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Sample records for predicts inferior survival

  1. 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

  2. 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

  3. Prolonged Delayed Graft Function Is Associated with Inferior Patient and Kidney Allograft Survivals

    PubMed Central

    de Sandes-Freitas, Tainá Veras; Felipe, Cláudia Rosso; Aguiar, Wilson Ferreira; Cristelli, Marina Pontello; Tedesco-Silva, Hélio; Medina-Pestana, José Osmar

    2015-01-01

    It is unclear if there is an association between the duration of delayed graft function (DGF) and kidney transplant (KT) outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412). Patients were grouped in quartiles according to duration of DGF (1–5, 6–10, 11–15, and >15 days, designated as prolonged DGF). The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064–4.184,p = 0.033) and more than 3 HLA mismatches (OR 1.819, CI95% 1.117–2.962,p = 0.016). The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001). Compared to patients without DGF, DGF(1–5), DGF(6–10), and DGF(11–15), patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003), graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001), death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001), and creatinine clearance (58.0±24.6 vs. 55.8±22.2 vs. 53.8±24.1 vs. 53.0±27.2 vs. 36.8±27.0 mL/min, p<0.001), respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270–6.618, p<0.001), death censored graft loss (OR 4.103, CI95% 2.055–8.193, p<0.001), and death (OR 3.065, CI95% 1.536–6.117, p = 0.001). Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year. PMID:26679933

  4. 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

  5. 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

  6. 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

  7. Predicting survival in chronic lymphocytic leukemia.

    PubMed

    Bazargan, Ali; Tam, Constantine S; Keating, Michael J

    2012-03-01

    There is increasing interest in the use of prognostic markers that may predict survival and guide management in patients diagnosed with the early stages of chronic lymphocytic leukemia (CLL). Currently, the most important traditional prognostic factors include clinical staging, lymphocyte doubling time and β2-microglobulin/thymidine kinase; and the most important novel markers include karyotypic aberrations (typically assessed by FISH probes or CpG oligonucleotide karyotyping) and IgVH mutation status. Although each of these factors have individually shown significant correlations with survival, there is increasing appreciation that the most complete information may be obtained by using a combination of several factors in prognostic normograms or models. In this article, we review the current state-of-the-art with regards to CLL prognostic factors and discuss how they can be applied in the clinic. PMID:22369330

  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. Two Genes Might Help Predict Breast Cancer Survival

    MedlinePlus

    ... fullstory_160503.html Two Genes Might Help Predict Breast Cancer Survival Research suggests that tracking DNA activity patterns ... activity of two genes may help predict certain breast cancer patients' chances of survival and guide their treatment, ...

  10. 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

  11. 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.

  12. [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.

  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. 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.

  15. 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

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

    PubMed

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

    2015-01-26

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

  17. 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.

  18. Physician predictions of graft survival following liver transplantation

    PubMed Central

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

    2007-01-01

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

  19. TET2 mutations were predictive of inferior prognosis in the presence of ASXL1 mutations in patients with chronic myelomonocytic leukemia

    PubMed Central

    Cui, Yajuan; Tong, Hongyan; Du, Xin; Li, Bing; Gale, Robert Peter; Qin, Tiejun; Liu, Jinqin; Xu, Zefeng; Zhang, Yue; Huang, Gang; Jin, Jie; Fang, Liwei; Zhang, Hongli; Pan, Lijuan; Hu, Naibo; Qu, Shiqiang

    2016-01-01

    Background Somatic mutations involving epigenetic regulators, histone modification and chromatin regulation, splicing components, transcription factors and signaling regulator genes are common in chronic myelomonocytic leukemia (CMML) patients. It has been consensus that ASXL1 mutations have adversely impact on overall survival (OS), while the effect of TET2 mutations remains controversial and undefined. Methods ASXL1 and TET2 mutations were analyzed in 141 patients with CMML using Sanger sequencing, with the aim to identify the interplay of ASXL1 and TET2 mutations in the prognosis of CMML. Results Sixty-five (46.1%) of the CMML patients harbored ASXL1 mutations (frameshift and nonsense), and 46 (32.6%) had TET2 mutations (frame shift, nonsense and missense). In a separate multivariable analysis that included the Mayo Prognostic Model as a single variable along with ASXL1wt/TET2wt, the respective hazard ratios of ASXL1mut/TET2mut, ASXL1mut/TET2wt and ASXL1wt/TET2mut were 4.7 (95% CI, 2.2–10.3; P<0.001), 2.2 (95% CI, 1.1–4.2; P=0.025) and 1.3 (95% CI, 0.6–2.5; P=0.521). Conclusions Our study showed that ASXL1 mutations predict inferior OS, and additional TET2 mutations were associated with poor survival in the presence of ASXL1 mutations of CMML patients. PMID:27777939

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

    PubMed Central

    Witteman, Jacqueline C. M.; Franco, Oscar H.; Stricker, Bruno H. C.; Breteler, Monique M. B.; Hofman, Albert; Tiemeier, Henning

    2010-01-01

    As life expectancy continually increases, it is imperative to identify determinants of survival to the extreme end of the lifespan and more importantly to identify factors that increase the chance of survival free of major morbidities. As such, the current study assessed 45 common disease factors as predictors of survival and morbidity-free survival to age 85 years. Within the Rotterdam Study, a population-based cohort, we evaluated morbidity-free participants who were able to attain age 85 within the study duration (n = 2,008). Risk factors were assessed at baseline (1990–1993), and mortality and morbidities were then collected continuously until mortality or the occurrence of their 85th birthday (average time of 7.9 years). Risk factors included demographic and lifestyle variables, health and morbidity indicators and physiological makers. Major morbidities examined included dementia, cancer, cerebrovascular accident, heart failure and myocardial infarction. Logistic regression analyses demonstrated that many of the variables were independently predictive for survival and for morbidity-free ageing to 85 years. These included being female, absence of left ventricular abnormalities, stable body weight, unimpaired instrumental activities of daily living, lower C-RP levels and higher levels of femoral neck bone mineral density and albumin. Relative to non-survival, predictors were stronger for morbidity-free survival than for total survival or survival with morbidity. This suggests that lifespan and healthy survival to older age can be relatively well predicted. Understanding predictors of a long and healthy lifespan is vital for developing primary and secondary preventions to help improve the quality of life of older adults and for reducing the financial burden of the rapidly escalating ageing population. PMID:20514522

  1. Expression of KLF4 is a predictive marker for survival in pediatric Burkitt lymphoma.

    PubMed

    Valencia-Hipόlito, Alberto; Hernández-Atenógenes, Miriam; Vega, Gabriel G; Maldonado-Valenzuela, Altagracia; Ramon, Guillermo; Mayani, Héctor; Peña Alonso, Yolanda; Martinez-Maza, Otoniel; Méndez-Tenorio, Alfonso; Huerta-Yepez, Sara; Bonavida, Benjamin; Vega, Mario I

    2014-08-01

    Krüppel-like factor 4 (KLF4) is expressed in a variety of tissues with diverse physiological functions and activities. KLF4 can also function as a tumor suppressor or an oncogene, depending on the cellular context. Its role in hematological malignancies is controversial. This study examined the expression levels of KLF4 by immunohistochemistry in 73 pediatric non-Hodgkin lymphomas (NHLs) in a tissue microarray and also on several B-NHL cell lines. Elevated levels of KLF4 expression were detected in 66% of lymphoma cases and were more frequent in the Burkitt lymphoma (p = 0.05) subtype. There was a significant predictive power for outcome with low KLF4 expression, predicting a favorable overall survival compared to high levels. Multivariate analyses confirmed the association of KLF4 expression with unfavorable overall survival (p < 0.005). These findings were consistent with analyses in existing NHL microarray datasets. The present findings revealed that KLF4 is overexpressed in Burkitt pediatric lymphoma and is a potential biomarker for inferior overall survival. PMID:24067139

  2. 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

  3. Inference for survival prediction under the regularized Cox model.

    PubMed

    Sinnott, Jennifer A; Cai, Tianxi

    2016-10-01

    When a moderate number of potential predictors are available and a survival model is fit with regularization to achieve variable selection, providing accurate inference on the predicted survival can be challenging. We investigate inference on the predicted survival estimated after fitting a Cox model under regularization guaranteeing the oracle property. We demonstrate that existing asymptotic formulas for the standard errors of the coefficients tend to underestimate the variability for some coefficients, while typical resampling such as the bootstrap tends to overestimate it; these approaches can both lead to inaccurate variance estimation for predicted survival functions. We propose a two-stage adaptation of a resampling approach that brings the estimated error in line with the truth. In stage 1, we estimate the coefficients in the observed data set and in [Formula: see text] resampled data sets, and allow the resampled coefficient estimates to vote on whether each coefficient should be 0. For those coefficients voted as zero, we set both the point and interval estimates to [Formula: see text] In stage 2, to make inference about coefficients not voted as zero in stage 1, we refit the penalized model in the observed data and in the [Formula: see text] resampled data sets with only variables corresponding to those coefficients. We demonstrate that ensemble voting-based point and interval estimators of the coefficients perform well in finite samples, and prove that the point estimator maintains the oracle property. We extend this approach to derive inference procedures for survival functions and demonstrate that our proposed interval estimation procedures substantially outperform estimators based on asymptotic inference or standard bootstrap. We further illustrate our proposed procedures to predict breast cancer survival in a gene expression study. PMID:27107008

  4. Inference for survival prediction under the regularized Cox model.

    PubMed

    Sinnott, Jennifer A; Cai, Tianxi

    2016-10-01

    When a moderate number of potential predictors are available and a survival model is fit with regularization to achieve variable selection, providing accurate inference on the predicted survival can be challenging. We investigate inference on the predicted survival estimated after fitting a Cox model under regularization guaranteeing the oracle property. We demonstrate that existing asymptotic formulas for the standard errors of the coefficients tend to underestimate the variability for some coefficients, while typical resampling such as the bootstrap tends to overestimate it; these approaches can both lead to inaccurate variance estimation for predicted survival functions. We propose a two-stage adaptation of a resampling approach that brings the estimated error in line with the truth. In stage 1, we estimate the coefficients in the observed data set and in [Formula: see text] resampled data sets, and allow the resampled coefficient estimates to vote on whether each coefficient should be 0. For those coefficients voted as zero, we set both the point and interval estimates to [Formula: see text] In stage 2, to make inference about coefficients not voted as zero in stage 1, we refit the penalized model in the observed data and in the [Formula: see text] resampled data sets with only variables corresponding to those coefficients. We demonstrate that ensemble voting-based point and interval estimators of the coefficients perform well in finite samples, and prove that the point estimator maintains the oracle property. We extend this approach to derive inference procedures for survival functions and demonstrate that our proposed interval estimation procedures substantially outperform estimators based on asymptotic inference or standard bootstrap. We further illustrate our proposed procedures to predict breast cancer survival in a gene expression study.

  5. Predicting Biochemical Failure and Overall Survival Through Intratherapy PSA Changes During Definitive External Beam Radiotherapy

    SciTech Connect

    Soto, Daniel E.; Andridge, Rebecca R.; Taylor, Jeremy M.G.; McLaughlin, Patrick W.; Sandler, Howard M.; Pan, Charlie C.

    2008-12-01

    Purpose: To determine whether intratherapy prostate-specific antigen (itPSA) changes during radiotherapy (RT) predict prostate cancer outcomes. Methods and Materials: We retrospectively identified patients treated with definitive external beam RT without hormonal therapy who had at least two itPSA measurements. We calculated the adjusted ratio of rise (ARR) in itPSA relative to the pretreatment baseline PSA for each patient. This was defined as ln(maximal itPSA + 1)/ln(baseline PSA + 1). We stratified patients according to an ARR of <1 vs. >1.1. This corresponded to an approximately <30% vs. >30% increase in PSA during RT. Univariate and multivariate analyses were performed examining for biochemical failure-free survival (BFFS) and overall survival (OS). Results: At a median follow-up of 74 months, we identified 307 patients who met our criteria. Univariate analysis revealed that patients with an ARR of <1.1 (n = 182) had statistically significant inferior BFFS and OS compared with those with an ARR of >1.1 (n = 125). The median BFFS and OS for these two groups was 51 vs. 101 months (p = 0.001) and 96 vs. 128 months (p = 0.01), respectively. On multivariate analysis, the effect of ARR on the risk of biochemical failure for patients with an ARR of <1.1 was significant (p = 0.03) only during the first year after RT. In contrast, the effect of the ARR on OS remained significant for a full 5 years (p = 0.05). Conclusion: The results of our study have shown that an ARR of <1.1 predicts for inferior BFFS and OS in patients treated with RT alone. PSA measurement during RT is a novel clinical tool that could be used to identify patients who might warrant more aggressive therapeutic intervention.

  6. Data-Driven Metabolic Pathway Compositions Enhance Cancer Survival Prediction

    PubMed Central

    Auslander, Noam; Wagner, Allon; Oberhardt, Matthew; Ruppin, Eytan

    2016-01-01

    Altered cellular metabolism is an important characteristic and driver of cancer. Surprisingly, however, we find here that aggregating individual gene expression using canonical metabolic pathways fails to enhance the classification of noncancerous vs. cancerous tissues and the prediction of cancer patient survival. This supports the notion that metabolic alterations in cancer rewire cellular metabolism through unconventional pathways. Here we present MCF (Metabolic classifier and feature generator), which incorporates gene expression measurements into a human metabolic network to infer new cancer-mediated pathway compositions that enhance cancer vs. adjacent noncancerous tissue classification across five different cancer types. MCF outperforms standard classifiers based on individual gene expression and on canonical human curated metabolic pathways. It successfully builds robust classifiers integrating different datasets of the same cancer type. Reassuringly, the MCF pathways identified lead to metabolites known to be associated with the pertaining specific cancer types. Aggregating gene expression through MCF pathways leads to markedly better predictions of breast cancer patients’ survival in an independent cohort than using the canonical human metabolic pathways (C-index = 0.69 vs. 0.52, respectively). Notably, the survival predictive power of individual MCF pathways strongly correlates with their power in predicting cancer vs. noncancerous samples. The more predictive composite pathways identified via MCF are hence more likely to capture key metabolic alterations occurring in cancer than the canonical pathways characterizing healthy human metabolism. PMID:27673682

  7. 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

  8. 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

  9. 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

  10. Evaluating Random Forests for Survival Analysis using Prediction Error Curves.

    PubMed

    Mogensen, Ulla B; Ishwaran, Hemant; Gerds, Thomas A

    2012-09-01

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

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

    PubMed

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

    2015-10-27

    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.

  12. 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

  13. Survival prediction and gene identification with penalized global AUC maximization.

    PubMed

    Liu, Zhenqiu; Gartenhaus, Ronald B; Chen, Xue-Wen; Howell, Charles D; Tan, Ming

    2009-12-01

    Identifying genes (biomarkers) and predicting the clinical outcomes with censored survival times are important for cancer prognosis and pathogenesis. In this article, we propose a novel method with L(1) penalized global AUC summary maximization (L(1)GAUCS). The L(1)GAUCS method is developed for simultaneous gene (feature) selection and survival prediction. L(1) penalty shrinks coefficients and produces some coefficients that are exactly zero, and therefore selects a small subset of genes (features). It is a well-known fact that many genes are highly correlated in gene expression data and the highly correlated genes may function together. We, therefore, define a correlation measure to identify those genes such that their expression level may be low but they are highly correlated with the downstream highly expressed genes selected with L(1)GAUCS. Partial pathways associated with the correlated genes are identified with DAVID (http://david.abcc.ncifcrf.gov/). Experimental results with chemotherapy and gene expression data demonstrate that the proposed procedures can be used for identifying important genes and pathways that are related to time to death due to cancer and for building a parsimonious model for predicting the survival of future patients. Software is available upon request from the first author.

  14. Selectivity of inferior temporal neurons for realistic pictures predicted by algorithms for image database navigation.

    PubMed

    Allred, Sarah; Liu, Yan; Jagadeesh, Bharathi

    2005-12-01

    Primates have a remarkable ability to perceive, recognize, and discriminate among the plethora of people, places, and things that they see, and neural selectivity in the primate inferotemporal (IT) cortex is thought to underlie this ability. Here we investigated the relationship between neural response and perception by recording from IT neurons in monkeys while they viewed realistic images. We then compared the similarity of neural responses elicited by images to the quantitative similarity of the images. Image similarity was approximated using several algorithms, two of which were designed to search image databases for perceptually similar images. Some algorithms for image similarity correlated well with human perception, and these algorithms explained part of the stimulus selectivity of IT neurons. Images that elicited similar neural responses were ranked as more similar by these algorithms than images that elicited different neural responses, and images ranked as similar by the algorithms elicited similar responses from neurons. Neural selectivity was predicted more accurately when the reference images for algorithm similarity elicited either very strong or very weak responses from the neuron. The degree to which algorithms for image similarity were correlated with human perception was related to the degree to which algorithms explained the selectivity of IT neurons, providing support for the proposal that the selectivity of IT neurons is related to perceptual similarity of images.

  15. Kernel mixture survival models for identifying cancer subtypes, predicting patient's cancer types and survival probabilities.

    PubMed

    Ando, Tomohiro; Imoto, Seiya; Miyano, Satoru

    2004-01-01

    One important application of microarray gene expression data is to study the relationship between the clinical phenotype of cancer patients and gene expression profiles on the whole-genome scale. The clinical phenotype includes several different types of cancers, survival times, relapse times, drug responses and so on. Under the situation that the subtypes of cancer have not been previously identified or known to exist, we develop a new kernel mixture modeling method that performs simultaneously identification of the subtype of cancer, prediction of the probabilities of both cancer type and patient's survival, and detection of a set of marker genes on which to base a diagnosis. The proposed method is successfully performed on real data analysis and simulation studies.

  16. Efron-type measures of prediction error for survival analysis.

    PubMed

    Gerds, Thomas A; Schumacher, Martin

    2007-12-01

    Estimates of the prediction error play an important role in the development of statistical methods and models, and in their applications. We adapt the resampling tools of Efron and Tibshirani (1997, Journal of the American Statistical Association92, 548-560) to survival analysis with right-censored event times. We find that flexible rules, like artificial neural nets, classification and regression trees, or regression splines can be assessed, and compared to less flexible rules in the same data where they are developed. The methods are illustrated with data from a breast cancer trial.

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

    PubMed

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

    2016-01-01

    Interoception is the sensing of physiological signals originating inside the body, such as hunger, pain and heart rate. People with greater sensitivity to interoceptive signals, as measured by, for example, tests of heart beat detection, perform better in laboratory studies of risky decision-making. However, there has been little field work to determine if interoceptive sensitivity contributes to success in real-world, high-stakes risk taking. Here, we report on a study in which we quantified heartbeat detection skills in a group of financial traders working on a London trading floor. We found that traders are better able to perceive their own heartbeats than matched controls from the non-trading population. Moreover, the interoceptive ability of traders predicted their relative profitability, and strikingly, how long they survived in the financial markets. Our results suggest that signals from the body - the gut feelings of financial lore - contribute to success in the markets. PMID:27641692

  18. Interoceptive Ability Predicts Survival on a London Trading Floor

    PubMed Central

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

    2016-01-01

    Interoception is the sensing of physiological signals originating inside the body, such as hunger, pain and heart rate. People with greater sensitivity to interoceptive signals, as measured by, for example, tests of heart beat detection, perform better in laboratory studies of risky decision-making. However, there has been little field work to determine if interoceptive sensitivity contributes to success in real-world, high-stakes risk taking. Here, we report on a study in which we quantified heartbeat detection skills in a group of financial traders working on a London trading floor. We found that traders are better able to perceive their own heartbeats than matched controls from the non-trading population. Moreover, the interoceptive ability of traders predicted their relative profitability, and strikingly, how long they survived in the financial markets. Our results suggest that signals from the body - the gut feelings of financial lore - contribute to success in the markets. PMID:27641692

  19. 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

  20. Down-regulation of α-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface

    PubMed Central

    Cheng, Tzu-Chun; Chen, Li-Ching; Chen, Ming-Yao; Chen, Wen-Ye; Lin, Yen-Kuang; Ho, Chi-Tang; Wu, Chih-Hsiung; Ho, Yuan-Soon

    2015-01-01

    α-L-fucosidase 1 (FUCA1) is a lysosomal enzyme that catalyzes the hydrolytic cleavage of the terminal fucose residue in breast cancer cells. FUCA1 mRNA levels were detected by real-time PCR, and there was a greater than 139-fold increase in FUCA1 mRNA expression in breast tumor samples compared with normal breast tissue samples (*P = 0.005, n = 236). Higher FUCA1 mRNA expression was preferentially detected in early-stage tumors (stage 0 to 2) compared with advanced-stage tumors (stage 3 to 4) (stage 0-1 versus stage 3, *P = 0.015; stage 0-1 versus stage 4, *P = 0.024). FUCA1 protein levels were higher in advanced-stage tumors concomitant with decreased fucosylated Lewis-x antigen expression, as evidenced using the immunohistochemical staining H-score method (*P < 0.001). Statistical analysis revealed that lower FUCA1 levels significantly predicted an inferior overall survival rate among triple-negative breast cancer (TNBC) patients compared with non-TNBC patients (*P = 0.009). Two stable FUCA1 siRNA knock-down MDA-MB-231 cell lines were established, and the results suggest that transient FUCA inhibition creates a selective pressure that triggers the metastasis of primary tumor cells, as detected by wound healing and invasion assays (*P < 0.01). The results suggest that FUCA1 may be a potential prognostic molecular target for clinical use, especially in TNBC patients. PMID:26204487

  1. 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

  2. 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

  3. Usefulness of ultrasonographic measurement of the diameter of the inferior vena cava to predict responsiveness to intravascular fluid administration in patients with cancer

    PubMed Central

    Arredondo-Armenta, Juan M.; Guevara-García, Humberto; Barragán-Dessavre, Mireya; García-Guillén, Francisco J.; Sánchez-Hurtado, Luis A.; Córdova-Sánchez, Bertha; Bautista-Ocampo, Andoreni R.; Herrera-Gómez, Angel; Meneses-García, Abelardo

    2016-01-01

    We conducted an observational, longitudinal prospective study in which we measured the diameters of the inferior vena cava (IVC) of 47 patients using ultrasonography. The aim of our study was to assess the state of blood volume and to determine the percentage of patients who responded to intravascular volume expansion. Only 17 patients (36%) responded to fluid management. A higher number of responding patients had cardiovascular failure compared with nonresponders (82% vs. 50%, P = 0.03). Among the patients with cardiovascular failure, the probability of finding responders was 4.6 times higher than that of not finding responders (odds ratio, 4.66; 95% confidence interval, 1.10–19.6; P = 0.04). No significant difference was observed in the mortality rate between the two groups (11% vs. 23%, P = 0.46). In conclusion, responding to intravascular volume expansion had no impact on patient survival in the intensive care unit. PMID:27695165

  4. Usefulness of ultrasonographic measurement of the diameter of the inferior vena cava to predict responsiveness to intravascular fluid administration in patients with cancer

    PubMed Central

    Arredondo-Armenta, Juan M.; Guevara-García, Humberto; Barragán-Dessavre, Mireya; García-Guillén, Francisco J.; Sánchez-Hurtado, Luis A.; Córdova-Sánchez, Bertha; Bautista-Ocampo, Andoreni R.; Herrera-Gómez, Angel; Meneses-García, Abelardo

    2016-01-01

    We conducted an observational, longitudinal prospective study in which we measured the diameters of the inferior vena cava (IVC) of 47 patients using ultrasonography. The aim of our study was to assess the state of blood volume and to determine the percentage of patients who responded to intravascular volume expansion. Only 17 patients (36%) responded to fluid management. A higher number of responding patients had cardiovascular failure compared with nonresponders (82% vs. 50%, P = 0.03). Among the patients with cardiovascular failure, the probability of finding responders was 4.6 times higher than that of not finding responders (odds ratio, 4.66; 95% confidence interval, 1.10–19.6; P = 0.04). No significant difference was observed in the mortality rate between the two groups (11% vs. 23%, P = 0.46). In conclusion, responding to intravascular volume expansion had no impact on patient survival in the intensive care unit.

  5. 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

  6. [A Case of Long-Term Survival of a Patient with Liver Metastasis of Colon Cancer and Suspected Inferior Vena Cava Invasion].

    PubMed

    Otani, Takahiro; Kameyama, Hitoshi; Kaneko, Kazuhiro; Sato, Tomoi; Suzuki, Susumu; Okada, Takayuki; Aono, Takashi; Muto, Ichiro; Hasegawa, Masaki; Sakata, Jun; Kobayashi, Takashi; Minagawa, Masahiro; Kosugi, Shin-ichi; Kurosaki, Isao; Wakai, Toshifumi

    2015-11-01

    A 58-year-old woman was diagnosed with a sigmoid colon cancer and synchronous liver metastasis. Because an obstruction of the sigmoid colon was identified, the patient underwent sigmoidectomy. Computed tomography(CT)findings suggested possible vena cava and hepatic vein invasion. Therefore, the decision was made to offer systemic chemotherapy. The patient underwent 6 courses of chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6). After 4 courses of chemotherapy, CT scans showed a significant reduction of the liver metastasis (reduction rate of 5 0%; a partial response) and demonstrated improved exclusion of the inferior vena cava and hepatic vein. After 6 courses of chemotherapy, we performed right trisegmentectomy of the liver and resection of the inferior vena cava and diaphragm. Postoperative pathological findings revealed negative margins, and no invasion of the inferior vena cava. The pathological response grade of the tumor after chemotherapy was determined to be Grade 2. Adjuvant chemotherapy was not performed because of the patient 's poor performance status. The patient was alive with no recurrence 8 years after resection of the liver metastasis. PMID:26805305

  7. 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

  8. 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

  9. 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

  10. Gene identification and survival prediction with Lp Cox regression and novel similarity measure.

    PubMed

    Liu, Zhenqiu; Jiang, Feng

    2009-01-01

    In this paper, Cox's proportional hazards model with Lp penalty method is developed for simultaneous gene selection and survival prediction. Lp penalty shrinks coefficients and produces some coefficients that are exactly zero, and therefore can be used to identify survival related downstream genes. We also define a novel similarity measure to hunt the regulatory genes that their gene expression changes may be low but they are highly correlated with the selected genes. Experimental results with gene expression data demonstrate that the proposed procedures can be used for identifying important gene clusters that are related to time to death due to cancer and for building parsimonious model for predicting the survival of future patients.

  11. 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

  12. 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

  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. MiRNA expression patterns predict survival in glioblastoma

    PubMed Central

    2011-01-01

    Background In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed. Methods 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom® Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. Results It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status. Conclusions At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required. PMID:22074483

  15. Characterization of wafer charging mechanisms and oxide survival prediction methodology

    SciTech Connect

    Lukaszek, W.; Dixon, W.; Vella, M.; Messick, C.; Reno, S.; Shideler, J.

    1994-04-01

    Unipolar, EEPROM-based peak potential sensors and current sensors have been used to characterize the I-V relationship of charging transients which devices normally experience during the course of ion implantation. The results indicate that the charging sources may appear to behave like current-sources or voltage-sources, depending on the impedance of the load. This behavior may be understood in terms of plasma concepts. The ability to empirically characterize the I-V characteristics of charging sources using the CHARM-2 monitor wafers opens the way for prediction of failure rates of oxides subjected to specific processes, if the oxide Q{sub bd} distributions are known.

  16. 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

  17. 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

  18. 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

  19. Use of respiratory function tests to predict survival in amyotrophic lateral sclerosis.

    PubMed

    Baumann, Fusun; Henderson, Robert D; Morrison, Stephen C; Brown, Michael; Hutchinson, N; Douglas, James A; Robinson, Peter J; McCombe, Pamela A

    2010-01-01

    Respiratory function tests (RFTs) are commonly used as a measure of progression in ALS. This study assessed the ability of various RFTs to predict survival in ALS patients. Subjects with ALS had one or more measurements of seated and supine FVC, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). Kaplan-Meier (KM) analysis was used to determine whether patients with abnormal RFTs had shorter survival than those with normal RFTs. The sensitivity and specificity of RFTs as predictors of two-year survival were calculated from receiver operating characteristic (ROC) curves. With KM analysis, subjects with abnormal values of seated FVC, supine FVC, MIP and MEP had significantly reduced survival compared to subjects with normal values. With ROC curves, a normal supine FVC was highly predictive for two-year survival and had superior sensitivity over seated FVC. Slower rates of decline in seated or supine FVC were strong predictors of two-year survival. Our study demonstrates that respiratory function measurements are useful to predict survival in ALS patients. We show that measurements of FVC in the supine position are worth including in the assessment of respiratory function in ALS.

  20. Forced vital capacity predicts long-term survival for curative-resected NSCLC.

    PubMed

    Guo, Xi; Cao, Hongxin; Xu, Jun; Yu, Jianyu; Zheng, Chunlong; Meng, Long; Du, Jiajun

    2014-09-01

    We conducted a retrospective study in patients with non-small cell lung cancer (NSCLC) who underwent curative lung resection to seek for better lung function parameters associated with long-term survival after lung resection. From January 2006 to December 2008, 470 patients who underwent lung resection with a postoperative diagnosis of NSCLC were studied. Median survival time was 60 months. Patients with pulmonary function values <80 % of predicted were defined as lung function impairment. Patients with impaired vital capacity, maximal voluntary ventilation, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) or diffusion capacity for carbon monoxide (DLCO) had significant shorter overall survival time (P = 0.024; P = 0.026; P < 0.001; P = 0.027; P = 0.007). In univariate analysis, VC, FVC, FEV1 and DLCO were found to have significant effect on overall survival. In multivariate analysis, FVC (HR, 2.029; 95 % CI 1.126-3.659; P = 0.019) was found to be an independent prognostic predictor of long-term overall survival. For cancer-specific survival, FVC (HR 2.404; 95 % CI 1.300-4.445; P = 0.005) was also found to be an independent prognostic predictor in multivariable analysis. Preoperative FVC, rather than FEV1 or DLCO, is an independent prognostic predictor for long-term survival. FVC is not only an indicator of lung function but also of great value for surgeons to predict survival after lung resection.

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

    PubMed

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

    2015-08-03

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

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

    PubMed

    Easton, Dexter M; Hirsch, Henry R

    2008-12-01

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

  3. 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

  4. Low Serum Vitamin D Levels Are Associated With Inferior Survival in Follicular Lymphoma: A Prospective Evaluation in SWOG and LYSA Studies

    PubMed Central

    Kelly, Jennifer L.; Salles, Gilles; Goldman, Bryan; Fisher, Richard I.; Brice, Pauline; Press, Oliver; Casasnovas, Olivier; Maloney, David G.; Soubeyran, Pierre; Rimsza, Lisa; Haioun, Corinne; Xerri, Luc; LeBlanc, Michael; Tilly, Hervé; Friedberg, Jonathan W.

    2015-01-01

    Purpose Recent literature reports a potential association between high vitamin D and improved lymphoma prognosis. We evaluated the impact of pretreatment vitamin D on follicular lymphoma (FL) outcome. Patients and Methods SWOG participants were previously untreated patients with FL enrolled onto SWOG clinical trials (S9800, S9911, or S0016) involving CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab) between 1998 and 2008. Participants included in our second independent cohort were also previously untreated patients with FL enrolled onto the Lymphoma Study Association (LYSA) PRIMA trial of rituximab plus chemotherapy (randomly assigned to rituximab maintenance v observation) between 2004 and 2007. Using the gold-standard liquid chromatography–tandem mass spectrometry method, 25-hydroxyvitamin D was measured in stored baseline serum samples. The primary end point was progression-free survival (PFS). Results After a median follow-up of 5.4 years, the adjusted PFS and overall survival hazard ratios for the SWOG cohort were 1.97 (95% CI, 1.10 to 3.53) and 4.16 (95% CI, 1.66 to 10.44), respectively, for those who were vitamin D deficient (< 20 ng/mL; 15% of cohort). After a median follow-up of 6.6 years, the adjusted PFS and overall survival hazard ratios for the LYSA cohort were 1.50 (95% CI, 0.93 to 2.42) and 1.92 (95% CI, 0.72 to 5.13), respectively, for those who were vitamin D deficient (< 10 ng/mL; 25% of cohort). Conclusion Although statistical significance was not reached in the LYSA cohort, the consistent estimates of association between low vitamin D levels and FL outcomes in two independent cohorts suggests that serum vitamin D might be the first potentially modifiable factor to be associated with FL survival. Further investigation is needed to determine the effects of vitamin D supplementation in this clinical setting. PMID:25823738

  5. A nomogram that predicts pathologic complete response to neoadjuvant chemoradiation also predicts survival outcomes after definitive chemoradiation for esophageal cancer

    PubMed Central

    Wang, Jingya; Allen, Pamela K.; Correa, Arlene M.; Maru, Dipen M.; Swisher, Stephen G.; Hofstetter, Wayne L.; Liao, Zhongxing; Ajani, Jaffer A.

    2015-01-01

    Background Pathologic complete response (pCR) to neoadjuvant chemoradiation for esophageal cancer is associated with improved outcomes. We evaluated whether a nomogram designed to predict who would have a pCR after trimodality therapy could also predict outcome after definitive chemoradiation. Methods Patients in this retrospective, single-institution analysis had received chemoradiation without surgery for esophageal cancer from 1998 through 2010; 333 such patients had complete information on all variables required for the pCR nomogram: sex; T status (by endoscopic sonography); tumor grade; tumor avidity on positron emission tomography (PET); and esophagogastroduodenoscopy (EGD)-directed biopsy results after chemoradiation. We used multivariate Cox regression to test potential associations between clinical outcomes [overall survival (OS), locoregional recurrence, and distant metastasis] and patient or treatment factors and the pCR nomogram score; the component variables of the nomogram were not reintroduced into the multivariate analysis. Results The median follow-up time for all patients (median age 66 years) was 18.2 months (30.7 months for those alive at the time of analysis). Patients with nomogram scores ≤125 (median for all patients) had significantly worse outcomes than patients with scores >125: median OS time 19.7 vs. 48.2 months; disease-free survival (DFS) time 6.1 vs. 31.1 months; locoregional failure-free survival time 17.7 months vs. not reached; and distant metastasis-free survival time 11.7 months vs. not reached (all P<0.001). Multivariate Cox regression analysis indicated that nomogram score independently predicted each survival outcome, along with other patient and disease factors. Conclusions The pCR nomogram score predicted survival outcomes in patients receiving definitive chemoradiation for esophageal cancer. Although this nomogram requires further validation, it may prove useful for stratifying patients for clinical trials designed to

  6. 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.

  7. 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

  8. 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.

  9. Reactive oxygen species-associated molecular signature predicts survival in patients with sepsis.

    PubMed

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

    2016-06-01

    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

  10. 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.

  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.

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

    PubMed

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

    2016-02-01

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

  13. 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

  14. 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

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

    PubMed

    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.

  16. 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

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

    PubMed

    Bi, Xi-wen; Wang, Liang; Zhang, Wen-wen; 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.

  18. Bilateral inferior turbinate osteoma

    PubMed Central

    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

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

    PubMed

    Wang, Ming; Long, Qi

    2016-09-01

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

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

    DOE PAGES

    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

  2. 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

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

    PubMed

    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

  4. 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.

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

    PubMed

    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.

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

    PubMed

    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

  7. 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

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

    PubMed

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

    2014-09-01

    Factors such as temperature, water activity (aw), substrate, culture media, serotype, and strain influence the survival of Salmonella in low-aw foods. Predictive models for Salmonella survival in low-aw foods at temperatures ranging from 21 to 80(u) C and water activities below 0.6 were previously developed. Literature data on survival of Salmonella in low-aw foods were analyzed in the present study to validate these predictive models and to determine global influencing factors. The results showed the Weibull model provided suitable fits to the data in 75% of the curves as compared with the log-linear model. The secondary models predicting the time required for log-decimal reduction (log δ) and shape factor (log β) values were useful in predicting the survival of Salmonella in low-aw foods. Statistical analysis indicated overall fail-safe secondary models, with 88% of the residuals in the acceptable and safe zones (<0.5 log CFU) and a 59% correlation coefficient (R(2) = 0.35). A high variability in log δ-values and log β-values was observed, emphasizing the importance of experimental design. Factors of significant influence on the times required for first log-decimal reduction included temperature, aw, product, and serotype. Log β-values were significantly influenced by serotype, the type of inoculum (wet or dry), and whether the recovery media was selective or not. The results of this analysis provide a general overview of survival kinetics of Salmonella in low-aw foods and its influencing factors. PMID:25198835

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

    PubMed

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

    2014-09-01

    Factors such as temperature, water activity (aw), substrate, culture media, serotype, and strain influence the survival of Salmonella in low-aw foods. Predictive models for Salmonella survival in low-aw foods at temperatures ranging from 21 to 80(u) C and water activities below 0.6 were previously developed. Literature data on survival of Salmonella in low-aw foods were analyzed in the present study to validate these predictive models and to determine global influencing factors. The results showed the Weibull model provided suitable fits to the data in 75% of the curves as compared with the log-linear model. The secondary models predicting the time required for log-decimal reduction (log δ) and shape factor (log β) values were useful in predicting the survival of Salmonella in low-aw foods. Statistical analysis indicated overall fail-safe secondary models, with 88% of the residuals in the acceptable and safe zones (<0.5 log CFU) and a 59% correlation coefficient (R(2) = 0.35). A high variability in log δ-values and log β-values was observed, emphasizing the importance of experimental design. Factors of significant influence on the times required for first log-decimal reduction included temperature, aw, product, and serotype. Log β-values were significantly influenced by serotype, the type of inoculum (wet or dry), and whether the recovery media was selective or not. The results of this analysis provide a general overview of survival kinetics of Salmonella in low-aw foods and its influencing factors.

  10. 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

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

    PubMed

    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.

  12. 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

  13. Predicting survival of grass shrimp (Palaemonetes pugio) exposed to naphthalene, fluorene, and dibenzothiophene.

    PubMed

    Unger, Michael A; Newman, Michael C; Vadas, George G

    2008-08-01

    The composition and persistence of dissolved polycyclic aromatic hydrocarbons (PAHs) released to the water column during oil spills are altered by weathering, tidal transport, and addition of dispersants. Conventional toxicity effect metrics, such as the median lethal concentration (LC50), are inaccurate predictors of mortality from all toxicant exposure duration/concentration combinations likely to occur during spills. In contrast, survival models can predict the proportions of animals dying as a consequence of exposures differing in duration and intensity. Extending previous work with ethylnaphthalene, dimethylnaphthalene, and phenanthrene, survival time models were developed that include exposure duration and concentration to predict time to death for grass shrimp (Palaemonetes pugio). Two additional PAHs (naphthalene and fluorene) and a heterocyclic aromatic hydrocarbon (dibenzothiophene) were evaluated for the present study. Preliminary explorations of these models confirmed that quantitative structure- activity regression models were possible for predicting survival model parameters from compound characteristics. Conventional 48-h LC50s also were calculated for the compounds and combined with published LC50s to predict relative PAH toxicity to P. pugio based on octanol-water partitioning. PMID:18380521

  14. 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.

  15. 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

  16. Gene signatures of drug resistance predict patient survival in colorectal cancer

    PubMed Central

    Zheng, Y; Zhou, J; Tong, Y

    2015-01-01

    Different combinations of 5-fluorouracil (5-FU), oxaliplatin, irinotecan and other newly developed agents have been used to treat colorectal cancer. Despite the advent of new treatment regimens, the 5-year survival rate for metastatic colorectal cancer remains low (~10%). Knowing the drug sensitivity of a given tumor for a particular agent could significantly impact decision making and treatment planning. Biomarkers are proven to be successful in characterizing patients into different response groups. Using survival prediction analysis, we have identified three independent gene signatures, which are associated with sensitivity of colorectal cancer cells to 5-FU, oxaliplatin or irinotecan. On the basis of the three gene signatures, three score systems were developed to stratify patients from sensitive to resistance. These score systems exhibited robustness in stratify patients in two independent clinical studies. Patients with high scores in all three drugs exhibited the lowest survival. PMID:25179828

  17. 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

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

    PubMed

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

    2014-06-22

    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.

  19. Longitudinal Temporal and Probabilistic Prediction of Survival in a Cohort of Patients With Advanced Cancer

    PubMed Central

    Perez-Cruz, Pedro E.; dos Santos, Renata; Silva, Thiago Buosi; Crovador, Camila Souza; Nascimento, Maria Salete de Angelis; Hall, Stacy; Fajardo, Julieta; Bruera, Eduardo; Hui, David

    2014-01-01

    Context Survival prognostication is important during end-of-life. The accuracy of clinician prediction of survival (CPS) over time has not been well characterized. Objectives To examine changes in prognostication accuracy during the last 14 days of life in a cohort of patients with advanced cancer admitted to two acute palliative care units and to compare the accuracy between the temporal and probabilistic approaches. Methods Physicians and nurses prognosticated survival daily for cancer patients in two hospitals until death/discharge using two prognostic approaches: temporal and probabilistic. We assessed accuracy for each method daily during the last 14 days of life comparing accuracy at day −14 (baseline) with accuracy at each time point using a test of proportions. Results 6718 temporal and 6621 probabilistic estimations were provided by physicians and nurses for 311 patients, respectively. Median (interquartile range) survival was 8 (4, 20) days. Temporal CPS had low accuracy (10–40%) and did not change over time. In contrast, probabilistic CPS was significantly more accurate (p<.05 at each time point) but decreased close to death. Conclusion Probabilistic CPS was consistently more accurate than temporal CPS over the last 14 days of life; however, its accuracy decreased as patients approached death. Our findings suggest that better tools to predict impending death are necessary. PMID:24746583

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Nomogram prediction for overall survival of patients diagnosed with cervical cancer

    PubMed Central

    Polterauer, S; Grimm, C; Hofstetter, G; Concin, N; Natter, C; Sturdza, A; Pötter, R; Marth, C; Reinthaller, A; Heinze, G

    2012-01-01

    Background: Nomograms are predictive tools that are widely used for estimating cancer prognosis. The aim of this study was to develop a nomogram for the prediction of overall survival (OS) in patients diagnosed with cervical cancer. Methods: Cervical cancer databases of two large institutions were analysed. Overall survival was defined as the clinical endpoint and OS probabilities were estimated using the Kaplan–Meier method. Based on the results of survival analyses and previous studies, relevant covariates were identified, a nomogram was constructed and validated using bootstrap cross-validation. Discrimination of the nomogram was quantified with the concordance probability. Results: In total, 528 consecutive patients with invasive cervical cancer, who had all nomogram variables available, were identified. Mean 5-year OS rates for patients with International Federation of Gynecologists and Obstetricians (FIGO) stage IA, IB, II, III, and IV were 99.0%, 88.6%, 65.8%, 58.7%, and 41.5%, respectively. Seventy-six cancer-related deaths were observed during the follow-up period. FIGO stage, tumour size, age, histologic subtype, lymph node ratio, and parametrial involvement were selected as nomogram covariates. The prognostic performance of the model exceeded that of FIGO stage alone and the model's estimated optimism-corrected concordance probability was 0.723, indicating accurate prediction of OS. We present the prediction model as nomogram and provide a web-based risk calculator (http://www.ccc.ac.at/gcu). Conclusion: Based on six easily available parameters, a novel statistical model to predict OS of patients diagnosed with cervical cancer was constructed and validated. The model was implemented in a nomogram and provides accurate prediction of individual patients' prognosis useful for patient counselling and deciding on follow-up strategies. PMID:22871885

  5. 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

  6. 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

  7. Random Survival Forests for Predicting the Bed Occupancy in the Intensive Care Unit

    PubMed Central

    Ruyssinck, Joeri; Houthooft, Rein; Couckuyt, Ivo; Gadeyne, Bram; Colpaert, Kirsten; Decruyenaere, Johan; De Turck, Filip; Dhaene, Tom

    2016-01-01

    Predicting the bed occupancy of an intensive care unit (ICU) is a daunting task. The uncertainty associated with the prognosis of critically ill patients and the random arrival of new patients can lead to capacity problems and the need for reactive measures. In this paper, we work towards a predictive model based on Random Survival Forests which can assist physicians in estimating the bed occupancy. As input data, we make use of the Sequential Organ Failure Assessment (SOFA) score collected and calculated from 4098 patients at two ICU units of Ghent University Hospital over a time period of four years. We compare the performance of our system with a baseline performance and a standard Random Forest regression approach. Our results indicate that Random Survival Forests can effectively be used to assist in the occupancy prediction problem. Furthermore, we show that a group based approach, such as Random Survival Forests, performs better compared to a setting in which the length of stay of a patient is individually assessed.

  8. A simulation study of predictive ability measures in a survival model I: explained variation measures.

    PubMed

    Choodari-Oskooei, Babak; Royston, Patrick; Parmar, Mahesh K B

    2012-10-15

    Measures of predictive ability play an important role in quantifying the clinical significance of prognostic factors. Several measures have been proposed to evaluate the predictive ability of survival models in the last two decades, but no single measure is consistently used. The proposed measures can be classified into the following categories: explained variation, explained randomness, and predictive accuracy. The three categories are conceptually different and are based on different principles. Several new measures have been proposed since Schemper and Stare's study in 1996 on some of the existing measures. This paper is the first of two papers that study the proposed measures systematically by applying a set of criteria that a measure of predictive ability should possess in the context of survival analysis. The present paper focuses on the explained variation category, and part II studies the proposed measures in the other categories. Simulation studies are used to examine the performance of five explained variation measures with respect to these criteria, discussing their strengths and shortcomings. Our simulation studies show that the measures proposed by Kent and O'Quigley, R(PM)(2), and Royston and Sauerbrei, R(D)(2), appear to be the best overall at quantifying predictive ability. However, it should be noted that neither measure is perfect; R(PM)(2) is sensitive to outliers and R(D)(2) to (marked) non-normality of the distribution of the prognostic index. The results show that the other measures perform poorly, primarily because they are adversely affected by censoring.

  9. Sample size considerations of prediction-validation methods in high-dimensional data for survival outcomes.

    PubMed

    Pang, Herbert; Jung, Sin-Ho

    2013-04-01

    A variety of prediction methods are used to relate high-dimensional genome data with a clinical outcome using a prediction model. Once a prediction model is developed from a data set, it should be validated using a resampling method or an independent data set. Although the existing prediction methods have been intensively evaluated by many investigators, there has not been a comprehensive study investigating the performance of the validation methods, especially with a survival clinical outcome. Understanding the properties of the various validation methods can allow researchers to perform more powerful validations while controlling for type I error. In addition, sample size calculation strategy based on these validation methods is lacking. We conduct extensive simulations to examine the statistical properties of these validation strategies. In both simulations and a real data example, we have found that 10-fold cross-validation with permutation gave the best power while controlling type I error close to the nominal level. Based on this, we have also developed a sample size calculation method that will be used to design a validation study with a user-chosen combination of prediction. Microarray and genome-wide association studies data are used as illustrations. The power calculation method in this presentation can be used for the design of any biomedical studies involving high-dimensional data and survival outcomes.

  10. 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.

  11. 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

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

    PubMed Central

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

    2016-01-01

    Pretreatment characteristics are suggested as predictive and/or prognostic factors for nasopharyngeal carcinoma (NPC); however, individual tumor radiosensitivities have previously not been considered. As boost planning is recommended for NPC, we performed interim assessments of magnetic resonance (MR) images for boost planning and retrospectively evaluated their predictive value for the survival of NPC patients. Radiation therapy via elective nodal irradiation (median dose: 39.6 Gy) with/without chemotherapy was used to treat 63 NPC patients. Boost irradiation (median total dose: 70 Gy) was performed based on the interim assessment. The largest lymph node (LN) was measured on MR images acquired at the time of interim assessment. The site of first failure was local in 8 (12.7%), regional in 7 (11.1%), and distant in 12 patients (19.0%). All 7 patients with regional failure harbored LNs ≥15 mm at interim assessment. We divided the 63 patients into two groups based on LN size [large (≥15 mm), n = 10 and small (<15 mm), n = 53]. Univariate analysis showed that 5-year overall survival (OS) and cause-specific survival (CSS) rates for large LNs were significantly lower than for small LNs (OS: 12.5% vs 70.5%, P < 0.001 and CSS: 25.0% vs 80.0%, P < 0.001). Multivariate analysis showed that large LNs were a significantly unfavorable factor for both OS (hazard ratio = 4.543, P = 0.002) and CSS (hazard ratio = 6.020, P = 0.001). The results suggest that LN size at interim assessment could predict survival in NPC patients. PMID:27242338

  13. 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

  14. 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

  15. A Simpler Creatinine Index Can Predict Long-Term Survival in Chinese Hemodialysis Patients

    PubMed Central

    Lee, Szu-Ying; Yang, Chung-Wei; Hung, Szu-Chun; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Background Low lean body mass (LBM) is an indicator of malnutrition inflammation syndrome, which is common in hemodialysis (HD) patients. The creatinine index (CI) has been validated as a reliable method to estimate LBM and evaluate the protein-energy status of HD patients. However, the traditional creatinine index formula was complex. We sought to investigate the impact of CI derived from a new simple formula on Chinese HD patient outcomes. Methods In this retrospective cohort study, we enrolled 1269 patients who initiated HD between February 1981 and February 2012 and followed them until the end of February 2013. CI was calculated using the simple creatinine kinetic model (CKM) formula. Multiple linear regression analysis and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. Results The 1269 HD patients were categorized into 3 groups according to the tertiles of calculated CI between men and women. Each group consisted of 423 patients (50.6% men, 49.4% women). Patients in the highest sex-specific tertile of CI had longer overall survival (HR, 0.46; P 0.002). BMI did not significantly associate with survival after adjustment (HR,0.99; P 0.613). Conclusions CI derived from the simple CKM formula serves as a good parameter than BMI to predict the survival of HD patients. The formula could extend its convenient use in clinical practice for HD patients. PMID:27780214

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

    PubMed

    Ascolani, Gianluca; Occhipinti, Annalisa; Liò, Pietro

    2015-05-01

    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.

  17. 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

  18. Cytokeratin-20 and Survivin-Expressing Circulating Tumor Cells Predict Survival in Metastatic Colorectal Cancer Patients by a Combined Immunomagnetic qRT-PCR Approach.

    PubMed

    Ning, Yan; Hanna, Diana L; Zhang, Wu; Mendez, Angela; Yang, Dongyun; El-Khoueiry, Rita; Matsusaka, Satoshi; Sunakawa, Yu; Stremitzer, Stefan; Parekh, Anish; Okazaki, Satoshi; Berger, Martin D; Barzi, Afsaneh; Lenz, Heinz-Josef

    2015-10-01

    Circulating tumor cells (CTC) express epithelial and stem cell-like genes, though current approved detection methods mainly use epithelial markers. We optimized a CTC isolation method that could capture their molecular heterogeneity and predict overall survival (OS) in metastatic colorectal cancer (mCRC) patients receiving various chemotherapy regimens. We combined immunomagnetic enrichment of CD45-negative, EpCAM-positive circulating cancer cells with qRT-PCR amplification of CK20 and survivin expression in 88 mCRC patients and 20 healthy controls. We then evaluated the prognostic value of baseline CTC CK20 and survivin expression in mCRC patients. The presence of elevated CTC CK20 or survivin expression distinguished mCRC patients from controls with sufficient sensitivity (79.6%) and specificity (85%). In univariate analysis, patients with high CTC-CK20 expression (9 vs. 33.2+ months, log-rank P < 0.001) or high CTC-survivin expression (10 vs. 33.2+ months, log-rank P = 0.032) had a significantly worse median OS than those with low expression of either marker. In multivariable analysis, the high CTC-CK20 group had significantly shortened OS (HR, 3.11; adjusted P = 0.01), and there was a trend toward inferior OS in the high CTC-survivin group (HR, 1.76; adjusted P = 0.099). Patients with either high CTC CK20 or survivin expression had inferior OS compared with those with low expression of both markers (HR, 4.39; 95% confidence interval, 1.56-12.35; adjusted P = 0.005). Colorectal cancer CTCs can be reliably isolated using epithelial and stem cell markers. CTC CK20 and survivin expression may effectively predict OS in mCRC patients receiving chemotherapy.

  19. 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

  20. Clinical Nomogram for Predicting Survival Outcomes in Early Mucinous Breast Cancer

    PubMed Central

    Jiang, Mengjie; Li, Dan; Jiang, Ting; Hong, Zhongwu; Wang, Fan; Li, Shuguang

    2016-01-01

    Background The features related to the prognosis of patients with mucinous breast cancer (MBC) remain controversial. We aimed to explore the prognostic factors of MBC and develop a nomogram for predicting survival outcomes. Methods The Surveillance, Epidemiology, and End Results (SEER) database was searched to identify 139611 women with resectable breast cancer from 1990 to 2007. Survival curves were generated using Kaplan-Meier methods. The 5-year and 10-year cancer-specific survival (CSS) rates were calculated using the Life-Table method. Based on Cox models, a nomogram was constructed to predict the probabilities of CSS for an individual patient. The competing risk regression model was used to analyse the specific survival of patients with MBC. Results There were 136569 (97.82%) infiltrative ductal cancer (IDC) patients and 3042 (2.18%) MBC patients. Patients with MBC had less lymph node involvement, a higher frequency of well-differentiated lesions, and more estrogen receptor (ER)-positive tumors. Patients with MBC had significantly higher 5 and10-year CSS rates (98.23 and 96.03%, respectively) than patients with IDC (91.44 and 85.48%, respectively). Univariate and multivariate analyses showed that MBC was an independent factor for better prognosis. As for patients with MBC, the event of death caused by another disease exceeded the event of death caused by breast cancer. A competing risk regression model further showed that lymph node involvement, poorly differentiated grade and advanced T-classification were independent factors of poor prognosis in patients with MBC. The Nomogram can accurately predict CSS with a high C-index (0.816). Risk scores developed from the nomogram can more accurately predict the prognosis of patients with MBC (C-index = 0.789) than the traditional TNM system (C-index = 0.704, P< 0.001). Conclusions Patients with MBC have a better prognosis than patients with IDC. Nomograms could help clinicians make more informed decisions in

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Accuracy of Life Tables in Predicting Overall Survival in Candidates for Radiotherapy for Prostate Cancer

    SciTech Connect

    Walz, Jochen; Gallina, Andrea; Hutterer, Georg; Perrotte, Paul; Shariat, Shahrokh F.; Graefen, Markus; McCormack, Michael; Benard, Francois; Valiquette, Luc; Saad, Fred; Karakiewicz, Pierre I.

    2007-09-01

    Purpose: To test the accuracy of life tables (LTs) in predicting survival in men treated with radiotherapy for localized prostate cancer. Methods and Materials: We selected the records of 3,176 patients treated with radiotherapy and who had no clinical evidence of disease relapse. Life table-derived life expectancy (LE) was defined for every individual using a population-specific LT. Age, Charlson Comorbidity Index (CCI), and LT-derived LE were then used as predictors of overall mortality in Cox regression models. Predictive accuracy (PA) was estimated with the Harrell's concordance index and was internally validated with 200 bootstrap resamples. Results: The actuarial median survival was 4.7 years (mean, 6.4 years). At radiotherapy, median age was 70.6 years, median CCI was 2, and median LT-derived LE was 12 years. All variables were statistically significant predictors of overall mortality (all p values <0.001). Age (PA, 60.2%), CCI (PA, 60.1%), and LT-derived LE (PA, 60.2%) were equally accurate. Finally, when age and CCI were combined (PA, 63.2%), both variables provided more accurate mortality predictions than either variable alone (all p values = 0.01). Conclusions: Life tables have a limited ability to predict LE in patients treated with radiotherapy for prostate cancer. We, therefore, recommend the use of multivariate prognostic models that integrate several variables, such as at least age and comorbidities, to estimate LE. This might help to improve LE estimation during prostate cancer treatment decision making.

  7. 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

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

    PubMed

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

    2012-01-01

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

  9. A Simple Risk Model to Predict Survival in Patients With Carcinoma of Unknown Primary Origin

    PubMed Central

    Huang, Chen-Yang; Lu, Chang-Hsien; Yang, Chan-Keng; Hsu, Hung-Chih; Kuo, Yung-Chia; Huang, Wen-Kuan; Chen, Jen-Shi; Lin, Yung-Chang; Chia-Yen, Hung; Shen, Wen-Chi; Chang, Pei-Hung; Yeh, Kun-Yun; Hung, Yu-Shin; Chou, Wen-Chi

    2015-01-01

    Abstract Carcinoma of unknown primary origin (CUP) is characterized by diverse histological subtypes and clinical presentations, ranging from clinically indolent to frankly aggressive behaviors. This study aimed to identify prognostic factors of CUP and to develop a simple risk model to predict survival in a cohort of Asian patients. We retrospectively reviewed 190 patients diagnosed with CUP between 2007 and 2012 at a single medical center in Taiwan. The clinicopathological parameters and outcomes of our cohort were analyzed. A risk model was developed using multivariate logistic regression and a prognostic score was generated. The prognostic score was calculated based on 3 independent prognostic variables: the Eastern Cooperative Oncology Group (ECOG) scale (0 points if the score was 1, 2 points if it was 2–4), visceral organ involvement (0 points if no involvement, 1 point if involved), and the neutrophil-to-lymphocyte ratio (0 points if ≤3, 1 point if >3). Patients were stratified into good (score 0), intermediate (score 1–2), and poor (score 3–4) prognostic groups based on the risk model. The median survival (95% confidence interval) was 1086 days (500–1617, n = 42), 305 days (237–372, n = 75), and 64 days (44–84, n = 73) for the good, intermediate, and poor prognostic groups, respectively. The c-statistics using the risk model and ECOG scale for the outcome of 1-year mortality were 0.80 and 0.70 (P = 0.038), respectively. In this study, we developed a simple risk model that accurately predicted survival in patients with CUP. This scoring system may be used to help patients and clinicians determine appropriate treatments. PMID:26632736

  10. Donor Chimerism Early after Reduced-intensity Conditioning Hematopoietic Stem Cell Transplantation Predicts Relapse and Survival

    PubMed Central

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

    2015-01-01

    The impact of early donor cell chimerism on outcomes of T-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill-defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T-cell chimerism was also assessed. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse and non-relapse mortality (NRM). 688 patients with hematologic malignancies (48% myeloid; 52% lymphoid) and a median age of 57 years (range, 18-74) undergoing RIC HSCT with T-replete donor grafts (97% peripheral blood; 92% HLA-matched) and median follow-up of 58.2 months (range, 12.6-120.7) were evaluated. In multivariable analysis total donor cell and T-cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most predictive. D100 total donor cell chimerism <90% was associated with increased relapse (HR 2.54, 95% CI 1.83-3.51, p<0.0001), impaired PFS (HR 2.01, 95% CI 1.53-2.65, p<0.0001) and worse OS (1.50, 95% CI 1.11-2.04, p=0.009), but not NRM (HR 0.76; 95% CI 0.44-2.27, p=0.33). There was no additional utility of incorporating sustained D30-D100 total donor cell chimerism, or T-cell chimerism. Low donor chimerism early after RIC HSCT is an independent risk factor for relapse and impaired survival. Donor chimerism assessment early after RIC HSCT can prognosticate for long-term outcomes and help identify high-risk patient cohorts that may benefit from additional therapeutic interventions. PMID:24907627

  11. Systemic Inflammatory Response and Elevated Tumour Markers Predict Worse Survival in Resectable Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Salmiheimo, Aino; Mustonen, Harri; Stenman, Ulf-Håkan; Puolakkainen, Pauli; Kemppainen, Esko; Seppänen, Hanna; Haglund, Caj

    2016-01-01

    Background Estimation of the prognosis of resectable pancreatic ductal adenocarcinoma (PDAC) currently relies on tumour-related factors such as resection margins and on lymph-node ratio (LNR) both inconveniently available only postoperatively. Our aim was to assess the accuracy of preoperative laboratory data in predicting PDAC prognosis. Methods Collection of laboratory and clinical data was retrospective from 265 consecutive patients undergoing surgery for PDAC at Helsinki University Hospital. Cancer-specific survival assessment utilized Kaplan-Meier analysis, and independent associations between factors were by the Cox regression model. Results During follow-up, 76% of the patients died of PDAC, with a median survival time of 19.6 months. In univariate analysis, CRP, albumin, CEA, and CA19-9 were significantly associated with postoperative cancer-specific survival. In multivariate analysis, taking into account age, gender, LNR, resection margins, tumour status, and adjuvant chemotherapy, the preoperative biomarkers independently associated with adverse prognosis were hypoalbuminemia (< 36 g/L, hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.10–2.19, p = 0.011), elevated CRP (> 5 mg/L, HR 1.44, 95% CI 1.03–2.02, p = 0.036), CEA (> 5 μg/L, HR 1.60, 95% CI 1.07–2.53, p = 0.047), and CA19-9 (≥555 kU/L, HR 1.91, 95% CI 1.18–3.08, p = 0.008). Conclusion For patients with resectable PDAC, preoperative CRP, along with albumin and tumour markers, is useful for predicting prognosis. PMID:27632196

  12. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML).

    PubMed

    Hanfstein, B; Müller, M C; Hehlmann, R; Erben, P; Lauseker, M; Fabarius, A; Schnittger, S; Haferlach, C; Göhring, G; Proetel, U; Kolb, H-J; Krause, S W; Hofmann, W-K; Schubert, J; Einsele, H; Dengler, J; Hänel, M; Falge, C; Kanz, L; Neubauer, A; Kneba, M; Stegelmann, F; Pfreundschuh, M; Waller, C F; Branford, S; Hughes, T P; Spiekermann, K; Baerlocher, G M; Pfirrmann, M; Hasford, J; Saußele, S; Hochhaus, A

    2012-09-01

    In the face of competing first-line treatment options for CML, early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation tyrosine kinase inhibitor (TKI). A total of 1303 newly diagnosed imatinib-treated patients (pts) were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). The persistence of BCR-ABL transcript levels >10% according to the international scale (BCR-ABL(IS)) at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with >1-10% BCR-ABL(IS) (41% of pts; 5-year OS: 94%; P=0.012) and from a group with ≤1% BCR-ABL(IS) (31% of pts; 5-year OS: 97%; P=0.004). Cytogenetics identified high-risk pts by >35% Philadelphia chromosome-positive metaphases (Ph+, 27% of pts; 5-year OS: 87%) compared with ≤35% Ph+ (73% of pts; 5-year OS: 95%; P=0.036). At 6 months, >1% BCR-ABL(IS) (37% of pts; 5-year OS: 89%) was associated with inferior survival compared with ≤1% (63% of pts; 5-year OS: 97%; P<0.001) and correspondingly >0% Ph+ (34% of pts; 5-year OS: 91%) compared with 0% Ph+ (66% of pts; 5-year OS: 97%; P=0.015). Treatment optimization is recommended for pts missing these landmarks. PMID:22446502

  13. Time to lowest postoperative carcinoembryonic antigen level is predictive on survival outcome in rectal cancer

    PubMed Central

    Yu, Huichuan; Luo, Yanxin; Wang, Xiaolin; Bai, Liangliang; Huang, Pinzhu; Wang, Lei; Huang, Meijin; Deng, Yanhong; Wang, Jianping

    2016-01-01

    This study was to investigate whether the time to the lowest postoperative CEA can predict cancer survival. We enrolled 155 rectal cancer patients in this retrospective and longitudinal cohort study. Deepness of response (DpR) of CEA refers to the relative change of the lowest postoperative CEA level from baseline, and time to DpR (TTDpR) refers to the time from surgery to the lowest postoperative CEA level. The median of TTDpR and DpR was 4.5 (range, 3.0–18.0) weeks and −67% (range, −99% to 114%) respectively. Patients with TTDpR 4.5 weeks. Using TTDpR as a continuous variable, the HR of DFS and OS was 1.13 (95% CI 1.06–1.22, P = 0.001) and 1.17 (95% CI 1.07–1.29, P = 0.001) respectively. On multivariate analysis, the predictive value of prolonged TTDpR remained [adjusted HRs: 1.12 (95% CI 1.03–1.21, P = 0.006) and 1.17 (95% CI 1.06–1.28, P = 0.001)]. These findings remained significant in patients with normal preoperative CEA. Our results showed prolonged TTDpR of CEA independently predicted unfavorable survival outcomes, regardless of whether preoperative CEA was elevated or not. PMID:27658525

  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

    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. Low preoperative albumin-globulin score predicts favorable survival in esophageal squamous cell carcinoma.

    PubMed

    Zhang, Fei; Sun, Peng; Wang, Zhi-Qiang; Wang, De Shen; Wang, Yun; Zhang, Dong-Sheng; Wang, Feng-Hua; Fu, Jian-Hua; Xu, Rui-Hua; Li, Yu-Hong

    2016-05-24

    This study retrospectively investigated the prognostic significance of the preoperative albumin-globulin score (AGS) and albumin/globulin ratio (AGR) in esophageal squamous cell carcinoma (ESCC). A cohort of 458 newly diagnosed ESCC patients who underwent radical esophagectomy in Sun Yat-sen University Cancer Center (Guangzhou, China) between January 2006 and December 2010 were selected into this study. The optimal cut-off value was identified to be 45.6 g/L, 26.9 g/L and 1.30 for albumin (ALB), globulin (GLB) and AGR in terms of survival, respectively. Patients with low ALB levels (< 45.6 g/L) and high GLB levels (≥ 26.9 g/L) were assigned an AGS of 2, those with only one of the two abnormalities were assigned an AGS of 1, and those with neither of the two abnormalities were assigned an AGS of 0. Univariate survival analysis showed that low AGS (0) was significantly associated with favorable disease free survival (DFS) [hazard ratio (HR), 0.635; 95% confidence interval (CI), 0.441-0.914; P = 0.015] and overall survival (OS) (HR, 0.578; 95% CI, 0.387-0.862; P = 0.007), and it remained an independent predictor for OS (HR, 0.630; 95% CI, 0.418-0.952; P = 0.028), but not for DFS (HR, 0.697; 95% CI, 0.479-1.061; P = 0.060) in multivariate models. High AGR (≥ 1.30) was also correlated with favorable DFS (HR, 0.626; 95% CI, 0.430-0.910; P = 0.014) and OS (HR, 0.622; 95% CI, 0.422-0.916; P = 0.016) in univariate analysis, but it failed to be an independent prognostic indicator for DFS (HR, 0.730; 95% CI, 0.494-1.078; P = 0.114) or OS (HR, 0.759; 95% CI, 0.507-1.137; P = 0.181) by multivariate analysis. Low preoperative AGS could serve as a valuable and convenient biochemical marker to predict favorable long-term survival in ESCC patients. PMID:27105522

  18. 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

  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. A Six-Gene Signature Predicts Survival of Patients with Localized Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Stratford, Jeran K.; Bentrem, David J.; Anderson, Judy M.; Fan, Cheng; Volmar, Keith A.; Marron, J. S.; Routh, Elizabeth D.; Caskey, Laura S.; Samuel, Jonathan C.; Der, Channing J.; Thorne, Leigh B.; Calvo, Benjamin F.; Kim, Hong Jin; Talamonti, Mark S.; Iacobuzio-Donahue, Christine A.; Hollingsworth, Michael A.; Perou, Charles M.; Yeh, Jen Jen

    2010-01-01

    Background Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease. For patients with localized PDAC, surgery is the best option, but with a median survival of less than 2 years and a difficult and prolonged postoperative course for most, there is an urgent need to better identify patients who have the most aggressive disease. Methods and Findings We analyzed the gene expression profiles of primary tumors from patients with localized compared to metastatic disease and identified a six-gene signature associated with metastatic disease. We evaluated the prognostic potential of this signature in a training set of 34 patients with localized and resected PDAC and selected a cut-point associated with outcome using X-tile. We then applied this cut-point to an independent test set of 67 patients with localized and resected PDAC and found that our signature was independently predictive of survival and superior to established clinical prognostic factors such as grade, tumor size, and nodal status, with a hazard ratio of 4.1 (95% confidence interval [CI] 1.7–10.0). Patients defined to be high-risk patients by the six-gene signature had a 1-year survival rate of 55% compared to 91% in the low-risk group. Conclusions Our six-gene signature may be used to better stage PDAC patients and assist in the difficult treatment decisions of surgery and to select patients whose tumor biology may benefit most from neoadjuvant therapy. The use of this six-gene signature should be investigated in prospective patient cohorts, and if confirmed, in future PDAC clinical trials, its potential as a biomarker should be investigated. Genes in this signature, or the pathways that they fall into, may represent new therapeutic targets. Please see later in the article for the Editors' Summary PMID:20644708

  1. Cardiac Magnetic Resonance Parameters Predict Transplantation-Free Survival in Patients With Fontan Circulation

    PubMed Central

    Rathod, Rahul H.; Prakash, Ashwin; Kim, Yuli Y.; Germanakis, Ioannis E.; Powell, Andrew J.; Gauvreau, Kimberlee; Geva, Tal

    2014-01-01

    Background Several clinical risk factors for death and heart transplantation have been identified in patients with Fontan circulation. It is unknown whether cardiac magnetic resonance (CMR) measurements of ventricular size and function are independently associated with these outcomes and further improve risk stratification. Methods and Results Data on Fontan patients who had a CMR study from 1/2002 to 1/2011 were retrospectively reviewed. The endpoint was time to death or listing for heart transplantation after the CMR study. The median age of the 215 patients was 18.3 years [25th, 75th percentiles: 14, 26] with a median age at Fontan of 3.6 years [2.3, 7.1]. Over a median post-CMR follow-up period of 4.1 years [2.6, 6.2], 24 patients (11%) reached the endpoint: 20 deaths, 3 transplants, and 1 transplant listing. In a multivariable Cox regression model with clinical parameters only, protein losing enteropathy (PLE) was associated with transplant-free survival. A multivariable model including clinical and CMR parameters showed that in addition to PLE, ventricular end-diastolic volume (EDVi) >125 mL/BSA1.3 was associated with transplant-free survival. A likelihood-ratio test comparing the 2 models showed that the addition of EDVi resulted in a significantly improved endpoint prediction (P<0.001) — C-index increased from 0.63 to 0.79. Conclusions CMR-derived ventricular EDVi is an independent predictor of transplant-free survival late after the Fontan operation and adds incremental value over clinical symptoms alone for risk stratification. PMID:24619103

  2. Undetectable ultrasensitive PSA after radical prostatectomy for prostate cancer predicts relapse-free survival.

    PubMed

    Doherty, A P; Bower, M; Smith, G L; Miano, R; Mannion, E M; Mitchell, H; Christmas, T J

    2000-12-01

    Radical retropubic prostatectomy is considered by many centres to be the treatment of choice for men aged less than 70 years with localized prostate cancer. A rise in serum prostate-specific antigen after radical prostatectomy occurs in 10-40% of cases. This study evaluates the usefulness of novel ultrasensitive PSA assays in the early detection of biochemical relapse. 200 patients of mean age 61. 2 years underwent radical retropubic prostatectomy. Levels < or = 0.01 ng ml-1 were considered undetectable. Mean pre-operative prostate-specific antigen was 13.3 ng ml-1. Biochemical relapse was defined as 3 consecutive rises. The 2-year biochemical disease-free survival for the 134 patients with evaluable prostate-specific antigen nadir data was 61.1% (95% CI: 51.6-70.6%). Only 2 patients with an undetectable prostate-specific antigen after radical retropubic prostatectomy biochemically relapsed (3%), compared to 47 relapses out of 61 patients (75%) who did not reach this level. Cox multivariate analysis confirms prostate-specific antigen nadir < or = 0.01 ng ml-1 to be a superb independent variable predicting a favourable biochemical disease-free survival (P < 0.0001). Early diagnosis of biochemical relapse is feasible with sensitive prostate-specific antigen assays. These assays more accurately measure the prostate-specific antigen nadir, which is an excellent predictor of biochemical disease-free survival. Thus, sensitive prostate-specific antigen assays offer accurate prognostic information and expedite decision-making regarding the use of salvage prostate-bed radiotherapy or hormone therapy.

  3. Using cross-validation to evaluate predictive accuracy of survival risk classifiers based on high-dimensional data.

    PubMed

    Simon, Richard M; Subramanian, Jyothi; Li, Ming-Chung; Menezes, Supriya

    2011-05-01

    Developments in whole genome biotechnology have stimulated statistical focus on prediction methods. We review here methodology for classifying patients into survival risk groups and for using cross-validation to evaluate such classifications. Measures of discrimination for survival risk models include separation of survival curves, time-dependent ROC curves and Harrell's concordance index. For high-dimensional data applications, however, computing these measures as re-substitution statistics on the same data used for model development results in highly biased estimates. Most developments in methodology for survival risk modeling with high-dimensional data have utilized separate test data sets for model evaluation. Cross-validation has sometimes been used for optimization of tuning parameters. In many applications, however, the data available are too limited for effective division into training and test sets and consequently authors have often either reported re-substitution statistics or analyzed their data using binary classification methods in order to utilize familiar cross-validation. In this article we have tried to indicate how to utilize cross-validation for the evaluation of survival risk models; specifically how to compute cross-validated estimates of survival distributions for predicted risk groups and how to compute cross-validated time-dependent ROC curves. We have also discussed evaluation of the statistical significance of a survival risk model and evaluation of whether high-dimensional genomic data adds predictive accuracy to a model based on standard covariates alone.

  4. Prevalence, predictive factors, and survival outcome of new-onset diabetes after liver transplantation

    PubMed Central

    Liu, Fu-Chao; Lin, Jr-Rung; Chen, Hsiu-Pin; Tsai, Yung-Fong; Yu, Huang-Ping

    2016-01-01

    Abstract The aim of the present nationwide population-based cohort study was to explore the prevalence, risk factors, and survival outcome of new-onset diabetes (NOD) in recipients after liver transplantation. The National Health Insurance Research Database of Taiwan was searched for ICD-9-codes, 2248 patients who had received liver transplant without pretransplant diabetes from July 1, 1998 to December 31, 2012 were included in the study. The preoperative risks factors were considered and analyzed using logistic regression analysis, following adjustments for age and sex. All patients were followed up until the end of the study or death. The final dataset included 189 patients with NOD and 2059 without diabetes after liver transplantation. The prevalence of NOD was 8.4% and in 64% NOD appeared in the first year after liver transplantation. Preoperative clinical events, alcoholic liver cirrhosis, and hepatic encephalopathy were the most important risk factors for NOD after liver transplantation. The mortality rate was lower in NOD recipients than in non-NOD recipients within 5 years. In this study, we provide evidence that NOD recipients had better 5-year survival outcomes in this clinical population. The most important identifiable predictive factors for NOD after liver transplantation were alcoholic hepatitis, ascites, hepatic coma, and esophageal varices. PMID:27336869

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

    PubMed Central

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

    2015-01-01

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

  6. BINNING SOMATIC MUTATIONS BASED ON BIOLOGICAL KNOWLEDGE FOR PREDICTING SURVIVAL: AN APPLICATION IN RENAL CELL CARCINOMA

    PubMed Central

    Kim, Dokyoon; Li, Ruowang; Dudek, Scott M.; Wallace, John R.; Ritchie, Marylyn D.

    2014-01-01

    Enormous efforts of whole exome and genome sequencing from hundreds to thousands of patients have provided the landscape of somatic genomic alterations in many cancer types to distinguish between driver mutations and passenger mutations. Driver mutations show strong associations with cancer clinical outcomes such as survival. However, due to the heterogeneity of tumors, somatic mutation profiles are exceptionally sparse whereas other types of genomic data such as miRNA or gene expression contain much more complete data for all genomic features with quantitative values measured in each patient. To overcome the extreme sparseness of somatic mutation profiles and allow for the discovery of combinations of somatic mutations that may predict cancer clinical outcomes, here we propose a new approach for binning somatic mutations based on existing biological knowledge. Through the analysis using renal cell carcinoma dataset from The Cancer Genome Atlas (TCGA), we identified combinations of somatic mutation burden based on pathways, protein families, evolutionary conversed regions, and regulatory regions associated with survival. Due to the nature of heterogeneity in cancer, using a binning strategy for somatic mutation profiles based on biological knowledge will be valuable for improved prognostic biomarkers and potentially for tailoring therapeutic strategies by identifying combinations of driver mutations. PMID:25592572

  7. Centromere and kinetochore gene misexpression predicts cancer patient survival and response to radiotherapy and chemotherapy

    PubMed Central

    Zhang, Weiguo; Mao, Jian-Hua; Zhu, Wei; Jain, Anshu K.; Liu, Ke; Brown, James B.; Karpen, Gary H.

    2016-01-01

    Chromosomal instability (CIN) is a hallmark of cancer that contributes to tumour heterogeneity and other malignant properties. Aberrant centromere and kinetochore function causes CIN through chromosome missegregation, leading to aneuploidy, rearrangements and micronucleus formation. Here we develop a Centromere and kinetochore gene Expression Score (CES) signature that quantifies the centromere and kinetochore gene misexpression in cancers. High CES values correlate with increased levels of genomic instability and several specific adverse tumour properties, and prognosticate poor patient survival for breast and lung cancers, especially early-stage tumours. They also signify high levels of genomic instability that sensitize cancer cells to additional genotoxicity. Thus, the CES signature forecasts patient response to adjuvant chemotherapy or radiotherapy. Our results demonstrate the prognostic and predictive power of the CES, suggest a role for centromere misregulation in cancer progression, and support the idea that tumours with extremely high CIN are less tolerant to specific genotoxic therapies. PMID:27577169

  8. 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

  9. 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

  10. Four-protein signature accurately predicts lymph node metastasis and survival in oral squamous cell carcinoma.

    PubMed

    Zanaruddin, Sharifah Nurain Syed; Saleh, Amyza; Yang, Yi-Hsin; Hamid, Sharifah; Mustafa, Wan Mahadzir Wan; Khairul Bariah, A A N; Zain, Rosnah Binti; Lau, Shin Hin; Cheong, Sok Ching

    2013-03-01

    The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering-demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5% and a sensitivity of 70%, with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P = .036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC.

  11. Four-protein signature accurately predicts lymph node metastasis and survival in oral squamous cell carcinoma.

    PubMed

    Zanaruddin, Sharifah Nurain Syed; Saleh, Amyza; Yang, Yi-Hsin; Hamid, Sharifah; Mustafa, Wan Mahadzir Wan; Khairul Bariah, A A N; Zain, Rosnah Binti; Lau, Shin Hin; Cheong, Sok Ching

    2013-03-01

    The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering-demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5% and a sensitivity of 70%, with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P = .036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC. PMID:23026198

  12. Histopathologic Response Criteria Predict Survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy

    PubMed Central

    Pataer, Apar; Kalhor, Neda; Correa, Arlene M.; Raso, Maria Gabriela; Erasmus, Jeremy J.; Kim, Edward S.; Behrens, Carmen; Lee, J. Jack; Roth, Jack A.; Stewart, David J.; Vaporciyan, Ara A.; Wistuba, Ignacio I.; Swisher, Stephen G.

    2012-01-01

    Introduction We evaluated the ability of histopathologic response criteria to predict overall survival (OS) and disease-free survival (DFS) in patients with surgically resected non-small cell lung cancer (NSCLC) treated with or without neoadjuvant chemotherapy. Methods Tissue specimens from 358 patients with NSCLC were evaluated by pathologists blinded to the patient treatment and outcome. The surgical specimens were reviewed for various histopathologic features in the tumor including percentage of residual viable tumor cells, necrosis, and fibrosis. The relationship between the histopathologic findings and OS was assessed. Results The percentage of residual viable tumor cells and surgical pathologic stage were associated with OS and DFS in 192 patients with NSCLC receiving neoadjuvant chemotherapy in multivariate analysis (p = 0.005 and p = 0.01, respectively). There was no association of OS or DFS with percentage of viable tumor cells in 166 patients with NSCLC who did not receive neoadjuvant chemotherapy (p = 0.31 and p = 0.45, respectively). Long-term OS and DFS were significantly prolonged in patients who had ≤10% viable tumor compared with patients with >10% viable tumor cells (5 years OS, 85% versus 40%, p < 0.0001 and 5 years DFS, 78% versus 35%, p < 0.001). Conclusion The percentages of residual viable tumor cells predict OS and DFS in patients with resected NSCLC after neoadjuvant chemotherapy even when controlled for pathologic stage. Histopathologic assessment of resected specimens after neoadjuvant chemotherapy could potentially have a role in addition to pathologic stage in assessing prognosis, chemotherapy response, and the need for additional adjuvant therapies. PMID:22481232

  13. Transaminase Activity Predicts Survival in Patients with Head and Neck Cancer

    PubMed Central

    Takenaka, Yukinori; Takemoto, Norihiko; Yasui, Toshimichi; Yamamoto, Yoshifumi; Uno, Atsuhiko; Miyabe, Haruka; Ashida, Naoki; Shimizu, Kotaro; Nakahara, Susumu; Hanamoto, Atshushi; Fukusumi, Takahito; Michiba, Takahiro; Cho, Hironori; Yamamoto, Masashi; Inohara, Hidenori

    2016-01-01

    Various serum biomarkers have been developed for predicting head and neck squamous cell carcinoma (HNSCC) prognosis. However, none of them have been proven to be clinically significant. A recent study reported that the ratio of aspartate aminotransaminase (AST) to alanine aminotransaminase (ALT) had a prognostic effect on non-metastatic cancers. This study aimed to examine the effect of the AST/ALT ratio on the survival of patients with HNSCC. Clinical data of 356 patients with locoregionally advanced HNSCC were collected. The effect of the AST/ALT ratio on overall survival was analyzed using a Cox proportional hazard model. Moreover, recursive partitioning analysis (RPA) was used to divide the patients into groups on the basis of the clinical stage and AST/ALT ratio. The prognostic ability of this grouping was validated using an independent data set (N = 167). The AST/ALT ratio ranged from 0.42 to 4.30 (median, 1.42) and was a prognostic factor for overall survival that was independent of age, primary sites, and tumor stage (hazard ratio: 1.36, confidence interval: 1.08−1.68, P = 0.010). RPA divided patients with stage IVA into the following two subgroups: high AST/ALT (≥2.3) and low AST/ALT (<2.3) subgroups. The 5-year survival rate for patients with stage III, stage IVA with a low AST/ALT ratio, stage IVA with a high AST/ALT ratio, and stage IVB were 64.8%, 49.2%, 28.6%, and 33.3%, respectively (p < 0.001). Compared with the low AST/ALT group, the adjusted hazard ratio for death was 2.17 for high AST/ALT group (confidence interval: 1.02–.22 P = 0.045). The AST/ALT ratio was demonstrated to be a prognostic factor of HNSCC. The ratio subdivided patients with stage IVA into low- and high-risk groups. Moreover, intensified treatment for the high-risk group may be considered. PMID:27732629

  14. Single Sample Expression-Anchored Mechanisms Predict Survival in Head and Neck Cancer

    PubMed Central

    Yang, Xinan; Regan, Kelly; Huang, Yong; Zhang, Qingbei; Li, Jianrong; Seiwert, Tanguy Y.; Cohen, Ezra E. W.; Xing, H. Rosie; Lussier, Yves A.

    2012-01-01

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

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

    PubMed

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

    2014-10-01

    The impact of early donor cell chimerism on outcomes of T cell-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T cell chimerism was also assessed. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse, and nonrelapse mortality (NRM). We evaluated 688 patients with hematologic malignancies (48% myeloid and 52% lymphoid) and a median age of 57 years (range, 18 to 74) undergoing RIC HSCT with T cell-replete donor grafts (97% peripheral blood; 92% HLA-matched), with a median follow-up of 58.2 months (range, 12.6 to 120.7). In multivariable analysis, total donor cell and T cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most predictive. D100 total donor cell chimerism <90% was associated with increased relapse (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.83 to 3.51; P < .0001), impaired PFS (HR, 2.01; 95% CI, 1.53 to 2.65; P < .0001), and worse OS (HR, 1.50; 95% CI, 1.11 to 2.04, P = .009), but not with NRM (HR, .76; 95% CI, .44 to 2.27; P = .33). There was no additional utility of incorporating sustained D30 to D100 total donor cell chimerism or T cell chimerism. Low donor chimerism early after RIC HSCT is an independent risk factor for relapse and impaired survival. Donor chimerism assessment early after RIC HSCT can prognosticate for long-term outcomes and help identify high-risk patient cohorts who may benefit from additional therapeutic interventions.

  16. A simulation study of predictive ability measures in a survival model II: explained randomness and predictive accuracy.

    PubMed

    Choodari-Oskooei, B; Royston, P; Parmar, Mahesh K B

    2012-10-15

    Several R(2) -type measures have been proposed to evaluate the predictive ability of a survival model. In Part I, we classified the measures into four categories and studied the measures in the explained variation category. In this paper, we study the remaining measures in a similar fashion, discussing their strengths and shortcomings. Simulation studies are used to examine the performance of the measures with respect to the criteria we set out in Part I. Our simulation studies showed that among the measures studied in this paper, the measures proposed by Kent and O'Quigley ρ(W)(2) (and its approximation ρ(W,A)(2)) and Schemper and Kaider R(SK)(2) perform better with respect to our criteria. However, our investigations showed that ρ(W)(2) is adversely affected by the distribution of covariate and the presence of influential observations. The results show that the other measures perform poorly, primarily because they are affected either by the degree of censoring or the follow-up period.

  17. 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

  18. 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.

  19. 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

  20. Target Inhibition Networks: Predicting Selective Combinations of Druggable Targets to Block Cancer Survival Pathways

    PubMed Central

    Tang, Jing; Karhinen, Leena; Xu, Tao; Szwajda, Agnieszka; Yadav, Bhagwan; Wennerberg, Krister; Aittokallio, Tero

    2013-01-01

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

  1. Incarcerated inferior lumbar (Petit's) hernia.

    PubMed

    Astarcioğlu, H; Sökmen, S; Atila, K; Karademir, S

    2003-09-01

    Petit's hernia is an uncommon abdominal wall defect in the inferior lumbar triangle. Colonic incarceration through the inferior lumbar triangle, which causes mechanical obstructive symptoms, necessitates particular diagnostic and management strategy. We present a rare case of inferior lumbar hernia, leading to mechanical bowel obstruction, successfully treated with prosthetic mesh reinforcement repair.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Absolute monocyte count predicts overall survival in mantle cell lymphomas: correlation with tumour-associated macrophages.

    PubMed

    Koh, Young Wha; Shin, Su-Jin; Park, Chansik; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

    2014-12-01

    Mantle cell lymphoma (MCL) is characterized by a variable clinical course in which patients can experience indolent disease or frequent relapses despite a good initial response to conventional therapy. Risk stratification of MCL is most frequently performed using the MCL International Prognostic Index (MIPI). Recent studies indicate that the peripheral blood absolute monocyte count (AMC) and tumour-associated macrophages may reflect the state of the tumour microenvironment in lymphomas. The significance of AMC and tumour-associated macrophages in the clinical course of MCL is unknown. The prognostic impact of the AMC, of CD68 expression and of CD163 expression was retrospectively examined in 103 MCL samples using the receiver operating characteristic curved. Patients with an AMC ≥ 375 cells/μL at diagnosis were more likely to present with advanced-stage disease (p = 0.026), leukocytosis (p < 0.001), lymphocytosis (p = 0.01) and granulocytosis (p = 0.003). On univariate analysis, a high AMC (≥375 cells/μL) correlated with poorer overall survival (OS) (p = 0.01). Neither CD68 nor CD163 expression was significantly associated with either OS or event-free survival. Multivariate analysis showed that a high AMC was a prognostic factor for OS, independent of the MIPI [hazards ratio (HR), 1.811; 95% confidence interval, 1.018-3.223; p = 0.043]. This study demonstrates that the AMC at the time of diagnosis is an independent prognostic factor for OS in MCL, which suggests the possibility that AMC may be used in addition to the MIPI to predict outcome in patients with MCL.

  8. 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

  9. Nomograms for predicting long-term survival in patients with non-metastatic nasopharyngeal carcinoma in an endemic area

    PubMed Central

    Meng, Xiang-Qi; Guo, Xiang; Qian, Chao-Nan; Wu, Pei-Hong; Huang, Pei-Yu

    2016-01-01

    Purpose Nomogram for predicting more than a 5-year survival for non-metastatic nasopharyngeal carcinoma (NPC) was lacking. This study aimed to develop the new nomograms to predict long-term survival in these patients. Results The median follow-up time for training set and test set was 95.2 months and 133.3 months, respectively. The significant predictors for death were age, gender, body mass index (BMI), T stage, N stage, lactate dehydrogenase (LDH), and radiotherapy techniques. For predicting recurrence, age, gender, T stage, LDH, and radiotherapy techniques were significant predictors, whereas age, gender, BMI, T stage, N stage and LDH were significant predictors for distant metastasis. The calibration curves showed the good agreements between nomogram-predicted and actual survival. The c-indices for predicting death, recurrence, and distant metastases between nomograms and the TNM staging system were 0.767 VS.0.686 (P<0.001), 0.655 VS.0.585 (P<0.001), and 0.881 VS.0.754 (P<0.001), respectively. These results were further confirmed in the test set. Methods On the basis of a retrospective study of 1593 patients (training set) who received radiotherapy alone or concurrent chemoradiotherapy from 2000 to 2004, significant predictors were identified and incorporated to build the nomograms. The calibration curves of nomogram-predicted survival versus the actual survival were plotted and reviewed. Bootstrap validation was performed to calculate the concordance index (c-index). These models were further validated in an independent prospective trial (test set, n=400). Conclusion The established nomograms suggest more-accurate long-term prediction for patients with non-metastatic NPC. PMID:27102440

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Isolated inferior mesenteric portal hypertension with giant inferior mesenteric vein and anomalous inferior mesenteric vein insertion

    PubMed Central

    Prasad, G. Raghavendra; Billa, Srikar; Bhandari, Pavaneel; Hussain, Aijaz

    2013-01-01

    Extrahepatic portal hypertension is not an uncommon disease in childhood, but isolated inferior mesenteric portal varices and lower gastrointestinal (GI) bleed have not been reported till date. A 4-year-old girl presented with lower GI bleed. Surgical exploration revealed extrahepatic portal vein obstruction with giant inferior mesenteric vein and colonic varices. Inferior mesenteric vein was joining the superior mesenteric vein. The child was treated successfully with inferior mesenteric – inferior vena caval anastomosis. The child was relieved of GI bleed during the follow-up. PMID:23798814

  18. A dynamic Bayesian network approach for time-specific survival probability prediction in patients after ventricular assist device implantation.

    PubMed

    Exarchos, Themis P; Rigas, George; Goletsis, Yorgos; Stefanou, Kostas; Jacobs, Steven; Trivella, Maria-Giovanna; Fotiadis, Dimitrios I

    2014-01-01

    In this work we present a decision support tool for the calculation of time-dependent survival probability for patients after ventricular assist device implantation. Two different models have been developed, a short term one which predicts survival for the first three months and a long term one that predicts survival for one year after implantation. In order to model the time dependencies between the different time slices of the problem, a dynamic Bayesian network (DBN) approach has been employed. DBNs order to capture the temporal events of the patient disease and the temporal data availability. High accuracy results have been reported for both models. The short and long term DBNs reached an accuracy of 96.97% and 93.55% respectively. PMID:25570664

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

    PubMed

    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

    2015-04-20

    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.

  20. A hybrid approach of gene sets and single genes for the prediction of survival risks with gene expression data.

    PubMed

    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.

  1. Platelet response during the second cycle of decitabine treatment predicts response and survival for myelodysplastic syndrome patients.

    PubMed

    Jung, Hyun Ae; Maeng, Chi Hoon; Kim, Moonjin; Kim, Sungmin; Jung, Chul Won; Jang, Jun Ho

    2015-06-30

    Despite the efficacy of decitabine to myelodysplastic syndrome (MDS), there is a wide range of responses, and no definite predictive marker has been identified. This study aimed to describe the efficacy of decitabine and to identify potential predictors of response and survival in patients with MDS. We retrospectively analyzed clinical data of MDS patients at Samsung Medical Center between August 2008 and August 2011. The response assessment was conducted using the International Working Group (IWG) response criteria for MDS. We analyzed 101 MDS patients (total 613 cycles) who received decitabine for a median of four cycles. The overall response was 52.5% (n = 53/101). The median time to any response was two cycles with the median overall survival of 16.7 months. Patients who showed hematologic improvement had significantly longer survival than those who did not (9.8 vs. 22.9 months, p = 0.004). The difference in OS was evident in the Intermediate-2/High risk group (p = 0.002) but not in the Intermediate-1 risk group (p = 0.145). Multivariate analysis confirmed that platelet response (no platelet transfusions for at least 3 days) during the second cycle of treatment was an independent predictor for response, OS and Leukemia free survival. Based on the results of this study, for patients with hematological improvement, recovery of platelet count by the second cycle of therapy can be used as an early predictive marker of improved survival and an increased response rate.

  2. 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

  3. Serum butyrylcholinesterase predicts survival after extracorporeal membrane oxygenation after cardiovascular surgery

    PubMed Central

    2014-01-01

    Introduction Risk stratification in patients undergoing extracorporeal membrane oxygenation (ECMO) support after cardiovascular surgery remains challenging, because data on specific outcome predictors are limited. Serum butyrylcholinesterase demonstrated a strong inverse association with all-cause and cardiovascular mortality in non-critically ill patients. We therefore evaluated the predictive value of preoperative serum butyrylcholinesterase levels in patients undergoing venoarterial ECMO support after cardiovascular surgery. Methods We prospectively included 191 patients undergoing venoarterial ECMO therapy after cardiovascular surgery at a university-affiliated tertiary care center in our registry. Results All-cause and cardiovascular mortality were defined as primary study end points. During a median follow-up time of 51 months (IQR, 34 to 71) corresponding to 4,197 overall months of follow-up, 65% of patients died. Cox proportional hazard regression analysis revealed a significant and independent inverse association between higher butyrylcholinesterase levels and all-cause mortality with an adjusted hazard ratio (HR) of 0.44 (95% CI, 0.25 to 0.78; P = 0.005), as well as cardiovascular mortality, with an adjusted HR of 0.38 (95% CI, 0.21 to 0.70; P = 0.002), comparing the third with the first tertile. Survival rates were higher in patients within the third tertile of butyrylcholinesterase compared with patients within the first tertile at 30 days (68% versus 44%) as well as at 6 years (47% versus 21%). Conclusions The current study revealed serum butyrylcholinesterase as a strong and independent inverse predictor of all-cause and cardiovascular mortality in patients undergoing venoarterial ECMO therapy after cardiovascular surgery. These findings advance the limited knowledge on risk stratification in patients undergoing ECMO support and represent a valuable addition for a comprehensive decision making before ECMO implantation. PMID:24479557

  4. Early donor chimerism levels predict relapse and survival after allogeneic stem-cell transplantation with reduced intensity conditioning

    PubMed Central

    Reshef, Ran; Hexner, Elizabeth O.; Loren, Alison W.; Frey, Noelle V.; Stadtmauer, Edward A.; Luger, Selina M.; Mangan, James K.; Gill, Saar I.; Vassilev, Pavel; Lafferty, Kathryn A.; Smith, Jacqueline; Van Deerlin, Vivianna M.; Mick, Rosemarie; Porter, David L.

    2014-01-01

    The success of hematopoietic stem-cell transplantation (HSCT) with reduced-intensity conditioning (RIC) is limited by a high rate of disease relapse. Early risk assessment could potentially improve outcomes by identifying appropriate patients for pre-emptive strategies that may ameliorate this high risk. Using a series of landmark analyses, we investigated the predictive value of early (day-30) donor chimerism measurements on disease relapse, graft-versus-host disease and survival in a cohort of 121 patients who were allografted with a uniform RIC regimen. Chimerism levels were analyzed as continuous variables. In multivariate analysis, day-30 whole blood chimerism levels were significantly associated with relapse (HR=0.90, p<0.001), relapse-free survival (HR=0.89, p<0.001) and overall survival (HR=0.94, p=0.01). Day-30 T-cell chimerism levels were also significantly associated with relapse (HR=0.97, p=0.002), relapse-free survival (HR=0.97, p<0.001) and overall survival (HR=0.99, p=0.05). Multivariate models that included T-cell chimerism provided a better prediction for these outcomes compared to whole blood chimerism. Day-30 chimerism levels were not associated with acute or chronic graft-versus-host disease. We found that high donor chimerism levels were significantly associated with a low lymphocyte count in the recipient prior to transplant, highlighting the impact of pre-transplant lymphopenia on the kinetics of engraftment after RIC HSCT. In summary, low donor chimerism levels are associated with relapse and mortality and can potentially be used as an early predictive and prognostic marker. These findings can be used to design novel approaches to prevent relapse and to improve survival after RIC HSCT. PMID:25016197

  5. 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

  6. Predicting the probability of abortion in dairy cows: a hierarchical Bayesian logistic-survival model using sequential pregnancy data.

    PubMed

    Thurmond, M C; Branscum, A J; Johnson, W O; Bedrick, E J; Hanson, T E

    2005-05-10

    Although abortion contributes substantially to poor reproductive health of dairy herds, little is known about the predictability of abortion based on age, previous abortion or gravidity (number of previous pregnancies). A poor understanding of effects of maternal factors on abortion risk exists, in part, because of methodological difficulties related to non-independence of multiple pregnancies of the same cow in analysis of fetal survival data. We prospectively examined sequential pregnancies to investigate relationships between fetal survival and putative dam risk factors for 2991 abortions from 24,706 pregnancies of 13,145 cows in nine California dairy herds. Relative risks and predicted probabilities of abortion (PPA) were estimated using a previously described hierarchical Bayesian logistic-survival model generalized to incorporate longitudinal data of multiple pregnancies from a single cow. The PPA increased with increasing dam age at conception, with increasing number of previous abortions, and if the previous pregnancy was aborted >60 days in gestation. The PPA decreased with increasing gravidity and with increasing number of days open. For cows that aborted, the median time to fetal death decreased slightly as gravidity increased. The study considers several methodological issues faced in epidemiologic investigations of fetal health, including multi-modal hazard functions, extensive censoring and non-independence of multiple pregnancies. The model improves our ability to predict bovine abortion and to characterize fetal survival, which have important applications to herd health management.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. Triple-Negative Subtype Predicts Poor Overall Survival and High Locoregional Relapse in Inflammatory Breast Cancer

    PubMed Central

    Li, Jing; Gonzalez-Angulo, Ana M.; Allen, Pamela K.; Yu, Tse K.; Woodward, Wendy A.; Ueno, Naoto T.; Lucci, Anthony; Krishnamurthy, Savitri; Gong, Yun; Bondy, Melissa L.; Yang, Wei; Willey, Jie S.; Cristofanilli, Massimo; Valero, Vicente

    2011-01-01

    Background. Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC. Methods. We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989–2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER+ (ER+/PR+ and HER-2−; n = 105), ER+HER-2+ (ER+/PR+ and HER-2+; n = 37), HER-2+ (ER−/PR− and HER-2+; n = 83), or triple-negative (TN) (ER−PR−HER-2−; n = 91). Kaplan–Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors. Results. The median age was 50 years (range, 24–83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER+ patients, 73.5% for ER+HER-2+ patients, 54.0% for HER=2+ patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001–.03). Conclusions. TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype. PMID:22147002

  15. 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...

  16. 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

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

    PubMed

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

    2014-10-22

    Social integration and support can have profound effects on human survival. The extent of this phenomenon in non-human animals is largely unknown, but such knowledge is important to understanding the evolution of both lifespan and sociality. Here, we report evidence that levels of affiliative social behaviour (i.e. 'social connectedness') with both same-sex and opposite-sex conspecifics predict adult survival in wild female baboons. In the Amboseli ecosystem in Kenya, adult female baboons that were socially connected to either adult males or adult females lived longer than females who were socially isolated from both sexes--females with strong connectedness to individuals of both sexes lived the longest. Female social connectedness to males was predicted by high dominance rank, indicating that males are a limited resource for females, and females compete for access to male social partners. To date, only a handful of animal studies have found that social relationships may affect survival. This study extends those findings by examining relationships to both sexes in by far the largest dataset yet examined for any animal. Our results support the idea that social effects on survival are evolutionarily conserved in social mammals.

  18. Cyclooxygenase-2 expression is associated with initiation of hepatocellular carcinoma, while prostaglandin receptor-1 expression predicts survival

    PubMed Central

    Yang, Hao-Jie; Jiang, Jing-Hang; Yang, Yu-Ting; Yang, Xiang-Di; Guo, Zhe; Qi, Ya-Peng; Zeng, Feng-Hua; Zhang, Ke-Lan; Chen, Neng-Zhi; Xiang, Bang-De; Li, Le-Qun

    2016-01-01

    AIM To determine whether cyclooxygenase-2 (COX-2) and prostaglandin E1 receptor (EP1) contribute to disease and whether they help predict prognosis. METHODS We retrospectively reviewed the records of 116 patients with hepatocellular carcinoma (HCC) who underwent surgery between 2008 and 2011 at our hospital. Expression of COX-2 and EP1 receptor was examined by immunohistochemistry of formalin-fixed, paraffin-embedded tissues using polyclonal antibodies. Possible associations between immunohistochemical scores and survival were determined. RESULTS Factors associated with poor overall survival (OS) were alpha-fetoprotein > 400 ng/mL, tumor size ≥ 5 cm, and high EP1 receptor expression, but not high COX-2 expression. Disease-free survival was not significantly different between patients with low or high levels of COX-2 or EP1. COX-2 immunoreactivity was significantly higher in well-differentiated HCC tissues (Edmondson grade I-II) than in poorly differentiated tissues (Edmondson grade III-IV) (P = 0.003). EP1 receptor immunoreactivity was significantly higher in poorly differentiated tissue than in well-differentiated tissue (P = 0.001). CONCLUSION COX-2 expression appears to be linked to early HCC events (initiation), while EP1 receptor expression may participate in tumor progression and predict survival.

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

    PubMed

    Yasrebi, Haleh

    2016-09-01

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

  20. 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

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

    PubMed

    Hayhoe, H N; Lapen, D R; Andrews, C J

    2003-03-01

    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 degrees 23'N, 75 degrees 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 ( degrees 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 degrees 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. PMID:12647092

  2. 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.

  3. Factors Predictive of Improved Survival in Patients With Brain Metastases From Gynecologic Cancer

    PubMed Central

    Gressel, Gregory M.; Lundsberg, Lisbet S.; Altwerger, Gary; Katchi, Tasleem; Azodi, Masoud; Schwartz, Peter E.; Ratner, Elena S.

    2015-01-01

    Objective The reported incidence of brain metastasis from epithelial ovarian cancer (EOC), endometrial cancer (EC), and cervical cancer (CC) is exceedingly rare. As the long-term survival for patients with gynecologic cancer increases, there has been a corresponding increase in the number of diagnosed intracranial metastases. We seek to report our experience with managing brain metastatic disease (BMD) in patients with gynecologic cancer. Methods A retrospective review of all patients with EOC, EC, and CC at our institution revealed 47 patients with concurrent BMD between 2000 and 2013. Demographic data, risk factors, treatment modalities, progression-free data, and overall survival data were collected. Results Median survival time in patients with brain metastasis from EOC, EC, and CC was 9.0, 4.5, and 3.0 months, respectively. Two-year overall survival rates were 31.6%, 13.6%, and 0%, respectively. Patients received surgery, radiation therapy alone, palliative care, or radiation plus surgery. Radiation combined with surgical resection resulted in a significant hazards ratio of 0.36 (95% confidence interval, 0.15–0.86), compared with radiation alone. Conclusions Our report provides a large single-institution experience of brain metastases from gynecologic cancer. Patients with BMD have poor prognoses; however, treatment with multimodal therapy including surgical resection and radiation may prolong overall survival. PMID:26332394

  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. 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.

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

    PubMed Central

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

    2012-01-01

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

  7. 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

  8. 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.

  9. Novel Pretreatment Scoring Incorporating C-reactive Protein to Predict Overall Survival in Advanced Hepatocellular Carcinoma with Sorafenib Treatment

    PubMed Central

    Nakanishi, Hiroyuki; Kurosaki, Masayuki; Tsuchiya, Kaoru; Yasui, Yutaka; Higuchi, Mayu; Yoshida, Tsubasa; Komiyama, Yasuyuki; Takaura, Kenta; Hayashi, Tsuguru; Kuwabara, Konomi; Nakakuki, Natsuko; Takada, Hitomi; Ueda, Masako; Tamaki, Nobuharu; Suzuki, Shoko; Itakura, Jun; Takahashi, Yuka; Izumi, Namiki

    2016-01-01

    Objectives This study aimed to build a prediction score of prognosis for patients with advanced hepatocellular carcinoma (HCC) after sorafenib treatment. Methods A total of 165 patients with advanced HCC who were treated with sorafenib were analyzed. Readily available baseline factors were used to establish a scoring system for the prediction of survival. Results The median survival time (MST) was 14.2 months. The independent prognostic factors were C-reactive protein (CRP) <1.0 mg/dL [hazard ratio (HR) =0.51], albumin >3.5 g/dL (HR =0.55), alpha-fetoprotein <200 ng/mL (HR =0.45), and a lack of major vascular invasion (HR =0.39). Each of these factors had a score of 1, and after classifying the patients into five groups, the total scores ranged from 0 to 4. Higher scores were linked to significantly longer survival (p<0.0001). Twenty-nine patients (17.6%) with a score of 4 had a MST as long as 36.5 months, whereas MST was as short as 2.4 and 3.7 months for seven (4.2%) and 22 (13.3%) patients with scores of 0 and 1, respectively. Conclusions A novel prognostic scoring system, which includes the CRP level, has the ability to stratify the prognosis of patients with advanced stage HCC after treatment with sorafenib. PMID:27781198

  10. Predicting Fluid Responsiveness Using Bedside Ultrasound Measurements of the Inferior Vena Cava and Physician Gestalt in the Emergency Department of an Urban Public Hospital in Sub-Saharan Africa

    PubMed Central

    Haeffele, Cathryn; Mfinanga, Juma A.; Mwafongo, Victor G.; Reynolds, Teri A.

    2016-01-01

    Background Bedside inferior vena cava (IVC) ultrasound has been proposed as a non-invasive measure of volume status. We compared ultrasound measurements of the caval index (CI) and physician gestalt to predict blood pressure response in patients requiring intravenous fluid resuscitation. Methods This was a prospective study of adult emergency department patients requiring fluid resuscitation. A structured data sheet was used to record serial vital signs and the treating clinician’s impression of patient volume status and cause of hypotension. Bedside ultrasound CI measurements were performed at baseline and after each 500mL of fluid. Receiver operating characteristic (ROC) curve analysis was performed to characterize the relationship between CI and Physician gestalt, and the change in mean arterial pressure (MAP). Results We enrolled 364 patients, 52% male, mean age 36 years. Indications for fluid resuscitation were haemorrhage (54%), dehydration (30%), and sepsis (17%). Receiver operating characteristic curve analysis found optimal CI cut-off values of 45%, 52% and 53% to predict a MAP rise of 5, 8 and 10 mmHg per litre of fluid, respectively. The sensitivity and specificity of CI of 50% for predicting a 10mmHg increase in MAP per litre were 88% (95%CI 81–93%) and 73% (95%CI 67–79%), respectively, area under the curve (AUC) = 0.85 (0.81–0.89). The sensitivity and specificity of physician gestalt estimate of volume depletion severity were 68% (95%CI 60–75%) and 86% (95%CI 80–90%), respectively, AUC = 0.83 (95% CI: 0.79–0.87). Those with a baseline CI ≥ 50% (51% of patients) had a 2.8-fold greater fluid responsiveness than those with a baseline CI<50% (p<0.0001). Conclusion Ultrasound measurement of the CI can predict blood pressure response among patients requiring intravenous fluid resuscitation and may be useful in early identification of patients who will benefit most from volume resuscitation, and those who will likely require other

  11. 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

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

    PubMed Central

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

    2016-01-01

    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

  13. 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.

  14. 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

  15. 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

  16. p53 Arg72Pro polymorphism predicts survival outcome in lung cancer patients in Indian population.

    PubMed

    Sreeja, Leelakumari; Syamala, Vani; Raveendran, Praveenkumar B; Santhi, Sarojam; Madhavan, Jayaprakash; Ankathil, Ravindran

    2008-02-01

    In response to many forms of cellular stress, including DNA damage, the p53 protein functions to induce growth arrest, DNA repair, or apoptosis. Common allele variants in the TP53 gene modulate pathways of lung carcinogenesis and susceptibility to or prognosis of lung cancer. The prognostic role of the polymorphism was assessed in 422 subjects using PCR-RFLP. Logistic regression analysis showed a dominant presentation of Pro/Pro homozygotes in lung carcinoma population than in control population (OR = 2.1, P = 0.003). We further investigated the association of p53 codon 72 polymorphism with prognosis in 170 lung cancer patients. Kaplan-Meier survival analyses showed a significant difference in survival between p53 variant genotypes and overall survival (P = 0.02). Cox regression analysis showed p53 Arg72Pro heterozygous genotype was overall an independent prognostic factor (Risk ratio of death, 2.2; P = 0.02), suggesting Pro72Pro genotype to be a potential risk factor favoring the development of lung carcinoma and that Arg72Pro genotype is independently associated with a poorer prognosis of lung cancer. PMID:18181044

  17. 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

  18. Neoadjuvant Chemotherapy Induces Expression Levels of Breast Cancer Resistance Protein That Predict Disease-Free Survival in Breast Cancer

    PubMed Central

    Kim, Baek; Fatayer, Hiba; Hanby, Andrew M.; Horgan, Kieran; Perry, Sarah L.; Valleley, Elizabeth M.A.; Verghese, Eldo T.; Williams, Bethany J.; Thorne, James L.; Hughes, Thomas A.

    2013-01-01

    Three main xenobiotic efflux pumps have been implicated in modulating breast cancer chemotherapy responses. These are P-glycoprotein (Pgp), Multidrug Resistance-associated Protein 1 (MRP1), and Breast Cancer Resistance Protein (BCRP). We investigated expression of these proteins in breast cancers before and after neoadjuvant chemotherapy (NAC) to determine whether their levels define response to NAC or subsequent survival. Formalin-fixed paraffin-embedded tissues were collected representing matched pairs of core biopsy (pre-NAC) and surgical specimen (post-NAC) from 45 patients with invasive ductal carcinomas. NAC regimes were anthracyclines +/− taxanes. Immunohistochemistry was performed for Pgp, MRP1 and BCRP and expression was quantified objectively using computer-aided scoring. Pgp and MRP1 were significantly up-regulated after exposure to NAC (Wilcoxon signed-rank p = 0.0024 and p<0.0001), while BCRP showed more variation in response to NAC, with frequent up- (59% of cases) and down-regulation (41%) contributing to a lack of significant difference overall. Pre-NAC expression of all markers, and post-NAC expression of Pgp and MRP1 did not correlate with NAC response or with disease-free survival (DFS). Post-NAC expression of BCRP did not correlate with NAC response, but correlated significantly with DFS (Log rank p = 0.007), with longer DFS in patients with low post-NAC BCRP expression. In multivariate Cox regression analyses, post-NAC BCRP expression levels proved to predict DFS independently of standard prognostic factors, with high expression associated with a hazard ratio of 4.04 (95% confidence interval 1.3–12.2; p = 0.013). We conclude that NAC-induced expression levels of BCRP predict survival after NAC for breast cancer, while Pgp and MRP1 expression have little predictive value. PMID:23658771

  19. 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.

  20. μ-Opioid Receptor Gene A118G Polymorphism Predicts Survival in Patients with Breast Cancer

    PubMed Central

    Bortsov, Andrey V.; Millikan, Robert C.; Belfer, Inna; Boortz-Marx, Richard L.; Arora, Harendra; McLean, Samuel A.

    2012-01-01

    Background Preclinical studies suggest that opioids may promote tumor growth. Genetic polymorphisms have been shown to affect opioid receptor function and to modify the clinical effects of morphine. In this study we assessed the association between six common polymorphisms in the μ-opioid receptor gene, including the well known A118G polymorphism, and breast cancer survival. Methods A total of 2,039 women ages 23–74 yr (38% African American, 62% European American, 55% postmenopausal) diagnosed with breast cancer between 1993 – 2001 were followed through 2006. Genotyping was performed using the TaqMan platform (Applied Biosystems Inc., Foster City, CA). Kaplan-Meyer curves, log-rank tests, and Cox proportional hazard models were used to examine the association between each genotype and survival. Results After Bonferroni adjustment for multiple testing, patient genotype at A118G was associated with breast cancer-specific mortality at 10 yr. Women with one or more copies of the G allele had decreased breast cancer-specific mortality (p < .001). This association was limited to invasive cases only; effect size appeared to increase with clinical stage. Cox regression model adjusted for age and ethnicity also showed decreased mortality in A/G and G/G genotypes compared to A/A genotype (hazard ratio = 0.57 [0.38, 0.85] and 0.32 [0.22, 0.49], respectively; p = .006). Conclusions These results suggest that opioid pathways may be involved in tumor growth. Further studies examining the association between genetic variants influencing opioid system function and cancer survival are warranted. PMID:22433205

  1. Visceral pleural invasion is not predictive of survival in lung cancer patients with smaller tumor size

    PubMed Central

    David, E; Thall, PF; Kalhor, N; Hofstetter, WL; Rice, DC; Roth, JA; Swisher, SG; Walsh, GL; Vaporciyan, AA; Wei, C; Mehran, RJ

    2015-01-01

    Background Visceral pleural invasion (VPI) is used as an indicator of adverse prognosis in non-small cell lung carcinoma (NSCLC). The purpose of this retrospective study was to evaluate the impact of VPI on disease-free survival (DFS) and overall survival (OS) in patients with node-negative NSCLC. Methods Between 1998 and 2009, 1166 patients with pathological N0M0 NSCLC underwent surgical resection by lobectomy. 214 patients with VPI were compared to 952 without. Results Median follow-up was 59 months. In multivariate analysis, VPI, larger tumor size, older age, female gender, and poor performance status were significantly associated with decreased OS. In contrast, larger tumor size, female gender, and poor performance, but notably not VPI, were associated with decreased DFS. After examining interactive effects of VPI and T subgroups, we found that VPI did not significantly affect either OS or DFS in the subgroups of patients with smaller tumor sizes T1a, T1b, or T2a. In contrast, a deleterious effect of VPI on DFS was seen for tumors > 5cm, T2b and T3, with the VPI-T3 interaction effect on DFS being statistically significant but not for OS. Conclusions The effect of VPI on survival in NSCLC varies greatly with tumor size, with VPI not strongly associated with OS or DFS in tumors less than 5cm, but showing large negative effects on DFS for T2b and T3 tumors. Using VPI to upstage T1 tumors to a higher T category is not warranted, since it would misrepresent these VPI-T subgroup effects. PMID:23643547

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

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

    PubMed

    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

    2015-08-01

    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.

  8. Fecal cortisol levels predict breeding but not survival of females in the short-lived rodent, Octodon degus.

    PubMed

    Ebensperger, Luis A; Tapia, Diego; Ramírez-Estrada, Juan; León, Cecilia; Soto-Gamboa, Mauricio; Hayes, Loren D

    2013-06-01

    The cort-adaptation hypothesis indicates that an association between glucocorticoid (cort) levels and fitness may vary with the extent to which reproduction or breeding effort is a major determinant of cort levels. Support for a context dependent association between cort and fitness comes mostly from relatively long-lived, bird species. We tested the hypothesis that there are gender and context (life-history) specific cort-fitness relationships in degus, a short-lived and generally semelparous social rodent. In particular, we used demographical records on a natural population to estimate adult survival through seasons and years and linked that to records of baseline cort (based on fecal cortisol metabolites). We found no evidence for a direct relationship between baseline cort and adult survival across seasons, and this lack of association was recorded irrespective of sex and life history stage. Yet, cort levels during early lactation predicted the probability that females produce a second litter during the same breeding season, supporting a connection between baseline cort levels and breeding effort. Overall, the differential effects of cort on survival and breeding supported that the extent of cort-fitness relationships depends on the fitness component examined.

  9. Design and Multiseries Validation of a Web-Based Gene Expression Assay for Predicting Breast Cancer Recurrence and Patient Survival

    PubMed Central

    Van Laar, Ryan K.

    2011-01-01

    Gene expression analysis is a valuable tool for determining the risk of disease recurrence and overall survival of an individual patient with breast cancer. The purpose of this study was to create and validate a robust prognostic algorithm and implement it within an online analysis environment. Genomic and clinical data from 477 clinically diverse patients with breast cancer were analyzed with Cox regression models to identify genes associated with outcome, independent of standard prognostic factors. Percentile-ranked expression data were used to train a “metagene” algorithm to stratify patients as having a high or low risk of recurrence. The classifier was applied to 1016 patients from five independent series. The 200-gene algorithm stratifies patients into risk groups with statistically and clinically significant differences in recurrence-free and overall survival. Multivariate analysis revealed the classifier to be the strongest predictor of outcome in each validation series. In untreated node-negative patients, 88% sensitivity and 44% specificity for 10-year recurrence-free survival was observed, with positive and negative predictive values of 32% and 92%, respectively. High-risk patients appear to significantly benefit from systemic adjuvant therapy. A 200-gene prognosis signature has been developed and validated using genomic and clinical data representing a range of breast cancer clinicopathological subtypes. It is a strong independent predictor of patient outcome and is available for research use. PMID:21458382

  10. Design and multiseries validation of a web-based gene expression assay for predicting breast cancer recurrence and patient survival.

    PubMed

    Van Laar, Ryan K

    2011-05-01

    Gene expression analysis is a valuable tool for determining the risk of disease recurrence and overall survival of an individual patient with breast cancer. The purpose of this study was to create and validate a robust prognostic algorithm and implement it within an online analysis environment. Genomic and clinical data from 477 clinically diverse patients with breast cancer were analyzed with Cox regression models to identify genes associated with outcome, independent of standard prognostic factors. Percentile-ranked expression data were used to train a "metagene" algorithm to stratify patients as having a high or low risk of recurrence. The classifier was applied to 1016 patients from five independent series. The 200-gene algorithm stratifies patients into risk groups with statistically and clinically significant differences in recurrence-free and overall survival. Multivariate analysis revealed the classifier to be the strongest predictor of outcome in each validation series. In untreated node-negative patients, 88% sensitivity and 44% specificity for 10-year recurrence-free survival was observed, with positive and negative predictive values of 32% and 92%, respectively. High-risk patients appear to significantly benefit from systemic adjuvant therapy. A 200-gene prognosis signature has been developed and validated using genomic and clinical data representing a range of breast cancer clinicopathological subtypes. It is a strong independent predictor of patient outcome and is available for research use.

  11. D-Dimer and Carcinoembryonic Antigen Levels: Useful Indicators for Predicting the Tumor Stage and Postoperative Survival.

    PubMed

    Tekeşin, Kemal; Bayrak, Savaş; Esatoğlu, Varol; Özdemir, Ebru; Özel, Leyla; Melih Kara, Veli

    2016-01-01

    The purpose of this prospective study is to determine the preoperative plasma D-dimer and serum Carcinoembryonic Antigen (CEA) levels of patients scheduled for curative surgical resection for colorectal cancer and to evaluate the significance of these levels on the prognosis and postoperative survival rate. One hundred sixty-five patients with colorectal cancer, who were scheduled to have elective resection between January 2008 and January 2011, were included in the study. A significant increase was observed in the D-dimer levels, particularly in poorly differentiated tumors. The distance covered by the tumor inside the walls of the colon and rectum (T-stage) was significant for both D-dimer and CEA levels. As the T-stage increased, there was also a significant increase in the D-dimer and CEA levels. A high significance and correlation level was detected between the TNM staging and both D-dimer and CEA. A significant relationship was found between the advanced tumor stage and short postoperative survival rate of patients with colorectal cancer. Therefore, the analysis of preoperative D-dimer and CEA levels can be useful in predicting the stage and differentiation of the tumor and the postoperative survival rate. PMID:27651789

  12. D-Dimer and Carcinoembryonic Antigen Levels: Useful Indicators for Predicting the Tumor Stage and Postoperative Survival

    PubMed Central

    Tekeşin, Kemal; Esatoğlu, Varol; Özdemir, Ebru; Özel, Leyla; Melih Kara, Veli

    2016-01-01

    The purpose of this prospective study is to determine the preoperative plasma D-dimer and serum Carcinoembryonic Antigen (CEA) levels of patients scheduled for curative surgical resection for colorectal cancer and to evaluate the significance of these levels on the prognosis and postoperative survival rate. One hundred sixty-five patients with colorectal cancer, who were scheduled to have elective resection between January 2008 and January 2011, were included in the study. A significant increase was observed in the D-dimer levels, particularly in poorly differentiated tumors. The distance covered by the tumor inside the walls of the colon and rectum (T-stage) was significant for both D-dimer and CEA levels. As the T-stage increased, there was also a significant increase in the D-dimer and CEA levels. A high significance and correlation level was detected between the TNM staging and both D-dimer and CEA. A significant relationship was found between the advanced tumor stage and short postoperative survival rate of patients with colorectal cancer. Therefore, the analysis of preoperative D-dimer and CEA levels can be useful in predicting the stage and differentiation of the tumor and the postoperative survival rate. PMID:27651789

  13. 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

  14. Preoperative CT-based nomogram for predicting overall survival in women with non-endometrioid carcinomas of the uterine corpus

    PubMed Central

    Lakhman, Yulia; Yakar, Derya; Goldman, Debra A.; Katz, Seth S.; Vargas, Hebert A.; Miccò, Maura; Zheng, Junting; Moskowitz, Chaya S.; Soslow, Robert A.; Hricak, Hedvig; Abu-Rustum, Nadeem R.; Sala, Evis

    2016-01-01

    Purpose To develop a preoperative CT-based nomogram for predicting overall survival (OS) in patients with non-endometrioid carcinomas of the uterine corpus. Methods Waiving informed consent, the institutional review board approved this HIPAA-compliant, retrospective study of 193 women with histopathologically proven uterine papillary serous carcinomas (UPSC), uterine clear cell carcinomas (UCCC), and uterine carcinosarcomas (UCS) who underwent primary surgical resection between May 1998 and December 2011, and had a preoperative CT ≤ 6 weeks before surgery. All CT scans were reviewed for local or/and regional tumor extent, presence of pelvic or/and paraaortic adenopathy, and presence of distant metastases. Univariate survival analysis was performed using log-rank test and Cox regression. Variables shown significant by the univariate analysis were evaluated with the multivariable Cox regression analysis and the results were used to create a nomogram for predicting OS. The predictive accuracy of the nomogram was assessed with the concordance probability index (c-index) and a 3-year calibration plot. Results Mean patient age was 67.2 years (range: 49.0–85.9); histology included UPSC (n=116), UCCC (n=27), and UCS (n=50). Median follow-up was 38.1 months (0.9–168.5 months). At multivariate analysis, patient age, ascites, and omental implants on CT were significant adverse predictors of OS and were used to build the nomogram. Concordance index for the nomogram was 0.640±0.028. Conclusion We developed a nomogram with a good concordance probability at predicting OS based on readily available pretreatment clinical and imaging characteristics. This preoperative nomogram has the potential to improve initial treatment planning and patient counseling. PMID:25549782

  15. Expression of transcription factor AP-2α predicts survival in epithelial ovarian cancer

    PubMed Central

    Anttila, M A; Kellokoski, J K; Moisio, K I; Mitchell, P J; Saarikoski, S; Syrjänen, K; Kosma, V-M

    2000-01-01

    The 52-kDa activator protein (AP)-2 is a DNA-binding transcription factor which has been reported to have growth inhibitory effects in cancer cell lines and in human tumours. In this study the expression of AP-2α was analysed in 303 epithelial ovarian carcinomas by immunohistochemistry (IHC) with a polyclonal AP-2α antibody and its mRNA status was determined by in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR). The immunohistochemical expression of AP-2α was correlated with clinicopathological variables, p21/WAF1 protein expression and survival. In normal ovaries, epithelial cells expressed AP-2α protein only in the cytoplasm. In carcinomas nuclear AP-2α expression was observed in 28% of the cases although cytoplasmic expression was more common (51%). The expression of AP-2α varied according to the histological subtype and differentiation. AP-2α and p21/WAF1 expressions did not correlate with each other. Both in univariate (P = 0.002) and multivariate analyses (relative risks (RR) 1.6, 95% confidence interval (CI) 1.13–2.18, P = 0.007) the high cytoplasmic AP-2α expression favoured the overall survival. In contrast, the nuclear AP-2α expression combined with low cytoplasmic expression increased the risk of dying of ovarian cancer (RR = 2.10, 95% CI 1.13–3.83, P = 0.018). The shift in the expression pattern of AP-2α (nuclear vs cytoplasmic) in carcinomas points out to the possibility that this transcription factor may be used by oncogenes in certain histological subtypes. Based on the mRNA analyses, the incomplete expression and translation of AP-2α in ovarian cancer may be due to post-transcriptional regulation. © 2000 Cancer Research Campaign PMID:10864206

  16. 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

  17. Germline and Somatic Mutations in Homologous Recombination Genes Predict Platinum Response and Survival in Ovarian, Fallopian Tube, and Peritoneal Carcinomas

    PubMed Central

    Pennington, Kathryn P.; Walsh, Tom; Harrell, Maria I.; Lee, Ming K.; Pennil, Christopher C.; Rendi, Mara H.; Thornton, Anne; Norquist, Barbara M.; Casadei, Silvia; Nord, Alexander S.; Agnew, Kathy J.; Pritchard, Colin C.; Scroggins, Sheena; Garcia, Rochelle L.; King, Mary-Claire; Swisher, Elizabeth M.

    2013-01-01

    Purpose Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination (HR) DNA repair genes is uncertain. Experimental Design Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the HR pathway. Results 31% of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 HR genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Non-serous ovarian carcinomas had similar rates of HR mutations to serous carcinomas (28% vs. 31%, p=0.6), including clear cell, endometrioid, and carcinosarcoma. The presence of germline and somatic HR mutations was highly predictive of primary platinum sensitivity (p=0.0002) and improved overall survival (p=0.0006), with median overall survival 66 months in germline HR mutation carriers, 59 months in cases with a somatic HR mutation, and 41 months for cases without an HR mutation. Conclusions Germline or somatic mutations in HR genes are present in almost one-third of ovarian carcinomas, including both serous and non-serous histologies. Somatic BRCA1/2 mutations and mutations in other HR genes have a similar positive impact on overall survival and platinum responsiveness as germline BRCA1/2 mutations. The similar rate of HR mutations in non-serous carcinomas supports their inclusion in PARP inhibitor clinical trials. PMID:24240112

  18. Microscopy image analysis of p63 immunohistochemically stained laryngeal cancer lesions for predicting patient 5-year survival.

    PubMed

    Ninos, Konstantinos; Kostopoulos, Spiros; Kalatzis, Ioannis; Sidiropoulos, Konstantinos; Ravazoula, Panagiota; Sakellaropoulos, George; Panayiotakis, George; Economou, George; Cavouras, Dionisis

    2016-01-01

    The aim of the present study was to design a microscopy image analysis (MIA) system for predicting the 5-year survival of patients with laryngeal squamous cell carcinoma, employing histopathology images of lesions, which had been immunohistochemically (IHC) stained for p63 expression. Biopsy materials from 42 patients, with verified laryngeal cancer and follow-up, were selected from the archives of the University Hospital of Patras, Greece. Twenty six patients had survived more than 5 years and 16 less than 5 years after the first diagnosis. Histopathology images were IHC stained for p63 expression. Images were first processed by a segmentation method for isolating the p63-expressed nuclei. Seventy-seven features were evaluated regarding texture, shape, and physical topology of nuclei, p63 staining, and patient-specific data. Those features, the probabilistic neural network classifier, the leave-one-out (LOO), and the bootstrap cross-validation methods, were used to design the MIA-system for assessing the 5-year survival of patients with laryngeal cancer. MIA-system accuracy was about 90 % and 85 %, employing the LOO and the Bootstrap methods, respectively. The image texture of p63-expressed nuclei appeared coarser and contained more edges in the 5-year non-survivor group. These differences were at a statistically significant level (p < 0.05). In conclusion, this study has proposed an MIA-system that may be of assistance to physicians, as a second opinion tool in assessing the 5-year survival of patients with laryngeal cancer, and it has revealed useful information regarding differences in nuclei texture between 5-year survivors and non-survivors. PMID:26285779

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. An expression based REST signature predicts patient survival and therapeutic response for glioblastoma multiforme

    PubMed Central

    Liang, Jianfeng; Meng, Qinghua; Zhao, Wanni; Tong, Pan; Li, Ping; Zhao, Yuanli; Zhao, Xiaodong; Li, Hua

    2016-01-01

    Proper regulation of neuronal gene expression is crucial for the development and differentiation of the central nervous system. The transcriptional repressor REST (repressor element-1 silencing transcription factor) is a key regulator in differentiation of pluripotent stem cells to neuronal progenitors and mature neurons. Dysregulated REST activity has been implicated in various diseases, among which the most deadly is glioblastoma multiforme (GBM). Here we have developed an expression-based REST signature (EXPREST), a device providing quantitative measurements of REST activity for GBM tumors. EXPREST robustly quantifies REST activity (REST score) using gene expression profiles in absence of clinic-pathologic assessments of REST. Molecular characterization of REST activity identified global alterations at the DNA, RNA, protein and microRNA levels, suggesting a widespread role of REST in GBM tumorigenesis. Although originally aimed to capture REST activity, REST score was found to be a prognostic factor for overall survival. Further, cell lines with enhanced REST activity was found to be more sensitive to IGF1R, VEGFR and ABL inhibitors. In contrast, cell lines with low REST score were more sensitive to cytotoxic drugs including Mitomycin, Camptothecin and Cisplatin. Together, our work suggests that therapeutic targeting of REST provides a promising opportunity for GBM treatment. PMID:27698411

  6. 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.

  7. Expression of dystroglycan correlates with tumor grade and predicts survival in renal cell carcinoma.

    PubMed

    Sgambato, Alessandro; Camerini, Andrea; Amoroso, Domenico; Genovese, Giannicola; De Luca, Filomena; Cecchi, Massimo; Migaldi, Mario; Rettino, Alessandro; Valsuani, Chiara; Tartarelli, Gianna; Donati, Sara; Siclari, Olimpia; Rossi, Giulio; Cittadini, Achille

    2007-12-01

    The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor aggressiveness. In this study expression of the DG subunit was evaluated by immunostaining in a series of renal epithelial cancers and its relation with traditional prognostic indicators and with the clinical outcome of the patients was evaluated. alphaDG expression was undetectable in a significant fraction of tumors (54%). In renal cell carcinomas (RCC) loss of alpha-DG staining correlated with higher tumor grade (p = 0.02) but not with tumor stage nor tumor size. In clear cell RCC patients loss of alphaDG staining correlated with an increased risk of recurrence (p = 0.002 by log-rank test) and death (p = 0.004) also when patients with lower grade or stage tumors were analyzed separately. In a multivariate analysis loss of DG staining confirmed to be and independent predictor of shorter disease-free (p = 0.001; RR = 4.9) and overall (p = 0.009; RR = 4.9) survival stronger than tumor grade and size. These findings demonstrate that loss of alphaDG expression, which correspond to loss of a functional DG complex, is a frequent event in human renal tumorigenesis and is an independent predictor of early recurrence and death for patients with clear cell RCC.

  8. Post-treatment serum lactic dehydrogenase as a predictive indicator for distant metastasis and survival of patients with nasopharyngeal carcinoma

    PubMed Central

    Dong, Bai-qiang; Xu, Yu-jin; Zheng, Yuan-da; Sun, Zhong-wen; Yang, Yang; Chen, Yuan-Yuan; Chen, Xiao-zhong; Chen, Ming

    2016-01-01

    Purpose To examine the function of serum lactic dehydrogenase (SLDH) level after intensity-modulated radiotherapy (IMRT) as a predictive factor for and loco-regional relapse free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS), and overall survival(OS) among patients with in-situ nasopharyngeal carcinoma (NPC). Results Compared with the normal pt-SLDH group, elevated pt-SLDH demonstrated significant lower DMFS (46 versus 66 months, hazard ratio (HR) 4.07, 95% CI 2.43–6.80, p < 0.001), DFS (46 versus 63 months, HR 2.78, 95% CI 1.70–4.53, p < 0.001), and OS (54 versus 66 months, HR 2.93, 95% CI 1.65–5.23, p < 0.001). Distant metastasis were observed in 32.8% (20/61) patients with elevated pt-SLDH, and 8% (54/678) in normal SLDH (odds ratio (OR) 6.13, 95% CI 3.35–11.18, p < 0.001). COX regression showed that pt-SLDH was an independent prognostic factors for OS (HR 2.91, 95% CI 1.57–5.41, p < 0.001), DMFS (HR 4.21, 95% CI 2.51–7.07, p < 0.001), LRFS (HR 2.53, 95% CI 1.22–5.24, p < 0.001), and DFS (HR 2.81, 95% CI 1.72–4.59, p < 0.001). Materials and Methods The records of 739 in-situ NPC patients admitted to Zhejiang Cancer Hospital between January 2007 and May 2012 were retrospectively reviewed. The relationships between post-treatment SLDH (pt-SLDH) and LRFS, DMFS, DFS, and OS were analyzed. Conclusions Our finding indicated that elevated pt-SLDH could be a simple available prognostic indicator for distant metastasis and survival for in-situ NPC patients. PMID:27050275

  9. Microvessel count predicts metastatic disease and survival in non-small cell lung cancer.

    PubMed

    Fontanini, G; Bigini, D; Vignati, S; Basolo, F; Mussi, A; Lucchi, M; Chine, S; Angeletti, C A; Harris, A L; Bevilacqua, G

    1995-09-01

    The growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early-stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non-small lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti-Factor VIII monoclonal antibody (Mab) in methacarn-fixed tumour samples. In univariat analysis, MC (P< 0.000001), sex (P=0.0036), histotype (P < 0.014), tumour status (P <0.007), and vessel invasion (P < 0.019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P<0.000003) retained the most important influence on nodal metastasis. The overall survival analysis calculated by the Kaplan-Meier method revealed that tumours with high MC ( > 25 vessels/field) were significantly associated with increased death risk (log-rank test P = 0.00067; Cox's test P = 0.00046; Gehan's Wilcoxon test P = 0.00108). In 94 patients, the development of metastatic disease during follow-up was significantly related to MC. Indeed, patients who developed metastasis during follow-up showed a higher MC, either as a dichotomous (P = 0.01) or as a continuous (P = 0.003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Survival characteristics and the applicability of predictive mathematical modelling to Listeria monocytogenes growth in sous vide products.

    PubMed

    Nyati, H

    2000-06-01

    Survival and growth of Listeria monocytogenes isolates during sous vide processing and storage, and the applicability of predictive modelling in determining the potential for growth of L. monocytogenes in broth models and in sous vide products was investigated. L. monocytogenes grew in anaerobic tryptose phosphate broth and in chicken and beef samples by 2 log cycles in 8 days at 3 degrees C and 4-5 log cycles in 6 days at 8 degrees C. However, heating to an internal temperature of 70 degrees C resulted in a 4-5 log reduction and 70 degrees C/2 min resulted in a reduction greater than 7 log cycles. Lowering the product pH to 5.0 was effective in inhibiting L. monocytogenes growth, whereas a sodium chloride concentration of 2% had a negligible effect on growth rates. The square root model (Ratkowsky et al., 1983) predicted L. monocytogenes growth rates at 0-25 degrees C with a coefficient of determination (R2 value) of 98.36-99.63% and a bias factor of 1.08 to 1.21 in beef, chicken and broth substrates of unmodified pH. In addition, the Response Surface Polynomial Model (Version 3.1, Buchanan et al., 1989) predicted generation times at 5-25 degrees C with a 0-17.4% difference between observed and expected generation times in tryptose phosphate broth at pH 7.3. There were however, large differences (25.5 vs. 5.3 h) between observed generation times at pH 5.6 (8 degrees C) and those predicted by the Pathogen Modelling Program in tryptose phosphate broth. A divergence from predicted values was also noted at lower temperatures (0-3.5 degrees C) in the square root model. PMID:10857538

  11. Value of volume-based metabolic parameters for predicting survival in breast cancer patients treated with neoadjuvant chemotherapy

    PubMed Central

    Kim, Tae Hee; Yoon, Joon-Kee; Kang, Doo Kyoung; Kang, Seok Yun; Jung, Yong Sik; Han, Sehwan; Kim, Ji Young; Yim, Hyunee; An, Young-Sil

    2016-01-01

    Abstract We evaluated the role of metabolic parameters in the prediction of disease recurrence in operable invasive ductal breast cancer patients treated with neoadjuvant chemotherapy (NAC). We retrospectively evaluated 139 female patients (mean age, 46.5 years; range: 27–72 years) with invasive ductal breast cancer, treated with NAC followed by surgery. All patients underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging at baseline and after completion of NAC before surgery. The prognostic significance of clinicopathological and imaging parameters for disease-free survival (DFS) was evaluated. Recurrence of cancer was detected in 31 of 139 patients (22.3%; follow-up period: 6–82 months). Baseline maximum standardized uptake value, metabolic tumor volume (MTV), and reduction rate (RR) of MTV after NAC were significant independent prognostic factors for DFS in a multivariate analysis (all P < 0.05). The survival functions differed significantly between low and high histological grades (P < 0.001). DFS of the patients with high baseline MTV (≥5.23 cm3) was significantly poorer than that of low MTV patients (P = 0.019). The survival function of the group with low RR of MTV after NAC (≤90.72%) was poorer than the higher RR of the MTV group (P = 0.008). Our findings suggest that breast cancer patients who have a high histological grade, large baseline MTV, or a small RR of MTV after NAC should receive great attention to check for possible recurrence. PMID:27741099

  12. 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

  13. Blood color is influenced by inflammation and independently predicts survival in hemodialysis patients: quantitative evaluation of blood color.

    PubMed

    Shibata, Masanori; Nagai, Kojiro; Doi, Toshio; Tawada, Hideo; Taniguchi, Shinkichi

    2012-11-01

    Blood color of dialysis patients can be seen routinely. Darkened blood color is often observed in critically ill patients generally because of decreased oxygen saturation, but little is known about the other factors responsible for the color intensity. In addition, quantitative blood color examination has not been performed yet. Therefore, no one has evaluated the predictive power of blood color. The aim of this study was to evaluate if blood color darkness reflects some medical problems and is associated with survival disadvantage. Study design is a prospective cohort study. One hundred sixty-seven patients were enrolled in this study. Quantification of blood color was done using a reflected light colorimeter. Demographic and clinical data were collected to find out the factors that can be related to blood color. Follow-ups were performed for 2 years to analyze the risk factors for their survival. Regression analysis showed that C-reactive protein and white blood cell count were negatively correlated with blood color. In addition, blood color was positively correlated with mean corpuscular hemoglobin concentration and serum sodium concentration as well as blood oxygen saturation. During a follow-up, 34 (20.4%) patients died. Cox regression analysis revealed that darkened blood color was an independent significant risk factor of mortality in hemodialysis patients as well as low albumin and low Kt/V. These results suggest that inflammation independently affects blood color and quantification of blood color is useful to estimate prognosis in patients undergoing hemodialysis. It is possible that early detection of blood color worsening can improve patients' survival.

  14. Predicting transport survival of brindle and red rock lobsters Jasus edwardsii using haemolymph biochemistry and behaviour traits.

    PubMed

    Simon, Cedric J; Mendo, Tania C; Green, Bridget S; Gardner, Caleb

    2016-11-01

    Mortality events during live transport of Jasus edwardsii rock lobsters are common around the time of season openings in Tasmania, with lobsters from deeper fishing areas with pale shell colouration (brindle) being perceived as more susceptible than shallow-water, red-coloured (red) lobsters. The aims of this study were to assess and predict the vulnerability of brindle and red lobsters to extended emersion exposure using pre- and post-emersion data which included 28 haemolymph biochemical parameters and 5 behaviour traits. No effect of lobster shell colour on haemolymph biochemistry, behaviour traits and their vulnerability to emersion was found. A combined survival of 97% after 40h and 57% after 64h in a first experiment, and 37% after 64h in a second experiment, was observed. Behaviour traits (i.e., righting response, tail flips and three reflex behaviours) were poor indicator of survival. Haemolymph parameters were either unaffected by emersion (e.g., Brix index, protein and lipids), affected by emersion but not associated with mortality (e.g., total haemocyte counts, calcium, magnesium, bicarbonate, glucose and uric acid), or associated with mortality following a recovery period (e.g., pH, the sodium to potassium ratio, urea, and the activity of amylase). A build-up of anaerobic end-products and nitrogenous waste most likely resulted in the mortality. A model based on lobster size and the pre-emersion concentration of haemolymph bicarbonate and haemocyanin was found to be a useful indicator of future survival. This study provides promising leads towards the development of a blood based vulnerability test for live crustacean prior transport. PMID:27395444

  15. Does inequality in self-assessed health predict inequality in survival by income? Evidence from Swedish data.

    PubMed

    van Doorslaer, Eddy; Gerdtham, Ulf G

    2003-11-01

    This paper empirically addresses two questions using a large, individual-level Swedish data set which links mortality data to health survey data. The first question is whether there is an effect of an individual's self-assessed health (SAH) on his subsequent survival probability and if this effect differs by socioeconomic factors. Our results indicate that the effect of SAH on mortality risk declines with age-probably because of adjustment towards 'milder' overall health evaluations at higher ages-but does not seem to differ by indicators of socioeconomic status (SES) like income or education. This finding suggests that there is no systematic adjustment of SAH by SES and therefore that any measured income-related inequality in SAH is unlikely to be biased by reporting error. The second question is: how much of the income-related inequality in mortality can be explained by income-related inequality in SAH? Using a decomposition method, we find that inequality in SAH accounts for only about 10% of mortality inequality if interactions are not allowed for, but its contribution is increased to about 28% if account is taken of the reporting tendencies by age. In other words, omitting the interaction between age and SAH leads to a substantial underestimation of the partial contribution of SAH inequality by income. These results suggest that the often observed inequalities in SAH by income do have predictive power for the-less often observed-inequalities in survival by income.

  16. Prediction of an organism's inactivation patterns from three single survival ratios determined at the end of three non-isothermal heat treatments.

    PubMed

    Corradini, Maria G; Normand, Mark D; Peleg, Micha

    2008-08-15

    Traditionally, an organism's heat resistance parameters have been determined from a set of experimental isothermal survival data. Sometimes, however, even approximating an isothermal profile, and/or obtaining counts at sufficiently short time intervals, is extremely difficult for technical and logistic reasons. The problem would be avoided if the survival parameters could be calculated from the final survival ratios determined at the end of non-isothermal heat treatments with known temperature profiles. Theoretically, if the heat resistance were characterized by three unknown survival parameters, they could be extracted by solving three simultaneous dynamic survival curves' equations. In practice, because of the three equation's complexity - they are themselves the numerical solutions of three differential rate equations - and because the experimental final survival ratios might have a scatter, realistic estimates of the survival parameters require short cut and averaging methods for their calculation. Such a method has been tried with published dynamic inactivation data on Salmonella enteritidis and Escherichia coli. The concept was validated by the ability of the Weibullian-Log logistic model, whose three survival parameters had been obtained directly from final experimental survival ratios only, to predict entire non-isothermal survival curves that had not been used in the model's formulation. The methodology need not be restricted to Weibullian and simpler survival patterns but its practicality might be lost if there are more than three survival parameters. In principle, the same procedure can be extended to biochemical processes that occur during heat preservation, especially at very high temperatures. Estimating inactivation kinetic parameters without isothermal data could also facilitate the quantification of microbial survival under realistic processing conditions and in the actual food rather than in a surrogate medium.

  17. 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.

  18. 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

  19. Prognostic nutritional index serves as a predictive marker of survival and associates with systemic inflammatory response in metastatic intrahepatic cholangiocarcinoma

    PubMed Central

    Zhang, Chenyue; Wang, Haiyong; Ning, Zhouyu; Xu, Litao; Zhuang, Liping; Wang, Peng; Meng, Zhiqiang

    2016-01-01

    Objective The significance of the prognostic nutritional index (PNI) has been widely reported and confirmed in many types of cancers. However, few studies are available indicating its prognostic power in patients with intrahepatic cholangiocarcinoma (ICC). Thus, we investigated its relationship with overall survival (OS) to evaluate its role in predicting survival in patients with ICC. Patients and methods Between October 2011 and October 2015, 173 consecutive patients with pathologically confirmed locally advanced or metastatic ICC were enrolled. First, the correlations between PNI and clinical factors were analyzed among these patients. Next, univariate and multivariate analyses were conducted to evaluate the association between PNI and OS among these patients with ICC. In addition, the relationships between PNI and three typical systemic inflammatory response (SIR) markers – the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), and the lymphocyte/monocyte ratio (LMR) – were also assessed. Results A lower PNI was linked with a shorter OS in patients with ICC, as reflected obviously in the Kaplan–Meier analyses. The patients with ICC were divided into the locally advanced group and the metastatic group. Further analyses revealed that PNI is not associated with OS in the locally advanced group. However, in the subgroup of patients with metastatic ICC, a lower PNI significantly correlated with a worsened OS. The OS for patients with a low PNI is 5 months, whereas the OS is 10.17 months for patients with a high PNI. Multivariate analyses revealed that PNI is independently correlated with OS. We finally proved that PNI is negatively proportional to NLR and PLR and positively proportional to LMR. Conclusion Our results demonstrate that decreased PNI signifies a poor OS and is associated with SIR in patients with metastatic ICC. Therefore, it may serve as a valuable predictive marker in patients with metastatic ICC. PMID:27799789

  20. 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

  1. 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

  2. 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

  3. 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

    2015-12-09

    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.

  4. 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

  5. Predicting population survival under future climate change: density dependence, drought and extraction in an insular bighorn sheep.

    PubMed

    Colchero, Fernando; Medellin, Rodrigo A; Clark, James S; Lee, Raymond; Katul, Gabriel G

    2009-05-01

    1. Our understanding of the interplay between density dependence, climatic perturbations, and conservation practices on the dynamics of small populations is still limited. This can result in uninformed strategies that put endangered populations at risk. Moreover, the data available for a large number of populations in such circumstances are sparse and mined with missing data. Under the current climate change scenarios, it is essential to develop appropriate inferential methods that can make use of such data sets. 2. We studied a population of desert bighorn sheep introduced to Tiburon Island, Mexico in 1975 and subjected to irregular extractions for the last 10 years. The unique attributes of this population are absence of predation and disease, thereby permitting us to explore the combined effect of density dependence, environmental variability and extraction in a 'controlled setting.' Using a combination of nonlinear discrete models with long-term field data, we constructed three basic Bayesian state space models with increasing density dependence (DD), and the same three models with the addition of summer drought effects. 3. We subsequently used Monte Carlo simulations to evaluate the combined effect of drought, DD, and increasing extractions on the probability of population survival under two climate change scenarios (based on the Intergovernmental Panel on Climate Change predictions): (i) increase in drought variability; and (ii) increase in mean drought severity. 4. The population grew from 16 individuals introduced in 1975 to close to 700 by 1993. Our results show that the population's growth was dominated by DD, with drought having a secondary but still relevant effect on its dynamics. 5. Our predictions suggest that under climate change scenario (i), extraction dominates the fate of the population, while for scenario (ii), an increase in mean drought affects the population's probability of survival in an equivalent magnitude as extractions. Thus, for the

  6. 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

  7. Biomarker discovery to improve prediction of breast cancer survival: using gene expression profiling, meta-analysis, and tissue validation

    PubMed Central

    Meng, Liwei; Xu, Yingchun; Xu, Chaoyang; Zhang, Wei

    2016-01-01

    Purpose Breast cancer is the leading cause of cancer death worldwide in women. The molecular mechanism for human breast cancer is unknown. Gene microarray has been widely used in breast cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis survival. So far, the valuable multigene signatures in clinical practice are unclear, and the biological importance of individual genes is difficult to detect, as the described signatures virtually do not overlap. Early prognosis of this disease, breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS), is vital in breast surgery. Methods Thus, this study reports gene expression profiling in large breast cancer cohorts from Gene Expression Omnibus, including GSE29044 (N=138) and GSE10780 (N=185) test series and four independent validation series GSE21653 (N=266), GSE20685 (N=327), GSE26971 (N=276), and GSE12776 (N=204). Significantly differentially expressed genes in human breast IDC and breast DCIS were detected by transcriptome microarray analysis. Results We created a set of three genes (MAMDC2, TSHZ2, and CLDN11) that were significantly correlated with disease-free survival of breast cancer patients using a univariate Cox regression model (significance level P<0.01) in a meta-analysis. Based on the risk score of the three genes, the test series patients could be separated into low-risk and high-risk groups with significantly different survival times. This signature was validated in the other three cohorts. The prognostic value of this three-gene signature was confirmed in the internal validation series and another four independent breast cancer data sets. The prognostic impact of one of the three genes, CLDN11, was confirmed by immunohistochemistry. CLDN11 was significantly overexpressed in human breast IDC as compared with normal breast tissues and breast DCIS. Conclusion Using novel gene expression profiling together with a meta-analysis validation

  8. Coronary Collaterals Predict Improved Survival and Allograft Function in Patients with Coronary Allograft Vasculopathy

    PubMed Central

    Lavine, Kory J.; Sintek, Marc; Novak, Eric; Ewald, Gregory; Geltman, Edward; Joseph, Susan; Pfeifer, John; Mann, Douglas

    2013-01-01

    Background Despite improvements in the care of patients who have received cardiac transplants, coronary allograft vasculopathy (CAV) remains the most prevalent cause of late allograft failure and cardiac mortality. Few proven therapies are available for this important disease. The presence of coronary collaterals imparts a favorable prognosis in patients with native ischemic heart disease; however, the impact of collaterals in CAV is unknown. Methods and results To determine whether the development of coronary collaterals is associated with improved outcomes in patients with CAV, we performed a retrospective analysis of patients followed in the heart transplant program at Barnes Jewish Hospital from 1994–2008. The primary endpoints included all cause mortality and the composite of all cause mortality, retransplantation, and inotrope dependence. We screened 493 patients and identified 59 (12%) subjects with moderate to severe CAV. Angiographically visible coronary collaterals were present in 34 (57%) subjects. Kaplan-Meier and Cox multivariable analyses revealed that patients with collaterals had reduced incidence of all cause mortality HR 0.20, p<0.001 and the composite endpoint HR 0.17, p<0.001. In addition, patients with collaterals had less severe heart failure symptoms as measured by NYHA class. Immunostaining of biopsy specimens revealed that among patients with CAV, the presence of coronary collaterals correlated with increased microvascular density, reduced fibrosis and lower LVEDP. Conclusions Together, these data demonstrate that the presence of coronary collaterals predicts a favorable prognosis in patients with CAV and suggests that interventions aimed at promoting collateral and microvascular growth may serve as effective therapies for this disease. PMID:23709657

  9. Circulating MicroRNA-150 Serum Levels Predict Survival in Patients with Critical Illness and Sepsis

    PubMed Central

    Vargas Cardenas, David; Vucur, Mihael; Scholten, David; Frey, Norbert; Koch, Alexander; Trautwein, Christian; Tacke, Frank; Luedde, Tom

    2013-01-01

    Background and Aims Down-regulation of miR-150 was recently linked to inflammation and bacterial infection. Furthermore, reduced serum levels of miR-150 were reported from a small cohort of patients with sepsis. We thus aimed at evaluating the diagnostic and prognostic value of miR-150 serum levels in patients with critically illness and sepsis. Methods miR-150 serum levels were analyzed in a cohort of 223 critically ill patients of which 138 fulfilled sepsis criteria and compared to 76 healthy controls. Results were correlated with clinical data and extensive sets of routine and experimental biomarkers. Results Measurements of miR-150 serum concentrations revealed only slightly reduced miR-150 serum levels in critically ill patients compared to healthy controls. Furthermore miR-150 levels did not significantly differ in critically ill patients with our without sepsis, indicating that miR-150 serum levels are not suitable for diagnostic establishment of sepsis. However, serum levels of miR-150 correlated with hepatic or renal dysfunction. Low miR-150 serum levels were associated with an unfavorable prognosis of patients, since low miR-150 serum levels predicted mortality with high diagnostic accuracy compared with established clinical scores and biomarkers. Conclusion Reduced miR-150 serum concentrations are associated with an unfavorable outcome in patients with critical illness, independent of the presence of sepsis. Besides a possible pathogenic role of miR-150 in critical illness, our study indicates a potential use of circulating miRNAs as a prognostic rather than diagnostic marker in critically ill patients. PMID:23372743

  10. 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

  11. 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

  12. Utility of cardiac magnetic resonance imaging, echocardiography and electrocardiography for the prediction of clinical response and long-term survival following cardiac resynchronisation therapy.

    PubMed

    Ellims, Andris H; Pfluger, Heinz; Elsik, Maros; Butler, Michelle J; Hare, James L; Taylor, Andrew J

    2013-08-01

    Cardiac resynchronisation therapy (CRT) can reduce symptoms, hospitalisations, and mortality in patients with severe left ventricular (LV) systolic dysfunction and electro-mechanical dyssynchrony. Unfortunately, approximately 30 % of eligible patients fail to respond to CRT. This study prospectively compared electrocardiography (ECG), echocardiography, and cardiac magnetic resonance (CMR) imaging for the prediction of response to CRT. We performed ECG, echocardiography and CMR on 46 patients prior to planned CRT implantation. Patients were divided into predicted responder and non-responder groups using previously described criteria for each modality. Changes in indicators of CRT response were recorded 6 months post-implantation, and later for transplant-free survival. Less dyspnoea, lower levels of N-terminal pro-brain natriuretic peptide, more LV reverse remodelling, and longer transplant-free survival were observed in predicted responders compared to predicted non-responders using each of the three modalities (p < 0.05 for each comparison). Additionally, for patients with QRS duration <150 ms and/or non-left bundle branch block (non-LBBB) QRS morphology, CMR predicted both clinical response and improved longer term transplant-free survival (80 % transplant-free survival in predicted responders vs. 20 % in predicted non-responders, p = 0.04). ECG and cardiac imaging techniques predict improvements in markers of response following CRT with similar accuracy. However, for CRT candidates with shorter, non-LBBB QRS complexes, a subgroup known to derive less benefit from CRT, CMR may predict those who are more likely to gain both symptomatic and survival benefits.

  13. 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"…

  14. 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

  15. Validation of the Memorial Sloan-Kettering Cancer Center Nomogram to Predict Disease-Specific Survival after R0 Resection in a Chinese Gastric Cancer Population

    PubMed Central

    Liu, Maoxing; Cui, Ming; Liu, Yiqiang; Wang, Zaozao; Chen, Lei; Yang, Hong; Zhang, Chenghai; Yao, Zhendan; Zhang, Nan; Ji, Jiafu; Qu, Hong; Su, Xiangqian

    2013-01-01

    Background Prediction of disease-specific survival (DSS) for individual patient with gastric cancer after R0 resection remains a clinical concern. Since the clinicopathologic characteristics of gastric cancer vary widely between China and western countries, this study is to evaluate a nomogram from Memorial Sloan-Kettering Cancer Center (MSKCC) for predicting the probability of DSS in patients with gastric cancer from a Chinese cohort. Methods From 1998 to 2007, clinical data of 979 patients with gastric cancer who underwent R0 resection were retrospectively collected from Peking University Cancer Hospital & Institute and used for external validation. The performance of the MSKCC nomogram in our population was assessed using concordance index (C-index) and calibration plot. Results The C-index for the MSKCC predictive nomogram was 0.74 in the Chinese cohort, compared with 0.69 for American Joint Committee on Cancer (AJCC) staging system (P<0.0001). This suggests that the discriminating value of MSKCC nomogram is superior to AJCC staging system for prognostic prediction in the Chinese population. Calibration plots showed that the actual survival of Chinese patients corresponded closely to the MSKCC nonogram-predicted survival probabilities. Moreover, MSKCC nomogram predictions demonstrated the heterogeneity of survival in stage IIA/IIB/IIIA/IIIB disease of the Chinese patients. Conclusion In this study, we externally validated MSKCC nomogram for predicting the probability of 5- and 9-year DSS after R0 resection for gastric cancer in a Chinese population. The MSKCC nomogram performed well with good discrimination and calibration. The MSKCC nomogram improved individualized predictions of survival, and may assist Chinese clinicians and patients in individual follow-up scheduling, and decision making with regard to various treatment options. PMID:24146811

  16. 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

  17. 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.

  18. Renal Failure Secondary to Thrombotic Complications of Suprarenal Inferior Vena Cava Filter in Cancer Patients

    SciTech Connect

    Marcy, Pierre-Yves; Magne, Nicolas; Frenay, Marc; Bruneton, Jean-Noel

    2001-07-15

    Purpose: To evaluate renal function before and after suprarenal inferior vena cava (IVC) filter placement.Methods: We describe, in a personal series of 13 consecutive cases (all of them stage IV cancer patients, one LGM filter, one Antheor filter, 11 Greenfield filters) in our institution, two cases of fatal renal vein thrombosis after placement of a suprarenal filter. Evaluation of renal function was based on serum urea (in mmol/L; normal 3.30-6.60), serum creatinine (in {mu}mol/L; normal <115.1), and calculation of serum creatinine clearance. Results and conclusion: This study suggests that in advanced-stage cancer patients who have a single functional kidney, renal functional insufficiency, or previous renal vein thrombosis, IVC filter placement above the renal veins may not be appropriate. Suprarenal filter placement should be performed only after analysis of predicted survival, after detailed discussions with the patient, and most importantly after renal function evaluation.

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

    PubMed

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

    2015-12-15

    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.

  1. 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

  2. Toxicokinetic-toxicodynamic modelling of survival of Gammarus pulex in multiple pulse exposures to propiconazole: model assumptions, calibration data requirements and predictive power.

    PubMed

    Nyman, Anna-Maija; Schirmer, Kristin; Ashauer, Roman

    2012-10-01

    Toxicokinetic-toxicodynamic (TKTD) models quantify the time-course of internal concentration, which is defined by uptake, elimination and biotransformation (TK), and the processes which lead to the toxic effects (TD). TKTD models show potential in predicting pesticide effects in fluctuating concentrations, but the data requirements and validity of underlying model assumptions are not known. We calibrated TKTD models to predict survival of Gammarus pulex in propiconazole exposure and investigated the data requirements. In order to assess the need of TK in survival models, we included or excluded simulated internal concentrations based on pre-calibrated TK. Adding TK did not improve goodness of fits. Moreover, different types of calibration data could be used to model survival, which might affect model parameterization. We used two types of data for calibration: acute toxicity (standard LC50, 4 d) or pulsed toxicity data (total length 10 d). The calibration data set influenced how well the survival in the other exposure scenario was predicted (acute to pulsed scenario or vice versa). We also tested two contrasting assumptions in ecotoxicology: stochastic death and individual tolerance distribution. Neither assumption fitted to data better than the other. We observed in 10-d toxicity experiments that pulsed treatments killed more organisms than treatments with constant concentration. All treatments received the same dose, i.e. the time-weighted average concentration was equal. We studied mode of toxic action of propiconazole and it likely acts as a baseline toxicant in G. pulex during 10-days of exposure for the endpoint survival.

  3. 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

  4. Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL

    PubMed Central

    Schuster, Tibor; Abbrederis, Kathrin; Blümel, Christina; Santi, Ivan; Rudelius, Martina; Wester, Hans-Jürgen; Peschel, Christian; Schwaiger, Markus; Dechow, Tobias; Keller, Ulrich

    2014-01-01

    Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure. PMID:24979177

  5. 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

  6. 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

  7. 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

  8. Identification and utilization of donor and recipient genetic variants to predict survival after HCT: are we ready for primetime?

    PubMed

    Sucheston-Campbell, Lara E; Clay, Alyssa; McCarthy, Philip L; Zhu, Qianqian; Preus, Leah; Pasquini, Marcelo; Onel, Kenan; Hahn, Theresa

    2015-03-01

    Overall survival following hematopoietic cell transplantation (HCT) has improved over the past two decades through better patient selection and advances in HLA typing, supportive care, and infection prophylaxis. Nonetheless, mortality rates are still unsatisfactory and transplant-related mortality remains a major cause of death after unrelated allogeneic HCT. Since there are no known pre-HCT, non-HLA biologic predictors of survival following transplant, for over a decade, scientists have been investigating the role of non-HLA germline genetic variation in survival and treatment-related mortality after HCT. Variation in single nucleotide polymorphisms (SNPs) has the potential to impact chemotherapy, radiation, and immune responses, leading to different post-HCT survival outcomes. In this paper, we address the current knowledge of the contribution of genetic variation to survival following HCT and discuss study design and methodology for investigating HCT survival on a genomic scale.

  9. Identification and utilization of donor and recipient genetic variants to predict survival after HCT: are we ready for primetime?

    PubMed

    Sucheston-Campbell, Lara E; Clay, Alyssa; McCarthy, Philip L; Zhu, Qianqian; Preus, Leah; Pasquini, Marcelo; Onel, Kenan; Hahn, Theresa

    2015-03-01

    Overall survival following hematopoietic cell transplantation (HCT) has improved over the past two decades through better patient selection and advances in HLA typing, supportive care, and infection prophylaxis. Nonetheless, mortality rates are still unsatisfactory and transplant-related mortality remains a major cause of death after unrelated allogeneic HCT. Since there are no known pre-HCT, non-HLA biologic predictors of survival following transplant, for over a decade, scientists have been investigating the role of non-HLA germline genetic variation in survival and treatment-related mortality after HCT. Variation in single nucleotide polymorphisms (SNPs) has the potential to impact chemotherapy, radiation, and immune responses, leading to different post-HCT survival outcomes. In this paper, we address the current knowledge of the contribution of genetic variation to survival following HCT and discuss study design and methodology for investigating HCT survival on a genomic scale. PMID:25700678

  10. 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

  11. Tumor marker analyses in patients with brain metastases: patterns of practice and implications for survival prediction research.

    PubMed

    Nieder, Carsten; Dalhaug, Astrid; Haukland, Ellinor; Mannsåker, Bård; Pawinski, Adam

    2015-08-01

    This study aims to explore patterns of practice of tumor marker analyses and potential prognostic impact of abnormal markers in patients with brain metastases from solid tumors. Previously, lactate dehydrogenase (LDH) and albumin were identified as relevant biomarkers. We performed a retrospective analysis of 120 patients with known LDH and albumin treated with whole-brain radiotherapy (WBRT) in two different situations: (1) brain metastases detected at initial cancer diagnosis (n = 46) and (2) brain metastases at later time points (n = 74, median interval 13 months). Twenty-six patients (57 %) from group 1 had at least one tumor marker analyzed, and 11 patients (24 %) had abnormal results. Twenty-two patients (30 %) from group 2 had at least one tumor marker analyzed, and 16 patients (22 %) had abnormal results. When assuming that LDH and albumin would be standard tests before WBRT, additional potential biomarkers were found in 36 % of patients with normal LDH and albumin. Marker positivity rates were for example 80 % for carcinoembryonic antigen (CEA) in colorectal cancer and 79 % for CA 15-3 in breast cancer. Abnormal markers were associated with presence of liver metastases. CA 15-3 values above median predicted shorter survival in patients with breast cancer (median 1.9 vs. 13.8 months, p = 0.1). Comparable trends were not observed for various markers in other tumor types. In conclusion, only a minority of patients had undergone tumor marker analyses. Final group sizes were too small to perform multivariate analyses or draw definitive conclusions. We hypothesize that CA 15-3 could be a promising biomarker that should be studied further.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. Getting ready for invasions: can background level of risk predict the ability of naïve prey to survive novel predators?

    PubMed

    Ferrari, Maud C O; Crane, Adam L; Brown, Grant E; Chivers, Douglas P

    2015-02-06

    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.

  19. A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery.

    PubMed

    Peng, Jian-Hong; Fang, Yu-Jing; Li, Cai-Xia; Ou, Qing-Jian; Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De Sen

    2016-04-19

    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.

  20. 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

  1. 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

  2. The pretreatment albumin to globulin ratio predicts survival in patients with natural killer/T-cell lymphoma.

    PubMed

    Bi, Xi-Wen; Wang, Liang; Zhang, Wen-Wen; Yan, Shu-Mei; Sun, Peng; Xia, Yi; Li, Zhi-Ming; Jiang, Wen-Qi

    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.

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

    PubMed

    el Aziz, Lamiss Mohamed Abd

    2014-12-01

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

  4. 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.

  5. Prognostic value of 13C-phenylalanine breath test on predicting survival in patients with chronic liver failure

    PubMed Central

    Gallardo-Wong, I; Morán, S; Rodríguez-Leal, G; Castañeda-Romero, B; Mera, R; Poo, J; Uribe, M; Dehesa, M

    2007-01-01

    AIM: To evaluate the prognostic value of percentage of 13C-phenylalanine oxidation (13C-PheOx) obtained by 13C-phenylalanine breath test (13C-PheBT) on the survival of patients with chronic liver failure. METHODS: The hepatic function was determined by standard liver blood tests and the percentage of 13C-PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox. RESULTS: Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78, 0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child-Pugh classes, age, creatinine and the percentage of 13C-PheOx (HR 0.338, 95% CI: 0.150-0.762, P = 0.009) were independent predictors of survival. When Child-Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin, creatinine, age and the percentage of 13C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival. CONCLUSION: Percentage of 13C-PheOx obtained by 13C-PheBT is a strong predictor of survival in patients with chronic liver disease. PMID:17729409

  6. 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

  7. Inferior alveolar nerve block: Alternative technique

    PubMed Central

    Thangavelu, K.; Kannan, R.; Kumar, N. Senthil

    2012-01-01

    Background: Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. Aim and Objective: The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. Materials and Methods: This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. Conclusion: This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages. PMID:25885503

  8. DNA Repair Capacity in Peripheral Lymphocytes Predicts Survival of Patients With Non–Small-Cell Lung Cancer Treated With First-Line Platinum-Based Chemotherapy

    PubMed Central

    Wang, Li-E; Yin, Ming; Dong, Qiong; Stewart, David J.; Merriman, Kelly W.; Amos, Christopher I.; Spitz, Margaret R.; Wei, Qingyi

    2011-01-01

    Purpose Platinum-based regimens are the standard chemotherapy for patients with advanced non–small-cell lung cancer (NSCLC). DNA repair capacity (DRC) in tumor cells plays an important role in resistance to platinum-based drugs. We have previously reported that efficient DRC, as assessed by an in vitro lymphocyte-based assay, was a determinant of poor survival in patients with NSCLC in a relatively small data set. In this larger independent study of 591 patients with NSCLC, we further evaluated whether DRC in peripheral lymphocytes predicts survival of patients with NSCLC who receive platinum-based chemotherapy. Patients and Methods All patients were recruited at The University of Texas MD Anderson Cancer Center and donated blood samples before the start of any chemotherapy. We measured DRC in cultured T lymphocytes by using the host-cell reactivation assay, and we assessed associations between DRC in peripheral lymphocytes and survival of patients with NSCLC who were treated with first-line platinum-based chemotherapy. Results We found an inverse association between DRC in peripheral lymphocytes and patient survival. Compared with patients in the low tertile of DRC, patients with NSCLC in the high tertile of DRC had significantly worse overall and 3-year survival (adjusted hazard ratio [HR], 1.33; 95% CI, 1.04 to 1.71; P = .023; and HR, 1.35; 95% CI, 1.04 to 1.76; P = .025, respectively). This trend was more pronounced in patients with early-stage tumors, adenocarcinoma, or squamous cell carcinoma. Conclusion We confirmed that DRC in peripheral lymphocytes is an independent predictor of survival for patients with NSCLC treated with platinum-based chemotherapy. PMID:21947825

  9. Genetic polymorphisms in circadian negative feedback regulation genes predict overall survival and response to chemotherapy in gastric cancer patients.

    PubMed

    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

  10. 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.

  11. 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.

  12. 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.

  13. Prediction of survival prognosis of non-small cell lung cancer by APE1 through regulation of epithelial-mesenchymal transition

    PubMed Central

    Duan, Wei; Huang, Chongbiao; Zheng, Xiangqian; Sun, Lei; Luo, Jingtao; Wang, Dong; Zhang, Sheng; Xin, Xiaojie; Gao, Ming

    2016-01-01

    The DNA base excision repair gene APE1 involves in DNA damage repair pathway and overexpression in a variety of human cancers. Analyses of patients with non-small cell lung cancer (NSCLC) suggested that multiple factors associated with prognosis of NSCLC patients. Further investigation showed that APE1 expression was able to predict the progression-free survival and overall survival in patients with NSCLC and correlated with lymph node metastasis. Intriguingly, as a stratification of APE1-141 SNPs in APE1 positive expression, we also found APE1-141 GT/GG was identified as a marker for prediction of poor survival in NSCLC patients. In the in vitro experiments, the results showed that when APE1 expression was inhibited by siRNA or AT101 (an APE1 inhibitor), the migration and invasion of NSCLC cells were suppressed. Furthermore, epithelial-mesenchymal transition (EMT) markers was tested to provide evidence that APE1 promoted NSCLC EMT through interaction with SirT1. Using NSCLC xenograft models, we confirmed that AT101 shrank tumor volumes and inhibited lymph node metastasis. In conclusion, APE1 could be a potential target for patients with NSCLC metastasis and AT101 is a potent inhibitor in further treatment of NSCLC patients. PMID:27074577

  14. Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study

    PubMed Central

    Ogura, Koichi; Fujiwara, Tomohiro; Yasunaga, Hideo; Matsui, Hiroki; Jeon, Dae‐Geun; Cho, Wan Hyeong; Hiraga, Hiroaki; Ishii, Takeshi; Yonemoto, Tsukasa; Kamoda, Hiroto; Ozaki, Toshifumi; Kozawa, Eiji; Nishida, Yoshihiro; Morioka, Hideo; Hiruma, Toru; Kakunaga, Shigeki; Ueda, Takafumi; Tsuda, Yusuke; Kawano, Hirotaka

    2015-01-01

    BACKGROUND In this era of individualized cancer treatment, data that could be applied to predicting the survival of patients with osteosarcoma are still limited because of the rarity of the disease and the difficulty in accumulating a sufficient number of patients. Therefore, a multi‐institutional collaboration was implemented to develop and externally validate nomograms that would predict metastasis‐free survival (MFS) and overall survival (OAS) for patients with nonmetastatic osteosarcoma. METHODS This study retrospectively examined 1070 patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic osteosarcoma. Data from Japanese patients (n = 557) were used to develop multivariate nomograms based on Cox regression. Six clinical and pathologic variables were built into nomograms estimating the probability of MFS and OAS 3 and 5 years after diagnosis. The model was internally validated for discrimination and calibration with bootstrap resampling and was externally validated with an independent patient cohort from Korea (n = 513). RESULTS A patient's age, tumor site, and histologic response were found to have a stronger influence on MFS and OAS in the model than sex, tumor size, or pathologic fracture. The nomograms and calibration plots based on these results well predicted the probability of MFS (concordance index, 0.631) and OAS (concordance index, 0.679). The concordance indices for external validation were 0.682 for MFS and 0.665 for OAS. CONCLUSIONS The nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery. Cancer 2015;121:3844–3852. © 2015 American Cancer Society. PMID:26194185

  15. Prediction of survival in resected non-small cell lung cancer using a protein-expression based risk model: Implications for personalized chemoprevention and therapy

    PubMed Central

    Gold, Kathryn A.; Kim, Edward S.; Liu, Diane D.; Yuan, Ping; Behrens, Carmen; Solis, Luisa M.; Kadara, Humam; Rice, David C.; Wistuba, Ignacio I.; Swisher, Stephen G.; Hofstetter, Wayne L.; Lee, J. Jack; Hong, Waun K.

    2014-01-01

    Purpose Patients with resected non-small cell lung cancer (NSCLC) are at risk for recurrence of disease but we do not have tools to predict which patients are at highest risk. We set out to create a risk model incorporating both clinical data and biomarkers. Methods We assembled a comprehensive database with archival tissues and clinical follow-up from patients with NSCLC resected between 2002-2005. Twenty-one proteins identified from our preclinical studies as related to lung carcinogenesis were investigated, including pathways related to metabolism, DNA repair, inflammation and growth factors. Expression of proteins was quantified using immunohistochemistry. Immunohistochemistry was chosen because it is widely available and can be performed on formalin-fixed paraffin-embedded specimens. Cox models were fitted to estimate effects of clinical factors and biomarkers on recurrence free survival (RFS) and overall survival (OS). Results 370 patients are included in our analysis. With median follow-up of 5.3 years, median overall survival is 6.4 years. 209 cases with recurrence or death were observed. Multicovariate risk models for RFS and OS were developed including relevant biomarkers, age and stage. Increased expression of pAMPK, pmTOR, EpCAM, and CASK were significant (p<0.05) predictors for favorable RFS; insulin receptor, CXCR2, and IGF1R predicted for unfavorable RFS. Significant (p<0.05) predictors for favorable OS include pAMPK, pmTOR, and EpCAM; CXCR2 and FEN1 predicted unfavorable OS. Conclusions We have developed a comprehensive risk model predictive for recurrence in our large retrospective database, which is one of the largest reported series of resected NSCLC. PMID:24366692

  16. 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

  17. Overexpression of CHD1L is positively associated with metastasis of lung adenocarcinoma and predicts patients poor survival.

    PubMed

    He, Li-Ru; Ma, Ning-Fang; Chen, Jie-Wei; Li, Bin-Kui; Guan, Xin-Yuan; Liu, Meng-Zhong; Xie, Dan

    2015-10-13

    CHD1L (chromodomain helicase/ATPase DNA binding protein 1-like gene) has been demonstrated as an oncogene in hepatocellular carcinoma (HCC), however, the role of CHD1L in non-small-cell lung cancer (NSCLC) tumorigenesis hasn't been elucidated. In this study, the expression and amplification status of CHD1L were examined by immunohistochemistry and fluorescence in situ hybridization respectively in 248 surgically resected NSCLCs. The associations between CHD1L expression and clinicopathologic features and the prognostic value of CHD1L were analyzed. Overexpression and amplification of CHD1L was found in 42.1% and 17.7% of NSCLCs, respectively. The frequency of CHD1L overexpression (53.2% vs. 28.1%, P = 0.002) and amplification (25.2% vs. 8.2%, P = 0.020) in adenocarcinoma (ADC), was much higher than that in squamous cell carcinoma (SCC). CHD1L overexpression was associated closely with ascending pN status (P < 0.001), advanced clinical stage (P = 0.001) and tumor distant metastasis (P = 0.001) in ADCs, but not in SCCs. For the whole cohort and ADC patients, univariate survival analysis demonstrated a significant association of CHD1L overexpression with shortened survival; and in multivariate analysis, CHD1L overexpression was evaluated as a independent predictor for overall survival and distant metastasis free survival. These results suggested that overexpression of CHD1L is positively associated with tumor metastasis of lung ADC, and might serve as a novel prognostic biomarker and potential therapeutic target for lung ADC patients.

  18. CHD1L Protein is overexpressed in human ovarian carcinomas and is a novel predictive biomarker for patients survival

    PubMed Central

    2012-01-01

    Background Our recent studies suggested that the chromodomain helicase DNA binding protein 1-like (CHD1L) gene plays an oncogenic role in human hepatocellular carcinoma. However, the status of CHD1L protein expression in ovarian cancer and its clinical/prognostic significance are obscure. Methods In this study, immunohistochemistry (IHC) for CHD1L was performed on a tissue microarray (TMA) containing 102 primary ovarian carcinomas and 44 metastatic lesions (omental metastasis). Receiver-operator curve (ROC) analysis was used to evaluate patients’ survival status. Results There is an augmented tendency of CHD1L expression in ovarian carcinoma metastasis than in primary lesions (P<0.05). A significant association was found between positive expression of CHD1L and tumors histological type (P <0.05). By univariate survival analysis of the ovarian carcinoma cohorts, positive expression of CHD1L was significantly correlated with shortened patient survival (mean 66.7 months versus 97.4 months, P<0.05). Moreover, CHD1L expression was evaluated to be a significant and independent prognostic factor in multivariate analysis (P<0.05). Conclusions These findings provide evidence that positive expression of CHD1L protein is significantly correlated with the metastasis proceeding of ovarian carcinoma, and CHD1L protein expression, as examined by IHC, may act as a novel prognostic biomarker for patients with ovarian carcinoma. PMID:23020525

  19. Impact of competitor species composition on predicting diameter growth and survival rates of Douglas-fir trees in southwestern Oregon

    USGS Publications Warehouse

    Bravo, Felipe; Hann, D.W.; Maguire, Douglas A.

    2001-01-01

    Mixed conifer and hardwood stands in southwestern Oregon were studied to explore the hypothesis that competition effects on individual-tree growth and survival will differ according to the species comprising the competition measure. Likewise, it was hypothesized that competition measures should extrapolate best if crown-based surrogates are given preference over diameter-based (basal area based) surrogates. Diameter growth and probability of survival were modeled for individual Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) trees growing in pure stands. Alternative models expressing one-sided and two-sided competition as a function of either basal area or crown structure were then applied to other plots in which Douglas-fir was mixed with other conifers and (or) hardwood species. Crown-based variables outperformed basal area based variables as surrogates for one-sided competition in both diameter growth and survival probability, regardless of species composition. In contrast, two-sided competition was best represented by total basal area of competing trees. Surrogates reflecting differences in crown morphology among species relate more closely to the mechanics of competition for light and, hence, facilitate extrapolation to species combinations for which no observations are available.

  20. 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

  1. 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.

  2. 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

  3. Validation of long-term survival prediction for scheduled abdominal aortic aneurysm repair with an independent calculator using only pre-operative variables.

    PubMed

    Carlisle, J B; Danjoux, G; Kerr, K; Snowden, C; Swart, M

    2015-06-01

    We observed survival after scheduled repair of abdominal aortic aneurysm in 1096 patients for a median (IQR [range]) of 3.0 (1.5-5.8 [0-15]) years: 943 patients had complete data, 250 of whom died. We compared discrimination and calibration of an external model with the Kaplan-Meier model generated from the study data. Integrated Brier misclassification scores for both models at 1-5 postoperative years were 0.04, 0.08, 0.11, 0.13 and 0.16, respectively. Harrel's concordance index at 1-5 postoperative years was 0.73, 0.71, 0.68, 0.67 and 0.66, respectively. Groups with median 5-year predicted mortality of 40% (n = 251), 18% (n = 414) and 8% (n = 164) had lower observed mortality than 114 patients with 70% predicted mortality, hazard ratio (95% CI): 0.58 (0.37-0.76), p = 0.0031; 0.30 (0.19-0.48), p = 1.7 × 10(-12) and 0.19 (0.13-0.27), p = 1.3 × 10(-10) , respectively, test for trend p = 5.6 × 10(-15) . Survival predicted by the external calculator was similar to the Kaplan-Meier estimate.

  4. 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

  5. The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer.

    PubMed

    Gujam, Fadia J A; Going, James J; Edwards, Joanne; Mohammed, Zahra M A; McMillan, Donald C

    2014-02-01

    Lymphovascular invasion (LBVI) has long been recognized as an essential step of metastases in patients with cancer. However, the process of invasion into lymphatic and blood vessels is still not well defined in breast cancer. To examine the evidence for LBVI, lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) in predicting survival in patients with primary operable breast cancer, and to evaluate the detection methods of vessel invasion. A systematic review of data published from 1964 to 2012 was undertaken according to a pre-defined protocol. There is robust evidence that general LBVI and LVI are independent prognostic factors of poorer survival. The prognostic role of BVI remains unclear. Most studies detected LBVI using H&E stained sections. The overall weighted average of the LBVI rate using immunostaining was higher (35%) than H&E (24%). The LBVI rate using H&E was variable (9-50%) and less variable using immunostaining (32-41%). The overall weighted average of the LVI rate was similar using H&E and immunostaining (33% vs. 25%). The LVI rate using H&E was variable (10-49%) and less variable using immunostaining (21-42%). The overall weighted average of the BVI rate was similar using H&E and/or classical staining and immunostaining (16% vs. 10%). The BVI rates using H&E and/or classical staining approach (4-46%) and immunostaining (1-29%) were both variable. The LBVI and LVI are powerful prognostic factors in primary operable breast cancer. However, BVI was rarely specifically examined and its role in predicting survival is not clear. Further work is required using reliable specific staining to establish the routine use of LVI and BVI in the prediction of outcome in patients with primary operable breast cancer.

  6. 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.

  7. Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas

    PubMed Central

    de Moll, Ellen H.; Fu, Yichun; Qian, Yingzhi; Perkins, Sara H.; Wieder, Shira; Gnjatic, Sacha; Remark, Romain; Bernardo, Sebastian G.; Moskalenko, Marina; Yao, Jonathan; Ferringer, Tammie; Chang, Rui; Chipuk, Jerry; Horst, Basil A.; Birge, Miriam B.; Phelps, Robert G.

    2015-01-01

    Introduction Ulcerated melanomas may have a unique biology and microenvironment. We test whether markers of immune infiltration correlate with clinical outcome in ulcerated compared to non-ulcerated primary melanoma tumors. Methods Sixty-two stage II–III cutaneous melanomas, 32 ulcerated and 30 non-ulcerated, were analyzed for tumor-infiltrating lymphocytes (TILs). Immunohistochemistry (IHC) was performed for CD2, a marker previously shown to correlate with overall survival (OS) and recurrence-free survival (RFS) in this patient population. IHC using antibody, VE1, to BRAF V600E was also performed on a subset of 41 tumors to assess the relationship of BRAF mutation to immune markers. Results We found, using Cox regression models, that the presence of TILs was associated with improved OS (p = 0.034) and RFS (p = 0.002) in ulcerated melanoma tumors, but not in non-ulcerated melanoma (p = 0.632, 0.416). CD2 expression also was correlated with improved OS (p = 0.021) and RFS (p = 0.001) in ulcerated melanoma, but no relationship was seen in non-ulcerated melanoma (p = 0.427, 0.682). In this small population, BRAF status did not correlate with TILs or CD2+ count. Conclusion Our data show that immune markers including TILs and CD2 count correlate more closely with survival in ulcerated melanomas than that in non-ulcerated melanomas. We propose that immune biomarkers may be particularly relevant to ulcerated, as compared to non-ulcerated, melanomas and that this merits study in larger populations. PMID:26076664

  8. 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.

  9. 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

  10. 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.

  11. Differentiating success from survival in modern implantology--key considerations for case selection, predicting complications and obtaining consent.

    PubMed

    Beaumont, J; McManus, G; Darcey, J

    2016-01-15

    The use of dental implants to restore edentulous areas has increased significantly since the 1970s and is now considered, by many, the gold standard restorative treatment. As such it has become increasingly important to understand what constitutes success for these rehabilitations. Increasing focus has been given to acknowledging the difference between success and survival: the two being potentially very different outcomes for such invasive and expensive treatment. This article aims to describe this distinction and ultimately the implications of this for both patient and clinician.

  12. Marital status independently predicts pancreatic cancer survival in patients treated with surgical resection: an analysis of the SEER database

    PubMed Central

    Wang, Xiao-Dong; Qian, Jian-Jun; Bai, Dou-Sheng; Li, Zhen-Nan; Jiang, Guo-Qing; Yao, Jie

    2016-01-01

    Marital status is an independent prognostic factor for survival in several cancers. To determine if that is also true for pancreatic cancer after surgical treatment, we examined 13,370 cases of pancreatic cancer reported to the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2012. We found that patients who were widowed at the time of diagnosis were more likely to be female, a high percentage were elderly, a high ratio were diagnosed in early years, and a high proportion of tumors were located at the head of the pancreas (P < 0.05). Marital status was confirmed to be an independent prognostic factor in both univariate and multivariate analyses (P < 0.05). In those with localized disease, 5-year pancreatic cancer cause-specific survival was 6.5% lower in widowed patients than married ones (38.6% vs. 32.1%), though this difference was not significant in a multivariate analysis (P = 0.084). In those with regional disease or distant metastasis, univariate and multivariate analyses indicated marital status to be an independent prognostic factor (P < 0.05). Thus marital status is an important prognostic factor in pancreatic cancer, and widowed patients are at greater risk of death than others. PMID:27036036

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. P2X7 receptor predicts postoperative cancer-specific survival of patients with clear-cell renal cell carcinoma

    PubMed Central

    Liu, Zheng; Liu, Yidong; Xu, Le; An, Huimin; Chang, Yuan; Yang, Yuanfeng; Zhang, Weijuan; Xu, Jiejie

    2015-01-01

    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

  19. 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.

  20. Functional organization of the left inferior precentral sulcus: dissociating the inferior frontal eye field and the inferior frontal junction.

    PubMed

    Derrfuss, J; Vogt, V L; Fiebach, C J; von Cramon, D Y; Tittgemeyer, M

    2012-02-15

    Two eye fields have been described in the human lateral frontal cortex: the frontal eye field (FEF) and the inferior frontal eye field (iFEF). The FEF has been extensively studied and has been found to lie at the ventral part of the superior precentral sulcus. Much less research, however, has focused on the iFEF. Recently, it was suggested that the iFEF is located at the dorsal part of the inferior precentral sulcus. A similar location was proposed for the inferior frontal junction area (IFJ), an area thought to be involved in cognitive control processes. The present study used fMRI to clarify the topographical and functional relationship of the iFEF and the IFJ in the left hemispheres of individual participants. The results show that both the iFEF and the IFJ are indeed located at the dorsal part of the inferior precentral sulcus. Nevertheless, the activations were spatially dissociable in every individual examined. The IFJ was located more towards the depth of the inferior precentral sulcus, close to the junction with the inferior frontal sulcus, whereas the iFEF assumed a more lateral, posterior and superior position. Furthermore, the results provided evidence for a functional double dissociation: the iFEF was activated only in a comparison of saccades vs. button presses, but not in a comparison of incongruent vs. congruent Stroop conditions, while the opposite pattern was found at the IFJ. These results provide evidence for a spatial and functional dissociation of two directly adjacent areas in the left posterior frontal lobe.

  1. 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

  2. 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

  3. Prognostic nutritional index before adjuvant chemotherapy predicts chemotherapy compliance and survival among patients with non-small-cell lung cancer

    PubMed Central

    Shimizu, Katsuhiko; Okita, Riki; Saisho, Shinsuke; Yukawa, Takuro; Maeda, Ai; Nojima, Yuji; Nakata, Masao

    2015-01-01

    Background Adjuvant chemotherapy after the complete resection of non-small-cell lung cancer (NSCLC) is now the standard of care. To improve survival, it is important to identify risk factors for the continuation of adjuvant chemotherapy. In this study, we analyzed chemotherapy compliance and magnitude of the prognostic impact of the prognostic nutritional index (PNI) before adjuvant chemotherapy. Methods We conducted a retrospective review of data from 106 patients who had received adjuvant chemotherapy. The adjuvant chemotherapy consisted of an oral tegafur agent (OT) or platinum-based chemotherapy (PB). The correlations between the PNI values and recurrence-free survival (RFS) were then evaluated. Results In the PB group, the percentage of patients who completed the four planned cycles of chemotherapy was not correlated with the PNI. In the OT group, however, a significant difference was observed in the percentage of patients who completed the planned chemotherapy according to the PNI before adjuvant chemotherapy. The RFS of patients with a PNI <50 before adjuvant chemotherapy was significantly poorer than that of the patients with a PNI ≥50. A multivariate analysis showed that nodal metastasis and PNI before chemotherapy were independent predictors of the RFS. However, PNI before surgery was not a predictor of the RFS. In the subgroup analysis, PNI before chemotherapy was independent predictor of the RFS in the OT group (P=0.019), but not in the PB group (P=0.095). Conclusion The PNI before adjuvant chemotherapy influenced the treatment compliance with the planned chemotherapy in the OT group, but not the PB group. In addition, a low PNI before adjuvant chemotherapy was associated with a poor RFS in a multivariate analysis, especially in the OT group. PMID:26504397

  4. Hepatic Dysfunction and Survival After Orthotopic Heart Transplantation: Application of the MELD Scoring System for Outcome Prediction

    PubMed Central

    Chokshi, Aalap; Cheema, Faisal H.; Schaefle, Kenneth J.; Jiang, Jeffrey; Collado, Elias; Shahzad, Khurram; Khawaja, Tuba; Farr, Maryjane; Takayama, Hiroo; Naka, Yoshifumi; Mancini, Donna; Schulze, P. Christian

    2012-01-01

    BACKGROUND The prevalence of heart failure (HF) is rising and the only corrective treatment is cardiac transplantation. Advanced HF is associated with congestive hepatopathy and progressive functional and ultrastructural changes of the liver. We hypothesized that hepatic dysfunction is associated with impaired clinical outcome after heart transplantation. METHODS Data of 617 adult patients (75% males, mean age of 53±12 years, mean BMI of 25±4 and mean ejection fraction of 19±9%) undergoing orthotopic heart transplantation (OHT) were analyzed retrospectively. Deviation from institutional normal ranges was used to define abnormal liver function. Standard model for end Stage liver disease (MELD) scores were calculated and a modified MELD score with albumin replacing INR (modMELD) was created to eliminate the confounding effects of anticoagulation. RESULTS Before OHT, AST, ALT and total bilirubin were elevated in 20%, 18% and 29% of the population, respectively. Total protein and albumin were decreased in 25 and 52% of the population, respectively. By 2 months post-transplantation, percentages of individuals with pathological values decreased significantly except ALT, total protein and albumin, all of which took longer to normalize. Individuals with a higher pre-transplantation MELD or modMELD score had worse outcome 30 days post-transplant and reduced long-term survival over a 10-year follow-up. CONCLUSIONS In this large, single-center retrospective study, we demonstrate dynamics of liver dysfunction after cardiac transplantation and that elevated MELD scores indicating impaired liver function are associated with poor clinical outcome following OHT. Therefore, preoperative liver dysfunction has a significant impact on survival of patients after cardiac transplantation. PMID:22458996

  5. Human mesothelioma induces defects in dendritic cell numbers and antigen-processing function which predict survival outcomes

    PubMed Central

    Cornwall, Scott M.J.; Wikstrom, Matthew; Musk, Arthur W.; Alvarez, John; Nowak, Anna K.; Nelson, Delia J.

    2016-01-01

    ABSTRACT Mesothelioma is an almost invariably fatal tumor with chemotherapy extending survival by a few months. One immunotherapeutic strategy is to target dendritic cells (DCs), key antigen-presenting cells involved in antigen presentation, to induce antigen-specific T cell responses. However, DC-targeting will only be effective if DCs are fit-for-purpose, and the functional status of DCs in mesothelioma patients was not clear. We found that mesothelioma patients have significantly decreased numbers of circulating myeloid (m)DC1 cells, mDC2 cells and plasmacytoid (p)DCs relative to healthy age and gender-matched controls. Blood monocytes from patients could not differentiate into immature monocyte-derived DCs (MoDCs), indicated by a significantly reduced ability to process antigen and reduced expression of costimulatory (CD40, CD80 and CD86) and MHC (HLA-DR) molecules, relative to controls. Activation of mesothelioma-derived MoDCs with LPS+/-IFNγ generated partially mature MoDCs, evident by limited upregulation of the maturation marker, CD83, and the costimulatory markers. Attempts to rescue mesothelioma-derived DC function using CD40Ligand(L) also failed, indicated by maintenance of antigen-processing capacity and limited upregulation of CD40, CD83, CD86 and HLA-DR. These data suggest that mesothelioma patients have significant numerical and functional DC defects and that their reduced capacity to process antigen and reduced expression of costimulatory molecules could induce anergized/tolerized T cells. Nonetheless, survival analyses revealed that individuals with mesothelioma and higher than median levels of mDC1s and/or whose MoDCs matured in response to LPS, IFNγ or CD40L lived longer, implying their selection for DC-targeting therapy could be promising especially if combined with another treatment modality. PMID:27057464

  6. 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

  7. 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

  8. 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

    Farnebo, Jacob; Wadelius, Agnes; Sandström, Per; Nilsson, Sten; Jacobsson, Hans; Blomqvist, Lennart; Ullén, Anders

    2016-08-01

    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

  9. Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients1

    PubMed Central

    Park, See-Hyoung; Noh, Sang Jae; Kim, Kyoung Min; Bae, Jun Sang; Kwon, Keun Sang; Jung, Sung Hoo; Kim, Jung Ryul; Lee, Ho; Chung, Myoung Ja; Moon, Woo Sung; Kang, Myoung Jae; Jang, Kyu Yun

    2015-01-01

    BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP1), γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA) tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS), and relapse-free survival (RFS) by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001). The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents. PMID:26310369

  10. Simultaneous Prediction of New Morbidity, Mortality, and Survival without New Morbidity from Pediatric Intensive Care: A New Paradigm for Outcomes Assessment

    PubMed Central

    Pollack, Murray M.; Holubkov, Richard; Funai, Tomohiko; Berger, John T.; Clark, Amy E.; Meert, Kathleen; Berg, Robert A.; Carcillo, Joseph; Wessel, David L.; Moler, Frank; Dalton, Heidi; Newth, Christopher J. L.; Shanley, Thomas; Harrison, Rick E.; Doctor, Allan; Jenkins, Tammara L.; Tamburro, Robert; Dean, J. Michael

    2015-01-01

    Objective Assessments of care including quality assessments adjusted for physiological status should include the development of new morbidities as well as mortalities. We hypothesized that morbidity, like mortality, is associated with physiological dysfunction and could be predicted simultaneously with mortality. Design Prospective cohort study from December 4, 2011 to April 7, 2013. Setting and Patients General and cardiac/cardiovascular pediatric intensive care units at 7 sites. Measurements and Main Results Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale (FSS), and defined as an increase of ≥ 3 from pre-illness to hospital discharge) were 4.6% (site range 2.6% to 7.7%) and unadjusted mortality rates were 2.7% (site range 1.3% – 5.0%). Morbidity and mortality were significantly (p<0.001) associated with physiological instability (measured with the PRISM III score) in dichotomous (survival, death) and trichotomous (survival without new morbidity, survival with new morbidity, death) models without covariate adjustments. Morbidity risk increased with increasing PRISM III scores and then decreased at the highest PRISM III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline FSS and the PRISM III score. The three-level goodness of fit test indicated satisfactory performance for the derivation and validation sets (p>0.20). Predictive ability assessed with the volume under the surface (VUS) was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (versus chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios. Conclusions New morbidities were associated with physiological status and can be modeled simultaneously with mortality. Trichotomous outcome models including both morbidity and mortality based on physiological status are suitable

  11. [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

  12. 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

  13. Evidence of mirror neurons in human inferior frontal gyrus.

    PubMed

    Kilner, James M; Neal, Alice; Weiskopf, Nikolaus; Friston, Karl J; Frith, Chris D

    2009-08-12

    There is much current debate about the existence of mirror neurons in humans. To identify mirror neurons in the inferior frontal gyrus (IFG) of humans, we used a repetition suppression paradigm while measuring neural activity with functional magnetic resonance imaging. Subjects either executed or observed a series of actions. Here we show that in the IFG, responses were suppressed both when an executed action was followed by the same rather than a different observed action and when an observed action was followed by the same rather than a different executed action. This pattern of responses is consistent with that predicted by mirror neurons and is evidence of mirror neurons in the human IFG.

  14. An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival.

    PubMed

    Miller, Lance D; Smeds, Johanna; George, Joshy; Vega, Vinsensius B; Vergara, Liza; Ploner, Alexander; Pawitan, Yudi; Hall, Per; Klaar, Sigrid; Liu, Edison T; Bergh, Jonas

    2005-09-20

    Perturbations of the p53 pathway are associated with more aggressive and therapeutically refractory tumors. However, molecular assessment of p53 status, by using sequence analysis and immunohistochemistry, are incomplete assessors of p53 functional effects. We posited that the transcriptional fingerprint is a more definitive downstream indicator of p53 function. Herein, we analyzed transcript profiles of 251 p53-sequenced primary breast tumors and identified a clinically embedded 32-gene expression signature that distinguishes p53-mutant and wild-type tumors of different histologies and outperforms sequence-based assessments of p53 in predicting prognosis and therapeutic response. Moreover, the p53 signature identified a subset of aggressive tumors absent of sequence mutations in p53 yet exhibiting expression characteristics consistent with p53 deficiency because of attenuated p53 transcript levels. Our results show the primary importance of p53 functional status in predicting clinical breast cancer behavior. PMID:16141321

  15. 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

  16. 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

  17. 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

  18. 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

  19. Aerobic vs. anaerobic scope: sibling species of fish indicate that temperature dependence of hypoxia tolerance can predict future survival.

    PubMed

    Sørensen, Christina; Munday, Philip L; Nilsson, Göran E

    2014-03-01

    The temperature dependence of aerobic scope has been suggested to be a major determinant of how marine animals will cope with future rises in environmental temperature. Here, we present data suggesting that in some animals, the temperature dependence of anaerobic scope (i.e., the capacity for surviving severe hypoxia) may determine present-day latitudinal distributions and potential for persistence in a warmer future. As a model for investigating the role of anaerobic scope, we studied two sibling species of coral-dwelling gobies, Gobiodon histrio, and G. erythrospilus, with different latitudinal distributions, but which overlap in equal abundance at Lizard Island (14°40'S) on the Great Barrier Reef. These species did not differ in the temperature dependence of resting oxygen consumption or critical oxygen concentration (the lowest oxygen level where resting oxygen consumption can be maintained). In contrast, the more equatorial species (G. histrio) had a better capacity to endure anaerobic conditions at oxygen levels below the critical oxygen concentration at the high temperatures (32-33 °C) more likely to occur near the equator, or in a warmer future. These results suggest that anaerobic scope, in addition to aerobic scope, could be important in determining the impacts of global warming on some marine animals.

  20. 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

  1. Predicted climate change effects on streambed scour and risks to Chinook salmon survival in the Middle Fork Salmon River, Idaho

    NASA Astrophysics Data System (ADS)

    Goode, J.; Buffington, J. M.; Tonina, D.; Isaak, D.; Tetzlaff, D.; Soulsby, C.; Wenger, S.; Thurow, R.; Nagel, D.; Luce, C.

    2011-12-01

    In response to recent climate warming trends in the Pacific Northwest, the frequency and magnitude of winter floods is expected to increase in some areas where rain-on-snow events occur. Eggs of fall spawning salmonids are incubating in the streambed at this time of year and may be at risk if streambed scour exceeds typical egg burial depths. We investigated how projected trends in streamflow associated with climate change may alter the probability of streambed scour below documented egg burial depths (15-50 cm) for Chinook salmon (Oncorhynchus tshawytscha) in the Middle Fork Salmon River (MFSR), central Idaho. Predictions are made for the magnitude and timing of current and future bankfull flows (approximated by the 2-year flood, Q2) at the basin scale by coupling digital elevation models with empirical predictions of grain size and bankfull shear stress, determined from field surveys of 120 channel reaches distributed throughout the basin. Historic and future values of Q2 were derived from the Variable Infiltration Capacity (VIC) hydrologic model at the scale of 1/16th degree cells. Future predictions of Q2 were derived from the VIC model using output from an ensemble of Global Climate Models under an A1B emissons scenario for the 2040s and 2080s. Predicted changes in both bankfull flow and the probability of scour to egg burial depths were examined at recent spawning sites (1995-2004 surveys) to assess ecological risk. We found that in the low gradient reaches (Slope <3%) where most spawning occurs, the probability of critical scour was consistently <0.1 under the historic scenario. Future scenarios indicated only a small increase in the length of streams subject to scour in the MFSR, and suggested that this high-elevation system could be largely resistant to climate-driven changes in flow, except under extreme warming scenarios. We are currently extending these analyses to lower elevation basins in rain-dominated and transitional (rain and snow) hydroclimates

  2. 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

  3. High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients.

    PubMed

    Barjesteh van Waalwijk van Doorn-Khosrovani, Sahar; Erpelinck, Claudia; van Putten, Wim L J; Valk, Peter J M; van der Poel-van de Luytgaarde, Sonja; Hack, Ronald; Slater, Rosalyn; Smit, Elisabeth M E; Beverloo, H Berna; Verhoef, Gregor; Verdonck, Leo F; Ossenkoppele, Gert J; Sonneveld, Pieter; de Greef, Georgine E; Löwenberg, Bob; Delwel, Ruud

    2003-02-01

    The proto-oncogene EVI1 encodes a DNA binding protein and is located on chromosome 3q26. The gene is aberrantly expressed in acute myeloid leukemia (AML) patients carrying 3q26 abnormalities. Two mRNAs are transcribed from this locus: EVI1 and a fusion of EVI1 with MDS1 (MDS1-EVI1), a gene located 5' of EVI1. The purpose of this study was to investigate which of the 2 gene products is involved in transformation in human AML. To discriminate between EVI1 and MDS1-EVI1 transcripts, distinct real-time quantitative polymerase chain reaction (PCR) assays were developed. Patients with 3q26 abnormalities often showed high EVI1 and MDS1-EVI1 expression. In a cohort of 319 AML patients, 4 subgroups could be distinguished: EVI1(+) and MDS1-EVI1(-) (6 patients; group I), EVI1(+) and MDS1-EVI1(+) (26 patients; group II), EVI1(-) and MDS1-EVI1(+) (12 patients; group III), and EVI1(-) and MDS1-EVI1(-) (275 patients; group IV). The only 4 patients with a 3q26 aberration belonged to groups I and II. Interestingly, high EVI1 and not MDS1-EVI1 expression was associated with unfavorable karyotypes (eg, -7/7q-) or complex karyotypes. Moreover, a significant correlation was observed between EVI1 expression and 11q23 aberrations (mixed lineage leukemia [MLL] gene involvement). Patients from groups I and II had significantly shorter overall and event-free survival than patients in groups III and IV. Our data demonstrate that high EVI1 expression is an independent poor prognostic marker within the intermediate- risk karyotypic group.

  4. 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

  5. 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

  6. Outcomes of Unilateral Inferior Oblique Myectomy Surgery in Inferior Oblique Overaction Due to Superior Oblique Palsy

    PubMed Central

    Yumuşak, Erhan; Yolcu, Ümit; Küçükevcilioğlu, Murat; Diner, Oktay; Mutlu, Fatih Mehmet

    2016-01-01

    Objectives: To present the outcomes of unilateral inferior oblique myectomy performed in patients with inferior oblique overaction due to superior oblique palsy. Materials and Methods: Twenty-seven eyes of 27 patients that underwent inferior oblique myectomy surgery for superior oblique palsy between 2002 and 2008 were included. Inferior oblique overaction scores (between 0-4) at preoperative, early postoperative (within 1 week after surgery) and late postoperative (earliest 6 months) visits were reviewed. Results: There were 12 male and 15 female patients. Eighteen were operated on the right eye, and 9 were operated on the left eye. The mean age was 15.62±13.31 years, and the mean follow-up was 17±11.28 months (range, 6-60 months). Patients who had horizontal component and V-pattern deviation were excluded. Preoperative and early postoperative inferior oblique overaction scores were 2.55±0.75 and 0.14±0.36, respectively, and the difference was statistically significant (p<0.01). This improvement was maintained up to the late postoperative period. Conclusion: Due to its promising short-term and long-term results, inferior oblique myectomy can be the first choice of surgery for inferior oblique overaction due to superior oblique palsy. PMID:27800253

  7. 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

  8. A predictive model for the influence of food components on survival of Listeria monocytogenes LM 54004 under high hydrostatic pressure and mild heat conditions.

    PubMed

    Gao, Yu-Long; Ju, Xing-Rong; Wu-Ding

    2007-07-15

    The combination of high hydrostatic pressure with mild temperature was explored to achieve a predictive model of microbial inactivation in food matrix processing. The pressure processing conditions were fixed at 448 MPa for 11 min at the treatment temperature of 41 degrees C, which have been determined as the optimum processing conditions considering six log-cycle reductions of Listeria monocytogenes. Based on the results, response surface methodology (RSM) was performed in the present work, the influence of food components like soybean protein (0-5.00%), sucrose (0.25-13.25%), bean oil (0-10.00%), and pH (4-10) of the food matrix on survival of L. monocytogenes by high pressure and mild heat was studied, and a quadratic predictive model for the influence of food components and pH of food matrix on L. monocytogenes reduction by high pressure and mild heat was built with RSM accurately. The experimental results showed that the efficiency of L. monocytogenes reduction in milk buffer and food matrix designed in the present work, under the HPP treatment process parameters described above, were different. The soybean protein (P=0.0086), sucrose (P<0.0001), and pH (P=0.0136) significantly affected reduction of L. monocytogenes, but the effect of bean oil on reduction of L. monocytogenes was not significant (P=0.1028). The predictive model is significant since the level of significance was P<0.0001 and the calculated F value (11.53) is much greater than the tabulated F value (F(0.01 (14, 5))=9.77). Moreover, the adequacy of the predictive model equation for predicting the level of L. monocytogenes reduction was verified effectively by the validation data.

  9. 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

  10. Does vascular endothelial growth factor (VEGF) predict local relapse and survival in radiotherapy-treated node-negative breast cancer?

    PubMed Central

    Linderholm, B; Tavelin, B; Grankvist, K; Henriksson, R

    1999-01-01

    The aim of this study was to determine the association of vascular endothelial growth factor (VEGF) content in 302 consecutive node-negative breast cancer (NNBC) patients treated with only locoregional radiotherapy to relapse free- (RFS) and overall survival (OS). VEGF content in tumour cytosols was measured by an enzymatic immunoassay for the major isoform VEGF165. The median age was 56 years, the median follow-up time 56 months. A wide range (0.01–144.79 pg μg−1 DNA) of VEGF content was found (median 1.92). Significant associations were found between VEGF and oestrogen receptor (ER) content, progesterone receptor (PR) and tumour size (P = 0.005). Univariate analysis displayed significant reduced RFS and OS for patients with higher VEGF content (P = 0.0113 and P = 0.0075 respectively). A total of 43 recurrences have been found (ten local relapses within the breast, five in the axillary or supraclavicular lymph nodes and 28 distant metastasis). There was no significant correlation between the localization of the relapse and the VEGF content. Multivariate analysis suggested VEGF as the only predictor of OS (relative risk (RR) = 3.6, 95% confidence interval (CI) = 0.97–13.37), and in patients with T1 tumours (n = 236) the multivariate analysis clearly displayed VEGF as the only independent predictor of both RFS and OS (RR = 5.1, CI = 1.07–24.59). In the sub-group with ER-positive tumours (n = 229), multivariate analysis showed VEGF as the only significant predictor of RFS and OS (RR = 10.44, CI = 1.26–86.38). The results suggest VEGF165 as a predictor of RFS and OS in NNBC patients treated with locoregional radiotherapy, comprising especially patients with favourable prognosis of T1 tumours, or ER-positive tumours. The high VEGF expression might define a radioresistant phenotype, or indicate an early distant spread which might require adjuvant systemic treatment. © 1999 Cancer Research Campaign PMID:10574263

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Discriminant Analysis of 18F-Fluoro-Thymidine Kinetic Parameters to Predict Survival in Patients with Recurrent High-Grade Glioma

    PubMed Central

    Wardak, Mirwais; Schiepers, Christiaan; Dahlbom, Magnus; Cloughesy, Timothy; Chen, Wei; Satyamurthy, Nagichettiar; Czernin, Johannes; Phelps, Michael E.; Huang, Sung-Cheng

    2011-01-01

    Purpose The primary objective of this study was to investigate if changes in 18F-FLT kinetic parameters, taken at an early stage after start of therapy, could predict overall survival (OS) and progression-free survival (PFS) in patients with recurrent malignant glioma undergoing treatment with bevacizumab and irinotecan. Experimental Design High-grade recurrent brain tumors were investigated in 18 patients (8M, 10F), 26-76 yr. Each had 3 dynamic PET studies: at baseline, and after 2 weeks, and 6 weeks from the start of treatment. 2.0 MBq/kg of 18F-FLT was injected intravenously and dynamic PET images acquired for 1 hr. Factor analysis generated factor images from which blood and tumor uptake curves were derived. A 3-compartment, 2-tissue model was applied to estimate the tumor 18F-FLT kinetic rate constants using a metabolite and partial volume corrected input function. Different combinations of predictor variables were exhaustively searched in a discriminant function to accurately classify patients into their known OS and PFS groups. A leave-one-out cross-validation technique was used to assess the generalizability of the model predictions. Results In this study population, changes in single parameters such as standardized uptake value or influx rate constant did not accurately classify patients into their respective OS groups (<1yr and ≥1yr) [hit-ratios ≤ 78%]. However, changes in a set of 18F-FLT kinetic parameters could perfectly separate these two groups of patients [hit-ratio=100%] and were also able to correctly classify patients into their respective PFS groups (<100 days and ≥100 days) [hit-ratio=88%]. Conclusions Discriminant analysis using changes in 18F-FLT kinetic parameters early during treatment appears to be a powerful method for evaluating the efficacy of therapeutic regimens. PMID:21868765

  16. 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

  17. Can an IL13 -1112 C/T (rs1800925) polymorphism predict responsiveness to neoadjuvant chemoradiotherapy and survival of Chinese Han patients with locally advanced rectal cancer?

    PubMed Central

    Chang, Hui; Xi, Shaoyan; Xiao, Weiwei; Zeng, Zhifan; Zhang, Huizhong; Xu, Ruihua; Gao, Yuanhong

    2016-01-01

    We sought to determine whether a polymorphism in the Interleukin 13 gene (IL13), 1112 C/T (rs1800925) predicts responsiveness to neoadjuvant chemoradiotherapy (neoCRT) and prognosis in Chinese Han patients with locally advanced rectal cancer (LARC). Pre-treatment biopsies of primary rectal lesion and surgical specimens were collected from 58 patients with LARC, who were treated with neoCRT and surgery. Tumor DNA was extracted from these biopsies and sequenced to analyze the rs1800925 polymorphism. The tumor response to neoCRT was categorized using a tumor regression grade (TRG, 0-2 were poor responders; 3-4 were good responders). Analyses of progression free survival (PFS) and overall survival (OS) were carried out using the Kaplan-Meier method. Of the forty-six patients for whom tumor DNA was successfully sequenced, 23 were good responders to neoCRT (11 patients with a pathological complete response, i.e. pCR) and the other 23 were poor responders. Good and poor responders were equally likely to have a C/C genotype at rs1800925 (73.9%) as a T/T or C/T genotype (26.1%). There were no differences between the C/C and T/T+C/T genotypes with respect to the ypT0-2 ratio (38.2% vs. 41.7%, P = 1.0), ypN0 nodal status (67.6% vs. 50.0%, P= 0.314), 6-year PFS (67.6% vs. 50%, P=0.274), or 6-year OS (76.5% vs. 66.7%, P=0.441). Thus, the IL13-1112 C/T (rs1800925) polymorphism does not predict responsiveness to neoCRT or prognosis of Chinese Han patients with LARC. PMID:27167201

  18. 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.

  19. GFAP and alpha1a-AR staining and nuclear morphometry of oligodendrogliomas by confocal microscopy and image analysis: useful parameters for predicting survival in oligodendrogliomas

    PubMed Central

    Moro-Rodríguez, Ernesto; Figols, Javier; Alvira, Mariano; Uranga-Ocio, José A; García-Poblete, Eduardo

    2008-01-01

    Objective This study attempts to evaluate the GFAP and alpha1a-AR staining and morphometrical nuclear features of oligodendrogliomas and their prognostic implications as compared to present histopathology classification and their survival outcome. Study design Surgical specimens from 24 patients with oligodendrogliomas during the period 1981–2000 were included. These cases were classified into two groups defined by the grade of the neoplasm: Group I: oligodendrogliomas grade II; Group II: oligodendrogliomas grade III and two groups based on the outcome status: Group of the alive cases and group of the death cases. Death rate for the groups were obtained by patients' charts. Descriptive statistics were used to examine the groups with respect to the morphometrical nuclear variables; area, perimeter, aspect, axes (major and minor), diameters (max, mean and min.), radius (max. and min.) margination, ratio of perimeter-area, roundness and sizes (length and width). In addition, an immunofluorescence method for GFAP and 1a-AR were performed and their area, density and intensity of staining were analyzed. Results Semiautomated quantitative morphometrical results showed that the variables of nuclear area (GII 48.87 μm2 vs. GIII 43.45 μm2 p-value = 0.02), aspect (GII 1.39 vs. GIII 1.55 p-value = 0.03), axis minor (GII 6.66 μm vs. GIII 6.01 μm p-value = 0.003), diameter minor (GII 5.93 μm vs. GIII 5.27 μm p-value = 0.002), radius minor (GII 2.64 μm vs. GIII 2.25 μm p-value = 0,003), perimeter-area (GII 0.0007 vs. GIII 0.0006 p-value = 0.04), size width (GII 6.60 μm vs. GIII 5.96 μm p-value = 0,003), and density of alpha1a-AR staining (GII 121.38 vs. GIII 146.03 p-value = 0.05) were statistically significant in regard of grade; and that the sum of density of GFAP (p-value = 0.01) and the intensity of alpha1a-AR (p-value = 0.01) were statistically significant in predicting survival. Conclusion These results suggest that some nuclear morphometrical features and the

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Testing predictions of the Janzen-Connell hypothesis: a meta-analysis of experimental evidence for distance- and density-dependent seed and seedling survival.

    PubMed

    Comita, Liza S; Queenborough, Simon A; Murphy, Stephen J; Eck, Jenalle L; Xu, Kaiyang; Krishnadas, Meghna; Beckman, Noelle; Zhu, Yan; Gómez-Aparicio, Lorena

    2014-07-01

    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

  7. In Vitro-Stimulated IL-6 Monocyte Secretion and In Vivo Peripheral Blood T Lymphocyte Activation Uniquely Predicted 15-Year Survival in Patients with Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Aarstad, Helene Hersvik; Vintermyr, Olav Karsten; Ulvestad, Elling; Kross, Kenneth; Heimdal, John Helge; Aarstad, Hans Jorgen

    2015-01-01

    The study was performed in order to determine whether peripheral blood monocyte in vitro function, and lymphocyte in vivo activation at diagnosis, was associated with HPV tumor infection status and 15-year survival in head and neck squamous cell carcinoma (HNSCC) patients. Sixty-five patients from a consecutive cohort of newly diagnosed HNSCCs, together with 18 control patients, were included in the study. Monocyte responsiveness was assessed by measuring monocyte in vitro interleukin (IL)-6 secretions after 24 hours of LPS stimulation in cultures with a serum-free medium. T lymphocyte activation was determined as the fraction of CD71-positive cells on CD3-positive cells by flow cytometry, whereas HPV infection was determined by PCR on formalin-fixed paraffin-embedded (FFPE) tumor tissue. Disease-specific survivals and overall survivals were determined 15 years following inclusion. HPV-positive HNSCC patients had a lower monocyte LPS-stimulated IL-6 response. A high LPS-stimulated monocyte IL-6 response predicted a decreased survival rate (P=0.019). A high percentage of CD71-positive T lymphocytes also predicted an impaired prognosis (P=0.021). The predictive power of IL-6 monocyte LPS-stimulated responses was retained when adjusted for age, gender and TNM stage of the patients. The monocyte and T lymphocyte survival predictions were independent of each other. The survival was particularly low with a combined high activated monocyte and T lymphocyte status. In a multivariate analysis, IL-6 secretion and the percentage of CD71-positive T lymphocytes both uniquely predicted survival independent of HPV infection status. It is postulated that the natural and adaptive immune systems are separately and additionally linked to the clinical aggressiveness of HNSCCs. PMID:26079381

  8. A prognostic model to predict survival in 867 World Health Organization-defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment.

    PubMed

    Passamonti, Francesco; Thiele, Jürgen; Girodon, Francois; Rumi, Elisa; Carobbio, Alessandra; Gisslinger, Heinz; Kvasnicka, Hans Michael; Ruggeri, Marco; Randi, Maria Luigia; Gangat, Naseema; Vannucchi, Alessandro Maria; Gianatti, Andrea; Gisslinger, Bettina; Müllauer, Leonhard; Rodeghiero, Francesco; d'Amore, Emanuele S G; Bertozzi, Irene; Hanson, Curtis A; Boveri, Emanuela; Marino, Filippo; Maffioli, Margherita; Caramazza, Domenica; Antonioli, Elisabetta; Carrai, Valentina; Buxhofer-Ausch, Veronika; Pascutto, Cristiana; Cazzola, Mario; Barbui, Tiziano; Tefferi, Ayalew

    2012-08-01

    Diagnosis of essential thrombocythemia (ET) has been updated in the last World Health Organization (WHO) classification. We developed a prognostic model to predict survival at diagnosis, named IPSET (International Prognostic Score for ET), studying patients with WHO-defined ET. Age 60 years or older, leukocyte count ≥ 11 × 10(9)/L, and prior thrombosis significantly affected survival, by multivariable Cox regression. On the basis of the hazard ratio, we assigned 2 points to age and 1 each to leukocyte count and thrombosis. So, the IPSET model allocated 867 patients into 3 risk categories with significantly different survival: low (sum of points = 0; median survival not reached), intermediate (sum = 1-2; median survival 24.5 years), and high (sum = 3-4, median survival 13.8 years). The IPSET model was further validated in 2 independent cohorts including 132 WHO-defined ET and 234 Polycythemia Vera Study Group-defined ET patients. The IPSET model was able to predict the occurrence of thrombosis, and not to predict post-ET myelofibrosis. In conclusion, IPSET, based on age ≥ 60 years, leukocyte count ≥ 11 × 10(9)/L, and history of thrombosis allows prognostic assessment of WHO-defined ET and the validation process makes IPSET applicable in all patients phenotypically appearing as ET.

  9. MicroRNA profiling predicts survival in anti-EGFR treated chemorefractory metastatic colorectal cancer patients with wild-type KRAS and BRAF.

    PubMed

    Mosakhani, Neda; Lahti, Leo; Borze, Ioana; Karjalainen-Lindsberg, Marja-Liisa; Sundström, Jari; Ristamäki, Raija; Osterlund, Pia; Knuutila, Sakari; Sarhadi, Virinder Kaur

    2012-11-01

    Anti-EGFR monoclonal antibodies (anti-EGFRmAb) serve in the treatment of metastatic colorectal cancer (mCRC), but patients with a mutation in KRAS/BRAF and nearly one-half of those without the mutation fail to respond. We performed microRNA (miRNA) analysis to find miRNAs predicting anti-EGFRmAb efficacy. Of the 99 mCRC patients, we studied differential miRNA expression by microarrays from primary tumors of 33 patients who had wild-type KRAS/BRAF and third- to sixth-line anti-EGFRmAb treatment, with/without irinotecan. We tested the association of each miRNA with overall survival (OS) by the Cox proportional hazards regression model. Significant miR-31* up-regulation and miR-592 down-regulation appeared in progressive disease versus disease control. miR-31* expression and down-regulation of its target genes SLC26A3 and ATN1 were verified by quantitative reverse transcriptase polymerase chain reaction. Clustering of patients based on miRNA expression revealed a significant difference in OS between patient clusters. Members of the let-7 family showed significant up-regulation in the patient cluster with poor OS. Additionally, miR-140-5p up-regulation and miR-1224-5p down-regulation were significantly associated with poor OS in both cluster analysis and the Cox proportional hazards regression model. In mCRC patients with wild-type KRAS/BRAF, miRNA profiling can efficiently predict the benefits of anti-EGFRmAb treatment. Larger series of patients are necessary for application of these miRNAs as predictive/prognostic markers.

  10. Prediction of a Required Log Reduction with Probability for Enterobacter sakazakii during High-Pressure Processing, Using a Survival/Death Interface Model▿

    PubMed Central

    Koseki, Shige; Matsubara, Maki; Yamamoto, Kazutaka

    2009-01-01

    A probabilistic model for predicting Enterobacter sakazakii inactivation in trypticase soy broth (TSB) and infant formula (IF) by high-pressure processing was developed. The modeling procedure is based on a previous model (S. Koseki and K. Yamamoto, Int. J. Food Microbiol. 116:136-143, 2007) that describes the probability of death of bacteria. The model developed in this study consists of a total of 300 combinations of pressure (400, 450, 500, 550, or 600 MPa), pressure-holding time (1, 3, 5, 10, or 20 min), temperature (25 or 40°C), inoculum level (3, 5, or 7 log10 CFU/ml), and medium (TSB or IF), with each combination tested in triplicate. For each replicate response of E. sakazakii, survival and death were scored with values of 0 and 1, respectively. Data were fitted to a logistic regression model in which the medium was treated as a dummy variable. The model predicted that the required pressure-holding times at 500 MPa for a 5-log reduction in IF with 90% achievement probability were 26.3 and 7.9 min at 25 and 40°C, respectively. The probabilities of achieving 5-log reductions in TSB and IF by treatment with 400 MPa at 25°C for 10 min were 92 and 3%, respectively. The model enabled the identification of a minimum processing condition for a required log reduction, regardless of the underlying inactivation kinetics pattern. Simultaneously, the probability of an inactivation effect under the predicted processing condition was also provided by taking into account the environmental factors mentioned above. PMID:19201951

  11. Prediction of a required log reduction with probability for Enterobacter sakazakii during high-pressure processing, using a survival/death interface model.

    PubMed

    Koseki, Shige; Matsubara, Maki; Yamamoto, Kazutaka

    2009-04-01

    A probabilistic model for predicting Enterobacter sakazakii inactivation in trypticase soy broth (TSB) and infant formula (IF) by high-pressure processing was developed. The modeling procedure is based on a previous model (S. Koseki and K. Yamamoto, Int. J. Food Microbiol. 116:136-143, 2007) that describes the probability of death of bacteria. The model developed in this study consists of a total of 300 combinations of pressure (400, 450, 500, 550, or 600 MPa), pressure-holding time (1, 3, 5, 10, or 20 min), temperature (25 or 40 degrees C), inoculum level (3, 5, or 7 log(10) CFU/ml), and medium (TSB or IF), with each combination tested in triplicate. For each replicate response of E. sakazakii, survival and death were scored with values of 0 and 1, respectively. Data were fitted to a logistic regression model in which the medium was treated as a dummy variable. The model predicted that the required pressure-holding times at 500 MPa for a 5-log reduction in IF with 90% achievement probability were 26.3 and 7.9 min at 25 and 40 degrees C, respectively. The probabilities of achieving 5-log reductions in TSB and IF by treatment with 400 MPa at 25 degrees C for 10 min were 92 and 3%, respectively. The model enabled the identification of a minimum processing condition for a required log reduction, regardless of the underlying inactivation kinetics pattern. Simultaneously, the probability of an inactivation effect under the predicted processing condition was also provided by taking into account the environmental factors mentioned above.

  12. Prostate-specific antigen doubling time predicts clinical outcome and survival in prostate cancer patients treated with combined radiation and hormone therapy

    SciTech Connect

    Lee, Andrew K. . E-mail: aklee@mdanderson.org; Levy, Larry B.; Cheung, Rex; Kuban, Deborah

    2005-10-01

    Purpose: To determine whether prostate-specific antigen (PSA) doubling time predicts clinical outcomes in patients with prostate cancer that has been treated with combined radiation and hormone therapy. Methods and Materials: We reviewed the medical records of 621 men with nonmetastatic prostate cancer treated with radiation therapy and hormone therapy between 1989 and 2003. 'Any' clinical failure was defined as any distant, nodal, or local failure, or the use of salvage therapy. 'True' clinical failure was defined as any distant, nodal, or local failure. PSA doubling time was calculated by using the log PSA values from patients with a PSA failure as defined by the American Society of Therapeutic Radiology Oncology consensus statement. One hundred thirty-seven men were at intermediate risk for PSA failure (as determined by T2b, Gleason score of 7, or PSA 10.1-0 ng/mL) and 484 men were at high risk for failure (T2c-4; Gleason 8-10; or PSA >20 ng/mL). Pretreatment PSA value, Gleason score, tumor stage, timing and duration of hormone therapy, radiation therapy dose, and PSA doubling time were analyzed for any associations with time to clinical failure by using Cox regression analysis. Estimates of survival were calculated by using the Kaplan-Meier method. Pairwise comparisons were made by using the log-rank test. Results: Sixty-two men experienced any clinical failure, and 22 men experienced true clinical failure. Multivariate analysis revealed that pretreatment PSA (p = 0.013), Gleason score (p = 0.0019), and a PSA doubling time (PSADT) {<=}8 months (p < 0.001) were independently associated with time to any clinical failure. Tumor stage, hormone therapy timing, hormone therapy duration, and radiation therapy dose were not statistically significant on multivariate or univariate analysis. Only hormone therapy duration (p 0.008) and PSADT {<=}8 months (<0.001) were significantly associated with time to true clinical failure. The estimated 5-year rate of any clinical

  13. T-bet expression in intratumoral lymphoid structures after neoadjuvant trastuzumab plus docetaxel for HER2-overexpressing breast carcinoma predicts survival

    PubMed Central

    Ladoire, S; Arnould, L; Mignot, G; Apetoh, L; Rébé, C; Martin, F; Fumoleau, P; Coudert, B; Ghiringhelli, F

    2011-01-01

    Background: In HER2-overexpressing breast cancer, accumulating preclinical evidences suggest that some chemotherapies, like trastuzumab, but also taxanes, are able to trigger a T helper 1 (Th1) anticancer immune response that contribute to treatment success. T helper 1 immune response is characterised by the expression of the transcription factor T-bet in CD4 T lymphocytes. We hypothesised that the presence of such T cells in the tumour immune infiltrates following neoadjuvant chemotherapy would predict patient survival. Methods: In a series of 102 consecutive HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy incorporating antracyclines or taxane and trastuzumab, we studied by immunohistochemistry the peritumoral lymphoid infiltration by T-bet+ lymphocytes before and after chemotherapy in both treatment groups. Kaplan–Meier analysis and Cox modelling were used to assess relapse-free survival (RFS). Results: Fifty-eight patients have been treated with trastuzumab–taxane and 44 patients with anthracyclines-based neoadjuvant chemotherapy. The presence of T-bet+ lymphocytes in peritumoral lymphoid structures after chemotherapy was significantly more frequent in patients treated with trastuzumab–taxane (P=0.0008). After a median follow-up of 40 months, the presence of T-bet+ lymphocytes after neoadjuvant chemotherapy confers significantly better RFS (log-rank test P=0.011) only in patients treated with trastuzumab–taxane. In this population, multivariate Cox regression model showed that only the presence of T-bet+ lymphocytes in peritumoral lymphoid structures after neoadjuvant chemotherapy was independently associated with improved RFS (P=0.04). Conclusion: These findings indicate that the tumour infiltration by T-bet+ Th1 lymphocytes following neoadjuvant trastuzumab–taxane may represent a new independent prognostic factor of improved outcome in HER2-overexpressing breast carcinoma. PMID:21750556

  14. Age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in refractory anaemia with ring sideroblasts and marked thrombocytosis.

    PubMed

    Broséus, J; Alpermann, T; Wulfert, M; Florensa Brichs, L; Jeromin, S; Lippert, E; Rozman, M; Lifermann, F; Grossmann, V; Haferlach, T; Germing, U; Luño, E; Girodon, F; Schnittger, S

    2013-09-01

    Refractory anaemia with ring sideroblasts (RARS) and marked thrombocytosis (RARS-T) is a provisional entity in the World Health Organisation 2008 classification and has previously been shown to have a high proportion of JAK2(V617F) (Janus Kinase 2) and SF3B1 (Splicing Factor 3B subunit 1) mutations. The purpose of the present study was to analyse the frequency of SF3B1 mutations in a large cohort of 111 patients with RARS-T and 33 patients with RARS and to explore the prognostic impact of SF3B1 mutational status on RARS-T. The frequency of SF3B1 mutations in RARS-T (96/111, 86.5%) and RARS (28/33, 84.8%) was similar. In RARS-T, median survival was better in SF3B1-mutated patients than in SF3B1-non-mutated patients (6.9 and 3.3 years, respectively, P=0.003). RARS can be differentiated from RARS-T by the frequency of JAK2(V617F) (0% vs 48.6%). In RARS-T patients, SF3B1 (P=0.021) and JAK2 mutations (P=0.016) were independent factors for a better prognosis. Altogether, our results confirm that RARS-T is an independent entity that should be recognised by the next World Health Organisation classification. The assessment of SF3B1 mutations is of prognostic interest in RARS-T patients. Younger age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in RARS-T. PMID:23594705

  15. Maxillary antral lavage using inferior meatal cannula anaesthesia.

    PubMed

    Mochloulis, G; Hern, J D; Hollis, L J; Tolley, N S

    1996-08-01

    Antral puncture and lavage through the inferior meatus is a minor but common otolaryngological procedure, usually performed under local anaesthesia. We describe a new method of introducing local anaesthetic into the inferior meatus, via the use of a soft intravenous cannula connected to a syringe containing 10 per cent cocaine paste. We have called this new technique inferior meatal cannula anaesthesia (IMCA).

  16. Rapid Recovery of CD3+CD8+ T Cells on Day 90 Predicts Superior Survival after Unmanipulated Haploidentical Blood and Marrow Transplantation

    PubMed Central

    Tian, Deng-Mei; Wang, Yu; Zhang, Xiao-Hui; Liu, Kai-Yan; Huang, Xiao-Jun; Chang, Ying-Jun

    2016-01-01

    Background Rapid immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is significantly associated with lower infection, relapse and possibly secondary malignancy rates. The aim of this study was to investigate the role of peripheral lymphocyte subsets, especially CD3+CD8+ cytotoxic T cell recovery, in predicting transplant outcomes, including the overall survival (OS) and non-relapse mortality (NRM) rates after unmanipulated haploidentical blood and marrow transplantation (HBMT). Methods Peripheral blood samples were obtained from 214 HBMT recipients with hematological malignancies. The peripheral lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, and CD19+ B cells) were analyzed by flow cytometry at days 30, 60, 90, 180, 270 and 360 after HBMT. Results The CD3+CD8+ cytotoxic T cell recovery at day 90 (CD3+CD8+-90) was correlated with bacterial infection (P = 0.001), NRM (P = 0.001), leukemia-free survival (LFS, P = 0.005), and OS (P = 0.001) at a cutoff value of 375 cells/μL CD3+CD8+ T cells. The incidence of bacterial infection in patients with the CD3+CD8+-90 at ≥375 cells/μL was significantly lower than that of cases with the CD3+CD8+-90 at <375 cells/μL after HBMT (14.6% versus 41.6%, P<0.001). Multivariate analysis showed the rapid recovery of CD3+CD8+ T cells at day 90 after HBMT was strongly associated with a lower incidence of NRM (HR = 0.30; 95% CI: 0.15–0.60; P = 0.000) and superior LFS (HR = 0.51; 95% CI: 0.32–0.82; P = 0.005) and OS (HR = 0.38; 95% CI: 0.23–0.63; P = 0.000). Conclusion The results suggest that the rapid recovery of CD3+CD8+ cytotoxic T cells at day 90 following HBMT could predict superior transplant outcomes. PMID:27276058

  17. Inferior sinus venosus defects: anatomic features and echocardiographic correlates.

    PubMed

    Plymale, Jennifer; Kolinski, Kellen; Frommelt, Peter; Bartz, Peter; Tweddell, James; Earing, Michael G

    2013-02-01

    Inferior sinus venosus defects (SVDs) are rare imperfections located in the inferior portion of the atrial septum, leading to an overriding inferior vena cava (IVC) and an interatrial connection. These defects have increased risk of anomalous pulmonary venous return (PAPVR) and often are confused with secundum atrial septal defects (ASDs) with inferior extension. The authors sought to review their experience with inferior SVDs and to establish at their institution an echocardiographic definition that differentiates inferior SVDs from secundum ASDs with inferior extension. The study identified 161 patients 1.5 to 32 years of age who had undergone repair of a secundum ASD with inferior extension or inferior SVD over the preceding 10 years. All surgical notes, preoperative transthoracic echocardiograms (TTEs), and preoperative transesophageal echocardiograms (TEEs) were reviewed. Based on the surgical notes, 147 patients were classified as having a secundum ASD (147/161, 91 %) and 14 patients (9 %) as having an inferior SVD. The study identified PAPVR in 7 % (1/14) of the patients with inferior SVDs and 3.5 % (5/14) of the patients with secundum ASDs. Surgical diagnosis and preoperative TTE correlated for 143 (89 %) of the 161 patients. Using a strict anatomic and echocardiographic definition with a blinded observer, the majority of the defects (14/18, 78 %) were reclassified correctly after review of their TTE images, and 100 % of the defects were correctly reclassified after TEE image review. Accurate diagnosis of inferior SVDs remains challenging. The data from this study demonstrate that use of a strict anatomic and echocardiographic definition (a defect that originates in the mouth of the IVC and continues into the inferoposterior border of the left atrium, leaving no residual atrial septal tissue at the inferior margin) allows for accurate differentiation between secundum ASDs with inferior extension and inferior SVDs. This differentiation is extremely important

  18. Prognostic significance of resting anterior thallium-201 defects in patients with inferior myocardial infarction

    SciTech Connect

    Gibson, R.S.; Taylor, G.J.; Watson, D.D.; Berger, B.C.; Crampton, R.S.; Martin, R.P.; Beller, G.A.

    1980-11-01

    To determine whether Tl-201 scintigraphy performed at rest during the late hospital phase of inferior myocardial infarction can predict subsequent coronary events, 25 patients with historical, enzymatic, and electrocardiographic criteria of transmural inferior infarction underwent serial imaging with computer quantification 7 to 35 days after admission. All 25 patients had inferior defects, and 13 (52%) also had anterior defects implying stenosis of the left anterior descending coronary artery. The patients were divided into those with inferior and anterior perfusion defects (Group 1) and those with inferior defects alone (Group 2). In Group 1, three patients had persistent defects in the anterior wall and ten had initial defects with redistribution. New or recurrent coronary events - which included new onset or progression of angina pectoris, sudden death, reinfarction, and congestive heart failure - were recorded over an average 7.2 months of followup (range 3 to 9 mo) for all patients. Ten of 13 (77%) patients in Group 1 had 17 coronary events and four of 12 (33%) patients in Group 2 had six coronary events (p < 0.02). Nine patients in Group 1 and three in Group 2 developed angina (p < 0.03). The apparently increased prevalence in Group 1 of sudden death (8% against 0%), reinfarction (8% against 0%), and congestive heart failure (46% against 25%) was not statistically significant. Thus resting T1-201 scintigraphy with computer quantification is a highly sensitive method to detect inferior myocardial infarction even in the late hospital phase. Moreover, it appears to identify those patients with inferior infarction at high risk for subsequent coronary events, presumably due to stenosis of the left anterior descending coronary artery.

  19. Predicting Overall Survival After Stereotactic Ablative Radiation Therapy in Early-Stage Lung Cancer: Development and External Validation of the Amsterdam Prognostic Model

    SciTech Connect

    Louie, Alexander V.; Haasbeek, Cornelis J.A.; Mokhles, Sahar; Rodrigues, George B.; Stephans, Kevin L.; Lagerwaard, Frank J.; Palma, David A.; Videtic, Gregory M.M.; Warner, Andrew; Takkenberg, Johanna J.M.; Reddy, Chandana A.; Maat, Alex P.W.M.; Woody, Neil M.; Slotman, Ben J.; Senan, Suresh

    2015-09-01

    Purpose: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS. A nomogram for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n=193) and SABR (n=543) datasets. Results: RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r{sup 2}=0.97) and external SABR (r{sup 2}=0.79) and surgical cohorts (r{sup 2}=0.91). Conclusions: The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities.

  20. Evidence of Mirror Neurons in Human Inferior Frontal Gyrus

    PubMed Central

    Kilner, James M.; Neal, Alice; Weiskopf, Nikolaus; Friston, Karl J.; Frith, Chris D.

    2009-01-01

    There is much current debate about the existence of mirror neurons in humans. To identify mirror neurons in the inferior frontal gyrus (IFG) of humans we employed a repetition suppression paradigm while measuring neural activity with functional magnetic resonance imaging. Subjects either executed or observed a series of actions. Here we show that in the IFG, responses were suppressed both when an executed action was followed by the same rather than a different observed action and when an observed action was followed by the same rather than a different executed action. This pattern of responses is consistent with that predicted by mirror neurons and is evidence of mirror neurons in the human IFG. PMID:19675249

  1. Prediction of biomarkers of therapeutic effects of patients with lung adenocarcinoma treated with gefitinib based on progression-free-survival by metabolomic fingerprinting.

    PubMed

    Zhuang, Jingcong; Tang, Xiaohu; Du, Zhenxia; Yang, Ming; Zhou, Ying

    2016-11-01

    Lung carcinoma is one of the most frequently diagnosed malignancy and threats human life and health. In clinical practice, gefitinib, one of the most well-known epidermal growth factor receptor tyrosine kinase inhibitors, was frequently used in the treatment of non-small cell lung carcinoma. However, this drug is not useful for all non-small cell patients. In this study, the biomarkers were found out to predict the therapeutic effects of gefitinib for lung carcinoma patients. Serum samples were collected from patients with advanced lung adenocarcinoma. The ultra-high performance liquid chromatography (UHPLC)-quadrupole-time of flight mass spectrometry (Q-TOF MS) was conducted to obtain the metabolic data for each patient. Partial least squares-discriminate analysis (PLS-DA) was performed to indicate the differences between metabolites of patients, and Cox proportional hazards regression analysis was used to eliminate the interference of the patient's gender, age, smoking history and disease stage. Thus, differential biomarkers were found. The combination of these biomarkers was statistically significant predictors based on progression-free survival. If these biomarkers can be further confirmed by the clinic, it could suggest the proper therapeutic schedule, and help to reduce patients' economic burden and medication side effects. PMID:27591660

  2. Regulatory T cells, especially ICOS+ FOXP3+ regulatory T cells, are increased in the hepatocellular carcinoma microenvironment and predict reduced survival

    PubMed Central

    Tu, Jian-Fei; Ding, Ya-Hui; Ying, Xi-Hui; Wu, Fa-Zong; Zhou, Xin-Mu; Zhang, Deng-Ke; Zou, Hai; Ji, Jian-Song

    2016-01-01

    Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3+, CD4+, and CD8+ cytotoxic lymphocytes (CTLs) as well as CD56+ NK cells and CD68+ macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3+ (FOXP3+) Tregs were found in intratumoural tissue. Additionally, regarding ICOS+ FOXP3+ Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3+ cells. Higher Treg levels in tumour tissues indicated a worse prognosis, and the FOXP3+ Tregs/CD4+ T cells ratio was an independent prognostic factor for OS. Therefore, FOXP3+ Tregs, especially ICOS+ FOXP3+ Tregs, contribute to the immunosuppressive HCC microenvironment. High tumour-infiltrating Tregs are thought to be an unfavourable prognostic indicator of HCC. PMID:27725696

  3. Inferior alveolar and lingual nerve imaging.

    PubMed

    Miloro, Michael; Kolokythas, Antonia

    2011-03-01

    At present, there are no objective testing modalities available for evaluation of iatrogenic injury to the terminal branches of the trigeminal nerve, making such clinical diagnosis and management complicated for the oral and maxillofacial surgeon. Several imaging modalities can assist in the preoperative risk assessment of the trigeminal nerve as related to commonly performed procedures in the vicinity of the nerve, mostly third molar surgery. This article provides a review of all available imaging modalities and their clinical application relative to preoperative injury risk assessment of the inferior alveolar nerve and lingual nerve, and postinjury and postsurgical repair recovery status.

  4. Influence of Software Tool and Methodological Aspects of Total Metabolic Tumor Volume Calculation on Baseline [18F]FDG PET to Predict Survival in Hodgkin Lymphoma

    PubMed Central

    Kanoun, Salim; Tal, Ilan; Berriolo-Riedinger, Alina; Rossi, Cédric; Riedinger, Jean-Marc; Vrigneaud, Jean-Marc; Legrand, Louis; Humbert, Olivier; Casasnovas, Olivier; Brunotte, François; Cochet, Alexandre

    2015-01-01

    Aim To investigate the respective influence of software tool and total metabolic tumor volume (TMTV0) calculation method on prognostic stratification of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) in newly diagnosed Hodgkin lymphoma (HL). Methods 59 patients with newly diagnosed HL were retrospectively included. [18F]FDG-PET was performed before any treatment. Four sets of TMTV0 were calculated with Beth Israel (BI) software: based on an absolute threshold selecting voxel with standardized uptake value (SUV) >2.5 (TMTV02.5), applying a per-lesion threshold of 41% of the SUVmax (TMTV041) and using a per-patient adapted threshold based on SUVmax of the liver (>125% and >140% of SUVmax of the liver background; TMTV0125 and TMTV0140). TMTV041 was also determined with commercial software for comparison of software tools. ROC curves were used to determine the optimal threshold for each TMTV0 to predict treatment failure. Results Median follow-up was 39 months. There was an excellent correlation between TMTV041 determined with BI and with the commercial software (r = 0.96, p<0.0001). The median TMTV0 value for TMTV041, TMTV02.5, TMTV0125 and TMTV0140 were respectively 160 (used as reference), 210 ([28;154] p = 0.005), 183 ([-4;114] p = 0.06) and 143ml ([-58;64] p = 0.9). The respective optimal TMTV0 threshold and area under curve (AUC) for prediction of progression free survival (PFS) were respectively: 313ml and 0.70, 432ml and 0.68, 450ml and 0.68, 330ml and 0.68. There was no significant difference between ROC curves. High TMTV0 value was predictive of poor PFS in all methodologies: 4-years PFS was 83% vs 42% (p = 0.006) for TMTV02.5, 83% vs 41% (p = 0.003) for TMTV041, 85% vs 40% (p<0.001) for TMTV0125 and 83% vs 42% (p = 0.004) for TMTV0140. Conclusion In newly diagnosed HL, baseline metabolic tumor volume values were significantly influenced by the choice of the method used for determination of volume. However, no significant

  5. A clinical prognostic scoring system for resectable gastric cancer to predict survival and benefit from paclitaxel- or oxaliplatin-based adjuvant chemotherapy

    PubMed Central

    Qian, Jing; Qian, Yingying; Wang, Jian; Gu, Bing; Pei, Dong; He, Shaohua; Zhu, Fang; Røe, Oluf Dimitri; Xu, Jin; Liu, Lianke; Gu, Yanhong; Guo, Renhua; Yin, Yongmei; Shu, Yongqian; Chen, Xiaofeng

    2016-01-01

    Background Gastrectomy with D2 lymphadenectomy is a standard procedure of curative resection for gastric cancer (GC). The aim of this study was to develop a simple and reliable prognostic scoring system for GC treated with D2 gastrectomy combined with adjuvant chemotherapy. Methods A prognostic scoring system was established based on clinical and laboratory data from 579 patients with localized GC without distant metastasis treated with D2 gastrectomy and adjuvant chemotherapy. Results From the multivariate model for overall survival (OS), five factors were selected for the scoring system: ≥50% metastatic lymph node rate, positive lymphovascular invasion, pathologic TNM Stage II or III, ≥5 ng/mL preoperative carcinoembryonic antigen level, and <110 g/L preoperative hemoglobin. Two models were derived using different methods. Model A identified low- and high-risk patients for OS (P<0.001), while Model B differentiated low-, intermediate-, and high-risk patients for OS (P<0.001). Stage III patients in the low-risk group had higher survival probabilities than Stage II patients. Both Model A (area under the curve [AUC]: 0.74, 95% confidence interval [CI]: 0.69–0.78) and Model B (AUC: 0.79, 95% CI: 0.72–0.83) were better predictors compared with the pathologic TNM classification (AUC: 0.62, 95% CI: 0.59–0.71, P<0.001). Adjuvant paclitaxel- or oxaliplatin-based or triple chemotherapy showed significantly better outcomes in patients classified as high risk, but not in those with low and intermediate risk. Conclusion A clinical three-tier prognostic risk scoring system was established to predict OS of GC treated with D2 gastrectomy and adjuvant chemotherapy. The potential advantage of this scoring system is that it can identify high-risk patients in Stage II or III who may benefit from paclitaxel- or oxaliplatin-based regimens. Prospective studies are needed to confirm these results before they are applied clinically. PMID:26966350

  6. Predicting survival in heart failure case and control subjects by use of fully automated methods for deriving nonlinear and conventional indices of heart rate dynamics

    NASA Technical Reports Server (NTRS)

    Ho, K. K.; Moody, G. B.; Peng, C. K.; Mietus, J. E.; Larson, M. G.; Levy, D.; Goldberger, A. L.

    1997-01-01

    BACKGROUND: Despite much recent interest in quantification of heart rate variability (HRV), the prognostic value of conventional measures of HRV and of newer indices based on nonlinear dynamics is not universally accepted. METHODS AND RESULTS: We have designed algorithms for analyzing ambulatory ECG recordings and measuring HRV without human intervention, using robust methods for obtaining time-domain measures (mean and SD of heart rate), frequency-domain measures (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to 0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of complexity, and detrended fluctuation analysis [DFA], a measure of long-term correlations). The study population consisted of chronic congestive heart failure (CHF) case patients and sex- and age-matched control subjects in the Framingham Heart Study. After exclusion of technically inadequate studies and those with atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory ECG recordings of 69 participants (mean age, 71.7+/-8.1 years). By use of separate Cox proportional-hazards models, the conventional measures SD (P<.01), LF (P<.01), VLF (P<.05), and TP (P<.01) and the nonlinear measure DFA (P<.05) were predictors of survival over a mean follow-up period of 1.9 years; other measures, including ApEn (P>.3), were not. In multivariable models, DFA was of borderline predictive significance (P=.06) after adjustment for the diagnosis of CHF and SD. CONCLUSIONS: These results demonstrate that HRV analysis of ambulatory ECG recordings based on fully automated methods can have prognostic value in a population-based study and that nonlinear HRV indices may contribute prognostic value to complement traditional HRV measures.

  7. Glutathione transferase-A2 S112T polymorphism predicts survival, transplant-related mortality, busulfan and bilirubin blood levels after allogeneic stem cell transplantation

    PubMed Central

    Bonifazi, Francesca; Storci, Gianluca; Bandini, Giuseppe; Marasco, Elena; Dan, Elisa; Zani, Elena; Albani, Fiorenzo; Bertoni, Sara; Bontadini, Andrea; De Carolis, Sabrina; Sapienza, Maria Rosaria; Rizzi, Simonetta; Motta, Maria Rosa; Ferioli, Martina; Garagnani, Paolo; Cavo, Michele; Mantovani, Vilma; Bonafè, Massimiliano

    2014-01-01

    Busulfan liver metabolism depends on glutathione, a crucial mediator of cellular and systemic stress. Here we investigated 40 polymorphisms at 27 loci involved in hepatic glutathione homeostasis, with the aim of testing their impact on the clinical outcome of 185 busulfan-conditioned allogeneic transplants. GSTA2 S112T serine allele homozygosity is an independent prognostic factor for poorer survival (RR=2.388), for increased any time- and 100-day transplant-related mortality (RR=4.912 and RR=5.185, respectively). The genotype also predicts a wider busulfan area under the concentration-time curve (1214.36±570.06 vs. 838.10±282.40 mMol*min) and higher post-transplant bilirubin serum levels (3.280±0.422 vs. 1.874+0.197 mg/dL). In vitro, busulfan elicits pro-inflammatory activation (increased NF-KappaB activity and interleukin-8 expression) in human hepatoma cells. At the same time, the drug down-regulates a variety of genes involved in bilirubin liver clearance: constitutive androstane receptor, multidrug resistance-associated protein, solute carrier organic anion transporters, and even GSTA2. It is worthy of note that GSTA2 also acts as an intra-hepatic bilirubin binding protein. These data underline the prognostic value of GSTA2 genetic variability in busulfan-conditioned allotransplants and suggest a patho-physiological model in which busulfan-induced inflammation leads to the impairment of post-transplant bilirubin metabolism. PMID:24056816

  8. Dynamic changes of RNA-sequencing expression for precision medicine: N-of-1-pathways Mahalanobis distance within pathways of single subjects predicts breast cancer survival

    PubMed Central

    Piegorsch, Walter W.; Lussier, Yves A.

    2015-01-01

    Motivation: The conventional approach to personalized medicine relies on molecular data analytics across multiple patients. The path to precision medicine lies with molecular data analytics that can discover interpretable single-subject signals (N-of-1). We developed a global framework, N-of-1-pathways, for a mechanistic-anchored approach to single-subject gene expression data analysis. We previously employed a metric that could prioritize the statistical significance of a deregulated pathway in single subjects, however, it lacked in quantitative interpretability (e.g. the equivalent to a gene expression fold-change). Results: In this study, we extend our previous approach with the application of statistical Mahalanobis distance (MD) to quantify personal pathway-level deregulation. We demonstrate that this approach, N-of-1-pathways Paired Samples MD (N-OF-1-PATHWAYS-MD), detects deregulated pathways (empirical simulations), while not inflating false-positive rate using a study with biological replicates. Finally, we establish that N-OF-1-PATHWAYS-MD scores are, biologically significant, clinically relevant and are predictive of breast cancer survival (P < 0.05, n = 80 invasive carcinoma; TCGA RNA-sequences). Conclusion: N-of-1-pathways MD provides a practical approach towards precision medicine. The method generates the magnitude and the biological significance of personal deregulated pathways results derived solely from the patient’s transcriptome. These pathways offer the opportunities for deriving clinically actionable decisions that have the potential to complement the clinical interpretability of personal polymorphisms obtained from DNA acquired or inherited polymorphisms and mutations. In addition, it offers an opportunity for applicability to diseases in which DNA changes may not be relevant, and thus expand the ‘interpretable ‘omics’ of single subjects (e.g. personalome). Availability and implementation: http://www.lussierlab.net/publications/N-of-1

  9. Tyrosinase-related protein 1 mRNA expression in lymph node metastases predicts overall survival in high-risk melanoma patients

    PubMed Central

    El Hajj, P; Journe, F; Wiedig, M; Laios, I; Salès, F; Galibert, M-D; Van Kempen, L C; Spatz, A; Badran, B; Larsimont, D; Awada, A; Ghanem, G

    2013-01-01

    Background: Clinical outcome of high-risk melanoma patients is not reliably predicted from histopathological analyses of primary tumours and is often adjusted during disease progression. Our study aimed at extending our previous findings in skin metastases to evaluate the prognostic value of tyrosinase-related protein 1 (TYRP1) in lymph node metastases of stages III and IV melanoma patients. Methods: TYRP1 mRNA expression in 104 lymph node metastases was quantified by real-time PCR and normalised to S100 calcium-binding protein B (S100B) mRNA expression to correct for tumour load. TYRP1/S100B ratios were calculated and median was used as cutoff value. TYRP1/S100B mRNA values were correlated to clinical follow-up and histopathological characteristics of the primary lesion. Results: A high TYRP1/S100B mRNA ratio significantly correlated with reduced disease-free (DFS) and overall survival (OS; Cox regression analysis, P=0.005 and 0.01, respectively), increased Breslow thickness (Spearman's rho test, P<0.001) and the presence of ulceration (Mann–Whitney test, P=0.02) of the primaries. Moreover, high TYRP1/S100B was of better prognostic value (lower P-value) for OS than Breslow thickness and ulceration. Finally, it was well conserved during disease progression with respect to high/low TYRP1 groups. Conclusion: High TYRP1/S100B mRNA expression in lymph node metastases from melanoma patients is associated with unfavourable clinical outcome. Its evaluation in lymph node metastases may refine initial prognosis for metastatic patients, may define prognosis for those with unknown or non-evaluable primary lesions and may allow different management of the two groups of patients. PMID:23519055

  10. Prostate-specific antigen nadir after high-dose-rate brachytherapy predicts long-term survival outcomes in high-risk prostate cancer

    PubMed Central

    Satoh, Takefumi; Ishiyama, Hiromichi; Tabata, Ken-ichi; Komori, Shouko; Sekiguchi, Akane; Ikeda, Masaomi; Kurosaka, Shinji; Fujita, Tetsuo; Kitano, Masashi; Hayakawa, Kazushige; Iwamura, Masatsugu

    2016-01-01

    Purpose To evaluate the prognostic value of prostate-specific antigen nadir (nPSA) after high-dose-rate (HDR) brachytherapy in clinically non-metastatic high-risk prostate cancer patients. Material and methods Data from 216 patients with high-risk or locally advanced prostate cancer who underwent HDR brachytherapy and external beam radiation therapy with long-term androgen deprivation therapy (ADT) between 2003 and 2008 were analyzed. The median prostate-specific antigen (PSA) level at diagnosis was 24 ng/ml (range: 3-338 ng/ml). The clinical stage was T1c-2a in 55 cases (26%), T2b-2c in 48 (22%), T3a in 75 (35%), and T3b-4 in 38 (17%). The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After 5 fractions, external beam radiation therapy with 10 fractions of 3 Gy was administered. All patients initially underwent neoadjuvant ADT for at least 6 months, and adjuvant ADT was continued for 36 months. The median follow-up was 7 years from the start of radiotherapy. Results The 7-year PSA relapse-free rate among patients with a post-radiotherapy nPSA level of ≤ 0.02 ng/ml was 94%, compared with 23% for patients with higher nPSA values (HR = 28.57; 95% CI: 12.04-66.66; p < 0.001). Multivariate analysis revealed that the nPSA value after radiotherapy was a significant independent predictor of biochemical failure, whereas pretreatment predictive values for worse biochemical control including higher level of initial PSA, Gleason score ≥ 8, positive biopsy core rate ≥ 67%, and T3b-T4, failed to reach independent predictor status. The 7-year cancer-specific survival rate among patients with a post-radiotherapy nPSA level of ≤ 0.02 ng/ml was 99%, compared with 82% for patients with higher nPSA values (HR = 32.25; 95% CI: 3.401-333.3; p = 0.002). Conclusions A post-radiotherapy nPSA value of ≤ 0.02 ng/ml was associated with better long-term biochemical tumor control even if patients had pretreatment predictive values for worse

  11. Distinguishing Low-Risk Luminal A Breast Cancer Subtypes with Ki-67 and p53 Is More Predictive of Long-Term Survival.

    PubMed

    Lee, Se Kyung; Bae, Soo Youn; Lee, Jun Ho; Lee, Hyun-Chul; Yi, Hawoo; Kil, Won Ho; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin

    2015-01-01

    Overexpression of p53 is the most frequent genetic alteration in breast cancer. Recently, many studies have shown that the expression of mutant p53 differs for each subtype of breast cancer and is associated with different prognoses. In this study, we aimed to determine the suitable cut-off value to predict the clinical outcome of p53 overexpression and its usefulness as a prognostic factor in each subtype of breast cancer, especially in luminal A breast cancer. Approval was granted by the Institutional Review Board of Samsung Medical Center. We analyzed a total of 7,739 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between Dec 1995 and Apr 2013. Luminal A subtype was defined as ER&PR + and HER2- and was further subclassified according to Ki-67 and p53 expression as follows: luminal A (Ki-67-,p53-), luminal A (Ki-67+, p53-), luminal A (Ki-67 -, p53+) and luminal A (Ki-67+, p53+). Low-risk luminal A subtype was defined as negative for both Ki-67 and p53 (luminal A [ki-67-, p53-]), and others subtypes were considered to be high-risk luminal A breast cancer. A cut-off value of 10% for p53 was a good predictor of clinical outcome in all patients and luminal A breast cancer patients. The prognostic role of p53 overexpression for OS and DFS was only significant in luminal A subtype. The combination of p53 and Ki-67 has been shown to have the best predictive power as calculated by the area under curve (AUC), especially for long-term overall survival. In this study, we have shown that overexpression of p53 and Ki-67 could be used to discriminate low-risk luminal A subtype in breast cancer. Therefore, using the combination of p53 and Ki-67 expression in discriminating low-risk luminal A breast cancer may improve the prognostic power and provide the greatest clinical utility.

  12. Anatomic Variant of Liver, Gall Bladder and Inferior Vena Cava.

    PubMed

    Sontakke, Yogesh Ashok; Gladwin, V; Chand, Parkash

    2016-07-01

    The morphology and relations of liver, gall bladder and inferior vena cava are cardinal. Their anatomical variations may be a reason for the adverse surgical outcome. During routine anatomy dissection of an abdomen, we noticed a variant liver, gall bladder and inferior vena cava in a 63-year-old male cadaver. In the specimen, a retrohepatic segment of inferior vena cava was found to be intrahepatic. On dissection, it was observed that inferior vena cava was covered entirely by a liver tissue on its dorsal aspect. In the same specimen, the gall bladder had undulated inferior surface. On dissection of the gall bladder, numerous mucosal folds were present in the interior. A band of fibrous tissue was found, which was extending from the right side of the gall bladder to the falciform ligament. Hence, preoperative scanning of congenital variations of the liver, gall bladder and inferior vena cava may be compassionate in planning safe surgeries and interventional abdominal procedures. PMID:27630832

  13. Anatomic Variant of Liver, Gall Bladder and Inferior Vena Cava

    PubMed Central

    Gladwin, V.; Chand, Parkash

    2016-01-01

    The morphology and relations of liver, gall bladder and inferior vena cava are cardinal. Their anatomical variations may be a reason for the adverse surgical outcome. During routine anatomy dissection of an abdomen, we noticed a variant liver, gall bladder and inferior vena cava in a 63-year-old male cadaver. In the specimen, a retrohepatic segment of inferior vena cava was found to be intrahepatic. On dissection, it was observed that inferior vena cava was covered entirely by a liver tissue on its dorsal aspect. In the same specimen, the gall bladder had undulated inferior surface. On dissection of the gall bladder, numerous mucosal folds were present in the interior. A band of fibrous tissue was found, which was extending from the right side of the gall bladder to the falciform ligament. Hence, preoperative scanning of congenital variations of the liver, gall bladder and inferior vena cava may be compassionate in planning safe surgeries and interventional abdominal procedures. PMID:27630832

  14. Total laparoscopic retrieval of inferior vena cava filter

    PubMed Central

    Benrashid, Ehsan; Adkar, Shaunak Sanjay; Bennett, Kyla Megan; Zani, Sabino

    2015-01-01

    While there is some local variability in the use of inferior vena cava filters and there has been some evolution in the indications for filter placement over time, inferior vena cava filters remain a standard option for pulmonary embolism prophylaxis. Indications are clear in certain subpopulations of patients, particularly those with deep venous thrombosis and absolute contraindications to anticoagulation. There are, however, a variety of reported inferior vena cava filter complications in the short and long term, making retrieval of the filter desirable in most cases. Here, we present the case of a morbidly obese patient complaining of chronic abdominal pain after inferior vena cava filter placement and malposition of the filter with extensive protrusion outside the inferior vena cava. She underwent successful laparoscopic retrieval of her malpositioned inferior vena cava filters after failure of a conventional endovascular approach. PMID:27489697

  15. Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

    SciTech Connect

    Wiegel, Thomas; Bartkowiak, Detlef; Bottke, Dirk; Thamm, Reinhard; Hinke, Axel; Stöckle, Michael; Wirth, Manfred; Störkel, Stephan; Golz, Reinhard; Engenhart-Cabillic, Rita; Hofmann, Rainer; Feldmann, Horst-Jürgen; Kälble, Tilman; Siegmann, Alessandra; Hinkelbein, Wolfgang; Steiner, Ursula; Miller, Kurt

    2015-02-01

    Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups

  16. Non-inferiority and networks: inferring efficacy from a web of data.

    PubMed

    Lin, Junjing; Gamalo-Siebers, Margaret; Tiwari, Ram

    2016-01-01

    In the absence of placebo-controlled trials, the efficacy of a test treatment can be alternatively examined by showing its non-inferiority to an active control; that is, the test treatment is not worse than the active control by a pre-specified margin. The margin is based on the effect of the active control over placebo in historical studies. In other words, the non-inferiority setup involves a network of direct and indirect comparisons between test treatment, active controls, and placebo. Given this framework, we consider a Bayesian network meta-analysis that models the uncertainty and heterogeneity of the historical trials into the non-inferiority trial in a data-driven manner through the use of the Dirichlet process and power priors. Depending on whether placebo was present in the historical trials, two cases of non-inferiority testing are discussed that are analogs of the synthesis and fixed-margin approach. In each of these cases, the model provides a more reliable estimate of the control given its effect in other trials in the network, and, in the case where placebo was only present in the historical trials, the model can predict the effect of the test treatment over placebo as if placebo had been present in the non-inferiority trial. It can further answer other questions of interest, such as comparative effectiveness of the test treatment among its comparators. More importantly, the model provides an opportunity for disproportionate randomization or the use of small sample sizes by allowing borrowing of information from a network of trials to draw explicit conclusions on non-inferiority.

  17. Non-inferiority and networks: inferring efficacy from a web of data.

    PubMed

    Lin, Junjing; Gamalo-Siebers, Margaret; Tiwari, Ram

    2016-01-01

    In the absence of placebo-controlled trials, the efficacy of a test treatment can be alternatively examined by showing its non-inferiority to an active control; that is, the test treatment is not worse than the active control by a pre-specified margin. The margin is based on the effect of the active control over placebo in historical studies. In other words, the non-inferiority setup involves a network of direct and indirect comparisons between test treatment, active controls, and placebo. Given this framework, we consider a Bayesian network meta-analysis that models the uncertainty and heterogeneity of the historical trials into the non-inferiority trial in a data-driven manner through the use of the Dirichlet process and power priors. Depending on whether placebo was present in the historical trials, two cases of non-inferiority testing are discussed that are analogs of the synthesis and fixed-margin approach. In each of these cases, the model provides a more reliable estimate of the control given its effect in other trials in the network, and, in the case where placebo was only present in the historical trials, the model can predict the effect of the test treatment over placebo as if placebo had been present in the non-inferiority trial. It can further answer other questions of interest, such as comparative effectiveness of the test treatment among its comparators. More importantly, the model provides an opportunity for disproportionate randomization or the use of small sample sizes by allowing borrowing of information from a network of trials to draw explicit conclusions on non-inferiority. PMID:26639225

  18. Inferiorly based thigh flap for reconstruction of defects around the knee joint

    PubMed Central

    Akhtar, Md. Sohaib; Khan, Arshad Hafeez; Khurram, Mohammed Fahud; Ahmad, Imran

    2014-01-01

    Background: Soft-tissue defects around the knees are common in injured limbs and in the same injury the leg is often involved and the thigh is spared. Furthermore due to pliable and relatively lax skin, we have used inferiorly based thigh flap to reconstruct defects around knee joint. Aims and Objectives: The aim of this study is to evaluate the use of inferiorly based thigh flap to cover soft-tissue defects over the proximal one-third of the leg, patellar region, knee, and lower thigh. Materials and Methods: This study was conducted during the period between October 2011 and February 2013. Inferiorly based anteromedial thigh fasciocutaneous flap was performed on 12 patients and inferiorly based anterolateral thigh fasciocutaneous flap on four patients. The sites of the soft-tissue defects included patellar regions, infrapatellar region, upper one-third of leg, lower thigh, and over the knee joint. Results: Patients were evaluated post-operatively in terms of viability of flap, the matching of the flap with the recipient site, and donor site morbidity. All the flaps survived well except one which developed distal marginal flap loss, one in which wound dehiscence was noticed, and two in which mild venous congestion was observed. Venous congestion in two patients subsided on its own within 3 days. One patient with wound dehiscence achieved complete healing by secondary intention. Patient who developed distal flap loss required debridement and skin grafting. No appreciable donor site morbidity was encountered. Skin colour and texture of the flap matched well with the recipient site. Conclusions: The inferiorly based thigh flap is a reliable flap to cover the defect over proximal one-third of the leg, patellar region, knee, and lower thigh. PMID:25190918

  19. Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma.

    PubMed

    Inagaki, Atsushi; Tajima, Emi; Uranishi, Miyuki; Totani, Haruhito; Asao, Yu; Ogura, Hiroka; Masaki, Ayako; Yoshida, Tatsuya; Mori, Fumiko; Ito, Asahi; Yano, Hiroki; Ri, Masaki; Kayukawa, Satoshi; Kataoka, Takae; Kusumoto, Shigeru; Ishida, Takashi; Hayami, Yoshihito; Hanamura, Ichiro; Komatsu, Hirokazu; Inagaki, Hiroshi; Matsuda, Yasufumi; Ueda, Ryuzo; Iida, Shinsuke

    2013-12-01

    CCND1, FGFR3 and c-MAF mRNA expression of tumor samples from 123 multiple myeloma patients were analyzed by global RQ/RT-PCR. CCND1, FGFR3 and c-MAF were positive in 44 (36%), 28 (23%) and 16 (13%) of patients, respectively. In 7 patients, both FGFR3 and c-MAF were positive. The expression of c-MAF was independent unfavorable prognostic factors for overall survival (OS). Autologous stem cell transplantation improved progression-free survival of CCND1-positive patients. Bortezomib, thalidomide or lenalidomide extended OS of FGFR3 and/or c-MAF-positive patients. Thus, CCND1, FGFR3 and c-MAF mRNA expression can predict survival and is useful for planning stratified treatment strategies for myeloma patients.

  20. Encoding of Stimulus Probability in Macaque Inferior Temporal Cortex.

    PubMed

    Bell, Andrew H; Summerfield, Christopher; Morin, Elyse L; Malecek, Nicholas J; Ungerleider, Leslie G

    2016-09-12

    Optimal perceptual decisions require sensory signals to be combined with prior information about stimulus probability. Although several theories propose that probabilistic information about stimulus occurrence is encoded in sensory cortex, evidence from neuronal recordings has not yet fully supported this view. We recorded activity from single neurons in inferior temporal cortex (IT) while monkeys performed a task that involved discriminating degraded images of faces and fruit. The relative probability of the cue being a face versus a fruit was manipulated by a latent variable that was not revealed to the monkeys and that changed unpredictably over the course of each recording session. In addition to responding to stimulus identity (face or fruit), population responses in IT encoded the long-term stimulus probability of whether a face or a fruit stimulus was more likely to occur. Face-responsive neurons showed reduced firing rates to expected faces, an effect consistent with "expectation suppression," but expected stimuli were decoded from multivariate population signals with greater accuracy. These findings support "predictive coding" theories, whereby neural signals in the mammalian visual system actively encode and update predictions about the local sensory environment.

  1. Lagged cells in the inferior colliculus of the awake ferret

    PubMed Central

    Shechter, Barak; Marvit, Peter; Depireux, Didier A

    2010-01-01

    Neurons in primary auditory cortex (AI) encode complex features of the spectral content of sound, such as direction selectivity. Recent findings of temporal symmetry in AI predict a specific organization of the subcortical input into cortex that contributes to the emergence of direction selectivity. We demonstrate two sub-populations of neurons in the central nucleus of the inferior colliculus, which differ in their steady-state temporal response profile: lagged and non-lagged. The lagged cells (23%) are shifted in temporal phase with respect to non-lagged cells and are characterized by an “inhibition first” and delayed excitation in their spectro-temporal receptive fields. Non-lagged cells (77%) have a canonical “excitation first” response. However, we find no difference in the response onset latency to pure tone stimuli between the two sub-populations. Given the homogeneity of tonal response latency, we predict that these lagged cells receive inhibitory input mediated by cortical feedback projections. PMID:20092554

  2. Prediction of Long-Term Survival in Patients with End-Stage Heart Failure Secondary to Ischemic Heart Disease: Surgical Correction and Volumetric Analysis

    PubMed Central

    Yoshida, Minoru; Hoshino, Joji; Kondo, Taichi; Isomura, Tadashi

    2015-01-01

    Purpose: Ischemic heart disease (IHD) may result in lethal conditions such as ischemic cardiomyopathy (ICM) and mitral regurgitation (MR). Methods: We hypothesized preoperative LV volume would be highly associated with long-term survival in such patients. We retrospectively evaluated effects of LV end-systolic volume index (LVESVI) on survival. Results: Patients were divided into two groups according to LVESVI; Group S (n = 19, <100 ml/m2), and L (n = 55, >100 ml/m2). There were 74 patients (male 61, female 13; 61 ± 10 y.o.). There was no statistical significance in preoperative parameters, including ejection fraction (EF), severity of MR, severity of tricuspid regurgitation (TR), and right ventricular systolic pressure (RVSP). After operation, LVESVI and severity of MR were statistically reduced in both groups. However, EF, severity of TR and RVSP were not statistically alleviated in both groups. In Group S, 5- and 10-year survival rates were 93% and 48%. In Group L, 5- and 10-year survival rates were 50% and 29%. There was a statistical difference in long-term survival between two groups. Conclusions: Preoperative LV volume would be one of the risk factors for long-term survival in patients with congestive heart failure secondary to IHD. Careful follow-up and optimal treatment should be recommended before LV dimension becomes too large. PMID:26073141

  3. Loss of expression of MHC class I-related chain A (MICA) is a frequent event and predicts poor survival in patients with hepatocellular carcinoma.

    PubMed

    Zhang, Jie; Xu, Zhuding; Zhou, Xingchun; Zhang, Haibin; Yang, Ning; Wu, Yousheng; Chen, Yibing; Yang, Guangshun; Ren, Tingting

    2014-01-01

    Natural killer (NK) cells are important effector cells for the first line of defense against tumor. Distant MHC class I homolog MICA has been identified as human ligand for NK cell activating receptor NKG2D. Engagement of MICA triggers NK cells and augments antigen-specific CTL anti-tumor immunity. However, the expression level of MICA and its clinical significance in hepatocellular carcinoma remains to be elucidated. In the present study, a hospital-based study cohort of 143 HCC patients was involved. MICA expression levels were determined by immunohistochemical staining. The association of MICA expression with tumor clinicopathologic features, disease-free survival, and overall survival of HCC patients were analyzed. Significantly decreased expression of MICA was detected in tumor specimens. MICA expression was significantly associated with AFP level (P < 0.001) and tumor node metastasis stage (P = 0.003). Patients with reduced level of MICA had a statistically significantly shorter disease-free survival and overall survival duration than patients with preserved expression of MICA. However, in multivariate analysis, MICA expression level was found not to be an independent prognostic factor for both disease-free survival and overall survival of HCC patients. Our findings suggest that decreased MICA expression may play an important role in HCC tumor evasion of host immunity, which warrants further investigation in future studies.

  4. Inferior fronto-temporo-occipital connectivity: a missing link between maltreated girls and neglectful mothers

    PubMed Central

    León, Inmaculada; Góngora, Daylin; Hernández-Cabrera, Juan A.; Byrne, Sonia; Bobes, María A.

    2016-01-01

    The neurobiological alterations resulting from adverse childhood experiences that subsequently may lead to neglectful mothering are poorly understood. Maternal neglect of an infant’s basic needs is the most prevalent type of child maltreatment. We tested white matter alterations in neglectful mothers, the majority of whom had also suffered maltreatment in their childhood, and compared them to a matched control group. The two groups were discriminated by a structural brain connectivity pattern comprising inferior fronto-temporo-occipital connectivity, which constitutes a major portion of the face-processing network and was indexed by fewer streamlines in neglectful mothers. Mediation and regression analyses showed that fewer streamlines in the right inferior longitudinal fasciculus tract (ILF-R) predicted a poorer quality of mother–child emotional availability observed during cooperative play and that effect depended on the respective interactions with left and right inferior fronto-occipital fasciculi (IFO-R/L), with no significant impact of psychopathological and cognitive conditions. Volume alteration in ILF-R but not in IFO-L modulated the impact of having been maltreated on emotional availability. The findings suggest the altered inferior fronto-temporal-occipital connectivity, affecting emotional visual processing, as a possible common neurological substrate linking a history of childhood maltreatment with maternal neglect. PMID:27342834

  5. Inferior fronto-temporo-occipital connectivity: a missing link between maltreated girls and neglectful mothers.

    PubMed

    Rodrigo, María José; León, Inmaculada; Góngora, Daylin; Hernández-Cabrera, Juan A; Byrne, Sonia; Bobes, María A

    2016-10-01

    The neurobiological alterations resulting from adverse childhood experiences that subsequently may lead to neglectful mothering are poorly understood. Maternal neglect of an infant's basic needs is the most prevalent type of child maltreatment. We tested white matter alterations in neglectful mothers, the majority of whom had also suffered maltreatment in their childhood, and compared them to a matched control group. The two groups were discriminated by a structural brain connectivity pattern comprising inferior fronto-temporo-occipital connectivity, which constitutes a major portion of the face-processing network and was indexed by fewer streamlines in neglectful mothers. Mediation and regression analyses showed that fewer streamlines in the right inferior longitudinal fasciculus tract (ILF-R) predicted a poorer quality of mother-child emotional availability observed during cooperative play and that effect depended on the respective interactions with left and right inferior fronto-occipital fasciculi (IFO-R/L), with no significant impact of psychopathological and cognitive conditions. Volume alteration in ILF-R but not in IFO-L modulated the impact of having been maltreated on emotional availability. The findings suggest the altered inferior fronto-temporal-occipital connectivity, affecting emotional visual processing, as a possible common neurological substrate linking a history of childhood maltreatment with maternal neglect. PMID:27342834

  6. Inferior fronto-temporo-occipital connectivity: a missing link between maltreated girls and neglectful mothers.

    PubMed

    Rodrigo, María José; León, Inmaculada; Góngora, Daylin; Hernández-Cabrera, Juan A; Byrne, Sonia; Bobes, María A

    2016-10-01

    The neurobiological alterations resulting from adverse childhood experiences that subsequently may lead to neglectful mothering are poorly understood. Maternal neglect of an infant's basic needs is the most prevalent type of child maltreatment. We tested white matter alterations in neglectful mothers, the majority of whom had also suffered maltreatment in their childhood, and compared them to a matched control group. The two groups were discriminated by a structural brain connectivity pattern comprising inferior fronto-temporo-occipital connectivity, which constitutes a major portion of the face-processing network and was indexed by fewer streamlines in neglectful mothers. Mediation and regression analyses showed that fewer streamlines in the right inferior longitudinal fasciculus tract (ILF-R) predicted a poorer quality of mother-child emotional availability observed during cooperative play and that effect depended on the respective interactions with left and right inferior fronto-occipital fasciculi (IFO-R/L), with no significant impact of psychopathological and cognitive conditions. Volume alteration in ILF-R but not in IFO-L modulated the impact of having been maltreated on emotional availability. The findings suggest the altered inferior fronto-temporal-occipital connectivity, affecting emotional visual processing, as a possible common neurological substrate linking a history of childhood maltreatment with maternal neglect.