Will male advertisement be a reliable indicator of paternal care, if offspring survival depends on male care?

PubMed

Kelly, Natasha B; Alonzo, Suzanne H

2009-09-07

Existing theory predicts that male signalling can be an unreliable indicator of paternal care, but assumes that males with high levels of mating success can have high current reproductive success, without providing any parental care. As a result, this theory does not hold for the many species where offspring survival depends on male parental care. We modelled male allocation of resources between advertisement and care for species with male care where males vary in quality, and the effect of care and advertisement on male fitness is multiplicative rather than additive. Our model predicts that males will allocate proportionally more of their resources to whichever trait (advertisement or paternal care) is more fitness limiting. In contrast to previous theory, we find that male advertisement is always a reliable indicator of paternal care and male phenotypic quality (e.g. males with higher levels of advertisement never allocate less to care than males with lower levels of advertisement). Our model shows that the predicted pattern of male allocation and the reliability of male signalling depend very strongly on whether paternal care is assumed to be necessary for offspring survival and how male care affects offspring survival and male fitness.

Spinal cord multi-parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis.

PubMed

Querin, G; El Mendili, M M; Lenglet, T; Delphine, S; Marchand-Pauvert, V; Benali, H; Pradat, P-F

2017-08-01

Assessing survival is a critical issue in patients with amyotrophic lateral sclerosis (ALS). Neuroimaging seems to be promising in the assessment of disease severity and several studies also suggest a strong relationship between spinal cord (SC) atrophy described by magnetic resonance imaging (MRI) and disease progression. The aim of the study was to determine the predictive added value of multimodal SC MRI on survival. Forty-nine ALS patients were recruited and clinical data were collected. Patients were scored on the Revised ALS Functional Rating Scale and manual muscle testing. They were followed longitudinally to assess survival. The cervical SC was imaged using the 3 T MRI system. Cord volume and cross-sectional area (CSA) at each vertebral level were computed. Diffusion tensor imaging metrics were measured. Imaging metrics and clinical variables were used as inputs for a multivariate Cox regression survival model. On building a multivariate Cox regression model with clinical and MRI parameters, fractional anisotropy, magnetization transfer ratio and CSA at C2-C3, C4-C5, C5-C6 and C6-C7 vertebral levels were significant. Moreover, the hazard ratio calculated for CSA at the C3-C4 and C5-C6 levels indicated an increased risk for patients with SC atrophy (respectively 0.66 and 0.68). In our cohort, MRI parameters seem to be more predictive than clinical variables, which had a hazard ratio very close to 1. It is suggested that multimodal SC MRI could be a useful tool in survival prediction especially if used at the beginning of the disease and when combined with clinical variables. To validate it as a biomarker, confirmation of the results in bigger independent cohorts of patients is warranted. © 2017 EAN.

The EPOS-CC Score: An Integration of Independent, Tumor- and Patient-Associated Risk Factors to Predict 5-years Overall Survival Following Colorectal Cancer Surgery.

PubMed

Haga, Yoshio; Ikejiri, Koji; Wada, Yasuo; Ikenaga, Masakazu; Koike, Shoichiro; Nakamura, Seiji; Koseki, Masato

2015-06-01

Surgical audit is an essential task for the estimation of postoperative outcome and comparison of quality of care. Previous studies on surgical audits focused on short-term outcomes, such as postoperative mortality. We propose a surgical audit evaluating long-term outcome following colorectal cancer surgery. The predictive model for this audit is designated as 'Estimation of Postoperative Overall Survival for Colorectal Cancer (EPOS-CC)'. Thirty-one tumor-related and physiological variables were prospectively collected in 889 patients undergoing elective resection for colorectal cancer between April 2005 and April 2007 in 16 Japanese hospitals. Postoperative overall survival was assessed over a 5-years period. The EPOS-CC score was established by selecting significant variables in a uni- and multivariate analysis and allocating a risk-adjusted multiplication factor to each variable using Cox regression analysis. For validation, the EPOS-CC score was compared to the predictive power of UICC stage. Inter-hospital variability of the observed-to-estimated 5-years survival was assessed to estimate quality of care. Among the 889 patients, 804 (90%) completed the 5-years follow-up. Univariate analysis displayed a significant correlation with 5-years survival for 14 physiological and nine tumor-related variables (p < 0.005). Highly significant p-values below 0.0001 were found for age, ASA score, severe pulmonary disease, respiratory history, performance status, hypoalbuminemia, alteration of hemoglobin, serum sodium level, and for all histological variables except tumor location. Age, TNM stage, lymphatic invasion, performance status, and serum sodium level were independent variables in the multivariate analysis and were entered the EPOS-CC model for the prediction of survival. Risk-adjusted multiplication factors between 1.5 (distant metastasis) and 0.16 (serum sodium level) were accorded to the different variables. The predictive power of EPOS-CC was superior to the one of UICC stage; area under the curve 0.87, 95% CI 0.85-0.90 for EPOS-CC, and 0.80, 0.76-0.83 for UICC stage, p < 0.001. Quality of care did not differ between hospitals. The EPOS-CC score including the independent variables age, performance status, serum sodium level, TNM stage, and lymphatic invasion is superior to the UICC stage in the prediction of 5-years overall survival. This higher accuracy might be explained by the inclusion of physiological factors, thus also taking non-tumor-associated deaths into account. Furthermore, EPOS-CC score may compare quality of care among different institutions. Future studies are necessary to further evaluate this score and help improving the prediction of long-term survival following colorectal cancer surgery.

Adjustments of individual-tree survival and diameter-growth equations to match whole-stand attributes

Treesearch

Quang V. Cao

2010-01-01

Individual-tree models are flexible and can perform well in predicting tree survival and diameter growth for a certain growing period. However, the resulting stand-level outputs often suffer from accumulation of errors and subsequently cannot compete with predictions from whole-stand models, especially when the projection period lengthens. Evaluated in this study were...

Integrated Cox's model for predicting survival time of glioblastoma multiforme.

PubMed

Ai, Zhibing; Li, Longti; Fu, Rui; Lu, Jing-Min; He, Jing-Dong; Li, Sen

2017-04-01

Glioblastoma multiforme is the most common primary brain tumor and is highly lethal. This study aims to figure out signatures for predicting the survival time of patients with glioblastoma multiforme. Clinical information, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism array data of patients with glioblastoma multiforme were retrieved from The Cancer Genome Atlas. Patients were separated into two groups by using 1 year as a cutoff, and a logistic regression model was used to figure out any variables that can predict whether the patient was able to live longer than 1 year. Furthermore, Cox's model was used to find out features that were correlated with the survival time. Finally, a Cox model integrated the significant clinical variables, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism was built. Although the classification method failed, signatures of clinical features, messenger RNA expression levels, and microRNA expression levels were figured out by using Cox's model. However, no single-nucleotide polymorphisms related to prognosis were found. The selected clinical features were age at initial diagnosis, Karnofsky score, and race, all of which had been suggested to correlate with survival time. Both of the two significant microRNAs, microRNA-221 and microRNA-222, were targeted to p27 Kip1 protein, which implied the important role of p27 Kip1 on the prognosis of glioblastoma multiforme patients. Our results suggested that survival modeling was more suitable than classification to figure out prognostic biomarkers for patients with glioblastoma multiforme. An integrated model containing clinical features, messenger RNA levels, and microRNA expression levels was built, which has the potential to be used in clinics and thus to improve the survival status of glioblastoma multiforme patients.

Serum biomarkers of bone metabolism in castration-resistant prostate cancer patients with skeletal metastases: results from SWOG 0421.

PubMed

Lara, Primo N; Ely, Benjamin; Quinn, David I; Mack, Philip C; Tangen, Catherine; Gertz, Erik; Twardowski, Przemyslaw W; Goldkorn, Amir; Hussain, Maha; Vogelzang, Nicholas J; Thompson, Ian M; Van Loan, Marta D

2014-04-01

Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration-resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value of bone biomarkers in sera from CRPC patients treated on a placebo-controlled phase III trial of docetaxel with or without the bone targeted endothelin-A receptor antagonist atrasentan (SWOG S0421). Markers for bone resorption (N-telopeptide and pyridinoline) and formation (C-terminal collagen propeptide and bone alkaline phosphatase) were assayed in pretreatment and serial sera. Cox proportional hazards regression models were fit for overall survival. Models were fit with main effects for marker levels and with/without terms for marker-treatment interaction, adjusted for clinical variables, to assess the prognostic and predictive value of atrasentan. Analysis was adjusted for multiple comparisons. Two-sided P values were calculated using the Wald test. Sera from 778 patients were analyzed. Elevated baseline levels of each of the markers were associated with worse survival (P < .001). Increasing marker levels by week nine of therapy were also associated with subsequent poor survival (P < .001). Patients with the highest marker levels (upper 25th percentile for all markers) not only had a poor prognosis (hazard ratio [HR] = 4.3; 95% confidence interval [CI] = 2.41 to 7.65; P < .001) but also had a survival benefit from atrasentan (HR = 0.33; 95% CI = 0.15 to 0.71; median survival = 13 [atrasentan] vs 5 months [placebo]; P interaction = .005). Serum bone metabolism markers have statistically significant independent prognostic value in CRPC. Importantly, a small group of patients (6%) with highly elevated markers of bone turnover appear to preferentially benefit from atrasentan therapy.

MMP-7, sFas and FasL serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer.

PubMed

Szarvas, Tibor; Sevcenco, Sabina; Módos, Orsolya; Keresztes, Dávid; Nyirády, Péter; Csizmarik, Anita; Ristl, Robin; Puhr, Martin; Hoffmann, Michèle J; Niedworok, Christian; Hadaschik, Boris; Maj-Hes, Agnieszka; Shariat, Shahrokh F; Kramer, Gero

2018-05-26

To assess the predictive value of pre-chemotherapy MMP-7, sFas, FasL serum levels as well as their changes during therapy. Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 CRPC patients; 21 docetaxel-resistant who received one single series and 75 docetaxel-sensitive who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. Higher pretreatment serum MMP-7, sFas and PSA levels were significantly associated with both docetaxel-resistance (p=0.007, p=0.001, p<0.001, respectively) and shorter cancer-specific survival (p<0.001, p=0.041, p<0.001, respectively). High MMP-7 remained an independent predictor of both docetaxel resistance (HR: 2.298, 95% CI: 1.354-3.899, p=0.002) and poor cancer-specific survival (HR=2.11, 95%Cl 1.36-3.30, p=0.001) in multivariable analyses. Higher increase of MMP-7 levels in the 2 nd treatment holiday and higher increase of PSA levels in the 1 st and 2 nd holidays were predictive of survival. Pretreatment serum MMP-7 levels may help to select CRPC patients who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 alone or in combination with PSA could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

PubMed Central

Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

2018-01-01

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

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

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

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

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

Classification Models to Predict Survival of Kidney Transplant Recipients Using Two Intelligent Techniques of Data Mining and Logistic Regression.

PubMed

Nematollahi, M; Akbari, R; Nikeghbalian, S; Salehnasab, C

2017-01-01

Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). Prediction of the transplant survival is of paramount importance. The objective of this study was to develop a model for predicting survival in kidney transplant recipients. In a cross-sectional study, 717 patients with ESRD admitted to Nemazee Hospital during 2008-2012 for renal transplantation were studied and the transplant survival was predicted for 5 years. The multilayer perceptron of artificial neural networks (MLP-ANN), logistic regression (LR), Support Vector Machine (SVM), and evaluation tools were used to verify the determinant models of the predictions and determine the independent predictors. The accuracy, area under curve (AUC), sensitivity, and specificity of SVM, MLP-ANN, and LR models were 90.4%, 86.5%, 98.2%, and 49.6%; 85.9%, 76.9%, 97.3%, and 26.1%; and 84.7%, 77.4%, 97.5%, and 17.4%, respectively. Meanwhile, the independent predictors were discharge time creatinine level, recipient age, donor age, donor blood group, cause of ESRD, recipient hypertension after transplantation, and duration of dialysis before transplantation. SVM and MLP-ANN models could efficiently be used for determining survival prediction in kidney transplant recipients.

Early post-transplant immune monitoring can predict long-term kidney graft survival: soluble CD30 levels, anti-HLA antibodies and IgA-anti-Fab autoantibodies.

PubMed

Amirzargar, Mohammad Ali; Amirzargar, Aliakbar; Basiri, Abbas; Hajilooi, Mehrdad; Roshanaei, Ghodratollah; Rajabi, Gholamreza; Mohammadiazar, Sina; Solgi, Ghasem

2014-01-01

This study aimed to investigate the predictive power of anti-HLA antibodies, sCD30 levels and IgA-anti-Fab autoantibody before and early after transplantation in relation to long-term kidney allograft survival. Pre- and post-transplant sera samples of 59 living-unrelated donor kidney recipients were tested for above risk factors by enzyme-linked immunoabsorbent assay. 15 out of 59 cases experienced rejection episodes (failure group). Pre- and post-transplant high sCD30 levels were significantly associated with graft failure (P=0.02 and P=0.004) and decreased 4 year graft survival (P = 0.009 and P = 0.001). Higher frequency of post-transplant HLA class-II antibody in the absence of class-I antibody was observed in failure group (P=0.007). Patients with post-transplant HLA class-I and class-II antibodies either alone or in combination showed significant lower 4 year graft survival. Recipients with high sCD30 levels in the presence of HLA class-I or class-II antibodies within 2 weeks post-transplant had poor graft survival (P = 0.004 and P = 0.002, respectively). High levels of post-transplant IgA-anti-Fab antibody was more frequent in functioning-graft patients (P = 0.00001), correlated with decreased serum creatinine levels (P = 0.01) and associated with improved graft survival (P = 0.008). Our findings indicate the deleterious effect of early post-transplant HLA antibodies and increased sCD30 levels dependently and protective effect of IgA-anti-Fab antibodies on long-term renal graft outcomes. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Development and validation of a prognostic nomogram for terminally ill cancer patients.

PubMed

Feliu, Jaime; Jiménez-Gordo, Ana María; Madero, Rosario; Rodríguez-Aizcorbe, José Ramón; Espinosa, Enrique; Castro, Javier; Acedo, Jesús Domingo; Martínez, Beatriz; Alonso-Babarro, Alberto; Molina, Raquel; Cámara, Juan Carlos; García-Paredes, María Luisa; González-Barón, Manuel

2011-11-02

Determining life expectancy in terminally ill cancer patients is a difficult task. We aimed to develop and validate a nomogram to predict the length of survival in patients with terminal disease. From February 1, 2003, to December 31, 2005, 406 consecutive terminally ill patients were entered into the study. We analyzed 38 features prognostic of life expectancy among terminally ill patients by multivariable Cox regression and identified the most accurate and parsimonious model by backward variable elimination according to the Akaike information criterion. Five clinical and laboratory variables were built into a nomogram to estimate the probability of patient survival at 15, 30, and 60 days. We validated and calibrated the nomogram with an external validation cohort of 474 patients who were treated from June 1, 2006, through December 31, 2007. The median overall survival was 29.1 days for the training set and 18.3 days for the validation set. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, lymphocyte levels, albumin levels, and time from initial diagnosis to diagnosis of terminal disease were retained in the multivariable Cox proportional hazards model as independent prognostic factors of survival and formed the basis of the nomogram. The nomogram had high predictive performance, with a bootstrapped corrected concordance index of 0.70, and it showed good calibration. External independent validation revealed 68% predictive accuracy. We developed a highly accurate tool that uses basic clinical and analytical information to predict the probability of survival at 15, 30, and 60 days in terminally ill cancer patients. This tool can help physicians making decisions on clinical care at the end of life.

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)

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

Lee, Hyun Jin; Han, Seungbong; Kim, Young Seok, E-mail: ysk@amc.seoul.kr

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 andmore » 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.« less

Predicting survival times for neuroblastoma patients using RNA-seq expression profiles.

PubMed

Grimes, Tyler; Walker, Alejandro R; Datta, Susmita; Datta, Somnath

2018-05-30

Neuroblastoma is the most common tumor of early childhood and is notorious for its high variability in clinical presentation. Accurate prognosis has remained a challenge for many patients. In this study, expression profiles from RNA-sequencing are used to predict survival times directly. Several models are investigated using various annotation levels of expression profiles (genes, transcripts, and introns), and an ensemble predictor is proposed as a heuristic for combining these different profiles. The use of RNA-seq data is shown to improve accuracy in comparison to using clinical data alone for predicting overall survival times. Furthermore, clinically high-risk patients can be subclassified based on their predicted overall survival times. In this effort, the best performing model was the elastic net using both transcripts and introns together. This model separated patients into two groups with 2-year overall survival rates of 0.40±0.11 (n=22) versus 0.80±0.05 (n=68). The ensemble approach gave similar results, with groups 0.42±0.10 (n=25) versus 0.82±0.05 (n=65). This suggests that the ensemble is able to effectively combine the individual RNA-seq datasets. Using predicted survival times based on RNA-seq data can provide improved prognosis by subclassifying clinically high-risk neuroblastoma patients. This article was reviewed by Subharup Guha and Isabel Nepomuceno.

Decreased expression of FOXF2 as new predictor of poor prognosis in stage I non-small cell lung cancer.

PubMed

Kong, Peng-Zhou; Li, Guang-Ming; Tian, Yin; Song, Bin; Shi, RuYi

2016-08-23

Forkhead box F2 (FOXF2) is relatively limited to the adult lung, but its contribution to non-small cell lung cancer (NSCLC) prognosis is unclear. FOXF2 mRNA levels in NSCLC were lower than that in paired normal lung tissues (P = 0.012). The FOXF2low patients had shorter survival time than the FOXF2high patients (P = 0.024) especially in stage I (P = 0.002), chemotherapy (P = 0.018) and < 60 age groups (P = 0.002). Lower FOXF2 mRNA levels could independently predict poorer survival for patients with NSCLC (HR = 2.384, 95% CI = 1.241-4.577; P = 0.009), especially in stage I (HR =4.367, 95% CI =1.599-11.925; P = 0.004). The two independent datasets confirmed our findings. We examined FOXF2 mRNA levels in 84 primary NSCLC and 8 normal lung tissues using qRT-PCR. Rank-sum tests and chi-square tests were used to assess the differences among groups with various clinicopathological factors. Kaplan-Meier tests were used to compare survival status in patients with different FOXF2 mRNA levels. Cox proportional hazards regression model was used to evaluate the predictive value of FOXF2 mRNA level in NSCLC patients. Independent validation was performed using an independent dataset (98 samples) and an online survival analysis software Kaplan-Meier plotter (1928 samples). Our results demonstrated that decreased FOXF2 expression is an independent predictive factor for poor prognosis of patients with NSCLC, especially in stage I NSCLC.

Association between serum ligands and the skin toxicity of anti-epidermal growth factor receptor antibody in metastatic colorectal cancer.

PubMed

Takahashi, Naoki; Yamada, Yasuhide; Furuta, Koh; Nagashima, Kengo; Kubo, Akiko; Sasaki, Yusuke; Shoji, Hirokazu; Honma, Yoshitaka; Iwasa, Satoru; Okita, Natsuko; Takashima, Atsuo; Kato, Ken; Hamaguchi, Tetsuya; Shimada, Yasuhiro

2015-05-01

Skin toxicity is a known clinical signature used to predict the prognosis of anti-epidermal growth factor receptor (EGFR) antibody treatment in metastatic colorectal cancer (mCRC). There are no biological markers to predict skin toxicity before anti-EGFR antibody treatment in mCRC patients. Between August 2008 and August 2011, pretreatment serum samples were obtained from KRAS wild-type (WT) patients who received anti-EGFR antibody treatment. Serum levels of ligands were measured by ELISA. A total of 103 KRAS WT patients were enrolled in the study. Progression-free survival and overall survival of patients with a high grade (grade 2-3) of skin toxicity were significantly longer than those with a low grade (grade 0-1) of skin toxicity (median progression-free survival, 6.4 months vs 2.4 months, P < 0.001; median overall survival, 14.6 months vs 7.1 months, P = 0.006). There were significant differences in distribution of serum levels of epiregulin (EREG), amphiregulin (AREG), and hepatocyte growth factor (HGF) between groups of low/high grade of skin toxicity (P < 0.048, P < 0.012, P < 0.012, respectively). In addition, serum levels of HGF, EREG, and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran-Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG, and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti-EGFR antibody treatment, which contribute to improvement of the management of skin toxicity and survival time in mCRC patients. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

PubMed

Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

2015-10-01

Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without BM invasion showing high level of bone marrow plasma vascular endothelial growth factor per platelet count had significantly shorter progression-free survival and overall survival. Bone marrow plasma vascular endothelial growth factor level per platelet count might be associated with bone marrow invasion by diffuse large B-cell lymphoma and is correlated with clinical outcomes after treatment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

PubMed

Hu, Peizhen; Chung, Leland W K; Berel, Dror; Frierson, Henry F; Yang, Hua; Liu, Chunyan; Wang, Ruoxiang; Li, Qinlong; Rogatko, Andre; Zhau, Haiyen E

2013-01-01

We reported (PLoS One 6 (12):e28670, 2011) that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC) tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE) tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1) expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma.

PubMed

Ponziani, Francesca Romana; Spinelli, Irene; Rinninella, Emanuele; Cerrito, Lucia; Saviano, Antonio; Avolio, Alfonso Wolfango; Basso, Michele; Miele, Luca; Riccardi, Laura; Zocco, Maria Assunta; Annicchiarico, Brigida Eleonora; Garcovich, Matteo; Biolato, Marco; Marrone, Giuseppe; De Gaetano, Anna Maria; Iezzi, Roberto; Giuliante, Felice; Vecchio, Fabio Maria; Agnes, Salvatore; Addolorato, Giovanni; Siciliano, Massimo; Rapaccini, Gian Lodovico; Grieco, Antonio; Gasbarrini, Antonio; Pompili, Maurizio

2017-12-28

To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) and to ascertain the factors predicting the achievement of disease control (DC). The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo (95%CI: 10.6-17.0). Only alphafetoprotein (AFP) serum level > 200 ng/mL and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up (HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year (HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC (OR = 0.263, 95%CI: 0.111-0.622, P = 0.002). The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis.

PubMed

Arias, Maria Theresa; Vande Casteele, Niels; Vermeire, Séverine; de Buck van Overstraeten, Anthony; Billiet, Thomas; Baert, Filip; Wolthuis, Albert; Van Assche, Gert; Noman, Maja; Hoffman, Ilse; D'Hoore, Andre; Gils, Ann; Rutgeerts, Paul; Ferrante, Marc

2015-03-01

Infliximab is effective for patients with refractory ulcerative colitis (UC), but few factors have been identified that predict long-term outcome of therapy. We aimed to identify a panel of markers associated with outcome of infliximab therapy to help physicians make personalized treatment decisions. We collected data from the first 285 patients with refractory UC (41% female; median age, 39 y) treated with infliximab before July 2012 at University Hospitals Leuven, in Belgium. We performed a Cox regression analysis to identify independent factors that predicted relapse-free and colectomy-free survival, and used these factors to create a panel of markers (risk panel). During a median follow-up period of 5 years, 61% of patients relapsed and 20% required colectomy. Independent predictors of relapse-free survival included short-term complete clinical response (odds ratio [OR], 3.75; 95% confidence interval [CI], 2.35-5.97; P < .001), mucosal healing (OR, 1.87; 95% CI, 1.17-2.98; P = .009), and absence of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) (OR, 1.96; 95% CI, 1.23-3.12; P = .005). Independent predictors of colectomy-free survival included short-term clinical response (OR, 7.74; 95% CI, 2.76-21.68; P < .001), mucosal healing (OR, 4.02; 95% CI, 1.16-13.97; P = .028), baseline level of C-reactive protein (CRP) of 5 mg/L or less (OR, 2.95; 95% CI, 1.26-6.89; P = .012), and baseline level of albumin of 35 g/L or greater (OR, 3.03; 95% CI, 1.12-8.22; P = .029). Based on serologic analysis of a subgroup of 112 patients, levels of infliximab greater than 2.5 μg/mL at week 14 of treatment predicted relapse-free survival (P < .001) and colectomy-free survival (P = .034). A risk panel that included levels of pANCA, CRP, albumin, clinical response, and mucosal healing identified patients at risk for UC relapse or colectomy (both P < .001). Clinical response and mucosal healing were confirmed as independent predictors of long-term outcome from infliximab therapy in patients with UC. We identified additional factors (levels of pANCA, CRP, and albumin) to create a risk panel that predicts long-term outcomes of therapy. Serum levels of infliximab at week 14 of treatment also were associated with patient outcomes. Our risk panel and short-term serum levels of infliximab therefore might be used to guide therapy. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Simple prognostic model for patients with advanced cancer based on performance status.

PubMed

Jang, Raymond W; Caraiscos, Valerie B; Swami, Nadia; Banerjee, Subrata; Mak, Ernie; Kaya, Ebru; Rodin, Gary; Bryson, John; Ridley, Julia Z; Le, Lisa W; Zimmermann, Camilla

2014-09-01

Providing survival estimates is important for decision making in oncology care. The purpose of this study was to provide survival estimates for outpatients with advanced cancer, using the Eastern Cooperative Oncology Group (ECOG), Palliative Performance Scale (PPS), and Karnofsky Performance Status (KPS) scales, and to compare their ability to predict survival. ECOG, PPS, and KPS were completed by physicians for each new patient attending the Princess Margaret Cancer Centre outpatient Oncology Palliative Care Clinic (OPCC) from April 2007 to February 2010. Survival analysis was performed using the Kaplan-Meier method. The log-rank test for trend was employed to test for differences in survival curves for each level of performance status (PS), and the concordance index (C-statistic) was used to test the predictive discriminatory ability of each PS measure. Measures were completed for 1,655 patients. PS delineated survival well for all three scales according to the log-rank test for trend (P < .001). Survival was approximately halved for each worsening performance level. Median survival times, in days, for each ECOG level were: EGOG 0, 293; ECOG 1, 197; ECOG 2, 104; ECOG 3, 55; and ECOG 4, 25.5. Median survival times, in days, for PPS (and KPS) were: PPS/KPS 80-100, 221 (215); PPS/KPS 60 to 70, 115 (119); PPS/KPS 40 to 50, 51 (49); PPS/KPS 10 to 30, 22 (29). The C-statistic was similar for all three scales and ranged from 0.63 to 0.64. We present a simple tool that uses PS alone to prognosticate in advanced cancer, and has similar discriminatory ability to more complex models. Copyright © 2014 by American Society of Clinical Oncology.

Protein profiles associated with survival in lung adenocarcinoma

PubMed Central

Chen, Guoan; Gharib, Tarek G; Wang, Hong; Huang, Chiang-Ching; Kuick, Rork; Thomas, Dafydd G.; Shedden, Kerby A.; Misek, David E.; Taylor, Jeremy M. G.; Giordano, Thomas J.; Kardia, Sharon L. R.; Iannettoni, Mark D.; Yee, John; Hogg, Philip J.; Orringer, Mark B.; Hanash, Samir M.; Beer, David G.

2003-01-01

Morphologic assessment of lung tumors is informative but insufficient to adequately predict patient outcome. We previously identified transcriptional profiles that predict patient survival, and here we identify proteins associated with patient survival in lung adenocarcinoma. A total of 682 individual protein spots were quantified in 90 lung adenocarcinomas by using quantitative two-dimensional polyacrylamide gel electrophoresis analysis. A leave-one-out cross-validation procedure using the top 20 survival-associated proteins identified by Cox modeling indicated that protein profiles as a whole can predict survival in stage I tumor patients (P = 0.01). Thirty-three of 46 survival-associated proteins were identified by using mass spectrometry. Expression of 12 candidate proteins was confirmed as tumor-derived with immunohistochemical analysis and tissue microarrays. Oligonucleotide microarray results from both the same tumors and from an independent study showed mRNAs associated with survival for 11 of 27 encoded genes. Combined analysis of protein and mRNA data revealed 11 components of the glycolysis pathway as associated with poor survival. Among these candidates, phosphoglycerate kinase 1 was associated with survival in the protein study, in both mRNA studies and in an independent validation set of 117 adenocarcinomas and squamous lung tumors using tissue microarrays. Elevated levels of phosphoglycerate kinase 1 in the serum were also significantly correlated with poor outcome in a validation set of 107 patients with lung adenocarcinomas using ELISA analysis. These studies identify new prognostic biomarkers and indicate that protein expression profiles can predict the outcome of patients with early-stage lung cancer. PMID:14573703

Circulating complexes between tumour necrosis factor-alpha and etanercept predict long-term efficacy of etanercept in juvenile idiopathic arthritis.

PubMed

Kahn, Robin; Berthold, Elisabet; Gullstrand, Birgitta; Schmidt, Tobias; Kahn, Fredrik; Geborek, Pierre; Saxne, Tore; Bengtsson, Anders A; Månsson, Bengt

2016-04-01

The relationship between tumour necrosis factor-alpha (TNF-α) and drug survival had not been studied in juvenile idiopathic arthritis (JIA), and there were no laboratory tests to predict the long-term efficacy of biological drugs for JIA. We studied whether serum levels of TNF-α, free or bound to etanercept, could predict long-term efficacy of etanercept in children with JIA. We included 41 biologic-naïve patients with JIA who started treatment with etanercept at Skåne University Hospital between 1999 and 2010. Serum taken at the start of treatment and at the six-week follow-up were analysed for TNF-α and the long-term efficacy of etanercept was assessed using the drug survival time. Levels of TNF-α increased significantly at the six-week follow-up, and this was almost exclusively comprised of TNF-α in complex with etanercept. The increase in TNF-α showed a dose-dependent correlation to long-term drug survival (p < 0.01). Increasing levels of circulating TNF-α at treatment initiation predicted long-term efficacy of etanercept in children with JIA, which may have been due to different pathophysiological mechanisms of inflammation. Our result may provide a helpful clinical tool, as high levels of circulating TNF-α/etanercept complexes could be used as a marker for the long-term efficacy of etanercept. ©2015 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

Patient volume per surgeon does not predict survival in adult level I trauma centers.

PubMed

Margulies, D R; Cryer, H G; McArthur, D L; Lee, S S; Bongard, F S; Fleming, A W

2001-04-01

The 1999 American College of Surgeons resources for optimal care document added the requirement that Level I trauma centers admit over 240 patients with Injury Severity Score (ISS) > 15 per year or that trauma surgeons care for at least 35 patients per year. The purpose of this study was to test the hypothesis that high volume of patients with ISS > 15 per individual trauma surgeon is associated with improved outcome. Data were obtained from the trauma registry of the five American College of Surgeons-verified adult Level I trauma centers in our mature trauma system between January 1, 1998, and March 31, 1999. Data abstracted included age, sex, Glasgow Coma Scale (GCS) score, intensive care unit length of stay, hospital length of stay, probability of survival (Ps), mechanism of injury, number of patients per each trauma surgeon and institution, and mortality. Multiple logistic regression was performed to select independent variables for modeling of survival. From the five Level I centers there were 11,932 trauma patients in this time interval; of these, 1,754 patients (14.7%) with ISS > 15 were identified and used for analysis. Patients with ISS > 15 varied from 173 to 625 per institution; trauma surgeons varied from 8 to 25 per institution; per-surgeon patient volume varied from 0.8 to 96 per year. Logistic regression analysis revealed that the best independent predictors of survival were Ps, GCS score, age, mechanism of injury, and institutional volume (p < 0.01). Age and institutional volume correlated negatively with survival. Analysis of per-surgeon patient caseload added no additional predictive value (p = 0.44). The significant independent predictors of survival in severely injured trauma patients are Ps, GCS score, age, mechanism of injury, and institutional volume. We found no statistically meaningful contribution to the prediction of survival on the basis of per-surgeon patient volume. Since this volume criterion for surgeon enpanelment and trauma center designation would not be expected to improve outcome, such a requirement should be justified by other measures or abandoned.

Urate levels predict survival in amyotrophic lateral sclerosis: Analysis of the expanded Pooled Resource Open-Access ALS clinical trials database.

PubMed

Paganoni, Sabrina; Nicholson, Katharine; Chan, James; Shui, Amy; Schoenfeld, David; Sherman, Alexander; Berry, James; Cudkowicz, Merit; Atassi, Nazem

2018-03-01

Urate has been identified as a predictor of amyotrophic lateral sclerosis (ALS) survival in some but not all studies. Here we leverage the recent expansion of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to study the association between urate levels and ALS survival. Pooled data of 1,736 ALS participants from the PRO-ACT database were analyzed. Cox proportional hazards regression models were used to evaluate associations between urate levels at trial entry and survival. After adjustment for potential confounders (i.e., creatinine and body mass index), there was an 11% reduction in risk of reaching a survival endpoint during the study with each 1-mg/dL increase in uric acid levels (adjusted hazard ratio 0.89, 95% confidence interval 0.82-0.97, P < 0.01). Our pooled analysis provides further support for urate as a prognostic factor for survival in ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. Muscle Nerve 57: 430-434, 2018. © 2017 Wiley Periodicals, Inc.

Level and change in perceived control predict 19-year mortality: findings from the Americans' changing lives study.

PubMed

Infurna, Frank J; Ram, Nilam; Gerstorf, Denis

2013-10-01

Perceived control plays an important role for health across adulthood and old age. However, little is known about the factors that account for such associations and whether changes in control (or control trajectory) uniquely predict major health outcomes over and above mean levels of control. Using data from the nationwide Americans' Changing Lives Study (House et al., 1990; N = 2,840, M age at T2: 56.32 years, range: 28-99, 64% women), we examined the extent to which mean levels and rates of change in perceived control over 16 years predict all-cause mortality over a 19-year follow-up period. Shared growth-survival models revealed that higher levels of and more positive changes in perceived control were associated with longer survival times, independent of sociodemographic correlates. We found that level effects of control were accounted for by well-being and health factors, whereas the change effects of control were not. Analyses also indicated an age-differential pattern, with the predictive effects of both levels and trajectories of control declining in old age. We discuss possible pathways through which perceived control operates to facilitate key health outcomes and consider how their malleability and effectiveness may change with increasing age.

Survival analysis: A consumer-friendly method to estimate the optimum sucrose level in probiotic petit suisse.

PubMed

Esmerino, E A; Paixão, J A; Cruz, A G; Garitta, L; Hough, G; Bolini, H M A

2015-11-01

For years, just-about-right (JAR) scales have been among the most used techniques to obtain sensory information about consumer perception, but recently, some researchers have harshly criticized the technique. The present study aimed to apply survival analysis to estimate the optimum sucrose concentration in probiotic petit suisse cheese and compare the survival analysis to JAR scales to verify which technique more accurately predicted the optimum sucrose concentration according to consumer acceptability. Two panels of consumers (total=170) performed affective tests to determine the optimal concentration of sucrose in probiotic petit suisse using 2 different methods of analysis: JAR scales (n=85) and survival analysis (n=85). Then an acceptance test was conducted using naïve consumers (n=100) between 18 and 60 yr old, with 2 samples of petit suisse, one with the ideal sucrose determined by JAR scales and the other with the ideal sucrose content determined by survival analysis, to determine which formulation was in accordance with consumer acceptability. The results indicate that the 2 sensory methods were equally effective in predicting the optimum sucrose level in probiotic petit suisse cheese, and no significant differences were detected in any of the characteristics related to liking evaluated. However, survival analysis has important advantages over the JAR scales. Survival analysis has shown the potential to be an advantageous tool for dairy companies because it was able to accurately predict the optimum sucrose content in a consumer-friendly way and was also practical for researchers because experimental sensory work is simpler and has been shown to be more cost effective than JAR scales without losses of consumer acceptability. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Simulating the effects of fluctuating dissolved oxygen on growth, reproduction, and survival of fish and shrimp.

PubMed

Miller Neilan, Rachael; Rose, Kenneth

2014-02-21

Individuals are commonly exposed to fluctuating levels of stressors, while most laboratory experiments focus on constant exposures. We develop and test a mathematical model for predicting the effects of low dissolved oxygen (hypoxia) on growth, reproduction, and survival using laboratory experiments on fish and shrimp. The exposure-effects model simulates the hourly reductions in growth and survival, and the reduction in reproduction (fecundity) at times of spawning, of an individual as it is exposed to constant or hourly fluctuating dissolved oxygen (DO) concentrations. The model was applied to seven experiments involving fish and shrimp that included constant and fluctuating DO exposures, with constant exposures used for parameter estimation and the model then used to simulate the growth, reproduction, and survival in the fluctuating treatments. Cumulative effects on growth, reproduction, and survival were predicted well by the model, but the model did not replay the observed episodic low survival days. Further investigation should involve the role of acclimation, possible inclusion of repair effects in reproduction and survival, and the sensitivity of model predictions to the shape of the immediate effects function. Additional testing of the model with other taxa, different patterns of fluctuating exposures, and different stressors is needed to determine the model's generality and robustness. © 2013 Elsevier Ltd. All rights reserved.

A four-gene signature predicts survival in clear-cell renal-cell carcinoma.

PubMed

Dai, Jun; Lu, Yuchao; Wang, Jinyu; Yang, Lili; Han, Yingyan; Wang, Ying; Yan, Dan; Ruan, Qiurong; Wang, Shaogang

2016-12-13

Clear-cell renal-cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma (RCC), accounting for about 80% of RCC. In order to find potential prognostic biomarkers in ccRCC, we presented a four-gene signature to evaluate the prognosis of ccRCC. SurvExpress and immunohistochemical (IHC) staining of tissue microarrays were used to analyze the association between the four genes and the prognosis of ccRCC. Data from TCGA dataset revealed a prognostic prompt function of the four genes (PTEN, PIK3C2A, ITPA and BCL3). Further discovery suggested that the four-gene signature predicted survival better than any of the four genes alone. Moreover, IHC staining demonstrated a consistent result with TCGA, indicating that the signature was an independent prognostic factor of survival in ccRCC. Univariate and multivariate Cox proportional hazard regression analysis were conducted to verify the association of clinicopathological variables and the four genes' expression levels with survival. The results further testified that the risk (four-gene signature) was an independent prognostic factors of both Overall Survival (OS) and Disease-free Survival (DFS) (P<0.05). In conclusion, the four-gene signature was correlated with the survival of ccRCC, and therefore, may help to provide significant clinical implications for predicting the prognosis of patients.

Linking Measures of Colony and Individual Honey Bee Health to Survival among Apiaries Exposed to Varying Agricultural Land Use

PubMed Central

Smart, Matthew; Pettis, Jeff; Rice, Nathan; Browning, Zac; Spivak, Marla

2016-01-01

We previously characterized and quantified the influence of land use on survival and productivity of colonies positioned in six apiaries and found that colonies in apiaries surrounded by more land in uncultivated forage experienced greater annual survival, and generally more honey production. Here, detailed metrics of honey bee health were assessed over three years in colonies positioned in the same six apiaries. The colonies were located in North Dakota during the summer months and were transported to California for almond pollination every winter. Our aim was to identify relationships among measures of colony and individual bee health that impacted and predicted overwintering survival of colonies. We tested the hypothesis that colonies in apiaries surrounded by more favorable land use conditions would experience improved health. We modeled colony and individual bee health indices at a critical time point (autumn, prior to overwintering) and related them to eventual spring survival for California almond pollination. Colony measures that predicted overwintering apiary survival included the amount of pollen collected, brood production, and Varroa destructor mite levels. At the individual bee level, expression of vitellogenin, defensin1, and lysozyme2 were important markers of overwinter survival. This study is a novel first step toward identifying pertinent physiological responses in honey bees that result from their positioning near varying landscape features in intensive agricultural environments. PMID:27027871

Linkages Between Anxiety and Outcomes in Heart Failure

PubMed Central

De Jong, Marla J.; Chung, Misook L.; Wu, Jia-Rong; Riegel, Barbara; Rayens, Mary Kay; Moser, Debra K.

2011-01-01

OBJECTIVE To investigate the relationship between anxiety and event-free survival (i.e., composite endpoint of death, emergency department visits, or hospitalizations) for patients with HF, and examine whether behavioral and physiologic mechanisms mediate any association between anxiety and outcomes. METHODS In this longitudinal study, patients with HF completed the anxiety subscale of the Brief Symptom Inventory, and heart rate variability and plasma norepinephrine level were measured. Dietary and medication adherence were measured with a 24-hour urine sodium level and the Medication Event Monitoring System, respectively. Patients were followed at least 1 year for event-free survival. RESULTS A total of 147 patients were enrolled. Patients with high anxiety had a shorter (HR 2.2, 95% CI 1.1–4.3, P = .03) period of event-free survival than patients with lower anxiety. Anxiety independently predicted medication adherence (P = .008), which in turn predicted event-free survival (HR 2.0, CI 1.2–3.3, P = .008). The effect of anxiety (P = .17) on event-free survival was less significant when the regression model included both anxiety and medication adherence than when the model only included anxiety (P = .03), indicating that medication adherence mediated the relationship between anxiety and event-free survival. CONCLUSION This is the first study to show that medication nonadherence links anxiety and event-free survival for patients with HF. Interventions that reduce anxiety and improve adherence may favorably benefit outcomes. PMID:21453974

Linking Measures of Colony and Individual Honey Bee Health to Survival among Apiaries Exposed to Varying Agricultural Land Use.

PubMed

Smart, Matthew; Pettis, Jeff; Rice, Nathan; Browning, Zac; Spivak, Marla

2016-01-01

We previously characterized and quantified the influence of land use on survival and productivity of colonies positioned in six apiaries and found that colonies in apiaries surrounded by more land in uncultivated forage experienced greater annual survival, and generally more honey production. Here, detailed metrics of honey bee health were assessed over three years in colonies positioned in the same six apiaries. The colonies were located in North Dakota during the summer months and were transported to California for almond pollination every winter. Our aim was to identify relationships among measures of colony and individual bee health that impacted and predicted overwintering survival of colonies. We tested the hypothesis that colonies in apiaries surrounded by more favorable land use conditions would experience improved health. We modeled colony and individual bee health indices at a critical time point (autumn, prior to overwintering) and related them to eventual spring survival for California almond pollination. Colony measures that predicted overwintering apiary survival included the amount of pollen collected, brood production, and Varroa destructor mite levels. At the individual bee level, expression of vitellogenin, defensin1, and lysozyme2 were important markers of overwinter survival. This study is a novel first step toward identifying pertinent physiological responses in honey bees that result from their positioning near varying landscape features in intensive agricultural environments.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

PubMed Central

Ponziani, Francesca Romana; Spinelli, Irene; Rinninella, Emanuele; Cerrito, Lucia; Saviano, Antonio; Avolio, Alfonso Wolfango; Basso, Michele; Miele, Luca; Riccardi, Laura; Zocco, Maria Assunta; Annicchiarico, Brigida Eleonora; Garcovich, Matteo; Biolato, Marco; Marrone, Giuseppe; De Gaetano, Anna Maria; Iezzi, Roberto; Giuliante, Felice; Vecchio, Fabio Maria; Agnes, Salvatore; Addolorato, Giovanni; Siciliano, Massimo; Rapaccini, Gian Lodovico; Grieco, Antonio; Gasbarrini, Antonio; Pompili, Maurizio

2017-01-01

AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) and to ascertain the factors predicting the achievement of disease control (DC). METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo (95%CI: 10.6-17.0). Only alphafetoprotein (AFP) serum level > 200 ng/mL and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up (HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year (HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC (OR = 0.263, 95%CI: 0.111-0.622, P = 0.002). CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients’ survival confers them as useful predictive tools for treatment management and clinical decisions. PMID:29359015

Cancer survival analysis using semi-supervised learning method based on Cox and AFT models with L1/2 regularization.

PubMed

Liang, Yong; Chai, Hua; Liu, Xiao-Ying; Xu, Zong-Ben; Zhang, Hai; Leung, Kwong-Sak

2016-03-01

One of the most important objectives of the clinical cancer research is to diagnose cancer more accurately based on the patients' gene expression profiles. Both Cox proportional hazards model (Cox) and accelerated failure time model (AFT) have been widely adopted to the high risk and low risk classification or survival time prediction for the patients' clinical treatment. Nevertheless, two main dilemmas limit the accuracy of these prediction methods. One is that the small sample size and censored data remain a bottleneck for training robust and accurate Cox classification model. In addition to that, similar phenotype tumours and prognoses are actually completely different diseases at the genotype and molecular level. Thus, the utility of the AFT model for the survival time prediction is limited when such biological differences of the diseases have not been previously identified. To try to overcome these two main dilemmas, we proposed a novel semi-supervised learning method based on the Cox and AFT models to accurately predict the treatment risk and the survival time of the patients. Moreover, we adopted the efficient L1/2 regularization approach in the semi-supervised learning method to select the relevant genes, which are significantly associated with the disease. The results of the simulation experiments show that the semi-supervised learning model can significant improve the predictive performance of Cox and AFT models in survival analysis. The proposed procedures have been successfully applied to four real microarray gene expression and artificial evaluation datasets. The advantages of our proposed semi-supervised learning method include: 1) significantly increase the available training samples from censored data; 2) high capability for identifying the survival risk classes of patient in Cox model; 3) high predictive accuracy for patients' survival time in AFT model; 4) strong capability of the relevant biomarker selection. Consequently, our proposed semi-supervised learning model is one more appropriate tool for survival analysis in clinical cancer research.

Tumour necrosis factor-α/etanercept complexes in serum predict long-term efficacy of etanercept treatment in seronegative rheumatoid arthritis.

PubMed

Berthold, E; Månsson, B; Gullstrand, B; Geborek, P; Saxne, T; Bengtsson, A A; Kahn, R

2018-01-01

To study whether serum levels of tumour necrosis factor-α (TNF-α), free or bound to etanercept, in biological-naïve adults with rheumatoid arthritis (RA) could predict the long-term efficacy of etanercept, measured as drug survival. We identified 145 biological-naïve patients with RA starting treatment with etanercept at the Department of Rheumatology, Skåne University Hospital (1999-2008), of whom 16 had seronegative and 129 seropositive RA. TNF-α in serum was quantified using enzyme-linked immunosorbent assay in samples from the onset of treatment and at 6 week follow-up. Drug survival time was used to evaluate the long-term efficacy of etanercept. Levels of TNF-α were significantly increased at follow-up compared to at the start. At the 6 week follow-up, circulating TNF-α mainly comprised TNF-α in complex with etanercept. Longer drug survival time correlated with increased TNF-α at 6 week follow-up in the patients with seronegative RA, but not in the seropositive patients. We demonstrated that levels of circulating TNF-α increased in almost all individuals after initiation of treatment with etanercept and that this increase mainly comprised TNF-α in complex with etanercept. More importantly, this increase may predict drug survival in adults with seronegative, but not seropositive, RA and suggests that measuring TNF-α/etanercept complexes in serum may be relevant in patients with seronegative RA.

Predicting impending death: inconsistency in speed is a selective and early marker.

PubMed

Macdonald, Stuart W S; Hultsch, David F; Dixon, Roger A

2008-09-01

Among older adults, deficits in both level and variability of speeded performance are linked to neurological impairment. This study examined whether and when speed (rate), speed (inconsistency), and traditional accuracy-based markers of cognitive performance foreshadow terminal decline and impending death. Victoria Longitudinal Study data spanning 12 years (5 waves) of measurement were assembled for 707 adults aged 59 to 95 years. Whereas 442 survivors completed all waves and relevant measures, 265 decedents participated on at least 1 occasion and subsequently died. Four main results were observed. First, Cox regressions evaluating the 3 cognitive predictors of mortality replicated previous results for cognitive accuracy predictors. Second, level (rate) of speeded performance predicted survival independent of demographic indicators, cardiovascular health, and cognitive performance level. Third, inconsistency in speed predicted survival independent of all influences combined. Fourth, follow-up random-effects models revealed increases in inconsistency in speed per year closer to death, with advancing age further moderating the accelerated growth. Hierarchical prediction patterns support the view that inconsistency in speed is an early behavioral marker of neurological dysfunction associated with impending death. (c) 2008 APA, all rights reserved

Predicting Impending Death: Inconsistency in Speed is a Selective and Early Marker

PubMed Central

MacDonald, Stuart W.S.; Hultsch, David F.; Dixon, Roger A.

2008-01-01

Among older adults, deficits in both level and variability of speeded performance are linked to neurological impairment. This study examined whether and when speed (rate), speed (inconsistency), and traditional accuracy-based markers of cognitive performance foreshadow terminal decline and impending death. Victoria Longitudinal Study data spanning 12 years (5 waves) of measurement were assembled for 707 adults aged 59 to 95 years. Whereas 442 survivors completed all waves and relevant measures, 265 decedents participated on at least one occasion and subsequently died. Four main results were observed. First, Cox regressions evaluating the three cognitive predictors of mortality replicated previous results for cognitive accuracy predictors. Second, level (rate) of speeded performance predicted survival independent of demographic indicators, cardiovascular health, and cognitive performance level. Third, inconsistency in speed predicted survival independent of all influences combined. Fourth, follow-up random-effects models revealed increases in inconsistency in speed per year closer to death, with advancing age further moderating the accelerated growth. Hierarchical prediction patterns support the view that inconsistency in speed is an early behavioral marker of neurological dysfunction associated with impending death. PMID:18808249

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

PubMed

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

2015-06-01

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

Inferring parturition and neonate survival from movement patterns of female ungulates: a case study using woodland caribou

PubMed Central

DeMars, Craig A; Auger-Méthé, Marie; Schlägel, Ulrike E; Boutin, Stan

2013-01-01

Analyses of animal movement data have primarily focused on understanding patterns of space use and the behavioural processes driving them. Here, we analyzed animal movement data to infer components of individual fitness, specifically parturition and neonate survival. We predicted that parturition and neonate loss events could be identified by sudden and marked changes in female movement patterns. Using GPS radio-telemetry data from female woodland caribou (Rangifer tarandus caribou), we developed and tested two novel movement-based methods for inferring parturition and neonate survival. The first method estimated movement thresholds indicative of parturition and neonate loss from population-level data then applied these thresholds in a moving-window analysis on individual time-series data. The second method used an individual-based approach that discriminated among three a priori models representing the movement patterns of non-parturient females, females with surviving offspring, and females losing offspring. The models assumed that step lengths (the distance between successive GPS locations) were exponentially distributed and that abrupt changes in the scale parameter of the exponential distribution were indicative of parturition and offspring loss. Both methods predicted parturition with near certainty (>97% accuracy) and produced appropriate predictions of parturition dates. Prediction of neonate survival was affected by data quality for both methods; however, when using high quality data (i.e., with few missing GPS locations), the individual-based method performed better, predicting neonate survival status with an accuracy rate of 87%. Understanding ungulate population dynamics often requires estimates of parturition and neonate survival rates. With GPS radio-collars increasingly being used in research and management of ungulates, our movement-based methods represent a viable approach for estimating rates of both parameters. PMID:24324866

Inferring parturition and neonate survival from movement patterns of female ungulates: a case study using woodland caribou.

PubMed

Demars, Craig A; Auger-Méthé, Marie; Schlägel, Ulrike E; Boutin, Stan

2013-10-01

Analyses of animal movement data have primarily focused on understanding patterns of space use and the behavioural processes driving them. Here, we analyzed animal movement data to infer components of individual fitness, specifically parturition and neonate survival. We predicted that parturition and neonate loss events could be identified by sudden and marked changes in female movement patterns. Using GPS radio-telemetry data from female woodland caribou (Rangifer tarandus caribou), we developed and tested two novel movement-based methods for inferring parturition and neonate survival. The first method estimated movement thresholds indicative of parturition and neonate loss from population-level data then applied these thresholds in a moving-window analysis on individual time-series data. The second method used an individual-based approach that discriminated among three a priori models representing the movement patterns of non-parturient females, females with surviving offspring, and females losing offspring. The models assumed that step lengths (the distance between successive GPS locations) were exponentially distributed and that abrupt changes in the scale parameter of the exponential distribution were indicative of parturition and offspring loss. Both methods predicted parturition with near certainty (>97% accuracy) and produced appropriate predictions of parturition dates. Prediction of neonate survival was affected by data quality for both methods; however, when using high quality data (i.e., with few missing GPS locations), the individual-based method performed better, predicting neonate survival status with an accuracy rate of 87%. Understanding ungulate population dynamics often requires estimates of parturition and neonate survival rates. With GPS radio-collars increasingly being used in research and management of ungulates, our movement-based methods represent a viable approach for estimating rates of both parameters.

Interaction between age and race alters predicted survival in colorectal cancer.

PubMed

Phatak, Uma R; Kao, Lillian S; Millas, Stefanos G; Wiatrek, Rebecca L; Ko, Tien C; Wray, Curtis J

2013-10-01

Racial disparities in colorectal cancer persist. Late stage at presentation and lack of stage-specific treatment may be contributing factors. We sought to evaluate the magnitude of disparity remaining after accounting for gender, stage, and treatment using predicted survival models. We used institutional tumor registries from a public health system (two hospitals) and a not-for-profit health system (nine hospitals) from 1995 to 2011. Demographics, stage at diagnosis, treatment, and survival were recorded. Hazard ratios (HRs) and predicted HRs were determined by Cox regression and postestimation analyses. There were 6,990 patients: 55.7 % white, 23.6 % African American, 15.1 % Hispanic, and 5.6 % Asian/other. Predictors of survival were surgery (HR 0.57, 95 % confidence interval [CI] 0.46-0.70), chemotherapy (HR 0.7, 95 % CI 0.62-0.79), female gender (HR 0.87, 95 % CI 0.83-0.90), age (HR 1.04, 95 % CI 1.03-1.05), and African American race (HR 3.6, 95 % CI 1.5-8.4). Balancing for stage, gender, and treatment reduced the predicted HRs for African Americans by 28 % and Hispanics by 17 %. In this model, African American and Hispanics still had the worst predicted HRs at younger ages, but whites had the worst predicted HR after age 75. Gender, stage, and treatment partially accounted for worsened survival in African Americans and Hispanics at all ages. At younger ages, race-related disparities remained which may reflect tumor biology or other unknown factors. Once gender, stage, and treatment are balanced at older ages, the increased mortality observed in whites may be due to factors such as comorbidities. Further system- and patient-level study is needed to investigate reasons for colorectal cancer survival disparities.

Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure.

PubMed

Rengo, Giuseppe; Galasso, Gennaro; Femminella, Grazia D; Parisi, Valentina; Zincarelli, Carmela; Pagano, Gennaro; De Lucia, Claudio; Cannavo, Alessandro; Liccardo, Daniela; Marciano, Caterina; Vigorito, Carlo; Giallauria, Francesco; Ferrara, Nicola; Furgi, Giuseppe; Filardi, Pasquale Perrone; Koch, Walter J; Leosco, Dario

2014-01-01

Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and short-term changes of this kinase after an exercise training programme can predict long-term survival in HF patients. For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37 ± 20 months. Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29 ± 0.52 to 1.16 ± 0.65 densitometric units, p < 0.0001). Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, HF patients who did not show reduced lymphocyte GRK2 protein levels after training presented the poorest outcome. Our data offer the first demonstration that changes of lymphocyte GRK2 after exercise training can strongly predict outcome in advanced HF.

Influence of membrane fatty acid composition and fluidity on airborne survival of Escherichia coli.

PubMed

Ng, Tsz Wai; Chan, Wing Lam; Lai, Ka Man

2018-04-01

Finding ways to predict and control the survival of bacterial aerosols can contribute to the development of ways to alleviate a number of crucial microbiological problems. Significant damage in the membrane integrity of Escherichia coli during aerosolization and airborne suspension has been revealed which has prompted the question of how the membrane fatty acid composition and fluidity influence the survival of airborne bacteria. Two approaches of using isogenic mutants and different growth temperatures were selected to manipulate the membrane fatty acid composition of E. coli before challenging the bacteria with different relative humidity (RH) levels in an aerosol chamber. Among the mutants (fabR - , cfa. fadA - ), fabR - had the lowest membrane fluidity index (FI) and generally showed a higher survival than the parental strain. Surprisingly, its resistance to airborne stress was so strong that its viability was fully maintained even after airborne suspension at 40% RH, a harsh RH level to bacterial survival. Moreover, E. coli cultured at 20 °C with a higher FI than that at 30 and 37 °C generally had a lower survival after aerosolization and airborne suspension. Unlike FI, individual fatty acid and cyclopropane fatty acid composition did not relate to the bacterial survival. Lipid peroxidation of the membrane was undetected in all the bacteria. Membrane fluidity plays a stronger role in determining the bacteria survival during airborne suspension than during aerosolization. Certain relationships between FI and bacteria survival were identified, which could help predict the transmission of bacteria under different conditions.

Evaluation of prognostic factors on recurrence after curative resections for hepatocellular carcinoma

PubMed Central

Han, Jae Hyun; Kim, Dong Goo; Na, Gun Hyung; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

2014-01-01

AIM: To select appropriate patients before surgical resection for hepatocellular carcinoma (HCC), especially those with advanced tumors. METHODS: From January 2000 to December 2012, we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital. We evaluated preoperative prognostic factors associated with histologic grade of tumor, recurrence and survival, especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). And then, we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm. RESULTS: Of the 298 patients, 129 (43.3%) developed recurrence during the follow-up period. The 5 year disease free survival and overall survival were 47.0% and 58.7% respectively. In multivariate analysis, a serum alpha-fetoprotein (AFP) level of > 100 ng/mL and a standardized uptake value (SUV) of PET-CT of > 3.5 were predictive factors for histologic grade of tumor, recurrence, and survival. Tumor size of > 5 cm and a relative enhancement ratio (RER) calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis. We established a scoring system to predict prognosis using AFP, SUV, and RER. In those with tumors of > 5 cm, it showed predicted both recurrence (P = 0.005) and survival (P = 0.001). CONCLUSION: The AFP, tumor size, SUV and RER are useful for prognosis preoperatively. An accurate prediction of prognosis is possible using our scoring system in large size tumors. PMID:25493027

Evaluation of prognostic factors on recurrence after curative resections for hepatocellular carcinoma.

PubMed

Han, Jae Hyun; Kim, Dong Goo; Na, Gun Hyung; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

2014-12-07

To select appropriate patients before surgical resection for hepatocellular carcinoma (HCC), especially those with advanced tumors. From January 2000 to December 2012, we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital. We evaluated preoperative prognostic factors associated with histologic grade of tumor, recurrence and survival, especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). And then, we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm. Of the 298 patients, 129 (43.3%) developed recurrence during the follow-up period. The 5 year disease free survival and overall survival were 47.0% and 58.7% respectively. In multivariate analysis, a serum alpha-fetoprotein (AFP) level of > 100 ng/mL and a standardized uptake value (SUV) of PET-CT of > 3.5 were predictive factors for histologic grade of tumor, recurrence, and survival. Tumor size of > 5 cm and a relative enhancement ratio (RER) calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis. We established a scoring system to predict prognosis using AFP, SUV, and RER. In those with tumors of > 5 cm, it showed predicted both recurrence (P = 0.005) and survival (P = 0.001). The AFP, tumor size, SUV and RER are useful for prognosis preoperatively. An accurate prediction of prognosis is possible using our scoring system in large size tumors.

CA19-9 serum levels predict micrometastases in patients with gastric cancer

PubMed Central

Potrc, Stojan; Mis, Katarina; Plankl, Mojca; Mars, Tomaz

2016-01-01

Abstract Background We explored the prognostic value of the up-regulated carbohydrate antigen (CA19-9) in node-negative patients with gastric cancer as a surrogate marker for micrometastases. Patients and methods Micrometastases were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for a subgroup of 30 node-negative patients. This group was used to determine the cut-off for preoperative CA19-9 serum levels as a surrogate marker for micrometastases. Then 187 node-negative T1 to T4 patients were selected to validate the predictive value of this CA19-9 threshold. Results Patients with micrometastases had significantly higher preoperative CA19-9 serum levels compared to patients without micrometastases (p = 0.046). CA19-9 serum levels were significantly correlated with tumour site, tumour diameter, and perineural invasion. Although not reaching significance, subgroup analysis showed better five-year survival rates for patients with CA19-9 serum levels below the threshold, compared to patients with CA19-9 serum levels above the cut-off. The cumulative survival for T2 to T4 node-negative patients was significantly better with CA19-9 serum levels below the cut-off (p = 0.04). Conclusions Preoperative CA19-9 serum levels can be used to predict higher risk for haematogenous spread and micrometastases in node-negative patients. However, CA19-9 serum levels lack the necessary sensitivity and specificity to reliably predict micrometastases. PMID:27247553

The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

PubMed Central

Bonanno, Laura; Costa, Carlota; Majem, Margarita; Sanchez, Jose Javier; Gimenez-Capitan, Ana; Rodriguez, Ignacio; Vergenegre, Alain; Massuti, Bartomeu; Favaretto, Adolfo; Rugge, Massimo; Pallares, Cinta; Taron, Miquel; Rosell, Rafael

2013-01-01

Platinum-based chemotherapy is the standard first-line treatment for non-oncogene-addicted non-small cell lung cancers (NSCLCs) and the analysis of multiple DNA repair genes could improve current models for predicting chemosensitivity. We investigated the potential predictive role of components of the 53BP1 pathway in conjunction with BRCA1. The mRNA expression of BRCA1, MDC1, CASPASE3, UBC13, RNF8, 53BP1, PIAS4, UBC9 and MMSET was analyzed by real-time PCR in 115 advanced NSCLC patients treated with first-line platinum-based chemotherapy. Patients expressing low levels of both BRCA1 and 53BP1 obtained a median progression-free survival of 10.3 months and overall survival of 19.3 months, while among those with low BRCA1 and high 53BP1 progression-free survival was 5.9 months (P <0.0001) and overall survival was 8.2 months (P=0.001). The expression of 53BP1 refines BRCA1-based predictive modeling to identify patients most likely to benefit from platinum-based chemotherapy. PMID:24197907

Predicting the size and elevation of future mountain forests: Scaling macroclimate to microclimate

NASA Astrophysics Data System (ADS)

Cory, S. T.; Smith, W. K.

2017-12-01

Global climate change is predicted to alter continental scale macroclimate and regional mesoclimate. Yet, it is at the microclimate scale that organisms interact with their physiochemical environments. Thus, to predict future changes in the biota such as biodiversity and distribution patterns, a quantitative coupling between macro-, meso-, and microclimatic parameters must be developed. We are evaluating the impact of climate change on the size and elevational distribution of conifer mountain forests by determining the microclimate necessary for new seedling survival at the elevational boundaries of the forest. This initial life stage, only a few centimeters away from the soil surface, appears to be the bottleneck to treeline migration and the expansion or contraction of a conifer mountain forest. For example, survival at the alpine treeline is extremely rare and appears to be limited to facilitated microsites with low sky exposure. Yet, abundant mesoclimate data from standard weather stations have rarely been scaled to the microclimate level. Our research is focusing on an empirical downscaling approach linking microclimate measurements at favorable seedling microsites to the meso- and macro-climate levels. Specifically, mesoclimate values of air temperature, relative humidity, incident sunlight, and wind speed from NOAA NCEI weather stations can be extrapolated to the microsite level that is physiologically relevant for seedling survival. Data will be presented showing a strong correlation between incident sunlight measured at 2-m and seedling microclimate, despite large differences from seedling/microsite temperatures. Our downscaling approach will ultimately enable predictions of microclimate from the much more abundant mesoclimate data available from a variety of sources. Thus, scaling from macro- to meso- to microclimate will be possible, enabling predictions of climate change models to be translated to the microsite level. This linkage between measurement scales will enable a more precise prediction of the effects of climate change on the future extent and elevational distribution of our mountain forests and an accompanying array of critical ecosystem services.

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

PubMed Central

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

2014-01-01

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

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.

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

PubMed Central

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

2015-01-01

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

The Preoperative Controlling Nutritional Status Score Predicts Survival After Curative Surgery in Patients with Pathological Stage I Non-small Cell Lung Cancer.

PubMed

Shoji, Fumihiro; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko

2017-02-01

The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; p<0.0001) were independent prognostic factors. In Kaplan-Meier analysis of recurrence-free survival (RFS), cancer-specific survival (CS), and overall survival (OS), the group with high CONUT score had a significantly shorter RFS, CS, and OS than did the low-CONUT score group by log-rank test (p=0.0458, p=0.0104 and p=0.0096, respectively). The preoperative CONUT score is both a predictive and prognostic factor in patients with pathological stage I NSCLC. This immuno-nutritional score can indicate patients at high risk of postoperative recurrence and death. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

The predicted influence of climate change on lesser prairie-chicken reproductive parameters

USGS Publications Warehouse

Grisham, Blake A.; Boal, Clint W.; Haukos, David A.; Davis, D.; Boydston, Kathy K.; Dixon, Charles; Heck, Willard R.

2013-01-01

The Southern High Plains is anticipated to experience significant changes in temperature and precipitation due to climate change. These changes may influence the lesser prairie-chicken (Tympanuchus pallidicinctus) in positive or negative ways. We assessed the potential changes in clutch size, incubation start date, and nest survival for lesser prairie-chickens for the years 2050 and 2080 based on modeled predictions of climate change and reproductive data for lesser prairie-chickens from 2001-2011 on the Southern High Plains of Texas and New Mexico. We developed 9 a priori models to assess the relationship between reproductive parameters and biologically relevant weather conditions. We selected weather variable(s) with the most model support and then obtained future predicted values from climatewizard.org. We conducted 1,000 simulations using each reproductive parameter's linear equation obtained from regression calculations, and the future predicted value for each weather variable to predict future reproductive parameter values for lesser prairie-chickens. There was a high degree of model uncertainty for each reproductive value. Winter temperature had the greatest effect size for all three parameters, suggesting a negative relationship between above-average winter temperature and reproductive output. The above-average winter temperatures are correlated to La Nina events, which negatively affect lesser prairie-chickens through resulting drought conditions. By 2050 and 2080, nest survival was predicted to be below levels considered viable for population persistence; however, our assessment did not consider annual survival of adults, chick survival, or the positive benefit of habitat management and conservation, which may ultimately offset the potentially negative effect of drought on nest survival.

The predicted influence of climate change on lesser prairie-chicken reproductive parameters.

PubMed

Grisham, Blake A; Boal, Clint W; Haukos, David A; Davis, Dawn M; Boydston, Kathy K; Dixon, Charles; Heck, Willard R

2013-01-01

The Southern High Plains is anticipated to experience significant changes in temperature and precipitation due to climate change. These changes may influence the lesser prairie-chicken (Tympanuchus pallidicinctus) in positive or negative ways. We assessed the potential changes in clutch size, incubation start date, and nest survival for lesser prairie-chickens for the years 2050 and 2080 based on modeled predictions of climate change and reproductive data for lesser prairie-chickens from 2001-2011 on the Southern High Plains of Texas and New Mexico. We developed 9 a priori models to assess the relationship between reproductive parameters and biologically relevant weather conditions. We selected weather variable(s) with the most model support and then obtained future predicted values from climatewizard.org. We conducted 1,000 simulations using each reproductive parameter's linear equation obtained from regression calculations, and the future predicted value for each weather variable to predict future reproductive parameter values for lesser prairie-chickens. There was a high degree of model uncertainty for each reproductive value. Winter temperature had the greatest effect size for all three parameters, suggesting a negative relationship between above-average winter temperature and reproductive output. The above-average winter temperatures are correlated to La Niña events, which negatively affect lesser prairie-chickens through resulting drought conditions. By 2050 and 2080, nest survival was predicted to be below levels considered viable for population persistence; however, our assessment did not consider annual survival of adults, chick survival, or the positive benefit of habitat management and conservation, which may ultimately offset the potentially negative effect of drought on nest survival.

Body mass index and cholesterol level predict surgical outcome in patients with hepatocellular carcinoma in Taiwan - a cohort study.

PubMed

Lee, Ya-Ling; Li, Wan-Chun; Tsai, Tung-Hu; Chiang, Hsin-Yu; Ting, Chin-Tsung

2016-04-19

Curative surgical resection (CSR) remains the most effective therapeutic intervention for patients with hepatocellular carcinoma (HCC); however, frequent post-surgical recurrence leads to high cancer related mortality. This study aimed to clarify the role of body mass index (BMI) and serum cholesterol level in predicting post-surgical outcomes in HCC patients after CSR. A total of 484 HCC patients including 213 BMIhigh and 271 BMIlow patients were included. Overall survival (OS) and recurrence-free survival (RFS) rates were examined in patients with differential BMI and serum cholesterol level. The analysis showed that significant different 1-, 3- and 5-year cumulative OS rates (P-value=0.015) and RFS rate (P-value=0.010) between BMIlow and BMIhigh patients. Further analysis in groups with differential serum cholesterol levels among BMIlow and BMIhigh patients indicated that the BMIlow/Chollow patients exhibited the significant lower cumulative OS and RFS rates in comparison with the remaining subjects (P-value=0.007 and 0.039 for OS and RFS rates, respectively). In conclusion, the coexistence of low BMI and low serum cholesterol level could serve as prognostic factors to predict post-operative outcomes in HCC patients undergoing surgical hepatectomy.

Soluble CD30 levels in recipients undergoing heart transplantation do not predict post-transplant outcome.

PubMed

Ypsilantis, Efthymios; Key, Timothy; Bradley, J Andrew; Morgan, C Helen; Tsui, Stephen; Parameshwar, Jayan; Taylor, Craig J

2009-11-01

The pre-transplant serum level of soluble CD30 (sCD30), a proteolytic derivative of the lymphocyte surface receptor CD30, has been suggested as a biomarker for immunologic risk after organ transplantation. Pre-transplant serum sCD30 levels were determined in 200 consecutive adult heart transplant recipients undertaken at a single center. Transplant outcome (acute rejection in the first 12 months and patient survival up to 5 years post-transplant) was determined. Patients treated with a left ventricular assist device (LVAD) prior to transplantation (n = 28) had higher levels of sCD30 (median 64 U/ml, range 12 to 112 U/ml) than those (n = 172) with no LVAD (median 36 U/ml, range 1 to 158 U/ml, p < 0.0001). Recipients were categorized according to whether sCD30 levels were "low" (lower quartile, <24 U/ml, n = 50), "intermediate" (24 to 58 U/ml, n = 100) or "high" (upper quartile, >58 U/ml, n = 50). Neither acute rejection nor recipient survival differed according to sCD30 level, with values (mean +/- SEM) of 0.30 +/- 0.04, 0.23 +/- 0.03 and 0.30 +/- 0.05 acute rejection episodes per 100 days in the low, intermediate and high groups, respectively, with recipient survival rates at 1 year of 77.7%, 84.9% and 86% and at 5 years of 73.6%, 67.9% and 75.8%, respectively. Pre-transplant serum sCD30 level does not predict acute allograft rejection or recipient survival after heart transplantation, although sCD30 levels are increased by LVAD, possibly as a result of biomaterial-host immune interaction.

Plasma serotonin level is a predictor for recurrence and poor prognosis in colorectal cancer patients.

PubMed

Xia, Yan; Wang, Dawei; Zhang, Nan; Wang, Zhihao; Pang, Li

2018-02-01

To investigate the prognostic value of plasma serotonin levels in colorectal cancer (CRC). Preoperative plasma serotonin levels of 150 healthy control (HC) cases, 150 benign colorectal polyp (BCP) cases, and 176 CRC cases were determined using radioimmunoassay assay. Serotonin levels were compared between HC, BCP, and CRC cases, and those in CRC patients were related to 5-year outcome. Plasma serotonin levels were markedly higher in CRC patients than in either HCs or BCP cases. An elevated serotonin level was significantly associated with advanced tumor node metastasis. Receiver operating characteristic curve analysis showed that the level of serotonin had a high predictive value for disease recurrence and mortality. Multivariate analysis revealed that high serotonin level was significantly associated with poor recurrence-free survival and overall survival. Our results suggest that a high peri-operative plasma serotonin level is useful as a prognostic biomarker for CRC recurrence and poor survival. © 2017 Wiley Periodicals, Inc.

Pretreatment TG/HDL-C Ratio Is Superior to Triacylglycerol Level as an Independent Prognostic Factor for the Survival of Triple Negative Breast Cancer Patients.

PubMed

Dai, Danian; Chen, Bo; Wang, Bin; Tang, Hailin; Li, Xing; Zhao, Zhiping; Li, Xuan; Xie, Xiaoming; Wei, Weidong

2016-01-01

Previous studies have reported that the triacylglycerol (TG) level and high-density lipoprotein cholesterol (HDL-C) are connected with breast cancer. However, the prognostic utility of the TG level and the TG/HDL-C ratio (THR) as conventional biomarkers in patients with triple negative breast cancer (TNBC) has not been elucidated. In this research, we investigate and compare the predictive value of the pretreatment serum TG level and THR in TNBC patients. We evaluated 221 patients with TNBC who had pretreatment conventional blood biochemical examinations and calculated the THR. Univariate and multivariate logistic regression analyses were used to assess the effect of the TG level and the THR on overall survival (OS) and disease-free survival (DFS). The optimal cutoff values of the TG level and the THR were determined to be 0.935 mmol/L and 0.600, respectively. As shown in a Kaplan-Meier analysis, TNBC patients with a high TG level and THR had shorter OS and DFS than patients in the low-level groups ( p < 0.05). The multivariate analysis suggested that the pretreatment THR level is an independent prognostic factor of OS (HR: 1.935; 95%CI: 1.032-3.629; p = 0.040) in TNBC patients. In conclusion, our data indicate that a high THR is an independent predictor and is superior to the TG level for predicting poor clinical outcomes in TNBC patients.

Prognostic significance of combined albumin-bilirubin and tumor-node-metastasis staging system in patients who underwent hepatic resection for hepatocellular carcinoma.

PubMed

Harimoto, Norifumi; Yoshizumi, Tomoharu; Sakata, Kazuhito; Nagatsu, Akihisa; Motomura, Takashi; Itoh, Shinji; Harada, Noboru; Ikegami, Toru; Uchiyama, Hideaki; Soejima, Yuji; Maehara, Yoshihiko

2017-11-01

In recent years, the establishment of new staging systems for hepatocellular carcinoma (HCC) has been reported worldwide. The system combining albumin-bilirubin (ALBI) with tumor-node-metastasis stage, developed by the Liver Cancer Study Group of Japan, was called the ALBI-T score. Patient data were retrospectively collected for 357 consecutive patients who had undergone hepatic resection for HCC with curative intent between January 2004 and December 2015. The overall survival and recurrence-free survival were compared by the Kaplan-Meier method, using different staging systems: the Japan integrated staging (JIS), modified JIS, and ALBI-T. Multivariate analysis identified five poor prognostic factors (higher age, poor differentiation, the presence of microvascular invasion, the presence of intrahepatic metastasis, and blood transfusion) that influenced overall survival, and four poor prognostic factors (the presence of intrahepatic metastasis, serum α-fetoprotein level, blood transfusion, and each staging system (JIS, modified JIS, and ALBI-T score)) that influenced recurrence-free survival. Patients for each these three staging system had a significantly worse prognosis regarding recurrence-free survival, but not with overall survival. The modified JIS score showed the lowest Akaike information criteria statistic value, indicating it had the best ability to predict overall survival compared with the other staging systems. This retrospective analysis showed that, in post-hepatectomy patients with HCC, the ALBI-T score is predictive of worse recurrence-free survival, even when adjustments are made for other known predictors. However, modified JIS is better than ALBI-T in predicting overall survival. © 2017 The Japan Society of Hepatology.

A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival.

PubMed

Botta, C; Di Martino, M T; Ciliberto, D; Cucè, M; Correale, P; Rossi, M; Tagliaferri, P; Tassone, P

2016-12-16

Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then selected 20 candidate genes involved in B-cell inflammation and we investigated their role in predicting clinical outcome, through univariate and multivariate analyses (log-rank test, logistic regression and Cox-regression model). We defined an 8-genes signature (IL8, IL10, IL17A, CCL3, CCL5, VEGFA, EBI3 and NOS2) identifying each condition (MGUS/smoldering/symptomatic-MM) with 84% accuracy. Moreover, six genes (IFNG, IL2, LTA, CCL2, VEGFA, CCL3) were found independently correlated with patients' survival. Patients whose MM cells expressed high levels of Th1 cytokines (IFNG/LTA/IL2/CCL2) and low levels of CCL3 and VEGFA, experienced the longest survival. On these six genes, we built a prognostic risk score that was validated in three additional independent datasets. In this study, we provide proof-of-concept that inflammation has a critical role in MM patient progression and survival. The inflammatory-gene prognostic signature validated in different datasets clearly indicates novel opportunities for personalized anti-MM treatment.

Pre- and Posttransplant IgA Anti-Fab Antibodies to Predict Long-term Kidney Graft Survival.

PubMed

Amirzargar, M A; Amirzargar, A; Basiri, A; Hajilooi, M; Roshanaei, G; Rajabi, G; Solgi, G

2015-05-01

Immunologic factors are reliable markers for allograft monitoring, because of their seminal role in rejection process. One of these factors is the immunoglobulin (Ig)A anti-Fab of the IgG antibody. This study aimed to evaluate the predictive value of pre- and posttransplant levels of this marker for kidney allograft function and survival. Sera samples of 59 living unrelated donor kidney recipients were collected before and after transplantation (days 7, 14, and 30) and investigated for IgA anti-Fab of IgG antibody levels using enzyme-linked immunosorbent assay in relation with allograft outcome. Among 59 patients, 15 cases (25%) including 10 with acute rejection and 5 with chronic rejection episodes showed graft failure during a mean of 5 years of follow-up. High posttransplant levels of IgA anti-Fab antibodies were observed more frequently in patients with stable graft function (SGF) compared with patients with graft failure (P = 2 × 10(-6)). None of patients with acute or chronic rejection episodes had high levels of IgA anti-Fab antibodies at day 30 posttransplant compared with the SGF group (P = 10(-6) and P = .01, respectively). In addition, high levels of IgA anti-Fab antibody correlated with lesser concentration of serum creatinine at 1 month posttransplantation (P = .01). Five-year graft survival was associated with high levels of pre- and posttransplant IgA anti-Fab antibodies (P = .02 and P = .003, respectively). Our findings indicate the protective effect of higher levels of IgA anti-Fab antibodies regarding to kidney allograft outcomes and long-term graft survival. Copyright © 2015 Elsevier Inc. All rights reserved.

The Predicted Influence of Climate Change on Lesser Prairie-Chicken Reproductive Parameters

PubMed Central

Grisham, Blake A.; Boal, Clint W.; Haukos, David A.; Davis, Dawn M.; Boydston, Kathy K.; Dixon, Charles; Heck, Willard R.

2013-01-01

The Southern High Plains is anticipated to experience significant changes in temperature and precipitation due to climate change. These changes may influence the lesser prairie-chicken (Tympanuchus pallidicinctus) in positive or negative ways. We assessed the potential changes in clutch size, incubation start date, and nest survival for lesser prairie-chickens for the years 2050 and 2080 based on modeled predictions of climate change and reproductive data for lesser prairie-chickens from 2001–2011 on the Southern High Plains of Texas and New Mexico. We developed 9 a priori models to assess the relationship between reproductive parameters and biologically relevant weather conditions. We selected weather variable(s) with the most model support and then obtained future predicted values from climatewizard.org. We conducted 1,000 simulations using each reproductive parameter’s linear equation obtained from regression calculations, and the future predicted value for each weather variable to predict future reproductive parameter values for lesser prairie-chickens. There was a high degree of model uncertainty for each reproductive value. Winter temperature had the greatest effect size for all three parameters, suggesting a negative relationship between above-average winter temperature and reproductive output. The above-average winter temperatures are correlated to La Niña events, which negatively affect lesser prairie-chickens through resulting drought conditions. By 2050 and 2080, nest survival was predicted to be below levels considered viable for population persistence; however, our assessment did not consider annual survival of adults, chick survival, or the positive benefit of habitat management and conservation, which may ultimately offset the potentially negative effect of drought on nest survival. PMID:23874549

Model for breast cancer survival: relative prognostic roles of axillary nodal status, TNM stage, estrogen receptor concentration, and tumor necrosis.

PubMed

Shek, L L; Godolphin, W

1988-10-01

The independent prognostic effects of certain clinical and pathological variables measured at the time of primary diagnosis were assessed with Cox multivariate regression analysis. The 859 patients with primary breast cancer, on which the proportional hazards model was based, had a median follow-up of 60 months. Axillary nodal status (categorized as N0, N1-3 or N4+) was the most significant and independent factor in overall survival, but inclusion of TNM stage, estrogen receptor (ER) concentration and tumor necrosis significantly improved survival predictions. Predictions made with the model showed striking subset survival differences within stage: 5-year survival from 36% (N4+, loge[ER] = 0, marked necrosis) to 96% (N0, loge[ER] = 6, no necrosis) in TNM I, and from 0 to 70% for the same categories in TNM IV. Results of the model were used to classify patients into four distinct risk groups according to a derived hazard index. An 8-fold variation in survival was seen with the highest (greater than 3) to lowest index values (less than 1). Each hazard index level included patients with varied combinations of the above factors, but could be considered to denote the same degree of risk of breast cancer mortality. A model with ER concentration, nodal status, and tumor necrosis was found to best predict survival after disease recurrence in 369 patients, thus confirming the enduring biological significance of these factors.

Development of a nomogram incorporating serum C-reactive protein level to predict overall survival of patients with advanced urothelial carcinoma and its evaluation by decision curve analysis.

PubMed

Ishioka, J; Saito, K; Sakura, M; Yokoyama, M; Matsuoka, Y; Numao, N; Koga, F; Masuda, H; Fujii, Y; Kawakami, S; Kihara, K

2012-09-25

The purpose of this study is to investigate the prognostic impact of C-reactive protein (CRP) on patients with advanced urothelial carcinoma and to develop a novel nomogram predicting survival. A total of 223 consecutive patients were treated at Tokyo Medical and Dental Hospital. A nomogram incorporating V was developed based on the result of a Cox proportional hazards model. Its efficacy and clinical usefulness was evaluated by concordance index (c-index) and decision curve analysis. Of the 223 patients, 184 (83%) died of cancer. Median follow-up periods of patients who died and those who remained alive were 5 and 11 months, respectively. We developed a novel nomogram incorporating Eastern Cooperative Oncology Group Performance Status, presence of visceral metastasis, haemoglobin and age. The c-index of the nomogram predicting survival probability 6 and 12 months after diagnosis was 0.788 and 0.765, respectively. Decision curve analyses revealed that the novel nomogram incorporating CRP had a superior net benefit than that without CRP for most of the examined probabilities. We demonstrated the prognostic impact of CRP that improved the predictive accuracy of a nomogram for survival probability in patients with advanced urothelial carcinoma.

Feature selection through validation and un-censoring of endovascular repair survival data for predicting the risk of re-intervention.

PubMed

Attallah, Omneya; Karthikesalingam, Alan; Holt, Peter J E; Thompson, Matthew M; Sayers, Rob; Bown, Matthew J; Choke, Eddie C; Ma, Xianghong

2017-08-03

Feature selection (FS) process is essential in the medical area as it reduces the effort and time needed for physicians to measure unnecessary features. Choosing useful variables is a difficult task with the presence of censoring which is the unique characteristic in survival analysis. Most survival FS methods depend on Cox's proportional hazard model; however, machine learning techniques (MLT) are preferred but not commonly used due to censoring. Techniques that have been proposed to adopt MLT to perform FS with survival data cannot be used with the high level of censoring. The researcher's previous publications proposed a technique to deal with the high level of censoring. It also used existing FS techniques to reduce dataset dimension. However, in this paper a new FS technique was proposed and combined with feature transformation and the proposed uncensoring approaches to select a reduced set of features and produce a stable predictive model. In this paper, a FS technique based on artificial neural network (ANN) MLT is proposed to deal with highly censored Endovascular Aortic Repair (EVAR). Survival data EVAR datasets were collected during 2004 to 2010 from two vascular centers in order to produce a final stable model. They contain almost 91% of censored patients. The proposed approach used a wrapper FS method with ANN to select a reduced subset of features that predict the risk of EVAR re-intervention after 5 years to patients from two different centers located in the United Kingdom, to allow it to be potentially applied to cross-centers predictions. The proposed model is compared with the two popular FS techniques; Akaike and Bayesian information criteria (AIC, BIC) that are used with Cox's model. The final model outperforms other methods in distinguishing the high and low risk groups; as they both have concordance index and estimated AUC better than the Cox's model based on AIC, BIC, Lasso, and SCAD approaches. These models have p-values lower than 0.05, meaning that patients with different risk groups can be separated significantly and those who would need re-intervention can be correctly predicted. The proposed approach will save time and effort made by physicians to collect unnecessary variables. The final reduced model was able to predict the long-term risk of aortic complications after EVAR. This predictive model can help clinicians decide patients' future observation plan.

The role of radiotherapy in the management of patients with diffuse low grade glioma: A systematic review and evidence-based clinical practice guideline.

PubMed

Ryken, Timothy C; Parney, Ian; Buatti, John; Kalkanis, Steven N; Olson, Jeffrey J

2015-12-01

(1) What is the optimal role of external beam radiotherapy in the management of adult patients with newly diagnosed low-grade glioma (LGG) in terms of improving outcome (i.e., survival, complications, seizure control or other reported outcomes of interest)? (2) Which radiation strategies (dose, timing, fractionation, stereotactic radiation, brachytherapy, chemotherapy) improve outcomes compared to standard external beam radiation therapy in the initial management of low grade gliomas in adults? (3) Do specific factors (e.g., age, volume, extent of resection, genetic subtype) identify subgroups with better outcomes following radiation therapy than the general population of adults with newly diagnosed low-grade gliomas? These recommendations apply to adults with newly diagnosed diffuse LGG. OUTCOMES IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA TREATED WITH RADIOTHERAPY: Level I Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong progression free survival, irrespective of extent of resection. Level II Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults as an equivalent alternative to observation in preserving cognitive function, irrespective of extent of resection. Level III Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults to improve seizure control in patients with epilepsy and subtotal resection. Level III Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong overall survival in patients with subtotal resection. Level III Consideration of the risk of radiation induced morbidity, including cognitive decline, imaging abnormalities, metabolic dysfunction and malignant transformation, is recommended when the delivery of radiotherapy is selected in the management of newly diagnosed low-grade glioma in adults. STRATEGIES OF RADIOTHERAPY IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA: Level I Lower dose radiotherapy is recommended as an equivalent alternative to higher dose immediate postoperative radiotherapy (45-50.4 vs. 59.4-64.8 Gy) in the management of newly diagnosed low-grade glioma in adults with reduced toxicity. Level III Delaying radiotherapy until recurrence or progression is recommended as an equivalent alternative to immediate postoperative radiotherapy in the management of newly diagnosed low-grade glioma in adults but may result in shorter time to progression. Level III The addition of chemotherapy to radiotherapy is not recommended over whole brain radiotherapy alone in the management of low-grade glioma, as it provides no additional survival benefit. Level III Limited-field radiotherapy is recommended over whole brain radiotherapy in the management of low-grade glioma. Level III Either stereotactic radiosurgery or brachytherapy are recommended as acceptable alternatives to external radiotherapy in selected patients. PROGNOSTIC FACTORS IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA TREATED WITH RADIOTHERAPY: Level II It is recommended that age greater than 40 years, astrocytic pathology, diameter greater than 6 cm, tumor crossing the midline and preoperative neurological deficit be considered as negative prognostic indicators when predicting overall survival in adult low grade glioma patients treated with radiotherapy. Level II It is recommended that smaller tumor size, extent of surgical resection and higher mini-mental status exam be considered as positive prognostic indicators when predicting overall survival and progression free survival in patients in adult low grade glioma patients treated with radiotherapy. Level III It is recommended that seizures at presentation, presence of oligodendroglial histological component and 1p19q deletion (along with additional relevant factors-see Table 1) be considered as positive prognostic indicators when predicting response to radiotherapy in adults with low grade gliomas. Level III It is recommended that increasing age, decreasing performance status, decreasing cognition, presence of astrocytic histological component (along with additional relevant factors (see Tables 1, 2) be considered as negative prognostic indicators when predicting response to radiotherapy.

Identification of miRNA-Mediated Core Gene Module for Glioma Patient Prediction by Integrating High-Throughput miRNA, mRNA Expression and Pathway Structure

PubMed Central

Han, Junwei; Shang, Desi; Zhang, Yunpeng; Zhang, Wei; Yao, Qianlan; Han, Lei; Xu, Yanjun; Yan, Wei; Bao, Zhaoshi; You, Gan; Jiang, Tao; Kang, Chunsheng; Li, Xia

2014-01-01

The prognosis of glioma patients is usually poor, especially in patients with glioblastoma (World Health Organization (WHO) grade IV). The regulatory functions of microRNA (miRNA) on genes have important implications in glioma cell survival. However, there are not many studies that have investigated glioma survival by integrating miRNAs and genes while also considering pathway structure. In this study, we performed sample-matched miRNA and mRNA expression profilings to systematically analyze glioma patient survival. During this analytical process, we developed pathway-based random walk to identify a glioma core miRNA-gene module, simultaneously considering pathway structure information and multi-level involvement of miRNAs and genes. The core miRNA-gene module we identified was comprised of four apparent sub-modules; all four sub-modules displayed a significant correlation with patient survival in the testing set (P-values≤0.001). Notably, one sub-module that consisted of 6 miRNAs and 26 genes also correlated with survival time in the high-grade subgroup (WHO grade III and IV), P-value = 0.0062. Furthermore, the 26-gene expression signature from this sub-module had robust predictive power in four independent, publicly available glioma datasets. Our findings suggested that the expression signatures, which were identified by integration of miRNA and gene level, were closely associated with overall survival among the glioma patients with various grades. PMID:24809850

DeepSurv: personalized treatment recommender system using a Cox proportional hazards deep neural network.

PubMed

Katzman, Jared L; Shaham, Uri; Cloninger, Alexander; Bates, Jonathan; Jiang, Tingting; Kluger, Yuval

2018-02-26

Medical practitioners use survival models to explore and understand the relationships between patients' covariates (e.g. clinical and genetic features) and the effectiveness of various treatment options. Standard survival models like the linear Cox proportional hazards model require extensive feature engineering or prior medical knowledge to model treatment interaction at an individual level. While nonlinear survival methods, such as neural networks and survival forests, can inherently model these high-level interaction terms, they have yet to be shown as effective treatment recommender systems. We introduce DeepSurv, a Cox proportional hazards deep neural network and state-of-the-art survival method for modeling interactions between a patient's covariates and treatment effectiveness in order to provide personalized treatment recommendations. We perform a number of experiments training DeepSurv on simulated and real survival data. We demonstrate that DeepSurv performs as well as or better than other state-of-the-art survival models and validate that DeepSurv successfully models increasingly complex relationships between a patient's covariates and their risk of failure. We then show how DeepSurv models the relationship between a patient's features and effectiveness of different treatment options to show how DeepSurv can be used to provide individual treatment recommendations. Finally, we train DeepSurv on real clinical studies to demonstrate how it's personalized treatment recommendations would increase the survival time of a set of patients. The predictive and modeling capabilities of DeepSurv will enable medical researchers to use deep neural networks as a tool in their exploration, understanding, and prediction of the effects of a patient's characteristics on their risk of failure.

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

PubMed

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

2013-01-01

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

Serum leptin level and waist-to-hip ratio (WHR) predict the overall survival of metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs).

PubMed

Artac, Mehmet; Bozcuk, Hakan; Kiyici, Aysel; Eren, Orhan Onder; Boruban, Melih Cem; Ozdogan, Mustafa

2013-04-01

Our objective was to determine whether serum leptin levels and obesity-related factors could affect outcome for metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs). Sixty MBC patients treated with first line hormonal therapy were enrolled in this study. Median age was 51 years (range 28-75). Median leptin level was 19400 pg/ml (1970-91900) and estradiol level 29.6 pg/ml (4.0-181.9). Factors associated with overall survival in univariate analysis were age and waist-to-hip ratio (WHR), whereas only WHR retained significance in the multivariate analysis. However, no factor was associated with progression-free survival. However, WHR was found to be a significant prognostic marker only if the leptin level was ≥19400 pg/ml (HR = 0.38; 95% CI: 0.16-0.91). This study suggests that serum leptin levels and WHR together may serve as potential prognostic markers in MBC patients treated with AIs.

A Multifactorial Analysis of Melanoma: Prognostic Histopathological Features Comparing Clark's and Breslow's Staging Methods

PubMed Central

Balch, Charles M.; Murad, Tariq M.; Soong, Seng-Jaw; Ingalls, Anna Lee; Halpern, Norman B.; Maddox, William A.

1978-01-01

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (≥4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors. PMID:736651

Review and evaluation of performance measures for survival prediction models in external validation settings.

PubMed

Rahman, M Shafiqur; Ambler, Gareth; Choodari-Oskooei, Babak; Omar, Rumana Z

2017-04-18

When developing a prediction model for survival data it is essential to validate its performance in external validation settings using appropriate performance measures. Although a number of such measures have been proposed, there is only limited guidance regarding their use in the context of model validation. This paper reviewed and evaluated a wide range of performance measures to provide some guidelines for their use in practice. An extensive simulation study based on two clinical datasets was conducted to investigate the performance of the measures in external validation settings. Measures were selected from categories that assess the overall performance, discrimination and calibration of a survival prediction model. Some of these have been modified to allow their use with validation data, and a case study is provided to describe how these measures can be estimated in practice. The measures were evaluated with respect to their robustness to censoring and ease of interpretation. All measures are implemented, or are straightforward to implement, in statistical software. Most of the performance measures were reasonably robust to moderate levels of censoring. One exception was Harrell's concordance measure which tended to increase as censoring increased. We recommend that Uno's concordance measure is used to quantify concordance when there are moderate levels of censoring. Alternatively, Gönen and Heller's measure could be considered, especially if censoring is very high, but we suggest that the prediction model is re-calibrated first. We also recommend that Royston's D is routinely reported to assess discrimination since it has an appealing interpretation. The calibration slope is useful for both internal and external validation settings and recommended to report routinely. Our recommendation would be to use any of the predictive accuracy measures and provide the corresponding predictive accuracy curves. In addition, we recommend to investigate the characteristics of the validation data such as the level of censoring and the distribution of the prognostic index derived in the validation setting before choosing the performance measures.

Baseline nutritional status is predictive of response to treatment and survival in patients treated by definitive chemoradiotherapy for a locally advanced esophageal cancer.

PubMed

Di Fiore, Frédéric; Lecleire, Stéphane; Pop, Daniela; Rigal, Olivier; Hamidou, Hadji; Paillot, Bernard; Ducrotté, Philippe; Lerebours, Eric; Michel, Pierre

2007-11-01

To assess the impact of baseline nutritional status on treatment response and survival in nonmetastatic patients with a locally advanced esophageal cancer (LAEC) treated with definitive chemoradiotherapy (CRT). One hundred five patients with LAEC treated by definitive CRT were retrospectively included. The CRT regimen was based on an external radiotherapy (RT) delivered concomitantly to a cisplatin-based chemotherapy (CT). Patients were considered to have a complete response (CR) to CRT when no residual tumor was detected on CT scan and esophagoscopy performed 2 months after the end of CRT. Multivariate analysis of predictive factors of response to CRT and survival were performed using a logistic regression and a Cox model, respectively. Mean value of baseline nutritional parameters was significantly different between nonresponder (N = 42) and responder (N = 63) patients to CRT (weight loss 10%vs 5.8%, P= 0.0047; serum albumin level 35 g/L vs 38.7 g/L, P= 0.0004; BMI 22.8 kg/m2vs 25.2 kg/m2, P= 0.01). In multivariate analysis, serum albumin level > 35 g/L was the only independent predictive factor of CR to CRT (P= 0.009). Independent prognostic factors of survival were BMI > 18 kg/m2 (P= 0.003), dysphagia Atkinson score <2 (P= 0.008), dose of RT > 50 Grays (Gy) (P < 0.0001) and CR to CRT (P < 0.0001). Survival was influenced by baseline nutritional status as well as dysphagia, dose of RT, and CR to CRT. Despite the retrospective design of the study, our results may provide the concept basis for performing a prospective nutritional intervention study in patients treated by definitive CRT for an esophageal cancer.

Time prediction of failure a type of lamps by using general composite hazard rate model

NASA Astrophysics Data System (ADS)

Riaman; Lesmana, E.; Subartini, B.; Supian, S.

2018-03-01

This paper discusses the basic survival model estimates to obtain the average predictive value of lamp failure time. This estimate is for the parametric model, General Composite Hazard Level Model. The random time variable model used is the exponential distribution model, as the basis, which has a constant hazard function. In this case, we discuss an example of survival model estimation for a composite hazard function, using an exponential model as its basis. To estimate this model is done by estimating model parameters, through the construction of survival function and empirical cumulative function. The model obtained, will then be used to predict the average failure time of the model, for the type of lamp. By grouping the data into several intervals and the average value of failure at each interval, then calculate the average failure time of a model based on each interval, the p value obtained from the tes result is 0.3296.

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. Copyright © 2015. Published by Elsevier Ltd.

Alpha-fetoprotein and (18)F-FDG positron emission tomography predict tumor recurrence better than Milan criteria in living donor liver transplantation.

PubMed

Hong, Geun; Suh, Kyung-Suk; Suh, Suk-Won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Paeng, Jin Chul; Yi, Nam-Joon; Lee, Kwang-Woong

2016-04-01

Given the organ shortage for liver transplantation (LT) and the limitations of the current morphology-based selection criteria, improved criteria are needed to achieve the maximum benefit of LT for hepatocellular carcinoma (HCC). We hypothesized that a combination of biological markers may better predict the prognosis than the Milan criteria. HCC patients (n=123) with preoperative data on serum alpha-fetoprotein (AFP) levels and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) positivity underwent live-donor LT between January 2003 and December 2009. The cut-off values for serum AFP levels (200 ng/ml) and (18)F-FDG PET positivity (1.10) for tumor recurrence were determined by c-statistics using receiver operating characteristic curves. Univariate and multivariate analyses with preoperative variables were performed to find pre-transplant prognostic factors. Disease-free survival rates and overall survival rates were analysed with regard to serum AFP levels and (18)F-FDG PET positivity. The 5-year disease-free survival rates and overall survival rates were 80.3% and 81.6% respectively. (18)F-FDG PET positivity (hazard ratio (HR) 9.766, 95% CI 3.557-26.816; p<0.001) and serum AFP level (HR 6.234, 95% CI 2.643-14.707; p<0.001) were the only significant pre-transplant prognostic factors in the multivariate analysis; tumor number and size were not significant. A combination of criteria showed that the biologically high-risk group (AFP level ⩾200 ng/ml and PET-positive) had an HR of 29.069 (95% CI 8.797-96.053; p<0.001) compared with the double-negative group. Use of the Milan criteria yielded an HR of 1.351 (95% CI 0.500-3.652; p=0.553). The combination of the serum AFP level and (18)F-FDG PET data predicted better outcomes than those using the Milan criteria, improving objectivity when adult-to-adult living donor LT is contemplated. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Identification of Rhizobium phaseoli Strains That Are Tolerant or Sensitive to Soil Acidity

PubMed Central

Lowendorf, Henry S.; Alexander, Martin

1983-01-01

A study was conducted to determine whether the survival of Rhizobium phaseoli in acid soils could be predicted on the basis of the tolerance of the organism to acidity in culture. Of 16 strains tested, all grew in culture at pH 4.6, but only those that grew at pH 3.8 survived in soils having pH values of 4.1 to 4.6. Strains that tolerated the lowest pH values in culture were tolerant of the highest aluminum concentrations. In one acid soil, an acid-tolerant strain was unable to survive in numbers greater than 100/g, but the poor survival was not related to the level of extractable aluminum or manganese in the soil. Reproduction of an acid-tolerant strain of R. phaseoli was enhanced in the rhizosphere of Phaseolus vulgaris in both acid and limed soils, but stimulation of an acid-sensitive strain by the plant occurred only in the limed soil. These results indicate that cultural tests can be used to predict the ability of R. phaseoli to survive in acid soil. PMID:16346239

Modelling survival: exposure pattern, species sensitivity and uncertainty.

PubMed

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B; Van den Brink, Paul J; Veltman, Karin; Vogel, Sören; Zimmer, Elke I; Preuss, Thomas G

2016-07-06

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

Modelling survival: exposure pattern, species sensitivity and uncertainty

NASA Astrophysics Data System (ADS)

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I.; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B.; van den Brink, Paul J.; Veltman, Karin; Vogel, Sören; Zimmer, Elke I.; Preuss, Thomas G.

2016-07-01

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

Predictive Value of Procalcitonin for Infection and Survival in Adult Cardiogenic Shock Patients Treated with Extracorporeal Membrane Oxygenation

PubMed Central

Kim, Do Wan; Cho, Hwa Jin; Kim, Gwan Sic; Song, Sang Yun; Na, Kook Joo; Oh, Sang Gi

2018-01-01

Procalcitonin (PCT) is a predictive marker for the occurrence of bacterial infection and the decision to terminate antibiotic treatment in critically ill patients. An unusual increase in PCT, regardless of infection, has been observed during extracorporeal membrane oxygenation (ECMO) support. We evaluated trends and the predictive value of PCT levels in adult cardiogenic shock during treatment with ECMO. We reviewed the clinical records of 38 adult cardiogenic shock patients undergoing veno-arterial ECMO support between January 2014 and December 2016. The exclusion criteria were age <18 years, pre-ECMO infection, and less than 48 hours of support. The mean patient age was 56.7±14.7 years and 12 (31.6%) patients were female. The mean duration of ECMO support was 9.0±7.6 days. The rates of successful ECMO weaning and survival to discharge were 55.3% (n=21) and 52.6% (n=20), respectively. There were 17 nosocomial infections in 16 (42.1%) patients. Peak PCT levels (mean 25.6±9.4 ng/mL) were reached within 48 hours after initiation of ECMO support and decreased to ≤5 ng/mL within one week. The change in PCT levels was not useful in predicting the occurrence of new nosocomial infections during the ECMO run. However, a PCT level >10 ng/mL during the first week of ECMO support was significantly associated with mortality (p<0.01). The change in PCT level was not useful in predicting new infection during ECMO support. However, higher PCT levels within the first week of the ECMO run are associated with significantly higher mortality. PMID:29399566

The value of time-averaged serum high-sensitivity C-reactive protein in prediction of mortality and dropout in peritoneal dialysis patients.

PubMed

Liu, Shou-Hsuan; Chen, Chao-Yu; Li, Yi-Jung; Wu, Hsin-Hsu; Lin, Chan-Yu; Chen, Yung-Chang; Chang, Ming-Yang; Hsu, Hsiang-Hao; Ku, Cheng-Lung; Tian, Ya-Chung

2017-01-01

C-reactive protein (CRP) is a useful biomarker for prediction of long-term outcomes in patients undergoing chronic dialysis. This observational cohort study evaluated whether the time-averaged serum high-sensitivity CRP (HS-CRP) level was a better predictor of clinical outcomes than a single HS-CRP level in patients undergoing peritoneal dialysis (PD). We classified 335 patients into three tertiles according to the time-averaged serum HS-CRP level and followed up regularly from January 2010 to December 2014. Clinical outcomes such as cardiovascular events, infection episodes, newly developed malignancy, encapsulating peritoneal sclerosis (EPS), dropout (death plus conversion to hemodialysis), and mortality were assessed. During a 5-year follow-up, 164 patients (49.0%) ceased PD; this included 52 patient deaths (15.5%), 100 patients (29.9%) who converted to hemodialysis, and 12 patients (3.6%) who received a kidney transplantation. The Kaplan-Meier survival analysis and log-rank test revealed a significantly worse survival accumulation in patients with high time-average HS-CRP levels. A multivariate Cox regression analysis revealed that a higher time-averaged serum HS-CRP level, older age, and the occurrence of cardiovascular events were independent mortality predictors. A higher time-averaged serum HS-CRP level, the occurrence of cardiovascular events, infection episodes, and EPS were important predictors of dropout. The receiver operating characteristic analysis verified that the value of the time-average HS-CRP level in predicting the 5-year mortality and dropout was superior to a single serum baseline HS-CRP level. This study shows that the time-averaged serum HS-CRP level is a better marker than a single baseline measurement in predicting the 5-year mortality and dropout in PD patients.

The place of targeted therapies in the management of non-small cell bronchial carcinoma. Molecular markers as predictors of tumor response and survival in lung cancer.

PubMed

Rosell, R; Moran, T; Fernanda Salazar, M; Mendez, P; De Aguirre, I; Ramirez, J-L; Isla, D; Cobo, M; Camps, C; Lopez-Vivanco, G; Alberola, V; Taron, M

2006-11-01

This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future. Abundant pre-clinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Low levels predict cisplatin sensitivity and antimicrotubule drug resistance, and the opposite occurs with high levels. The main core of recent research has centered on epidermal growth factor receptor (EGFR) mutations and gene copy numbers. For the first time, EGFR mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas, with a threefold increase in time to progression and survival in patients receiving EGFR tyrosine-kinase inhibitors. Evidence has also been accumulated on the crosstalk between estrogen and EGFR receptor pathways, paving the way for clinical trials of EGFR tyrosine-kinase inhibitors plus aromatase inhibitors. Understanding the relevance of these findings can help to change the clinical practice in oncology towards customizing chemotherapy and targeted therapies, leading to improvement both in survival and in cost-effectiveness.

Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

PubMed

Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

2012-04-01

We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

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.

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

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

PubMed Central

Cross, Brian W.; Johnson, Timothy V.; DeRosa, Austin B.; Ogan, Kenneth; Pattaras, John G.; Nieh, Peter T.; Kucuk, Omer; Harris, Wayne B.; Master, Viraj A.

2012-01-01

Objectives. To determine the relationship between preoperative erythrocyte sedimentation rate (ESR) and overall survival in localized renal cell carcinoma (RCC) following nephrectomy. Methods. 167 patients undergoing nephrectomy for localized RCC had ESR levels measured preoperatively. Receiver Operating Characteristics curves were used to determine Area Under the Curve and relative sensitivity and specificity of preoperative ESR in predicting overall survival. Cut-offs for low (0.0–20.0 mm/hr), intermediate (20.1–50.0 mm/hr), and high risk (>50.0 mm/hr) groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based groups on overall survival. Univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results. Overall, 55.2% were low risk, while 27.0% and 17.8% were intermediate and high risk, respectively. Median (95% CI) survival was 44.1 (42.6–45.5) months, 35.5 (32.3–38.8) months, and 32.1 (25.5–38.6) months, respectively. After controlling for other patient and tumor characteristics, intermediate and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735–27.649) and 18.5-fold (HR: 18.531, 95% CI: 2.117–162.228) increased risk of overall mortality, respectively. Conclusion. Preoperative ESR values represent a robust predictor of overall survival following nephrectomy in localized RCC. PMID:22900160

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study.

PubMed

Hamilton, C A; Miller, A; Casablanca, Y; Horowitz, N S; Rungruang, B; Krivak, T C; Richard, S D; Rodriguez, N; Birrer, M J; Backes, F J; Geller, M A; Quinn, M; Goodheart, M J; Mutch, D G; Kavanagh, J J; Maxwell, G L; Bookman, M A

2018-02-01

To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. Published by Elsevier Inc.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study

PubMed Central

Hamilton, C. A.; Miller, A.; Casablanca, Y.; Horowitz, N. S.; Rungruang, B.; Krivak, T. C.; Richard, S. D.; Rodriguez, N.; Birrer, M.J.; Backes, F.J.; Geller, M.A.; Quinn, M.; Goodheart, M.J.; Mutch, D.G.; Kavanagh, J.J.; Maxwell, G. L.; Bookman, M. A.

2018-01-01

Objective To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Methods Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10 years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). Results The analysis dataset included 3,010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. Conclusions The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. PMID:29195926

Population dynamics of hispid cotton rats (Sigmodon hispidus) across a nitrogen-amended landscape

USGS Publications Warehouse

Clark, J.E.; Hellgren, E.C.; Jorgensen, E.E.; Tunnell, S.J.; Engle, David M.; Leslie, David M.

2003-01-01

We conducted a mark-recapture experiment to examine the population dynamics of hispid cotton rats (Sigmodon hispidus) in response to low-level nitrogen amendments (16.4 kg nitrogen/ha per year) and exclosure fencing in an old-field grassland. The experimental design consisted of sixteen 0.16-ha plots with 4 replicates of each treatment combination. We predicted that densities, reproductive success, movement probabilities, and survival rates of cotton rats would be greater on nitrogen-amended plots because of greater aboveground biomass and canopy cover. Population densities of cotton rats tended to be highest on fenced nitrogen plots, but densities on unfenced nitrogen plots were similar to those on control and fenced plots. We observed no distinct patterns in survival rates, reproductive success, or movement probabilities with regard to nitrogen treatments. However, survival rates and reproductive success tended to be higher for cotton rats on fenced plots than for those on unfenced plots and this was likely attributable to decreased predation on fenced plots. As low-level nitrogen amendments continue to be applied, we predict that survival, reproduction, and population-growth rates of cotton rats on control plots, especially fenced plots with no nitrogen amendment, will eventually exceed those on nitrogen-amended plots as a result of higher plant-species diversity, greater food availability, and better quality cover.

Radiomic texture-curvature (RTC) features for precision medicine of patients with rheumatoid arthritis-associated interstitial lung disease

NASA Astrophysics Data System (ADS)

Watari, Chinatsu; Matsuhiro, Mikio; Näppi, Janne J.; Nasirudin, Radin A.; Hironaka, Toru; Kawata, Yoshiki; Niki, Noboru; Yoshida, Hiroyuki

2018-03-01

We investigated the effect of radiomic texture-curvature (RTC) features of lung CT images in the prediction of the overall survival of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We retrospectively collected 70 RA-ILD patients who underwent thin-section lung CT and serial pulmonary function tests. After the extraction of the lung region, we computed hyper-curvature features that included the principal curvatures, curvedness, bright/dark sheets, cylinders, blobs, and curvature scales for the bronchi and the aerated lungs. We also computed gray-level co-occurrence matrix (GLCM) texture features on the segmented lungs. An elastic-net penalty method was used to select and combine these features with a Cox proportional hazards model for predicting the survival of the patient. Evaluation was performed by use of concordance index (C-index) as a measure of prediction performance. The C-index values of the texture features, hyper-curvature features, and the combination thereof (RTC features) in predicting patient survival was estimated by use of bootstrapping with 2,000 replications, and they were compared with an established clinical prognostic biomarker known as the gender, age, and physiology (GAP) index by means of two-sided t-test. Bootstrap evaluation yielded the following C-index values for the clinical and radiomic features: (a) GAP index: 78.3%; (b) GLCM texture features: 79.6%; (c) hypercurvature features: 80.8%; and (d) RTC features: 86.8%. The RTC features significantly outperformed any of the other predictors (P < 0.001). The Kaplan-Meier survival curves of patients stratified to low- and high-risk groups based on the RTC features showed statistically significant (P < 0.0001) difference. Thus, the RTC features can provide an effective imaging biomarker for predicting the overall survival of patients with RA-ILD.

Predicting 6- and 12-Month Risk of Mortality in Patients With Platinum-Resistant Advanced-Stage Ovarian Cancer: Prognostic Model to Guide Palliative Care Referrals.

PubMed

Foote, Jonathan; Lopez-Acevedo, Micael; Samsa, Gregory; Lee, Paula S; Kamal, Arif H; Alvarez Secord, Angeles; Havrilesky, Laura J

2018-02-01

Predictive models are increasingly being used in clinical practice. The aim of the study was to develop a predictive model to identify patients with platinum-resistant ovarian cancer with a prognosis of less than 6 to 12 months who may benefit from immediate referral to hospice care. A retrospective chart review identified patients with platinum-resistant epithelial ovarian cancer who were treated at our institution between 2000 and 2011. A predictive model for survival was constructed based on the time from development of platinum resistance to death. Multivariate logistic regression modeling was used to identify significant survival predictors and to develop a predictive model. The following variables were included: time from diagnosis to platinum resistance, initial stage, debulking status, number of relapses, comorbidity score, albumin, hemoglobin, CA-125 levels, liver/lung metastasis, and the presence of a significant clinical event (SCE). An SCE was defined as a malignant bowel obstruction, pleural effusion, or ascites occurring on or before the diagnosis of platinum resistance. One hundred sixty-four patients met inclusion criteria. In the regression analysis, only an SCE and the presence of liver or lung metastasis were associated with poorer short-term survival (P < 0.001). Nine percent of patients with an SCE or liver or lung metastasis survived 6 months or greater and 0% survived 12 months or greater, compared with 85% and 67% of patients without an SCE or liver or lung metastasis, respectively. Patients with platinum-resistant ovarian cancer who have experienced an SCE or liver or lung metastasis have a high risk of death within 6 months and should be considered for immediate referral to hospice care.

Developing an analytical tool for evaluating EMS system design changes and their impact on cardiac arrest outcomes: combining geographic information systems with register data on survival rates

PubMed Central

2013-01-01

Background Out-of-hospital cardiac arrest (OHCA) is a frequent and acute medical condition that requires immediate care. We estimate survival rates from OHCA in the area of Stockholm, through developing an analytical tool for evaluating Emergency Medical Services (EMS) system design changes. The study also is an attempt to validate the proposed model used to generate the outcome measures for the study. Methods and results This was done by combining a geographic information systems (GIS) simulation of driving times with register data on survival rates. The emergency resources comprised ambulance alone and ambulance plus fire services. The simulation model predicted a baseline survival rate of 3.9 per cent, and reducing the ambulance response time by one minute increased survival to 4.6 per cent. Adding the fire services as first responders (dual dispatch) increased survival to 6.2 per cent from the baseline level. The model predictions were validated using empirical data. Conclusion We have presented an analytical tool that easily can be generalized to other regions or countries. The model can be used to predict outcomes of cardiac arrest prior to investment in EMS design changes that affect the alarm process, e.g. (1) static changes such as trimming the emergency call handling time or (2) dynamic changes such as location of emergency resources or which resources should carry a defibrillator. PMID:23415045

Validation of the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) pulmonary hypertension prediction model in a unique population and utility in the prediction of long-term survival.

PubMed

Cogswell, Rebecca; Kobashigawa, Erin; McGlothlin, Dana; Shaw, Robin; De Marco, Teresa

2012-11-01

The Registry to Evaluate Early and Long-Term Pulmonary Arterial (PAH) Hypertension Disease Management (REVEAL) model was designed to predict 1-year survival in patients with PAH. Multivariate prediction models need to be evaluated in cohorts distinct from the derivation set to determine external validity. In addition, limited data exist on the utility of this model in the prediction of long-term survival. REVEAL model performance was assessed to predict 1-year and 5-year outcomes, defined as survival or composite survival or freedom from lung transplant, in 140 patients with PAH. The validation cohort had a higher proportion of human immunodeficiency virus (7.9% vs 1.9%, p < 0.0001), methamphetamine use (19.3% vs 4.9%, p < 0.0001), and portal hypertension PAH (16.4% vs 5.1%, p < 0.0001) compared with the development cohort. The C-index of the model to predict survival was 0.765 at 1 year and 0.712 at 5 years of follow-up. The C-index of the model to predict composite survival or freedom from lung transplant was 0.805 and 0.724 at 1 and 5 years of follow-up, respectively. Prediction by the model, however, was weakest among patients with intermediate-risk predicted survival. The REVEAL model had adequate discrimination to predict 1-year survival in this small but clinically distinct validation cohort. Although the model also had predictive ability out to 5 years, prediction was limited among patients of intermediate risk, suggesting our prediction methods can still be improved. Copyright © 2012. Published by Elsevier Inc.

Cox-nnet: An artificial neural network method for prognosis prediction of high-throughput omics data.

PubMed

Ching, Travers; Zhu, Xun; Garmire, Lana X

2018-04-01

Artificial neural networks (ANN) are computing architectures with many interconnections of simple neural-inspired computing elements, and have been applied to biomedical fields such as imaging analysis and diagnosis. We have developed a new ANN framework called Cox-nnet to predict patient prognosis from high throughput transcriptomics data. In 10 TCGA RNA-Seq data sets, Cox-nnet achieves the same or better predictive accuracy compared to other methods, including Cox-proportional hazards regression (with LASSO, ridge, and mimimax concave penalty), Random Forests Survival and CoxBoost. Cox-nnet also reveals richer biological information, at both the pathway and gene levels. The outputs from the hidden layer node provide an alternative approach for survival-sensitive dimension reduction. In summary, we have developed a new method for accurate and efficient prognosis prediction on high throughput data, with functional biological insights. The source code is freely available at https://github.com/lanagarmire/cox-nnet.

Demisability and survivability sensitivity to design-for-demise techniques

NASA Astrophysics Data System (ADS)

Trisolini, Mirko; Lewis, Hugh G.; Colombo, Camilla

2018-04-01

The paper is concerned with examining the effects that design-for-demise solutions can have not only on the demisability of components, but also on their survivability that is their capability to withstand impacts from space debris. First two models are introduced. A demisability model to predict the behaviour of spacecraft components during the atmospheric re-entry and a survivability model to assess the vulnerability of spacecraft structures against space debris impacts. Two indices that evaluate the level of demisability and survivability are also proposed. The two models are then used to study the sensitivity of the demisability and of the survivability indices as a function of typical design-for-demise options. The demisability and the survivability can in fact be influenced by the same design parameters in a competing fashion that is while the demisability is improved, the survivability is worsened and vice versa. The analysis shows how the design-for-demise solutions influence the demisability and the survivability independently. In addition, the effect that a solution has simultaneously on the two criteria is assessed. Results shows which, among the design-for-demise parameters mostly influence the demisability and the survivability. For such design parameters maps are presented, describing their influence on the demisability and survivability indices. These maps represent a useful tool to quickly assess the level of demisability and survivability that can be expected from a component, when specific design parameters are changed.

Pretreatment 14-3-3 epsilon level is predictive for advanced extranodal NK/T cell lymphoma therapeutic response to asparaginase-based chemotherapy.

PubMed

Qiu, Yajuan; Zhou, Zhiyuan; Li, Zhaoming; Lu, Lisha; Li, Ling; Li, Xin; Wang, Xinhua; Zhang, Mingzhi

2017-03-01

The aim of the present study was to identify the potential relevant biomarkers to predict the therapeutic response of advanced extranodal natural killer/T cell lymphoma(ENKTL) treated with asparaginase-based treatment. Proteomic technology is used to identify differentially expressed proteins between chemotherapy-resistant and chemotherapy-sensitive patients. Then enzyme-linked immunosorbent assay is used to validate the predictive value of selective biomarkers. A total of 61 upregulated and 22 downregulated proteins are identified in chemotherapy-resistant patients compared with chemotherapy-sensitive patients. Furthermore, they validated that pretreatment high level 14-3-3 epsilon(ε)(≥61.95 ng/mL, 84.0 and 95.2% for sensitivity and specificity, respectively) is associated with poor 2-year overall survival (OS) (5.3 vs 68.8%, p<0.0001) and PFS (4.5 vs 76.9%, p<0.0001). In multivariate survival analysis, pretreatment high level 14-3-3 epsilon significantly is correlated with both inferior OS (p = 0.033) and PFS (p = 0.005). These findings indicate that pretreatment high level 14-3-3 epsilon is an independent predictor of chemotherapy-resistance and poor prognosis for patients with advanced ENKTL in the era of asparaginase. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Neutrophil gelatinase‐associated lipocalin level is a prognostic factor for survival in rat and human chronic liver diseases

PubMed Central

Yoshikawa, Kyoko; Iwasa, Motoh; Kojima, Shinichi; Yoshizawa, Naohiko; Tempaku, Mina; Sugimoto, Ryosuke; Yamamoto, Norihiko; Sugimoto, Kazushi; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

2017-01-01

Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end‐stage liver disease and Child‐Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase‐associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme‐linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real‐time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll‐like receptor 4, and interleukin‐6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow‐up period of 9.9 months. The patients with blood NGAL ≤119 ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119 ng/mL. Conclusion: Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. (Hepatology Communications 2017;1:946–956) PMID:29404502

Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients.

PubMed

Safford, Shawn D; Coleman, R Edward; Gockerman, Jon P; Moore, Joseph; Feldman, Jerome; Onaitis, Mark W; Tyler, Douglas S; Olson, John A

2004-11-01

Iodine-131 metaiodobenzylguanidine (131I-MIBG) is useful for imaging carcinoid tumors and recently has been applied to the palliative treatment of metastatic carcinoid in small studies. The authors now report their results on the therapeutic utility of high-dose 131I-MIBG treatment in a large group of patients with metastatic carcinoid tumors. The authors performed a retrospective review of 98 patients with metastatic carcinoid who were treated at their institution with 131I-MIBG over a 15-year period. Endpoints examined included the World Health Organization criteria for treatment response: symptoms, hormone (5-hydroxyindoleacetic acid [5-HIAA]) production, and clinical tumor response. Patients received a median dose of 401 +/- 202 millicuries (mCi) 131I-MIBG. The median survival after treatment was 2.3 years. Patients who experienced a symptomatic response had improved survival (5.76 years vs. 2.09 years; P < 0.01). For the 56 patients who had 5-HIAA levels monitored, the mean urine 5-HIAA levels decreased significantly after 131I-MIBG treatment (126 +/- 122 ng/mL vs. 91 +/- 125 ng/mL; P < 0.01); however, the patients with reduced 5-HIAA levels did not experience improved survival (4.11 years vs. 3.42 years; P = 0.2). Patients who received an initial 131I-MIBG dose > 400 mCi lived longer than patients who received < 400 mCi (4.69 years vs. 1.86 years; P = 0.05). Radiographic tumor response did not predict survival. Toxicity included pancytopenia, thrombocytopenia, nausea, and emesis. The current data support 131I-MIBG treatment in select patients with metastatic carcinoid who progress despite optimal medical management. Improved survival was predicted best by symptomatic response to 131I-MIBG treatment, but not by hormone or radiographic response.

Soluble CD30 in renal transplant recipients: is it a good biomarker to predict rejection?

PubMed

Azarpira, Negar; Aghdaie, Mahdokht Hosein; Malekpour, Zahra

2010-01-01

It has been suggested that the serum soluble CD30 (sCD30) level may be a poten-tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum samples. Ninety-nine patients were divided in two separate groups: Group A in whom sample collection was done one day before transplantation and Group B where sample collection was done five days after transplantation. Younger recipients (aged less than 20 years) had higher sCD30 levels (P= 0.02). There was neither significant difference in the incidence of acute rejection nor incomplete response rate after anti rejection therapy in relation to pre transplant or post transplant sCD30. We could not find a significantly inferior graft survival rate in the high sCD30 group. In conclusion, younger patients had higher sCD30 concentrations however no correlation existed between the serum concentrations and occurrence of rejection episodes or graft survival.

Decreased expression of serine protease inhibitor family G1 (SERPING1) in prostate cancer can help distinguish high-risk prostate cancer and predicts malignant progression.

PubMed

Peng, Shengmeng; Du, Tao; Wu, Wanhua; Chen, Xianju; Lai, Yiming; Zhu, Dingjun; Wang, Qiong; Ma, Xiaoming; Lin, Chunhao; Li, Zean; Guo, Zhenghui; Huang, Hai

2018-06-11

The aim of this study was to investigate the associations of serine proteinase inhibitor family G1 (SERPING1) down-regulation with poor prognosis in patients with prostate cancer (PCa). Furthermore, we aim to find more novel and effective PCa molecular markers to provide an early screening of PCa, distinguish patients with aggressive PCa, predict the prognosis, or reduce the economic burden of PCa. SERPING1 protein expression in both human PCa and normal prostate tissues was detected by immunohistochemical staining, which intensity was analyzed in association with clinical pathological parameters such Gleason score, pathological grade, clinical stage, tumor stage, lymph node metastasis, and distant metastasis. Moreover, we used The Cancer Genome Atlas (TCGA) Database, Taylor Database, and Oncomine dataset to validate our immunohistochemical results and investigated the value of SERPING1 in PCa at mRNA level. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the relationship between SERPING1 and prognosis of patients with PCa. The outcome showed that SERPING1 was expressed mainly in cytoplasm of grand cells of prostate tissue and was significantly expressed less in PCa (P<0.001). Furthermore, in the tissue microarray of our samples, decreasing expression of SERPING1 was correlated with the higher Gleason score (P = 0.004), the higher pathological grade (P = 0.01) and the advanced tumor stage (P = 0.005) at protein level. In TCGA dataset and Taylor Dataset, low-expressed SERPING1 was correlated with the younger patient (P = 0.02 in TCGA, P = 0.044 in Taylor) and the higher Gleason score (P = 0.019 in TCGA, P<0.001 in Taylor) at mRNA level. Kaplan-Meier analysis revealed that the lower mRNA of SERPING1 predicted lower overall survivals (P = 0.027 in TCGA), lower disease-free survival (P = 0.029) and lower biochemical recurrence-free survival (P = 0.011 in Taylor). Data from Oncomine database shown that SERPING1 low expression implying higher malignancy of prostate lesions. Using multivariate analysis, we also found that SERPING1 expression was independent prognostic marker of poor disease-free survival and biochemical recurrence-free survival. SERPING1 may play an important role in PCa and can be serve as a novel marker in diagnosis and prognostic prediction in PCa. In addition, levels of SERPING1 can help identify low-risk prostate to provide reference for patients with PCa to accept active surveillance and reduce overtreatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Duration of resuscitation efforts for in-hospital cardiac arrest by predicted outcomes: Insights from Get With The Guidelines – Resuscitation✩

PubMed Central

Bradley, Steven M.; Liu, Wenhui; Chan, Paul S.; Girotra, Saket; Goldberger, Zahary D.; Valle, Javier A.; Perman, Sarah M.; Nallamothu, Brahmajee K.

2017-01-01

Background The duration of resuscitation efforts has implications for patient survival of in-hospital cardiac arrest (IHCA). It is unknown if patients with better predicted survival of IHCA receive longer attempts at resuscitation. Methods In a multicenter observational cohort of 40,563 adult non-survivors of resuscitation efforts for IHCA between 2000 and 2012, we determined the pre-arrest predicted probability of survival to discharge with good neurologic status, categorized into very low (<1%), low (1–3%), average (>3%–15%), and above average (>15%). We then determined the association between predicted arrest survival probability and the duration of resuscitation efforts. Results The median duration of resuscitation efforts among all non-survivors was 19 min (interquartile range 13–28 min). Overall, the median duration of resuscitation efforts was longer in non-survivors with a higher predicted probability of survival with good neurologic status (median of 16, 17, 20, and 23 min among the groups predicted to have very low, low, average, and above probabilities, respectively; P < 0.001). However, the duration of resuscitation was often discordant with predicted survival, including longer than median duration of resuscitation efforts in 40.4% of patients with very low predicted survival and shorter than median duration of resuscitation efforts in 31.9% of patients with above average predicted survival. Conclusions The duration of resuscitation efforts in patients with IHCA was generally consistent with their predicted survival. However, nearly a third of patients with above average predicted outcomes received shorter than average (less than 19 min) duration of resuscitation efforts. PMID:28039064

Soluble E-cadherin is an independent pretherapeutic factor for long-term survival in gastric cancer.

PubMed

Chan, Annie On-On; Chu, Kent-Man; Lam, Shiu-Kum; Wong, Benjamin Chun-Yu; Kwok, Ka-Fai; Law, Simon; Ko, Samuel; Hui, Wai-Mo; Yueng, Yui-Hung; Wong, John

2003-06-15

To evaluate whether pretherapeutic serum soluble E-cadherin is an independent factor predicting long-term survival in gastric cancer. Gastric cancer remains the second leading cause of cancer-related deaths in the world, but a satisfactory tumor marker is currently unavailable for gastric cancer. Soluble E-cadherin has recently been found to have prognostic value in gastric cancer. One hundred sixteen patients with histologically proven gastric adenocarcinoma were included in the trial. Pretherapeutic serum was collected, and soluble E-cadherin was assayed using a commercially available enzyme-linked immunosorbent assay kit. The patients were followed up prospectively at the outpatient clinic. There were 75 men and 41 women, with a mean (+/- SD) age of 66 +/- 14 years. Forty-eight percent of tumors were located in the gastric antrum. The median survival time was 11 months. The mean pretherapeutic value of soluble E-cadherin was 9,159 ng/mL (range, 6,002 to 10,025 ng/mL), and the mean pretherapeutic level of carcinoembryonic antigen was 11 ng/mL (range, 0.3 to 4,895 ng/mL). On multivariate analysis, soluble E-cadherin is an independent factor predicting long-term survival. Ninety percent of patients with a serum level of E-cadherin greater than 10,000 ng/mL had a survival time of less than 3 years (P =.009). Soluble E-cadherin is a potentially valuable pretherapeutic prognostic factor in patients with gastric cancer.

A laboratory marker, FIB-4 index, as a predictor for long-term outcomes of hepatocellular carcinoma patients after curative hepatic resection.

PubMed

Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Kaneoka, Yuji; Maeda, Atsuyuki

2015-04-01

Liver fibrosis is associated with the prognosis of patients with hepatocellular carcinoma (HCC) after treatment. The laboratory marker for liver fibrosis, the FIB-4 index, is reportedly correlated with the degree of liver fibrosis. We evaluated the predictive value of FIB-4 index on the recurrence and survival of HCC patients who underwent curative hepatectomy. A total of 431 consecutive patients who underwent hepatectomy for primary, nonrecurrent HCC were analyzed. The FIB-4 index was calculated from the patient's age, serum alanine aminotransferase and aspartate aminotransferase levels, and platelet count at the time of HCC diagnosis. Postoperative recurrence and survival rates were compared according to tumor characteristics, tumor markers, Child-Pugh class, and the FIB-4 index. The pretreatment FIB-4 index was associated with recurrence and survival rates, independent of HCC progression or tumor marker levels in a multivariate analysis. Recurrence rates after hepatectomy were higher in patients with a FIB-4 index >3.25 versus ≤3.25 (5-year recurrence rates 69.6% vs 54.8%; P = .0049). Survival was also worse in patients with a FIB-4 index >3.25 than those with a FIB-4 index ≤3.25 (5-year survival rates 67.1% vs 72.2%; P = .0030). The FIB-4 index is a predictive marker for long-term outcomes in patients with HCC treated with curative hepatic resection. Copyright © 2015 Elsevier Inc. All rights reserved.

The prognostic value of stromal FK506-binding protein 1 and androgen receptor in prostate cancer outcome.

PubMed

Leach, Damien A; Trotta, Andrew P; Need, Eleanor F; Risbridger, Gail P; Taylor, Renea A; Buchanan, Grant

2017-02-01

Improving our ability to predict cancer progression and response to conservative or radical intent therapy is critical if we are to prevent under or over treatment of individual patients. Whereas the majority of solid tumors now have a range of molecular and/or immunological markers to help define prognosis and treatment options, prostate cancer still relies mainly on histological grading and clinical parameters. We have recently reported that androgen receptor (AR) expression in stroma inversely associates with prostate cancer-specific survival, and that stromal AR reduces metastasis. For this paper, we tested the hypothesis that the AR-regulated gene FKBP51 could be used as a marker of AR activity to better predict outcome. Using immunohistochemistry on a cohort of 64 patient-matched benign and malignant prostate tissues, we assessed patient outcome by FKBP51 and AR levels. Immunoblot and RT-qPCR were used to demonstrate androgen regulation of FKBP51 in primary and primary human prostatic fibroblasts and fibroblast cell-lines. As predicted by FKBP51 level, high AR activity in cancer stroma was associated with longer median survival (1,306 days) compared with high AR alone (699 days), whereas those with low AR and/or low FKBP51 did poorly (384 and 338 days, respectively). Survival could not be predicted on the basis cancer epithelial AR levels or activity, and was not associated with immunoreactivity in patient matched benign tissues. FKBP51 improves the ability of stromal AR to predict prostate cancer-specific mortality. By adding additional immunological assessment, similar to what is already in place in a number of other cancers, we could better serve patients with prostate cancer in prognosis and informed treatment choices. Prostate 77:185-195, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Long-Term Survival Prediction for Coronary Artery Bypass Grafting: Validation of the ASCERT Model Compared With The Society of Thoracic Surgeons Predicted Risk of Mortality.

PubMed

Lancaster, Timothy S; Schill, Matthew R; Greenberg, Jason W; Ruaengsri, Chawannuch; Schuessler, Richard B; Lawton, Jennifer S; Maniar, Hersh S; Pasque, Michael K; Moon, Marc R; Damiano, Ralph J; Melby, Spencer J

2018-05-01

The recently developed American College of Cardiology Foundation-Society of Thoracic Surgeons (STS) Collaboration on the Comparative Effectiveness of Revascularization Strategy (ASCERT) Long-Term Survival Probability Calculator is a valuable addition to existing short-term risk-prediction tools for cardiac surgical procedures but has yet to be externally validated. Institutional data of 654 patients aged 65 years or older undergoing isolated coronary artery bypass grafting between 2005 and 2010 were reviewed. Predicted survival probabilities were calculated using the ASCERT model. Survival data were collected using the Social Security Death Index and institutional medical records. Model calibration and discrimination were assessed for the overall sample and for risk-stratified subgroups based on (1) ASCERT 7-year survival probability and (2) the predicted risk of mortality (PROM) from the STS Short-Term Risk Calculator. Logistic regression analysis was performed to evaluate additional perioperative variables contributing to death. Overall survival was 92.1% (569 of 597) at 1 year and 50.5% (164 of 325) at 7 years. Calibration assessment found no significant differences between predicted and actual survival curves for the overall sample or for the risk-stratified subgroups, whether stratified by predicted 7-year survival or by PROM. Discriminative performance was comparable between the ASCERT and PROM models for 7-year survival prediction (p < 0.001 for both; C-statistic = 0.815 for ASCERT and 0.781 for PROM). Prolonged ventilation, stroke, and hospital length of stay were also predictive of long-term death. The ASCERT survival probability calculator was externally validated for prediction of long-term survival after coronary artery bypass grafting in all risk groups. The widely used STS PROM performed comparably as a predictor of long-term survival. Both tools provide important information for preoperative decision making and patient counseling about potential outcomes after coronary artery bypass grafting. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

[Hyperbaric oxygen therapy adjunctive to surgical debridement in management of Fournier's gangrene: usefulness of a severity index score in predicting disease gravity and patient survival].

PubMed

Janane, A; Hajji, F; Ismail, T O; Chafiqui, J; Ghadouane, M; Ameur, A; Abbar, M; Albouzidi, A

2011-06-01

Hyperbaric oxygen therapy (HBOT) concomitant to surgery has been reported to reduce Fournier's gangrene (FG) mortality compared to exclusive surgical debridement. Most report from centers with relatively few patients using only surgical procedure. To assess efficiency of aggressive debridement with adjunctive HBOT. To evaluate Fournier's gangrene severity score index (FGSI) predictive value. 70 Fournier's gangrene (FG) treated by surgical debridement and HBOT. Data were evaluated physical examination findings, admission and final laboratory tests, surgical debridement extent, and antibiotic used. Patients had adjunctive (HBOT). FGSI, developed to assign a score describing the acuity of disease, was used. This index presents patients' vital signs, metabolic parameters (sodium, potassium, creatinine, and bicarbonate levels, and white blood cell count) and computes a score relating to the severity of disease at that time. Data were assessed according to whether the patient survived or died. All patients underwent surgical debridement. Wound debridement was regularly performed in the post operative period. Of 70 patients, 8 died (11.4%) and 62 survived (88.5%). Difference in age between survivors (median age, 50.0 yr) and non survivors (median age, 54.5 yr) was not significant (p=0.321). Median extent of body surface area involved in necrotizing process in patients who survived and did not survive was 2.4% and 4.9%, respectively (p=0.001). Except for albumin, no significant differences were found between survivors and nonsurvivors. Median admission FGSI scores for survivors and non survivors were 2.1±2.0 and 4.2±3.8, (p=0.331). FGSI score did not predict disease severity and the patient's survival. Metabolic aberrations, extent of disease seemed to be important risk factors for predicting FG severity and patient survival. Copyright © 2010 AEU. Published by Elsevier Espana. All rights reserved.

Cytokine Profiling of Ascites at Primary Surgery Identifies an Interaction of Tumor Necrosis Factor-α and Interleukin-6 in Predicting Reduced Progression-Free Survival in Epithelial Ovarian Cancer

PubMed Central

Kolomeyevskaya, Nonna; Eng, Kevin H.; Khan, Anm Nazmul H.; Grzankowski, Kassondra S.; Singel, Kelly L.; Moysich, Kirsten; Segal, Brahm H.

2015-01-01

Objectives Epithelial ovarian cancer (EOC) typically presents with advanced disease. Even with optimal debulking and response to adjuvant chemotherapy, the majority of patients will have disease relapse. We evaluated cytokine and chemokine profiles in ascites at primary surgery as biomarkers for progression-free survival (PFS) and overall survival (OS) in patients with advanced EOC. Methods Retrospective analysis of patients (n =70) who underwent surgery at Roswell Park Cancer Institute between 2002-12, followed by platinum-based chemotherapy. Results The mean age at diagnosis was 61.8 years, 85.3% had serous EOC, and 95.7% had stage IIIB, IIIC, or IV disease. Univariate analysis showed that ascites levels of tumor necrosis factor (TNF)-α were associated with reduced PFS after primary surgery. Although the ascites concentration of interleukin (IL)-6 was not by itself predictive of PFS, we found that stratifying patients by high TNF-α and high IL-6 levels identified a sub-group of patients at high risk for rapid disease relapse. This effect was largely independent of clinical prognostic variables. Conclusions The combination of high TNF-α and high IL-6 ascites levels at primary surgery predicts worse PFS in patients with advanced EOC. These results suggest an interaction between ascites TNF-α and IL-6 in driving tumor progression and resistance to chemotherapy in advanced EOC, and raise the potential for pre-treatment ascites levels of these cytokines as prognostic biomarkers. This study involved a small sample of patients and was an exploratory analysis; therefore, findings require validation in a larger independent cohort. PMID:26001328

Cytokine profiling of ascites at primary surgery identifies an interaction of tumor necrosis factor-α and interleukin-6 in predicting reduced progression-free survival in epithelial ovarian cancer.

PubMed

Kolomeyevskaya, Nonna; Eng, Kevin H; Khan, Anm Nazmul H; Grzankowski, Kassondra S; Singel, Kelly L; Moysich, Kirsten; Segal, Brahm H

2015-08-01

Epithelial ovarian cancer (EOC) typically presents with advanced disease. Even with optimal debulking and response to adjuvant chemotherapy, the majority of patients will have disease relapse. We evaluated cytokine and chemokine profiles in ascites at primary surgery as biomarkers for progression-free survival (PFS) and overall survival (OS) in patients with advanced EOC. Retrospective analysis of patients (n =70) who underwent surgery at Roswell Park Cancer Institute between 2002 and 2012, followed by platinum-based chemotherapy. The mean age at diagnosis was 61.8 years, 85.3% had serous EOC, and 95.7% had stage IIIB, IIIC, or IV disease. Univariate analysis showed that ascites levels of tumor necrosis factor (TNF)-α were associated with reduced PFS after primary surgery. Although the ascites concentration of interleukin (IL)-6 was not by itself predictive of PFS, we found that stratifying patients by high TNF-α and high IL-6 levels identified a sub-group of patients at high risk for rapid disease relapse. This effect was largely independent of clinical prognostic variables. The combination of high TNF-α and high IL-6 ascites levels at primary surgery predicts worse PFS in patients with advanced EOC. These results suggest an interaction between ascites TNF-α and IL-6 in driving tumor progression and resistance to chemotherapy in advanced EOC, and raise the potential for pre-treatment ascites levels of these cytokines as prognostic biomarkers. This study involved a small sample of patients and was an exploratory analysis; therefore, findings require validation in a larger independent cohort. Copyright © 2015 Elsevier Inc. All rights reserved.

Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

DTIC Science & Technology

2013-09-01

10]. However, the level of IFP has been shown to predict disease free survival for cervix cancer (34% disease free survival (DFS) if IFP > 19 mmHg...in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res, 2001. 61(17): p. 6400-5. 12... cancer (LABC). Monitoring tumor response is advantageous for patients. This project aims to using the subharmonic signals from ultrasound contrast agents

Wild Mammalian Biomonitors for Assessing Impacts of Environmental Contamination on Population and Community Ecology

DTIC Science & Technology

1993-06-01

will be compared to common laboratory bioassay tests (fathea minnow survival, rice seed germination test, etc.), relative to their ability to pre- ’dict...rice seed germination , and Ceriodaphnia assays. At the ecosystem level, in situ small mammal total biomass, sex ratios, reproduction, recruit- ment...bioassay tests (fathead minnow survival, rice seed germination test, etc.), relative to their ability to predict ecotoxicity risks (as indexed by

Modeling the eco-physiology of the purple mauve stinger, Pelagia noctiluca using Dynamic Energy Budget theory

NASA Astrophysics Data System (ADS)

Augustine, Starrlight; Rosa, Sara; Kooijman, Sebastiaan A. L. M.; Carlotti, François; Poggiale, Jean-Christophe

2014-11-01

Parameters for the standard Dynamic Energy Budget (DEB) model were estimated for the purple mauve stinger, Pelagia noctiluca, using literature data. Overall, the model predictions are in good agreement with data covering the full life-cycle. The parameter set we obtain suggests that P. noctiluca is well adapted to survive long periods of starvation since the predicted maximum reserve capacity is extremely high. Moreover we predict that the reproductive output of larger individuals is relatively insensitive to changes in food level while wet mass and length are. Furthermore, the parameters imply that even if food were scarce (ingestion levels only 14% of the maximum for a given size) an individual would still mature and be able to reproduce. We present detailed model predictions for embryo development and discuss the developmental energetics of the species such as the fact that the metabolism of ephyrae accelerates for several days after birth. Finally we explore a number of concrete testable model predictions which will help to guide future research. The application of DEB theory to the collected data allowed us to conclude that P. noctiluca combines maximizing allocation to reproduction with rather extreme capabilities to survive starvation. The combination of these properties might explain why P. noctiluca is a rapidly growing concern to fisheries and tourism.

Serum albumin predicts survival in patients with hilar cholangiocarcinoma

PubMed Central

Waghray, Abhijeet; Sobotka, Anastasia; Marrero, Carlos Romero; Estfan, Bassam; Aucejo, Federico

2017-01-01

Background and aims: Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma. Methods: All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation. Results: A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P < 0.01), cancer antigen 19‐9 ≤200 U/mL (P = 0.03), carcinoembryonic antigen ≤10 ìg/L (P < 0.01) or patients without a history of cirrhosis (P < 0.01) or diabetes (P = 0.02) were associated with a greater length of overall survival. A serum albumin level >3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14–0.70) with a survival benefit of 44 weeks. Conclusion: This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival. PMID:27389416

Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

PubMed

Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

2017-03-16

We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

Two-Level Weld-Material Homogenization for Efficient Computational Analysis of Welded Structure Blast-Survivability

NASA Astrophysics Data System (ADS)

Grujicic, M.; Arakere, G.; Hariharan, A.; Pandurangan, B.

2012-06-01

The introduction of newer joining technologies like the so-called friction-stir welding (FSW) into automotive engineering entails the knowledge of the joint-material microstructure and properties. Since, the development of vehicles (including military vehicles capable of surviving blast and ballistic impacts) nowadays involves extensive use of the computational engineering analyses (CEA), robust high-fidelity material models are needed for the FSW joints. A two-level material-homogenization procedure is proposed and utilized in this study to help manage computational cost and computer storage requirements for such CEAs. The method utilizes experimental (microstructure, microhardness, tensile testing, and x-ray diffraction) data to construct: (a) the material model for each weld zone and (b) the material model for the entire weld. The procedure is validated by comparing its predictions with the predictions of more detailed but more costly computational analyses.

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. Copyright © 2015. Published by Elsevier Ltd.

The PREM score: a graphical tool for predicting survival in very preterm births.

PubMed

Cole, T J; Hey, E; Richmond, S

2010-01-01

To develop a tool for predicting survival to term in babies born more than 8 weeks early using only information available at or before birth. 1456 non-malformed very preterm babies of 22-31 weeks' gestation born in 2000-3 in the north of England and 3382 births of 23-31 weeks born in 2000-4 in Trent. Survival to term, predicted from information available at birth, and at the onset of labour or delivery. Development of a logistic regression model (the prematurity risk evaluation measure or PREM score) based on gestation, birth weight for gestation and base deficit from umbilical cord blood. Gestation was by far the most powerful predictor of survival to term, and as few as 5 extra days can double the chance of survival. Weight for gestation also had a powerful but non-linear effect on survival, with weight between the median and 85th centile predicting the highest survival. Using this information survival can be predicted almost as accurately before birth as after, although base deficit further improves the prediction. A simple graph is described that shows how the two main variables gestation and weight for gestation interact to predict the chance of survival. The PREM score can be used to predict the chance of survival at or before birth almost as accurately as existing measures influenced by post-delivery condition, to balance risk at entry into a controlled trial and to adjust for differences in "case mix" when assessing the quality of perinatal care.

Antiangiogenic Therapy for Glioblastoma: Current Status and Future Prospects

PubMed Central

Batchelor, Tracy T.; Reardon, David A.; de Groot, John F.; Wick, Wolfgang; Weller, Michael

2014-01-01

Glioblastoma is characterized by high expression levels of pro-angiogenic cytokines and microvascular proliferation, highlighting the potential value of treatments targeting angiogenesis. Antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action. Ultimately, however, alternative pro-angiogenic signal transduction pathways are activated leading to the development of resistance, even in tumors that initially respond. The identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority. Despite promising phase 2 clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in 4 randomized phase 3 trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin recurrent glioblastoma. However, future studies are warranted: predictive markers may allow appropriate patient enrichment, combination with chemotherapy may ultimately prove successful in improving overall survival, and novel agents targeting multiple pro-angiogenic pathways may prove effective. PMID:25398844

Predictive and therapeutic markers in ovarian cancer

DOEpatents

Gray, Joe W.; Guan, Yinghui; Kuo, Wen-Lin; Fridlyand, Jane; Mills, Gordon B.

2013-03-26

Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.

Value of 18F-FDG PET/CT Combined With Tumor Markers in the Evaluation of Ascites.

PubMed

Han, Na; Sun, Xun; Qin, Chunxia; Hassan Bakari, Khamis; Wu, Zhijian; Zhang, Yongxue; Lan, Xiaoli

2018-05-01

The purpose of this study is to investigate the value of 18 F-FDG PET/CT combined with assessment of tumor markers in serum or ascites for the diagnosing and determining the prognosis of benign and malignant ascites. Patients with ascites of unknown cause who underwent evaluation with FDG PET/CT were included in this retrospective study. The maximum standardized uptake value (SUV max ) and levels of the tumor markers carbohydrate antigen-125 (CA-125) and carcinoembryonic antigen (CEA) in serum and ascites were recorded. The diagnostic values of FDG PET/CT, CEA and CA-125 levels in serum or ascites, and the combination of imaging plus tumor marker assessment were evaluated. Factors that were predictive of survival were also analyzed. A total of 177 patients were included. Malignant ascites was eventually diagnosed in 104 patients, and benign ascites was diagnosed in the remaining 73 patients. With the use of FDG PET/CT, 44 patients (42.3%) were found to have primary tumors. The sensitivity, specificity, and accuracy of FDG PET/CT were 92.3%, 83.6%, and 88.7%, respectively. CA-125 levels in serum and ascites showed much better sensitivity than did CEA levels, but they showed significantly lower specificity. If the combination of tumor markers and FDG PET/CT was analyzed, the sensitivity, specificity, and accuracy of tumor markers in serum were 96.6%, 78.1%, and 88.7%, and those of tumor markers in ascites were 97.7%, 80.0%, and 90.4%, respectively. Sex may be an important factor affecting survival time (hazard ratio, 0.471; p = 0.004), but age, CEA level, and FDG PET/CT findings could not predict survival. FDG PET/CT combined with assessment of tumor markers, especially CEA, increased the efficacy of diagnosis of ascites of unknown causes. Male sex conferred a poorer prognosis, whereas age, CEA level, and FDG uptake had no predictive significance in patients with malignant ascites.

Using Serum α-Fetoprotein for Prognostic Prediction in Patients with Hepatocellular Carcinoma: What is the Most Optimal Cutoff?

PubMed Central

Hsu, Chia-Yang; Liu, Po-Hong; Lee, Yun-Hsuan; Hsia, Cheng-Yuan; Huang, Yi-Hsiang; Lin, Han-Chieh; Chiou, Yi-You; Lee, Fa-Yauh; Huo, Teh-Ia

2015-01-01

Background and Aims The prognostic ability of α-fetoprotein (AFP) for patients with hepatocellular carcinoma (HCC) was examined by using different cutoff values. The optimal AFP cutoff level is still unclear. Methods A total of 2579 HCC patients were consecutively enrolled in Taiwan, where hepatitis B is the major etiology of chronic liver disease. Four frequently used AFP cutoff levels, 20, 200, 400, 1000 ng/mL, were investigated. One-to-one matched pairs between patients having AFP higher and lower than the cutoffs were selected by using the propensity model. The adjusted hazard ratios of survival difference were calculated with Cox proportional hazards model. Results Patients with a higher AFP level were associated with more severe cirrhosis, more frequent vascular invasion, higher tumor burden and poorer performance status (all p<0.0001). In the propensity model, 4 groups of paired patients were selected, and there was no difference found in the comparison of baseline characteristics (all p>0.05). Patients with AFP <20 ng/mL had significantly better long-term survival than patients with AFP ≧20 ng/mL (p<0.0001), and patients with AFP <400 ng/mL had significantly better overall outcome than patients with AFP ≧400 ng/mL (p = 0.0186). There was no difference of long-term survival between patients divided by AFP levels of 200 and 1000 ng/mL. The adjusted hazard ratios of AFP ≧20 ng/mL and AFP ≧400 ng/mL were 1.545 and 1.471 (95% confidence interval: 1.3–1.838 and 1.178–1.837), respectively. Conclusions This study shows the independently predictive ability of baseline serum AFP level in HCC patients. AFP levels of 20 and 400 ng/mL are considered feasible cutoffs to predict long-term outcome in unselected HCC patients. PMID:25738614

Predictive value of different proportion of lesion HLA-G expression in colorectal cancer.

PubMed

Zhang, Rui-Li; Zhang, Xia; Dong, Shan-Shan; Hu, Bing; Han, Qiu-Yue; Zhang, Jian-Gang; Zhou, Wen-Jun; Lin, Aifen; Yan, Wei-Hua

2017-12-08

Differential expression of HLA-G has been observed among cancer types and tumors from individuals with the same type of cancer; however, its clinical significance is rather limited. In this study, expression and predictive relevance of HLA-G expression in 457 primary colorectal cancer (CRC, n colon = 232, n rectal = 225) patients was investigated. Data showed 70.7% (323/457) of the CRC were HLA-G expression when the above 5% (HLA-G Low ) was considered as positive, which wasn't associated with patient survival ( p = 0.109). However, HLA-G expression above 55% (HLA-G High ) was associated with a worse prognosis of CRC patients ( p = 0.042). Furthermore, a shorter survival was found for the female ( p = 0.042) and elder ( p = 0.037) patients whose HLA-G expression was above HLA-G Low level. HLA-G expression above HLA-G High level showed a worse prognosis for female ( p = 0.013), elder ( p = 0.023), colon cancer ( p = 0.016), advanced tumor burden (T 3+4 , p = 0.018), regional lymph node status (N 1+2 , p = 0.044), and advanced clinical stage patients (AJCC III+IV , p = 0.037). In conclusion, our results demonstrated for the first time that combination of differential lesion HLA-G expression notably improved the value of traditional survival prediction for CRC patients.

Deformable image registration as a tool to improve survival prediction after neoadjuvant chemotherapy for breast cancer: results from the ACRIN 6657/I-SPY-1 trial

NASA Astrophysics Data System (ADS)

Jahani, Nariman; Cohen, Eric; Hsieh, Meng-Kang; Weinstein, Susan P.; Pantalone, Lauren; Davatzikos, Christos; Kontos, Despina

2018-02-01

We examined the ability of DCE-MRI longitudinal features to give early prediction of recurrence-free survival (RFS) in women undergoing neoadjuvant chemotherapy for breast cancer, in a retrospective analysis of 106 women from the ISPY 1 cohort. These features were based on the voxel-wise changes seen in registered images taken before treatment and after the first round of chemotherapy. We computed the transformation field using a robust deformable image registration technique to match breast images from these two visits. Using the deformation field, parametric response maps (PRM) — a voxel-based feature analysis of longitudinal changes in images between visits — was computed for maps of four kinetic features (signal enhancement ratio, peak enhancement, and wash-in/wash-out slopes). A two-level discrete wavelet transform was applied to these PRMs to extract heterogeneity information about tumor change between visits. To estimate survival, a Cox proportional hazard model was applied with the C statistic as the measure of success in predicting RFS. The best PRM feature (as determined by C statistic in univariable analysis) was determined for each of the four kinetic features. The baseline model, incorporating functional tumor volume, age, race, and hormone response status, had a C statistic of 0.70 in predicting RFS. The model augmented with the four PRM features had a C statistic of 0.76. Thus, our results suggest that adding information on the texture of voxel-level changes in tumor kinetic response between registered images of first and second visits could improve early RFS prediction in breast cancer after neoadjuvant chemotherapy.

Predicting neo-adjuvant chemotherapy response and progression-free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F-18 FDG PET/CT and diffusion-weighted MR imaging.

PubMed

Yoon, Hai-Jeon; Kim, Yemi; Chung, Jin; Kim, Bom Sahn

2018-03-30

Predicting response to neo-adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion-weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co-occurrence matrix, the voxel-alignment matrix, neighborhood intensity difference matrix, intensity size-zone matrix (ISZM), normalized gray-level co-occurrence matrix (NGLCM), neighboring gray-level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression-free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow-up period of 17.3 months, 14 patients experienced recurrence. High-intensity zone emphasis (HIZE) and high-intensity short-zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence. © 2018 Wiley Periodicals, Inc.

Using cure models for analyzing the influence of pathogens on salmon survival

USGS Publications Warehouse

Ray, Adam R; Perry, Russell W.; Som, Nicholas A.; Bartholomew, Jerri L

2014-01-01

Parasites and pathogens influence the size and stability of wildlife populations, yet many population models ignore the population-level effects of pathogens. Standard survival analysis methods (e.g., accelerated failure time models) are used to assess how survival rates are influenced by disease. However, they assume that each individual is equally susceptible and will eventually experience the event of interest; this assumption is not typically satisfied with regard to pathogens of wildlife populations. In contrast, mixture cure models, which comprise logistic regression and survival analysis components, allow for different covariates to be entered into each part of the model and provide better predictions of survival when a fraction of the population is expected to survive a disease outbreak. We fitted mixture cure models to the host–pathogen dynamics of Chinook Salmon Oncorhynchus tshawytscha and Coho Salmon O. kisutch and the myxozoan parasite Ceratomyxa shasta. Total parasite concentration, water temperature, and discharge were used as covariates to predict the observed parasite-induced mortality in juvenile salmonids collected as part of a long-term monitoring program in the Klamath River, California. The mixture cure models predicted the observed total mortality well, but some of the variability in observed mortality rates was not captured by the models. Parasite concentration and water temperature were positively associated with total mortality and the mortality rate of both Chinook Salmon and Coho Salmon. Discharge was positively associated with total mortality for both species but only affected the mortality rate for Coho Salmon. The mixture cure models provide insights into how daily survival rates change over time in Chinook Salmon and Coho Salmon after they become infected with C. shasta.

A Risk Stratification Model for Lung Cancer Based on Gene Coexpression Network and Deep Learning

PubMed Central

2018-01-01

Risk stratification model for lung cancer with gene expression profile is of great interest. Instead of previous models based on individual prognostic genes, we aimed to develop a novel system-level risk stratification model for lung adenocarcinoma based on gene coexpression network. Using multiple microarray, gene coexpression network analysis was performed to identify survival-related networks. A deep learning based risk stratification model was constructed with representative genes of these networks. The model was validated in two test sets. Survival analysis was performed using the output of the model to evaluate whether it could predict patients' survival independent of clinicopathological variables. Five networks were significantly associated with patients' survival. Considering prognostic significance and representativeness, genes of the two survival-related networks were selected for input of the model. The output of the model was significantly associated with patients' survival in two test sets and training set (p < 0.00001, p < 0.0001 and p = 0.02 for training and test sets 1 and 2, resp.). In multivariate analyses, the model was associated with patients' prognosis independent of other clinicopathological features. Our study presents a new perspective on incorporating gene coexpression networks into the gene expression signature and clinical application of deep learning in genomic data science for prognosis prediction. PMID:29581968

Modelling survival: exposure pattern, species sensitivity and uncertainty

PubMed Central

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I.; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B.; Van den Brink, Paul J.; Veltman, Karin; Vogel, Sören; Zimmer, Elke I.; Preuss, Thomas G.

2016-01-01

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans. PMID:27381500

LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia.

PubMed

Kaderi, Mohd Arifin; Kanduri, Meena; Buhl, Anne Mette; Sevov, Marie; Cahill, Nicola; Gunnarsson, Rebeqa; Jansson, Mattias; Smedby, Karin Ekström; Hjalgrim, Henrik; Jurlander, Jesper; Juliusson, Gunnar; Mansouri, Larry; Rosenquist, Richard

2011-08-01

The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers. Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome. High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients. LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.

The clinical utility of fibrin-related biomarkers in sepsis.

PubMed

Toh, Julien M H; Ken-Dror, Gie; Downey, Colin; Abrams, Simon T

2013-12-01

Sepsis is associated with systemic inflammatory responses and induction of intravascular fibrin formation. Our aim is to investigate whether three fibrin-related markers (FRM) reflect the extent of coagulation activation in vivo and evaluate their clinical usefulness in identifying as well as monitoring patients with sepsis. Fibrin-degradation products (FDP), D-dimer and soluble fibrin monomer assays were measured on plasma samples from patients in the ICU with sepsis (n = 37), systemic inflammatory response syndrome (SIRS) (n = 35) and healthy individuals (n = 15). The levels were correlated with each other and also with fibrinogen, prothrombin time, platelets and antithrombin III. Clinical correlation was also performed for the diagnosis of sepsis and longitudinal monitoring for survival or death.There was strong correlation between the three FRM (r = 0.38-0.93, P < 0.0001) with only fibrin monomer correlating significantly with prothrombin time, fibrinogen and platelet levels. Clinically, all three FRM could discriminate between patients with sepsis, SIRS and healthy individuals with FDP, and D-dimer showing statistical significance (P < 0.05). No FRM predicted outcome from a single measurement but FDP was significantly able to predict patient survival from serial samples [mean FDP (μg/ml) from 35.36 to 21.37 (first to third ICU-day), P < 0.05]. Fibrin monomer appears the most sensitive indicator of coagulation activation, whereas D-dimer and FDP levels can significantly differentiate ICU patients with sepsis from those without. In addition, FDP would be preferable for monitoring with its statistically significant time-dependent prediction of survival or death from sepsis.

Metallic ureteral stents in malignant ureteral obstruction: clinical factors predicting stent failure.

PubMed

Chow, Po-Ming; Hsu, Jui-Shan; Huang, Chao-Yuan; Wang, Shuo-Meng; Lee, Yuan-Ju; Huang, Kuo-How; Yu, Hong-Jheng; Pu, Yeong-Shiau; Liang, Po-Chin

2014-06-01

To provide clinical outcomes of the Resonance metallic ureteral stent in patients with malignant ureteral obstruction, as well as clinical factors predicting stent failure. Cancer patients who have received Resonance stents from July 2009 to March 2012 for ureteral obstruction were included for chart review. Stent failure was detected by clinical symptoms, image studies, and renal function tests. Survival analysis for stent duration was used to estimate patency rate and factors predicting stent failure. A total of 117 stents were inserted successfully into 94 ureteral units in 79 patients. There were no major complications. These stents underwent survival analysis and proportional hazard regression. The median duration for the stents was 5.77 months. In multivariate analysis, age (P=0.043), preoperative serum creatinine level (P=0.0174), and cancer type (P=0.0494) were significant factors associated with stent failure. Cancer treatment before and after stent insertion had no effect on stent duration. Resonance stents are effective and safe in relieving malignant ureteral obstructions. Old age and high serum creatinine level are predictors for stent failure. Stents in patients with lower gastrointestinal cancers have longer functional duration.

pH Level as a Marker for Predicting Death among Patients with Vibrio vulnificus Infection, South Korea, 2000–2011

PubMed Central

Yun, Na Ra; Lee, Jun; Han, Mi Ah

2015-01-01

Vibrio vulnificus infection can progress to necrotizing fasciitis and death. To improve the likelihood of patient survival, an early prognosis of patient outcome is clinically important for emergency/trauma department doctors. To identify an accurate and simple predictor for death among V. vulnificus–infected persons, we reviewed clinical data for 34 patients at a hospital in South Korea during 2000–2011; of the patients, 16 (47%) died and 18 (53%) survived. For nonsurvivors, median time from hospital admission to death was 15 h (range 4–70). For predicting death, the areas under the receiver operating characteristic curves of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and initial pH were 0.746 and 0.972, respectively (p = 0.005). An optimal cutoff pH of <7.35 had a sensitivity of 100% and specificity of 83%. Compared with the APACHE II score, the initial arterial blood pH level in V. vulnificus-infected patients was a more accurate predictive marker for death. PMID:25627847

pH level as a marker for predicting death among patients with Vibrio vulnificus infection, South Korea, 2000-2011.

PubMed

Yun, Na Ra; Kim, Dong-Min; Lee, Jun; Han, Mi Ah

2015-02-01

Vibrio vulnificus infection can progress to necrotizing fasciitis and death. To improve the likelihood of patient survival, an early prognosis of patient outcome is clinically important for emergency/trauma department doctors. To identify an accurate and simple predictor for death among V. vulnificus-infected persons, we reviewed clinical data for 34 patients at a hospital in South Korea during 2000-2011; of the patients, 16 (47%) died and 18 (53%) survived. For nonsurvivors, median time from hospital admission to death was 15 h (range 4-70). For predicting death, the areas under the receiver operating characteristic curves of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and initial pH were 0.746 and 0.972, respectively (p = 0.005). An optimal cutoff pH of <7.35 had a sensitivity of 100% and specificity of 83%. Compared with the APACHE II score, the initial arterial blood pH level in V. vulnificus-infected patients was a more accurate predictive marker for death.

Relations between nutritional condition and survival of North American elk Cervus elaphus

USGS Publications Warehouse

Bender, L.C.; Cook, J.G.; Cook, R.C.; Hall, P.B.

2008-01-01

We related annual and seasonal survival of four populations of elk Cervus elaphus in the Pacific Northwest, USA, to measures and indices of individual nutritional condition. Among populations, for all mortality (human and non-human causes) sources inclusive, annual survival of adult females was correlated with a rump body condition score (rs = 0.627, P = 0.071), and survival over spring-summer-autumn (SSA) was correlated with mean ingesta-free body fat (IFBF; rs = 0.567, P = 0.088) and rump body condition score (rBCS; rs = 0.615, P = 0.050). For non-human mortality sources only, survival through SSA was correlated with IFBF (rs = 0.567, P = 0.088) and rBCS (rs = 0.615, P = 0.050), and survival over winter was correlated with withers body condition score (rs = 0.677, P = 0.045). For human-caused mortality sources only, survival over SSA was correlated with rBCS (rs = 0.696, P = 0.036) and IFBF (rs = 0.696, P = 0.036). For individuals, logistic analysis found that individual likelihood of dying from all mortality sources inclusive was best predicted (??2 = 8.3, P = 0.004, ?? = -1.24) by longissimus dorsi (loin) muscle thickness, a measure of protein catabolism. For only non-human mortality sources, a model (??2 = 16.1, P = 0.0003) containing both loin muscle thickness (??2 = 5.7, P = 0.017, ??= -1.02) and percent ingesta-free body fat (??2 = 4.9, P = 0.027, ?? = -0.35) best predicted individual susceptibility to mortality. Odds ratios indicated that odds of dying increased approximately 3X for each centimeter of loin muscle catabolized and 1.4X for each percent less body fat. No condition indices at the individual level were related to survival from human-caused mortality sources. Our study populations were characterized by low-marginal condition (i.e. mean ingesta-free body fat levels of 5.9-12.3% for lactating cows in late autumn); this likely increased the prominence of measures of muscle catabolism relative to fat accretion in influencing individual elk survival. Elk populations throughout the Pacific Northwest likely show similar condition levels, and consequently individuals are predisposed to mortality to a much greater degree than under optimal foraging conditions. Management strategies which assume that nutritional condition affects vulnerability only at or near condition levels associated with ecological carrying capacity (i.e. near starvation mortality) may overestimate the impact of proximate mortality factors on adult female elk. ?? Wildlife Biology (2008).

Pretreatment Dysphagia Inventory and videofluorographic swallowing study as prognostic indicators of early survival outcomes in head and neck cancer.

PubMed

Yang, Chan Joo; Roh, Jong-Lyel; Choi, Kyoung Hyo; Kim, Min-Ju; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2015-05-15

The prognostic role of swallowing-related, pretreatment subjective and objective findings has not been investigated in detail. The authors evaluated the association between pretreatment MD Anderson Dysphagia Inventory (MDADI) or videofluorographic swallowing study (VFSS) results and standard outcomes, including early recurrence and survival, in patients with treatment-naïve head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC (n = 191) who received treatment at the authors' institution and were examined by self-administered MDADI questionnaires and VFSS were prospectively enrolled. MDADI and VFSS findings were analyzed in correlation with clinicopathologic variables, and factors that predicted 2-year disease-free survival (DFS) and overall survival (OS) were identified using a Cox proportional-hazards regression model. The 2-year OS and DFS rates were 80.1% and 77.5%, respectively. Clinical tumor (T) and lymph node (N) classifications, overall TNM stage, sex, tumor site, and educational level were significantly associated with specific MDADI subdomains, whereas Karnofsky performance score was significantly associated with all MDADI subdomains. After controlling for clinical factors, total scores, global assessment scores, and emotional and physical MDADI subscores were significantly predictive of 2-year OS and DFS (P < .05 for each). VFSS findings were not significantly associated with survival (P > .05). The current results provide evidence of the prognostic role of the MDADI in predicting early survival outcomes in patients with HNSCC. The MDADI may be a practical and noninvasive method for the identification of patients at risk who would benefit from close follow-up. © 2015 American Cancer Society.

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

PubMed

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

2017-04-01

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

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. © 2016 John Wiley & Sons Ltd.

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

USGS Publications Warehouse

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

2015-01-01

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.

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

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

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

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

Significance of SYT8 For the Detection, Prediction, and Treatment of Peritoneal Metastasis From Gastric Cancer.

PubMed

Kanda, Mitsuro; Shimizu, Dai; Tanaka, Haruyoshi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Iwata, Naoki; Niwa, Yukiko; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Murotani, Kenta; Fujiwara, Michitaka; Kodera, Yasuhiro

2018-03-01

To develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of gastric cancer (GC). Advanced GC frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable. We conducted a recurrence pattern-specific transcriptome analysis in an independent cohort of 16 patients with stage III GC who underwent curative gastrectomy and adjuvant S-1 for screening candidate molecules specific for peritoneal metastasis of GC. Next, another 340 patients were allocated to discovery and validation sets (1:2) to evaluate the diagnostic and predictive value of the candidate molecule. The results of quantitative reverse-transcription PCR and immunohistochemical analysis were correlated with clinical characteristics and survival. The effects of siRNA-mediated knockdown on phenotype and fluorouracil sensitivity of GC cells were evaluated in vitro, and the therapeutic effects of siRNAs were evaluated using a mouse xenograft model. Synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. In the discovery set, the optimal cut-off of SYT8 expression was established as 0.005. Expression levels of SYT8 mRNA in GC tissues were elevated in the validation set comprising patients with peritoneal recurrence or metastasis. SYT8 levels above the cut-off value were significantly and specifically associated with peritoneal metastasis, and served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. The survival difference between patients with SYT8 levels above and below the cut-off was associated with patients who received adjuvant chemotherapy. Inhibition of SYT8 expression by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells. SYT8 represents a promising target for the detection, prediction, and treatment of peritoneal metastasis of GC.

Circulating Soluble Receptor Activator of Nuclear Factor Kappa B Ligand and C-C Motif Ligand 3 Correlate With Survival in Patients With Waldenström Macroglobulinemia.

PubMed

Eleutherakis-Papaiakovou, Evangelos; Kastritis, Efstathios; Gavriatopoulou, Maria; Christoulas, Dimitrios; Roussou, Maria; Ntanasis-Stathopoulos, Ioannis; Kanellias, Nikolaos; Papatheodorou, Athanasios; Dimopoulos, Meletios A; Terpos, Evangelos

2018-06-01

Serum receptor activator of nuclear factor κB ligand (sRANKL) and chemokine (C-C) motif ligand 3 (CCL-3) have been reported to be elevated in Waldenström macroglobulinemia (WM) patients. However, there are no published data regarding the prognostic value of these molecules in WM regarding progression-free and overall survival. To evaluate the effect of these markers of bone remodeling on survival parameters, we prospectively evaluated serum cytokines and biological markers in 55 patients with symptomatic WM before they received any kind of treatment. Serum levels of CCL-3 and bone remodeling markers were also evaluated in asymptomatic WM and IgM monoclonal gammopathy of undetermined significance. Furthermore, we assessed bone marrow biopsy samples from newly diagnosed WM patients for CCL-3 and RANKL expression. High circulating sRANKL values predicted shorter median overall survival (46 months vs. not reached, P = .025). High serum levels of CCL-3 predicted shorter median progression-free survival (27 months vs. not reached, P = .048). At bone marrow biopsy evaluation, the whole number of the neoplastic cells revealed strong cytoplasmic positivity for CCL-3, while the neoplastic clone did not express RANKL. We conclude that WM cells produce CCL-3 and possibly enhance the production of RANKL in the bone microenvironment. The correlation of sRANKL and CCL-3 with survival reveals the importance of these cytokines in disease biology and highlights the significance of the interactions between WM and stromal cells for the development of WM. Finally, these findings provide the rationale for the use of anti-RANKL and anti-CCL-3 drugs in animal models of WM before their clinical evaluation. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of saline drinking water on early gosling development

USGS Publications Warehouse

Stolley, D.S.; Bissonette, J.A.; Kadlec, J.A.; Coster, D.

1999-01-01

Relatively high levels of saline drinking water may adversely affect the growth, development, and survival of young waterfowl. Saline drinking water was suspect in the low survival rate of Canada goose (Branta canadensis) goslings at Fish Springs National Wildlife Refuge (FSNWR) in western Utah. Hence, we investigated the effects of saline drinking water on the survival and growth of captive, wild-strain goslings from day 1-28 following hatch. We compared survival and growth (as measured by body mass, wing length, and culmen length) between a control group on tap water with a mean specific conductivity of 650 ??S/cm, and 2 saline water treatments: (1) intermediate level (12,000 ??S/cm), and (2) high level (18,000 ??S/cm). Gosling mortality occurred only in the 18,000 ??S/cm treatment group (33%; n = 9). Slopes of regressions of mean body mass, wing length, and culmen length on age were different from each other (P < 0.05), except for culmen length for the intermediate and high treatment levels. We predict that free-ranging wild goslings will experience mortality at even lower salinity levels than captive goslings because of the combined effects of depressed growth and environmental stresses, including hot desert temperatures and variable food quality over summer.

CT Imaging Biomarkers Predict Clinical Outcomes After Pancreatic Cancer Surgery

PubMed Central

Zhu, Liang; Shi, Xiaohua; Xue, Huadan; Wu, Huanwen; Chen, Ge; Sun, Hao; He, Yonglan; Jin, Zhengyu; Liang, Zhiyong; Zhang, Zhuoli

2016-01-01

Abstract This study aimed to determine whether changes in contrast-enhanced computed tomography (CT) parameters could predict postsurgery overall and progression-free survival (PFS) in pancreatic cancer patients. Seventy-nine patients with a final pathological diagnosis of pancreatic adenocarcinoma were included in this study from June 2008 to August 2012. Dynamic contrast-enhanced (DCE) CT of tumors was obtained before curative-intent surgery. Absolute enhancement change (AEC) and relative enhancement change (REC) were evaluated on DCE-CT. PFS and overall survival (OS) were compared based on CT enhancement patterns. The markers of fibrogenic alpha-smooth muscle antigen (α-SMA) and periostin in tumor specimens were evaluated by immunohistochemical staining. The χ2 test was performed to determine whether CT enhancement patterns were associated with α-SMA-periostin expression levels (recorded as positive or negative). Lower REC (<0.9) was associated with shorter PFS (HR 0.51, 95% CI: 0.31–0.89) and OS (HR 0.44, 95% CI: 0.25–0.78). The α-SMA and periostin expression level were negatively correlated with REC (both P = 0). Among several CT enhancement parameters, REC was the best predictor of patient postsurgery survival. Low REC was associated with a short progression-free time and poor survival. The pathological studies suggested that REC might be a reflection of cancer fibrogenic potential. PMID:26844495

Establishment and Validation of RNA-Based Predictive Models for Understanding Survival of Vibrio parahaemolyticus in Oysters Stored at Low Temperatures

PubMed Central

Liao, Chao; Zhao, Yong

2017-01-01

ABSTRACT This study developed RNA-based predictive models describing the survival of Vibrio parahaemolyticus in Eastern oysters (Crassostrea virginica) during storage at 0, 4, and 10°C. Postharvested oysters were inoculated with a cocktail of five V. parahaemolyticus strains and were then stored at 0, 4, and 10°C for 21 or 11 days. A real-time reverse transcription-PCR (RT-PCR) assay targeting expression of the tlh gene was used to evaluate the number of surviving V. parahaemolyticus cells, which was then used to establish primary molecular models (MMs). Before construction of the MMs, consistent expression levels of the tlh gene at 0, 4, and 10°C were confirmed, and this gene was used to monitor the survival of the total V. parahaemolyticus cells. In addition, the tdh and trh genes were used for monitoring the survival of virulent V. parahaemolyticus. Traditional models (TMs) were built based on data collected using a plate counting method. From the MMs, V. parahaemolyticus populations had decreased 0.493, 0.362, and 0.238 log10 CFU/g by the end of storage at 0, 4, and 10°C, respectively. Rates of reduction of V. parahaemolyticus shown in the TMs were 2.109, 1.579, and 0.894 log10 CFU/g for storage at 0, 4, and 10°C, respectively. Bacterial inactivation rates (IRs) estimated with the TMs (−0.245, −0.152, and −0.121 log10 CFU/day, respectively) were higher than those estimated with the MMs (−0.134, −0.0887, and −0.0732 log10 CFU/day, respectively) for storage at 0, 4, and 10°C. Higher viable V. parahaemolyticus numbers were predicted using the MMs than using the TMs. On the basis of this study, RNA-based predictive MMs are the more accurate and reliable models and can prevent false-negative results compared to TMs. IMPORTANCE One important method for validating postharvest techniques and for monitoring the behavior of V. parahaemolyticus is to establish predictive models. Unfortunately, previous predictive models established based on plate counting methods or on DNA-based PCR can underestimate or overestimate the number of surviving cells. This study developed and validated RNA-based molecular predictive models to describe the survival of V. parahaemolyticus in oysters during low-temperature storage (0, 4, and 10°C). The RNA-based predictive models show the advantage of being able to count all of the culturable, nonculturable, and stressed cells. By using primers targeting the tlh gene and pathogenesis-associated genes (tdh and trh), real-time RT-PCR can evaluate the total surviving V. parahaemolyticus population as well as differentiate the pathogenic ones from the total population. Reliable and accurate predictive models are very important for conducting risk assessment and management of pathogens in food. PMID:28087532

Establishment and Validation of RNA-Based Predictive Models for Understanding Survival of Vibrio parahaemolyticus in Oysters Stored at Low Temperatures.

PubMed

Liao, Chao; Zhao, Yong; Wang, Luxin

2017-03-15

This study developed RNA-based predictive models describing the survival of Vibrio parahaemolyticus in Eastern oysters ( Crassostrea virginica ) during storage at 0, 4, and 10°C. Postharvested oysters were inoculated with a cocktail of five V. parahaemolyticus strains and were then stored at 0, 4, and 10°C for 21 or 11 days. A real-time reverse transcription-PCR (RT-PCR) assay targeting expression of the tlh gene was used to evaluate the number of surviving V. parahaemolyticus cells, which was then used to establish primary molecular models (MMs). Before construction of the MMs, consistent expression levels of the tlh gene at 0, 4, and 10°C were confirmed, and this gene was used to monitor the survival of the total V. parahaemolyticus cells. In addition, the tdh and trh genes were used for monitoring the survival of virulent V. parahaemolyticus Traditional models (TMs) were built based on data collected using a plate counting method. From the MMs, V. parahaemolyticus populations had decreased 0.493, 0.362, and 0.238 log 10 CFU/g by the end of storage at 0, 4, and 10°C, respectively. Rates of reduction of V. parahaemolyticus shown in the TMs were 2.109, 1.579, and 0.894 log 10 CFU/g for storage at 0, 4, and 10°C, respectively. Bacterial inactivation rates (IRs) estimated with the TMs (-0.245, -0.152, and -0.121 log 10 CFU/day, respectively) were higher than those estimated with the MMs (-0.134, -0.0887, and -0.0732 log 10 CFU/day, respectively) for storage at 0, 4, and 10°C. Higher viable V. parahaemolyticus numbers were predicted using the MMs than using the TMs. On the basis of this study, RNA-based predictive MMs are the more accurate and reliable models and can prevent false-negative results compared to TMs. IMPORTANCE One important method for validating postharvest techniques and for monitoring the behavior of V. parahaemolyticus is to establish predictive models. Unfortunately, previous predictive models established based on plate counting methods or on DNA-based PCR can underestimate or overestimate the number of surviving cells. This study developed and validated RNA-based molecular predictive models to describe the survival of V. parahaemolyticus in oysters during low-temperature storage (0, 4, and 10°C). The RNA-based predictive models show the advantage of being able to count all of the culturable, nonculturable, and stressed cells. By using primers targeting the tlh gene and pathogenesis-associated genes ( tdh and trh ), real-time RT-PCR can evaluate the total surviving V. parahaemolyticus population as well as differentiate the pathogenic ones from the total population. Reliable and accurate predictive models are very important for conducting risk assessment and management of pathogens in food. Copyright © 2017 American Society for Microbiology.

Resource allocation and post-reproductive degeneration in the freshwater cnidarian Hydra oligactis (Pallas, 1766).

PubMed

Tökölyi, Jácint; Ősz, Zsófia; Sebestyén, Flóra; Barta, Zoltán

2017-02-01

Freshwater hydra are among the few animal groups that show negligible senescence and can maintain high survival and reproduction rates when kept under stable conditions in the laboratory. Yet, one species of Hydra (H. oligactis) undergoes a senescence-like process in which polyps degenerate and die after sexual reproduction. The ultimate factors responsible for this phenomenon are unclear. High mortality in reproducing animals could be the consequence of increased allocation of resources to reproduction at the expense of somatic maintenance. This hypothesis predicts that patterns of reproduction and survival are influenced by resource availability. To test this prediction we investigated survival and reproduction at different levels of food availability in 10 lineages of H. oligactis derived from a single Hungarian population. Sexual reproduction was accompanied by reduced survival, but a substantial proportion of animals regenerated after sexual reproduction and continued reproducing asexually. Polyps belonging to different lineages showed differences in their propensity to initiate sexual reproduction, gonad number and survival rate. Food availability significantly affected fecundity (number of eggs or testes produced), with the largest number of gonads being produced by animals kept on a high food regime. On the other hand, survival rate was not affected by the amount of food. These results show that survival is conserved at the expense of reproduction in this population when food is low. It remains a question still to be answered why survival is prioritized over reproduction in this population. Copyright © 2016 Elsevier GmbH. All rights reserved.

Low BRAF and NRAS expression levels are associated with clinical benefit from DTIC therapy and prognosis in metastatic melanoma.

PubMed

Birkeland, Einar; Busch, Christian; Berge, Elisabet Ognedal; Geisler, Jürgen; Jönsson, Göran; Lillehaug, Johan Richard; Knappskog, Stian; Lønning, Per Eystein

2013-10-01

Metastatic melanoma is characterized by a poor response to chemotherapy. Furthermore, there is a lack of established predictive and prognostic markers. In this single institution study, we correlated mutation status and expression levels of BRAF and NRAS to dacarbazine (DTIC) treatment response as well as progression-free and overall survival in a cohort of 85 patients diagnosed with advanced melanoma. Neither BRAF nor NRAS mutation status correlated to treatment response. However, patients with tumors harboring NRAS mutations had a shorter overall survival (p < 0.001) compared to patients with tumors wild-type for NRAS. Patients having a clinical benefit (objective response or stable disease at 3 months) on DTIC therapy had lower BRAF and NRAS expression levels compared to patients progressing on therapy (p = 0.037 and 0.003, respectively). For BRAF expression, this association was stronger among patients with tumors wild-type for BRAF (p = 0.005). Further, low BRAF as well as NRAS expression levels were associated with a longer progression-free survival in the total population (p = 0.004 and <0.001, respectively). Contrasting low NRAS expression levels, which were associated with improved overall survival in the total population (p = 0.01), low BRAF levels were associated with improved overall survival only among patients with tumors wild-type for BRAF (p = 0.013). These findings indicate that BRAF and NRAS expression levels may influence responses to DTIC as well as prognosis in patients with advanced melanoma.

A clinicopathologic prediction model for postoperative recurrence in stage Ia non-small cell lung cancer.

PubMed

Zhang, Yang; Sun, Yihua; Xiang, Jiaqing; Zhang, Yawei; Hu, Hong; Chen, Haiquan

2014-10-01

Controversy remains over the appropriate postoperative management for patients with stage Ia non-small cell lung cancer who underwent complete surgical resection as a result of a heterogeneous prognosis. We aimed to identify the predictive factors for recurrence in these patients to aid in the decision making. We reviewed 344 patients with stage Ia non-small cell lung cancer to analyze the associations between recurrence-free survival and the following clinicopathologic variables: age, gender, smoking history, family history, preoperative serum carcinoembryonic antigen level, type of surgical resection, tumor location, tumor histology, lymphovascular invasion, tumor differentiation, and pathologic T status. Cox multivariate survival analysis revealed that central tumor location (P=.019), stage T1b (P=.006), high histologic grade (including large cell carcinoma, solid predominant, micropapillary predominant, and invasive mucinous adenocarcinoma, P=.007), poor differentiation (P=.022), and lymphovascular invasion (P=.035) were independently associated with recurrence-free survival. A nomogram for predicting the probability of 3-year recurrence-free survival was developed using the 5 variables. This model shows good calibration, reasonable discrimination (concordance index=0.733), and small overfitting (2.6%) demonstrated by bootstrapping. We developed a clinicopathologic prediction model for postoperative recurrence in stage Ia non-small cell lung cancer. This model can help with the selection of appropriate postoperative therapeutic strategies for these patients. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Predicting tidal marsh survival or submergence to sea-level rise using Holocene data

NASA Astrophysics Data System (ADS)

Horton, B.; Shennan, I.; Bradley, S.; Cahill, N.; Kirwan, M. L.; Kopp, R. E.; Shaw, T.

2017-12-01

Rising sea level threatens to permanently submerge tidal marsh environments if they cannot accrete faster than the rate of relative sea-level rise (RSLR). But regional and global model simulations of the future ability of marshes to maintain their elevation with respect to the tidal frame are uncertain. The compilation of empirical data for tidal marsh vulnerability is, therefore, essential to address disparities across these simulations. A hitherto unexplored source of empirical data are Holocene records of tidal marsh evolution. In particular, the marshes of Great Britain have survived and submerged while RSLR varied between -7.7 and 15.2 mm/yr, primarily because of the interplay between global ice-volume changes and regional isostatic processes. Here, we reveal the limits to marsh vulnerability are revealed through the analysis of over 400 reconstructions of tidal marsh submergence and conversion to tidal mud flat or open water from 54 regions in Great Britain during the Holocene. Holocene records indicate a 90% probability of tidal marsh submergence at sites with RSLR exceeding 7.3 mm/yr (95% CI: 6.6-8.6 mm/yr). Although most modern tidal marshes in Great Britain have not yet reached these sea-level rise limits, our empirical data suggest widespread concern over their ability to survive rates of sea-level rise in the 21st century under high emission scenarios. Integrating over the uncertainties in both sea-level rise predictions and the response of tidal marshes to sea-level rise, all of Great Britain has a >80% probability of marsh submergence under RCP 8.5 by 2100, with areas of south and eastern England, where the rate of RSLR is increased by glacio-isostatic subsidence, achieving this probability by 2040.

Smart Extraction and Analysis System for Clinical Research.

PubMed

Afzal, Muhammad; Hussain, Maqbool; Khan, Wajahat Ali; Ali, Taqdir; Jamshed, Arif; Lee, Sungyoung

2017-05-01

With the increasing use of electronic health records (EHRs), there is a growing need to expand the utilization of EHR data to support clinical research. The key challenge in achieving this goal is the unavailability of smart systems and methods to overcome the issue of data preparation, structuring, and sharing for smooth clinical research. We developed a robust analysis system called the smart extraction and analysis system (SEAS) that consists of two subsystems: (1) the information extraction system (IES), for extracting information from clinical documents, and (2) the survival analysis system (SAS), for a descriptive and predictive analysis to compile the survival statistics and predict the future chance of survivability. The IES subsystem is based on a novel permutation-based pattern recognition method that extracts information from unstructured clinical documents. Similarly, the SAS subsystem is based on a classification and regression tree (CART)-based prediction model for survival analysis. SEAS is evaluated and validated on a real-world case study of head and neck cancer. The overall information extraction accuracy of the system for semistructured text is recorded at 99%, while that for unstructured text is 97%. Furthermore, the automated, unstructured information extraction has reduced the average time spent on manual data entry by 75%, without compromising the accuracy of the system. Moreover, around 88% of patients are found in a terminal or dead state for the highest clinical stage of disease (level IV). Similarly, there is an ∼36% probability of a patient being alive if at least one of the lifestyle risk factors was positive. We presented our work on the development of SEAS to replace costly and time-consuming manual methods with smart automatic extraction of information and survival prediction methods. SEAS has reduced the time and energy of human resources spent unnecessarily on manual tasks.

Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

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

Vadhavkar, Nikhil; Pham, Christopher; Georgescu, Walter

In contrast to the classic view of static DNA double-strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (m). As X-ray dose increases, the probability of having DSB clusters increases as does the probability of misrepair and cell death. Experimental work characterizing the X-ray dose dependence of radiation-induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSBs at the submicronmore » level. Two mechanisms for DSB clustering, namely random coalescence of DSBs versus active movement of DSBs into repair domains are compared and tested. Simulations that best predicted both RIF dose dependence and cell survival after X-ray irradiation favored the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ~;;1.55 m sides. Applying the same approach to high-linear energy transfer (LET) ion tracks, we are able to predict experimental RIF/m along tracks with an overall relative error of 12percent, for LET ranging between 30 350 keV/m and for three different ions. Finally, cell death was predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. Relative biological effectiveness (RBE) predictions for cell survival of MCF10A exposed to high-LET showed an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the submicron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. Conversely, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our model are based on experimental RIF and are three times larger than the hypothetical LEM voxel used to fit survival curves. Our model is therefore an alternative to previous approaches that provides a testable biological mechanism (i.e., RIF). In addition, we propose that DSB pairing will help develop more accurate alternatives to the linear cancer risk model (LNT) currently used for regulating exposure to very low levels of ionizing radiation.« less

Risk score for pediatric intensive care unit admission in children undergoing hematopoietic stem cell transplantation and analysis of predictive factors for survival.

PubMed

González-Vicent, Marta; Marín, Catalina; Madero, Luis; Sevilla, Julián; Díaz, Miguel Angel

2005-10-01

The authors retrospectively analyzed postransplantation events in 198 children who underwent hematopoietic stem cell transplantation (HSCT) between 1998 and 2002 to obtain a risk score for pediatric intensive care unit (PICU) admission and to ascertain variables predicting a poor outcome. Thirty-six patients (18%) were admitted to the PICU. Median age was 9 years (range 1-18). On univariate analysis, variables significantly associated with PICU admission were male gender (P = 0.01), more than first complete remission (P = 0.003), allogeneic transplantation (P = 0.001), engraftment syndrome (P = 0.03), and acute graft-versus-host disease grade of at least two (P = 0.05). According to this, patients were divided in two levels of risk (low and high), with a respective probability of PICU admission of 8.8 +/- 2.2% and 63.8 +/- 8.8% (P < 0.0001). Seventeen (47%) patients were discharged from the PICU. The probability of event-free survival after PICU admission at 3 years was 24.2 +/- 7%. On univariate analysis, variables with a negative impact on event-free survival were type of transplantation, inotropic support, a C-reactive protein level of at least 10 mg/dL, and a high O-PRISM score. On multivariate analysis, the only variable that influenced event-free survival was the O-PRISM score (< or =10 points, 54.6 +/- 15.3%; >10 points, 8.6 +/- 5.8%; P = 0.007). In conclusion, the risk of PICU admission may be easily estimated using simple variables. A high O-PRISM score at the time of PICU admission predicts a dismal outcome.

Adverse Outcome Pathways and Extrapolation Tools to Advance the Three Rs in Ecotoxicology

EPA Science Inventory

Adverse outcome pathways (AOPs) are conceptual frameworks for identifying and organizing predictive and causal linkages between cellular-level responses and endpoints conventionally considered in ecological risk assessment (e.g., effects on survival, growth/development, and repro...

Prognostic impact of RITA expression in patients with anal squamous cell carcinoma treated with chemoradiotherapy.

PubMed

Rödel, Franz; Steinhäuser, Kerstin; Kreis, Nina-Naomi; Friemel, Alexandra; Martin, Daniel; Wieland, Ulrike; Rave-Fränk, Margret; Balermpas, Panagiotis; Fokas, Emmanouil; Louwen, Frank; Rödel, Claus; Yuan, Juping

2018-02-01

RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive. In our retrospective study immunohistochemical evaluation of RITA was performed on 140 pre-treatment specimens and was correlated with clinical and histopathologic characteristics and clinical endpoints cumulative incidence of local control (LC), distant recurrence (DC), disease-free survival (DFS) and overall survival (OS). We observed significant inverse correlations between RITA expression and tumour grading, the levels of HPV-16 virus DNA load, CD8 (+) tumour infiltrating lymphocytes and programmed death protein (PD-1) immunostaining. In univariate analyses, elevated levels of RITA expression were predictive for decreased local control (p = 0.001), decreased distant control (p = 0.040), decreased disease free survival (p = 0.001) and overall survival (p < 0.0001), whereas in multivariate analyses RITA expression remained significant for decreased local control (p = 0.009), disease free survival (p = 0.032) and overall survival (p = 0.012). These data indicate that elevated levels of pretreatment RITA expression are correlated with unfavourable clinical outcome in anal carcinoma treated with concomitant chemoradiotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamic detection of N-terminal pro-B-type natriuretic peptide helps to predict the outcome of patients with major trauma.

PubMed

Qian, A; Zhang, M; Zhao, G

2015-02-01

NT-proBNP and BNP have been demonstrated to be prognostic markers in cardiac disease and sepsis. However, the prognostic value and the dynamic changes of BNP or NT-proBNP in trauma patients remain unclear. The present study was conducted to investigate the dynamic changes of NT-proBNP in patients with major trauma (injury severity score ≥16), determine whether NT-proBNP could be used as a simple index to predict mortality in major trauma patients. This prospective observational study included 60 patients with major trauma. Serum NT-proBNP levels were measured on the 1st, 3rd and 7th day after injury The NT-proBNP levels in survivors were compared with those in non-survivors. The efficacy of NT-proBNP to predict survival was analyzed using receiver operating characteristic curves. An analysis of correlations between NT-proBNP and various factors, including injury severity score, Glasgow coma score, acute physiology and chronic health evaluation II, central venous pressure, creatine kinase-MB, cardiac troponin I and procalcitonin (PCT) was performed. NT-proBNP levels in patients with traumatic brain injury were compared with those in patients without traumatic brain injury. A comparison of NT-proBNP levels between patients with and without sepsis was also performed at each time point. NT-proBNP levels in non-survivors were significantly higher than those in survivors at all the indicated time points. In the group of non-survivors, NT-proBNP levels on the 7th day were markedly higher than those on the 1st day. In contrast, NT-proBNP levels in survivors showed a reduction over time. The efficacy of NT-proBNP to predict survival was analyzed using ROC curves, and there was no difference in the area under the ROC between NT-proBNP and APACHE II/ISS at the three time points. A significant correlation was found between NT-proBNP and ISS on the 1st day, NT-proBNP and CK-MB, Tn-I and APACHE II on the 3rd day, NT-proBNP and PCT on the 7th day. There were no significant differences in NT-proBNP levels between patients with or without brain trauma at all the indicated time points. NT-proBNP levels in patients with sepsis were significantly higher than those in patients without sepsis at all the indicated time points. These findings suggest that dynamic detection of serum NT-proBNP might help to predict death in patients with major trauma. A high level of NT-proBNP at admission or maintained for several days after trauma indicates poor survival.

Predicting long-term graft survival in adult kidney transplant recipients.

PubMed

Pinsky, Brett W; Lentine, Krista L; Ercole, Patrick R; Salvalaggio, Paolo R; Burroughs, Thomas E; Schnitzler, Mark A

2012-07-01

The ability to accurately predict a population's long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population's long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and compared with the population's actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted survival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population's long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.

Serum albumin predicts survival in patients with hilar cholangiocarcinoma.

PubMed

Waghray, Abhijeet; Sobotka, Anastasia; Marrero, Carlos Romero; Estfan, Bassam; Aucejo, Federico; Narayanan Menon, K V

2017-02-01

Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma. All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation. A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P < 0.01), cancer antigen 19-9 ≤200 U/mL (P = 0.03), carcinoembryonic antigen ≤10 ìg/L (P < 0.01) or patients without a history of cirrhosis (P < 0.01) or diabetes (P = 0.02) were associated with a greater length of overall survival. A serum albumin level >3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14-0.70) with a survival benefit of 44 weeks. This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival. © The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University.

Survival Analysis of Papillary Thyroid Carcinoma in Relation to Stage and Recurrence Risk: A 20-Year Experience in Pakistan.

PubMed

Hassan, Aamna; Razi, Mairah; Riaz, Saima; Khalid, Madeeha; Nawaz, M Khalid; Syed, Aamir Ali; Bashir, Humayun

2016-08-01

The aim of this study was to evaluate the overall and progression-free survival of papillary thyroid carcinoma (PTC), comparing the American Thyroid Association (ATA) guideline for risk of recurrence with the TNM staging system with dynamic assessment at 2 years. This study is a retrospective analysis of 689 PTC patients over a 20-year period at a single center. Disease-free survival based on the TNM staging and ATA recurrence risk was calculated using Kaplan-Meier curves. Dynamic response assessment during the first 2 years was compared for both systems. Survival was calculated based on age, baseline resectability, and postthyroidectomy serum tumor marker levels. Six hundred eighty-nine (72.2%) of the total thyroid cancer patients had PTC. Four hundred sixty-nine patients were females, and 220 patients were males. The age range was 6 to 87 years. Five hundred thirty-five patients were resectable, and 56 patients were unresectable. One hundred fifty-one patients were excluded due to insufficient information on recurrence risk. By ATA categorization, 39% had low risk, no disease-related mortality; 44% had intermediate risk, 3 died; and 17% had high risk, 32 died. The 5-year disease-free survival was 54%, 26%, and 5% in low-, intermediate-, and high-risk groups, respectively. The log-rank test showed a significant difference in the percent survival (P < 0.01). TNM stage wise, in terms of survival, 1.3% in stage I, 2.2% in stage II, 0% in stage III, and 37.5% in stage IV died. The 20-year disease-free survival showed the following: stage I, 43%; stage II, 28%; stage III, 18%; and stage IV, 2%. There is significant difference in survival rate (P < 0.01). Both ATA risk classification and TNM staging were significant predictors of disease-free survival. On bivariate analysis, ATA classification (hazards ratio, 2.1; 95% confidence interval, 1.64-2.67; P = 0.001) was better predictive of overall survival versus TNM classification (hazards ratio, 1.3; 95% confidence interval, 1.11-1.43; P = 0.063). The ATA risk stratification and continuous reassessment during the first 2 years predicts disease-free survival better than the TNM staging. Age older than 45 years, unresectable disease, and elevated postthyroidectomy thyroglobulin levels dictate a poorer prognosis.

Integrating multiple molecular sources into a clinical risk prediction signature by extracting complementary information.

PubMed

Hieke, Stefanie; Benner, Axel; Schlenl, Richard F; Schumacher, Martin; Bullinger, Lars; Binder, Harald

2016-08-30

High-throughput technology allows for genome-wide measurements at different molecular levels for the same patient, e.g. single nucleotide polymorphisms (SNPs) and gene expression. Correspondingly, it might be beneficial to also integrate complementary information from different molecular levels when building multivariable risk prediction models for a clinical endpoint, such as treatment response or survival. Unfortunately, such a high-dimensional modeling task will often be complicated by a limited overlap of molecular measurements at different levels between patients, i.e. measurements from all molecular levels are available only for a smaller proportion of patients. We propose a sequential strategy for building clinical risk prediction models that integrate genome-wide measurements from two molecular levels in a complementary way. To deal with partial overlap, we develop an imputation approach that allows us to use all available data. This approach is investigated in two acute myeloid leukemia applications combining gene expression with either SNP or DNA methylation data. After obtaining a sparse risk prediction signature e.g. from SNP data, an automatically selected set of prognostic SNPs, by componentwise likelihood-based boosting, imputation is performed for the corresponding linear predictor by a linking model that incorporates e.g. gene expression measurements. The imputed linear predictor is then used for adjustment when building a prognostic signature from the gene expression data. For evaluation, we consider stability, as quantified by inclusion frequencies across resampling data sets. Despite an extremely small overlap in the application example with gene expression and SNPs, several genes are seen to be more stably identified when taking the (imputed) linear predictor from the SNP data into account. In the application with gene expression and DNA methylation, prediction performance with respect to survival also indicates that the proposed approach might work well. We consider imputation of linear predictor values to be a feasible and sensible approach for dealing with partial overlap in complementary integrative analysis of molecular measurements at different levels. More generally, these results indicate that a complementary strategy for integrating different molecular levels can result in more stable risk prediction signatures, potentially providing a more reliable insight into the underlying biology.

Cox-nnet: An artificial neural network method for prognosis prediction of high-throughput omics data

PubMed Central

Ching, Travers; Zhu, Xun

2018-01-01

Artificial neural networks (ANN) are computing architectures with many interconnections of simple neural-inspired computing elements, and have been applied to biomedical fields such as imaging analysis and diagnosis. We have developed a new ANN framework called Cox-nnet to predict patient prognosis from high throughput transcriptomics data. In 10 TCGA RNA-Seq data sets, Cox-nnet achieves the same or better predictive accuracy compared to other methods, including Cox-proportional hazards regression (with LASSO, ridge, and mimimax concave penalty), Random Forests Survival and CoxBoost. Cox-nnet also reveals richer biological information, at both the pathway and gene levels. The outputs from the hidden layer node provide an alternative approach for survival-sensitive dimension reduction. In summary, we have developed a new method for accurate and efficient prognosis prediction on high throughput data, with functional biological insights. The source code is freely available at https://github.com/lanagarmire/cox-nnet. PMID:29634719

Can we customize chemotherapy? Individualizing cytotoxic regimens in advanced non-small-cell lung cancer.

PubMed

Rosell, Rafael; Manegold, Christian; Moran, Teresa; Garrido, Pilar; Blanco, Remei; Lianes, Pilar; Stahel, Rolf; Trigo, Jose Manuel; Wei, Jia; Taron, Miquel

2008-03-01

Metastatic non-small-cell lung cancer remains a fatal disease with a median survival of < 1 year. A critical challenge is to develop predictive markers for customizing platinum-based treatment. The first studies focused on the excision repair cross-complementing 1 (ERCC1) gene in this difficult task. Several layers of evidence indicate that ERCC1 mRNA expression could be a predictive marker for cisplatin alone or in combination with certain drugs such as etoposide, gemcitabine, and 5-fluorouracil but not in combination with antimicrotubule drugs. Several retrospective studies demonstrated an impressive survival advantage for gemcitabine plus cisplatin but not for other combinations in tumors with low ERCC1 expression. A customized phase III ERCC1-based trial met the primary endpoint of improvement in response but not in survival, leading us to hypothesize that docetaxel might not be the most appropriate partner for cisplatin in the presence of low ERCC1 levels or for gemcitabine in the presence of high ERCC1 levels. A phase II study demonstrated the feasibility of combining carboplatin, gemcitabine, docetaxel, and vinorelbine according to ERCC1 and ribonucleotide reductase subunit M1 expression levels. These findings highlight the importance of continual learning, and decision-making strategies for customizing treatment should reflect the limitations of our knowledge. Copyright © 2008 Elsevier Inc. All rights reserved.

Serum biological antioxidant potential predicts the prognosis of hemodialysis patients.

PubMed

Ishii, Tomoko; Ohtake, Takayasu; Okamoto, Koji; Mochida, Yasuhiro; Ishioka, Kunihiro; Oka, Machiko; Maesato, Kyoko; Ikee, Ryota; Moriya, Hidekazu; Hidaka, Sumi; Doi, Kent; Noiri, Eisei; Fujita, Toshiro; Kobayashi, Shuzo

2011-01-01

It is well known that oxidative stress is enhanced in patients with end-stage renal disease. However, little is known about the relationship between serum antioxidant capacity and clinical outcome in hemodialysis (HD) patients. We examined the relationship between serum biomarkers of oxidative stress and clinical outcomes including all-cause mortality, hospitalization rate and incidence of cardiovascular events in HD patients. As biomarkers of oxidative stress, we measured serum levels of coenzyme Q10 (CoQ10) and biological antioxidant potential (BAP). 108 patients were observed for 30 months as the follow-up periods. The survival group (n = 83) showed significantly higher BAP values compared with those in death groups (n = 25; p < 0.05). When serum BAP levels were divided into two groups by their median value, the group with higher BAP values had a better survival rate than that with lower BAP values on the Kaplan-Meier survival analysis (p = 0.05). Although serum levels of CoQ10 did not show any association with clinical outcomes, lower BAP was selected as an independent risk factor for all-cause mortality as well as the absence of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers therapy by age-adjusted Cox regression analysis. This study indicated that BAP could predict the prognosis of HD patients. Copyright © 2010 S. Karger AG, Basel.

Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

PubMed

Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Kadono, Yoshifumi; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

2016-03-01

To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

Demographic population model for American shad: will access to additional habitat upstream of dams increase population sizes?

USGS Publications Warehouse

Harris, Julianne E.; Hightower, Joseph E.

2012-01-01

American shad Alosa sapidissima are in decline in their native range, and modeling possible management scenarios could help guide their restoration. We developed a density-dependent, deterministic, stage-based matrix model to predict the population-level results of transporting American shad to suitable spawning habitat upstream of dams on the Roanoke River, North Carolina and Virginia. We used data on sonic-tagged adult American shad and oxytetracycline-marked American shad fry both above and below dams on the Roanoke River with information from other systems to estimate a starting population size and vital rates. We modeled the adult female population over 30 years under plausible scenarios of adult transport, effective fecundity (egg production), and survival of adults (i.e., to return to spawn the next year) and juveniles (from spawned egg to age 1). We also evaluated the potential effects of increased survival for adults and juveniles. The adult female population size in the Roanoke River was estimated to be 5,224. With no transport, the model predicted a slow population increase over the next 30 years. Predicted population increases were highest when survival was improved during the first year of life. Transport was predicted to benefit the population only if high rates of effective fecundity and juvenile survival could be achieved. Currently, transported adults and young are less likely to successfully out-migrate than individuals below the dams, and the estimated adult population size is much smaller than either of two assumed values of carrying capacity for the lower river; therefore, transport is not predicted to help restore the stock under present conditions. Research on survival rates, density-dependent processes, and the impacts of structures to increase out-migration success would improve evaluation of the potential benefits of access to additional spawning habitat for American shad.

Serum decoy receptor 3 level: a predictive marker for nodal metastasis and survival among oral cavity cancer patients.

PubMed

Tu, Hsi-Feng; Liu, Chung-Ji; Liu, Shyun-Yeu; Chen, Yu-Ping; Yu, En-Hao; Lin, Shu-Chun; Chang, Kuo-Wei

2011-03-01

Validating markers for prediction of nodal metastasis could be beneficial in treatment of oral cavity cancer. Decoy receptor 3 (DcR3), locus on 20q13, functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor (TNFR) family. This study analyzed the serum level of DcR3 in relationship to the clinical parameters of oral cavity cancer patients together with detection of DcR3 genomic copy number in primary and recurrent tumors. Elevated serum DcR3 was associated with nodal metastasis and worse prognosis. Gain of DcR3 copy number was detected in 17% of primary tumor tissue but not found in healthy areca chewers. Tissue from recurrent tumors showed more frequent DcR3 copy number alteration (48%) than the paired primary tumor tissue. Serum DcR3 level is a predictor for the nodal metastasis and survival among oral cavity cancer patients and the DcR3 copy number alteration could underlie oral carcinogenesis progression. Copyright © 2010 Wiley Periodicals, Inc.

Predicting responses to climate change requires all life-history stages.

PubMed

Zeigler, Sara

2013-01-01

In Focus: Radchuk, V., Turlure, C. & Schtickzelle, N. (2013) Each life stage matters: the importance of assessing response to climate change over the complete life cycle in butterflies. Journal of Animal Ecology, 82, 275-285. Population-level responses to climate change depend on many factors, including unexpected interactions among life history attributes; however, few studies examine climate change impacts over complete life cycles of focal species. Radchuk, Turlure & Schtickzelle () used experimental and modelling approaches to predict population dynamics for the bog fritillary butterfly under warming scenarios. Although they found that warming improved fertility and survival of all stages with one exception, populations were predicted to decline because overwintering larvae, whose survival declined with warming, were disproportionately important contributors to population growth. This underscores the importance of considering all life history stages in analyses of climate change's effects on population dynamics. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

Pleural Fluid Adenosine Deaminase (ADA) Predicts Survival in Patients with Malignant Pleural Effusion.

PubMed

Terra, Ricardo Mingarini; Antonangelo, Leila; Mariani, Alessandro Wasum; de Oliveira, Ricardo Lopes Moraes; Teixeira, Lisete Ribeiro; Pego-Fernandes, Paulo Manuel

2016-08-01

Systemic and local inflammations have been described as relevant prognostic factors in patients with cancer. However, parameters that stand for immune activity in the pleural space have not been tested as predictors of survival in patients with malignant pleural effusion. The objective of this study was to evaluate pleural lymphocytes and Adenosine Deaminase (ADA) as predictors of survival in patients with recurrent malignant pleural effusion. Retrospective cohort study includes patients who underwent pleurodesis for malignant pleural effusion in a tertiary center. Pleural fluid protein concentration, lactate dehydrogenase, glucose, oncotic cytology, cell count, and ADA were collected before pleurodesis and analyzed. Survival analysis was performed considering pleurodesis as time origin, and death as the event. Backwards stepwise Cox regression was used to find predictors of survival. 156 patients (out of 196 potentially eligible) were included in this study. Most were female (72 %) and breast cancer was the most common underlying malignancy (53 %). Pleural fluid ADA level was stratified as low (<15 U/L), normal (15 ≤ ADA < 40), and high (≥40). Low and high ADA levels were associated with worse survival when compared to normal ADA (logrank: 0.0024). In multivariable analysis, abnormal ADA (<15 or ADA ≥ 40) and underlying malignancies different from lymphoma, lung, or breast cancer were associated with worse survival. Pleural fluid cell count and lymphocytes number and percentage did not correlate with survival. Pleural fluid Adenosine Deaminase levels (<15 or ≥40 U/L) and neoplasms other than lung, breast, or lymphoma are independent predictors of worse survival in patients with malignant pleural effusion who undergo pleurodesis.

Movement and survival of an amphibian in relation to sediment and culvert design

USGS Publications Warehouse

Honeycutt, R.K; Lowe, W.H.; Hossack, Blake R.

2016-01-01

Habitat disturbance from stream culverts can affect aquatic organisms by increasing sedimentation or forming barriers to movement. Land managers are replacing many culverts to reduce these negative effects, primarily for stream fishes. However, these management actions are likely to have broad implications for many organisms, including amphibians in small streams. To assess the effects of culverts on movement and survival of the Idaho giant salamander (Dicamptodon aterrimus), we used capture-mark-recapture surveys and measured sediment in streams with 2 culvert types (i.e., unimproved culverts, improved culverts) and in streams without culverts (i.e., reference streams). We predicted culverts would increase stream sediment levels, limit movement, and reduce survival of Idaho giant salamanders. We also determined the effect of sediment levels on survival of salamanders because although sediment is often associated with distribution and abundance of stream amphibians, links with vital rates remain unclear. To estimate survival, we used a spatial Cormack–Jolly–Seber (CJS) model that explicitly incorporated information on movement, eliminating bias in apparent survival estimated from traditional (i.e., non-spatial) CJS models caused by permanent emigration beyond the study area. To demonstrate the importance of using spatial data in studies of wildlife populations, we compared estimates from the spatial CJS to estimates of apparent survival from a traditional CJS model. Although high levels of sediment reduced survival of salamanders, culvert type was unrelated to sediment levels or true survival of salamanders. Across all streams, we documented only 15 movement events between study reaches. All movement events were downstream, and they occurred disproportionately in 1 stream, which precluded measuring the effect of culvert design on movement. Although movement was low overall, the variance among streams was high enough to bias estimates of apparent survival compared to true survival. Our results suggest that where sedimentation occurs from roads and culverts, survival of the Idaho giant salamander could be reduced. Though culverts clearly do not completely block downstream movements of Idaho giant salamanders, the degree to which culvert improvements affect movements under roads in comparison to unimproved culverts remains unclear, especially for rare, but potentially important, upstream movements.

Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone.

PubMed

Ikeda, Kimiyuki; Shiratori, Masanori; Chiba, Hirofumi; Nishikiori, Hirotaka; Yokoo, Keiki; Saito, Atsushi; Hasegawa, Yoshihiro; Kuronuma, Koji; Otsuka, Mitsuo; Yamada, Gen; Takahashi, Hiroki

2017-10-01

Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease with poor prognosis. Pirfenidone, the first antifibrotic drug, suppresses the decline in forced vital capacity (FVC) and improves prognosis in some, but not all, patients with IPF; therefore, an indicator for identifying improved outcomes in pirfenidone therapy is desirable. This study aims to clarify whether baseline parameters can be predictors of disease progression and prognosis in patients with IPF treated with pirfenidone. We retrospectively investigated patients with IPF who started treatment with pirfenidone between December 2008 and November 2014 at the Sapporo Medical University Hospital. Patients treated with pirfenidone for ≥6 months were enrolled in this study and were observed until November 2015. We investigated the association of clinical characteristics, pulmonary function test results, and blood examination results at the start of pirfenidone with the outcome of patients. Sixty patients were included in this study. In multivariate logistic regression analysis, % predicted FVC and serum surfactant protein (SP)-D levels were predictors of a ≥10% decline in FVC in the initial 12 months. In the Cox proportional hazards model, these two factors predicted progression-free survival. Pack-years, % predicted diffusing capacity for carbon monoxide, and SP-D levels predicted overall survival. The serum SP-D level was a predictor of disease progression and prognosis in patients with IPF treated with pirfenidone. In addition, this analysis describes the relative usefulness of other clinical parameters at baseline in estimating the prognosis of patients with IPF who are candidates for pirfenidone therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fitness plus American Society of Anesthesiologists grade improve outcome prediction after endovascular aneurysm repair.

PubMed

Boult, Margaret; Cowled, Prue; Barnes, Mary; Fitridge, Robert A

2017-09-01

Although the American Society of Anesthesiologists (ASA) grade was established for statistical purposes, it is often used prognostically. However, older patients undergoing elective surgery are typically ASA III, which limits patient stratification. We look at the prognostic effect on early complications and survival of using ASA and self-reported physical fitness to stratify patients undergoing endovascular repair of abdominal aortic aneurysms. Data were extracted from a trial database. All patients were assigned a fitness level (A (fit) or B (unfit)) based on their self-reported ability to walk briskly for 1 km or climb two flights of stairs. Fitness was used to stratify ASA III patients, with fitter patients assigned ASA IIIA and less fit patients ASA IIIB. Outcomes assessed included survival, reinterventions, endoleak, all early and late complications and early operative complications. A combined ASA/fitness scale (II, IIIA, IIIB and IV) correlated with 1- and 3-year survival (1-year P = 0.001, 3-year P = 0.001) and early and late complications (P = 0.001 and P = 0.05). On its own, ASA predicted early complications (P = 0.0004) and survival (1-year P = 0.01, 3-year P = 0.01). Fitness alone was predictive for survival (1-year P = 0.001, 3-year P = 0.001) and late complications (P = 0.009). This study shows that even a superficial assessment of fitness is reflected in surgical outcomes, with fitter ASA III patients showing survival patterns similar to ASA II patients. Physicians should be alert to differences in fitness between patients in the ASA III group, despite similarities based on preexisting severe systemic disease. © 2017 Royal Australasian College of Surgeons.

Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis.

PubMed

Benza, Raymond L; Miller, Dave P; Foreman, Aimee J; Frost, Adaani E; Badesch, David B; Benton, Wade W; McGoon, Michael D

2015-03-01

Data from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) were used previously to develop a risk score calculator to predict 1-year survival. We evaluated prognostic implications of changes in the risk score and individual risk-score parameters over 12 months. Patients were grouped by decreased, unchanged, or increased risk score from enrollment to 12 months. Kaplan-Meier estimates of subsequent 1-year survival were made based on change in the risk score during the initial 12 months of follow-up. Cox regression was used for multivariable analysis. Of 2,529 patients in the analysis cohort, the risk score was decreased in 800, unchanged in 959, and increased in 770 at 12 months post-enrollment. Six parameters (functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide levels, and pericardial effusion) each changed sufficiently over time to improve or worsen risk scores in ≥5% of patients. One-year survival estimates in the subsequent year were 93.7%, 90.3%, and 84.6% in patients with a decreased, unchanged, and increased risk score at 12 months, respectively. Change in risk score significantly predicted future survival, adjusting for risk at enrollment. Considering follow-up risk concurrently with risk at enrollment, follow-up risk was a much stronger predictor, although risk at enrollment maintained a significant effect on future survival. Changes in REVEAL risk scores occur in most patients with pulmonary arterial hypertension over a 12-month period and are predictive of survival. Thus, serial risk score assessments can identify changes in disease trajectory that may warrant treatment modifications. Copyright © 2015 International Society for Heart and Lung Transplantation. All rights reserved.

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

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

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 Lowermore » 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 survivals of 0.77 and 0.69 for chin1pit and lgrStlhd, while the data control's survivals were 0.79 and 0.68. The differences are 0.02 and 0.01 (respectively), nearly identical. However, from MCN to BON, COMPASS predicted survivals of 0.74 and 0.69 while the data controls survivals were 0.47 and 0.53 respectively. Differences of 0.27 and 0.16. In summary: Travel and survival of chin1pit and lgrStlhd stocks were well modeled in the upper reaches. Fish in the lower reaches down through BON suffered unmodeled mortality, and/or passed BON undetected. A drop in bypass fraction and unmodeled mortality during the run could produce such patterns by shifting the observed median passage day to appear artificially early.« less

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients.

PubMed

Shen, Shutong; Gao, Rongrong; Bei, Yihua; Li, Jin; Zhang, Haifeng; Zhou, Yanli; Yao, Wenming; Xu, Dongjie; Zhou, Fang; Jin, Mengchao; Wei, Siqi; Wang, Kai; Xu, Xuejuan; Li, Yongqin; Xiao, Junjie; Li, Xinli

2017-01-01

Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed. © 2017 The Author(s). Published by S. Karger AG, Basel.

Overall survival and self-reported fatigue in patients with esophageal cancer.

PubMed

Stauder, M C; Romero, Y; Kabat, B; Atherton, P J; Geno, D; Deschamps, C; Jatoi, A; Sloan, J A; Botros, M; Jung, K W; Arora, A S; Miller, R C

2013-02-01

A prospective cohort study was conducted to analyze whether self-reported fatigue predicts overall survival in patients with esophageal cancer. Patients enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry between September 2001 and January 2009 who completed a baseline quality of life instrument were eligible for evaluation. The fatigue component was scored on a 0-10 scale, with 0 as extreme fatigue. Patients were categorized as having a decreased energy level if they reported a score of ≤ 5. Fatigue scores ≥ 6 reflect normal levels of energy. Data from a total of 659 enrolled patients were analyzed. A total of 392 (59 %) and 267 (41 %) patients reported decreased and normal energy, respectively. Univariate analysis indicates patients with normal energy had improved 5-year survival compared to patients with decreased energy (37 vs 28 %, hazard ratio (HR) 0.74, p = 0.006). Among the patients with locally advanced disease, the same relationship was seen (28 vs 17 %, HR = 0.67, p = 0.003); this remained significant on multivariate analysis (HR = 0.71, p = 0.015). A decreased energy level is associated with poor survival in patients with esophageal cancer. Thus, patients with high levels of fatigue should be referred for psychological support and be considered for therapy aimed at amelioration of fatigue symptoms.

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

PubMed

Wang, S; Sun, Z; Wang, S

1996-11-01

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

NA{sup +}, K{sup +}-ATPase, histopathological, and genetic responses of Corbicula fluminea to sediment-associated copper

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

Brown, S.

1995-12-31

Time-dependent responses to sediment-associated copper were studies at hierarchical levels of biological organization along an extreme concentration gradient (40 to 40,000 mg/kg total Cu). Laboratory and in situ estimates of molecular to tissue-level responses (Na/K-ATPase activity, DNA content, histopathology) were monitored in Corbicula fluminea (Asiatic clam), and compared with laboratory and field based survival of Corbicula and Elimia teres (an indigenous Gastropoda). Mollusc survival was, in turn, compared with effects on macrobenthic community composition along the stream/[Cu] gradient. Relationships between selected sediment characteristics and the bioavailability and toxicity of sediment associated copper were also investigated. Sediment-associated copper depressed Na/K-ATPase activitymore » and led to histopathological damage of renal and gill epithelia (vacuolization, degeneration), indicating that impaired ion regulation was an important mechanism of toxicity. Concurrent reductions in DNA content were believed to be secondary effects due to cell death, not an indication of genotoxicity. Sublethal responses were significantly correlated with survival in both species; however, while survival in situ was indicative of differences in community structure, laboratory-based survival was not. Copper levels in tissues were indicative of exposure, but were not significantly correlated with adverse effects. Copper levels in sediments, interstitial water, and overlying water varied independently of sediment characteristics except pH. Cu/AVS ratios were predictive of Corbicula and Elimia survival, but were not significantly related to differences in community structure. Instead, macrobenthic community structure was influenced by other sediment factors (grain size, Eh, pH).« less

External validation of a 5-year survival prediction model after elective abdominal aortic aneurysm repair.

PubMed

DeMartino, Randall R; Huang, Ying; Mandrekar, Jay; Goodney, Philip P; Oderich, Gustavo S; Kalra, Manju; Bower, Thomas C; Cronenwett, Jack L; Gloviczki, Peter

2018-01-01

The benefit of prophylactic repair of abdominal aortic aneurysms (AAAs) is based on the risk of rupture exceeding the risk of death from other comorbidities. The purpose of this study was to validate a 5-year survival prediction model for patients undergoing elective repair of asymptomatic AAA <6.5 cm to assist in optimal selection of patients. All patients undergoing elective repair for asymptomatic AAA <6.5 cm (open or endovascular) from 2002 to 2011 were identified from a single institutional database (validation group). We assessed the ability of a prior published Vascular Study Group of New England (VSGNE) model (derivation group) to predict survival in our cohort. The model was assessed for discrimination (concordance index), calibration (calibration slope and calibration in the large), and goodness of fit (score test). The VSGNE derivation group consisted of 2367 patients (70% endovascular). Major factors associated with survival in the derivation group were age, coronary disease, chronic obstructive pulmonary disease, renal function, and antiplatelet and statin medication use. Our validation group consisted of 1038 patients (59% endovascular). The validation group was slightly older (74 vs 72 years; P < .01) and had a higher proportion of men (76% vs 68%; P < .01). In addition, the derivation group had higher rates of advanced cardiac disease, chronic obstructive pulmonary disease, and baseline creatinine concentration (1.2 vs 1.1 mg/dL; P < .01). Despite slight differences in preoperative patient factors, 5-year survival was similar between validation and derivation groups (75% vs 77%; P = .33). The concordance index of the validation group was identical between derivation and validation groups at 0.659 (95% confidence interval, 0.63-0.69). Our validation calibration in the large value was 1.02 (P = .62, closer to 1 indicating better calibration), calibration slope of 0.84 (95% confidence interval, 0.71-0.97), and score test of P = .57 (>.05 indicating goodness of fit). Across different populations of patients, assessment of age and level of cardiac, pulmonary, and renal disease can accurately predict 5-year survival in patients with AAA <6.5 cm undergoing repair. This risk prediction model is a valid method to assess mortality risk in determining potential overall survival benefit from elective AAA repair. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Individual Differences in Well-Being in Older Breast Cancer Survivors

PubMed Central

Perkins, Elizabeth A.; Small, Brent J.; Balducci, Lodovico; Extermann, Martine; Robb, Claire; Haley, William E.

2007-01-01

Older women who survive breast cancer may differ significantly in their long-term well-being. Using a risk and protective factors model, we studied predictors of well-being in 127 women age 70 and above with a history of at least one year's survival of breast cancer. Mean post-cancer survivorship was 5.1 years. Using life satisfaction, depression and general health perceptions as outcome variables, we assessed whether demographic variables, cancer-related variables, health status and psychosocial resources predicted variability in well-being using correlational and hierarchical regression analyses. Higher age predicted increased depression but was not associated with life satisfaction or general health perceptions. Cancer-related variables, including duration of survival, and type of cancer treatment, were not significantly associated with survivors' well-being. Poorer health status was associated with poorer well-being in all three dependent variables. After controlling for demographics, cancer-related variables, and health status, higher levels of psychosocial resources including optimism, mastery, spirituality and social support predicted better outcome in all three dependent variables. While many older women survive breast cancer without severe sequelae, there is considerable variability in their well-being after survivorship. Successful intervention with older breast cancer survivors might include greater attention not only to cancer-specific concerns, but also attention to geriatric syndromes and functional impairment, and enhancement of protective psychosocial resources. PMID:17240157

The prognostic significance of prostate specific antigen in metastatic hormone-resistant prostate cancer.

PubMed Central

Fosså, S. D.; Waehre, H.; Paus, E.

1992-01-01

Twenty-seven of 152 patients (18%) with progressing hormone resistant prostate cancer had normal serum levels of prostate specific antigen (PSA less than or equal to 10 micrograms l-1), when referred for secondary treatment. PSA was significantly correlated with the extent of skeletal metastases (R: 0.35) and the levels of hemoglobin (R: -0.19) and serum alkaline phosphatase (R: 0.30). In a multivariate Cox regression analysis the survival of the 152 patients was not correlated with the PSA level but with the patients performance status, the level of hemoglobin, and the time between primary hormone treatment and relapse. The lack of serum PSA to predict survival may be explained by a heterogenous composition of hormone resistant prostate cancer as regards differentiated and/or PSA producing vs undifferentiated and/or PSA non-producing cells. PMID:1379059

Predicting renal graft failure by sCD30 levels and de novo HLA antibodies at 1year post-transplantation.

PubMed

Wang, Dong; Wu, Guojun; Chen, Jinhua; Yu, Ziqiang; Wu, Weizhen; Yang, Shunliang; Tan, Jianming

2012-06-01

HLA antibodies and sCD30 levels were detected in the serum sampled from 620 renal graft recipients at 1 year post-transplantation, which were followed up for 5 years. Six-year graft and patient survivals were 81.6% and 91.0%. HLA antibodies were detected in 45 recipients (7.3%), of whom there were 14 cases with class I antibodies, 26 cases with class II, and 5 cases with both class I and II. Much more graft loss was record in recipients with HLA antibodies than those without antibodies (60% vs. 15.1%, p<0.001). Significantly higher sCD30 levels were recorded in recipients suffering graft loss than the others (73.9±48.8 U/mL vs. 37.3±14.6 U/mL, p<0.001). Compared with those with high sCD30 levels, recipients with low sCD30 levels (<50 U/mL) had much better 6-year graft survival (92.4% vs. 46.6%, p<0.001). Further statistical analysis showed that detrimental effect of de novo HLA antibodies and high sCD30 on graft survival was not only independent but also additive. Therefore, post-transplantation monitoring of HLA antibodies and sCD30 levels is necessary and recipients with elevated sCD30 level and/or de novo HLA antibody should be paid more attention in order to achieve better graft survival. Copyright © 2012 Elsevier B.V. All rights reserved.

Survival, growth and reproduction of non-indigenous Nile tilapia, Oreochromis niloticus (Linnaeus 1758). I. Physiological capabilities in various temperatures and salinities

USGS Publications Warehouse

Schofield, Pamela J.; Peterson, Mark S.; Lowe, Michael R.; Brown-Peterson, Nancy J.; Slack, William T.

2011-01-01

The physiological tolerances of non-native fishes is an integral component of assessing potential invasive risk. Salinity and temperature are environmental variables that limit the spread of many non-native fishes. We hypothesised that combinations of temperature and salinity will interact to affect survival, growth, and reproduction of Nile tilapia, Oreochromis niloticus, introduced into Mississippi, USA. Tilapia withstood acute transfer from fresh water up to a salinity of 20 and survived gradual transfer up to 60 at typical summertime (30°C) temperatures. However, cold temperature (14°C) reduced survival of fish in saline waters ≥10 and increased the incidence of disease in freshwater controls. Although fish were able to equilibrate to saline waters in warm temperatures, reproductive parameters were reduced at salinities ≥30. These integrated responses suggest that Nile tilapia can invade coastal areas beyond their point of introduction. However, successful invasion is subject to two caveats: (1) wintertime survival depends on finding thermal refugia, and (2) reproduction is hampered in regions where salinities are ≥30. These data are vital to predicting the invasion of non-native fishes into coastal watersheds. This is particularly important given the predicted changes in coastal landscapes due to global climate change and sea-level rise.

Physical activity increases survival after heart valve surgery.

PubMed

Lund, K; Sibilitz, K L; Berg, S K; Thygesen, L C; Taylor, R S; Zwisler, A D

2016-09-01

Increased physical activity predicts survival and reduces risk of readmission in patients with coronary heart disease. However, few data show how physical activity is associated with survival and readmission after heart valve surgery. Objective were to assess the association between physical activity levels 6-12 months after heart valve surgery and (1) survival, (2) hospital readmission 18-24 months after surgery and (3) participation in exercise-based cardiac rehabilitation. Prospective cohort study with registry data from The CopenHeart survey, The Danish National Patient Register and The Danish Civil Registration System of 742 eligible patients. Physical activity was quantified with the International Physical Activity Questionnaire and analysed using Kaplan-Meier analysis and Cox regression and logistic regression methods. Patients with a moderate to high physical activity level had a reduced risk of mortality (3 deaths in 289 patients, 1%) compared with those with a low physical activity level (13 deaths in 235 patients, 5.5%) with a fully adjusted HR of 0.19 (95% CI 0.05 to 0.70). In contrast, physical activity level was not associated with the risk of hospital readmission. Patients who participated in exercise-based cardiac rehabilitation (n=297) were more likely than the non-participants (n=200) to have a moderate or high physical activity level than a low physical activity level (fully adjusted OR: 1.52, 95% CI 1.03 to 2.24). Moderate to high levels of physical activity after heart valve surgery are positively associated with higher survival rates and participation in cardiac rehabilitation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Mitochondrial reactive oxygen species and complex II levels are associated with the outcome of hepatocellular carcinoma

PubMed Central

WU, JIANHUA; ZHAO, FEI; ZHAO, YUFEI; GUO, ZHANJUN

2015-01-01

In the present study, two oxidative stress parameters, reactive oxygen species (ROS) and mitochondrial respiratory complex II, were evaluated in the mitochondria of hepatocellular carcinoma (HCC) cells to determine the association between these parameters and the carcinogenesis and clinical outcome of HCC. High levels of ROS and low levels of complex II were found to be associated with reduced post-operative survival in HCC patients using the log-rank test. Furthermore, multivariate analysis confirmed that the levels of ROS [relative risk (RR)=2.867; 95% confidence interval (CI), 1.062–7.737; P=0.038] and complex II (RR=5.422; 95% CI, 1.273–23.088; P=0.022) were independent predictors for the survival of patients with HCC. Therefore, the analysis of ROS and complex II levels may provide a useful research and therapeutic tool for the prediction of HCC prognosis and treatment. PMID:26622849

Value of α-fetoprotein as an early biomarker for treatment response to sorafenib therapy in advanced hepatocellular carcinoma.

PubMed

Sánchez, Ana Isabel Plano; Roces, Lucía Velasco; García, Isabel Zapico; López, Eva Lázaro; Hernandez, Miguel Angel Calleja; Parejo, Maria Isabel Baena; Peña-Díaz, Jaime

2018-06-01

Sorafenib is an oral multikinase inhibitor with antiangiogenic and antiproliferative properties, and is used as the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Previous studies have identified an improvement in overall survival and progression-free survival in patients with a manageable toxicity profile. α-fetoprotein (AFP) has been revealed to be of great diagnostic and predictive value for tumour staging in multiple studies; however, its role as a predictive factor of response to treatment with sorafenib is not entirely clear. The present study aimed to determine the effectiveness of sorafenib and investigate the value of AFP as a predictive factor of early response to sorafenib in patients with HCC. Effectiveness was analysed based on median overall survival (mOS) time, while to analyse the possible predictive value of AFP, patients were classified into two groups: Non-responders (≤20% AFP reduction) and responders (>20% AFP reduction) at 6-8 weeks of treatment when compared with basal AFP level. For assessment of toxicity, any adverse effects were recorded. A total of 167 patients were included, who collectively exhibited a mOS time of 11 months with a median treatment duration of 5 months. The mOS time was significantly higher for patients with better hepatic function (12 months in cases of Child-Pugh score A vs. 8 months in cases of Child-Pugh score B; P=0.03) and with basal AFP values ≤200 ng/ml (14 months vs. 8 months in patients with AFP levels >200 ng/ml; P=0.01). A >20% reduction of AFP at 6-8 weeks was determined to be a positive predictive factor upon multivariate analysis (P=0.002), obtaining, for the responder patients, an mOS of 18 months compared with 10 months (P=0.004) for the non-responders. The main adverse reactions were hand-foot syndrome (35/167; 21%), diarrhoea (39/167; 23.4%), anorexia (29/167; 17.4%) and arterial hypertension (30/167; 18%). In conclusion, a >20% drop in AFP at 6-8 weeks may be useful as a predictive factor of response to sorafenib, as indicated by its association with longer survival times in patients with advanced HCC following treatment with sorafenib in the present study.

The future-orientation of memory: Planning as a key component mediating the high levels of recall found with survival processing

PubMed Central

Klein, Stanley B.; Robertson, Theresa E.; Delton, Andrew W.

2013-01-01

In a series of papers, Nairne and colleagues have demonstrated that tasks encouraging participants to judge words for relevance to survival led to better recall than did tasks lacking survival relevance. Klein, Robertson, and Delton (2010) presented data suggesting that the future-directed temporal orientation of the survival task (e.g., planning), rather than survival per se, accounts for the good recall found with the task. In the present studies we manipulated the amount of survival and planning processing encouraged by a set of encoding tasks. Participants performed tasks that encouraged processing stimuli for their relevance to (a) both survival and planning, (b) planning, but not survival, or (c) survival but not planning. We predicted, and found, that recall performance associated with tasks encouraging planning (i.e., survival with planning and planning without survival) should exceed tasks that encouraged survival but not planning (i.e., survival without planning). We draw several conclusions. First, planning is a necessary component of the superior recall found in the survival paradigm. Second, memory, from an evolutionary perspective, is inherently prospective—tailored by natural selection to support future decisions and judgements that cannot be known in advance with certainty. PMID:21229456

Pathway-based personalized analysis of cancer

PubMed Central

Drier, Yotam; Sheffer, Michal; Domany, Eytan

2013-01-01

We introduce Pathifier, an algorithm that infers pathway deregulation scores for each tumor sample on the basis of expression data. This score is determined, in a context-specific manner, for every particular dataset and type of cancer that is being investigated. The algorithm transforms gene-level information into pathway-level information, generating a compact and biologically relevant representation of each sample. We demonstrate the algorithm’s performance on three colorectal cancer datasets and two glioblastoma multiforme datasets and show that our multipathway-based representation is reproducible, preserves much of the original information, and allows inference of complex biologically significant information. We discovered several pathways that were significantly associated with survival of glioblastoma patients and two whose scores are predictive of survival in colorectal cancer: CXCR3-mediated signaling and oxidative phosphorylation. We also identified a subclass of proneural and neural glioblastoma with significantly better survival, and an EGF receptor-deregulated subclass of colon cancers. PMID:23547110

Implementing a novel movement-based approach to inferring parturition and neonate caribou calf survival.

PubMed

Bonar, Maegwin; Ellington, E Hance; Lewis, Keith P; Vander Wal, Eric

2018-01-01

In ungulates, parturition is correlated with a reduction in movement rate. With advances in movement-based technologies comes an opportunity to develop new techniques to assess reproduction in wild ungulates that are less invasive and reduce biases. DeMars et al. (2013, Ecology and Evolution 3:4149-4160) proposed two promising new methods (individual- and population-based; the DeMars model) that use GPS inter-fix step length of adult female caribou (Rangifer tarandus caribou) to infer parturition and neonate survival. Our objective was to apply the DeMars model to caribou populations that may violate model assumptions for retrospective analysis of parturition and calf survival. We extended the use of the DeMars model after assigning parturition and calf mortality status by examining herd-wide distributions of parturition date, calf mortality date, and survival. We used the DeMars model to estimate parturition and calf mortality events and compared them with the known parturition and calf mortality events from collared adult females (n = 19). We also used the DeMars model to estimate parturition and calf mortality events for collared female caribou with unknown parturition and calf mortality events (n = 43) and instead derived herd-wide estimates of calf survival as well as distributions of parturition and calf mortality dates and compared them to herd-wide estimates generated from calves fitted with VHF collars (n = 134). For our data, the individual-based method was effective at predicting calf mortality, but was not effective at predicting parturition. The population-based method was more effective at predicting parturition but was not effective at predicting calf mortality. At the herd-level, the predicted distributions of parturition date from both methods differed from each other and from the distribution derived from the parturition dates of VHF-collared calves (log-ranked test: χ2 = 40.5, df = 2, p < 0.01). The predicted distributions of calf mortality dates from both methods were similar to the observed distribution derived from VHF-collared calves. Both methods underestimated herd-wide calf survival based on VHF-collared calves, however, a combination of the individual- and population-based methods produced herd-wide survival estimates similar to estimates generated from collared calves. The limitations we experienced when applying the DeMars model could result from the shortcomings in our data violating model assumptions. However despite the differences in our caribou systems, with proper validation techniques the framework in the DeMars model is sufficient to make inferences on parturition and calf mortality.

Implementing a novel movement-based approach to inferring parturition and neonate caribou calf survival

PubMed Central

Ellington, E. Hance; Lewis, Keith P.; Vander Wal, Eric

2018-01-01

In ungulates, parturition is correlated with a reduction in movement rate. With advances in movement-based technologies comes an opportunity to develop new techniques to assess reproduction in wild ungulates that are less invasive and reduce biases. DeMars et al. (2013, Ecology and Evolution 3:4149–4160) proposed two promising new methods (individual- and population-based; the DeMars model) that use GPS inter-fix step length of adult female caribou (Rangifer tarandus caribou) to infer parturition and neonate survival. Our objective was to apply the DeMars model to caribou populations that may violate model assumptions for retrospective analysis of parturition and calf survival. We extended the use of the DeMars model after assigning parturition and calf mortality status by examining herd-wide distributions of parturition date, calf mortality date, and survival. We used the DeMars model to estimate parturition and calf mortality events and compared them with the known parturition and calf mortality events from collared adult females (n = 19). We also used the DeMars model to estimate parturition and calf mortality events for collared female caribou with unknown parturition and calf mortality events (n = 43) and instead derived herd-wide estimates of calf survival as well as distributions of parturition and calf mortality dates and compared them to herd-wide estimates generated from calves fitted with VHF collars (n = 134). For our data, the individual-based method was effective at predicting calf mortality, but was not effective at predicting parturition. The population-based method was more effective at predicting parturition but was not effective at predicting calf mortality. At the herd-level, the predicted distributions of parturition date from both methods differed from each other and from the distribution derived from the parturition dates of VHF-collared calves (log-ranked test: χ2 = 40.5, df = 2, p < 0.01). The predicted distributions of calf mortality dates from both methods were similar to the observed distribution derived from VHF-collared calves. Both methods underestimated herd-wide calf survival based on VHF-collared calves, however, a combination of the individual- and population-based methods produced herd-wide survival estimates similar to estimates generated from collared calves. The limitations we experienced when applying the DeMars model could result from the shortcomings in our data violating model assumptions. However despite the differences in our caribou systems, with proper validation techniques the framework in the DeMars model is sufficient to make inferences on parturition and calf mortality. PMID:29466451

Protein phosphatase 2A (PP2A) inhibitor CIP2A indicates resistance to radiotherapy in rectal cancer.

PubMed

Birkman, Eva-Maria; Elzagheid, Adam; Jokilehto, Terhi; Avoranta, Tuulia; Korkeila, Eija; Kulmala, Jarmo; Syrjänen, Kari; Westermarck, Jukka; Sundström, Jari

2018-03-01

Preoperative (chemo)radiotherapy, (C)RT, is an essential part of the treatment of rectal cancer patients, but tumor response to this therapy among patients is variable. Thus far, there are no clinical biomarkers that could be used to predict response to (C)RT or to stratify patients into different preoperative treatment groups according to their prognosis. Overexpression of cancerous inhibitor of protein phosphatase 2A (CIP2A) has been demonstrated in several cancers and is frequently associated with reduced survival. Recently, high CIP2A expression has also been indicated to contribute to radioresistance in head and neck squamous cell carcinoma, but few studies have examined the connection between CIP2A and radiation response regarding other malignancies. We have evaluated CIP2A protein expression levels in relation to tumor regression after preoperative (C)RT and survival of rectal adenocarcinoma patients. The effects of CIP2A knockdown by siRNA on cell survival were further investigated in colorectal cancer cells exposed to radiation. Patients with low-CIP2A-expressing tumors had more frequently moderate or excellent response to long-course (C)RT than patients with high-CIP2A-expressing tumors. They also had higher 36-month disease-specific survival (DSS) rate in categorical analysis. In the multivariate analysis, low CIP2A expression level remained as an independent predictive factor for increased DSS. Suppression of CIP2A transcription by siRNA was found to sensitize colorectal cancer cells to irradiation and decrease their survival in vitro. In conclusion, these results suggest that by contributing to radiosensitivity of cancer cells, low CIP2A protein expression level associates with a favorable response to long-course (C)RT in rectal cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Simulated biologic intelligence used to predict length of stay and survival of burns.

PubMed

Frye, K E; Izenberg, S D; Williams, M D; Luterman, A

1996-01-01

From July 13, 1988, to May 14, 1995, 1585 patients with burns and no other injuries besides inhalation were treated; 4.5% did not survive. Artificial neural networks were trained on patient presentation data with known outcomes on 90% of the randomized cases. The remaining cases were then used to predict survival and length of stay in cases not trained on. Survival was predicted with more than 98% accuracy and length of stay to within a week with 72% accuracy in these cases. For anatomic area involved by burn, burns involving the feet, scalp, or both had the largest negative effect on the survival prediction. In survivors burns involving the buttocks, transport to this burn center by the military or by helicopter, electrical burns, hot tar burns, and inhalation were associated with increasing the length of stay prediction. Neural networks can be used to accurately predict the clinical outcome of a burn. What factors affect that prediction can be investigated.

Basic arterial blood gas biomarkers as a predictor of mortality in tetralogy of Fallot patients.

PubMed

Bhardwaj, Vandana; Kapoor, Poonam Malhotra; Irpachi, Kalpana; Ladha, Suruchi; Chowdhury, Ujjwal Kumar

2017-01-01

Serum lactate and base deficit have been shown to be a predictor of morbidity and mortality in critically ill patients. Poor preoperative oxygenation appears to be one of the significant factors that affects early mortality in tetralogy of Fallot (TOF). There is little published literature evaluating the utility of serum lactate, base excess (BE), and oxygen partial pressure (PO 2 ) as simple, widely available, prognostic markers in patients undergoing surgical repair of TOF. This prospective, observational study was conducted in 150 TOF patients, undergoing elective intracardiac repair. PO 2 , BE, and lactate levels at three different time intervals were recorded. Arterial blood samples were collected after induction (T1), after cardiopulmonary bypass (T2), and 48 h (T3) after surgery in the Intensive Care Unit (ICU). To observe the changes in PO 2 , BE, and lactate levels over a period of time, repeated measures analysis was performed with Bonferroni method. The receiver operating characteristics (ROC) analysis was used to find area under curve (AUC) and cutoff values of various biomarkers for predicting mortality in ICU. The patients who could not survive showed significant elevated lactate levels at baseline (T1) and postoperatively (T2) as compared to patients who survived after surgery (P < 0.001). However, in nonsurvivors, the BE value decreased significantly in the postoperative period in comparison to survivors (-2.8 ± 4.27 vs. 5.04 ± 2.06) (P < 0.001). In nonsurvivors, there was a significant fall of PO 2 to a mean value of 59.86 ± 15.09 in ICU (T3), whereas those who survived had a PO 2 of 125.86 ± 95.09 (P < 0.001). The ROC curve analysis showed that lactate levels (T3) have highest mortality predictive value (AUC: 96.9%) as compared to BE (AUC: 94.5%) and PO 2 (AUC: 81.1%). Serum lactate and BE may be used as prognostic markers to predict mortality in patients undergoing TOF repair. The routine analysis of these simple, fast, widely available, and cost-effective biomarkers should be encouraged to predict prognosis of TOF patients.

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

Camouflage predicts survival in ground-nesting birds.

PubMed

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

2016-01-29

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.

Measuring Institutional Quality in Head and Neck Surgery Using Hospital-Level Data: Negative Margin Rates and Neck Dissection Yield.

PubMed

Schoppy, David W; Rhoads, Kim F; Ma, Yifei; Chen, Michelle M; Nussenbaum, Brian; Orosco, Ryan K; Rosenthal, Eben L; Divi, Vasu

2017-11-01

Negative margins and lymph node yields (LNY) of 18 or more from neck dissections in patients with head and neck squamous cell carcinomas (HNSCC) have been associated with improved patient survival. It is unclear whether these metrics can be used to identify hospitals with improved outcomes. To determine whether 2 patient-level metrics would predict outcomes at the hospital level. A retrospective review of records from the National Cancer Database (NCDB) was used to identify patients who underwent primary surgery and concurrent neck dissection for HNSCC between 2004 and 2013. The percentage of patients at each hospital with negative margins on primary resection and an LNY 18 or more from a neck dissection was quantified. Cox proportional hazard models were used to define the association between hospital performance on these metrics and overall survival. Margin status and lymph node yield at hospital level. Overall survival (OS). We identified 1008 hospitals in the NCDB where 64 738 patients met inclusion criteria. Of the 64 738 participants, 45 170 (69.8%) were men and 19 568 (30.2%) were women. The mean SD age of included patients was 60.5 (12.0) years. Patients treated at hospitals attaining the combined metric of a 90% or higher negative margin rate and 80% or more of cases with LNYs of 18 or more experienced a significant reduction in mortality (hazard ratio [HR] 0.93; 95% CI, 0.89-0.98). This benefit in survival was independent of the patient-level improvement associated with negative margins (HR, 0.73; 95% CI, 0.71-0.76) and LNY of 18 or more (HR, 0.85; 95% CI, 0.83-0.88). Including these metrics in the model neutralized the association of traditional measures of hospital quality (volume and teaching status). Treatment at hospitals that attain a high rate of negative margins and LNY of 18 or more is associated with improved survival in patients undergoing surgery for HNSCC. These surgical outcome measures predicted outcomes independent of traditional, but generally nonmodifiable characteristics. Tracking of these metrics may help identify high-quality centers and provide guidance for institution-level quality improvement.

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. © 2015 Wiley Periodicals, Inc.

Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a European HR-NBL1/SIOPEN study.

PubMed

Viprey, Virginie F; Gregory, Walter M; Corrias, Maria V; Tchirkov, Andrei; Swerts, Katrien; Vicha, Ales; Dallorso, Sandro; Brock, Penelope; Luksch, Roberto; Valteau-Couanet, Dominique; Papadakis, Vassilios; Laureys, Genevieve; Pearson, Andrew D; Ladenstein, Ruth; Burchill, Susan A

2014-04-01

To evaluate the hypothesis that detection of neuroblastoma mRNAs by reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in peripheral blood (PB) and bone marrow aspirates (BM) from children with stage 4 neuroblastoma are clinically useful biomarkers of risk. RTqPCR for paired-like homeobox 2b (PHOX2B), tyrosine hydroxylase (TH), and doublecortin (DCX) mRNA in PB and BM of children enrolled onto the High-Risk Neuroblastoma Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group (HR-NBL1/SIOPEN) was performed at diagnosis and after induction therapy. High levels of TH, PHOX2B, or DCX mRNA in PB or BM at diagnosis strongly predicted for worse event-free survival (EFS) and overall survival (OS) in a cohort of 290 children. After induction therapy, high levels of these mRNAs predicted worse EFS and OS in BM but not in PB. Combinations of mRNAs in BM did not add to the predictive power of any single mRNA. However, in the original (n = 182) and validation (n = 137) PB cohorts, high TH (log10TH > 0.8) or high PHOX2B (log10PHOX2B > 0.28) identify 19% of children as ultrahigh risk, with 5-year EFS and OS rates of 0%; OS rate was 25% (95% CI, 16% to 36%) and EFS rate was 38% (95% CI, 28% to 49%) in the remaining children. The magnitude of reduction in mRNA level between diagnosis and postinduction therapy in BM or PB was not of additional predictive value. High levels of TH and PHOX2B mRNA in PB at diagnosis objectively identify children with ultrahigh-risk disease who may benefit from novel treatment approaches. The level of TH, PHOX2B, and DCX mRNA in BM and/or PB at diagnosis might contribute to an algorithm to improve stratification of children for treatment.

Individual traits as determinants of time to death under extreme drought in Pinus sylvestris L.

PubMed

Garcia-Forner, Núria; Sala, Anna; Biel, Carme; Savé, Robert; Martínez-Vilalta, Jordi

2016-10-01

Plants exhibit a variety of drought responses involving multiple interacting traits and processes, which makes predictions of drought survival challenging. Careful evaluation of responses within species, where individuals share broadly similar drought resistance strategies, can provide insight into the relative importance of different traits and processes. We subjected Pinus sylvestris L. saplings to extreme drought (no watering) leading to death in a greenhouse to (i) determine the relative effect of predisposing factors and responses to drought on survival time, (ii) identify and rank the importance of key predictors of time to death and (iii) compare individual characteristics of dead and surviving trees sampled concurrently. Time until death varied over 3 months among individual trees (from 29 to 147 days). Survival time was best predicted (higher explained variance and impact on the median survival time) by variables related to carbon uptake and carbon/water economy before and during drought. Trees with higher concentrations of monosaccharides before the beginning of the drought treatment and with higher assimilation rates prior to and during the treatment survived longer (median survival time increased 25-70 days), even at the expense of higher water loss. Dead trees exhibited less than half the amount of nonstructural carbohydrates (NSCs) in branches, stem and relative to surviving trees sampled concurrently. Overall, our results indicate that the maintenance of carbon assimilation to prevent acute depletion of NSC content above some critical level appears to be the main factor explaining survival time of P. sylvestris trees under extreme drought. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2016-06-01

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

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

PubMed

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

2016-02-01

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

Immunity and fitness in a wild population of Eurasian kestrels Falco tinnunculus

NASA Astrophysics Data System (ADS)

Parejo, Deseada; Silva, Nadia

2009-10-01

The immune system of vertebrates consists of several components that partly interact and complement each other. Therefore, the assessment of the overall effectiveness of immune defence requires the simultaneous measurement of different immune components. In this study, we investigated intraspecific variability of innate [i.e. natural antibodies (NAb) and complement] and acquired (i.e. leucocyte profiles) immunity and its relationship with fitness correlates (i.e. blood parasite load and reproductive success in adults and body mass and survival until fledging in nestlings) in the Eurasian kestrel Falco tinnunculus. Immunity differed between nestlings and adults and also between adult males and females. Adult kestrels with higher levels of complement were less parasitised by Haemoproteus, and males with higher values of NAbs showed a higher reproductive success. In nestlings, the H/L ratio was negatively related to body mass. Survival until fledging was predicted by all measured immunological variables of nestlings as well as by their fathers' level of complement. This is the first time that innate immunity is linked to survival in a wild bird. Thus, intraspecific variation in different components of immunity predicts variation in fitness prospects in kestrels, which highlights the importance of measuring innate immune components together with components of the acquired immunity in studies assessing the effectiveness of the immune system in wild animals.

Prediction of survival without morbidity for infants born at under 33 weeks gestational age: a user-friendly graphical tool.

PubMed

Shah, Prakesh S; Ye, Xiang Y; Synnes, Anne; Rouvinez-Bouali, Nicole; Yee, Wendy; Lee, Shoo K

2012-03-01

To develop models and a graphical tool for predicting survival to discharge without major morbidity for infants with a gestational age (GA) at birth of 22-32 weeks using infant information at birth. Retrospective cohort study. Canadian Neonatal Network data for 2003-2008 were utilised. Neonates born between 22 and 32 weeks gestation admitted to neonatal intensive care units in Canada. Survival to discharge without major morbidity defined as survival without severe neurological injury (intraventricular haemorrhage grade 3 or 4 or periventricular leukomalacia), severe retinopathy (stage 3 or higher), necrotising enterocolitis (stage 2 or 3) or chronic lung disease. Of the 17 148 neonates who met the eligibility criteria, 65% survived without major morbidity. Sex and GA at birth were significant predictors. Birth weight (BW) had a significant but non-linear effect on survival without major morbidity. Although maternal information characteristics such as steroid use, improved the prediction of survival without major morbidity, sex, GA at birth and BW for GA predicted survival without major morbidity almost as accurately (area under the curve: 0.84). The graphical tool based on the models showed how the GA and BW for GA interact, to enable prediction of outcomes especially for small and large for GA infants. This graphical tool provides an improved and easily interpretable method to predict survival without major morbidity for very preterm infants at the time of birth. These curves are especially useful for small and large for GA infants.

MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

PubMed

Eminaga, Okyaz; Wei, Wei; Hawley, Sarah J; Auman, Heidi; Newcomb, Lisa F; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Carroll, Peter R; Gleave, Martin E; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; McKenney, Jesse K; Feng, Ziding; Fazli, Ladan; Brooks, James D

2016-01-01

The uncertainties inherent in clinical measures of prostate cancer (CaP) aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC) predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters. MUC1 IHC was performed on a multi-institutional tissue microarray (TMA) resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test. The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS) (HR: 1.24, CI 1.03-1.49, P = 0.02), although not with disease specific survival (DSS, P>0.5). On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS), but was weakly associated with overall survival (OS). In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.

Cross-species prediction of human survival probabilities for accelerated anthrax vaccine absorbed (AVA) regimens and the potential for vaccine and antibiotic dose sparing.

PubMed

Stark, G V; Sivko, G S; VanRaden, M; Schiffer, J; Taylor, K L; Hewitt, J A; Quinn, C P; Nuzum, E O

2016-12-12

Anthrax vaccine adsorbed (AVA, BioThrax) was recently approved by the Food and Drug Administration (FDA) for a post-exposure prophylaxis (PEP) indication in adults 18-65years of age. The schedule is three doses administered subcutaneous (SC) at 2-week intervals (0, 2, and 4weeks), in conjunction with a 60-day course of antimicrobials. The Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) developed an animal model to support assessment of a shortened antimicrobial PEP duration following Bacillus anthracis exposure. A nonhuman primate (NHP) study was completed to evaluate the efficacy of a two dose anthrax vaccine absorbed (AVA) schedule (0, 2weeks) aerosol challenged with high levels of B. anthracis spores at week4- the time point at which humans would receive the third vaccination of the approved PEP schedule. Here we use logistic regression models to combine the survival data from the NHP study along with serum anthrax lethal toxin neutralizing activity (TNA) and anti-PA IgG measured by enzyme linked immunosorbent assay (ELISA) data to perform a cross-species analysis to estimate survival probabilities in vaccinated human populations at this time interval (week4 of the PEP schedule). The bridging analysis demonstrated that high levels of NHP protection also yield high predicted probability of human survival just 2weeks after the second dose of vaccine with the full or half antigen dose regimen. The absolute difference in probability of human survival between the full and half antigen dose was estimated to be at most approximately 20%, indicating that more investigation of the half-antigen dose for vaccine dose sparing strategies may be warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Presymptomatic electrophysiological tests predict clinical onset and survival in SOD1(G93A) ALS mice.

PubMed

Mancuso, Renzo; Osta, Rosario; Navarro, Xavier

2014-12-01

We assessed the predictive value of electrophysiological tests as a marker of clinical disease onset and survival in superoxide-dismutase 1 (SOD1)(G93A) mice. We evaluated the accuracy of electrophysiological tests in differentiating transgenic versus wild-type mice. We made a correlation analysis of electrophysiological parameters and the onset of symptoms, survival, and number of spinal motoneurons. Presymptomatic electrophysiological tests show great accuracy in differentiating transgenic versus wild-type mice, with the most sensitive parameter being the tibialis anterior compound muscle action potential (CMAP) amplitude. The CMAP amplitude at age 10 weeks correlated significantly with clinical disease onset and survival. Electrophysiological tests increased their survival prediction accuracy when evaluated at later stages of the disease and also predicted the amount of lumbar spinal motoneuron preservation. Electrophysiological tests predict clinical disease onset, survival, and spinal motoneuron preservation in SOD1(G93A) mice. This is a methodological improvement for preclinical studies. © 2014 Wiley Periodicals, Inc.

Cardiovascular Event Prediction by Machine Learning: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Ambale-Venkatesh, Bharath; Yang, Xiaoying; Wu, Colin O; Liu, Kiang; Hundley, W Gregory; McClelland, Robyn; Gomes, Antoinette S; Folsom, Aaron R; Shea, Steven; Guallar, Eliseo; Bluemke, David A; Lima, João A C

2017-10-13

Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. To test the ability of random survival forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores. We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%-25%). Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487. © 2017 American Heart Association, Inc.

Predicting survival of Escherichia coli O157:H7 in dry fermented sausage using artificial neural networks.

PubMed

Palanichamy, A; Jayas, D S; Holley, R A

2008-01-01

The Canadian Food Inspection Agency required the meat industry to ensure Escherichia coli O157:H7 does not survive (experiences > or = 5 log CFU/g reduction) in dry fermented sausage (salami) during processing after a series of foodborne illness outbreaks resulting from this pathogenic bacterium occurred. The industry is in need of an effective technique like predictive modeling for estimating bacterial viability, because traditional microbiological enumeration is a time-consuming and laborious method. The accuracy and speed of artificial neural networks (ANNs) for this purpose is an attractive alternative (developed from predictive microbiology), especially for on-line processing in industry. Data from a study of interactive effects of different levels of pH, water activity, and the concentrations of allyl isothiocyanate at various times during sausage manufacture in reducing numbers of E. coli O157:H7 were collected. Data were used to develop predictive models using a general regression neural network (GRNN), a form of ANN, and a statistical linear polynomial regression technique. Both models were compared for their predictive error, using various statistical indices. GRNN predictions for training and test data sets had less serious errors when compared with the statistical model predictions. GRNN models were better and slightly better for training and test sets, respectively, than was the statistical model. Also, GRNN accurately predicted the level of allyl isothiocyanate required, ensuring a 5-log reduction, when an appropriate production set was created by interpolation. Because they are simple to generate, fast, and accurate, ANN models may be of value for industrial use in dry fermented sausage manufacture to reduce the hazard associated with E. coli O157:H7 in fresh beef and permit production of consistently safe products from this raw material.

Efficacy of a composite biological age score to predict ten-year survival among Kansas and Nebraska Mennonites.

PubMed

Uttley, M; Crawford, M H

1994-02-01

In 1980 and 1981 Mennonite descendants of a group of Russian immigrants participated in a multidisciplinary study of biological aging. The Mennonites live in Goessel, Kansas, and Henderson, Nebraska. In 1991 the survival status of the participants was documented by each church secretary. Data are available for 1009 individuals, 177 of whom are now deceased. They ranged from 20 to 95 years in age when the data were collected. Biological ages were computed using a stepwise multiple regression procedure based on 38 variables previously identified as being related to survival, with chronological age as the dependent variable. Standardized residuals place participants in either a predicted-younger or a predicted-older group. The independence of the variables biological age and survival status is tested with the chi-square statistic. The significance of biological age differences between surviving and deceased Mennonites is determined by t test values. The two statistics provide consistent results. Predicted age group classification and survival status are related. The group of deceased participants is generally predicted to be older than the group of surviving participants, although neither statistic is significant for all subgroups of Mennonites. In most cases, however, individuals in the predicted-older groups are at a relatively higher risk of dying compared with those in the predicted-younger groups, although the increased risk is not always significant.

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 (0.79–0.83). The model used to predict the probability of death at 30 days included the presence of asthenia and anorexia and the level of consciousness, and this model produced AUCs of 0.78 (0.77–0.80) and 0.77 (0.75–0.79). Conclusion: For patients with advanced cancer treated by PHCTs, the use of classification schemes and decision trees based on specific symptoms can help clinicians predict survival at 7 and 30 days. PMID:24922117

Association between split selection instability and predictive error in survival trees.

PubMed

Radespiel-Tröger, M; Gefeller, O; Rabenstein, T; Hothorn, T

2006-01-01

To evaluate split selection instability in six survival tree algorithms and its relationship with predictive error by means of a bootstrap study. We study the following algorithms: logrank statistic with multivariate p-value adjustment without pruning (LR), Kaplan-Meier distance of survival curves (KM), martingale residuals (MR), Poisson regression for censored data (PR), within-node impurity (WI), and exponential log-likelihood loss (XL). With the exception of LR, initial trees are pruned by using split-complexity, and final trees are selected by means of cross-validation. We employ a real dataset from a clinical study of patients with gallbladder stones. The predictive error is evaluated using the integrated Brier score for censored data. The relationship between split selection instability and predictive error is evaluated by means of box-percentile plots, covariate and cutpoint selection entropy, and cutpoint selection coefficients of variation, respectively, in the root node. We found a positive association between covariate selection instability and predictive error in the root node. LR yields the lowest predictive error, while KM and MR yield the highest predictive error. The predictive error of survival trees is related to split selection instability. Based on the low predictive error of LR, we recommend the use of this algorithm for the construction of survival trees. Unpruned survival trees with multivariate p-value adjustment can perform equally well compared to pruned trees. The analysis of split selection instability can be used to communicate the results of tree-based analyses to clinicians and to support the application of survival trees.

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

PubMed

Müller-Tidow, Carsten; 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

2010-11-04

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.

Prognostic roles of pathology markers immunoexpression and clinical parameters in Hepatoblastoma.

PubMed

Wu, Jia-Feng; Chang, Hsiu-Hao; Lu, Meng-Yao; Jou, Shiann-Tarng; Chang, Kai-Chi; Ni, Yen-Hsuan; Chang, Mei-Hwei

2017-08-29

Hepatoblastoma, a leading primary hepatic malignant tumor in children, is originated from primitive hepatic stem cells. We aimed to elucidate the relationships between the histological distribution of β-catenin and hepatic stem cell markers with the clinical outcomes of hepatoblastoma. Immunohistochemistry was applied to detect β-catenin and hepatic stem cell markers expression in 31 hepatoblastoma tumors. We analyzed the relationship between the stem cell markers and the clinical course of hepatoblastoma. Thirty-one hepatoblastoma patients were diagnosed at a mean age of 2.58 ± 3.78 years, and 7 (22.58%) died. A lack of anticipated decrease in alpha-fetal protein levels after neoadjuvant chemotherapy indicated a higher mortality rate. Nuclear β-catenin expression was significantly associated with membranous epithelial cell adhesion molecule (EpCAM) expression in hepatoblastoma tumor specimens. The co-expression of nuclear β-catenin and membranous EpCAM together with an age at diagnosis ≤1.25 years were predictive of an alpha-fetoprotein level < 1200 ng/mL after neoadjuvant chemotherapy (P < 0.05). An alpha-fetoprotein level < 1200 ng/mL after neoadjuvant chemotherapy and age at hepatoblastoma diagnosis ≤1.25 years are both predictors of better overall and native liver survival in hepatoblastoma patients. Presence of membranous EpCAM with nuclear β-catenin and younger diagnostic age of hepatoblastoma are predictive of serum alpha-fetoprotein levels drop after chemotherapy. Younger diagnostic age and lower alpha-fetoprotein levels after neoadjuvant chemotherapy and are predictive of better overall and native liver survival in hepatoblastoma patients.

The effect of health programs on breastfeeding and child mortality in Peninsular Malaysia.

PubMed

Anderson, K H

1984-01-01

Examining household behavior in Peninsular Malaysia, this study attempts to determine if the availability of certain government health programs significantly alters breastfeeding and if these changes in input prices significantly affect mortality rates and fertility decisions. To explain the interrelationships, an economic model of the demand for infant survival and fertility and the derived demand for breastfeeding is developed. Using household and community level data, the demand equations are then estimated and the results discussed in relation to the predictions of the model and the prospect of additional government inputs. The theoretical model predicts that, if income effects are small: a decline in the price of children (hospital distance) will increase fertility, decrease survival and reduce breastfeeding; a decline in the price of health goods inputs (hospital distance and sanitation) will reduce fertility and increase survival; and a decline in the price of contraceptives (family planning distance) will reduce fertility but increase survival and breastfeeding. The empirical results support some of the model's predictions. In communities with modern sanitation, breastfeeding was shorter on average, as predicted, but differences in mortality were not detected and fertility was actually higher. The latter effect can result from an income effect in the price decline that exceeds the cross substitution effect. Distance to a hospital was positively associated with breastfeeding length. This is expected if the effect of distance on the price of children exceeds the effect of distance on the price of survival. Hospital distance had no impact on either survival or fertility. Distance to a family planning clinic had no effect on breastfeeding or fertility but had a slight positive association with mortality. This positive relationship is expected if fertility and survival are substitutes. Parental schooling and race also are important in determining demand. As economic development proceeds and educational attainment increases, breastfeeding and fertility declined and survival increased. The Chinese, the wealthiest racial group, had lower fertility and mortality and breastfed less than Malays or Indians. The empirical results failed to support the prediction of differences in male and female survival. The results suggest some interesting implications. If breastfeeding has been declining in low income countries such as Malaysia as they develop, the culprit may be the economic development process itself, which increases the value of a woman's time and raises family income. The decline in breastfeeding does not necessarily imply a significant increase in infant mortality if good substitutes for breastfeeding exist. In addition, breastfeeding is highly substitutable with many government programs designed to reduce mortality. In designing policies which will bring about a decline in infant mortality rates, both cross substitution and joint production must be considered. Programs that can be most successful in reducing mortality will be the programs that are the least substitutable with breastfeeding.

Predicting survival using clinical risk scores and non-HLA immunogenetics.

PubMed

Balavarca, Y; Pearce, K; Norden, J; Collin, M; Jackson, G; Holler, E; Dressel, R; Kolb, H-J; Greinix, H; Socie, G; Toubert, A; Rocha, V; Gluckman, E; Hromadnikova, I; Sedlacek, P; Wolff, D; Holtick, U; Dickinson, A; Bickeböller, H

2015-11-01

Previous studies of non-histocompatibility leukocyte antigen (HLA) gene single-nucleotide polymorphisms (SNPs) on subgroups of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) revealed an association with transplant outcome. This study further evaluated the association of non-HLA polymorphisms with overall survival in a cohort of 762 HSCT patients using data on 26 polymorphisms in 16 non-HLA genes. When viewed in addition to an already established clinical risk score (EBMT-score), three polymorphisms: rs8177374 in the gene for MyD88-adapter-like (MAL; P=0.026), rs9340799 in the oestrogen receptor gene (ESR; P=0.003) and rs1800795 in interleukin-6 (IL-6; P=0.007) were found to be associated with reduced overall survival, whereas the haplo-genotype (ACC/ACC) in IL-10 was protective (P=0.02). The addition of these non-HLA polymorphisms in a Cox regression model alongside the EBMT-score improved discrimination between risk groups and increased the level of prediction compared with the EBMT-score alone (gain in prediction capability for EBMT-genetic-score 10.8%). Results also demonstrated how changes in clinical practice through time have altered the effects of non-HLA analysis. The study illustrates the significance of non-HLA genotyping prior to HSCT and the importance of further investigation into non-HLA gene polymorphisms in risk prediction.

Ecological effects of the invasive giant madagascar day gecko on endemic mauritian geckos: applications of binomial-mixture and species distribution models.

PubMed

Buckland, Steeves; Cole, Nik C; Aguirre-Gutiérrez, Jesús; Gallagher, Laura E; Henshaw, Sion M; Besnard, Aurélien; Tucker, Rachel M; Bachraz, Vishnu; Ruhomaun, Kevin; Harris, Stephen

2014-01-01

The invasion of the giant Madagascar day gecko Phelsuma grandis has increased the threats to the four endemic Mauritian day geckos (Phelsuma spp.) that have survived on mainland Mauritius. We had two main aims: (i) to predict the spatial distribution and overlap of P. grandis and the endemic geckos at a landscape level; and (ii) to investigate the effects of P. grandis on the abundance and risks of extinction of the endemic geckos at a local scale. An ensemble forecasting approach was used to predict the spatial distribution and overlap of P. grandis and the endemic geckos. We used hierarchical binomial mixture models and repeated visual estimate surveys to calculate the abundance of the endemic geckos in sites with and without P. grandis. The predicted range of each species varied from 85 km2 to 376 km2. Sixty percent of the predicted range of P. grandis overlapped with the combined predicted ranges of the four endemic geckos; 15% of the combined predicted ranges of the four endemic geckos overlapped with P. grandis. Levin's niche breadth varied from 0.140 to 0.652 between P. grandis and the four endemic geckos. The abundance of endemic geckos was 89% lower in sites with P. grandis compared to sites without P. grandis, and the endemic geckos had been extirpated at four of ten sites we surveyed with P. grandis. Species Distribution Modelling, together with the breadth metrics, predicted that P. grandis can partly share the equivalent niche with endemic species and survive in a range of environmental conditions. We provide strong evidence that smaller endemic geckos are unlikely to survive in sympatry with P. grandis. This is a cause of concern in both Mauritius and other countries with endemic species of Phelsuma.

Validation of serum amyloid α as an independent biomarker for progression-free and overall survival in metastatic renal cell cancer patients.

PubMed

Vermaat, Joost S; Gerritse, Frank L; van der Veldt, Astrid A; Roessingh, Wijnand M; Niers, Tatjana M; Oosting, Sjoukje F; Sleijfer, Stefan; Roodhart, Jeanine M; Beijnen, Jos H; Schellens, Jan H; Gietema, Jourik A; Boven, Epie; Richel, Dick J; Haanen, John B; Voest, Emile E

2012-10-01

We recently identified apolipoprotein A2 (ApoA2) and serum amyloid α (SAA) as independent prognosticators in metastatic renal cell carcinoma (mRCC) patients, thereby improving the accuracy of the Memorial-Sloan Kettering Cancer Center (MSKCC) model. Validate these results prospectively in a separate cohort of mRCC patients treated with tyrosine kinase inhibitors (TKIs). For training we used 114 interferon-treated mRCC patients (inclusion 2001-2006). For validation we studied 151 TKI-treated mRCC patients (inclusion 2003-2009). Using Cox proportional hazards regression analysis, SAA and ApoA2 were associated with progression-free survival (PFS) and overall survival (OS). In 72 TKI-treated patients, SAA levels were analyzed longitudinally as a potential early marker for treatment effect. Baseline ApoA2 and SAA levels significantly predicted PFS and OS in the training and validation cohorts. Multivariate analysis identified SAA in both separate patient sets as a robust and independent prognosticator for PFS and OS. In contrast to our previous findings, ApoA2 interacted with SAA in the validation cohort and did not contribute to a better predictive accuracy than SAA alone and was therefore excluded from further analysis. According to the tertiles of SAA levels, patients were categorized in three risk groups, demonstrating accurate risk prognostication. SAA as a single biomarker showed equal prognostic accuracy when compared with the multifactorial MSKCC risk mode. Using receiver operating characteristic analysis, SAA levels >71 ng/ml were designated as the optimal cut-off value in the training cohort, which was confirmed for its significant sensitivity and specificity in the validation cohort. Applying SAA >71 ng/ml as an additional risk factor significantly improved the predictive accuracy of the MSKCC model in both independent cohorts. Changes in SAA levels after 6-8 wk of TKI treatment had no value in predicting treatment outcome. SAA but not ApoA2 was shown to be a robust and independent prognosticator for PFS and OS in mRCC patients. When incorporated in the MSKCC model, SAA showed additional prognostic value for patient management. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Ectopic High Expression of E2-EPF Ubiquitin Carrier Protein Indicates a More Unfavorable Prognosis in Brain Glioma.

PubMed

Zhang, Xiaohui; Zhao, Fangbo; Zhang, Shujun; Song, Yichun

2017-04-01

Ubiquitination of proteins meant for elimination is a primary method of eukaryotic cellular protein degradation. The ubiquitin carrier protein E2-EPF is a key degradation enzyme that is highly expressed in many tumors. However, its expression and prognostic significance in brain glioma are still unclear. The aim of this study was to reveal how the level of E2-EPF relates to prognosis in brain glioma. Thirty low-grade and 30 high-grade brain glioma samples were divided into two tissue microarrays each. Levels of E2-EPF protein were examined by immunohistochemistry and immunofluorescence. Quantitative real-time polymerase chain reaction was used to analyze the level of E2-EPF in 60 glioma and 3 normal brain tissue samples. The relationship between E2-EPF levels and prognosis was analyzed by Kaplan-Meier survival curves. E2-EPF levels were low in normal brain tissue samples but high in glioma nuclei. E2-EPF levels gradually increased as glioma grade increased (p < 0.05). Ectopic E2-EPF levels in high-grade glioma were significantly higher than in low-grade glioma (p < 0.01). The 5-year survival rate of glioma patients with high E2-EPF levels was shorter than in patients with low expression (p < 0.05). Furthermore, the 5-year survival rate of patients with ectopic E2-EPF was significantly shorter than patients with only nuclear E2-EPF (p < 0.01). These results suggest that higher E2-EPF levels, especially ectopic, are associated with higher grade glioma and shorter survival. E2-EPF levels may play a key role in predicting the prognosis for patients with brain glioma.

Stochastic variation in avian survival rates: Life-history predictions, population consequences, and the potential responses to human perturbations and climate change

USGS Publications Warehouse

Schmutz, Joel A.; Thomson, David L.; Cooch, Evan G.; Conroy, Michael J.

2009-01-01

Stochastic variation in survival rates is expected to decrease long-term population growth rates. This expectation influences both life-history theory and the conservation of species. From this expectation, Pfister (1998) developed the important life-history prediction that natural selection will have minimized variability in those elements of the annual life cycle (such as adult survival rate) with high sensitivity. This prediction has not been rigorously evaluated for bird populations, in part due to statistical difficulties related to variance estimation. I here overcome these difficulties, and in an analysis of 62 populations, I confirm her prediction by showing a negative relationship between the proportional sensitivity (elasticity) of adult survival and the proportional variance (CV) of adult survival. However, several species deviated significantly from this expectation, with more process variance in survival than predicted. For instance, projecting the magnitude of process variance in annual survival for American redstarts (Setophaga ruticilla) for 25 years resulted in a 44% decline in abundance without assuming any change in mean survival rate. For most of these species with high process variance, recent changes in harvest, habitats, or changes in climate patterns are the likely sources of environmental variability causing this variability in survival. Because of climate change, environmental variability is increasing on regional and global scales, which is expected to increase stochasticity in vital rates of species. Increased stochasticity in survival will depress population growth rates, and this result will magnify the conservation challenges we face.

Pretreatment Carbohydrate Antigen 19-9 Level Indicates Tumor Response, Early Distant Metastasis, Overall Survival, and Therapeutic Selection in Localized and Unresectable Pancreatic Cancer

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

Yoo, Tae; Lee, Woo Jin; Woo, Sang Myung

2011-11-15

Purpose: The use of chemoradiotherapy (CRT) for localized and unresectable pancreatic cancer has been disputed because of high probability of distant metastasis. Thus, we analyzed the effect of clinical parameters on tumor response, early distant metastasis within 3 months (DM{sup 3m}), and overall survival to identify an indicator for selecting patients who would benefit from CRT. Methods and Materials: This study retrospectively analyzed the data from 84 patients with localized and unresectable pancreatic cancer who underwent CRT between August 2002 and October 2009. Sex, age, tumor size, histological differentiation, N classification, pre- and post-treatment carbohydrate antigen (CA) 19-9 level, andmore » CA 19-9 percent decrease were analyzed to identify risk factors associated with tumor response, DM{sup 3m}, and overall survival. Results: For all 84 patients, the median survival time was 12.5 months (range, 2-31.9 months), objective response (complete response or partial response) to CRT was observed in 28 patients (33.3%), and DM{sup 3m} occurred in 24 patients (28.6%). Multivariate analysis showed that pretreatment CA 19-9 level ({<=}400 vs. >400 U/ml) was significantly associated with tumor response (45.1% vs. 15.2%), DM{sup 3m} (19.6% vs. 42.4%), and median overall survival time (15.1 vs. 9.7 months) (p < 0.05 for all three parameters). Conclusion: For patients with localized and unresectable pancreatic cancer, pretreatment CA 19-9 level could be helpful in predicting tumor response, DM{sup 3m}, and overall survival and identifying patients who will benefit from CRT.« less

Cancer survival classification using integrated data sets and intermediate information.

PubMed

Kim, Shinuk; Park, Taesung; Kon, Mark

2014-09-01

Although numerous studies related to cancer survival have been published, increasing the prediction accuracy of survival classes still remains a challenge. Integration of different data sets, such as microRNA (miRNA) and mRNA, might increase the accuracy of survival class prediction. Therefore, we suggested a machine learning (ML) approach to integrate different data sets, and developed a novel method based on feature selection with Cox proportional hazard regression model (FSCOX) to improve the prediction of cancer survival time. FSCOX provides us with intermediate survival information, which is usually discarded when separating survival into 2 groups (short- and long-term), and allows us to perform survival analysis. We used an ML-based protocol for feature selection, integrating information from miRNA and mRNA expression profiles at the feature level. To predict survival phenotypes, we used the following classifiers, first, existing ML methods, support vector machine (SVM) and random forest (RF), second, a new median-based classifier using FSCOX (FSCOX_median), and third, an SVM classifier using FSCOX (FSCOX_SVM). We compared these methods using 3 types of cancer tissue data sets: (i) miRNA expression, (ii) mRNA expression, and (iii) combined miRNA and mRNA expression. The latter data set included features selected either from the combined miRNA/mRNA profile or independently from miRNAs and mRNAs profiles (IFS). In the ovarian data set, the accuracy of survival classification using the combined miRNA/mRNA profiles with IFS was 75% using RF, 86.36% using SVM, 84.09% using FSCOX_median, and 88.64% using FSCOX_SVM with a balanced 22 short-term and 22 long-term survivor data set. These accuracies are higher than those using miRNA alone (70.45%, RF; 75%, SVM; 75%, FSCOX_median; and 75%, FSCOX_SVM) or mRNA alone (65.91%, RF; 63.64%, SVM; 72.73%, FSCOX_median; and 70.45%, FSCOX_SVM). Similarly in the glioblastoma multiforme data, the accuracy of miRNA/mRNA using IFS was 75.51% (RF), 87.76% (SVM) 85.71% (FSCOX_median), 85.71% (FSCOX_SVM). These results are higher than the results of using miRNA expression and mRNA expression alone. In addition we predict 16 hsa-miR-23b and hsa-miR-27b target genes in ovarian cancer data sets, obtained by SVM-based feature selection through integration of sequence information and gene expression profiles. Among the approaches used, the integrated miRNA and mRNA data set yielded better results than the individual data sets. The best performance was achieved using the FSCOX_SVM method with independent feature selection, which uses intermediate survival information between short-term and long-term survival time and the combination of the 2 different data sets. The results obtained using the combined data set suggest that there are some strong interactions between miRNA and mRNA features that are not detectable in the individual analyses. Copyright © 2014 Elsevier B.V. All rights reserved.

A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis.

PubMed

Passamonti, F; Giorgino, T; Mora, B; Guglielmelli, P; Rumi, E; Maffioli, M; Rambaldi, A; Caramella, M; Komrokji, R; Gotlib, J; Kiladjian, J J; Cervantes, F; Devos, T; Palandri, F; De Stefano, V; Ruggeri, M; Silver, R T; Benevolo, G; Albano, F; Caramazza, D; Merli, M; Pietra, D; Casalone, R; Rotunno, G; Barbui, T; Cazzola, M; Vannucchi, A M

2017-12-01

Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms with variable risk of evolution into post-PV and post-ET myelofibrosis, from now on referred to as secondary myelofibrosis (SMF). No specific tools have been defined for risk stratification in SMF. To develop a prognostic model for predicting survival, we studied 685 JAK2, CALR, and MPL annotated patients with SMF. Median survival of the whole cohort was 9.3 years (95% CI: 8-not reached-NR-). Through penalized Cox regressions we identified negative predictors of survival and according to beta risk coefficients we assigned 2 points to hemoglobin level <11 g/dl, to circulating blasts ⩾3%, and to CALR-unmutated genotype, 1 point to platelet count <150 × 10 9 /l and to constitutional symptoms, and 0.15 points to any year of age. Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM) allocated SMF patients into four risk categories with different survival (P<0.0001): low (median survival NR; 133 patients), intermediate-1 (9.3 years, 95% CI: 8.1-NR; 245 patients), intermediate-2 (4.4 years, 95% CI: 3.2-7.9; 126 patients), and high risk (2 years, 95% CI: 1.7-3.9; 75 patients). Finally, we found that the MYSEC-PM represents the most appropriate tool for SMF decision-making to be used in clinical and trial settings.

Expression profiles of loneliness-associated genes for survival prediction in cancer patients.

PubMed

You, Liang-Fu; Yeh, Jia-Rong; Su, Mu-Chun

2014-01-01

Influence of loneliness on human survival has been established epidemiologically, but genomic research remains undeveloped. We identified 34 loneliness-associated genes which were statistically significant for high- lonely and low-lonely individuals. With the univariate Cox proportional hazards regression model, we obtained corresponding regression coefficients for loneliness-associated genes fo individual cancer patients. Furthermore, risk scores could be generated with the combination of gene expression level multiplied by corresponding regression coefficients of loneliness-associated genes. We verified that high-risk score cancer patients had shorter mean survival time than their low-risk score counterparts. Then we validated the loneliness-associated gene signature in three independent brain cancer cohorts with Kaplan-Meier survival curves (n=77, 85 and 191), significantly separable by log-rank test with hazard ratios (HR) >1 and p-values <0.0001 (HR=2.94, 3.82, and 1.78). Moreover, we validated the loneliness-associated gene signature in bone cancer (HR=5.10, p-value=4.69e-3), lung cancer (HR=2.86, p-value=4.71e-5), ovarian cancer (HR=1.97, p-value=3.11e-5), and leukemia (HR=2.06, p-value=1.79e-4) cohorts. The last lymphoma cohort proved to have an HR=3.50, p-value=1.15e-7. Loneliness- associated genes had good survival prediction for cancer patients, especially bone cancer patients. Our study provided the first indication that expression of loneliness-associated genes are related to survival time of cancer patients.

Prognostic value of plasma fibrinogen levels in patients with localized upper tract urothelial carcinoma.

PubMed

Tanaka, Nobuyuki; Kikuchi, Eiji; Matsumoto, Kazuhiro; Hayakawa, Nozomi; Ide, Hiroki; Miyajima, Akira; Nakamura, So; Oya, Mototsugu

2013-05-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Upper tract urothelial carcinoma (UTUC) is relatively uncommon, accounting for only ~5% of urothelial malignancies and 10% of all renal tumours. Radical nephroureterectomy (RNU) with bladder cuff excision is the surgical standard of care for treating localized UTUC, but the prognosis for patients who undergo RNU remains poor. Evidence suggests that an interactive relationship exists between haemostatic factors and tumour biology. A number of procoagulant and fibrinolytic factors have been found to be overexpressed in tumours. One of these factors is plasma fibrinogen. Recent studies have shown that elevated pre-therapeutic plasma fibrinogen levels are associated with worse outcome in various malignancies; however, the prognostic value of plasma fibrinogen levels for UTUC has not yet been reported. To the best of our knowledge, this is the first paper to evaluate the prognostic impact of preoperative plasma fibrinogen levels in patients with localized UTUC treated surgically. We believe that the present results may assist in decision-making with respect to the need for lymph node dissection and neoadjuvant chemotherapy. To investigate the prognostic value of plasma fibrinogen levels as a predictor of patient outcome in upper tract urothelial carcinoma (UTUC). A total of 218 patients who underwent radical nephroureterectomy (RNU) for localized UTUC (pTa-4N0M0) were identified between 1995 and 2009. The association between preoperative plasma fibrinogen levels and clinicopathological variables was analysed. Forty-five patients experienced tumour recurrence, and 36 died from disease during the mean follow-up of 51 months. The mean (sd) preoperative plasma fibrinogen level was 362 (103) mg/dL. Kaplan-Meier curves showed that subsequent tumour recurrence was strongly predicted in patients with preoperative plasma fibrinogen levels ≥450 mg/dL, and similar results were observed for cancer-specific survival. On multivariate analysis we found that a preoperative plasma fibrinogen level of ≥450 mg/dL was an independent risk factor for subsequent tumour recurrence and cancer-specific survival. The 5-year recurrence-free survival rate was 56.9% in patients with plasma fibrinogen levels ≥450 mg/dL and 81.5% in patients with plasma fibrinogen levels <450 mg/dL (P < 0.001). The 5-year cancer-specific survival rate was 59.5% in patients with plasma fibrinogen levels of ≥450 mg/dL and 84.8% in patients with plasma fibrinogen levels <450 mg/dL (P < 0.001). On multivariate analysis, controlling for preoperative indicators, a preoperative plasma fibrinogen level of ≥450 mg/dL predicted worse pathological features, such as ≥pT3 disease and positive lymphovascular invasion, in surgical specimens. Preoperative elevated plasma fibrinogen level was an independent predictor for poor survival after RNU and for worse pathological features. Plasma fibrinogen levels may become a useful biomarker, particularly because of its low associated cost and easy accessibility. © 2012 BJU International.

Magnetic resonance spectroscopy metabolite profiles predict survival in paediatric brain tumours.

PubMed

Wilson, Martin; Cummins, Carole L; Macpherson, Lesley; Sun, Yu; Natarajan, Kal; Grundy, Richard G; Arvanitis, Theodoros N; Kauppinen, Risto A; Peet, Andrew C

2013-01-01

Brain tumours cause the highest mortality and morbidity rate of all childhood tumour groups and new methods are required to improve clinical management. (1)H magnetic resonance spectroscopy (MRS) allows non-invasive concentration measurements of small molecules present in tumour tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to investigate whether MRS detectable molecules can predict the survival of paediatric brain tumour patients. Short echo time (30ms) single voxel (1)H MRS was performed on children attending Birmingham Children's Hospital with a suspected brain tumour and 115 patients were included in the survival analysis. Patients were followed-up for a median period of 35 months and Cox-Regression was used to establish the prognostic value of individual MRS detectable molecules. A multivariate model of survival was also investigated to improve prognostic power. Lipids and scyllo-inositol predicted poor survival whilst glutamine and N-acetyl aspartate predicted improved survival (p<0.05). A multivariate model of survival based on three MRS biomarkers predicted survival with a similar accuracy to histologic grading (p<5e-5). A negative correlation between lipids and glutamine was found, suggesting a functional link between these molecules. MRS detectable biomolecules have been identified that predict survival of paediatric brain tumour patients across a range of tumour types. The evaluation of these biomarkers in large prospective studies of specific tumour types should be undertaken. The correlation between lipids and glutamine provides new insight into paediatric brain tumour metabolism that may present novel targets for therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anthrax vaccine-induced antibodies provide cross-species prediction of survival to aerosol challenge.

PubMed

Fay, Michael P; Follmann, Dean A; Lynn, Freyja; Schiffer, Jarad M; Stark, Gregory V; Kohberger, Robert; Quinn, Conrad P; Nuzum, Edwin O

2012-09-12

Because clinical trials to assess the efficacy of vaccines against anthrax are not ethical or feasible, licensure for new anthrax vaccines will likely involve the Food and Drug Administration's "Animal Rule," a set of regulations that allow approval of products based on efficacy data only in animals combined with immunogenicity and safety data in animals and humans. U.S. government-sponsored animal studies have shown anthrax vaccine efficacy in a variety of settings. We examined data from 21 of those studies to determine whether an immunological bridge based on lethal toxin neutralization activity assay (TNA) can predict survival against an inhalation anthrax challenge within and across species and genera. The 21 studies were classified into 11 different settings, each of which had the same animal species, vaccine type and formulation, vaccination schedule, time of TNA measurement, and challenge time. Logistic regression models determined the contribution of vaccine dilution dose and TNA on prediction of survival. For most settings, logistic models using only TNA explained more than 75% of the survival effect of the models with dose additionally included. Cross-species survival predictions using TNA were compared to the actual survival and shown to have good agreement (Cohen's κ ranged from 0.55 to 0.78). In one study design, cynomolgus macaque data predicted 78.6% survival in rhesus macaques (actual survival, 83.0%) and 72.6% in rabbits (actual survival, 64.6%). These data add support for the use of TNA as an immunological bridge between species to extrapolate data in animals to predict anthrax vaccine effectiveness in humans.

Long-Term Sustainability of Evidence-Based Prevention Interventions and Community Coalitions Survival: a Five and One-Half Year Follow-up Study.

PubMed

Johnson, Knowlton; Collins, David; Shamblen, Steve; Kenworthy, Tara; Wandersman, Abraham

2017-07-01

This study examines (1) coalition survival, (2) prevalence of evidence-based prevention interventions (EBPIs) to reduce substance abuse implemented as part of the Tennessee Strategic Prevention Framework (SPF) State Incentive Grant (SIG), (3) EBPI sustainability, and (4) factors that predict EBPI sustainability. Secondary data were collected on 27 SPF SIG-funded coalitions and 88 EBPI and non-EBPI implementations. Primary data were collected by a telephone interview/web survey five and one-half years after the SPF SIG ended. Results from secondary data show that 25 of the 27 coalitions survived beyond the SPF SIG for one to five and one-half years; 19 coalitions (70%) were still active five and one-half years later. Further, 88 EBPIs and non-EBPIs were implemented by 27 county SPF SIG coalitions. Twenty-one (21) of 27 coalitions (78%) implemented one to three EBPIs, totaling 37 EBPI implementations. Based on primary survey data on 29 of the 37 EBPI implementations, 28 EBPIs (97%) were sustained between two and five and one-half years while 22 EBPI implementations (76%) were sustained for five and one-half years. When controlling for variability among coalitions (nesting of EBPIs in coalitions), increases in data resources (availability of five types of prevention data) was a strong predictor of length of EBPI sustainability. Positive change in extramural funding resources and level of expertise during SPF SIG implementation, as well as level of coalition formalization at the end of the SPF SIG predicted EBPI sustainability length. One intervention attribute (trialability) also predicted length of sustainability. Implications are discussed.

A gene expression signature associated with survival in metastatic melanoma

PubMed Central

Mandruzzato, Susanna; Callegaro, Andrea; Turcatel, Gianluca; Francescato, Samuela; Montesco, Maria C; Chiarion-Sileni, Vanna; Mocellin, Simone; Rossi, Carlo R; Bicciato, Silvio; Wang, Ena; Marincola, Francesco M; Zanovello, Paola

2006-01-01

Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM) to identify genes associated with patient survival, and supervised principal components (SPC) to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells. PMID:17129373

Association of Adjuvant Chemotherapy With Survival in Patients With Stage II or III Gastric Cancer

PubMed Central

Jiang, Yuming; Li, Tuanjie; Liang, Xiaoling; Hu, Yanfeng; Huang, Lei; Liao, Zhenchen; Zhao, Liying; Han, Zhen; Zhu, Shuguang; Wang, Menglan; Xu, Yangwei; Qi, Xiaolong; Liu, Hao; Yang, Yang; Yu, Jiang; Liu, Wei; Cai, Shirong

2017-01-01

Importance The current staging system of gastric cancer is not adequate for defining a prognosis and predicting the patients most likely to benefit from chemotherapy. Objective To construct a survival prediction model based on specific tumor and patient characteristics that enables individualized predictions of the net survival benefit of adjuvant chemotherapy for patients with stage II or stage III gastric cancer. Design, Setting, and Participants In this multicenter retrospective analysis, a survival prediction model was constructed using data from a training cohort of 746 patients with stage II or stage III gastric cancer who satisfied the study’s inclusion criteria and underwent surgery between January 1, 2004, and December 31, 2012, at Nanfang Hospital in Guangzhou, China. Patient and tumor characteristics were included as covariates, and their association with overall survival and disease-free survival with and without adjuvant chemotherapy was assessed. The model was internally validated for discrimination and calibration using bootstrap resampling. To externally validate the model, data were included from a validation cohort of 973 patients with stage II or stage III gastric cancer who met the inclusion criteria and underwent surgery at First Affiliated Hospital in Guangzhou, China, and at West China Hospital of Sichuan Hospital in Chendu, China, between January 1, 2000, and June 30, 2009. Data were analyzed from July 10, 2016, to September 1, 2016. Main Outcomes and Measures Concordance index and decision curve analysis for each measure associated with postoperative overall survival and disease-free survival. Results Of the 1719 patients analyzed, 1183 (68.8%) were men and 536 (31.2%) were women and the median (interquartile range) age was 57 (49-66) years. Age, location, differentiation, carcinoembryonic antigen, cancer antigen 19-9, depth of invasion, lymph node metastasis, and adjuvant chemotherapy were significantly associated with overall survival and disease-free survival, with P < .05. The survival prediction model demonstrated good calibration and discrimination, with relatively high bootstrap-corrected concordance indexes in the training and validation cohorts. In the validation cohort, the concordance index for overall survival was 0.693 (95% CI, 0.671-0.715) and for disease-free survival was 0.704 (95% CI, 0.681-0.728). Two nomograms and a calculating tool were built on the basis of specific input variables to estimate an individual’s net survival gain attributable to adjuvant chemotherapy. Conclusions and Relevance The survival prediction model can be used to make individualized predictions of the expected survival benefit from the addition of adjuvant chemotherapy for patients with stage II or stage III gastric cancer. PMID:28538950

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

Hu, Zhi; Huang, Ge; Sadanandam, Anguraj

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

Preliminary study of tumor heterogeneity in imaging predicts two year survival in pancreatic cancer patients.

PubMed

Chakraborty, Jayasree; Langdon-Embry, Liana; Cunanan, Kristen M; Escalon, Joanna G; Allen, Peter J; Lowery, Maeve A; O'Reilly, Eileen M; Gönen, Mithat; Do, Richard G; Simpson, Amber L

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States with a five-year survival rate of 7.2% for all stages. Although surgical resection is the only curative treatment, currently we are unable to differentiate between resectable patients with occult metastatic disease from those with potentially curable disease. Identification of patients with poor prognosis via early classification would help in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant therapy. PDAC ranges in appearance from homogeneously isoattenuating masses to heterogeneously hypovascular tumors on CT images; hence, we hypothesize that heterogeneity reflects underlying differences at the histologic or genetic level and will therefore correlate with patient outcome. We quantify heterogeneity of PDAC with texture analysis to predict 2-year survival. Using fuzzy minimum-redundancy maximum-relevance feature selection and a naive Bayes classifier, the proposed features achieve an area under receiver operating characteristic curve (AUC) of 0.90 and accuracy (Ac) of 82.86% with the leave-one-image-out technique and an AUC of 0.80 and Ac of 75.0% with three-fold cross-validation. We conclude that texture analysis can be used to quantify heterogeneity in CT images to accurately predict 2-year survival in patients with pancreatic cancer. From these data, we infer differences in the biological evolution of pancreatic cancer subtypes measurable in imaging and identify opportunities for optimized patient selection for therapy.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-02-16

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

Prognostic value of pretreatment serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in patients with esophageal squamous cell carcinoma.

PubMed

Huang, Hao; Wang, Xue-Ping; Li, Xiao-Hui; Chen, Hao; Zheng, Xin; Lin, Jian-Hua; Kang, Ting; Zhang, Lin; Chen, Pei-Song

2017-08-14

The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients. Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models. LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457-0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163-1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1-T2 subgroup, T3-T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3-T4 subgroup and N1-N2 subgroup). Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC.

NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients

PubMed Central

Prochazka, Katharina T; Melchardt, Thomas; Posch, Florian; Schlick, Konstantin; Deutsch, Alexander; Beham-Schmid, Christine; Weiss, Lukas; Gary, Thomas; Neureiter, Daniel; Klieser, Eckhard; Greil, Richard; Neumeister, Peter; Egle, Alexander; Pichler, Martin

2016-01-01

Background: Blood-based parameters are gaining increasing interest as potential prognostic biomarkers in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this study was to comprehensively evaluate the prognostic significance of pretreatment plasma uric acid levels in patients with newly diagnosed DLBCL. Methods: The clinical course of 539 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian high-volume centres with rituximab-based immunochemotherapy was evaluated retrospectively. The prognostic influence of uric acid on overall survival (OS) and progression-free survival (PFS) were studied including multi-state modelling, and analysis of conditional survival. Results: Five-year OS and PFS were 50.4% (95% CI: 39.2–60.6) and 44.0% (33.4–54.0) in patients with uric acid levels above the 75th percentile of the uric acid distribution (Q3, cut-off: 6.8 mg dl−1), and 66.2% (60.4–71.5) and 59.6% (53.7–65.0%) in patients with lower levels (log-rank P=0.002 and P=0.0045, respectively). In univariable time-to-event analysis, elevated uric acid levels were associated with a worse PFS (hazard ratio (HR) per 1 log increase in uric acid 1.47, 95% CI: 1.10–1.97, P=0.009) and a worse OS (HR=1.60, 95% CI: 1.16–2.19, P=0.004). These associations prevailed upon multivariable adjustment for the NCCN-IPI score. Uric acid levels significantly improved the predictive performance of the R-IPI and NCCN-IPI scores, and in multi-state analysis, it emerged as a highly significant predictor of an increased risk of death without developing recurrence (transition-HR=4.47, 95% CI: 2.17–9.23, P<0.0001). Conclusions: We demonstrate that elevated uric acid levels predict poor long-term outcomes in DLBCL patients beyond the NCCN-IPI risk index. PMID:27764838

MDM2 is an important prognostic and predictive factor for platin-pemetrexed therapy in malignant pleural mesotheliomas and deregulation of P14/ARF (encoded by CDKN2A) seems to contribute to an MDM2-driven inactivation of P53.

PubMed

Walter, R F H; Mairinger, F D; Ting, S; Vollbrecht, C; Mairinger, T; Theegarten, D; Christoph, D C; Schmid, K W; Wohlschlaeger, J

2015-03-03

Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation. A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS). OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P⩽0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival. MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients.

Outcome of cervix uteri cancer patients: Clinical treatment results and toxicity profile in a retrospective study from Saudi Arabia.

PubMed

El Sayed, Mohamed E; Bahadur, Yasir A; Hassouna, Ashraf H; Fawzy, Ehab E; Nasr, Azza M; Sadiq, Bakr B; Dada, Reyad; Sait, Khalid H; Anfinan, Nisrin M

2017-10-01

This study evaluated the survival outcome, pattern of failure and prognostic factors in cervix uteri cancer patients. We reviewed the data of 60 patients with stages IB-IVA cancer who were treated between January 2004 and December 2010. Most patients (n = 50; 83%) had squamous cell carcinoma. Stage IIB was the most common presentation (n = 41; 68%). Forty-seven patients (78%) received Cisplatin concurrent with radiotherapy (CRT). The 2- and 4-year overall survival (OS) was 82% and 79%, respectively. Prolongation of the overall treatment time (OAT) for greater than 56 days, advanced stage and pretreatment hemoglobin (Hb) levels (<10 g/dL) negatively predicted OS (P = 0.039, P = 0.044 and P = 0.008, respectively). The 2- and 4-year disease-free survival (DFS) rates were 80% and 69%, respectively. Vaginal infiltration and brachytherapy (orthogonal versus CT-based planning) were significant factors for the prediction of relapse (P = 0.048 and P = 0.049, respectively). The 2- and 4-year loco-regional control (LRC) rates were 78% and 70%, respectively, and the distant metastasis-free survival (DMFS) rates were 82% and 79%, respectively. Vaginal infiltration was the only negative predictive factor for LRC (P = 0.045), and pathological tumor grade was the only factor indicative of distant metastases (P = 0.037). Grade 3 or 4 late rectal reactions were reported in two patients (3%), and no patients developed grade 3 or 4 urinary reactions. The treatment results in our cervix uteri cancer patients and the prognostic factors are comparable to those of previous reports. Orthogonal brachytherapy planning and vaginal infiltration negatively predicted relapse. © 2016 John Wiley & Sons Australia, Ltd.

Empirical evidence that metabolic theory describes the temperature dependency of within-host parasite dynamics.

PubMed

Kirk, Devin; Jones, Natalie; Peacock, Stephanie; Phillips, Jessica; Molnár, Péter K; Krkošek, Martin; Luijckx, Pepijn

2018-02-01

The complexity of host-parasite interactions makes it difficult to predict how host-parasite systems will respond to climate change. In particular, host and parasite traits such as survival and virulence may have distinct temperature dependencies that must be integrated into models of disease dynamics. Using experimental data from Daphnia magna and a microsporidian parasite, we fitted a mechanistic model of the within-host parasite population dynamics. Model parameters comprising host aging and mortality, as well as parasite growth, virulence, and equilibrium abundance, were specified by relationships arising from the metabolic theory of ecology. The model effectively predicts host survival, parasite growth, and the cost of infection across temperature while using less than half the parameters compared to modeling temperatures discretely. Our results serve as a proof of concept that linking simple metabolic models with a mechanistic host-parasite framework can be used to predict temperature responses of parasite population dynamics at the within-host level.

Empirical evidence that metabolic theory describes the temperature dependency of within-host parasite dynamics

PubMed Central

Jones, Natalie; Peacock, Stephanie; Phillips, Jessica; Molnár, Péter K.; Krkošek, Martin; Luijckx, Pepijn

2018-01-01

The complexity of host–parasite interactions makes it difficult to predict how host–parasite systems will respond to climate change. In particular, host and parasite traits such as survival and virulence may have distinct temperature dependencies that must be integrated into models of disease dynamics. Using experimental data from Daphnia magna and a microsporidian parasite, we fitted a mechanistic model of the within-host parasite population dynamics. Model parameters comprising host aging and mortality, as well as parasite growth, virulence, and equilibrium abundance, were specified by relationships arising from the metabolic theory of ecology. The model effectively predicts host survival, parasite growth, and the cost of infection across temperature while using less than half the parameters compared to modeling temperatures discretely. Our results serve as a proof of concept that linking simple metabolic models with a mechanistic host–parasite framework can be used to predict temperature responses of parasite population dynamics at the within-host level. PMID:29415043

National Early Warning Score (NEWS) as an emergency department predictor of disease severity and 90-day survival in the acutely dyspneic patient - a prospective observational study.

PubMed

Bilben, Bente; Grandal, Linda; Søvik, Signe

2016-06-02

National Early Warning Score (NEWS) was designed to detect deteriorating patients in hospital wards, specifically those at increased risk of ICU admission, cardiac arrest, or death within 24 h. NEWS is not validated for use in Emergency Departments (ED), but emerging data suggest it may be useful. A criticism of NEWS is that patients with chronic poor oxygenation, e.g. severe chronic obstructive pulmonary disease (COPD), will have elevated NEWS also in the absence of acute deterioration, possibly reducing the predictive power of NEWS in this subgroup. We wanted to prospectively evaluate the usefulness of NEWS in unselected adult patients emergently presenting in a Norwegian ED with respiratory distress as main symptom. In respiratory distressed patients, NEWS was calculated on ED arrival, after 2-4 h, and the next day. Manchester Triage Scale (MTS) category, age, gender, comorbidity (ASA score), ICU-admission, ventilatory support, and discharge diagnoses were noted. Survival status was tracked for >90 days through the Population Registry. Data are medians (25-75th percentiles). Factors predicting 90-day survival were analysed with multiple logistic regression. We included 246 patients; 71 years old (60-80), 89 % home-dwelling, 74 % ASA 3-4, 72 % MTS 1-2, 88 % admitted to hospital. NEWS on arrival was 5 (3-7). NEWS correlated closely with MTS category and maximum in-hospital level of care (ED, ward, high-dependency unit, ICU). Sixteen patients died in-hospital, 26 died after discharge within 90 days. Controlled for age, ASA score, and COPD, a higher NEWS on ED arrival predicted poorer 90-day survival. Increased NEWS also correlated with decreased 30-day- and in-hospital survival and a decreased probability for home-dwelling patients to be discharged directly home. In respiratory distressed patients, NEWS on ED arrival correlated closely with triage category and need of ICU admission and predicted long-term out-of-hospital survival controlled for age, comorbidity, and COPD. NEWS should be explored in the ED setting to determine its role in clinical decision-making and in communication along the acute care chain.

Differences of protein expression profiles, KRAS and BRAF mutation, and prognosis in right-sided colon, left-sided colon and rectal cancer.

PubMed

Gao, Xian Hua; Yu, Guan Yu; Gong, Hai Feng; Liu, Lian Jie; Xu, Yi; Hao, Li Qiang; Liu, Peng; Liu, Zhi Hong; Bai, Chen Guang; Zhang, Wei

2017-08-11

To compare protein expression levels, gene mutation and survival among Right-Sided Colon Cancer (RSCC), Left-Sided Colon Cancer (LSCC) and rectal cancer patients, 57 cases of RSCC, 87 LSCC and 145 rectal cancer patients were included retrospectively. Our results demonstrated significant differences existed among RSCC, LSCC and rectal cancer regarding tumor diameter, differentiation, invasion depth and TNM stage. No significant difference was identified in expression levels of MLH1, MSH2, MSH6, PMS2, β-Tubulin III, P53, Ki67 and TOPIIα, and gene mutation of KRAS and BRAF among three groups. Progression Free Survival (PFS) of RSCC was significantly lower than that of LRCC and rectal cancer. In univariate analyses, RSCC, preoperative chemoradiotherapy, poor differentiation, advanced TNM stage, elevated serum CEA and CA19-9 level, tumor deposit, perineural and vascular invasion were found to be predictive factors of shorter PFS. In multivariate analyses, only differentiation and TNM stages were found to be independent predictors of PFS. In conclusion, compared with LSCC and rectal cancer, RSCC has larger tumor size, poor differentiation, advanced TNM stage and shorter survival. The shorter survival in RSCC might be attributed to the advanced tumor stage caused by its inherent position feature of proximal colon rather than genetic difference.

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

PubMed

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

2014-02-01

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

Machine learning models in breast cancer survival prediction.

PubMed

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

2016-01-01

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

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 for research studies, and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality. PMID:25985385

Riser pattern is a predictor of kidney mortality among patients with chronic kidney disease.

PubMed

Nakai, Kentaro; Fujii, Hideki; Watanabe, Kentaro; Watanabe, Shuhei; Awata, Rie; Kono, Keiji; Yonekura, Yuriko; Goto, Shunsuke; Nishi, Shinichi

Hypertension is a crucial risk factor for cardiovascular death and loss of residual kidney function. Absence of the nocturnal decline in blood pressure (BP) predicts cardiovascular events and poor prognosis. However, characteristics of hypertension in moderate-to-severe chronic kidney disease (CKD) have not been fully evaluated. We aimed to assess the circadian variation of BP and kidney survival in CKD patients. Patients who were examined by 24-h ambulatory BP monitoring (ABPM) and estimated glomerular filtration rate (eGFR), <45 ml/min/1.73 m(2), were enrolled in the study. The impacts of BP circadian rhythm and brain natriuretic peptide (BNP) on kidney survival were evaluated. A total of 124 patients were enrolled. The average age was 64 ± 14 years, 57% were male, and 43% had diabetes. Forty-five percent of patients had a non-dipper pattern, 35% had a riser pattern, 19% had a dipper pattern, and 1% had an extreme-dipper pattern. The prevalence of diabetes and plasma BNP levels was higher and eGFR was lower in the riser-pattern group than in the non-riser-pattern group. Kidney survival rates were significantly worse in the riser-pattern group than in the non-riser-pattern group (p < 0.05). Moreover, among riser and non-riser pattern groups divided by BNP levels, the riser group with higher BNP level showed the worst kidney survival (p < 0.05). The riser pattern is frequently associated with several conditions at higher risk for kidney survival. Patients with a rising pattern and higher BNP levels have a worse kidney prognosis.

N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study.

PubMed

Cheng, Hui; Fan, Wei-Ze; Wang, Sheng-Chi; Liu, Zhao-Hui; Zang, Hui-Ling; Wang, Li-Zhong; Liu, Hong-Juan; Shen, Xiao-Hui; Liang, Shao-Qing

2015-06-01

Using biomarkers to predict mortality in patient with severe sepsis or septic shock is of importance, as these patients frequently have high mortality and unsatisfied outcome. N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) play extremely important roles in prognostic value in the mortality of severe sepsis and septic shock. The present study was retrospectively designed to evaluate the predicting mortality of NT-proBNP and cTnI in elderly patients with severe sepsis or septic shock administered in the intensive care unit (ICU) and also to evaluate whether the predicting ability of Acute Physiology and Chronic Health Evaluation II (APACHE-II) score or C-reactive protein (CRP) was increased in combination with the biomarkers. A cohort of 430 patients (aged ≥65 years) with severe sepsis or septic shock admitted to our ICU between October 2011 and December 2013 was included in the study. Patient data including clinical, laboratory, and survival and mortality were collected. All patients were examined with NT-proBNP, cTnI, CRP, and APACHE-II score and were categorized as the survived and deceased groups according to the outcome 30 days after ICU treatment. The levels of NT-proBNP and cTnI (P < .01) or CRP (P < .05) were significantly higher in the deceased group than those in the survived group. The predicting mortality of APACHE-II score alone was low but largely improved, when it was combined with both NT-proBNP and cTnI (P < .05). The alteration of NT-proBNP and cTnI levels strongly predicated the ICU prognosis in elderly patients with severe sepsis or septic shock. N-terminal pro-brain natriuretic peptide and cTnI were superior to CRP in predicting mortality. The predicting ability of APACHE-II score was improved only when combined with NT-proBNP and cTnI. Copyright © 2014 Elsevier Inc. All rights reserved.

An individual-based model of zebrafish population dynamics accounting for energy dynamics.

PubMed

Beaudouin, Rémy; Goussen, Benoit; Piccini, Benjamin; Augustine, Starrlight; Devillers, James; Brion, François; Péry, Alexandre R R

2015-01-01

Developing population dynamics models for zebrafish is crucial in order to extrapolate from toxicity data measured at the organism level to biological levels relevant to support and enhance ecological risk assessment. To achieve this, a dynamic energy budget for individual zebrafish (DEB model) was coupled to an individual based model of zebrafish population dynamics (IBM model). Next, we fitted the DEB model to new experimental data on zebrafish growth and reproduction thus improving existing models. We further analysed the DEB-model and DEB-IBM using a sensitivity analysis. Finally, the predictions of the DEB-IBM were compared to existing observations on natural zebrafish populations and the predicted population dynamics are realistic. While our zebrafish DEB-IBM model can still be improved by acquiring new experimental data on the most uncertain processes (e.g. survival or feeding), it can already serve to predict the impact of compounds at the population level.

An Individual-Based Model of Zebrafish Population Dynamics Accounting for Energy Dynamics

PubMed Central

Beaudouin, Rémy; Goussen, Benoit; Piccini, Benjamin; Augustine, Starrlight; Devillers, James; Brion, François; Péry, Alexandre R. R.

2015-01-01

Developing population dynamics models for zebrafish is crucial in order to extrapolate from toxicity data measured at the organism level to biological levels relevant to support and enhance ecological risk assessment. To achieve this, a dynamic energy budget for individual zebrafish (DEB model) was coupled to an individual based model of zebrafish population dynamics (IBM model). Next, we fitted the DEB model to new experimental data on zebrafish growth and reproduction thus improving existing models. We further analysed the DEB-model and DEB-IBM using a sensitivity analysis. Finally, the predictions of the DEB-IBM were compared to existing observations on natural zebrafish populations and the predicted population dynamics are realistic. While our zebrafish DEB-IBM model can still be improved by acquiring new experimental data on the most uncertain processes (e.g. survival or feeding), it can already serve to predict the impact of compounds at the population level. PMID:25938409

Facial morphology predicts male fitness and rank but not survival in Second World War Finnish soldiers.

PubMed

Loehr, John; O'Hara, Robert B

2013-08-23

We investigated fitness, military rank and survival of facial phenotypes in large-scale warfare using 795 Finnish soldiers who fought in the Winter War (1939-1940). We measured facial width-to-height ratio-a trait known to predict aggressive behaviour in males-and assessed whether facial morphology could predict survival, lifetime reproductive success (LRS) and social status. We found no difference in survival along the phenotypic gradient, however, wider-faced individuals had greater LRS, but achieved a lower military rank.

DNA damage induction and/or repair as mammalian cell biomarker for the prediction of cellular radiation response

NASA Astrophysics Data System (ADS)

Baumstark-Khan, C.

DNA damage and its repair processes are key factors in cancer induction and also in the treatment of malignancies. Cancer prevention during extended space missions becomes a topic of great importance for space radiobiology. The knowledge of individual responsiveness would allow the protection strategy to be tailored optimally in each case. Radiobiological analysis of cultured cells derived from tissue explants from individuals has shown that measurement of the surviving fraction after 2 Gy (SF2) may be used to predict the individual responsiveness. However, clonogenic assays are timeconsuming, thus alternative assays for the determination of radiore-sponse are being sought. For that reason CHO cell strains having different repair capacities were used for examining whether DNA strand break repair is a suitable experimental design to allow predictive statements. Cellular survival (CFA assay) and DNA strand breaks (total DNA strand breaks: FADU technique; DSBs: non-denaturing elution) were determined in parallel immediately after irradiation as well as after a 24 hour recovery period according to dose. There were no correlations between the dose-response curves of the initial level of DNA strand breaks and parameters that describe clonogenic survival curves (SF2). A good correlation exists between intrinsic cellular radioresistance and the extent of residual DNA strand breaks.

Predictive model for survival in patients with gastric cancer.

PubMed

Goshayeshi, Ladan; Hoseini, Benyamin; Yousefli, Zahra; Khooie, Alireza; Etminani, Kobra; Esmaeilzadeh, Abbas; Golabpour, Amin

2017-12-01

Gastric cancer is one of the most prevalent cancers in the world. Characterized by poor prognosis, it is a frequent cause of cancer in Iran. The aim of the study was to design a predictive model of survival time for patients suffering from gastric cancer. This was a historical cohort conducted between 2011 and 2016. Study population were 277 patients suffering from gastric cancer. Data were gathered from the Iranian Cancer Registry and the laboratory of Emam Reza Hospital in Mashhad, Iran. Patients or their relatives underwent interviews where it was needed. Missing values were imputed by data mining techniques. Fifteen factors were analyzed. Survival was addressed as a dependent variable. Then, the predictive model was designed by combining both genetic algorithm and logistic regression. Matlab 2014 software was used to combine them. Of the 277 patients, only survival of 80 patients was available whose data were used for designing the predictive model. Mean ?SD of missing values for each patient was 4.43?.41 combined predictive model achieved 72.57% accuracy. Sex, birth year, age at diagnosis time, age at diagnosis time of patients' family, family history of gastric cancer, and family history of other gastrointestinal cancers were six parameters associated with patient survival. The study revealed that imputing missing values by data mining techniques have a good accuracy. And it also revealed six parameters extracted by genetic algorithm effect on the survival of patients with gastric cancer. Our combined predictive model, with a good accuracy, is appropriate to forecast the survival of patients suffering from Gastric cancer. So, we suggest policy makers and specialists to apply it for prediction of patients' survival.

Men presenting with prostate-specific antigen (PSA) values of over 100 ng/mL.

PubMed

Ang, Mann; Rajcic, Branimir; Foreman, Darren; Moretti, Kim; O'Callaghan, Michael E

2016-04-01

To investigate overall survival and prostate cancer-specific mortality in men with prostate cancer presenting with a PSA level <100 ng/mL at the time of diagnosis. Five-thousand seven hundred and sixteen patients with prostate cancer and a recorded diagnostic PSA level extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Men included were diagnosed between January 1998 and August 2013. Patients were divided into groups according to diagnostic PSA level: <20, 20-≤100, 100-≤200 ng/mL, 200-≤500 ng/mL, and >500 ng/mL. Outcomes measured include overall survival and prostate cancer-specific mortality. Clinical stage, Gleason score and the presence of bony metastasis was evaluated to determine if they were prognostic factors in patients with PSA over 100 at diagnosis. Cox proportional hazards and competing risks regression were used to model overall survival and prostate cancer-specific mortality outcomes respectively. Of this cohort, 241 patients (4.2%) had a diagnostic PSA level >100 ng/mL. Patients with PSA >100 ng/mL have a significant reduction in five (29.1% vs 62.5% vs 87%) and ten-year (18.2% vs 36.7% vs 70.7%) overall survival when compared to men with diagnostic PSA 20-100 and <20 ng/mL respectively. In this group, prostate cancer-specific mortality was associated with Gleason score and metastases, but not PSA level at diagnosis. Overall survival was associated with PSA level, Gleason score and age. There was a linear increase in risk (overall survival) as PSA increased until 200 and no association thereafter. Models of overall survival and prostate cancer-specific mortality incorporating a risk stratification developed by Izumi et al. predicted overall survival but not prostate cancer-specific mortality. The use of this stratification did not improve model accuracy. Only a small number of men (4.2%) with prostate cancer present with PSA >100 ng/mL at diagnosis. Overall survival at five and ten years was significantly poorer in patients with PSA >100 ng/mL. In this cohort of men presenting with PSA >100 at diagnosis, PSA level was not associated with prostate cancer-specific mortality. Gleason score and metastases are significant prognostic factors in this group of men. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

EAST Multicenter Trial on Targeted Temperature Management for Hanging-Induced Cardiac Arrest.

PubMed

Hsu, Cindy H; Haac, Bryce E; Drake, Mack; Bernard, Andrew C; Aiolfi, Alberto; Inaba, Kenji; Hinson, Holly E; Agarwal, Chinar; Galante, Joseph; Tibbits, Emily M; Johnson, Nicholas J; Carlbom, David; Mirhoseini, Mina F; Patel, Mayur B; OʼBosky, Karen R; Chan, Christian; Udekwu, Pascal O; Farrell, Megan; Wild, Jeffrey L; Young, Katelyn A; Cullinane, Daniel C; Gojmerac, Deborah J; Weissman, Alexandra; Callaway, Clifton; Perman, Sarah M; Guerrero, Mariana; Aisiku, Imoigele P; Seethala, Raghu R; Co, Ivan N; Madhok, Debbie Y; Darger, Bryan; Kim, Dennis Y; Spence, Lara; Scalea, Thomas M; Stein, Deborah M

2018-04-19

We sought to determine the outcome of suicidal hanging and the impact of targeted temperature management (TTM) on hanging-induced cardiac arrest (CA) through an Eastern Association for the Surgery of Trauma (EAST) multicenter retrospective study. We analyzed hanging patient data and TTM variables from January 1992 to December 2015. Cerebral performance category (CPC) score of 1 or 2 was considered good neurologic outcome, while CPC of 3 or 4 was considered poor outcome. Classification and Regression Trees (CART) recursive partitioning was used to develop multivariate predictive models for survival and neurological outcome. Total of 692 hanging patients from 17 centers were analyzed for this study. Their overall survival rate was 77%, and the CA survival rate was 28.6%. The CA patients had significantly higher severity of illness and worse outcome than the non-CA patients. Of the 175 CA patients who survived to hospital admission, 81 patients (46.3%) received post-cardiac arrest TTM. The unadjusted survival of TTM CA patients (24.7% vs 39.4%, p<0.05) and good neurologic outcome (19.8% vs 37.2%, p<0.05) were worse than non-TTM CA patients. However, when subgroup analyses were performed between those with admission GCS of 3-8, the differences between TTM and non-TTM CA survival (23.8% vs 30.0%, p=0.37) and good neurologic outcome (18.8% vs 28.7%, p=0.14) were not significant. TTM implementation and post-cardiac arrest management varied between the participating centers. CART models identified variables predictive of favorable and poor outcome for hanging and TTM patients with excellent accuracy. CA hanging patients had worse outcome than non-CA patients. TTM CA patients had worse unadjusted survival and neurologic outcome than non-TTM patients. These findings may be explained by their higher severity of illness, variable TTM implementation, and differences in post-cardiac arrest management. Future prospective studies are necessary to ascertain the effect of TTM on hanging outcome and to validate our CART models. Therapeutic study, level III; prognostic study, level III.

Investigation of the factors influencing the survival of Bifidobacterium longum in model acidic solutions and fruit juices.

PubMed

Nualkaekul, Sawaminee; Salmeron, Ivan; Charalampopoulos, Dimitris

2011-12-01

The survival of Bifidobacterium longum NCIMB 8809 was studied during refrigerated storage for 6weeks in model solutions, based on which a mathematical model was constructed describing cell survival as a function of pH, citric acid, protein and dietary fibre. A Central Composite Design (CCD) was developed studying the influence of four factors at three levels, i.e., pH (3.2-4), citric acid (2-15g/l), protein (0-10g/l), and dietary fibre (0-8g/l). In total, 31 experimental runs were carried out. Analysis of variance (ANOVA) of the regression model demonstrated that the model fitted well the data. From the regression coefficients it was deduced that all four factors had a statistically significant (P<0.05) negative effect on the log decrease [log10N0 week-log10N6 week], with the pH and citric acid being the most influential ones. Cell survival during storage was also investigated in various types of juices, including orange, grapefruit, blackcurrant, pineapple, pomegranate and strawberry. The highest cell survival (less than 0.4log decrease) after 6weeks of storage was observed in orange and pineapple, both of which had a pH of about 3.8. Although the pH of grapefruit and blackcurrant was similar (pH ∼3.2), the log decrease of the former was ∼0.5log, whereas of the latter was ∼0.7log. One reason for this could be the fact that grapefruit contained a high amount of citric acid (15.3g/l). The log decrease in pomegranate and strawberry juices was extremely high (∼8logs). The mathematical model was able to predict adequately the cell survival in orange, grapefruit, blackcurrant, and pineapple juices. However, the model failed to predict the cell survival in pomegranate and strawberry, most likely due to the very high levels of phenolic compounds in these two juices. Copyright © 2011 Elsevier Ltd. All rights reserved.

Impact of socioeconomic status on survival for patients with anal cancer.

PubMed

Lin, Daniel; Gold, Heather T; Schreiber, David; Leichman, Lawrence P; Sherman, Scott E; Becker, Daniel J

2018-04-15

Although outcomes for patients with squamous cell carcinoma of the anus (SCCA) have improved, the gains in benefit may not be shared uniformly among patients of disparate socioeconomic status. In the current study, the authors investigated whether area-based median household income (MHI) is predictive of survival among patients with SCCA. Patients diagnosed with SCCA from 2004 through 2013 in the Surveillance, Epidemiology, and End Results registry were included. Socioeconomic status was defined by census-tract MHI level and divided into quintiles. Multivariable Cox proportional hazards models and logistic regression were used to study predictors of survival and radiotherapy receipt. A total of 9550 cases of SCCA were included. The median age of the patients was 58 years, 63% were female, 85% were white, and 38% were married. In multivariable analyses, patients living in areas with lower MHI were found to have worse overall survival and cancer-specific survival (CSS) compared with those in the highest income areas. Mortality hazard ratios for lowest to highest income were 1.32 (95% confidence interval [95% CI], 1.18-1.49), 1.31 (95% CI, 1.16-1.48), 1.19 (95% CI, 1.06-1.34), and 1.16 (95% CI, 1.03-1.30). The hazard ratios for CSS similarly ranged from 1.34 to 1.22 for lowest to highest income. Older age, black race, male sex, unmarried marital status, an earlier year of diagnosis, higher tumor grade, and later American Joint Committee on Cancer stage of disease also were associated with worse CSS. Income was not found to be associated with the odds of initiating radiotherapy in multivariable analysis (odds ratio of 0.87 for lowest to highest income level; 95% CI, 0.63-1.20). MHI appears to independently predict CSS and overall survival in patients with SCCA. Black race was found to remain a predictor of SCCA survival despite controlling for income. Further study is needed to understand the mechanisms by which socioeconomic inequalities affect cancer care and outcomes. Cancer 2018;124:1791-7. © 2018 American Cancer Society. © 2018 American Cancer Society.

Differential regulation of pathogens: the role of habitat disturbance in predicting prevalence of Sin Nombre virus.

PubMed

Lehmer, Erin M; Clay, Christine A; Pearce-Duvet, Jessica; St Jeor, Stephen; Dearing, M Denise

2008-03-01

Deer mice (Peromyscus maniculatus) are the primary reservoir for Sin Nombre virus (SNV), a North American hantavirus that causes disease with high mortality in humans. Recent studies have proposed that habitat disturbance affects prevalence of SNV in deer mice; however, the outcomes proposed in these studies are in opposition to each other. Our objectives were to test these divergent hypotheses by: (1) measuring SNV infection in deer mice within a patchwork of disturbance; and (2) evaluating the relationships between SNV prevalence, population density and demography as possible mechanisms. In 2003 and 2004, we sampled 1,297 deer mice from 17 sites with varying levels of disturbance in the Great Basin Desert. Across sites and years, SNV prevalence varied from 0.0 to 38.9%. We found a negative relationship between SNV prevalence and disturbance. Although we found no direct relationship between SNV prevalence and deer mouse density, we found that density was highest on sites with the lowest levels of disturbance. The number of deer mice that survived across seasons (e.g., trans-seasonal survivors) differed across levels of disturbance and was greatest on our least disturbed study sites [Formula: see text] moderate on sites with intermediate levels of disturbance (x = 5.61%) and zero on highly disturbed sites. On low-disturbance sites, a greater proportion of trans-seasonal survivors were SNV seropositive (28.80%) compared to the intermediate-disturbance sites (16.67). Collectively, our results indicate that habitat disturbance plays a predictive role in SNV prevalence, with highly disturbed sites having reduced long-term survival of deer mice, including survival of infected individuals.

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up

PubMed Central

Schoindre, Yoland; Jallouli, Moez; Tanguy, Marie-Laure; Ghillani, Pascale; Galicier, Lionel; Aumaître, Olivier; Francès, Camille; Le Guern, Véronique; Lioté, Frédéric; Smail, Amar; Limal, Nicolas; Perard, Laurent; Desmurs-Clavel, Hélène; Thi Huong, Du Le; Asli, Bouchra; Kahn, Jean-Emmanuel; Sailler, Laurent; Ackermann, Félix; Papo, Thomas; Sacré, Karim; Fain, Olivier; Stirnemann, Jérôme; Cacoub, Patrice; Leroux, Gaëlle; Cohen-Bittan, Judith; Hulot, Jean-Sébastien; Lechat, Philippe; Musset, Lucile; Piette, Jean-Charles; Amoura, Zahir; Souberbielle, Jean-Claude; Costedoat-Chalumeau, Nathalie

2014-01-01

Objectives Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Methods Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). Results The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). Conclusions We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate. PMID:25379192

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up.

PubMed

Schoindre, Yoland; Jallouli, Moez; Tanguy, Marie-Laure; Ghillani, Pascale; Galicier, Lionel; Aumaître, Olivier; Francès, Camille; Le Guern, Véronique; Lioté, Frédéric; Smail, Amar; Limal, Nicolas; Perard, Laurent; Desmurs-Clavel, Hélène; Le Thi Huong, Du; Asli, Bouchra; Kahn, Jean-Emmanuel; Sailler, Laurent; Ackermann, Félix; Papo, Thomas; Sacré, Karim; Fain, Olivier; Stirnemann, Jérôme; Cacoub, Patrice; Leroux, Gaëlle; Cohen-Bittan, Judith; Hulot, Jean-Sébastien; Lechat, Philippe; Musset, Lucile; Piette, Jean-Charles; Amoura, Zahir; Souberbielle, Jean-Claude; Costedoat-Chalumeau, Nathalie

2014-01-01

Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.

Limits on the adaptability of coastal marshes to rising sea level

USGS Publications Warehouse

Kirwan, Matthew L.; Guntenspergen, Glenn R.; D'Alpaos, Andrea; Morris, James T.; Mudd, Simon M.; Temmerman, Stijn

2010-01-01

Assumptions of a static landscape inspire predictions that about half of the world's coastal wetlands will submerge during this century in response to sea-level acceleration. In contrast, we use simulations from five numerical models to quantify the conditions under which ecogeomorphic feedbacks allow coastal wetlands to adapt to projected changes in sea level. In contrast to previous sea-level assessments, we find that non-linear feedbacks among inundation, plant growth, organic matter accretion, and sediment deposition, allow marshes to survive conservative projections of sea-level rise where suspended sediment concentrations are greater than ~20 mg/L. Under scenarios of more rapid sea-level rise (e.g., those that include ice sheet melting), marshes will likely submerge near the end of the 21st century. Our results emphasize that in areas of rapid geomorphic change, predicting the response of ecosystems to climate change requires consideration of the ability of biological processes to modify their physical environment.

GENOMIC PREDICTOR OF RESPONSE AND SURVIVAL FOLLOWING TAXANE-ANTHRACYCLINE CHEMOTHERAPY FOR INVASIVE BREAST CANCER

PubMed Central

Hatzis, Christos; Pusztai, Lajos; Valero, Vicente; Booser, Daniel J.; Esserman, Laura; Lluch, Ana; Vidaurre, Tatiana; Holmes, Frankie; Souchon, Eduardo; Martin, Miguel; Cotrina, José; Gomez, Henry; Hubbard, Rebekah; Chacón, J. Ignacio; Ferrer-Lozano, Jaime; Dyer, Richard; Buxton, Meredith; Gong, Yun; Wu, Yun; Ibrahim, Nuhad; Andreopoulou, Eleni; Ueno, Naoto T.; Hunt, Kelly; Yang, Wei; Nazario, Arlene; DeMichele, Angela; O’Shaughnessy, Joyce; Hortobagyi, Gabriel N.; Symmans, W. Fraser

2017-01-01

CONTEXT Accurate prediction of who will (or won’t) have high probability of survival benefit from standard treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN Development of different predictive signatures for resistance and response to neoadjuvant chemotherapy (stratified according to estrogen receptor (ER) status) from gene expression microarrays of newly diagnosed breast cancer (310 patients). Then prediction of breast cancer treatment-sensitivity using the combination of signatures for: 1) sensitivity to endocrine therapy, 2) chemo-resistance, and 3) chemo-sensitivity. Independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. SETTING Prospective multicenter study to develop and test genomic predictors for neoadjuvant chemotherapy. PATIENTS Newly diagnosed HER2-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens then endocrine therapy (if hormone receptor-positive). MAIN OUTCOME MEASURES Distant relapse-free survival (DRFS) if predicted treatment-sensitive and absolute risk reduction (ARR, difference in DRFS of the two predicted groups) at median follow-up (3 years), and their 95% confidence intervals (CI). RESULTS Patients in the independent validation cohort (99% clinical Stage II–III) who were predicted to be treatment-sensitive (28% of total) had DRFS of 92% (CI 85–100) and survival benefit compared to others (absolute risk reduction (ARR) 18%; CI 6–28). Predictions were accurate if breast cancer was ER-positive (30% predicted sensitive, DRFS 97%, CI 91–100; ARR 11%, CI 0.1–21) or ER-negative (26% predicted sensitive, DRFS 83%, CI 68–100; ARR 26%, CI 4–28), and were significant in multivariate analysis after adjusting for relevant clinical-pathologic characteristics. Other genomic predictors showed paradoxically worse survival if predicted to be responsive to chemotherapy. CONCLUSION A genomic predictor combining ER status, predicted chemo-resistance, predicted chemo-sensitivity, and predicted endocrine sensitivity accurately identified patients with survival benefit following taxane-anthracycline chemotherapy. PMID:21558518

Prognostic Value of Serum Caspase-Cleaved Cytokeratin-18 Levels before Liver Transplantation for One-Year Survival of Patients with Hepatocellular Carcinoma

PubMed Central

Lorente, Leonardo; Rodriguez, Sergio T.; Sanz, Pablo; Pérez-Cejas, Antonia; Padilla, Javier; Díaz, Dácil; González, Antonio; Martín, María M.; Jiménez, Alejandro; Barrera, Manuel A.

2016-01-01

Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301–73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%–84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival. PMID:27618033

Edmondson-Steiner grade: A crucial predictor of recurrence and survival in hepatocellular carcinoma without microvascular invasio.

PubMed

Zhou, Li; Rui, Jing-An; Zhou, Wei-Xun; Wang, Shao-Bin; Chen, Shu-Guang; Qu, Qiang

2017-07-01

Microvascular invasion (MVI), an important pathologic parameter, has been proven to be a powerful predictor of long-term prognosis in hepatocellular carcinoma (HCC). However, prognostic factors in HCC without MVI remain unknown. The present study aimed to identify the risk factors of recurrence and poor post-resectional survival in this type of HCC. A total of 109 patients with MVI-absent HCC underwent radical hepatectomy were enrolled. The influence of clinicopathologic variables on recurrence and patient survival was assessed using univariate and multivariate analyses. Chi-square test found that Edmondson-Steiner grade and satellite nodule were significantly associated with recurrence, while the former was the single marker for early recurrence. Stepwise logistic regression analysis demonstrated the independent predictive role of Edmondson-Steiner grade for recurrence. On the other hand, Edmondson-Steiner grade, serum AFP level and satellite nodule were significant for overall and disease-free survival in univariate analysis, whereas tumor size was linked to disease-free survival. Of the variables, Edmondson-Steiner grade, serum AFP level and satellite nodule were independent indicators. Edmondson-Steiner grade, a histological classification, carries robust prognostic implications for all the endpoints for prognosis, thus being potential to be a crucial prognosticator in HCC without MVI. Copyright © 2017 Elsevier GmbH. All rights reserved.

Predicting Which Childhood Memories Persist: Contributions of Memory Characteristics

ERIC Educational Resources Information Center

Peterson, Carole; Morris, Gwynn; Baker-Ward, Lynne; Flynn, Susan

2014-01-01

This investigation identified memory-level predictors of the survivability of 4- to 13-year-old children's earliest recollections over a 2-year period. Data previously reported by Peterson, Warren, and Short (2011) were coded for inclusion of emotion terms and thematic, chronological, and contextual narrative coherence. In addition, the…

Using multiple classifiers for predicting the risk of endovascular aortic aneurysm repair re-intervention through hybrid feature selection.

PubMed

Attallah, Omneya; Karthikesalingam, Alan; Holt, Peter Je; Thompson, Matthew M; Sayers, Rob; Bown, Matthew J; Choke, Eddie C; Ma, Xianghong

2017-11-01

Feature selection is essential in medical area; however, its process becomes complicated with the presence of censoring which is the unique character of survival analysis. Most survival feature selection methods are based on Cox's proportional hazard model, though machine learning classifiers are preferred. They are less employed in survival analysis due to censoring which prevents them from directly being used to survival data. Among the few work that employed machine learning classifiers, partial logistic artificial neural network with auto-relevance determination is a well-known method that deals with censoring and perform feature selection for survival data. However, it depends on data replication to handle censoring which leads to unbalanced and biased prediction results especially in highly censored data. Other methods cannot deal with high censoring. Therefore, in this article, a new hybrid feature selection method is proposed which presents a solution to high level censoring. It combines support vector machine, neural network, and K-nearest neighbor classifiers using simple majority voting and a new weighted majority voting method based on survival metric to construct a multiple classifier system. The new hybrid feature selection process uses multiple classifier system as a wrapper method and merges it with iterated feature ranking filter method to further reduce features. Two endovascular aortic repair datasets containing 91% censored patients collected from two centers were used to construct a multicenter study to evaluate the performance of the proposed approach. The results showed the proposed technique outperformed individual classifiers and variable selection methods based on Cox's model such as Akaike and Bayesian information criterions and least absolute shrinkage and selector operator in p values of the log-rank test, sensitivity, and concordance index. This indicates that the proposed classifier is more powerful in correctly predicting the risk of re-intervention enabling doctor in selecting patients' future follow-up plan.

The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery.

PubMed

Rutten, I J G; Ubachs, J; Kruitwagen, R F P M; van Dijk, D P J; Beets-Tan, R G H; Massuger, L F A G; Olde Damink, S W M; Van Gorp, T

2017-04-01

Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS). Ovarian cancer patients (n = 216) treated with PDS were enrolled retrospectively. Total skeletal muscle surface area was measured on axial computed tomography at the level of the third lumbar vertebra. Optimum stratification was used to find the optimal skeletal muscle index cut-off to define sarcopenia (≤38.73 cm 2 /m 2 ). Cox-regression and Kaplan-Meier analysis were used to analyse the relationship between sarcopenia and OS. The effect of sarcopenia on the development of major surgical complications was studied with logistic regression. Kaplan-Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p = 0.010). Sarcopenia univariably predicted OS (HR 1.536 (95% CI 1.105-2.134), p = 0.011) but was not significant in multivariable Cox-regression analysis (HR 1.362 (95% CI 0.968-1.916), p = 0.076). Significant predictors for OS in multivariable Cox-regression analysis were complete PDS, treatment in a specialised centre and the development of major complications. Sarcopenia was not predictive of major complications. Sarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery. However a strong trend towards a survival disadvantage for patients with sarcopenia was seen. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival. Complete cytoreduction remains the strongest predictor of ovarian cancer survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Effect of marital quality on eight-year survival of patients with heart failure.

PubMed

Rohrbaugh, Michael J; Shoham, Varda; Coyne, James C

2006-10-15

Recent evidence suggests that psychosocial factors such as self-efficacy, psychological distress, perceived social support, and marital quality have prognostic significance for morbidity and mortality after heart failure. Previously, we reported that interview and observational measures of marital quality obtained from 189 patients with heart failure (139 men and 50 women) and their spouses predicted all-cause patient mortality during the next 4 years, independent of the baseline illness severity (New York Heart Association class). We present additional follow-up results for this sample, with Cox regression analyses showing that a couple-level composite measure of marital quality continued to predict survival during an 8-year period (p <0.001), especially when the patient was a woman, and did so substantially better than individual (patient-level) risk and protective factors, such as psychological distress, hostility, neuroticism, self-efficacy, optimism, and breadth of perceived emotional support. In conclusion, relationship factors may be especially relevant in managing a difficult chronic condition such as heart failure, which makes stringent and complex demands on patients and their families.

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

USDA-ARS?s Scientific Manuscript database

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...

Corticosterone manipulation reveals differences in hierarchical organization of multidimensional reproductive trade-offs in r-strategist and K-strategist females.

PubMed

Lancaster, L T; Hazard, L C; Clobert, J; Sinervo, B R

2008-03-01

Life history trade-offs are often hierarchical with decisions at one level affecting lower level trade-offs. We investigated trade-off structure in female side-blotched lizards (Uta stansburiana), which exhibit two evolved strategies: yellow-throated females are K-strategists and orange-throated are r-strategists. Corticosterone treatment was predicted to differentially organize these females' reproductive decisions. Corticosterone-treated yellow females suppressed reproduction but survived well, and augmented egg mass without decreasing clutch size. Conversely, corticosterone enhanced mortality and reproductive rates in orange females, and increased egg mass only after lengthy exposure. Corticosterone did not affect post-laying condition, suggesting that corticosterone increased egg mass through enhanced energy acquisition (income breeding). Corticosterone enhanced survival of lightweight females, but decreased survival of heavy females, introducing a foraging vs. predation trade-off. We conclude that rather than being a direct, functional relationship, observed trade-offs between offspring size and number represent evolved differences in hierarchical organization of multidimensional trade-offs, particularly in response to stress.

Kidney graft recipients with pretransplantation HLA CLASS I antibodies and high soluble CD30 are at high risk for graft loss.

PubMed

Rodríguez, Libia M; París, Sara C; Arbeláez, Mario; Cotes, José M; Süsal, Caner; Torres, Yolanda; García, Luís F

2007-08-01

In the present study, we investigated whether pretransplantation HLA class I and class II antibodies and pretransplantation levels of soluble CD30 (sCD30) and IgA anti-Fab autoantibodies are predictive of kidney allograft survival. Pretransplantation sera of 504 deceased-donor kidney recipients were tested for IgG HLA class I and class II antibodies, sCD30, and IgA anti-Fab levels using the CTS 4 ELISA kit. Kidney graft survival was estimated by Kaplan-Meier method and multivariate Cox regression. Regardless of the presence of HLA class II antibodies, recipients with high HLA class I reactivity had lower 1-year graft survival than recipients with low reactivity (p < 0.01). Recipients with high sCD30 had lower 5-year graft survival rate than those with low sCD30 (p < 0.01). The sCD30 effect was observed in presensitized and nonsensitized recipients, demonstrated a synergistic effect with HLA class I antibodies (p < 0.001), and appeared to be neutralized in recipients with no HLA class II mismatches. IgA anti-Fab did not influence kidney graft survival. Our results indicate that high pretransplantation sCD30 levels and HLA class I positivity increase the risk of kidney graft loss regardless of other factors. Consequently, such determinations should be routinely performed to estimate recipients' risks of graft rejection before transplantation.

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

PubMed

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

2017-01-01

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

Decision curve analysis and external validation of the postoperative Karakiewicz nomogram for renal cell carcinoma based on a large single-center study cohort.

PubMed

Zastrow, Stefan; Brookman-May, Sabine; Cong, Thi Anh Phuong; Jurk, Stanislaw; von Bar, Immanuel; Novotny, Vladimir; Wirth, Manfred

2015-03-01

To predict outcome of patients with renal cell carcinoma (RCC) who undergo surgical therapy, risk models and nomograms are valuable tools. External validation on independent datasets is crucial for evaluating accuracy and generalizability of these models. The objective of the present study was to externally validate the postoperative nomogram developed by Karakiewicz et al. for prediction of cancer-specific survival. A total of 1,480 consecutive patients with a median follow-up of 82 months (IQR 46-128) were included into this analysis with 268 RCC-specific deaths. Nomogram-estimated survival probabilities were compared with survival probabilities of the actual cohort, and concordance indices were calculated. Calibration plots and decision curve analyses were used for evaluating calibration and clinical net benefit of the nomogram. Concordance between predictions of the nomogram and survival rates of the cohort was 0.911 after 12, 0.909 after 24 months and 0.896 after 60 months. Comparison of predicted probabilities and actual survival estimates with calibration plots showed an overestimation of tumor-specific survival based on nomogram predictions of high-risk patients, although calibration plots showed a reasonable calibration for probability ranges of interest. Decision curve analysis showed a positive net benefit of nomogram predictions for our patient cohort. The postoperative Karakiewicz nomogram provides a good concordance in this external cohort and is reasonably calibrated. It may overestimate tumor-specific survival in high-risk patients, which should be kept in mind when counseling patients. A positive net benefit of nomogram predictions was proven.

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

Increasing maternal healthcare use in Rwanda: implications for child nutrition and survival.

PubMed

Pierce, Hayley; Heaton, Tim B; Hoffmann, John

2014-04-01

Rwanda has made great progress in improving maternal utilization of health care through coordination of external aid and more efficient health policy. Using data from the 2005 and 2010 Rwandan Demographic and Health Surveys, we examine three related questions regarding the impact of expansion of health care in Rwanda. First, did the increased use of health center deliveries apply to women across varying levels of education, economic status, and area of residency? Second, did the benefits associated with being delivered at a health center diminish as utilization became more widespread? Finally, did inequality in child outcomes decline as a result of increased health care utilization? Propensity score matching was used to address the selectivity that arises when choosing to deliver at a hospital. In addition, the regression models include a linear model to predict child nutritional status and Cox regression to predict child survival. The analysis shows that the largest increases in delivery at a health center occur among less educated, less wealthy, and rural Rwandan women. In addition, delivery at a health center is associated with better nutritional status and survival and the benefit is not diminished following the dramatic increase in use of health centers. Finally, educational, economic and residential inequality in child survival and nutrition did not decline. Copyright © 2014 Elsevier Ltd. All rights reserved.

Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

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

Mitchell, Darren M.; McAleese, Jonathan; Park, Richard M.

2007-12-01

Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapymore » was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.« less

Surgical resection versus liver transplantation for hepatocellular carcinoma within the Hangzhou criteria: a preoperative nomogram-guided treatment strategy.

PubMed

Li, Yang; Ruan, Dan-Yun; Jia, Chang-Chang; Zhao, Hui; Wang, Guo-Ying; Yang, Yang; Jiang, Nan

2017-10-15

With the expansion of surgical criteria, the comparative efficacy between surgical resection (SR) and liver transplantation (LT) for hepatocellular carcinoma is inconclusive. This study aimed to develop a prognostic nomogram for predicting recurrence-free survival of hepatocellular carcinoma patients after resection and explored the possibility of using nomogram as treatment algorithm reference. From 2003 to 2012, 310 hepatocellular carcinoma patients within Hangzhou criteria undergoing resection or liver transplantation were included. Total tumor volume, albumin level, HBV DNA copies and portal hypertension were included for constructing the nomogram. The resection patients were stratified into low- and high-risk groups by the median nomogram score of 116. Independent risk factors were identified and a visually orientated nomogram was constructed using a Cox proportional hazards model to predict the recurrence risk for SR patients. The low-risk SR group had better outcomes compared with the high-risk SR group (3-year recurrence-free survival rate, 71.1% vs 35.9%; 3-year overall survival rate, 89.8% vs 78.9%, both P<0.001). The high-risk SR group was associated with a worse recurrence-free survival rate but similar overall survival rate compared with the transplantation group (3-year recurrence-free survival rate, 35.9% vs 74.1%, P<0.001; 3-year overall survival rate, 78.9% vs 79.6%, P>0.05). This nomogram offers individualized recurrence risk evaluation for hepatocellular carcinoma patients within Hangzhou criteria receiving resection. Transplantation should be considered the first-line treatment for high-risk patients. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

Overview of different scoring systems in Fournier’s Gangrene and assessment of prognostic factors

PubMed Central

Doluoğlu, Ömer Gökhan; Karagöz, Mehmet Ali; Kılınç, Muhammet Fatih; Karakan, Tolga; Yücetürk, Cem Nedim; Sarıcı, Haşmet; Özgür, Berat Cem; Eroğlu, Muzaffer

2016-01-01

Objective In this study we aimed to evaluate prognostic factors for the survival of patients with Fournier’s gangrene (FG), and overview different validated scoring systems for outcome prediction. Material and methods We retrospectively analyzed the data of 39 patients treated for FG in our clinic. Data were collected on medical history, symptoms, physical examination findings, vital signs, laboratory parameters at admission and at the end of treatment, timing and extent of surgical debridement, and the antibiotic treatment used. The Fournier’s Gangrene Severity Index (FGSI) and Charlson Comorbidity Index (CCI) were used to predict outcome. The data were analyzed in relation with the survival of the patients. Mann-Whitney U test, chi -square test, Wilcoxon signed rank test, and Cox regression analysis were used for the statistical analysis. Results Of 39 patients analyzed, 8 (20.5%) died and 31 (79.5%) survived. The median FGSI score on admission was 2 (0–9) for the survivors and 6 (2–14) for the non-survivors (p=0.004). The median CCI scores of the survivors and non-survivors were 2 (0–10) and 6.5 (5–11), respectively (p=0.001). Except for urea, albumin and hematocrit levels, no significant differences were found between survivors and non-survivors for other laboratory parameters on admission. Lower albumin levels and advanced age were found to be associated with mortality. Conclusion High blood urea, low albumin, and low hematocrit levels were associated with poor prognosis. High CCI and FGSI scores could be associated with a poor prognosis in patients with FG. PMID:27635295

Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67.

PubMed

Xu, Junnan; Guo, Xiangyu; Jing, Mingxi; Sun, Tao

2018-01-01

Cancer immunoediting is the process of eliminating highly immunogenic tumor cells by somatic evolution and protecting the host from tumor development in the host immune system. Frequencies of somatic mutations or tumor mutation burden (TMB) were associated with immunogenicity of breast cancer. This study aimed to predict the level of TMB in patients with breast cancer by the expression of estrogen (ER), progesterone (PR), HER-2, and Ki-67, thereby anticipating the prognosis of patients and the possible response to immunotherapy. In 53 patients with breast cancer, the 453 multigenes panel based on NGS was used to determine the TMB value of breast cancer in the patient's primary tumor tissues. The predicted TMB value was divided into 4 groups: A (0-3.33), B (3.33-5.56), C (5.56-8.89), and D (>8.89), according to the quartile method, with group A as reference level. Logistic regression was used to analyze the risk ratio of each molecule type, and the prediction model was established. Survival probabilities by covariates were assessed using Kaplan-Meier estimator survival analysis and Cox's proportional hazards models. In 53 patients, the TMB value measured by the NGS polygenic panel was between 0 and 14.4/Mb. TMB distribution in 53 cases of breast cancer tissue: 18 cases in A group, 22 cases in B group, 10 cases in C group, and 3 cases in D group. HER-2 expression positivity was significantly associated with TMB (HER-2 positive vs HER-2 negative, odds ratio [OR] =34.81, 95% confidence interval [CI]: 3.711-821.689, P =0.0065). Higher TMB was distributed in the patients who were Ki-67 expression positive (>14%) than those who were Ki-67 expression negative (≤14%) (OR =0.217, 95% CI: 0.054-0.806, P =0.0242). However, no significant differences of TMB were found between ER-positive group and ER-negative group (OR =3.133, 95% CI: 0.124-127.687, P =0.4954) and between PR-positive group and PR-negative group in terms of TMB (OR =1.702, 95% CI: 0.162-20.335, P =0.6492). The predicted model is TMB = -1.14×ER +0.53×PR +3.55×HER-2-1.53×Ki-67+ CONSTANT (INTERCEPT). Patients with low TMB had a better disease-free survival (DFS) than those with high TMB (83 vs 59 m, P =0.002). In a multivariate analysis, high TMB (>5.56) was an independent predictive factor for decreased DFS (adjusted hazard ratio [HR], 5.594; 95% CI: 1.694-18.473; P = 0.005). The preliminary results suggest that the level of TMB value in patients with breast cancer can be predicted based on the expression levels of ER, PR, HER-2, and Ki-67, which may indicate the prognostic and predictive value of immunotherapy in patients with breast cancer.

Simple Clinical Score to Predict 24-Week Survival Times in Patients with Inoperable Malignant Distal Biliary Obstruction as a Tool for Selecting Palliative Metallic or Plastic Stents.

PubMed

Sripongpun, Pimsiri; Attasaranya, Siriboon; Chamroonkul, Naichaya; Sookpaisal, Theerapong; Khow-Ean, Uthai; Siripun, Aroon; Kongkamol, Chanon; Piratvisuth, Teerha; Ovartlarnporn, Bancha

2018-06-01

Endoscopic biliary drainage (EBD) is the mainstay treatment for inoperable malignant distal biliary obstruction (MDBO). Some authorities suggest that metallic stents are more cost-effective than plastic stents in patients with expected survival of at least 6 months. However, studies attempting to define the predictive factors for such survival times are limited. This study aims to develop a scoring system for predicting a survival time of <24 weeks in these patients. Patients with MDBO from inoperable periampullary cancers who underwent EBD at Songklanagarind Hospital during 2004-2009 were retrospectively analyzed. Baseline clinical, laboratory, and imaging data were retrieved. The survival time data were retrieved from the medical records and Thailand's civil registration database. Multivariate Cox regression model coefficients were used in the development of a survival time prediction scoring system. Ninety-eight patients were included. The overall median survival was 17.6 weeks. Fifty-seven (58.1%) survived <24 weeks. By multivariate analysis, cancer type and liver metastasis were significant predictive factors. The Simple Clinical Score (SCS) was calculated from (2× liver metastasis) + (1× pancreatic cancer) - (2× ampullary cancer) - (1× cholangiocarcinoma), when 1 and 0 were used for the presence and absence of each factor, respectively. The cutoff value of the score ≥0 had a sensitivity and specificity of 0.77 and 0.63, respectively, for predicting a survival time of <24 weeks, with AUC of 0.76. The median survival of patients with SCS <0 and ≥0 was 36.6 and 13.1 weeks, respectively. The scoring system from this study may be beneficial for clinicians to select the appropriate stents in endoscopic biliary drainage in inoperable MDBO patients.

SU-E-T-427: Cell Surviving Fractions Derived From Tumor-Volume Variation During Radiotherapy for Non-Small Cell Lung Cancer: Comparison with Predictive Assays

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

Chvetsov, A; Schwartz, J; Mayr, N

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 eachmore » 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 variation curves measured during radiotherapy with conventional fractionation. The proposed method can be used for treatment evaluation and adaptation.« less

An artificial neural network improves prediction of observed survival in patients with laryngeal squamous carcinoma.

PubMed

Jones, Andrew S; Taktak, Azzam G F; Helliwell, Timothy R; Fenton, John E; Birchall, Martin A; Husband, David J; Fisher, Anthony C

2006-06-01

The accepted method of modelling and predicting failure/survival, Cox's proportional hazards model, is theoretically inferior to neural network derived models for analysing highly complex systems with large datasets. A blinded comparison of the neural network versus the Cox's model in predicting survival utilising data from 873 treated patients with laryngeal cancer. These were divided randomly and equally into a training set and a study set and Cox's and neural network models applied in turn. Data were then divided into seven sets of binary covariates and the analysis repeated. Overall survival was not significantly different on Kaplan-Meier plot, or with either test model. Although the network produced qualitatively similar results to Cox's model it was significantly more sensitive to differences in survival curves for age and N stage. We propose that neural networks are capable of prediction in systems involving complex interactions between variables and non-linearity.

Biomarkers for the early detection of relapses in metastatic colorectal cancers.

PubMed

Chereches, Gabriela; Barbos, Otilia; Buiga, Rares; Balacescu, Ovidiu; Iancu, Dana; Todor, Nicolae; Balacescu, Loredana; Miron, Nicu; Bejinariu, Nona; Ciuleanu, Tudor-Eliade

2017-01-01

To assess prognostic/predictive value of carcinoembryonic antigen (CEA), transthyretin (TRT), αenolase (NNE), β2-microglobulin (β2-micro), B-cell activating factor (BAFF) and circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) patients treated with chemotherapy with or without bevacizumab. 72 histologically confirmed mCRC patients treated at Oncology Institute Cluj were included. Biomarker levels were measured through validated methods. A manual method was used for CTCs, involving hemolysis, cytospin centrifugation and immunocytochemical staining for pan-cytokeratin. Statistical endpoints were response, progression- free survival (PFS) and overall survival (OS). Initial chemotherapy was fluoropyrimidine/oxaliplatin-based in 93.1%; bevacizumab was added in 58.3% of the patients. Median PFS and OS were 16.4 and 24.4 months. Two-year OS for CR & PR vs SD vs PD were 90% vs 48% vs 12%, respectively (p<0.01). Two-year OS for chemo/ bevacizumab vs chemotherapy: 65% vs 42% (p=0.09). Baseline CEA ≥5 ng/ml had a negative prognostic impact on OS and PFS (p<0.01). High baseline CEA was predictive of improved OS when adding bevacizumab (2-year OS chemo/bevacizumab vs chemo: 60% vs 17%, p<0.01); adding bevacizumab in patients with normal CEA did not improve OS (p=0.29). Higher than cut-off values for TRT had a positive OS prognostic value (p<0.01); higher levels for NNE, β2-microglobulin and BAFF had a negative impact (p<0.01). Two-year OS for baseline <1 CTC/ml vs ≥1 CTC/ ml was 74% vs 64% respectively (p=0.15). The evaluated biomarkers could be useful prognostic factors for survival. Baseline CEA also has predictive value, suggesting that patients with low levels do not benefit from bevacizumab. A non-statistically significant correlation was observed between the number of CTCs and outcome.

Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Andersson, Roland

2016-10-01

To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion. Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS. Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis. LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.

Dynamic patient counseling: a novel concept in idiopathic pulmonary fibrosis.

PubMed

Brown, A Whitney; Shlobin, Oksana A; Weir, Nargues; Albano, Maria C; Ahmad, Shahzad; Smith, Mary; Leslie, Kevin; Nathan, Steven D

2012-10-01

The characteristics of long-term survivors with idiopathic pulmonary fibrosis (IPF) have never been fully elucidated. We sought to illustrate the attenuated mortality and describe the characteristics of patients with IPF who survived at least 5 years beyond their initial presentation. Patients with IPF evaluated between 1997 and 2006 were identified through the clinic database. Patients who survived beyond 5 years from the time of their evaluation were compared with those who died or underwent lung transplantation within 5 years. Survival analyses were performed from the time of initial evaluation and contingent on annualized survival thereafter. Eighty-seven patients who survived at least 5 years formed the comparator group to whom other patients were contrasted. These patients had a higher BMI, FVC % predicted, FEV1 % predicted, total lung capacity % predicted, and diffusing capacity of lung for carbon monoxide % predicted, but a lower FEV1/FVC ratio and lower mean pulmonary artery pressures. More than one-half of these patients had moderate or severe disease at the time of presentation. Our annualized contingent survival analyses revealed a progressively increasing median survival dependent on the duration of the disease. Although we were able to demonstrate differences in our 5-year survivors, rather than being a distinct group, these patients appear to exist within a continuum of improving survival dependent on prior disease duration. This progressively improving time-dependent prognosis mandates the serial reevaluation of an individual patient’s projected outcomes. The implementation of dynamic counseling is an important concept in more accurately predicting life expectancy for patients with IPF who are frequently haunted by the prospects of a dismal survival.

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

PubMed

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

2016-03-22

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

Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer.

PubMed

Cheng, Nai-Ming; Fang, Yu-Hua Dean; Lee, Li-yu; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Liao, Chun-Ta; Yang, Lan-Yan; Hsu, Ching-Han; Yen, Tzu-Chen

2015-03-01

The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.

Prospective analysis of adoptive TIL therapy in patients with metastatic melanoma: response, impact of anti-CTLA4, and biomarkers to predict clinical outcome.

PubMed

Forget, Marie-Andrée; Haymaker, Cara; Hess, Kenneth R; Meng, Yuzhong Jeff; Creasy, Caitlin; Karpinets, Tatiana V; Fulbright, Orenthial J; Roszik, Jason; Woodman, Scott E; Kim, Young Uk; Sakellariou-Thompson, Donastas; Bhatta, Ankit; Wahl, Arely; Flores, Esteban; Thorsen, Shawne T; Tavera, Rene J; Ramachandran, Renjith; Gonzalez, Audrey M; Toth, Christopher; Wardell, Seth; Mansaray, Rahmatu; Patel, Vruti; Carpio, Destiny Joy; Vaughn, Carol S; Farinas, Chantell M; Velasquez, Portia G; Hwu, Wen-Jen; Patel, Sapna P; Davies, Michael A; Diab, Adi; Glitza, Isabella C; Tawbi, Hussein; Wong, Michael K K; Cain, Suzanne; Ross, Merrick I; Lee, Jeffrey E; Gershenwald, Jeffrey E; Lucci, Anthony; Royal, Richard; Cormier, J N; Wargo, Jennifer A; Radvanyi, Laszlo G; Torres Cabala, Carlos A; Beroukhim, Rameen; Hwu, Patrick; Amaria, Rodabe N; Bernatchez, Chantale

2018-05-30

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has consistently demonstrated clinical efficacy in metastatic melanoma. Recent widespread use of checkpoint blockade has shifted the treatment landscape, raising questions regarding impact of these therapies on response to TIL and appropriate immunotherapy sequence. Seventy-four metastatic melanoma patients were treated with autologous TIL and evaluated for clinical response according to irRC, overall survival and progression free survival. Immunologic factors associated with response were also evaluated. Best overall response for the entire cohort was 42%; 47% in 43 checkpoint naïve patients, 38% when patients were exposed to anti-CTLA4 alone (21 patients) and 33% if also exposed to anti-PD1 (9 patients) prior to TIL ACT. Median overall survival was 17.3 months; 24.6 months in CTLA4 naïve patients and 8.6 months in patients with prior CTLA4 blockade. The latter patients were infused with fewer TIL and experienced a shorter duration of response. Infusion of higher numbers of TIL with CD8 predominance and expression of BTLA correlated with improved response in anti-CTLA-4 naive patients, but not in anti-CTLA-4 refractory patients. Baseline serum levels of IL-9 predicted response to TIL ACT, while TIL persistence, tumor recognition and mutation burden did not correlate with outcome. This study demonstrates the deleterious effects of prior exposure to anti-CTLA4 on TIL ACT response and shows that baseline IL-9 levels can potentially serve as a predictive tool to appropriately select sequence for immunotherapies. Copyright ©2018, American Association for Cancer Research.

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

PubMed

Pereira, Elena; Camacho-Vanegas, Olga; 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

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

A Model-Free Machine Learning Method for Risk Classification and Survival Probability Prediction.

PubMed

Geng, Yuan; Lu, Wenbin; Zhang, Hao Helen

2014-01-01

Risk classification and survival probability prediction are two major goals in survival data analysis since they play an important role in patients' risk stratification, long-term diagnosis, and treatment selection. In this article, we propose a new model-free machine learning framework for risk classification and survival probability prediction based on weighted support vector machines. The new procedure does not require any specific parametric or semiparametric model assumption on data, and is therefore capable of capturing nonlinear covariate effects. We use numerous simulation examples to demonstrate finite sample performance of the proposed method under various settings. Applications to a glioma tumor data and a breast cancer gene expression survival data are shown to illustrate the new methodology in real data analysis.

Factors predicting survival following noninvasive ventilation in amyotrophic lateral sclerosis.

PubMed

Peysson, S; Vandenberghe, N; Philit, F; Vial, C; Petitjean, T; Bouhour, F; Bayle, J Y; Broussolle, E

2008-01-01

The involvement of respiratory muscles is a major predicting factor for survival in amyotrophic lateral sclerosis (ALS). Recent studies show that noninvasive ventilation (NIV) can relieve symptoms of alveolar hypoventilation. However, factors predicting survival in ALS patients when treated with NIV need to be clarified. We conducted a retrospective study of 33 consecutive ALS patients receiving NIV. Ten patients had bulbar onset. We determined the median survivals from onset, diagnosis and initiation of NIV and factors predicting survival. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. The median initial and maximal total uses of NIV were 10 and 14 h/24h. The overall median survival from ALS onset was 34.2 months and worsened with increasing age and bulbar onset of the disease. The median survival from initiation of NIV was 8.4 months and was significantly poorer in patients with advanced age or with airway mucus accumulation. Survival from initiation of NIV was not influenced by respiratory parameters or bulbar symptoms. Advanced age at diagnosis and airway mucus accumulation represent poorer prognostic factors of ALS patients treated with NIV. NIV is a helpful treatment of sleep-disordered breathing, including patients with bulbar involvement. Copyright 2008 S. Karger AG, Basel.

Predictive blood plasma biomarkers for EGFR inhibitor-induced skin rash.

PubMed

Hichert, Vivien; Scholl, Catharina; Steffens, Michael; Paul, Tanusree; Schumann, Christian; Rüdiger, Stefan; Boeck, Stefan; Heinemann, Volker; Kächele, Volker; Seufferlein, Thomas; Stingl, Julia

2017-05-23

Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib, gefitinib, cetuximab and panitumumab. A common adverse effect is a typical papulopustular acneiform rash, whose occurrence and severity are positively correlated with overall survival in several cancer types. We studied molecules involved in epidermal growth factor receptor signaling which are quantifiable in plasma, with the aim of identifying biomarkers for the severity of rash. With a predictive value for the rash these biomarkers may also have a prognostic value for survival and disease outcome.The concentrations of amphiregulin, hepatocyte growth factor (HGF) and calcidiol were determined by specific enzyme-linked immunosorbent assays in plasma samples from 211 patients.We observed a significant inverse correlation between the plasma concentration of HGF and overall survival in patients with an inhibitor-induced rash (p-value = 0.0075; mean overall survival low HGF: 299 days, high HGF: 240 days) but not in patients without rash. The concentration of HGF was also significantly inversely correlated with severity of rash (p-value = 0.00124).High levels of HGF lead to increased signaling via its receptor MET, which can activate numerous pathways which are normally also activated by epidermal growth factor receptor. Increased HGF/MET signaling might compensate the inhibitory effect of epidermal growth factor receptor inhibitors in skin as well as tumor cells, leading to less severe skin rash and decreased efficacy of the anti-tumor therapy, rendering the plasma concentration of HGF a candidate for predictive biomarkers.

Prognostic value of combined preoperative fibrinogen and neutrophil–lymphocyte ratio in patients with hepatocellular carcinoma after liver transplantation

PubMed Central

Chen, Mao-Gen; Wang, Xiao-Ping; Ju, Wei-Qiang; Zhao, Qiang; Wu, Lin-Wei; Ren, Qing-Qi; Guo, Zhi-Yong; Wang, Dong-Ping; Zhu, Xiao-Feng; Ma, Yi; He, Xiao-Shun

2017-01-01

Objectives Elevated plasma fibrinogen (Fib) correlated with patient's prognosis in several solid tumors. However, few studies have illuminated the relationship between preoperative Fib and prognosis of HCC after liver transplantation. We aimed to clarify the prognostic value of Fib and whether the prognostic accuracy can be enhanced by the combination of Fib and neutrophil–lymphocyte ratio (NLR). Results Fib was correlated with Child-pugh stage, alpha-fetoprotein (AFP), size of largest tumor, macro- and micro-vascular invasion. Univariate analysis showed preoperative Fib, AFP, NLR, size of largest tumor, tumor number, macro- and micro- vascular invasion were significantly associated with disease-free survival (DFS) and overall survival (OS) in HCC patients with liver transplantation. After multivariate analysis, only Fib and macro-vascular invasion were independently correlated with DFS and OS. Survival analysis showed that preoperative Fib > 2.345 g/L predicted poor prognosis of patients HCC after liver transplantation. Preoperative Fib showed prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of Fib and NLR. Materials and Methods Data were collected retrospectively from 130 HCC patients who underwent liver transplantation. Preoperative Fib, NLR and clinicopathologic variables were analyzed. The survival analysis was performed by the Kaplan-Meier method, and compared by the log-rank test. Univariate and multivariate analyses were performed to identify the prognostic factors for DFS and OS. Conclusions Preoperative Fib is an independent effective predictor of prognosis for HCC patients, higher levels of Fib predict poorer outcomes and the combination of Fib and NLR enlarges the prognostic accuracy of testing. PMID:27935864

Systematic review of FDG-PET prediction of complete pathological response and survival in rectal cancer.

PubMed

Memon, Sameer; Lynch, A Craig; Akhurst, Timothy; Ngan, Samuel Y; Warrier, Satish K; Michael, Michael; Heriot, Alexander G

2014-10-01

Advances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of (18)F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. A search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. Seventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). SUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.

Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals.

PubMed

Huang, Hai; Du, Tao; Zhang, Yiming; Lai, Yiming; Li, Kaiwen; Fan, Xinxing; Zhu, Dingjun; Lin, Tianxin; Xu, Kewei; Huang, Jian; Liu, Leyuan; Guo, Zhenghui

2017-05-01

SHARPIN, SHANK-associated RH domain interacting protein, associates with a linear ubiquitin chain assembly complex (LUBAC) to regulate inflammation and immunity. It has been reported that SHARPIN is highly expressed in several human tumors including ovarian cancer and liver cancer. We found that SHARPIN is also highly expressed in prostate cancer cell lines of DU145, LNCAP, and PC-3. Suppression of SHARPIN caused an inhibition of NF-κB signal and decreases in tumorigenesis of cultured cells in NOD/SCID mouse model. Overexpression of SHARPIN in prostate cancer cells promoted cell growth and reduced apoptosis through NF-kB/ERK/Akt pathway and apoptosis-associated proteins. We analyzed the expression of SHARPIN in prostate cancer tissues from 95 patients and its relationship with other clinical characteristics associated with PCA malignancies and patient survivals, and examined the impacts of SHARPIN suppression with siRNA on proliferation, angiogenesis, invasion, and expression levels of MMP-9 of prostate cancer cells and metastasis to lung by these cells in nude mice. High levels of SHARPIN were associated with high malignancies of PCA and predicted shorter survivals of PCA patients. Suppression of SHARPIN impaired cell proliferation, angiogenesis, and invasion and reduced levels of MMP-9 in prostate cancer cells and reduced the size of metastatic lung tumors induced by these cells in mice. SHARPIN enhances the metastasis of prostate cancer and impair patient survivals. Prostate 77:718-728, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Validation of the Social Security Administration Life Tables (2004-2014) in Localized Prostate Cancer Patients within the Surveillance, Epidemiology, and End Results database.

PubMed

Preisser, Felix; Bandini, Marco; Mazzone, Elio; Nazzani, Sebastiano; Marchioni, Michele; Tian, Zhe; Saad, Fred; Pompe, Raisa S; Shariat, Shahrokh F; Heinzer, Hans; Montorsi, Francesco; Huland, Hartwig; Graefen, Markus; Tilki, Derya; Karakiewicz, Pierre I

2018-05-22

Accurate life expectancy estimation is crucial in clinical decision-making including management and treatment of clinically localized prostate cancer (PCa). We hypothesized that Social Security Administration (SSA) life tables' derived survival estimates closely follow observed survival of PCa patients. To test this relationship, we examined 10-yr overall survival rates in patients with clinically localized PCa and compared it with survival estimates derived from the SSA life tables. Within the Surveillance, Epidemiology, and End Results database (2004), we identified patients aged >50-<90yr. Follow-up was at least 10 yr for patients who did not die of disease or other causes. Monte Carlo method was used to define individual survival in years, according to the SSA life tables (2004-2014). Subsequently, SSA life tables' predicted survival was compared with observed survival rates in Kaplan-Meier analyses. Subgroup analyses were stratified according to treatment type and D'Amico risk classification. Overall, 39191 patients with localized PCa were identified. At 10-yr follow-up, the SSA life tables' predicted survival was 69.5% versus 73.1% according to the observed rate (p<0.0001). The largest differences between estimated versus observed survival rates were recorded for D'Amico low-risk PCa (8.0%), brachytherapy (9.1%), and radical prostatectomy (8.6%) patients. Conversely, the smallest differences were recorded for external beam radiotherapy (1.7%) and unknown treatment type (1.6%) patients. Overall, SSA life tables' predicted life expectancy closely approximate observed overall survival rates. However, SSA life tables' predicted rates underestimate by as much as 9.1% the survival in brachytherapy patients, as well as in D'Amico low-risk and radical prostatectomy patients. In these patient categories, an adjustment for the degree of underestimation might be required when counseling is provided in clinical practice. Social Security Administration (SSA) life tables' predicted life expectancy closely approximate observed overall survival rates. However, SSA life tables' predicted rates underestimate by as much as 9.1% the survival in brachytherapy patients, as well as in D'Amico low-risk and radical prostatectomy patients. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Predicting Survival From Large Echocardiography and Electronic Health Record Datasets: Optimization With Machine Learning.

PubMed

Samad, Manar D; Ulloa, Alvaro; Wehner, Gregory J; Jing, Linyuan; Hartzel, Dustin; Good, Christopher W; Williams, Brent A; Haggerty, Christopher M; Fornwalt, Brandon K

2018-06-09

The goal of this study was to use machine learning to more accurately predict survival after echocardiography. Predicting patient outcomes (e.g., survival) following echocardiography is primarily based on ejection fraction (EF) and comorbidities. However, there may be significant predictive information within additional echocardiography-derived measurements combined with clinical electronic health record data. Mortality was studied in 171,510 unselected patients who underwent 331,317 echocardiograms in a large regional health system. We investigated the predictive performance of nonlinear machine learning models compared with that of linear logistic regression models using 3 different inputs: 1) clinical variables, including 90 cardiovascular-relevant International Classification of Diseases, Tenth Revision, codes, and age, sex, height, weight, heart rate, blood pressures, low-density lipoprotein, high-density lipoprotein, and smoking; 2) clinical variables plus physician-reported EF; and 3) clinical variables and EF, plus 57 additional echocardiographic measurements. Missing data were imputed with a multivariate imputation by using a chained equations algorithm (MICE). We compared models versus each other and baseline clinical scoring systems by using a mean area under the curve (AUC) over 10 cross-validation folds and across 10 survival durations (6 to 60 months). Machine learning models achieved significantly higher prediction accuracy (all AUC >0.82) over common clinical risk scores (AUC = 0.61 to 0.79), with the nonlinear random forest models outperforming logistic regression (p < 0.01). The random forest model including all echocardiographic measurements yielded the highest prediction accuracy (p < 0.01 across all models and survival durations). Only 10 variables were needed to achieve 96% of the maximum prediction accuracy, with 6 of these variables being derived from echocardiography. Tricuspid regurgitation velocity was more predictive of survival than LVEF. In a subset of studies with complete data for the top 10 variables, multivariate imputation by chained equations yielded slightly reduced predictive accuracies (difference in AUC of 0.003) compared with the original data. Machine learning can fully utilize large combinations of disparate input variables to predict survival after echocardiography with superior accuracy. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Improving Gastric Cancer Outcome Prediction Using Single Time-Point Artificial Neural Network Models

PubMed Central

Nilsaz-Dezfouli, Hamid; Abu-Bakar, Mohd Rizam; Arasan, Jayanthi; Adam, Mohd Bakri; Pourhoseingholi, Mohamad Amin

2017-01-01

In cancer studies, the prediction of cancer outcome based on a set of prognostic variables has been a long-standing topic of interest. Current statistical methods for survival analysis offer the possibility of modelling cancer survivability but require unrealistic assumptions about the survival time distribution or proportionality of hazard. Therefore, attention must be paid in developing nonlinear models with less restrictive assumptions. Artificial neural network (ANN) models are primarily useful in prediction when nonlinear approaches are required to sift through the plethora of available information. The applications of ANN models for prognostic and diagnostic classification in medicine have attracted a lot of interest. The applications of ANN models in modelling the survival of patients with gastric cancer have been discussed in some studies without completely considering the censored data. This study proposes an ANN model for predicting gastric cancer survivability, considering the censored data. Five separate single time-point ANN models were developed to predict the outcome of patients after 1, 2, 3, 4, and 5 years. The performance of ANN model in predicting the probabilities of death is consistently high for all time points according to the accuracy and the area under the receiver operating characteristic curve. PMID:28469384

Prognostic value of preoperative serum CA 242 in Esophageal squamous cell carcinoma cases.

PubMed

Feng, Ji-Feng; Huang, Ying; Chen, Qi-Xun

2013-01-01

Carbohydrate antigen (CA) 242 is inversely related to prognosis in many cancers. However, few data regarding CA 242 in esophageal cancer (EC) are available. The aim of this study was to determine the prognostic value of CA 242 and propose an optimum cut-off point in predicting survival difference in patients with esophageal squamous cell carcinoma (ESCC). A retrospective analysis was conducted of 192 cases. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimum cuf- off point. Univariate and multivariate analyses were performed to evaluate prognostic parameters for survival. The positive rate for CA 242 was 7.3% (14/192). The ROC curve for survival prediction gave an optimum cut-off of 2.15 (U/ml). Patients with CA 242 ≤ 2.15 U/ml had significantly better 5-year survival than patients with CA 242 >2.15 U/ml (45.4% versus 22.6%; P=0.003). Multivariate analysis showed that differentiation (P=0.033), CA 242 (P=0.017), T grade (P=0.004) and N staging (P<0.001) were independent prognostic factors. Preoperative CA 242 is a predictive factor for long-term survival in ESCC, especially in nodal-negative patients. We conclude that 2.15 U/ml may be the optimum cuf-off point for CA 242 in predicting survival in ESCC.

Parametric response mapping cut-off values that predict survival of hepatocellular carcinoma patients after TACE.

PubMed

Nörthen, Aventinus; Asendorf, Thomas; Shin, Hoen-Oh; Hinrichs, Jan B; Werncke, Thomas; Vogel, Arndt; Kirstein, Martha M; Wacker, Frank K; Rodt, Thomas

2018-04-21

Parametric response mapping (PRM) is a novel image-analysis technique applicable to assess tumor viability and predict intrahepatic recurrence of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). However, to date, the prognostic value of PRM for prediction of overall survival in HCC patients undergoing TACE is unclear. The objective of this explorative, single-center study was to identify cut-off values for voxel-specific PRM parameters that predict the post TACE overall survival in HCC patients. PRM was applied to biphasic CT data obtained at baseline and following 3 TACE treatments of 20 patients with HCC tumors ≥ 2 cm. The individual portal venous phases were registered to the arterial phases followed by segmentation of the largest lesion, i.e., the region of interest (ROI). Segmented voxels with their respective arterial and portal venous phase density values were displayed as a scatter plot. Voxel-specific PRM parameters were calculated and compared to patients' survival at 1, 2, and 3 years post treatment to identify the maximal predictive parameters. The hypervascularized tissue portion of the ROI was found to represent an independent predictor of the post TACE overall survival. For this parameter, cut-off values of 3650, 2057, and 2057 voxels, respectively, were determined to be optimal to predict overall survival at 1, 2, and 3 years after TACE. Using these cut points, patients were correctly classified as having died with a sensitivity of 80, 92, and 86% and as still being alive with a specificity of 60, 75, and 83%, respectively. The prognostic accuracy measured by area under the curve (AUC) values ranged from 0.73 to 0.87. PRM may have prognostic value to predict post TACE overall survival in HCC patients.

Effect of inulin on the physicochemical properties, flow behavior and probiotic survival of frozen yogurt.

PubMed

Rezaei, Rahil; Khomeiri, Morteza; Aalami, Mehran; Kashaninejad, Mahdi

2014-10-01

This study investigated the effect of inulin (0, 1 and 2 %), on some physicochemical properties of frozen yogurt, as well as its effect on flow behavior and probiotic survival. The results showed that the addition of inulin improved overrun, viscosity and melting properties significantly (p < 0.05); when added at 2 % level, it also had significant effect on pH. Total acceptability of samples revealed that frozen yogurt with 2 % inulin had the most appealing sensory characteristics. The flow behavior of all samples showed their pseudoplastic nature; power law was the best model to predict their flow behavior. In terms of probiotic survival, the sample with 2 % inulin significantly improved the viability of Lactobacillus acidophilus and Bifidobacterium lactis.

Neurofilament Subunit L Levels in the Cerebrospinal Fluid and Serum of Patients with Amyotrophic Lateral Sclerosis.

PubMed

Gong, Zhong-Ying; Lv, Gao-Peng; Gao, Li-Na; Lu, Yi; Guo, Jie; Zang, Da-Wei

2018-06-13

There are no reliable biomarkers that could evaluate the disease burden in amyotrophic lateral sclerosis (ALS). The aim of our study is to evaluate the changes in cerebrospinal fluid (CSF) and serum neurofilament subunit L (NF-L) in patients with ALS and to analyze the correlations between the levels of NF-L and clinical parameters. CSF and serum samples were obtained from 80 ALS patients and 40 controls. The levels of NF-L in CSF and serum were assessed, and disease progression parameters including duration, revised ALS Functional Rating Scale (ALSFRS-r) score, disease progression rate (DPR), upper motor neuron (UMN) score, and survival were analyzed by registered neurologists. All samples were measured using a commercial enzyme-linked immunosorbent assay. Statistical analyses were performed using Prism software. Compared to the controls, the ALS patients displayed significantly increased levels of NF-L; these values were negatively correlated with the ALSFRS-r score and positively correlated with the decrease in ALSFRS-r score, DPR, and UMN score. There was no correlation between levels of NF-L and duration. In addition, the cumulative survival rate in ALS patients with a low level of NF-L was higher than in patients with a high level of NF-L. NF-L levels increased in CSF and serum of patients with ALS. NF-L may thus be a neurodegenerative biomarker for predicting ALS severity and progression, and the survival of patients with this disease. © 2018 S. Karger AG, Basel.

Serum lactate dehydrogenase with a systemic inflammation score is useful for predicting response and survival in patients with newly diagnosed diffuse large B-cell lymphoma.

PubMed

Jung, Sung-Hoon; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

2015-01-01

We evaluated the relationship between serum lactate dehydrogenase (LDH) level with systemic inflammation score and survival in 213 patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. The patients were classified into 3 groups based on LDH with the Glasgow Prognostic Score (L-GPS). A score of 2 was assigned to patients with elevated C-reactive protein, hypoalbuminemia and elevated LDH, a score of 1 to those with one or two abnormalities and a score of 0 to those with no abnormality. In multivariate analysis, independent poor prognostic factors for progression-free survival were L-GPS 2 [hazard ratio (HR) 5.415, p = 0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR 3.504, p = 0.001) and bulky lesion (HR 2.030, p = 0.039). Independent poor prognostic factors for overall survival were L-GPS 2 (HR 5.898, p = 0.001) and ECOG PS ≥2 (HR 3.525, p = 0.001). The overall response rate for the R-CHOP chemotherapy decreased according to the L-GPS; it was 96.7% at L-GPS 0, 87% at L-GPS 1 and 75% at L-GPS 2 (p = 0.009). L-GPS based on systemic inflammatory indicators may be a useful clinical prognostic indicator for survival, and predicts the response for R-CHOP chemotherapy in patients with newly diagnosed DLBCL. © 2014 S. Karger AG, Basel.

Limnology of nine small lakes, Matanuska-Susitna Borough, Alaska, and the survival and growth rates of rainbow trout

USGS Publications Warehouse

Woods, P.F.

1985-01-01

The survival and growth rates of rainbow trout (Salmo gairdnieri) were concurrently measured with selected limnological characteristics in nine small (surface area < 25 sq hectometers) lakes in the Matanuska-Susitna Borough. The project goal was to develop empirical models for predicting rainbow trout growth rates from the following variables: total phosphorus concentration, chlorophyll a concentration, Secchi disc transparency, or the morphoedaphic index--a means of characterizing potential biological productivity. No suitable model could be developed from the data collected during 1982 and 1983. The lack of significant correlation was attributed in part to the wide variation in survival of rainbow trout. Winterkills, caused by severe depletion of dissolved oxygen, were suspected in four of the lakes. Varied levels of fishing pressure and competition with threespine stickleback (Gasterosteus aculeatus) also influenced survival of rainbow trout but their effects were overshadowed by winterkill. Predictive capability was also reduced because of inconsistencies in rankings generated by each of the four limnological variables chosen as indicators of potential biological productivity. A lake ranked low in productivity by one variable was commonly ranked high in productivity by another variable. The survivability of rainbow trout stocked in lakes such as these nine may be a more important indicator of potential biomass production than are indicators of lake fertility. Assessments of a lake 's susceptibility to winterkill and the degree of competition with threespine stickleback are suggested as important topics for additional research. (Author 's abstract)

Extreme-Risk Prostate Adenocarcinoma Presenting With Prostate-Specific Antigen (PSA) >40 ng/ml: Prognostic Significance of the Preradiation PSA Nadir

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

Alexander, Abraham S.; University of British Columbia, Vancouver, British Columbia; Mydin, Aminudin

2011-12-01

Purpose: To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml. Methods and Materials: A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration andmore » pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined. Results: Median follow-up time was 6.45 years (range, 0.09-15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level ({<=}0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS (p = 0.033) and OS (p = 0.018) rates, whereas age, T stage, Gleason score, and ADT duration ({<=}6 versus >6 months) were not predictive of outcomes. Conclusion: In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.« less

Loss of Bad expression confers poor prognosis in non-small cell lung cancer.

PubMed

Huang, Yi; Liu, Dan; Chen, Bojiang; Zeng, Jing; Wang, Lei; Zhang, Shangfu; Mo, Xianming; Li, Weimin

2012-09-01

Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P < 0.05). Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P < 0.05). Overall survival time was also drastically shortened for Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P < 0.05). In conclusion, this study provided clinical evidence that loss of Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.

Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis.

PubMed

Wu, Jiayuan; Tan, Wenkai; Chen, Lin; Huang, Zhe; Mai, Shao

2018-03-02

C-reactive protein/albumin ratio (CAR) was originally used as a novel inflammation-based prognostic score in predicting outcomes in septic patients. Recently, more and more studies have reported the prognostic value of pretreatment CAR in solid tumors. However, the results remain controversial rather than conclusive. We conducted a meta-analysis based on 24 studies with 10203 patients to explore the relationship between CAR and survival outcomes in patients with solid tumors. The correlation between CAR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was applied to be the effect size estimate. The overall results showed that elevated CAR was associated with shorter overall survival (OS) (including 23 studies and 10067 patients) and poorer disease-free survival (DFS) (including 6 studies and 2904 patients). Significant associations between high CAR level and poor OS were also found in the subgroup analyses of study region, cancer type, primary treatment, clinical stage, cut-off selection, sample size, and cut-off value. Moreover, subgroup analyses demonstrated that study region, primary treatment, clinical stage, sample size, and cut-off value did not alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was correlated with certain phenotypes of tumor aggressiveness, such as poor histological grade, serious clinical stage, advanced tumor depth, positive lymph node metastasis, and positive distant metastasis. Together, our meta-analysis suggests that elevated level of serum CAR predicts worse survival and unfavorable clinical characteristics in cancer patients, and CAR may serve as an effective prognostic factor for solid tumors.

A Nationwide Survey About Palliative Sedation Involving Japanese Palliative Care Specialists: Intentions and Key Factors Used to Determine Sedation as Proportionally Appropriate.

PubMed

Hamano, Jun; Morita, Tatsuya; Ikenaga, Masayuki; Abo, Hirofumi; Kizawa, Yoshiyuki; Tunetou, Satoru

2018-03-01

Although there has long been debate about physicians' intentions and what physicians consider to be proportionally appropriate when performing palliative sedation, few large studies have been performed. To identify physicians' intentions when starting continuous deep sedation and to clarify what factors determine whether physicians regard sedation as proportionally appropriate in relation to expected survival, the patients' wishes, and refractoriness. A nationwide questionnaire survey of Japanese palliative care specialists was performed from August to December 2016. We defined continuous deep sedation as the continuous use of sedatives to relieve intolerable and refractory symptoms with the loss of consciousness until death. Of the 695 palliative care specialists enrolled, 440 were analyzed (response rate, 69%). A total of 95% and 87% of the physicians reported that they explicitly intended to perform symptom palliation and decrease consciousness levels, respectively. Moreover, 38% answered that they explicitly intended to maintain unconsciousness until death, and 11% reported that they intended to shorten survival to some extent. The respondents considered that continuous deep sedation is more appropriate when the predicted survival is shorter, the patients' wishes are consistent and clear, and confidence in the refractoriness of symptoms is higher. Japanese palliative care specialists explicitly intend to control symptoms and reduce the level of consciousness when performing continuous deep sedation, but there are differences in their intentions with regard to maintaining unconsciousness until death. Predicted survival, patients' wishes, and confidence in refractoriness are associated with physicians' judgment that sedation is proportionally appropriate. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Machine Learning of Three-dimensional Right Ventricular Motion Enables Outcome Prediction in Pulmonary Hypertension: A Cardiac MR Imaging Study.

PubMed

Dawes, Timothy J W; de Marvao, Antonio; Shi, Wenzhe; Fletcher, Tristan; Watson, Geoffrey M J; Wharton, John; Rhodes, Christopher J; Howard, Luke S G E; Gibbs, J Simon R; Rueckert, Daniel; Cook, Stuart A; Wilkins, Martin R; O'Regan, Declan P

2017-05-01

Purpose To determine if patient survival and mechanisms of right ventricular failure in pulmonary hypertension could be predicted by using supervised machine learning of three-dimensional patterns of systolic cardiac motion. Materials and Methods The study was approved by a research ethics committee, and participants gave written informed consent. Two hundred fifty-six patients (143 women; mean age ± standard deviation, 63 years ± 17) with newly diagnosed pulmonary hypertension underwent cardiac magnetic resonance (MR) imaging, right-sided heart catheterization, and 6-minute walk testing with a median follow-up of 4.0 years. Semiautomated segmentation of short-axis cine images was used to create a three-dimensional model of right ventricular motion. Supervised principal components analysis was used to identify patterns of systolic motion that were most strongly predictive of survival. Survival prediction was assessed by using difference in median survival time and area under the curve with time-dependent receiver operating characteristic analysis for 1-year survival. Results At the end of follow-up, 36% of patients (93 of 256) died, and one underwent lung transplantation. Poor outcome was predicted by a loss of effective contraction in the septum and free wall, coupled with reduced basal longitudinal motion. When added to conventional imaging and hemodynamic, functional, and clinical markers, three-dimensional cardiac motion improved survival prediction (area under the receiver operating characteristic curve, 0.73 vs 0.60, respectively; P < .001) and provided greater differentiation according to difference in median survival time between high- and low-risk groups (13.8 vs 10.7 years, respectively; P < .001). Conclusion A machine-learning survival model that uses three-dimensional cardiac motion predicts outcome independent of conventional risk factors in patients with newly diagnosed pulmonary hypertension. Online supplemental material is available for this article.

Pressure-Flow During Exercise Catheterization Predicts Survival in Pulmonary Hypertension.

PubMed

Hasler, Elisabeth D; Müller-Mottet, Séverine; Furian, Michael; Saxer, Stéphanie; Huber, Lars C; Maggiorini, Marco; Speich, Rudolf; Bloch, Konrad E; Ulrich, Silvia

2016-07-01

Pulmonary hypertension manifests with impaired exercise capacity. Our aim was to investigate whether the mean pulmonary arterial pressure to cardiac output relationship (mPAP/CO) predicts transplant-free survival in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Hemodynamic data according to right heart catheterization in patients with PAH and CTEPH at rest and during supine incremental cycle exercise were analyzed. Transplant-free survival and predictive value of hemodynamics were assessed by using Kaplan-Meier and Cox regression analyses. Seventy patients (43 female; 54 with PAH, 16 with CTEPH; median (quartiles) age, 65 [50; 73] years; mPAP, 34 [29; 44] mm Hg; cardiac index, 2.8 [2.3; 3.5] [L/min]/m(2)) were followed up for 610 (251; 1256) days. Survival at 1, 3, 5, and 7 years was 89%, 81%, 71%, and 59%. Age, World Health Organization-functional class, 6-min walk test, and mixed-venous oxygen saturation (but not resting hemodynamics) predicted transplant-free survival. Maximal workload (hazard ratio [HR], 0.94 [95% CI, 0.89-0.99]; P = .027), peak cardiac index (HR, 0.51 [95% CI, 0.27-0.95]; P = .034), change in cardiac index, 0.25 [95% CI, 0.06-0.94]; P = .040), and mPAP/CO (HR, 1.02 [95% CI, 1.01-1.03]; P = .003) during exercise predicted survival. Values for mPAP/CO predicted 3-year transplant-free survival with an area under the curve of 0.802 (95% CI, 0.66-0.95; P = .004). In this collective of patients with PAH or CTEPH, the pressure-flow relationship during exercise predicted transplant-free survival and correlated with established markers of disease severity and outcome. Right heart catheterization during exercise may provide important complementary prognostic information in the management of pulmonary hypertension. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Information theory of adaptation in neurons, behavior, and mood.

PubMed

Sharpee, Tatyana O; Calhoun, Adam J; Chalasani, Sreekanth H

2014-04-01

The ability to make accurate predictions of future stimuli and consequences of one's actions are crucial for the survival and appropriate decision-making. These predictions are constantly being made at different levels of the nervous system. This is evidenced by adaptation to stimulus parameters in sensory coding, and in learning of an up-to-date model of the environment at the behavioral level. This review will discuss recent findings that actions of neurons and animals are selected based on detailed stimulus history in such a way as to maximize information for achieving the task at hand. Information maximization dictates not only how sensory coding should adapt to various statistical aspects of stimuli, but also that reward function should adapt to match the predictive information from past to future. Copyright © 2013 Elsevier Ltd. All rights reserved.

High p-Smad2 expression in stromal fibroblasts predicts poor survival in patients with clinical stage I to IIIA non-small cell lung cancer.

PubMed

Chen, Yongbing; Xing, Pengfei; Chen, Yuanyuan; Zou, Li; Zhang, Yongsheng; Li, Feng; Lu, Xueguan

2014-11-05

Increasing evidence indicates that the TGFβ/Smad signaling pathway plays a prominent role in tumor initiation, progression, and metastasis. Therefore, we investigate the expression of p-Smad2 in surgical resection specimens from non-small cell lung cancer, and evaluate the prognostic significance of p-Smad2 expression in stromal fibroblasts and cancer cells for patients with clinical stage I to IIIA non-small cell lung cancer. The immunohistochemical expression of p-Smad2 was evaluated in 78 formalin-fixed paraffin-embedded surgical resection specimens from clinical stage I to IIIA non-small cell lung cancer. Correlations between p-Smad2 expression and clinicopathologic characteristics were determined by Chi-square test. The prognostic significance of p-Smad2 expression in stromal fibroblasts and cancer cells with regard to overall survival was determined by Kaplan-Meier. There were 38.5% (30/78) and 92.3% (72/78) patients with high p-Smad2 expression in stromal fibroblasts and cancer cells, respectively. There was a positive correlation between the p-Smad2 expression level in stromal fibroblasts and the p-Smad2 expression level in cancer cells (χ2=4.176, P=0.045). No significant correlation of p-Smad2 expression in stromal fibroblasts or cancer cells with any of clinicopathologic characteristics was found. The 3-year overall survival rates with low and high p-Smad2 expression in stromal fibroblasts were 53.7% and 37.7%, respectively (χ2=3.86, P=0.049). No significant association was found between low and high p-Smad2 expression in cancer cells with respect to overall survival, respectively (χ2=0.34, P=0.562). The results suggested that high p-Smad2 expression in stromal fibroblasts predicted poor survival in patients with clinical stage I to IIIA non-small cell lung cancer.

Tick exposure and extreme climate events impact survival and threaten the persistence of a long-lived lizard.

PubMed

Jones, Alice R; Bull, C Michael; Brook, Barry W; Wells, Konstans; Pollock, Kenneth H; Fordham, Damien A

2016-03-01

Assessing the impacts of multiple, often synergistic, stressors on the population dynamics of long-lived species is becoming increasingly important due to recent and future global change. Tiliqua rugosa (sleepy lizard) is a long-lived skink (>30 years) that is adapted to survive in semi-arid environments with varying levels of parasite exposure and highly seasonal food availability. We used an exhaustive database of 30 years of capture-mark-recapture records to quantify the impacts of both parasite exposure and environmental conditions on the lizard's survival rates and long-term population dynamics. Lizard abundance was relatively stable throughout the study period; however, there were changing patterns in adult and juvenile apparent survival rates, driven by spatial and temporal variation in levels of tick exposure and temporal variation in environmental conditions. Extreme weather events during the winter and spring seasons were identified as important environmental drivers of survival. Climate models predict a dramatic increase in the frequency of extreme hot and dry winter and spring seasons in our South Australian study region; from a contemporary probability of 0.17 up to 0.47-0.83 in 2080 depending on the emissions scenario. Our stochastic population model projections showed that these future climatic conditions will induce a decline in the abundance of this long-lived reptile of up to 67% within 30 years from 2080, under worst case scenario modelling. The results have broad implications for future work investigating the drivers of population dynamics and persistence. We highlight the importance of long-term data sets and accounting for synergistic impacts between multiple stressors. We show that predicted increases in the frequency of extreme climate events have the potential to considerably and negatively influence a long-lived species, which might previously have been assumed to be resilient to environmental perturbations. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Acylcarnitines profile best predicts survival in horses with atypical myopathy

PubMed Central

Detilleux, Johann; Cello, Christophe; Amory, Hélène; Marcillaud-Pitel, Christel; Richard, Eric; van Galen, Gaby; van Loon, Gunther; Lefère, Laurence; Votion, Dominique-Marie

2017-01-01

Equine atypical myopathy (AM) is caused by hypoglycin A intoxication and is characterized by a high fatality rate. Predictive estimation of survival in AM horses is necessary to prevent unnecessary suffering of animals that are unlikely to survive and to focus supportive therapy on horses with a possible favourable prognosis of survival. We hypothesized that outcome may be predicted early in the course of disease based on the assumption that the acylcarnitine profile reflects the derangement of muscle energetics. We developed a statistical model to prognosticate the risk of death of diseased animals and found that estimation of outcome may be drawn from three acylcarnitines (C2, C10:2 and C18 -carnitines) with a high sensitivity and specificity. The calculation of the prognosis of survival makes it possible to distinguish the horses that will survive from those that will die despite severe signs of acute rhabdomyolysis in both groups. PMID:28846683

Predictors of Dropout in Psychodynamic Psychotherapy of Borderline Personality Disorder

PubMed Central

SMITH, THOMAS E.; KOENIGSBERG, HAROLD W.; YEOMANS, FRANK E.; CLARKIN, JOHN F.; SELZER, MICHAEL A.

1995-01-01

This study aimed to identify patient factors that predict early dropout from psychodynamic psychotherapy for borderline personality disorder (BPD). Thirty-six BPD patients began an open-ended course of twice per week psychodynamic psychotherapy that was defined in a treatment manual and supervised. Dropout rates were 31% and 36% at 3 and 6 months of therapy, respectively. Survival analysis techniques demonstrated that age and hostility ratings predicted early dropout, with continuers more likely to be older and expressing lower levels of hostility than dropouts. Many variables hypothesized to predict dropout failed to do so. Both the positive and negative findings are discussed relative to the literature. PMID:22700251

Acute coronary syndrome vs nonspecific troponin elevation: clinical predictors and survival analysis.

PubMed

Alcalai, Ronny; Planer, David; Culhaoglu, Afsin; Osman, Aydin; Pollak, Arthur; Lotan, Chaim

2007-02-12

Although troponin is considered a specific marker for the diagnosis of acute coronary syndrome (ACS), recent studies have shown troponin elevation in a variety of nonischemic conditions. Our aim was to determine the predictors for the diagnosis of ACS in the presence of an abnormal troponin level. All patients with abnormal troponin T levels were analyzed. Demographic and clinical data were collected and death was recorded. The study group was divided into 2 subgroups: ACS vs nonthrombotic troponin elevation. A multivariate logistic regression analysis was performed to define variables that predict the diagnosis of ACS. The positive predictive value (PPV) for ACS diagnosis was calculated, and a survival analysis was performed. During the study period, 615 patients had elevated troponin T levels. Only 326 patients (53%) received a main diagnosis of ACS, while 254 (41%) had nonthrombotic troponin elevation; for 35 patients (6%), the diagnosis was not conclusive. Positive predictors for the diagnosis of ACS were age between 40 and 70 years, history of hypertension or ischemic heart disease, normal renal function, and a troponin T level higher than 1.0 ng/mL. The overall PPV of troponin T for ACS diagnosis was only 56% (95% CI, 52%-60%). The PPV of troponin T level higher than 1.0 ng/mL in the presence of normal renal function was 90% but was as low as 27% for values of 0.1 to 1.0 ng/mL for elderly patients with renal failure. In-hospital and long-term survival rates were significantly better (P<.001) for patients with ACS. Nonspecific troponin elevation is a common finding among hospitalized patients and correlates with worse prognosis. The diagnosis of myocardial infarction should still mostly be based on the clinical presentation. The predictors and algorithm suggested in this study might increase the diagnostic accuracy of ACS and direct the appropriate treatment.

Tumor heterogeneity measured on F-18 fluorodeoxyglucose positron emission tomography/computed tomography combined with plasma Epstein-Barr Virus load predicts prognosis in patients with primary nasopharyngeal carcinoma.

PubMed

Chan, Sheng-Chieh; Chang, Kai-Ping; Fang, Yu-Hua Dean; Tsang, Ngan-Ming; Ng, Shu-Hang; Hsu, Cheng-Lung; Liao, Chun-Ta; Yen, Tzu-Chen

2017-01-01

Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC. Retrospective cohort study. We examined 101 patients with primary NPC who underwent pretreatment 18 F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features. The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P = .0002), and uniformity (P = .001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P < .001). Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity. 4 Laryngoscope, 127:E22-E28, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Meta-analysis of the prognostic value of abnormally expressed lncRNAs in hepatocellular carcinoma.

PubMed

Qu, Zhen; Yuan, Chun-Hui; Yin, Chang-Qing; Guan, Qing; Chen, Hao; Wang, Fu-Bing

2016-01-01

Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in hepatocellular carcinoma (HCC), and may have the potential to serve as prognostic markers. In this study, a meta-analysis was conducted to systematically evaluate the prognostic value of various lncRNAs in HCC. Eligible literatures were systematically collected from PubMed, Embase, Web of Science, and Cochrane Library (up to December 30, 2015). The main outcomes including overall survival, relapse-free survival, and disease-free survival were analyzed. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. A total of 2,991 patients with HCC in People's Republic of China from 27 studies were included in the analysis. The level of lncRNAs showed a significant association with clinical outcomes. Abnormally elevated lncRNA transcription level predicted poor overall survival (HR: 1.68, 95% CI: 1.20-2.34, P=0.002; I (2)=75.5%, P=0.000) and relapse-free survival (HR: 2.08, 95% CI: 1.65-2.61, P<0.001; I (2)=24.0%, P=0.215), while no association was observed with disease-free survival of HCC patients (HR: 1.39, 95% CI: 0.51-3.78, P=0.524; I (2)=81.3%, P=0.005). Subgroup analysis further showed that lncRNA transcription level was significantly associated with tumor size (relative risk [RR]: 1.19, 95% CI: 1.01-1.39, P=0.035), microvascular invasion (RR: 1.44, 95% CI: 1.10-1.89, P=0.009), and portal vein tumor thrombus (RR: 1.50, 95% CI: 1.03-2.20, P=0.036). Publication bias and sensitivity analysis further confirmed the stability of our results. Our present meta-analysis indicates that abnormal lncRNA transcription level may serve as a promising indicator for prognostic evaluation of patients with HCC in People's Republic of China.

Combining Gene Signatures Improves Prediction of Breast Cancer Survival

PubMed Central

Zhao, Xi; Naume, Bjørn; Langerød, Anita; Frigessi, Arnoldo; Kristensen, Vessela N.; Børresen-Dale, Anne-Lise; Lingjærde, Ole Christian

2011-01-01

Background Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123) and test set (n = 81), respectively. Gene sets from eleven previously published gene signatures are included in the study. Principal Findings To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014). Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001). The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. Conclusion Combining the predictive strength of multiple gene signatures improves prediction of breast cancer survival. The presented methodology is broadly applicable to breast cancer risk assessment using any new identified gene set. PMID:21423775

Prediction of Conditional Probability of Survival After Surgery for Gastric Cancer: A Study Based on Eastern and Western Large Data Sets.

PubMed

Zhong, Qing; Chen, Qi-Yue; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lin, Jian-Xian; Lu, Jun; Cao, Long-Long; Lin, Mi; Tu, Ru-Hong; Zheng, Chao-Hui; Huang, Chang-Ming

2018-04-20

The dynamic prognosis of patients who have undergone curative surgery for gastric cancer has yet to be reported. Our objective was to devise an accurate tool for predicting the conditional probability of survival for these patients. We analyzed 11,551 gastric cancer patients from the Surveillance, Epidemiology, and End Results database. Two-thirds of the patients were selected randomly for the development set and one-third for the validation set. Two nomograms were constructed to predict the conditional probability of overall survival and the conditional probability of disease-specific survival, using conditional survival methods. We then applied these nomograms to the 4,001 patients in the database from Fujian Medical University Union Hospital, Fuzhou, China, one of the most active Chinese institutes. The 5-year conditional probability of overall survival of the patients was 41.6% immediately after resection and increased to 52.8%, 68.2%, and 80.4% at 1, 2, and 3 years after gastrectomy. The 5-year conditional probability of disease-specific survival "increased" from 48.9% at the time of gastrectomy to 59.8%, 74.7%, and 85.5% for patients surviving 1, 2, and 3 years, respectively. Sex; race; age; depth of tumor invasion; lymph node metastasis; and tumor size, site, and grade were associated with overall survival and disease-specific survival (P <.05). Within the Surveillance, Epidemiology, and End Results validation set, the accuracy of the conditional probability of overall survival nomogram was 0.77, 0.81, 0.82, and 0.82 at 1, 3, 5, and 10 years after gastrectomy, respectively. Within the other validation set from the Fujian Medical University Union Hospital (n = 4,001), the accuracy of the conditional probability of overall survival nomogram was 0.76, 0.79, 0.77, and 0.77 at 1, 3, 5, and 10 years, respectively. The accuracy of the conditional probability of disease-specific survival model was also favorable. The calibration curve demonstrated good agreement between the predicted and observed survival rates. Based on the large Eastern and Western data sets, we developed and validated the first conditional nomogram for prediction of conditional probability of survival for patients with gastric cancer to allow consideration of the duration of survivorship. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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

Silva, Andrew Oliveira, E-mail: andrewbiomed@gmail.com; Dalsin, Eloisa, E-mail: dalsineloisa@gmail.com; Onzi, Giovana Ravizzoni, E-mail: gioonzi@gmail.com

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

MGMT expression levels predict disease stabilisation, progression-free and overall survival in patients with advanced melanomas treated with DTIC.

PubMed

Busch, Christian; Geisler, Jürgen; Lillehaug, Johan R; Lønning, Per Eystein

2010-07-01

Metastatic melanoma responds poorly to systemic treatment. We report the results of a prospective single institution study evaluating O(6)-methylguanine-DNA methyltransferase (MGMT) status as a potential predictive and/or prognostic marker among patients treated with dacarbazine (DTIC) 800-1000 mg/m(2) monotherapy administered as a 3-weekly schedule for advanced malignant melanomas. The study was approved by the Regional Ethical Committee. Surgical biopsies from metastatic or loco-regional deposits obtained prior to DTIC treatment were snap-frozen immediately upon removal and stored in liquid nitrogen up to processing. Median time from enrolment to end of follow-up was 67 months. MGMT expression levels evaluated by qRT-PCR correlated significantly to DTIC benefit (CR/PR/SD; p=0.005), time to progression (TTP) (p=0.005) and overall survival (OS) (p=0.003). MGMT expression also correlated to Breslow thickness in the primary tumour (p=0.014). While MGMT promoter hypermethylation correlated to MGMT expression, MGMT promoter hypermethylation did not correlate to treatment benefit, TTP or OS, suggesting that other factors may be critical in determining MGMT expression levels in melanomas. In a Cox proportional regression analysis, serum lactate dehydrogenase (LDH, p<0.001), MGMT expression (p=0.022) and p16(INK4a) expression (p=0.037) independently predicted OS, while TTP correlated to DTIC benefit after 6 weeks only (p=0.001). Our data reveal MGMT expression levels to be associated with disease stabilisation and prognosis in patients receiving DTIC monotherapy for advanced melanoma. The role of MGMT expression as a predictor to DTIC sensitivity versus a general prognostic factor in advanced melanomas warrants further evaluation. Copyright 2010 Elsevier Ltd. All rights reserved.

Elevated serum levels of TPS and CYFRA 21-1 predict poor prognosis in advanced non-small-cell lung cancer patients treated with gefitinib.

PubMed

Chen, Fengsheng; Luo, Xi; Zhang, Jinbiao; Lu, Yang; Luo, Rongcheng

2010-09-01

Serum concentrations of tissue polypeptide-specific antigen (TPS) and Cytokeratin-19-Fragments (CYFRA 21-1) before operation or chemotherapy have been proved to be a useful prognostic tool for patients with NSCLC, but the related data for advanced NSCLC patients treated with gefitinib are limited. We retrospectively reviewed 122 advanced NSCLC patients treated with gefitinib between April 2002 and August 2007. Multiple clinical factors including pretreatment serum levels of TPS and CYFRA 21-1, age, gender, performance status (PS), smoking history, stage, histology, the number of prior chemotherapy and the patients' clinical outcomes were analyzed. Patients without elevated serum TPS levels had a more RR (36.8%) than those with elevated serum TPS levels (18.5%) (P = 0.023), nevertheless, a similar result was not seen in patients with normal CYFRA 21-1 levels. For patients with normal vs. high TPS levels, the median survival times (MSTs) were 15.9 vs. 7.3 months (P = 0.001). For patients with normal vs. high CYFRA 21-1, the MSTs were 15.4 vs. 7.5 months (P = 0.003). Moreover, for patients with both elevated, vs. one elevated and both normal TPS and CYFRA 21-1 levels, the MSTs were 5.4 vs. 11.4 months (P = 0.001), and 16.5 months (P < 0.001), respectively. In multivariate analysis, TPS (P = 0.001) and CYFRA 21-1 (P = 0.005) alone or combination (P < 0.001) remained significant correlation to survival. In NSCLC patients with gefitinib therapy, pretreatment serum levels of TPS and CYFRA 21-1 alone or combined might be independent prognostic factors, and the pretreatment serum TPS level may predict the tumor response.

The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer

PubMed Central

Yamaguchi, Rin; Nishimura, Reiki; Osako, Tomofumi; Arima, Nobuyuki; Okumura, Yasuhiro; Okido, Masayuki; Yamada, Mai; Kai, Masaya; Kishimoto, Junji; Oda, Yoshinao; Nakamura, Masafumi

2017-01-01

This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0.016). There was a strong interaction between PD-L1 expression and TILs that was associated with both recurrence-free survival (P = 0.0018) and overall survival (P = 0.015). Multivariate Cox proportional hazards model analysis showed that PD-L1-positive/TILs-low was an independent negative prognostic factor for both recurrence-free survival and overall survival. Our findings suggest that PD-L1-positive/TILs-low tumors are associated with a poor prognosis in patients with TNBC, and that it is important to focus on the combination of PD-L1 expression on tumor cells and TILs present in the tumor microenvironment. These biomarkers may be useful for stratification of TNBCs and for predicting prognosis and developing novel cancer immunotherapies. PMID:28107186

Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques

PubMed Central

Macyszyn, Luke; Akbari, Hamed; Pisapia, Jared M.; Da, Xiao; Attiah, Mark; Pigrish, Vadim; Bi, Yingtao; Pal, Sharmistha; Davuluri, Ramana V.; Roccograndi, Laura; Dahmane, Nadia; Martinez-Lage, Maria; Biros, George; Wolf, Ronald L.; Bilello, Michel; O'Rourke, Donald M.; Davatzikos, Christos

2016-01-01

Background MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). Methods One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. Results Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. Conclusions By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood–brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients. PMID:26188015

Pretreatment Pokemon Level as a Predictor of Response to Cisplatin and Paclitaxel in Patients with Unresectable Non-Small Cell Lung Cancer.

PubMed

Zhang, Quan-Le; Xing, Xi-Zhi; Li, Feng-Yan; Xing, Ya-Juan; Li, Jing

2015-01-01

We firstly investigated the expression of Pokemon in patients with non-small cell lung cancer (NSCLC), then characterized the role of Pokemon in evaluating the response to combined cisplatin and paclitaxel chemotherapy and prognosis. In this study, 61 patients with previously untreated locally advanced or metastatic NSCLC were treated with a combination chemotherapy comprising cisplatin and paclitaxel. The correlation between serum expression of Pokemon and effectiveness of chemotherapy was assessed. The expression level of Pokemon in NSCLC patients was higher than that in healthy controls (p = 0.000), and was correlated with tumor size and TNM stage (p < 0.05). Kaplan-Meier analysis and Cox proportional hazard model demonstrated a poor response and shorter survival time in patients with pretreatment Pokemon levels in excess of 135.09 ng/ml compared to those with Pokemon levels below 135.09 ng/ml (p = 0.013). Pokemon ≥ 135.09 ng/ml was an independent risk factor for survival time in NSCLC patients undergoing combination chemotherapy (p = 0.018). The serum level of Pokemon correlated with efficacy of cisplatin and paclitaxel combination chemotherapy and survival time, which indicated that Pokemon may be a potentially useful biomarker for predicting treatment effectiveness of first-line chemotherapy and prognosis in NSCLC. © 2015 S. Karger GmbH, Freiburg.

Predictive Factors of Downstaging of Hepatocellular Carcinoma Beyond the Milan Criteria Treated with Intra-arterial Therapies

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

Bova, Valentina; Miraglia, Roberto, E-mail: rmiraglia@ismett.edu; Maruzzelli, Luigi

2013-04-15

This study was designed to analyze the clinical results in patients suitable for liver transplantation with hepatocellular carcinoma (HCC) who exceeded Milan criteria, which underwent intra-arterial therapies (IAT), to determine predictive factors of successful downstaging. A total of 277 consecutive patients with cirrhosis and HCC were treated by IAT (transarterial oily chemoembolization, transarterial chemoembolization, transarterial embolization) in a single center. Eighty patients exceed the Milan criteria. Patients with infiltrative HCC, hypovascular HCC, and portal vein thrombosis were excluded, with a final study population of 48 patients. Tumor response to IAT was evaluated with CT and/or MRI according to modified RECISTmore » criteria. Successful downstaging was defined as a reduction in the number and size of viable tumors to within the Milan criteria, and serum alpha-fetoprotein (AFP) <100 ng/mL, for at least 6 months. Nineteen patients (39 %) had their tumors successfully downstaged; 29 patients (61 %) did not. Multivariate analysis showed that AFP level <100 ng/mL and 3-year calculated survival probability using the Metroticket calculator were the only independent predictors of successful downstaging (p < 0.023 and p < 0.049 respectively). Biological characteristics of HCC as AFP levels <100 ng/mL and high 3-year calculated survival probability may predict a good response to downstage after IAT.« less

Modeling time-to-event (survival) data using classification tree analysis.

PubMed

Linden, Ariel; Yarnold, Paul R

2017-12-01

Time to the occurrence of an event is often studied in health research. Survival analysis differs from other designs in that follow-up times for individuals who do not experience the event by the end of the study (called censored) are accounted for in the analysis. Cox regression is the standard method for analysing censored data, but the assumptions required of these models are easily violated. In this paper, we introduce classification tree analysis (CTA) as a flexible alternative for modelling censored data. Classification tree analysis is a "decision-tree"-like classification model that provides parsimonious, transparent (ie, easy to visually display and interpret) decision rules that maximize predictive accuracy, derives exact P values via permutation tests, and evaluates model cross-generalizability. Using empirical data, we identify all statistically valid, reproducible, longitudinally consistent, and cross-generalizable CTA survival models and then compare their predictive accuracy to estimates derived via Cox regression and an unadjusted naïve model. Model performance is assessed using integrated Brier scores and a comparison between estimated survival curves. The Cox regression model best predicts average incidence of the outcome over time, whereas CTA survival models best predict either relatively high, or low, incidence of the outcome over time. Classification tree analysis survival models offer many advantages over Cox regression, such as explicit maximization of predictive accuracy, parsimony, statistical robustness, and transparency. Therefore, researchers interested in accurate prognoses and clear decision rules should consider developing models using the CTA-survival framework. © 2017 John Wiley & Sons, Ltd.

N-terminal pro B-type natriuretic peptide predicts mortality in patients with left ventricular hypertrophy.

PubMed

Garcia, Santiago; Akbar, Muhammad S; Ali, Syed S; Kamdar, Forum; Tsai, Michael Y; Duprez, Daniel A

2010-09-03

Left ventricular hypertrophy adversely affects outcomes in patients with hypertension. Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) adds incremental prognostic information in patients with hypertension and left ventricular hypertrophy (LVH) is not well established. We aimed to study the prognostic value of NT-proBNP in hypertensive patients with LVH. Echocardiography was performed in 232 patients (mean age 61±15, 102 males, 130 females) for the diagnosis of left ventricular hypertrophy. Left ventricular mass was measured according to The American Society of Echocardiography guidelines. A blood sample was taken for NT-proBNP determination. NT-proBNP levels were analyzed in quartiles after log transformation. Long term survival was established by review of electronic medical records. Arterial hypertension was present in 130 patients (56%) and left ventricular hypertrophy was present in 105 patients (45%). In patients with left ventricular hypertrophy, NT-proBNP levels predicted long term survival (Chi-square=10, p=0.01). After adjusting by age, presence of coronary artery disease, ejection fraction, diabetes status, and hypertension; patients in highest NT pro-BNP quartile were twice as likely to die when compared to patients in the lowest NT-ptoBNP quartile (OR=2.2, 95% CI=1.0-4.6, p=0.03). NT-proBNP is an independent predictor of survival in patients with hypertension and increased left ventricular mass. Copyright © 2009 Elsevier B.V. All rights reserved.

Retention in a Computer-based Outreach Intervention For Chronically Ill Rural Women

PubMed Central

Weinert, Clarann; Cudney, Shirley; Hill, Wade G.

2009-01-01

The study's purpose was to examine retention factors in a computer intervention with 158 chronically ill rural women. After a 22 week intervention, 18.9 percent of the women had dropped out. A Cox regression survival analysis was performed to assess the effects of selected covariates on retention. Reasons for dropping were tallied and categorized. Major reasons for dropping were: lack of time; decline in health status, and non-participation in study activities. Four covariates predicted survival time: level of computer skills, marital status, work outside of home, and impact of social events on participants' lives. Retention-enhancing strategies are suggested for implementation. PMID:18226760

Serum levels of IGF-1 and IGF-BP3 are associated with event-free survival in adult Ewing sarcoma patients treated with chemotherapy.

PubMed

de Groot, Stefanie; Gelderblom, Hans; Fiocco, Marta; Bovée, Judith Vmg; van der Hoeven, Jacobus Jm; Pijl, Hanno; Kroep, Judith R

2017-01-01

Activation of the insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis, tumor progression, and therapy resistance in solid tumors. We examined whether variability in serum levels of IGF-1, IGF-2, and IGF-binding protein 3 (IGF-BP3) can predict event-free survival (EFS) and overall survival (OS) in Ewing sarcoma patients treated with chemotherapy. Serum levels of IGF-1, IGF-2, and IGF-BP3 of 22 patients with localized or metastasized Ewing sarcoma treated with six cycles of vincristine/ifosfamide/doxorubicin/etoposide (VIDE) chemotherapy were recorded. Baseline levels were compared with presixth cycle levels using paired t -tests and were tested for associations with EFS and OS. Continuous variables were dichotomized according to the Contal and O'Quigley procedure. Survival analyses were performed using Cox regression analysis. High baseline IGF-1 and IGF-BP3 serum levels were associated with EFS (hazard ratio [HR] 0.075, 95% confidence interval [CI] 0.009-0.602 and HR 0.090, 95% CI 0.011-0.712, respectively) in univariate and multivariate analyses (HR 0.063, 95% CI 0.007-0.590 and HR 0.057, 95% CI 0.005-0.585, respectively). OS was improved, but this was not statistically significant. IGF-BP3 and IGF-2 serum levels increased during treatment with VIDE chemotherapy ( P =0.055 and P =0.023, respectively). High circulating serum levels of IGF-1 and IGF-BP3 and the molar ratio of IGF-1:IGF-BP3 serum levels were associated with improved EFS and a trend for improved OS in Ewing sarcoma patients treated with VIDE chemotherapy. These findings suggest the need for further investigation of the IGF-1 pathway as a biomarker of disease progression in patients with Ewing sarcoma.

Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.

PubMed

Megchelenbrink, Wout; Katzir, Rotem; Lu, Xiaowen; Ruppin, Eytan; Notebaart, Richard A

2015-09-29

Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

Upregulation of c-mesenchymal epithelial transition expression and RAS mutations are associated with late lung metastasis and poor prognosis in colorectal carcinoma.

PubMed

Liu, Jianhua; Zeng, Weiqiang; Huang, Chengzhi; Wang, Junjiang; Xu, Lishu; Ma, Dong

2018-05-01

The present study aimed to investigate whether c-mesenchymal epithelial transition factor (C-MET) overexpression combined with RAS (including KRAS, NRAS and HRAS ) or BRAF mutations were associated with late distant metastases and the prognosis of patients with colorectal cancer (CRC). A total of 374 patients with stage III CRC were classified into 4 groups based on RAS/BRAF and C-MET status for comprehensive analysis. Mutations in RAS / BRAF were determined using Sanger sequencing and C-MET expression was examined using immunohistochemistry. The associations between RAS/BRAF mutations in combination with C-MET overexpression and clinicopathological variables including survival were evaluated. In addition, their predictive value for late distant metastases were statistically analyzed via logistic regression and receiver operating characteristic analysis. Among 374 patients, mutations in KRAS, NRAS, HRAS, BRAF and C-MET overexpression were observed in 43.9, 2.4, 0.3, 5.9 and 71.9% of cases, respectively. Considering RAS/BRAF mutations and C-MET overexpression, vascular invasion (P=0.001), high carcino-embryonic antigen level (P=0.031) and late distant metastases (P<0.001) were more likely to occur in patients of group 4. Furthermore, survival analyses revealed RAS/BRAF mutations may have a more powerful impact on survival than C-MET overexpression, although they were both predictive factors for adverse prognosis. Further logistic regression suggested that RAS/BRAF mutations and C-MET overexpression may predict late distant metastases. In conclusion, RAS/BRAF mutations and C-MET overexpression may serve as predictive indicators for metastatic behavior and poor prognosis of CRC.

Nomograms for predicting graft function and survival in living donor kidney transplantation based on the UNOS Registry.

PubMed

Tiong, H Y; Goldfarb, D A; Kattan, M W; Alster, J M; Thuita, L; Yu, C; Wee, A; Poggio, E D

2009-03-01

We developed nomograms that predict transplant renal function at 1 year (Modification of Diet in Renal Disease equation [estimated glomerular filtration rate]) and 5-year graft survival after living donor kidney transplantation. Data for living donor renal transplants were obtained from the United Network for Organ Sharing registry for 2000 to 2003. Nomograms were designed using linear or Cox regression models to predict 1-year estimated glomerular filtration rate and 5-year graft survival based on pretransplant information including demographic factors, immunosuppressive therapy, immunological factors and organ procurement technique. A third nomogram was constructed to predict 5-year graft survival using additional information available by 6 months after transplantation. These data included delayed graft function, any treated rejection episodes and the 6-month estimated glomerular filtration rate. The nomograms were internally validated using 10-fold cross-validation. The renal function nomogram had an r-square value of 0.13. It worked best when predicting estimated glomerular filtration rate values between 50 and 70 ml per minute per 1.73 m(2). The 5-year graft survival nomograms had a concordance index of 0.71 for the pretransplant nomogram and 0.78 for the 6-month posttransplant nomogram. Calibration was adequate for all nomograms. Nomograms based on data from the United Network for Organ Sharing registry have been validated to predict the 1-year estimated glomerular filtration rate and 5-year graft survival. These nomograms may facilitate individualized patient care in living donor kidney transplantation.

Survival Prediction in Pancreatic Ductal Adenocarcinoma by Quantitative Computed Tomography Image Analysis.

PubMed

Attiyeh, Marc A; Chakraborty, Jayasree; Doussot, Alexandre; Langdon-Embry, Liana; Mainarich, Shiana; Gönen, Mithat; Balachandran, Vinod P; D'Angelica, Michael I; DeMatteo, Ronald P; Jarnagin, William R; Kingham, T Peter; Allen, Peter J; Simpson, Amber L; Do, Richard K

2018-04-01

Pancreatic cancer is a highly lethal cancer with no established a priori markers of survival. Existing nomograms rely mainly on post-resection data and are of limited utility in directing surgical management. This study investigated the use of quantitative computed tomography (CT) features to preoperatively assess survival for pancreatic ductal adenocarcinoma (PDAC) patients. A prospectively maintained database identified consecutive chemotherapy-naive patients with CT angiography and resected PDAC between 2009 and 2012. Variation in CT enhancement patterns was extracted from the tumor region using texture analysis, a quantitative image analysis tool previously described in the literature. Two continuous survival models were constructed, with 70% of the data (training set) using Cox regression, first based only on preoperative serum cancer antigen (CA) 19-9 levels and image features (model A), and then on CA19-9, image features, and the Brennan score (composite pathology score; model B). The remaining 30% of the data (test set) were reserved for independent validation. A total of 161 patients were included in the analysis. Training and test sets contained 113 and 48 patients, respectively. Quantitative image features combined with CA19-9 achieved a c-index of 0.69 [integrated Brier score (IBS) 0.224] on the test data, while combining CA19-9, imaging, and the Brennan score achieved a c-index of 0.74 (IBS 0.200) on the test data. We present two continuous survival prediction models for resected PDAC patients. Quantitative analysis of CT texture features is associated with overall survival. Further work includes applying the model to an external dataset to increase the sample size for training and to determine its applicability.

Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS.

PubMed

Nielsen, M J; Lehmann, J; Leeming, D J; Schierwagen, R; Klein, S; Jansen, C; Strassburg, C P; Bendtsen, F; Møller, S; Sauerbruch, T; Karsdal, M A; Krag, A; Trebicka, J

2015-11-01

Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS). We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated. Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients. This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.

Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

PubMed

Yamada, Yasutaka; Sakamoto, Shinichi; Amiya, Yoshiyasu; Sasaki, Makoto; Shima, Takayuki; Komiya, Akira; Suzuki, Noriyuki; Akakura, Koichiro; Ichikawa, Tomohiko; Nakatsu, Hiroomi

2018-05-04

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml -1 ), intermediate (100-999 ng ml -1 ), and high (≥1000 ng ml -1 ). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

Expression of CD10 predicts tumor progression and unfavorable prognosis in malignant melanoma.

PubMed

Oba, Junna; Nakahara, Takeshi; Hayashida, Sayaka; Kido, Makiko; Xie, Lining; Takahara, Masakazu; Uchi, Hiroshi; Miyazaki, Shogo; Abe, Takeru; Hagihara, Akihito; Moroi, Yoichi; Furue, Masutaka

2011-12-01

CD10 expression in malignant melanoma (MM) has been reported to increase according to tumor progression and metastasis; however, its association with patient outcome has not been clarified. We examined the immunohistochemical expression of CD10 in MM to determine whether or not it could serve as a marker for tumor progression and prognosis. A total of 64 formalin-fixed, paraffin-embedded samples of primary MM were immunostained for CD10. Similarly, 40 samples of melanocytic nevus and 20 of metastatic MM were analyzed for comparison. The following clinicopathologic variables were evaluated: age, gender, histologic type, tumor site, Breslow thickness, Clark level, the presence or absence of ulceration and tumor-infiltrating lymphocytes, and survival. Statistical analyses were performed to assess for associations. Several parameters were analyzed for survival using the Kaplan-Meier method and Cox proportional hazards model. Immunohistochemical analysis revealed that 34 of 64 cases (53%) of primary MM expressed CD10, compared with 15 of 20 cases (75%) of metastatic MM and only 4 of 40 cases (10%) of nevus. There was a significant positive relationship between CD10 expression and Breslow thickness, Clark level, and ulceration. Univariate analysis revealed 4 significant factors for shorter survival periods: CD10 expression, high Breslow thickness, high Clark level, and the presence of ulceration (P < .01 each). In multivariate analysis, CD10 expression was revealed to be a statistically significant and independent prognostic factor. The major limitation was the small sample size. CD10 expression may serve as a progression marker and can predict unfavorable prognosis in patients with MM. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

The predictive value of early molecular response in chronic myeloid leukaemia patients treated with imatinib in a single real-world medical centre in a developing country.

PubMed

Bee, Ping Chong; Sekaran, Veera; Ng, Richard Rui Jie; Kweh, Ting Yi; Gan, Gin Gin

2017-03-01

The prognosis of patients with chronic myeloid leukaemia (CML) has improved since the introduction of imatinib. However, patients who do not achieve complete cytogenetic response (CCyR) and major molecular response (MMR) have poorer prognosis. Recent clinical trials have demonstrated that early and deeper cytogenetic and molecular responses predict a better long-term outcome. This study aimed to analyse the relationship between early molecular response and clinical outcome in a real-life setting. This retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia. A total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and event-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients. Our data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients. Copyright: © Singapore Medical Association

Changes in highly sensitive alpha-fetoprotein for the prediction of the outcome in patients with hepatocellular carcinoma after hepatectomy.

PubMed

Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Ito, Takanori; Maeda, Atsuyuki; Kaneoka, Yuji; Kagebayashi, Chiaki; Satomura, Shinji

2014-06-01

We investigated changes in highly sensitive lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (hsAFP-L3) measured using a novel method and its predictive ability for prognosis in patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy, comparing to other HCC tumor markers, that is, AFP, des-gamma-carboxy prothrombin (DCP), and AFP-L3 measured with conventional method (cAFP-L3). AFP, DCP, and AFP-L3 including both cAFP-L3 and hsAFP-L3 were measured before and after curative hepatectomy in 187 patients. The percentage of patients with elevated tumor marker levels pre- and postoperatively was compared, and recurrence-free and overall survival rates were analyzed based on changes in tumor markers. The percentages of patients with elevated AFP, DCP, and cAFP-L3 decreased postoperatively. In contrast, the percentage of patients with elevated hsAFP-L3 did not decrease postoperatively. Both recurrence-free and overall survival rates were significantly lower in patients whose tumor marker levels remained elevated postoperatively than patients without tumor marker elevation postoperatively. Recurrence-free and overall survival rates of patients in whom hsAFP-L3 became elevated postoperatively despite normal preoperative hsAFP-L3 levels were significantly lower than those of patients with normal hsAFP-L3 postoperatively, and were similar to those of patients with persistent elevation. Preoperative elevations of AFP, DCP, and cAFP normalized in many patients postoperatively, but not for hsAFP-L3. The elevation of hsAFP-L3 identifies patients with poor prognosis despite the normalization of AFP and DCP. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project.

PubMed

Avet-Loiseau, H; Durie, B G M; Cavo, M; Attal, M; Gutierrez, N; Haessler, J; Goldschmidt, H; Hajek, R; Lee, J H; Sezer, O; Barlogie, B; Crowley, J; Fonseca, R; Testoni, N; Ross, F; Rajkumar, S V; Sonneveld, P; Lahuerta, J; Moreau, P; Morgan, G

2013-03-01

The combination of serum β2-microglobulin and albumin levels has been shown to be highly prognostic in myeloma as the International Staging System (ISS). The aim of this study was to assess the independent contributions of ISS stage and cytogenetic abnormalities in predicting outcomes. A retrospective analysis of international studies looking at both ISS and cytogenetic abnormalities was performed in order to assess the potential role of combining ISS stage and cytogenetics to predict survival. This international effort used the International Myeloma Working Group database of 12 137 patients treated worldwide for myeloma at diagnosis, of whom 2309 had cytogenetic studies and 5387 had analyses by fluorescent in situ hybridization (iFISH). Comprehensive analyses used 2642 patients with sufficient iFISH data available. Using the comprehensive iFISH data, combining both t(4;14) and deletion (17p), along with ISS stage, significantly improved the prognostic assessment in terms of progression-free survival and overall survival. The additional impact of patient age and use of high-dose therapy was also demonstrated. In conclusion, the combination of iFISH data with ISS staging significantly improves risk assessment in myeloma.

Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: A potential predictor of postoperative recurrence.

PubMed

Nanno, Yoshihide; Toyama, Hirochika; Matsumoto, Ippei; Otani, Kyoko; Asari, Sadaki; Goto, Tadahiro; Ajiki, Tetsuo; Zen, Yoh; Fukumoto, Takumi; Ku, Yonson

The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients' survival. Plasma CgA levels ranged 2.9-30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence (P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total (P < 0.001) and in G2 patients (P = 0.020). Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence. Copyright © 2016. Published by Elsevier B.V.

Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension

PubMed Central

Condliffe, Robin; Pickworth, Josephine A.; Hopkinson, Kay; Walker, Sara J.; Hameed, Abdul G.; Suntharaligam, Jay; Soon, Elaine; Treacy, Carmen; Pepke-Zaba, Joanna; Francis, Sheila E.; Crossman, David C.; Newman, Christopher M. H.; Elliot, Charles A.; Morton, Allison C.; Morrell, Nicholas W.; Kiely, David G.; Lawrie, Allan

2012-01-01

We previously reported that osteoprotegerin (OPG) is regulated by pathways associated with pulmonary arterial hypertension (PAH), and is present at elevated levels within pulmonary vascular lesions and sera from patients with idiopathic PAH (IPAH). Since OPG is a naturally secreted protein, we investigated the relationship between serum OPG and disease severity and outcome in patients with IPAH and animal models. OPG mRNA expression was measured in pulmonary artery smooth muscle cells (PASMC) from pulmonary arteries of patients with and without IPAH. Serum concentrations of OPG were measured in a retrospective and prospective group of patients. OPG levels were compared with phenotypic data and other putative PAH biomarkers. Prognostic significance was assessed and levels compared with healthy controls. Correlation of OPG and pulmonary vascular remodeling was also performed in rodent models of PAH. OPG mRNA was significantly increased 2-fold in PASMC isolated from explanted PAH lungs compared with control. Serum OPG concentrations were markedly elevated in IPAH compared with controls. In Cohort 1 OPG levels significantly correlated with mean right atrial pressure and cardiac index, while in Cohort 2 significant correlations existed between age-adjusted OPG levels and gas transfer. In both cohorts an OPG concentration above a ROC-derived threshold of 4728 pg/ml predicted poorer survival. In two rodent models, OPG correlated with the degree of pulmonary vascular remodeling. OPG levels are significantly elevated in patients with idiopathic PAH and are of prognostic significance. The role of OPG as a potential biomarker and therapeutic target merits further investigation. PMID:22558516

Development of a predictive model for 6 month survival in patients with venous thromboembolism and solid malignancy requiring IVC filter placement.

PubMed

Huang, Steven Y; Odisio, Bruno C; Sabir, Sharjeel H; Ensor, Joe E; Niekamp, Andrew S; Huynh, Tam T; Kroll, Michael; Gupta, Sanjay

2017-07-01

Our purpose was to develop a predictive model for short-term survival (i.e. <6 months) following inferior vena cava filter placement in patients with venous thromboembolism (VTE) and solid malignancy. Clinical and laboratory parameters were retrospectively reviewed for patients with solid malignancy who received a filter between January 2009 and December 2011 at a tertiary care cancer center. Multivariate Cox proportional hazards modeling was used to assess variables associated with 6 month survival following filter placement in patients with VTE and solid malignancy. Significant variables were used to generate a predictive model. 397 patients with solid malignancy received a filter during the study period. Three variables were associated with 6 month survival: (1) serum albumin [hazard ratio (HR) 0.496, P < 0.0001], (2) recent or planned surgery (<30 days) (HR 0.409, P < 0.0001), (3) TNM staging (stage 1 or 2 vs. stage 4, HR 0.177, P = 0.0001; stage 3 vs. stage 4, HR 0.367, P = 0.0002). These variables were used to develop a predictive model to estimate 6 month survival with an area under the receiver operating characteristic curve of 0.815, sensitivity of 0.782, and specificity of 0.715. Six month survival in patients with VTE and solid malignancy requiring filter placement can be predicted from three patient variables. Our predictive model could be used to help physicians decide whether a permanent or retrievable filter may be more appropriate as well as to assess the risks and benefits for filter retrieval within the context of survival longevity in patients with cancer.

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging

PubMed Central

Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

2015-01-01

AIM: To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. METHODS: The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. RESULTS: At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites, patients with AFP ≥ 200 ng/mL had a shorter survival (28 mo vs 39 mo). For stage B patients, survival for the corresponding groups was 12, 18, 19 and 22 mo. The one-, two-, and three-year survival rates for stage A patients without ascites and AFP < 200 ng/mL were 94%, 77%, and 71%, respectively, and for patients with ascites and AFP ≥ 200 ng/mL were 83%, 24%, and 22%, respectively (P < 0.001). Adding ascites and AFP ≥ 200 ng/mL improved the discriminatory ability for predicting prognosis (area under the curve, 0.618 vs 0.579 for BCLC, P < 0.001). CONCLUSION: Adding AFP and ascites to the BCLC staging classification can improve prognosis prediction for early and intermediate stages of hepatocellular carcinoma. PMID:25987792

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging.

PubMed

Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

2015-05-14

To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites, patients with AFP ≥ 200 ng/mL had a shorter survival (28 mo vs 39 mo). For stage B patients, survival for the corresponding groups was 12, 18, 19 and 22 mo. The one-, two-, and three-year survival rates for stage A patients without ascites and AFP < 200 ng/mL were 94%, 77%, and 71%, respectively, and for patients with ascites and AFP ≥ 200 ng/mL were 83%, 24%, and 22%, respectively (P < 0.001). Adding ascites and AFP ≥ 200 ng/mL improved the discriminatory ability for predicting prognosis (area under the curve, 0.618 vs 0.579 for BCLC, P < 0.001). Adding AFP and ascites to the BCLC staging classification can improve prognosis prediction for early and intermediate stages of hepatocellular carcinoma.

Low Serum Interleukin-13 Levels Correlate with Poorer Prognoses for Colorectal Cancer Patients

PubMed Central

Saigusa, Susumu; Tanaka, Koji; Inoue, Yasuhiro; Toiyama, Yuji; Okugawa, Yoshinaga; Iwata, Takashi; Mohri, Yasuhiko; Kusunoki, Masato

2014-01-01

Interleukin-13 (IL-13) is an immunosuppressive cytokine produced by several immune cells and cancer cells. The aim of this retrospective study was to determine if serum IL-13 levels have an association with clinical outcome in patients with colorectal cancer. A total of 241 patients with colorectal cancer were enrolled in the present study. Preoperative serum IL-13 concentrations were measured by enzyme-linked immunosorbent assay. We analyzed the association of serum IL-13 levels with clinicopathological variables. Patients with lymph node metastasis, lymphatic invasion, vascular invasion, distant metastases or advanced stage of disease had significantly lower serum IL-13 levels. Low serum IL-13 was significantly associated with both poor recurrence-free and overall survival. Multivariate analysis showed that low IL-13 levels were an independent predictive marker for poor prognosis. In conclusion, our data suggest that low serum IL-13 levels may be a useful predictive marker for poor prognosis in colorectal cancer. PMID:24833143

Modeling Disjunct Gray Wolf Populations in Semi-Wild Landscapes

Treesearch

Robert G. Haight; David J. Mladenoff; Adrian P. Wydeven

1998-01-01

Gray wolves (Canis lupus) in parts of the United States and Europe live in networks of disjunct populations, many of which are close to human settlement. Because wolf management goals include sustaining disjunct populations, it is important to ask what types of areas and protections are needed for population survival. To predict the effects of different levels of human...

Integration of somatic mutation, expression and functional data reveals potential driver genes predictive of breast cancer survival.

PubMed

Suo, Chen; Hrydziuszko, Olga; Lee, Donghwan; Pramana, Setia; Saputra, Dhany; Joshi, Himanshu; Calza, Stefano; Pawitan, Yudi

2015-08-15

Genome and transcriptome analyses can be used to explore cancers comprehensively, and it is increasingly common to have multiple omics data measured from each individual. Furthermore, there are rich functional data such as predicted impact of mutations on protein coding and gene/protein networks. However, integration of the complex information across the different omics and functional data is still challenging. Clinical validation, particularly based on patient outcomes such as survival, is important for assessing the relevance of the integrated information and for comparing different procedures. An analysis pipeline is built for integrating genomic and transcriptomic alterations from whole-exome and RNA sequence data and functional data from protein function prediction and gene interaction networks. The method accumulates evidence for the functional implications of mutated potential driver genes found within and across patients. A driver-gene score (DGscore) is developed to capture the cumulative effect of such genes. To contribute to the score, a gene has to be frequently mutated, with high or moderate mutational impact at protein level, exhibiting an extreme expression and functionally linked to many differentially expressed neighbors in the functional gene network. The pipeline is applied to 60 matched tumor and normal samples of the same patient from The Cancer Genome Atlas breast-cancer project. In clinical validation, patients with high DGscores have worse survival than those with low scores (P = 0.001). Furthermore, the DGscore outperforms the established expression-based signatures MammaPrint and PAM50 in predicting patient survival. In conclusion, integration of mutation, expression and functional data allows identification of clinically relevant potential driver genes in cancer. The documented pipeline including annotated sample scripts can be found in http://fafner.meb.ki.se/biostatwiki/driver-genes/. yudi.pawitan@ki.se Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Climate warming causes life-history evolution in a model for Atlantic cod (Gadus morhua).

PubMed

Holt, Rebecca E; Jørgensen, Christian

2014-01-01

Climate change influences the marine environment, with ocean warming being the foremost driving factor governing changes in the physiology and ecology of fish. At the individual level, increasing temperature influences bioenergetics and numerous physiological and life-history processes, which have consequences for the population level and beyond. We provide a state-dependent energy allocation model that predicts temperature-induced adaptations for life histories and behaviour for the North-East Arctic stock (NEA) of Atlantic cod (Gadus morhua) in response to climate warming. The key constraint is temperature-dependent respiratory physiology, and the model includes a number of trade-offs that reflect key physiological and ecological processes. Dynamic programming is used to find an evolutionarily optimal strategy of foraging and energy allocation that maximizes expected lifetime reproductive output given constraints from physiology and ecology. The optimal strategy is then simulated in a population, where survival, foraging behaviour, growth, maturation and reproduction emerge. Using current forcing, the model reproduces patterns of growth, size-at-age, maturation, gonad production and natural mortality for NEA cod. The predicted climate responses are positive for this stock; under a 2°C warming, the model predicted increased growth rates and a larger asymptotic size. Maturation age was unaffected, but gonad weight was predicted to more than double. Predictions for a wider range of temperatures, from 2 to 7°C, show that temperature responses were gradual; fish were predicted to grow faster and increase reproductive investment at higher temperatures. An emergent pattern of higher risk acceptance and increased foraging behaviour was also predicted. Our results provide important insight into the effects of climate warming on NEA cod by revealing the underlying mechanisms and drivers of change. We show how temperature-induced adaptations of behaviour and several life-history traits are not only mediated by physiology but also by trade-offs with survival, which has consequences for conservation physiology.

Climate warming causes life-history evolution in a model for Atlantic cod (Gadus morhua)

PubMed Central

Holt, Rebecca E.; Jørgensen, Christian

2014-01-01

Climate change influences the marine environment, with ocean warming being the foremost driving factor governing changes in the physiology and ecology of fish. At the individual level, increasing temperature influences bioenergetics and numerous physiological and life-history processes, which have consequences for the population level and beyond. We provide a state-dependent energy allocation model that predicts temperature-induced adaptations for life histories and behaviour for the North-East Arctic stock (NEA) of Atlantic cod (Gadus morhua) in response to climate warming. The key constraint is temperature-dependent respiratory physiology, and the model includes a number of trade-offs that reflect key physiological and ecological processes. Dynamic programming is used to find an evolutionarily optimal strategy of foraging and energy allocation that maximizes expected lifetime reproductive output given constraints from physiology and ecology. The optimal strategy is then simulated in a population, where survival, foraging behaviour, growth, maturation and reproduction emerge. Using current forcing, the model reproduces patterns of growth, size-at-age, maturation, gonad production and natural mortality for NEA cod. The predicted climate responses are positive for this stock; under a 2°C warming, the model predicted increased growth rates and a larger asymptotic size. Maturation age was unaffected, but gonad weight was predicted to more than double. Predictions for a wider range of temperatures, from 2 to 7°C, show that temperature responses were gradual; fish were predicted to grow faster and increase reproductive investment at higher temperatures. An emergent pattern of higher risk acceptance and increased foraging behaviour was also predicted. Our results provide important insight into the effects of climate warming on NEA cod by revealing the underlying mechanisms and drivers of change. We show how temperature-induced adaptations of behaviour and several life-history traits are not only mediated by physiology but also by trade-offs with survival, which has consequences for conservation physiology. PMID:27293671

Heat transfer and vascular cambium necrosis in the boles of trees during surface fires

Treesearch

M. B. Dickinson

2002-01-01

Heat-transfer and cell-survival models are used to link surface fire behavior with vascular cambium necrosis from heating by flames. Vascular cambium cell survival was predicted with a numerical model based on the kinetics of protein denaturation and parameterized with data from the literature. Cell survival was predicted for vascular cambium temperature regimes...

A quantitative study of shape descriptors from glioblastoma multiforme phenotypes for predicting survival outcome

PubMed Central

Desrosiers, Christian; Hassan, Lama; Tanougast, Camel

2016-01-01

Objective: Predicting the survival outcome of patients with glioblastoma multiforme (GBM) is of key importance to clinicians for selecting the optimal course of treatment. The goal of this study was to evaluate the usefulness of geometric shape features, extracted from MR images, as a potential non-invasive way to characterize GBM tumours and predict the overall survival times of patients with GBM. Methods: The data of 40 patients with GBM were obtained from the Cancer Genome Atlas and Cancer Imaging Archive. The T1 weighted post-contrast and fluid-attenuated inversion-recovery volumes of patients were co-registered and segmented into delineate regions corresponding to three GBM phenotypes: necrosis, active tumour and oedema/invasion. A set of two-dimensional shape features were then extracted slicewise from each phenotype region and combined over slices to describe the three-dimensional shape of these phenotypes. Thereafter, a Kruskal–Wallis test was employed to identify shape features with significantly different distributions across phenotypes. Moreover, a Kaplan–Meier analysis was performed to find features strongly associated with GBM survival. Finally, a multivariate analysis based on the random forest model was used for predicting the survival group of patients with GBM. Results: Our analysis using the Kruskal–Wallis test showed that all but one shape feature had statistically significant differences across phenotypes, with p-value < 0.05, following Holm–Bonferroni correction, justifying the analysis of GBM tumour shapes on a per-phenotype basis. Furthermore, the survival analysis based on the Kaplan–Meier estimator identified three features derived from necrotic regions (i.e. Eccentricity, Extent and Solidity) that were significantly correlated with overall survival (corrected p-value < 0.05; hazard ratios between 1.68 and 1.87). In the multivariate analysis, features from necrotic regions gave the highest accuracy in predicting the survival group of patients, with a mean area under the receiver-operating characteristic curve (AUC) of 63.85%. Combining the features of all three phenotypes increased the mean AUC to 66.99%, suggesting that shape features from different phenotypes can be used in a synergic manner to predict GBM survival. Conclusion: Results show that shape features, in particular those extracted from necrotic regions, can be used effectively to characterize GBM tumours and predict the overall survival of patients with GBM. Advances in knowledge: Simple volumetric features have been largely used to characterize the different phenotypes of a GBM tumour (i.e. active tumour, oedema and necrosis). This study extends previous work by considering a wide range of shape features, extracted in different phenotypes, for the prediction of survival in patients with GBM. PMID:27781499

The obesity paradox in elderly patients with heart failure: analysis of nutritional status.

PubMed

Casas-Vara, Antonio; Santolaria, Francisco; Fernández-Bereciartúa, Ainhoa; González-Reimers, Emilio; García-Ochoa, Alfonso; Martínez-Riera, Antonio

2012-06-01

The obesity paradox refers to the improved survival of obese compared with non-obese elderly or diseased patients for reasons that are not clear. To assess the relative roles of fat and other factors in this improved survival, we analyzed the prognostic value of overweight and obesity elderly patients with heart failure (HF), controlling for other nutritional data such as midarm anthropometrics, serum proteins, and muscle strength. Two hundred forty-four patients (83.2 ± 0.5 y old) hospitalized for HF were included. A nutritional survey was performed in all patients. After discharge, the patients were followed up by telephone. Fourteen patients (5.7%) died during hospitalization. The median survival was 984 d. Patients with better nutritional status as assessed by the body mass index (BMI), subjective score, midarm muscle area, triceps skinfold thickness, handgrip, lymphocyte count, and serum albumin, prealbumin, and cholesterol levels showed better short- and long-term prognoses. Obese patients with a BMI above 30 kg/m(2) showed a better long-term prognosis than those with a BMI from 25 to 30 kg/m(2), those with a BMI from 20 to 25 kg/m(2), and those with a BMI lower than 20 kg/m(2). However, survival was not significantly related to a triceps skinfold thickness above the 95th percentile. Obese and overweight patients were younger and had better a nutritional status than those with a normal or decreased BMI as shown by the anthropometrics, subjective score, handgrip, lymphocyte count, hemoglobin, and serum albumin, prealbumin, and cholesterol levels. All the nutritional data correlated closely with each other. New York Heart Association class also correlated with nutrition-derived data: as the HF class increased, the nutritional status deteriorated. On multivariate analysis, to predict long-term survival, neither BMI nor triceps skinfold thickness showed an independent predictive value, whereas a larger midarm muscle area did. The obesity paradox was confirmed in this series of elderly patients with HF. Those with a high BMI and improved survival had a better nutritional status and New York Heart Association functional class than those with a lower BMI, which may explain the differences in survival. Copyright © 2012 Elsevier Inc. All rights reserved.

Influence of soil texture, moisture, and surface cracks on the performance of a root-feeding flea beetle, Longitarsus bethae (Coleoptera: Chrysomelidae), a biological control agent for Lantana camara (Verbenaceae).

PubMed

Simelane, David O

2007-06-01

Laboratory studies were conducted to determine the influence of soil texture, moisture and surface cracks on adult preference and survival of the root-feeding flea beetle, Longitarsus bethae Savini and Escalona (Coleoptera: Chrysomelidae), a natural enemy of the weed, Lantana camara L. (Verbenaceae). Adult feeding, oviposition preference, and survival of the immature stages of L. bethae were examined at four soil textures (clayey, silty loam, sandy loam, and sandy soil), three soil moisture levels (low, moderate, and high), and two soil surface conditions (with or without surface cracks). Both soil texture and moisture had no influence on leaf feeding and colonization by adult L. bethae. Soil texture had a significant influence on oviposition, with adults preferring to lay on clayey and sandy soils to silty or sandy loam soils. However, survival to adulthood was significantly higher in clayey soils than in other soil textures. There was a tendency for females to deposit more eggs at greater depth in both clayey and sandy soils than in other soil textures. Although oviposition preference and depth of oviposition were not influenced by soil moisture, survival in moderately moist soils was significantly higher than in other moisture levels. Development of immature stages in high soil moisture levels was significantly slower than in other soil moisture levels. There were no variations in the body size of beetles that emerged from different soil textures and moisture levels. Females laid almost three times more eggs on cracked than on noncracked soils. It is predicted that clayey and moderately moist soils will favor the survival of L. bethae, and under these conditions, damage to the roots is likely to be high. This information will aid in the selection of suitable release sites where L. bethae would be most likely to become established.

[The survival prediction model of advanced gallbladder cancer based on Bayesian network: a multi-institutional study].

PubMed

Tang, Z H; Geng, Z M; Chen, C; Si, S B; Cai, Z Q; Song, T Q; Gong, P; Jiang, L; Qiu, Y H; He, Y; Zhai, W L; Li, S P; Zhang, Y C; Yang, Y

2018-05-01

Objective: To investigate the clinical value of Bayesian network in predicting survival of patients with advanced gallbladder cancer(GBC)who underwent curative intent surgery. Methods: The clinical data of patients with advanced GBC who underwent curative intent surgery in 9 institutions from January 2010 to December 2015 were analyzed retrospectively.A median survival time model based on a tree augmented naïve Bayes algorithm was established by Bayesia Lab software.The survival time, number of metastatic lymph nodes(NMLN), T stage, pathological grade, margin, jaundice, liver invasion, age, sex and tumor morphology were included in this model.Confusion matrix, the receiver operating characteristic curve and area under the curve were used to evaluate the accuracy of the model.A priori statistical analysis of these 10 variables and a posterior analysis(survival time as the target variable, the remaining factors as the attribute variables)was performed.The importance rankings of each variable was calculated with the polymorphic Birnbaum importance calculation based on the posterior analysis results.The survival probability forecast table was constructed based on the top 4 prognosis factors. The survival curve was drawn by the Kaplan-Meier method, and differences in survival curves were compared using the Log-rank test. Results: A total of 316 patients were enrolled, including 109 males and 207 females.The ratio of male to female was 1.0∶1.9, the age was (62.0±10.8)years.There was 298 cases(94.3%) R0 resection and 18 cases(5.7%) R1 resection.T staging: 287 cases(90.8%) T3 and 29 cases(9.2%) T4.The median survival time(MST) was 23.77 months, and the 1, 3, 5-year survival rates were 67.4%, 40.8%, 32.0%, respectively.For the Bayesian model, the number of correctly predicted cases was 121(≤23.77 months) and 115(>23.77 months) respectively, leading to a 74.86% accuracy of this model.The prior probability of survival time was 0.503 2(≤23.77 months) and 0.496 8(>23.77 months), the importance ranking showed that NMLN(0.366 6), margin(0.350 1), T stage(0.319 2) and pathological grade(0.258 9) were the top 4 prognosis factors influencing the postoperative MST.These four factors were taken as observation variables to get the probability of patients in different survival periods.Basing on these results, a survival prediction score system including NMLN, margin, T stage and pathological grade was designed, the median survival time(month) of 4-9 points were 66.8, 42.4, 26.0, 9.0, 7.5 and 2.3, respectively, there was a statistically significant difference in the different points( P <0.01). Conclusions: The survival prediction model of GBC based on Bayesian network has high accuracy.NMLN, margin, T staging and pathological grade are the top 4 risk factors affecting the survival of patients with advanced GBC who underwent curative resection.The survival prediction score system based on these four factors could be used to predict the survival and to guide the decision making of patients with advanced GBC.

AR-V7 in circulating tumor cells cluster as a predictive biomarker of abiraterone acetate and enzalutamide treatment in castration-resistant prostate cancer patients.

PubMed

Okegawa, Takatsugu; Ninomiya, Naoki; Masuda, Kazuki; Nakamura, Yu; Tambo, Mitsuhiro; Nutahara, Kikuo

2018-06-01

We examined whether androgen receptor splice variant 7 (AR-V7) in circulating tumor cell(CTC)clusters can be used to predict survival in patients with bone metastatic castration resistant-prostate cancer (mCRPC) treated with abiraterone or enzalutamide. We retrospectively enrolled 98 patients with CRPC on abiraterone or enzalutamide, and investigated the prognostic value of CTC cluster detection (+ v -) and AR-V7 detection (+ v -) using a CTC cluster detection - based AR-V7 mRNA assay. We examined ≤50% prostate-specific antigen (PSA) responses, PSA progression-free survival (PSA-PFS), clinical and radiological progression-free survival (radiologic PSF), and overall survival (OS). We then assessed whether AR-V7 expression in CTC clusters identified after On-chip multi-imaging flow cytometry was related to disease progression and survival after first-line systemic therapy. All abiraterone-treated or enzalutamide-treated patients received prior docetaxel. The median follow-up was 20.7 (range: 3.0-37.0) months in the abiraterone and enzalutamide cohorts, respectively. Forty-nine of the 98 men (50.0%) were CTC cluster (-), 23 of the 98 men (23.5%) were CTC cluster(+)/AR-V7(-), and 26 of the 98 men (26.5%) were CTC cluster(+)/AR-V7(+). CTC cluster(+)/AR-V7(+) patients were more likely to have EOD ≥3 at diagnosis (P = 0.003), pain (P = 0.023), higher alkaline phosphatase levels (P < 0.001), and visceral metastases (P < 0.001). On multivariable analysis, pretherapy CTC cluster(+), CTC cluster(+)/AR-V7(-), and ALP >UNL were independently associated with a poor PSA-PFS, radiographic PFS, and OS in abiraterone-treated patients and enzalutamide-treated patients. The CTC clusters and AR-V7-positive CTC clusters detected were important for assessing the response to abiraterone or enzalutamide therapy and for predicting disease outcome. © 2018 Wiley Periodicals, Inc.

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 arrhythmias.

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

PubMed

Lee, E S; Jung, S Y; Kim, J Y; Kim, J J; Yoo, T K; Kim, Y G; Lee, K S; Lee, E S; Kim, E K; Min, J W; Han, W; Noh, D Y; Moon, H G

2016-05-01

We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment.

PubMed

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

2015-08-01

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. Prospective cohort study from December 4, 2011, to April 7, 2013. General and cardiac/cardiovascular PICUs at seven sites. Randomly selected PICU patients from their first PICU admission. None. Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale and defined as an increase of ≥ 3 from preillness to hospital discharge) were 4.6% (site range, 2.6-7.7%) 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 Pediatric Risk of Mortality III score) in dichotomous (survival and death) and trichotomous (survival without new morbidity, survival with new morbidity, and death) models without covariate adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality III scores and then decreased at the highest Pediatric Risk of Mortality III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline Functional Status Scale, and the Pediatric Risk of Mortality 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 was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (vs chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios. 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 for research studies and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality.

Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression

PubMed Central

Kim, Sun-Hee; Hashimoto, Yuuri; Cho, Sung-Nam; Roszik, Jason; Milton, Denái R.; Dal, Fulya; Kim, Sangwon F.; Menter, David G.; Yang, Peiying; Ekmekcioglu, Suhendan; Grimm, Elizabeth A.

2016-01-01

Summary COX-2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase-1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS-mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy. PMID:26801201

Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

PubMed

O'Leary, Ben; Hrebien, Sarah; Morden, James P; Beaney, Matthew; Fribbens, Charlotte; Huang, Xin; Liu, Yuan; Bartlett, Cynthia Huang; Koehler, Maria; Cristofanilli, Massimo; Garcia-Murillas, Isaac; Bliss, Judith M; Turner, Nicholas C

2018-03-01

CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

Significance of Onodera's prognostic nutritional index in patients with colorectal cancer: a large cohort study in a single Chinese institution.

PubMed

Jian-Hui, Chen; Iskandar, Edward Arthur; Cai, Sh-Irong; Chen, Chuang-Qi; Wu, Hui; Xu, Jian-Bo; He, Yu-Long

2016-03-01

The preoperative nutritional and immunological statuses have an important impact in predicting the survival outcome of patients with various types of malignant tumors. Our study aimed to explore the clinical significance and predictive prognostic potential of Onodera's prognostic nutritional index (PNI) in patients with colorectal carcinoma. This retrospective study included a total of 1321 patients who were diagnosed with colorectal cancer and who had been surgically treated between January 1994 and December 2007. The PNI level was determined according the following formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm(3)). The impact of PNI on clinicopathological features and overall survival (OS) was determined. The optimal cutoff value of PNI was set at 45. Patients in the low-PNI group had a greater potential to have aggressive histological features, advanced tumors (T), nodal involvement (N), metastasis (M), and TNM stage than those in the high-PNI group. The low-PNI group had a worse OS than the high-PNI group (5-year survival rate 56.1 vs 64.8 %, respectively; P < 0.05). Furthermore, the PNI value was an independent prognostic factor for colorectal cancer in this study. The OS was significantly lower in the low-PNI group than in the high-PNI group in patients with TNM stage II and III diseases. Preoperative PNI is a simple and useful marker to predict clinicopathological features and long-term survival outcome in patients with colorectal carcinoma. PNI analysis should be included in the routine assessment of patients with locally advanced colorectal cancer.

Mutation supply and the repeatability of selection for antibiotic resistance

NASA Astrophysics Data System (ADS)

van Dijk, Thomas; Hwang, Sungmin; Krug, Joachim; de Visser, J. Arjan G. M.; Zwart, Mark P.

2017-10-01

Whether evolution can be predicted is a key question in evolutionary biology. Here we set out to better understand the repeatability of evolution, which is a necessary condition for predictability. We explored experimentally the effect of mutation supply and the strength of selective pressure on the repeatability of selection from standing genetic variation. Different sizes of mutant libraries of antibiotic resistance gene TEM-1 β-lactamase in Escherichia coli, generated by error-prone PCR, were subjected to different antibiotic concentrations. We determined whether populations went extinct or survived, and sequenced the TEM gene of the surviving populations. The distribution of mutations per allele in our mutant libraries followed a Poisson distribution. Extinction patterns could be explained by a simple stochastic model that assumed the sampling of beneficial mutations was key for survival. In most surviving populations, alleles containing at least one known large-effect beneficial mutation were present. These genotype data also support a model which only invokes sampling effects to describe the occurrence of alleles containing large-effect driver mutations. Hence, evolution is largely predictable given cursory knowledge of mutational fitness effects, the mutation rate and population size. There were no clear trends in the repeatability of selected mutants when we considered all mutations present. However, when only known large-effect mutations were considered, the outcome of selection is less repeatable for large libraries, in contrast to expectations. We show experimentally that alleles carrying multiple mutations selected from large libraries confer higher resistance levels relative to alleles with only a known large-effect mutation, suggesting that the scarcity of high-resistance alleles carrying multiple mutations may contribute to the decrease in repeatability at large library sizes.

Empirical study of the dependence of the results of multivariable flexible survival analyses on model selection strategy.

PubMed

Binquet, C; Abrahamowicz, M; Mahboubi, A; Jooste, V; Faivre, J; Bonithon-Kopp, C; Quantin, C

2008-12-30

Flexible survival models, which avoid assumptions about hazards proportionality (PH) or linearity of continuous covariates effects, bring the issues of model selection to a new level of complexity. Each 'candidate covariate' requires inter-dependent decisions regarding (i) its inclusion in the model, and representation of its effects on the log hazard as (ii) either constant over time or time-dependent (TD) and, for continuous covariates, (iii) either loglinear or non-loglinear (NL). Moreover, 'optimal' decisions for one covariate depend on the decisions regarding others. Thus, some efficient model-building strategy is necessary.We carried out an empirical study of the impact of the model selection strategy on the estimates obtained in flexible multivariable survival analyses of prognostic factors for mortality in 273 gastric cancer patients. We used 10 different strategies to select alternative multivariable parametric as well as spline-based models, allowing flexible modeling of non-parametric (TD and/or NL) effects. We employed 5-fold cross-validation to compare the predictive ability of alternative models.All flexible models indicated significant non-linearity and changes over time in the effect of age at diagnosis. Conventional 'parametric' models suggested the lack of period effect, whereas more flexible strategies indicated a significant NL effect. Cross-validation confirmed that flexible models predicted better mortality. The resulting differences in the 'final model' selected by various strategies had also impact on the risk prediction for individual subjects.Overall, our analyses underline (a) the importance of accounting for significant non-parametric effects of covariates and (b) the need for developing accurate model selection strategies for flexible survival analyses. Copyright 2008 John Wiley & Sons, Ltd.

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

PubMed

Smith, Brian J; Mezhir, James J

2014-10-01

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

DCE-MRI as a predictor of clinical outcome in canine spontaneous soft-tissue sarcomas treated with thermoradiotherapy

PubMed Central

Viglianti, BL; Lora-Michiels, M; Poulson, JM; Lan, Lan; Yu, D; Sanders, L; Craciunescu, O; Vujaskovic, Z; Thrall, DE; MacFall, J; Charles, HC; Wong, T; Dewhirst, MW

2009-01-01

Purpose This study tests whether DCE-MRI parameters obtained from canine patients with soft tissue sarcomas, treated with hyperthermia and radiotherapy, are predictive of therapeutic outcome. Experimental Design 37 dogs with soft tissue sarcomas had DCE-MRI performed prior to and following the first hyperthermia. Signal enhancement for tumor and reference muscle were fitted empirically, yielding a washin/washout rate for the contrast agent, tumor AUC calculated from 0 to 60s, 90s, and the time of maximal enhancement in the reference muscle. These parameters were then compared to local tumor control, metastasis free survival, and overall survival. Results Pre-therapy rate of contrast agent washout was positively predictive of improved overall survival and metastasis free survival with hazard ratio of 0.67 (p = 0.015) and 0.68 (p = 0.012) respectively. After the first hyperthermia washin rate, AUC60, AUC90, and AUCt-max, were predictive of improved overall survivaloverall survival and metastasis free survival with hazard ratio ranging from 0.46 to 0.53 (p < 0.002) and 0.44 to 0.55 (p < 0.004), respectively. DCE-MRI parameters were compared with extracellular pH and 31-P-MR spectroscopy results (previously published) in the same patients demonstrating a correlation. This suggested that an increase in perfusion after therapy was effective in eliminating excess acid from the tumor. Conclusions This study demonstrates that DCE-MRI has utility predicting overall survivaloverall survival and metastasis free survival in canine patients with soft tissue sarcomas. To our knowledge, this is the first time that DCE-MRI parameters have been shown to be predictive of clinical outcome for soft tissue sarcomas. PMID:19622579

Comparisons of survival predictions using survival risk ratios based on International Classification of Diseases, Ninth Revision and Abbreviated Injury Scale trauma diagnosis codes.

PubMed

Clarke, John R; Ragone, Andrew V; Greenwald, Lloyd

2005-09-01

We conducted a comparison of methods for predicting survival using survival risk ratios (SRRs), including new comparisons based on International Classification of Diseases, Ninth Revision (ICD-9) versus Abbreviated Injury Scale (AIS) six-digit codes. From the Pennsylvania trauma center's registry, all direct trauma admissions were collected through June 22, 1999. Patients with no comorbid medical diagnoses and both ICD-9 and AIS injury codes were used for comparisons based on a single set of data. SRRs for ICD-9 and then for AIS diagnostic codes were each calculated two ways: from the survival rate of patients with each diagnosis and when each diagnosis was an isolated diagnosis. Probabilities of survival for the cohort were calculated using each set of SRRs by the multiplicative ICISS method and, where appropriate, the minimum SRR method. These prediction sets were then internally validated against actual survival by the Hosmer-Lemeshow goodness-of-fit statistic. The 41,364 patients had 1,224 different ICD-9 injury diagnoses in 32,261 combinations and 1,263 corresponding AIS injury diagnoses in 31,755 combinations, ranging from 1 to 27 injuries per patient. All conventional ICD-9-based combinations of SRRs and methods had better Hosmer-Lemeshow goodness-of-fit statistic fits than their AIS-based counterparts. The minimum SRR method produced better calibration than the multiplicative methods, presumably because it did not magnify inaccuracies in the SRRs that might occur with multiplication. Predictions of survival based on anatomic injury alone can be performed using ICD-9 codes, with no advantage from extra coding of AIS diagnoses. Predictions based on the single worst SRR were closer to actual outcomes than those based on multiplying SRRs.

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

PubMed

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

2016-01-01

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

Social Relationships, Inflammation, and Cancer Survival.

PubMed

Boen, Courtney E; Barrow, David A; Bensen, Jeannette T; Farnan, Laura; Gerstel, Adrian; Hendrix, Laura H; Yang, Yang Claire

2018-05-01

Background: Social stressors, such as social relationship deficits, have been increasingly linked to chronic disease outcomes, including cancer. However, critical gaps exist in our understanding of the nature and strength of such links, as well as the underlying biological mechanisms relating social relationships to cancer progression and survival. Methods: Utilizing novel questionnaire and biomarker data from the UNC Health Registry/Cancer Survivorship Cohort, this study examines the associations between diverse measures of social support and mortality risk among individuals with cancer ( N = 1,004). We further assess the role of multiple serum markers of inflammation, including high-sensitivity C-reactive protein (CRP), IL6, TNFα, and VEGF, as potential mediators in the social relationship-cancer link. Results: The findings revealed that one's appraisal of their social support was associated with cancer mortality, such that individuals reporting higher levels of social support satisfaction had lower mortality risk than individuals reporting lower levels of satisfaction. The amount of support received, on the other hand, was not predictive of cancer survival. We further found evidence that inflammatory processes may undergird the link between social support satisfaction and mortality among individuals with cancer, with individuals reporting higher levels of social support satisfaction having lower levels of CRP, IL6, and TNFα. Conclusions: These results provide new knowledge of the biosocial processes producing population disparities in cancer outcomes. Impact: Our study offers new insights for intervention efforts aimed at promoting social connectedness as a means for improving cancer survival. Cancer Epidemiol Biomarkers Prev; 27(5); 541-9. ©2018 AACR . ©2018 American Association for Cancer Research.

Association of Sepsis-Related Mortality with Early Increase of TIMP-1/MMP-9 Ratio

PubMed Central

Lorente, Leonardo; Martín, María M.; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan M.; Orbe, Josune; Rodríguez, José A.; Jiménez, Alejandro; Páramo, José A.

2014-01-01

Objective Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions. Methods Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality. Results We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8. Conclusions The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome. PMID:24727739

Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio.

PubMed

Lorente, Leonardo; Martín, María M; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan M; Orbe, Josune; Rodríguez, José A; Jiménez, Alejandro; Páramo, José A

2014-01-01

Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions. Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality. We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8. The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome.

Predictive Genes in Adjacent Normal Tissue Are Preferentially Altered by sCNV during Tumorigenesis in Liver Cancer and May Rate Limiting

PubMed Central

Lamb, John R.; Zhang, Chunsheng; Xie, Tao; Wang, Kai; Zhang, Bin; Hao, Ke; Chudin, Eugene; Fraser, Hunter B.; Millstein, Joshua; Ferguson, Mark; Suver, Christine; Ivanovska, Irena; Scott, Martin; Philippar, Ulrike; Bansal, Dimple; Zhang, Zhan; Burchard, Julja; Smith, Ryan; Greenawalt, Danielle; Cleary, Michele; Derry, Jonathan; Loboda, Andrey; Watters, James; Poon, Ronnie T. P.; Fan, Sheung T.; Yeung, Chun; Lee, Nikki P. Y.; Guinney, Justin; Molony, Cliona; Emilsson, Valur; Buser-Doepner, Carolyn; Zhu, Jun; Friend, Stephen; Mao, Mao; Shaw, Peter M.; Dai, Hongyue; Luk, John M.; Schadt, Eric E.

2011-01-01

Background In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ∼250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. PMID:21750698

Maximal exercise testing variables and 10-year survival: fitness risk score derivation from the FIT Project.

PubMed

Ahmed, Haitham M; Al-Mallah, Mouaz H; McEvoy, John W; Nasir, Khurram; Blumenthal, Roger S; Jones, Steven R; Brawner, Clinton A; Keteyian, Steven J; Blaha, Michael J

2015-03-01

To determine which routinely collected exercise test variables most strongly correlate with survival and to derive a fitness risk score that can be used to predict 10-year survival. This was a retrospective cohort study of 58,020 adults aged 18 to 96 years who were free of established heart disease and were referred for an exercise stress test from January 1, 1991, through May 31, 2009. Demographic, clinical, exercise, and mortality data were collected on all patients as part of the Henry Ford ExercIse Testing (FIT) Project. Cox proportional hazards models were used to identify exercise test variables most predictive of survival. A "FIT Treadmill Score" was then derived from the β coefficients of the model with the highest survival discrimination. The median age of the 58,020 participants was 53 years (interquartile range, 45-62 years), and 28,201 (49%) were female. Over a median of 10 years (interquartile range, 8-14 years), 6456 patients (11%) died. After age and sex, peak metabolic equivalents of task and percentage of maximum predicted heart rate achieved were most highly predictive of survival (P<.001). Subsequent addition of baseline blood pressure and heart rate, change in vital signs, double product, and risk factor data did not further improve survival discrimination. The FIT Treadmill Score, calculated as [percentage of maximum predicted heart rate + 12(metabolic equivalents of task) - 4(age) + 43 if female], ranged from -200 to 200 across the cohort, was near normally distributed, and was found to be highly predictive of 10-year survival (Harrell C statistic, 0.811). The FIT Treadmill Score is easily attainable from any standard exercise test and translates basic treadmill performance measures into a fitness-related mortality risk score. The FIT Treadmill Score should be validated in external populations. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

A Pilot Study of Circulating MicroRNA-125b as a Diagnostic and Prognostic Biomarker for Epithelial Ovarian Cancer.

PubMed

Zhu, Tao; Gao, Wen; Chen, Xi; Zhang, Ying; Wu, Meijuan; Zhang, Ping; Wang, Shihua

2017-01-01

Early diagnosis of epithelial ovarian cancer is critical for patient survival. The objective of this pilot study is to identify a circulating micro (mi)RNA as a potential biomarker for epithelial ovarian cancer. A total of 135 epithelial ovarian cancer patients and 54 benign ovarian tumor patients were recruited for this study. Using customized TaqMan low density miRNA arrays, we first screened expression levels of 48 miRNAs in sera from 18 epithelial ovarian cancer patients and 16 benign ovarian tumor patients. The most significantly and differentially expressed miRNA was then further examined in all serum samples using real-time polymerase chain reaction. Its expression was further analyzed in relationship with clinicopathological factors and patient survival. Array screening data showed that expression levels of serum miRNA-20a, miRNA-125b, miRNA-126, miRNA-355, and let-7c were significantly different between malignant and benign ovarian tumor patients. Subsequent real-time polymerase chain reaction results showed that serum miRNA-125b levels were significantly higher in epithelial ovarian cancer patients compared to benign controls. Moreover, serum miRNA-125b levels were significantly higher in ovarian cancer patients in early stages I and II, and in patients having no residual tumor following surgery, but were not associated with differentiation and histological types of ovarian cancer. Notably, the higher level of miR-125b was significantly positively correlated with progression-free survival (P = 0.035) and marginally, with overall survival (P = 0.069). miRNA-125b plays an important role in the pathogenesis and progression of epithelial ovarian cancer. Circulating miRNA-125b has the potential to become a novel biomarker for early diagnosis and prognosis prediction of epithelial ovarian cancer.

Symbiont diversity may help coral reefs survive moderate climate change.

PubMed

Baskett, Marissa L; Gaines, Steven D; Nisbet, Roger M

2009-01-01

Given climate change, thermal stress-related mass coral-bleaching events present one of the greatest anthropogenic threats to coral reefs. While corals and their symbiotic algae may respond to future temperatures through genetic adaptation and shifts in community compositions, the climate may change too rapidly for coral response. To test this potential for response, here we develop a model of coral and symbiont ecological dynamics and symbiont evolutionary dynamics. Model results without variation in symbiont thermal tolerance predict coral reef collapse within decades under multiple future climate scenarios, consistent with previous threshold-based predictions. However, model results with genetic or community-level variation in symbiont thermal tolerance can predict coral reef persistence into the next century, provided low enough greenhouse gas emissions occur. Therefore, the level of greenhouse gas emissions will have a significant effect on the future of coral reefs, and accounting for biodiversity and biological dynamics is vital to estimating the size of this effect.

Whole blood FPR1 mRNA expression predicts both non‐small cell and small cell lung cancer

PubMed Central

Vachani, Anil; Pass, Harvey I.; Rom, William N.; Ryden, Kirk; Weiss, Glen J.; Hogarth, D. K.; Runger, George; Richards, Donald; Shelton, Troy; Mallery, David W.

2018-01-01

While long‐term survival rates for early‐stage lung cancer are high, most cases are diagnosed in later stages that can negatively impact survival rates. We aim to design a simple, single biomarker blood test for early‐stage lung cancer that is robust to preclinical variables and can be readily implemented in the clinic. Whole blood was collected in PAXgene tubes from a training set of 29 patients, and a validation set of 260 patients, of which samples from 58 patients were prospectively collected in a clinical trial specifically for our study. After RNA was extracted, the expressions of FPR1 and a reference gene were quantified by an automated one‐step Taqman RT‐PCR assay. Elevated levels of FPR1 mRNA in whole blood predicted lung cancer status with a sensitivity of 55% and a specificity of 87% on all validation specimens. The prospectively collected specimens had a significantly higher 68% sensitivity and 89% specificity. Results from patients with benign nodules were similar to healthy volunteers. No meaningful correlation was present between our test results and any clinical characteristic other than lung cancer diagnosis. FPR1 mRNA levels in whole blood can predict the presence of lung cancer. Using this as a reflex test for positive lung cancer screening computed tomography scans has the potential to increase the positive predictive value. This marker can be easily measured in an automated process utilizing off‐the‐shelf equipment and reagents. Further work is justified to explain the source of this biomarker. PMID:29313979

Predictors of indoor absolute humidity and estimated effects on influenza virus survival in grade schools

PubMed Central

2013-01-01

Background Low absolute humidity (AH) has been associated with increased influenza virus survival and transmissibility and the onset of seasonal influenza outbreaks. Humidification of indoor environments may mitigate viral transmission and may be an important control strategy, particularly in schools where viral transmission is common and contributes to the spread of influenza in communities. However, the variability and predictors of AH in the indoor school environment and the feasibility of classroom humidification to levels that could decrease viral survival have not been studied. Methods Automated sensors were used to measure temperature, humidity and CO2 levels in two Minnesota grade schools without central humidification during two successive winters. Outdoor AH measurements were derived from the North American Land Data Assimilation System. Variability in indoor AH within classrooms, between classrooms in the same school, and between schools was assessed using concordance correlation coefficients (CCC). Predictors of indoor AH were examined using time-series Auto-Regressive Conditional Heteroskedasticity models. Classroom humidifiers were used when school was not in session to assess the feasibility of increasing indoor AH to levels associated with decreased influenza virus survival, as projected from previously published animal experiments. Results AH varied little within classrooms (CCC >0.90) but was more variable between classrooms in the same school (CCC 0.81 for School 1, 0.88 for School 2) and between schools (CCC 0.81). Indoor AH varied widely during the winter (range 2.60 to 10.34 millibars [mb]) and was strongly associated with changes in outdoor AH (p < 0.001). Changes in indoor AH on school weekdays were strongly associated with CO2 levels (p < 0.001). Over 4 hours, classroom humidifiers increased indoor AH by 4 mb, an increase sufficient to decrease projected 1-hour virus survival by an absolute value of 30% during winter months. Conclusions During winter, indoor AH in non-humidified grade schools varies substantially and often to levels that are very low. Indoor results are predicted by outdoor AH over a season and CO2 levels (which likely reflects human activity) during individual school days. Classroom humidification may be a feasible approach to increase indoor AH to levels that may decrease influenza virus survival and transmission. PMID:23383620

Relationship of plasma cell-free DNA level with mortality and prognosis in patients with Crimean-Congo hemorrhagic fever.

PubMed

Bakir, Mehmet; Engin, Aynur; Kuskucu, Mert Ahmet; Bakir, Sevtap; Gündag, Omür; Midilli, Kenan

2016-07-01

Crimean-Congo hemorrhagic fever (CCHF) is a viral infection. Circulating plasma cell-free DNA (pcf-DNA) is a novel marker indicating cellular damage. So far, the role of pcf-DNA did not investigate in CCHF patients. In the current study, pcf-DNA levels were investigated in CCHF patients with different clinical severity grades to explore the relationship between circulating pcf-DNA level, virus load, and disease severity. Seventy-two patients were categorized as mild, intermediate, and severe based on severity grading scores. The pcf-DNA level was obtained from all participants on admission and from the survivors on the day of the discharge. The controls consisted of 31 healthy. Although the pcf-DNA level at admission was higher in patients than in the controls, the difference was not statistically significant (P = 0.291). However, at admission and in the convalescent period, the difference between pcf-DNA levels in mild, intermediate, and severe patient groups was significant. The pcf-DNA level in severe patients was higher than in the others. Furthermore, compared to survivors, non-survivors had higher pcf-DNA levels at admission (P = 0.001). A direct relationship was found between the pcf-DNA level and the viral load on the day of discharge in surviving patients. ROC curve analysis identified a pcf-DNA level of 0.42 as the optimal cut-off for prediction of mortality. The positive predictive value, negative predictive value, specificity, and sensitivity for predicting mortality was 100%, 72%, 100%, and 79%, respectively. In summary, our findings revealed that pcf-DNA levels may be used as a biomarker in predicting CHHF prognosis. © 2015 Wiley Periodicals, Inc.

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

PubMed Central

Tsao, May N.; Rades, Dirk; Wirth, Andrew; Lo, Simon S.; Danielson, Brita L.; Gaspar, Laurie E.; Sperduto, Paul W.; Vogelbaum, Michael A.; Radawski, Jeffrey D.; Wang, Jian Z.; Gillin, Michael T.; Mohideen, Najeeb; Hahn, Carol A.; Chang, Eric L.

2012-01-01

Purpose To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Conclusions Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone). PMID:25925626

Prediction of postnatal outcomes in fetuses with isolated congenital diaphragmatic hernias using different lung-to-head ratio measurements.

PubMed

Kehl, Sven; Siemer, Jörn; Brunnemer, Suna; Weiss, Christel; Eckert, Sven; Schaible, Thomas; Sütterlin, Marc

2014-05-01

The purpose of this study was to compare different methods for measuring the fetal lung area-to-head circumference ratio and to investigate their prediction of postpartum survival and the need for neonatal extracorporeal membrane oxygenation (ECMO) therapy in fetuses with isolated congenital diaphragmatic hernias. This prospective study included 118 fetuses of at least 20 weeks' gestation with isolated left-sided congenital diaphragmatic hernias. The lung-to-head ratio was measured with 3 different methods (longest diameter, anteroposterior diameter, and tracing). To eliminate the influence of gestational age, the observed-to-expected lung-to-head ratio was calculated. Receiver operating characteristic (ROC) curves were calculated for the statistical prediction of survival and need for ECMO therapy by the observed-to-expected lung-to-head ratio measured with the different methods. For survival and ECMO necessity 118 and 102 cases (16 neonates were not eligible for ECMO) were assessed, respectively. For prediction of postpartum survival and ECMO necessity, the areas under the ROC curves and 95% confidence intervals showed very similar results for the 3 methods for prediction of survival (tracing, 0.8445 [0.7553-0.9336]; longest diameter, 0.8248 [0.7360-0.9136]; and anteroposterior diameter, 0.8002 [0.7075-0.8928]) and for ECMO necessity (tracing, 0.7344 [0.6297-0.8391]; longest diameter, 0.7128 [0.6027-0.8228]; and anteroposterior diameter, 0.7212 [0.6142-0.8281]). Comparisons between the areas under the ROC curves showed that the tracing method was superior to the anteroposterior diameter method in predicting postpartum survival (P = .0300). Lung-to-head ratio and observed-to-expected lung-to-head ratio measurements were shown to accurately predict postnatal survival and the need for ECMO therapy in fetuses with left-sided congenital diaphragmatic hernias. Tracing the limits of the lungs seems to be the favorable method for calculating the fetal lung area.

L-Dopa decarboxylase (DDC) constitutes an emerging biomarker in predicting patients' survival with stomach adenocarcinomas.

PubMed

Florou, Dimitra; Papadopoulos, Iordanis N; Fragoulis, Emmanuel G; Scorilas, Andreas

2013-02-01

Stomach adenocarcinoma represents a major health problem and is regarded as the second commonest cause of cancer-associated mortality, universally, since it is still difficult to be perceived at a curable stage. Several lines of evidence have pointed out that the expression of L-Dopa decarboxylase (DDC) gene and/or protein becomes distinctively modulated in several human neuroendocrine neoplasms as well as adenocarcinomas. In order to elucidate the clinical role of DDC on primary gastric adenocarcinomas, we determined qualitatively and quantitatively the mRNA levels of the gene with regular PCR and real-time PCR by using the comparative threshold cycle method, correspondingly, and detected the expression of DDC protein by immunoblotting in cancerous and normal stomach tissue specimens. A statistically significant association was disclosed between DDC expression and gastric intestinal histotype as well as tumor localization at the distal third part of the stomach (p = 0.025 and p = 0.029, respectively). Univariate and multivariate analyses highlighted the powerful prognostic importance of DDC in relation to disease-free survival and overall survival of gastric cancer patients. According to Kaplan-Meier curves, the relative risk of relapse was found to be decreased in DDC-positive (p = 0.031) patients who, also, exhibited higher overall survival rates (p = 0.016) than those with DDC-negative tumors. This work is the first to shed light on the potential clinical usefulness of DDC, as an efficient tumor biomarker in gastric cancer. The provided evidence underlines the propitious predictive value of DDC expression in the survival of stomach adenocarcinoma patients.

Mortality-related Factors in Patients with Malignant Obstructive Jaundice.

PubMed

Kurniawan, Juferdy; Hasan, Irsan; Gani, Rino Alvani; Simadibrata, Marcellus

2016-10-01

to obtain survival rate and mortality-related factors of malignant obstructive jaundice patients. all medical records of obstructive jaundice inpatient at Cipto Mangunkusumo Hospital, Jakarta from January 2010 to December 2013 were reviewed retrospectively. The following factors were analyzed in terms of mortality: age, gender, sepsis, hypoalbumin, serum bilirubin level, serum CA 19-9 level, billiary drainage, non-ampulla Vateri carcinoma, and comorbid factors. total 181 out of 402 patients were enrolled in this study with male proportion was 58.6%, and patients aged 50 years or above was 57.5%. Multivariate analysis showed that only sepsis, unsuccessful or no prior biliary drainage and Charlson comorbid score ≥4 were independent predictors of mortality. Patients with significant prognostic factors had median survival 14 days compared with overall median survival 26 days. Score ≥2 identified as the highest prognostic score threshold with sensitivity 68%, specificity 75%, and AUC on ROC curve 0.769. sepsis, unsuccessful or no prior bilirary drainage, and Charlson comorbid score ≥4 are factors significantly associated with shortened survival in malignant obstructive jaundice patients. Prognostic score  ≥2 was determined to classify patients into high risk mortality group. Mortality of patients with those significant prognostic factors can be predicted in 76.9%.

T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases.

PubMed

Katz, Steven C; Donkor, Charan; Glasgow, Kristen; Pillarisetty, Venu G; Gönen, Mithat; Espat, N Joseph; Klimstra, David S; D'Angelica, Michael I; Allen, Peter J; Jarnagin, William; Dematteo, Ronald P; Brennan, Murray F; Tang, Laura H

2010-12-01

Tumour-infiltrating lymphocytes (TILs) have been shown to predict survival in numerous malignancies. The importance of TILs in primary pancreatic neuroendocrine tumours (NETs) and NET liver metastases (NETLMs) has not been defined. We identified 87 patients with NETs and 39 with NETLMs who had undergone resection. Immunohistochemistry was performed to determine TIL counts. Recurrence-free survival (RFS) and overall survival (OS) were determined using the log-rank test. The median follow-up time was 62 months in NET patients and 48 months in NETLM patients. Vascular invasion and histologic grade were the only independent predictors of outcome for NETs and NETLMs, respectively. Analysis of intermediate-grade NETs indicated that a dense T cell (CD3+) infiltrate was associated with a median RFS of 128 months compared with 61 months for those with low levels of intratumoral T cells (P= 0.05, univariate analysis). Examination of NETLMs revealed that a low level of infiltrating regulatory T cells (Treg, FoxP3+) was a predictor of prolonged survival (P < 0.01, univariate analysis). A robust T cell infiltrate is associated with improved RFS following resection of intermediate-grade NETs, whereas the presence of more Treg correlated with shorter OS after treatment of NETLMs. Further study of the immune response to intermediate-grade NETs and NETLMs is warranted.

Proteomic Analysis of Cytokeratin Isoforms Uncovers Association with Survival in Lung Adenocarcinoma1

PubMed Central

Gharib, Tarek G.; Chen, Guoan; Wang, Hong; Huang, Chiang-Ching; Prescott, Michael S.; Shedden, Kerby; Misek, David E.; Thomas, Dafydd G.; Giordano, Thomas J.; Taylor, Jeremy M.G.; Kardia, Sharon; Yee, John; Orringer, Mark B.; Hanash, Samir; Beer, David G.

2002-01-01

Abstract Cytokeratins (CK) are intermediate filaments whose expression is often altered in epithelial cancer. Systematic identification of lung adenocarcinoma proteins using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry has uncovered numerous CK isoforms. In this study, 93 lung adenocarcinomas (64 stage I and 29 stage III) and 10 uninvolved lung samples were quantitatively examined for protein expression. Fourteen of 21 isoforms of CK 7, 8, 18, and 19 occurred at significantly higher levels (P<.05) in tumors compared to uninvolved adjacent tissue. Specific isoforms of the four types of CK identified correlated with either clinical outcome or individual clinical-pathological parameters. All five of the CK7 isoforms associated with patient survival represented cleavage products. Two of five CK7 isoforms (nos. 2165 and 2091), one of eight CK8 isoforms (no. 439), and one of three CK19 isoforms (no. 1955) were associated with survival and significantly correlated to their mRNA levels, suggesting that transcription underlies overexpression of these CK isoforms. Our data indicate substantial heterogeneity among CK in lung adenocarcinomas resulting from posttranslational modifications, some of which correlated with patient survival and other clinical parameters. Therefore, specific isoforms of individual CK may have utility as diagnostic or predictive markers in lung adenocarcinomas. PMID:12192603

The Effect of Elevated CO2 and Temperature on the Hatch Rate and Survival of Estuarine Forage Fish

NASA Astrophysics Data System (ADS)

Merlo, L. R.; Gobler, C.

2016-02-01

The World Oceans are acidifying and warming, yet little is known regarding how these processes will combine to impact fish populations. In estuaries, microbial respiration of eutrophication-enhanced organic matter can create elevated CO2 levels during late spring and summer seasons when thermal extremes can occur and temperate fish spawn. Here, we report on experiments that exposed fish embryos (e.g. Menidia beryllina, inland silverside) to normal and elevated CO2 (400 and 2,000 ppm) and the range of temperatures experienced within temperate estuaries during the spawning season (16 - 30C). Fish survival and growth rates were quantified from hatching through early life, larval stages. Temperature controlled egg hatching times, with elevated temperatures leading to more rapid hatch rates. Elevated levels of CO2 significantly depressed post-hatch survival of fish. Survival rates of fish exposed to elevated CO2 at lower than ideal temperatures were significantly lower than predicted by either variable individually indicating the ability of these stressors to synergistically interact. Since embryonic stages have been identified as being highly sensitive to acidification, this finding may be associated with the extended exposure of eggs to high CO2 at lower temperatures. The physiological mechanisms driving experimental trends and broader ecological implications of the study will be discussed.

EMX2 gene expression predicts liver metastasis and survival in colorectal cancer.

PubMed

Aykut, Berk; Ochs, Markus; Radhakrishnan, Praveen; Brill, Adrian; Höcker, Hermine; Schwarz, Sandra; Weissinger, Daniel; Kehm, Roland; Kulu, Yakup; Ulrich, Alexis; Schneider, Martin

2017-08-22

The Empty Spiracles Homeobox (EMX-) 2 gene has been associated with regulation of growth and differentiation in neuronal development. While recent studies provide evidence that EMX2 regulates tumorigenesis of various solid tumors, its role in colorectal cancer remains unknown. We aimed to assess the prognostic significance of EMX2 expression in stage III colorectal adenocarcinoma. Expression levels of EMX2 in human colorectal cancer and adjacent mucosa were assessed by qRT-PCR technology, and results were correlated with clinical and survival data. siRNA-mediated knockdown and adenoviral delivery-mediated overexpression of EMX2 were performed in order to investigate its effects on the migration of colorectal cancer cells in vitro. Compared to corresponding healthy mucosa, colorectal tumor samples had decreased EMX2 expression levels. Furthermore, EMX2 down-regulation in colorectal cancer tissue was associated with distant metastasis (M1) and impaired overall patient survival. In vitro knockdown of EMX2 resulted in increased tumor cell migration. Conversely, overexpression of EMX2 led to an inhibition of tumor cell migration. EMX2 is frequently down-regulated in human colorectal cancer, and down-regulation of EMX2 is a prognostic marker for disease-free and overall survival. EMX2 might thus represent a promising therapeutic target in colorectal cancer.

SU-F-R-04: Radiomics for Survival Prediction in Glioblastoma (GBM)

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

Zhang, H; Molitoris, J; Bhooshan, N

Purpose: To develop a quantitative radiomics approach for survival prediction of glioblastoma (GBM) patients treated with chemoradiotherapy (CRT). Methods: 28 GBM patients who received CRT at our institution were retrospectively studied. 255 radiomic features were extracted from 3 gadolinium-enhanced T1 weighted MRIs for 2 regions of interest (ROIs) (the surgical cavity and its surrounding enhancement rim). The 3 MRIs were at pre-treatment, 1-month and 3-month post-CRT. The imaging features comprehensively quantified the intensity, spatial variation (texture), geometric property and their spatial-temporal changes for the 2 ROIs. 3 demographics features (age, race, gender) and 12 clinical parameters (KPS, extent of resection,more » whether concurrent temozolomide was adjusted/stopped and radiotherapy related information) were also included. 4 Machine learning models (logistic regression (LR), support vector machine (SVM), decision tree (DT), neural network (NN)) were applied to predict overall survival (OS) and progression-free survival (PFS). The number of cases and percentage of cases predicted correctly were collected and AUC (area under the receiver operating characteristic (ROC) curve) were determined after leave-one-out cross-validation. Results: From univariate analysis, 27 features (1 demographic, 1 clinical and 25 imaging) were statistically significant (p<0.05) for both OS and PFS. Two sets of features (each contained 24 features) were algorithmically selected from all features to predict OS and PFS. High prediction accuracy of OS was achieved by using NN (96%, 27 of 28 cases were correctly predicted, AUC = 0.99), LR (93%, 26 of 28 cases were correctly predicted, AUC = 0.95) and SVM (93%, 26 of 28 cases were correctly predicted, AUC = 0.90). When predicting PFS, NN obtained the highest prediction accuracy (89%, 25 of 28 cases were correctly predicted, AUC = 0.92). Conclusion: Radiomics approach combined with patients’ demographics and clinical parameters can accurately predict survival in GBM patients treated with CRT.« less

Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques.

PubMed

Macyszyn, Luke; Akbari, Hamed; Pisapia, Jared M; Da, Xiao; Attiah, Mark; Pigrish, Vadim; Bi, Yingtao; Pal, Sharmistha; Davuluri, Ramana V; Roccograndi, Laura; Dahmane, Nadia; Martinez-Lage, Maria; Biros, George; Wolf, Ronald L; Bilello, Michel; O'Rourke, Donald M; Davatzikos, Christos

2016-03-01

MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood-brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prognostic factors in patients with advanced cancer: use of the patient-generated subjective global assessment in survival prediction.

PubMed

Martin, Lisa; Watanabe, Sharon; Fainsinger, Robin; Lau, Francis; Ghosh, Sunita; Quan, Hue; Atkins, Marlis; Fassbender, Konrad; Downing, G Michael; Baracos, Vickie

2010-10-01

To determine whether elements of a standard nutritional screening assessment are independently prognostic of survival in patients with advanced cancer. A prospective nested cohort of patients with metastatic cancer were accrued from different units of a Regional Palliative Care Program. Patients completed a nutritional screen on admission. Data included age, sex, cancer site, height, weight history, dietary intake, 13 nutrition impact symptoms, and patient- and physician-reported performance status (PS). Univariate and multivariate survival analyses were conducted. Concordance statistics (c-statistics) were used to test the predictive accuracy of models based on training and validation sets; a c-statistic of 0.5 indicates the model predicts the outcome as well as chance; perfect prediction has a c-statistic of 1.0. A training set of patients in palliative home care (n = 1,164) was used to identify prognostic variables. Primary disease site, PS, short-term weight change (either gain or loss), dietary intake, and dysphagia predicted survival in multivariate analysis (P < .05). A model including only patients separated by disease site and PS with high c-statistics between predicted and observed responses for survival in the training set (0.90) and validation set (0.88; n = 603). The addition of weight change, dietary intake, and dysphagia did not further improve the c-statistic of the model. The c-statistic was also not altered by substituting physician-rated palliative PS for patient-reported PS. We demonstrate a high probability of concordance between predicted and observed survival for patients in distinct palliative care settings (home care, tertiary inpatient, ambulatory outpatient) based on patient-reported information.

Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by (18)F-FDG PET/CT in squamous cell carcinoma of the oral cavity.

PubMed

Ryu, In Sun; Kim, Jae Seung; Roh, Jong-Lyel; Cho, Kyung-Ja; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2014-03-01

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by (18)F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC. Of 162 patients with OSCC evaluated preoperatively by (18)F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUVmax), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS). The median (range) SUVmax, MTV and TLG were 7.3 (0.7-41.9), 4.5 ml (0.7-115.1 ml) and 18.3 g (2.4-224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36%). By univariate and multivariate analyses, MTV (P = 0.018) and TLG (P = 0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0% and 62.0%, respectively. Univariate and multivariate analyses revealed that MTV (P = 0.001) and TLG (P = 0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV (P = 0.001), TLG (P = 0.002) and the involved resection margin (P = 0.007) were independent predictive factors for OS. Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC.

Performance of International Classification of Diseases-based injury severity measures used to predict in-hospital mortality: A systematic review and meta-analysis.

PubMed

Gagné, Mathieu; Moore, Lynne; Beaudoin, Claudia; Batomen Kuimi, Brice Lionel; Sirois, Marie-Josée

2016-03-01

The International Classification of Diseases (ICD) is the main classification system used for population-based injury surveillance activities but does not contain information on injury severity. ICD-based injury severity measures can be empirically derived or mapped, but no single approach has been formally recommended. This study aimed to compare the performance of ICD-based injury severity measures to predict in-hospital mortality among injury-related admissions. A systematic review and a meta-analysis were conducted. MEDLINE, EMBASE, and Global Health databases were searched from their inception through September 2014. Observational studies that assessed the performance of ICD-based injury severity measures to predict in-hospital mortality and reported discriminative ability using the area under a receiver operating characteristic curve (AUC) were included. Metrics of model performance were extracted. Pooled AUC were estimated under random-effects models. Twenty-two eligible studies reported 72 assessments of discrimination on ICD-based injury severity measures. Reported AUC ranged from 0.681 to 0.958. Of the 72 assessments, 46 showed excellent (0.80 ≤ AUC < 0.90) and 6 outstanding (AUC ≥ 0.90) discriminative ability. Pooled AUC for ICD-based Injury Severity Score (ICISS) based on the product of traditional survival proportions was significantly higher than measures based on ICD mapped to Abbreviated Injury Scale (AIS) scores (0.863 vs. 0.825 for ICDMAP-ISS [p = 0.005] and ICDMAP-NISS [p = 0.016]). Similar results were observed when studies were stratified by the type of data used (trauma registry or hospital discharge) or the provenance of survival proportions (internally or externally derived). However, among studies published after 2003 the Trauma Mortality Prediction Model based on ICD-9 codes (TMPM-9) demonstrated superior discriminative ability than ICISS using the product of traditional survival proportions (0.850 vs. 0.802, p = 0.002). Models generally showed poor calibration. ICISS using the product of traditional survival proportions and TMPM-9 predict mortality more accurately than those mapped to AIS codes and should be preferred for describing injury severity when ICD is used to record injury diagnoses. Systematic review and meta-analysis, level III.

Joint modeling of longitudinal data and discrete-time survival outcome.

PubMed

Qiu, Feiyou; Stein, Catherine M; Elston, Robert C

2016-08-01

A predictive joint shared parameter model is proposed for discrete time-to-event and longitudinal data. A discrete survival model with frailty and a generalized linear mixed model for the longitudinal data are joined to predict the probability of events. This joint model focuses on predicting discrete time-to-event outcome, taking advantage of repeated measurements. We show that the probability of an event in a time window can be more precisely predicted by incorporating the longitudinal measurements. The model was investigated by comparison with a two-step model and a discrete-time survival model. Results from both a study on the occurrence of tuberculosis and simulated data show that the joint model is superior to the other models in discrimination ability, especially as the latent variables related to both survival times and the longitudinal measurements depart from 0. © The Author(s) 2013.

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

PubMed Central

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

2013-01-01

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

SU-E-J-256: Predicting Metastasis-Free Survival of Rectal Cancer Patients Treated with Neoadjuvant Chemo-Radiotherapy by Data-Mining of CT Texture Features of Primary Lesions

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

Zhong, H; Wang, J; Shen, L

Purpose: The purpose of this study is to investigate the relationship between computed tomographic (CT) texture features of primary lesions and metastasis-free survival for rectal cancer patients; and to develop a datamining prediction model using texture features. Methods: A total of 220 rectal cancer patients treated with neoadjuvant chemo-radiotherapy (CRT) were enrolled in this study. All patients underwent CT scans before CRT. The primary lesions on the CT images were delineated by two experienced oncologists. The CT images were filtered by Laplacian of Gaussian (LoG) filters with different filter values (1.0–2.5: from fine to coarse). Both filtered and unfiltered imagesmore » were analyzed using Gray-level Co-occurrence Matrix (GLCM) texture analysis with different directions (transversal, sagittal, and coronal). Totally, 270 texture features with different species, directions and filter values were extracted. Texture features were examined with Student’s t-test for selecting predictive features. Principal Component Analysis (PCA) was performed upon the selected features to reduce the feature collinearity. Artificial neural network (ANN) and logistic regression were applied to establish metastasis prediction models. Results: Forty-six of 220 patients developed metastasis with a follow-up time of more than 2 years. Sixtyseven texture features were significantly different in t-test (p<0.05) between patients with and without metastasis, and 12 of them were extremely significant (p<0.001). The Area-under-the-curve (AUC) of ANN was 0.72, and the concordance index (CI) of logistic regression was 0.71. The predictability of ANN was slightly better than logistic regression. Conclusion: CT texture features of primary lesions are related to metastasisfree survival of rectal cancer patients. Both ANN and logistic regression based models can be developed for prediction.« less

Assessment of right ventricular adaptability to loading conditions can improve the timing of listing to transplantation in patients with pulmonary arterial hypertension.

PubMed

Dandel, Michael; Knosalla, Christoph; Kemper, Dagmar; Stein, Julia; Hetzer, Roland

2015-03-01

Right ventricle (RV) performance is load dependent, and right-sided heart failure (RHF) is the main cause of death in pulmonary arterial hypertension (PAH). Prediction of RV worsening for timely identification of patients needing transplantation (Tx) is paramount. Assessment of RV adaptability to load has proved useful in certain clinical circumstances. This study assessed its predictive value for RHF-free and Tx-free outcome with PAH. Between 2006 and 2012, all potential Tx candidates with PAH, without RHF at the first evaluation, were selected for follow-up (except congenital heart diseases). At selection and at each follow-up, N-terminal prohormone brain natriuretic peptide (NT-proBNP) and the 6-minute walk distance were measured, and RV adaptability to load was assessed by echocardiography. Collected data were tested for the ability to predict RV stability and Tx-free survival. During a 12-month to 92-month follow-up, RHF developed in 23 of 79 evaluated patients, despite similar medication and no differences in initial RV size and ejection fraction compared with the patients who remained stable. However, unstable patients had an initially lower RV load-adaptation index and afterload-corrected peak global systolic longitudinal strain-rate values as well as higher RV dyssynchrony, tricuspid regurgitation, and NT-proBNP levels (p ≤ 0.01). At certain cutoff values, these variables appeared predictive for 1-year and 3-year freedom from RHF and 3-year Tx-free survival. An RV load-adaptation index reduction of ≥20% showed the highest predictive value (90.0%) for short-term (≤1 year) RV decompensation. Assessment of RV adaptability to load allows prediction of RV function and Tx-free survival with severe PAH during the next 1 to 3 years. This can improve the timing of listing for Tx. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

An inflammation-related nomogram for predicting the survival of patients with non-small cell lung cancer after pulmonary lobectomy.

PubMed

Wang, Ying; Qu, Xiao; Kam, Ngar-Woon; Wang, Kai; Shen, Hongchang; Liu, Qi; Du, Jiajun

2018-06-26

Emerging inflammatory response biomarkers are developed to predict the survival of patients with cancer, the aim of our study is to establish an inflammation-related nomogram based on the classical predictive biomarkers to predict the survivals of patients with non-small cell lung cancer (NSCLC). Nine hundred and fifty-two NSCLC patients with lung cancer surgery performed were enrolled into this study. The cutoffs of inflammatory response biomarkers were determined by Receiver operating curve (ROC). Univariate and multivariate analysis were conducted to select independent prognostic factors to develop the nomogram. The median follow-up time was 40.0 months (range, 1 to 92 months). The neutrophil to lymphocyte ratio (cut-off: 3.10, HR:1.648, P = 0.045) was selected to establish the nomogram which could predict the 5-year OS probability. The C-index of nomogram was 0.72 and the 5-year OS calibration curve displayed an optimal agreement between the actual observed outcomes and the predictive results. Neutrophil to lymphocyte ratio was shown to be a valuable biomarker for predicting survival of patients with NSCLC. The addition of neutrophil to lymphocyte ratio could improve the accuracy and predictability of the nomogram in order to provide reference for clinicians to assess patient outcomes.

Estimating the probability of survival of individual shortleaf pine (Pinus echinata mill.) trees

Treesearch

Sudip Shrestha; Thomas B. Lynch; Difei Zhang; James M. Guldin

2012-01-01

A survival model is needed in a forest growth system which predicts the survival of trees on individual basis or on a stand basis (Gertner, 1989). An individual-tree modeling approach is one of the better methods available for predicting growth and yield as it provides essential information about particular tree species; tree size, tree quality and tree present status...

Analysis of Four Scoring Systems for the Prognosis of Patients with Metastasis of the Vertebral Column.

PubMed

Pollner, Péter; Horváth, Anna; Mezei, Tamás; Banczerowski, Péter; Czigléczki, Gábor

2018-04-01

Metastatic spinal diseases are common health problems and there is no consensus on the appropriate treatment of metastases in several conditions. Using clinical measures (e.g., survival time and functional status), prognosis prediction systems advise on the appropriate interventions. The aim of this article is to assess and compare 4 widely used scoring systems (revised Tokuhashi, Tomita, van der Linden, and modified Bauer scores) on a single-center cohort. A retrospective study was designed of 329 patients who were subjected to surgery because of metastatic spinal diseases. Subpopulations according to the classifications of the 4 scoring systems were identified. The overall survival was calculated with the Kaplan-Meier formula. The difference between the survival curves of subpopulations was analyzed with log-rank tests. The consistency rates for the 4 scoring systems are calculated as well. The follow-up period was 8 years. The median survival time was 222 days. The overall survival of prognostic categories in 3 scoring systems was significantly different from each other, but we found no differences between the categories of the van der Linden system. In this cohort, the revised Tokuhashi system gave the best approximation for survival, with a mean predictive capability 60.5%. The evaluation of 4 standard scoring systems showed that 3 were self-consistent, although none of systems was able to predict the survival in our cohort. Based on the predictive capability, the revised Tokuhashi system may provide the best predictions with careful examination of individual cases. Copyright © 2018 Elsevier Inc. All rights reserved.

Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival.

PubMed

Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

2015-10-20

Stomatin-like protein 2 (SLP-2, also known as STOML2) is a stomatin homologue of uncertain function. SLP-2 overexpression has been suggested to be associated with cancer progression, resulting in adverse clinical outcomes in patients. Our study aim to investigate SLP-2 expression in epithelial ovarian cancer cells and its correlation with patient survival. SLP-2 mRNA and protein expression levels were analysed in five epithelial ovarian cancer cell lines and normal ovarian epithelial cells using real-time PCR and western blotting analysis. SLP-2 expression was investigated in eight matched-pair samples of epithelial ovarian cancer and adjacent noncancerous tissues from the same patients. Using immunohistochemistry, we examined the protein expression of paraffin-embedded specimens from 140 patients with epithelial ovarian cancer, 20 cases with borderline ovarian tumours, 20 cases with benign ovarian tumours, and 20 cases with normal ovarian tissues. Statistical analyses were applied to evaluate the clinicopathological significance of SLP-2 expression. SLP-2 mRNA and protein expression levels were significantly up-regulated in epithelial ovarian cancer cell lines and cancer tissues compared with normal ovarian epithelial cells and adjacent noncancerous ovarian tissues. Immunohistochemistry analysis revealed that the relative overexpression of SLP-2 was detected in 73.6 % (103/140) of the epithelial ovarian cancer specimens, 45.0 % (9/20) of the borderline ovarian specimens, 30.0 % (6/20) of the benign ovarian specimens and none of the normal ovarian specimens. SLP-2 protein expression in epithelial ovarian cancer was significantly correlated with the tumour stage (P < 0.001). Epithelial ovarian cancer patients with higher SLP-2 protein expression levels had shorter progress free survival and overall survival times compared to patients with lower SLP-2 protein expression levels. Multivariate analyses showed that SLP-2 expression levels were an independent prognostic factor for survival in epithelial ovarian cancer patients. SLP-2 mRNA and proteins were overexpressed in epithelial ovarian cancer tissues. SLP-2 protein overexpression was associated with advanced stage disease. Patients with higher SLP-2 protein expression had shorter progress free survival and poor overall survival times. Thus, SLP-2 protein expression was an independent prognostic factor for patients with epithelial ovarian cancer.

Interaction Analysis of Longevity Interventions Using Survival Curves.

PubMed

Nowak, Stefan; Neidhart, Johannes; Szendro, Ivan G; Rzezonka, Jonas; Marathe, Rahul; Krug, Joachim

2018-01-06

A long-standing problem in ageing research is to understand how different factors contributing to longevity should be expected to act in combination under the assumption that they are independent. Standard interaction analysis compares the extension of mean lifespan achieved by a combination of interventions to the prediction under an additive or multiplicative null model, but neither model is fundamentally justified. Moreover, the target of longevity interventions is not mean life span but the entire survival curve. Here we formulate a mathematical approach for predicting the survival curve resulting from a combination of two independent interventions based on the survival curves of the individual treatments, and quantify interaction between interventions as the deviation from this prediction. We test the method on a published data set comprising survival curves for all combinations of four different longevity interventions in Caenorhabditis elegans . We find that interactions are generally weak even when the standard analysis indicates otherwise.

Interaction Analysis of Longevity Interventions Using Survival Curves

PubMed Central

Nowak, Stefan; Neidhart, Johannes; Szendro, Ivan G.; Rzezonka, Jonas; Marathe, Rahul; Krug, Joachim

2018-01-01

A long-standing problem in ageing research is to understand how different factors contributing to longevity should be expected to act in combination under the assumption that they are independent. Standard interaction analysis compares the extension of mean lifespan achieved by a combination of interventions to the prediction under an additive or multiplicative null model, but neither model is fundamentally justified. Moreover, the target of longevity interventions is not mean life span but the entire survival curve. Here we formulate a mathematical approach for predicting the survival curve resulting from a combination of two independent interventions based on the survival curves of the individual treatments, and quantify interaction between interventions as the deviation from this prediction. We test the method on a published data set comprising survival curves for all combinations of four different longevity interventions in Caenorhabditis elegans. We find that interactions are generally weak even when the standard analysis indicates otherwise. PMID:29316622

Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma

PubMed Central

Huang, Gloria S.; Chiu, Lydia G.; Gebb, Juliana S.; Gunter, Marc J.; Sukumvanich, Paniti; Goldberg, Gary L.; Einstein, Mark H.

2009-01-01

Objective The purpose of this study was to determine the clinical utility of CA125 measurement in patients with uterine carcinosarcoma (CS). Methods Ninety-five consecutive patients treated for CS at a single institution were identified. All 54 patients who underwent preoperative CA125 measurement were included in the study. Data were abstracted from the medical records. Tests of association between preoperative CA125 and previously identified clinicopathologic prognostic factors were performed using Fisher’s exact test and Pearson chi-square test. To evaluate relationship of CA125 elevation and survival, a Cox proportional hazard model was used for multivariate analysis, incorporating all of prognostic factors identified by univariate analysis. Results Preoperative CA125 was significantly associated with the presence of extrauterine disease (P<0.001), deep myometrial invasion (P<0.001), and serous histology of the epithelial component (P=0.005). Using univariate survival analysis, stage (HR=1.808, P=0.004), postoperative CA125 level (HR=9.855, P<0.001), and estrogen receptor positivity (HR=0.314, P=0.029) were significantly associated with survival. In the multivariate model, only postoperative CA125 level remained significantly associated with poor survival (HR=5.725, P=0.009). Conclusion Preoperative CA125 elevation is a marker of extrauterine disease and deep myometrial invasion in patients with uterine CS. Postoperative CA125 elevation is an independent prognostic factor for poor survival. These findings indicate that CA125 may be a clinically useful serum marker in the management of patients with CS. PMID:17935762

In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival.

PubMed

Ladoire, Sylvain; Mignot, Grégoire; Dabakuyo, Sandrine; Arnould, Laurent; Apetoh, Lionel; Rébé, Cedric; Coudert, Bruno; Martin, Francois; Bizollon, Marie Hélène; Vanoli, André; Coutant, Charles; Fumoleau, Pierre; Bonnetain, Franck; Ghiringhelli, François

2011-07-01

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Predictive factors of tumor control and survival after radiosurgery for local failures of nasopharyngeal carcinoma.

PubMed

Chua, Daniel T T; Sham, Jonathan S T; Hung, Kwan-Ngai; Leung, Lucullus H T; Au, Gordon K H

2006-12-01

Stereotactic radiosurgery has been employed as a salvage treatment of local failures of nasopharyngeal carcinoma (NPC). To identify patients that would benefit from radiosurgery, we reviewed our data with emphasis on factors that predicted treatment outcome. A total of 48 patients with local failures of NPC were treated by stereotactic radiosurgery between March 1996 and February 2005. Radiosurgery was administered using a modified linear accelerator with single or multiple isocenters to deliver a median dose of 12.5 Gy to the target periphery. Median follow-up was 54 months. Five-year local failure-free probability after radiosurgery was 47.2% and 5-year overall survival rate was 46.9%. Neuroendocrine complications occurred in 27% of patients but there were no treatment-related deaths. Time interval from primary radiotherapy, retreatment T stage, prior local failures and tumor volume were significant predictive factors of local control and/or survival whereas age was of marginal significance in predicting survival. A radiosurgery prognostic scoring system was designed based on these predictive factors. Five-year local failure-free probabilities in patients with good, intermediate and poor prognostic scores were 100%, 42.5%, and 9.6%. The corresponding five-year overall survival rates were 100%, 51.1%, and 0%. Important factors that predicted tumor control and survival after radiosurgery were identified. Patients with good prognostic score should be treated by radiosurgery in view of the excellent results. Patients with intermediate prognostic score may also be treated by radiosurgery but those with poor prognostic score should receive other salvage treatments.

Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

PubMed

Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

2018-04-01

We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation,we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples.

PubMed

Fekete, Tibor; Rásó, Erzsébet; Pete, Imre; Tegze, Bálint; Liko, István; Munkácsy, Gyöngyi; Sipos, Norbert; Rigó, János; Györffy, Balázs

2012-07-01

Transcriptomic analysis of global gene expression in ovarian carcinoma can identify dysregulated genes capable to serve as molecular markers for histology subtypes and survival. The aim of our study was to validate previous candidate signatures in an independent setting and to identify single genes capable to serve as biomarkers for ovarian cancer progression. As several datasets are available in the GEO today, we were able to perform a true meta-analysis. First, 829 samples (11 datasets) were downloaded, and the predictive power of 16 previously published gene sets was assessed. Of these, eight were capable to discriminate histology subtypes, and none was capable to predict survival. To overcome the differences in previous studies, we used the 829 samples to identify new predictors. Then, we collected 64 ovarian cancer samples (median relapse-free survival 24.5 months) and performed TaqMan Real Time Polimerase Chain Reaction (RT-PCR) analysis for the best 40 genes associated with histology subtypes and survival. Over 90% of subtype-associated genes were confirmed. Overall survival was effectively predicted by hormone receptors (PGR and ESR2) and by TSPAN8. Relapse-free survival was predicted by MAPT and SNCG. In summary, we successfully validated several gene sets in a meta-analysis in large datasets of ovarian samples. Additionally, several individual genes identified were validated in a clinical cohort. Copyright © 2011 UICC.

Prognostic implication of serum hepatocyte growth factor in stage II/III breast cancer patients who received neoadjuvant chemotherapy.

PubMed

Kim, Hyori; Youk, Jeonghwan; Yang, Yaewon; Kim, Tae-Yong; Min, Ahrum; Ham, Hye-Seon; Cho, Seongcheol; Lee, Kyung-Hun; Keam, Bhumsuk; Han, Sae-Won; Oh, Do-Youn; Ryu, Han Suk; Han, Wonshik; Park, In Ae; Kim, Tae-You; Noh, Dong-Young; Im, Seock-Ah

2016-03-01

In stage II/III breast cancer, neoadjuvant chemotherapy (NAC) is a standard treatment. Although several biomarkers are used to predict prognosis in breast cancer, there is no reliable predictive biomarker for NAC success. Recently, the hepatocyte growth factor (HGF) and cMet signaling pathway demonstrated to be involved in breast cancer tumor progression, and its potential as a biomarker is under active investigation. In this study, we assessed the potential of serum HGF as a prognostic biomarker for NAC efficacy. Venous blood samples were drawn from patients diagnosed with stage II/III breast cancer and treated with NAC in Seoul National University Hospital from August 2004 to November 2009. Serum HGF level was determined using an ELISA system. We reviewed the medical records of the patients and investigated the association of HGF level with patients' clinicopathologic characteristics. A total of 121 female patients (median age = 45 years old) were included. Median level of HGF was 934 pg/ml (lower quartile: 772, upper quartile: 1145 pg/ml). Patients with higher HGF level than median value were significantly more likely to have clinically detectable regional node metastasis (p = 0.017, Fisher's exact test). Patients with complete and partial response according to the American Joint Committee on Cancer 7th Edition criteria tended to have higher HGF level (p = 0.105 by t test). Patients with an HGF level higher than the upper quartile value had longer relapse-free survival than the other patients (106 vs. 85 months, p = 0.008). High serum HGF levels in breast cancer patients are associated with clinically detectable regional node metastasis and, paradoxically, with longer relapse-free survival in stage II/III breast cancer.

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

PubMed

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

2011-10-01

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

Evaluation of initial plasma lactate values as a predictor of gastric necrosis and initial and subsequent plasma lactate values as a predictor of survival in dogs with gastric dilatation-volvulus: 84 dogs (2003-2007).

PubMed

Green, Tiffany I; Tonozzi, Caroline C; Kirby, Rebecca; Rudloff, Elke

2011-02-01

To test whether an initial plasma lactate ≥ 6.0 mmol/L is associated with the presence of macroscopic gastric wall necrosis and overall survival in dogs presenting with gastric dilatation-volvulus (GDV). Additionally, if no association was identified we sought to identify a different predictive initial plasma lactate concentration and to examine whether serial plasma lactate concentrations provide better prediction of survival. Retrospective study over a 5-year period (2003-2007). Urban private referral small animal teaching hospital. Eighty-four client-owned dogs with a diagnosis of GDV and plasma lactate measurements. None. There was no statistically significant relationship found between survival and the presence of macroscopic gastric wall necrosis with the initial plasma lactate ≥ 6 mmol/L. There was a significant relationship between the initial plasma lactate >2.9 mmol/L for predicting necrosis and <4.1 mmol/L for predicting survival to discharge. Forty dogs that had an increased initial plasma lactate (>2.5 mmol/L) also had a subsequent plasma lactate measured within 12 hours of presentation, with 37/40 dogs surviving and 70% of these surviving dogs having the subsequent lactate decrease by ≥ 50% within 12 hours. The 3/40 that died failed to decrease their plasma lactate by ≥ 50% from the initial blood lactate. The results of this study indicate that an initial presenting plasma lactate concentration ≥ 6.0 mmol/L is not predictive of macroscopic gastric wall necrosis or survival in dogs presenting with GDV. A decrease in plasma lactate concentrations ≥ 50% within 12 hours may be a good indicator for survival. Limitations to the study include its retrospective nature, the small number of patients, and the number of dogs that were euthanized rather than allowed to progress to a natural outcome. © Veterinary Emergency and Critical Care Society 2011.

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

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

DeVries, Alexander Friedrich; Piringer, Gudrun, E-mail: gudrun.piringer@hotmail.com; Kremser, Christian

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 inputmore » 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.« less

Post-Discharge Survival Outcomes of Patients with Advanced Cancer from the University of Texas MD Anderson Cancer Center Investigational Cancer Therapeutics (Phase I Trials) Inpatient Unit.

PubMed

Kinahan, Holly; Maiti, Abhishek; Hess, Kenneth; Dempsey, Jennifer; Beatty, Laura; Baldwin, Sarah; Hong, David S; Naing, Aung; Fu, Siqing; Tsimberidou, Apostolia M; Piha-Paul, Sarina; Janku, Filip; Karp, Daniel; Reddy, Suresh; Yennu, Sriram; Epner, Daniel; Bruera, Eduardo; Meric-Bernstam, Funda; Falchook, Gerald; Subbiah, Vivek

2017-01-01

Patients with advanced cancer who progress on standard therapy are potential candidates for phase I clinical trials. Due to their aggressive disease and complex comorbid conditions, these patients often need inpatient admission. This study assessed the outcomes of such patients after they were discharged to hospice care. We performed a retrospective analysis of patients with solid tumor malignancies who were discharged to hospice care from the inpatient service. One hundred thirty-three patients were included in the study cohort. All patients had metastatic disease and an Eastern Cooperative Oncology Group performance status ≥3. The median survival after discharge to hospice from an inpatient setting was 16 days, with a survival rate of 5% at 3 months after discharge. The median survival after the last cancer treatment was 46 days, with survival of 17% at 3 months, and 5% at 6 months. Patients with lactate dehydrogenase (LDH) >618 IU/L had a median post-discharge survival of 11 days versus 20 days for patients with LDH ≤618 IU/L. Patients with metastatic cancer participating in phase I trials who have poor performance status and require inpatient admission have a very short survival after discharge to hospice. A high LDH level predicts an even shorter survival. © 2016 S. Karger AG, Basel.

Plasma matrix metalloproteinase-9 better predicts outcome than N-terminal protype-B natriuretic peptide in patients with systolic heart failure and a high prevalence of coronary artery disease.

PubMed

Dini, Frank Lloyd; Buralli, Simona; Bajraktari, Gani; Elezi, Shpend; Duranti, Emiliano; Metelli, Maria Rita; Carpi, Angelo; Taddei, Stefano

2010-05-01

Metalloproteinases have been proposed as biochemical markers of left ventricular (LV) remodeling in systolic heart failure (HF). However, their role in the prognostic stratification of these patients remains controversial. In the present study, we aimed at investigating the value of plasma metalloproteinases-3 and -9 in comparison with N-terminal protype-B natriuretic peptide in patients with systolic HF. One hundred and 27 consecutive patients hospitalized for systolic HF (LV ejection fraction < 45%) were enrolled. Coronary artery disease (CAD) was the aetiology in 67% of the study patients. Plasma metalloproteinases-3 and -9 and N-terminal protype-B natriuretic peptide levels were assessed. A complete echocardiographic and Doppler examination was also performed. Follow-up period was 24-15 months. On univariate analysis, a number of measurements predicted cardiac events in the following order of power: NYHA class >2, LV ejection fraction < 25%, metalloproteinases-9 > 238 ng/ml, mitral E wave deceleration time < 150 ms, N-terminal protype-B natriuretic peptide > 1586 pg/ml and metalloproteinases-3 > 15 ng/ml. However, on multivariate analysis the only independent variables of cardiac events were NYHA class (OR=2.26, p=0.059) and plasma metalloproteinases-9 (OR=2.00, p=0.029). On Kaplan-Meier survival analysis, patients with elevated levels of metalloproteinases-9 exhibited a significantly worse event free-survival at 45 months than those without (21% vs. 54%, log-rank: 13.93, p=0.0002). A worse survival was also observed in patients with elevated N-terminal protype-B natriuretic peptide levels with respect to those without (18% vs. 46%, log-rank: 9.11, p=0.025). Our results demonstrated the value of plasma metalloproteinases-9 levels for prognostication of patients with systolic HF and a high prevalence of CAD. 2009. Published by Elsevier SAS.

Disease-Free Survival after Hepatic Resection in Hepatocellular Carcinoma Patients: A Prediction Approach Using Artificial Neural Network

PubMed Central

Ho, Wen-Hsien; Lee, King-Teh; Chen, Hong-Yaw; Ho, Te-Wei; Chiu, Herng-Chia

2012-01-01

Background A database for hepatocellular carcinoma (HCC) patients who had received hepatic resection was used to develop prediction models for 1-, 3- and 5-year disease-free survival based on a set of clinical parameters for this patient group. Methods The three prediction models included an artificial neural network (ANN) model, a logistic regression (LR) model, and a decision tree (DT) model. Data for 427, 354 and 297 HCC patients with histories of 1-, 3- and 5-year disease-free survival after hepatic resection, respectively, were extracted from the HCC patient database. From each of the three groups, 80% of the cases (342, 283 and 238 cases of 1-, 3- and 5-year disease-free survival, respectively) were selected to provide training data for the prediction models. The remaining 20% of cases in each group (85, 71 and 59 cases in the three respective groups) were assigned to validation groups for performance comparisons of the three models. Area under receiver operating characteristics curve (AUROC) was used as the performance index for evaluating the three models. Conclusions The ANN model outperformed the LR and DT models in terms of prediction accuracy. This study demonstrated the feasibility of using ANNs in medical decision support systems for predicting disease-free survival based on clinical databases in HCC patients who have received hepatic resection. PMID:22235270

Unique protein expression signatures of survival time in kidney renal clear cell carcinoma through a pan-cancer screening.

PubMed

Han, Guangchun; Zhao, Wei; Song, Xiaofeng; Kwok-Shing Ng, Patrick; Karam, Jose A; Jonasch, Eric; Mills, Gordon B; Zhao, Zhongming; Ding, Zhiyong; Jia, Peilin

2017-10-03

In 2016, it is estimated that there will be 62,700 new cases of kidney cancer in the United States, and 14,240 patients will die from the disease. Because the incidence of kidney renal clear cell carcinoma (KIRC), the most common type of kidney cancer, is expected to continue to increase in the US, there is an urgent need to find effective diagnostic biomarkers for KIRC that could help earlier detection of and customized treatment strategies for the disease. Accordingly, in this study we systematically investigated KIRC's prognostic biomarkers for survival using the reverse phase protein array (RPPA) data and the high throughput sequencing data from The Cancer Genome Atlas (TCGA). With comprehensive data available in TCGA, we systematically screened protein expression based survival biomarkers in 10 major cancer types, among which KIRC presented many protein prognostic biomarkers of survival time. This is in agreement with a previous report that expression level changes (mRNAs, microRNA and protein) may have a better performance for prognosis of KIRC. In this study, we also identified 52 prognostic genes for KIRC, many of which are involved in cell-cycle and cancer signaling, as well as 15 tumor-stage-specific prognostic biomarkers. Notably, we found fewer prognostic biomarkers for early-stage than for late-stage KIRC. Four biomarkers (the RPPA protein IDs: FASN, ACC1, Cyclin_B1 and Rad51) were found to be prognostic for survival based on both protein and mRNA expression data. Through pan-cancer screening, we found that many protein biomarkers were prognostic for patients' survival in KIRC. Stage-specific survival biomarkers in KIRC were also identified. Our study indicated that these protein biomarkers might have potential clinical value in terms of predicting survival in KIRC patients and developing individualized treatment strategies. Importantly, we found many biomarkers in KIRC at both the mRNA expression level and the protein expression level. These biomarkers shared a significant overlap, indicating that they were technically replicable.

Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients

PubMed Central

Meguro, Makoto; Mizuguchi, Toru; Nishidate, Toshihiko; Okita, Kenji; Ishii, Masayuki; Ota, Shigenori; Ueki, Tomomi; Akizuki, Emi; Hirata, Koichi

2015-01-01

AIM: To clarify the utility of using des-γ-carboxy prothrombin (DCP) and α-fetoprotein (AFP) levels to predict the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) and the hepatitis C virus (HCV) infections. METHODS: A total of 205 patients with HCC (105 patients with HBV infection 100 patients with HCV infection) who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively. Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy, and cutoff levels were calculated. Patients in the HBV and HCV groups were classified into three groups: a group with low AFP and DCP levels (LL group), a group in which one of the two parameters was high and the other was low (HL group), and a group with high AFP and DCP levels (HH group). Liver function parameters, the postoperative recurrence-free survival rate, and postoperative overall survival were compared between groups. The survival curves were compared by log-rank test using the Kaplan-Meier method. Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis. RESULTS: The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/mL and 60 mAU/mL, respectively; for preoperative DCP levels, the cutoff levels were 21.0 ng/mL in the HBV group and 67 mAU/mL in the HCV group. The HBV group was significantly different from the other groups in terms of vascular invasion, major hepatectomy, volume of intraoperative blood loss, and surgical duration. Significant differences were found between the LL group, the HL group, and the HH group in terms of both mean disease-free survival time (MDFST) and mean overall survival time (MOST): 64.81 ± 7.47 vs 36.63 ± 7.62 vs 18.98 ± 6.17 mo (P = 0.001) and 85.30 ± 6.55 vs 59.44 ± 7.87 vs 46.57 ± 11.20 mo (P = 0.018). In contrast, the HCV group exhibited a significant difference in tumor size, vascular invasion, volume of intraoperative blood loss, and surgical duration; however, no significant difference was observed between the three groups in liver function parameters except for albumin levels. In the LL group, the HL group, and the HH group, the MDFST was 50.09 ± 5.90, 31.01 ± 7.21, and 14.81 ± 3.08 mo (log-rank test, P < 0.001), respectively, and the MOST was 79.45 ± 8.30, 58.82 ± 7.56, and 32.87 ± 6.31 mo (log-rank test, P < 0.001), respectively. CONCLUSION: In the HBV group, the prognosis was poor when either AFP or DCP levels were high. In the HCV group, the prognosis was good when either or both levels were low; however, the prognosis was poor when both levels were high. High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups. The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis. PMID:25945007

miR-125b predicts childhood acute lymphoblastic leukaemia poor response to BFM chemotherapy treatment.

PubMed

Piatopoulou, Despina; Avgeris, Margaritis; Marmarinos, Antonios; Xagorari, Marieta; Baka, Margarita; Doganis, Dimitrios; Kossiva, Lydia; Scorilas, Andreas; Gourgiotis, Dimitrios

2017-09-05

Despite the favourable survival rates of childhood acute lymphoblastic leukaemia (ALL), a significant number of patients present resistance to antileukaemic agents and dismal prognosis. In this study, we analysed miR-125b expression in childhood ALL and evaluated its clinical utility for patients treated with Berlin-Frankfurt-Münster (BFM) protocol. The study included 272 bone marrow specimens obtained on diagnosis and on BFM day 33 from 125 patients and 64 healthy children. Following extraction, RNA was polyadenylated and reverse transcribed. miR-125b levels were quantified by quantitative PCR. Cytogenetics, immunohistotype and MRD were analysed according to international guidelines. Downregulated miR-125b levels were detected in childhood ALL patients and correlated with adverse prognosis. Following BFM induction, miR-125b levels were significantly increased, however, elevated day 33/diagnosis miR-125b ratio was associated with unfavourable disease features. Loss of miR-125b during diagnosis and higher day 33/diagnosis ratio were correlated with stronger risk for disease short-term relapse and patients' worse survival. Moreover, multivariate regression models highlighted the independent prognostic value of miR-125b for childhood ALL. Finally, the combination of miR-125b with clinically used disease markers clearly enhanced the prediction of patients' resistance to BFM chemotherapy. miR-125b significantly improves the prognosis of childhood ALL patients' outcome under BFM treatment.

PARP1 expression, activity and ex vivo sensitivity to the PARP inhibitor, talazoparib (BMN 673), in chronic lymphocytic leukaemia

PubMed Central

Herriott, Ashleigh; Tudhope, Susan J.; Junge, Gesa; Rodrigues, Natalie; Patterson, Miranda J.; Woodhouse, Laura; Lunec, John; Hunter, Jill E.; Mulligan, Evan A.; Cole, Michael; Allinson, Lisa M.; Wallis, Jonathan P.; Marshall, Scott; Wang, Evelyn; Curtin, Nicola J.; Willmore, Elaine

2015-01-01

In chronic lymphocytic leukemia (CLL), mutation and loss of p53 and ATM abrogate DNA damage signalling and predict poorer response and shorter survival. We hypothesised that poly (ADP-ribose) polymerase (PARP) activity, which is crucial for repair of DNA breaks induced by oxidative stress or chemotherapy, may be an additional predictive biomarker and a target for therapy with PARP inhibitors. We measured PARP activity in 109 patient-derived CLL samples, which varied widely (192 – 190052 pmol PAR/106 cells) compared to that seen in healthy volunteer lymphocytes (2451 – 7519 pmol PAR/106 cells). PARP activity was associated with PARP1 protein expression and endogenous PAR levels. PARP activity was not associated with p53 or ATM loss, Binet stage, IGHV mutational status or survival, but correlated with Bcl-2 and Rel A (an NF-kB subunit). Levels of 8-hydroxy-2′-deoxyguanosine in DNA (a marker of oxidative damage) were not associated with PAR levels or PARP activity. The potent PARP inhibitor, talazoparib (BMN 673), inhibited CD40L-stimulated proliferation of CLL cells at nM concentrations, independently of Binet stage or p53/ATM function. PARP activity is highly variable in CLL and correlates with stress-induced proteins. Proliferating CLL cells (including those with p53 or ATM loss) are highly sensitive to the PARP inhibitor talazoparib. PMID:26539646

Increased body mass index is associated with improved overall survival in extranodal natural killer/T-cell lymphoma, nasal type.

PubMed

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Liu, Xi-Yu; Zhou, Fang; OuYang, Zhou; Sun, Zhong-Yi; Huang, Li-Jun; He, Jun-Qiao; Yao, Yuan; Fan, Zhou; Tang, Tian; Jiang, Wen-Qi

2017-01-17

The role of body mass index (BMI) in lymphoma survival outcomes is controversial. The prognostic significance of BMI in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is unclear. We evaluated the prognostic role of BMI in patients with ENKTL. We retrospectively analyzed 742 patients with newly diagnosed ENKTL. The prognostic value of BMI was compared between patients with low BMIs (< 20.0 kg/m2) and patients with high BMIs (≥ 20.0 kg/m2). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) was also evaluated and compared with that of the BMI classification. Patients with low BMIs tended to exhibit higher Eastern Cooperative Oncology Group performance status (ECOG PS) scores (≥ 2) (P = 0.001), more frequent B symptoms (P < 0.001), lower albumin levels (P < 0.001), higher KPI scores (P = 0.03), and lower rates of complete remission (P < 0.001) than patients with high BMIs, as well as inferior progression-free survival (PFS, P = 0.003), and inferior overall survival (OS, P = 0.001). Multivariate analysis demonstrated that age > 60 years, mass > 5 cm, stage III/IV, elevated LDH levels, albumin levels < 35 g/L and low BMIs were independent adverse predictors of OS. The BMI classification was found to be superior to the IPI with respect to predicting patient outcomes among low-risk patients and the KPI with respect to distinguishing between intermediate-low- and high-intermediate-risk patients. Higher BMI at the time of diagnosis is associated with improved overall survival in ENKTL. Using the BMI classification may improve the IPI and KPI prognostic models.

Increased body mass index is associated with improved overall survival in extranodal natural killer/T-cell lymphoma, nasal type

PubMed Central

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Liu, Xi-Yu; Zhou, Fang; OuYang, Zhou; Sun, Zhong-Yi; Huang, Li-Jun; He, Jun-Qiao; Yao, Yuan; Fan, Zhou; Tang, Tian; Jiang, Wen-Qi

2017-01-01

Objectives: The role of body mass index (BMI) in lymphoma survival outcomes is controversial. The prognostic significance of BMI in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is unclear. We evaluated the prognostic role of BMI in patients with ENKTL. Methods: We retrospectively analyzed 742 patients with newly diagnosed ENKTL. The prognostic value of BMI was compared between patients with low BMIs (< 20.0 kg/m2) and patients with high BMIs (≥ 20.0 kg/m2). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) was also evaluated and compared with that of the BMI classification. Results: Patients with low BMIs tended to exhibit higher Eastern Cooperative Oncology Group performance status (ECOG PS) scores (≥ 2) (P = 0.001), more frequent B symptoms (P < 0.001), lower albumin levels (P < 0.001), higher KPI scores (P = 0.03), and lower rates of complete remission (P < 0.001) than patients with high BMIs, as well as inferior progression-free survival (PFS, P = 0.003), and inferior overall survival (OS, P = 0.001). Multivariate analysis demonstrated that age > 60 years, mass > 5 cm, stage III/IV, elevated LDH levels, albumin levels < 35 g/L and low BMIs were independent adverse predictors of OS. The BMI classification was found to be superior to the IPI with respect to predicting patient outcomes among low-risk patients and the KPI with respect to distinguishing between intermediate-low- and high-intermediate-risk patients. Conclusions: Higher BMI at the time of diagnosis is associated with improved overall survival in ENKTL. Using the BMI classification may improve the IPI and KPI prognostic models. PMID:28002803

Recovery of Serum Cholesterol Predicts Survival After Left Ventricular Assist Device Implantation

PubMed Central

Vest, Amanda R.; Kennel, Peter J.; Maldonado, Dawn; Young, James B.; Mountis, Maria M.; Naka, Yoshifumi; Colombo, Paolo C.; Mancini, Donna M.; Starling, Randall C.; Schulze, P. Christian

2017-01-01

Background Advanced systolic heart failure is associated with myocardial and systemic metabolic abnormalities, including low levels of total cholesterol and low-density lipoprotein. Low cholesterol and low-density lipoprotein have been associated with greater mortality in heart failure. Implantation of a left ventricular assist device (LVAD) reverses some of the metabolic derangements of advanced heart failure. Methods and Results A cohort was retrospectively assembled from 2 high-volume implantation centers, totaling 295 continuous-flow LVAD recipients with ≥2 cholesterol values available. The cohort was predominantly bridge-to-transplantation (67%), with median age of 59 years and 49% ischemic heart failure cause. Total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels all significantly increased after LVAD implantation (median values from implantation to 3 months post implantation 125–150 mg/dL, 67–85 mg/dL, 32–42 mg/dL, and 97–126 mg/dL, respectively). On Cox proportional hazards modeling, patients achieving recovery of total cholesterol levels, defined as a median or greater change from pre implantation to 3 months post-LVAD implantation, had significantly better unadjusted survival (hazard ratio, 0.445; 95% confidence interval, 0.212–0.932) and adjusted survival (hazard ratio, 0.241; 95% confidence interval, 0.092–0.628) than those without cholesterol recovery after LVAD implantation. The continuous variable of total cholesterol at 3 months post implantation and the cholesterol increase from pre implantation to 3 months were also both significantly associated with survival during LVAD support. Conclusions Initiation of continuous-flow LVAD support was associated with significant recovery of all 4 lipid variables. Patients with a greater increase in total cholesterol by 3 months post implantation had superior survival during LVAD support. PMID:27623768

Country-Level Macroeconomic Indicators Predict Early Post-Allogeneic Hematopoietic Cell Transplantation Survival in Acute Lymphoblastic Leukemia: A CIBMTR Analysis.

PubMed

Wood, William A; Brazauskas, Ruta; Hu, Zhen-Huan; Abdel-Azim, Hisham; Ahmed, Ibrahim A; Aljurf, Mahmoud; Badawy, Sherif; Beitinjaneh, Amer; George, Biju; Buchbinder, David; Cerny, Jan; Dedeken, Laurence; Diaz, Miguel Angel; Freytes, Cesar O; Ganguly, Siddhartha; Gergis, Usama; Almaguer, David Gomez; Gupta, Ashish; Hale, Gregory; Hashmi, Shahrukh K; Inamoto, Yoshihiro; Kamble, Rammurti T; Adekola, Kehinde; Kindwall-Keller, Tamila; Knight, Jennifer; Kumar, Lalit; Kuwatsuka, Yachiyo; Law, Jason; Lazarus, Hillard M; LeMaistre, Charles; Olsson, Richard F; Pulsipher, Michael A; Savani, Bipin N; Schultz, Kirk R; Saad, Ayman A; Seftel, Matthew; Seo, Sachiko; Shea, Thomas C; Steinberg, Amir; Sullivan, Keith; Szwajcer, David; Wirk, Baldeep; Yared, Jean; Yong, Agnes; Dalal, Jignesh; Hahn, Theresa; Khera, Nandita; Bonfim, Carmem; Atsuta, Yoshiko; Saber, Wael

2018-03-19

For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (alloHCT) offers a potential cure. Life-threatening complications can arise from alloHCT that require the application of sophisticated health care delivery. The impact of country-level economic conditions on post-transplantation outcomes is not known. Our objective was to assess whether these variables were associated with outcomes for patients transplanted for ALL. Using data from the Center for Blood and Marrow Transplant Research, we included 11,261 patients who received a first alloHCT for ALL from 303 centers across 38 countries between the years of 2005 and 2013. Cox regression models were constructed using the following macroeconomic indicators as main effects: Gross national income per capita, health expenditure per capita, and Human Development Index (HDI). The outcome was overall survival at 100 days following transplantation. In each model, transplants performed within lower resourced environments were associated with inferior overall survival. In the model with the HDI as the main effect, transplants performed in the lowest HDI quartile (n = 697) were associated with increased hazard for mortality (hazard ratio, 2.42; 95% confidence interval, 1.64 to 3.57; P < .001) in comparison with transplants performed in the countries with the highest HDI quartile. This translated into an 11% survival difference at 100 days (77% for lowest HDI quartile versus 88% for all other quartiles). Country-level macroeconomic indices were associated with lower survival at 100 days after alloHCT for ALL. The reasons for this disparity require further investigation. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints

PubMed Central

Thompson, John R; Spata, Enti; Abrams, Keith R

2015-01-01

We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta-analytical methods are implemented using illustrative examples in relapsing–remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions. PMID:26271918

Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints.

PubMed

Bujkiewicz, Sylwia; Thompson, John R; Spata, Enti; Abrams, Keith R

2017-10-01

We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta-analytical methods are implemented using illustrative examples in relapsing-remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions.

Prognostic Value of Plasma Epstein-Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era.

PubMed

Chen, Wen-Hui; Tang, Lin-Quan; Guo, Shan-Shan; Chen, Qiu-Yan; Zhang, Lu; Liu, Li-Ting; Qian, Chao-Nan; Guo, Xiang; Xie, Dan; Zeng, Mu-Sheng; Mai, Hai-Qiang

2016-02-01

This study aimed to evaluate the prognostic value of plasma Epstein-Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level < 4000  copies/mL, patients with an EBV DNA ≥ 4000  copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68-84]) versus (93%, 95% CI [90-96], P < 0.001), DMFS (83%, 95% CI [76-89]) versus (97%, 95% CI [94-99], P < 0.001), and OS (85%, 95% CI [78-92]) versus (98%, 95% CI [95-100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80-6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036-3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647-14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701-8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252-5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.

Surrogate and Intermediate Endpoints in Randomized Trials: What's the Goal?

PubMed

Korn, Edward L; Freidlin, Boris

2018-05-15

Establishing trial-level surrogacy of an intermediate endpoint for predicting survival benefit in future trials is extremely challenging because of the extrapolations required, but there are other useful drug development and patient management applications of intermediate endpoints. Clin Cancer Res; 24(10); 2239-40. ©2018 AACR See related article by Mushti et al., p. 2268 . ©2018 American Association for Cancer Research.

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

Developmental genes significantly afflicted by aberrant promoter methylation and somatic mutation predict overall survival of late-stage colorectal cancer.

PubMed

An, Ning; Yang, Xue; Cheng, Shujun; Wang, Guiqi; Zhang, Kaitai

2015-12-22

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.

EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma.

PubMed

Caudron, Anne; Battistella, Maxime; Feugeas, Jean-Paul; Pages, Cécile; Basset-Seguin, Nicole; Mazouz Dorval, Sarra; Funck Brentano, Elisa; Sadoux, Aurélie; Podgorniak, Marie-Pierre; Menashi, Suzanne; Janin, Anne; Lebbé, Céleste; Mourah, Samia

2016-08-01

CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10(-8) ). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Can beaches survive climate change?

USGS Publications Warehouse

Vitousek, Sean; Barnard, Patrick L.; Limber, Patrick W.

2017-01-01

Anthropogenic climate change is driving sea level rise, leading to numerous impacts on the coastal zone, such as increased coastal flooding, beach erosion, cliff failure, saltwater intrusion in aquifers, and groundwater inundation. Many beaches around the world are currently experiencing chronic erosion as a result of gradual, present-day rates of sea level rise (about 3 mm/year) and human-driven restrictions in sand supply (e.g., harbor dredging and river damming). Accelerated sea level rise threatens to worsen coastal erosion and challenge the very existence of natural beaches throughout the world. Understanding and predicting the rates of sea level rise and coastal erosion depends on integrating data on natural systems with computer simulations. Although many computer modeling approaches are available to simulate shoreline change, few are capable of making reliable long-term predictions needed for full adaption or to enhance resilience. Recent advancements have allowed convincing decadal to centennial-scale predictions of shoreline evolution. For example, along 500 km of the Southern California coast, a new model featuring data assimilation predicts that up to 67% of beaches may completely erode by 2100 without large-scale human interventions. In spite of recent advancements, coastal evolution models must continue to improve in their theoretical framework, quantification of accuracy and uncertainty, computational efficiency, predictive capability, and integration with observed data, in order to meet the scientific and engineering challenges produced by a changing climate.

Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement.

PubMed

Córdova-Sánchez, Bertha M; Mejía-Vilet, Juan M; Morales-Buenrostro, Luis E; Loyola-Rodríguez, Georgina; Uribe-Uribe, Norma O; Correa-Rotter, Ricardo

2016-07-01

Several classification schemes have been developed for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with actual debate focusing on their clinical and prognostic performance. Sixty-two patients with renal biopsy-proven AAV from a single center in Mexico City diagnosed between 2004 and 2013 were analyzed and classified under clinical (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], renal limited vasculitis [RLV]), serological (proteinase 3 anti-neutrophil cytoplasmic antibodies [PR3-ANCA], myeloperoxidase anti-neutrophil cytoplasmic antibodies [MPO-ANCA], ANCA negative), and histopathological (focal, crescenteric, mixed-type, sclerosing) categories. Clinical presentation parameters were compared at baseline between classification groups, and the predictive value of different classification categories for disease and renal remission, relapse, renal, and patient survival was analyzed. Serological classification predicted relapse rate (PR3-ANCA hazard ratio for relapse 2.93, 1.20-7.17, p = 0.019). There were no differences in disease or renal remission, renal, or patient survival between clinical and serological categories. Histopathological classification predicted response to therapy, with a poorer renal remission rate for sclerosing group and those with less than 25 % normal glomeruli; in addition, it adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival. On multivariate models, renal replacement therapy (RRT) requirement (HR 8.07, CI 1.75-37.4, p = 0.008) and proteinuria (HR 1.49, CI 1.03-2.14, p = 0.034) at presentation predicted renal survival, while age (HR 1.10, CI 1.01-1.21, p = 0.041) and infective events during the induction phase (HR 4.72, 1.01-22.1, p = 0.049) negatively influenced patient survival. At present, ANCA-based serological classification may predict AAV relapses, but neither clinical nor serological categories predict renal or patient survival. Age, renal function and proteinuria at presentation, histopathology, and infectious complications constitute the main outcome predictors and should be considered for individualized management.

Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy

DTIC Science & Technology

2011-09-01

predict disease free survival for cervix cancer (34% disease free survival (DFS) if IFP > 19 mmHg, 68% DFS if IFP < 19 mmHg (p = 0.002)) [11]. Thus, the...pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res...Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy PRINCIPAL INVESTIGATOR: Flemming Forsberg, Ph.D

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

PubMed

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

2015-08-01

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

Single Nucleotide Polymorphisms of Stemness Genes Predicted to Regulate RNA Splicing, microRNA and Oncogenic Signaling are Associated with Prostate Cancer Survival.

PubMed

Freedman, Jennifer A; Wang, Yanru; Li, Xuechan; Liu, Hongliang; Moorman, Patricia G; George, Daniel J; Lee, Norman H; Hyslop, Terry; Wei, Qingyi; Patierno, Steven R

2018-05-03

Prostate cancer is a clinically and molecularly heterogeneous disease, with variation in outcomes only partially predicted by grade and stage. Additional tools to distinguish indolent from aggressive disease are needed. Phenotypic characteristics of stemness correlate with poor cancer prognosis. Given this correlation, we identified single nucleotide polymorphisms (SNPs) of stemness-related genes and examined their associations with prostate cancer survival. SNPs within stemness-related genes were analyzed for association with overall survival of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Significant SNPs predicted to be functional were selected for linkage disequilibrium analysis and combined and stratified analyses. Identified SNPs were evaluated for association with gene expression. SNPs of CD44 (rs9666607), ABCC1 (rs35605 and rs212091) and GDF15 (rs1058587) were associated with prostate cancer survival and predicted to be functional. A role for rs9666607 of CD44 and rs35605 of ABCC1 in RNA splicing regulation, rs212091 of ABCC1 in miRNA binding site activity and rs1058587 of GDF15 in causing an amino acid change was predicted. These SNPs represent potential novel prognostic markers for overall survival of prostate cancer and support a contribution of the stemness pathway to prostate cancer patient outcome.

Local irradiation does not enhance the effect of immunostimulatory AdCD40L gene therapy combined with low dose cyclophosphamide in melanoma patients

PubMed Central

Irenaeus, Sandra; Schiza, Aglaia; Mangsbo, Sara M.; Wenthe, Jessica; Eriksson, Emma; Krause, Johan; Sundin, Anders; Ahlström, Håkan; Tötterman, Thomas H.; Loskog, Angelica; Ullenhag, Gustav J.

2017-01-01

Background AdCD40L is an immunostimulatory gene therapy under evaluation for advanced melanoma, including ocular melanoma. Herein, we present the final data of a Phase I/IIa trial using AdCD40L alone or in combination with low dose cyclophosphamide +/- radiation therapy. Methods AdCD40L is a replication-deficient adenovirus carrying the gene for CD40 ligand (CD40L). Twenty-four patients with advanced melanoma were enrolled and treated with AdCD40L monotherapy, or combined with cyclophosphamide +/- single fraction radiotherapy. The patients were monitored for 10 weeks using immunological and radiological evaluations and thereafter for survival. Results AdCD40L treatment was safe and well tolerated both alone and in combination with cyclophosphamide as well as local radiotherapy. Four out of twenty-four patients had >1 year survival. Addition of cyclophosphamide was beneficial but adding radiotherapy did not further extend survival. High initial plasma levels of IL12 and MIP3b correlated to overall survival, whereas IL8 responses post-treatment correlated negatively with survival. Interestingly, antibody reactions to the virus correlated negatively with post IL6 and pre IL1b levels in blood. Conclusions AdCD40L was safely administered to patients and effect was improved by cyclophosphamide but not by radiotherapy. Immune activation profile at baseline may predict responders better than shortly after treatment. PMID:29108250

Estimate of survival of patients admitted to a palliative care unit: a prospective study.

PubMed

Bruera, E; Miller, M J; Kuehn, N; MacEachern, T; Hanson, J

1992-02-01

In a prospective open study, 61 consecutive patients with advanced cancer admitted to a Palliative Care Unit underwent survival estimation by two independent physicians after a complete medical exam performed during the first day of admission. An independent research nurse also assessed each patient during the first day of admission. The assessment included activity, pain, nausea, depression, anxiety, anorexia, dry mouth, dyspnea, dysphagia, weight loss, and cognitive status. After the assessment was completed, patients were followed until discharge or death. In 47 evaluable patients, logistic regression showed a significant correlation between survival and dysphagia, cognitive failure, and weight loss. Accordingly, an "indicator of poor prognosis" was considered to exist in any patient who demonstrated weight loss of 10 kg or more plus cognitive failure (Mini-Mental State Questionnaire less than 24) plus dysphagia to solids or liquids. This indicator had a similar level of sensitivity, specificity, and overall accuracy, and a higher level of significance as compared with the assessment by physician #1 and physician #2, respectively. Our data suggest that three simple determinations, which may be performed by a nurse, can predict survival more or less than 4 wk as well as the assessments of two skilled physicians. These results need to be confirmed in other trials with large numbers of patients. Perhaps confirmation of these results and identification of other prognostic factors will result in staging systems for survival estimation of terminally ill cancer patients.

Minimal residual disease in chronic lymphocytic leukaemia.

PubMed

García Vela, José Antonio; García Marco, José Antonio

2018-02-23

Minimal residual disease (MRD) assessment is an important endpoint in the treatment of chronic lymphocytic leukaemia (CLL). It is highly predictive of prolonged progression-free survival (PFS) and overall survival and could be considered a surrogate for PFS in the context of chemoimmunotherapy based treatment. Evaluation of MRD level by flow cytometry or molecular techniques in the era of the new BCR and Bcl-2 targeted inhibitors could identify the most cost-effective and durable treatment sequencing. A therapeutic approach guided by the level of MRD might also determine which patients would benefit from an early stop or consolidation therapy. In this review, we discuss the different MRD methods of analysis, which source of tumour samples must be analysed, the future role of the detection of circulating tumour DNA, and the potential role of MRD negativity in clinical practice in the modern era of CLL therapy. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

[Value of procalcitonin on predicting the severity and prognosis in patients with early ARDS: a prospective observation study].

PubMed

Yu, Zhixin; Ji, Musen; Hu, Xiulan; Yan, Jun; Jin, Zhaochen

2017-01-01

To investigate the value of procalcitonin (PCT) on predicting the severity and prognosis in patients with early acute respiratory distress syndrome (ARDS). A prospective observation study was conducted. A total of 113 patients with ARDS undergoing mechanical ventilation admitted to intensive care unit (ICU) of Affiliated People's Hospital of Jiangsu University from October 2012 to April 2016 were enrolled. Based on oxygenation index (PaO 2 /FiO 2 ), the patients were classified into mild, moderate, and severe groups according to Berlin Definition. Twenty-five healthy volunteers were served as controls. Demographics, acute physiology and chronic health evaluation II (APACHE II) score, and Murray lung injury score were recorded. Within 24 hours after diagnosis of ARDS, the serum levels of PCT and C-reactive protein (CRP) were determined by enzyme-linked fluorescence analysis (ELFA) and immune turbidimetric method, respectively. The patients were also divided into survival and non-survival groups according to clinical outcome within 28-day follow-up, and the clinical data were compared between the two groups. Spearman rank correlation was applied to determine the correlation between variables. The predictive value of the parameters on 28-day mortality was evaluated with receiver operating characteristic curve (ROC). Kaplan-Meier survival curve analysis was used to compare different PCT levels of patients with 28-day cumulative survival rate. After excluding patients who did not meet the inclusion criteria and loss to follow-up, the final 89 patients were enrolled in the analysis. Among 89 ARDS patients analyzed, 27 of them were mild, 34 moderate, and 28 severe ARDS. No significant differences were found in age and gender between ARDS and healthy control groups. Infection and trauma were the most common etiology of ARDS (55.1% and 34.8%, respectively). Compared with healthy control group, both CRP and PCT in serum of ARDS group were higher [CRP (mg/L): 146.32 (111.31, 168.49) vs. 6.08 (4.47, 7.89), PCT (μg/L): 3.46 (1.98, 5.56) vs. 0.02 (0.01, 0.04), both P < 0.01], and the two showed sustained upward trends with the ARDS course of disease. Compared with mild group, severe group had significantly higher APACHE II and Murray scores. Spearman rank correlation analysis showed that both serum PCT and CRP in patients with ARDS was correlated well with APACHE II score (r values were 0.669 and 0.601, respectively, both P < 0.001), while PCT was weakly but positively correlated with Murray score (r = 0.294, P = 0.005), but not the case of CRP (r = 0.203, P = 0.052). APACHE II score and serum PCT in non-survival group (n = 38) were significantly higher than those of the survival group [n = 51; APACHE II score: 26.00 (23.00, 28.50) vs. 21.00 (17.00, 25.00), PCT (μg/L): 6.38 (2.82, 9.49) vs. 3.09 (1.08, 3.57), both P < 0.01], but Murray score and CRP level were similar between survivors and non-survivors. The areas under ROC curve (AUC) of APACHE II score and PCT for predicting 28-day mortality were 0.781 and 0.793, respectively, which were better than those of AUC of Murray score and CRP (0.606 and 0.561, respectively, all P < 0.05). The AUC of APACHE II score combined with PCT was significantly higher than that of PCT (0.859 vs. 0.793, P = 0.048) or APACHE II score alone (0.859 vs. 0.781, P = 0.038). Using a PCT cut-off value of > 4.35 μg/L for predicting 28-day mortality, the sensitivity and specificity was 92.2% and 63.2%, respectively, and the positive and negative likelihood ratios were 2.50 and 0.12 respectively. Kaplan-Meier survival curve analysis indicated that the patients whose PCT more than 4.35 μg/L, had lower 28-day cummulative survival rate as compared with those with PCT ≤ 4.35 μg/L (log-rank test: χ 2 = 5.013, P = 0.025). The elevated serum PCT level in patients with ARDS seems to be correlated well with the severity of lung injury, and appears to be a useful prognostic marker of outcome in the early phases of ARDS.

The Epidemiology of In-Hospital Cardiopulmonary Resuscitation in Older Adults: 1992-2005

PubMed Central

Ehlenbach, William J.; Barnato, Amber E.; Curtis, J. Randall; Kreuter, William; Koepsell, Thomas D.; Deyo, Richard A.; Stapleton, Renee D.

2010-01-01

BACKGROUND It is unknown whether survival after in-hospital cardiopulmonary resuscitation (CPR) is improving and which patient and hospital characteristics predict survival. METHODS We examined fee-for-service Medicare data from 1992 to 2005 to identify beneficiaries ≥ 65 years old who received CPR in US hospitals. We examined temporal trends in the incidence of and survival after CPR, as well as patient and hospital-level predictors of survival to discharge. RESULTS We identified 433,985 cases of in-hospital CPR and 18.3% survived to discharge (95% CI 18.2-18.5%). Survival was static during this period. The incidence of CPR was 2.73 events per 1000 admissions and was higher among non-white patients. The proportion of dying patients receiving in-hospital CPR prior to death increased over time and was higher for non-white patients. Patients who were male, older, had more co-morbid illness, or were admitted from a skilled nursing facility had lower survival. Adjusted odds of survival for black patients were 23.6% lower than similar white patients (95% CI 21.2%-25.9%). The association between race and survival was partially explained by hospital effects: black patients were more likely to receive CPR in hospitals with lower post-CPR survival. Among patients surviving in-hospital CPR, the proportion of patients discharged home decreased over time. CONCLUSIONS Survival following in-hospital CPR did not improve from 1992-2005 and the proportion of patients receiving in-hospital CPR prior to death increased while the proportion of survivors discharged home after CPR decreased. Black race was associated with higher rates of CPR, but lower survival after CPR. PMID:19571280

A nomogram to predict the survival of stage IIIA-N2 non-small cell lung cancer after surgery.

PubMed

Mao, Qixing; Xia, Wenjie; Dong, Gaochao; Chen, Shuqi; Wang, Anpeng; Jin, Guangfu; Jiang, Feng; Xu, Lin

2018-04-01

Postoperative survival of patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) is highly heterogeneous. Here, we aimed to identify variables associated with postoperative survival and develop a tool for survival prediction. A retrospective review was performed in the Surveillance, Epidemiology, and End Results database from January 2004 to December 2009. Significant variables were selected by use of the backward stepwise method. The nomogram was constructed with multivariable Cox regression. The model's performance was evaluated by concordance index and calibration curve. The model was validated via an independent cohort from the Jiangsu Cancer Hospital Lung Cancer Center. A total of 1809 patients with stage IIIA-N2 NSCLC who underwent surgery were included in the training cohort. Age, sex, grade, histology, tumor size, visceral pleural invasion, positive lymph nodes, lymph nodes examined, and surgery type (lobectomy vs pneumonectomy) were identified as significant prognostic variables using backward stepwise method. A nomogram was developed from the training cohort and validated using an independent Chinese cohort. The concordance index of the model was 0.673 (95% confidence interval, 0.654-0.692) in training cohort and 0.664 in validation cohort (95% confidence interval, 0.614-0.714). The calibration plot showed optimal consistency between nomogram predicted survival and observed survival. Survival analyses demonstrated significant differences between different subgroups stratified by prognostic scores. This nomogram provided the individual survival prediction for patients with stage IIIA-N2 NSCLC after surgery, which might benefit survival counseling for patients and clinicians, clinical trial design and follow-up, as well as postoperative strategy-making. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Soluble ST2 Plasma Concentrations Predict Mortality in HBV-Related Acute-on-Chronic Liver Failure

PubMed Central

Mo, Zhishuo; Zhu, Jianyun; Pang, Xiuqing; Wu, Zhebin; Wang, Ke; Li, Xinhua; Xie, Dongying; Gao, Zhiliang

2015-01-01

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a rapidly progressing and frequently fatal condition. The aim of this study was to determine whether interleukin- (IL-) 33 and soluble ST2 (sST2) were associated with disease severity and mortality in HBV-ACLF. We found that plasma levels of sST2 but not IL-33 were higher in HBV-ACLF patients compared with chronic hepatitis B (CHB) patients and healthy controls. However, plasma levels of IL-33, TNF-α, IFN-γ, and IL-10 did not correlate with sST2 levels. Similarly, immunohistochemistry revealed low IL-33 expression and high ST2 expression in liver sections of patients with HBV-ACLF. Evaluation of dynamic changes of sST2 in HBV-ACLF showed that plasma sST2 levels increased over time in patients who died during the 180-day follow-up but decreased in those who survived. In addition, plasma sST2 level after week 1 correlated with disease severity, as assessed by total bilirubin, prothrombin time, and model for end-stage liver disease score. Results of Kaplan-Meier survival analysis showed that higher sST2 concentration (≥87 ng/mL) at week 3 was associated with poor survival. These findings indicate the potential usefulness of sST2 as a predictor of disease severity and in making treatment decisions for patients with HBV-ACLF. PMID:25892854

Overestimation of marsh vulnerability to sea level rise

USGS Publications Warehouse

Kirwan, Matthew L.; Temmerman, Stijn; Skeehan, Emily E.; Guntenspergen, Glenn R.; Fagherazzi, Sergio

2016-01-01

Coastal marshes are considered to be among the most valuable and vulnerable ecosystems on Earth, where the imminent loss of ecosystem services is a feared consequence of sea level rise. However, we show with a meta-analysis that global measurements of marsh elevation change indicate that marshes are generally building at rates similar to or exceeding historical sea level rise, and that process-based models predict survival under a wide range of future sea level scenarios. We argue that marsh vulnerability tends to be overstated because assessment methods often fail to consider biophysical feedback processes known to accelerate soil building with sea level rise, and the potential for marshes to migrate inland.

Correlation of Higher Levels of Soluble TNF-R1 with a Shorter Survival, Independent of Age, in Recurrent Glioblastoma

PubMed Central

Ahluwalia, Manmeet S.; Bou-Anak, Stephanie; Burgett, Monica E.; Sarmey, Nehaw; Khosla, Divya; Dahiya, Saurabh; Weil, Robert J.; Bae, Eunnyung; Huang, Ping; McGraw, Mary; Grove, Lisa M.; Olman, Mitchell A.; Prayson, Richard A.; Suh, John H.; Gillespie, G. Yancey; Barnholtz-Sloan, Jill; Nowacki, Amy S.; Barnett, Gene H.; Gladson, Candece L.

2016-01-01

The circulating levels of soluble tumor necrosis factor receptor-1 (sTNF-R1) and sTNF-R2 are altered in numerous diseases, including several types of cancer. Correlations with the risk of progression in some cancers, as well as systemic manifestations of the disease and therapeutic side-effects, have been described. However, there is very little information on the levels of these soluble receptors in glioblastoma (GBM). Here, we report on an exploratory retrospective study of the levels of sTNF-Rs in the vascular circulation of patients with GBM. Banked samples were obtained from 112 GBM patients (66 untreated, newly-diagnosed patients and 46 with recurrent disease) from two institutions. The levels of sTNF-R1 in the plasma were significantly lower in patients with newly-diagnosed or recurrent GBM than apparently healthy individuals and correlated with the intensity of expression of TNF-R1 on the tumor-associated endothelial cells (ECs) in the corresponding biopsies. Elevated levels of sTNF-R1 in patients with recurrent, but not newly-diagnosed GBM, were significantly associated with a shorter survival, independent of age (p=0.02) or steroid medication. In contrast, the levels of circulating sTNF-R2 were significantly higher in recurrent GBM than healthy individuals and there was no significant correlation with expression of TNF-R2 on the tumor-associated ECs or survival time. The results indicate that larger, prospective studies are warranted to determine the predictive value of the levels of sTNF-R1 in patients with recurrent GBM and the factors that regulate the levels of sTNF-Rs in the circulation in GBM patients. PMID:27858267

MGMT promoter methylation determined by HRM in comparison to MSP and pyrosequencing for predicting high-grade glioma response.

PubMed

Switzeny, Olivier J; Christmann, Markus; Renovanz, Mirjam; Giese, Alf; Sommer, Clemens; Kaina, Bernd

2016-01-01

The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) causes resistance of cancer cells to alkylating agents and, therefore, is a well-established predictive marker for high-grade gliomas that are routinely treated with alkylating drugs. Since MGMT is highly epigenetically regulated, the MGMT promoter methylation status is taken as an indicator of MGMT silencing, predicting the outcome of glioma therapy. MGMT promoter methylation is usually determined by methylation specific PCR (MSP), which is a labor intensive and error-prone method often used semi-quantitatively. Searching for alternatives, we used closed-tube high resolution melt (HRM) analysis, which is a quantitative method, and compared it with MSP and pyrosequencing regarding its predictive value. We analyzed glioblastoma cell lines with known MGMT activity and formalin-fixed samples from IDH1 wild-type high-grade glioma patients (WHO grade III/IV) treated with radiation and temozolomide by HRM, MSP, and pyrosequencing. The data were compared as to progression-free survival (PFS) and overall survival (OS) of patients exhibiting the methylated and unmethylated MGMT status. A promoter methylation cut-off level relevant for PFS and OS was determined. In a multivariate Cox regression model, methylation of MGMT promoter of high-grade gliomas analyzed by HRM, but not MSP, was found to be an independent predictive marker for OS. Univariate Kaplan-Meier analyses revealed for PFS and OS a significant and better discrimination between methylated and unmethylated tumors when quantitative HRM was used instead of MSP. Compared to MSP and pyrosequencing, the HRM method is simple, cost effective, highly accurate and fast. HRM is at least equivalent to pyrosequencing in quantifying the methylation level. It is superior in predicting PFS and OS of high-grade glioma patients compared to MSP and, therefore, can be recommended being used routinely for determination of the MGMT status of gliomas.

Can Mathematical Models Predict the Outcomes of Prostate Cancer Patients Undergoing Intermittent Androgen Deprivation Therapy?

NASA Astrophysics Data System (ADS)

Everett, R. A.; Packer, A. M.; Kuang, Y.

Androgen deprivation therapy is a common treatment for advanced or metastatic prostate cancer. Like the normal prostate, most tumors depend on androgens for proliferation and survival but often develop treatment resistance. Hormonal treatment causes many undesirable side effects which significantly decrease the quality of life for patients. Intermittently applying androgen deprivation in cycles reduces the total duration with these negative effects and may reduce selective pressure for resistance. We extend an existing model which used measurements of patient testosterone levels to accurately fit measured serum prostate specific antigen (PSA) levels. We test the model's predictive accuracy, using only a subset of the data to find parameter values. The results are compared with those of an existing piecewise linear model which does not use testosterone as an input. Since actual treatment protocol is to re-apply therapy when PSA levels recover beyond some threshold value, we develop a second method for predicting the PSA levels. Based on a small set of data from seven patients, our results showed that the piecewise linear model produced slightly more accurate results while the two predictive methods are comparable. This suggests that a simpler model may be more beneficial for a predictive use compared to a more biologically insightful model, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting. Nevertheless, both models are an important step in this direction.

Can Mathematical Models Predict the Outcomes of Prostate Cancer Patients Undergoing Intermittent Androgen Deprivation Therapy?

NASA Astrophysics Data System (ADS)

Everett, R. A.; Packer, A. M.; Kuang, Y.

2014-04-01

Androgen deprivation therapy is a common treatment for advanced or metastatic prostate cancer. Like the normal prostate, most tumors depend on androgens for proliferation and survival but often develop treatment resistance. Hormonal treatment causes many undesirable side effects which significantly decrease the quality of life for patients. Intermittently applying androgen deprivation in cycles reduces the total duration with these negative effects and may reduce selective pressure for resistance. We extend an existing model which used measurements of patient testosterone levels to accurately fit measured serum prostate specific antigen (PSA) levels. We test the model's predictive accuracy, using only a subset of the data to find parameter values. The results are compared with those of an existing piecewise linear model which does not use testosterone as an input. Since actual treatment protocol is to re-apply therapy when PSA levels recover beyond some threshold value, we develop a second method for predicting the PSA levels. Based on a small set of data from seven patients, our results showed that the piecewise linear model produced slightly more accurate results while the two predictive methods are comparable. This suggests that a simpler model may be more beneficial for a predictive use compared to a more biologically insightful model, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting. Nevertheless, both models are an important step in this direction.

Examining Racial Differences in Diffuse Large B-Cell Lymphoma Presentation and Survival

PubMed Central

Flowers, Christopher R.; Shenoy, Pareen J.; Borate, Uma; Bumpers, Kevin; Douglas-Holland, Tanyanika; King, Nassoma; Brawley, Otis W.; Lipscomb, Joseph; Lechowicz, Mary Jo; Sinha, Rajni; Grover, Rajinder S.; Bernal-Mizrachi, Leon; Kowalski, Jeanne; Donnellan, Will; The, Angelina; Reddy, Vishnu; Jaye, David L.; Foran, James

2014-01-01

We performed a retrospective cohort analysis of 701 (533 White and 144 Black) patients with DLBCL treated at two referral centers in southern United States between 1981-2010. Median age of diagnosis for Blacks was 50 years vs. 57 years for Whites (p<0.001). A greater percentage of Blacks presented with elevated lactate dehydrogenase levels, B-symptoms, and performance status≥2. More Whites (8%) than Blacks (3%) had positive family history of lymphoma (p=0.048). There were no racial differences in the use of R-CHOP (52% Black vs. 47% White, p=0.73). While black race predicted worse survival among patients treated with CHOP (Hazard ratio [HR] 1.8, p<0.001), treatment with R-CHOP was associated with improved survival irrespective of race (HR 0.61, p=0.01). Future studies should examine biological differences that may underlie the observed racial differences in presentation and outcome. PMID:22800091

Primary gastric mucosa associated lymphoid tissue lymphoma: Clinical data predicted treatment outcome

PubMed Central

Todorovic, Milena; Balint, Bela; Jevtic, Miodrag; Suvajdzic, Nada; Ceric, Amela; Stamatovic, Dragana; Markovic, Olivera; Perunicic, Maja; Marjanovic, Slobodan; Krstic, Miodrag

2008-01-01

AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages I to IV) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo. RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%. CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival. PMID:18416467

Prediction of Response to Sorafenib in Hepatocellular Carcinoma: A Putative Marker Panel by Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS).

PubMed

Kim, Hyunsoo; Yu, Su Jong; Yeo, Injun; Cho, Young Youn; Lee, Dong Hyeon; Cho, Yuri; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Sungyoung; Jun, Jongsoo; Park, Taesung; Yoon, Jung-Hwan; Kim, Youngsoo

2017-07-01

Sorafenib is the only standard treatment for unresectable hepatocellular carcinoma (HCC), but it provides modest survival benefits over placebo, necessitating predictive biomarkers of the response to sorafenib. Serum samples were obtained from 115 consecutive patients with HCC before sorafenib treatment and analyzed by multiple reaction monitoring-mass spectrometry (MRM-MS) and ELISA to quantify candidate biomarkers. We verified a triple-marker panel to be predictive of the response to sorafenib by MRM-MS, comprising CD5 antigen-like (CD5L), immunoglobulin J (IGJ), and galectin-3-binding protein (LGALS3BP), in HCC patients. This panel was a significant predictor (AUROC > 0.950) of the response to sorafenib treatment, having the best cut-off value (0.4) by multivariate analysis. In the training set, patients who exceeded this cut-off value had significantly better overall survival (median, 21.4 months) than those with lower values (median, 8.6 months; p = 0.001). Further, a value that was lower than this cutoff was an independent predictor of poor overall survival [hazard ratio (HR), 2.728; 95% confidence interval (CI), 1.312-5.672; p = 0.007] and remained an independent predictive factor of rapid progression (HR, 2.631; 95% CI, 1.448-4.780; p = 0.002). When applied to the independent validation set, levels of the cut-off value for triple-marker panel maintained their prognostic value for poor clinical outcomes. On the contrast, the triple-marker panel was not a prognostic factor for patients who were treated with transarterial chemoembolization (TACE). The discriminatory signature of a triple-marker panel provides new insights into targeted proteomic biomarkers for individualized sorafenib therapy. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A Gene Signature to Determine Metastatic Behavior in Thymomas

PubMed Central

Gökmen-Polar, Yesim; Wilkinson, Jeff; Maetzold, Derek; Stone, John F.; Oelschlager, Kristen M.; Vladislav, Ioan Tudor; Shirar, Kristen L.; Kesler, Kenneth A.; Loehrer, Patrick J.; Badve, Sunil

2013-01-01

Purpose Thymoma represents one of the rarest of all malignancies. Stage and completeness of resection have been used to ascertain postoperative therapeutic strategies albeit with limited prognostic accuracy. A molecular classifier would be useful to improve the assessment of metastatic behaviour and optimize patient management. Methods qRT-PCR assay for 23 genes (19 test and four reference genes) was performed on multi-institutional archival primary thymomas (n = 36). Gene expression levels were used to compute a signature, classifying tumors into classes 1 and 2, corresponding to low or high likelihood for metastases. The signature was validated in an independent multi-institutional cohort of patients (n = 75). Results A nine-gene signature that can predict metastatic behavior of thymomas was developed and validated. Using radial basis machine modeling in the training set, 5-year and 10-year metastasis-free survival rates were 77% and 26% for predicted low (class 1) and high (class 2) risk of metastasis (P = 0.0047, log-rank), respectively. For the validation set, 5-year metastasis-free survival rates were 97% and 30% for predicted low- and high-risk patients (P = 0.0004, log-rank), respectively. The 5-year metastasis-free survival rates for the validation set were 49% and 41% for Masaoka stages I/II and III/IV (P = 0.0537, log-rank), respectively. In univariate and multivariate Cox models evaluating common prognostic factors for thymoma metastasis, the nine-gene signature was the only independent indicator of metastases (P = 0.036). Conclusion A nine-gene signature was established and validated which predicts the likelihood of metastasis more accurately than traditional staging. This further underscores the biologic determinants of the clinical course of thymoma and may improve patient management. PMID:23894276

Genetic variability of VEGF pathway genes in six randomized phase III trials assessing the addition of bevacizumab to standard therapy.

PubMed

de Haas, Sanne; Delmar, Paul; Bansal, Aruna T; Moisse, Matthieu; Miles, David W; Leighl, Natasha; Escudier, Bernard; Van Cutsem, Eric; Carmeliet, Peter; Scherer, Stefan J; Pallaud, Celine; Lambrechts, Diether

2014-10-01

Despite extensive translational research, no validated biomarkers predictive of bevacizumab treatment outcome have been identified. We performed a meta-analysis of individual patient data from six randomized phase III trials in colorectal, pancreatic, lung, renal, breast, and gastric cancer to explore the potential relationships between 195 common genetic variants in the vascular endothelial growth factor (VEGF) pathway and bevacizumab treatment outcome. The analysis included 1,402 patients (716 bevacizumab-treated and 686 placebo-treated). Twenty variants were associated (P < 0.05) with progression-free survival (PFS) in bevacizumab-treated patients. Of these, 4 variants in EPAS1 survived correction for multiple testing (q < 0.05). Genotype-by-treatment interaction tests revealed that, across these 20 variants, 3 variants in VEGF-C (rs12510099), EPAS1 (rs4953344), and IL8RA (rs2234671) were potentially predictive (P < 0.05), but not resistant to multiple testing (q > 0.05). A weak genotype-by-treatment interaction effect was also observed for rs699946 in VEGF-A, whereas Bayesian genewise analysis revealed that genetic variability in VHL was associated with PFS in the bevacizumab arm (q < 0.05). Variants in VEGF-A, EPAS1, and VHL were located in expression quantitative loci derived from lymphoblastoid cell lines, indicating that they affect the expression levels of their respective gene. This large genetic analysis suggests that variants in VEGF-A, EPAS1, IL8RA, VHL, and VEGF-C have potential value in predicting bevacizumab treatment outcome across tumor types. Although these associations did not survive correction for multiple testing in a genotype-by-interaction analysis, they are among the strongest predictive effects reported to date for genetic variants and bevacizumab efficacy.

Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection.

PubMed

Kuroda, Daisuke; Sawayama, Hiroshi; Kurashige, Junji; Iwatsuki, Masaaki; Eto, Tsugio; Tokunaga, Ryuma; Kitano, Yuki; Yamamura, Kensuke; Ouchi, Mayuko; Nakamura, Kenichi; Baba, Yoshifumi; Sakamoto, Yasuo; Yamashita, Yoichi; Yoshida, Naoya; Chikamoto, Akira; Baba, Hideo

2018-03-01

Controlling Nutritional Status (CONUT), as calculated from serum albumin, total cholesterol concentration, and total lymphocyte count, was previously shown to be useful for nutritional assessment. The current study investigated the potential use of CONUT as a prognostic marker in gastric cancer patients after curative resection. Preoperative CONUT was retrospectively calculated in 416 gastric cancer patients who underwent curative resection at Kumamoto University Hospital from 2005 to 2014. The patients were divided into two groups: CONUT-high (≥4) and CONUT-low (≤3), according to time-dependent receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. CONUT-high patients were significantly older (p < 0.001) and had a lower body mass index (p = 0.019), deeper invasion (p < 0.001), higher serum carcinoembryonic antigen (p = 0.037), and higher serum carbohydrate antigen 19-9 (p = 0.007) compared with CONUT-low patients. CONUT-high patients had significantly poorer overall survival (OS) compared with CONUT-low patients according to univariate and multivariate analyses (hazard ratio: 5.09, 95% confidence interval 3.12-8.30, p < 0.001). In time-dependent ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 5-year OS than the neutrophil lymphocyte ratio, the Modified Glasgow Prognostic Score, or pStage. When the time-dependent AUC curve was used to predict OS, CONUT tended to maintain its predictive accuracy for long-term survival at a significantly higher level for an extended period after surgery when compared with the other markers tested. CONUT is useful for not only estimating nutritional status but also for predicting long-term OS in gastric cancer patients after curative resection.

Timing of referral for lung transplantation for cystic fibrosis: overemphasis on FEV1 may adversely affect overall survival.

PubMed

Doershuk, C F; Stern, R C

1999-03-01

(1) Report our experience with referral for lung transplantation. (2) Review survival in cvstic fibrosis (CF) patients without lung transplantation after FEV1 remains < 30% predicted for 1 years. Retrospective review. A university hospital CF center. (1) Forty-five patients referred for lung transplantation evaluation, and (2) 178 patients without Burkholderia sp infection, with the above FEVl criterion. Survival. (1) One- and 2-year survival after transplantation was 55% and 45%, respectively. However, among patients without transplants with FEVl < 30% predicted, median survival, 1986 to 1990, ie, before the transplant era, was 4.6 years with 25% living > 9 years (before 1986, 25% lived > 6 vears). (2) Survival after transplantation was not correlated to any of the following: age, sex, genotype, FEVI percent predicted, insulin-dependent diabetes mellitus, or with waiting time before transplantation, and did not seem to be correlated to serum bicarbonate or percent ideal body weight. Four of five patients already infected with Burkholderia species died within 5 months of transplantation; the fifth died at 17 months. All five died of pulmonary or extrapulmonarv infection with Burkholderia species Use of FEV! < 30% predicted to automatically establish transplantation eligibility could lead to decreased overall survival for CF patients. Referral for evaluation and transplantation should also be based on oxygen requirement, rate of deterioration, respiratory microbiology, quality of life, frequency of IV antibiotic therapy, and other considerations. If pulmonary status has unexpectedly improved when the patient is at or near the top of the waiting list, total survival may be improved by "inactivating the patient" until progression is again evident.

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.

The RNA-binding protein PCBP2 facilitates gastric carcinoma growth by targeting miR-34a

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

Hu, Cheng-En; Liu, Yong-Chao; Zhang, Hui-Dong

Highlights: • PCBP2 is overexpressed in human gastric cancer. • PCBP2 high expression predicts poor survival. • PCBP2 regulates gastric cancer growth in vitro and in vivo. • PCBP2 regulates gastric cancer apoptosis by targeting miR-34a. - Abstract: Gastric carcinoma is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. However, the mechanism underling gastric cancer is still not fully understood. Here in the present study, we identify the RNA-binding protein PCBP2 as an oncogenic protein in human gastric carcinoma. Our results show that PCBP2 is up-regulated in human gastric cancer tissuesmore » compared to adjacent normal tissues, and that high level of PCBP2 predicts poor overall and disease-free survival. Knockdown of PCBP2 in gastric cancer cells inhibits cell proliferation and colony formation in vitro, whereas opposing results are obtained when PCBP2 is overexpressed. Our in vivo subcutaneous xenograft results also show that PCBP2 can critically regulate gastric cancer cell growth. In addition, we find that PCBP2-depletion induces apoptosis in gastric cancer cells via up-regulating expression of pro-apoptotic proteins and down-regulating anti-apoptotic proteins. Mechanically, we identify that miR-34a as a target of PCBP2, and that miR-34a is critically essential for the function of PCBP2. In summary, PCBP2 promotes gastric carcinoma development by regulating the level of miR-34a.« less

Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) interacts with estrogen receptor and predicted poor survival in breast cancer.

PubMed

Huang, Nai-Si; Chi, Ya-Yun; Xue, Jing-Yan; Liu, Meng-Ying; Huang, Sheng; Mo, Miao; Zhou, Shu-Ling; Wu, Jiong

2016-06-21

Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1), a lncRNA that was first recognized as a prognostic parameter for patient survival of stage I lung cancer, is up-regulated in multiple human malignancies, including breast cancer. However, the mechanism of its function remained elusive. In the current study, by examining MALAT1 expression on mRNA level, we demonstrated that compared with MCF10A, MALAT1 expression was up-regulated in the majority of breast cancer cell lines (9/12). In 26 pairs of estrogen receptor (ER)-positive breast cancer samples, MALAT1 expression was significantly up-regulated compared with adjacent normal tissues (P = 0.012). Furthermore, of 204 breast cancer patients, high MALAT1 expression was associated with positive ER (P = 0.023) and progesterone receptor (PR) (P = 0.024) status. Further analysis using TCGA database revealed that ER and its target genes PGR and CCND1, were overexpressed in MALAT1 altered group compared with unaltered group, both on the mRNA and protein level. Lastly, we verified MALAT1's prognostic value in breast cancer. At the cut-off value of 75%, MALAT1 was the only independent prognostic factor of recurrence-free survival (RFS) in ER-negative patients in a multivariate Cox regression model (hazard ratio [HR] = 2.83, 95% confidence interval [CI] 1.02-7.83). MALAT1 overexpression was also associated with poor RFS in tamoxifen treated ER-positive breast cancer patients, which might serve as a potential biomarker to predict endocrine treatment sensitivity.

Assessing uncertainty in ecological systems using global sensitivity analyses: a case example of simulated wolf reintroduction effects on elk

USGS Publications Warehouse

Fieberg, J.; Jenkins, Kurt J.

2005-01-01

Often landmark conservation decisions are made despite an incomplete knowledge of system behavior and inexact predictions of how complex ecosystems will respond to management actions. For example, predicting the feasibility and likely effects of restoring top-level carnivores such as the gray wolf (Canis lupus) to North American wilderness areas is hampered by incomplete knowledge of the predator-prey system processes and properties. In such cases, global sensitivity measures, such as Sobola?? indices, allow one to quantify the effect of these uncertainties on model predictions. Sobola?? indices are calculated by decomposing the variance in model predictions (due to parameter uncertainty) into main effects of model parameters and their higher order interactions. Model parameters with large sensitivity indices can then be identified for further study in order to improve predictive capabilities. Here, we illustrate the use of Sobola?? sensitivity indices to examine the effect of parameter uncertainty on the predicted decline of elk (Cervus elaphus) population sizes following a hypothetical reintroduction of wolves to Olympic National Park, Washington, USA. The strength of density dependence acting on survival of adult elk and magnitude of predation were the most influential factors controlling elk population size following a simulated wolf reintroduction. In particular, the form of density dependence in natural survival rates and the per-capita predation rate together accounted for over 90% of variation in simulated elk population trends. Additional research on wolf predation rates on elk and natural compensations in prey populations is needed to reliably predict the outcome of predatora??prey system behavior following wolf reintroductions.

Linking resources with demography to understand resource limitation for bears

USGS Publications Warehouse

Reynolds-Hogland, M. J.; Pacifici, L.B.; Mitchell, M.S.

2007-01-01

1. Identifying the resources that limit growth of animal populations is essential for effective conservation; however, resource limitation is difficult to quantify. Recent advances in geographical information systems (GIS) and resource modelling can be combined with demographic modelling to yield insights into resource limitation. 2. Using long-term data on a population of black bears Ursus americanus, we evaluated competing hypotheses about whether availability of hard mast (acorns and nuts) or soft mast (fleshy fruits) limited bears in the southern Appalachians, USA, during 1981-2002. The effects of clearcutting on habitat quality were also evaluated. Annual survival, recruitment and population growth rate were estimated using capture-recapture data from 101 females. The availability of hard mast, soft mast and clearcuts was estimated with a GIS, as each changed through time as a result of harvest and succession, and then availabilities were incorporated as covariates for each demographic parameter. 3. The model with the additive availability of hard mast and soft mast across the landscape predicted survival and population growth rate. Availability of young clearcuts predicted recruitment, but not population growth or survival. 4. Availability of hard mast stands across the landscape and availability of soft mast across the landscape were more important than hard mast production and availability of soft mast in young clearcuts, respectively. 5. Synthesis and applications. Our results indicate that older stands, which support high levels of hard mast and moderate levels of soft mast, should be maintained to sustain population growth of bears in the southern Appalachians. Simultaneously, the acreage of intermediate aged stands (10-25 years), which support very low levels of both hard mast and soft mast, should be minimized. The approach used in this study has broad application for wildlife management and conservation. State and federal wildlife agencies often possess long-term data on both resource availability and capture-recapture for wild populations. Combined, these two data types can be used to estimate survival, recruitment, population growth, elasticities of vital rates and the effects of resource availability on demographic parameters. Hence data that are traditionally used to understand population trends can be used to evaluate how and why demography changes over time. ?? 2007 The Authors.

Zoom in at African country level: potential climate induced changes in areas of suitability for survival of malaria vectors.

PubMed

Tonnang, Henri E Z; Tchouassi, David P; Juarez, Henry S; Igweta, Lilian K; Djouaka, Rousseau F

2014-05-07

Predicting anopheles vectors' population densities and boundary shifts is crucial in preparing for malaria risks and unanticipated outbreaks. Although shifts in the distribution and boundaries of the major malaria vectors (Anopheles gambiae s.s. and An. arabiensis) across Africa have been predicted, quantified areas of absolute change in zone of suitability for their survival have not been defined. In this study, we have quantified areas of absolute change conducive for the establishment and survival of these vectors, per African country, under two climate change scenarios and based on our findings, highlight practical measures for effective malaria control in the face of changing climatic patterns. We developed a model using CLIMEX simulation platform to estimate the potential geographical distribution and seasonal abundance of these malaria vectors in relation to climatic factors (temperature, rainfall and relative humidity). The model yielded an eco-climatic index (EI) describing the total favourable geographical locations for the species. The EI values were classified and exported to a GIS package. Using ArcGIS, the EI shape points were clipped to the extent of Africa and then converted to a raster layer using Inverse Distance Weighted (IDW) interpolation method. Generated maps were then transformed into polygon-based geo-referenced data set and their areas computed and expressed in square kilometers (km(2)). Five classes of EI were derived indicating the level of survivorship of these malaria vectors. The proportion of areas increasing or decreasing in level of survival of these malaria vectors will be more pronounced in eastern and southern African countries than those in western Africa. Angola, Ethiopia, Kenya, Mozambique, Tanzania, South Africa and Zambia appear most likely to be affected in terms of absolute change of malaria vectors suitability zones under the selected climate change scenarios. The potential shifts of these malaria vectors have implications for human exposure to malaria, as recrudescence of the disease is likely to be recorded in several new areas and regions. Therefore, the need to develop, compile and share malaria preventive measures, which can be adapted to different climatic scenarios, remains crucial.

Zoom in at African country level: potential climate induced changes in areas of suitability for survival of malaria vectors

PubMed Central

2014-01-01

Background Predicting anopheles vectors’ population densities and boundary shifts is crucial in preparing for malaria risks and unanticipated outbreaks. Although shifts in the distribution and boundaries of the major malaria vectors (Anopheles gambiae s.s. and An. arabiensis) across Africa have been predicted, quantified areas of absolute change in zone of suitability for their survival have not been defined. In this study, we have quantified areas of absolute change conducive for the establishment and survival of these vectors, per African country, under two climate change scenarios and based on our findings, highlight practical measures for effective malaria control in the face of changing climatic patterns. Methods We developed a model using CLIMEX simulation platform to estimate the potential geographical distribution and seasonal abundance of these malaria vectors in relation to climatic factors (temperature, rainfall and relative humidity). The model yielded an eco-climatic index (EI) describing the total favourable geographical locations for the species. The EI values were classified and exported to a GIS package. Using ArcGIS, the EI shape points were clipped to the extent of Africa and then converted to a raster layer using Inverse Distance Weighted (IDW) interpolation method. Generated maps were then transformed into polygon-based geo-referenced data set and their areas computed and expressed in square kilometers (km2). Results Five classes of EI were derived indicating the level of survivorship of these malaria vectors. The proportion of areas increasing or decreasing in level of survival of these malaria vectors will be more pronounced in eastern and southern African countries than those in western Africa. Angola, Ethiopia, Kenya, Mozambique, Tanzania, South Africa and Zambia appear most likely to be affected in terms of absolute change of malaria vectors suitability zones under the selected climate change scenarios. Conclusion The potential shifts of these malaria vectors have implications for human exposure to malaria, as recrudescence of the disease is likely to be recorded in several new areas and regions. Therefore, the need to develop, compile and share malaria preventive measures, which can be adapted to different climatic scenarios, remains crucial. PMID:24885061

Rapid learning in practice: A lung cancer survival decision support system in routine patient care data

PubMed Central

Dekker, Andre; Vinod, Shalini; Holloway, Lois; Oberije, Cary; George, Armia; Goozee, Gary; Delaney, Geoff P.; Lambin, Philippe; Thwaites, David

2016-01-01

Background and purpose A rapid learning approach has been proposed to extract and apply knowledge from routine care data rather than solely relying on clinical trial evidence. To validate this in practice we deployed a previously developed decision support system (DSS) in a typical, busy clinic for non-small cell lung cancer (NSCLC) patients. Material and methods Gender, age, performance status, lung function, lymph node status, tumor volume and survival were extracted without review from clinical data sources for lung cancer patients. With these data the DSS was tested to predict overall survival. Results 3919 lung cancer patients were identified with 159 eligible for inclusion, due to ineligible histology or stage, non-radical dose, missing tumor volume or survival. The DSS successfully identified a good prognosis group and a medium/poor prognosis group (2 year OS 69% vs. 27/30%, p < 0.001). Stage was less discriminatory (2 year OS 47% for stage I–II vs. 36% for stage IIIA–IIIB, p = 0.12) with most good prognosis patients having higher stage disease. The DSS predicted a large absolute overall survival benefit (~40%) for a radical dose compared to a non-radical dose in patients with a good prognosis, while no survival benefit of radical radiotherapy was predicted for patients with a poor prognosis. Conclusions A rapid learning environment is possible with the quality of clinical data sufficient to validate a DSS. It uses patient and tumor features to identify prognostic groups in whom therapy can be individualized based on predicted outcomes. Especially the survival benefit of a radical versus non-radical dose predicted by the DSS for various prognostic groups has clinical relevance, but needs to be prospectively validated. PMID:25241994

Stereotactic Body Radiotherapy Versus Surgery for Medically Operable Stage I Non-Small-Cell Lung Cancer: A Markov Model-Based Decision Analysis

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

Louie, Alexander V.; Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca; Department of Epidemiology/Biostatistics, University of Western Ontario, London, ON

Purpose: To compare the quality-adjusted life expectancy and overall survival in patients with Stage I non-small-cell lung cancer (NSCLC) treated with either stereotactic body radiation therapy (SBRT) or surgery. Methods and Materials: We constructed a Markov model to describe health states after either SBRT or lobectomy for Stage I NSCLC for a 5-year time frame. We report various treatment strategy survival outcomes stratified by age, sex, and pack-year history of smoking, and compared these with an external outcome prediction tool (Adjuvant{exclamation_point} Online). Results: Overall survival, cancer-specific survival, and other causes of death as predicted by our model correlated closely withmore » those predicted by the external prediction tool. Overall survival at 5 years as predicted by baseline analysis of our model is in favor of surgery, with a benefit ranging from 2.2% to 3.0% for all cohorts. Mean quality-adjusted life expectancy ranged from 3.28 to 3.78 years after surgery and from 3.35 to 3.87 years for SBRT. The utility threshold for preferring SBRT over surgery was 0.90. Outcomes were sensitive to quality of life, the proportion of local and regional recurrences treated with standard vs. palliative treatments, and the surgery- and SBRT-related mortalities. Conclusions: The role of SBRT in the medically operable patient is yet to be defined. Our model indicates that SBRT may offer comparable overall survival and quality-adjusted life expectancy as compared with surgical resection. Well-powered prospective studies comparing surgery vs. SBRT in early-stage lung cancer are warranted to further investigate the relative survival, quality of life, and cost characteristics of both treatment paradigms.« less

Factors predictive of survival after stapler hepatectomy of hepatocellular carcinoma: a multivariate, single-center analysis.

PubMed

Hoffmann, Katrin; Müller-Bütow, Verena; Franz, Clemens; Hinz, Ulf; Longerich, Thomas; Büchler, Markus W; Schemmer, Peter

2014-02-01

New technical devices for hepatic parenchymal transection have improved perioperative safety and patient survival. The aim of the present study was to determine the oncological outcome after stapler hepatectomy in patients with HCC. Data of 95 patients who underwent stapler hepatectomy for HCC between 2001 and 2011 were analyzed retrospectively regarding clinical safety of the procedure and predictive factors for survial. Thirty-nine minor (≤2 segments) and 56 major (≥3 segments) hepatic resections were performed. The median survival was 47.5 months, after 36 months follow-up. Low grading, tumors ≥5 cm, multiple nodules and liver cirrhosis were predictors of decreased overall survival using multivariate analysis with hazard ratio(HR)=2.62, 2.41, 2.05, and 1.92 respectively. An estimated intra-operative blood loss of ≥1.2l was inversely correlated to disease free survival (HR=1.96). Stapler hepatectomy is a safe procedure in patients with HCC. Substantial intraoperative blood loss and the presence of cirrhosis independently predict the overall probability of patient survival. Intraoperative blood loss directly impacts HCC recurrence.

Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer

PubMed Central

Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

2017-01-01

Purpose This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). Materials and Methods We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). Results In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Conclusion Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes. PMID:27669704

Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer.

PubMed

Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

2017-07-01

This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.

Clinical and histopathologic independent prognostic factors in oral squamous cell carcinoma: a retrospective study of 334 cases.

PubMed

Arduino, Paolo G; Carrozzo, Marco; Chiecchio, Andrea; Broccoletti, Roberto; Tirone, Federico; Borra, Eleonora; Bertolusso, Giorgio; Gandolfo, Sergio

2008-08-01

This retrospective hospital-based study reviewed and evaluated the outcome of patients with oral squamous cell carcinoma (OSCC) with the aim of identifying factors affecting the clinical course and survival rate. Patients with a follow-up of at least 12 months were included. The data collected were statistically analyzed for the presence of factors valuable for prognosis; survival curves were processed in accordance with the Kaplan-Meier method. Differences in the expression of variables in different grading levels were investigated. Cox's proportional hazard model for Z(i) covariates (grading, age, T, N) also was calculated. Mean patient age was 67.7 years in women (n = 152) and 62.4 years in men (n = 182). A total of 98 patients were identified with Broder's/World Health Organization grade 1 histology, 176 with grade 2, and 55 with grade 3; 5 patients were identified as grade 4 (carcinoma in situ). Gender and risk factors seemed to be unrelated to prognosis, whereas a significant increase in mortality was seen in patients over age 70. Histological grading, tumor size, and neck involvement were related, as independent factors, in predicting survival in patients with OSCC (QM-H > 3.9). Gender, age, and risk factors had no statistical relationship with cancer histological differentiation. Our analysis reveals a statistically significant relationship among histological Broder's grading of malignancy, tumor size, locoregional involvement, and survival rates, underscoring the utility of tumor differentiation in predicting the clinical course and outcome of OSCC.

Validation of Clinical Scoring Systems ART and ABCR after Transarterial Chemoembolization of Hepatocellular Carcinoma.

PubMed

Kloeckner, Roman; Pitton, Michael B; Dueber, Christoph; Schmidtmann, Irene; Galle, Peter R; Koch, Sandra; Wörns, Marcus A; Weinmann, Arndt

2017-01-01

To perform an external validation of the Assessment for Retreatment with Transarterial Chemoembolization (ART) and α-fetoprotein (AFP), Barcelona Clinic Liver Cancer (BCLC), Child-Pugh, and response (ABCR) scores and to compare them in terms of prognostic power. From 2000 to 2015, 871 patients with hepatocellular carcinoma underwent transarterial chemoembolization at a tertiary referral hospital, and 176 met all inclusion and exclusion criteria for both scores and were analyzed. Nineteen percent (n = 34) had BCLC stage A disease and 81% had stage B disease. Thirty-nine patients (22%) presented with elevated AFP levels. Overall survival was calculated. Scores were validated and compared with a Harrell C-index, integrated Brier score (IBS), and prediction error curves. Before the second chemoembolization procedure, 22 patients (12%) showed an increase of 1 point in Child-Pugh score and 51 patients (22%) had an increase of ≥ 2 points. Thirty-one patients (23%) showed a > 25% increase in aspartate aminotransferase level, and 114 (65%) showed a response to treatment. Consequently, 127 patients (72%) had a low ART score and 49 (28%) had a high ART score. One hundred fifty-eight patients (90%) had a low ABCR score, whereas 18 (10%) had a high ABCR score. Low and high ART score groups had median survival durations of 20.8 and 15.3 mo, respectively. Harrell C-indexes were 0.572 and 0.608, and IBSs were 0.135 and 0.128, for ART and ABCR, respectively. For both scores, an increase in Child-Pugh score ≥ 2 points and a radiologic response were significantly associated with survival. Both scores were of limited predictive value, and neither was sufficient to support clear-cut clinical decisions. Further effort is necessary to determine criteria for making valid clinical predictions. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Differences in baseline factors and survival between normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis in COPD exacerbation: A pilot study.

PubMed

Lun, Chung-Tat; Tsui, Miranda S N; Cheng, Suet-Lai; Chan, Veronica L; Leung, Wah-Shing; Cheung, Alice P S; Chu, Chung-Ming

2016-01-01

Patients with chronic obstructive pulmonary disease (COPD) experiencing acute exacerbation (AE-COPD) with decompensated respiratory acidosis are known to have poor outcomes in terms of recurrent respiratory failure and death. However, the outcomes of AE-COPD patients with compensated respiratory acidosis are not known. We performed a 1-year prospective, single-centre, cohort study in patients surviving the index admission for AE-COPD to compare baseline factors between groups with normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis. Survival analysis was done to examine time to readmissions, life-threatening events and death. A total of 250 patients fulfilling the inclusion and exclusion criteria were recruited and 245 patients were analysed. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with lower FEV1 % (P < 0.001), higher GOLD stage (P = 0.003, <0.001) and higher BODE index (P = 0.038, 0.001) and a shorter time to life-threatening events (P < 0.001). Comparing compensated and decompensated respiratory acidosis, there was no difference in FEV1 (% predicted) (P = 0.15), GOLD stage (P = 0.091), BODE index (P = 0.158) or time to life-threatening events (P = 0.301). High PaCO2 level (P = 0.002) and previous use of non-invasive ventilation (NIV) in acute setting (P < 0.001) are predictive factors of future life-threatening events by multivariate analysis. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with poorer lung function and higher risk of future life-threatening events. High PaCO2 level and past history of NIV use in acute settings were predictive factors for future life-threatening events. Compensated respiratory acidosis warrants special attention and optimization of medical therapy as it poses risk of life-threatening events. © 2015 Asian Pacific Society of Respirology.

Bridging non-human primate correlates of protection to reassess the Anthrax Vaccine Adsorbed booster schedule in humans.

PubMed

Schiffer, Jarad M; Chen, Ligong; Dalton, Shannon; Niemuth, Nancy A; Sabourin, Carol L; Quinn, Conrad P

2015-07-17

Anthrax Vaccine Adsorbed (AVA, BioThrax) is approved for use in humans as a priming series of 3 intramuscular (i.m.) injections (0, 1, 6 months; 3-IM) with boosters at 12 and 18 months, and annually thereafter for those at continued risk of infection. A reduction in AVA booster frequency would lessen the burden of vaccination, reduce the cumulative frequency of vaccine associated adverse events and potentially expand vaccine coverage by requiring fewer doses per schedule. Because human inhalation anthrax studies are neither feasible nor ethical, AVA efficacy estimates are determined using cross-species bridging of immune correlates of protection (COP) identified in animal models. We have previously reported that the AVA 3-IM priming series provided high levels of protection in non-human primates (NHP) against inhalation anthrax for up to 4 years after the first vaccination. Penalized logistic regressions of those NHP immunological data identified that anti-protective antigen (anti-PA) IgG concentration measured just prior to infectious challenge was the most accurate single COP. In the present analysis, cross-species logistic regression models of this COP were used to predict probability of survival during a 43 month study in humans receiving the current 3-dose priming and 4 boosters (12, 18, 30 and 42 months; 7-IM) and reduced schedules with boosters at months 18 and 42 only (5-IM), or at month 42 only (4-IM). All models predicted high survival probabilities for the reduced schedules from 7 to 43 months. The predicted survival probabilities for the reduced schedules were 86.8% (4-IM) and 95.8% (5-IM) at month 42 when antibody levels were lowest. The data indicated that 4-IM and 5-IM are both viable alternatives to the current AVA pre-exposure prophylaxis schedule. Published by Elsevier Ltd.

Stratification based on reproductive state reveals contrasting patterns of age-related variation in demographic parameters in the kittiwake

USGS Publications Warehouse

Cam, E.; Monnat, J.-Y.

2000-01-01

Heterogeneity in individual quality can be a major obstacle when interpreting age-specific variation in life-history traits. Heterogeneity is likely to lead to within-generation selection, and patterns observed at the population level may result from the combination of hidden patterns specific to subpopulations. Population-level patterns are not relevant to hypotheses concerning the evolution of age-specific reproductive strategies if they differ from patterns at the individual level. We addressed the influence of age and a variable used as a surrogate of quality (yearly reproductive state) on survival and breeding probability in the kittiwake. We found evidence of an effect of age and quality on both demographic parameters. Patterns observed in breeders are consistent with the selection hypothesis, which predicts age-related increases in survival and traits positively correlated with survival. Our results also reveal unexpected age effects specific to subgroups: the influence of age on survival and future breeding probability is not the same in nonbreeders and breeders. These patterns are observed in higher-quality breeding habitats, where the influence of extrinsic factors on breeding state is the weakest. Moreover, there is slight evidence of an influence of sex on breeding probability (not on survival), but the same overall pattern is observed in both sexes. Our results support the hypothesis that age-related variation in demographic parameters observed at the population level is partly shaped by heterogeneity among individuals. They also suggest processes specific to subpopulations. Recent theoreticaI developments lay emphasis on integration of sources of heterogeneity in optimization models to account for apparently 'sub-optimal' empirical patterns. Incorporation of sources of heterogeneity is also the key to investigation of age-related reproductive strategies in heterogeneous populations. Thwarting 'heterogeneity's ruses' has become a major challenge: for detecting and understanding natural processes, and a constructive confrontation between empirical and theoretical studies.

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

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

Zhang, Hui; Liu, Tao; Zhang, Zhen

Ovarian cancer remains the most lethal gynecological malignancy in the developed world, despite recent advances in genomic information and treatment. To better understand this disease, define an integrated proteogenomic landscape, and identify factors associated with homologous repair deficiency (HRD) and overall survival, we performed a comprehensive proteomic characterization of ovarian high-grade serous carcinomas (HGSC) previously characterized by The Cancer Genome Atlas (TCGA). We observed that messenger RNA transcript abundance did not reliably predict abundance for 10,030 proteins across 174 tumors. Clustering of tumors based on protein abundance identified five subtypes, two of which correlated robustly with mesenchymal and proliferative subtypes,more » while tumors characterized as immunoreactive or differentiated at the transcript level were intermixed at the protein level. At the genome level, HGSC is characterized by a complex landscape of somatic copy number alterations (CNA), which individually do not correlate significantly with survival. Correlation of CNAs with protein abundances identified loci with significant trans regulatory effects mapping to pathways associated with proliferation, cell motility/invasion, and immune regulation, three known hallmarks of cancer. Using the trans regulated proteins we also created models significantly correlated with patient survival by multivariate analysis. Integrating protein abundance with specific post-translational modification data identified subnetworks correlated with HRD status; specifically, acetylation of Lys12 and Lys16 on histone H4 was associated with HRD status. Using quantitative phosphoproteomics data covering 4,420 proteins as reflective of pathway activity, we identified the PDGFR and VEGFR signaling pathways as significantly up-regulated in patients with short overall survival, independent of PDGFR and VEGFR protein levels, potentially informing the use of anti-angiogenic therapies. Components of the Rho/Rac/Cdc42 cell motility pathways were also significantly enriched for short survival. Overall, proteomics provided new insights into ovarian cancer not apparent from genomic analysis and enabling a deeper understanding of HGSC with the potential to inform targeted therapeutics.« less

The Prognostic Significance of Elevated Serum Ferritin Levels Prior to Transplantation in Patients With Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation (autoHSCT): Role of Iron Overload.

PubMed

Sivgin, Serdar; Karamustafaoglu, Mehmet Fatih; Yildizhan, Esra; Zararsiz, Gokmen; Kaynar, Leylagul; Eser, Bulent; Cetin, Mustafa; Unal, Ali

2016-08-01

Hematopoietic stem cell transplantation is a common and preferred treatment of lymphomas in many centers. Our goal was to determine the association between pretransplant iron overload and survival in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT). A total of 165 patients with lymphoma, who underwent autoHSCT between the years of 2007 and 2014, were included in this study. Ferritin levels were used to determine iron status; the cut-off value was 500 ng/mL. The relationship between iron overload and survival was assessed by statistical analysis. The median ferritin level in the normal ferritin (ferritin < 500) group was 118 ng/mL (range, 9-494 ng/mL) and in the high-ferritin group (ferritin ≥ 500), it was 908 ng/mL (range, 503-4549 ng/mL). A total of 64 (38.8%) patients died during follow-up. Of these patients that died, 52 (81.25%) were in the high-ferritin group, and 12 (18.75%) were in the normal ferritin group (P ≤ .001). Twelve (14.1%) of 85 patients died in the normal ferritin group, and 52 (65.0%) of 80 patients died in the high-ferritin group. The overall mortality was significantly higher in the high-ferritin group (P < .001). The median overall survival was 42 months (range, 25-56 months) in the normal-ferritin group and20 months (range, 5-46) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). The median disease-free survival was 39 months (range, 16-56) in the normal ferritin group and 10 months (range, 3-29) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). Elevated serum ferritin levels might predict poorer survival in autoHSCT recipients. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of constraint-based system-level models of microbial metabolism.

PubMed

Navid, Ali

2012-01-01

Genome-scale models of metabolism are valuable tools for using genomic information to predict microbial phenotypes. System-level mathematical models of metabolic networks have been developed for a number of microbes and have been used to gain new insights into the biochemical conversions that occur within organisms and permit their survival and proliferation. Utilizing these models, computational biologists can (1) examine network structures, (2) predict metabolic capabilities and resolve unexplained experimental observations, (3) generate and test new hypotheses, (4) assess the nutritional requirements of the organism and approximate its environmental niche, (5) identify missing enzymatic functions in the annotated genome, and (6) engineer desired metabolic capabilities in model organisms. This chapter details the protocol for developing genome-scale models of metabolism in microbes as well as tips for accelerating the model building process.

Modeling Dynamics of Cell-to-Cell Variability in TRAIL-Induced Apoptosis Explains Fractional Killing and Predicts Reversible Resistance

PubMed Central

Bertaux, François; Stoma, Szymon; Drasdo, Dirk; Batt, Gregory

2014-01-01

Isogenic cells sensing identical external signals can take markedly different decisions. Such decisions often correlate with pre-existing cell-to-cell differences in protein levels. When not neglected in signal transduction models, these differences are accounted for in a static manner, by assuming randomly distributed initial protein levels. However, this approach ignores the a priori non-trivial interplay between signal transduction and the source of this cell-to-cell variability: temporal fluctuations of protein levels in individual cells, driven by noisy synthesis and degradation. Thus, modeling protein fluctuations, rather than their consequences on the initial population heterogeneity, would set the quantitative analysis of signal transduction on firmer grounds. Adopting this dynamical view on cell-to-cell differences amounts to recast extrinsic variability into intrinsic noise. Here, we propose a generic approach to merge, in a systematic and principled manner, signal transduction models with stochastic protein turnover models. When applied to an established kinetic model of TRAIL-induced apoptosis, our approach markedly increased model prediction capabilities. One obtains a mechanistic explanation of yet-unexplained observations on fractional killing and non-trivial robust predictions of the temporal evolution of cell resistance to TRAIL in HeLa cells. Our results provide an alternative explanation to survival via induction of survival pathways since no TRAIL-induced regulations are needed and suggest that short-lived anti-apoptotic protein Mcl1 exhibit large and rare fluctuations. More generally, our results highlight the importance of accounting for stochastic protein turnover to quantitatively understand signal transduction over extended durations, and imply that fluctuations of short-lived proteins deserve particular attention. PMID:25340343

Soluble CD30 and Hepatocyte growth factor as predictive markers of antibody-mediated rejection of the kidney allograft.

PubMed

Pavlova, Yelena; Viklicky, Ondrej; Slatinska, Janka; Bürgelova, Marcela; Süsal, Caner; Skibova, Jelena; Honsová, Eva; Striz, Ilja; Kolesar, Libor; Slavcev, Antonij

2011-07-01

Our retrospective study was aimed to assess the relevance of pre- and post-transplant measurements of serum concentrations of the soluble CD30 molecule (soluble CD30, sCD30) and the cytokine Hepatocyte growth factor (HGF) for prediction of the risk for development of antibody-mediated rejection (AMR) in kidney transplant patients. Evaluation of sCD30, HGF levels and the presence of HLA-specific antibodies in a cohort of 205 patients was performed before, 2weeks and 6months after transplantation. Patients were followed up for kidney graft function and survival for two years. We found a tendency of higher incidence of AMR in retransplanted patients with elevated pre-transplant sCD30 (≥100U/ml) (p=0.051), however no such correlation was observed in first-transplant patients. Kidney recipients with simultaneously high sCD30 and HLA-specific antibodies (sCD30+/Ab+) before transplantation had significantly lower AMR-free survival compared to the other patient groups (p<0.001). HGF concentrations were not associated with the incidence of AMR at any time point of measurement, nevertheless, the combined analysis HGF and sCD30 showed increased incidence of AMR in recipients with elevated pretransplant sCD30 and low HGF levels. the predictive value of pretransplant sCD30 for the development of antibody-mediated rejection after transplantation is significantly potentiated by the co-presence of HLA specific antibodies. The role of HGF as a rejection-protective factor in patients with high pretransplant HGF levels would need further investigation. Copyright © 2011 Elsevier B.V. All rights reserved.

Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia.

PubMed

Gao, Rui; Chen, Rui-Ze; Xia, Yi; Liang, Jin-Hua; Wang, Li; Zhu, Hua-Yuan; Zhu Wu, Jia-; Fan, Lei; Li, Jian-Yong; Yang, Tao; Xu, Wei

2018-02-19

Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL. © 2018 UICC.

Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy.

PubMed

Tietze, Julia K; Angelova, Daniela; Heppt, Markus V; Ruzicka, Thomas; Berking, Carola

2017-07-01

The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T-cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56 dim and CD56 bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56 dim NK cells, whereas the baseline levels of CD56 bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56 dim and CD56 bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56 dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56 bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56 dim NK cells as well as normal baseline levels of CD56 bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56 dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56 bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD56 dim and CD56 bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A New Clinicobiological Scoring System for the Prediction of Infection-Related Mortality and Survival after Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Forcina, Alessandra; Rancoita, Paola M V; Marcatti, Magda; Greco, Raffaella; Lupo-Stanghellini, Maria Teresa; Carrabba, Matteo; Marasco, Vincenzo; Di Serio, Clelia; Bernardi, Massimo; Peccatori, Jacopo; Corti, Consuelo; Bondanza, Attilio; Ciceri, Fabio

2017-12-01

Infection-related mortality (IRM) is a substantial component of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). No scores have been developed to predict IRM before transplantation. Pretransplantation clinical and biochemical data were collected from a study cohort of 607 adult patients undergoing allo-HSCT between January 2009 and February 2017. In a training set of 273 patients, multivariate analysis revealed that age >60 years (P = .003), cytomegalovirus host/donor serostatus different from negative/negative (P < .001), pretransplantation IgA level <1.11 g/L (P = .004), and pretransplantation IgM level <.305 g/L (P = .028) were independent predictors of increased IRM. Based on these results, we developed and subsequently validated a 3-tiered weighted prognostic index for IRM in a retrospective set of patients (n = 219) and a prospective set of patients (n = 115). Patients were assigned to 3 different IRM risk classes based on this index score. The score significantly predicted IRM in the training set, retrospective validation set, and prospective validation set (P < .001, .044, and .011, respectively). In the training set, 100-day IRM was 5% for the low-risk group, 11% for the intermediate-riak group, and 16% for the high-risk groups. In the retrospective validation set, the respective 100-day IRM values were 7%, 17%, and 28%, and in the prospective set, they were 0%, 5%, and 7%. This score predicted also overall survival (P < .001 in the training set, P < 041 in the retrospective validation set, and P < .023 in the prospective validation set). Because pretransplantation levels of IgA/IgM can be modulated by the supplementation of enriched immunoglobulins, these results suggest the possibility of prophylactic interventional studies to improve transplantation outcomes. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study.

PubMed

Wolf, Gregory T; Chepeha, Douglas B; Bellile, Emily; Nguyen, Ariane; Thomas, Daffyd; McHugh, Jonathan

2015-01-01

Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined. Complete TIL and clinical data were available for 39 patients. Levels of CD4, CD8, FoxP3 (Treg), CD68 and NK cells were assessed by immunohistochemistry in tumor cores on a tissue microarray. Associations with clinical variables, tobacco and alcohol use and histologic features were assessed using Spearman correlation coefficient and the non-parametric Kruskal-Wallis testing. Time-to-event outcomes were determined using univariate and multivariate Cox models. Median follow up was 60 months. The ratio of CD4/CD8 (p=.01) and CD8 infiltrates (p=.05) were associated with tumor recurrence but not overall survival. Lower CD4 infiltrates were associated with alcohol use (p=.005) and poor tumor differentiation (p=.02). Interestingly, higher levels of CD68+ macrophages were found associated with positive nodes (p=.06) and poorer overall survival (p=.07). Overall and DSS survival were significantly shorter for patients with positive nodes, extracapsular spread, or perineural invasion. Infiltrating immune cell levels in oral cavity cancer appear influenced by health behaviors and tumor characteristics. In contrast to oropharynx cancer, infiltrates of CD68 positive tumor associated macrophages may contribute to metastatic behavior and outcome in advanced oral cavity carcinoma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tumor Infiltrating Lymphocytes (TIL) and Prognosis in Oral Cavity Squamous Carcinoma: A Preliminary Study

PubMed Central

Wolf, Gregory T.; Chepeha, Douglas B.; Bellile, Emily; Nguyen, Ariane; Thomas, Daffyd; McHugh, Jonathan

2014-01-01

Objectives Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined. Methods Complete TIL and clinical data were available for 39 patients. Levels of CD4, CD8, FoxP3 (Treg), CD68 and NK cells were assessed by immunohistochemistry in tumor cores on a tissue microarray. Associations with clinical variables, tobacco and alcohol use and histologic features were assessed using Spearman correlation coefficient and the non-parametric Kruskal-Wallis testing. Timeto-event outcomes were determined using univariate and multivariate Cox models. Median follow up was 60 months. Results The ratio of CD4/CD8 (p=.01) and CD8 infiltrates (p=.05) were associated with tumor recurrence but not overall survival. Lower CD4 infiltrates were associated with alcohol use (p=.005) and poor tumor differentiation (p=.02). Interestingly, there higher levels of CD68+ macrophages were found associated with positive nodes (p=.06) and poorer overall survival (p=.07). Overall and DSS survival were significantly shorter for patients with positive nodes, extracapsular spread , or perineural invasion. Conclusions Infiltrating immune cell levels in oral cavity cancer appear influenced by health behaviors and tumor characteristics. In contrast to oropharynx cancer, infiltrates of CD68 positive tumor associated macrophages may contribute to metastatic behavior and outcome in advanced oral cavity carcinoma. PMID:25283344

Habitat fragmentation effects on annual survival of the federally protected eastern indigo snake

USGS Publications Warehouse

Breininger, D.R.; Mazerolle, M.J.; Bolt, M.R.; Legare, M.L.; Drese, J.H.; Hines, J.E.

2012-01-01

The eastern indigo snake (Drymarchon couperi) is a federally listed species, most recently threatened by habitat loss and habitat degradation. In an effort to estimate snake survival, a total of 103 individuals (59 males, 44 females) were followed using radio-tracking from January 1998 to March 2004 in three landscape types that had increasing levels of habitat fragmentation: (1) conservation cores; (2) conservation areas along highways; (3) suburbs. Because of a large number of radio-tracking locations underground for which the state of snakes (i.e. alive or dead) could not be assessed, we employed a multistate approach to model snake apparent survival and encounter probability of live and dead snakes. We predicted that male snakes in suburbs would have the lowest annual survival. We found a transmitter implantation effect on snake encounter probability, as snakes implanted on a given occasion had a lower encounter probability on the next visit compared with snakes not implanted on the previous occasion. Our results indicated that adult eastern indigo snakes have relatively high survival in conservation core areas, but greatly reduced survival in conservation areas along highways and in suburbs. These findings indicate that habitat fragmentation is likely to be the critical factor for species' persistence.

Landmark Estimation of Survival and Treatment Effect in a Randomized Clinical Trial

PubMed Central

Parast, Layla; Tian, Lu; Cai, Tianxi

2013-01-01

Summary In many studies with a survival outcome, it is often not feasible to fully observe the primary event of interest. This often leads to heavy censoring and thus, difficulty in efficiently estimating survival or comparing survival rates between two groups. In certain diseases, baseline covariates and the event time of non-fatal intermediate events may be associated with overall survival. In these settings, incorporating such additional information may lead to gains in efficiency in estimation of survival and testing for a difference in survival between two treatment groups. If gains in efficiency can be achieved, it may then be possible to decrease the sample size of patients required for a study to achieve a particular power level or decrease the duration of the study. Most existing methods for incorporating intermediate events and covariates to predict survival focus on estimation of relative risk parameters and/or the joint distribution of events under semiparametric models. However, in practice, these model assumptions may not hold and hence may lead to biased estimates of the marginal survival. In this paper, we propose a semi-nonparametric two-stage procedure to estimate and compare t-year survival rates by incorporating intermediate event information observed before some landmark time, which serves as a useful approach to overcome semi-competing risks issues. In a randomized clinical trial setting, we further improve efficiency through an additional calibration step. Simulation studies demonstrate substantial potential gains in efficiency in terms of estimation and power. We illustrate our proposed procedures using an AIDS Clinical Trial Protocol 175 dataset by estimating survival and examining the difference in survival between two treatment groups: zidovudine and zidovudine plus zalcitabine. PMID:24659838

The extension of total gain (TG) statistic in survival models: properties and applications.

PubMed

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

2015-07-01

The results of multivariable regression models are usually summarized in the form of parameter estimates for the covariates, goodness-of-fit statistics, and the relevant p-values. These statistics do not inform us about whether covariate information will lead to any substantial improvement in prediction. Predictive ability measures can be used for this purpose since they provide important information about the practical significance of prognostic factors. R (2)-type indices are the most familiar forms of such measures in survival models, but they all have limitations and none is widely used. In this paper, we extend the total gain (TG) measure, proposed for a logistic regression model, to survival models and explore its properties using simulations and real data. TG is based on the binary regression quantile plot, otherwise known as the predictiveness curve. Standardised TG ranges from 0 (no explanatory power) to 1 ('perfect' explanatory power). The results of our simulations show that unlike many of the other R (2)-type predictive ability measures, TG is independent of random censoring. It increases as the effect of a covariate increases and can be applied to different types of survival models, including models with time-dependent covariate effects. We also apply TG to quantify the predictive ability of multivariable prognostic models developed in several disease areas. Overall, TG performs well in our simulation studies and can be recommended as a measure to quantify the predictive ability in survival models.

Development and Validation of a Scoring System to Predict Outcomes of Patients With Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy.

PubMed

Lammers, Willem J; Hirschfield, Gideon M; Corpechot, Christophe; Nevens, Frederik; Lindor, Keith D; Janssen, Harry L A; Floreani, Annarosa; Ponsioen, Cyriel Y; Mayo, Marlyn J; Invernizzi, Pietro; Battezzati, Pier M; Parés, Albert; Burroughs, Andrew K; Mason, Andrew L; Kowdley, Kris V; Kumagi, Teru; Harms, Maren H; Trivedi, Palak J; Poupon, Raoul; Cheung, Angela; Lleo, Ana; Caballeria, Llorenç; Hansen, Bettina E; van Buuren, Henk R

2015-12-01

Approaches to risk stratification for patients with primary biliary cirrhosis (PBC) are limited, single-center based, and often dichotomous. We aimed to develop and validate a better model for determining prognoses of patients with PBC. We performed an international, multicenter meta-analysis of 4119 patients with PBC treated with ursodeoxycholic acid at liver centers in 8 European and North American countries. Patients were randomly assigned to derivation (n = 2488 [60%]) and validation cohorts (n = 1631 [40%]). A risk score (GLOBE score) to predict transplantation-free survival was developed and validated with univariate and multivariable Cox regression analyses using clinical and biochemical variables obtained after 1 year of ursodeoxycholic acid therapy. Risk score outcomes were compared with the survival of age-, sex-, and calendar time-matched members of the general population. The prognostic ability of the GLOBE score was evaluated alongside those of the Barcelona, Paris-1, Rotterdam, Toronto, and Paris-2 criteria. Age (hazard ratio = 1.05; 95% confidence interval [CI]: 1.04-1.06; P < .0001); levels of bilirubin (hazard ratio = 2.56; 95% CI: 2.22-2.95; P < .0001), albumin (hazard ratio = 0.10; 95% CI: 0.05-0.24; P < .0001), and alkaline phosphatase (hazard ratio = 1.40; 95% CI: 1.18-1.67; P = .0002); and platelet count (hazard ratio/10 units decrease = 0.97; 95% CI: 0.96-0.99; P < .0001) were all independently associated with death or liver transplantation (C-statistic derivation, 0.81; 95% CI: 0.79-0.83, and validation cohort, 0.82; 95% CI: 0.79-0.84). Patients with risk scores >0.30 had significantly shorter times of transplant-free survival than matched healthy individuals (P < .0001). The GLOBE score identified patients who would survive for 5 years and 10 years (responders) with positive predictive values of 98% and 88%, respectively. Up to 22% and 21% of events and nonevents, respectively, 10 years after initiation of treatment were correctly reclassified in comparison with earlier proposed criteria. In subgroups of patients aged <45, 45-52, 52-58, 58-66, and ≥66 years, age-specific GLOBE-score thresholds beyond which survival significantly deviated from matched healthy individuals were -0.52, 0.01, 0.60, 1.01 and 1.69, respectively. Transplant-free survival could still be accurately calculated by the GLOBE score with laboratory values collected at 2-5 years after treatment. We developed and validated scoring system (the GLOBE score) to predict transplant-free survival of ursodeoxycholic acid-treated patients with PBC. This score might be used to select strategies for treatment and care. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.