cancer cells and regulates endogenous expression of PFKL at both the mRNA and protein levels. In line with this, overexpression of miR-128 decreased glucose uptake and lactate production, as well as increased cellular ATP content. Interestingly, knockdown of miR-128 was shown to promote lung cancer cell growth and colony formation. Moreover, we observed that miR-128 expression inversely correlated with PFKL mRNA levels in clinic lung cancer samples and that increased PFKL expression predicted poor overall survival in lung cancer patients. Mechanistically, we showed that miR-128 regulates PFKL via a feedback loop that involves inhibition of the AKT signaling pathway. Together, our results suggest that miR-128 acts as a metabolic regulator in lung cancer cells that may be therapeutically exploited. PMID:27186417

  17. Expression of Tumor Necrosis Factor-Alpha-Mediated Genes Predicts Recurrence-Free Survival in Lung Cancer

    PubMed Central

    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. PMID:25548907

  18. Negative association between GATA3 and fascin could predict relapse-free and overall survival in patients with breast cancer.

    PubMed

    Min, Kyueng-Whan; Kim, Dong-Hoon; Do, Sung-Im; Chae, Seoung Wan; Kim, Kyungeun; Sohn, Jin Hee; Pyo, Jung-Soo; Lee, Hyun Joo; Kim, Dong Hyun; Oh, Sukjoong; Choi, Seon Hyeong; Park, Yong Lai; Park, Chan Heun; Kim, Eun-Kyung; Kwon, Mi Jung; Seo, Jinwon; Moon, Kyoung Min

    2016-04-01

    GATA3 and fascin proteins are known prognostic markers in several cancers. GATA3 is a key regulator of mammary gland morphogenesis and luminal cell differentiation, whereas fascin is a pro-metastatic actin-bundling protein. In this study, we analyzed and compared the predictive abilities of GATA3 and fascin for clinical outcomes of patients with breast cancer. The combined expression pattern based on GATA3-/+ and fascin-/+ was evaluated by immunostaining using a tissue microarray, and relationships between protein expression and several clinicopathological parameters were analyzed. GATA3 expression was associated with good prognostic parameters, but fascin was correlated with poor prognostic parameters. On comparing GATA3 and fascin, we found an inverse relationship between fascin and GATA3 expressions. On analysis of combined markers, GATA3+/fascin- was correlated with improved clinical outcomes compared to GATA3-/fascin+. Univariate and multivariate analyses revealed significant differences in relapse-free and overall survival between GATA3+/fascin- and GATA3-/fascin+. Combined marker analysis of GATA3/fascin showed an inverse association and improved prognostic information for patients with breast cancer. PMID:26719157

  19. Inferior mirages: an improved model.

    PubMed

    Young, Andrew T

    2015-02-01

    A quantitative model of the inferior mirage is presented, based on a realistic temperature profile in the convective boundary layer, using Monin-Obukhov similarity theory. The top of the inverted image is determined by the logarithmic part of the profile; the bottom is the apparent horizon, which depends on optical obstruction by roughness elements. These effects of surface roughness are included in the model, which is illustrated with a simulation. The vertical magnification varies throughout the mirage, becoming infinite at Minnaert's ill-named "vanishing line"-which makes green flashes apparent to the naked eye. PMID:25967823

  20. Patient features predicting long‐term survival and health‐related quality of life after radical surgery for non‐small cell lung cancer

    PubMed Central

    Rauma, Ville; Sintonen, Harri; Räsänen, Jari; Ilonen, Ilkka

    2016-01-01

    Abstract Background This study presents a retrospective evaluation of patient, disease, and treatment features predicting long‐term survival and health‐related quality of life (HRQoL) among patients who underwent surgery for non‐small cell lung cancer (NSCLC). Methods Between January 2000 and June 2009, 586 patients underwent surgery at the Helsinki University Hospital. The 276 patients still alive in June 2011 received two validated quality of life questionnaires (QLQ): the generic 15D and the cancer‐specific EORTC QLQ‐C30 + QLQ‐LC13. We used binary and linear regression analysis modeling to identify patient, disease, and treatment characteristics that predicted survival and long‐term HRQoL. Results When taking into account patient, disease, and treatment characteristics, long‐term survival was quite predictable (69.5% correct), but not long‐term HRQoL (R 2 between 0.041 and 0.119). Advanced age at the time of surgery, male gender, comorbidity (measured with the Charlson comorbidity index), clinical and pathological stages II‐IV, and postoperative infectious complications predicted a lower survival rate. Features associated with poorer long‐term HRQoL (measured with the 15D) were comorbidity, postoperative complications, and the use of the video‐assisted thoracoscopic surgery (VATS) technique. Conclusions Long‐term HRQoL is only moderately predictable, while prediction of long‐term survival is more reliable. Lower HRQoL is associated with comorbidities, complications, use of the VATS technique, and reduced pulmonary function, while adjuvant therapy is associated with higher HRQoL. PMID:27148419

  1. T-cell Landscape in a Primary Melanoma Predicts the Survival of Patients with Metastatic Disease after Their Treatment with Dendritic Cell Vaccines.

    PubMed

    Vasaturo, Angela; Halilovic, Altuna; Bol, Kalijn F; Verweij, Dagmar I; Blokx, Willeke A M; Punt, Cornelis J A; Groenen, Patricia J T A; van Krieken, J Han J M; Textor, Johannes; de Vries, I Jolanda M; Figdor, Carl G

    2016-06-15

    Tumor-infiltrating lymphocytes appear to be a predictor of survival in many cancers, including cutaneous melanoma. We applied automated multispectral imaging to determine whether density and distribution of T cells within primary cutaneous melanoma tissue correlate with survival of metastatic melanoma patients after dendritic cell (DC) vaccination. CD3(+) T cell infiltration in primary tumors from 77 metastatic melanoma patients was quantified using the ratio of intratumoral versus peritumoral T-cell densities (I/P ratio). Patients with longer survival after DC vaccination had stronger T-cell infiltration than patients with shorter survival in a discovery cohort of 19 patients (P = 0.000026) and a validation cohort of 39 patients (P = 0.000016). I/P ratio was the strongest predictor of survival in a multivariate analysis including M substage and serum lactate dehydrogenase level. To evaluate I/P ratio as a predictive biomarker, we analyzed 19 chemotherapy-treated patients. Longer survival times of DC-vaccinated compared with chemotherapy-treated patients was observed for high (P = 0.000566), but not low (P = 0.154) I/P ratios. In conclusion, T-cell infiltration into primary melanoma is a strong predictor of survival after DC vaccination in metastatic melanoma patients who, on average, started this therapy several years after primary tumor resection. The infiltration remains predictive even after adjustment for late-stage prognostic markers. Our findings suggest that the I/P ratio is a potential predictive biomarker for treatment selection. Cancer Res; 76(12); 3496-506. ©2016 AACR. PMID:27197179

  2. The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone

    PubMed Central

    Molenaar, Remco J.; Verbaan, Dagmar; Lamba, Simona; Zanon, Carlo; Jeuken, Judith W.M.; Boots-Sprenger, Sandra H.E.; Wesseling, Pieter; Hulsebos, Theo J.M.; Troost, Dirk; van Tilborg, Angela A.; Leenstra, Sieger; Vandertop, W. Peter; Bardelli, Alberto; van Noorden, Cornelis J.F.; Bleeker, Fonnet E.

    2014-01-01

    Background Genetic and epigenetic profiling of glioblastomas has provided a comprehensive list of altered cancer genes of which only O6-methylguanine-methyltransferase (MGMT) methylation is used thus far as a predictive marker in a clinical setting. We investigated the prognostic significance of genetic and epigenetic alterations in glioblastoma patients. Methods We screened 98 human glioblastoma samples for genetic and epigenetic alterations in 10 genes and chromosomal loci by PCR and multiplex ligation-dependent probe amplification (MLPA). We tested the association between these genetic and epigenetic alterations and glioblastoma patient survival. Subsequently, we developed a 2-gene survival predictor. Results Multivariate analyses revealed that mutations in isocitrate dehydrogenase 1 (IDH1), promoter methylation of MGMT, irradiation dosage, and Karnofsky Performance Status (KFS) were independent prognostic factors. A 2-gene predictor for glioblastoma survival was generated. Based on the genetic and epigenetic status of IDH1 and MGMT, glioblastoma patients were stratified into 3 clinically different genotypes: glioblastoma patients with IDH1mt/MGMTmet had the longest survival, followed by patients with IDH1mt/MGMTunmet or IDH1wt/MGMTmet, and patients with IDH1wt/MGMTunmet had the shortest survival. This 2-gene predictor was an independent prognostic factor and performed significantly better in predicting survival than either IDH1 mutations or MGMT methylation alone. The predictor was validated in 3 external datasets. Discussion The combination of IDH1 mutations and MGMT methylation outperforms either IDH1 mutations or MGMT methylation alone in predicting survival of glioblastoma patients. This information will help to increase our understanding of glioblastoma biology, and it may be helpful for baseline comparisons in future clinical trials. PMID:24510240

  3. The Use of the Chuang's Prognostic Scale to Predict the Survival of Metastatic Colorectal Cancer Patients Receiving Palliative Systemic Anticancer Therapy

    PubMed Central

    Alsirafy, Samy A; Zaki, Omar; Sakr, Amr Y; Farag, Dina E; El-Sherief, Wessam A; Mohammed, Abha A

    2016-01-01

    Background: With the increasing number of agents active against cancer, advanced cancer patients including metastatic colorectal cancer (mCRC) patients may continue receiving palliative systemic anticancer therapy (PSAT) near the end-of-life. Validated palliative prognostic models, such as the Chuang's prognostic scale (CPS), may be helpful in identifying mCRC patients with limited survival who are unlikely to benefit from PSAT. Aim: To test the ability of the CPS to predict the survival of mCRC under treatment with PSAT. Methods: CPS was prospectively assessed in 36 mCRC patients who were receiving PSAT. The scale is based on eight items: ascites, edema, cognitive impairment, liver and lung metastases, performance status, tiredness, and weight loss. The total CPS score ranges from 0 to 8.5 with the higher score indicating worse prognosis. Results: Patients were divided into two groups using a CPS cutoff score of 5, Group 1 with a CPS score ≤5 and Group 2 with a CPS score >5. Using this cutoff value, 3-month mortality was predicted with a positive predictive value of 71%, a negative predictive value of 77%, a sensitivity of 67%, a specificity of 81% and an overall accuracy of 75%. Group 1 patients had a longer median survival of 149 days (95% confidence interval [CI]: 82-216) in comparison to Group 2 patients who had a median survival of 61 days (95% CI: 35-87). The difference in survival was statistically significant (P = 0.01). Conclusion: CPS may be useful in identifying mCRC patients with limited survival who are unlikely to benefit from PSAT. PMID:27559261

  4. The effect of sire predicted transmitting ability for production traits on fertility, survivability, and health of Holstein dairy cows.

    PubMed

    Bicalho, Rodrigo Carvalho; Foditsch, Carla; Gilbert, Rob; Oikonomou, Georgios

    2014-01-15

    The major objective of this study was to evaluate, using survival analysis and multivariable regression models, the relationship of sire predicted transmitting ability (PTA) for production traits with their daughters' milk production, fat, and protein percentage (PROPCT), reproductive performance, postpartum disease incidence, and survivability. Data were collected from six large commercial dairy farms, and data analysis included 22,205 cows. Information regarding each sire's genetic evaluation included the following: PTA for fat yield (FAT), fat percentage (FATPCT), milk yield (MILK), protein yield, and PROPCT. Sire PTA was categorized into quartiles to facilitate data analysis and interpretation. Retained placenta, metritis, displaced abomasum, and clinical mastitis were diagnosed and treated by farm personnel. The overall average daily milk production, milk fat and PROPCT during the first 10 months of lactation was higher for the cows in the highest quartile of sire PTA, and cows in the lowest quartile had lower averages. There was no significant association between sire PTA for production traits and first test day fat to protein ratio or the incidence of postpartum disease. Sire PTA for MILK, FATPCT, and PROPCT were significantly associated with the hazard of pregnancy. The median days from calving to conception were 159, 155, 170, and 181 days for cows in the sire PTA for MILK quartiles 1, 2, 3, and 4, respectively. Sire PTA for PROPCT and FATPCT were also significantly associated with the hazard of pregnancy. The median days from calving to conception were 175, 189, 152, and 145 for cows in the sire PTA for PROPCT groups 1, 2, 3, and 4, respectively. Additionally, cows in the highest quartile for sire PTA for FATPCT had the lowest median days from calving to conception (144 days) and cows in lowest quartile had the highest median interval (177 days). Sire PTA for FAT was the only sire PTA significantly associated with the hazard of death/culling. When

  5. INTERDEPENDENT SUPERIORITY AND INFERIORITY FEELINGS

    PubMed Central

    Ingham, Harrington V.

    1949-01-01

    It is postulated that in neurotic persons who have unrealistic feelings of superiority and inferiority the two are interdependent. This is a departure from the concept of previous observers that either one or the other is primary and its opposite is overcompensation. The author postulates considerable parallelism, with equal importance for each. He submits that the neurotic person forms two logic-resistant compartments for the two opposed self-estimates and that treatment which makes inroads of logic upon one compartment, simultaneously does so upon the other. Two examples are briefly reported. The neurotic benefits sought in exaggeration of capability are the same as those sought in insistence upon inferiority: Presumption of superiority at once bids for approbation and delivers the subject from the need to prove himself worthy of it in dreaded competition; exaggeration of incapability baits sympathy and makes competition unnecessary because failure is conceded. Some of the characteristics of abnormal self-estimates that distinguish them from normal are: Preoccupation with self, resistance to logical explanation of personality problems, inconsistency in reasons for beliefs in adequacy on the one hand and inadequacy on the other, unreality, rationalization of faults, and difficulty and vacillation in the selection of adequate goals. PMID:15390573

  6. The Predictive Power of Serum α-Fetoprotein and Des-γ-Carboxy Prothrombin for Survival Varies by Tumor Size in Hepatocellular Carcinoma.

    PubMed

    Tsugawa, Daisuke; Fukumoto, Takumi; Kido, Masahiro; Takebe, Atsushi; Tanaka, Motofumi; Kuramitsu, Kaori; Matsumoto, Ippei; Ajiki, Tetsuo; Koyama, Tatsuki; Ku, Yonson

    2016-01-01

    Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are frequently used as tumor markers in hepatocellular carcinoma (HCC). The authors hypothesized different patient populations with varying tumor sizes would influence the predictive power of tumor markers for survival in HCC patients. The authors investigated the influence of tumor size on predictive powers of AFP and DCP. 181 patients underwent hepatectomy for HCC from 2003 to 2008 at Kobe University Hospital. Tumor markers were measured before and at 1 month post-hepatectomy. The Cox proportional-hazards model revealed that preoperative serum AFP was associated with survival; its effects depended on tumor size. Hazard ratios (HRs) for preoperative AFP were maximum for medium-sized HCC, and for DCP, HRs were maximum in small-sized tumors. Post-hepatectomy, both tumor markers were associated with survival, revealing significant interactions with tumor size. HRs for postoperative AFP were greater than 1 for relatively wide range tumors (3-11 cm). HRs for postoperative DCP increased with tumor size, with a strong prognostic predictive power for tumors >5 cm. The predictive power of serum tumor markers varied by tumor size in HCC patients. By selecting the appropriate tumor marker, its predictive power can be improved. PMID:27363395

  7. Chromosomal translocations independently predict treatment failure, treatment-free survival and overall survival in B-cell chronic lymphocytic leukemia patients treated with cladribine.

    PubMed

    Van Den Neste, E; Robin, V; Francart, J; Hagemeijer, A; Stul, M; Vandenberghe, P; Delannoy, A; Sonet, A; Deneys, V; Costantini, S; Ferrant, A; Robert, A; Michaux, L

    2007-08-01

    Chromosomal translocations represent an important prognostic indicator in B-cell chronic lymphocytic leukemia (B-CLL). However, their value had been neither determined in homogeneously treated patients nor compared to that of IgV(H) mutational status. Sixty-five B-CLL patients were investigated using cytogenetics, interphase fluorescence in situ hybridization (FISH), analysis of IgV(H) and of TP53 mutational status before treatment with 2-chloro-2'-deoxyadenosine (CdA). Translocations (n=45) were detected in 42% of the patients, including both balanced (n=12) and unbalanced (n=33) types. IgV(H) was mutated in 43% of the patients. Patients with translocations were more heavily pretreated (P=0.05), presented with more complex karyotypes (P<0.001), 17p abnormalities and TP53 mutations, and had a higher failure rate (59 vs 21% in patients without translocations, P=0.004). Patients with unbalanced translocations displayed a shorter median treatment-free survival (TFS, 6.9 vs 35.9 months, log rank 22.72, P<0.001) and overall survival (OS, 13.0 vs 68.0 months, log rank 16.51, P<0.001), as compared to patients without translocation. In multivariate analysis, unbalanced translocations were independently associated with therapeutic failure, short TFS and short OS. IgV(H) mutational status was independently associated with risk of failure and TFS, but not OS. In B-CLL patients treated with CdA, translocations are strong predictors of outcome. PMID:17541398

  8. Diffusion MR Characteristics Following Concurrent Radiochemotherapy Predicts Progression-Free and Overall Survival in Newly Diagnosed Glioblastoma

    PubMed Central

    Chang, Warren; Pope, Whitney B.; Harris, Robert J.; Hardy, Anthony J.; Leu, Kevin; Mody, Reema R.; Nghiemphu, Phioanh L.; Lai, Albert; Cloughesy, Timothy F.; Ellingson, Benjamin M.

    2015-01-01

    The standard of care for newly diagnosed glioblastoma (GBM) is surgery, then radiotherapy (RT) with concurrent temozolomide (TMZ), followed by adjuvant TMZ. We hypothesized patients with low diffusivity measured using apparent diffusion coefficient (ADC) histogram analysis evaluated after RT+TMZ, prior to adjuvant TMZ, would have a significantly shorter progression-free (PFS) and overall survival (OS). To test this hypothesis we evaluated 120 patients with newly diagnosed GBM receiving RT+TMZ followed by adjuvant TMZ. MRI was performed after completion of RT+TMZ, prior to initiation of adjuvant TMZ. A double Gaussian mixed model was used to describe the ADC histograms within the enhancing tumor, where ADCL and ADCH were defined as the mean ADC value of the lower and higher Gaussian distribution, respectively. An ADCL value of 1.0 um2/ms and ADCH value of 1.6 um2/ms were used to stratify patients into high and low risk categories. Results suggest patients with low ADCL had significantly shorter PFS (Cox Hazard Ratio = 0.12, P = 0.0006). OS was significantly shorter with low ADCL tumors, showing a median OS of 407 vs. 644 days (Cox Hazard Ratio = 0.31, P = 0.047). ADCH was not predictive of PFS or OS when accounting for age and ADCL. In summary, newly diagnosed glioblastoma patients with low ADCL after completion of RT+TMZ are likely to progress and die earlier than patients with higher ADCL. Results suggest ADC histogram analysis may be useful for patient risk stratification following completion of RT+TMZ. PMID:26740971

  9. A Novel and Validated Inflammation-Based Score (IBS) Predicts Survival in Patients With Hepatocellular Carcinoma Following Curative Surgical Resection: A STROBE-Compliant Article.

    PubMed

    Fu, Yi-Peng; Ni, Xiao-Chun; Yi, Yong; Cai, Xiao-Yan; He, Hong-Wei; Wang, Jia-Xing; Lu, Zhu-Feng; Han, Xu; Cao, Ya; Zhou, Jian; Fan, Jia; Qiu, Shuang-Jian

    2016-02-01

    As chronic inflammation is involved in the pathogenesis and progression of hepatocellular carcinoma (HCC), we investigated the prognostic accuracy of a cluster of inflammatory scores, including the Glasgow Prognostic Score, modified Glasgow Prognostic Score, platelet to lymphocyte ratio, Prognostic Nutritional Index, Prognostic Index, and a novel Inflammation-Based Score (IBS) integrated preoperative and postoperative neutrophil to lymphocyte ratio in 2 independent cohorts. Further, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy.Prognostic value of inflammatory scores and Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training cohort of 772 patients with HCC underwent hepatectomy. Independent predictors of survival identified in multivariate analysis were validated in an independent set of 349 patients with an overall similar clinical feature.In both training and validation cohorts, IBS, microscopic vascular invasion, and BCLC stage emerged as independent factors of overall survival (OS) and recurrence-free survival (RFS). The predictive capacity of the IBS in both OS and RFS appeared superior to that of the other inflammatory scores in terms of C-index. Additionally, the formulated nomogram comprised IBS resulted in more accurate prognostic prediction compared with BCLC stage alone.IBS is a novel and validated prognostic indicator of HCC after curative resection, and a robust HCC nomogram including IBS was developed to predict survival for patients after hepatectomy. PMID:26886627

  10. Tissue microRNA-21 expression predicted recurrence and poor survival in patients with colorectal cancer – a meta-analysis

    PubMed Central

    Chen, Zexin; Liu, Hui; Jin, Wen; Ding, Zheyuan; Zheng, Shuangshuang; Yu, Yunxian

    2016-01-01

    Objective MicroRNA-21 (miR-21) has been shown to play an important role in cancer prognosis. We performed a meta-analysis to evaluate the prognostic effect of miR-21 from tissues and serum on survival of the patients with colorectal cancer (CRC). Methods Relevant studies were identified by searching PubMed, Embase, and Cochrane Library. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of total and subgroup analyses, for overall survival (OS) and disease-free survival (DFS), were calculated to investigate the association between miR-21 expression and CRC prognosis. Results Our analysis included eleven studies (3,669 subjects). In addition, four studies explored the association between miR-21 and DFS, and ten studies focused on the prognostic value of miR-21 for OS. Our results indicated that increased miR-21 expression of tissues predicted both poor DFS and OS in patients with CRC (DFS: HR =1.59, 95% CI =1.20–2.10; OS: HR =1.53, 95% CI =1.23–1.90). Consistent results were observed among colon cancer and quantitative real-time polymerase chain reaction subgroups. Conclusion Meta-analysis indicated that miR-21 predicted recurrence and poor survival in patients with CRC. miR-21 may be more suitable to predict cancer prognosis in colon cancer patients. PMID:27226723

  11. Inferior vena cava injury repair, a successful outcome.

    PubMed

    Adhikary, S; Shakya, V C; Dhungel, K; Rajbanshi, S; Shakya, V; Khaniya, S; Maskey, P

    2012-03-01

    Inferior ver a cava (IVC) injuries are very very infrequent; yet it still happens to be the most frequently injured retroperitoneal vascular structure. Fifty percent of the patients can't even make it to the hospital. Even when half of them manage to attend the hospital the mortality rates for the great vessel injury are still very high perhaps due to the low index of suspicion, delayed or inadequate volume resuscitation, difficulty in diagnosis and also due to some technical problems associated in its repair. We present a young male with an abdominal stab injury who had a near transected inferior vena cava at operation. Aggressive perioperative management and the correct judgement by our team at the right time possibly made the patient survive. The rarity of this condition and a review of the literature with some discussion are presented. PMID:23441500

  12. Predictive accuracy comparison of MELD and Child-Turcotte-Pugh scores for survival in patients underwent TIPS placement: a systematic meta-analytic review

    PubMed Central

    Zhou, Chunze; Hou, Changlong; Cheng, Delei; Tang, Wenjing; Lv, Weifu

    2015-01-01

    Background: Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease (MELD) scores have been used commonly to predict the survival in the patients with liver diseases underwent transjugular intrahepatic portosystemic shunt (TIPS). However, a debate has continued for years whether CTP could be replaced by MELD score. We performed a systematic meta-analytic review to compare the prediction capability of both scores in survival among patients with TIPS. Methods: Retrospective cohort studies among patients with TIPS were published as of May 2013 were identified by systematically searching four electronic literature database, such as Ovid Medline, PubMed, EMBASE, and ISI Web of Science. The difference of standardized mean difference (SMD) of c-statistics for the predictive accuracy of 1-, 3-, 6-, and 12-month survival for both MELD and CP scores, defined as effect size (ES), was calculated for each individual study and then pooled across studies using standard meta-analyses with a random effects model. Publication bias was evaluated using funnel plots and Kendall’s rank correlation tests. Results: 174 researches articles or conference abstracts were searched and reviewed using the combination of relevant terms in the articles. Finally, 11 articles were defined as eligible studies to evaluate simultaneously the predictive accuracy of MELD and CTP scores. In the meta-analyses, MELD score was superior to CP score in predicting 3-month survival after TIPS (mean ES, 0.63; 95% confidence interval [CI], 0.13-1.14; P=0.01), but the predictive capability in 1-month, 6-month, and 12-month survival was not significant (1-month: mean ES, 0.79; 95% CI, -0.24-1.83; P=0.13; 6-month: mean ES, 0.46; 95% CI, -2.46-3.37; P=0.76; 12-month: mean ES, 0.36; 95% CI, -0.25-0.96; P=0.25). Conclusions: No enough evidence are confirmed so far that MELD score is better than CTP score to assess the overall prognosis after TIPS, especially long-term predictions, but 3-month predictive

  13. Lung function score including a parameter of small airway disease as a highly predictive indicator of survival after allogeneic hematopoietic cell transplantation.

    PubMed

    Nakamae, Mika; Yamashita, Mariko; Koh, Hideo; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Nakane, Takahiko; Nakashima, Yasuhiro; Hirose, Asao; Hino, Masayuki; Nakamae, Hirohisa

    2016-06-01

    Some studies on the predictive value of determining pulmonary function prior to allogeneic hematopoietic cell transplantation (allo-HCT) have shown a significant association between pulmonary function test (PFT) parameters and pulmonary complications, and mortality. However, the percentage of patients showing abnormalities in pretransplant PFT parameters is low. We comprehensively evaluated the effect of pretransplant PFT parameters, including a marker of small airway disease (ratio of the airflow rate of 50% vital capacity to the airflow rate of 25% vital capacity (V˙50/V˙25), on outcomes in 206 evaluable patients who underwent allo-HCT at our institute. Notable among the significant parameters in a univariable analysis, V˙50/V˙25 was the most powerful indicator of survival following allo-HCT (delta-Akaike information criterion [∆AIC] = 12.47, ∆χ(2)  = 14.47; P = 0.0001). Additionally, a pretransplant lung function score (pLFS) established by applying three parameters with superior predictive values including V˙50/V˙25 represented a better discriminating variable for the prediction of survival. Our data demonstrate that a pLFS incorporating a parameter of small airway disease, rather than the parameters of central airway obstruction, may be useful for predicting patient survival following allo-HCT. PMID:27018997

  14. SU-E-T-427: Cell Surviving Fractions Derived From Tumor-Volume Variation During Radiotherapy for Non-Small Cell Lung Cancer: Comparison with Predictive Assays

    SciTech Connect

    Chvetsov, A; Schwartz, J; Mayr, N; Yartsev, S

    2014-06-01

    Purpose: To show that a distribution of cell surviving fractions S{sub 2} in a heterogeneous group of patients can be derived from tumor-volume variation curves during radiotherapy for non-small cell lung cancer. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage (MV) computed tomography (CT). Statistical distributions of cell surviving fractions S{sup 2} and cell clearance half-lives of lethally damaged cells T1/2 have been reconstructed in each patient group by using a version of the two-level cell population tumor response model and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Non-small cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractions S{sub 2} for non-small cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sup 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Comparison of the reconstructed cell surviving fractions with patient survival data shows that the patient survival time decreases as the cell surviving fraction increases. Conclusion: The data obtained in this work suggests that the cell surviving fractions S{sub 2} can be reconstructed from the tumor volume

  15. Potential of Baseline Computed Tomography to Predict Long-Term Survival of Patients With Locally Advanced Esophageal Cancer Treated With Preoperative Chemotherapy

    PubMed Central

    Wang, Zhi-Long; Chen, Ying; Li, Xiao-Ting; Chen, Ke-Neng; Sun, Ying-Shi

    2016-01-01

    Abstract In this study, we evaluated the efficacy of baseline computed tomography (CT) signs and postoperative TN stages on survival of patients with advanced esophageal squamous cell carcinoma with preoperative chemotherapy. Consecutive patients (n = 130) with preoperative chemotherapy and radical esophagectomy from January 2006 to December 2011 were enrolled in this study retrospectively. Pathological T and N stages were confirmed by surgery. Baseline CT signs of tumor length, tumor thickness, outer membrane features, total number of lymph node (tLN), short diameter of the largest lymph node (SDL), and clinical T and N stages were measured. Eight-year overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan–Meier and Cox proportional hazards regression analyses to determine associations between baseline CT signs and survival outcomes. Kaplan–Meier analysis showed that tLN number, largest LN short axis diameter, pT, and pN stages all correlated with OS significantly. And the total tLN number, SDL and pN stages significantly correlated with DFS. In Cox analyses, total tLN number (>6) and pN stage were significantly associated with OS (hazard ratio [HR]: 1.55 [95% CI, 1.13–2.11, P = 0.006] and HR: 1.49 [95% CI, 1.17–1.90, P = 0.001], respectively). Cox regression analysis showed that OS index was predictive of 1- to 3-year survival. Total number of lymph node in baseline CT provides equal efficiency compared to pN stages in the prediction of 8-year long-term survival outcomes for advanced esophageal squamous cell carcinoma patients with preoperative chemotherapy. PMID:27149488

  16. Potential of Baseline Computed Tomography to Predict Long-Term Survival of Patients With Locally Advanced Esophageal Cancer Treated With Preoperative Chemotherapy: A Retrospective Cohort Study.

    PubMed

    Wang, Zhi-Long; Chen, Ying; Li, Xiao-Ting; Chen, Ke-Neng; Sun, Ying-Shi

    2016-05-01

    In this study, we evaluated the efficacy of baseline computed tomography (CT) signs and postoperative TN stages on survival of patients with advanced esophageal squamous cell carcinoma with preoperative chemotherapy. Consecutive patients (n = 130) with preoperative chemotherapy and radical esophagectomy from January 2006 to December 2011 were enrolled in this study retrospectively. Pathological T and N stages were confirmed by surgery. Baseline CT signs of tumor length, tumor thickness, outer membrane features, total number of lymph node (tLN), short diameter of the largest lymph node (SDL), and clinical T and N stages were measured. Eight-year overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier and Cox proportional hazards regression analyses to determine associations between baseline CT signs and survival outcomes. Kaplan-Meier analysis showed that tLN number, largest LN short axis diameter, pT, and pN stages all correlated with OS significantly. And the total tLN number, SDL and pN stages significantly correlated with DFS. In Cox analyses, total tLN number (>6) and pN stage were significantly associated with OS (hazard ratio [HR]: 1.55 [95% CI, 1.13-2.11, P = 0.006] and HR: 1.49 [95% CI, 1.17-1.90, P = 0.001], respectively). Cox regression analysis showed that OS index was predictive of 1- to 3-year survival. Total number of lymph node in baseline CT provides equal efficiency compared to pN stages in the prediction of 8-year long-term survival outcomes for advanced esophageal squamous cell carcinoma patients with preoperative chemotherapy. PMID:27149488

  17. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die based upon high IL-6 levels

    PubMed Central

    Vyas, Dinesh; Javadi, Pardis; DiPasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-01-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 hours following cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 hours after the septic insult. The first aim of this study was to see if earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die based upon high IL-6 levels. Mice (n=184) were subjected to CLP, had IL-6 levels drawn six hours later and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning six or twelve hours post-operatively. Overall one-week survival improved from 25.5% to 35.9% with earlier administration of antibiotics (p<0.05). In mice with IL-6 levels >14,000 pg/ml, 25% survived if imipenem was started at 6 hours, while none survived if antibiotics were started later (p<0.05). Based upon these results, we examined whether targeted antibody therapy could improve survival in mice with elevated IL-6 levels. A different cohort of mice (n=54) had their blood drawn six hours after CLP and then were randomized to receive either monoclonal anti-IL-6 IgG or irrelevant rat IgG. Anti-IL-6 antibody failed to improve either overall survival or outcome in mice with IL-6 levels >14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6. PMID:15947070

  18. IDH mutations in primary myelofibrosis predict leukemic transformation and shortened survival: clinical evidence for leukemogenic collaboration with JAK2V617F.

    PubMed

    Tefferi, A; Jimma, T; Sulai, N H; Lasho, T L; Finke, C M; Knudson, R A; McClure, R F; Pardanani, A

    2012-03-01

    Isocitrate dehydrogenase (IDH) mutations are frequent in blast-phase myeloproliferative neoplasms and might therefore contribute to leukemic transformation. We examined this possibility in 301 consecutive patients with chronic-phase primary myelofibrosis (PMF). The mutant IDH was detected in 12 patients (4%): 7 IDH2 (5 R140Q, 1 R140W and 1 R172G) and 5 IDH1 (3 R132S and 2 R132C). In all, 6 (50%) of the 12 IDH-mutated patients also expressed JAK2V617F. Overall, 18 (6%) patients displayed only MPL and 164 (54.3%) only JAK2 mutations. Multivariable analysis that accounted for conventional risk factors disclosed inferior overall survival (OS; P=0.03) and leukemia-free survival (LFS; P=0.003) in IDH-mutated patients: OS hazard ratio (HR) was 0.39 (95% confidence interval (95% CI) 0.2-0.75), 0.50 (95% CI 0.27-0.95) and 0.53 (95% CI 0.23-1.2) for patients with no, JAK2 or MPL mutations, respectively. Further analysis disclosed a more pronounced effect for the mutant IDH on OS and LFS in the presence (P=0.0002 and P<0.0001, respectively) as opposed to the absence (P=0.34 and P=0.64) of concomitant JAK2V617F. Analysis of paired samples obtained during chronic- and blast-phase disease revealed the presence of both IDH and JAK2 mutations at both time points. Our observations suggest that IDH mutations in PMF are independent predictors of leukemic transformation and raise the possibility of leukemogenic collaboration with JAK2V617F. PMID:21912393

  19. Rapid prediction of trauma patient survival by analysis of heart rate complexity: impact of reducing data set size.

    PubMed

    Batchinsky, Andriy I; Salinas, Jose; Kuusela, Tom; Necsoiu, Corina; Jones, John; Cancio, Leopoldo C

    2009-12-01

    Heart rate complexity (HRC) is an emerging "new vital sign" for critically ill and injured patients. Traditionally, 800-beat data sets have been used to calculate HRC variables, thus limiting their practical use in an emergency. We sought to investigate whether data set reductions diminish the use of HRC to predict mortality in prehospital trauma patients. Ectopy-free, 800-beat sections of electrocardiogram (EKG) were collected from 31 prehospital trauma patients during their helicopter transport to a level 1 trauma center. Twenty patients survived (survivors) and 11 died (nonsurvivors) after admission. HRC was assessed via approximate entropy (ApEn), sample entropy (SampEn), and similarity of distributions (SOD). The amplitude of high-frequency oscillations was measured via the method of complex demodulation. This analysis was repeated in data sets of 800, 600, 400, 200, and 100 beats. For 800 beats, ApEn and SampEn were lower in nonsurvivors than in survivors, and SOD was higher. With data set reduction, ApEn in survivors and nonsurvivors gradually approached each other but remained different until the 200-beat dataset. Sample entropy did not change with data shortening and remained lower in nonsurvivors in all data sets. Similarity of distributions was nearly constant within groups for all data sets and discriminated survivors from nonsurvivors in 800- and 100-beat data sets. High-frequency amplitude distinguished survivors from nonsurvivors in 400-, 200-, and 100-beat data sets. Logistic regression was performed for the 800-, 200-, and 100-beat data sets, retaining SampEn as a predictor of mortality (area under the receiver-operating-characteristic curves, 0.821-0.895). HRC decreased in nonsurvivors versus survivors. This finding was confirmed for data sets as short as 100 beats by computationally different metrics. SampEn, SOD, and complex demodulation were relatively unaffected by data set reduction. These metrics may be useful for rapid identification of

  20. TH-E-BRF-05: Comparison of Survival-Time Prediction Models After Radiotherapy for High-Grade Glioma Patients Based On Clinical and DVH Features

    SciTech Connect

    Magome, T; Haga, A; Igaki, H; Sekiya, N; Masutani, Y; Sakumi, A; Mukasa, A; Nakagawa, K

    2014-06-15

    Purpose: Although many outcome prediction models based on dose-volume information have been proposed, it is well known that the prognosis may be affected also by multiple clinical factors. The purpose of this study is to predict the survival time after radiotherapy for high-grade glioma patients based on features including clinical and dose-volume histogram (DVH) information. Methods: A total of 35 patients with high-grade glioma (oligodendroglioma: 2, anaplastic astrocytoma: 3, glioblastoma: 30) were selected in this study. All patients were treated with prescribed dose of 30–80 Gy after surgical resection or biopsy from 2006 to 2013 at The University of Tokyo Hospital. All cases were randomly separated into training dataset (30 cases) and test dataset (5 cases). The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. The candidate features included the 12 clinical features (tumor location, extent of surgical resection, treatment duration of radiotherapy, etc.), and the 192 DVH features (maximum dose, minimum dose, D95, V60, etc.). The effective features for the prediction were selected according to a step-wise method by using 30 training cases. The prediction accuracy was evaluated by a coefficient of determination (R{sup 2}) between the predicted and actual survival time for the training and test dataset. Results: In the multiple regression analysis, the value of R{sup 2} between the predicted and actual survival time was 0.460 for the training dataset and 0.375 for the test dataset. On the other hand, in the ANN analysis, the value of R{sup 2} was 0.806 for the training dataset and 0.811 for the test dataset. Conclusion: Although a large number of patients would be needed for more accurate and robust prediction, our preliminary Result showed the potential to predict the outcome in the patients with high-grade glioma. This work was partly supported by

  1. A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery

    PubMed Central

    Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De-Sen

    2016-01-01

    Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment. PMID:27008710

  2. Getting ready for invasions: can background level of risk predict the ability of naïve prey to survive novel predators?

    PubMed Central

    Ferrari, Maud C. O.; Crane, Adam L.; Brown, Grant E.; Chivers, Douglas P.

    2015-01-01

    Factors predicting the outcome of predator invasions on native prey communities are critical to our understanding of invasion ecology. Here, we tested whether background level of risk affected the survival of prey to novel predators, both native and invasive, predicting that high-risk environments would better prepare prey for invasions. We used naïve woodfrog as our prey and exposed them to a high or low risk regime either as embryos (prenatal exposure) or as larvae (recent exposure). Tadpoles were then tested for their survival in the presence of 4 novel predators: two dytiscid beetles, crayfish and trout. Survival was affected by both risk level and predator type. High risk was beneficial to prey exposed to the dytiscids larvae (ambush predators), but detrimental to prey exposed to crayfish or trout (pursuit predators). No effect of ontogeny of risk was found. We further documented that high-risk tadpoles were overall more active than their low-risk counterparts, explaining the patterns found with survival. Our results provide insights into the relationship between risk and resilience to predator invasions. PMID:25655436

  3. Ribonucleotide Reductase Subunit M2 Predicts Survival in Subgroups of Patients with Non-Small Cell Lung Carcinoma: Effects of Gender and Smoking Status

    PubMed Central

    Mah, Vei; Alavi, Mohammad; Márquez-Garbán, Diana C.; Maresh, Erin L.; Kim, Sara R.; Horvath, Steve; Bagryanova, Lora; Huerta-Yepez, Sara; Chia, David; Pietras, Richard

    2015-01-01

    Background Ribonucleotide reductase catalyzes the conversion of ribonucleotide diphosphates to deoxyribonucleotide diphosphates. The functional enzyme consists of two subunits - one large (RRM1) and one small (RRM2 or RRM2b) subunit. Expression levels of each subunit have been implicated in prognostic outcomes in several different types of cancers. Experimental Design Immunohistochemistry for RRM1 and RRM2 was performed on a lung cancer tissue microarray (TMA) and analyzed. 326 patients from the microarray were included in this study. Results In non-small cell lung cancer (NSCLC), RRM2 expression was strongly predictive of disease-specific survival in women, non-smokers and former smokers who had quit at least 10 years prior to being diagnosed with lung cancer. Higher expression was associated with worse survival. This was not the case for men, current smokers and those who had stopped smoking for shorter periods of time. RRM1 was not predictive of survival outcomes in any subset of the patient group. Conclusion RRM2, but not RRM1, is a useful predictor of survival outcome in certain subsets of NSCLC patients. PMID:26001082

  4. Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma.

    PubMed

    Hong, Ying-Fen; Chen, Zhan-Hong; Ma, Xiao-Kun; Li, Xing; Wu, Dong-Hao; Chen, Jie; Dong, Min; Wei, Li; Wang, Tian-Tian; Ruan, Dan-Yun; Lin, Ze-Xiao; Wen, Jing-Yun; Lin, Qu; Jia, Chang-Chang; Wu, Xiang-Yuan

    2016-04-01

    Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD-based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients

  5. Higher infused lymphocyte dose predicts higher lymphocyte recovery, which in turn, predicts superior overall survival following autologous hematopoietic stem cell transplantation for multiple myeloma.

    PubMed

    Hiwase, Devendra K; Hiwase, Smita; Bailey, Michael; Bollard, Geraldine; Schwarer, Anthony P

    2008-01-01

    Autologous stem cell transplantation (ASCT) is the standard of care for patients with multiple myeloma (MM) younger than 70 years. However, despite this aggressive therapy most patients will still die of progressive disease. Recent reports have suggested that lymphocyte recovery is an important predictor of relapse or progressive disease in a number of hematologic malignancies including MM. We have conducted retrospective analysis of factors that could predict overall (OS) and progression free survival (PFS) in patients with MM who had ASCT. One hundred nineteen patients with multiple myeloma underwent ASCT. The median OS and PFS were 64 and 32 months, respectively. Univariate and multivariate analysis using Cox proportional hazards regression model showed that absolute lymphocyte count on day 30 following ASCT (ALC-30), international staging system (ISS) stage at diagnosis, and age at diagnosis significantly influenced OS and PFS following ASCT. OS (96 versus 48 months, P = .04) and PFS (43 versus 29 months, P = .03) following ASCT were higher in patients with ALC-30 >or=1.0 x 10(9)/L compared to patients ALC-30 <1.0 x 10(9)/L. Higher ALC-60, ALC-100, ALC-180, and ALC-365 did not predict superior OS and PFS. Patients with early-stage disease had significantly higher OS (ISS stages I, II, and III: 96, 53, and 29 months, respectively; P = .0023) and PFS (ISS stages I, II, and III: 55.5, 31, and 12 months, respectively; P = .027) compared to patients with advanced-stage disease at diagnosis. On univariate analysis, the type of initial chemotherapy (melphalan, VAD, PCAB), lymphocyte count on day of leukapheresis, and the lymphocyte dose infused (LY-DO) significantly influenced lymphocyte recovery following ASCT. Patients who received higher lymphocyte dose (LY-DO) >or=0.2 x 10(9)/kg had higher median ALC-15 (0.25 versus 0.19 x 10(9)/L; P = .3), ALC-30 (1.20 versus 0.99 x 10(9)/L; P = .08), ALC-60 (1.90 versus 1.01 x 10(9)/L; P = .013), ALC-100 (1.58 versus 1.03 x 10

  6. Preoperative body composition is influenced by the stage of operable pancreatic adenocarcinoma but does not predict survival after Whipple's procedure

    PubMed Central

    Aslani, Alireza; Gill, Anthony J; Roach, Paul J; Allen, Barry J; Smith, Ross C

    2010-01-01

    Objectives: Cachexia is common in pancreatic cancer and may have an influence on longterm survival but few studies have investigated this in patients with operable tumours. Therefore, this study was carried out to document body composition status in patients with pancreatic adenocarcinoma (PCa) presenting for a Whipple's procedure (WP) and to relate the findings to histopathology and longterm survival. Methods: Body composition was measured 1 day before a WP for ductal PCa in 36 patients (15 men, 21 women) aged 41–81 years. Results for total body nitrogen (TBN), nitrogen index (NI), total body water (TBW), fat mass (FM) and total body potassium (TBK) were compared with results in 73 age- and sex-matched controls. Patients' survival and details from histopathology synoptic reports were documented. Results: Patients undergoing WPs had low TBK values (P < 0.001) and females had lower body fat (P= 0.007) compared with controls. Five of 36 presented with significant protein deficiency, but this was not associated with a prolonged length of stay or reduced survival. The 12 patients who had involved surgical margins had larger tumours and reduced weight (P= 0.015), FM (P= 0.001), TBN (P= 0.045), TBK (P= 0.014) and survival (P= 0.036). However, multivariate Cox's regression analysis only included FM along with vascular invasion and margin status as independent predictors of survival. Conclusions: PCa patients undergoing a WP have reduced body fat and TBK compared with community controls while those with stage III tumours had greater deficits of fat, TBK and protein stores. However, preoperative body composition was a poor predictor of postoperative survival after pathological data were considered. PMID:20590908

  7. Inferior vena caval masses identified by echocardiography

    NASA Technical Reports Server (NTRS)

    Sun, J. P.; Asher, C. R.; Xu, Y.; Huang, V.; Griffin, B. P.; Stewart, W. J.; Novick, A. C.; Thomas, J. D.

    1999-01-01

    The most common cause of an inferior vena caval mass is renal cell carcinoma that extends through the lumen, occurring in 47 of 62 patients (85%). Detection of an inferior vena caval mass affects the surgical approach requiring cardiopulmonary bypass for resection when the mass extends to the heart.

  8. The pretreatment albumin to globulin ratio predicts survival in patients with natural killer/T-cell lymphoma

    PubMed Central

    Bi, Xi-wen; Wang, Liang; Zhang, Wen-wen; Yan, Shu-mei; Sun, Peng; Xia, Yi; Li, Zhi-ming

    2016-01-01

    Background. The pretreatment albumin to globulin ratio (AGR) has been reported to be a predictor of survival in several types of cancer. The aim of this study was to evaluate the prognostic impact of AGR in patients with natural killer/T-cell lymphoma (NKTCL). Methods. We retrospectively reviewed the available serum biochemistry results for 331 NKTCL patients before treatment. AGR was calculated as albumin/(total protein—albumin), and a cut-off value of 1.3 was used to define AGR as low or high. Survival analysis was used to assess the prognostic value of AGR. Results. A low AGR (<1.3) was associated with significantly more adverse clinical features, including old age, poor performance status, advanced stage, elevated lactate dehydrogenase, B symptoms, and high International Prognostic Index (IPI) and natural killer/T-cell lymphoma prognostic index (NKPI) scores. Patients with a low AGR had a significantly lower 5-year overall survival (44.5 vs. 65.2%, P < 0.001) and progression-free survival (33.1 vs. 57.4%, P < 0.001). In the multivariate analysis, a low AGR remained an independent predictor of poorer survival. Additionally, AGR distinguished patients with different outcomes in the IPI low-risk group and in the NKPI high-risk group. Discussion. Pretreatment AGR may serve as a simple and effective predictor of prognosis in patients with NKTCL. PMID:26966671

  9. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    SciTech Connect

    Song, Changhoon; Kim, Kyubo; Chie, Eui Kyu; Kim, Jin Ho; Jang, Jin-Young; Kim, Sun Whe; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W.

    2013-11-01

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

  10. Development of predictive models for the survival of Campylobacter jejuni (ATCC 43051) on cooked chicken breast patties and in broth as a function of temperature.

    PubMed

    Yoon, K S; Burnette, C N; Oscar, T P

    2004-01-01

    The objective of this study was to model the kinetics of the survival of Campylobacter jejuni on cooked chicken breast patties and in broth as a function of temperature. Both patties and broth were inoculated with 10(6) stationary-phase cells of a single strain of C. jejuni (ATCC 43051) and incubated at constant temperatures from 4 to 30 degrees C in 2 degrees C increments under aerobic conditions. In most cases, a three-phase linear model fit the primary survival curves well (r2 = 0.97 to 0.99) at all incubation temperatures regardless of model medium, indicating the presence of a resistant subpopulation of C. jejuni that would not be eliminated without thermal processing. Secondary models predicting lag time (LT) and specific death rate (SDR) as functions of temperature were also developed. The Davey and Boltzmann models were identified as appropriate secondary models for LT and SDR, respectively, on the basis of goodness of fit (Boltzmann model, r2 = 0.96; Davey model, r2 = 0.93) and prediction bias and accuracy factor tests. The results obtained indicate that C. jejuni can survive well at both refrigeration and ambient temperatures regardless of model medium. Reduced survival of C. jejuni, characterized by shorter lag times and faster death rates, was observed both on patties and in broth at ambient temperatures. In addition, the average maximum reduction of C. jejuni at 4 to 30 degrees C was 1.5 log units regardless of storage temperature or model medium. These findings suggest that C. jejuni found on contaminated poultry products has the potential to survive under conditions that are not permissive for growth and thus could cause foodborne illness if the poultry is not sufficiently cooked. PMID:14717353

  11. High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning

    PubMed Central

    Reshef, Ran; Huffman, Austin P.; Gao, Amy; Luskin, Marlise R.; Frey, Noelle V.; Gill, Saar I.; Hexner, Elizabeth O.; Kambayashi, Taku; Loren, Alison W.; Luger, Selina M.; Mangan, James K.; Nasta, Sunita D.; Richman, Lee P.; Sell, Mary; Stadtmauer, Edward A.; Vonderheide, Robert H.; Mick, Rosemarie; Porter, David L.

    2015-01-01

    Purpose To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. Patients and Methods We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. Results Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 108 CD8 cells per kilogram optimally segregated patients receiving CD8hi and CD8lo grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8hi graft, whereas approximately half of younger donors provided CD8hi grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8lo doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8hi doses (P = .03), but not for recipients of younger unrelated donor CD8lo grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. Conclusion Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT. PMID:26056179

  12. A novel five gene signature derived from stem-like side population cells predicts overall and recurrence-free survival in NSCLC.

    PubMed

    Perumal, Deepak; Singh, Sandeep; Yoder, Sean J; Bloom, Gregory C; Chellappan, Srikumar P

    2012-01-01

    Gene expression profiling has been used to characterize prognosis in various cancers. Earlier studies had shown that side population cells isolated from Non-Small Cell Lung Cancer (NSCLC) cell lines exhibit cancer stem cell properties. In this study we apply a systems biology approach to gene expression profiling data from cancer stem like cells isolated from lung cancer cell lines to identify novel gene signatures that could predict prognosis. Microarray data from side population (SP) and main population (MP) cells isolated from 4 NSCLC lines (A549, H1650, H460, H1975) were used to examine gene expression profiles associated with stem like properties. Differentially expressed genes that were over or under-expressed at least two fold commonly in all 4 cell lines were identified. We found 354 were upregulated and 126 were downregulated in SP cells compared to MP cells; of these, 89 up and 62 downregulated genes (average 2 fold changes) were used for Principle Component Analysis (PCA) and MetaCore pathway analysis. The pathway analysis demonstrated representation of 4 up regulated genes (TOP2A, AURKB, BRRN1, CDK1) in chromosome condensation pathway and 1 down regulated gene FUS in chromosomal translocation. Microarray data was validated using qRT-PCR on the 5 selected genes and all showed robust correlation between microarray and qRT-PCR. Further, we analyzed two independent gene expression datasets that included 360 lung adenocarcinoma patients from NCI Director's Challenge Set for overall survival and 63 samples from Sungkyunkwan University (SKKU) for recurrence free survival. Kaplan-Meier and log-rank test analysis predicted poor survival of patients in both data sets. Our results suggest that genes involved in chromosome condensation are likely related with stem-like properties and might predict survival in lung adenocarcinoma. Our findings highlight a gene signature for effective identification of lung adenocarcinoma patients with poor prognosis and designing

  13. CT Perfusion Imaging Can Predict Patients' Survival and Early Response to Transarterial Chemo-Lipiodol Infusion for Liver Metastases from Colorectal Cancers

    PubMed Central

    Lv, Wei-Fu; Cheng, De-Lei; Zhou, Chun-Ze; Ni, Ming; Lu, Dong

    2015-01-01

    Objective To prospectively evaluate the performance of computed tomography perfusion imaging (CTPI) in predicting the early response to transarterial chemo-lipiodol infusion (TACLI) and survival of patients with colorectal cancer liver metastases (CRLM). Materials and Methods Computed tomography perfusion imaging was performed before and 1 month after TACLI in 61 consecutive patients. Therapeutic response was evaluated on CT scans 1 month and 4 months after TACLI; the patients were classified as responders and non-responders based on 4-month CT scans after TACLI. The percentage change of CTPI parameters of target lesions were compared between responders and non-responders at 1 month after TACLI. The optimal parameter and cutoff value were determined. The patients were divided into 2 subgroups according to the cutoff value. The log-rank test was used to compare the survival rates of the 2 subgroups. Results Four-month images were obtained from 58 patients, of which 39.7% were responders and 60.3% were non-responders. The percentage change in hepatic arterial perfusion (HAP) 1 month after TACLI was the optimal predicting parameter (p = 0.003). The best cut-off value was -21.5% and patients who exhibited a ≥ 21.5% decrease in HAP had a significantly higher overall survival rate than those who exhibited a < 21.5% decrease (p < 0.001). Conclusion Computed tomography perfusion imaging can predict the early response to TACLI and survival of patients with CRLM. The percentage change in HAP after TACLI with a cutoff value of -21.5% is the optimal predictor. PMID:26175580

  14. Functional intronic ERCC1 polymorphism from regulomeDB can predict survival in lung cancer after surgery

    PubMed Central

    Jeon, Hyo-Sung; Choi, Yi Young; Choi, Jin Eun; Kang, Hyo-Gyoung; Jung, Deuk Kju; Jin, Chengcheng; Do, Sook Kyung; Yoo, Seung Soo; Seok, Yangki; Lee, Eung Bae; Shin, Kyung Min; Jeong, Ji Yun; Lee, Won Kee; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Kim, Young Tae; Jheon, Sanghoon; Park, Jae Yong

    2015-01-01

    We searched for potential regulatory single nucleotide polymorphisms (SNPs) in excision repair cross-complementing group 1 (ERCC1) using RegulomeDB, a database integrating information from the Encyclopedia of DNA Elements (ENCODE) project, and investigated their association with survival after surgery in non-small cell lung cancer (NSCLC). Among 364 SNPs found within ERCC1 region using RegulomeDB, four top priority SNPs (rs2298881C>A, rs1049739A>G, rs10415949A>G and rs6509214G>T) were selected for this study. The four SNPs were investigated in 316 patients. A replication study was performed (n = 579). Of the four SNPs analyzed in the discovery set, rs2298881C>A and rs6509214G>T were significantly associated with survival outcomes. The association was consistently observed only for rs2298881C>A in the validation cohort. In combined analysis, rs2298881C>A was significantly associated with worse overall survival and disease-free survival (P = 0.0002 and 0.02, respectively). A decreased reporter gene expression for rs2298881 A allele was observed compared with C allele by luciferase assay (P = 0.02). ERCC1 rs2298881C>A, an intronic SNP, is the first genetic polymorphism with functional evidence of regulating its expression, and the SNP is associated with prognosis of NSCLC. Our result supports the role of RegulomeDB as a comprehensive source of prioritized candidate SNPs for genetic association studies. PMID:26056042

  15. IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy.

    PubMed

    Minniti, Giuseppe; Scaringi, Claudia; Arcella, Antonella; Lanzetta, Gaetano; Di Stefano, Domenica; Scarpino, Stefania; Bozzao, Alessandro; Pace, Andrea; Villani, Veronica; Salvati, Maurizio; Esposito, Vincenzo; Giangaspero, Felice; Enrici, Riccardo Maurizi

    2014-06-01

    Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12-89 months), median and 5-year overall survival rates were 50.5 months (95 % CI, 37.8-63.2) and 38% (95 % CI, 25.7-50.7%), and median and 5-year progression-free survival rates were 36 months (95% CI, 28.5-44.0) and 22 % (95 % CI, 10-34%), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60% of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age < 50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated. PMID:24748470

  16. Black ethnicity predicts better survival on dialysis despite greater deprivation and co-morbidity: a UK study

    PubMed Central

    Cole, Nicholas; Bedford, Michael; Cai, Andrew; Jones, Chris; Cairns, Hugh; Jayawardene, Satish

    2014-01-01

    Background: Observational studies from the United States have identified black race as conferring a survival advantage on dialysis. This study represents the first large single-center study from a UK dialysis unit examining the outcome of ethnic minorities on renal replacement therapy (RRT). Methods: A retrospective analysis of all patients of white or black race initiating RRT at King’s College Hospital Renal Unit, London, between 1996 and 2008 was performed. A total of 1,340 patients were studied, of which 952 (71%) were of white race, and 388 (29%) were of black race. Kaplan-Meier survival curves, the log rank test and Cox’s proportional hazard models were used to compare survival between groups. Results: The results revealed black ethnicity to be associated with a significant survival benefit on dialysis. This was the case even after adjustment for age, gender, diabetes, transplantation, and deprivation. In those patients not transplanted, black race conferred a hazard ratio (HR) of 0.51 (95% CI 0.41 – 0.63) over 5 years. Conclusions: This study provides evidence for a lower mortality rate amongst black patients on dialysis in comparison with their white counterparts in the UK. The reasons behind this remain poorly understood but a lower incidence of cardiovascular disease in black patients and more kidney-limited disease may be important. PMID:24985953

  17. Genetic polymorphisms in circadian negative feedback regulation genes predict overall survival and response to chemotherapy in gastric cancer patients

    PubMed Central

    Qu, Falin; Qiao, Qing; Wang, Nan; Ji, Gang; Zhao, Huadong; He, Li; Wang, Haichao; Bao, Guoqiang

    2016-01-01

    Circadian negative feedback loop (CNFL) genes play important roles in cancer development and progression. To evaluate the effects of single nucleotide polymorphisms (SNPs) in CNFL genes on the survival of GC patients, 13 functional SNPs from 5 CNFL genes were genotyped in a cohort of 1030 resected GC patients (704 in the training set, 326 in the validation set) to explore the association of SNPs with overall survival (OS). Among the 13 SNPs, three SNPs (rs1056560 in CRY1, rs3027178 in PER1 and rs228729 in PER3) were significantly associated with OS of GC in the training set, and verified in the validation set and pooled analysis. Furthermore, a dose-dependent cumulative effect of these SNPs on GC survival was observed, and survival tree analysis showed higher order interactions between these SNPs. In addition, protective effect conferred by adjuvant chemotherapy (ACT) on GC was observed in patients with variant alleles (TG/GG) of rs1056560, but not in those with homozygous wild (TT) genotype. Functional assay suggested rs1056560 genotypes significantly affect CRY1 expression in cancer cells. Our study presents that SNPs in the CNFL genes may be associated with GC prognosis, and provides the guidance in selecting potential GC patients most likely responsive to ACT. PMID:26927666

  18. Biochemical Response to Ursodeoxycholic Acid Predicts Survival in a North American Cohort of Primary Biliary Cirrhosis Patients

    PubMed Central

    Lammert, Craig; Juran, Brian D.; Schlicht, Erik; Chan, Landon L.; Atkinson, Elizabeth J.; de Andrade, Mariza; Lazaridis, Konstantinos N.

    2014-01-01

    Background Biochemical response to Ursodeoxycholic Acid among patients with Primary Biliary Cirrhosis remains variable and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with Ursodeoxycholic Acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Methods 398 PBC patients from the Mayo Clinic PBC Genetic Epidemiology (MCPGE) Registry were assessed for Ursodeoxycholic Acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Results 302 (76%) patients were responders and 96 (24%) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (Hazard Ratio (HR): 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR: 1.9) and patients with late stage disease (HR: 2.7) after age and sex adjustment. Conclusions The Toronto criteria are capable of identifying Ursodeoxycholic Acid-treated Primary Biliary Cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival. PMID:24317935

  19. Methodology to predict long-term cancer survival from short-term data using Tobacco Cancer Risk and Absolute Cancer Cure models

    NASA Astrophysics Data System (ADS)

    Mould, R. F.; Lederman, M.; Tai, P.; Wong, J. K. M.

    2002-11-01

    Three parametric statistical models have been fully validated for cancer of the larynx for the prediction of long-term 15, 20 and 25 year cancer-specific survival fractions when short-term follow-up data was available for just 1-2 years after the end of treatment of the last patient. In all groups of cases the treatment period was only 5 years. Three disease stage groups were studied, T1N0, T2N0 and T3N0. The models are the Standard Lognormal (SLN) first proposed by Boag (1949 J. R. Stat. Soc. Series B 11 15-53) but only ever fully validated for cancer of the cervix, Mould and Boag (1975 Br. J. Cancer 32 529-50), and two new models which have been termed Tobacco Cancer Risk (TCR) and Absolute Cancer Cure (ACC). In each, the frequency distribution of survival times of defined groups of cancer deaths is lognormally distributed: larynx only (SLN), larynx and lung (TCR) and all cancers (ACC). All models each have three unknown parameters but it was possible to estimate a value for the lognormal parameter S a priori. By reduction to two unknown parameters the model stability has been improved. The material used to validate the methodology consisted of case histories of 965 patients, all treated during the period 1944-1968 by Dr Manuel Lederman of the Royal Marsden Hospital, London, with follow-up to 1988. This provided a follow-up range of 20- 44 years and enabled predicted long-term survival fractions to be compared with the actual survival fractions, calculated by the Kaplan and Meier (1958 J. Am. Stat. Assoc. 53 457-82) method. The TCR and ACC models are better than the SLN model and for a maximum short-term follow-up of 6 years, the 20 and 25 year survival fractions could be predicted. Therefore the numbers of follow-up years saved are respectively 14 years and 19 years. Clinical trial results using the TCR and ACC models can thus be analysed much earlier than currently possible. Absolute cure from cancer was also studied, using not only the prediction models which

  20. Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

    SciTech Connect

    Dikken, Johan L.; Coit, Daniel G.; Baser, Raymond E.; Gönen, Mithat; Goodman, Karyn A.; Brennan, Murray F.; Jansen, Edwin P.M.; Boot, Henk; Velde, Cornelis J.H. van de; Cats, Annemieke; Verheij, Marcel

    2014-03-01

    Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

  1. Predictions of human tolerance to cold water immersion while wearning advanced integrated garment ensembles with and without survival rafts or exogenous heating. Final report, April-September 1992

    SciTech Connect

    Shender, B.S.; Kaufman, J.

    1993-12-30

    US Navy interest in garments providing integrated protection against chemical agents, hyperthermia, hypobaria, and hypothermia has led to fabrication of prototype multi-purpose garments. As part of the development process, these garments need to be tested for the protection they provide against these hazards. Mathematical modeling can be used to simulate the thermal protection provided by the various garment designs and minimize laboratory testing. It can also be used to establish guidelines on the amount of clothing insulation required to withstand exposures of various durations under conditions of thermal stress. This paper reports on the theoretical evaluation of hypothermia protection provided by various tactical aircrew garments during simulated head-out cold water immersion (CWI) using the Texas Human Thermal Model (10) (referred to THTM, below), as modified by the Naval Air Warfare Center Aircraft Division Warminster for use with low CLO values (7). THTM can aid in clothing design by allowing specification of insulation values for up to fifteen body segments. This is an improvement over earlier work (8), in which researchers based their conclusions on an overall mean CLO value for garments. Also included in this paper is an algorithm to predict the effects of using open and closed survival rafts while wearing a CWU-62/P on rectal and mean skin temperature during survival scenarios. Lastly, THTM was used to predict the amount of exogenous heating required to survive 6 hour CWI while wearing CWU-27YP and CWU-62/P garment ensembles.

  2. Predictions of human tolerance to cold water immersion while wearing advanced integrated garment ensembles with and without survival rafts or exogenous heating. Final report, April-September 1992

    SciTech Connect

    Shender, B.S.; Kaufman, J.

    1993-12-30

    US Navy interest in garments providing integrated protection against chemical agents, hyperthermia, hypobaria, and hypothermia has led to fabrication of prototype multi-purpose garments. As part of the development process, these garments need to be tested for the protection they provide against these hazards. Mathematical modeling can be used to simulate the thermal protection provided by the various garment designs and minimize laboratory testing. It can also be used to establish guidelines on the amount of clothing insulation required to withstand exposures of various durations under conditions of thermal stress. This paper reports on the theoretical evaluation of hypothermia protection provided by various tactical aircrew garments during simulated head-out cold water immersion (CWI) using the Texas Human Thermal Model (10) (referred to THTM, below), as modified by the Naval Air Warfare Center Aircraft Division THTM for use with low CLO values (7). THTM can aid in clothing design by allowing specification of insulation values for up to fifteen body segments. This is an improvement over earlier work (8), in which researchers based their conclusions on an overall mean THTM value for garments. Also included in this paper is an algorithm to predict the effects of using open and closed survival rafts while wearing a CWU-62/P on rectal and mean skin temperature during survival scenarios. Lastly, THTM was used to predict the amount of exogenous heating required to survive 6 hour CWI while wearing CWU-27/P and CWU-62/P garment ensembles.

  3. Using the reactive scope model to understand why stress physiology predicts survival during starvation in Galápagos marine iguanas.

    PubMed

    Romero, L Michael

    2012-05-01

    Even though the term "stress" is widely used, a precise definition is notoriously difficult. Notwithstanding this difficulty, stress continues to be an important concept in biology because it attempts to describe how animals cope with environmental change under emergency conditions. Without a precise definition, however, it becomes nearly impossible to make testable a priori predictions about how physiological and hormonal systems will respond to emergency conditions and what the ultimate impact on the animal will be. The reactive scope model is a recent attempt to formulate testable predictions. This model provides a physiological basis to explain why corticosterone negative feedback, but not baseline corticosterone concentrations, corticosterone responses to acute stress, or the interrenal capacity to secrete corticosterone, is correlated with survival during famine conditions in Galápagos marine iguanas. Reactive scope thus provides a foundation for interpreting and predicting physiological stress responses. PMID:22101208

  4. Geometrical Measures Obtained from Pretreatment Postcontrast T1 Weighted MRIs Predict Survival Benefits from Bevacizumab in Glioblastoma Patients

    PubMed Central

    Sepúlveda, Juan M.; Peralta, Sergi; Gil-Gil, Miguel J.; Reynes, Gaspar; Herrero, Ana; De Las Peñas, Ramón; Luque, Raquel; Capellades, Jaume

    2016-01-01

    Background Antiangiogenic therapies for glioblastoma (GBM) such as bevacizumab (BVZ), have been unable to extend survival in large patient cohorts. However, a subset of patients having angiogenesis-dependent tumors might benefit from these therapies. Currently, there are no biomarkers allowing to discriminate responders from non-responders before the start of the therapy. Methods 40 patients from the randomized GENOM009 study complied the inclusion criteria (quality of images, clinical data available). Of those, 23 patients received first line temozolomide (TMZ) for eight weeks and then concomitant radiotherapy and TMZ. 17 patients received BVZ+TMZ for seven weeks and then added radiotherapy to the treatment. Clinical variables were collected, tumors segmented and several geometrical measures computed including: Contrast enhancing (CE), necrotic, and total volumes; equivalent spherical CE width; several geometric measures of the CE ‘rim’ geometry and a set of image texture measures. The significance of the results was studied using Kaplan-Meier and Cox proportional hazards analysis. Correlations were assessed using Spearman correlation coefficients. Results Kaplan-Meier and Cox proportional hazards analysis showed that total, CE and inner volume (p = 0.019, HR = 4.258) and geometric heterogeneity of the CE areas (p = 0.011, HR = 3.931) were significant parameters identifying response to BVZ. The group of patients with either regular CE areas (small geometric heterogeneity, median difference survival 15.88 months, p = 0.011) or those with small necrotic volume (median survival difference 14.50 months, p = 0.047) benefited substantially from BVZ. Conclusion Imaging biomarkers related to the irregularity of contrast enhancing areas and the necrotic volume were able to discriminate GBM patients with a substantial survival benefit from BVZ. A prospective study is needed to validate our results. PMID:27557121

  5. Accelerated muscle and adipose tissue loss may predict survival in pancreatic cancer patients: the relationship with diabetes and anaemia.

    PubMed

    Di Sebastiano, Katie M; Yang, Lin; Zbuk, Kevin; Wong, Raimond K; Chow, Tom; Koff, David; Moran, Gerald R; Mourtzakis, Marina

    2013-01-28

    Weight loss leading to cachexia is associated with poor treatment response and reduced survival in pancreatic cancer patients. We aim to identify indicators that allow for early detection that will advance our understanding of cachexia and will support targeted anti-cachexia therapies. A total of fifty pancreatic cancer patients were analysed for skeletal muscle and visceral adipose tissue (VAT) changes using computed tomography (CT) scans. These changes were related to physical characteristics, secondary disease states and treatment parameters. Overall, patients lost 1.72 (SD 3.29) kg of muscle and 1.04 (SD 1.08) kg of VAT during the disease trajectory (413 (SD 213) d). After sorting patients into tertiles by rate of VAT and muscle loss, patients losing VAT at > -0.40 kg/100 d had poorer survival outcomes compared with patients with < -0.10 kg/100 d of VAT loss (P= 0.020). Patients presenting with diabetes at diagnosis demonstrated significantly more and accelerated VAT loss compared with non-diabetic patients. In contrast, patients who were anaemic at the first CT scan lost significantly more muscle tissue and at accelerated rates compared with non-anaemic patients. Accelerated rates of VAT loss are associated with reduced survival. Identifying associated features of cachexia, such as diabetes and anaemia, is essential for the early detection of cachexia and may facilitate the attenuation of complications associated with cachexia. PMID:23021109

  6. Marital status independently predicts gastric cancer survival after surgical resection--an analysis of the SEER database

    PubMed Central

    Yang, Zhen; Pan, Gaofeng; Zhang, Ziping; Wang, WeiHua; Liu, Shaoqun; Zhang, Dongbin; Jiang, Daowen; Liu, Weiyan

    2016-01-01

    Marital status was found to be an independent prognostic factor for survival in various cancer types, but it hasn't been studied in gastric cancer. The Surveillance, Epidemiology and End Results database was used to compare survival outcomes with marital status. A total of 16,106 eligible patients were identified. Patients in the widowed group had the highest proportion of women, more common site of stomach, more prevalence of elderly patients, higher percentage of adenocarcinoma, and more tumors at localized stage (P < 0.05). Patients in married group had better 5year cause-specific survival (CSS) than those unmarried (P < 0.05). Further analysis showed that widowed patients always presented the lowest CSS compared with that of other groups. Widowed patients had 7.1% reduction in 5-year CSS compared with married patients at Localized stage (77.2% vs 70.1%, P < 0.001), 9.6% reduction at Regional stage (38.2% vs 28.6%, P < 0.001), and 4.7% reduction at Distant stage (13.3% vs 8.6%, P < 0.001). These results showed that unmarried patients were at greater risk of cancer specific mortality. Despite favorable clinicpathological characteristics, widowed patients were at highest risk of death compared with other groups. PMID:26840093

  7. Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

    SciTech Connect

    Zelefsky, Michael J.; Gomez, Daniel R.; Polkinghorn, William R.; Pei, Xin; Kollmeier, Marisa

    2013-07-01

    Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5 years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.

  8. Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

    NASA Technical Reports Server (NTRS)

    Armoundas, A. A.; Rosenbaum, D. S.; Ruskin, J. N.; Garan, H.; Cohen, R. J.

    1998-01-01

    OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular

  9. Comparison of Bayesian network and support vector machine models for two-year survival prediction in lung cancer patients treated with radiotherapy

    SciTech Connect

    Jayasurya, K.; Fung, G.; Yu, S.; Dehing-Oberije, C.; De Ruysscher, D.; Hope, A.; De Neve, W.; Lievens, Y.; Lambin, P.; Dekker, A. L. A. J.

    2010-04-15

    Purpose: Classic statistical and machine learning models such as support vector machines (SVMs) can be used to predict cancer outcome, but often only perform well if all the input variables are known, which is unlikely in the medical domain. Bayesian network (BN) models have a natural ability to reason under uncertainty and might handle missing data better. In this study, the authors hypothesize that a BN model can predict two-year survival in non-small cell lung cancer (NSCLC) patients as accurately as SVM, but will predict survival more accurately when data are missing. Methods: A BN and SVM model were trained on 322 inoperable NSCLC patients treated with radiotherapy from Maastricht and validated in three independent data sets of 35, 47, and 33 patients from Ghent, Leuven, and Toronto. Missing variables occurred in the data set with only 37, 28, and 24 patients having a complete data set. Results: The BN model structure and parameter learning identified gross tumor volume size, performance status, and number of positive lymph nodes on a PET as prognostic factors for two-year survival. When validated in the full validation set of Ghent, Leuven, and Toronto, the BN model had an AUC of 0.77, 0.72, and 0.70, respectively. A SVM model based on the same variables had an overall worse performance (AUC 0.71, 0.68, and 0.69) especially in the Ghent set, which had the highest percentage of missing the important GTV size data. When only patients with complete data sets were considered, the BN and SVM model performed more alike. Conclusions: Within the limitations of this study, the hypothesis is supported that BN models are better at handling missing data than SVM models and are therefore more suitable for the medical domain. Future works have to focus on improving the BN performance by including more patients, more variables, and more diversity.

  10. A Case of the Inferior Mesenteric Artery Arising from the Superior Mesenteric Artery in a Korean Woman

    PubMed Central

    Yoo, Seung Jin; Ku, Min Jung; Cho, Sa Sun

    2011-01-01

    Anatomical variations of the inferior mesenteric artery are extremely uncommon, since the inferior mesenteric artery is regularly diverged at the level of the third lumbar vertebra. We found a rare case in which the inferior mesenteric artery arose from the superior mesenteric artery. The findings were made during a routine dissection of the cadaver of an 82-yr-old Korean woman. This is the tenth report on this anomaly, the second female and the first Korean. The superior mesenteric artery normally arising from abdominal aorta sent the inferior mesenteric artery as the second branch. The longitudinal anastomosis vessels between the superior mesenteric artery and inferior mesenteric artery survived to form the common mesenteric artery. This anatomical variation concerning the common mesenteric artery is of clinical importance, performing procedures containing the superior mesenteric artery. PMID:22022194

  11. Validity of the Graded Prognostic Assessment-Derived Index to Predict Brain-Metastatic Patients' Survival After Gamma Knife Radiosurgery

    SciTech Connect

    Chiou, Shang-Ming

    2010-11-15

    Purpose: To appraise whether the graded prognostic assessment (GPA)-derived index is valid for selecting patients with brain metastases for Gamma Knife (GK) radiosurgery. Methods and Materials: A total of 56 consecutive patients in recursive partioning analysis (RPA) Class I (n = 19, 34%) and II (n = 37, 66%) formed the basis of this retrospective study. Their mean age was of 57 years with mean Karnofsky performance score of 77. Primary cancers stemmed mainly from the lungs (59%). A total of 45 patients (80%) harbored multiple tumors. The mean clinical follow-up period was 9 months. Results: Kaplan-Meier analysis demonstrated that the overall median survival time (MST) for the whole series was 11.5 months: 16.5 vs. 6.5 months for RPA class I and II (p = 0.017). Multivariate Cox analysis revealed that female patients and a pre-GK good functional state were favorable prognostic factors. The favorable MST was in patients with a GPA score of 3 to 4 (17 months) followed by a GPA score of 2 to 2.5 (11 months) and GPA score 0 to 1.5 (6.5 months), but without statistical differences (p = 0.413) in between. A modified index (MGPA) is proposed with gender as a cofactor, then there existed a distinct survival differences (p = 0.028) between patients with an MGPA score of 3.5 to 5 (15 months) and with an MGPA score of 0 to 3 (7 months). In addition, the original GPA index failed to imply the difference of MST in patients with lung origin. Conclusions: The GPA-derived index is not applicable to our set of patients for comparing their survival after GK radiosurgery. The gender of the patients is a suggested cofactor to further refine the greater prognostic accuracy of the GPA index.

  12. Postoperative Insulin-Like Growth Factor 1 Levels Reflect the Graft’s Function and Predict Survival after Liver Transplantation

    PubMed Central

    Mocchegiani, Federico; Coletta, Martina; Brugia, Marina; Montalti, Roberto; Fava, Giammarco; Taccaliti, Augusto; Risaliti, Andrea; Vivarelli, Marco

    2015-01-01

    Background The reduction of insulin-like growth factor 1 (IGF-1) plasma levels is associated with the degree of liver dysfunction and mortality in cirrhotic patients. However, little research is available on the recovery of the IGF-1 level and its prognostic role after liver transplantation (LT). Methods From April 2010 to May 2011, 31 patients were prospectively enrolled (25/6 M/F; mean age±SEM: 55.2±1.4 years), and IGF-1 serum levels were assessed preoperatively and at 15, 30, 90, 180 and 365 days after transplantation. The influence of the donor and recipient characteristics (age, use of extended criteria donor grafts, D-MELD and incidence of early allograft dysfunction) on hormonal concentration was analyzed. The prognostic role of IGF-1 level on patient survival and its correlation with routine liver function tests were also investigated. Results All patients showed low preoperative IGF-1 levels (mean±SEM: 29.5±2.1), and on postoperative day 15, a significant increase in the IGF-1 plasma level was observed (102.7±11.7 ng/ml; p<0.0001). During the first year after LT, the IGF-1 concentration remained significantly lower in recipients transplanted with older donors (>65 years) or extended criteria donor grafts. An inverse correlation between IGF-1 and bilirubin serum levels at day 15 (r = -0.3924, p = 0.0320) and 30 (r = -0.3894, p = 0.0368) was found. After multivariate analysis, early (within 15 days) IGF-1 normalization [Exp(b) = 3.913; p = 0.0484] was the only prognostic factor associated with an increased 3-year survival rate. Conclusion IGF-1 postoperative levels are correlated with the graft’s quality and reflect liver function. Early IGF-1 recovery is associated with a higher 3-year survival rate after LT. PMID:26186540

  13. P2X7 receptor predicts postoperative cancer-specific survival of patients with clear-cell renal cell carcinoma.

    PubMed

    Liu, Zheng; Liu, Yidong; Xu, Le; An, Huimin; Chang, Yuan; Yang, Yuanfeng; Zhang, Weijuan; Xu, Jiejie

    2015-09-01

    The P2X7 receptor, an ATP-gated plasma membrane ion channel, is involved in inflammation, apoptosis and cell proliferation, and thereby plays a crucial role during oncogenic transformation in various malignancies. This study aims to evaluate the impact of P2X7 receptor expression on postoperative cancer-specific survival of patients with clear-cell renal cell carcinoma (ccRCC). A total of 273 patients with ccRCC undergoing nephrectomy at a single institution were retrospectively enrolled in this study, among which 86 patients died of this disease and six patients died of other causes. Clinicopathologic features and cancer-specific survival (CSS) were recorded. P2X7 expression was assessed by immunohistochemistry in clinical specimens. Kaplan-Meier method with log rank test was performed to compare survival curves. Cox regression models were used to evaluate the prognostic values of variables on CSS. Concordance index was calculated to assess prognostic accuracy of prognostic models. Median follow-up period was 90 months (range, 11-120 months). Intratumoral P2X7 expression was significantly lower than peritumoral tissues (P < 0.001). Moreover, high intratumoral P2X7 expression, which was significantly associated with shorten CSS (P < 0.001), high TNM stage (P = 0.038), Fuhrman grade (P = 0.035), SSIGN (stage, size, grade, and necrosis) score (P = 0.021) and University of California Integrated Staging System (UISS) score (P = 0.007), was indicated to be an independent prognostic factor for CSS (hazard ratio [HR], 1.693; P = 0.034). The prognostic accuracy of TNM stage, UISS and SSIGN scoring models was improved when intratumoral P2X7 expression was added. Intratumoral P2X7 expression is a potential independent adverse prognostic indicator for postoperative CSS of patients with ccRCC. PMID:26179886

  14. Loggerhead sea turtle environmental sex determination: implications of moisture and temperature for climate change based predictions for species survival.

    PubMed

    Wyneken, Jeanette; Lolavar, Alexandra

    2015-05-01

    It has been proposed that because marine turtles have environmentally determined sex by incubation temperature, elevated temperatures might skew sex ratios to unsustainable levels, leading to extinction. Elevated temperatures may also reduce availability of suitable nesting sites via sea level rise. Increased tropical storm activity can directly affect nest site moisture, embryonic development, and the probability that nests will survive. Here, we question some of these assumptions and review the limits of sex ratio estimates. Sea turtles may be more resilient to climate change than previously thought, in part because of hitherto unappreciated mechanisms for coping with variable incubation conditions. PMID:25877336

  15. Hyperferritinemia at diagnosis predicts relapse and overall survival in younger AML patients with intermediate-risk cytogenetics.

    PubMed

    Lebon, Delphine; Vergez, François; Bertoli, Sarah; Harrivel, Véronique; De Botton, Stéphane; Micol, Jean-Baptiste; Marolleau, Jean-Pierre; Récher, Christian

    2015-08-01

    The prognostic value of ferritin level at diagnosis in AML patients is unknown. We studied 162 younger AML patients with intermediate-risk cytogenetics who received intensive chemotherapy. The median ferritin level at diagnosis was 633 μg/L and 128 (79%) patients had a ferritin level above the upper normal limit. Hyperferritinemia was significantly associated with a higher cumulative incidence of relapse as well as poorer disease-free and overall survival. In multivariate analysis, hyperferritinemia remained an independent poor prognosis factor. The level of ferritin at diagnosis has a major impact on relapse suggesting a link between inflammation, oxidative stress and chemoresistance in AML. PMID:26002512

  16. Developmental genes significantly afflicted by aberrant promoter methylation and somatic mutation predict overall survival of late-stage colorectal cancer

    PubMed Central

    An, Ning; Yang, Xue; Cheng, Shujun; Wang, Guiqi; Zhang, Kaitai

    2015-01-01

    Carcinogenesis is an exceedingly complicated process, which involves multi-level dysregulations, including genomics (majorly caused by somatic mutation and copy number variation), DNA methylomics, and transcriptomics. Therefore, only looking into one molecular level of cancer is not sufficient to uncover the intricate underlying mechanisms. With the abundant resources of public available data in the Cancer Genome Atlas (TCGA) database, an integrative strategy was conducted to systematically analyze the aberrant patterns of colorectal cancer on the basis of DNA copy number, promoter methylation, somatic mutation and gene expression. In this study, paired samples in each genomic level were retrieved to identify differentially expressed genes with corresponding genetic or epigenetic dysregulations. Notably, the result of gene ontology enrichment analysis indicated that the differentially expressed genes with corresponding aberrant promoter methylation or somatic mutation were both functionally concentrated upon developmental process, suggesting the intimate association between development and carcinogenesis. Thus, by means of random walk with restart, 37 significant development-related genes were retrieved from a priori-knowledge based biological network. In five independent microarray datasets, Kaplan–Meier survival and Cox regression analyses both confirmed that the expression of these genes was significantly associated with overall survival of Stage III/IV colorectal cancer patients. PMID:26691761

  17. Downregulation of RPL15 may predict poor survival and associate with tumor progression in pancreatic ductal adenocarcinoma

    PubMed Central

    Liu, De-Jun; Hua, Rong; Ren, Lin-Lin; Li, Cheng-Tao; Sun, Yong-Wei; Chen, Hao-Yan; Fang, Jing-Yuan; Hong, Jie

    2015-01-01

    Early diagnosis and treatment in pancreatic ductal adenocarcinoma (PDAC) is still a challenge worldwide. The poor survival of PDAC patients mainly due to early metastasis when first diagnosed and lack of prognostic biomarker. Ribosomal protein L15 (RPL15), an RNA-binding protein, is a component of ribosomal 60S subunit. It was reported that RPL15 is dysregulated in various type of cancers. However, little is known about the role of RPL15 in PDAC carcinogenesis and progression. Herein, we clarified RPL15 expression status may serve as an independent prognostic biomarker in three independent PDAC patient cohorts. We found that RPL15 was dramatically decreased in PDAC tissues and cell lines. The high expression of RPL15 was inversely correlated with TNM stage, histological differentiation, T classification and vascular invasion. Low expression of RPL15 was significantly associated with poor overall survival of PDAC patients. Furthermore, we demonstrated that the reduction of RPL15 may promote invasion ability of pancreatic cell by inducing EMT process. In conclusion, decreased RPL15 expression is associated with invasiveness of PDAC cells, and RPL15 expression status may serve as a reliable prognostic biomarker in PDAC patients. PMID:26498693

  18. Protein Kinase CK2 Expression Predicts Relapse Survival in ERα Dependent Breast Cancer, and Modulates ERα Expression in Vitro

    PubMed Central

    Williams, Marlon D.; Nguyen, Thu; Carriere, Patrick P.; Tilghman, Syreeta L.; Williams, Christopher

    2015-01-01

    The heterotetrameric protein kinase CK2 has been associated with oncogenic transformation, and our previous studies have shown that it may affect estrogenic signaling. Here, we investigate the role of the protein kinase CK2 in regulating ERα (estrogen receptor α) signaling in breast cancer. We determined the correlation of CK2α expression with relapse free breast cancer patient survival utilizing Kaplan Meier Plotter (kmplot.com/analysis/) to mine breast cancer microarrays repositories. Patients were stratified according to ERα status, histological grade, and hormonal therapy. Luciferase reporter assays and flow cytometry were implemented to determine the impact of CK2 inhibition on ERE-mediated gene expression and expression of ERα protein. CK2α expression is associated with shorter relapse free survival among ERα (+) patients with grade 1 or 2 tumors, as well as among those patients receiving hormonal therapy. Biochemical inhibition of CK2 activity results in increased ER-transactivation as well as increased expression among ERα (+) and ERα (−) breast cancer cell lines. These findings suggest that CK2 may contribute to estrogen-independent cell proliferation and breast tumor progression, and may potentially serve as a biomarker and pharmacological target in breast cancer. PMID:26703694

  19. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission.

    PubMed

    Cowan, Andrew J; Stevenson, Philip A; Cassaday, Ryan D; Graf, Solomon A; Fromm, Jonathan R; Wu, David; Holmberg, Leona A; Till, Brian G; Chauncey, Thomas R; Smith, Stephen D; Philip, Mary; Orozco, Johnnie J; Shustov, Andrei R; Green, Damian J; Libby, Edward N; Bensinger, William I; Shadman, Mazyar; Maloney, David G; Press, Oliver W; Gopal, Ajay K

    2016-02-01

    Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 2.38 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR. PMID:26348890

  20. Co-Expression of Bmi-1 and Podoplanin Predicts Overall Survival in Patients With Squamous Cell Carcinoma of the Head and Neck Treated With Radio(chemo)therapy

    SciTech Connect

    Vormittag, Laurenz; Thurnher, Dietmar; Geleff, Silvana; Pammer, Johannes; Heiduschka, Gregor; Brunner, Markus; Grasl, Matthaeus Ch.; Erovic, Boban M.

    2009-03-01

    Purpose: This study was conducted to determine the expression of Bmi-1 and podoplanin in healthy oral mucosa and in untreated tumor tissues samples of patients with squamous cell carcinomas of the head and neck. All patients were treated by primary radio(chemo)therapy. Methods and Materials: The expression of Bmi-1 and podoplanin was immunohistochemically evaluated in 12 normal oral mucosa and 63 tumor specimens and correlated with patients' clinical data. Results: In healthy mucosa expression of Bmi-1 and podoplanin was restricted to the basal cell layer. Expression of both proteins was found in 79% and 86% of our tumor samples, respectively. In 17 and 8 samples, Bmi-1 and podoplanin were co-expressed at the invasive border or diffuse in the bulk of the tumor, respectively. Univariate analysis showed that the co-expression of Bmi-1 and podoplanin correlated to decreased overall survival (p = 0.044). Moreover, multivariate testing identified high expression of podoplanin (p = 0.044), co-expression of Bmi-1 and podoplanin (p = 0.007) and lack of response to therapy (p < 0.0001) as predictors of shortened overall survival in patients treated with primary radio(chemo)therapy. Conclusions: Bmi-1 and podoplanin are expressed at the invasive front of squamous cell carcinomas of the head and neck. Co-expression of Bmi-1 and podoplanin predicts significantly overall survival of patients treated with primary radio(chemo)therapy.

  1. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    SciTech Connect

    Jabbour, Salma K.; Kim, Sinae; Haider, Syed A.; Xu, Xiaoting; Wu, Alson; Surakanti, Sujani; Aisner, Joseph; Langenfeld, John; Yue, Ning J.; Haffty, Bruce G.; Zou, Wei

    2015-07-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

  2. MET Gene Copy Number Predicts Worse Overall Survival in Patients with Non-Small Cell Lung Cancer (NSCLC); A Systematic Review and Meta-Analysis

    PubMed Central

    Dimou, Anastasios; Non, Lemuel; Chae, Young Kwang; Tester, William J.; Syrigos, Konstantinos N.

    2014-01-01

    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. PMID:25232729

  3. Treatment of Metastatic Breast Cancer in a Real-World Scenario: Is Progression-Free Survival With First Line Predictive of Benefit From Second and Later Lines?

    PubMed Central

    Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Minisini, Alessandro Marco; Rihawi, Karim; Fasola, Gianpiero

    2015-01-01

    Introduction. Despite the availability of several therapeutic options for metastatic breast cancer (MBC), no robust predictive factors are available to help clinical decision making. Nevertheless, a decreasing benefit from first line to subsequent lines of treatment is commonly observed. The aim of this study was to assess the impact of benefit from first-line therapy on outcome with subsequent lines. Methods. We analyzed a consecutive series of 472 MBC patients treated with chemotherapy (CT) and/or endocrine therapy (ET) between 2004 and 2012. We evaluated progression-free survival (PFS) at first (PFS1), second, third, and fourth therapeutic lines, according to treatment (ET and/or CT) and tumor subtypes. Results. In the whole cohort, median overall survival was 34 months, and median PFS1 was 9 months. A 6-month benefit was shown by 289 patients (63.5%) at first line, 128 (40.5%) at second line, 76 (33.8%) at third line, and 34 (23.3%) at fourth line. Not having a 6-month benefit at PFS1 was associated with less chance of benefit at second line (odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.29–0.77, p = .0026) and at any line beyond first (OR: 0.39; 95% CI: 0.24–0.62, p < .0001). In the total series, after stratification for tumor subtypes, a strong predictive effect was observed among HER2-positive tumors (OR: 0.2; 95% CI: 0.05–0.73, p = .0152). Conclusion. Our results suggest that the absence of at least a 6-month benefit in terms of PFS with first-line therapy predicts a reduced probability of benefit from subsequent therapeutic lines, especially in HER2-positive disease. Implications for Practice: This study supports evidence showing that the absence of a 6-month benefit in terms of progression-free survival with first-line therapy predicts a lack of benefit from subsequent therapeutic lines in metastatic breast cancer. The random distribution of benefit experienced by a subset of the cohort further spurs an interest in identifying predictive

  4. The predicting value of postoperative body temperature on long-term survival in patients with rectal cancer.

    PubMed

    Yu, Huichuan; Luo, Yanxin; Peng, Hui; Kang, Liang; Huang, Meijin; Luo, Shuangling; Chen, Wenhao; Yang, Zihuan; Wang, Jianping

    2015-09-01

    This study aimed to assess the association between postoperative body temperature and prognosis in patients with rectal cancer. Five hundred and seven patients with stage I to III rectal cancers were enrolled in the current study. Basal body temperature (BBT, measured at 6 am) and maximal body temperature (MBT) on each day after surgery were analyzed retrospectively. Patients were divided into two equal groups according to the median of BBT and MBT at each day. The primary end points were disease-free survival (DFS) and overall survival (OS). The univariate and multivariate analyses showed that patients with low D0-MBT (<37.4 °C) had lower 3-year DFS [adjusted hazard ratio (HR) 1.56 (95 % CI 1.08-2.24, P = 0.017)] as well as OS [adjusted HR 1.72 (95 % CI 1.05-2.82, P = 0.032)] rate as compared to those with high D0-MBT (>37.4 °C). In the subset of 318 patients with T3 stage tumor and the subgroup of 458 patients without blood transfusion as well, low D0-MBT continues to be an independent predictor of DFS/OS with an adjusted HR equal to 1.48 (95 % CI 1.02-2.24, P = 0.046)/1.68 (95 % CI 1.04-2.99, P = 0.048) and 1.45 (95 % CI 1.02-2.13, P = 0.048)/1.59 (95 % CI 1.01-2.74, P = 0.049), respectively. In addition, we found that patients have higher risk of 1-year recurrence if those were exhibiting low preoperative BBT (<36.6 °C) (17 vs. 10 %, P = 0.034). Low body temperature (D0-MBT < 37.4 °C) after surgery was an independent predictor of poor survival outcomes in patients with rectal cancer. PMID:25976505

  5. IGHV gene mutational status and 17p deletion are independent molecular predictors in a comprehensive clinical-biological prognostic model for overall survival prediction in chronic lymphocytic leukemia

    PubMed Central

    2012-01-01

    Background Prognostic index for survival estimation by clinical-demographic variables were previously proposed in chronic lymphocytic leukemia (CLL) patients. Our objective was to test in a large retrospective cohort of CLL patients the prognostic power of biological and clinical-demographic variable in a comprehensive multivariate model. A new prognostic index was proposed. Methods Overall survival and time to treatment in 620 untreated CLL patients were analyzed retrospectively to evaluate the multivariate independence and predictive power of mutational status of immunoglobulin heavy chain variable gene segments (IGHV), high-risk chromosomal aberration such as 17p or 11q deletions, CD38 and ZAP-70 expression, age, gender, Binet stage, β2-microglobulin levels, absolute lymphocyte count and number of lymph node regions. Results IGHV mutational status and 17p deletion were the sole biological variables with independent prognostic relevance in a multivariate model for overall survival, which included easily measurable clinical parameters (Binet staging, β2-microglobulin levels) and demographics (age and gender). Analysis of time to treatment in Binet A patients below 70 years of age showed that IGHV was the most important predictor. A novel 6-variable clinical-biological prognostic index was developed and internally validated, which assigned 3 points for Binet C stage, 2 points/each for Binet B stage and for age > 65 years, 1 point/each for male gender, high β2-microglobulin levels, presence of an unmutated IGHV gene status or 17p deletion. Patients were classified at low-risk (score = 0-1; 21%), intermediate-risk (score 2-5; 63% of cases), high-risk (score 6-9; 16% of cases). Projected 5-year overall survival was 98%, 90% and 58% in low-, intermediate- and high-risk groups, respectively. A nomogram for individual patient survival estimation was also proposed. Conclusions Data indicate that IGHV mutational status and 17p deletion may be integrated with clinical

  6. Increased Proportion of Variance Explained and Prediction Accuracy of Survival of Breast Cancer Patients with Use of Whole-Genome Multiomic Profiles.

    PubMed

    Vazquez, Ana I; Veturi, Yogasudha; Behring, Michael; Shrestha, Sadeep; Kirst, Matias; Resende, Marcio F R; de Los Campos, Gustavo

    2016-07-01

    Whole-genome multiomic profiles hold valuable information for the analysis and prediction of disease risk and progression. However, integrating high-dimensional multilayer omic data into risk-assessment models is statistically and computationally challenging. We describe a statistical framework, the Bayesian generalized additive model ((BGAM), and present software for integrating multilayer high-dimensional inputs into risk-assessment models. We used BGAM and data from The Cancer Genome Atlas for the analysis and prediction of survival after diagnosis of breast cancer. We developed a sequence of studies to (1) compare predictions based on single omics with those based on clinical covariates commonly used for the assessment of breast cancer patients (COV), (2) evaluate the benefits of combining COV and omics, (3) compare models based on (a) COV and gene expression profiles from oncogenes with (b) COV and whole-genome gene expression (WGGE) profiles, and (4) evaluate the impacts of combining multiple omics and their interactions. We report that (1) WGGE profiles and whole-genome methylation (METH) profiles offer more predictive power than any of the COV commonly used in clinical practice (e.g., subtype and stage), (2) adding WGGE or METH profiles to COV increases prediction accuracy, (3) the predictive power of WGGE profiles is considerably higher than that based on expression from large-effect oncogenes, and (4) the gain in prediction accuracy when combining multiple omics is consistent. Our results show the feasibility of omic integration and highlight the importance of WGGE and METH profiles in breast cancer, achieving gains of up to 7 points area under the curve (AUC) over the COV in some cases. PMID:27129736

  7. Increased Proportion of Variance Explained and Prediction Accuracy of Survival of Breast Cancer Patients with Use of Whole-Genome Multiomic Profiles

    PubMed Central

    Vazquez, Ana I.; Veturi, Yogasudha; Behring, Michael; Shrestha, Sadeep; Kirst, Matias; Resende, Marcio F. R.; de los Campos, Gustavo

    2016-01-01

    Whole-genome multiomic profiles hold valuable information for the analysis and prediction of disease risk and progression. However, integrating high-dimensional multilayer omic data into risk-assessment models is statistically and computationally challenging. We describe a statistical framework, the Bayesian generalized additive model ((BGAM), and present software for integrating multilayer high-dimensional inputs into risk-assessment models. We used BGAM and data from The Cancer Genome Atlas for the analysis and prediction of survival after diagnosis of breast cancer. We developed a sequence of studies to (1) compare predictions based on single omics with those based on clinical covariates commonly used for the assessment of breast cancer patients (COV), (2) evaluate the benefits of combining COV and omics, (3) compare models based on (a) COV and gene expression profiles from oncogenes with (b) COV and whole-genome gene expression (WGGE) profiles, and (4) evaluate the impacts of combining multiple omics and their interactions. We report that (1) WGGE profiles and whole-genome methylation (METH) profiles offer more predictive power than any of the COV commonly used in clinical practice (e.g., subtype and stage), (2) adding WGGE or METH profiles to COV increases prediction accuracy, (3) the predictive power of WGGE profiles is considerably higher than that based on expression from large-effect oncogenes, and (4) the gain in prediction accuracy when combining multiple omics is consistent. Our results show the feasibility of omic integration and highlight the importance of WGGE and METH profiles in breast cancer, achieving gains of up to 7 points area under the curve (AUC) over the COV in some cases. PMID:27129736

  8. Interferon-γ Production by Peripheral Lymphocytes Predicts Survival of Tumor-Bearing Mice Receiving Dual PD-1/CTLA-4 Blockade.

    PubMed

    McNamara, Michael J; Hilgart-Martiszus, Ian; Barragan Echenique, Diego M; Linch, Stefanie N; Kasiewicz, Melissa J; Redmond, William L

    2016-08-01

    Immune checkpoint inhibitors are transforming the way cancer is treated. However, these therapies do not benefit all patients and frequently cause significant immune-related adverse events. Biomarkers that identify patients with a favorable early response to therapy are essential for guiding treatment decisions and improving patient outcomes. In this report of our study, we present evidence that shortly after administration of dual PD-1/CTLA-4 blockade, the proinflammatory capacity of peripheral lymphocytes is predictive of tumor progression and survival outcomes in multiple murine models. Specifically, we observed that the quantity of interferon-γ (IFNγ) produced by peripheral lymphocytes in response to CD3/CD28 stimulation was robustly correlated with subsequent survival outcomes. In the tumor models and early time points assessed in this study, this relationship was considerably more predictive than a host of other potential biomarkers, several of which have been previously reported. Overall, these findings suggest that measuring the capacity of peripheral lymphocytes to produce IFNγ may help identify which patients are benefitting from combination anti-PD-1/anti-CTLA-4 immunotherapy. Cancer Immunol Res; 4(8); 650-7. ©2016 AACR. PMID:27262113

  9. Prediction of the ability to purge clonogenic B cell lymphoma from normal BM in vitro by heat: their survival curves correspond to a curve reflecting mortality in humans.

    PubMed

    Moriyama, Y; Goto, T; Hashimoto, S; Nikkuni, K; Saito, H; Kishi, K; Takahashi, M; Shibata, A; Endo, K

    1993-06-01

    To develop new purging regimens for ABMT the ability to predict potential for purging of tumor cells from BM is important. Since the sensitivity of human B cell lymphoma to hyperthermia is not known, we examined its effect on the growth of B cell lymphoma cell lines (Raji and Daudi) in vitro to evaluate potential for purging clonogenic tumor cells from normal marrow by heat, using a limiting dilution assay to measure log depletion of tumor cells in a 20-fold excess of normal BM. When exposed to heat (42-43 degrees C) for 120 min, both clonogenic Raji and Daudi cells were dramatically reduced (a 4-to-6 log reduction) with time, whereas at 42 degrees C over half and at 43 degrees C 10% of normal granulocyte-macrophage progenitor cells survived for the same time period. This high level of lymphoma cell depletion by heat correlated with that of immunologic and pharmacologic studies. In addition, these survival curves during heating were found to correlate with the Gompertz-Makeham formula--a law of human mortality. This formula may be useful in predicting the purging effect of heat. These results suggest that in vitro hyperthermia could be applied effectively for the elimination of residual, clonogenic lymphoma cells in autologous marrow grafts before ABMT. PMID:8334423

  10. The prognostic significance of β-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: β-catenin predicts overall survival.

    PubMed

    Schneider, Sven; Thurnher, Dietmar; Seemann, Rudolf; Brunner, Markus; Kadletz, Lorenz; Ghanim, Bahil; Aumayr, Klaus; Heiduschka, Gregor; Lill, Claudia

    2016-05-01

    Minor salivary gland carcinoma is a rare and heterogeneous type of cancer. Molecular prognostic and predictive markers are sparse. The aim of this study was to identify new prognostic and predictive markers in minor salivary gland carcinoma. 50 tissue samples of carcinomas of the minor salivary glands (adenoid cystic carcinoma n = 23, mucoepidermoid carcinoma n = 12, adenocarcinoma n = 10, carcinoma ex pleomorphic adenoma n = 2, salivary duct carcinoma n = 1, clear cell carcinoma n = 1, basal cell carcinoma n = 1) were immunohistochemically stained for β-catenin, cyclin D1 and PIN1. Expression patterns were analyzed and correlated to clinical outcome of 37 patients with complete clinical data. High expression of membranous β-catenin was linked to significantly better overall survival in patients with adenoid cystic carcinoma (log rank test, χ (2) = 13.3, p = .00397, Bonferroni corrected p = .024). PIN1 and cyclin D1 did not show any significant correlation to patients' clinical outcome. Expression of β-catenin in adenoid cystic carcinoma of the minor salivary glands significantly correlates with better overall survival. Hence, evaluation of β-catenin might serve as a clinical prognostic marker. PMID:25801951

  11. The Diastolic Pulmonary Gradient (DPG) does not Predict Survival in Patients with Pulmonary Hypertension due to Left Heart Disease (PH-LHD)

    PubMed Central

    Tampakakis, Emmanouil; Leary, Peter J; Selby, Van N; De Marco, Teresa A; Cappola, Thomas P; Felker, Michael G; Russell, Stuart D.; Kasper, Edward K.; Tedford, Ryan J

    2014-01-01

    Objectives To evaluate if diastolic pulmonary gradient (DPG) can predict survival in patients with pulmonary hypertension due to left heart disease (PH-LHD). Background Patients with combined post- and pre-capillary PH-LHD have worse prognosis than those with passive pulmonary hypertension. The transpulmonary gradient (TPG) and pulmonary vascular resistance (PVR) have commonly been used to identify high-risk patients. However, these parameters have significant shortcomings and do not always correlate with pulmonary vasculature remodeling. Recently, it has been suggested that DPG may be better marker, yet its prognostic ability in patients with cardiomyopathy has not been fully assessed. Methods A retrospective cohort of 1236 patients evaluated for unexplained cardiomyopathy at Johns Hopkins Hospital was studied. All patients underwent right heart catheterization and were followed until death, cardiac transplantation or the end of the study period (mean time 4.4 years). The relationships between DPG, TPG or PVR and survival in subjects with PH-LHD (n=469) were evaluated with Cox Proportional Hazards Regression and Kaplan Meier analyses. Results DPG was not significantly associated with mortality (HR 1.02; p=0.10) in PH-LHD whereas elevated TPG and PVR predicted death (HR 1.02, p=0.046 and HR 1.11, p=0.002, respectively). Similarly, DPG did not differentiate survivors from non-survivors at any selected cutpoints including a DPG of 7mmHg. Conclusions In this retrospective study of patients with cardiomyopathy and PH-LHD, an elevated DPG was not associated with worse survival. PMID:25453535

  12. Progression-free and overall survival in metastatic castration-resistant prostate cancer treated with abiraterone acetate can be predicted with serial C11-acetate PET/CT

    PubMed Central

    Farnebo, Jacob; Wadelius, Agnes; Sandström, Per; Nilsson, Sten; Jacobsson, Hans; Blomqvist, Lennart; Ullén, Anders

    2016-01-01

    Abstract In this retrospective study, we evaluated the benefit of repeated carbon 11 (C11)-acetate positron emission tomography/computed tomography (PET/CT) to assess response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). A total of 30 patients with mCRPC were monitored with C11-acetate PET/CT and PSA levels during their treatment with AA. Retrospective evaluation of their response was made after 102 days (median; range 70–155) of treatment. Statistical analyses were employed to detect predictors of progression-free survival (PFS) and overall survival (OS), and potential correlation between serum levels of PSA, standardized uptake values (SUVpeak), and bone lesion index measured from PET were investigated. At follow-up 10 patients exhibited partial response (PR), 10 progressive disease (PD), and 10 stable disease (SD), as assessed by PET/CT. In survival analysis, both PR and PD were significantly associated with PFS and OS. CT response was also associated with OS, but only 19/30 patients demonstrated a lesion meeting target lesion criteria according to RECIST 1.1. No PET/CT baseline characteristic was significantly associated with PFS or OS. A PSA response (reduction in the level by >50%) could also predict PFS and OS. In the subgroup lacking a PSA response, those with PD had significantly shorter OS than those with PR or SD. PFS and OS in patients with mCRPC treated with AA can be predicted from repeated C11-acetate PET/CT. This may be of particular clinical value in patients who do not exhibit a PSA response to treatment. PMID:27495034

  13. Hypertrophy of the Inferior Olivary Nucleus Impacts Perception of Gravity

    PubMed Central

    Tarnutzer, Alexander A.; Palla, Antonella; Marti, Sarah; Schuknecht, Bernhard; Straumann, Dominik

    2012-01-01

    Interruption of the dentato-olivary projections, interconnecting the dentate nucleus (DN) and the contralateral inferior olivary nucleus (ION), is predicted to interfere with the DN’ role in estimating direction of gravity. In a patient with pendular nystagmus due to hypertrophy of the ION secondary to predominantly right-sided ponto-mesencephalic hemorrhage, perceived vertical shifted from clockwise to counter-clockwise deviations within 4 months. We hypothesize that synchronized oscillations of ION neurons induce a loss of inhibitory control, leading to hyperactivity of the contralateral DN and, as a result, to perceived vertical roll–tilt to the side of the over-active DN. PMID:22593754

  14. Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival

    PubMed Central

    Facchini, Gaetano; Caffo, Orazio; Ortega, Cinzia; D'Aniello, Carmine; Di Napoli, Marilena; Cecere, Sabrina C.; Della Pepa, Chiara; Crispo, Anna; Maines, Francesca; Ruatta, Fiorella; Iovane, Gelsomina; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Pignata, Sandro; Cavaliere, Carla

    2016-01-01

    Background: Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. Patients and Methods: We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. Results: We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6–6.5) and the median OS was 17.1 months (8.8–25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12–0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06–0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. Conclusion: A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS. PMID:27242530

  15. Myofibroblastic cell activation and neovascularization predict native liver survival and development of esophageal varices in biliary atresia

    PubMed Central

    Suominen, Janne S; Lampela, Hanna; Heikkilä, Päivi; Lohi, Jouko; Jalanko, Hannu; Pakarinen, Mikko P

    2014-01-01

    AIM: To study the relation between collagen 1, α-smooth muscle actin (α-SMA) and CD34 expression and the most essential portoenterostomy (PE) outcomes. METHODS: Liver specimens were obtained at PE from 33 biliary atresia (BA) patients for immunohistochemical analysis of collagen 1, α-SMA and CD34. Liver biopsies from 35 organ donors were used as controls. Expression patterns were related to clinical data including age at PE, serum total and conjugated bilirubin concentration at the time of PE and during follow-up, incidence of esophageal varices in follow-up upper gastrointestinal endoscopies, and native liver survival as well as to detailed histopathological findings. RESULTS: Collagen 1 (16.4% vs 4.5%, P < 0.0001), α-SMA (17.9% vs 4.6%, P < 0.0001) and CD34 (4.9% vs 3.8%, P = 0.017) were markedly overexpressed in BA patients compared with controls. Patients who underwent liver transplantation by age of two years had significantly higher expression of collagen 1 (18.6% vs 13.7%, P = 0.024), α-SMA (20.4% vs 15.4%, P = 0.009) and CD34 (5.9% vs 4.0%, P = 0.029) at PE compared with native liver survivors. CD34-positive microvessels were identified in the centrizonal region close to central vein in every BA patient. In majority of BA cases (56%) neovascularization was frequent as CD34-positive microvessels were observed in over half of the hepatic lobules. In controls, the CD34-positive microvessels were rare as they were completely absent in 40 % and were found in less than 5 % of the hepatic lobules in the rest. The difference between BA patients and controls was significant (P < 0.0001). Patients who developed esophageal varices by two years had significantly higher expression of CD34 at PE compared with patients without varices (5.6% vs 4.0%, P = 0.019). Expression of α-SMA (r = 0.758, P < 0.0001) and collagen 1 (r = 0.474, P = 0.016), and the amount of CD34-positive microvessels (r = 0.356, P = 0.047) were related to patient age at PE. CONCLUSION: Hepatic

  16. [Ventricular Septal Perforation after Inferior Myocardial Infarction].

    PubMed

    Sato, Hisashi; Nakayama, Yoshihiro; Tanaka, Hideya; Takahashi, Baku

    2016-07-01

    We report a rare case of ventricular septal perforation (VSP) after inferior myocardial infarction. Surgical repair of VSP after inferior infarction is technically difficult because of its anatomical location. An 81-year-old female presented with dyspnea on the 8th day after percutaneous coronary intervention for acute inferior myocardial infarction. Echocardiography revealed a ventricular septal perforation. Urgent operation was performed. There was a VSP around the base of the ventricular septum. The myocardial infarction extended to the adjacent muscle of the mitral valve annulus. Two bovine pericardial patches were used in the left ventricular cavity. The patches were sewn on the mitral valve annulus which was the only normal tissue in the region. The 1st patch was used to close the VSP directly, and the 2nd patch was sutured to the normal myocardium to exclude the infracted area. No residual shunt flow was observed. The postoperative course was uneventful. PMID:27365060

  17. Lateralization Technique and Inferior Alveolar Nerve Transposition

    PubMed Central

    Sanches, Marco Antonio; Ramalho, Gabriel Cardoso; Manzi, Marcello Roberto

    2016-01-01

    Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics. PMID:27433360

  18. [Inferior alveolar nerve repositioning in implant surgery].

    PubMed

    Ardekian, L; Salnea, J; Abu el-Naaj, I; Gutmacher, T; Peled, M

    2001-04-01

    Severe resorption of the posterior mandible possesses one of the most difficult restorative challenges to the implant surgery today. This resorption may prevent the placement of dental implants without the potentially damage to the inferior alveolar nerve. To create the opportunity of insertion dental implants of adequately length in those cases, the technique of nerve repositioning has been advocated. The purpose of this article is to describe two cases of nerve repositioning combined with placement of dental implants. Both cases showed appropriate postoperative healing without damage to the inferior alveolar nerve. The inferior alveolar nerve repositioning technique seems to be an acceptable alternative to augmentation procedure prior to dental implants placement in cases exhibiting atrophic posterior mandibular ridges. PMID:11494807

  19. Predicting risk of entry into foster care from early childhood experiences: A survival analysis using LONGSCAN data

    PubMed Central

    Thompson, Richard; White, Catherine Roller

    2015-01-01

    This study examined whether a multi-domain model of maltreatment informed by an ecological framework—including factors related to the child, caregiver, family, neighborhood, and dimensions of maltreatment experience—predicted entry into foster care between the ages of 4 and 18 among children with no prior foster care experience. To determine which factors predict entry into foster care, secondary data analyses were conducted utilizing a sub-sample from LONGSCAN (Longitudinal Studies of Child Abuse and Neglect) of 942 children and their primary caregivers. Results demonstrate that there are important predictors for entry into out-of-home placement across multiple ecological domains. Characteristics related to child, caregiver, and family characteristics, and neighborhood context, as well as dimensions of maltreatment (particularly emotional maltreatment), predicted risk of placement in out-of-home care. Implications for child welfare practice are discussed. This examination of the effects of multiple ecological domains adds to our understanding of children’s risk of removal and entry into out-of-home placement. PMID:25982428

  20. Predicting risk of entry into foster care from early childhood experiences: A survival analysis using LONGSCAN data.

    PubMed

    English, Diana J; Thompson, Richard; White, Catherine Roller

    2015-07-01

    This study examined whether a multi-domain model of maltreatment informed by an ecological framework-including factors related to the child, caregiver, family, neighborhood, and dimensions of maltreatment experience-predicted entry into foster care between the ages of 4 and 18 among children with no prior foster care experience. To determine which factors predict entry into foster care, secondary data analyses were conducted utilizing a sub-sample from LONGSCAN (Longitudinal Studies of Child Abuse and Neglect) of 942 children and their primary caregivers. Results demonstrate that there are important predictors for entry into out-of-home placement across multiple ecological domains. Characteristics related to child, caregiver, and family characteristics, and neighborhood context, as well as dimensions of maltreatment (particularly emotional maltreatment), predicted risk of placement in out-of-home care. Implications for child welfare practice are discussed. This examination of the effects of multiple ecological domains adds to our understanding of children's risk of removal and entry into out-of-home placement. PMID:25982428

  1. Unilateral Breast Reconstruction Using Bilateral Inferior Gluteal Artery Perforator Flaps

    PubMed Central

    Muto, Mayu; Ogawa, Marina; Shibuya, Mai; Yasumura, Kazunori; Kobayashi, Shinji; Ishikawa, Takashi; Maegawa, Jiro

    2015-01-01

    Background: For reconstructing moderate-to-high projection breasts in nulliparous patients with insufficient abdominal tissue or prior abdominal surgeries, a unilateral inferior gluteal artery perforator (IGAP) flap is an alternative procedure. In patients with slim hips, however, unilateral gluteal tissue is insufficient and inferior gluteal crease displacement may develop postoperatively. Donor-site asymmetry is also a major disadvantage. In these circumstances, bilateral IGAP flaps provide sufficient tissue without significant gluteal deformity. Methods: We retrospectively reviewed 20 patients who underwent unilateral breast reconstruction using bilateral IGAP flaps by a single surgeon between November 2007 and December 2012. A quantitative outcome assessment was performed and compared with that of 22 unilateral IGAP flap patients operated on by the same surgeon. Results: Twenty patients underwent reconstruction with 40 IGAP flaps. Of the 40 flaps, 39 survived and 1 developed total necrosis due to repeated venous thrombosis. In 15 of 20 patients, the size of reconstructed breast was comparable to that of the contralateral breast. Final inset flap weight was 462.3 g for bilateral flaps and 244.3 g for unilateral flaps. Total operating time was 671.1 minutes (bilateral flaps) and 486.8 minutes (unilateral flaps). Conclusions: Use of bilateral IGAP flaps for breast reconstruction helps to avoid asymmetry of the inferior buttock volume and shape. Bilateral flaps provide sufficient tissue volume and allow for reconstruction of a breast comparable to the unaffected side. In patients with moderate-to-high projection breast whose abdominal tissue cannot be used for reconstruction, IGAP flaps may be a suitable alternative. PMID:25878925

  2. Tensile properties of the inferior glenohumeral ligament.

    PubMed

    Bigliani, L U; Pollock, R G; Soslowsky, L J; Flatow, E L; Pawluk, R J; Mow, V C

    1992-03-01

    The tensile properties of the inferior glenohumeral ligament have been determined in 16 freshly frozen cadaver shoulders. The inferior glenohumeral ligament was divided into three anatomical regions: a superior band, an anterior axillary pouch, and a posterior axillary pouch. This yielded 48 bone-ligament-bone specimens, which were tested to failure in uniaxial tension. The superior band was consistently the thickest region, averaging 2.79 mm. The thickness of the inferior glenohumeral ligament decreased from antero-superiorly to postero-inferiorly. The resting length of all three anatomical regions was not statistically different. Total specimen strain to failure for all bone-ligament-bone specimens averaged 27%. Variations occurred between the three regions, with the anterior pouch specimens failing at a higher strain (34%) than those from the superior band (24%) or the posterior pouch (23%). Strain to failure for the ligament midsubstance (11%) was found to be significantly less than that for the entire specimen (27%). Thus, larger strain must occur near the insertion sites of the inferior glenohumeral ligament. Stress at failure was found to be nearly identical for the three regions of the ligament, averaging 5.5 MPa. These values are lower than those reported for other soft tissues, such as the anterior cruciate ligament and patellar tendon. The anterior pouch was found to be less stiff than the other two regions, perhaps suggesting that it is composed of more highly crimped collagen fibers. Three failure sites were seen for the inferior glenohumeral ligament: the glenoid insertion (40%), the ligament substance (35%), and the humeral insertion (25%). In addition, significant capsular stretching occurred before failure, regardless of the failure mode. PMID:1740736

  3. Anatomy of Inferior Mesenteric Artery in Fetuses

    PubMed Central

    Nuzhat, Ayesha

    2016-01-01

    Aim. To analyze Inferior Mesenteric Artery in fetuses through its site of origin, length, diameter, and variation of its branches. Method. 100 fetuses were collected from various hospitals in Warangal at Kakatiya Medical College in Andhra Pradesh, India, and were divided into two groups, group I (second-trimester fetuses) and group II (third-trimester fetuses), followed by dissection. Result. (1) Site of Origin. In group I fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra in 33 out of 34 fetuses (97.2%). In one fetus it was at first lumbar vertebra, 2.8%. In all group II fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra. (2) Length. In group I fetuses it ranged between 18 and 30 mm, average being 24 mm except in one fetus where it was 48 mm. In group II fetuses the length ranged from 30 to 34 mm, average being 32 mm. (3) Diameter. In group I fetuses it ranged from 0.5 to 1 mm, and in group II fetuses it ranged from 1 to 2 mm, average being 1.5 mm. (4) Branches. Out of 34 fetuses of group I, 4 fetuses showed variation. In one fetus left colic artery was arising from abdominal aorta, 2.9%. In 3 fetuses, Inferior Mesenteric Artery was giving a branch to left kidney, 8.8%. Out of 66 fetuses in group II, 64 had normal branching. In one fetus left renal artery was arising from Inferior Mesenteric Artery, 1.5%, and in another fetus one accessory renal artery was arising from Inferior Mesenteric Artery and entering the lower pole of left kidney. Conclusion. Formation, course, and branching pattern of an artery depend on development and origin of organs to attain the actual adult position. PMID:27313956

  4. Anatomy of Inferior Mesenteric Artery in Fetuses.

    PubMed

    Nuzhat, Ayesha

    2016-01-01

    Aim. To analyze Inferior Mesenteric Artery in fetuses through its site of origin, length, diameter, and variation of its branches. Method. 100 fetuses were collected from various hospitals in Warangal at Kakatiya Medical College in Andhra Pradesh, India, and were divided into two groups, group I (second-trimester fetuses) and group II (third-trimester fetuses), followed by dissection. Result. (1) Site of Origin. In group I fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra in 33 out of 34 fetuses (97.2%). In one fetus it was at first lumbar vertebra, 2.8%. In all group II fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra. (2) Length. In group I fetuses it ranged between 18 and 30 mm, average being 24 mm except in one fetus where it was 48 mm. In group II fetuses the length ranged from 30 to 34 mm, average being 32 mm. (3) Diameter. In group I fetuses it ranged from 0.5 to 1 mm, and in group II fetuses it ranged from 1 to 2 mm, average being 1.5 mm. (4) Branches. Out of 34 fetuses of group I, 4 fetuses showed variation. In one fetus left colic artery was arising from abdominal aorta, 2.9%. In 3 fetuses, Inferior Mesenteric Artery was giving a branch to left kidney, 8.8%. Out of 66 fetuses in group II, 64 had normal branching. In one fetus left renal artery was arising from Inferior Mesenteric Artery, 1.5%, and in another fetus one accessory renal artery was arising from Inferior Mesenteric Artery and entering the lower pole of left kidney. Conclusion. Formation, course, and branching pattern of an artery depend on development and origin of organs to attain the actual adult position. PMID:27313956

  5. Signaling pathway models as biomarkers: Patient-specific simulations of JNK activity predict the survival of neuroblastoma patients.

    PubMed

    Fey, Dirk; Halasz, Melinda; Dreidax, Daniel; Kennedy, Sean P; Hastings, Jordan F; Rauch, Nora; Munoz, Amaya Garcia; Pilkington, Ruth; Fischer, Matthias; Westermann, Frank; Kolch, Walter; Kholodenko, Boris N; Croucher, David R

    2015-12-22

    Signaling pathways control cell fate decisions that ultimately determine the behavior of cancer cells. Therefore, the dynamics of pathway activity may contain prognostically relevant information different from that contained in the static nature of other types of biomarkers. To investigate this hypothesis, we characterized the network that regulated stress signaling by the c-Jun N-terminal kinase (JNK) pathway in neuroblastoma cells. We generated an experimentally calibrated and validated computational model of this network and used the model to extract prognostic information from neuroblastoma patient-specific simulations of JNK activation. Switch-like JNK activation mediates cell death by apoptosis. An inability to initiate switch-like JNK activation in the simulations was significantly associated with poor overall survival for patients with neuroblastoma with or without MYCN amplification, indicating that patient-specific simulations of JNK activation could stratify patients. Furthermore, our analysis demonstrated that extracting information about a signaling pathway to develop a prognostically useful model requires understanding of not only components and disease-associated changes in the abundance or activity of the components but also how those changes affect pathway dynamics. PMID:26696630

  6. 17β-Hydroxysteroid dehydrogenase type 10 predicts survival of patients with colorectal cancer and affects mitochondrial DNA content.

    PubMed

    Amberger, Albert; Deutschmann, Andrea J; Traunfellner, Pia; Moser, Patrizia; Feichtinger, René G; Kofler, Barbara; Zschocke, Johannes

    2016-04-28

    Mitochondrial energy production is reduced in tumor cells, and altered mitochondrial respiration contributes to tumor progression. Synthesis of proteins coded by mitochondrial DNA (mtDNA) requires the correct processing of long polycistronic precursor RNA molecules. Mitochondrial RNase P, composed of three different proteins (MRPP1, HSD10, and MRPP3), is necessary for correct RNA processing. Here we analyzed the role of RNase P proteins in colorectal cancer. High HSD10 expression was found in 28%; high MRPP1 expression in 40% of colorectal cancers, respectively. Expression of both proteins was not significantly associated with clinicopathological parameters. Survival analysis revealed that loss of HSD10 expression is associated with poor prognosis. Cox regression demonstrated that patients with high HSD10 tumors are at lower risk. High HSD10 expression was significantly associated with high mtDNA content in tumor tissue. A causal effect of HSD10 overexpression or knock down with increased or reduced mtDNA levels, respectively, was confirmed in tumor cell lines. Our data suggest that HSD10 plays a role in alterations of energy metabolism by regulating mtDNA content in colorectal carcinomas, and HSD10 protein analysis may be of prognostic value. PMID:26884257

  7. Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

    PubMed Central

    Armoundas, A; Rosenbaum, D; Ruskin, J; Garan, H; Cohen, R

    1998-01-01

    Objective—To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias.
Design—Analysis of new data from a previously published prospective investigation.
Setting—Electrophysiology laboratory of a major referral hospital.
Patients and interventions—43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0.
Main outcome measures—Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival.
Results—The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. 
Conclusions—T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk

  8. Value of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in prediction of the overall survival of esophageal cancer patients treated with chemoradiotherapy

    PubMed Central

    Li, Yimin; Lin, Qin; Luo, Zuoming; Zhao, Long; Zhu, Luchao; Sun, Long; Wu, Hua

    2015-01-01

    This study is to investigate the value of the metabolic parameters measured by sequential FDG PET/CT in predicting the overall survival of patients with esophageal squamous cell carcinoma (ESCC). A total of 160 patients who were newly diagnosed as ESCC patients and treated with chemoradiotherapy were included in this study. The FDG PET/CT was carried out prior to radiotherapy (PET1), when the cumulative dose of radiotherapy reached 50 Gy (PET2), at the end of radiotherapy (PET3) and 1 month after radiotherapy (PET4). The max of the standard uptake value (SUVmax) of the primary tumor, the metabolic tumor volume (MTV) and the total lesion glycolisis (TLG) prior to treatment were measured. The correlation of the measured parameters and the derived parameters of SUVmax with the overall survival was analyzed. The relatively reduced percentage of the SUVmax of PET3 and PET4 to the SUVmax of PET1 and PET2, had predictive value for the overall survival. The area under researcher operation curve (ROC) was between 0.62 and 0.73 (P < 0.01). The MTV and TLG prior to treatment might be used to predict the overall survival, and the area under ROC were both 0.69 (P < 0.001). Sequential FDG PET/CT scanning is useful to predict the overall survival of chemoradiotherapy for ESCC. The metabolic parameters and the derived parameters of FDG PET/CT have predictive values for overall survival. PMID:26379889

  9. Value of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in prediction of the overall survival of esophageal cancer patients treated with chemoradiotherapy.

    PubMed

    Li, Yimin; Lin, Qin; Luo, Zuoming; Zhao, Long; Zhu, Luchao; Sun, Long; Wu, Hua

    2015-01-01

    This study is to investigate the value of the metabolic parameters measured by sequential FDG PET/CT in predicting the overall survival of patients with esophageal squamous cell carcinoma (ESCC). A total of 160 patients who were newly diagnosed as ESCC patients and treated with chemoradiotherapy were included in this study. The FDG PET/CT was carried out prior to radiotherapy (PET1), when the cumulative dose of radiotherapy reached 50 Gy (PET2), at the end of radiotherapy (PET3) and 1 month after radiotherapy (PET4). The max of the standard uptake value (SUVmax) of the primary tumor, the metabolic tumor volume (MTV) and the total lesion glycolisis (TLG) prior to treatment were measured. The correlation of the measured parameters and the derived parameters of SUVmax with the overall survival was analyzed. The relatively reduced percentage of the SUVmax of PET3 and PET4 to the SUVmax of PET1 and PET2, had predictive value for the overall survival. The area under researcher operation curve (ROC) was between 0.62 and 0.73 (P < 0.01). The MTV and TLG prior to treatment might be used to predict the overall survival, and the area under ROC were both 0.69 (P < 0.001). Sequential FDG PET/CT scanning is useful to predict the overall survival of chemoradiotherapy for ESCC. The metabolic parameters and the derived parameters of FDG PET/CT have predictive values for overall survival. PMID:26379889

  10. Phosphatase PTP4A3 Promotes Triple-Negative Breast Cancer Growth and Predicts Poor Patient Survival.

    PubMed

    den Hollander, Petra; Rawls, Kathryn; Tsimelzon, Anna; Shepherd, Jonathan; Mazumdar, Abhijit; Hill, Jamal; Fuqua, Suzanne A W; Chang, Jenny C; Osborne, C Kent; Hilsenbeck, Susan G; Mills, Gordon B; Brown, Powel H

    2016-04-01

    Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and women diagnosed with TNBC currently lack targeted treatment options. To identify novel targets for TNBC, we evaluated phosphatase expression in breast tumors and characterized their contributions to in vitro and in vivo growth of TNBC. Using Affymetrix microarray analysis of 102 breast cancers, we identified 146 phosphatases that were significantly differentially expressed in TNBC compared with estrogen receptor (ER)-positive tumors. Of these, 19 phosphatases were upregulated (0.66-fold; FDR = 0.05) in TNBC compared with ER-positive breast cancers. We knocked down 17 overexpressed phosphatases in four triple-negative and four ER-positive breast cancer lines using specific siRNAs and found that depletion of six of these phosphatases significantly reduced growth and anchorage-independent growth of TNBC cells to a greater extent than ER-positive cell lines. Further analysis of the phosphatase PTP4A3 (also known as PRL-3) demonstrated its requirement for G1-S cell-cycle progression in all breast cancer cells, but PTP4A3 regulated apoptosis selectively in TNBC cells. In addition, PTP4A3 inhibition reduced the growth of TNBC tumors in vivo Moreover, in silico analysis revealed the PTP4A3 gene to be amplified in 29% of basal-like breast cancers, and high expression of PTP4A3 could serve as an independent prognostic indicator for worse overall survival. Collectively, these studies define the importance of phosphatase overexpression in TNBC and lay the foundation for the development of new targeted therapies directed against phosphatases or their respective signaling pathways for TNBC patients. Cancer Res; 76(7); 1942-53. ©2016 AACR. PMID:26921331

  11. A refined risk score for acute GVHD that predicts response to initial therapy, survival and transplant-related mortality

    PubMed Central

    MacMillan, Margaret L.; Robin, Marie; Harris, Andrew C.; DeFor, Todd E.; Martin, Paul J.; Alousi, Amin; Ho, Vincent T.; Bolaños-Meade, Javier; Ferrara, James L.M.; Jones, Richard; Arora, Mukta; Blazar, Bruce R.; Holtan, Shernan G.; Jacobsohn, David; Pasquini, Marcelo; Socie, Gerard; Antin, Joseph H.; Levine, John E.; Weisdorf, Daniel J.

    2015-01-01

    To develop a novel acute graft-versus-host disease (GVHD) Risk Score, we examined the GVHD clinical stage and grade of 1723 patients at the onset of treatment with systemic steroids. Using clinical grouping, descriptive statistics and recursive partitioning, we identified poorly responsive, high-risk (HR) acute GVHD by the number of involved organs and severity of GVHD at onset. The overall response [(complete response/partial response (CR/PR)] rate 28 days after initiation of steroid therapy for acute GVHD was lower in the 269 patients with HR-GVHD than in the 1454 patients with standard risk (SR)-GVHD [44% (95% CI 38–50%) vs. 68% (95% CI 66–70%), p<0.001. Patients with HR-GVHD were less likely to respond at day 28 [odds ratio (OR), 0.3, 95% CI 0.2–0.4, p<0.001], and had higher risks of mortality [relative risk (RR) 2.1, 95% CI 1.7–2.6, P<0.001] and transplant-related mortality (RR 2.5, 95% CI 2.0–3.2%, p<0.001) compared to patients with SR-GVHD. This refined definition of acute GVHD risk is a better predictor of response, survival and transplant-related mortality than other published acute GVHD risk scores. Patients with HR-GVHD are candidates for studies investigating new treatment approaches. Likewise, patients with SR-GVHD are candidates for studies investigating less toxic therapy. PMID:25585275

  12. Connexin 43 expression predicts poor progression-free survival in patients with non-muscle invasive urothelial bladder cancer

    PubMed Central

    Poyet, Cédric; Buser, Lorenz; Roudnicky, Filip; Detmar, Michael; Hermanns, Thomas; Mannhard, Doris; Höhn, Andrej; Rüschoff, Jan; Zhong, Qing; Sulser, Tullio; Moch, Holger; Wild, Peter J

    2015-01-01

    Objectives To evaluate the protein expression of connexin 43 (Cx43) in primary urothelial bladder cancer and test its association with the histopathological characteristics and clinical outcome. Methods A tissue microarray containing 348 tissue samples from 174 patients with primary urothelial carcinomas of the bladder was immunohistochemically stained for Cx43. The intensity of staining was semiquantitatively evaluated (score 0, 1+, 2+), and the association with clinicopathological features was assessed. Univariable and multivariable analyses were performed to identify predictors for progression-free survival (PFS). Results Membranous Cx43 immunoreactivity was detected in 118 (67.8%) of 174 analysable urothelial carcinomas, of which 31 (17.8%) showed even a strong (score 2+) and mainly homogeneous staining. Strong expression levels of Cx43 (score 2+) were associated with higher tumour grade, multiplicity and increased proliferation (all p<0.05). In the subgroup of patients with stage pTa and pT1 bladder tumours (n=158), strong Cx43 expression (p<0.001), solid growth pattern (p<0.001) and increased Ki-67 proliferation fraction (p<0.05) were significantly associated with shorter PFS in an univariable Cox regression analysis. In multivariable Cox regression models, Cx43 immunoreactivity and histological growth pattern remained highly significant and adverse risk factors for PFS. Conclusions The expression levels of Cx43 are frequent in non-muscle invasive bladder cancer (NMIBC), with high expression levels being associated with poor prognosis. Routine assessment of Cx43 expression may improve the identification of high-risk NMIBC. PMID:26251520

  13. Elevated expression of KIF18A enhances cell proliferation and predicts poor survival in human clear cell renal carcinoma

    PubMed Central

    CHEN, QI; CAO, BIN; NAN, NING; WANG, YU; ZHAI, XU; LI, YOUFANG; CHONG, TIE

    2016-01-01

    The function of kinesin family member 18A (KIF18A) in human renal cell carcinoma (RCC) is unclear. The purpose of the current study was to determine the expression and prognostic significance of KIF18A in RCC. Specimens from 273 RCC patients undergoing nephrectomies were studied. Expression of KIF18A mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR) or quantitative PCR, and the expression of KIF18A protein was examined by immunohistochemistry and western blotting. The expression of KIF18A in clear-cell RCC cell lines was decreased using small interfering RNA targeting KIF18A, and increased by transfection with KIF18A cDNA. The proliferative ability of RCC cells in vitro and in vivo was detected by WST-1 assay and an animal xenograft model with BALB/c nude mice, respectively. The association between KIF18A expression and overall survival was calculated using Kaplan-Meier analysis. The results showed that KIF18A expression was significantly increased in RCC tissues compared with normal kidney tissues. The level of KIF18A expression was significantly associated with tumor stage, histological grade, metastasis and tumor size. Moreover, KIF18A increased the proliferation of RCC cells in vitro and in vivo. KIF18A expression was upregulated in RCC and enhanced the proliferation of RCC cells. Therefore, it appears that KIF18A plays a key role in the carcinogenesis and progression of RCC, and is a novel candidate prognostic marker for RCC patients. Furthermore, silencing KIF18A expression may serve as a new therapeutic strategy against RCC. PMID:27347065

  14. Identification of a DNA methylation signature to predict disease-free survival in locally advanced rectal cancer

    PubMed Central

    Claus, Rainer; Weichenhan, Dieter; Jung, Klaus; Kitz, Julia; Grade, Marian; Wolff, Hendrik A.; Jo, Peter; Doyen, Jérôme; Gérard, Jean-Pierre; Johnsen, Steven A.; Plass, Christoph; Beißbarth, Tim; Ghadimi, Michael

    2014-01-01

    In locally advanced rectal cancer a preoperative predictive biomarker is necessary to adjust treatment specifically for those patients expected to suffer relapse. We applied whole genome methylation CpG island array analyses to an initial set of patients (n=11) to identify differentially methylated regions (DMRs) that separate a good from a bad prognosis group. Using a quantitative high-resolution approach, candidate DMRs were first validated in a set of 61 patients (test set) and then confirmed DMRs were further validated in additional independent patient cohorts (n=71, n=42). We identified twenty highly discriminative DMRs and validated them in the test set using the MassARRAY technique. Ten DMRs could be confirmed which allowed separation into prognosis groups (p=0.0207, HR=4.09). The classifier was validated in two additional cohorts (n=71, p=0.0345, HR=3.57 and n=42, p=0.0113, HR=3.78). Interestingly, six of the ten DMRs represented regions close to the transcriptional start sites of genes which are also marked by the Polycomb Repressor Complex component EZH2. In conclusion we present a classifier comprising 10 DMRs which predicts patient prognosis with a high degree of accuracy. These data may now help to discriminate between patients that may respond better to standard treatments from those that may require alternative modalities. PMID:25261372

  15. Fra-1 is a key driver of colon cancer metastasis and a Fra-1 classifier predicts disease-free survival

    PubMed Central

    Iskit, Sedef; Schlicker, Andreas; Wessels, Lodewyk; Peeper, Daniel S.

    2015-01-01

    Fra-1 (Fos-related antigen-1) is a member of the AP-1 (activator protein-1) family of transcription factors. We previously showed that Fra-1 is necessary for breast cancer cells to metastasize in vivo, and that a classifier comprising genes that are expressed in a Fra-1-dependent fashion can predict breast cancer outcome. Here, we show that Fra-1 plays an important role also in colon cancer progression. Whereas Fra-1 depletion does not affect 2D proliferation of human colon cancer cells, it impairs growth in soft agar and in suspension. Consistently, subcutaneous tumors formed by Fra-1-depleted colon cancer cells are three times smaller than those produced by control cells. Most remarkably, when injected intravenously, Fra-1 depletion causes a 200-fold reduction in tumor burden. Moreover, a Fra-1 classifier generated by comparing RNA profiles of parental and Fra-1-depleted colon cancer cells can predict the prognosis of colon cancer patients. Functional pathway analysis revealed Wnt as one of the central pathways in the classifier, suggesting a possible mechanism of Fra-1 function in colon cancer metastasis. Our results demonstrate that Fra-1 is an important determinant of the metastatic potential of human colon cancer cells, and that the Fra-1 classifier can be used as a prognostic predictor in colon cancer patients. PMID:26646695

  16. Two-gene signature improves the discriminatory power of IASLC/ATS/ERS classification to predict the survival of patients with early-stage lung adenocarcinoma

    PubMed Central

    Sun, Yifeng; Hou, Likun; Yang, Yu; Xie, Huikang; Yang, Yang; Li, Zhigang; Zhao, Heng; Gao, Wen; Su, Bo

    2016-01-01

    Background In this study, we investigated the contribution of a gene expression–based signature (composed of BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK, RND3, SH3BGR) to survival prediction for early-stage lung adenocarcinoma categorized by the new International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS) classification. We also aimed to verify whether gene signature improves the risk discrimination of IASLC/ATS/ERS classification in early-stage lung adenocarcinoma. Patients and methods Total RNA was extracted from 93 patients with pathologically confirmed TNM stage Ia and Ib lung adenocarcinoma. The mRNA expression levels of ten genes in the signature (BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK, RND3, and SH3BGR) were detected using real-time polymerase chain reaction. Each patient was categorized according to the new IASLC/ATS/ERS classification by accessing hematoxylin–eosin-stained slides. The corresponding Kaplan–Meier survival analysis by the log-rank statistic, multivariate Cox proportional hazards modeling, and c-index calculation were conducted using the programming language R (Version 2.15.1) with the “risksetROC” package. Results The multivariate analysis demonstrated that the risk factor of the ten-gene expression signature can significantly improve the discriminatory value of TNM staging in survival prediction, but not the value of the IASLC/ATS/ERS classification. Further analysis suggested that only BRCA1 and ERBB3 in the signature were independent risk factors after adjusting for the IASLC/ATS/ERS classification by Cox regression. A new algorithm of the two-gene expression signature containing BRCA1 and ERBB3 was generated. Adding the two-gene signature into the IASLC/ATS/ERS classification model further improved the discriminatory c-statistic from 0.728 to 0.756. Conclusion The two-gene signature composed of BRCA1 and ERBB3 was an independent

  17. Inferior vena cava resection with hepatectomy: challenging but justified

    PubMed Central

    Malde, Deep J; Khan, Aamir; Prasad, K Rajendra; Toogood, Giles J; Lodge, J Peter A

    2011-01-01

    Objective The aim of this study was to evaluate the clinical outcome of hepatectomy combined with inferior vena cava (IVC) resection and reconstruction for treatment of invasive liver tumours. Methods From February 1995 to September 2010, 2146 patients underwent liver resections in our hospital's hepatopancreatobiliary unit. Of these, 35 (1.6%) patients underwent hepatectomy with IVC resection. These patients were included in this study. Data were analysed from a prospectively collected database. Results Resections were carried out for colorectal liver metastasis (CRLM) (n = 21), hepatocellular carcinoma (n = 6), cholangiocarcinoma (n = 3) and other conditions (n = 5). Resections were carried out with total vascular occlusion in 34 patients and without in one patient. In situ hypothermic perfusion was performed in 13 patients; the ante situm technique was used in three patients, and ex vivo resection was used in six patients. There were four early deaths from multiple organ failure. Postoperative complications occurred in 14 patients, three of whom required re-operation. Median overall survival was 29 months and cumulative 5-year survival was 37.7%. Rates of 1-, 2- and 5-year survival were 75.9%, 58.7% and 19.6%, respectively, in CRLM patients. Conclusions Aggressive surgical management of liver tumours with IVC involvement offers the only hope for cure in selected patients. Resection by specialist teams affords acceptable perioperative morbidity and mortality rates. PMID:21999594

  18. Predictive value of the age-adjusted charlson comorbidity index on perioperative complications and survival in patients undergoing primary debulking surgery for advanced epithelial ovarian cancer

    PubMed Central

    Suidan, Rudy S.; Leitao, Mario M.; Zivanovic, Oliver; Gardner, Ginger J.; Long Roche, Kara C.; Sonoda, Yukio; Levine, Douglas A.; Jewell, Elizabeth L.; Brown, Carol L.; Abu-Rustum, Nadeem R.; Charlson, Mary E.; Chi, Dennis S.

    2016-01-01

    Objective To assess the ability of the Age-Adjusted Charlson Comorbidity index (ACCI) to predict perioperative complications and survival in patients undergoing primary debulking for advanced epithelial ovarian cancer (EOC). Methods Data were analyzed for all patients with stage IIIB-IV EOC who underwent primary cytoreduction from 1/2001–1/2010 at our institution. Patients were divided into 3 groups based on an ACCI of 0–1, 2–3, and ≥4. Clinical and survival outcomes were assessed and compared. Results We identified 567 patients; 199 (35%) had an ACCI of 0–1, 271 (48%) had an ACCI of 2–3, and 97 (17%) had an ACCI of ≥4. The ACCI was significantly associated with the rate of complete gross resection (0–1=44%, 2–3=32%, and ≥4=32%; p=0.02), but was not associated with the rate of minor (47% vs 47% vs 43%, p=0.84) or major (18% vs 19% vs 16%, p=0.8) complications. The ACCI was also significantly associated with progression-free (PFS) and overall survival (OS). Median PFS for patients with an ACCI of 0–1, 2–3, and ≥4 was 20.3, 16, and 15.4 months, respectively (p=0.02). Median OS for patients with an ACCI of 0–1, 2–3, and ≥4 was 65.3, 49.9, and 42.3 months, respectively (p<0.001). On multivariate analysis, the ACCI remained a significant prognostic factor for both PFS (p=0.02) and OS (p<0.001). Conclusions The ACCI was not associated with perioperative complications in patients undergoing primary cytoreduction for advanced EOC, but was a significant predictor of PFS and OS. Prospective clinical trials in ovarian cancer should consider stratifying for an age-comorbidity covariate. PMID:26037900

  19. Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer.

    PubMed

    Seeber, Andreas; Untergasser, Gerold; Spizzo, Gilbert; Terracciano, Luigi; Lugli, Alessandro; Kasal, Armin; Kocher, Florian; Steiner, Normann; Mazzoleni, Guido; Gastl, Guenther; Fong, Dominic

    2016-08-01

    Regulated intramembrane proteolysis (RIP) has been shown to be an important mechanism for oncogenic activation of EpCAM through nuclear translocation of the intracellular domain EpICD. Recently, we identified two different membranous EpCAM variants namely EpCAM(MF) (full-length) and EpCAM(MT) (truncated) to be expressed in the majority of human epithelial tumors. The aim of our study was to evaluate the potential role of these two protein variants as additional prognostic biomarkers in colorectal cancer. In most studies only one antibody targeting the extracellular domain of EpCAM (EpEX) has been used, whereas in the present study additionally an antibody which detects the intracellular domain (EpICD) was applied to discriminate between different EpCAM variants. Using immunohistochemistry, we analyzed the expression of EpCAM(MF) and EpCAM(MT) variants in 640 patients with colorectal cancer and determined their correlations with other prognostic factors and clinical outcome. A statistically significant association was observed for EpCAM(MT) with advanced tumor stage (p < 0.001), histological grade (p = 0.01), vascular (p < 0.001) and marginal (p = 0.002) invasion. Survival analysis demonstrated reduced overall survival (p < 0.004) in patients with tumors expressing the EpCAM(MT) phenotype when compared to patients with tumors expressing the EpCAM(MF) variant. In conclusion, this study for the first time indicates that expression of EpCAM(MT) is associated with a more aggressive phenotype and predicts poor survival in patients with colorectal cancer. PMID:26996277

  20. Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma

    PubMed Central

    Cai, Jinquan; Sun, Ying; Wang, Guangzhi; Li, Yongli; Li, Ruiyan; Feng, Yan; Han, Bo; Li, Jianlong; Tian, Yu; Yi, Liye; Jiang, Chuanlu

    2016-01-01

    Background Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM. Method The mRNA expression profiles of all MMP genes were obtained from the Chinese Glioma Genome Atlas (CGGA), the Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the GSE16011 dataset. MGMT methylation status was also examined by pyrosequencing. The correlation of MMP9 expression with tumor progression was explored in glioma specimens of all grades. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the association of MMP9 expression with survival and response to temozolomide. Results MMP9 was the only significant prognostic factor in three datasets for primary glioblastoma patients. Our results indicated that MMP9 expression is correlated with glioma grade (p<0.0001). Additionally, low expression of MMP9 was correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066), and MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS: p = 0.032). Additionally, the GBM patients with low MMP9 expression benefited from temozolomide (TMZ) chemotherapy regardless of the MGMT methylation status. Conclusions Patients with primary GBMs with low MMP9 expression may have longer survival and may benefit from temozolomide chemotherapy. PMID:27022952

  1. Combined heavy smoking and drinking predicts overall but not disease-free survival after curative resection of locoregional esophageal squamous cell carcinoma

    PubMed Central

    Sun, Peng; Chen, Cui; Zhang, Fei; Yang, Hang; Bi, Xi-Wen; An, Xin; Wang, Feng-Hua; Jiang, Wen-Qi

    2016-01-01

    Introduction The prognostic impact of smoking and drinking on esophageal squamous cell carcinoma (ESCC) was scarcely discussed. We investigated the prognostic value of smoking and drinking and their relationships with clinicopathological characteristics in a large cohort of patients with locoregional ESCC. Patients and methods We retrospectively analyzed 488 patients who underwent curative treatment at a single institution between January 2007 and December 2008. A chi-square test was used to evaluate the relationships between smoking and drinking and clinicopathological variables, the Kaplan–Meier method was used for 5-year overall survival (OS) and disease-free survival, and Cox proportional hazards models were applied for univariate and multivariate analyses of variables with respect to OS and disease-free survival. Results Heavy smokers were more likely to have advanced Tumor-Node-Metastases (TNM) stage and higher neutrophil/lymphocyte ratio at diagnosis (P<0.05). Drinkers were more likely to have advanced TNM stage, to present with a larger tumor, and to undergo multidisciplinary treatment (P<0.05). For patients who used neither heavy tobacco nor alcohol, used either tobacco or alcohol, and used both, the 5-year OS rates and OS times were 57.4%, 46.4%, and 39.1% (P<0.05) and not reached, 55.2 months, and 41.2 months (P<0.05), respectively. On multivariate analysis, patients who both heavily smoked and drank had 1.392 times the risk of dying during follow-up compared with neither-users (95% CI =1.020–1.901, P=0.037). Conclusion We identified that combined heavy smoking and drinking might predict poor prognosis in ESCC patients. PMID:27471400

  2. Factors that predict progression-free survival in Chinese lung adenocarcinoma patients treated with epidermal growth factor receptor tyrosine kinase inhibitors

    PubMed Central

    Cui, Shaohua; Xiong, Liwen; Lou, Yuqing; Shi, Huangping; Gu, Aiqin; Zhao, Yizhuo; Chu, Tianqing; Wang, Huimin; Zhang, Wei; Dong, Lili

    2016-01-01

    Background Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown efficacy in patients with advanced lung cancers, survival predictors with these drugs have not been extensively investigated. This study was performed to explore factors that may predict progression-free survival (PFS) in Chinese lung adenocarcinoma patients treated with EGFR-TKIs. Methods We retrospectively collected clinicopathologic data on 208 patients who received either gefitinib, erlotinib or icotinib, including the patients’ EGFR mutation status and levels of six serum tumor markers [carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCC), cytokeratin-19 fragments (CYFRA21-1) and lactate dehydrogenase (LDH)]. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with PFS. Results At the study cutoff date, 189 (90.9%) of the patients met the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria for progressive disease (PD), while 19 (9.1%) had stable disease (SD). The median PFS of the 208 patients was 12.4 months (95% CI, 11.0–13.8 months). In the multivariate analysis using a Cox proportional hazard model, a non-smoking history [hazard ratio (HR) =2.460; 95% CI, 1.484–4.079; P<0.001], first-line treatment (HR =1.500; 95% CI, 1.062–2.119; P=0.021), and a high pretreatment serum level of CEA (HR =1.424; 95% CI 1.026–1.977; P=0.035) were found to be significant predictors of a longer PFS. Conclusions In Chinese lung adenocarcinoma patients treated with EGFR-TKIs, a non-smoking history, first-line EGFR-TKIs treatment and a high serum level of CEA were independent predictors of a longer PFS along with an EGFR-activating mutation. PMID:26904214

  3. Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma

    PubMed Central

    Lu, Shi-Dong; Wang, Yan-Yan; Peng, Ning-Fu; Peng, Yu-Chong; Zhong, Jian-Hong; Qin, Hong-Gui; Xiang, Bang-De; You, Xue-Mei; Ma, Liang; Li, Le-Qun

    2016-01-01

    Abstract This study aims to clarify the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) for patients with hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR). The prognostic value of the NLR for HCC patients has not been definitely reviewed by large studies, especially for those with different Barcelona Clinic Liver Cancer (BCLC) stages. A consecutive sample of 963 HCC patients who underwent potentially curative HR was classified as having low or high NLR using a cut-off value of 2.81. Overall survival (OS) and tumor recurrence were compared for patients with low or high NLR across the total population, as well as in subgroups of patients in BCLC stages 0/A, B, or C. Clinicopathological parameters, including NLR, were evaluated to identify risk factors of OS and tumor recurrence after potentially curative hepatic resection. Multivariate analyses were performed using the Cox proportional hazards model or subdistribution hazard regression model. Multivariate analyses showed that NLR (>2.81), tumor number (>3), incomplete capsule, serum albumin (≤35 g/L), alanine transaminase activity (>40 U/L), and macrovascular invasion were risk factors for low OS, whereas NLR (>2.81), tumor size (>5 cm), alpha fetal protein concentration (>400 ng/L), and macrovascular invasion were risk factors for low tumor recurrence. NLR > 2.81 was significantly associated with poor OS and tumor recurrence in the total patient population (both P < 0.001), as well as in the subgroups of patients in BCLC stages 0/A or B (all P < 0.05). Moreover, those with high NLR were associated with low OS (P = 0.027), and also with slightly higher tumor recurrence than those with low NLR for the subgroups in BCLC stage B (P = 0.058). Neither association, however, was observed among patients with BCLC stage C disease. NLR may be an independent predictor of low OS and tumor recurrence after potentially curative HR in HCC patients

  4. The KIT D816V allele burden predicts survival in patients with mastocytosis and correlates with the WHO type of the disease

    PubMed Central

    Hoermann, Gregor; Gleixner, Karoline V.; Dinu, Graziella E.; Kundi, Michael; Greiner, Georg; Wimazal, Friedrich; Hadzijusufovic, Emir; Mitterbauer, Gerlinde; Mannhalter, Christine; Valent, Peter; Sperr, Wolfgang R.

    2016-01-01

    KIT D816V is present in a majority of patients with systemic mastocytosis (SM). We determined the KIT D816V allele burden by quantitative real-time PCR in bone marrow and peripheral blood of 105 patients with mastocytosis. KIT D816V was detected in 92/105 patients (88%). Significant differences in the median allele burden were observed among disease subgroups; cutaneous mastocytosis (0.042%), indolent SM (0.285%), smoldering SM (5.991%), aggressive SM (9.346%) and SM with associated hematologic non-mast cell lineage disease (3.761%) (P<0.001). The KIT D816V burden also correlated with serum tryptase (R=0.5, P<0.005) but not with mast cell infiltration in bone marrow or mediator symptoms. Moreover, the allele burden was of prognostic significance regarding survival (P<0.01). Patients responding to cytoreductive therapy showed a significant decrease in KIT D816V (P<0.03). To conclude, the KIT D816V burden correlates with the variant of mastocytosis, predicts survival, and is a valuable follow-up parameter in SM. PMID:24750133

  5. Nonlinear dimensionality reduction of CT histogram based feature space for predicting recurrence-free survival in non-small-cell lung cancer

    NASA Astrophysics Data System (ADS)

    Kawata, Y.; Niki, N.; Ohmatsu, H.; Aokage, K.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

    2015-03-01

    Advantages of CT scanners with high resolution have allowed the improved detection of lung cancers. In the recent release of positive results from the National Lung Screening Trial (NLST) in the US showing that CT screening does in fact have a positive impact on the reduction of lung cancer related mortality. While this study does show the efficacy of CT based screening, physicians often face the problems of deciding appropriate management strategies for maximizing patient survival and for preserving lung function. Several key manifold-learning approaches efficiently reveal intrinsic low-dimensional structures latent in high-dimensional data spaces. This study was performed to investigate whether the dimensionality reduction can identify embedded structures from the CT histogram feature of non-small-cell lung cancer (NSCLC) space to improve the performance in predicting the likelihood of RFS for patients with NSCLC.

  6. Molecule survival in magnetized protostellar disk winds. II. Predicted H2O line profiles versus Herschel/HIFI observations

    NASA Astrophysics Data System (ADS)

    Yvart, W.; Cabrit, S.; Pineau des Forêts, G.; Ferreira, J.

    2016-01-01

    Context. The origin of molecular protostellar jets and their role in extracting angular momentum from the accreting system are important open questions in star formation research. In the first paper of this series we showed that a dusty magneto-hydrodynamic (MHD) disk wind appeared promising to explain the pattern of H2 temperature and collimation in the youngest jets. Aims: We wish to see whether the high-quality H2O emission profiles of low-mass protostars, observed for the first time by the HIFI spectrograph on board the Herschel satellite, remain consistent with the MHD disk wind hypothesis, and which constraints they would set on the underlying disk properties. Methods: We present synthetic H2O line profiles predictions for a typical MHD disk wind solution with various values of disk accretion rate, stellar mass, extension of the launching area, and view angle. We compare them in terms of line shapes and intensities with the HIFI profiles observed by the WISH key program towards a sample of 29 low-mass Class 0 and Class 1 protostars. Results: A dusty MHD disk wind launched from 0.2-0.6 AU AU to 3-25 AU can reproduce to a remarkable degree the observed shapes and intensities of the broad H2O component observed in low-mass protostars, both in the fundamental 557 GHz line and in more excited lines. Such a model also readily reproduces the observed correlation of 557 GHz line luminosity with envelope density, if the infall rate at 1000 AU is 1-3 times the disk accretion rate in the wind ejection region. It is also compatible with the typical disk size and bolometric luminosity in the observed targets. However, the narrower line profiles in Class 1 sources suggest that MHD disk winds in these sources, if present, would have to be slower and/or less water rich than in Class 0 sources. Conclusions: MHD disk winds appear as a valid (though not unique) option to consider for the origin of the broad H2O component in low-mass protostars. ALMA appears ideally suited to

  7. Quantitative fibrosis estimation by image analysis predicts development of decompensation, composite events and defines event-free survival in chronic hepatitis B patients.

    PubMed

    Bihari, Chhagan; Rastogi, Archana; Sen, Bijoya; Bhadoria, Ajeet Singh; Maiwall, Rakhi; Sarin, Shiv K

    2016-09-01

    The extent of fibrosis is a major determinant of the clinical outcome in patients with chronic liver diseases. We undertook this study to explore the degree of fibrosis in baseline liver biopsies to predict clinical outcomes in chronic hepatitis B (CHB) patients. Fibrosis quantification was done by image analysis on Masson's trichrome-stained sections and correlated with clinical and biochemical parameters, liver stiffness and hepatic vein pressure gradient (n = 96). Follow-up information collected related to clinical outcome. A total of 964 cases was analyzed. Median quantitative fibrosis (QF) was 3.7% (interquartile range, 1.6%-9.7%) with substantial variation in various stages. Median QF was F0, 1% (0.7%-1.65%); F1, 3.03% (2.07%-4.0%); F2, 7.1% (5.6%-8.7%); F3, 12.7% (10.15%-16.7%); F4, 26.9% (20.3%-36.4%). QF positively correlated with METAVIR staging, liver stiffness measurement, and hepatic vein pressure gradient. Eighty-nine cases developed liver-related events: decompensation, hepatocellular carcinoma, liver transplantation and death. Cox regression analysis after adjusting for METAVIR staging-QF, albumin, and AST for composite events; QF and albumin for decompensation; and only QF for hepatocellular carcinoma-were found to be significant predictors of clinical outcomes. QF categorized into five stages: QF1, 0%-5%; QF2, 5.1%-10%; QF3, 10.1%-15%; QF4, 15.1%-20%; QF5, >20.1%. In patients with advanced stages of QF, probability of event-free survival found to be low. Quantitative fibrosis in baseline liver biopsy predicts progression of the disease and disease outcome in CHB patients. QF defines the probability of event-free survival in CHB cases. PMID:27189343

  8. Integrative Pathway Analysis of Metabolic Signature in Bladder Cancer: A Linkage to The Cancer Genome Atlas Project and Prediction of Survival

    PubMed Central

    von Rundstedt, Friedrich-Carl; Rajapakshe, Kimal; Ma, Jing; Arnold, James M.; Gohlke, Jie; Putluri, Vasanta; Krishnapuram, Rashmi; Piyarathna, D. Badrajee; Lotan, Yair; Gödde, Daniel; Roth, Stephan; Störkel, Stephan; Levitt, Jonathan M.; Michailidis, George; Sreekumar, Arun; Lerner, Seth P.; Coarfa, Cristian; Putluri, Nagireddy

    2016-01-01

    Purpose We used targeted mass spectrometry to study the metabolic fingerprint of urothelial cancer and determine whether the biochemical pathway analysis gene signature would have a predictive value in independent cohorts of patients with bladder cancer. Materials and Methods Pathologically evaluated, bladder derived tissues, including benign adjacent tissue from 14 patients and bladder cancer from 46, were analyzed by liquid chromatography based targeted mass spectrometry. Differential metabolites associated with tumor samples in comparison to benign tissue were identified by adjusting the p values for multiple testing at a false discovery rate threshold of 15%. Enrichment of pathways and processes associated with the metabolic signature were determined using the GO (Gene Ontology) Database and MSigDB (Molecular Signature Database). Integration of metabolite alterations with transcriptome data from TCGA (The Cancer Genome Atlas) was done to identify the molecular signature of 30 metabolic genes. Available outcome data from TCGA portal were used to determine the association with survival. Results We identified 145 metabolites, of which analysis revealed 31 differential metabolites when comparing benign and tumor tissue samples. Using the KEGG (Kyoto Encyclopedia of Genes and Genomes) Database we identified a total of 174 genes that correlated with the altered metabolic pathways involved. By integrating these genes with the transcriptomic data from the corresponding TCGA data set we identified a metabolic signature consisting of 30 genes. The signature was significant in its prediction of survival in 95 patients with a low signature score vs 282 with a high signature score (p = 0.0458). Conclusions Targeted mass spectrometry of bladder cancer is highly sensitive for detecting metabolic alterations. Applying transcriptome data allows for integration into larger data sets and identification of relevant metabolic pathways in bladder cancer progression. PMID:26802582

  9. Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

    SciTech Connect

    McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

    2010-03-01

    Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk) on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit

  10. Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis

    PubMed Central

    Ruderman, Michael A.; Wilson, Deirdra F.; Reid, Savanna

    2015-01-01

    Objective This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). Background Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. Methods Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. Results Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05–4.17), drug violations (HR 2.44 95% CI: 2.00–2.98), non-violent violations (HR 2.14 95% CI: 1.73–2.64), violent and serious violations (HR 1.88 95% CI: 1.45–2.43), and technical violations (HR 1.86 95% CI: 1.37–2.53). Conclusions Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted. PMID:26492490

  11. Joint Analyses of Longitudinal and Time-to-Event Data in Research on Aging: Implications for Predicting Health and Survival

    PubMed Central

    Arbeev, Konstantin G.; Akushevich, Igor; Kulminski, Alexander M.; Ukraintseva, Svetlana V.; Yashin, Anatoliy I.

    2014-01-01

    Longitudinal data on aging, health, and longevity provide a wealth of information to investigate different aspects of the processes of aging and development of diseases leading to death. Statistical methods aimed at analyses of time-to-event data jointly with longitudinal measurements became known as the “joint models” (JM). An important point to consider in analyses of such data in the context of studies on aging, health, and longevity is how to incorporate knowledge and theories about mechanisms and regularities of aging-related changes that accumulate in the research field into respective analytic approaches. In the absence of specific observations of longitudinal dynamics of relevant biomarkers manifesting such mechanisms and regularities, traditional approaches have a rather limited utility to estimate respective parameters that can be meaningfully interpreted from the biological point of view. A conceptual analytic framework for these purposes, the stochastic process model of aging (SPM), has been recently developed in the biodemographic literature. It incorporates available knowledge about mechanisms of aging-related changes, which may be hidden in the individual longitudinal trajectories of physiological variables and this allows for analyzing their indirect impact on risks of diseases and death. Despite, essentially, serving similar purposes, JM and SPM developed in parallel in different disciplines with very limited cross-referencing. Although there were several publications separately reviewing these two approaches, there were no publications presenting both these approaches in some detail. Here, we overview both approaches jointly and provide some new modifications of SPM. We discuss the use of stochastic processes to capture biological variation and heterogeneity in longitudinal patterns and important and promising (but still largely underused) applications of JM and SPM to predictions of individual and population mortality and health

  12. Circulating MicroRNA-223 Serum Levels Do Not Predict Sepsis or Survival in Patients with Critical Illness

    PubMed Central

    Benz, Fabian; Tacke, Frank; Luedde, Mark; Trautwein, Christian; Luedde, Tom; Koch, Alexander; Roderburg, Christoph

    2015-01-01

    Background and Aims. Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis. Methods. We used i.v. injection of lipopolysaccharide (LPS) as well as cecal pole ligation and puncture (CLP) for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU). Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers. Results. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score) showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality. Conclusion. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum levels do not

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

    PubMed Central

    Graupera, Isabel; Solà, Elsa; Fabrellas, Núria; Moreira, Rebeca; Solé, Cristina; Huelin, Patricia; de la Prada, Gloria; Pose, Elisa; Ariza, Xavier; Risso, Alessandro; Albertos, Sonia; Morales-Ruiz, Manuel; Jiménez, Wladimiro; Ginès, Pere

    2016-01-01

    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. AIM: To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis. METHODS: 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. RESULTS: 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. CONCLUSION: Urine, but not plasma, MCP-1 levels are associated with hospital readmission, development of complications of cirrhosis, and mortality. These

  14. Hepatocellular carcinoma with extension to the heart via the inferior vena cava

    PubMed Central

    Lewis, Brian

    2015-01-01

    Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related mortality worldwide. Most cases of HCC are associated with cirrhosis from various causes such as alcohol or viral hepatitis. Most patients are symptomatic as a result of cirrhosis itself or secondary to tumor extension. These tumors have an affinity for the vasculature and often invade the portal system. HCC rarely causes invasion of the inferior vena cava or the heart. We, however, present a case of HCC in a patient without cirrhosis who remained asymptomatic despite having tumor extension to the heart by way of the inferior vena cava. The mean survival in patients with intracardiac extension with or without aggressive treatment or intervention is approximately 4 months, but our patient greatly exceeded survival expectations after treatment with sorafenib. PMID:25829663

  15. Predicting future threats to the long-term survival of Gila Trout using a high-resolution simulation of climate change

    SciTech Connect

    Kennedy, Thomas L.; Gutzler, David S.; Leung, Lai R.

    2008-11-20

    Regional climates are a major factor in determining the distribution of many species. Anthropogenic inputs of greenhouse gases into the atmosphere have been predicted to cause rapid climatic changes in the next 50-100 years. Species such as the Gila Trout (Onchorhynchus gilae) that have small ranges, limited dispersal capabilities, and narrow physiological tolerances will become increasingly susceptible to extinction as their climate envelope changes. This study uses a regional climate change simulation (Leung et al. 2004) to determine changes in the climate envelope for Gila Trout, which is sensitive to maximum temperature, associated with a plausible scenario for greenhouse gas increases. The model predicts approximately a 2° C increase in temperature and a doubling by the mid 21st Century in the annual number of days during which temperature exceeds 37°C, and a 25% increase in the number of days above 32°C, across the current geographical range of Gila Trout. At the same time summer rainfall decreases by more than 20%. These climate changes would reduce their available habitat by decreasing the size of their climate envelope. Warmer temperatures coupled with a decrease in summer precipitation would also tend to increase the intensity and frequency of forest fires that are a major threat to their survival. The climate envelope approach utilized here could be used to assess climate change threats to other rare species with limited ranges and dispersal capabilities.

  16. Testing predictions of the Janzen–Connell hypothesis: a meta-analysis of experimental evidence for distance- and density-dependent seed and seedling survival

    PubMed Central

    Comita, Liza S; Queenborough, Simon A; Murphy, Stephen J; Eck, Jenalle L; Xu, Kaiyang; Krishnadas, Meghna; Beckman, Noelle; Zhu, Yan; Gómez-Aparicio, Lorena

    2014-01-01

    The Janzen–Connell hypothesis proposes that specialist natural enemies, such as herbivores and pathogens, maintain diversity in plant communities by reducing survival rates of conspecific seeds and seedlings located close to reproductive adults or in areas of high conspecific density. Variation in the strength of distance- and density-dependent effects is hypothesized to explain variation in plant species richness along climatic gradients, with effects predicted to be stronger in the tropics than the temperate zone and in wetter habitats compared to drier habitats. We conducted a comprehensive literature search to identify peer-reviewed experimental studies published in the 40+ years since the hypothesis was first proposed. Using data from these studies, we conducted a meta-analysis to assess the current weight of evidence for the distance and density predictions of the Janzen–Connell hypothesis. Overall, we found significant support for both the distance- and density-dependent predictions. For all studies combined, survival rates were significantly reduced near conspecifics compared to far from conspecifics, and in areas with high densities of conspecifics compared to areas with low conspecific densities. There was no indication that these results were due to publication bias. The strength of distance and density effects varied widely among studies. Contrary to expectations, this variation was unrelated to latitude, and there was no significant effect of study region. However, we did find a trend for stronger distance and density dependence in wetter sites compared to sites with lower annual precipitation. In addition, effects were significantly stronger at the seedling stage compared to the seed stage. Synthesis. Our study provides support for the idea that distance- and density-dependent mortality occurs in plant communities world-wide. Available evidence suggests that natural enemies are frequently the cause of such patterns, consistent with the Janzen

  17. Prediction of 18-month survival in patients with primary myelodysplastic syndrome. A regression model and scoring system based on the combination of chromosome findings and the Bournemouth score.

    PubMed

    Parlier, V; van Melle, G; Beris, P; Schmidt, P M; Tobler, A; Haller, E; Bellomo, M J

    1995-06-01

    The predictive potential of six selected factors was assessed in 72 patients with primary myelodysplastic syndrome using univariate and multivariate logistic regression analysis of survival at 18 months. Factors were age (above median of 69 years), dysplastic features in the three myeloid bone marrow cell lineages, presence of chromosome defects, all metaphases abnormal, double or complex chromosome defects (C23), and a Bournemouth score of 2, 3, or 4 (B234). In the multivariate approach, B234 and C23 proved to be significantly associated with a reduction in the survival probability. The similarity of the regression coefficients associated with these two factors means that they have about the same weight. Consequently, the model was simplified by counting the number of factors (0, 1, or 2) present in each patient, thus generating a scoring system called the Lausanne-Bournemouth score (LB score). The LB score combines the well-recognized and easy-to-use Bournemouth score (B score) with the chromosome defect complexity, C23 constituting an additional indicator of patient outcome. The predicted risk of death within 18 months calculated from the model is as follows: 7.1% (confidence interval: 1.7-24.8) for patients with an LB score of 0, 60.1% (44.7-73.8) for an LB score of 1, and 96.8% (84.5-99.4) for an LB score of 2. The scoring system presented here has several interesting features. The LB score may improve the predictive value of the B score, as it is able to recognize two prognostic groups in the intermediate risk category of patients with B scores of 2 or 3. It has also the ability to identify two distinct prognostic subclasses among RAEB and possibly CMML patients. In addition to its above-described usefulness in the prognostic evaluation, the LB score may bring new insights into the understanding of evolution patterns in MDS. We used the combination of the B score and chromosome complexity to define four classes which may be considered four possible states of

  18. Multidirectional Instability Accompanying an Inferior Labral Cyst

    PubMed Central

    Ji, Jong-Hun; Kim, Sung-Jae

    2010-01-01

    Paralabral cyst of the shoulder joint can be observed in 2% to 4% of the general population, particularly in men during the third and fourth decade. On average, these cysts measure 10 mm to 20 mm in diameter and are located preferentially on the postero-superior aspect of the glenoid. The MRI has increased the frequency of the diagnosis of paralabral cysts of the shoulder joint. Paralabral cysts of the shoulder joint usually develop in the proximity of the labrum. The relationship between shoulder instability and labral tears is well known, however, the association of shoulder instability with a paralabral cyst is rare. Shoulder instability may cause labral injury or labral injury may cause shoulder instability, and then injured tear develops paralabral cyst. In our patient, the inferior paralabral cyst may be associated with inferior labral tears and instability MRI. PMID:20514270

  19. A novel technique for inferior rectus recession

    PubMed Central

    Gokyigit, Birsen; Akar, Serpil; Yilmaz, Omer Faruk

    2014-01-01

    Purpose To introduce a novel technique of inferior rectus recession operation to allow larger amounts of recession without causing lower lid retraction and to compare this method with the results obtained in standard inferior rectus recession. Material and methods This study included 20 patients operated on in the authors’ clinic. The median age of the patients was 24.5±18.6 (4–73) years and the median follow-up was 9.3±11.8 (3–43) months. Ten patients operated on with the standard method were labeled Group 1 and ten patients operated on with the new method were labeled Group 2. Without exceeding 4 mm, inferior rectus recession to the whole muscle was performed in Group 1 patients. Inferior rectus recession was also performed on patients in Group 2 following the new method. Using a spatula, approximately 10% of the muscle surface fibers were detached intact as a thin layer, and the remaining 90% of deeper fibers were recessed 4–8 mm as planned. Patients’ preoperative deviations and lower lid positions were recorded. The same parameters were checked in the first and third month postoperatively. Both groups were evaluated retrospectively by screening their files, and the Mann–Whitney U test was used for statistical evaluation. Results Lower lid retraction was seen in four patients of Group 1. There was no retraction in Group 2. While there was a need to perform additional vertical muscle procedures for vertical deviations and lower lid retractions in Group 1, it was observed that there was no need for additional procedures in Group 2 patients. There was a statistically meaningful difference between the two procedures (P<0.05). Conclusion This novel technique was found to be an effective surgical method for permitting more recession without the risk of lower lid retraction. PMID:24492531

  20. CK2α phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients.

    PubMed

    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

    CK2α has diverse effects on the tumorigenesis owing to its kinase activity, which phosphorylates various proteins involved in tumorigenesis. We, therefore, investigated the expression and role of CK2α in the phosphorylation of deleted in breast cancer 1 (DBC1) in gastric carcinomas. We used 187 gastric carcinomas and human gastric can