Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

PubMed

Rakha, E A; Soria, D; Green, A R; Lemetre, C; Powe, D G; Nolan, C C; Garibaldi, J M; Ball, G; Ellis, I O

2014-04-02

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes. Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

How Many Measurements Are Needed to Estimate Blood Pressure Variability Without Loss of Prognostic Information?

PubMed Central

2014-01-01

BACKGROUND Average real variability (ARV) is a recently proposed index for short-term blood pressure (BP) variability. We aimed to determine the minimum number of BP readings required to compute ARV without loss of prognostic information. METHODS ARV was calculated from a discovery dataset that included 24-hour ambulatory BP measurements for 1,254 residents (mean age = 56.6 years; 43.5% women) of Copenhagen, Denmark. Concordance between ARV from full (≥80 BP readings) and randomly reduced 24-hour BP recordings was examined, as was prognostic accuracy. A test dataset that included 5,353 subjects (mean age = 54.0 years; 45.6% women) with at least 48 BP measurements from 11 randomly recruited population cohorts was used to validate the results. RESULTS In the discovery dataset, a minimum of 48 BP readings allowed an accurate assessment of the association between cardiovascular risk and ARV. In the test dataset, over 10.2 years (median), 806 participants died (335 cardiovascular deaths, 206 cardiac deaths) and 696 experienced a major fatal or nonfatal cardiovascular event. Standardized multivariable-adjusted hazard ratios (HRs) were computed for associations between outcome and BP variability. Higher diastolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.19), and cardiac (HR = 1.19) mortality and fatal combined with nonfatal cerebrovascular events (HR = 1.16). Higher systolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.17), and cardiac (HR = 1.24) mortality. CONCLUSIONS Forty-eight BP readings over 24 hours were observed to be adequate to compute ARV without meaningful loss of prognostic information. PMID:23955605

New breast cancer prognostic factors identified by computer-aided image analysis of HE stained histopathology images

PubMed Central

Chen, Jia-Mei; Qu, Ai-Ping; Wang, Lin-Wei; Yuan, Jing-Ping; Yang, Fang; Xiang, Qing-Ming; Maskey, Ninu; Yang, Gui-Fang; Liu, Juan; Li, Yan

2015-01-01

Computer-aided image analysis (CAI) can help objectively quantify morphologic features of hematoxylin-eosin (HE) histopathology images and provide potentially useful prognostic information on breast cancer. We performed a CAI workflow on 1,150 HE images from 230 patients with invasive ductal carcinoma (IDC) of the breast. We used a pixel-wise support vector machine classifier for tumor nests (TNs)-stroma segmentation, and a marker-controlled watershed algorithm for nuclei segmentation. 730 morphologic parameters were extracted after segmentation, and 12 parameters identified by Kaplan-Meier analysis were significantly associated with 8-year disease free survival (P < 0.05 for all). Moreover, four image features including TNs feature (HR 1.327, 95%CI [1.001 - 1.759], P = 0.049), TNs cell nuclei feature (HR 0.729, 95%CI [0.537 - 0.989], P = 0.042), TNs cell density (HR 1.625, 95%CI [1.177 - 2.244], P = 0.003), and stromal cell structure feature (HR 1.596, 95%CI [1.142 - 2.229], P = 0.006) were identified by multivariate Cox proportional hazards model to be new independent prognostic factors. The results indicated that CAI can assist the pathologist in extracting prognostic information from HE histopathology images for IDC. The TNs feature, TNs cell nuclei feature, TNs cell density, and stromal cell structure feature could be new prognostic factors. PMID:26022540

Heart failure and anemia: Effects on prognostic variables.

PubMed

Cattadori, Gaia; Agostoni, Piergiuseppe; Corrà, Ugo; Sinagra, Gianfranco; Veglia, Fabrizio; Salvioni, Elisabetta; Bonomi, Alice; La Gioia, Rocco; Scardovi, Angela B; Ferraironi, Alessandro; Emdin, Michele; Metra, Marco; Di Lenarda, Andrea; Limongelli, Giuseppe; Raimondo, Rosa; Re, Federica; Guazzi, Marco; Belardinelli, Romualdo; Parati, Gianfranco; Caravita, Sergio; Magrì, Damiano; Lombardi, Carlo; Frigerio, Maria; Oliva, Fabrizio; Girola, Davide; Mezzani, Alessandro; Farina, Stefania; Mapelli, Massimo; Scrutinio, Domenico; Pacileo, Giuseppe; Apostolo, Anna; Iorio, AnnaMaria; Paolillo, Stefania; Filardi, Pasquale Perrone; Gargiulo, Paola; Bussotti, Maurizio; Marchese, Giovanni; Correale, Michele; Badagliacca, Roberto; Sciomer, Susanna; Palermo, Pietro; Contini, Mauro; Giannuzzi, Pantaleo; Battaia, Elisa; Cicoira, Mariantonietta; Clemenza, Francesco; Minà, Chiara; Binno, Simone; Passino, Claudio; Piepoli, Massimo F

2017-01-01

Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for males), normal (12-15 for females, 13-15 for males) and high (>15) Hb, respectively. Median follow-up was 1363days (606-1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO 2 ), ventilatory efficiency (VE/VCO 2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO 2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO 2 slope was associated with poor prognosis only in patients with low and normal Hb. Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO 2 and LVEF, but not VE/VCO 2 slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva.

PubMed

Gadducci, Angiolo; Tana, Roberta; Barsotti, Cecilia; Guerrieri, Maria Elena; Genazzani, Andrea Riccardo

2012-07-01

Several clinical-pathological parameters have been related to survival of patients with invasive squamous cell carcinoma of the vulva, whereas few studies have investigated the ability of biological variables to predict the clinical outcome of these patients. The present paper reviews the literature data on the prognostic relevance of lymph node-related parameters, primary tumor-related parameters, FIGO stage, blood variables, and tissue biological variables. Regarding these latter, the paper takes into account the analysis of DNA content, cell cycle-regulatory proteins, apoptosis-related proteins, epidermal growth factor receptor [EGFR], and proteins that are involved in tumor invasiveness, metastasis and angiogenesis. At present, the lymph node status and FIGO stage according to the new 2009 classification system are the main predictors for vulvar squamous cell carcinoma, whereas biological variables do not have yet a clinical relevance and their role is still investigational. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2013-05-03

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

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

PubMed Central

2013-01-01

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

HPV RNA CISH score identifies two prognostic groups in a p16 positive oropharyngeal squamous cell carcinoma population.

PubMed

Augustin, Jérémy; Mandavit, Marion; Outh-Gauer, Sophie; Grard, Ophélie; Gasne, Cassandre; Lépine, Charles; Mirghani, Haïtham; Hans, Stéphane; Bonfils, Pierre; Denize, Thomas; Bruneval, Patrick; Bishop, Justin A; Fontugne, Jacqueline; Péré, Hélène; Tartour, Eric; Badoual, Cécile

2018-06-20

HPV-related and HPV-unrelated oropharyngeal squamous cell carcinomas are two distinct entities according to the Union for International Cancer Control, with a better prognosis conferred to HPV-related oropharyngeal squamous cell carcinomas. However, variable clinical outcomes are observed among patients with p16 positive oropharyngeal squamous cell carcinoma, which is a surrogate marker of HPV infection. We aimed to investigate the prognostic value of RNA CISH against E6 and E7 transcripts (HPV RNA CISH) to predict such variability. We retrospectively included 50 histologically confirmed p16 positive oropharyngeal squamous cell carcinomas (p16 positive immunostaining was defined by a strong staining in 70% or more of tumor cells). HPV RNA CISH staining was assessed semi-quantitatively to define two scores: RNA CISH "low" and RNA CISH "high". Negative HPV RNA CISH cases were scored as RNA CISH "low". This series contained 29 RNA CISH low cases (58%) and 21 RNA CISH high cases (42%). Clinical and pathologic baseline characteristics were similar between the two groups. RNA CISH high staining was associated with a better overall survival in both univariate and multivariate analyses (p = 0.033 and p = 0.042, respectively). Other recorded parameters had no prognostic value. In conclusion, HPV RNA CISH might be an independent prognostic marker in p16 positive oropharyngeal squamous cell carcinomas and might help guide therapeutics.

Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma.

PubMed

Mendrzyk, Frank; Radlwimmer, Bernhard; Joos, Stefan; Kokocinski, Felix; Benner, Axel; Stange, Daniel E; Neben, Kai; Fiegler, Heike; Carter, Nigel P; Reifenberger, Guido; Korshunov, Andrey; Lichter, Peter

2005-12-01

Medulloblastoma is the most common malignant brain tumor in children. Despite multimodal aggressive treatment, nearly half of the patients die as a result of this tumor. Identification of molecular markers for prognosis and development of novel pathogenesis-based therapies depends crucially on a better understanding of medulloblastoma pathomechanisms. We performed genome-wide analysis of DNA copy number imbalances in 47 medulloblastomas using comparative genomic hybridization to large insert DNA microarrays (matrix-CGH). The expression of selected candidate genes identified by matrix-CGH was analyzed immunohistochemically on tissue microarrays representing medulloblastomas from 189 clinically well-documented patients. To identify novel prognostic markers, genomic findings and protein expression data were correlated to patient survival. Matrix-CGH analysis revealed frequent DNA copy number alterations of several novel candidate regions. Among these, gains at 17q23.2-qter (P < .01) and losses at 17p13.1 to 17p13.3 (P = .04) were significantly correlated to poor prognosis. Within 17q23.2-qter and 7q21.2, two of the most frequently gained chromosomal regions, confined amplicons were identified that contained the PPM1D and CDK6 genes, respectively. Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168 and CDK6 in 50 (30%) of 169 medulloblastomas. Overexpression of CDK6 correlated significantly with poor prognosis (P < .01) and represented an independent prognostic marker of overall survival on multivariate analysis (P = .02). We identified CDK6 as a novel molecular marker that can be determined by immunohistochemistry on routinely processed tissue specimens and may facilitate the prognostic assessment of medulloblastoma patients. Furthermore, increased protein-levels of PPM1D and CDK6 may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms.

The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma

PubMed Central

2013-01-01

Background Elevated Glasgow Prognostic Score (GPS) has been related to poor prognosis in patients with hepatocellular carcinoma (HCC) undergoing surgical resection or receiving sorafenib. The aim of this study was to investigate the prognostic value of GPS in patients with various stages of the disease and with different liver functional status. Methods One hundred and fifty patients with newly diagnosed HCC were prospectively evaluated. Patients were divided according to their GPS scores. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with overall survival; the identified variables were then compared with those of other validated staging systems. Results Elevated GPS were associated with increased asparate aminotransferase (P<0.0001), total bilirubin (P<0.0001), decreased albumin (P<0.0001), α-fetoprotein (P=0.008), larger tumor diameter (P=0.003), tumor number (P=0.041), vascular invasion (P=0.0002), extra hepatic metastasis (P=0.02), higher Child-Pugh scores (P<0.0001), and higher Cancer Liver Italian Program scores (P<0.0001). On multivariate analysis, the elevated GPS was independently associated with worse overall survival. Conclusions Our results demonstrate that the GPS can serve as an independent marker of poor prognosis in patients with HCC in various stages of disease and different liver functional status. PMID:23374755

Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis.

PubMed

Reddy, Sreekanth P; Britto, Ramona; Vinnakota, Katyayni; Aparna, Hebbar; Sreepathi, Hari Kishore; Thota, Balaram; Kumari, Arpana; Shilpa, B M; Vrinda, M; Umesh, Srikantha; Samuel, Cini; Shetty, Mitesh; Tandon, Ashwani; Pandey, Paritosh; Hegde, Sridevi; Hegde, A S; Balasubramaniam, Anandh; Chandramouli, B A; Santosh, Vani; Kondaiah, Paturu; Somasundaram, Kumaravel; Rao, M R Satyanarayana

2008-05-15

Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis. We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade II--diffuse astrocytoma, grade III--anaplastic astrocytoma, and grade IV--glioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51). We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage-inducible alpha (GADD45alpha) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45alpha and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45alpha conferred better survival while the coexpression of FSTL1 with p53 was associated with poor survival. Our study reveals that GADD45alpha and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 are primary GBM-specific diagnostic markers. Whereas GADD45alpha overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM

[Prognostic factors of early breast cancer].

PubMed

Almagro, Elena; González, Cynthia S; Espinosa, Enrique

2016-02-19

Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Do Optimal Prognostic Thresholds in Continuous Physiological Variables Really Exist? Analysis of Origin of Apparent Thresholds, with Systematic Review for Peak Oxygen Consumption, Ejection Fraction and BNP

PubMed Central

Leong, Tora; Rehman, Michaela B.; Pastormerlo, Luigi Emilio; Harrell, Frank E.; Coats, Andrew J. S.; Francis, Darrel P.

2014-01-01

Background Clinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies. Objectives We studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO2), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF). Data Sources and Eligibility Criteria Studies testing pVO2, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed. Methods First, we examined studies testing pVO2, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk. Results 33 studies (8946 patients) tested a pVO2 threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10–18 ml/kg/min) but was overwhelmingly controlled by the individual study population's mean pVO2 (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001). Second, survival simulations always discovered a “most significant” threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001). Limitations This study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds. Key Findings First, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies' average pVO2, EF or BNP. Second

Prognostic indices for early mortality in ischaemic stroke - meta-analysis.

PubMed

Mattishent, K; Kwok, C S; Mahtani, A; Pelpola, K; Myint, P K; Loke, Y K

2016-01-01

Several models have been developed to predict mortality in ischaemic stroke. We aimed to evaluate systematically the performance of published stroke prognostic scores. We searched MEDLINE and EMBASE in February 2014 for prognostic models (published between 2003 and 2014) used in predicting early mortality (<6 months) after ischaemic stroke. We evaluated discriminant ability of the tools through meta-analysis of the area under the curve receiver operating characteristic curve (AUROC) or c-statistic. We evaluated the following components of study validity: collection of prognostic variables, neuroimaging, treatment pathways and missing data. We identified 18 articles (involving 163 240 patients) reporting on the performance of prognostic models for mortality in ischaemic stroke, with 15 articles providing AUC for meta-analysis. Most studies were either retrospective, or post hoc analyses of prospectively collected data; all but three reported validation data. The iSCORE had the largest number of validation cohorts (five) within our systematic review and showed good performance in four different countries, pooled AUC 0.84 (95% CI 0.82-0.87). We identified other potentially useful prognostic tools that have yet to be as extensively validated as iSCORE - these include SOAR (2 studies, pooled AUC 0.79, 95% CI 0.78-0.80), GWTG (2 studies, pooled AUC 0.72, 95% CI 0.72-0.72) and PLAN (1 study, pooled AUC 0.85, 95% CI 0.84-0.87). Our meta-analysis has identified and summarized the performance of several prognostic scores with modest to good predictive accuracy for early mortality in ischaemic stroke, with the iSCORE having the broadest evidence base. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Newly identified poor prognostic factors for adult T-cell leukemia-lymphoma treated with allogeneic hematopoietic stem cell transplantation.

PubMed

Tokunaga, Masahito; Uto, Hirofumi; Takeuchi, Shogo; Nakano, Nobuaki; Kubota, Ayumu; Tokunaga, Mayumi; Takatsuka, Yoshifusa; Seto, Masao; Ido, Akio; Utsunomiya, Atae

2017-01-01

To explore pre-transplantation prognostic factors for adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 70 patients at our institute (63 acute type and seven lymphoma type patients). Forty-five patients died after HSCT and the three-year overall survival (OS) rate was 35.2%. By univariate analysis, the adverse prognostic factors for OS were performance status ≥2, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score ≥3, European Group for Blood and Marrow Transplantation (EBMT) risk score ≥5, HSCT from an HLA-mismatched donor, serum soluble interleukin-2 receptor (sIL-2R) level ≥10,000 U/mL, lymphocyte count ≥4000/μL, and hemoglobin <9 g/dL at the time of HSCT. EBMT risk score and sIL-2R were identified as significant adverse prognostic factors using multivariate analysis. This analysis clearly demonstrates for the first time that HCT-CI and EBMT risk scores are reliable prognostic factors for ATL patients receiving allo-HSCT.

Osteosarcoma of the spine: prognostic variables for local recurrence and overall survival, a multicenter ambispective study.

PubMed

Dekutoski, Mark B; Clarke, Michelle J; Rose, Peter; Luzzati, Alessandro; Rhines, Laurence D; Varga, Peter P; Fisher, Charles G; Chou, Dean; Fehlings, Michael G; Reynolds, Jeremy J; Williams, Richard; Quraishi, Nasir A; Germscheid, Niccole M; Sciubba, Daniel M; Gokaslan, Ziya L; Boriani, Stefano

2016-07-01

OBJECTIVE Primary spinal osteosarcomas are rare and aggressive neoplasms. Poor outcomes can occur, as obtaining marginal margins is technically demanding; further Enneking-appropriate en bloc resection can have significant morbidity. The goal of this study is to identify prognostic variables for local recurrence and mortality in surgically treated patients diagnosed with a primary osteosarcoma of the spine. METHODS A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by AOSpine Knowledge Forum Tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified in 2 cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI), as defined by pathology margin matching Enneking-recommended surgical margins. Prognostic variables were analyzed in reference to local recurrence and survival. RESULTS Between 1987 and 2012, 58 patients (32 female patients) underwent surgical treatment for primary spinal osteosarcoma. Patients were followed for a mean period of 3.5 ± 3.5 years (range 0.5 days to 14.3 years). The median survival for the entire cohort was 6.7 years postoperative. Twenty-four (41%) patients died, and 17 (30%) patients suffered a local recurrence, 10 (59%) of whom died. Twenty-nine (53%) patients underwent EA resection while 26 (47%) patients underwent EI resection with a postoperative median survival of 6.8 and 3.7 years, respectively (p = 0.048). EI patients had a higher rate of local recurrence than EA patients (p = 0.001). Patient age, previous surgery, biopsy type, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. CONCLUSIONS Osteosarcoma of the spine presents a significant challenge, and most patients die in spite of aggressive surgery. There is a significant decrease in recurrence and an increase in survival with en bloc resection (EA

Histologic prognosticators in feline osteosarcoma: a comparison with phenotypically similar canine osteosarcoma.

PubMed

Dimopoulou, Maria; Kirpensteijn, Jolle; Moens, Hester; Kik, Marja

2008-07-01

To investigate the histologic characteristics of feline osteosarcoma (OS) and compare the histologic data with phenotypically comparable canine OS. The effects of histologic and clinical variables on survival statistics were evaluated. Retrospective study. Cats (n=62) and dogs (22). Medical records of 62 cats with OS were reviewed for clinically relevant data. Clinical outcome was obtained by telephone interview. Histologic characteristics of OS were classified using a standardized grading system. Histologic characteristics in 22 feline skeletal OS were compared with 22 canine skeletal OS of identical location and subtype. Prognostic variables for clinical outcome were determined using multivariate analysis. Feline OS was characterized by moderate to abundant cellular pleomorphism, low mitotic index, small to moderate amounts of matrix, high cellularity, and a moderate amount of necrosis. There was no significant difference between histologic variables in feline and canine OS. Histologic grade, surgery, and mitotic index significantly influenced clinical outcome as determined by multivariate analysis. Tumor invasion into vessels was not identified as a significant prognosticator. Feline and canine skeletal OS have similar histologic but different prognostic characteristics. Prognosis for cats with OS is related to histologic grade and mitotic index of the tumor.

Heart rate variability enhances the prognostic value of established parameters in patients with congestive heart failure.

PubMed

Krüger, C; Lahm, T; Zugck, C; Kell, R; Schellberg, D; Schweizer, M W F; Kübler, W; Haass, M

2002-12-01

This prospective study evaluated whether heart rate variability (HRV) assessed from Holter ECG has prognostic value in addition to established parameters in patients with congestive heart failure (CHF). The study included 222 patients with CHF due to dilated or ischemic cardiomyopathy (left ventricular ejection fraction LVEF 21+/-1%; mean+/-SEM). During a mean follow-up of 15+/-1 months, 38 (17%) patients died and 45 (20%) were hospitalized due to worsening of CHF. The HRV parameter SDNN (standard deviation of all intervals between normal beats) was significantly lower in non-surviving or hospitalized than in event-free patients (118+/-6 vs 142+/-5 ms), as were LVEF (18+/-1 vs 23+/-1%), and peak oxygen uptake during exercise (peak VO(2)) (12.8+/-0.5 vs 15.6+/-0.5 ml/min/kg). While each of these parameters was a risk predictor in univariate analysis, multivariate analysis revealed that HRV provides both independent and additional prognostic information with respect to the risk 'cardiac mortality or deterioration of CHF'. It is concluded that the determination of HRV enhances the prognostic power given by the most widely used parameters LVEF and peak VO(2) in the prediction of mortality or deterioration of CHF and thus enables to improve risk stratification.

Prognostication in Philadelphia Chromosome Negative Myeloproliferative Neoplasms: a Review of the Recent Literature.

PubMed

Zhou, Amy; Afzal, Amber; Oh, Stephen T

2017-10-01

The prognosis for patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is highly variable. All Ph-negative MPNs carry an increased risk for thrombotic complications, bleeding, and leukemic transformation. Several clinical, biological, and molecular prognostic factors have been identified in recent years, which provide important information in guiding management of patients with Ph-negative MPNs. In this review, we critically evaluate the recent published literature and discuss important new developments in clinical and molecular factors that impact survival, disease transformation, and thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Recent studies have identified several clinical factors and non-driver mutations to have prognostic impact on Ph-negative MPNs independent of conventional risk stratification and prognostic models. In polycythemia vera (PV), leukocytosis, abnormal karyotype, phlebotomy requirement on hydroxyurea, increased bone marrow fibrosis, and mutations in ASXL1, SRSF2, and IDH2 were identified as additional adverse prognostic factors. In essential thrombocythemia (ET), JAK2 V617F mutation, splenomegaly, and mutations in SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2 were found to be additional negative prognostic factors. Bone marrow fibrosis and mutations in ASXL1, SRSF2, EZH2, and IDH1/2 have been found to be additional prognostic factors in primary myelofibrosis (PMF). CALR mutations appear to be a favorable prognostic factor in PMF, which has not been clearly demonstrated in ET. The prognosis for patients with PV, ET, and PMF is dependent upon the presence or absence of several clinical, biological, and molecular risk factors. The significance of additional risk factors identified in these recent studies will need further validation in prospective studies to determine how they may be best utilized in the management of these disorders.

CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease.

PubMed

Hamblin, Terry J; Orchard, Jenny A; Ibbotson, Rachel E; Davis, Zadie; Thomas, Peter W; Stevenson, Freda K; Oscier, David G

2002-02-01

Although the presence or absence of somatic mutations in the immunoglobulin variable region (IgV(H)) genes in chronic lymphocytic leukemia (B-CLL) identifies subtypes with very different prognoses, the assay is technically complex and unavailable to most laboratories. CD38 expression has been suggested as a surrogate marker for the 2 subtypes. IgV(H) mutations and CD38 expression in 145 patients with B-CLL with a long follow-up were compared. The 2 assays gave discordant results in 41 patients (28.3%). Multivariate analysis demonstrated that Binet stage, IgV(H) mutations and CD38 were independent prognostic indicators. Median survival time in patients whose cells had unmutated IgV(H) genes and expressed CD38 was 8 years; in those with mutated IgV(H) genes not expressing CD38, it was 26 years. For those with discordant results, median survival time was 15 years. Thus, although CD38 expression does not identify the same 2 subsets as IgV(H) mutations in CLL, it is an independent risk factor that can be used with IgV(H) mutations and clinical stage to select patients with B-CLL with the worst prognoses. Using cryopreserved cells taken at intervals during the course of the disease, however, changes of CD38 expression over time were demonstrated in 10 of 41 patients. Causes of the variation of CD38 expression require further study. Additional prospective studies are required for comparing CD38 expression with other prognostic factors and for taking sequential measurements during the course of the disease.

Incidence and prognostic factors for postoperative frozen shoulder after shoulder surgery: a prospective cohort study.

PubMed

Koorevaar, Rinco C T; Van't Riet, Esther; Ipskamp, Marcel; Bulstra, Sjoerd K

2017-03-01

Frozen shoulder is a potential complication after shoulder surgery. It is a clinical condition that is often associated with marked disability and can have a profound effect on the patient's quality of life. The incidence, etiology, pathology and prognostic factors of postoperative frozen shoulder after shoulder surgery are not known. The purpose of this explorative study was to determine the incidence of postoperative frozen shoulder after various operative shoulder procedures. A second aim was to identify prognostic factors for postoperative frozen shoulder after shoulder surgery. 505 consecutive patients undergoing elective shoulder surgery were included in this prospective cohort study. Follow-up was 6 months after surgery. A prediction model was developed to identify prognostic factors for postoperative frozen shoulder after shoulder surgery using the TRIPOD guidelines. We nominated five potential predictors: gender, diabetes mellitus, type of physiotherapy, arthroscopic surgery and DASH score. Frozen shoulder was identified in 11% of the patients after shoulder surgery and was more common in females (15%) than in males (8%). Frozen shoulder was encountered after all types of operative procedures. A prediction model based on four variables (diabetes mellitus, specialized shoulder physiotherapy, arthroscopic surgery and DASH score) discriminated reasonably well with an AUC of 0.712. Postoperative frozen shoulder is a serious complication after shoulder surgery, with an incidence of 11%. Four prognostic factors were identified for postoperative frozen shoulder: diabetes mellitus, arthroscopic surgery, specialized shoulder physiotherapy and DASH score. The combination of these four variables provided a prediction rule for postoperative frozen shoulder with reasonable fit. Level II, prospective cohort study.

Using Cox's proportional hazards model for prognostication in carcinoma of the upper aero-digestive tract.

PubMed

Wolfensberger, M

1992-01-01

One of the major short comings of the traditional TNM system is its limited potential for prognostication. With the development of multifactorial analysis techniques, such as Cox's proportional hazards model, it has become possible to simultaneously evaluate a large number of prognostic variables. Cox's model allows both the identification of prognostically relevant variables and the quantification of their prognostic influence. These characteristics make it a helpful tool for analysis as well as for prognostication. The goal of the present study was to develop a prognostic index for patients with carcinoma of the upper aero-digestive tract which makes use of all prognostically relevant variables. To accomplish this, the survival data of 800 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx were analyzed. Sixty-one variables were screened for prognostic significance; of these only 19 variables (including age, tumor location, T, N and M stages, resection margins, capsular invasion of nodal metastases, and treatment modality) were found to significantly correlate with prognosis. With the help of Cox's equation, a prognostic index (PI) was computed for every combination of prognostic factors. To test the proposed model, the prognostic index was applied to 120 patients with carcinoma of the oral cavity or oropharynx. A comparison of predicted and observed survival showed good overall correlation, although actual survival tended to be better than predicted.

Identifying Context Variables in Research.

ERIC Educational Resources Information Center

Piazza, Carolyn L.

1987-01-01

Identifies context variables in written composition from theoretical perspectives in cognitive psychology, sociology, and anthropology. Considers how multiple views of context from across the disciplines can build toward a broader definition of writing. (JD)

A contemporary review of management and prognostic factors of upper tract urothelial carcinoma.

PubMed

Leow, Jeffrey J; Orsola, Anna; Chang, Steven L; Bellmunt, Joaquim

2015-04-01

Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. Although the main treatment is radical nephroureterectomy (NU), oncologic outcomes are not comparable to lower tract urothelial cancers. Identifying prognostic factors can help guide management and potentially improve outcomes. This article systematically reviews current literature on prognostic factors and management options for UTUC. A comprehensive literature search was performed to identify all studies examining prognostic factors and management options for UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to November 2014. An updated systematic review was performed. Preoperative prognostic factors for UTUC patients include age, race, performance status, obesity, smoking status, elevated fibrinogen levels, hydronephrosis, tumor size, multi-focality, location, clinical grade and previous/synchronous bladder cancer. Postoperative variables include tumor stage/grade, multifocality, nodal involvement, lympho-vascular invasion, initial ureteral location, necrosis, sessile architecture, variant histologies and presence of tissue ALDH1 and SOX2. Curative treatment of choice is NU, with lymphadenectomy conferring survival benefits. Minimally invasive surgery has equivalent oncologic and better peri-operative outcomes compared to open surgery. Conservative therapy includes adjuvant BCG and intravesical mitomycin C. Two randomized trials investigating postoperative instillation of mitomycin C suggest bladder recurrence benefits. Adjuvant chemo-radiotherapy may be useful for patients with advanced T3/4 and/or N+ disease. Gold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery. Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy. Copyright © 2015 Elsevier Ltd. All

Co-expression modules construction by WGCNA and identify potential prognostic markers of uveal melanoma.

PubMed

Wan, Qi; Tang, Jing; Han, Yu; Wang, Dan

2018-01-01

Uveal melanoma is an aggressive cancer which has a high percentage recurrence and with a worse prognosis. Identify the potential prognostic markers of uveal melanoma may provide information for early detection of recurrence and treatment. RNA sequence data of uveal melanoma and patient clinic traits were obtained from The Cancer Genome Atlas (TCGA) database. Co-expression modules were built by weighted gene co -expression network analysis (WGCNA) and applied to investigate the relationship underlying modules and clinic traits. Besides, functional enrichment analysis was performed on these co-expression genes from interested modules. First, using WGCNA, identified 21 co-expression modules were constructed by the 10975 genes from the 80 human uveal melanoma samples. The number of genes in these modules ranged from 42 to 5091. Found four co -expression modules significantly correlated with three clinic traits (status, recurrence and recurrence Time). Module red, and purple positively correlated with patient's life status and recurrence Time. Module green positively correlates with recurrence. The result of functional enrichment analysis showed that the module magenta was mainly enriched genetic material assemble processes, the purple module was mainly enriched in tissue homeostasis and melanosome membrane and the module red was mainly enriched metastasis of cell, suggesting its critical role in the recurrence and development of the disease. Additionally, identified the hug gene (top connectivity with other genes) in each module. The hub gene SLC17A7, NTRK2, ABTB1 and ADPRHL1 might play a vital role in recurrence of uveal melanoma. Our findings provided the framework of co-expression gene modules of uveal melanoma and identified some prognostic markers might be detection of recurrence and treatment for uveal melanoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytogenetic prognostication within medulloblastoma subgroups.

PubMed

Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

2014-03-20

Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

[The prognostic value of variables from the quality assurance program and of the rehabilitation-discharge report of the LVA Baden-Württemberg for early retirement: results of a retrospective cohort-study].

PubMed

Küpper-Nybelen, J; Rothenbacher, D; Jacobi, E; Brenner, H

2003-12-01

Since 1997 the LVA Baden-Württemberg pension insurance agency has implemented an instrument to measure the outcome quality of in-patient rehabilitation. The objective of this study was to evaluate the prognostic value of various short-term rehabilitation success markers and of variables of the quality assurance program and the rehab-discharge report of the LVA Baden-Württemberg on early retirement by means of a retrospective cohort study. The analysis was based on routinely registered data of patients who underwent in-hospital rehabilitation in a hospital accredited by the LVA Baden-Württemberg between June 1997 and June 1999. Baseline data included information from medical discharge reports and from the quality assurance programme. Follow-up information with regard to disability was collected until July 2000. The prognostic value of the quality assurance programme and of 4 standardized documented items from the medical discharge report was estimated by proportional hazards regression. In this analysis 6,823 patients aged 30-59 years who underwent an in-patient rehab programme between June 1997 and July 1999 in 5 of 6 LVA rehab clinics were included. During follow-up (mean duration: 1.8 years) 908 (13.3%) patients retired because of health-related disability. The variables with the strongest prognostic values were the evaluation of the patient health status by the physician and the patients themselves and the capacity to work. The variables with the highest prognostic value were the evaluation on a 1-6 visual analogue scale; a better assessment by one mark of the health status by physician and patient himself, respectively, was associated with a 53% and 40% reduced risk of disability. Fitness for work at discharge was the most prognostic variable from the discharge report. Patients who were able to work had a 78% reduced risk of disability compared to patients unable to work. Also of prognostic relevance were a positive performance and the duration of the

Latent class analysis derived subgroups of low back pain patients - do they have prognostic capacity?

PubMed

Molgaard Nielsen, Anne; Hestbaek, Lise; Vach, Werner; Kent, Peter; Kongsted, Alice

2017-08-09

Heterogeneity in patients with low back pain is well recognised and different approaches to subgrouping have been proposed. One statistical technique that is increasingly being used is Latent Class Analysis as it performs subgrouping based on pattern recognition with high accuracy. Previously, we developed two novel suggestions for subgrouping patients with low back pain based on Latent Class Analysis of patient baseline characteristics (patient history and physical examination), which resulted in 7 subgroups when using a single-stage analysis, and 9 subgroups when using a two-stage approach. However, their prognostic capacity was unexplored. This study (i) determined whether the subgrouping approaches were associated with the future outcomes of pain intensity, pain frequency and disability, (ii) assessed whether one of these two approaches was more strongly or more consistently associated with these outcomes, and (iii) assessed the performance of the novel subgroupings as compared to the following variables: two existing subgrouping tools (STarT Back Tool and Quebec Task Force classification), four baseline characteristics and a group of previously identified domain-specific patient categorisations (collectively, the 'comparator variables'). This was a longitudinal cohort study of 928 patients consulting for low back pain in primary care. The associations between each subgroup approach and outcomes at 2 weeks, 3 and 12 months, and with weekly SMS responses were tested in linear regression models, and their prognostic capacity (variance explained) was compared to that of the comparator variables listed above. The two previously identified subgroupings were similarly associated with all outcomes. The prognostic capacity of both subgroupings was better than that of the comparator variables, except for participants' recovery beliefs and the domain-specific categorisations, but was still limited. The explained variance ranged from 4.3%-6.9% for pain intensity and

Prognostic factors in multiple myeloma: selection using Cox's proportional hazard model.

PubMed

Pasqualetti, P; Collacciani, A; Maccarone, C; Casale, R

1996-01-01

The pretreatment characteristics of 210 patients with multiple myeloma, observed between 1980 and 1994, were evaluated as potential prognostic factors for survival. Multivariate analysis according to Cox's proportional hazard model identified in the 160 dead patients with myeloma, among 26 different single prognostic variables, the following factors in order of importance: beta 2-microglobulin; bone marrow plasma cell percentage, hemoglobinemia, degree of lytic bone lesions, serum creatinine, and serum albumin. By analysis of these variables a prognostic index (PI), that considers the regression coefficients derived by Cox's model of all significant factors, was obtained. Using this it was possible to separate the whole patient group into three stages: stage I (PI < 1.485, 67 patients), stage II (PI: 1.485-2.090, 76 patients), and stage III (PI > 2.090, 67 patients), with a median survivals of 68, 36 and 13 months (P < 0.0001), respectively. Also the responses to therapy (P < 0.0001) and the survival curves (P < 0.00001) presented significant differences among the three subgroups. Knowledge of these factors could be of value in predicting prognosis and in planning therapy in patients with multiple myeloma.

Risk stratification using stress echocardiography: incremental prognostic value over historic, clinical, and stress electrocardiographic variables across a wide spectrum of bayesian pretest probabilities for coronary artery disease.

PubMed

Bangalore, Sripal; Gopinath, Devi; Yao, Siu-Sun; Chaudhry, Farooq A

2007-03-01

We sought to evaluate the risk stratification ability and incremental prognostic value of stress echocardiography over historic, clinical, and stress electrocardiographic (ECG) variables, over a wide spectrum of bayesian pretest probabilities of coronary artery disease (CAD). Stress echocardiography is an established technique for the diagnosis of CAD. However, data on incremental prognostic value of stress echocardiography over historic, clinical, and stress ECG variables in patients with known or suggested CAD is limited. We evaluated 3259 patients (60 +/- 13 years, 48% men) undergoing stress echocardiography. Patients were grouped into low (<15%), intermediate (15-85%), and high (>85%) pretest CAD likelihood subgroups using standard software. The historical, clinical, stress ECG, and stress echocardiographic variables were recorded for the entire cohort. Follow-up (2.7 +/- 1.1 years) for confirmed myocardial infarction (n = 66) and cardiac death (n = 105) was obtained. For the entire cohort, an ischemic stress echocardiography study confers a 5.0 times higher cardiac event rate than the normal stress echocardiography group (4.0% vs 0.8%/y, P < .0001). Furthermore, Cox proportional hazard regression model showed incremental prognostic value of stress echocardiography variables over historic, clinical, and stress ECG variables across all pretest probability subgroups (global chi2 increased from 5.1 to 8.5 to 20.1 in the low pretest group, P = .44 and P = .01; from 20.9 to 28.2 to 116 in the intermediate pretest group, P = .47 and P < .0001; and from 17.5 to 36.6 to 61.4 in the high pretest group, P < .0001 for both groups). A normal stress echocardiography portends a benign prognosis (<1% event rate/y) in all pretest probability subgroups and even in patients with high pretest probability and yields incremental prognostic value over historic, clinical, and stress ECG variables across all pretest probability subgroups. The best incremental value is, however, in the

Prognostic value of clinical variables and liver histology for development of fibrosis and cirrhosis in autoimmune hepatitis.

PubMed

Puustinen, Lauri; Boyd, Sonja; Mustonen, Harri; Arkkila, Perttu; Arola, Johanna; Färkkilä, Martti

2017-03-01

In autoimmune hepatitis, data on the prognostic value of baseline liver biopsy and the sequential histology is controversial. Our aim was to evaluate the prognostic value of clinical variables and biopsy at the time of diagnosis and during the disease course. All 98 patients in our hospital during 1995-2012 were included. Sequential biopsies were available in 66 patients. Analyses based on clinical and histological variables were performed to find parameters predicting the progression of fibrosis, and development of cirrhosis. At the time of diagnosis, 7% were cirrhotic. Fibrosis progressed in 28 (42%) patients, remained stable in 26 (39%) and resolved in 12 (18%) patients. Findings which predicted fibrosis progression, were baseline total inflammation (odds ratio 1.7, 95% CI 1.01-2.8), cumulative total inflammation (1.8, 95% CI 1.01-3.2, rosette formation (2.8, 95% CI 1.1-7.1), absence of pericholangitis (0.4, 95% CI 0.1-1.0) and necrosis (1.4, 95% CI 1.0-2.0). Risk factors for the development of cirrhosis were cholestasis (4.6, 95% CI 1.2-16.9), interphase inflammation (3.4, 95% CI 1.1-10.4), and necrosis (3.3, 95% CI 1.2-9.7). In a cumulative model, cumulative total inflammation (4.5, 95% CI 1.4-15.0), necrosis (6.7, 95% CI 1.3-34.6), or cumulative immunoglobulin G load (61.8, 95% CI 2.0-1954.3) were risk factors. None of the patients with histological pericholangitis or granulomas developed cirrhosis. The histology provides prognostic information regarding progression of fibrosis or the development of cirrhosis. The total cumulative inflammatory activity predicts the progression of fibrosis, whereas baseline fibrosis, interphase inflammation, cholestasis, necrosis, as well as the cumulative total inflammation and cumulative immunoglobulin G, are risk factors for cirrhosis.

Cytogenetic Prognostication Within Medulloblastoma Subgroups

PubMed Central

Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

2014-01-01

Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID

Prognostic indicators of 6-month mortality in elderly people with advanced dementia: A systematic review

PubMed Central

Brown, Meghan A; Sampson, Elizabeth L; Jones, Louise

2013-01-01

Background: For end-of-life dementia patients, palliative care offers a better quality of life than continued aggressive or burdensome medical interventions. To provide the best care options to dementia sufferers, validated, reliable, sensitive, and accurate prognostic tools to identify end-of-life dementia stages are necessary. Aim: To identify accurate prognosticators of mortality in elderly advanced dementia patients consistently reported in the literature. Design: Systematic literature review. Data sources: PubMed, Embase, and PsycINFO databases were searched up to September 2012. Reference lists of included studies were also searched. Inclusion criteria were studies measuring factors specifically related to 6-month outcome in patients diagnosed with dementia in any residential or health-care setting. Results: Seven studies met the inclusion criteria, five of which were set in the United States and two in Israel. Methodology and prognostic outcomes varied greatly between the studies. All but one study found that Functional Assessment Staging phase 7c, currently widely used to assess hospice admission eligibility in the United States, was not a reliable predictor of 6-month mortality. The most common prognostic variables identified related to nutrition/nourishment, or eating habits, followed by increased risk on dementia severity scales and comorbidities. Conclusions: Although the majority of studies agreed that the Functional Assessment Staging 7c criterion was not a reliable predictor of 6-month mortality, we found a lack of prognosticator concordance across the literature. Further studies are essential to identify reliable, sensitive, and specific prognosticators, which can be applied to the clinical setting and allow increased availability of palliative care to dementia patients. PMID:23175514

Prognostic factors in patients with metastatic spinal cord compression secondary to melanoma: a systematic review.

PubMed

Hadden, Nicholas J; McIntosh, Jerome R D; Jay, Samuel; Whittaker, Paula J

2018-02-01

Melanoma is one of the most common primary tumours associated with metastatic spinal cord compression (MSCC). The aim of this review is to identify prognostic factors specifically for MSCC secondary to melanoma. A systematic search of literature was performed in MEDLINE, Embase and the Cochrane Library to identify studies reporting prognostic factors for patients with MSCC secondary to melanoma. Two studies, involving a total of 39 patients, fulfilled the inclusion criteria. The variables associated with increased survival were receiving postoperative radiotherapy, receiving chemotherapy, perioperative lactate dehydrogenase level less than or equal to 8.0 µkat/l, preoperative haemoglobin level more than 11.5 mg/dl, an interval of 4 or more years between melanoma diagnosis and skeletal metastasis, absence of further skeletal metastases, absence of visceral metastases, Eastern Cooperative Oncology Group Performance Status of 2 or less, two or fewer involved vertebrae, being ambulatory preradiotherapy and an interval of more than 7 days between developing motor deficits and radiotherapy. The variables associated with good functional outcome were slow development of motor dysfunction, good performance status and being ambulatory before radiotherapy. The most important prognostic factors for survival are Eastern Cooperative Oncology Group Performance Status of 2 or less and absence of visceral metastases. There is a lack of studies looking specifically at prognostic factors for patients with MSCC secondary to melanoma, and the number of patients involved in the existing studies is small.

Systematic review of current prognostication systems for primary gastrointestinal stromal tumors.

PubMed

Khoo, Chun Yuet; Chai, Xun; Quek, Richard; Teo, Melissa C C; Goh, Brian K P

2018-04-01

The advent of tyrosine kinase inhibitors as adjuvant therapy has revolutionized the management of GIST and emphasized the need for accurate prognostication systems. Numerous prognostication systems have been proposed for GIST but at present it remains unknown which system is superior. The present systematic review aims to summarize current prognostication systems for primary treatment-naive GIST. A literature review of the Pubmed and Embase databases was performed to identify all published articles in English, from the 1st January 2002 to 28th Feb 2017, reporting on clinical prognostication systems of GIST. Twenty-three articles on GIST prognostication systems were included. These systems were classified as categorical systems, which stratify patients into risk groups, or continuous systems, which provide an individualized form of risk assessment. There were 16 categorical systems in total. There were 4 modifications of the National Institute of Health (NIH) system, 2 modifications of Armed Forces Institute of Pathology (AFIP) criteria and 3 modifications of Joensuu (modified NIH) criteria. Of the 7 continuous systems, there were 3 prognostic nomograms, 3 mathematical models and 1 prognostic heat/contour maps. Tumor size, location and mitotic count remain the main variables used in these systems. Numerous prognostication systems have been proposed for the risk stratification of GISTs. The most widely used systems today are the NIH, Joensuu modified NIH, AFIP and the Memorial Sloan Kettering Cancer Center nomogram. More validation and comparison studies are required to determine the optimal prognostication system for GIST. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Identifying causal linkages between environmental variables and African conflicts

NASA Astrophysics Data System (ADS)

Nguy-Robertson, A. L.; Dartevelle, S.

2017-12-01

Environmental variables that contribute to droughts, flooding, and other natural hazards are often identified as factors contributing to conflict; however, few studies attempt to quantify these causal linkages. Recent research has demonstrated that the environment operates within a dynamical system framework and the influence of variables can be identified from convergent cross mapping (CCM) between shadow manifolds. We propose to use CCM to identify causal linkages between environmental variables and incidences of conflict. This study utilizes time series data from Climate Forecast System ver. 2 and MODIS satellite sensors processed using Google Earth Engine to aggregate country and regional trends. These variables are then compared to Armed Conflict Location & Event Data Project observations at similar scales. Results provide relative rankings of variables and their linkage to conflict. Being able to identify which factors contributed more strongly to a conflict can allow policy makers to prepare solutions to mitigate future crises. Knowledge of the primary environmental factors can lead to the identification of other variables to examine in the causal network influencing conflict.

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

PubMed

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

2018-05-01

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

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

PubMed Central

Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

2015-01-01

Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model.

PubMed

Scarisbrick, Julia J; Prince, H Miles; Vermeer, Maarten H; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L; Rodríguez-Peralto, Jose L; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T; Duvic, Madeleine; Whittaker, Sean J; Kim, Youn H

2015-11-10

Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value

Comparative Profiling of Primary Colorectal Carcinomas and Liver Metastases Identifies LEF1 as a Prognostic Biomarker

PubMed Central

Lin, Albert Y.; Chua, Mei-Sze; Choi, Yoon-La; Yeh, William; Kim, Young H.; Azzi, Raymond; Adams, Gregg A.; Sainani, Kristin; van de Rijn, Matt; So, Samuel K.; Pollack, Jonathan R.

2011-01-01

Purpose We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). Patients and Methods We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Results Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1. Conclusion Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. PMID:21383983

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

PubMed

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

2014-12-03

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

Prognostic categories and timing of negative prognostic communication from critical care physicians to family members at end-of-life in an intensive care unit.

PubMed

Gutierrez, Karen M

2013-09-01

Negative prognostic communication is often delayed in intensive care units, which limits time for families to prepare for end-of-life. This descriptive study, informed by ethnographic methods, was focused on exploring critical care physician communication of negative prognoses to families and identifying timing influences. Prognostic communication of critical care physicians to nurses and family members was observed and physicians and family members were interviewed. Physician perception of prognostic certainty, based on an accumulation of empirical data, and the perceived need for decision-making, drove the timing of prognostic communication, rather than family needs. Although prognoses were initially identified using intuitive knowledge for patients in one of the six identified prognostic categories, utilizing decision-making to drive prognostic communication resulted in delayed prognostic communication to families until end-of-life (EOL) decisions could be justified with empirical data. Providers will better meet the needs of families who desire earlier prognostic information by separating prognostic communication from decision-making and communicating the possibility of a poor prognosis based on intuitive knowledge, while acknowledging the uncertainty inherent in prognostication. This sets the stage for later prognostic discussions focused on EOL decisions, including limiting or withdrawing treatment, which can be timed when empirical data substantiate intuitive prognoses. This allows additional time for families to anticipate and prepare for end-of-life decision-making. © 2012 John Wiley & Sons Ltd.

Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury.

PubMed

Ritter, Anne C; Wagner, Amy K; Szaflarski, Jerzy P; Brooks, Maria M; Zafonte, Ross D; Pugh, Mary Jo V; Fabio, Anthony; Hammond, Flora M; Dreer, Laura E; Bushnik, Tamara; Walker, William C; Brown, Allen W; Johnson-Greene, Doug; Shea, Timothy; Krellman, Jason W; Rosenthal, Joseph A

2016-09-01

Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury. Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011-2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value < 0.20 that were used to fit initial prognostic models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models and to internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism). The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively. The prognostic model for PTS

Symptomatic spinal metastasis: A systematic literature review of the preoperative prognostic factors for survival, neurological, functional and quality of life in surgically treated patients and methodological recommendations for prognostic studies

PubMed Central

Nater, Anick; Martin, Allan R.; Sahgal, Arjun; Choi, David

2017-01-01

Purpose While several clinical prediction rules (CPRs) of survival exist for patients with symptomatic spinal metastasis (SSM), these have variable prognostic ability and there is no recognized CPR for health related quality of life (HRQoL). We undertook a critical appraisal of the literature to identify key preoperative prognostic factors of clinical outcomes in patients with SSM who were treated surgically. The results of this study could be used to modify existing or develop new CPRs. Methods Seven electronic databases were searched (1990–2015), without language restriction, to identify studies that performed multivariate analysis of preoperative predictors of survival, neurological, functional and HRQoL outcomes in surgical patients with SSM. Individual studies were assessed for class of evidence. The strength of the overall body of evidence was evaluated using GRADE for each predictor. Results Among 4,818 unique citations, 17 were included; all were in English, rated Class III and focused on survival, revealing a total of 46 predictors. The strength of the overall body of evidence was very low for 39 and low for 7 predictors. Due to considerable heterogeneity in patient samples and prognostic factors investigated as well as several methodological issues, our results had a moderately high risk of bias and were difficult to interpret. Conclusions The quality of evidence for predictors of survival was, at best, low. We failed to identify studies that evaluated preoperative prognostic factors for neurological, functional, or HRQoL outcomes in surgical patients with SSM. We formulated methodological recommendations for prognostic studies to promote acquiring high-quality evidence to better estimate predictor effect sizes to improve patient education, surgical decision-making and development of CPRs. PMID:28225772

Quantitative Analysis of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy

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

Cui, Yi; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo; Song, Jie

Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board–approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT {sup 18}F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162more » robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e

Prognostication in Pulmonary Arterial Hypertension with Submaximal Exercise Testing.

PubMed

Khatri, Vinod; Neal, Jennifer E; Burger, Charles D; Lee, Augustine S

2015-02-06

The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Artery Hypertension Disease Management) registry risk score (RRRS). Sixty-five consecutive patients with idiopathic and associated pulmonary arterial hypertension (PAH) underwent right-heart catheterization, echocardiogram, 6MWT and a three-minute SET (Shape-HF™). Analyses explored the association between SET variables and prognosis predicted by the RRRS. Although multiple SET variables correlated with the RRRS on univariate analyses, only V E /V CO2 (r = 0.57, p < 0.0001) remained an independent predictor in multivariate analysis (β = 0.05, p = 0.0371). Additionally, the V E /V CO2 was the most discriminatory (area under receiver operating characteristic curve, 0.84) in identifying the highest-risk category (RRRS ≥ 10), with an optimal cut-off of 40.6, resulting in a high sensitivity (92%) and negative-predictive value (97%), but a lower specificity (67%). SETs, particularly the V E /V CO2 , appear to have prognostic value when compared to the RRRS. If validated in prospective trials, SET should prove superior to the 6MWT or the RRRS, with significant implications for both future clinical trials and clinical practice.

Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death

PubMed Central

Heaphy, Christopher M.; Yoon, Ghil Suk; Peskoe, Sarah B.; Joshu, Corinne E.; Lee, Thomas K.; Giovannucci, Edward; Mucci, Lorelei A.; Kenfield, Stacey A.; Stampfer, Meir J.; Hicks, Jessica L.; De Marzo, Angelo M.; Platz, Elizabeth A.; Meeker, Alan K.

2013-01-01

Current prognostic indicators are imperfect predictors of outcome in men with clinicallylocalized prostate cancer. Thus, tissue-based markers are urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability and such instability is a hallmark of metastatic lesions, we hypothesized that alterations in telomere length in the primary cancer would predict risk of progression to metastasis and prostate cancer death. To test this hypothesis, we conducted a prospective cohort study of 596 surgically treated men who participated in the ongoing Health Professionals Follow-up Study. Men who had the combination of more variable telomere length among prostate cancer cells (cell-to-cell) and shorter telomere length in prostate cancer-associated stromal cells were substantially more likely to progress to metastasis or die of their prostate cancer. These findings point to the translational potential of this telomere biomarker for prognostication and risk stratification for individualized therapeutic and surveillance strategies. PMID:23779129

The importance of histopathological and clinical variables in predicting the evolution of colon cancer.

PubMed

Diculescu, Mircea; Iacob, Răzvan; Iacob, Speranţa; Croitoru, Adina; Becheanu, Gabriel; Popeneciu, Valentin

2002-09-01

It has been a consensus that prognostic factors should always be taken into account before planning treatment in colorectal cancer. A 5 year prospective study was conducted, in order to assess the importance of several histopathological and clinical prognostic variables in the prediction of evolution in colon cancer. Some of the factors included in the analysis are still subject to dispute by different authors. 46 of 53 screened patients qualified to enter the study and underwent a potentially curative resection of the tumor, followed, when necessary, by adjuvant chemotherapy. Univariate and multivariate analyses were carried out in order to identify independent prognostic indicators. The endpoint of the study was considered the recurrence of the tumor or the detection of metastases. 65.2% of the patients had a good evolution during the follow up period. Multivariate survival analysis performed by Cox proportional hazard model identified 3 independent prognostic factors: Dukes stage (p = 0.00002), the grade of differentiation (p = 0.0009) and the weight loss index, representing the weight loss of the patient divided by the number of months when it was actually lost (p = 0.02). Age under 40 years, sex, microscopic aspect of the tumor, tumor location, anemia degree were not identified by our analysis as having prognostic importance. Histopathological factors continue to be the most valuable source of information regarding the possible evolution of patients with colorectal cancer. Individual clinical symptoms or biological parameters such as erytrocyte sedimentation rate or hemoglobin level are of little or no prognostic value. More research is required relating to the impact of a performance status index (which could include also weight loss index) as another reliable prognostic variable.

Prognostic indicators for dogs with dilated cardiomyopathy.

PubMed

Borgarelli, Michele; Santilli, Roberto A; Chiavegato, David; D'Agnolo, Gino; Zanatta, Renato; Mannelli, Alessandro; Tarducci, Alberto

2006-01-01

The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic, and Doppler echocardiographic variables in dogs with dilated cardiomyopathy. The relationship to survival of 11 variables was evaluated in 63 dogs. Studied variables were age at time of diagnosis, class of heart failure (HF), dyspnea, ascites, atrial fibrillation (AF), ejection fraction (EF), E-point septal separation, end-diastolic volume index, end-systolic volume index (ESV-I), and restrictive or nonrestrictive transmitral flow (TMF) pattern. Median survival time was 671 days (lower 95% confidence limit, 350 days). Survival curves showed that severity of HF, ascites, ESV-I greater than 140 mL/m2, EF less than 25%, and restrictive TMF pattern had a significant negative relation to survival time. Thirty-nine dogs with both sinus rhythm and AF presented adequate TMF recordings; in these dogs, after stratification by TMF pattern, the restrictive TMF pattern was the most important negative prognostic indicator. We conclude that in dogs with dilated cardiomyopathy the restrictive TMF pattern appears to represent a useful prognostic indicator. Class of HF, ascites, ESV-I, and EF are also useful indexes if an adequate TMF pattern is not recorded.

Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups.

PubMed

Bosse, Tjalling; Nout, Remi A; McAlpine, Jessica N; McConechy, Melissa K; Britton, Heidi; Hussein, Yaser R; Gonzalez, Carlene; Ganesan, Raji; Steele, Jane C; Harrison, Beth T; Oliva, Esther; Vidal, August; Matias-Guiu, Xavier; Abu-Rustum, Nadeem R; Levine, Douglas A; Gilks, C Blake; Soslow, Robert A

2018-05-01

mixture of molecular subtypes of endometrial carcinoma, rather than a homogeneous group. The addition of molecular markers identifies prognostic subgroups, with potential therapeutic implications.

Sex and SUVmax: sex-dependent prognostication in early non-small cell lung cancer.

PubMed

Wainer, Zoe; Daniels, Marissa G; Callahan, Jason; Binns, David; Hicks, Rodney J; Antippa, Phillip; Russell, Prudence A; Alam, Naveed Z; Conron, Matthew; Solomon, Benjamin; Wright, Gavin M

2012-11-01

The identification of robust prognostic factors for patients with early-stage non-small cell lung cancer (NSCLC) is clinically important. The International Association for the Study of Lung Cancer has identified both sex and the maximum standardized uptake value (SUVmax) of (18)F-FDG in the primary tumor as measured by PET as potential prognostic variables. We examined the prognostic value of SUVmax in a surgical cohort of patients with NSCLC and disaggregated the findings by sex. Patients who had undergone a preoperative PET/CT scan and surgical resection with curative intent from 2001 to 2009 were identified from a prospective database. An SUVmax cutoff was calculated using receiver-operating-characteristic curves. Overall survival was correlated with SUVmax for the whole cohort and disaggregated by sex. Inclusion criteria were met by 189 patients: 127 (67%) men and 62 (33%) women. Five-year survival was 54.6% for the whole cohort, 47.7% for men, and 68.2% for women. SUVmax correlated negatively with survival in a univariate analysis for the whole cohort (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.54-4.09; P < 0.001) and men (HR, 3.42; 95% CI, 1.94-6.05; P < 0.001) but not for women (HR, 1.61; 95% CI, 0.43-3.12; P = 0.77), using 8 as a cutoff. In multivariate analysis, SUVmax correlated with overall survival for the whole cohort (HR, 1.70; 95% CI, 1.05-2.99; P = 0.05) and men (HR, 2.40; 95% CI, 1.32-4.37; P = 0.004) but not for women (HR, 0.80; 95% CI, 0.15-4.47; P = 0.80). SUVmax independently predicted overall survival for men but not for women in this surgical cohort. Our results suggest that SUVmax is an independent prognostic variable in men with surgically treated early NSCLC.

Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma

PubMed Central

McCabe, Martin G.; Bäcklund, L. Magnus; Leong, Hui Sun; Ichimura, Koichi; Collins, V. Peter

2011-01-01

Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies. PMID:21292688

Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning.

PubMed

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

2016-07-01

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

Problems Identifying Independent and Dependent Variables

ERIC Educational Resources Information Center

Leatham, Keith R.

2012-01-01

This paper discusses one step from the scientific method--that of identifying independent and dependent variables--from both scientific and mathematical perspectives. It begins by analyzing an episode from a middle school mathematics classroom that illustrates the need for students and teachers alike to develop a robust understanding of…

Distinguishing prognostic and predictive biomarkers: An information theoretic approach.

PubMed

Sechidis, Konstantinos; Papangelou, Konstantinos; Metcalfe, Paul D; Svensson, David; Weatherall, James; Brown, Gavin

2018-05-02

The identification of biomarkers to support decision-making is central to personalised medicine, in both clinical and research scenarios. The challenge can be seen in two halves: identifying predictive markers, which guide the development/use of tailored therapies; and identifying prognostic markers, which guide other aspects of care and clinical trial planning, i.e. prognostic markers can be considered as covariates for stratification. Mistakenly assuming a biomarker to be predictive, when it is in fact largely prognostic (and vice-versa) is highly undesirable, and can result in financial, ethical and personal consequences. We present a framework for data-driven ranking of biomarkers on their prognostic/predictive strength, using a novel information theoretic method. This approach provides a natural algebra to discuss and quantify the individual predictive and prognostic strength, in a self-consistent mathematical framework. Our contribution is a novel procedure, INFO+, which naturally distinguishes the prognostic vs predictive role of each biomarker and handles higher order interactions. In a comprehensive empirical evaluation INFO+ outperforms more complex methods, most notably when noise factors dominate, and biomarkers are likely to be falsely identified as predictive, when in fact they are just strongly prognostic. Furthermore, we show that our methods can be 1-3 orders of magnitude faster than competitors, making it useful for biomarker discovery in 'big data' scenarios. Finally, we apply our methods to identify predictive biomarkers on two real clinical trials, and introduce a new graphical representation that provides greater insight into the prognostic and predictive strength of each biomarker. R implementations of the suggested methods are available at https://github.com/sechidis. konstantinos.sechidis@manchester.ac.uk. Supplementary data are available at Bioinformatics online.

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

PubMed

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

2013-01-01

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

Patient Characteristics, Treatment Patterns and Prognostic Factors in Squamous Cell Bladder Cancer.

PubMed

Zahoor, Haris; Elson, Paul; Stephenson, Andrew; Haber, Georges-Pascal; Kaouk, Jihad; Fergany, Amr; Lee, Byron; Koshkin, Vadim; Ornstein, Moshe; Gilligan, Timothy; Garcia, Jorge A; Rini, Brian; Grivas, Petros

2018-04-01

Squamous cell carcinoma (SCC) is an uncommon histologic subtype of bladder cancer with limited data on treatment patterns, outcomes, and prognostic factors. "Real world" information might inform decision-making, prognostic estimates, and clinical trial designs. A retrospective review of patients with tissue-confirmed bladder SCC treated at Cleveland Clinic from 2007 to 2016 was performed. Data on patient characteristics, treatment patterns, and clinical follow-up were extracted. Univariate analysis was used to identify predictors of overall survival (OS), recurrence-free survival (RFS) and time to recurrence. Of 58 identified patients, 42 had complete data available. Median age at diagnosis was 67 years (range, 37-90). Hematuria was the most common (71%) presenting symptom; 32 patients had pure SCC and 10 predominant/extensive squamous differentiation without major differences noted in clinicopathologic variables or outcomes among those 2 groups. Overall, 35 patients underwent cystectomy with 5 receiving neoadjuvant and 1 adjuvant chemotherapy, whereas 3 had chemotherapy for recurrent disease. Of patients with cystectomy, most had locally advanced disease (75% pT3/4, 35% pN+). Overall, 10 patients progressed and 14 died; median OS was not reached. The 2-year estimated OS, RFS, and cumulative incidence of recurrence were 61% ± 9%, 50% ± 9%, and 32% ± 9%, respectively. Hydronephrosis, older age (70 years or older), lymphovascular invasion, nodal metastases, and advanced T stage were associated with 1 or more poor outcomes. In patients with resectable bladder SCC, radical cystectomy remains the main treatment modality. The role of perioperative chemotherapy remains unclear. The identified prognostic factors might be helpful for prognostication, treatment discussion, and trial eligibility/stratification. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic value of lymph node ratio in head and neck squamous cell carcinoma.

PubMed

Talmi, Yoav P; Takes, Robert P; Alon, Eran E; Nixon, Iain J; López, Fernando; de Bree, Remco; Rodrigo, Juan P; Shaha, Ashok R; Halmos, Gyorgy B; Rinaldo, Alessandra; Ferlito, Alfio

2018-05-01

Lymph node ratio (LNR) is increasingly reported as a potential prognostic tool. The purpose of this review was to analyze the available literature on the prognostic significance of LNR in head and neck squamous cell carcinoma (HNSCC). A PubMed internet search was performed and articles meeting selection criteria were reviewed. Twenty-eight studies were identified in the literature dealing with the prognostic value of LNR. The published results are variable with a range of cutoff values of LNR associated with prognosis (overall survival [OS] and/or disease-specific survival [DSS]) between 0.02 and 0.20, with an average of 0.09. The LNR is reported to be of value in assessing prognosis in the patients with HNSCC. Although it is easy to calculate and could be considered in the staging of these patients, the currently available evidence in the literature does not yet provide a solid base for implementation. © 2018 Wiley Periodicals, Inc.

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

PubMed

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

2015-01-01

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

The prognostic value of heart rate variability in the elderly, changing the perspective: from sympathovagal balance to chaos theory.

PubMed

Nicolini, Paola; Ciulla, Michele M; De Asmundis, Carlo; Magrini, Fabio; Brugada, Pedro

2012-05-01

Heart rate variability (HRV) is the temporal beat-to-beat variation in successive RR intervals on an electrocardiographic (ECG) recording and it reflects the regulation of the heart rate (HR) by the autonomic nervous system (ANS). HRV analysis is a noninvasive tool for the assessment of autonomic function that gained momentum in the late 1980s when its clinical relevance as a predictor of mortality was established by a milestone study by Kleiger et al. in patients with postacute myocardial infarction. In the last few decades, the increasing availability of commercial ECG devices offering HRV analysis has made HRV a favorite marker for risk stratification in the setting of cardiovascular disease. The rapid aging of the world population and the growing popularity of HRV have also fueled interest for the prognostic value of HRV in the elderly, outside a specific cardiological context. However, the discussion of HRV measures in the elderly is still very much centered on the rather reductionistic model of sympathovagal balance, with the orthosympathetic and parasympathetic limbs of the ANS exercising opposing effects on the heart via autonomic tone. The expanding application of nonlinear dynamics to medicine has brought to the forefront the notion of system complexity, embedded in the mathematical concepts of chaos theory and fractals, and provides an opportunity to suggest a broader interpretation for the prognostic significance of HRV, especially in the elderly. Although the use of novel indices of HRV may be hampered by practical issues, a more holistic approach to HRV may still be safeguarded if traditional time- and frequency-domain measures are viewed in terms of autonomic modulation. This review focuses on HRV in geriatric populations. It considers studies on the prognostic value of HRV in elderly subjects, discussing the potential confounding effect of erratic rhythm, and concentrates on the conceptual distinction between autonomic tone and autonomic modulation

Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer.

PubMed

Chen, Jie; Li, Yan; Zheng, Qiupeng; Bao, Chunyang; He, Jian; Chen, Bin; Lyu, Dongbin; Zheng, Biqiang; Xu, Yu; Long, Ziwen; Zhou, Ye; Zhu, Huiyan; Wang, Yanong; He, Xianghuo; Shi, Yingqiang; Huang, Shenglin

2017-03-01

Circular RNAs (circRNAs) comprise a novel class of widespread non-coding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs in human cancer remain elusive. Here we identified at least 5500 distinct circRNA candidates and a series of circRNAs that are differentially expressed in gastric cancer (GC) tissues compared with matched normal tissues. We further characterized one circRNA derived from the PVT1 gene and termed it as circPVT1. The expression of circPVT1 is often upregulated in GC tissues due to the amplification of its genomic locus. circPVT1 may promote cell proliferation by acting as a sponge for members of the miR-125 family. The level of circPVT1 was observed as an independent prognostic marker for overall survival and disease-free survival of patients with GC. Our findings suggest that circPVT1 is a novel proliferative factor and prognostic marker in GC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prognostic factors for specific lower extremity and spinal musculoskeletal injuries identified through medical screening and training load monitoring in professional football (soccer): a systematic review

PubMed Central

Sergeant, Jamie C; Parkes, Matthew J; Callaghan, Michael J

2017-01-01

Background Medical screening and load monitoring procedures are commonly used in professional football to assess factors perceived to be associated with injury. Objectives To identify prognostic factors (PFs) and models for lower extremity and spinal musculoskeletal injuries in professional/elite football players from medical screening and training load monitoring processes. Methods The MEDLINE, AMED, EMBASE, CINAHL Plus, SPORTDiscus and PubMed electronic bibliographic databases were searched (from inception to January 2017). Prospective and retrospective cohort studies of lower extremity and spinal musculoskeletal injury incidence in professional/elite football players aged between 16 and 40 years were included. The Quality in Prognostic Studies appraisal tool and the modified Grading of Recommendations Assessment, Development and Evaluation synthesis approach was used to assess the quality of the evidence. Results Fourteen studies were included. 16 specific lower extremity injury outcomes were identified. No spinal injury outcomes were identified. Meta-analysis was not possible due to heterogeneity and study quality. All evidence related to PFs and specific lower extremity injury outcomes was of very low to low quality. On the few occasions where multiple studies could be used to compare PFs and outcomes, only two factors demonstrated consensus. A history of previous hamstring injuries (HSI) and increasing age may be prognostic for future HSI in male players. Conclusions The assumed ability of medical screening tests to predict specific musculoskeletal injuries is not supported by the current evidence. Screening procedures should currently be considered as benchmarks of function or performance only. The prognostic value of load monitoring modalities is unknown. PMID:29177074

Evaluating biomarkers for prognostic enrichment of clinical trials.

PubMed

Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

2017-12-01

A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

Prognostic discrimination in "good-risk" chronic granulocytic leukemia.

PubMed

Sokal, J E; Cox, E B; Baccarani, M; Tura, S; Gomez, G A; Robertson, J E; Tso, C Y; Braun, T J; Clarkson, B D; Cervantes, F

1984-04-01

The prognostic significance of disease features recorded at the time of diagnosis was examined among 813 patients with Philadelphia chromosome-positive, nonblastic chronic granulocytic leukemia (CGL) collected from six European and American series. The survival pattern for this population was typical of "good-risk" patients, and median survival was 47 mo. There were multiple interrelationships among different disease features, which led to highly significant correlations with survival for some that had no primary prognostic significance, such as hematocrit. Multivariable regression analysis indicated that spleen size and the percentage of circulating blasts were the most important prognostic indicators. These features, and age, behaved as continuous variables with progressively unfavorable import at higher values. The platelet count did not influence survival significantly at values below 700 X 10(9)/liter but was increasingly unfavorable above this level. Basophils plus eosinophils over 15%, more than 5% marrow blasts, and karyotypic abnormalities in addition to the Ph1 were also significant unfavorable signs. The Cox model, generated with four variables representing percent blasts, spleen size, platelet count, and age, provided a useful representation of risk status in this population, with good fit between predicted and observed survival over more than a twofold survival range. A hazard function derived from half of the patient population successfully segregated the remainder into three groups with significantly different survival patterns. We conclude that it should be possible to identify a lower risk group of patients with a 2-yr survival of 90%, subsequent risk averaging somewhat less than 20%/yr and median survival of 5 yr, an intermediate group, and a high-risk group with a 2-yr survival of 65%, followed by a death rate of about 35%/yr and median survival of 2.5 yr.

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

PubMed

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

2018-03-01

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

Multicollinearity in prognostic factor analyses using the EORTC QLQ-C30: identification and impact on model selection.

PubMed

Van Steen, Kristel; Curran, Desmond; Kramer, Jocelyn; Molenberghs, Geert; Van Vreckem, Ann; Bottomley, Andrew; Sylvester, Richard

2002-12-30

Clinical and quality of life (QL) variables from an EORTC clinical trial of first line chemotherapy in advanced breast cancer were used in a prognostic factor analysis of survival and response to chemotherapy. For response, different final multivariate models were obtained from forward and backward selection methods, suggesting a disconcerting instability. Quality of life was measured using the EORTC QLQ-C30 questionnaire completed by patients. Subscales on the questionnaire are known to be highly correlated, and therefore it was hypothesized that multicollinearity contributed to model instability. A correlation matrix indicated that global QL was highly correlated with 7 out of 11 variables. In a first attempt to explore multicollinearity, we used global QL as dependent variable in a regression model with other QL subscales as predictors. Afterwards, standard diagnostic tests for multicollinearity were performed. An exploratory principal components analysis and factor analysis of the QL subscales identified at most three important components and indicated that inclusion of global QL made minimal difference to the loadings on each component, suggesting that it is redundant in the model. In a second approach, we advocate a bootstrap technique to assess the stability of the models. Based on these analyses and since global QL exacerbates problems of multicollinearity, we therefore recommend that global QL be excluded from prognostic factor analyses using the QLQ-C30. The prognostic factor analysis was rerun without global QL in the model, and selected the same significant prognostic factors as before. Copyright 2002 John Wiley & Sons, Ltd.

lncRNA co-expression network model for the prognostic analysis of acute myeloid leukemia

PubMed Central

Pan, Jia-Qi; Zhang, Yan-Qing; Wang, Jing-Hua; Xu, Ping; Wang, Wei

2017-01-01

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy with great variability of prognostic behaviors. Previous studies have reported that long non-coding RNAs (lncRNAs) play an important role in AML and may thus be used as potential prognostic biomarkers. However, thus use of lncRNAs as prognostic biomarkers in AML and their detailed mechanisms of action in this disease have not yet been well characterized. For this purpose, in the present study, the expression levels of lncRNAs and mRNAs were calculated using the RNA-seq V2 data for AML, following which a lncRNA-lncRNA co-expression network (LLCN) was constructed. This revealed a total of 8 AML prognosis-related lncRNA modules were identified, which displayed a significant correlation with patient survival (p≤0.05). Subsequently, a prognosis-related lncRNA module pathway network was constructed to interpret the functional mechanism of the prognostic modules in AML. The results indicated that these prognostic modules were involved in the AML pathway, chemokine signaling pathway and WNT signaling pathway, all of which play important roles in AML. Furthermore, the investigation of lncRNAs in these prognostic modules suggested that an lncRNA (ZNF571-AS1) may be involved in AML via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway by regulating KIT and STAT5. The results of the present study not only provide potential lncRNA modules as prognostic biomarkers, but also provide further insight into the molecular mechanisms of action of lncRNAs. PMID:28204819

Variable prognostic value of blood pressure response to exercise.

PubMed

Kato, Yuko; Suzuki, Shinya; Uejima, Tokuhisa; Semba, Hiroaki; Yamashita, Takeshi

2018-01-01

The aim of this study was to evaluate the impact of patient background including exercise capacity on the relationship between the blood pressure (BP) response to exercise and prognosis in patients visiting a cardiovascular hospital. A total of 2134 patients who were referred to our hospital underwent symptom-limited maximal cardiopulmonary exercise testing, and were followed through medical records and mail. The BP response to exercise was defined as the difference between peak and rest systolic BP. The end point was set as cardiovascular events including cardiovascular death, acute coronary syndrome, hospitalization for heart failure, and cerebral infarction. During a median follow-up period of 3 years, 179 (8%) patients reached the end point (2.5%/year). Multivariate analysis showed that BP response was independently and negatively associated with the occurrence of the end point. This prognostic significance of BP response was consistent regardless of left ventricular ejection fraction, renal function, presence of heart failure symptoms, the presence of organic heart disease, and hypertension. However, peak VO 2 showed a significant interaction with the effects of BP response on the end point, suggesting that the prognostic value of BP response was limited in patients with preserved exercise capacity. The role of BP response to exercise as the predictor depends on exercise capacity of each patient. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Development and validation of a prognostic index for 4-year mortality in older adults.

PubMed

Lee, Sei J; Lindquist, Karla; Segal, Mark R; Covinsky, Kenneth E

2006-02-15

Both comorbid conditions and functional measures predict mortality in older adults, but few prognostic indexes combine both classes of predictors. Combining easily obtained measures into an accurate predictive model could be useful to clinicians advising patients, as well as policy makers and epidemiologists interested in risk adjustment. To develop and validate a prognostic index for 4-year mortality using information that can be obtained from patient report. Using the 1998 wave of the Health and Retirement Study (HRS), a population-based study of community-dwelling US adults older than 50 years, we developed the prognostic index from 11,701 individuals and validated the index with 8009. Individuals were asked about their demographic characteristics, whether they had specific diseases, and whether they had difficulty with a series of functional measures. We identified variables independently associated with mortality and weighted the variables to create a risk index. Death by December 31, 2002. The overall response rate was 81%. During the 4-year follow-up, there were 1361 deaths (12%) in the development cohort and 1072 deaths (13%) in the validation cohort. Twelve independent predictors of mortality were identified: 2 demographic variables (age: 60-64 years, 1 point; 65-69 years, 2 points; 70-74 years, 3 points; 75-79 years, 4 points; 80-84 years, 5 points, >85 years, 7 points and male sex, 2 points), 6 comorbid conditions (diabetes, 1 point; cancer, 2 points; lung disease, 2 points; heart failure, 2 points; current tobacco use, 2 points; and body mass index <25, 1 point), and difficulty with 4 functional variables (bathing, 2 points; walking several blocks, 2 points; managing money, 2 points, and pushing large objects, 1 point. Scores on the risk index were strongly associated with 4-year mortality in the validation cohort, with 0 to 5 points predicting a less than 4% risk, 6 to 9 points predicting a 15% risk, 10 to 13 points predicting a 42% risk, and 14 or

Novel immunological and nutritional-based prognostic index for gastric cancer.

PubMed

Sun, Kai-Yu; Xu, Jian-Bo; Chen, Shu-Ling; Yuan, Yu-Jie; Wu, Hui; Peng, Jian-Jun; Chen, Chuang-Qi; Guo, Pi; Hao, Yuan-Tao; He, Yu-Long

2015-05-21

To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer. We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias. Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively. PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer.

A retrospective clinical study of cervical restorations: longevity and failure-prognostic variables.

PubMed

Namgung, C; Rho, Y J; Jin, B H; Lim, B S; Cho, B H

2013-01-01

The aim of this retrospective clinical study was to compare the longevity of cervical restorations between resin composite (RC) and glass ionomer (GI) and to investigate variables predictive of their outcome. The clinical performance of the two restorative materials in function was compared using the ratings of the modified United States Public Health Service (USPHS) criteria. A total of 479 cervical restorations were included in the study. Ninety-one already-replaced restorations were reviewed from dental records. The other 388 restorations still in function were evaluated according to the modified USPHS criteria by two investigators. Longevity and prognostic variables were analyzed with the Kaplan-Meier survival analysis and multivariate Cox proportional hazard model. The clinical performances of the two materials were evaluated according to the ratings of the USPHS criteria and compared using the Pearson chi-square test and Fisher exact test. The longevity was not significantly different between RC and GI (median survival time, 10.4 ± 0.7 and 11.5 ± 1.1 years, respectively). The main reasons for failure were loss of retention (82.2%) and secondary caries (17.8%). The longevity of cervical restoration was significantly influenced by tooth group and operator group (Wald test, p<0.05), while material, gender, presence or absence of systemic diseases, arch, and reason for treatment did not affect the longevity. Contrary to the longevity, the clinical performance of RC was superior to GI in the criteria of retention, marginal discoloration, and marginal adaptation, but similar in secondary caries, wear, and postoperative sensitivity.

Practical prognostic index for patients with metastatic recurrent breast cancer: retrospective analysis of 2,322 patients from the GEICAM Spanish El Alamo Register.

PubMed

Puente, Javier; López-Tarruella, Sara; Ruiz, Amparo; Lluch, Ana; Pastor, Miguel; Alba, Emilio; de la Haba, Juan; Ramos, Manuel; Cirera, Luis; Antón, Antonio; Llombart, Antoni; Plazaola, Arrate; Fernández-Aramburo, Antonio; Sastre, Javier; Díaz-Rubio, Eduardo; Martin, Miguel

2010-07-01

Women with recurrent metastatic breast cancer from a Spanish hospital registry (El Alamo, GEICAM) were analyzed in order to identify the most helpful prognostic factors to predict survival and to ultimately construct a practical prognostic index. The inclusion criteria covered women patients diagnosed with operable invasive breast cancer who had metastatic recurrence between 1990 and 1997 in GEICAM hospitals. Patients with stage IV breast cancer at initial diagnosis or with isolated loco-regional recurrence were excluded from this analysis. Data from 2,322 patients with recurrent breast cancer after primary treatment (surgery, radiation and systemic adjuvant treatment) were used to construct the prognostic index. The prognostic index score for each individual patient was calculated by totalling up the scores of each independent variable. The maximum score obtainable was 26.1. Nine-hundred and sixty-two patients who had complete data for all the variables were used in the computation of the prognostic index score. We were able to stratify them into three prognostic groups based on the prognostic index score: 322 patients in the good risk group (score < or =13.5), 308 patients in the intermediate risk group (score 13.51-15.60) and 332 patients in the poor risk group (score > or =15.61). The median survivals for these groups were 3.69, 2.27 and 1.02 years, respectively (P < 0.0001). In conclusion, risk scores are extraordinarily valuable tools, highly recommendable in the clinical practice.

A New Prognostic Staging System for Rectal Cancer

PubMed Central

Ueno, Hideki; Price, Ashley B.; Wilkinson, Kay H.; Jass, Jeremy R.; Mochizuki, Hidetaka; Talbot, Ian C.

2004-01-01

Objective: To clarify the appropriateness of tumor “budding,” a quantifiable histologic variable, as 1 parameter in the construction of a new prognostic grading system for rectal cancer. Summary Background Data: Patient division according to an accurate prognostic prediction could enhance the effectiveness of postoperative adjuvant therapy and follow-up. Patients and Methods: Tumor budding was defined as an isolated cancer cell or a cluster composed of fewer than 5 cells in the invasive frontal region, and was divided into 2 grades based on its number within a microscopic field of ×250. We analyzed 2 discrete cohorts comprising 638 and 476 patients undergoing potentially curative surgery. Results: In the first cohort, high-grade budding (10 or more foci in a field) was observed in 30% of patients and was significantly associated with a lower 5-year survival rate (41%) than low-grade budding (84%). Similarly, in the second cohort, the 5-year survival rate was 43% in high-grade budding patients and 83% in low-grade budding patients. In both cohorts, multivariate analyses verified budding to be an independent prognosticator, together with nodal involvement and extramural spread. These 3 variables were given weighted scores, and the score range was divided to provide 5 prognostic groups (97%; 86%; 61%; 39%; 17% 5-year survival). The model was tested on the second cohort, and similar prognostic results were obtained. Conclusions: We propose that because of its relevance to prognosis and its reproducibility, budding is an excellent parameter for use in a grading system to provide a confident prediction of clinical outcome. PMID:15492565

A Prognostic Model for One-year Mortality in Patients Requiring Prolonged Mechanical Ventilation

PubMed Central

Carson, Shannon S.; Garrett, Joanne; Hanson, Laura C.; Lanier, Joyce; Govert, Joe; Brake, Mary C.; Landucci, Dante L.; Cox, Christopher E.; Carey, Timothy S.

2009-01-01

Objective A measure that identifies patients who are at high risk of mortality after prolonged ventilation will help physicians communicate prognosis to patients or surrogate decision-makers. Our objective was to develop and validate a prognostic model for 1-year mortality in patients ventilated for 21 days or more. Design Prospective cohort study. Setting University-based tertiary care hospital Patients 300 consecutive medical, surgical, and trauma patients requiring mechanical ventilation for at least 21 days were prospectively enrolled. Measurements and Main Results Predictive variables were measured on day 21 of ventilation for the first 200 patients and entered into logistic regression models with 1-year and 3-month mortality as outcomes. Final models were validated using data from 100 subsequent patients. One-year mortality was 51% in the development set and 58% in the validation set. Independent predictors of mortality included requirement for vasopressors, hemodialysis, platelet count ≤150 ×109/L, and age ≥50. Areas under the ROC curve for the development model and validation model were 0.82 (se 0.03) and 0.82 (se 0.05) respectively. The model had sensitivity of 0.42 (se 0.12) and specificity of 0.99 (se 0.01) for identifying patients who had ≥90% risk of death at 1 year. Observed mortality was highly consistent with both 3- and 12-month predicted mortality. These four predictive variables can be used in a simple prognostic score that clearly identifies low risk patients (no risk factors, 15% mortality) and high risk patients (3 or 4 risk factors, 97% mortality). Conclusions Simple clinical variables measured on day 21 of mechanical ventilation can identify patients at highest and lowest risk of death from prolonged ventilation. PMID:18552692

Current state of prognostication and risk stratification in myelodysplastic syndromes.

PubMed

Zeidan, Amer M; Gore, Steven D; Padron, Eric; Komrokji, Rami S

2015-03-01

Myelodysplastic syndromes (MDS) are characterized by significant biologic and clinical heterogeneity. Because of the wide outcome variability, accurate prognostication is vital to high-quality risk-adaptive care of MDS patients. In this review, we discuss the current state of prognostic schemes for MDS and overview efforts aimed at utilizing molecular aberrations for prognostication in clinical practice. Several prognostic instruments have been developed and validated with increasing accuracy and complexity. Oncologists should be aware of the inherent limitations of these prognostic tools as they counsel patients and make clinical decisions. As more therapies are becoming available for MDS, the focus of model development is shifting from prognostic to treatment-specific predictive instruments. In addition to providing additional prognostic data beyond traditional clinical and pathologic parameters, the improved understanding of the genetic landscape and pathophysiologic consequences in MDS may allow the construction of treatment-specific predictive instruments. How to best use the results of molecular mutation testing to inform clinical decision making in MDS is still a work in progress. Important steps in this direction include standardization in performance and interpretation of assays and better understanding of the independent prognostic importance of the recurrent mutations, especially the less frequent ones.

Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma.

PubMed

Mundt, Filip; Johansson, Henrik J; Forshed, Jenny; Arslan, Sertaç; Metintas, Muzaffer; Dobra, Katalin; Lehtiö, Janne; Hjerpe, Anders

2014-03-01

Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome

State of the art and taxonomy of prognostics approaches, trends of prognostics applications and open issues towards maturity at different technology readiness levels

NASA Astrophysics Data System (ADS)

Javed, Kamran; Gouriveau, Rafael; Zerhouni, Noureddine

2017-09-01

Integrating prognostics to a real application requires a certain maturity level and for this reason there is a lack of success stories about development of a complete Prognostics and Health Management system. In fact, the maturity of prognostics is closely linked to data and domain specific entities like modeling. Basically, prognostics task aims at predicting the degradation of engineering assets. However, practically it is not possible to precisely predict the impending failure, which requires a thorough understanding to encounter different sources of uncertainty that affect prognostics. Therefore, different aspects crucial to the prognostics framework, i.e., from monitoring data to remaining useful life of equipment need to be addressed. To this aim, the paper contributes to state of the art and taxonomy of prognostics approaches and their application perspectives. In addition, factors for prognostics approach selection are identified, and new case studies from component-system level are discussed. Moreover, open challenges toward maturity of the prognostics under uncertainty are highlighted and scheme for an efficient prognostics approach is presented. Finally, the existing challenges for verification and validation of prognostics at different technology readiness levels are discussed with respect to open challenges.

Clinical Efficacy and Its Prognostic Factor of Percutaneous Endoscopic Lumbar Annuloplasty and Nucleoplasty for the Treatment of Patients with Discogenic Low Back Pain.

PubMed

Lee, Jung Hwan; Lee, Sang-Ho

2017-09-01

The choice of appropriate treatment of discogenic low back pain (DLBP) frequently is difficult. This study sought to identify the clinical efficacy of percutaneous endoscopic lumbar annuloplasty and nucleoplasty (PELAN) to treat patients with DLBP and to investigate prognostic clinical or radiologic variables. Eighty-nine patients with a diagnosis of DLBP who underwent PELAN were included. Numeric Rating Scale (NRS) for back pain, Oswestry Disability Index % (ODI%), and modified Macnab criteria were measured at short-term (3-4 weeks) and long-term follow-up period (at least 12 months) to investigate clinical efficacy of PELAN. The subjects were defined as successful group in case of 50% or more reduction of NRS, 40% or more reduction of ODI%, and good or excellent response of Macnab criteria. Clinical and radiologic variables were compared between successful and unsuccessful outcomes group to determine prognostic variables. NRS and ODI% were significantly reduced at short- and long-term follow-up after PELAN. Sixty-two (69.7%) and 68 (76.4%) obtained successful NRS reduction and 59 (66.3%) and 68 (76.4%) accomplished successful ODI% reduction at short-term and long-term follow-up, respectively. Successful Mcnab response was found in 61% at short term and 65.2% at long term. Pain during waist flexion among clinical variables was significantly related to good clinical outcomes and Modic change among radiologic variables was significantly related to poor clinical outcomes. PELAN provided favorable outcomes in patients with DLBP who were refractory to conservative treatments. Flexion pain was good prognostic, and Modic change was a poor prognostic variable. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic Indexes for Brain Metastases: Which Is the Most Powerful?

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

Arruda Viani, Gustavo, E-mail: gusviani@gmail.com; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

Purpose: The purpose of the present study was to compare the prognostic indexes (PIs) of patients with brain metastases (BMs) treated with whole brain radiotherapy (WBRT) using an artificial neural network. This analysis is important, because it evaluates the prognostic power of each PI to guide clinical decision-making and outcomes research. Methods and Materials: A retrospective prognostic study was conducted of 412 patients with BMs who underwent WBRT between April 1998 and March 2010. The eligibility criteria for patients included having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the artificial neural network. The input neural datamore » consisted of all prognostic factors included in the 5 PIs (recursive partitioning analysis, graded prognostic assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The data set was randomly divided into 300 training and 112 testing examples for survival prediction. All 5 PIs were compared using our database of 412 patients with BMs. The sensibility of the 5 indexes to predict survival according to their input variables was determined statistically using receiver operating characteristic curves. The importance of each variable from each PI was subsequently evaluated. Results: The overall 1-, 2-, and 3-year survival rate was 22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly associated with survival (recursive partitioning analysis, P < .0001; GPA, P < .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany score, P < .0001). Comparing the areas under the curves, the GPA was statistically most sensitive in predicting survival (GPA, 86%; recursive partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany score, 77%; P < .001). Among the variables included in each PI, the performance status and presence of extracranial metastases were the most important factors. Conclusion: A variety of prognostic models describe

On Applying the Prognostic Performance Metrics

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2009-01-01

Prognostics performance evaluation has gained significant attention in the past few years. As prognostics technology matures and more sophisticated methods for prognostic uncertainty management are developed, a standardized methodology for performance evaluation becomes extremely important to guide improvement efforts in a constructive manner. This paper is in continuation of previous efforts where several new evaluation metrics tailored for prognostics were introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. Several shortcomings identified, while applying these metrics to a variety of real applications, are also summarized along with discussions that attempt to alleviate these problems. Further, these metrics have been enhanced to include the capability of incorporating probability distribution information from prognostic algorithms as opposed to evaluation based on point estimates only. Several methods have been suggested and guidelines have been provided to help choose one method over another based on probability distribution characteristics. These approaches also offer a convenient and intuitive visualization of algorithm performance with respect to some of these new metrics like prognostic horizon and alpha-lambda performance, and also quantify the corresponding performance while incorporating the uncertainty information.

New prognostic model for extranodal natural killer/T cell lymphoma, nasal type.

PubMed

Cai, Qingqing; Luo, Xiaolin; Zhang, Guanrong; Huang, Huiqiang; Huang, Hui; Lin, Tongyu; Jiang, Wenqi; Xia, Zhongjun; Young, Ken H

2014-09-01

Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) <60 g/L, fasting blood glucose (FBG) >100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p < 0.001). Our new prognostic model had a better prognostic value than did the KPI model alone (p < 0.001). Our proposed prognostic model for ENKTL, including the newly identified prognostic indicators, TP and FBG, demonstrated a balanced distribution of patients into different risk groups with better prognostic discrimination compared with the KPI model alone.

AIC identifies optimal representation of longitudinal dietary variables.

PubMed

VanBuren, John; Cavanaugh, Joseph; Marshall, Teresa; Warren, John; Levy, Steven M

2017-09-01

The Akaike Information Criterion (AIC) is a well-known tool for variable selection in multivariable modeling as well as a tool to help identify the optimal representation of explanatory variables. However, it has been discussed infrequently in the dental literature. The purpose of this paper is to demonstrate the use of AIC in determining the optimal representation of dietary variables in a longitudinal dental study. The Iowa Fluoride Study enrolled children at birth and dental examinations were conducted at ages 5, 9, 13, and 17. Decayed or filled surfaces (DFS) trend clusters were created based on age 13 DFS counts and age 13-17 DFS increments. Dietary intake data (water, milk, 100 percent-juice, and sugar sweetened beverages) were collected semiannually using a food frequency questionnaire. Multinomial logistic regression models were fit to predict DFS cluster membership (n=344). Multiple approaches could be used to represent the dietary data including averaging across all collected surveys or over different shorter time periods to capture age-specific trends or using the individual time points of dietary data. AIC helped identify the optimal representation. Averaging data for all four dietary variables for the whole period from age 9.0 to 17.0 provided a better representation in the multivariable full model (AIC=745.0) compared to other methods assessed in full models (AICs=750.6 for age 9 and 9-13 increment dietary measurements and AIC=762.3 for age 9, 13, and 17 individual measurements). The results illustrate that AIC can help researchers identify the optimal way to summarize information for inclusion in a statistical model. The method presented here can be used by researchers performing statistical modeling in dental research. This method provides an alternative approach for assessing the propriety of variable representation to significance-based procedures, which could potentially lead to improved research in the dental community. © 2017 American

Neurological prognostication of outcome in patients in coma after cardiac arrest.

PubMed

Rossetti, Andrea O; Rabinstein, Alejandro A; Oddo, Mauro

2016-05-01

Management of coma after cardiac arrest has improved during the past decade, allowing an increasing proportion of patients to survive, thus prognostication has become an integral part of post-resuscitation care. Neurologists are increasingly confronted with raised expectations of next of kin and the necessity to provide early predictions of long-term prognosis. During the past decade, as technology and clinical evidence have evolved, post-cardiac arrest prognostication has moved towards a multimodal paradigm combining clinical examination with additional methods, consisting of electrophysiology, blood biomarkers, and brain imaging, to optimise prognostic accuracy. Prognostication should never be based on a single indicator; although some variables have very low false positive rates for poor outcome, multimodal assessment provides resassurance about the reliability of a prognostic estimate by offering concordant evidence. Copyright © 2016 Elsevier Ltd. All rights reserved.

A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer.

PubMed

Hayashi, Nakamasa; Takahashi, Hideaki; Hasegawa, Yuzo; Higuchi, Fumi; Takahashi, Masamichi; Makino, Keishi; Takagaki, Masatoshi; Akimoto, Jiro; Okuda, Takeshi; Okita, Yoshiko; Mitsuya, Koichi; Hirashima, Yasuyuki; Narita, Yoshitaka; Nakasu, Yoko

2017-06-02

The prevalence of brain metastases (BM) from uterine cancer has recently increased because of the improvement of overall survival (OS) of patients with uterine cancer due to its early detection and improved local control as a result of new effective treatments. However, little information is available regarding their clinical characteristics and prognosis, because oncologists have encountered BM from uterine cancer on rare occasions. Records from 81 patients with uterine BM were collected from 10 institutes in Japan. These were used in a multi-institutional study to identify prognostic factors and develop a graded prognostic assessment (GPA) for patients with BM from uterine cancer. Median OS after the development of BM was 7 months (95% confidence interval, 4 to 10 months). Multivariate analysis revealed that there were survival differences according to the existence of extracranial metastases and number of BM. In the present uterine-GPA, a score of 0 was assigned to those patients with ≥5 BM and extracranial metastasis, a score of 2 was assigned to those patients with one to four BM or without extracranial metastasis, and a score of 4 was assigned to those patients with one to four BM and without extracranial metastasis. The median OS for patients with a uterine-GPA scores of 0, 2, and 4 was 3, 7, and 22 months, respectively. A survival analysis confirmed the presence of statistically significant differences between these groups (p < 0.05). The results were validated by data obtained from the National Report of Brain Tumor Registry of Japan. Uterine GPA incorporates two simple clinical parameters of high prognostic significance and can be used to predict the expected survival times in patients with BM from uterine cancer. Its use may help in determining an appropriate treatment for individual patients with BM.

Updating and prospective validation of a prognostic model for high sickness absence.

PubMed

Roelen, C A M; Heymans, M W; Twisk, J W R; van Rhenen, W; Pallesen, S; Bjorvatn, B; Moen, B E; Magerøy, N

2015-01-01

To further develop and validate a Dutch prognostic model for high sickness absence (SA). Three-wave longitudinal cohort study of 2,059 Norwegian nurses. The Dutch prognostic model was used to predict high SA among Norwegian nurses at wave 2. Subsequently, the model was updated by adding person-related (age, gender, marital status, children at home, and coping strategies), health-related (BMI, physical activity, smoking, and caffeine and alcohol intake), and work-related (job satisfaction, job demands, decision latitude, social support at work, and both work-to-family and family-to-work spillover) variables. The updated model was then prospectively validated for predictions at wave 3. 1,557 (77 %) nurses had complete data at wave 2 and 1,342 (65 %) at wave 3. The risk of high SA was under-estimated by the Dutch model, but discrimination between high-risk and low-risk nurses was fair after re-calibration to the Norwegian data. Gender, marital status, BMI, physical activity, smoking, alcohol intake, job satisfaction, job demands, decision latitude, support at the workplace, and work-to-family spillover were identified as potential predictors of high SA. However, these predictors did not improve the model's discriminative ability, which remained fair at wave 3. The prognostic model correctly identifies 73 % of Norwegian nurses at risk of high SA, although additional predictors are needed before the model can be used to screen working populations for risk of high SA.

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

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

Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.

2008-10-20

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

Early Prognostication Markers in Cardiac Arrest Patients Treated with Hypothermia

PubMed Central

Karapetkova, Maria; Koenig, Matthew A.; Jia, Xiaofeng

2015-01-01

Background and purpose Established prognostication markers, such as clinical findings, electroencephalography (EEG), and biochemical markers, used by clinicians to predict neurologic outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. Methods MEDLINE and EMBASE were searched for evidence on the current standards for neurologic outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers, and multimodal approaches for prognostication were included and reviewed. Results While the prognostic accuracy of various tests has been questioned after TH, pupillary light reflexes and somatosensory evoked potentials (SSEP) are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 hours after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as MRI and CT, can identify functional and structural brain injury, but are not readily available at the patient’s bedside because of limited availability and high costs. Conclusions A multimodal algorithm composed of neurological examination, EEG-based quantitative testing, and SSEP, in conjunction with newer MRI sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed later than 72 hours after CA. PMID:26228521

Early prognostication markers in cardiac arrest patients treated with hypothermia.

PubMed

Karapetkova, M; Koenig, M A; Jia, X

2016-03-01

Established prognostication markers, such as clinical findings, electroencephalography (EEG) and biochemical markers, used by clinicians to predict neurological outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. MEDLINE and Embase were searched for evidence on the current standards for neurological outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers and multimodal approaches for prognostication are included and reviewed. Whilst the prognostic accuracy of various tests after TH has been questioned, pupillary light reflexes and somatosensory evoked potentials are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 h after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as magnetic resonance imaging and computed tomography, can identify functional and structural brain injury but are not readily available at the patient's bedside because of limited availability and high costs. A multimodal algorithm composed of neurological examination, EEG-based quantitative testing and somatosensory evoked potentials, in conjunction with newer magnetic resonance imaging sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed more than 72 h after CA. © 2015 EAN.

Identify the dominant variables to predict stream water temperature

NASA Astrophysics Data System (ADS)

Chien, H.; Flagler, J.

2016-12-01

Stream water temperature is a critical variable controlling water quality and the health of aquatic ecosystems. Accurate prediction of water temperature and the assessment of the impacts of environmental variables on water temperature variation are critical for water resources management, particularly in the context of water quality and aquatic ecosystem sustainability. The objective of this study is to measure stream water temperature and air temperature and to examine the importance of streamflow on stream water temperature prediction. The measured stream water temperature and air temperature will be used to test two hypotheses: 1) streamflow is a relatively more important factor than air temperature in regulating water temperature, and 2) by combining air temperature and streamflow data stream water temperature can be more accurately estimated. Water and air temperature data loggers are placed at two USGS stream gauge stations #01362357and #01362370, located in the upper Esopus Creek watershed in Phonecia, NY. The ARIMA (autoregressive integrated moving average) time series model is used to analyze the measured water temperature data, identify the dominant environmental variables, and predict the water temperature with identified dominant variable. The preliminary results show that streamflow is not a significant variable in predicting stream water temperature at both USGS gauge stations. Daily mean air temperature is sufficient to predict stream water temperature at this site scale.

Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis.

PubMed

Pichler, Martin; Stiegelbauer, Verena; Vychytilova-Faltejskova, Petra; Ivan, Cristina; Ling, Hui; Winter, Elke; Zhang, Xinna; Goblirsch, Matthew; Wulf-Goldenberg, Annika; Ohtsuka, Masahisa; Haybaeck, Johannes; Svoboda, Marek; Okugawa, Yoshinaga; Gerger, Armin; Hoefler, Gerald; Goel, Ajay; Slaby, Ondrej; Calin, George Adrian

2017-03-01

Purpose: Characterization of colorectal cancer transcriptome by high-throughput techniques has enabled the discovery of several differentially expressed genes involving previously unreported miRNA abnormalities. Here, we followed a systematic approach on a global scale to identify miRNAs as clinical outcome predictors and further validated them in the clinical and experimental setting. Experimental Design: Genome-wide miRNA sequencing data of 228 colorectal cancer patients from The Cancer Genome Atlas dataset were analyzed as a screening cohort to identify miRNAs significantly associated with survival according to stringent prespecified criteria. A panel of six miRNAs was further validated for their prognostic utility in a large independent validation cohort ( n = 332). In situ hybridization and functional experiments in a panel of colorectal cancer cell lines and xenografts further clarified the role of clinical relevant miRNAs. Results: Six miRNAs (miR-92b-3p, miR-188-3p, miR-221-5p, miR-331-3p, miR-425-3p, and miR-497-5p) were identified as strong predictors of survival in the screening cohort. High miR-188-3p expression proves to be an independent prognostic factor [screening cohort: HR = 4.137; 95% confidence interval (CI), 1.568-10.917; P = 0.004; validation cohort: HR = 1.538; 95% CI, 1.107-2.137; P = 0.010, respectively]. Forced miR-188-3p expression increased migratory behavior of colorectal cancer cells in vitro and metastases formation in vivo ( P < 0.05). The promigratory role of miR-188-3p is mediated by direct interaction with MLLT4, a novel identified player involved in colorectal cancer cell migration. Conclusions: miR-188-3p is a novel independent prognostic factor in colorectal cancer patients, which can be partly explained by its effect on MLLT4 expression and migration of cancer cells. Clin Cancer Res; 23(5); 1323-33. ©2016 AACR . ©2016 American Association for Cancer Research.

Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis

PubMed Central

Pichler, Martin; Stiegelbauer, Verena; Vychytilova-Faltejskova, Petra; Ivan, Cristina; Ling, Hui; Winter, Elke; Zhang, Xinna; Goblirsch, Matthew; Wulf-Goldenberg, Annika; Ohtsuka, Masahisa; Haybaeck, Johannes; Svoboda, Marek; Okugawa, Yoshinaga; Gerger, Armin; Hoefler, Gerald; Goel, Ajay; Slaby, Ondrej; Calin, George Adrian

2017-01-01

Purpose Characterization of colorectal cancer transcriptome by high-throughput techniques has enabled the discovery of several differentially expressed genes involving previously unreported miRNA abnormalities. Here, we followed a systematic approach on a global scale to identify miRNAs as clinical outcome predictors and further validated them in the clinical and experimental setting. Experimental Design Genome-wide miRNA sequencing data of 228 colorectal cancer patients from The Cancer Genome Atlas dataset were analyzed as a screening cohort to identify miRNAs significantly associated with survival according to stringent prespecified criteria. A panel of six miRNAs was further validated for their prognostic utility in a large independent validation cohort (n = 332). In situ hybridization and functional experiments in a panel of colorectal cancer cell lines and xenografts further clarified the role of clinical relevant miRNAs. Results Six miRNAs (miR-92b-3p, miR-188-3p, miR-221-5p, miR-331-3p, miR-425-3p, and miR-497-5p) were identified as strong predictors of survival in the screening cohort. High miR-188-3p expression proves to be an independent prognostic factor [screening cohort: HR = 4.137; 95% confidence interval (CI), 1.568–10.917; P = 0.004; validation cohort: HR = 1.538; 95% CI, 1.107–2.137; P = 0.010, respectively]. Forced miR-188-3p expression increased migratory behavior of colorectal cancer cells in vitro and metastases formation in vivo (P < 0.05). The promigratory role of miR-188-3p is mediated by direct interaction with MLLT4, a novel identified player involved in colorectal cancer cell migration. Conclusions miR-188-3p is a novel independent prognostic factor in colorectal cancer patients, which can be partly explained by its effect on MLLT4 expression and migration of cancer cells. PMID:27601590

PDGFRA amplification is common in pediatric and adult high-grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma

PubMed Central

Phillips, Joanna J.; Aranda, Derick; Ellison, David W.; Judkins, Alexander R.; Croul, Sidney E.; Brat, Daniel J.; Ligon, Keith L.; Horbinski, Craig; Venneti, Sriram; Zadeh, Gelareh; Santi, Mariarita; Zhou, Shengmei; Appin, Christina L.; Sioletic, Stefano; Sullivan, Lisa M.; Martinez-Lage, Maria; Robinson, Aaron E.; Yong, William H.; Cloughesy, Timothy; Lai, Albert; Phillips, Heidi S.; Marshall, Roxanne; Mueller, Sabine; Haas-Kogan, Daphne A.; Molinaro, Annette M.; Perry, Arie

2013-01-01

High-grade astrocytomas (HGAs), corresponding to WHO grades III (AA) and IV (GBM), are biologically aggressive and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non-amplified (normal and polysomy) or amplified (low-level and high-level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and IDH1R132H mutation was a significant independent prognostic factor (p=0.01). In HGAs, PDGFRA amplification is common and can manifest as high-level and focal or low-level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs. PMID:23438035

A Distributed Prognostic Health Management Architecture

NASA Technical Reports Server (NTRS)

Bhaskar, Saha; Saha, Sankalita; Goebel, Kai

2009-01-01

This paper introduces a generic distributed prognostic health management (PHM) architecture with specific application to the electrical power systems domain. Current state-of-the-art PHM systems are mostly centralized in nature, where all the processing is reliant on a single processor. This can lead to loss of functionality in case of a crash of the central processor or monitor. Furthermore, with increases in the volume of sensor data as well as the complexity of algorithms, traditional centralized systems become unsuitable for successful deployment, and efficient distributed architectures are required. A distributed architecture though, is not effective unless there is an algorithmic framework to take advantage of its unique abilities. The health management paradigm envisaged here incorporates a heterogeneous set of system components monitored by a varied suite of sensors and a particle filtering (PF) framework that has the power and the flexibility to adapt to the different diagnostic and prognostic needs. Both the diagnostic and prognostic tasks are formulated as a particle filtering problem in order to explicitly represent and manage uncertainties; however, typically the complexity of the prognostic routine is higher than the computational power of one computational element ( CE). Individual CEs run diagnostic routines until the system variable being monitored crosses beyond a nominal threshold, upon which it coordinates with other networked CEs to run the prognostic routine in a distributed fashion. Implementation results from a network of distributed embedded devices monitoring a prototypical aircraft electrical power system are presented, where the CEs are Sun Microsystems Small Programmable Object Technology (SPOT) devices.

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study

PubMed Central

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log(des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment. PMID:28458303

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study.

PubMed

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

PubMed Central

Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

2015-01-01

Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white

Prognostic factors in prostate cancer.

PubMed

Braeckman, Johan; Michielsen, Dirk

2007-01-01

In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

Distributed Prognostics based on Structural Model Decomposition

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, I.

2014-01-01

Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based models are constructed that describe the operation of a system and how it fails. Such approaches consist of an estimation phase, in which the health state of the system is first identified, and a prediction phase, in which the health state is projected forward in time to determine the end of life. Centralized solutions to these problems are often computationally expensive, do not scale well as the size of the system grows, and introduce a single point of failure. In this paper, we propose a novel distributed model-based prognostics scheme that formally describes how to decompose both the estimation and prediction problems into independent local subproblems whose solutions may be easily composed into a global solution. The decomposition of the prognostics problem is achieved through structural decomposition of the underlying models. The decomposition algorithm creates from the global system model a set of local submodels suitable for prognostics. Independent local estimation and prediction problems are formed based on these local submodels, resulting in a scalable distributed prognostics approach that allows the local subproblems to be solved in parallel, thus offering increases in computational efficiency. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the distributed approach, compare the performance with a centralized approach, and establish its scalability. Index Terms-model-based prognostics, distributed prognostics, structural model decomposition ABBREVIATIONS

The Prognostic Value of Hemoglobin Concentration in Postoperative Radiotherapy of 835 Patients With Laryngeal Cancer

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

Rutkowski, Tomasz; Suwinski, Rafal; Idasiak, Adam

2007-11-15

Purpose: To investigate the prognostic value of hemoglobin (Hb) concentration in patients with laryngeal cancer treated with postoperative radiotherapy (pRT). Methods and Materials: The records of 835 patients who underwent pRT between 1980 and 2003 were reviewed. Most patients (526 of 835 patients; 63%) were in advanced clinical stages (T3-T4) and 371 of 835 patients (44%) were node positive. Total laryngectomy had been performed in 676 of 835 patients (81%). Median Hb concentration before (Hb0) and after pRT (Hb1) was the same (13.3 g/dl). However, individual differences between Hb1 and Hb0 (dHb) varied within a broad range (-8.8; 5.0 g/dl).more » Univariate and multivariate analyses were performed to identify variables significantly associated with locoregional control (LRC), metastases-free survival, and overall survival. Results: Patients with dHb greater than 0 had significantly improved 5-year LRC compared with those with dHb of 0 or less (80% vs. 72%, p = 0.01). Conversely, when categorized, neither Hb0 nor Hb1 had a significant influence on LRC. In multivariate analysis, dHb remained a prognostic factor for LRC (p = 0.01) among the other variables, which included overall radiation treatment time and nodal status. None of the Hb-related variables significantly influenced metastases-free or overall survival. Conclusion: Individual change in Hb concentration during the course of pRT (dHb) rather than Hb level before or after pRT appeared as an independent prognostic factor for LRC in this set of patients.« less

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms.

PubMed

Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2017-06-01

The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs. © 2017 Society for Endocrinology.

Prognostic markers in localized prostate cancer: from microscopes to molecules.

PubMed

Harding, M A; Theodorescu, D

Management of patients diagnosed with localized prostate cancer is complicated by the diverse natural history of the disease and variable response to treatment. Prognostic criteria currently in use cannot fully predict tumor behavior and thus limit the ability to recommend treatment regimens with the assurance that they are the best course of action for each individual patient. The search for better prognostic markers is now focussed on the molecular mechanisms which underlay tumor behavior, such as altered cell cycle progression, apoptosis, neuroendocrine differentiation, and angiogenesis. As the number of potential molecular markers increases, it is becoming evident that no single marker will provide the prognostic information necessary to make a significant improvement in patient care. In addition, it seems likely that traditional methods of assessing the prognostic value of this multitude of new markers will prove inadequate. In this review, we briefly examine the current state of prognostication in localized prostate cancer and some of the promising new molecular markers. Next, we examine how new technologies may allow the multiplex analysis of vast numbers of markers and how computational methods such as artificial neural networks will provide meaningful interpretation of the data. In the near future, such an integrated approach may provide a comprehensive prognostic tool for localized prostate cancer.

Review and Analysis of Algorithmic Approaches Developed for Prognostics on CMAPSS Dataset

NASA Technical Reports Server (NTRS)

Ramasso, Emannuel; Saxena, Abhinav

2014-01-01

Benchmarking of prognostic algorithms has been challenging due to limited availability of common datasets suitable for prognostics. In an attempt to alleviate this problem several benchmarking datasets have been collected by NASA's prognostic center of excellence and made available to the Prognostics and Health Management (PHM) community to allow evaluation and comparison of prognostics algorithms. Among those datasets are five C-MAPSS datasets that have been extremely popular due to their unique characteristics making them suitable for prognostics. The C-MAPSS datasets pose several challenges that have been tackled by different methods in the PHM literature. In particular, management of high variability due to sensor noise, effects of operating conditions, and presence of multiple simultaneous fault modes are some factors that have great impact on the generalization capabilities of prognostics algorithms. More than 70 publications have used the C-MAPSS datasets for developing data-driven prognostic algorithms. The C-MAPSS datasets are also shown to be well-suited for development of new machine learning and pattern recognition tools for several key preprocessing steps such as feature extraction and selection, failure mode assessment, operating conditions assessment, health status estimation, uncertainty management, and prognostics performance evaluation. This paper summarizes a comprehensive literature review of publications using C-MAPSS datasets and provides guidelines and references to further usage of these datasets in a manner that allows clear and consistent comparison between different approaches.

Prognostic significance of day-by-day variability of home blood pressure on progression to macroalbuminuria in patients with diabetes.

PubMed

Ushigome, Emi; Matsumoto, Shinobu; Oyabu, Chikako; Kitagawa, Noriyuki; Tanaka, Toru; Hasegawa, Goji; Ohnishi, Masayoshi; Tsunoda, Sei; Ushigome, Hidetaka; Yokota, Isao; Nakamura, Naoto; Oda, Yohei; Asano, Mai; Tanaka, Muhei; Yamazaki, Masahiro; Fukui, Michiaki

2018-05-01

Previously, we have shown in cross-sectional analysis of patients with type 2 diabetes mellitus that the presence of diabetic nephropathy is associated with increased home blood pressure (HBP) variability. We now examine the prognostic significance of HBP variability in substantially the same cohort. We performed a prospective cohort study of type 2 diabetes patients. We analyzed 714 patients. Major exclusion criteria are missing data of urinary albumin excretion and newly prescribed or stopped renin-angiotensin system inhibitors during 2-year follow-up. Patients were instructed to perform triplicate morning and evening HBP measurements for 14 consecutive days. We computed day-by-day HBP variability as within-patient standard deviation (SD) and coefficient of variation (CV) of measurements. During the follow-up period of 2 years, 23 patients progressed to macroalbuminuria. The changing risk of progression to macroalbuminuria with increasing day-by-day variability of morning SBP was better depicted using smoothing spline analyses. Patients with greater SD of morning SBP tended to significantly progress to macroalbuminuria [odds ratio: 5.24 (95% confidence interval: 2.10-13.03; P > 0.001)]. Patients with greater CV of morning SBP also tended to significantly progress to macroalbuminuria [odds ratio: 3.36 (95% confidence interval: 1.39-8.12; P = 0.007)]. Day-by-day variability of morning SBP was proven as an independent predictor for progression to macroalbuminuria in patients with type 2 diabetes.

Construction of a new, objective prognostic score for terminally ill cancer patients: a multicenter study.

PubMed

Suh, Sang-Yeon; Choi, Youn Seon; Shim, Jae Yong; Kim, Young Sung; Yeom, Chang Hwan; Kim, Daeyoung; Park, Shin Ae; Kim, Sooa; Seo, Ji Yeon; Kim, Su Hyun; Kim, Daegyeun; Choi, Sung-Eun; Ahn, Hong-Yup

2010-02-01

The goal of this study was to develop a new, objective prognostic score (OPS) for terminally ill cancer patients based on an integrated model that includes novel objective prognostic factors. A multicenter study of 209 terminally ill cancer patients from six training hospitals in Korea were prospectively followed until death. The Cox proportional hazard model was used to adjust for the influence of clinical and laboratory variables on survival time. The OPS was calculated from the sum of partial scores obtained from seven significant predictors determined by the final model. The partial score was based on the hazard ratio of each predictor. The accuracy of the OPS was evaluated. The overall median survival was 26 days. On the multivariate analysis, reduced oral intake, resting dyspnea, low performance status, leukocytosis, elevated bilirubin, elevated creatinine, and elevated lactate dehydrogenase (LDH) were identified as poor prognostic factors. The range of OPS was from 0.0 to 7.0. For the above cutoff point of 3.0, the 3-week prediction sensitivity was 74.7%, the specificity was 76.5%, and the overall accuracy was 75.5%. We developed the new OPS, without clinician's survival estimates but including a new prognostic factor (LDH). This new instrument demonstrated accurate prediction of the 3-week survival. The OPS had acceptable accuracy in this study population (training set). Further validation is required on an independent population (testing set).

Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

PubMed

Corrado, C; Santarelli, M T; Pavlovsky, S; Pizzolato, M

1989-12-01

Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

Prognostic factors in Acanthamoeba keratitis.

PubMed

Kaiserman, Igor; Bahar, Irit; McAllum, Penny; Srinivasan, Sathish; Elbaz, Uri; Slomovic, Allan R; Rootman, David S

2012-06-01

To assess the prognostic factors influencing visual prognosis and length of treatment after acanthamoeba keratitis (AK). Forty-two AK eyes of 41 patients treated between 1999 and 2006 were included. A diagnosis of AK was made on the basis of culture results with a corresponding clinical presentation. We calculated the prognostic effect of the various factors on final visual acuity and the length of treatment. Multivariate regression analysis was used to adjust for the simultaneous effects of the various prognostic factors. Mean follow-up was 19.7 ± 21.0 months. Sixty-four percent of cases had > 1 identified risk factor for AK, the most common risk factor being contact lens wear (92.9% of eyes). At presentation, median best spectacle corrected visual acuity (BCVA) was 20/200 (20/30 to Hand Motion [HM]) that improved after treatment to 20/50 (20/20 to Counting Fingers [CF]). Infection acquired by swimming or related to contact lenses had significantly better final BCVA (p = 0.03 and p = 0.007, respectively). Neuritis and pseudodendrites were also associated with better final BCVA (p = 0.04 and p = 0.05, respectively). Having had an epithelial defect on presentation and having been treated with topical steroid were associated with worse final best spectacle corrected visual acuity (BSCVA) (p = 0.0006 and p = 0.04). Multivariate regression analysis found a good initial visual acuity (p = 0.002), infections related to swimming (p = 0.01), the absence of an epithelial defect (p = 0.03), having been treated with chlorhexidine (p = 0.05), and not having receive steroids (p = 0.003) to significantly forecast a good final BCVA. We identified several prognostic factors that can help clinicians evaluate the expected visual damage of the AK infection and thus tailor treatment accordingly. Copyright © 2012 Canadian Ophthalmological Society. All rights reserved.

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

PubMed

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

2017-04-01

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

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

PubMed

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

2010-01-01

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

Prognostic importance of glycaemic variability on hospital mortality in patients hospitalised in Internal Medicine Departments.

PubMed

Sáenz-Abad, D; Gimeno-Orna, J A; Pérez-Calvo, J I

2015-12-01

The objective was to assess the prognostic importance of various glycaemic control measures on hospital mortality. Retrospective, analytical cohort study that included patients hospitalised in internal medicine departments with a diagnosis related to diabetes mellitus (DM), excluding acute decompensations. The clinical endpoint was hospital mortality. We recorded clinical, analytical and glycaemic control-related variables (scheduled insulin administration, plasma glycaemia at admission, HbA1c, mean glycaemia (MG) and in-hospital glycaemic variability and hypoglycaemia). The measurement of hospital mortality predictors was performed using univariate and multivariate logistic regression. A total of 384 patients (50.3% men) were included. The mean age was 78.5 (SD, 10.3) years. The DM-related diagnoses were type 2 diabetes (83.6%) and stress hyperglycaemia (6.8%). Thirty-one (8.1%) patients died while in hospital. In the multivariate analysis, the best model for predicting mortality (R(2)=0.326; P<.0001) consisted, in order of importance, of age (χ(2)=8.19; OR=1.094; 95% CI 1.020-1.174; P=.004), Charlson index (χ(2)=7.28; OR=1.48; 95% CI 1.11-1.99; P=.007), initial glycaemia (χ(2)=6.05; OR=1.007; 95% CI 1.001-1.014; P=.014), HbA1c (χ(2)=5.76; OR=0.59; 95% CI 0.33-1; P=.016), glycaemic variability (χ(2)=4.41; OR=1.031; 95% CI 1-1.062; P=.036), need for corticosteroid treatment (χ(2)=4.03; OR=3.1; 95% CI 1-9.64; P=.045), administration of scheduled insulin (χ(2)=3.98; OR=0.26; 95% CI 0.066-1; P=.046) and systolic blood pressure (χ(2)=2.92; OR=0.985; 95% CI 0.97-1.003; P=.088). An increase in initial glycaemia and in-hospital glycaemic variability predict the risk of mortality for hospitalised patients with DM. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Interpretative variability and its impact on the prognostic value of myocardial fatty acid imaging in asymptomatic hemodialysis patients in a multicenter trial in Japan.

PubMed

Kiriyama, Tomonari; Kumita, Shin-Ichiro; Moroi, Masao; Nishimura, Tsunehiko; Tamaki, Nagara; Hasebe, Naoyuki; Kikuchi, Kenjiro

2015-01-01

The severity of impaired fatty acid utilization in the myocardium can predict cardiac death in asymptomatic patients on hemodialysis. However, interpretive variability and its impact on the prognostic value of myocardial fatty acid imaging are unknown. A total of 677 patients who received hemodialysis for ≥ 20 years and had one or more cardiovascular risk factors underwent (123)I-labeled β-methyl iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) at 48 hospitals across Japan. SPECT images were interpreted by experts at the nuclear core laboratory and by readers with varying skill levels at clinical centers, based on the standard 17-segment model and 5-point scoring systems, independently. The κ values only reached fair agreement both for overall impression (κ=0.298, normal vs. abnormal) and for categorical impression (κ=0.244, normal vs. mildly abnormal vs. severely abnormal). The normalcy rate was lower in readers at the clinical centers (60.9%) than in experts (69.9%). In contrast to the results assessed by experts, a Kaplan-Meier analysis based on the interpretation by readers at the clinical centers failed to distinguish the risk of events in patients with normal scans from that of patients with mildly abnormal scans. Considerable variability and its impact on prognostic value were observed in the visual interpretation of BMIPP SPECT images between experts and readers at the clinical centers.

Expression of thymidylate synthase (TS) and its prognostic significance in patients with cutaneous angiosarcoma.

PubMed

Shimizu, A; Kaira, K; Okubo, Y; Utsumi, D; Bolag, A; Yasuda, M; Takahashi, K; Ishikawa, O

2017-01-01

Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.

Prognostic value of indeterminable anaerobic threshold in heart failure.

PubMed

Agostoni, Piergiuseppe; Corrà, Ugo; Cattadori, Gaia; Veglia, Fabrizio; Battaia, Elisa; La Gioia, Rocco; Scardovi, Angela B; Emdin, Michele; Metra, Marco; Sinagra, Gianfranco; Limongelli, Giuseppe; Raimondo, Rosa; Re, Federica; Guazzi, Marco; Belardinelli, Romualdo; Parati, Gianfranco; Magrì, Damiano; Fiorentini, Cesare; Cicoira, Mariantonietta; Salvioni, Elisabetta; Giovannardi, Marta; Mezzani, Alessandro; Scrutinio, Domenico; Di Lenarda, Andrea; Mantegazza, Valentina; Ricci, Roberto; Apostolo, Anna; Iorio, Annamaria; Paolillo, Stefania; Palermo, Pietro; Contini, Mauro; Vassanelli, Corrado; Passino, Claudio; Piepoli, Massimo F

2013-09-01

In patients with heart failure (HF), during maximal cardiopulmonary exercise test, anaerobic threshold (AT) is not always identified. We evaluated whether this finding has a prognostic meaning. We recruited and prospectively followed up, in 14 dedicated HF units, 3058 patients with systolic (left ventricular ejection fraction <40%) HF in stable clinical conditions, New York Heart Association class I to III, who underwent clinical, laboratory, echocardiographic, and cardiopulmonary exercise test investigations at study enrollment. We excluded 921 patients who did not perform a maximal exercise, based on lack of achievement of anaerobic metabolism (peak respiratory quotient ≤1.05). Primary study end point was a composite of cardiovascular death and urgent cardiac transplant, and secondary end point was all-cause death. Median follow-up was 3.01 (1.39-4.98) years. AT was identified in 1935 out of 2137 patients (90.54%). At multivariable logistic analysis, failure in detecting AT resulted significantly in reduced peak oxygen uptake and higher metabolic exercise and cardiac and kidney index score value, a powerful prognostic composite HF index (P<0.001). At multivariable analysis, the following variables were significantly associated with primary study end point: peak oxygen uptake (% pred; P<0.001; hazard ratio [HR]=0.977; confidence interval [CI]=0.97-0.98), ventilatory efficiency slope (P=0.01; HR=1.02; CI=1.01-1.03), hemoglobin (P<0.05; HR=0.931; CI=0.87-1.00), left ventricular ejection fraction (P<0.001; HR=0.948; CI=0.94-0.96), renal function (modification of diet in renal disease; P<0.001; HR=0.990; CI=0.98-0.99), sodium (P<0.05; HR=0.967; CI=0.94-0.99), and AT nonidentification (P<0.05; HR=1.41; CI=1.06-1.89). Nonidentification of AT remained associated to prognosis also when compared with metabolic exercise and cardiac and kidney index score (P<0.01; HR=1.459; CI=1.09-1.10). Similar results were obtained for the secondary study end point. The inability to

GPU Accelerated Prognostics

NASA Technical Reports Server (NTRS)

Gorospe, George E., Jr.; Daigle, Matthew J.; Sankararaman, Shankar; Kulkarni, Chetan S.; Ng, Eley

2017-01-01

Prognostic methods enable operators and maintainers to predict the future performance for critical systems. However, these methods can be computationally expensive and may need to be performed each time new information about the system becomes available. In light of these computational requirements, we have investigated the application of graphics processing units (GPUs) as a computational platform for real-time prognostics. Recent advances in GPU technology have reduced cost and increased the computational capability of these highly parallel processing units, making them more attractive for the deployment of prognostic software. We present a survey of model-based prognostic algorithms with considerations for leveraging the parallel architecture of the GPU and a case study of GPU-accelerated battery prognostics with computational performance results.

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

PubMed

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

2010-08-01

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

Prognostic Disclosures to Children: A Historical Perspective.

PubMed

Sisk, Bryan A; Bluebond-Langner, Myra; Wiener, Lori; Mack, Jennifer; Wolfe, Joanne

2016-09-01

Prognostic disclosure to children has perpetually challenged clinicians and parents. In this article, we review the historical literature on prognostic disclosure to children in the United States using cancer as an illness model. Before 1948, there was virtually no literature focused on prognostic disclosure to children. As articles began to be published in the 1950s and 1960s, many clinicians and researchers initially recommended a "protective" approach to disclosure, where children were shielded from the harms of bad news. We identified 4 main arguments in the literature at this time supporting this "protective" approach. By the late 1960s, however, a growing number of clinicians and researchers were recommending a more "open" approach, where children were included in discussions of diagnosis, which at the time was often synonymous with a terminal prognosis. Four different arguments in the literature were used at this time supporting this "open" approach. Then, by the late 1980s, the recommended approach to prognostic disclosure in pediatrics shifted largely from "never tell" to "always tell." In recent years, however, there has been a growing appreciation for the complexity of prognostic disclosure in pediatrics. Current understanding of pediatric disclosure does not lead to simple "black-and-white" recommendations for disclosure practices. As with most difficult questions, we are left to balance competing factors on a case-by-case basis. We highlight 4 categories of current considerations related to prognostic disclosure in pediatrics, and we offer several approaches to prognostic disclosure for clinicians who care for these young patients and their families. Copyright © 2016 by the American Academy of Pediatrics.

Diffusion-weighted MRI derived apparent diffusion coefficient identifies prognostically distinct subgroups of pediatric diffuse intrinsic pontine glioma.

PubMed

Lober, Robert M; Cho, Yoon-Jae; Tang, Yujie; Barnes, Patrick D; Edwards, Michael S; Vogel, Hannes; Fisher, Paul G; Monje, Michelle; Yeom, Kristen W

2014-03-01

While pediatric diffuse intrinsic pontine gliomas (DIPG) remain fatal, recent data have shown subgroups with distinct molecular biology and clinical behavior. We hypothesized that diffusion-weighted MRI can be used as a prognostic marker to stratify DIPG subsets with distinct clinical behavior. Apparent diffusion coefficient (ADC) values derived from diffusion-weighted MRI were computed in 20 consecutive children with treatment-naïve DIPG tumors. The median ADC for the cohort was used to stratify the tumors into low and high ADC groups. Survival, gender, therapy, and potential steroid effects were compared between the ADC groups. Median age at diagnosis was 6.6 (range 2.3-13.2) years, with median follow-up seven (range 1-36) months. There were 14 boys and six girls. Seventeen patients received radiotherapy, five received chemotherapy, and six underwent cerebrospinal fluid diversion. The median ADC of 1,295 × 10(-6) mm(2)/s for the cohort partitioned tumors into low or high diffusion groups, which had distinct median survivals of 3 and 13 months, respectively (log-rank p < 0.001). Low ADC tumors were found only in boys, whereas high ADC tumors were found in both boys and girls. Available tissue specimens in three low ADC tumors demonstrated high-grade histology, whereas one high ADC tumor demonstrated low-grade histology with a histone H3.1 K27M mutation and high-grade metastatic lesion at autopsy. ADC derived from diffusion-weighted MRI may identify prognostically distinct subgroups of pediatric DIPG.

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

PubMed

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

2014-07-01

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

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

PubMed

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

2016-09-01

Carpal tunnel syndrome (CTS) is a common problem, that can be effectively managed by surgery. Screening for prognostic factors is important to identify workers who are at a greater risk of a poor work outcome in order to implement tailored interventions to facilitate their return-to-work. To synthesize the best available evidence on the association of preoperative prognostic factors with work-related outcomes in people who have undergone carpal tunnel surgery. Participants included those who were employed at the time of surgery, underwent carpal tunnel surgery and planned to return-to-work. The primary outcome was return-to-work. Quantitative studies investigating at least one prognostic factor for a work-related outcome in studies of workers who had carpal tunnel surgery were considered. Eleven electronic databases were searched from their respective inception date up to July 2015. A total of 3893 publications were reviewed. The quality of the included studies was assessed by two reviewers using a modified version of an appraisal tool (Joanna Briggs Institute Meta-analysis of Statistical Assessment and Review Instrument [JBI-MAStARI]). The following criteria were evaluated: study population representativeness, clearly defined prognostic factors and outcomes, potential confounding variables and appropriate statistical analysis. Data extraction was performed using a modified version of the standardized extraction tool from JBI-MAStARI. Statistical pooling was not possible. Findings are presented in tables and narrative format. Eleven studies (13 publications) investigating 93 prognostic factors for delayed return-to-work or prolonged work disability outcomes and 27 prognostic factors for work role functioning in 4187 participants were identified.Prognostic factors associated with workers' increased likelihood of an earlier return-to-work in a moderate-to-high-quality study included worker expected or desired fewer days off work, occupation, lower pain anxiety and if

Prognostics for Microgrid Components

NASA Technical Reports Server (NTRS)

Saxena, Abhinav

2012-01-01

Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

Diagnostic and Prognostic Models for Generator Step-Up Transformers

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

Vivek Agarwal; Nancy J. Lybeck; Binh T. Pham

In 2014, the online monitoring (OLM) of active components project under the Light Water Reactor Sustainability program at Idaho National Laboratory (INL) focused on diagnostic and prognostic capabilities for generator step-up transformers. INL worked with subject matter experts from the Electric Power Research Institute (EPRI) to augment and revise the GSU fault signatures previously implemented in the Electric Power Research Institute’s (EPRI’s) Fleet-Wide Prognostic and Health Management (FW-PHM) Suite software. Two prognostic models were identified and implemented for GSUs in the FW-PHM Suite software. INL and EPRI demonstrated the use of prognostic capabilities for GSUs. The complete set of faultmore » signatures developed for GSUs in the Asset Fault Signature Database of the FW-PHM Suite for GSUs is presented in this report. Two prognostic models are described for paper insulation: the Chendong model for degree of polymerization, and an IEEE model that uses a loading profile to calculates life consumption based on hot spot winding temperatures. Both models are life consumption models, which are examples of type II prognostic models. Use of the models in the FW-PHM Suite was successfully demonstrated at the 2014 August Utility Working Group Meeting, Idaho Falls, Idaho, to representatives from different utilities, EPRI, and the Halden Research Project.« less

Serum total hCGβ level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract.

PubMed

Douglas, J; Sharp, A; Chau, C; Head, J; Drake, T; Wheater, M; Geldart, T; Mead, G; Crabb, S J

2014-04-02

Serum total human chorionic gonadotrophin β subunit (hCGβ) level might have prognostic value in urothelial transitional cell carcinoma (TCC) but has not been investigated for independence from other prognostic variables. We utilised a clinical database of patients receiving chemotherapy between 2005 and 2011 for urothelial TCC and an independent cohort of radical cystectomy patients for validation purposes. Prognostic variables were tested by univariate Kaplan-Meier analyses and log-rank tests. Statistically significant variables were then assessed by multivariate Cox regression. Total hCGβ level was dichotomised at < vs ≥2 IU l(-1). A total of 235 chemotherapy patients were eligible. For neoadjuvant chemotherapy, established prognostic factors including low ECOG performance status, normal haemoglobin, lower T stage and suitability for cisplatin-based chemotherapy were associated with favourable survival in univariate analyses. In addition, low hCGβ level was favourable when assessed either before (median survival not reached vs 1.86 years, P=0.001) or on completion of chemotherapy (4.27 vs 0.42 years, P=0.000002). This was confirmed in multivariate analyses and in patients receiving first- and second-line palliative chemotherapy, and in a radical cystectomy validation set. Serum total hCGβ level is an independent prognostic factor in patients receiving chemotherapy for urothelial TCC in both curative and palliative settings.

Exercise oscillatory breathing and increased ventilation to carbon dioxide production slope in heart failure: an unfavorable combination with high prognostic value.

PubMed

Guazzi, Marco; Arena, Ross; Ascione, Aniello; Piepoli, Massimo; Guazzi, Maurizio D

2007-05-01

Increased slope of exercise ventilation to carbon dioxide production (VE/VCO2) is an established prognosticator in patients with heart failure. Recently, the occurrence of exercise oscillatory breathing (EOB) has emerged as an additional strong indicator of survival. The aim of this study is to define the respective prognostic significance of these variables and whether excess risk may be identified when either respiratory disorder is present. In 288 stable chronic HF patients (average left ventricular ejection fraction, 33 +/- 13%) who underwent cardiopulmonary exercise testing, the prognostic relevance of VE/VCO2 slope, EOB, and peak VO2 was evaluated by multivariate Cox regression. During a mean interval of 28 +/- 13 months, 62 patients died of cardiac reasons. Thirty-five percent presented with EOB. Among patients exhibiting EOB, 54% had an elevated VE/VCO2 slope. The optimal threshold value for the VE/VCO2 slope identified by receiver operating characteristic analysis was < 36.2 or > or = 36.2 (sensitivity, 77%; specificity, 64%; P < .001). Univariate predictors of death included low left ventricular ejection fraction, low peak VO2, high VE/VCO2 slope, and EOB presence. Multivariate analysis selected EOB as the strongest predictor (chi2, 46.5; P < .001). The VE/VCO2 slope (threshold, < 36.2 or > or = 36.2) was the only other exercise test variable retained in the regression (residual chi2, 5.9; P = .02). The hazard ratio for subjects with EOB and a VE/VCO2 slope > or = 36.2 was 11.4 (95% confidence interval, 4.9-26.5; P < .001). These findings identify EOB as a strong survival predictor even more powerful than VE/VCO2 slope. Exercise oscillatory breathing presence does not necessarily imply an elevated VE/VCO2 slope, but combination of either both yields to a burden of risk remarkably high.

Long-term prognosis of epilepsy, prognostic patterns and drug resistance: a population-based study.

PubMed

Giussani, G; Canelli, V; Bianchi, E; Erba, G; Franchi, C; Nobili, A; Sander, J W; Beghi, E

2016-07-01

Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs. © 2016 EAN.

[Upper gastrointestinal bleeding: usefulness of prognostic scores].

PubMed

Badel, S; Dorta, G; Carron, P-N

2011-08-24

Upper gastrointestinal bleeding is a potentially serious event, usually requiring urgent endoscopic treatment. Better stratification of the risk of complication or death could optimize management and improve patient outcomes, while ensuring adequate resource allocation. Several prognostic scores have been developed, in order to identify high risk patients, who require immediate treatment, and patients at low risk for whom endoscopy may be delayed. An ideal prognostic score should be accurate, simple, reproducible, and prospectively validated in different populations. Published scores meet these requirements only partially, and thus can only be used as part of an integrative diagnostic and therapeutic process.

Prognostic index for chronic- and smoldering-type adult T-cell leukemia-lymphoma.

PubMed

Katsuya, Hiroo; Shimokawa, Mototsugu; Ishitsuka, Kenji; Kawai, Kazuhiro; Amano, Masahiro; Utsunomiya, Atae; Hino, Ryosuke; Hanada, Shuichi; Jo, Tatsuro; Tsukasaki, Kunihiro; Moriuchi, Yukiyoshi; Sueoka, Eisaburo; Yoshida, Shinichiro; Suzushima, Hitoshi; Miyahara, Masaharu; Yamashita, Kiyoshi; Eto, Tetsuya; Suzumiya, Junji; Tamura, Kazuo

2017-07-06

Adult T-cell leukemia-lymphoma (ATL) has been divided into 4 clinical subtypes: acute, lymphoma, chronic, and smoldering. The aim of this study is to develop a novel prognostic index (PI) for chronic and smoldering ATL. We conducted a nationwide retrospective survey on ATL patients, and 248 fully eligible individuals were used in this analysis. In the univariate analysis, sex, performance status, log 10 (soluble interleukin-2 receptor [sIL-2R]), neutrophils count, and lymphadenopathy showed values of P < .05 in training samples. A multivariate analysis was performed on these factors, and only log 10 (sIL-2R) was identified as an independent prognostic factor in training samples. Using a regression coefficient of this variable, a prognostic model was formulated to identify different levels of risk: indolent ATL-PI (iATL-PI) = 1.51 × log 10 (sIL-2R [U/mL]). The values calculated by iATL-PI were divided into 3 groups using a quartile point. In the validation sample, median survival times (MSTs) were 1.6 years, 5.5 years, and not reached for patients in the high-, intermediate-, and low-risk groups, respectively ( P < .0001). To make the scoring system clinically practicable, we simplified iATL-PI according to trichotomizing sIL-2R at 1000 and 6000 U/mL, using a quartile point. Patients with more than 6000 U/mL sIL-2R were categorized into the high-risk group, less than and equal to 1000 U/mL into the low-risk group, and the others into the intermediate-risk group, and MSTs were 1.6 years, not reached, and 5.5 years, respectively ( P < .0001). iATL-PI has potential as a novel tool for a risk-adapted therapeutic approach. © 2017 by The American Society of Hematology.

Reporting and Methodology of Multivariable Analyses in Prognostic Observational Studies Published in 4 Anesthesiology Journals: A Methodological Descriptive Review.

PubMed

Guglielminotti, Jean; Dechartres, Agnès; Mentré, France; Montravers, Philippe; Longrois, Dan; Laouénan, Cedric

2015-10-01

Prognostic research studies in anesthesiology aim to identify risk factors for an outcome (explanatory studies) or calculate the risk of this outcome on the basis of patients' risk factors (predictive studies). Multivariable models express the relationship between predictors and an outcome and are used in both explanatory and predictive studies. Model development demands a strict methodology and a clear reporting to assess its reliability. In this methodological descriptive review, we critically assessed the reporting and methodology of multivariable analysis used in observational prognostic studies published in anesthesiology journals. A systematic search was conducted on Medline through Web of Knowledge, PubMed, and journal websites to identify observational prognostic studies with multivariable analysis published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anaesthesia, and Anaesthesia in 2010 and 2011. Data were extracted by 2 independent readers. First, studies were analyzed with respect to reporting of outcomes, design, size, methods of analysis, model performance (discrimination and calibration), model validation, clinical usefulness, and STROBE (i.e., Strengthening the Reporting of Observational Studies in Epidemiology) checklist. A reporting rate was calculated on the basis of 21 items of the aforementioned points. Second, they were analyzed with respect to some predefined methodological points. Eighty-six studies were included: 87.2% were explanatory and 80.2% investigated a postoperative event. The reporting was fairly good, with a median reporting rate of 79% (75% in explanatory studies and 100% in predictive studies). Six items had a reporting rate <36% (i.e., the 25th percentile), with some of them not identified in the STROBE checklist: blinded evaluation of the outcome (11.9%), reason for sample size (15.1%), handling of missing data (36.0%), assessment of colinearity (17.4%), assessment of interactions (13.9%), and calibration (34

Differentially Variable Component Analysis (dVCA): Identifying Multiple Evoked Components using Trial-to-Trial Variability

NASA Technical Reports Server (NTRS)

Knuth, Kevin H.; Shah, Ankoor S.; Truccolo, Wilson; Ding, Ming-Zhou; Bressler, Steven L.; Schroeder, Charles E.

2003-01-01

Electric potentials and magnetic fields generated by ensembles of synchronously active neurons in response to external stimuli provide information essential to understanding the processes underlying cognitive and sensorimotor activity. Interpreting recordings of these potentials and fields is difficult as each detector records signals simultaneously generated by various regions throughout the brain. We introduce the differentially Variable Component Analysis (dVCA) algorithm, which relies on trial-to-trial variability in response amplitude and latency to identify multiple components. Using simulations we evaluate the importance of response variability to component identification, the robustness of dVCA to noise, and its ability to characterize single-trial data. Finally, we evaluate the technique using visually evoked field potentials recorded at incremental depths across the layers of cortical area VI, in an awake, behaving macaque monkey.

Prognostic significance of DNA ploidy in adenocarcinoma of the pancreas. A flow cytometric study of paraffin-embedded specimens.

PubMed

Porschen, R; Remy, U; Bevers, G; Schauseil, S; Hengels, K J; Borchard, F

1993-06-15

The prognostic significance of tumor DNA ploidy in patients with cancer of the pancreas has not been defined because conflicting results have been reported. DNA content was measured in 56 ductal adenocarcinomas of the pancreas. DNA ploidy status was evaluated by flow cytometry in nuclei isolated from paraffin-embedded tumor tissues. An abnormal DNA stemline was observed in 27 (48%) patients. The percentage of aneuploid tumors was significantly increased in tumors classified as Stage III/IV (53%) compared with those classified as Stage I (22%). A borderline significant association existed between DNA ploidy and radicality of surgery (P = 0.08). The median survival of patients with diploid carcinomas was 6.9 months (standard error, +/- 0.9) in comparison to 4.5 +/- 1.2 months for patients with aneuploid tumors (P = 0.013 by generalized Wilcoxon test; P = 0.023 by generalized Savage test). Although a selection bias cannot be excluded, survival of patients with a radical resection was longer than that of patients with a nonradical resection (P = 0.0008 and P = 0.0085, respectively). In addition, presence of distant metastasis (P = 0.0006 [Wilcoxon test] and P = 0.033 [Savage test]) could be identified as a prognostic factor. In a Cox regression model, results of surgery and DNA ploidy were independent prognostic variables. Because DNA ploidy has a significant impact on prognosis in pancreatic cancer, it should be used as a variable for stratified randomization of patients in therapeutic trials.

[Exercise stress test and dobutamine stress echocardiography for the prognostic stratification after uncomplicated acute myocardial infarction].

PubMed

Vitiello, Nicola; Cirillo, Raffaele; Granato, Luigi; Coppola, Vincenzo; di Palma, Francesco

2007-05-01

Exercise stress test and dobutamine stress echocardiography are usually performed early after an uncomplicated acute myocardial infarction in the prognostic stratification of patients to define the optimal diagnostic and therapeutic procedure. The aim of this study was to evaluate if the association of an imaging test could increase exercise test capability to identify patients with residual ischemia and patients at high risk of events in the follow-up. Four hundred and forty-two consecutive patients underwent exercise stress testing and dobutamine stress echocardiography before discharge and subsequently coronary angiography within 30 days. In case of submaximal negative result at the exercise test, this was repeated 20 days after discharge. The follow-up lasted 26.8 +/- 9 months. The endpoints were death, reinfarction, and unstable angina requiring hospitalization or revascularization intervention. Both tests and their association showed a higher sensitivity in males; in females dobutamine stress echocardiography had a higher specificity. In females, the addition of dobutamine stress echocardiography increased either the negative or the positive prognostic values of exercise stress test by 31% and 5.6%, respectively. In males, the negative prognostic value increased by 15.5%, whereas the positive prognostic value decreased by 12%. A low exercise capability (<6 METs) showed an event predictive value independent of test results and any other variables. The event-free survival curves correlated with exercise capability differed shortly after the first months both in males and females. These results suggest different stratification procedures with regard to gender: in males, the exercise stress test might be sufficient at discharge, to be repeated 20 days later, if submaximal negative. In females, it seems to be useful to associate an imaging test at discharge. In any case, the exercise stress test remains the main step in the stratification procedure also for its

Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival.

PubMed

Zidan, Jamal; Karen, Drumea; Stein, Moshe; Rosenblatt, Edward; Basher, Walid; Kuten, Abraham

2003-03-01

The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival. A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty-three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival. The median follow-up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21-year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant). The pathologic and clinical behaviors of PTC and FVPTC were comparable. Prognostic factors, treatment, and survival also were similar. Patients in both groups must be treated identically. Copyright 2003 American Cancer Society.

Field potential soil variability index to identify precision agriculture opportunity

USDA-ARS?s Scientific Manuscript database

Precision agriculture (PA) technologies used for identifying and managing within-field variability are not widely used despite decades of advancement. Technological innovations in agronomic tools, such as canopy reflectance or electrical conductivity sensors, have created opportunities to achieve a ...

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

PubMed

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

2014-01-01

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

Fibroblast growth factor receptor 1 and cytokeratin 20 expressions and their relation to prognostic variables in bladder cancer.

PubMed

Abdul-Maksoud, Rehab S; Shalaby, Sally M; Elsayed, Walid S H; Elkady, Saad

2016-10-15

Tumor grade and stage are currently the most important prognostic variables in bladder cancer but establishing additional criteria is still needed for effective treatment. The aim of the study was to assess the expression of fibroblast growth factor receptor 1 (FGFR1) and cytokeratin 20 (CK20) in cancer bladder (CB) and to evaluate their association with the clinicopathological features of the disease. The study included 80 patients diagnosed as bladder cancer of different stages and grades and 80 patients with nonmalignant urothelial diseases of matched age and sex to the malignant group. The expressions of FGFR1 and CK20 in tissue samples were determined by RT-PCR and immunohistochemistry. The expression levels of FGFR1 and CK20 were increased in the malignant group when compared to the control group (P<0.001 for each). Analysis of their expression showed that levels of FGFR1 and CK20 were significantly higher in invasive tumor stages (pT2-pT4) than in non-invasive stages (pTis, pTa, pT1) (P<0.001). Interestingly, the sensitivity and specificity of combined detection with CK20 and FGFR1 for the differentiation between invasive and non-invasive stages of bladder cancer reached 97.5% and 92.5%, respectively. Our results determined overexpression of both FGFR1 and CK20 in CB specimens. The alterations in the expression of FGFR1 and CK20 were associated with disease stage and grade. Lastly, combined detection of FGFR1 and CK20 had a high predictive prognostic value in differentiating invasive from non-invasive carcinoma. Copyright © 2016 Elsevier B.V. All rights reserved.

Prognostic factors and scoring system for survival in colonic perforation.

PubMed

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

2005-01-01

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

Prognostic value of Child-Turcotte criteria in medically treated cirrhosis.

PubMed

Christensen, E; Schlichting, P; Fauerholdt, L; Gluud, C; Andersen, P K; Juhl, E; Poulsen, H; Tygstrup, N

1984-01-01

The Child- Turcotte criteria (CTC) (based on serum bilirubin and albumin, ascites, neurological disorder and nutrition) are established prognostic factors in patients with cirrhosis having portacaval shunt surgery. The objective of this study was to evaluate the prognostic value of CTC in conservatively treated cirrhosis. Patients (n = 245) with histologically verified cirrhosis from a control group of a controlled clinical trial were studied. Data at entry into the trial were used to classify patients according to CTC. Survival curves for up to 16 years were made, and survival rates were compared using the log-rank test. Survival decreased significantly with increasing degree of abnormality (A----B----C) of albumin (p less than 0.001), ascites (p less than 0.001), bilirubin (p = 0.02) and nutritional status (p = 0.03). Survival was insignificantly influenced by neurological status (p = 0.11) probably because none of the patients had hepatic coma at entry into the trial. The five variables in CTC were combined to a score. With increasing score, the median survival time decreased from 6.4 years (score 5) to 2 months (scores 12 or more). Furthermore, the mortality from hepatic failure, gastrointestinal bleeding or hepatocellular carcinoma increased significantly with increasing score. CTC provide valuable and easily obtainable prognostic information in cirrhosis. However, CTC are inferior to a prognostic index based on multivariate analysis of prognostic factors.

Prognostic nomogram for previously untreated adult patients with acute myeloid leukemia

PubMed Central

Zheng, Zhuojun; Li, Xiaodong; Zhu, Yuandong; Gu, Weiying; Xie, Xiaobao; Jiang, Jingting

2016-01-01

This study was designed to perform an acceptable prognostic nomogram for acute myeloid leukemia. The clinical data from 311 patients from our institution and 165 patients generated with Cancer Genome Atlas Research Network were reviewed. A prognostic nomogram was designed according to the Cox's proportional hazard model to predict overall survival (OS). To compare the capacity of the nomogram with that of the current prognostic system, the concordance index (C-index) was used to validate the accuracy as well as the calibration curve. The nomogram included 6 valuable variables: age, risk stratifications based on cytogenetic abnormalities, status of FLT3-ITD mutation, status of NPM1 mutation, expression of CD34, and expression of HLA-DR. The C-indexes were 0.71 and 0.68 in the primary and validation cohort respectively, which were superior to the predictive capacity of the current prognostic systems in both cohorts. The nomogram allowed both patients with acute myeloid leukemia and physicians to make prediction of OS individually prior to treatment. PMID:27689396

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

PubMed

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

2017-05-01

Incidence of symptomatic spinal metastasis has increased owing to improvement in treatment of the disease. One of the key factors that influences decision-making is expected patient survival. To our knowledge, no systematic reviews or meta-analysis have been conducted that review independent prognostic factors in spinal metastases. This study aimed to determine independent prognostic factors that affect outcome in patients with metastatic spine disease. This is a systematic literature review and meta-analysis of publications for prognostic factors in spinal metastatic disease. Pooled patient results from cohort and observational studies. Meta-analysis for poor prognostic factors as determined by hazard ratio (HR) and 95% confidential interval (95% CI). We systematically searched relevant publications in PubMed and Embase. The following search terms were used: ("'spinal metastases'" OR "'vertebral metastases'" OR "spinal metastasis" OR 'vertebral metastases') AND ('"prognostic factors"' OR "'survival'"). Inclusion criteria were prospective and retrospective cohort series that report HR and 95% CI of independent prognostic factors from multivariate analysis. Two reviewers independently assessed all papers. The quality of included papers was assessed by using Newcastle-Ottawa Scale for cohort studies and publication bias was assessed by using funnel plot, Begg test, and Egger test. The prognostic factors that were mentioned in at least three publications were pooled. Meta-analysis was performed using HR and 95% CI as the primary outcomes of interest. Heterogeneity was assessed using the I 2 method. A total of 3,959 abstracts (1,382 from PubMed and 2,577 from Embase) were identified through database search and 40 publications were identified through review of cited publications. The reviewers selected a total of 51 studies for qualitative synthesis and 43 studies for meta-analysis. Seventeen poor prognostic factors were identified. These included presence of a

SU-F-R-24: Identifying Prognostic Imaging Biomarkers in Early Stage Lung Cancer Using Radiomics

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

Zeng, X; Wu, J; Cui, Y

2016-06-15

Purpose: Patients diagnosed with early stage lung cancer have favorable outcomes when treated with surgery or stereotactic radiotherapy. However, a significant proportion (∼20%) of patients will develop metastatic disease and eventually die of the disease. The purpose of this work is to identify quantitative imaging biomarkers from CT for predicting overall survival in early stage lung cancer. Methods: In this institutional review board-approved HIPPA-compliant retrospective study, we retrospectively analyzed the diagnostic CT scans of 110 patients with early stage lung cancer. Data from 70 patients were used for training/discovery purposes, while those of remaining 40 patients were used for independentmore » validation. We extracted 191 radiomic features, including statistical, histogram, morphological, and texture features. Cox proportional hazard regression model, coupled with the least absolute shrinkage and selection operator (LASSO), was used to predict overall survival based on the radiomic features. Results: The optimal prognostic model included three image features from the Law’s feature and wavelet texture. In the discovery cohort, this model achieved a concordance index or CI=0.67, and it separated the low-risk from high-risk groups in predicting overall survival (hazard ratio=2.72, log-rank p=0.007). In the independent validation cohort, this radiomic signature achieved a CI=0.62, and significantly stratified the low-risk and high-risk groups in terms of overall survival (hazard ratio=2.20, log-rank p=0.042). Conclusion: We identified CT imaging characteristics associated with overall survival in early stage lung cancer. If prospectively validated, this could potentially help identify high-risk patients who might benefit from adjuvant systemic therapy.« less

An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

PubMed Central

2010-01-01

Background Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. Methods We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. Results An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. Conclusions This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples. PMID:20584321

Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia.

PubMed

Such, Esperanza; Germing, Ulrich; Malcovati, Luca; Cervera, José; Kuendgen, Andrea; Della Porta, Matteo G; Nomdedeu, Benet; Arenillas, Leonor; Luño, Elisa; Xicoy, Blanca; Amigo, Mari L; Valcarcel, David; Nachtkamp, Kathrin; Ambaglio, Ilaria; Hildebrandt, Barbara; Lorenzo, Ignacio; Cazzola, Mario; Sanz, Guillermo

2013-04-11

The natural course of chronic myelomonocytic leukemia (CMML) is highly variable but a widely accepted prognostic scoring system for patients with CMML is not available. The main aim of this study was to develop a new CMML-specific prognostic scoring system (CPSS) in a large series of 558 patients with CMML (training cohort, Spanish Group of Myelodysplastic Syndromes) and to validate it in an independent series of 274 patients (validation cohort, Heinrich Heine University Hospital, Düsseldorf, Germany, and San Matteo Hospital, Pavia, Italy). The most relevant variables for overall survival (OS) and evolution to acute myeloblastic leukemia (AML) were FAB and WHO CMML subtypes, CMML-specific cytogenetic risk classification, and red blood cell (RBC) transfusion dependency. CPSS was able to segregate patients into 4 clearly different risk groups for OS (P < .001) and risk of AML evolution (P < .001) and its predictive capability was confirmed in the validation cohort. An alternative CPSS with hemoglobin instead of RBC transfusion dependency offered almost identical prognostic capability. This study confirms the prognostic impact of FAB and WHO subtypes, recognizes the importance of RBC transfusion dependency and cytogenetics, and offers a simple and powerful CPSS for accurately assessing prognosis and planning therapy in patients with CMML.

The biological and prognostic significance of angiotropism in uveal melanoma.

PubMed

Barnhill, Raymond L; Ye, Mengliang; Batistella, Aude; Stern, Marc-Henri; Roman-Roman, Sergio; Dendale, Rémi; Lantz, Olivier; Piperno-Neumann, Sophie; Desjardins, Laurence; Cassoux, Nathalie; Lugassy, Claire

2017-02-27

Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and a prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy. Clinical, histopathological, and molecular variables included patient age, gender, extraocular extension, tumor location (ciliary body or not), optic nerve invasion, angiotropism, neurotropism, melanoma cell type, BAP1 mutation, and monosomy 3. Angiotropism was defined as melanoma cells arrayed along the abluminal vascular surfaces without intravasation in the sclera and/or episcleral tissue. The study included 51 women (57.3%) and 38 men with mean and median age: 63 years (range: 25-92). Mean follow-up was 4.4 years (range: 0.2 to 11). Fifty-three (59.6%) patients developed metastases and 48 (53.9%) were dead from metastases at last follow-up. Other principal variables recorded were angiotropism in 43.8%, extraocular extension in 7.9%, epithelioid/mixed cell type in 73.1%, BAP1 mutation in 41.3%, and monosomy 3 in 53.6% of cases. On multivariate analysis, extraocular extension, angiotropism, and monosomy 3 were predictive of metastasis, whereas tumor diameter, epithelioid cell type, angiotropism, and monosomy 3 were predictive of death. Chi-square test confirmed an association between angiotropism and metastasis and death but none with BAP1 mutation and monosomy 3. In conclusion, angiotropism and monosomy 3 were independent prognostic factors for both metastases and death in UM. However, irrespective of any prognostic value, the true importance of angiotropism is its biological significance as a marker of

Quantitative multiplex quantum dot in-situ hybridisation based gene expression profiling in tissue microarrays identifies prognostic genes in acute myeloid leukaemia

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

Tholouli, Eleni; MacDermott, Sarah; Hoyland, Judith

2012-08-24

Highlights: Black-Right-Pointing-Pointer Development of a quantitative high throughput in situ expression profiling method. Black-Right-Pointing-Pointer Application to a tissue microarray of 242 AML bone marrow samples. Black-Right-Pointing-Pointer Identification of HOXA4, HOXA9, Meis1 and DNMT3A as prognostic markers in AML. -- Abstract: Measurement and validation of microarray gene signatures in routine clinical samples is problematic and a rate limiting step in translational research. In order to facilitate measurement of microarray identified gene signatures in routine clinical tissue a novel method combining quantum dot based oligonucleotide in situ hybridisation (QD-ISH) and post-hybridisation spectral image analysis was used for multiplex in-situ transcript detection inmore » archival bone marrow trephine samples from patients with acute myeloid leukaemia (AML). Tissue-microarrays were prepared into which white cell pellets were spiked as a standard. Tissue microarrays were made using routinely processed bone marrow trephines from 242 patients with AML. QD-ISH was performed for six candidate prognostic genes using triplex QD-ISH for DNMT1, DNMT3A, DNMT3B, and for HOXA4, HOXA9, Meis1. Scrambled oligonucleotides were used to correct for background staining followed by normalisation of expression against the expression values for the white cell pellet standard. Survival analysis demonstrated that low expression of HOXA4 was associated with poorer overall survival (p = 0.009), whilst high expression of HOXA9 (p < 0.0001), Meis1 (p = 0.005) and DNMT3A (p = 0.04) were associated with early treatment failure. These results demonstrate application of a standardised, quantitative multiplex QD-ISH method for identification of prognostic markers in formalin-fixed paraffin-embedded clinical samples, facilitating measurement of gene expression signatures in routine clinical samples.« less

Prognostic Factors in Severe Chagasic Heart Failure

PubMed Central

Costa, Sandra de Araújo; Rassi, Salvador; Freitas, Elis Marra da Madeira; Gutierrez, Natália da Silva; Boaventura, Fabiana Miranda; Sampaio, Larissa Pereira da Costa; Silva, João Bastista Masson

2017-01-01

Background Prognostic factors are extensively studied in heart failure; however, their role in severe Chagasic heart failure have not been established. Objectives To identify the association of clinical and laboratory factors with the prognosis of severe Chagasic heart failure, as well as the association of these factors with mortality and survival in a 7.5-year follow-up. Methods 60 patients with severe Chagasic heart failure were evaluated regarding the following variables: age, blood pressure, ejection fraction, serum sodium, creatinine, 6-minute walk test, non-sustained ventricular tachycardia, QRS width, indexed left atrial volume, and functional class. Results 53 (88.3%) patients died during follow-up, and 7 (11.7%) remained alive. Cumulative overall survival probability was approximately 11%. Non-sustained ventricular tachycardia (HR = 2.11; 95% CI: 1.04 - 4.31; p<0.05) and indexed left atrial volume ≥ 72 mL/m2 (HR = 3.51; 95% CI: 1.63 - 7.52; p<0.05) were the only variables that remained as independent predictors of mortality. Conclusions The presence of non-sustained ventricular tachycardia on Holter and indexed left atrial volume > 72 mL/m2 are independent predictors of mortality in severe Chagasic heart failure, with cumulative survival probability of only 11% in 7.5 years. PMID:28443956

Surgical Management and Prognostic Factors of Vulvovaginal Melanoma.

PubMed

Ditto, Antonino; Bogani, Giorgio; Martinelli, Fabio; Di Donato, Violante; Laufer, Joel; Scasso, Santiago; Chiappa, Valentina; Signorelli, Mauro; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

2016-07-01

The aim of the study was to evaluate the surgical management and the role of different prognostic factors on survival outcomes of women affected by genital (i.e., vulvar and vaginal) melanoma. Data of patients undergoing primary surgical treatment for genital melanoma were evaluated in this retrospective study. Baseline, pathological, and postoperative variables were tested to identify prognostic factors. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox proportional hazards models. Overall, 98 patients met the inclusion criteria. Sixty-seven (68%) and 31 (32%) patients in this study population were diagnosed with vulvar and vaginal melanoma, respectively. Median (range) DFS and OS were 12 (1-70) and 22 (1-70) months, respectively. Considering factors influencing DFS, we observed that at multivariate analysis, only vaginal localization (hazard ratio [HR] = 3.72; 95% CI = 1.05-13.2) and number of mitoses (HR = 1.24; 95% CI = 1.11-1.39) proved to be associated with worse DFS. Nodal status was the only independent factor influencing 5-year OS in patients with vulvar (HR = 1.76; 95% CI = 1.22-2.54; p = .002) and vaginal (HR = 3.65; 95% CI = 1.08-12.3; p = .03) melanoma. Genital melanomas are characterized by a poor prognosis. Number of mitoses and lymph node status are the main factors influencing survival. Surgery is the mainstay of treatment. A correct and prompt diagnosis is paramount.

Variability in Predictions from Online Tools: A Demonstration Using Internet-Based Melanoma Predictors.

PubMed

Zabor, Emily C; Coit, Daniel; Gershenwald, Jeffrey E; McMasters, Kelly M; Michaelson, James S; Stromberg, Arnold J; Panageas, Katherine S

2018-02-22

Prognostic models are increasingly being made available online, where they can be publicly accessed by both patients and clinicians. These online tools are an important resource for patients to better understand their prognosis and for clinicians to make informed decisions about treatment and follow-up. The goal of this analysis was to highlight the possible variability in multiple online prognostic tools in a single disease. To demonstrate the variability in survival predictions across online prognostic tools, we applied a single validation dataset to three online melanoma prognostic tools. Data on melanoma patients treated at Memorial Sloan Kettering Cancer Center between 2000 and 2014 were retrospectively collected. Calibration was assessed using calibration plots and discrimination was assessed using the C-index. In this demonstration project, we found important differences across the three models that led to variability in individual patients' predicted survival across the tools, especially in the lower range of predictions. In a validation test using a single-institution data set, calibration and discrimination varied across the three models. This study underscores the potential variability both within and across online tools, and highlights the importance of using methodological rigor when developing a prognostic model that will be made publicly available online. The results also reinforce that careful development and thoughtful interpretation, including understanding a given tool's limitations, are required in order for online prognostic tools that provide survival predictions to be a useful resource for both patients and clinicians.

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

Prognostic value of heart rate variability footprint and standard deviation of average 5-minute intrinsic R-R intervals for mortality in cardiac resynchronization therapy patients.

PubMed

Gilliam, F Roosevelt; Singh, Jagmeet P; Mullin, Christopher M; McGuire, Maureen; Chase, Kellie J

2007-10-01

Cardiac resynchronization therapy devices provide effective therapy for heart failure. Heart rate variability (HRV) parameters in the device such as HRV footprint and SD of average 5-minute intrinsic R-R intervals (SDANN) are related to autonomic function and may be used to identify patients with a higher risk of mortality. We examined the relationship between HRV and mortality in a prospective cohort study. The 842 patients (mean age, 67.7 +/- 11.2; 23.5 % female; New York Heart Association class III, 88.6%; class IV, 11.4%) included in the analysis were implanted with a cardiac resynchronization therapy with defibrillation device and had baseline HRV measurements available. During a median of 11.6 months of follow-up, 7.8% (66/842) of patients died. Heart rate variability footprint and SDANN were significant predictors of mortality (all P < .05); patients with lower HRV values were at greater risk for death, compared with patients with higher HRV values. Heart rate variability changes over time tended to predict the risk of mortality in follow-up (P = nonsignificant); patients with low baseline HRV and small changes in HRV during the follow-up period were at the highest risk for death (7% mortality for SDANN and 8.9% for HRV footprint), and patients with high baseline HRV and large changes in HRV were at the lowest risk (1.5% mortality for SDANN and 2.4% for HRV footprint). Results were consistent when adjusted for age, sex, body mass index, and diastolic blood pressure. Continuously measured device HRV parameters provide prognostic information about patient mortality that may be helpful for risk stratification.

Prognostic factors for chronic headache

PubMed Central

Bowers, Hannah; Caldwell, Fiona; Mistry, Dipesh; Underwood, Martin; Matharu, Manjit; Pincus, Tamar

2017-01-01

Objective: To identify predictors of prognosis and trial outcomes in prospective studies of people with chronic headache. Methods: This was a systematic review of published literature in peer-reviewed journals. We included (1) randomized controlled trials (RCTs) of interventions for chronic headache that reported subgroup analyses and (2) prospective cohort studies, published in English, since 1980. Participants included adults with chronic headache (including chronic headache, chronic migraine, and chronic tension-type headache with or without medication overuse headache). We searched key databases using free text and MeSH terms. Two reviewers independently extracted data and assessed the methodologic quality of studies and overall quality of evidence identified using appropriate published checklists. Results: We identified 16,556 titles, removed 663 duplicates, and reviewed 199 articles, of which 27 were included in the review—17 prospective cohorts and 10 RCTs with subgroup analyses reported. There was moderate-quality evidence indicating that depression, anxiety, poor sleep and stress, medication overuse, and poor self-efficacy for managing headaches are potential prognostic factors for poor prognosis and unfavorable outcomes from preventive treatment in chronic headache. There was inconclusive evidence about treatment expectations, age, age at onset, body mass index, employment, and several headache features. Conclusions: This review identified several potential predictors of poor prognosis and worse outcome postinterventions in people with chronic headache. The majority of these are modifiable. The findings also highlight the need for more longitudinal high-quality research of prognostic factors in chronic headache. PMID:28615422

Statistical considerations on prognostic models for glioma

PubMed Central

Molinaro, Annette M.; Wrensch, Margaret R.; Jenkins, Robert B.; Eckel-Passow, Jeanette E.

2016-01-01

Given the lack of beneficial treatments in glioma, there is a need for prognostic models for therapeutic decision making and life planning. Recently several studies defining subtypes of glioma have been published. Here, we review the statistical considerations of how to build and validate prognostic models, explain the models presented in the current glioma literature, and discuss advantages and disadvantages of each model. The 3 statistical considerations to establishing clinically useful prognostic models are: study design, model building, and validation. Careful study design helps to ensure that the model is unbiased and generalizable to the population of interest. During model building, a discovery cohort of patients can be used to choose variables, construct models, and estimate prediction performance via internal validation. Via external validation, an independent dataset can assess how well the model performs. It is imperative that published models properly detail the study design and methods for both model building and validation. This provides readers the information necessary to assess the bias in a study, compare other published models, and determine the model's clinical usefulness. As editors, reviewers, and readers of the relevant literature, we should be cognizant of the needed statistical considerations and insist on their use. PMID:26657835

The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China

PubMed Central

Bi, Xiwen; Yang, Hang; An, Xin; Wang, Fenghua; Jiang, Wenqi

2016-01-01

Background We propose a novel prognostic parameter for esophageal squamous cell carcinoma (ESCC)—hemoglobin/red cell distribution width (HB/RDW) ratio. Its clinical prognostic value and relationship with other clinicopathological characteristics were investigated in ESCC patients. Results The optimal cut-off value was 0.989 for the HB/RDW ratio. The HB/RDW ratio (P= 0.035), tumor depth (P = 0.020) and lymph node status (P<0.001) were identified to be an independent prognostic factors of OS by multivariate analysis, which was validated by bootstrap resampling. Patients with a low HB/RDW ratio had a 1.416 times greater risk of dying during follow-up compared with those with a high HB/RDW (95% CI = 1.024–1.958, P = 0.035). Materials and Methods We retrospectively analyzed 362 patients who underwent curative treatment at a single institution between January 2007 and December 2008. The chi-square test was used to evaluate relationships between the HB/RDW ratio and other clinicopathological variables; the Kaplan–Meier method was used to analyze the 5-year overall survival (OS); and the Cox proportional hazards models were used for univariate and multivariate analyses of variables related to OS. Conclusion A significant association was found between the HB/RDW ratio and clinical characteristics and survival outcomes in ESCC patients. Based on these findings, we believe that the HB/RDW ratio is a novel and promising prognostic parameter for ESCC patients. PMID:27223088

Structural identifiability of cyclic graphical models of biological networks with latent variables.

PubMed

Wang, Yulin; Lu, Na; Miao, Hongyu

2016-06-13

Graphical models have long been used to describe biological networks for a variety of important tasks such as the determination of key biological parameters, and the structure of graphical model ultimately determines whether such unknown parameters can be unambiguously obtained from experimental observations (i.e., the identifiability problem). Limited by resources or technical capacities, complex biological networks are usually partially observed in experiment, which thus introduces latent variables into the corresponding graphical models. A number of previous studies have tackled the parameter identifiability problem for graphical models such as linear structural equation models (SEMs) with or without latent variables. However, the limited resolution and efficiency of existing approaches necessarily calls for further development of novel structural identifiability analysis algorithms. An efficient structural identifiability analysis algorithm is developed in this study for a broad range of network structures. The proposed method adopts the Wright's path coefficient method to generate identifiability equations in forms of symbolic polynomials, and then converts these symbolic equations to binary matrices (called identifiability matrix). Several matrix operations are introduced for identifiability matrix reduction with system equivalency maintained. Based on the reduced identifiability matrices, the structural identifiability of each parameter is determined. A number of benchmark models are used to verify the validity of the proposed approach. Finally, the network module for influenza A virus replication is employed as a real example to illustrate the application of the proposed approach in practice. The proposed approach can deal with cyclic networks with latent variables. The key advantage is that it intentionally avoids symbolic computation and is thus highly efficient. Also, this method is capable of determining the identifiability of each single parameter and

Comparison of the prognostic utility of the revised International Prognostic Scoring System and the French Prognostic Scoring System in azacitidine-treated patients with myelodysplastic syndromes.

PubMed

Zeidan, Amer M; Lee, Ju-Whei; Prebet, Thomas; Greenberg, Peter; Sun, Zhuoxin; Juckett, Mark; Smith, Mitchell R; Paietta, Elisabeth; Gabrilove, Janice; Erba, Harry P; Tallman, Martin S; Gore, Steven D

2014-08-01

The revised International Prognostic Scoring System (IPSS-R) was developed in a cohort of untreated myelodysplastic syndromes (MDS) patients. A French Prognostic Scoring System (FPSS) was recently reported to identify differential survival among azacitidine-treated patients with high-risk MDS. We applied the FPSS and IPSS-R to 150 patients previously randomized to azacitidine monotherapy or a combination of azacitidine with entinostat (a histone deacetylase inhibitor). Neither score predicted response but both discriminated patients with different overall survival (OS; median OS, FPSS: 9·7, 14·7, and 25·3 months, P = 0·018; IPSS-R: 12·5, 11·3, 20·8, and 36 months, P = 0·005). Statistical analysis suggested no improvement in OS prediction for the FPSS over the IPSS-R in azacitidine-treated patients. © 2014 John Wiley & Sons Ltd.

Network-based approach to identify prognostic biomarkers for estrogen receptor-positive breast cancer treatment with tamoxifen.

PubMed

Liu, Rong; Guo, Cheng-Xian; Zhou, Hong-Hao

2015-01-01

This study aims to identify effective gene networks and prognostic biomarkers associated with estrogen receptor positive (ER+) breast cancer using human mRNA studies. Weighted gene coexpression network analysis was performed with a complex ER+ breast cancer transcriptome to investigate the function of networks and key genes in the prognosis of breast cancer. We found a significant correlation of an expression module with distant metastasis-free survival (HR = 2.25; 95% CI .21.03-4.88 in discovery set; HR = 1.78; 95% CI = 1.07-2.93 in validation set). This module contained genes enriched in the biological process of the M phase. From this module, we further identified and validated 5 hub genes (CDK1, DLGAP5, MELK, NUSAP1, and RRM2), the expression levels of which were strongly associated with poor survival. Highly expressed MELK indicated poor survival in luminal A and luminal B breast cancer molecular subtypes. This gene was also found to be associated with tamoxifen resistance. Results indicated that a network-based approach may facilitate the discovery of biomarkers for the prognosis of ER+ breast cancer and may also be used as a basis for establishing personalized therapies. Nevertheless, before the application of this approach in clinical settings, in vivo and in vitro experiments and multi-center randomized controlled clinical trials are still needed.

Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

PubMed Central

Grande, Michele; Milito, Giovanni; Attinà, Grazia Maria; Cadeddu, Federica; Muzi, Marco Gallinella; Nigro, Casimiro; Rulli, Francesco; Farinon, Attilio Maria

2008-01-01

Background The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data. Methods Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable. Results On survival analysis we found that depth of tumour invasion (P < 0.001; F-ratio 2.11), type of operation (P < 0.001; F-ratio 3.51) and CT scanning (P < 0.001; F-ratio 5.21) were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour. Conclusion The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted. PMID:18778464

Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma.

PubMed

Atanasov, Georgi; Schierle, Katrin; Hau, Hans-Michael; Dietel, Corinna; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Englisch, Julianna Paulina; Robson, Simon C; Reutzel-Selke, Anja; Pascher, Andreas; Jonas, Sven; Pratschke, Johann; Benzing, Christian; Schmelzle, Moritz

2017-02-01

Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies.

Optical Spectra of Four Objects Identified with Variable Radio Sources

NASA Astrophysics Data System (ADS)

Chavushyan, V.; Mujica, R.; Gorshkov, A. G.; Konnikova, V. K.; Mingaliev, M. G.

2000-06-01

We obtained optical spectra of four objects identified with variable radio sources. Three objects (0029+0554, 0400+0550, 2245+0500) were found to be quasars with redshifts of 1.314, 0.761, and 1.091. One object (2349+0534) has a continuum spectrum characteristic of BL Lac objects. We analyze spectra of the radio sources in the range 0.97-21.7 GHz for the epoch 1997 and in the range 3.9-11.1 GHz for the epoch 1990, as well as the pattern of variability of their flux densities on time scales of 1.5 and 7 years.

The NHLBI LAM Registry: Prognostic physiological and radiological biomarkers emerge from a 15-year prospective longitudinal analysis.

PubMed

Gupta, Nishant; Lee, Hye-Seung; Ryu, Jay H; Taveira-DaSilva, Angelo M; Beck, Gerald J; Lee, Jar-Chi; McCarthy, Kevin; Finlay, Geraldine A; Brown, Kevin K; Ruoss, Stephen J; Avila, Nilo A; Moss, Joel; McCormack, Francis X

2018-06-22

The natural history of lymphangioleiomyomatosis is mainly derived from retrospective cohort analyses and remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM. A linear mixed effects model was employed to compute the rate of decline of FEV1, and identify variables impacting FEV1 decline among 217 registry patients who enrolled from 1998-2001. Prognostic variables associated with progression to death/lung transplantation were identified using a Cox proportional hazard model. Mean annual decline of FEV1 was 89±53 ml/year, and remained remarkably constant regardless of baseline lung function. FEV1 decline was more rapid in those with greater cyst profusion on CT scan (p=0.02), and in premenopausal subjects (118ml/year) compared to postmenopausal subjects (74ml/year), (p=0.003). There were 26 deaths and 43 lung transplants during the evaluation period. Estimated 5-, 10-, 15-, and 20-year transplant-free survival rates were 95%, 85%, 75%, and 64%, respectively. Postmenopausal status (hazard ratio 0.30, p=0.0002) and higher baseline FEV1 (hazard ratio 0.97, p=0.008) or DLCO (hazard ratio 0.97, p=0.001) were independently associated with a lower risk of progression to death or lung transplantation. The median transplant-free survival in patients with LAM is greater than 20 years. Menopausal status as well as structural and physiological markers of disease severity significantly affect the rate of decline of FEV1 and progression to death or lung transplantation in LAM. Copyright © 2018. Published by Elsevier Inc.

Multivariate analysis of prognostic factors in synovial sarcoma.

PubMed

Koh, Kyoung Hwan; Cho, Eun Yoon; Kim, Dong Wook; Seo, Sung Wook

2009-11-01

Many studies have described the diversity of synovial sarcoma in terms of its biological characteristics and clinical features. Moreover, much effort has been expended on the identification of prognostic factors because of unpredictable behaviors of synovial sarcomas. However, with the exception of tumor size, published results have been inconsistent. We attempted to identify independent risk factors using survival analysis. Forty-one consecutive patients with synovial sarcoma were prospectively followed from January 1997 to March 2008. Overall and progression-free survival for age, sex, tumor size, tumor location, metastasis at presentation, histologic subtype, chemotherapy, radiation therapy, and resection margin were analyzed, and standard multivariate Cox proportional hazard regression analysis was used to evaluate potential prognostic factors. Tumor size (>5 cm), nonlimb-based tumors, metastasis at presentation, and a monophasic subtype were associated with poorer overall survival. Multivariate analysis showed metastasis at presentation and monophasic tumor subtype affected overall survival. For the progression-free survival, monophasic subtype was found to be only 1 prognostic factor. The study confirmed that histologic subtype is the single most important independent prognostic factors of synovial sarcoma regardless of tumor stage.

Doubt and belief in physicians' ability to prognosticate during critical illness: The perspective of surrogate decision makers

PubMed Central

Zier, Lucas S.; Burack, Jeffrey H.; Micco, Guy; Chipman, Anne K.; Frank, James A.; Luce, John M.; White, Douglas B.

2009-01-01

Objectives: Although discussing a prognosis is a duty of physicians caring for critically ill patients, little is known about surrogate decision-makers' beliefs about physicians' ability to prognosticate. We sought to determine: 1) surrogates' beliefs about whether physicians can accurately prognosticate for critically ill patients; and 2) how individuals use prognostic information in their role as surrogate decision-makers. Design, Setting, and Patients: Multicenter study in intensive care units of a public hospital, a tertiary care hospital, and a veterans' hospital. We conducted semistructured interviews with 50 surrogate decision-makers of critically ill patients. We analyzed the interview transcripts using grounded theory methods to inductively develop a framework to describe surrogates' beliefs about physicians' ability to prognosticate. Validation methods included triangulation by multidisciplinary analysis and member checking. Measurements and Main Results: Overall, 88% (44 of 50) of surrogates expressed doubt about physicians' ability to prognosticate for critically ill patients. Four distinct themes emerged that explained surrogates' doubts about prognostic accuracy: a belief that God could alter the course of the illness, a belief that predicting the future is inherently uncertain, prior experiences where physicians' prognostications were inaccurate, and experiences with prognostication during the patient's intensive care unit stay. Participants also identified several factors that led to belief in physicians' prognostications, such as receiving similar prognostic estimates from multiple physicians and prior experiences with accurate prognostication. Surrogates' doubts about prognostic accuracy did not prevent them from wanting prognostic information. Instead, most surrogate decision-makers view physicians' prognostications as rough estimates that are valuable in informing decisions, but are not determinative. Surrogates identified the act of prognostic

Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability.

PubMed

Ring, Caroline L; Pearce, Robert G; Setzer, R Woodrow; Wetmore, Barbara A; Wambaugh, John F

2017-09-01

The thousands of chemicals present in the environment (USGAO, 2013) must be triaged to identify priority chemicals for human health risk research. Most chemicals have little of the toxicokinetic (TK) data that are necessary for relating exposures to tissue concentrations that are believed to be toxic. Ongoing efforts have collected limited, in vitro TK data for a few hundred chemicals. These data have been combined with biomonitoring data to estimate an approximate margin between potential hazard and exposure. The most "at risk" 95th percentile of adults have been identified from simulated populations that are generated either using standard "average" adult human parameters or very specific cohorts such as Northern Europeans. To better reflect the modern U.S. population, we developed a population simulation using physiologies based on distributions of demographic and anthropometric quantities from the most recent U.S. Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES) data. This allowed incorporation of inter-individual variability, including variability across relevant demographic subgroups. Variability was analyzed with a Monte Carlo approach that accounted for the correlation structure in physiological parameters. To identify portions of the U.S. population that are more at risk for specific chemicals, physiologic variability was incorporated within an open-source high-throughput (HT) TK modeling framework. We prioritized 50 chemicals based on estimates of both potential hazard and exposure. Potential hazard was estimated from in vitro HT screening assays (i.e., the Tox21 and ToxCast programs). Bioactive in vitro concentrations were extrapolated to doses that produce equivalent concentrations in body tissues using a reverse dosimetry approach in which generic TK models are parameterized with: 1) chemical-specific parameters derived from in vitro measurements and predicted from chemical structure; and 2) with

A Generic Software Architecture For Prognostics

NASA Technical Reports Server (NTRS)

Teubert, Christopher; Daigle, Matthew J.; Sankararaman, Shankar; Goebel, Kai; Watkins, Jason

2017-01-01

Prognostics is a systems engineering discipline focused on predicting end-of-life of components and systems. As a relatively new and emerging technology, there are few fielded implementations of prognostics, due in part to practitioners perceiving a large hurdle in developing the models, algorithms, architecture, and integration pieces. As a result, no open software frameworks for applying prognostics currently exist. This paper introduces the Generic Software Architecture for Prognostics (GSAP), an open-source, cross-platform, object-oriented software framework and support library for creating prognostics applications. GSAP was designed to make prognostics more accessible and enable faster adoption and implementation by industry, by reducing the effort and investment required to develop, test, and deploy prognostics. This paper describes the requirements, design, and testing of GSAP. Additionally, a detailed case study involving battery prognostics demonstrates its use.

Comparison of the Prognostic Utility of the Diverse Molecular Data among lncRNA, DNA Methylation, microRNA, and mRNA across Five Human Cancers

PubMed Central

Xu, Li; Fengji, Liang; Changning, Liu; Liangcai, Zhang; Yinghui, Li; Yu, Li; Shanguang, Chen; Jianghui, Xiong

2015-01-01

Introduction Advances in high-throughput technologies have generated diverse informative molecular markers for cancer outcome prediction. Long non-coding RNA (lncRNA) and DNA methylation as new classes of promising markers are emerging as key molecules in human cancers; however, the prognostic utility of such diverse molecular data remains to be explored. Materials and Methods We proposed a computational pipeline (IDFO) to predict patient survival by identifying prognosis-related biomarkers using multi-type molecular data (mRNA, microRNA, DNA methylation, and lncRNA) from 3198 samples of five cancer types. We assessed the predictive performance of both single molecular data and integrated multi-type molecular data in patient survival stratification, and compared their relative importance in each type of cancer, respectively. Survival analysis using multivariate Cox regression was performed to investigate the impact of the IDFO-identified markers and traditional variables on clinical outcome. Results Using the IDFO approach, we obtained good predictive performance of the molecular datasets (bootstrap accuracy: 0.71–0.97) in five cancer types. Impressively, lncRNA was identified as the best prognostic predictor in the validated cohorts of four cancer types, followed by DNA methylation, mRNA, and then microRNA. We found the incorporating of multi-type molecular data showed similar predictive power to single-type molecular data, but with the exception of the lncRNA + DNA methylation combinations in two cancers. Survival analysis of proportional hazard models confirmed a high robustness for lncRNA and DNA methylation as prognosis factors independent of traditional clinical variables. Conclusion Our study provides insight into systematically understanding the prognostic performance of diverse molecular data in both single and aggregate patterns, which may have specific reference to subsequent related studies. PMID:26606135

Diagnostic and prognostic epigenetic biomarkers in cancer.

PubMed

Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

2015-01-01

Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

Serum prognostic biomarkers in head and neck cancer patients.

PubMed

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J; Tainsky, Michael A

2014-08-01

A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Prospective cohort study. A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient's serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Poor overall survival was associated with African Americans (hazard ratio [HR] for death = 2.61; 95% confidence interval [CI]: 1.58-4.33; P = .000), advanced stage (HR = 2.79; 95% CI: 1.40-5.57; P = .004), and recurrent disease (HR = 6.66; 95% CI: 2.54-17.44; P = .000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Serum Prognostic Biomarkers in Head and Neck Cancer Patients

PubMed Central

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S.; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H.; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J.; Tainsky, Michael A.

2014-01-01

Objectives/Hypothesis A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Study Design Prospective cohort study. Methods A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient’s serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Results Poor overall survival was associated with African Americans (hazard ratio [HR] for death =2.61; 95% confidence interval [CI]: 1.58–4.33; P =.000), advanced stage (HR =2.79; 95% CI: 1.40–5.57; P =.004), and recurrent disease (HR =6.66; 95% CI: 2.54–17.44; P =.000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. Conclusions The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. PMID:24347532

Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics.

PubMed

Cheng, Mei-Ling; Wang, Chao-Hung; Shiao, Ming-Shi; Liu, Min-Hui; Huang, Yu-Yen; Huang, Cheng-Yu; Mao, Chun-Tai; Lin, Jui-Fen; Ho, Hung-Yao; Yang, Ning-I

2015-04-21

Identification of novel biomarkers is needed to improve the diagnosis and prognosis of heart failure (HF). Metabolic disturbance is remarkable in patients with HF. This study sought to assess the diagnostic and prognostic values of metabolomics in HF. Mass spectrometry-based profiling of plasma metabolites was performed in 515 participants; the discovery phase study enrolled 51 normal control subjects and 183 HF patients, and the validation study enrolled 63 control subjects and 218 patients with stage C HF. Another independent group of 32 patients with stage C HF who recovered to New York Heart Association functional class I at 6 and 12 months was profiled as the "recovery" group. A panel of metabolites, including histidine, phenylalanine, spermidine, and phosphatidylcholine C34:4, has a diagnostic value similar to B-type natriuretic peptide (BNP). In the recovery group, the values of this panel significantly improved at 6 and 12 months. To evaluate the prognostic values, events were defined as the combined endpoints of death or HF-related re-hospitalization. A metabolite panel, which consisted of the asymmetric methylarginine/arginine ratio, butyrylcarnitine, spermidine, and the total amount of essential amino acids, provided significant prognostic values (p < 0.0001) independent of BNP and traditional risk factors. The prognostic value of the metabolite panel was better than that of BNP (area under the curve of 0.85 vs. 0.74 for BNP) and Kaplan-Meier curves (log rank: 17.5 vs. 9.95). These findings were corroborated in the validation study. Metabolomics demonstrate powerful diagnostic value in estimating HF-related metabolic disturbance. The profile of metabolites provides better prognostic value versus conventional biomarkers. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Clinical performance validation of PITX2 DNA methylation as prognostic biomarker in patients with head and neck squamous cell carcinoma.

PubMed

Sailer, Verena; Gevensleben, Heidrun; Dietrich, Joern; Goltz, Diane; Kristiansen, Glen; Bootz, Friedrich; Dietrich, Dimo

2017-01-01

Despite advances in combined modality therapy, outcomes in head and neck squamous cell cancer (HNSCC) remain dismal with five-year overall survival rates of less than 50%. Prognostic biomarkers are urgently needed to identify patients with a high risk of death after initial curative treatment. Methylation status of the paired-like homeodomain transcription factor 2 (PITX2) has recently emerged as a powerful prognostic biomarker in various cancers. In the present study, the clinical performance of PITX2 methylation was validated in a HNSCC cohort by means of an independent analytical platform (Infinium HumanMethylation450 BeadChip, Illumina, Inc.). A total of 528 HNSCC patients from The Cancer Genome Atlas (TCGA) were included in the study. Death was defined as primary endpoint. PITX2 methylation was correlated with overall survival and clinicopathological parameters. PITX2 methylation was significantly associated with sex, tumor site, p16 status, and grade. In univariate Cox proportional hazards analysis, PITX2 hypermethylation analyzed as continuous and dichotomized variable was significantly associated with prolonged overall survival of HNSCC patients (continuous: hazard ratio (HR) = 0.19 [95%CI: 0.04-0.88], p = 0.034; dichotomized: HR = 0.52 [95%CI: 0.33-0.84], p = 0.007). In multivariate Cox analysis including established clinicopathological parameters, PITX2 promoter methylation was confirmed as prognostic factor (HR = 0.28 [95%CI: 0.09-0.84], p = 0.023). Using an independent analytical platform, PITX2 methylation was validated as a prognostic biomarker in HNSCC patients, identifying patients that potentially benefit from intensified surveillance and/or administration of adjuvant/neodjuvant treatment, i.e. immunotherapy.

A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer.

PubMed

Sho, Shonan; Court, Colin M; Winograd, Paul; Russell, Marcia M; Tomlinson, James S

2017-12-01

Approximately 20-40% of stage II/III colorectal cancer (CRC) patients develop relapse. Clinicopathological factors alone are limited in detecting these patients, resulting in potential under/over-treatment. We sought to identify a prognostic tumor mutational profile that could predict CRC recurrence. Whole-exome sequencing data were obtained for 207 patients with stage II/III CRC from The Cancer Genome Atlas. Mutational landscape in relapse-free versus relapsed cohort was compared using Fisher's exact test, followed by multivariate Cox regression to identify genes associated with cancer recurrence. Bootstrap-validation was used to examine internal/external validity. We identified five prognostic genes (APAF1, DIAPH2, NTNG1, USP7, and VAV2), which were combined to form a prognostic mutation panel. Patients with ≥1 mutation(s) within this five-gene panel had worse prognosis (3-yr relapse-free survival [RFS]: 53.0%), compared to patients with no mutation (3-yr RFS: 84.3%). In multivariate analysis, the five-gene panel remained prognostic for cancer recurrence independent of stage and high-risk features (hazard ratio 3.63, 95%CI [1.93-6.83], P < 0.0001). Furthermore, its prognostic accuracy was superior to the American Joint Commission on Cancer classification (concordance-index: 0.70 vs 0.54). Our proposed mutation panel identifies CRC patients at high-risk for recurrence, which may help guide adjuvant therapy and post-operative surveillance protocols. © 2017 Wiley Periodicals, Inc.

A novel gene expression-based prognostic scoring system to predict survival in gastric cancer

DOE PAGES

Wang, Pin; Wang, Yunshan; Hang, Bo; ...

2016-07-11

Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A networkmore » was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.« less

A novel gene expression-based prognostic scoring system to predict survival in gastric cancer

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

Wang, Pin; Wang, Yunshan; Hang, Bo

Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A networkmore » was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.« less

Toward IVHM Prognostics

NASA Technical Reports Server (NTRS)

Walsh, Kevin; Venti, Mike

2007-01-01

This viewgraph presentation reviews the prognostics of Integrated Vehicle Health Management. The contents include: 1) Aircraft Operations-Today's way of doing business; 2) Prognostics; 3) NASA's instrumentation data-system rack; 4) Data mining for IVHM; 5) NASA GRC's C-MAPSS generic engine model; and 6) Concluding thoughts.

The Prognostic Influence of BRAF Mutation and other Molecular, Clinical and Laboratory Parameters in Stage IV Colorectal Cancer.

PubMed

Karadima, Maria L; Saetta, Angelica A; Chatziandreou, Ilenia; Lazaris, Andreas C; Patsouris, Efstratios; Tsavaris, Nikolaos

2016-10-01

Our aim was to evaluate the predictive and prognostic influence of BRAF mutation and other molecular, clinical and laboratory parameters in stage IV colorectal cancer (CRC). 60 patients were included in this retrospective analysis, and 17 variables were examined for their relation with treatment response and survival. KRAS mutation was identified in 40.3 % of cases, BRAF and PIK3CA in 8.8 % and 10.5 % respectively. 29.8 % of patients responded to treatment. Median survival time was 14.3 months. Weight loss, fever, abdominal metastases, blood transfusion, hypoalbuminaimia, BRAF and PIK3CA mutations, CRP and DNA Index were associated with survival. In multivariate analysis, male patients had 3.8 times higher probability of response, increased DNA Index was inversely correlated with response and one unit raise of DNA Index augmented 6 times the probability of death. Our findings potentiate the prognostic role of BRAF, PIK3CA mutations and ploidy in advanced CRC.

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

PubMed

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

the standardised extraction tool from the JBI-MAStARI. Prognostic factors and the accompanying odds ratio reported for the significance of these factors that were identified by multivariate regression, were extracted from each included study. Studies results were pooled in statistical meta-analysis using Review Manager 5.1. Where statistical pooling was not possible, the findings were presented in narrative form. Seven studies (four prospective cohort and three retrospective cohort) investigating 22 factors in total were included. Fixed effects meta-analysis showed: hypotension [OR=1.66, 95%CI, 1.14-2.41, p=0.008] and thrombocytopenia [OR=3.92, 95%CI, 2.19-7.01, p<0.00001)] were associated with high-risk of adverse outcomes for febrile neutropenia. Other factors that were statistically significant from single studies included: age of patients, clinical presentation at fever onset, presence or absence of co-morbidities, infections, duration and severity of neutropenia state. Five prognostic factors failed to demonstrate an association between the variables and the outcomes measured and they include: presence of pneumonia, total febrile days, median days to fever, recovery from neutropenia and presence of moderate clinical symptoms in association with Gram-negative bacteraemia. Despite the overall limitations identified in the included studies, this review has provided a synthesis of the best available evidence for the prognostic factors used in risk stratification of febrile neutropenia patients. However, the dynamic aspects of prognostic model development, validation and utilisation have not been addressed adequately thus far. Given the findings of this review, it is timely to address these issues and improve the utilisation of prognostic models in the management of febrile neutropenia patients. The identified factors are similar to the factors in current prognostic models. However, additional factors that were reported to be statistically significant in this review

Application of molecular biology of differentiated thyroid cancer for clinical prognostication.

PubMed

Marotta, Vincenzo; Sciammarella, Concetta; Colao, Annamaria; Faggiano, Antongiulio

2016-11-01

Although cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF V600E is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF V600E and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated. © 2016 Society for Endocrinology.

Realizing the Translational Potential of Telomere Length Variation as a Tissue-Based Prognostic Marker for Prostate Cancer

DTIC Science & Technology

2014-10-01

Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer PRINCIPAL INVESTIGATOR: Elizabeth A. Platz CONTRACTING...Translational Potential of Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer 5b. GRANT NUMBER W81XWH-12-1-0545 5c...combination of telomere length variability in prostate cancer cells and short telomere length in cancer-associated stromal cells is an independent

Prognostic significance of the prognostic nutritional index in esophageal cancer patients undergoing neoadjuvant chemotherapy.

PubMed

Nakatani, M; Migita, K; Matsumoto, S; Wakatsuki, K; Ito, M; Nakade, H; Kunishige, T; Kitano, M; Kanehiro, H

2017-08-01

Nutritional status is one of the most important issues faced by cancer patients. Several studies have shown that a low preoperative nutritional status is associated with a worse prognosis in patients with various types of cancer, including esophageal cancer (EC). Recently, neoadjuvant chemotherapy (NAC) and/or radiotherapy have been accepted as the standard treatment for resectable advanced EC. However, NAC has the potential to deteriorate the nutritional status of a patient. This study aimed to evaluate the prognostic significance of the nutritional status for EC patients who underwent NAC. We retrospectively reviewed 66 squamous cell EC patients who underwent NAC consisting of docetaxel, cisplatin, and 5-fluorouracil followed by subtotal esophagectomy at Nara Medical University Hospital between January 2009 and August 2015. To assess the patients' nutritional status, the prognostic nutritional index (PNI) before commencing NAC and prior to the operation was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count in the peripheral blood (per mm3). The cutoff value of the PNI was set at 45. A multivariable analysis was performed to identify prognostic factors for overall survival (OS) and relapse-free survival (RFS). The mean pre-NAC and preoperative PNI were 50.2 ± 5.7 and 48.1 ± 4.7, respectively (P = 0.005). The PNI decreased following NAC in 44 (66.7%) patients. Before initiating NAC, 9 (13.6%) patients had a low PNI, and 12 (18.2%) patients had a low PNI prior to the operation. The pre-NAC PNI and preoperative PNI were significantly associated with the OS (P = 0.013 and P = 0.004, respectively) and RFS (P = 0.036 and P = 0.005, respectively) rates. The multivariable analysis identified the preoperative PNI as an independent prognostic factor for poor OS and RFS, although the pre-NAC PNI was not an independent predictor. Our results suggest that the preoperative PNI is a useful marker for predicting the long-term outcomes of EC patients

Seizure Freedom Rates and Prognostic Indicators After Resection of Gangliogliomas: A Review.

PubMed

Bonney, Phillip A; Glenn, Chad A; Ebeling, Peter A; Conner, Andrew K; Boettcher, Lillian B; Cameron, Drew M; Battiste, James D; Sughrue, Michael E

2015-12-01

Gangliogliomas are rare tumors that comprise up to 40% of lesional epilepsy. Seizure control represents an important quality-of-life determinant in patients with these tumors. Here we present results of a literature review addressing rates of seizure freedom in in patients with gangliogliomas. Across studies, seizure freedom occurred in 63%-100% of patients. Many studies included follow-up times of greater than 5 years, suggesting that the responses are durable. We discuss potential prognostic factors associated with seizure freedom, including the duration of epilepsy, patient age, frequency and semiology of seizures, tumor location, extent of surgical resection, and operative strategy, including surgical approach and use of invasive monitoring. Although significant differences in study populations and treatments preclude meta-analysis, we discuss prognostic factors identified in individual studies. Increased extent of resection, lesser duration of epilepsy, and younger age at surgery have been associated with increased seizure freedom rates in at least 2 studies each. Although all studies were retrospective in nature and are consequently limited by the weaknesses inherent to such investigations, the literature suggests that surgery is able to relieve most ganglioglioma patients--regardless of patient demographics, tumor characteristics, and operative variables--of seizures. Copyright © 2015 Elsevier Inc. All rights reserved.

Lifecycle Prognostics Architecture for Selected High-Cost Active Components

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

N. Lybeck; B. Pham; M. Tawfik

There are an extensive body of knowledge and some commercial products available for calculating prognostics, remaining useful life, and damage index parameters. The application of these technologies within the nuclear power community is still in its infancy. Online monitoring and condition-based maintenance is seeing increasing acceptance and deployment, and these activities provide the technological bases for expanding to add predictive/prognostics capabilities. In looking to deploy prognostics there are three key aspects of systems that are presented and discussed: (1) component/system/structure selection, (2) prognostic algorithms, and (3) prognostics architectures. Criteria are presented for component selection: feasibility, failure probability, consequences of failure,more » and benefits of the prognostics and health management (PHM) system. The basis and methods commonly used for prognostics algorithms are reviewed and summarized. Criteria for evaluating PHM architectures are presented: open, modular architecture; platform independence; graphical user interface for system development and/or results viewing; web enabled tools; scalability; and standards compatibility. Thirteen software products were identified and discussed in the context of being potentially useful for deployment in a PHM program applied to systems in a nuclear power plant (NPP). These products were evaluated by using information available from company websites, product brochures, fact sheets, scholarly publications, and direct communication with vendors. The thirteen products were classified into four groups of software: (1) research tools, (2) PHM system development tools, (3) deployable architectures, and (4) peripheral tools. Eight software tools fell into the deployable architectures category. Of those eight, only two employ all six modules of a full PHM system. Five systems did not offer prognostic estimates, and one system employed the full health monitoring suite but lacked

Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system.

PubMed

Baldini, Luca; Goldaniga, Maria; Guffanti, Andrea; Broglia, Chiara; Cortelazzo, Sergio; Rossi, Andrea; Morra, Enrica; Colombi, Mariangela; Callea, Vincenzo; Pogliani, Enrico; Ilariucci, Fiorella; Luminari, Stefano; Morel, Pierre; Merlini, Giampaolo; Gobbi, Paolo

2005-07-20

To evaluate the clinicohematologic variables at diagnosis that are prognostically related to neoplastic progression in patients with immunoglobulin M (IgM) monoclonal gammopathies of undetermined significance (MGUS), and indolent Waldenström's macroglobulinemia (IWM), and propose a scoring system to identify subsets of patients at different risk. We evaluated 217 patients with IgM MGUS and 201 with IWM (male-female ratio, 131:86 and 117:84; mean age, 63.7 and 63.6 years, respectively) diagnosed on the basis of serum monoclonal component (MC) levels and bone marrow lymphoplasmacytic infiltration degree. The variables selected by univariate analyses were multivariately investigated; on the basis of their individual relative hazards, a scoring system was devised to identify subsets of patients at different risk of evolution. After a median follow-up of 56.1 and 60.2 months, 15 of 217 MGUS and 45 of 201 IWM patients, respectively, required chemotherapy for symptomatic WM (13 and 36), non-Hodgkin's lymphoma (2 and 6) and amyloidosis (0 and 3). The median time to evolution (TTE) was not reached for MGUS and was 141.5 months for IWM. The variables adversely related to evolution were qualitatively the same in both groups: MC levels, Hb concentrations and sex. A scoring system based on these parameters identified three risk groups with highly significant differences in TTE in both groups (P < .0001). MGUS and IWM identify disease entities with different propensities for symptomatic neoplastic evolution. As both have the same prognostic determinants of progression, we propose a practical scoring system that, identifying different risks of malignant evolution, may allow an individualized clinical approach.

PROGNOSTIC VALUE OF SHAPE-DESCRIPTIVE FACTORS FOR THE PROGRESSION OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PubMed

Pfau, Maximilian; Lindner, Moritz; Goerdt, Lukas; Thiele, Sarah; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; Sadda, SriniVas R; Holz, Frank G; Fleckenstein, Monika

2018-05-16

To systematically compare the prognostic value of multiple shape-descriptive factors in the natural course of the disease. A total of 296 eyes of 201 patients (female patients 130; mean age: 72.2 ± 13.08 years) with a median follow-up of 2.38 years from 2 prospective, noninterventional natural history studies (Fundus-Autofluorescence-in-Age-related-Macular-Degeneration [clinicaltrials.gov identifier NCT00393692], Directional-Spread-in-Geographic-Atrophy [NCT02051998]) were included in the analysis. Serial fundus autofluorescence images were annotated using semiautomated image analysis software to determine the lesion area, circularity, perimeter, and caliper diameters. These variables and the fundus autofluorescence phenotype were evaluated for prediction of the future square root progression rates using linear mixed-effects models. For the combined model, leave-one-out cross validation on patient level (Scenario 1: previously unknown patient) resulted in a goodness-to-fit (R value) of 0.244 and leave-one-out cross validation on visit level (Scenario 2: previous observation of the patient) in a R value of 0.391. This indicated that shape-descriptive factors could explain 24.4% of the variance in geographic atrophy progression in previously unknown patients and 39.1% in patients with previous observation. These findings confirm the relevance of shape-descriptive factors and previous progression as prognostic variables for geographic atrophy progression. However, a substantial part of the remaining variation in geographic atrophy progression seems to depend on other variables, some of which are visible in optical coherence tomography.

Prognostic implications of adhesion molecule expression in colorectal cancer.

PubMed

Seo, Kyung-Jin; Kim, Maru; Kim, Jeana

2015-01-01

Research on the expression of adhesion molecules, E-cadherin (ECAD), CD24, CD44 and osteopontin (OPN) in colorectal cancer (CRC) has been limited, even though CRC is one of the leading causes of cancer-related deaths. This study was conducted to evaluate the expression of adhesion molecules in CRC and to determine their relationships with clinicopathologic variables, and the prognostic significance. The expression of ECAD, CD24, CD44 and OPN was examined in 174 stage II and III CRC specimens by immunohistochemistry of TMA. Negative ECAD expression was significantly correlated with advanced nodal stage and poor tumor differentiation. Multivariate analysis showed that both negative expression of ECAD and positive expression of CD24 were independent prognostic factors for disease-free survival (DFS) in CRC patients (P<0.001, relative risk [RR] = 5.596, 95% CI = 2.712-11.549; P = 0.038, RR = 3.768, 95% CI = 1.077-13.185, respectively). However, for overall survival (OS), only ECAD negativity showed statistically significant results in multivariate analysis (P<0.001, RR = 4.819, 95% CI = 2.515-9.234). Positive expression of CD24 was associated with poor OS in univariate analysis but was of no prognostic value in multivariate analysis. In conclusion, our study suggests that among these four adhesion molecules, ECAD and CD24 expression can be considered independent prognostic factors. The role of CD44 and OPN may need further evaluation.

Prognostic implications of adhesion molecule expression in colorectal cancer

PubMed Central

Seo, Kyung-Jin; Kim, Maru; Kim, Jeana

2015-01-01

Research on the expression of adhesion molecules, E-cadherin (ECAD), CD24, CD44 and osteopontin (OPN) in colorectal cancer (CRC) has been limited, even though CRC is one of the leading causes of cancer-related deaths. This study was conducted to evaluate the expression of adhesion molecules in CRC and to determine their relationships with clinicopathologic variables, and the prognostic significance. The expression of ECAD, CD24, CD44 and OPN was examined in 174 stage II and III CRC specimens by immunohistochemistry of TMA. Negative ECAD expression was significantly correlated with advanced nodal stage and poor tumor differentiation. Multivariate analysis showed that both negative expression of ECAD and positive expression of CD24 were independent prognostic factors for disease-free survival (DFS) in CRC patients (P<0.001, relative risk [RR] = 5.596, 95% CI = 2.712-11.549; P = 0.038, RR = 3.768, 95% CI = 1.077-13.185, respectively). However, for overall survival (OS), only ECAD negativity showed statistically significant results in multivariate analysis (P<0.001, RR = 4.819, 95% CI = 2.515-9.234). Positive expression of CD24 was associated with poor OS in univariate analysis but was of no prognostic value in multivariate analysis. In conclusion, our study suggests that among these four adhesion molecules, ECAD and CD24 expression can be considered independent prognostic factors. The role of CD44 and OPN may need further evaluation. PMID:26097606

Prognostic factors in sensory recovery after digital nerve repair.

PubMed

Bulut, Tuğrul; Akgün, Ulaş; Çıtlak, Atilla; Aslan, Cihan; Şener, Ufuk; Şener, Muhittin

2016-01-01

The prognostic factors that affect sensory nerve recovery after digital nerve repair are variable because of nonhomogeneous data, subjective tests, and different assessment/scoring methods. The aim of this study was to evaluate the success of sensory nerve recovery after digital nerve repair and to investigate the prognostic factors in sensorial healing. Ninety-six digital nerve repairs of 63 patients were retrospectively evaluated. All nerves were repaired with end-to-end neurorraphy. The static two-point discrimination (s2PD) and Semmes Weinstein monofilament (SWM) tests were performed to evaluate sensory recovery. The association between prognostic factors such as gender, age, involved digit, time from injury to repair, length of follow-up, smoking, concomitant injuries, type of injury, and sensory recovery results were assessed. The s2PD test demonstrated excellent results in 26 nerves (27%), good results in 61 nerves (64%), and poor results in 9 nerves (9%). The results of the SWM test according to Imai classification showed that 31 nerves (32%) were normal, light touch was diminished in 38 nerves (40%), protective sensation was diminished in 17 nerves (18%), loss of protective sensation occurred in 5 nerves (5%), and 5 nerves (5%) were anesthetic. There was a negative relationship between age, smoking, concomitant injuries, and sensory recovery. Our results demonstrate that concomitant tendon, bone and vascular injuries, older age, and smoking were associated with worse sensory nerve recovery results. However, all digital nerve injuries should be repaired, regardless of these prognostic factors.

Prognostic significance of perioperative nutritional parameters in patients with gastric cancer.

PubMed

Oh, Sung Eun; Choi, Min-Gew; Seo, Jeong-Meen; An, Ji Yeong; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung

2018-02-20

It has been suggested that nutritional status is related to the survival outcomes of cancer patients. The purpose of the current research is to evaluate the importance of the prognosis of various nutritional parameters during the perioperative period in patients with gastric cancer. This study enrolled patients with gastric cancer who underwent D2 gastrectomy at the Department of Surgery, Samsung Medical Center, in 2008. The prognostic significance of nutritional parameters was analyzed, along with other clinical and pathological variables, preoperatively and postoperatively at 3, 6, and 12 months. The total number of patients was 1415. The mean values of nutritional parameters, weight, body mass index (BMI), hemoglobin, total cholesterol, and total lymphocyte count (TLC) decreased significantly over time after surgery. On the contrary, albumin and prognostic nutritional index (PNI) score increased significantly during the postoperative follow-up period. Preoperatively, low BMI (<18.5 kg/m 2 ) and low TLC level (<1000 per mm 3 ) were revealed as independent prognostic factors in multivariate analysis. Low preoperative TLC level and decline in PNI (ΔPNI < -2.2) at postoperative 3 months; low preoperative TLC level and decline in TLC (ΔTLC < -279.9 per mm 3 ) at postoperative 6 months; and low preoperative BMI, albumin, and TLC levels at postoperative 12 months were independent nutritional prognostic indicators. Various perioperative nutritional parameters were confirmed as independent prognostic factors in patients with gastric cancer. Our results imply prognostic benefit from careful nutritional support for patients with poor nutritional parameters. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non-muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review.

PubMed

Soukup, Viktor; Čapoun, Otakar; Cohen, Daniel; Hernández, Virginia; Babjuk, Marek; Burger, Max; Compérat, Eva; Gontero, Paolo; Lam, Thomas; MacLennan, Steven; Mostafid, A Hugh; Palou, Joan; van Rhijn, Bas W G; Rouprêt, Morgan; Shariat, Shahrokh F; Sylvester, Richard; Yuan, Yuhong; Zigeuner, Richard

2017-11-01

Tumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. This article

Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer

PubMed Central

Han, Wonshik; Han, Mi-Ryung; Kang, Jason Jongho; Bae, Ji-Yeon; Lee, Ji Hyun; Bae, Young Ju; Lee, Jeong Eon; Shin, Hyuk-Jae; Hwang, Ki-Tae; Hwang, Sung-Eun; Kim, Sung-Won; Noh, Dong-Young

2006-01-01

Background A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer. Methods We performed array comparative genomic hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 28 fresh-frozen ER-positive breast cancer tissues. All of the patients included had received at least 1 year of tamoxifen treatment. Nine patients had distant recurrence within 5 years (Recurrence group) of diagnosis and 19 patients were alive without disease at least 5 years after diagnosis (Non-recurrence group). Results Potential prognostic variables were comparable between the two groups. In an unsupervised clustering analysis, samples from each group were well separated. The most common regions of gain in all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as called by CGH-Explorer software. The average frequency of copy number changes was similar between the two groups. The most significant chromosomal alterations found more often in the Recurrence group using two different statistical methods were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjusted p values <0.001). In subgroup analysis according to lymph node status, loss of 11p15 and 1p36 were found more often in Recurrence group with borderline significance within the lymph node positive patients (adjusted p = 0.052). Conclusion Our array CGH analysis with BAC clones could detect various genomic alterations in ER-positive breast cancers, and Recurrence group samples showed a significantly different pattern of DNA copy number changes than did Non-recurrence group samples. PMID:16608533

Autophagy-related prognostic signature for breast cancer.

PubMed

Gu, Yunyan; Li, Pengfei; Peng, Fuduan; Zhang, Mengmeng; Zhang, Yuanyuan; Liang, Haihai; Zhao, Wenyuan; Qi, Lishuang; Wang, Hongwei; Wang, Chenguang; Guo, Zheng

2016-03-01

Autophagy is a process that degrades intracellular constituents, such as long-lived or damaged proteins and organelles, to buffer metabolic stress under starvation conditions. Deregulation of autophagy is involved in the progression of cancer. However, the predictive value of autophagy for breast cancer prognosis remains unclear. First, based on gene expression profiling, we found that autophagy genes were implicated in breast cancer. Then, using the Cox proportional hazard regression model, we detected autophagy prognostic signature for breast cancer in a training dataset. We identified a set of eight autophagy genes (BCL2, BIRC5, EIF4EBP1, ERO1L, FOS, GAPDH, ITPR1 and VEGFA) that were significantly associated with overall survival in breast cancer. The eight autophagy genes were assigned as a autophagy-related prognostic signature for breast cancer. Based on the autophagy-related signature, the training dataset GSE21653 could be classified into high-risk and low-risk subgroups with significantly different survival times (HR = 2.72, 95% CI = (1.91, 3.87); P = 1.37 × 10(-5)). Inactivation of autophagy was associated with shortened survival of breast cancer patients. The prognostic value of the autophagy-related signature was confirmed in the testing dataset GSE3494 (HR = 2.12, 95% CI = (1.48, 3.03); P = 1.65 × 10(-3)) and GSE7390 (HR = 1.76, 95% CI = (1.22, 2.54); P = 9.95 × 10(-4)). Further analysis revealed that the prognostic value of the autophagy signature was independent of known clinical prognostic factors, including age, tumor size, grade, estrogen receptor status, progesterone receptor status, ERBB2 status, lymph node status and TP53 mutation status. Finally, we demonstrated that the autophagy signature could also predict distant metastasis-free survival for breast cancer. © 2015 Wiley Periodicals, Inc.

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

PubMed

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

2004-01-01

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

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

PubMed

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

2010-07-01

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

Prognostic scores in oesophageal or gastric variceal bleeding.

PubMed

Ohmann, C; Stöltzing, H; Wins, L; Busch, E; Thon, K

1990-05-01

Numerous scoring systems have been developed for the prediction of outcome of variceal bleeding; however, only a few have been evaluated adequately. The object of this study was to improve the classical Child-Pugh score (CPS) and to test other scores from the literature. Patients (n = 82) with endoscopically confirmed variceal bleeding and long-term sclerotherapy were included in the study. Linear logistic regression (LR) was applied to different sets of prognostic variables with regard to 30-day mortality. In addition, scores from the literature were evaluated on the data set. Performance was measured by the accuracy and receiver-operating characteristic curves. The application of LR to all five CPS variables (accuracy, 80%) was superior to the classical CPS (70%). LR with selection from the CPS variables or from other sets of variables resulted in no improvement. Compared with CPS only three scores from the literature, mainly based on subsets of the CPS variables, showed an improved accuracy. It is concluded that CPS is still a good scoring system; however, it can be improved by statistical analysis using the same variables.

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.

Examining Preservice Science Teachers' Skills of Formulating Hypotheses and Identifying Variables

ERIC Educational Resources Information Center

Aydogdu, Bülent

2015-01-01

The aim of this study is to examine preservice science teachers' skills of formulating hypotheses and identifying variables. The research has a phenomenological research design. The data was gathered qualitatively. In this study, preservice science teachers were first given two scenarios (Scenario-1 & Scenario-2) containing two different…

Prognostic factors for non-success in patients with sciatica and disc herniation.

PubMed

Haugen, Anne Julsrud; Brox, Jens Ivar; Grøvle, Lars; Keller, Anne; Natvig, Bård; Soldal, Dag; Grotle, Margreth

2012-09-22

Few studies have investigated prognostic factors for patients with sciatica, especially for patients treated without surgery. The aim of this study was to identify factors associated with non-success after 1 and 2 years of follow-up and to test the prognostic value of surgical treatment for sciatica. The study was a prospective multicentre observational study including 466 patients with sciatica and lumbar disc herniation. Potential prognostic factors were sociodemographic characteristics, back pain history, kinesiophobia, emotional distress, pain, comorbidity and clinical examination findings. Study participation did not alter treatment considerations for the patients in the clinics. Patients reported on the questionnaires if surgery of the disc herniation had been performed. Uni- and multivariate logistic regression analyses were used to evaluate factors associated with non-success, defined as Maine-Seattle Back Questionnaire score of ≥5 (0-12) (primary outcome) and Sciatica Bothersomeness Index ≥7 (0-24) (secondary outcome). Rates of non-success were at 1 and 2 years 44% and 39% for the main outcome and 47% and 42% for the secondary outcome. Approximately 1/3 of the patients were treated surgically. For the main outcome variable, in the final multivariate model non-success at 1 year was significantly associated with being male (OR 1.70 [95% CI; 1.06 - 2.73]), smoker (2.06 [1.31 - 3.25]), more back pain (1.0 [1.01 - 1.02]), more comorbid subjective health complaints (1.09 [1.03 - 1.15]), reduced tendon reflex (1.62 [1.03 - 2.56]), and not treated surgically (2.97 [1.75 - 5.04]). Further, factors significantly associated with non-success at 2 years were duration of back problems >; 1 year (1.92 [1.11 - 3.32]), duration of sciatica >; 3 months (2.30 [1.40 - 3.80]), more comorbid subjective health complaints (1.10 [1.03 - 1.17]) and kinesiophobia (1.04 [1.00 - 1.08]). For the secondary outcome variable

Capillary refill: prognostic value in Kenyan children

PubMed Central

Pamba, A; Maitland, K

2004-01-01

Aims: To determine whether delayed capillary refill time (>3 seconds) is a useful prognostic indicator in Kenyan children admitted to hospital. Methods: A total of 4160 children admitted to Kilifi District Hospital with malaria, malarial anaemia, acute respiratory tract infection (ARI), severe anaemia (haemoglobin <50 g/l), gastroenteritis, malnutrition, meningitis, or septicaemia were studied. Results: Overall, delayed capillary refill time (dCRT), present in 346/4160 (8%) of the children, was significantly more common in fatal cases (44/189, 23%) than survivors (7.5%), and had useful prognostic value. In children admitted with malaria, gastroenteritis, or malnutrition, likelihood ratio tests suggested that dCRT was useful in identifying high risk groups for mortality, but its prognostic value in anaemia, ARI, and sepsis was unclear due to low case fatality or limited numbers. The severity features of impaired consciousness and deep breathing were significantly associated both with the presence of dCRT and fatal outcome. In children, with either of these severity features, a less stringent value of dCRT(>2 s) identified 50% of children with hypotension (systolic BP <2SD) and 40% of those requiring volume resuscitation (for metabolic acidosis). Conclusions: Although CRT is a simple bedside test, which may be used in resource poor settings as a guide to the circulatory status, dCRT should not be relied on in the absence of other features of severity. In non-severe disease, the additional presence of hypoxia, a moderately raised creatinine (>80 µmol/l), or a raised white cell count should prompt the need for fluid expansion. PMID:15383440

Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies.

PubMed

Bruix, Jordi; Cheng, Ann-Lii; Meinhardt, Gerold; Nakajima, Keiko; De Sanctis, Yoriko; Llovet, Josep

2017-11-01

Sorafenib, an oral multikinase inhibitor, significantly prolonged overall survival (OS) vs. placebo in patients with unresectable hepatocellular carcinoma (HCC) in two phase III studies, SHARP (Sorafenib HCC Assessment Randomized Protocol) and Asia Pacific (AP). To assess prognostic factors for HCC and predictive factors of sorafenib benefit, we conducted a pooled exploratory analysis from these placebo-controlled phase III studies. To identify potential prognostic factors for OS, univariate and multivariate (MV) analyses were performed for baseline variables by Cox proportional hazards model. Hazard ratios (HRs) and median OS were evaluated across pooled subgroups. To assess factors predictive of sorafenib benefit, the interaction term between treatment for each subgroup was evaluated by Cox proportional hazard model. In 827 patients (448 sorafenib; 379 placebo) analyzed, strong prognostic factors for poorer OS identified from MV analysis in both treatment arms were presence of macroscopic vascular invasion (MVI), high alpha-fetoprotein (AFP), and high neutrophil-to-lymphocyte ratio (NLR; ⩽ vs. >median [3.1]). Sorafenib OS benefit was consistently observed across all subgroups. Significantly greater OS sorafenib benefit vs. placebo was observed in patients without extrahepatic spread (EHS; HR, 0.55 vs. 0.84), with hepatitis C virus (HCV) (HR, 0.47 vs. 0.81), and a low NLR (HR, 0.59 vs. 0.84). In this exploratory analysis, presence of MVI, high AFP, and high NLR were prognostic factors of poorer OS. Sorafenib benefit was consistently observed irrespective of prognostic factors. Lack of EHS, HCV, and lower NLR were predictive of a greater OS benefit with sorafenib. This exploratory pooled analysis showed that treatment with sorafenib provides a survival benefit in all subgroups of patients with HCC; however, the magnitude of benefit is greater in patients with disease confined to the liver (without extrahepatic spread), or in those with hepatitis C virus, or a

Prognostic value of echocardiographic indices of left atrial morphology and function in dogs with myxomatous mitral valve disease.

PubMed

Baron Toaldo, Marco; Romito, Giovanni; Guglielmini, Carlo; Diana, Alessia; Pelle, Nazzareno G; Contiero, Barbara; Cipone, Mario

2018-05-01

The prognostic relevance of left atrial (LA) morphological and functional variables, including those derived from speckle tracking echocardiography (STE), has been little investigated in veterinary medicine. To assess the prognostic value of several echocardiographic variables, with a focus on LA morphological and functional variables in dogs with myxomatous mitral valve disease (MMVD). One-hundred and fifteen dogs of different breeds with MMVD. Prospective cohort study. Conventional morphologic and echo-Doppler variables, LA areas and volumes, and STE-based LA strain analysis were performed in all dogs. A survival analysis was performed to test for the best echocardiographic predictors of cardiac-related death. Most of the tested variables, including all LA STE-derived variables were univariate predictors of cardiac death in Cox proportional hazard analysis. Because of strong correlation between many variables, only left atrium to aorta ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS < 30%), and contraction strain index (CSI per 1% increase) were entered in the univariate analysis, and all were predictors of cardiac death. However, only the MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76-11.24; P < .001) and LAVmax (HR, 2.32; CI, 1.10-4.89; P = .024) remained statistically significant in the multivariable analysis. The assessment of LA dimension and function provides useful prognostic information in dogs with MMVD. Considering all the LA variables, LAVmax appears the strongest predictor of cardiac death, being superior to LA/Ao and STE-derived variables. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Prognostic value of echocardiographic indices of left atrial morphology and function in dogs with myxomatous mitral valve disease

PubMed Central

Romito, Giovanni; Guglielmini, Carlo; Diana, Alessia; Pelle, Nazzareno G.; Contiero, Barbara; Cipone, Mario

2018-01-01

Background The prognostic relevance of left atrial (LA) morphological and functional variables, including those derived from speckle tracking echocardiography (STE), has been little investigated in veterinary medicine. Objectives To assess the prognostic value of several echocardiographic variables, with a focus on LA morphological and functional variables in dogs with myxomatous mitral valve disease (MMVD). Animals One‐hundred and fifteen dogs of different breeds with MMVD. Methods Prospective cohort study. Conventional morphologic and echo‐Doppler variables, LA areas and volumes, and STE‐based LA strain analysis were performed in all dogs. A survival analysis was performed to test for the best echocardiographic predictors of cardiac‐related death. Results Most of the tested variables, including all LA STE‐derived variables were univariate predictors of cardiac death in Cox proportional hazard analysis. Because of strong correlation between many variables, only left atrium to aorta ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS < 30%), and contraction strain index (CSI per 1% increase) were entered in the univariate analysis, and all were predictors of cardiac death. However, only the MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76‐11.24; P < .001) and LAVmax (HR, 2.32; CI, 1.10‐4.89; P = .024) remained statistically significant in the multivariable analysis. Conclusions and Clinical Importance The assessment of LA dimension and function provides useful prognostic information in dogs with MMVD. Considering all the LA variables, LAVmax appears the strongest predictor of cardiac death, being superior to LA/Ao and STE‐derived variables. PMID:29572938

The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4.

PubMed

Pinheiro, Céline; Miranda-Gonçalves, Vera; Longatto-Filho, Adhemar; Vicente, Anna L S A; Berardinelli, Gustavo N; Scapulatempo-Neto, Cristovam; Costa, Ricardo F A; Viana, Cristiano R; Reis, Rui M; Baltazar, Fátima; Vazquez, Vinicius L

2016-06-02

BRAF mutations are known drivers of melanoma development and, recently, were also described as players in the Warburg effect, while this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma patients. Therefore, the aim of this work was to evaluate the expression and prognostic value of a panel of glycolytic metabolism-related proteins in a series of melanomas. The immunohistochemical expression of MCT1, MCT4, GLUT1, and CAIX was evaluated in 356 patients presenting melanoma and 20 patients presenting benign nevi. Samples included 20 benign nevi, 282 primary melanomas, 117 lymph node and 54 distant metastases samples. BRAF mutation was observed in 29/92 (31.5%) melanoma patients and 17/20 (85%) benign nevi samples. NRAS mutation was observed in 4/36 (11.1%) melanoma patients and 1/19 (5.3%) benign nevi samples. MCT4 and GLUT1 expression was significantly increased in metastatic samples, and MCT1, MCT4 and GLUT1 were significantly associated with poor prognostic variables. Importantly, MCT1 and MCT4 were associated with shorter overall survival. In conclusion, the present study brings new insights on metabolic aspects of melanoma, paving the way for the development of new-targeted therapies.

Using prognostic models in CLL to personalize approach to clinical care: Are we there yet?

PubMed

Mina, Alain; Sandoval Sus, Jose; Sleiman, Elsa; Pinilla-Ibarz, Javier; Awan, Farrukh T; Kharfan-Dabaja, Mohamed A

2018-03-01

Four decades ago, two staging systems were developed to help stratify CLL into different prognostic categories. These systems, the Rai and the Binet staging, depended entirely on abnormal exam findings and evidence of anemia and thrombocytopenia. Better understanding of biologic, genetic, and molecular characteristics of CLL have contributed to better appreciating its clinical heterogeneity. New prognostic models, the GCLLSG prognostic index and the CLL-IPI, emerged. They incorporate biologic and genetic information related to CLL and are capable of predicting survival outcomes and cases anticipated to need therapy earlier in the disease course. Accordingly, these newer models are helping develop better informed surveillance strategies and ultimately tailor treatment intensity according to presence (or lack thereof) of certain prognostic markers. This represents a step towards personalizing care of CLL patients. We anticipate that as more prognostic factors continue to be identified, the GCLLSG prognostic index and CLL-IPI models will undergo further revisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognostic value of the oxygen uptake efficiency slope and other exercise variables in patients with coronary artery disease.

PubMed

Coeckelberghs, Ellen; Buys, Roselien; Goetschalckx, Kaatje; Cornelissen, Véronique A; Vanhees, Luc

2016-02-01

Peak exercise capacity is an independent predictor for mortality in patients with coronary artery disease. However, sometimes cardiopulmonary exercise tests are stopped prematurely. Therefore, submaximal exercise measures such as the oxygen uptake efficiency slope have been introduced. The aim of this study was to assess the prognostic value of the oxygen uptake efficiency slope and other exercise parameters, in patients with coronary artery disease. Between 2000 and 2011, 1409 patients with coronary artery disease (age 60.7 ± 9.9 years; 1205 males) underwent cardiopulmonary exercise tests. A maximal effort was not reached in 161 (11.5%) patients. The oxygen uptake efficiency slope was calculated and information on mortality was obtained. Cox proportional hazards regression analyses were used to assess the relation of oxygen uptake efficiency slope and other gas exchange variables with all-cause and cardiovascular mortality. Receiver operating characteristic curve analyses was performed to define optimal cut-off values. During an average follow-up of 7.45 ± 3.20 years (range 0.16-13.95 years), 158 patients died, among which 68 patients for cardiovascular reasons. The oxygen uptake efficiency slope was related to all-cause (hazard ratio: 0.568, p < 0.001) and cardiovascular (hazard ratio: 0.461, p < 0.001) mortality. When significant covariates were entered in the analysis, oxygen uptake efficiency slope remained related to mortality (p < 0.05). When other submaximal exercise parameters were added to the model, oxygen uptake efficiency slope and minute ventilation/carbon dioxide production slope also remained significantly related to mortality. The oxygen uptake efficiency slope is an independent predictor for all-cause and cardiovascular mortality in patients with coronary artery disease, irrespective of a truly maximal effort during cardiopulmonary exercise tests. Furthermore, the oxygen uptake efficiency slope provides prognostic information

Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

PubMed

Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

2017-03-07

Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the

[Biases in the study of prognostic factors].

PubMed

Delgado-Rodríguez, M

1999-01-01

The main objective is to detail the main biases in the study of prognostic factors. Confounding bias is illustrated with social class, a prognostic factor still discussed. Within selection bias several cases are commented: response bias, specially frequent when the patients of a clinical trial are used; the shortcomings in the formation of an inception cohort; the fallacy of Neyman (bias due to the duration of disease) when the study begins with a cross-sectional study; the selection bias in the treatment of survivors for the different treatment opportunity of those living longer; the bias due to the inclusion of heterogeneous diagnostic groups; and the selection bias due to differential information losses and the use of statistical multivariate procedures. Within the biases during follow-up, an empiric rule to value the impact of the number of losses is given. In information bias the Will Rogers' phenomenon and the usefulness of clinical databases are discussed. Lastly, a recommendation against the use of cutoff points yielded by bivariate analyses to select the variable to be included in multivariate analysis is given.

Computed tomographic findings in dogs with head trauma and development of a novel prognostic computed tomography-based scoring system.

PubMed

Chai, Orit; Peery, Dana; Bdolah-Abram, Tali; Moscovich, Efrat; Kelmer, Efrat; Klainbart, Sigal; Milgram, Joshua; Shamir, Merav H

2017-09-01

OBJECTIVE To characterize CT findings and outcomes in dogs with head trauma and design a prognostic scale. ANIMALS 27 dogs admitted to the Koret School Veterinary Teaching Hospital within 72 hours after traumatic head injury that underwent CT imaging of the head. PROCEDURES Data were extracted from medical records regarding dog signalment, history, physical and neurologic examination findings, and modified Glasgow coma scale scores. All CT images were retrospectively evaluated by a radiologist unaware of dog status. Short-term (10 days after trauma) and long-term (≥ 6 months after trauma) outcomes were determined, and CT findings and other variables were analyzed for associations with outcome. A prognostic CT-based scale was developed on the basis of the results. RESULTS Cranial vault fractures, parenchymal abnormalities, or both were identified via CT in 24 of 27 (89%) dogs. Three (11%) dogs had only facial bone fractures. Intracranial hemorrhage was identified in 16 (59%) dogs, cranial vault fractures in 15 (56%), midline shift in 14 (52%), lateral ventricle asymmetry in 12 (44%), and hydrocephalus in 7 (26%). Hemorrhage and ventricular asymmetry were significantly and negatively associated with short- and long-term survival, respectively. The developed 7-point prognostic scale included points for hemorrhage, midline shift or lateral ventricle asymmetry, cranial vault fracture, and depressed fracture (1 point each) and infratentorial lesion (3 points). CONCLUSIONS AND CLINICAL RELEVANCE The findings reported here may assist in determining prognoses for other dogs with head trauma. The developed scale may be useful for outcome assessment of dogs with head trauma; however, it must be validated before clinical application.

A Distributed Approach to System-Level Prognostics

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, Indranil

2012-01-01

Prognostics, which deals with predicting remaining useful life of components, subsystems, and systems, is a key technology for systems health management that leads to improved safety and reliability with reduced costs. The prognostics problem is often approached from a component-centric view. However, in most cases, it is not specifically component lifetimes that are important, but, rather, the lifetimes of the systems in which these components reside. The system-level prognostics problem can be quite difficult due to the increased scale and scope of the prognostics problem and the relative Jack of scalability and efficiency of typical prognostics approaches. In order to address these is ues, we develop a distributed solution to the system-level prognostics problem, based on the concept of structural model decomposition. The system model is decomposed into independent submodels. Independent local prognostics subproblems are then formed based on these local submodels, resul ting in a scalable, efficient, and flexible distributed approach to the system-level prognostics problem. We provide a formulation of the system-level prognostics problem and demonstrate the approach on a four-wheeled rover simulation testbed. The results show that the system-level prognostics problem can be accurately and efficiently solved in a distributed fashion.

Generic Software Architecture for Prognostics (GSAP) User Guide

NASA Technical Reports Server (NTRS)

Teubert, Christopher Allen; Daigle, Matthew John; Watkins, Jason; Sankararaman, Shankar; Goebel, Kai

2016-01-01

The Generic Software Architecture for Prognostics (GSAP) is a framework for applying prognostics. It makes applying prognostics easier by implementing many of the common elements across prognostic applications. The standard interface enables reuse of prognostic algorithms and models across systems using the GSAP framework.

Glycosyltransferase gene expression identifies a poor prognostic colorectal cancer subtype associated with mismatch repair deficiency and incomplete glycan synthesis.

PubMed

Noda, Masaru; Okayama, Hirokazu; Tachibana, Kazunoshin; Sakamoto, Wataru; Saito, Katsuharu; Thar Min, Aung Kyi; Ashizawa, Mai; Nakajima, Takahiro; Aoto, Keita; Momma, Tomoyuki; Katakura, Kyoko; Ohki, Shinji; Kono, Koji

2018-05-29

We aimed to discover glycosyltransferase gene (glycogene)-derived molecular subtypes of colorectal cancer (CRC) associated with patient outcomes. Transcriptomic and epigenomic datasets of non-tumor, pre-cancerous, cancerous tissues and cell lines with somatic mutations, mismatch repair status, clinicopathological and survival information, were assembled (n=4223) and glycogene profiles were analyzed. Immunohistochemistry for a glycogene, GALNT6, was conducted in adenoma and carcinoma specimens (n=403). The functional role and cell surface glycan profiles were further investigated by in vitro loss-of-function assays and lectin microarray analysis. We initially developed and validated a 15-glycogene signature that can identify a poor-prognostic subtype, which closely related to deficient mismatch repair (dMMR) and GALNT6 downregulation. The association of decreased GALNT6 with dMMR was confirmed in multiple datasets of tumors and cell lines, and was further recapitulated by immunohistochemistry, where approximately 15% tumors exhibited loss of GALNT6 protein. GALNT6 mRNA and protein was expressed in premalignant/preinvasive lesions but was subsequently downregulated in a subset of carcinomas, possibly through epigenetic silencing. Decreased GALNT6 was independently associated with poor prognosis in the immunohistochemistry cohort and an additional microarray meta-cohort, by multivariate analyses, and its discriminative power of survival was particularly remarkable in stage III patients. GALNT6 silencing in SW480 cells promoted invasion, migration, chemoresistance and increased cell surface expression of a cancer-associated truncated O-glycan, Tn-antigen. The 15-glycogene signature and the expression levels of GALNT6 mRNA and protein each serve as a novel prognostic biomarker, highlighting the role of dysregulated glycogenes in cancer-associated glycan synthesis and poor prognosis. Copyright ©2018, American Association for Cancer Research.

Bicarbonate can improve the prognostic value of the MELD score for critically ill patients with cirrhosis.

PubMed

Chen, Cheng-Yi; Pan, Chi-Feng; Wu, Chih-Jen; Chen, Han-Hsiang; Chen, Yu-Wei

2014-07-01

The prognosis of critically ill patients with cirrhosis is poor. Our aim was to identify an objective variable that can improve the prognostic value of the Model of End-Stage Liver Disease (MELD) score in patients who have cirrhosis and are admitted to the intensive care unit (ICU). This retrospective cohort study included 177 patients who had liver cirrhosis and were admitted to the ICU. Data pertaining to arterial blood gas-related parameters and other variables were obtained on the day of ICU admission. The overall ICU mortality rate was 36.2%. The bicarbonate (HCO3) level was found to be an independent predictor of ICU mortality (odds ratio, 2.3; 95% confidence interval [CI], 1.0-4.8; p = 0.038). A new equation was constructed (MELD-Bicarbonate) by replacing total bilirubin by HCO3 in the original MELD score. The area under the receiver operating characteristic curve for predicting ICU mortality was 0.76 (95% CI, 0.69-0.84) for the MELD-Bicarbonate equation, 0.73 (95% CI, 0.65-0.81) for the MELD score, and 0.71 (95% CI, 0.63-0.80) for the Acute Physiology and Chronic Health Evaluation II score. Bicarbonate level assessment, as an objective and reproducible laboratory test, has significant predictive value in critically ill patients with cirrhosis. In contrast, the predictive value of total bilirubin is not as prominent in this setting. The MELD-Bicarbonate equation, which included three variables (international normalized ratio, creatinine level, and HCO3 level), showed better prognostic value than the original MELD score in critically ill patients with cirrhosis.

Distilling the Verification Process for Prognostics Algorithms

NASA Technical Reports Server (NTRS)

Roychoudhury, Indranil; Saxena, Abhinav; Celaya, Jose R.; Goebel, Kai

2013-01-01

The goal of prognostics and health management (PHM) systems is to ensure system safety, and reduce downtime and maintenance costs. It is important that a PHM system is verified and validated before it can be successfully deployed. Prognostics algorithms are integral parts of PHM systems. This paper investigates a systematic process of verification of such prognostics algorithms. To this end, first, this paper distinguishes between technology maturation and product development. Then, the paper describes the verification process for a prognostics algorithm as it moves up to higher maturity levels. This process is shown to be an iterative process where verification activities are interleaved with validation activities at each maturation level. In this work, we adopt the concept of technology readiness levels (TRLs) to represent the different maturity levels of a prognostics algorithm. It is shown that at each TRL, the verification of a prognostics algorithm depends on verifying the different components of the algorithm according to the requirements laid out by the PHM system that adopts this prognostics algorithm. Finally, using simplified examples, the systematic process for verifying a prognostics algorithm is demonstrated as the prognostics algorithm moves up TRLs.

Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.

PubMed

Beuschlein, Felix; Weigel, Jens; Saeger, Wolfgang; Kroiss, Matthias; Wild, Vanessa; Daffara, Fulvia; Libé, Rosella; Ardito, Arianna; Al Ghuzlan, Abir; Quinkler, Marcus; Oßwald, Andrea; Ronchi, Cristina L; de Krijger, Ronald; Feelders, Richard A; Waldmann, Jens; Willenberg, Holger S; Deutschbein, Timo; Stell, Anthony; Reincke, Martin; Papotti, Mauro; Baudin, Eric; Tissier, Frédérique; Haak, Harm R; Loli, Paola; Terzolo, Massimo; Allolio, Bruno; Müller, Hans-Helge; Fassnacht, Martin

2015-03-01

Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently. The aim of this study was to identify markers with prognostic value for patients in this clinical setting. From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I-III were identified. As an independent validation cohort, 250 patients from three European countries were included. Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS). Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR] for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10-19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone. This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC.

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

PubMed

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

2016-06-01

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

[Visit-to-visit blood pressure variability: clinical and prognostic significance].

PubMed

Kotovskaia, Iu V; Troitskaia, E A; Kobalava, Zh D

2014-01-01

The phenomenon of variability of blood pressure (BP) was studied for a long time, but recently it has received increased attention, with the focus shifted from short-term BP variability, estimated at daily monitoring for clinical blood pressure variability from visit to visit, which can be regarded as one of the indicators quality control of blood pressure with prolonged treatment. In light of the recent years of clinical data from visit to visit BP variability seems a promising new target for antihypertensive therapy.

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

PubMed

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

2017-08-01

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

Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework.

PubMed

Mijderwijk, Hendrik-Jan; Stolker, Robert Jan; Duivenvoorden, Hugo J; Klimek, Markus; Steyerberg, Ewout W

2018-01-01

Surgical procedures are increasingly carried out in a day-case setting. Along with this increase, psychological outcomes have become prominent. The objective was to evaluate prospectively the prognostic effects of sociodemographic, medical, and psychological variables assessed before day-case surgery on psychological outcomes after surgery. The study was carried out between October 2010 and September 2011. We analyzed 398 mixed patients, from a randomized controlled trial, undergoing day-case surgery at a university medical center. Structural equation modeling was used to jointly study presurgical prognostic variables relating to sociodemographics (age, sex, nationality, marital status, having children, religion, educational level, employment), medical status (BMI, heart rate), and psychological status associated with anxiety (State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS-A)), fatigue (Multidimensional Fatigue Inventory (MFI)), aggression (State-Trait Anger Scale (STAS)), depressive moods (HADS-D), self-esteem, and self-efficacy. We studied psychological outcomes on day 7 after surgery, including anxiety, fatigue, depressive moods, and aggression regulation. The final prognostic model comprised the following variables: anxiety (STAI, HADS-A), fatigue (MFI), depression (HADS-D), aggression (STAS), self-efficacy, sex, and having children. The corresponding psychological variables as assessed at baseline were prominent (i.e. standardized regression coefficients ≥ 0.20), with STAI-Trait score being the strongest predictor overall. STAI-State (adjusted R2 = 0.44), STAI-Trait (0.66), HADS-A (0.45) and STAS-Trait (0.54) were best predicted. We provide a prognostic model that adequately predicts multiple postoperative outcomes in day-case surgery. Consequently, this enables timely identification of vulnerable patients who may require additional medical or psychological preventive treatment or-in a worst-case scenario-could be

Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.

PubMed

Sumazin, Pavel; Chen, Yidong; Treviño, Lisa R; Sarabia, Stephen F; Hampton, Oliver A; Patel, Kayuri; Mistretta, Toni-Ann; Zorman, Barry; Thompson, Patrick; Heczey, Andras; Comerford, Sarah; Wheeler, David A; Chintagumpala, Murali; Meyers, Rebecka; Rakheja, Dinesh; Finegold, Milton J; Tomlinson, Gail; Parsons, D Williams; López-Terrada, Dolores

2017-01-01

Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pretreatment tumors have been molecularly profiled, and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pretreatment HBs at diagnosis. Our analysis of 88 clinically annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated nuclear factor, erythroid 2-like 2 activity; high lin-28 homolog B, high mobility group AT-hook 2, spalt-like transcription factor 4, and alpha-fetoprotein expression; and high coordinated expression of oncofetal proteins and stem-cell markers, while low-risk tumors had low lin-28 homolog B and lethal-7 expression and high hepatic nuclear factor 1 alpha activity. Analysis of immunohistochemical assays using antibodies targeting these genes in a prospective study of 35 HBs suggested that these candidate biomarkers have the potential to improve risk stratification and guide treatment decisions for HB patients at diagnosis; our results pave the way for clinical collaborative studies to validate candidate biomarkers and test their potential to improve outcome for HB patients. (Hepatology 2017;65:104-121). © 2016 by the American Association for the Study of Liver Diseases.

Improving the Prognostic Ability through Better Use of Standard Clinical Data - The Nottingham Prognostic Index as an Example

PubMed Central

Winzer, Klaus-Jürgen; Buchholz, Anika; Schumacher, Martin; Sauerbrei, Willi

2016-01-01

Background Prognostic factors and prognostic models play a key role in medical research and patient management. The Nottingham Prognostic Index (NPI) is a well-established prognostic classification scheme for patients with breast cancer. In a very simple way, it combines the information from tumor size, lymph node stage and tumor grade. For the resulting index cutpoints are proposed to classify it into three to six groups with different prognosis. As not all prognostic information from the three and other standard factors is used, we will consider improvement of the prognostic ability using suitable analysis approaches. Methods and Findings Reanalyzing overall survival data of 1560 patients from a clinical database by using multivariable fractional polynomials and further modern statistical methods we illustrate suitable multivariable modelling and methods to derive and assess the prognostic ability of an index. Using a REMARK type profile we summarize relevant steps of the analysis. Adding the information from hormonal receptor status and using the full information from the three NPI components, specifically concerning the number of positive lymph nodes, an extended NPI with improved prognostic ability is derived. Conclusions The prognostic ability of even one of the best established prognostic index in medicine can be improved by using suitable statistical methodology to extract the full information from standard clinical data. This extended version of the NPI can serve as a benchmark to assess the added value of new information, ranging from a new single clinical marker to a derived index from omics data. An established benchmark would also help to harmonize the statistical analyses of such studies and protect against the propagation of many false promises concerning the prognostic value of new measurements. Statistical methods used are generally available and can be used for similar analyses in other diseases. PMID:26938061

DGKI methylation status modulates the prognostic value of MGMT in glioblastoma patients treated with combined radio-chemotherapy with temozolomide.

PubMed

Etcheverry, Amandine; Aubry, Marc; Idbaih, Ahmed; Vauleon, Elodie; Marie, Yannick; Menei, Philippe; Boniface, Rachel; Figarella-Branger, Dominique; Karayan-Tapon, Lucie; Quillien, Veronique; Sanson, Marc; de Tayrac, Marie; Delattre, Jean-Yves; Mosser, Jean

2014-01-01

Consistently reported prognostic factors for glioblastoma (GBM) are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status. 399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1) and MGMT-methylated patients (population 2). Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2. The nomogram-based stratification of the cohort identified two risk groups (high/low) with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram. Our results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future.

Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule

PubMed Central

Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A.; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

2016-01-01

Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity. PMID:27782157

Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule.

PubMed

Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

2016-10-26

Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity.

Prognostic value of relative adrenal insufficiency after out-of-hospital cardiac arrest.

PubMed

Pene, Frédéric; Hyvernat, Hervé; Mallet, Vincent; Cariou, Alain; Carli, Pierre; Spaulding, Christian; Dugue, Marie-Annick; Mira, Jean-Paul

2005-05-01

To assess the prevalence of relative adrenal insufficiency in patients successfully resuscitated after cardiac arrest, and its prognostic role in post-resuscitation disease. A prospective observational single-center study in a medical intensive care unit. 64 patients hospitalised in the intensive care unit after successful resuscitation for out-of-hospital cardiac arrest. A corticotropin-stimulation test was performed between 12 and 24 h following admission: serum cortisol level was measured before and 60 min after administration of tetracosactide 250 microg. Patients with an incremental response less than 9 microg/dl were considered to have relative adrenal insufficiency (non-responders). Variables were expressed as medians and interquartile ranges. 33 patients (52%) had relative adrenal insufficiency. Baseline cortisol level was higher in non-responders than in responders (41 [27.2-55.5] vs. 22.8 [15.7-35.1] microg/dl respectively, P=0.001). A long interval before initiation of cardiopulmonary resuscitation was associated with relative adrenal insufficiency (5 [3-10] vs. 3 [3-5] min, P=0.03). Of the 38 patients with post-resuscitation shock, 13 died of irreversible multiorgan failure. The presence of relative adrenal insufficiency was identified as a poor prognostic factor of shock-related mortality (log-rank P=0.02). A trend towards higher mortality in non-responders was identified in a multivariate logistic regression analysis (odds ratio 6.77, CI 95% 0.94-48.99, P=0.058). Relative adrenal insufficiency occurs frequently after successful resuscitation of out-of-hospital cardiac arrest, and appears to be associated with a poor prognosis in cases of post-resuscitation shock. The role of corticosteroid supplementation should be evaluated in this setting.

P21, COX-2, and E-cadherin are potential prognostic factors for esophageal squamous cell carcinoma.

PubMed

Lin, Yao; Shen, Lu-Yan; Fu, Hao; Dong, Bin; Yang, He-Li; Yan, Wan-Pu; Kang, Xiao-Zheng; Dai, Liang; Zhou, Hai-Tao; Yang, Yong-Bo; Liang, Zhen; Chen, Ke-Neng

2017-02-01

Much research effort has been devoted to identifying prognostic factors for esophageal squamous cell carcinoma (ESCC) by immunohistochemistry; however, no conclusive findings have been reached thus far. We hypothesized that certain molecules identified in previous studies might serve as useful prognostic markers for ESCC. Therefore, the aim of the current study was to validate the most relevant markers showing potential for ESCC prognosis in our prospective esophageal cancer database. A literature search was performed using the PubMed database for papers published between 1980 and 2015 using the following key words: 'esophageal cancer,' 'prognosis,' and 'immunohistochemistry.' Literature selection criteria were established to identify the most widely studied markers, and we further validated the selected markers in a cohort from our single-surgeon team, including 153 esophageal cancer patients treated from 2000 to 2010. A total of 1799 articles were identified, 82 of which met the selection criteria. Twelve markers were found to be the most widely studied, and the validation results indicated that only P21, COX-2, and E-cadherin were independent prognostic factors for ESCC patients in this series. The systemic review and cohort validation suggest that P21, COX-2, and E-cadherin are potential prognostic factors for ESCC, paving the way for more targeted prospective validation in the future. © 2016 International Society for Diseases of the Esophagus.

A Pilot Proteogenomic Study with Data Integration Identifies MCT1 and GLUT1 as Prognostic Markers in Lung Adenocarcinoma.

PubMed

Stewart, Paul A; Parapatics, Katja; Welsh, Eric A; Müller, André C; Cao, Haoyun; Fang, Bin; Koomen, John M; Eschrich, Steven A; Bennett, Keiryn L; Haura, Eric B

2015-01-01

We performed a pilot proteogenomic study to compare lung adenocarcinoma to lung squamous cell carcinoma using quantitative proteomics (6-plex TMT) combined with a customized Affymetrix GeneChip. Using MaxQuant software, we identified 51,001 unique peptides that mapped to 7,241 unique proteins and from these identified 6,373 genes with matching protein expression for further analysis. We found a minor correlation between gene expression and protein expression; both datasets were able to independently recapitulate known differences between the adenocarcinoma and squamous cell carcinoma subtypes. We found 565 proteins and 629 genes to be differentially expressed between adenocarcinoma and squamous cell carcinoma, with 113 of these consistently differentially expressed at both the gene and protein levels. We then compared our results to published adenocarcinoma versus squamous cell carcinoma proteomic data that we also processed with MaxQuant. We selected two proteins consistently overexpressed in squamous cell carcinoma in all studies, MCT1 (SLC16A1) and GLUT1 (SLC2A1), for further investigation. We found differential expression of these same proteins at the gene level in our study as well as in other public gene expression datasets. These findings combined with survival analysis of public datasets suggest that MCT1 and GLUT1 may be potential prognostic markers in adenocarcinoma and druggable targets in squamous cell carcinoma. Data are available via ProteomeXchange with identifier PXD002622.

Mayo Alliance Prognostic Model for Myelodysplastic Syndromes: Integration of Genetic and Clinical Information.

PubMed

Tefferi, Ayalew; Gangat, Naseema; Mudireddy, Mythri; Lasho, Terra L; Finke, Christy; Begna, Kebede H; Elliott, Michelle A; Al-Kali, Aref; Litzow, Mark R; Hook, C Christopher; Wolanskyj, Alexandra P; Hogan, William J; Patnaik, Mrinal M; Pardanani, Animesh; Zblewski, Darci L; He, Rong; Viswanatha, David; Hanson, Curtis A; Ketterling, Rhett P; Tang, Jih-Luh; Chou, Wen-Chien; Lin, Chien-Chin; Tsai, Cheng-Hong; Tien, Hwei-Fang; Hou, Hsin-An

2018-06-01

To develop a new risk model for primary myelodysplastic syndromes (MDS) that integrates information on mutations, karyotype, and clinical variables. Patients with World Health Organization-defined primary MDS seen at Mayo Clinic (MC) from December 28, 1994, through December 19, 2017, constituted the core study group. The National Taiwan University Hospital (NTUH) provided the validation cohort. Model performance, compared with the revised International Prognostic Scoring System, was assessed by Akaike information criterion and area under the curve estimates. The study group consisted of 685 molecularly annotated patients from MC (357) and NTUH (328). Multivariate analysis of the MC cohort identified monosomal karyotype (hazard ratio [HR], 5.2; 95% CI, 3.1-8.6), "non-MK abnormalities other than single/double del(5q)" (HR, 1.8; 95% CI, 1.3-2.6), RUNX1 (HR, 2.0; 95% CI, 1.2-3.1) and ASXL1 (HR, 1.7; 95% CI, 1.2-2.3) mutations, absence of SF3B1 mutations (HR, 1.6; 95% CI, 1.1-2.4), age greater than 70 years (HR, 2.2; 95% CI, 1.6-3.1), hemoglobin level less than 8 g/dL in women or less than 9 g/dL in men (HR, 2.3; 95% CI, 1.7-3.1), platelet count less than 75 × 10 9 /L (HR, 1.5; 95% CI, 1.1-2.1), and 10% or more bone marrow blasts (HR, 1.7; 95% CI, 1.1-2.8) as predictors of inferior overall survival. Based on HR-weighted risk scores, a 4-tiered Mayo alliance prognostic model for MDS was devised: low (89 patients), intermediate-1 (104), intermediate-2 (95), and high (69); respective median survivals (5-year overall survival rates) were 85 (73%), 42 (34%), 22 (7%), and 9 months (0%). The Mayo alliance model was subsequently validated by using the external NTUH cohort and, compared with the revised International Prognostic Scoring System, displayed favorable Akaike information criterion (1865 vs 1943) and area under the curve (0.87 vs 0.76) values. We propose a simple and contemporary risk model for MDS that is based on a limited set of genetic and clinical variables

Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma

PubMed Central

Pinto, A; Andre, S; Pereira, T; Nobrega, S; Soares, J

2001-01-01

Aims—To investigate the prognostic value of recently proposed flow cytometric S-phase fraction (SPF) variables (average SPF and SPF tertiles) compared with conventional SPF, and to compare the one with the best predictive value with the immunohistochemical Ki-67 index in breast carcinoma. Methods—A short term follow up study (median, 39.6 months) of a large series of patients (n = 306) was conducted. DNA ploidy was analysed on fresh/frozen tumour samples by flow cytometry, and the SPF was calculated from the DNA histogram using an algorithm. The Ki-67 index was assessed on paraffin wax embedded material by immunohistochemistry (cut off point, 10%). The two methods were compared by means of κ statistics, and the prognostic significance of both in relation to disease free survival (DFS) and overall survival (OS) was determined. Results—SPF and Ki-67 analysis was performed on 234 (76.5%) and 295 (96.4%) tumours, respectively. The two assessments were simultaneously available in 230 cases. All SPF variables analysed in the whole series significantly correlated with disease evolution, with the conventional median SPF (cut off point, 6.1%) showing the highest predictive value in relation to both DFS (p = 0.0001) and OS (p = 0.0003). SPF tertiles and median SPF evaluated according to DNA ploidy status had no prognostic significance. The Ki-67 index showed a trend in relation to DFS (p = 0.086) that did not reach significance, and no correlation with OS was found (p = 0.264). The comparative analysis of SPF and Ki-67 revealed some agreement between the two methods (agreement, 69.13%; κ statistic, 0.3844; p < 0.001), especially in the subgroup of diploid tumours. Conclusions—Flow cytometric SPF is a better prognosticator than the Ki-67 index, but only SPF variables applied in the whole series show potential clinical usefulness. Key Words: breast carcinoma • DNA flow cytometry • immunohistochemistry • S-phase fraction • Ki-67 • prognosis PMID:11429427

Marital status is a prognostic factor in amyotrophic lateral sclerosis.

PubMed

Spataro, R; Volanti, P; Lo Coco, D; La Bella, V

2017-12-01

Several variables have been linked to a shorter survival in patients with amyotrophic lateral sclerosis (ALS), for example, female sex, older age, site of disease onset, rapid disease progression, and a relatively short diagnostic delay. With regard to marital status, previous studies suggested that living with a partner might be associated to a longer survival and a higher likelihood to proceed to tracheostomy. Therefore, to further strengthen this hypothesis, we investigated the role of marital status as a prognostic variable in a cohort of ALS patients. We performed a retrospective analysis on 501 consecutive ALS patients for which a complete disease's natural history and clinical/demographic data were available. At diagnosis, 409 patients (81.6%) were married or lived with a stable partner, whereas 92 patients (18.4%) were single/widowed/divorced. In our ALS cohort, being married was associated with a median longer survival (married, 35 months [24-50] vs unmarried, 27 months [18-42]; P<.004). Moreover, married and unmarried patients were significantly different in many clinical and demographic variables, including age at disease onset, gender, body mass index, and number of children. Cox regression analysis showed that age at onset, diagnostic delay, and marital status were independent predictors of survival. In unmarried patients, female sex was also significantly associated with shorter survival. Marital status is a prognostic factor in ALS, and it significantly affects survival. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Model-Based Prognostics of Hybrid Systems

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Roychoudhury, Indranil; Bregon, Anibal

2015-01-01

Model-based prognostics has become a popular approach to solving the prognostics problem. However, almost all work has focused on prognostics of systems with continuous dynamics. In this paper, we extend the model-based prognostics framework to hybrid systems models that combine both continuous and discrete dynamics. In general, most systems are hybrid in nature, including those that combine physical processes with software. We generalize the model-based prognostics formulation to hybrid systems, and describe the challenges involved. We present a general approach for modeling hybrid systems, and overview methods for solving estimation and prediction in hybrid systems. As a case study, we consider the problem of conflict (i.e., loss of separation) prediction in the National Airspace System, in which the aircraft models are hybrid dynamical systems.

Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification.

PubMed

Andreiuolo, Felipe; Le Teuff, Gwénaël; Bayar, Mohamed Amine; Kilday, John-Paul; Pietsch, Torsten; von Bueren, André O; Witt, Hendrik; Korshunov, Andrey; Modena, Piergiorgio; Pfister, Stefan M; Pagès, Mélanie; Castel, David; Giangaspero, Felice; Chimelli, Leila; Varlet, Pascale; Rutkowski, Stefan; Frappaz, Didier; Massimino, Maura; Grundy, Richard; Grill, Jacques

2017-01-01

Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS) was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed. Among complete cases with 5-year median follow-up (n = 470; 131 deaths), TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR) = 2.19 95%CI = [1.29; 3.76] (p = 0.004), while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004) in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295) in supratentorial (interaction p value = 0.015). The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group. Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma.

Identifying Student Difficulties with Control of Variables Reasoning

NASA Astrophysics Data System (ADS)

Boudreaux, Andrew

2005-03-01

Emerging standards for the science learning of precollege students can be regarded as a statement of what constitutes science literacy.^1 These standards emphasize basic concepts such as mass, volume and density, and fundamental process skills such as proportional reasoning, the interpretation of graphs and other representations, and the control of variables in the design of experiments. At Western Washington University, the liberal arts physics course is a general university requirement and for many students one of the only physical science course taken between high school and college graduation. Thus the pre-course understandings of these students can be taken as a measure of the level of science literacy attained in precollege education. An effort is underway at Western Washington University to examine what students know and are able to do both before and after course instruction. Preliminary results indicate that in many cases students have serious conceptual and reasoning difficulties with the material. An example that involves the interpretation of experimental results in deciding whether a particular variable influences (i.e., affects) or determines (i.e., predicts) a given result will be discussed. Evidence from written questions will be presented to identify specific student difficulties.^1See, for example, Project 2061, American Association for the Advancement of Science. 1990. Science for All Americans.New York, NY: Oxford University Press.

Perioperative and long-term outcome of thymectomy for myasthenia gravis: comparison of surgical approaches and prognostic analysis.

PubMed

Liu, Cheng-wu; Luo, Meng; Mei, Jian-dong; Zhu, Yun-ke; Pu, Qiang; Ma, Lin; Che, Guo-wei; Lin, Yi-dan; Wu, Zhu; Wang, Yun; Kou, Ying-li; Liu, Lun-xu

2013-01-01

Thymectomy is an established treatment for myasthenia gravis (MG), and video-assisted thoracoscopic surgery (VATS) thymectomy has become an acceptable surgical procedure. This study aimed to compare the results of VATS thymectomy and open thymectomy and to identify the prognostic factors after thymectomy. The clinical data of 187 consecutive thymectomies performed between July 2000 and December 2009 were retrospectively reviewed; 75 open thymectomies and 112 VATS thymectomies. Clinical efficacy and variables influencing outcome were assessed by Kaplan-Meier survival curves and Cox proportional hazards regression analysis. The operative blood loss in the VATS group was significantly less than that in the open group ((62.14 ± 55.43) ml vs. (137.87 ± 165.25) ml, P < 0.05). The postoperative crisis rate increased with the severity of preoperative MG and the prescription dose of anticholinesterase. Complete follow-up information of patients more than 12 months after the thymectomy was obtained on 151 cases, 89 cases from the VATS group and 62 cases from the open group, with a mean follow-up period of 59.3 months, range from 12 to 117 months. Complete stable remission (CSR) was the end point for evaluation of the treatment results. The overall five-year CSR rate was 57.5%. Two good prognostic factors were identified; preoperative prescription of anticholinesterase alone (P = 0.035) and non-thymomatous MG (P = 0.003). The five-year CSR rate of the ocular type of MG reached a high level of 67.4%. Thymectomy can achieve good long-term CSR in MG, and VATS is an ideal alternative method. High-dose prescription of anticholinesterase and the advanced stage by Myasthenia Gravis Foundation of America (MGFA) classification have higher risks of postoperative crisis. Preoperative prescription of anticholinesterase alone and non-thymomatous MG are good prognostic factors. Thymectomy should also be considered for the ocular type of MG.

Prognostic indicators associated with early mortality of wild raptors admitted to a wildlife rehabilitation centre in Spain.

PubMed

Molina-López, Rafael A; Casal, Jordi; Darwich, Laila

2015-03-01

Assessment of the prognostic indicators of wildlife casualties is critical in wildlife rehabilitation practice, to optimize the use of economical resources, and to protect animal welfare. Few studies have been conducted in this field. To identify the prognostic indicators associated with raptor mortality during the first week of hospitalization. Complete medical records of 1722 wild raptor cases admitted to a wildlife rehabilitation centre from 1995 to 2007 were used. Regression models were created to determine mortality-related factors for different variables (order, sex, body condition (BC), clinical signs, and available haematological and biochemical parameters). In the bivariate analysis, the presence of nervous (OR = 11.9, 95%CI:5.1-27.6) or musculoskeletal (OR = 12.1, 95%CI:5.8-25.3) signs, a poor BC (OR = 32.9, 95%CI:19-81.2), and low values of packed cell volume (PCV), haemoglobin or total solids (TS), were all associated with early mortality. After adjusting variables in the multivariate model, BC was excluded due to co-linearity with other variables, and alteration of the nervous system was the only significant risk factor (OR = 4.0; 95%CI:1.9-8.8). In species specific analysis, poor prognosis was related to neurological signs in Athene noctua, poor BC in Strix aluco, trauma in Acciptiter nisus and Tyto alba, low PCV in Buteo buteo and Falco tinnunculus and low TS in Falco tinnunculus. Raptors with a poor BC, low values of PCV and those presenting with neurological signs, had the highest risk of dying in the first days of admittance. Thus, either medical care or humane euthanasia for poor prognosis should be performed to address animal welfare.

TEPAPA: a novel in silico feature learning pipeline for mining prognostic and associative factors from text-based electronic medical records.

PubMed

Lin, Frank Po-Yen; Pokorny, Adrian; Teng, Christina; Epstein, Richard J

2017-07-31

Vast amounts of clinically relevant text-based variables lie undiscovered and unexploited in electronic medical records (EMR). To exploit this untapped resource, and thus facilitate the discovery of informative covariates from unstructured clinical narratives, we have built a novel computational pipeline termed Text-based Exploratory Pattern Analyser for Prognosticator and Associator discovery (TEPAPA). This pipeline combines semantic-free natural language processing (NLP), regular expression induction, and statistical association testing to identify conserved text patterns associated with outcome variables of clinical interest. When we applied TEPAPA to a cohort of head and neck squamous cell carcinoma patients, plausible concepts known to be correlated with human papilloma virus (HPV) status were identified from the EMR text, including site of primary disease, tumour stage, pathologic characteristics, and treatment modalities. Similarly, correlates of other variables (including gender, nodal status, recurrent disease, smoking and alcohol status) were also reliably recovered. Using highly-associated patterns as covariates, a patient's HPV status was classifiable using a bootstrap analysis with a mean area under the ROC curve of 0.861, suggesting its predictive utility in supporting EMR-based phenotyping tasks. These data support using this integrative approach to efficiently identify disease-associated factors from unstructured EMR narratives, and thus to efficiently generate testable hypotheses.

Distributed Prognostic Health Management with Gaussian Process Regression

NASA Technical Reports Server (NTRS)

Saha, Sankalita; Saha, Bhaskar; Saxena, Abhinav; Goebel, Kai Frank

2010-01-01

Distributed prognostics architecture design is an enabling step for efficient implementation of health management systems. A major challenge encountered in such design is formulation of optimal distributed prognostics algorithms. In this paper. we present a distributed GPR based prognostics algorithm whose target platform is a wireless sensor network. In addition to challenges encountered in a distributed implementation, a wireless network poses constraints on communication patterns, thereby making the problem more challenging. The prognostics application that was used to demonstrate our new algorithms is battery prognostics. In order to present trade-offs within different prognostic approaches, we present comparison with the distributed implementation of a particle filter based prognostics for the same battery data.

Interobserver variability in identification of breast tumors in MRI and its implications for prognostic biomarkers and radiogenomics

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

Saha, Ashirbani, E-mail: as698@duke.edu; Grimm, La

Purpose: To assess the interobserver variability of readers when outlining breast tumors in MRI, study the reasons behind the variability, and quantify the effect of the variability on algorithmic imaging features extracted from breast MRI. Methods: Four readers annotated breast tumors from the MRI examinations of 50 patients from one institution using a bounding box to indicate a tumor. All of the annotated tumors were biopsy proven cancers. The similarity of bounding boxes was analyzed using Dice coefficients. An automatic tumor segmentation algorithm was used to segment tumors from the readers’ annotations. The segmented tumors were then compared between readersmore » using Dice coefficients as the similarity metric. Cases showing high interobserver variability (average Dice coefficient <0.8) after segmentation were analyzed by a panel of radiologists to identify the reasons causing the low level of agreement. Furthermore, an imaging feature, quantifying tumor and breast tissue enhancement dynamics, was extracted from each segmented tumor for a patient. Pearson’s correlation coefficients were computed between the features for each pair of readers to assess the effect of the annotation on the feature values. Finally, the authors quantified the extent of variation in feature values caused by each of the individual reasons for low agreement. Results: The average agreement between readers in terms of the overlap (Dice coefficient) of the bounding box was 0.60. Automatic segmentation of tumor improved the average Dice coefficient for 92% of the cases to the average value of 0.77. The mean agreement between readers expressed by the correlation coefficient for the imaging feature was 0.96. Conclusions: There is a moderate variability between readers when identifying the rectangular outline of breast tumors on MRI. This variability is alleviated by the automatic segmentation of the tumors. Furthermore, the moderate interobserver variability in terms of the

Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

PubMed Central

Li, Yong-Jiang; Yang, Xi; Zhang, Wen-Biao; Yi, Cheng; Wang, Feng; Li, Ping

2017-01-01

Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte–monocyte ratio (LMR), and neutrophil–platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma. PMID:29033609

Prognostic indicators of poor short-term outcome of physiotherapy intervention in women with stress urinary incontinence.

PubMed

Hendriks, Erik J M; Kessels, Alfons G H; de Vet, Henrica C W; Bernards, Arnold T M; de Bie, Rob A

2010-03-01

To identify prognostic indicators independently associated with poor outcome of physiotherapy intervention in women with primary or recurrent stress urinary incontinence (stress UI). A prospective cohort study was performed in physiotherapy practices in primary care to identify prognostic indicators 12 weeks after initiation of physiotherapy intervention. Patients were referred by general practitioners or urogynecologists. Risk factors for stress UI were examined as potential prognostic indicators of poor outcome. The primary outcomes were defined as poor outcome on the binary Leakage Severity scale (LS scale) and the binary global perceived effectiveness (GPE) score. Two hundred sixty-seven women, with a mean age of 47.7 (SD = 8.3), with stress UI for at least 6 months were included. At 12 weeks, 43% and 59% of the women were considered recovered on the binary LS scale and the binary GPE score, respectively. Prognostic indicators associated with poor outcome included 11 indicators based on the binary LS scale and 8 based on the binary GPE score. The prognostic indicators shared by both models show that poor recovery was associated with women with severe stress UI, POP-Q stage > II, poor outcome of physiotherapy intervention for a previous UI episode, prolonged second stage of labor, BMI > 30, high psychological distress, and poor physical health. This study provides robust evidence of clinically meaningful prognostic indicators of poor short-term outcome. These findings need to be confirmed by replication studies. (c) 2009 Wiley-Liss, Inc.

Comparative effectiveness of incorporating a hypothetical DCIS prognostic marker into breast cancer screening.

PubMed

Trentham-Dietz, Amy; Ergun, Mehmet Ali; Alagoz, Oguzhan; Stout, Natasha K; Gangnon, Ronald E; Hampton, John M; Dittus, Kim; James, Ted A; Vacek, Pamela M; Herschorn, Sally D; Burnside, Elizabeth S; Tosteson, Anna N A; Weaver, Donald L; Sprague, Brian L

2018-02-01

Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Prognostic scores after surgical treatment for cervical intraepithelial neoplasia: a proposed model and possible implications for post-operative follow-up.

PubMed

Andrade, Carlos E M C; Scapulatempo-Neto, Cristovam; Longatto-Filho, Adhemar; Vieira, Marcelo A; Tsunoda, Audrey T; Da Silva, Ismael D C G; Fregnani, José Humberto T G

2014-09-01

To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia. Cohort study. Patient inclusion and follow-up occurred retrospectively and prospectively. Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Women (n = 242) diagnosed with cervical intraepithelial neoplasia who were submitted to conization. Immediately prior to surgical treatment, a cervical cytology sample was collected from each individual included in the study by endocervical brushing and stored in a preservative solution with methanol. A human papilloma virus-DNA test was conducted using an aliquot of the endocervical brushings. The surgical specimens were subjected to immunohistochemical analysis of p16 (immunohistochemical analysis 4a) protein expression. Two-year disease-free survival rates calculated for each study variable. Identified variables in the multivariate Cox model were used for elaboration of prognostic scores. Variables associated with outcome included age (p = 0.033), tobacco use (p < 0.001), final histopathological diagnosis (p = 0.007), surgical margins (p < 0.001), high-risk human papilloma virus status (p = 0.008), human papilloma virus-16 status (p < 0.001) and immunoexpression of p16 in the cytoplasm (p = 0.049). By the Cox model, independent risk factors for disease recurrence/persistence were: tobacco use (hazard risk = 3.0; 95% confidence interval 1.6-5.6), positive surgical margins (hazard risk = 3.2; 95% confidence interval 1.6-6.1), human papilloma virus-16 (hazard risk = 3.3; 95% confidence interval 1.6-6.9) and age over 45 years (hazard risk = 2.7; 95% confidence interval 1.1-6.6). Establishment of a prognostic score can represent a valuable tool for determining the risk of cervical intraepithelial neoplasia recurrence after conization. The use of clinical (age and tobacco use), pathological (surgical margins) and molecular (human papilloma virus-16 genotyping) factors can facilitate more

Prognostic factors versus markers of response to treatment versus surrogate endpoints: Three different concepts.

PubMed

Sormani, Maria Pia

2017-03-01

Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments.

Conventional clinical and prognostic variables in 150 oral squamous cell carcinoma cases from the indigenous population of Karachi

PubMed Central

Alamgir, Muhammad Mohiuddin; Jamal, Qamar; Mirza, Talat

2016-01-01

Objective: To analyze clinical and prognostic variables of Oral Squamous Cell Carcinoma (OSCC) cases from the indigenous population of Karachi and to correlate with the common risk factor of tobacco habit. Methods: The study was conducted at Ziauddin University, Karachi. One hundred fifty OSCC cases were collected from the Oncology Department of Ziauddin University Hospital, North Nazimabad, Karachi and Otolaryngology ward of Civil Hospital, Karachi, during 2011 and 2015. The reporting included demographic details and variables like intra-oral subsites, clinical stage and histological grade. Recurrence of tumor after initial resection was also documented. Results: The patient’s population comprised of 98 males and 52 females. The mean age was 47.1± 12.22 (range:20-78 years). Maximum numbers were seen in the 41–50 years age group. Urdu-speaking community was the most affected ethnic group (n=75). Clinico-pathological analysis revealed that majority of cases were moderately differentiated (59%) and were either clinical stage II (35%) or IV (29%) tumors. The most common intra-oral subsite came out to be buccal mucosa of cheeks (56%) followed by lateral borders of tongue (21%), lips (13%), alveolar (6%), palate (2.6%) floor of mouth (1.3%), etc. Recurrence was observed in 08 out of 150 cases. All patients underwent primary resection±neck dissection and reconstruction where possible. Conclusions: Overall experience with oral squamous cell carcinoma shows that it has a high tendency for local invasion as well as dissemination to regional lymph nodes, i.e. cervical lymph nodes, both are associated with a poor prognosis. Preventable risk factor of tobacco chewing has been observed in majority of these cases. PMID:27375712

Conventional clinical and prognostic variables in 150 oral squamous cell carcinoma cases from the indigenous population of Karachi.

PubMed

Alamgir, Muhammad Mohiuddin; Jamal, Qamar; Mirza, Talat

2016-01-01

To analyze clinical and prognostic variables of Oral Squamous Cell Carcinoma (OSCC) cases from the indigenous population of Karachi and to correlate with the common risk factor of tobacco habit. The study was conducted at Ziauddin University, Karachi. One hundred fifty OSCC cases were collected from the Oncology Department of Ziauddin University Hospital, North Nazimabad, Karachi and Otolaryngology ward of Civil Hospital, Karachi, during 2011 and 2015. The reporting included demographic details and variables like intra-oral subsites, clinical stage and histological grade. Recurrence of tumor after initial resection was also documented. The patient's population comprised of 98 males and 52 females. The mean age was 47.1± 12.22 (range:20-78 years). Maximum numbers were seen in the 41-50 years age group. Urdu-speaking community was the most affected ethnic group (n=75). Clinico-pathological analysis revealed that majority of cases were moderately differentiated (59%) and were either clinical stage II (35%) or IV (29%) tumors. The most common intra-oral subsite came out to be buccal mucosa of cheeks (56%) followed by lateral borders of tongue (21%), lips (13%), alveolar (6%), palate (2.6%) floor of mouth (1.3%), etc. Recurrence was observed in 08 out of 150 cases. All patients underwent primary resection±neck dissection and reconstruction where possible. Overall experience with oral squamous cell carcinoma shows that it has a high tendency for local invasion as well as dissemination to regional lymph nodes, i.e. cervical lymph nodes, both are associated with a poor prognosis. Preventable risk factor of tobacco chewing has been observed in majority of these cases.

Prognostic factors for non-success in patients with sciatica and disc herniation

PubMed Central

2012-01-01

Background Few studies have investigated prognostic factors for patients with sciatica, especially for patients treated without surgery. The aim of this study was to identify factors associated with non-success after 1 and 2 years of follow-up and to test the prognostic value of surgical treatment for sciatica. Methods The study was a prospective multicentre observational study including 466 patients with sciatica and lumbar disc herniation. Potential prognostic factors were sociodemographic characteristics, back pain history, kinesiophobia, emotional distress, pain, comorbidity and clinical examination findings. Study participation did not alter treatment considerations for the patients in the clinics. Patients reported on the questionnaires if surgery of the disc herniation had been performed. Uni- and multivariate logistic regression analyses were used to evaluate factors associated with non-success, defined as Maine–Seattle Back Questionnaire score of ≥5 (0–12) (primary outcome) and Sciatica Bothersomeness Index ≥7 (0–24) (secondary outcome). Results Rates of non-success were at 1 and 2 years 44% and 39% for the main outcome and 47% and 42% for the secondary outcome. Approximately 1/3 of the patients were treated surgically. For the main outcome variable, in the final multivariate model non-success at 1 year was significantly associated with being male (OR 1.70 [95% CI; 1.06 − 2.73]), smoker (2.06 [1.31 − 3.25]), more back pain (1.0 [1.01 − 1.02]), more comorbid subjective health complaints (1.09 [1.03 − 1.15]), reduced tendon reflex (1.62 [1.03 − 2.56]), and not treated surgically (2.97 [1.75 − 5.04]). Further, factors significantly associated with non-success at 2 years were duration of back problems >; 1 year (1.92 [1.11 − 3.32]), duration of sciatica >; 3 months (2.30 [1.40 − 3.80]), more comorbid subjective health complaints (1.10 [1.03 − 1.17]) and kinesiophobia (1.04 [1

A Linearized Prognostic Cloud Scheme in NASAs Goddard Earth Observing System Data Assimilation Tools

NASA Technical Reports Server (NTRS)

Holdaway, Daniel; Errico, Ronald M.; Gelaro, Ronald; Kim, Jong G.; Mahajan, Rahul

2015-01-01

A linearized prognostic cloud scheme has been developed to accompany the linearized convection scheme recently implemented in NASA's Goddard Earth Observing System data assimilation tools. The linearization, developed from the nonlinear cloud scheme, treats cloud variables prognostically so they are subject to linearized advection, diffusion, generation, and evaporation. Four linearized cloud variables are modeled, the ice and water phases of clouds generated by large-scale condensation and, separately, by detraining convection. For each species the scheme models their sources, sublimation, evaporation, and autoconversion. Large-scale, anvil and convective species of precipitation are modeled and evaporated. The cloud scheme exhibits linearity and realistic perturbation growth, except around the generation of clouds through large-scale condensation. Discontinuities and steep gradients are widely used here and severe problems occur in the calculation of cloud fraction. For data assimilation applications this poor behavior is controlled by replacing this part of the scheme with a perturbation model. For observation impacts, where efficiency is less of a concern, a filtering is developed that examines the Jacobian. The replacement scheme is only invoked if Jacobian elements or eigenvalues violate a series of tuned constants. The linearized prognostic cloud scheme is tested by comparing the linear and nonlinear perturbation trajectories for 6-, 12-, and 24-h forecast times. The tangent linear model performs well and perturbations of clouds are well captured for the lead times of interest.

A novel prognostic six-CpG signature in glioblastomas.

PubMed

Yin, An-An; Lu, Nan; Etcheverry, Amandine; Aubry, Marc; Barnholtz-Sloan, Jill; Zhang, Lu-Hua; Mosser, Jean; Zhang, Wei; Zhang, Xiang; Liu, Yu-He; He, Ya-Long

2018-03-01

We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation. An integrative analysis of multidimensional TCGA data was performed to molecularly characterize different risk tumors. The six-CpG risk-score signature robustly predicted overall survival (OS) in all discovery and validation cohorts and in a treatment-independent manner. It also predicted progression-free survival (PFS) in available patients. The multimarker epigenetic signature was demonstrated as an independent prognosticator and had better performance than known molecular indicators such as glioma-CpG island methylator phenotype (G-CIMP) and proneural subtype. The defined risk subgroups were molecularly distinct; high-risk tumors were biologically more aggressive with concordant activation of proangiogenic signaling at multimolecular levels. Accordingly, we observed better OS benefits of bevacizumab-contained therapy to high-risk patients in independent sets, supporting its implication in guiding usage of antiangiogenic therapy. Finally, the six-CpG signature refined the risk classification based on G-CIMP and MGMT methylation status. The novel six-CpG signature is a robust and independent prognostic indicator for GBMs and is of promising value to improve personalized management. © 2018 John Wiley & Sons Ltd.

Identifying Useful Auxiliary Variables for Incomplete Data Analyses: A Note on a Group Difference Examination Approach

ERIC Educational Resources Information Center

Raykov, Tenko; Marcoulides, George A.

2014-01-01

This research note contributes to the discussion of methods that can be used to identify useful auxiliary variables for analyses of incomplete data sets. A latent variable approach is discussed, which is helpful in finding auxiliary variables with the property that if included in subsequent maximum likelihood analyses they may enhance considerably…

Prognostic factors in children with acute myeloid leukaemia and excellent response to remission induction therapy.

PubMed

Karol, Seth E; Coustan-Smith, Elaine; Cao, Xueyuan; Shurtleff, Sheila A; Raimondi, Susana C; Choi, John K; Ribeiro, Raul C; Dahl, Gary V; Bowman, William Paul; Taub, Jeffrey W; Degar, Barbara; Leung, Wing; Downing, James R; Pui, Ching-Hon; Rubnitz, Jeffrey E; Campana, Dario; Inaba, Hiroto

2015-01-01

Minimal residual disease (MRD) is a strong prognostic factor in children and adolescents with acute myeloid leukaemia (AML) but nearly one-quarter of patients who achieve MRD-negative status still relapse. The adverse prognostic factors among MRD-negative patients remain unknown. We analysed the AML02 study cohort to identify demographic and genetic prognostic factors. Among the presenting features, certain 11q23 abnormalities, such as t(6;11) and t(10;11), acute megakaryoblastic leukaemia without the t(1;22), and age ≥10 years were associated with inferior outcome in patients who had MRD-negative status after either remission induction I or II. By contrast, those with rearrangement of CBF genes had superior outcome. Our study identifies patient populations for whom close post-remission MRD monitoring to detect and treat emerging relapse and adjustment in treatment intensity might be indicated. © 2014 John Wiley & Sons Ltd.

Prognostic factors for early severity in a childhood multiple sclerosis cohort.

PubMed

Mikaeloff, Yann; Caridade, Guillaume; Assi, Saada; Suissa, Samy; Tardieu, Marc

2006-09-01

The goal was to identify prognostic factors for an early severe course in a cohort of patients with childhood-onset multiple sclerosis, for the construction of a predictive tool. The cohort consisted of 197 children from the French Kid Sclérose en Plaques neuropediatric cohort with relapsing/remitting multiple sclerosis beginning before the age of 16 years. Patients were included from 1990 to 2003. We used multivariate survival analysis (Cox model) to evaluate the prognostic value of clinical, MRI, and biological covariates at onset for the occurrence of a third attack or severe disability ("severity" outcome). The cohort was monitored for a mean of 5.5 +/- 3.6 years. The "severity" outcome was recorded for 144 patients (73%). The risk of severity was higher for girls, for a time between the first and second attacks of < 1 year, for childhood-onset multiple sclerosis MRI criteria at onset, for an absence of severe mental state changes at onset, and for a progressive course. A derived childhood-onset multiple sclerosis potential index for early severity was found to have a positive predictive value for severity of > 35% for the upper 2 quartiles. The clinical and MRI prognostic factors for early severity that were identified were used as the basis of a predictive tool, which will be validated in another cohort. This tool should make it possible to identify subgroups at risk of early severe disease and should facilitate therapeutic studies.

Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography.

PubMed

Abidov, Aiden; Hachamovitch, Rory; Rozanski, Alan; Hayes, Sean W; Santos, Marcia M; Sciammarella, Maria G; Cohen, Ishac; Gerlach, James; Friedman, John D; Germano, Guido; Berman, Daniel S

2004-09-01

The aim of this research was to determine whether presence of atrial fibrillation (AF) provides incremental prognostic information relative to myocardial perfusion single-photon emission computed tomography (MPS) with respect to risk of cardiac death (CD). The prognostic significance of AF in patients undergoing MPS is not known. A total of 16,048 consecutive patients undergoing MPS were followed-up for a mean of 2.21 +/- 1.15 years for the development of CD. Of those, 384 patients (2.4%) had AF. Cox proportional hazards method was used to compare clinical and perfusion data for the prediction of CD in patients with and without AF. Atrial fibrillation was a significant predictor of CD in patients with normal (1.6% per year vs. 0.4% per year in non-AF patients), mildly abnormal (6.3% per year vs. 1.2% per year), and severely abnormal MPS (6.4% per year vs. 3.7% per year) (p < 0.001 for all). By multivariable analysis, AF patients had worse survival (p = 0.001) even after adjustment for the variables most predictive of CD: age, diabetes, shortness of breath, use of vasodilator stress, rest heart rate, and the nuclear variables. In the 4,239 patients with left ventricular ejection fraction evaluated by gated MPS, AF demonstrated incremental prognostic value not only over clinical and nuclear variables, but also over left ventricular ejection in predicting CD (p = 0.014). The presence of AF independently increases the risk of cardiac events over perfusion and function variables in patients undergoing MPS. Patients with AF have a high risk of CD, even when MPS is only mildly abnormal. Whether patients with AF and mildly abnormal MPS constitute a group more deserving of early referral to cardiac catheterization is a question warranting further study.

Combination immunohistochemistry for SMAD4 and Runt-related transcription factor 3 may identify a favorable prognostic subgroup of pancreatic ductal adenocarcinomas.

PubMed

Lee, Yangkyu; Lee, Hyejung; Park, Hyunjin; Kim, Jin-Won; Hwang, Jin-Hyeok; Kim, Jaihwan; Yoon, Yoo-Seok; Han, Ho-Seong; Kim, Haeryoung

2017-09-29

SMAD4/DPC4 mutations have been associated with aggressive behavior in pancreatic ductal adenocarcinomas (PDAC), and it has recently been suggested that RUNX3 expression combined with SMAD4 status may predict the metastatic potential of PDACs. We evaluated the prognostic utility of SMAD4/RUNX3 status in human PDACs by immunohistochemistry. Immunohistochemical stains were performed for SMAD4 and RUNX3 on 210 surgically resected PDACs, and the results were correlated with the clinicopathological features. Loss of SMAD4 expression was associated with poor overall survival (OS) ( p = 0.015) and progression-free survival (PFS) ( p = 0.044). Nuclear RUNX3 expression was associated with decreased OS ( p = 0.010) and PFS ( p = 0.009), and more frequent in poorly differentiated PDACs ( p = 0.037). On combining RUNX3/SMAD4 status, RUNX3-/SMAD4+ PDACs demonstrated longer OS ( p = 0.008, median time; RUNX3-/SMAD4+ 34 months, others 17 months) and PFS ( p = 0.009, median time; RUNX3-/SMAD4+ 29 months, others 8 months) compared to RUNX3+/SMAD4+ and SMAD4- groups; RUNX3-/SMAD4+ was a significant independent predictive factor for both OS [ p = 0.025, HR 1.842 (95% CI 1.079-3.143)] and PFS [ p = 0.020, HR 1.850 (95% CI 1.100-3.113)]. SMAD4-positivity with RUNX3-negativity was a significant independent predictive factor for favorable OS and PFS in PDAC. This is the first and large clinicopathological study of RUNX3/SMAD4 expression status in human PDAC. Combination immunohistochemistry for SMAD4 and RUNX3 may help identify a favorable prognostic subgroup of PDAC.

Survival and prognostic factors for hepatocellular carcinoma: an Egyptian multidisciplinary clinic experience.

PubMed

Abdelaziz, Ashraf Omar; Elbaz, Tamer Mahmoud; Shousha, Hend Ibrahim; Ibrahim, Mostafa Mohamed; Rahman El-Shazli, Mostafa Abdel; Abdelmaksoud, Ahmed Hosni; Aziz, Omar Abdel; Zaki, Hisham Atef; Elattar, Inas Anwar; Nabeel, Mohamed Mahmoud

2014-01-01

Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was 56.5 ± 7.7 years. All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.

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

Identifying Variability in Mental Models Within and Between Disciplines Caring for the Cardiac Surgical Patient.

PubMed

Brown, Evans K H; Harder, Kathleen A; Apostolidou, Ioanna; Wahr, Joyce A; Shook, Douglas C; Farivar, R Saeid; Perry, Tjorvi E; Konia, Mojca R

2017-07-01

The cardiac operating room is a complex environment requiring efficient and effective communication between multiple disciplines. The objectives of this study were to identify and rank critical time points during the perioperative care of cardiac surgical patients, and to assess variability in responses, as a correlate of a shared mental model, regarding the importance of these time points between and within disciplines. Using Delphi technique methodology, panelists from 3 institutions were tasked with developing a list of critical time points, which were subsequently assigned to pause point (PP) categories. Panelists then rated these PPs on a 100-point visual analog scale. Descriptive statistics were expressed as percentages, medians, and interquartile ranges (IQRs). We defined low response variability between panelists as an IQR ≤ 20, moderate response variability as an IQR > 20 and ≤ 40, and high response variability as an IQR > 40. Panelists identified a total of 12 PPs. The PPs identified by the highest number of panelists were (1) before surgical incision, (2) before aortic cannulation, (3) before cardiopulmonary bypass (CPB) initiation, (4) before CPB separation, and (5) at time of transfer of care from operating room (OR) to intensive care unit (ICU) staff. There was low variability among panelists' ratings of the PP "before surgical incision," moderate response variability for the PPs "before separation from CPB," "before transfer from OR table to bed," and "at time of transfer of care from OR to ICU staff," and high response variability for the remaining 8 PPs. In addition, the perceived importance of each of these PPs varies between disciplines and between institutions. Cardiac surgical providers recognize distinct critical time points during cardiac surgery. However, there is a high degree of variability within and between disciplines as to the importance of these times, suggesting an absence of a shared mental model among disciplines caring for

Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.

PubMed

Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

2015-01-01

Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability--the basis of cluster generation--is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.

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

PubMed

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

2015-08-15

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

Prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma.

PubMed

Berzina, Anna; Azarjana, Kristine; Cema, Ingrida; Pjanova, Dace; Rivosh, Alexander

2011-01-01

OBJECTIVE. To describe the prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma and to identify the variables associated with mortality from this disease. MATERIAL AND METHODS. Patients treated for head and neck melanoma in the Oncology Centre of Latvia, Riga during a 10-year period were identified. Records from 124 cases were analyzed in a descriptive, retrospective study. For each patient, information regarding age, sex, tumor anatomic site, as well as ulceration, histological tumor subtypes, Breslow thickness and Clark invasion level was viewed. Disease specific survival rates were calculated. The frequencies of all study variables and their 95% confidence intervals were determined. Kaplan-Meier survival curves were produced to illustrate the survival differences for each variable. RESULTS. The patients' mean age was 67.36 years. The study included 81 females (65.32%) and 43 males (34.67%). The prevalent anatomical site for cutaneous head and neck melanoma was the cheek - 49% (n=55) and the intraocular site for mucosal melanoma (61.5%). A high percentage of thick cutaneous melanoma was detected. In 53 cases (47.3%) out of 112 cutaneous melanoma the tumor ulceration was found. Nodular melanoma subtype was predominating (38%). The incidence of cutaneous melanoma has increased unequally whereas mucosal melanoma of the head and neck is an uncommon cancer and the incidence rates in Latvia during a ten year period are decreasing. CONCLUSION. Female sex, advanced age, facial skin, tumor thickness, nodular subtype and ulceration carried a relevant risk of poor prognosis.

Dynamic prognostication using conditional survival analysis for patients with operable lung adenocarcinoma

PubMed Central

Kim, Wooil; Lee, Ho Yun; Jung, Sin-Ho; Woo, Min-Ah; Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Zo, Jae Ill; Shim, Young Mog; Han, Joungho; Jeong, Ji Yun; Choi, Joon Young; Lee, Kyung Soo

2017-01-01

Purpose To evaluate conditional survival among patients with surgically resected stage I-IIIa lung adenocarcinoma and identify changes in prognostic contributions for various prognostic factors over time. Patients and Methods We performed conditional survival analysis at each t0 (=0, 1, 2, 3, 4, 5 years) for 723 consecutive patients who underwent surgical resection for lung adenocarcinoma, stratified by various clinico-demographic features, as well as pathologic and imaging (tumor-shadow disappearance ratio [TDR] on CT and maximum standardized uptake value [SUVmax] on PET) characteristics. Uni- and multivariableCox regression analyses were performed to evaluate relationships between those variables and conditional survival. Results Three-year conditional overall survival (OS) and disease-free survival (DFS) were 92.12% and 75.51% at baseline, but improved steadily up to 98.33% and 95.95% at 5 years after surgery. In contrast to demographic factors, pathologic (stage, subtype, pathologic grade and differentiation) and radiologic factors (TDR and SUVmax) maintained a statistically significant association with subseqeunt 3-year OS until 3 years after surgery. According to the multivariableanalysis, high SUVmax and low TDR value were independent predictors of subsequent 3-year OS and DFS at baseline, 1 and 2 years after surgery, respectively. Conclusion Our findings based on CS provide theoretical background for clinicians to plan longer period of surveillance following lung adenocarcinoma resection in survivors with preoperatively high SUVmax and low TDR on PET-CT and chest CT, respectively. PMID:27793026

Prognostic factors in non-surgically treated sciatica: a systematic review.

PubMed

Ashworth, Julie; Konstantinou, Kika; Dunn, Kate M

2011-09-25

When present sciatica is considered an obstacle to recovery in low back pain patients, yet evidence is limited regarding prognostic factors for persistent disability in this patient group. The aim of this study is to describe and summarise the evidence regarding prognostic factors for sciatica in non-surgically treated cohorts. Understanding the prognostic factors in sciatica and their relative importance may allow the identification of patients with particular risk factors who might benefit from early or specific types of treatment in order to optimise outcome. A systematic literature search was conducted using Medline, EMBASE and CINAHL electronic databases. Prospective cohort studies describing subjects with sciatica and measuring pain, disability or recovery outcomes were included. Studies of cohorts comprised entirely of surgically treated patients were excluded and mixed surgically and conservatively treated cohorts were included only if the results were analysed separately by treatment group or if the analysis was adjusted for treatment. Seven adequate or high quality eligible studies were identified. There were conflicting but mainly negative results regarding the influence of baseline pain severity, neurological deficit, nerve root tension signs, duration of symptoms and radiological findings on outcome. A number of factors including age, gender, smoking, previous history of sciatica and heaviness of work do not appear to influence outcome. In contrast to studies of low back pain and purely surgically treated sciatica cohorts, psychological factors were rarely investigated. At present, the heterogeneity of the available studies makes it difficult to draw firm conclusions about sciatica prognosis, and highlights the need for further research for this group of patients. Large scale prospective studies of high methodological quality, using a well-defined, consistent definition of sciatica and investigating psychosocial factors alongside clinical and

Prognostic factors in non-surgically treated sciatica: A systematic review

PubMed Central

2011-01-01

Background When present sciatica is considered an obstacle to recovery in low back pain patients, yet evidence is limited regarding prognostic factors for persistent disability in this patient group. The aim of this study is to describe and summarise the evidence regarding prognostic factors for sciatica in non-surgically treated cohorts. Understanding the prognostic factors in sciatica and their relative importance may allow the identification of patients with particular risk factors who might benefit from early or specific types of treatment in order to optimise outcome. Methods A systematic literature search was conducted using Medline, EMBASE and CINAHL electronic databases. Prospective cohort studies describing subjects with sciatica and measuring pain, disability or recovery outcomes were included. Studies of cohorts comprised entirely of surgically treated patients were excluded and mixed surgically and conservatively treated cohorts were included only if the results were analysed separately by treatment group or if the analysis was adjusted for treatment. Results Seven adequate or high quality eligible studies were identified. There were conflicting but mainly negative results regarding the influence of baseline pain severity, neurological deficit, nerve root tension signs, duration of symptoms and radiological findings on outcome. A number of factors including age, gender, smoking, previous history of sciatica and heaviness of work do not appear to influence outcome. In contrast to studies of low back pain and purely surgically treated sciatica cohorts, psychological factors were rarely investigated. Conclusions At present, the heterogeneity of the available studies makes it difficult to draw firm conclusions about sciatica prognosis, and highlights the need for further research for this group of patients. Large scale prospective studies of high methodological quality, using a well-defined, consistent definition of sciatica and investigating psychosocial

[Microvascular descompression for trigeminal neuralgia: prognostic [corrected] factors].

PubMed

Alberione, F; Arena, A; Matera, R

2008-06-01

We describe our experience of the MVD in the typical trigeminal neuralgia and identify the prognostic factors. A retrospective studio of 89 cases between 1995-2005 was used. The prognostic significant data evaluated were demographics data; duration of neuralgia; the affected divisions involved; surgical findings; used material for the decompression. The data analysis was made with the chi(2) test. We have found an excellent outcome in 77% one year later. The age and the antecedent of hypertension disease were not statistically significant. A poor outcome was observed for: female sex, neuralgia lasting longer than two years, the three divisions involved, venous compression and the muscle used as surgical material. The MVD is an effective and reliable technique. The use of muscle is not recommended. When the three trigeminal divisions are involved we should choose another technique.

The degree of circumferential tumour involvement as a prognostic factor in oesophageal cancer.

PubMed

Sillah, Karim; Pritchard, Susan A; Watkins, Gillian R; McShane, James; West, Catharine M; Page, Richard; Welch, Ian M

2009-08-01

Tumour length is an adverse prognostic factor in oesophageal cancer. However, the prognostic role of the degree of oesophageal circumference (DOC) involved by tumour with or without resection margin invasion is not clear. This work assessed the relationship between DOC involved by tumour, clinico-pathological variables and prognosis. The clinico-pathological details of 320 patients who underwent potentially curative oesophagogastrectomy for cancer between 1994 and 2007 were analysed. The DOC involved with tumour measured macroscopically on the resected specimen was classified as small (<2.5 cm, n = 115), large (> or = 2.5 cm, n = 144) or circumferential (i.e. involving the whole circumference, n = 61). Univariate and multivariate survival analyses were carried out. The DOC with tumour was higher in ulcerating tumours than stenosing or polypoidal types (p = 0.017). Tumour length, T-stage, neoadjuvant chemotherapy and vascular invasion were independently associated with DOC with tumour on multivariate analysis (p < 0.05 for all). DOC > or = 2.5 cm was an adverse prognostic factor in univariate analysis (p = 0.002) with a hazard ratio of 1.52 [95% CI 1.13-2.04] compared with those <2.5 cm. Circumferential tumours had a similar prognosis to tumours > or = 2.5 cm (p = 0.60). The prognostic significance of DOC with tumour was lost in multivariate analysis where the factors retaining independence were patient age, T-stage, lymph node metastasis, vascular invasion and positive resection margins. However, when patients were stratified by use of neoadjuvant chemotherapy (n = 121), the DOC with tumour retained prognostic significance on multivariate analysis in the 199 patients who did not undergo neoadjuvant chemotherapy (p = 0.04). The DOC with tumour appears to provide prognostic information in oesophageal cancer surgery, especially in patients who do not undergo preoperative chemotherapy.

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

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Sankararaman, Shankar

2013-01-01

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

Extent of, and variables associated with, blood pressure variability among older subjects.

PubMed

Morano, Arianna; Ravera, Agnese; Agosta, Luca; Sappa, Matteo; Falcone, Yolanda; Fonte, Gianfranco; Isaia, Gianluca; Isaia, Giovanni Carlo; Bo, Mario

2018-02-23

Blood pressure variability (BPV) may have prognostic implications for cardiovascular risk and cognitive decline; however, BPV has yet to be studied in old and very old people. Aim of the present study was to evaluate the extent of BPV and to identify variables associated with BPV among older subjects. A retrospective study of patients aged ≥ 65 years who underwent 24-h ambulatory blood pressure monitoring (ABPM) was carried out. Three different BPV indexes were calculated for systolic and diastolic blood pressure (SBP and DBP): standard deviation (SD), coefficient of variation (CV), and average real variability (ARV). Demographic variables and use of antihypertensive medications were considered. The study included 738 patients. Mean age was 74.8 ± 6.8 years. Mean SBP and DBP SD were 20.5 ± 4.4 and 14.6 ± 3.4 mmHg. Mean SBP and DBP CV were 16 ± 3 and 20 ± 5%. Mean SBP and DBP ARV were 15.7 ± 3.9 and 11.8 ± 3.6 mmHg. At multivariate analysis older age, female sex and uncontrolled mean blood pressure were associated with both systolic and diastolic BPV indexes. The use of calcium channel blockers and alpha-adrenergic antagonists was associated with lower systolic and diastolic BPV indexes, respectively. Among elderly subjects undergoing 24-h ABPM, we observed remarkably high indexes of BPV, which were associated with older age, female sex, and uncontrolled blood pressure values.

Identifying Decadal to Multi-decadal Variability in the Pacific by Empirical Mode Decomposition

NASA Astrophysics Data System (ADS)

Sommers, L. A.; Hamlington, B.; Cheon, S. H.

2016-12-01

Large scale climate variability in the Pacific Ocean like that associated with ENSO and the Pacific Decadal Oscillation (PDO) has been shown to have a significant impact on climate and sea level across a range of timescales. The changes related to these climate signals have worldwide impacts on fisheries, weather, and precipitation patterns among others. Understanding these inter-annual to multi-decadal oscillations is imperative to longer term climate forecasts and understanding how climate will behave, and its effect on changes in sea level. With a 110-year reconstruction of sea level, we examine decadal to multi-decadal variability seen in the sea level fluctuations in the Pacific Ocean. Using empirical mode decomposition (EMD), we break down regional sea level into a series of intrinsic mode functions (IMFs) and attempt attribution of these IMFs to specific climate modes of variability. In particular, and not unexpectedly, we identify IMFs associated with the PDO, finding correlations between the PDO Index and IMFs in the Pacific Ocean upwards of 0.6-0.8 over the 110-year reconstructed record. Perhaps more significantly, we also find evidence of a longer multi-decadal signal ( 50-60 years) in the higher order IMFs. This lower frequency variability has been suggested in previous literature as influencing GMSL, but here we find a regional pattern associated with this multi-decadal signal. By identifying and separating these periodic climate signals, we can gain a better understanding of how the sea level variability associated with these modes can impact sea level on short timescales and serve to exacerbate the effects of long-term sea level change.

[Prognostic estimation in critical patients. Validation of a new and very simple system of prognostic estimation of survival in an intensive care unit].

PubMed

Abizanda, R; Padron, A; Vidal, B; Mas, S; Belenguer, A; Madero, J; Heras, A

2006-04-01

To make the validation of a new system of prognostic estimation of survival in critical patients (EPEC) seen in a multidisciplinar Intensive care unit (ICU). Prospective analysis of a patient cohort seen in the ICU of a multidisciplinar Intensive Medicine Service of a reference teaching hospital with 19 beds. Four hundred eighty four patients admitted consecutively over 6 months in 2003. Data collection of a basic minimum data set that includes patient identification data (gender, age), reason for admission and their origin, prognostic estimation of survival by EPEC, MPM II 0 and SAPS II (the latter two considered as gold standard). Mortality was evaluated on hospital discharge. EPEC validation was done with analysis of its discriminating capacity (ROC curve), calibration of its prognostic capacity (Hosmer Lemeshow C test), resolution of the 2 x 2 Contingency tables around different probability values (20, 50, 70 and mean value of prognostic estimation). The standardized mortality rate (SMR) for each one of the methods was calculated. Linear regression of the EPEC regarding the MPM II 0 and SAPS II was established and concordance analyses were done (Bland-Altman test) of the prediction of mortality by the three systems. In spite of an apparently good linear correlation, similar accuracy of prediction and discrimination capacity, EPEC is not well-calibrated (no likelihood of death greater than 50%) and the concordance analyses show that more than 10% of the pairs were outside the 95% confidence interval. In spite of its ease of application and calculation and of incorporating delay of admission in ICU as a variable, EPEC does not offer any predictive advantage on MPM II 0 or SAPS II, and its predictions adapt to reality worse.

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data

PubMed Central

Guinney, Justin; Wang, Tao; Laajala, Teemu D; Winner, Kimberly Kanigel; Bare, J Christopher; Neto, Elias Chaibub; Khan, Suleiman A; Peddinti, Gopal; Airola, Antti; Pahikkala, Tapio; Mirtti, Tuomas; Yu, Thomas; Bot, Brian M; Shen, Liji; Abdallah, Kald; Norman, Thea; Friend, Stephen; Stolovitzky, Gustavo; Soule, Howard; Sweeney, Christopher J; Ryan, Charles J; Scher, Howard I; Sartor, Oliver; Xie, Yang; Aittokallio, Tero; Zhou, Fang Liz; Costello, James C

2016-01-01

Summary Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest—namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data.

PubMed

Guinney, Justin; Wang, Tao; Laajala, Teemu D; Winner, Kimberly Kanigel; Bare, J Christopher; Neto, Elias Chaibub; Khan, Suleiman A; Peddinti, Gopal; Airola, Antti; Pahikkala, Tapio; Mirtti, Tuomas; Yu, Thomas; Bot, Brian M; Shen, Liji; Abdallah, Kald; Norman, Thea; Friend, Stephen; Stolovitzky, Gustavo; Soule, Howard; Sweeney, Christopher J; Ryan, Charles J; Scher, Howard I; Sartor, Oliver; Xie, Yang; Aittokallio, Tero; Zhou, Fang Liz; Costello, James C

2017-01-01

Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a

Development, validation and psychometric properties of a diagnostic/prognostic tool for breakthrough pain in mixed chronic-pain patients.

PubMed

Samolsky Dekel, Boaz Gedaliahu; Remondini, Francesca; Gori, Alberto; Vasarri, Alessio; Di Nino, GianFranco; Melotti, Rita Maria

2016-02-01

Breakthrough pain (BTP) shows variable prevalence in different clinical contexts of cancer and non-cancer patients. BTP diagnostic tools with demonstrated reliability, validation and prognostic capability are lacking. We report the development, psychometric and validation properties of a diagnostic/prognostic tool, the IQ-BTP, for BTP recognition, its likelihood and clinical features among chronic-pain (CP) patients. n=120 consecutive mixed cancer/non-cancer CP in/outpatients. Development, psychometric analyses and formal validation included: Face/Content validity (by 'experts' opinion and assessing the relationship between the IQ-BTP classes and criteria derived from BTP operational-case-definition); Construct validity, by Principle Component Analysis (PCA); and the strength of Spearman correlation between IQ-BTP classes and the Brief Pain Inventory (BPI) items; Reliability, by Cronbach's alpha statistics. Associations with clinical/demographic moderators were assessed applying χ(2) analysis. Potential-BTP was found in 36.7% of patients (38.4% of non-cancer and 32.4% of cancer patients). Among these the likelihood for BTP diagnosis was 'high' in 25%, 'intermediate' in 41% and, 'low' 34% of patients. Analyses showed significant differences between IQ-BTP classes and between the latter BPI pain-item scores. Correlation between IQ-BTP classes and BPI items was moderate. PCA and scree test identified 3 components accounting for 62.3% of the variance. Cronbach's alpha was 0.71. The IQ-BTP showed satisfactory psychometric and validation properties. With adequate feasibility it enabled the allocating of cancer/non-cancer CP patients in three prognostic classes. Results are sufficient to warrant a subsequent impact study of the IQ-BTP as prognostic model and screening tool for BTP in both CP populations. Copyright © 2016 Elsevier B.V. All rights reserved.

Prognostic residual mean flow in an ocean general circulation model and its relation to prognostic Eulerian mean flow

DOE PAGES

Saenz, Juan A.; Chen, Qingshan; Ringler, Todd

2015-05-19

Recent work has shown that taking the thickness-weighted average (TWA) of the Boussinesq equations in buoyancy coordinates results in exact equations governing the prognostic residual mean flow where eddy–mean flow interactions appear in the horizontal momentum equations as the divergence of the Eliassen–Palm flux tensor (EPFT). It has been proposed that, given the mathematical tractability of the TWA equations, the physical interpretation of the EPFT, and its relation to potential vorticity fluxes, the TWA is an appropriate framework for modeling ocean circulation with parameterized eddies. The authors test the feasibility of this proposition and investigate the connections between the TWAmore » framework and the conventional framework used in models, where Eulerian mean flow prognostic variables are solved for. Using the TWA framework as a starting point, this study explores the well-known connections between vertical transfer of horizontal momentum by eddy form drag and eddy overturning by the bolus velocity, used by Greatbatch and Lamb and Gent and McWilliams to parameterize eddies. After implementing the TWA framework in an ocean general circulation model, we verify our analysis by comparing the flows in an idealized Southern Ocean configuration simulated using the TWA and conventional frameworks with the same mesoscale eddy parameterization.« less

Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

PubMed

Jary, Marine; Lecomte, Thierry; Bouché, Olivier; Kim, Stefano; Dobi, Erion; Queiroz, Lise; Ghiringhelli, Francois; Etienne, Hélène; Léger, Julie; Godet, Yann; Balland, Jérémy; Lakkis, Zaher; Adotevi, Olivier; Bonnetain, Franck; Borg, Christophe; Vernerey, Dewi

2016-11-15

In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p < 0.0001). This score had a good discrimination ability (C-index = 0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values. © 2016 UICC.

Tools to identify linear combination of prognostic factors which maximizes area under receiver operator curve.

PubMed

Todor, Nicolae; Todor, Irina; Săplăcan, Gavril

2014-01-01

The linear combination of variables is an attractive method in many medical analyses targeting a score to classify patients. In the case of ROC curves the most popular problem is to identify the linear combination which maximizes area under curve (AUC). This problem is complete closed when normality assumptions are met. With no assumption of normality search algorithm are avoided because it is accepted that we have to evaluate AUC n(d) times where n is the number of distinct observation and d is the number of variables. For d = 2, using particularities of AUC formula, we described an algorithm which lowered the number of evaluations of AUC from n(2) to n(n-1) + 1. For d > 2 our proposed solution is an approximate method by considering equidistant points on the unit sphere in R(d) where we evaluate AUC. The algorithms were applied to data from our lab to predict response of treatment by a set of molecular markers in cervical cancers patients. In order to evaluate the strength of our algorithms a simulation was added. In the case of no normality presented algorithms are feasible. For many variables computation time could be increased but acceptable.

[Prognostic scores for pulmonary embolism].

PubMed

Junod, Alain

2016-03-23

Nine prognostic scores for pulmonary embolism (PE), based on retrospective and prospective studies, published between 2000 and 2014, have been analyzed and compared. Most of them aim at identifying PE cases with a low risk to validate their ambulatory care. Important differences in the considered outcomes: global mortality, PE-specific mortality, other complications, sizes of low risk groups, exist between these scores. The most popular score appears to be the PESI and its simplified version. Few good quality studies have tested the applicability of these scores to PE outpatient care, although this approach tends to already generalize in the medical practice.

A new approach to hazardous materials transportation risk analysis: decision modeling to identify critical variables.

PubMed

Clark, Renee M; Besterfield-Sacre, Mary E

2009-03-01

We take a novel approach to analyzing hazardous materials transportation risk in this research. Previous studies analyzed this risk from an operations research (OR) or quantitative risk assessment (QRA) perspective by minimizing or calculating risk along a transport route. Further, even though the majority of incidents occur when containers are unloaded, the research has not focused on transportation-related activities, including container loading and unloading. In this work, we developed a decision model of a hazardous materials release during unloading using actual data and an exploratory data modeling approach. Previous studies have had a theoretical perspective in terms of identifying and advancing the key variables related to this risk, and there has not been a focus on probability and statistics-based approaches for doing this. Our decision model empirically identifies the critical variables using an exploratory methodology for a large, highly categorical database involving latent class analysis (LCA), loglinear modeling, and Bayesian networking. Our model identified the most influential variables and countermeasures for two consequences of a hazmat incident, dollar loss and release quantity, and is one of the first models to do this. The most influential variables were found to be related to the failure of the container. In addition to analyzing hazmat risk, our methodology can be used to develop data-driven models for strategic decision making in other domains involving risk.

[Prognostic and predictive molecular markers for urologic cancers].

PubMed

Hartmann, A; Schlomm, T; Bertz, S; Heinzelmann, J; Hölters, S; Simon, R; Stoehr, R; Junker, K

2014-04-01

Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.

Expression Levels of KMT2C and SLC20A1 Identified by Information-theoretical Analysis Are Powerful Prognostic Biomarkers in Estrogen Receptor-positive Breast Cancer.

PubMed

Sato, Keiko; Akimoto, Kazunori

2017-06-01

In general, it has been considered that estrogen receptor-positive (ER + ) breast cancer has a good prognosis and is responsive to endocrine therapy. However, one third of patients with ER + breast cancer exhibit endocrine therapy resistance, and many patients develop recurrence and die 5 to 10 years after diagnosis. In ER +  breast cancer, a major problem is to distinguish those patients most likely to develop recurrence or metastatic disease within 10 years after diagnosis from those with a sufficiently good prognosis. We downloaded the messenger RNA expression data and the clinical information for 401 patients with ER +  breast cancer from the cBioPortal for Cancer Genomics. An information-theoretical approach was used to identify the prognostic factors for survival in patients with ER + breast cancer and to classify those patients according to the prognostic factors. The information-theoretical approach contributed to the identification of KMT2C and SLC20A1 as prognostic biomarkers in ER + breast cancer. We found that low KMT2C expression was associated with a poor outcome and high SLC20A1 expression was associated with a poor outcome. Both levels of KMT2C and SLC20A1 expression were significantly and strongly associated with the differentiation of survival. The 10-year survival rate for ER + patients with low KMT2C and high SLC20A1 expression was 0%. In contrast, for ER + patients with high KMT2C and low SLC20A1 expression, the 10-year survival rate was 86.78%. Our results strongly suggest that clinical examination of the expression of both KMT2C and SLC20A1 in ER + breast cancer will be very useful for the determination of prognosis and therapy. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Prognostic and diagnostic impact of fibrinogen, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on thymic epithelial tumors outcome

PubMed Central

Janik, Stefan; Raunegger, Thomas; Hacker, Philipp; Ghanim, Bahil; Einwallner, Elisa; Müllauer, Leonhard; Schiefer, Ana-Iris; Moser, Julia; Klepetko, Walter; Ankersmit, Hendrik Jan; Moser, Bernhard

2018-01-01

Background Peripheral blood-derived inflammation-based markers, such as Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Fibrinogen have been identified as prognostic markers in various solid malignancies. Here we aimed to investigate the prognostic and diagnostic impact of NLR, PLR, and Fibrinogen in patients with thymic epithelial tumors (TETs). Results Pretreatment Fibrinogen serum concentrations, NLRs and PLRs were highest in patients with TCs and advanced tumor stages. High pretreatment Fibrinogen serum concentration (≥452.5 mg/dL) was significantly associated with worse cause specific survival (CSS; p = 0.001) and freedom from recurrence (FFR; p = 0.043), high NLR (≥4.0) with worse FFR (p = 0.008), and high PLR (≥136.5) with worse CSS (p = 0.032). Longitudinal analysis revealed that compared to patients without tumor recurrence, patients with tumor recurrence had significantly higher NLR (11.8 ± 4.0 vs. 4.70 ± 0.5; p = 0.001) and PLR (410.8 ± 149.1 vs. 228.3 ± 23.7; p = 0.031). Conclusion Overall, Fibrinogen serum concentrations, NLRs, and PLRs were associated with higher tumor stage, more aggressive tumor behavior, recurrence, and worse outcome. Prospective multicenter studies of the diagnostic and prognostic potential of Fibrinogen, NLR, and PLR are warranted. Methods This retrospective analysis included 122 patients with TETs who underwent surgical resection between 1999-2015. Fibrinogen serum concentrations, NLRs, and PLRs were measured in patients preoperatively, postoperatively, and later during follow-up. These markers were analyzed for association with several clinical variables, including tumor stage, tumor subtype, FFR, and CSS and to evaluate their prognostic and diagnostic impact for detecting tumor recurrence. PMID:29774108

A new prognostic score for elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: the prognostic role of blood monocyte and lymphocyte counts is absent.

PubMed

Procházka, Vít; Pytlík, Robert; Janíková, Andrea; Belada, David; Sálek, David; Papajík, Tomáš; Campr, Vít; Fürst, Tomáš; Furstova, Jana; Trněný, Marek

2014-01-01

Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet. In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥ 60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥ 1, age ≥ 70, bulk ≥ 7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics. The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.

Technical Needs for Prototypic Prognostic Technique Demonstration for Advanced Small Modular Reactor Passive Components

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

Meyer, Ryan M.; Coble, Jamie B.; Hirt, Evelyn H.

2013-05-17

This report identifies a number of requirements for prognostics health management of passive systems in AdvSMRs, documents technical gaps in establishing a prototypical prognostic methodology for this purpose, and describes a preliminary research plan for addressing these technical gaps. AdvSMRs span multiple concepts; therefore a technology- and design-neutral approach is taken, with the focus being on characteristics that are likely to be common to all or several AdvSMR concepts. An evaluation of available literature is used to identify proposed concepts for AdvSMRs along with likely operational characteristics. Available operating experience of advanced reactors is used in identifying passive components thatmore » may be subject to degradation, materials likely to be used for these components, and potential modes of degradation of these components. This information helps in assessing measurement needs for PHM systems, as well as defining functional requirements of PHM systems. An assessment of current state-of-the-art approaches to measurements, sensors and instrumentation, diagnostics and prognostics is also documented. This state-of-the-art evaluation, combined with the requirements, may be used to identify technical gaps and research needs in the development, evaluation, and deployment of PHM systems for AdvSMRs. A preliminary research plan to address high-priority research needs for the deployment of PHM systems to AdvSMRs is described, with the objective being the demonstration of prototypic prognostics technology for passive components in AdvSMRs. Greater efficiency in achieving this objective can be gained through judicious selection of materials and degradation modes that are relevant to proposed AdvSMR concepts, and for which significant knowledge already exists. These selections were made based on multiple constraints including the analysis performed in this document, ready access to laboratory-scale facilities for materials testing and measurement

Identifying dissolved oxygen variability and stress in tidal freshwater streams of northern New Zealand.

PubMed

Wilding, Thomas K; Brown, Edmund; Collier, Kevin J

2012-10-01

Tidal streams are ecologically important components of lotic network, and we identify dissolved oxygen (DO) depletion as a potentially important stressor in freshwater tidal streams of northern New Zealand. Other studies have examined temporal DO variability within rivers and we build on this by examining variability between streams as a basis for regional-scale predictors of risk for DO stress. Diel DO variability in these streams was driven by: (1) photosynthesis by aquatic plants and community respiration which produced DO maxima in the afternoon and minima early morning (range, 0.6-4.7 g/m(3)) as a product of the solar cycle and (2) tidal variability as a product of the lunar cycle, including saline intrusions with variable DO concentrations plus a small residual effect on freshwater DO for low-velocity streams. The lowest DO concentrations were observed during March (early autumn) when water temperatures and macrophyte biomass were high. Spatial comparisons indicated that low-gradient tidal streams were at greater risk of DO depletions harmful to aquatic life. Tidal influence was stronger in low-gradient streams, which typically drain more developed catchments, have lower reaeration potential and offer conditions more suitable for aquatic plant proliferation. Combined, these characteristics supported a simple method based on the extent of low-gradient channel for identifying coastal streams at risk of DO depletion. High-risk streams can then be targeted for riparian planting, nutrient limits and water allocation controls to reduce potential ecological stress.

Prognostic factors and recurrence of hepatitis B-related hepatocellular carcinoma after argon-helium cryoablation: a prospective study.

PubMed

Wang, Chunping; Lu, Yinying; Chen, Yan; Feng, Yongyi; An, Linjing; Wang, Xinzhen; Su, Shuhui; Bai, Wenlin; Zhou, Lin; Yang, Yongping; Xu, Dongping

2009-01-01

To determine the long-term prognosis of hepatocellular carcinoma (HCC) after argon-helium cryoablation and identify the risk factors that predict metastasis and recurrence. A total of 156 patients with hepatitis B-related HCC less than 5 cm in diameter who underwent curative cryoablation were followed up prospectively for tumor metastasis and recurrence. Immunohistochemistry was used to analyze the expression of vascular endothelial growth factor (VEGF). HBV basal core promoter (BCP) and precore mutations were detected by DNA sequence analysis. Post-treatment prognostic factors influencing survival, tumor metastasis and recurrence were assessed by univariate and multivariate analyses. The variables included the expression of VEGF in HCC tissues, clinical and pathologic characteristics of patients, and HBV features (HBV DNA level, HBV genotype, BCP mutation). The median follow-up period of the 156 patients was 37 months (range 8-48 months). The 1-, 2-, and 3-year overall survival rates were 92, 82 and 64%, respectively. The 1-, 2-, and 3-year recurrence-free survival rates were 72, 56 and 43%, respectively. Eighty-five patients (54.5%) had tumor recurrence or metastasis. The multivariate analysis showed that Child-Pugh class and the expression of VEGF in HCC tissues could be used as independent prognostic factors for overall survival. Meanwhile, the expression of VEGF in HCC tissues and HBV BCP mutations were found to be independent prognostic factors for recurrence-free survival. Strong expression of VEGF in HCC tissues and HBV BCP mutations are important risk predictors for recurrence or metastasis of HCC smaller than 5 cm in diameter.

Aneurysmal subarachnoid hemorrhage prognostic decision-making algorithm using classification and regression tree analysis.

PubMed

Lo, Benjamin W Y; Fukuda, Hitoshi; Angle, Mark; Teitelbaum, Jeanne; Macdonald, R Loch; Farrokhyar, Forough; Thabane, Lehana; Levine, Mitchell A H

2016-01-01

Classification and regression tree analysis involves the creation of a decision tree by recursive partitioning of a dataset into more homogeneous subgroups. Thus far, there is scarce literature on using this technique to create clinical prediction tools for aneurysmal subarachnoid hemorrhage (SAH). The classification and regression tree analysis technique was applied to the multicenter Tirilazad database (3551 patients) in order to create the decision-making algorithm. In order to elucidate prognostic subgroups in aneurysmal SAH, neurologic, systemic, and demographic factors were taken into account. The dependent variable used for analysis was the dichotomized Glasgow Outcome Score at 3 months. Classification and regression tree analysis revealed seven prognostic subgroups. Neurological grade, occurrence of post-admission stroke, occurrence of post-admission fever, and age represented the explanatory nodes of this decision tree. Split sample validation revealed classification accuracy of 79% for the training dataset and 77% for the testing dataset. In addition, the occurrence of fever at 1-week post-aneurysmal SAH is associated with increased odds of post-admission stroke (odds ratio: 1.83, 95% confidence interval: 1.56-2.45, P < 0.01). A clinically useful classification tree was generated, which serves as a prediction tool to guide bedside prognostication and clinical treatment decision making. This prognostic decision-making algorithm also shed light on the complex interactions between a number of risk factors in determining outcome after aneurysmal SAH.

Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy.

PubMed

Saito, Yuki; Omura, Go; Yasuhara, Kazuo; Rikitake, Ryoko; Akashi, Ken; Fukuoka, Osamu; Yoshida, Masafumi; Ando, Mizuo; Asakage, Takahiro; Yamasoba, Tatsuya

2017-08-01

We aimed to determinate the prognostic value of lymphovascular invasion in the specimens resected during total laryngopharyngectomy for hypopharyngeal carcinoma. Patients who underwent total laryngopharyngectomy at our institution between 2004 and 2014 were included in this study and retrospectively analyzed. We then discriminated for vascular invasion and lymphatic invasion of the primary tumor in all cases. We reviewed 135 records (120 men and 15 women; age range, 36-84 years). Tumors with lymphatic invasion tended to be associated with more metastatic lymph nodes and extracapsular spread (ECS) of metastatic lymph nodes. Tumors with vascular invasion tended to be associated with nonpyriform sinus locations. In a multivariate analysis, nonpyriform sinus locations, >3 metastatic lymph nodes, and vascular invasion remained significant prognostic factors for overall survival (OS); in recursive partitioning analysis, ECS and vascular invasion remained important categorical variables for OS. Vascular invasion is a strong prognostic biomarker for advanced hypopharyngeal carcinoma. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1535-1543, 2017. © 2017 Wiley Periodicals, Inc.

Combination immunohistochemistry for SMAD4 and Runt-related transcription factor 3 may identify a favorable prognostic subgroup of pancreatic ductal adenocarcinomas

PubMed Central

Lee, Yangkyu; Lee, Hyejung; Park, Hyunjin; Kim, Jin-Won; Hwang, Jin-Hyeok; Kim, Jaihwan; Yoon, Yoo-Seok; Han, Ho-Seong; Kim, Haeryoung

2017-01-01

Purposes SMAD4/DPC4 mutations have been associated with aggressive behavior in pancreatic ductal adenocarcinomas (PDAC), and it has recently been suggested that RUNX3 expression combined with SMAD4 status may predict the metastatic potential of PDACs. We evaluated the prognostic utility of SMAD4/RUNX3 status in human PDACs by immunohistochemistry. Materials and Methods Immunohistochemical stains were performed for SMAD4 and RUNX3 on 210 surgically resected PDACs, and the results were correlated with the clinicopathological features. Results Loss of SMAD4 expression was associated with poor overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.044). Nuclear RUNX3 expression was associated with decreased OS (p = 0.010) and PFS (p = 0.009), and more frequent in poorly differentiated PDACs (p = 0.037). On combining RUNX3/SMAD4 status, RUNX3-/SMAD4+ PDACs demonstrated longer OS (p = 0.008, median time; RUNX3-/SMAD4+ 34 months, others 17 months) and PFS (p = 0.009, median time; RUNX3-/SMAD4+ 29 months, others 8 months) compared to RUNX3+/SMAD4+ and SMAD4- groups; RUNX3-/SMAD4+ was a significant independent predictive factor for both OS [p = 0.025, HR 1.842 (95% CI 1.079-3.143)] and PFS [p = 0.020, HR 1.850 (95% CI 1.100-3.113)]. Conclusions SMAD4-positivity with RUNX3-negativity was a significant independent predictive factor for favorable OS and PFS in PDAC. This is the first and large clinicopathological study of RUNX3/SMAD4 expression status in human PDAC. Combination immunohistochemistry for SMAD4 and RUNX3 may help identify a favorable prognostic subgroup of PDAC. PMID:29100342

An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

PubMed

Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

2018-01-02

Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p < 0.001) and OS (p < 0.001). The 3-year OS for patients with ICPS =0, ICPS =1, ICPS =2 and ICPS =3 were 95.6, 88.2, 76.0 and 62.2%, respectively (p < 0.001). The 3-year PFS for patients with ICPS = 0-1, ICPS = 2 and ICPS = 3 were 84.8, 71.6 and 54.5%, respectively (p < 0.001). The prognostic value of the ICPS model indicated that the degree of systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be

TU-CD-BRB-08: Radiomic Analysis of FDG-PET Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated with SBRT

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

Cui, Y; Shirato, H; Song, J

2015-06-15

Purpose: This study aims to identify novel prognostic imaging biomarkers in locally advanced pancreatic cancer (LAPC) using quantitative, high-throughput image analysis. Methods: 86 patients with LAPC receiving chemotherapy followed by SBRT were retrospectively studied. All patients had a baseline FDG-PET scan prior to SBRT. For each patient, we extracted 435 PET imaging features of five types: statistical, morphological, textural, histogram, and wavelet. These features went through redundancy checks, robustness analysis, as well as a prescreening process based on their concordance indices with respect to the relevant outcomes. We then performed principle component analysis on the remaining features (number ranged frommore » 10 to 16), and fitted a Cox proportional hazard regression model using the first 3 principle components. Kaplan-Meier analysis was used to assess the ability to distinguish high versus low-risk patients separated by median predicted survival. To avoid overfitting, all evaluations were based on leave-one-out cross validation (LOOCV), in which each holdout patient was assigned to a risk group according to the model obtained from a separate training set. Results: For predicting overall survival (OS), the most dominant imaging features were wavelet coefficients. There was a statistically significant difference in OS between patients with predicted high and low-risk based on LOOCV (hazard ratio: 2.26, p<0.001). Similar imaging features were also strongly associated with local progression-free survival (LPFS) (hazard ratio: 1.53, p=0.026) on LOOCV. In comparison, neither SUVmax nor TLG was associated with LPFS (p=0.103, p=0.433) (Table 1). Results for progression-free survival and distant progression-free survival showed similar trends. Conclusion: Radiomic analysis identified novel imaging features that showed improved prognostic value over conventional methods. These features characterize the degree of intra-tumor heterogeneity reflected on FDG

Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis.

PubMed

Gao, Haiyan; Yang, Mei; Zhang, Xiaolan

2018-04-01

The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation. The multigene prognostic assay was exploited based on the statistically significant pathways and its prognostic function was tested using train set and verified using the gene expression data and survival data of Luminal A breast cancer patients downloaded from the Gene Expression Omnibus. A total of 300 DEGs were identified between good and poor outcome groups, including 176 upregulated genes and 124 downregulated genes. The DEGs may be used to effectively distinguish Luminal A samples with different prognoses verified by hierarchical clustering analysis. There were 9 pathways screened as significant pathways and a total of 18 DEGs involved in these 9 pathways were identified as prognostic biomarkers. According to the survival analysis and receiver operating characteristic curve, the obtained 18-gene prognostic assay exhibited good prognostic function with high sensitivity and specificity to both the train and test samples. In conclusion the 18-gene prognostic assay including the key genes, transcription factor 7-like 2, anterior parietal cortex and lymphocyte enhancer factor-1 may provide a new method for predicting outcomes and may be conducive to the promotion of precision medicine for Luminal A breast cancer.

An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation.

PubMed

Candido Dos Reis, Francisco J; Wishart, Gordon C; Dicks, Ed M; Greenberg, David; Rashbass, Jem; Schmidt, Marjanka K; van den Broek, Alexandra J; Ellis, Ian O; Green, Andrew; Rakha, Emad; Maishman, Tom; Eccles, Diana M; Pharoah, Paul D P

2017-05-22

PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: a meta-analysis

PubMed Central

Shao, Yingjie; Xu, Bin; Chen, Lujun; Zhou, Qi; Hu, Wenwei; Zhang, Dachuan; Wu, Changping; Tao, Min; Zhu, Yibei; Jiang, Jingting

2017-01-01

Background In patients with gastric cancer, the prognostic value of tumor-infiltrating lymphocytes (TILs) is still controversial. A meta-analysis was performed to evaluate the prognostic value of TILs in gastric cancer. Materials and methods We identify studies from PubMed, Embase and the Cochrane Library to assess the prognostic effect of TILs in patients with gastric cancer. Fixed-effects models or random-effects models were used estimate the pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS), which depend on the heterogeneity. Results A total of 31 observational studies including 4,185 patients were enrolled. For TILs subsets, the amount of CD8+, FOXP3+, CD3+, CD57+, CD20+, CD45RO+, Granzyme B+ and T-bet+ lymphocytes was significantly associated with improved survival (P < 0.05); moreover, the amount of CD3+ TILs in intra-tumoral compartment (IT) was the most significant prognostic marker (pooled HR = 0.52; 95% CI = 0.43–0.63; P < 0.001). However, CD4+ TILs was not statistically associated with patients’ survival. FOXP3+ TILs showed bidirectional prognostic roles which had positive effect in IT (pooled HR = 1.57; 95% CI = 1.04–2.37; P = 0.033) and negative effect in extra-tumoral compartment (ET) (pooled HR = 0.76; 95% CI = 0.60–0.96; P = 0.022). Conclusions This meta-analysis suggests that some TIL subsets could serve as prognostic biomarkers in gastric cancer. High-quality randomized controlled trials are needed to decide if these TILs could serve as targets for immunotherapy in gastric cancer. PMID:28915679

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

PubMed

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

2018-01-01

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

Prognostic Factors for Outcomes of In-Flight Sudden Cardiac Arrest on Commercial Airlines.

PubMed

Alves, Paulo M; DeJohn, Charles A; Ricaurte, Eduard M; Mills, William D

In-flight cardiac arrest (IFCA) is a relatively rare but challenging event. Outcomes and prognostic factors are not entirely understood for victims of IFCAs in commercial aviation. This was a retrospective cohort study of airline passengers who experienced IFCA. Demographic and operational variables were studied to identify association in a multivariate logistic regression model with the outcome of survival-to-hospital. In-flight medical emergencies were processed by a ground-based medical center. Subsequent comparisons were made between reported shockable-rhythm (RSR) and reported non-shockable-rhythm (RNSR) groups. Logistic regression was also used to identify predictors for shock advised and flight diversions using a case control study design. Significant predictors for survival-to-hospital were RSR and remaining flight time to destination. The percentage of RSR cases was 24.6%. The survival to hospital admission was 22.7% (22/97) for passengers in RSR compared with 2.4% (7/297) in the RNSR group. The adjusted odds ratio for survival-to-hospital for the RSR group compared to the RNSR group was 13.6 (5.5-33.5). The model showed odds for survival to hospital decreased with longer scheduled remaining flight duration with adjusted OR = 0.701 (0.535-0.920) per hour increase. No correlation between diversions and survival for RSR cases was found. Survival-to-hospital from IFCAs is best when an RSR is present. The percentage of RSR cases was lower than in other out-of-hospital cardiac arrest (OHCA) settings, which suggests delayed discovery. Flight diversions did not significantly affect resuscitation outcome. We emphasize good quality cardio-pulmonary resuscitation (CPR) and early defibrillation as key factors for IFCA survival. Alves PM, DeJohn CA, Ricaurte EM, Mills WD. Prognostic factors for outcomes of in-flight sudden cardiac arrest on commercial airlines. Aerosp Med Hum Perform. 2016; 87(10):862-868.

Prognostic value of circulating microRNAs in upper tract urinary carcinoma

PubMed Central

Ingelmo-Torres, Mercedes; Lozano, Juan José; Capitán, David; Alcaraz, Antonio; Mengual, Lourdes

2018-01-01

The identification of upper tract urinary carcinoma (UTUC) prognostic biomarkers is urgently needed to predict tumour progression. This study aimed to identify serum microRNAs (miRNAs) that may be useful as minimally invasive predictive biomarkers of tumour progression and survival in UTUC patients. To this end, 33 UTUC patients who underwent radical nephroureterectomy at the Hospital Clinic of Barcelona were prospectively included. Expression of 800 miRNAs was evaluated in serum samples from these patients using nCounter® miRNA Expression Assays. The study was divided into an initial discovery phase (n=12) and a validation phase (n=21). Cox regression analysis was used for survival analysis. The median follow-up (range) of the series was 42 months (9-100 months). In the discovery phase, 38 differentially expressed miRNAs were identified between progressing and non-progressing UTUC patients (p<0.05). Validation of these 38 miRNAs in an independent set of UTUC patients confirmed the differential expression in 18 of them (p<0.05). Cox Regression analysis showed miR-151b and pathological stage as significant prognostic factors for tumour progression (HR=0.33, p<0.001 and HR=2.62, p=0.006, respectively) and cancer specific survival (HR=0.25, p<0.001 and HR=3.98, p=0.003, respectively). Survival curves revealed that miR-151b is able to discriminate between two groups of UTUC patients with a highly significant different probability of tumour progression (p=0.006) and cancer specific survival (p=0.034). Although the data needs to be externally validated, miRNA analysis in serum appears to be a valuable prognostic tool in UTUC patients. Particularly, differential expression of miR-151b in serum may serve as a minimally invasive prognostic tool in UTUC. PMID:29682178

Prognostic value of circulating microRNAs in upper tract urinary carcinoma.

PubMed

Montalbo, Ruth; Izquierdo, Laura; Ingelmo-Torres, Mercedes; Lozano, Juan José; Capitán, David; Alcaraz, Antonio; Mengual, Lourdes

2018-03-30

The identification of upper tract urinary carcinoma (UTUC) prognostic biomarkers is urgently needed to predict tumour progression. This study aimed to identify serum microRNAs (miRNAs) that may be useful as minimally invasive predictive biomarkers of tumour progression and survival in UTUC patients. To this end, 33 UTUC patients who underwent radical nephroureterectomy at the Hospital Clinic of Barcelona were prospectively included. Expression of 800 miRNAs was evaluated in serum samples from these patients using nCounter® miRNA Expression Assays. The study was divided into an initial discovery phase (n=12) and a validation phase (n=21). Cox regression analysis was used for survival analysis. The median follow-up (range) of the series was 42 months (9-100 months). In the discovery phase, 38 differentially expressed miRNAs were identified between progressing and non-progressing UTUC patients (p<0.05). Validation of these 38 miRNAs in an independent set of UTUC patients confirmed the differential expression in 18 of them (p<0.05). Cox Regression analysis showed miR-151b and pathological stage as significant prognostic factors for tumour progression (HR=0.33, p<0.001 and HR=2.62, p=0.006, respectively) and cancer specific survival (HR=0.25, p<0.001 and HR=3.98, p=0.003, respectively). Survival curves revealed that miR-151b is able to discriminate between two groups of UTUC patients with a highly significant different probability of tumour progression (p=0.006) and cancer specific survival (p=0.034). Although the data needs to be externally validated, miRNA analysis in serum appears to be a valuable prognostic tool in UTUC patients. Particularly, differential expression of miR-151b in serum may serve as a minimally invasive prognostic tool in UTUC.

Prognostics of Proton Exchange Membrane Fuel Cells stack using an ensemble of constraints based connectionist networks

NASA Astrophysics Data System (ADS)

Javed, Kamran; Gouriveau, Rafael; Zerhouni, Noureddine; Hissel, Daniel

2016-08-01

Proton Exchange Membrane Fuel Cell (PEMFC) is considered the most versatile among available fuel cell technologies, which qualify for diverse applications. However, the large-scale industrial deployment of PEMFCs is limited due to their short life span and high exploitation costs. Therefore, ensuring fuel cell service for a long duration is of vital importance, which has led to Prognostics and Health Management of fuel cells. More precisely, prognostics of PEMFC is major area of focus nowadays, which aims at identifying degradation of PEMFC stack at early stages and estimating its Remaining Useful Life (RUL) for life cycle management. This paper presents a data-driven approach for prognostics of PEMFC stack using an ensemble of constraint based Summation Wavelet- Extreme Learning Machine (SW-ELM) models. This development aim at improving the robustness and applicability of prognostics of PEMFC for an online application, with limited learning data. The proposed approach is applied to real data from two different PEMFC stacks and compared with ensembles of well known connectionist algorithms. The results comparison on long-term prognostics of both PEMFC stacks validates our proposition.

Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease.

PubMed

Romberg-Camps, M J L; Dagnelie, P C; Kester, A D M; Hesselink-van de Kruijs, M A M; Cilissen, M; Engels, L G J B; Van Deursen, C; Hameeteman, W H A; Wolters, F L; Russel, M G V M; Stockbrügger, R W

2009-02-01

Disease course in inflammatory bowel disease (IBD) is variable and difficult to predict. To optimize prognosis, it is of interest to identify phenotypic characteristics at disease onset and other prognostic factors that predict disease course. The aim of this study was to evaluate such factors in a population-based IBD group. IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. A follow-up questionnaire was developed and medical records were reviewed. Patients were classified according to phenotype at diagnosis and risk factors were registered. Disease severity, cumulative medication use, and "surgical" and "nonsurgical" recurrence rates were calculated as outcome parameters. In total, 476 Crohn's disease (CD), 630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery. In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%, respectively. In CD, small bowel localization and stricturing disease were negative prognostic factors for surgery, as was young age. Overall recurrence rate was increased by young age and current smoking. In UC, extensive colitis increased surgical risk. In UC, older age at diagnosis initially increased recurrence risk but was subsequently protective. This population-based IBD study showed high recurrence rates in the first year. In CD, small bowel localization, stricturing disease, and young age were predictive for disease recurrence. In UC, extensive colitis and older age at diagnosis were negative prognostic predictors.

Prognosticators and risk grouping in patients with lung metastasis from nasopharyngeal carcinoma: a more accurate and appropriate assessment of prognosis.

PubMed

Cao, Xun; Luo, Rong-Zhen; He, Li-Ru; Li, Yong; Lin, Wen-Qian; Chen, You-Fang; Wen, Zhe-Sheng

2011-08-26

Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC. A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves. The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%. In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports.

Combined evaluation of the Glasgow prognostic score and carcinoembryonic antigen concentration prior to hepatectomy predicts postoperative outcomes in patients with liver metastasis from colorectal cancer.

PubMed

Kobayashi, Takashi; Kawakamil, Masayo; Hara, Yoshiaki; Shioiri, Sadaaki; Yasuno, Masamichi; Teruya, Masanori; Kaminishi, Michio

2014-01-01

Little is known about the ability of the inflammation-based Glasgow prognostic score (GPS). 106 patients who underwent curative resection for colorectal liver metastasis (CRLM) were analyzed. Patients with an elevated Creactive protein concentration (>10 mg/L) and hypoalbuminemia (<35 g/L) at admission were assigned a GPS 2, those with only 1 of these biochemical abnormalities were assigned a GPS 1, and those without either abnormality were assigned a GPS 0. Multivariate analysis showed that 2 variables, carcinoembryonic antigen (CEA) concentration > 30 ng/mL and a GPS 1 or 2, were independently prognostic of survival. Patients were classified into 3 groups on the basis of these 2 variables. Patients with GPS 1 or 2 and CEA concentration > 30 ng/mL were assigned a new score of 2, those with either 1 factor were assigned a new score of 1, and those with neither factors were assigned a new score of 0. The 5-year overall survival rates of new scores of 0, 1, 2 were 71.5%, 31.6%, and 0%, respectively (P < 0.0001). This simple staging system may be able to identify a subgroup of patients who are eligible for curative resection but show poor prognosis.

Prognostic Relevance of Urinary Bladder Cancer Susceptibility Loci

PubMed Central

Grotenhuis, Anne J.; Dudek, Aleksandra M.; Verhaegh, Gerald W.; Witjes, J. Alfred; Aben, Katja K.; van der Marel, Saskia L.; Vermeulen, Sita H.; Kiemeney, Lambertus A.

2014-01-01

In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive evaluation of the prognostic relevance of all confirmed UBC susceptibility loci. Detailed clinical data concerning diagnosis, stage, treatment, and disease course of a population-based series of 1,602 UBC patients were collected retrospectively based on a medical file survey. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed, and log-rank tests calculated, to evaluate the association between 12 confirmed UBC susceptibility variants and recurrence and progression in non-muscle invasive bladder cancer (NMIBC) patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients, association of these variants with overall survival was tested. Subgroup analyses by tumor aggressiveness and smoking status were performed in NMIBC patients. In the overall NMIBC group (n = 1,269), a statistically significant association between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR = 1.08 (95% CI: 0.76–1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23–2.66), P for trend = 2.6×10−3). In subgroup analyses, several other variants showed suggestive, though non-significant, prognostic relevance for recurrence and progression in NMIBC and survival in MIBC. This study provides suggestive evidence that genetic loci involved in UBC etiology may influence disease prognosis. Elucidation of the causal variant(s) could further our understanding of the mechanism of disease, could point to new therapeutic targets, and might aid in improvement of prognostic tools. PMID:24586564

Clinicopathological significance and prognostic value of myoinvasive patterns in endometrial endometrioid carcinoma.

PubMed

Amălinei, Cornelia; Aignătoaei, Anda Maria; Balan, Raluca Anca; Giuşcă, Simona Eliza; Lozneanu, Ludmila; Avădănei, Elena Roxana; Căruntu, Irina Draga

2018-01-01

Endometrioid endometrial carcinoma has an overall good prognosis. However, variable five-year survival rates (92%-42%) have been reported in FIGO stage I, suggesting the involvement of other factors related to tumor biological behavior. These may be related to the role played by epithelial-mesenchymal transition (EMT) and cancer stem cells in endometrial carcinogenesis. In this context, our review highlights the prognostic significance of several types of myoinvasion in low grade, low stage endometrioid endometrial carcinoma, as a reflection of these molecular changes at the invasive front. According to recently introduced myoinvasive patterns, the diffusely infiltrating and microcystic, elongated, and fragmented (MELF) patterns show loss of hormone receptors, along with EMT and high expression of cancer stem cell markers, being associated with a poor prognosis. Additionally, MELF pattern exhibits a high incidence of lymphovascular invasion and lymph node metastases. Conversely, the broad front pattern has a good prognosis and a low expression of EMT and stem cells markers. Similarly, the adenomyosis (AM)-like and adenoma malignum patterns of invasion are associated to a favorable prognosis, but nevertheless, they raise diagnostic challenges. AM-like pattern must be differentiated from carcinoma invasion of AM foci, while adenoma malignum pattern creates difficulties in appreciating the depth of myoinvasion and requires differential diagnosis with other conditions. Another pattern expecting its validation and prognostic significance value is the nodular fasciitis-like stroma and large cystic growth pattern. In practice, the knowledge of these patterns of myoinvasion may be valuable for the correct assessment of stage, may improve prognosis evaluation and may help identify molecules for future targeted therapies.

Intrinsic Molecular Subtypes of Glioma Are Prognostic and Predict Benefit From Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Combination With Other Prognostic Factors in Anaplastic Oligodendroglial Brain Tumors: A Report From EORTC Study 26951

PubMed Central

Erdem-Eraslan, Lale; Gravendeel, Lonneke A.; de Rooi, Johan; Eilers, Paul H.C.; Idbaih, Ahmed; Spliet, Wim G.M.; den Dunnen, Wilfred F.A.; Teepen, Johannes L.; Wesseling, Pieter; Sillevis Smitt, Peter A.E.; Kros, Johan M.; Gorlia, Thierry; van den Bent, Martin J.; French, Pim J.

2013-01-01

Purpose Intrinsic glioma subtypes (IGSs) are molecularly similar tumors that can be identified based on unsupervised gene expression analysis. Here, we have evaluated the clinical relevance of these subtypes within European Organisation for Research and Treatment of Cancer (EORTC) 26951, a randomized phase III clinical trial investigating adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study includes gene expression profiles of formalin-fixed, paraffin-embedded (FFPE) clinical trial samples. Patients and Methods Gene expression profiling was performed in 140 samples, 47 fresh frozen samples and 93 FFPE samples, on HU133_Plus_2.0 and HuEx_1.0_st arrays, respectively. Results All previously identified six IGSs are present in EORTC 26951. This confirms that different molecular subtypes are present within a well-defined histologic subtype. Intrinsic subtypes are highly prognostic for overall survival (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance status, and tumor location), molecular (1p/19q loss of heterozygosity [LOH], IDH1 mutation, and MGMT methylation), and histologic parameters. Combining known molecular (1p/19q LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (proportion of explained variation, 30% v 23% for each individual group of factors). Specific genetic changes (IDH1, 1p/19q LOH, and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p/19q LOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone versus 12.8 years after RT/PCV (P = .0349; hazard ratio, 2.18; 95% CI, 1.06 to 4.50). Conclusion Intrinsic subtypes are highly prognostic in EORTC 26951 and improve outcome prediction when combined with other prognostic factors. Tumors

The prognostic significance of circulating serum amyloid A and CXC chemokine ligand 4 in osteosarcoma.

PubMed

Flores, Ricardo J; Kelly, Aaron J; Li, Yiting; Chen, Xiang; McGee, Colin; Krailo, Mark; Barkauskas, Donald A; Hicks, John; Man, Tsz-Kwong

2017-12-01

Osteosarcoma (OS) is the most common pediatric bone cancer.  Despite advances in treatment regimens, the survival rate remains 60-70%.  There is an urgent need to identify prognostic biomarkers, so that targeted therapies can be developed to improve the outcome. Our laboratory has previously identified that circulating serum amyloid A (SAA) and CXC chemokine ligand 4 (CXCL4) are upregulated in patients with OS.  In this study, we tested if they could be used as prognostic biomarkers.  We used enzyme-linked immunosorbent assays to measure their concentrations in serum samples (n = 233) and immunohistochemistry to examine their expressions in primary tumors (n = 37).  Prognostic significance of the serum concentrations and tumor expressions of the biomarkers was then evaluated. Patients with "high SAA" and "low CXCL4" circulating levels at diagnosis significantly correlated with a worse outcome (HR = 1.68, P = 0.014), which was independent of the metastatic status.  These patients also exhibited a significantly higher rate of poor histologic response to chemotherapy.  Furthermore, low tumor expression of CXCL4 correlated with poor survival (HR = 3.57, P = 0.005). Our results demonstrate that circulating SAA and CXCL4 may serve as prognostic biomarkers in OS.  Targeting CXCL4 has been reported, suggesting that it may be exploited as a therapeutic target in OS. © 2017 Wiley Periodicals, Inc.

The Prognostic Significance of Circulating Serum Amyloid A and CXC Chemokine Ligand 4 in Osteosarcoma

PubMed Central

Flores, Ricardo J.; Kelly, Aaron J.; Li, Yiting; Chen, Xiang; McGee, Colin; Krailo, Mark; Barkauskas, Donald A.; Hicks, John; Man, Tsz-Kwong

2017-01-01

BACKGROUND Osteosarcoma is the most common pediatric bone cancer. Despite advances in treatment regimens, the survival rate remains 60–70%. There is an urgent need to identify prognostic biomarkers, so that targeted therapies can be developed to improve the outcome. PROCEDURE Our lab has previously identified that circulating Serum Amyloid A (SAA) and CXC Chemokine Ligand 4 (CXCL4) are upregulated in patients with osteosarcoma. In this study, we tested if they could be used as prognostic biomarkers. We used ELISAs to measure their concentrations in serum samples (n = 233), and immunohistochemistry to examine expressions in primary tumors (n = 37). Prognostic significance of the serum concentrations and tumor expressions of the biomarkers was then evaluated. RESULTS Patients with “High SAA” and “Low CXCL4” circulating levels at diagnosis significantly correlated with a worse outcome (HR = 1.68, p = 0.014), which was independent of the metastatic status. These patients also exhibited a significantly higher rate of poor histological response to chemotherapy. Furthermore, low tumor expression of CXCL4 correlated with poor survival (HR = 3.57, p = 0.005). CONCLUSIONS Our results demonstrate that circulating SAA and CXCL4 may serve as prognostic biomarkers in osteosarcoma. Targeting CXCL4 has been reported, suggesting that it may be exploited as a therapeutic target in osteosarcoma. PMID:28544777

Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients

PubMed Central

Carmona-Bayonas, A; Gómez, J; González-Billalabeitia, E; Canteras, M; Navarrete, A; Gonzálvez, M L; Vicente, V; Ayala de la Peña, F

2011-01-01

Background: Predictive models to identify low-risk febrile neutropenia (FN) have been developed with heterogeneous samples, which included stable and unstable patients, solid tumours, acute leukaemia and bone marrow transplantation. These models fail to recognise 5–15% of cases with unexpected complications, and literature specifically addressing apparently stable patients (ASPs) is scarce. Methods: We reviewed 861 episodes of FN in outpatients with solid tumours, including 692 (80%) episodes with apparent clinical stability. We aimed to investigate the prognosis of this latter group and explore the possibility of stratifying it according to the presenting features. A case–control study was performed and the MASCC index was evaluated. Results: The rates of complications and bacteraemia in ASPs were 7.3% and 6.2%, respectively. The MASCC index yielded a low sensitivity to detect complications (36%). Prognostic factors were identified: ECOG performance status ⩾2, chronic bronchitis, chronic heart failure, stomatitis NCI grade ⩾2, monocytes <200 mm−3 and stress hyperglycaemia. Conclusion: A very simple assessment is useful to classify the patients with FN according to the risk of complications. A few additional variables may predict the clinical course of the patients. We additionally show that the MASCC index applied to this specific group has a low sensitivity to predict complications. PMID:21811253

Forecasting municipal solid waste generation using prognostic tools and regression analysis.

PubMed

Ghinea, Cristina; Drăgoi, Elena Niculina; Comăniţă, Elena-Diana; Gavrilescu, Marius; Câmpean, Teofil; Curteanu, Silvia; Gavrilescu, Maria

2016-11-01

For an adequate planning of waste management systems the accurate forecast of waste generation is an essential step, since various factors can affect waste trends. The application of predictive and prognosis models are useful tools, as reliable support for decision making processes. In this paper some indicators such as: number of residents, population age, urban life expectancy, total municipal solid waste were used as input variables in prognostic models in order to predict the amount of solid waste fractions. We applied Waste Prognostic Tool, regression analysis and time series analysis to forecast municipal solid waste generation and composition by considering the Iasi Romania case study. Regression equations were determined for six solid waste fractions (paper, plastic, metal, glass, biodegradable and other waste). Accuracy Measures were calculated and the results showed that S-curve trend model is the most suitable for municipal solid waste (MSW) prediction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project.

PubMed

Shafiq, Ali; Brawner, Clinton A; Aldred, Heather A; Lewis, Barry; Williams, Celeste T; Tita, Christina; Schairer, John R; Ehrman, Jonathan K; Velez, Mauricio; Selektor, Yelena; Lanfear, David E; Keteyian, Steven J

2016-04-01

Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction is well established, there are limited data on the value of CPX variables in patients with HF and preserved ejection fraction (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. This was a retrospective analysis of patients with HFpEF (ejection fraction ≥ 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production slope (VE/VCO2 slope) and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant. We identified 173 HFpEF patients (45% women, 58% non-white, age 54 ± 14 years) with complete CPX data. During a median follow-up of 5.2 years, there were 42 deaths and 5 cardiac transplants. The 1-, 3-, and 5-year cumulative event-free survival was 96%, 90%, and 82%, respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and β-blockade therapy, ppMVO2 was the strongest predictor of the end point (Wald χ(2) = 15.0, hazard ratio per 10%, P < .001), followed by peak VO2 (Wald χ(2) = 11.8, P = .001). VE/VCO2 slope (Wald χ(2)= 0.4, P = .54) and EOV (Wald χ(2) = 0.15, P = .70) had no significant association to the composite outcome. These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic factors of whiplash-associated disorders: a systematic review of prospective cohort studies.

PubMed

Scholten-Peeters, Gwendolijne G M; Verhagen, Arianne P; Bekkering, Geertruida E; van der Windt, Daniëlle A W M; Barnsley, Les; Oostendorp, Rob A B; Hendriks, Erik J M

2003-07-01

We present a systematic review of prospective cohort studies. Our aim was to assess prognostic factors associated with functional recovery of patients with whiplash injuries. The failure of some patients to recover following whiplash injury has been linked to a number of prognostic factors. However, there is some inconsistency in the literature and there have been no systematic attempts to analyze the level of evidence for prognostic factors in whiplash recovery. Studies were selected for inclusion following a comprehensive search of MEDLINE, EMBASE, CINAHL, the database of the Dutch Institute of Allied Health Professions up until April 2002 and hand searches of the reference lists of retrieved articles. Studies were selected if the objective was to assess prognostic factors associated with recovery; the design was a prospective cohort study; the study population included at least an identifiable subgroup of patients suffering from a whiplash injury; and the paper was a full report published in English, German, French or Dutch. The methodological quality was independently assessed by two reviewers. A study was considered to be of 'high quality' if it satisfied at least 50% of the maximum available quality score. Two independent reviewers extracted data and the association between prognostic factors and functional recovery was calculated in terms of risk estimates. Fifty papers reporting on twenty-nine cohorts were included in the review. Twelve cohorts were considered to be of 'high quality'. Because of the heterogeneity of patient selection, type of prognostic factors and outcome measures, no statistical pooling was able to be performed. Strong evidence was found for high initial pain intensity being an adverse prognostic factor. There was strong evidence that for older age, female gender, high acute psychological response, angular deformity of the neck, rear-end collision, and compensation not being associated with an adverse prognosis. Several physical (e

Metrics for Offline Evaluation of Prognostic Performance

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2010-01-01

Prognostic performance evaluation has gained significant attention in the past few years. Currently, prognostics concepts lack standard definitions and suffer from ambiguous and inconsistent interpretations. This lack of standards is in part due to the varied end-user requirements for different applications, time scales, available information, domain dynamics, etc. to name a few. The research community has used a variety of metrics largely based on convenience and their respective requirements. Very little attention has been focused on establishing a standardized approach to compare different efforts. This paper presents several new evaluation metrics tailored for prognostics that were recently introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. These metrics have the capability of incorporating probabilistic uncertainty estimates from prognostic algorithms. In addition to quantitative assessment they also offer a comprehensive visual perspective that can be used in designing the prognostic system. Several methods are suggested to customize these metrics for different applications. Guidelines are provided to help choose one method over another based on distribution characteristics. Various issues faced by prognostics and its performance evaluation are discussed followed by a formal notational framework to help standardize subsequent developments.

Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report

NASA Technical Reports Server (NTRS)

Cornhill, Dennis; Bharadwaj, Raj; Mylaraswamy, Dinkar

2013-01-01

This document outlines a set of metrics for evaluating the diagnostic and prognostic schemes developed for the Vehicle Integrated Prognostic Reasoner (VIPR), a system-level reasoner that encompasses the multiple levels of large, complex systems such as those for aircraft and spacecraft. VIPR health managers are organized hierarchically and operate together to derive diagnostic and prognostic inferences from symptoms and conditions reported by a set of diagnostic and prognostic monitors. For layered reasoners such as VIPR, the overall performance cannot be evaluated by metrics solely directed toward timely detection and accuracy of estimation of the faults in individual components. Among other factors, overall vehicle reasoner performance is governed by the effectiveness of the communication schemes between monitors and reasoners in the architecture, and the ability to propagate and fuse relevant information to make accurate, consistent, and timely predictions at different levels of the reasoner hierarchy. We outline an extended set of diagnostic and prognostics metrics that can be broadly categorized as evaluation measures for diagnostic coverage, prognostic coverage, accuracy of inferences, latency in making inferences, computational cost, and sensitivity to different fault and degradation conditions. We report metrics from Monte Carlo experiments using two variations of an aircraft reference model that supported both flat and hierarchical reasoning.

A Novel UAV Electric Propulsion Testbed for Diagnostics and Prognostics

NASA Technical Reports Server (NTRS)

Gorospe, George E., Jr.; Kulkarni, Chetan S.

2017-01-01

This paper presents a novel hardware-in-the-loop (HIL) testbed for systems level diagnostics and prognostics of an electric propulsion system used in UAVs (unmanned aerial vehicle). Referencing the all electric, Edge 540T aircraft used in science and research by NASA Langley Flight Research Center, the HIL testbed includes an identical propulsion system, consisting of motors, speed controllers and batteries. Isolated under a controlled laboratory environment, the propulsion system has been instrumented for advanced diagnostics and prognostics. To produce flight like loading on the system a slave motor is coupled to the motor under test (MUT) and provides variable mechanical resistance, and the capability of introducing nondestructive mechanical wear-like frictional loads on the system. This testbed enables the verification of mathematical models of each component of the propulsion system, the repeatable generation of flight-like loads on the system for fault analysis, test-to-failure scenarios, and the development of advanced system level diagnostics and prognostics methods. The capabilities of the testbed are extended through the integration of a LabVIEW-based client for the Live Virtual Constructive Distributed Environment (LVCDC) Gateway which enables both the publishing of generated data for remotely located observers and prognosers and the synchronization the testbed propulsion system with vehicles in the air. The developed HIL testbed gives researchers easy access to a scientifically relevant portion of the aircraft without the overhead and dangers encountered during actual flight.

Incremental Prognostic Value of Apparent Diffusion Coefficient Histogram Analysis in Head and Neck Squamous Cell Carcinoma.

PubMed

Li, Xiaoxia; Yuan, Ying; Ren, Jiliang; Shi, Yiqian; Tao, Xiaofeng

2018-03-26

We aimed to investigate the incremental prognostic value of apparent diffusion coefficient (ADC) histogram analysis in patients with head and neck squamous cell carcinoma (HNSCC) and integrate it into a multivariate prognostic model. A retrospective review of magnetic resonance imaging findings was conducted in patients with pathologically confirmed HNSCC between June 2012 and December 2015. For each tumor, six histogram parameters were derived: the 10th, 50th, and 90th percentiles of ADC (ADC 10 , ADC 50 , and ADC 90 ); mean ADC values (ADC mean ); kurtosis; and skewness. The clinical variables included age, sex, smoking status, tumor volume, and tumor node metastasis stage. The association of these histogram and clinical variables with overall survival (OS) was determined. Further validation of the histogram parameters as independent biomarkers was performed using multivariate Cox proportional hazard models combined with clinical variables, which was compared to the clinical model. Models were assessed with C index and receiver operating characteristic curve analyses for the 12- and 36-month OS. Ninety-six patients were eligible for analysis. Median follow-up was 877 days (range, 54-1516 days). A total of 29 patients died during follow-up (30%). Patients with higher ADC values (ADC 10  > 0.958 × 10 -3 mm 2 /s, ADC 50  > 1.089 × 10 -3 mm 2 /s, ADC 90  > 1.152 × 10 -3 mm 2 /s, ADC mean  > 1.047 × 10 -3 mm 2 /s) and lower kurtosis (≤0.967) were significant predictors of poor OS (P < .100 for all). After adjusting for sex and tumor node metastasis stage, the ADC 90 and kurtosis are both significant predictors of OS with hazard ratios = 1.00 (95% confidence interval: 1.001-1.004) and 0.58 (95% confidence interval: 0.37-0.90), respectively. By adding the ADC parameters into the clinical model, the C index and diagnostic accuracies for the 12- and 36-month OS showed significant improvement. ADC histogram analysis has

Combined evaluation of the FAS cell surface death receptor and CD8+ tumor infiltrating lymphocytes as a prognostic biomarker in breast cancer

PubMed Central

Blok, Erik J.; van den Bulk, Jitske; Dekker-Ensink, N. Geeske; Derr, Remco; Kanters, Corné; Bastiaannet, Esther; Kroep, Judith R.; van de Velde, Cornelis J.H.; Kuppen, Peter J.K.

2017-01-01

Multiple studies showed the prognostic capacities of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), but not in other subtypes. We evaluated tumor expression of FAS, a key receptor in T-cell mediated apoptosis, as possible explanation for this differential prognostic value of TILs. Furthermore, we evaluated the prognostic relevance of FAS, both as an independent biomarker and in relation to CD8-positive T-cell presence. The study cohort consisted of 667 breast cancer patients treated in the LUMC between 1997 and 2009. FAS expression was determined using immunohistochemistry and the percentage of FAS-positive tumor cells was quantified. Furthermore, the number of CD8-positive infiltrating cells was determined, and its prognostic relevance was associated to FAS-expression using stratified survival analysis. In TNBC, FAS was averagely expressed in 49% of tumor cells, whereas ER-positive subtypes showed an average Fas expression of 16-20%. In the entire cohort, FAS was identified as significant prognostic marker for recurrence (adjusted HR 0.53, 95% CI 0.36-0.77) and borderline significant marker for overall survival (adjusted HR 0.72, 95% CI 0.52-1.01). Upon stratification for FAS-expression, CD8+ TILs were only prognostic at high levels (above median) of FAS expression in ER-negative disease. In summary, FAS was identified as an independent prognostic marker for recurrence free survival in breast cancer, with large variation in expression by receptor subtypes. Interestingly, the prognostic effect of CD8+ TILs in ER-negative disease was only valid for tumors with a high FAS expression. PMID:28121628

Combined evaluation of the FAS cell surface death receptor and CD8+ tumor infiltrating lymphocytes as a prognostic biomarker in breast cancer.

PubMed

Blok, Erik J; van den Bulk, Jitske; Dekker-Ensink, N Geeske; Derr, Remco; Kanters, Corné; Bastiaannet, Esther; Kroep, Judith R; van de Velde, Cornelis J H; Kuppen, Peter J K

2017-02-28

Multiple studies showed the prognostic capacities of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), but not in other subtypes. We evaluated tumor expression of FAS, a key receptor in T-cell mediated apoptosis, as possible explanation for this differential prognostic value of TILs. Furthermore, we evaluated the prognostic relevance of FAS, both as an independent biomarker and in relation to CD8-positive T-cell presence. The study cohort consisted of 667 breast cancer patients treated in the LUMC between 1997 and 2009. FAS expression was determined using immunohistochemistry and the percentage of FAS-positive tumor cells was quantified. Furthermore, the number of CD8-positive infiltrating cells was determined, and its prognostic relevance was associated to FAS-expression using stratified survival analysis. In TNBC, FAS was averagely expressed in 49% of tumor cells, whereas ER-positive subtypes showed an average Fas expression of 16-20%. In the entire cohort, FAS was identified as significant prognostic marker for recurrence (adjusted HR 0.53, 95% CI 0.36-0.77) and borderline significant marker for overall survival (adjusted HR 0.72, 95% CI 0.52-1.01). Upon stratification for FAS-expression, CD8+ TILs were only prognostic at high levels (above median) of FAS expression in ER-negative disease. In summary, FAS was identified as an independent prognostic marker for recurrence free survival in breast cancer, with large variation in expression by receptor subtypes. Interestingly, the prognostic effect of CD8+ TILs in ER-negative disease was only valid for tumors with a high FAS expression.

Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register.

PubMed

Moreno Berggren, Daniel; Folkvaljon, Yasin; Engvall, Marie; Sundberg, Johan; Lambe, Mats; Antunovic, Petar; Garelius, Hege; Lorenz, Fryderyk; Nilsson, Lars; Rasmussen, Bengt; Lehmann, Sören; Hellström-Lindberg, Eva; Jädersten, Martin; Ejerblad, Elisabeth

2018-06-01

The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population-based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population-based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) and the World Health Organization (WHO) Classification-based Prognostic Scoring System (WPSS). We also present population-based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy-related MDS (t-MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2·9 per 100 000 inhabitants. IPSS-R had a significantly better prognostic power than IPSS (P < 0·001). There was a trend for better prognostic power of IPSS-R compared to WPSS (P = 0·05) and for WPSS compared to IPSS (P = 0·07). IPSS-R was superior to both IPSS and WPSS for patients aged ≤70 years. Patients with t-MDS had a worse outcome compared to de novo MDS (d-MDS), however, the validity of the prognostic scoring systems was comparable for d-MDS and t-MDS. In conclusion, population-based studies are important to validate prognostic scores in a 'real-world' setting. In our nationwide cohort, the IPSS-R showed the best predictive power. © 2018 John Wiley & Sons Ltd.

Independent Prognostic Value of Stroke Volume Index in Patients With Immunoglobulin Light Chain Amyloidosis.

PubMed

2018-05-01

Heart involvement is the most important prognostic determinant in AL amyloidosis patients. Echocardiography is a cornerstone for the diagnosis and provides important prognostic information. We studied 754 patients with AL amyloidosis who underwent echocardiographic assessment at the Mayo Clinic, including a Doppler-derived measurement of stroke volume (SV) within 30 days of their diagnosis to explore the prognostic role of echocardiographic variables in the context of a well-established soluble cardiac biomarker staging system. Reproducibility of SV, myocardial contraction fraction, and left ventricular strain was assessed in a separate, yet comparable, study cohort of 150 patients from the Pavia Amyloidosis Center. The echocardiographic measures most predictive for overall survival were SV index <33 mL/min, myocardial contraction fraction <34%, and cardiac index <2.4 L/min/m 2 with respective hazard ratios (95% confidence intervals) of 2.95 (2.37-3.66), 2.36 (1.96-2.85), and 2.32 (1.91-2.80). For the subset that had left ventricular strain performed, the prognostic cut point was -14% (hazard ratios, 2.70; 95% confidence intervals, 1.84-3.96). Each parameter was independent of systolic blood pressure, Mayo staging system (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and troponin), and ejection fraction on multivariable analysis. Simple predictive models for survival, including biomarker staging along with SV index or left ventricular strain, were generated. SV index prognostic performance was similar to left ventricular strain in predicting survival in AL amyloidosis, independently of biomarker staging. Because SV index is routinely calculated and widely available, it could serve as the preferred echocardiographic measure to predict outcomes in AL amyloidosis patients. © 2018 American Heart Association, Inc.

Expression of ARs in triple negative breast cancer tumors: a potential prognostic factor?

PubMed

Giannos, Aris; Filipits, Martin; Zagouri, Flora; Brandstetter, Anita; Tsigginou, Alexandra; Sotiropoulou, Maria; Papaspyrou, Irene; Sergentanis, Theodoros N; Psaltopoulou, Theodora; Rodolakis, Alexandros; Antsaklis, Aris; Dimopoulos, Meletios-Athanasios; Dimitrakakis, Constantine

2015-01-01

In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26-1.70, P=0.393). AR expression does not seem to play a prognostic role in TNBC.

Survival rate and prognostic factors of conventional osteosarcoma in Northern Thailand: A series from Chiang Mai University Hospital.

PubMed

Pruksakorn, Dumnoensun; Phanphaisarn, Areerak; Arpornchayanon, Olarn; Uttamo, Nantawat; Leerapun, Taninnit; Settakorn, Jongkolnee

2015-12-01

Osteosarcoma is a common and aggressive primary malignant bone tumor occurring in children and adolescents. It is one of the most aggressive human cancers and the most common cause of cancer-associated limb loss. As treatment in Thailand has produced a lower survival rate than in developed countries; therefore, this study identified survival rate and the poor prognostic factors of osteosarcoma in Northern Thailand. The retrospective cases of osteosarcoma, diagnosis between 1 January 1996 and 31 December 2013, were evaluated. Five and ten year overall survival rates were analyzed using time-to-event analysis. Potential prognostic factors were identified by multivariate regression analysis. There were 208 newly diagnosed osteosarcomas during that period, and 144 cases met the criteria for analysis. The majority of the osteosarcoma cases (78.5%) were aged 0-24 years. The overall 5- and 10-year survival rates were 37.9% and 33.6%, respectively. Presence of metastasis at initial examination, delayed and against treatment co-operation, and axial skeletal location were identified as independent prognostic factors for survival, with hazard ratios of 4.3, 2.5 and 3.8, and 3.1, respectively. This osteosarcoma cohort had a relatively poor overall survival rate. The prognostic factors identified would play a critical role in modifying survival rates of osteosarcoma patients; as rapid disease recognition, a better treatment counselling, as well as improving of chemotherapeutic regimens were found to be important in improving the overall survival rate in Thailand. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-03-22

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

Prognostic score to predict mortality during TB treatment in TB/HIV co-infected patients.

PubMed

Nguyen, Duc T; Jenkins, Helen E; Graviss, Edward A

2018-01-01

Estimating mortality risk during TB treatment in HIV co-infected patients is challenging for health professionals, especially in a low TB prevalence population, due to the lack of a standardized prognostic system. The current study aimed to develop and validate a simple mortality prognostic scoring system for TB/HIV co-infected patients. Using data from the CDC's Tuberculosis Genotyping Information Management System of TB patients in Texas reported from 01/2010 through 12/2016, age ≥15 years, HIV(+), and outcome being "completed" or "died", we developed and internally validated a mortality prognostic score using multiple logistic regression. Model discrimination was determined by the area under the receiver operating characteristic (ROC) curve (AUC). The model's good calibration was determined by a non-significant Hosmer-Lemeshow's goodness of fit test. Among the 450 patients included in the analysis, 57 (12.7%) died during TB treatment. The final prognostic score used six characteristics (age, residence in long-term care facility, meningeal TB, chest x-ray, culture positive, and culture not converted/unknown), which are routinely collected by TB programs. Prognostic scores were categorized into three groups that predicted mortality: low-risk (<20 points), medium-risk (20-25 points) and high-risk (>25 points). The model had good discrimination and calibration (AUC = 0.82; 0.80 in bootstrap validation), and a non-significant Hosmer-Lemeshow test p = 0.71. Our simple validated mortality prognostic scoring system can be a practical tool for health professionals in identifying TB/HIV co-infected patients with high mortality risk.

Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer.

PubMed

Yu, Jun; Wu, William K K; Li, Xiangchun; He, Jun; Li, Xiao-Xing; Ng, Simon S M; Yu, Chang; Gao, Zhibo; Yang, Jie; Li, Miao; Wang, Qiaoxiu; Liang, Qiaoyi; Pan, Yi; Tong, Joanna H; To, Ka F; Wong, Nathalie; Zhang, Ning; Chen, Jie; Lu, Youyong; Lai, Paul B S; Chan, Francis K L; Li, Yingrui; Kung, Hsiang-Fu; Yang, Huanming; Wang, Jun; Sung, Joseph J Y

2015-04-01

Characterisation of colorectal cancer (CRC) genomes by next-generation sequencing has led to the discovery of novel recurrently mutated genes. Nevertheless, genomic data has not yet been used for CRC prognostication. To identify recurrent somatic mutations with prognostic significance in patients with CRC. Exome sequencing was performed to identify somatic mutations in tumour tissues of 22 patients with CRC, followed by validation of 187 recurrent and pathway-related genes using targeted capture sequencing in additional 160 cases. Seven significantly mutated genes, including four reported (APC, TP53, KRAS and SMAD4) and three novel recurrently mutated genes (CDH10, FAT4 and DOCK2), exhibited high mutation prevalence (6-14% for novel cancer genes) and higher-than-expected number of non-silent mutations in our CRC cohort. For prognostication, a five-gene-signature (CDH10, COL6A3, SMAD4, TMEM132D, VCAN) was devised, in which mutation(s) in one or more of these genes was significantly associated with better overall survival independent of tumor-node-metastasis (TNM) staging. The median survival time was 80.4 months in the mutant group versus 42.4 months in the wild type group (p=0.0051). The prognostic significance of this signature was successfully verified using the data set from the Cancer Genome Atlas study. The application of next-generation sequencing has led to the identification of three novel significantly mutated genes in CRC and a mutation signature that predicts survival outcomes for stratifying patients with CRC independent of TNM staging. 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.

Conceptualizing prognostic awareness in advanced cancer: a systematic review.

PubMed

Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

2014-09-01

This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. © The Author(s) 2013.

Conceptualizing prognostic awareness in advanced cancer: A systematic review

PubMed Central

Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

2015-01-01

This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients’ understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. PMID:24157936

Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in melanoma patients: A meta-analysis.

PubMed

Zhan, Hui; Ma, Jian-Ying; Jian, Qi-Chao

2018-05-29

Recently, the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) has been widely evaluated in many cancers. Here we assessed the prognostic value of pretreatment NLR in melanoma. A range of online databases was systematically searched up to March,2018 for identify available studies which assessed the prognostic significance of NLR. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) were weighted by generic inverse-variance and pooled in random effects meta-analysis. Twelve studies with 4593 individuals were included. Patients with elevated NLR had a significantly shorter overall survival (OS) (HR: 1.56, 95% CI: 1.28-1.90, p < .001) and disease-free survival (DFS)/progression-free survival (PFS) (HR = 1.86; 95% CI = 1.24-2.80; P = .003). Subgroup analyses showed that the negative prognostic effect of elevated NLR on OS remained substantial in North American and Europen populations and patients with non-metastatic and metastatic stage. Additionally, elevated NLR was related to worse OS in patients with melanoma, regardless of the sample size and the cut-off value. Our findings suggest that elevated pretreatment NLR was associated with poor prognosis in melanoma patients, suggesting NLR might be a prognostic factor in patients with melanoma. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2008-01-01

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

Functional Analysis of Problem Behavior: A Systematic Approach for Identifying Idiosyncratic Variables

PubMed Central

Roscoe, Eileen M.; Schlichenmeyer, Kevin J.; Dube, William V.

2015-01-01

When inconclusive functional analysis (FA) outcomes occur, a number of modifications have been made to enhance the putative establishing operation or consequence associated with behavioral maintenance. However, a systematic method for identifying relevant events to test during modified FAs has not been evaluated. The purpose of this study was to develop and evaluate a technology for systematically identifying events to test in a modified FA after an initial FA led to inconclusive outcomes. Six individuals whose initial FA showed little or no responding or high levels only in the control condition participated. An indirect assessment (IA) questionnaire developed for identifying idiosyncratic variables was administered, and a descriptive analysis (DA) was conducted. Results from the IA only or a combination of the IA and DA were used to inform modified FA test and control conditions. Conclusive FA outcomes were obtained with five of the six participants during the modified FA phase. PMID:25930176

SPP1 and AGER as potential prognostic biomarkers for lung adenocarcinoma.

PubMed

Zhang, Weiguo; Fan, Junli; Chen, Qiang; Lei, Caipeng; Qiao, Bin; Liu, Qin

2018-05-01

Overdue treatment and prognostic evaluation lead to low survival rates in patients with lung adenocarcinoma (LUAD). To date, effective biomarkers for prognosis are still required. The aim of the present study was to screen differentially expressed genes (DEGs) as biomarkers for prognostic evaluation of LUAD. DEGs in tumor and normal samples were identified and analyzed for Kyoto Encyclopedia of Genes and Genomes/Gene Ontology functional enrichments. The common genes that are up and downregulated were selected for prognostic analysis using RNAseq data in The Cancer Genome Atlas. Differential expression analysis was performed with 164 samples in GSE10072 and GSE7670 datasets. A total of 484 DEGs that were present in GSE10072 and GSE7670 datasets were screened, including secreted phosphoprotein 1 (SPP1) that was highly expressed and DEGs ficolin 3, advanced glycosylation end-product specific receptor (AGER), transmembrane protein 100 that were lowly expressed in tumor tissues. These four key genes were subsequently verified using an independent dataset, GSE19804. The gene expression model was consistent with GSE10072 and GSE7670 datasets. The dysregulation of highly expressed SPP1 and lowly expressed AGER significantly reduced the median survival time of patients with LUAD. These findings suggest that SPP1 and AGER are risk factors for LUAD, and these two genes may be utilized in the prognostic evaluation of patients with LUAD. Additionally, the key genes and functional enrichments may provide a reference for investigating the molecular expression mechanisms underlying LUAD.

Prognostic factors and outcome in anorexia nervosa: a follow-up study.

PubMed

Errichiello, Luca; Iodice, Davide; Bruzzese, Dario; Gherghi, Marco; Senatore, Ignazio

2016-03-01

Anorexia nervosa is an eating disorder characterized by food restriction, irrational fear of gaining weight and consequent weight loss. High mortality rates have been reported, mostly due to suicide and malnutrition. Good outcomes largely vary between 18 and 42%. We aimed to assess outcome and prognostic factors of a large group of patients with anorexia nervosa. Moreover we aimed to identify clusters of prognostic factors related to specific outcomes. We retrospectively reviewed data of 100 patients diagnosed with anorexia nervosa previously hospitalized in a tertiary level structure. Then we performed follow-up structured telephone interviews. We identified four dead patients, while 34% were clinically recovered. In univariate analysis, short duration of inpatient treatment (p = 0.003), short duration of disorder (p = 0.001), early age at first inpatient treatment (p = 0.025) and preserved insight (p = 0.029) were significantly associated with clinical recovery at follow-up. In multiple logistic regression analysis, duration of first inpatient treatment, duration of disorder and preserved insight maintained their association with outcome. Moreover multiple correspondence analysis and cluster analysis allowed to identify different typologies of patients with specific features. Notably, group 1 was characterized by two or more inpatient treatments, BMI ≤ 14, absence of insight, history of long-term inpatient treatments, first inpatient treatment ≥30 days. While group 4 was characterized by preserved insight, BMI ≥ 16, first inpatient treatment ≤14 days, no more than one inpatient treatment, no psychotropic drugs intake, duration of illness ≤4 years. We confirmed the association between short duration of inpatient treatment, short duration of disorder, early age at first inpatient treatment, preserved insight and clinical recovery. We also differentiated patients with anorexia nervosa in well-defined outcome groups according to specific clusters of

Prognostic Factors for Neurologic Outcome in Patients with Carotid Artery Stenting

PubMed Central

Hung, Chi-Sheng; Lin, Mao-Shin; Chen, Ying-Hsien; Huang, Ching-Chang; Li, Hung-Yuan; Kao, Hsien-Li

2016-01-01

Background Carotid artery stenting (CAS) is a valid treatment for patients with carotid artery stenosis. The long-term outcome and prognostic factors in Asian population after CAS are not clear. This study aimed to identify the prognostic factors among Asian patients who have undergone CAS. Methods We retrospectively analyzed 246 patients with CAS. Annual carotid duplex ultrasound was used to identify restenosis. Peri-procedural complications, restenosis, neurologic outcomes, and mortality were recorded. Cox regression analyses were used to identify prognostic factors. Results The mean follow-up time was 49.2 months. Procedural success was achieved in 237 patients (98.3%), and protection devices were used in 208 patients (84.5%). Within 30 days of CAS, 13 (4.3% per procedure) peri-procedural complications occurred. During the follow-up period, 24 (9.7%) patients developed restenosis, and 37 (15.0%) developed ischemic strokes. In a multiple logistic regression analysis, head and neck radiotherapy [hazard ratio (HR) = 9.9, 95% confidence interval (CI), 3.38-29.1, p < .001], stent diameter (HR = 0.72, 95% CI, 0.58-0.89, p = .003), and predilatation (HR = 3.08 95% CI, 1.21-7.81, p = .018) were independent predictors for restenosis. In Cox regression analysis, hypercholesterolemia (HR = 0.25, 95% CI, 0.07-0.94, p = .04), head and neck radiotherapy (HR = 6.2, 95% CI, 1.8-21.3, p = .004), and restenosis (HR = 3.6, 95% CI, 1.1-11.18, p = .04) were predictors for recurrent ipsilateral ischemic stroke. Conclusions CAS provides reliable long-term results in Asian patients with carotid stenosis. Restenosis is associated with an increased rate of recurrent stroke and should be monitored carefully following CAS. PMID:27122951

The association of 83 plasma proteins with CHD mortality, BMI, HDL-, and total-cholesterol in men: applying multivariate statistics to identify proteins with prognostic value and biological relevance.

PubMed

Heidema, A Geert; Thissen, Uwe; Boer, Jolanda M A; Bouwman, Freek G; Feskens, Edith J M; Mariman, Edwin C M

2009-06-01

In this study, we applied the multivariate statistical tool Partial Least Squares (PLS) to analyze the relative importance of 83 plasma proteins in relation to coronary heart disease (CHD) mortality and the intermediate end points body mass index, HDL-cholesterol and total cholesterol. From a Dutch monitoring project for cardiovascular disease risk factors, men who died of CHD between initial participation (1987-1991) and end of follow-up (January 1, 2000) (N = 44) and matched controls (N = 44) were selected. Baseline plasma concentrations of proteins were measured by a multiplex immunoassay. With the use of PLS, we identified 15 proteins with prognostic value for CHD mortality and sets of proteins associated with the intermediate end points. Subsequently, sets of proteins and intermediate end points were analyzed together by Principal Components Analysis, indicating that proteins involved in inflammation explained most of the variance, followed by proteins involved in metabolism and proteins associated with total-C. This study is one of the first in which the association of a large number of plasma proteins with CHD mortality and intermediate end points is investigated by applying multivariate statistics, providing insight in the relationships among proteins, intermediate end points and CHD mortality, and a set of proteins with prognostic value.

Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

PubMed Central

Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.

2015-01-01

Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170

A consensus prognostic gene expression classifier for ER positive breast cancer

PubMed Central

Teschendorff, Andrew E; Naderi, Ali; Barbosa-Morais, Nuno L; Pinder, Sarah E; Ellis, Ian O; Aparicio, Sam; Brenton, James D; Caldas, Carlos

2006-01-01

Background A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. Results Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation. Conclusion The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors. PMID:17076897

PROGNOSTIC SIGNIFICANCE OF CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERISTICS OF MEDULLOBLASTOMAS IN THE PROSPECTIVE HIT2000 MULTICENTER CLINICAL TRIAL COHORT

PubMed Central

Pietsch, Torsten; Schmidt, Rene; Remke, Marc; Korshunov, Andrey; Hovestadt, Volker; Jones, David TW; Felsberg, Jörg; Kaulich, Kerstin; Goschzik, Tobias; Kool, Marcel; Northcott, Paul A.; von Hoff, Katja; von Bueren, André O.; Friedrich, Carsten; Skladny, Heyko; Fleischhack, Gudrun; Taylor, Michael D.; Cremer, Friedrich; Lichter, Peter; Faldum, Andreas; Reifenberger, Guido; Rutkowski, Stefan; Pfister, Stefan M.

2014-01-01

BACKGROUND: This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. METHODS: Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a validation (n = 57) dataset. All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. RESULTS: By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, TOP2A copy-number, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining “intermediate molecular risk” population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified and validated, with speckled synaptophysin expression indicating worse outcome. CONCLUSIONS: Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk-stratification of medulloblastoma. A simple clinico-pathological risk score for “intermediate molecular risk” patients was identified, which deserves further validation

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

PubMed Central

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

2015-01-01

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

Prognostic pathologic factors in radical cystectomy after neoadjuvant chemotherapy.

PubMed

Brimo, Fadi; Downes, Michelle R; Jamaspishvili, Tamara; Berman, David; Barkan, Guliz A; Athanazio, Daniel; Abro, Schuharazad; Visram, Kash; Yilmaz, Asli; Solanki, Shraddha; Hahn, Elan; Siemens, Robert; Kassouf, Wassim; Trpkov, Kiril

2018-05-18

We undertook a systematic evaluation of the prognostic value of numerous histologic factors in 165 radical cystectomies (RC) of patients with invasive urothelial carcinoma who underwent surgery after neoadjuvant chemotherapy (NAC). Tumor regression grade (TRG) and therapy-related stromal and epithelial changes were also recorded. Locally advanced disease (≥pT2 and/or pN+) was present in 64% of patients, 22% had no evidence of residual carcinoma (pT0+pN0) and 28% had no evidence of residual muscle invasive carcinoma (≤pT1+N0). TRG 1, 2, and 3 were found in 32%, 15%, and 50% of patients, respectively. Histologic variants of UC were reported in 25% of cases. The most common therapy-related stromal change was fibroblastic reaction (78%) and the most common epithelial change in residual UC was smudgy and poorly preserved chromatin (28%). Prominent stromal and epithelial changes were noted in 41% and 5% of RC, respectively. Progression was found in 45% of patients and cancer-related deaths occurred in 30%. Multivariate analysis showed that the only independent prognostic parameters for progression were T stage, N stage, lymphovascular invasion, and the margin status. Similarly, only T stage, N stage, and the margin status correlated with cancer-related deaths. Neither TRG, nor any of the stromal or epithelial-related variables correlated with outcome. We confirm that the traditional and routinely-reported histologic parameters in RC post-NAC remain the most powerful prognosticators of disease course. The significance of TRG in the bladder remains unconfirmed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Development and Validation of a Lifecycle-based Prognostics Architecture with Test Bed Validation

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

Hines, J. Wesley; Upadhyaya, Belle; Sharp, Michael

applying the Bayesian method to lifecycle prognostics consisted of identifying the prior, which is the RUL estimate and uncertainty from the previous prognostics type, and combining it with observational data related to the newer prognostics type. The resulting lifecycle prognostics algorithm uses all available information throughout the component lifecycle.« less

Quantitative modeling of clinical, cellular, and extracellular matrix variables suggest prognostic indicators in cancer: a model in neuroblastoma.

PubMed

Tadeo, Irene; Piqueras, Marta; Montaner, David; Villamón, Eva; Berbegall, Ana P; Cañete, Adela; Navarro, Samuel; Noguera, Rosa

2014-02-01

Risk classification and treatment stratification for cancer patients is restricted by our incomplete picture of the complex and unknown interactions between the patient's organism and tumor tissues (transformed cells supported by tumor stroma). Moreover, all clinical factors and laboratory studies used to indicate treatment effectiveness and outcomes are by their nature a simplification of the biological system of cancer, and cannot yet incorporate all possible prognostic indicators. A multiparametric analysis on 184 tumor cylinders was performed. To highlight the benefit of integrating digitized medical imaging into this field, we present the results of computational studies carried out on quantitative measurements, taken from stromal and cancer cells and various extracellular matrix fibers interpenetrated by glycosaminoglycans, and eight current approaches to risk stratification systems in patients with primary and nonprimary neuroblastoma. New tumor tissue indicators from both fields, the cellular and the extracellular elements, emerge as reliable prognostic markers for risk stratification and could be used as molecular targets of specific therapies. The key to dealing with personalized therapy lies in the mathematical modeling. The use of bioinformatics in patient-tumor-microenvironment data management allows a predictive model in neuroblastoma.

Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management

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

Kopelson, G.; Linggood, R.M.; Kleinman, G.M.

1983-01-15

For 43 medulloblatoma patients who had five-and ten-year actuarial survival rates of 56%, prognostic factors of statistical significance included: T-stage, M-stage and histopathologic tumor score. Posterior fossa local control rates were also function of T-stage and TS. Combining TS with T-stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS less than or equal to 5) histology had a 92% ten-year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group, increasing the irradiation dose alone maymore » improve survival because these tumors exhibited an irradiation dose-response relationship. However, it is the poor prognosis group which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.« less

Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure

PubMed Central

Rengo, Giuseppe; Pagano, Gennaro; Filardi, Pasquale Perrone; Femminella, Grazia Daniela; Parisi, Valentina; Cannavo, Alessandro; Liccardo, Daniela; Komici, Klara; Gambino, Giuseppina; D’Amico, Maria Loreta; de Lucia, Claudio; Paolillo, Stefania; Trimarco, Bruno; Vitale, Dino Franco; Ferrara, Nicola; Koch, Walter J; Leosco, Dario

2016-01-01

Rationale Sympathetic nervous system (SNS) hyperactivity is associated with poor prognosis in patients with HF, yet routine assessment of SNS activation is not recommended for clinical practice. Myocardial G protein-coupled receptor kinase 2 (GRK2) is up-regulated in heart failure (HF) patients, causing dysfunctional β-adrenergic receptor signaling. Importantly, myocardial GRK2 levels correlate with levels found in peripheral lymphocytes of HF patients. Objective The independent prognostic value of blood GRK2 measurements in HF patients has never been investigated, thus, the purpose of the present study was to evaluate whether lymphocyte GRK2 levels predict clinical outcome in HF patients. Methods and Results We prospectively studied 257 HF patients with mean left ventricular ejection fraction (LVEF) of 31.4±8.5%. At the time of enrollment, plasma norepinephrine, serum NT-proBNP and lymphocyte GRK2 levels, as well as clinical and instrumental variables were measured. The prognostic value of GRK2 to predict cardiovascular (CV) death and all-cause mortality was assessed using the Cox proportional hazard model including demographic, clinical, instrumental and laboratory data. Over a mean follow-up period of 37.5±20.2 months (range: 3–60 months) there were 102 CV deaths. Age, LVEF, NYHA class, Chronic Obstructive Pulmonary Disease, Chronic Kidney Disease, N-terminal-pro Brain Natriuretic Peptide, and lymphocyte GRK2 protein levels were independent predictors of CV mortality in HF patients. GRK2 levels showed an additional prognostic and clinical value over demographic and clinical variables. The independent prognostic value of lymphocyte GRK2 levels was also confirmed for all-cause mortality. Conclusion Lymphocyte GRK2 protein levels can independently predict prognosis in patients with HF. PMID:26884616

Incorporating prognostic imaging biomarkers into clinical practice

PubMed Central

Miles, Kenneth A.

2013-01-01

Abstract A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from predictive imaging biomarkers and imaging markers of response. A range of tumour characteristics of potential prognostic value can be measured using a variety imaging modalities. However, none has currently been adopted into routine clinical practice. This article considers key examples of emerging prognostic imaging biomarkers and proposes an evaluation framework that aims to demonstrate clinical efficacy and so support their introduction into the clinical arena. With appropriate validation within an established evaluation framework, prognostic imaging biomarkers have the potential to contribute to individualized cancer care, in some cases reducing the financial burden of expensive cancer treatments by facilitating their more rational use. PMID:24060808

An Integrated Approach for Gear Health Prognostics

NASA Technical Reports Server (NTRS)

He, David; Bechhoefer, Eric; Dempsey, Paula; Ma, Jinghua

2012-01-01

In this paper, an integrated approach for gear health prognostics using particle filters is presented. The presented method effectively addresses the issues in applying particle filters to gear health prognostics by integrating several new components into a particle filter: (1) data mining based techniques to effectively define the degradation state transition and measurement functions using a one-dimensional health index obtained by whitening transform; (2) an unbiased l-step ahead RUL estimator updated with measurement errors. The feasibility of the presented prognostics method is validated using data from a spiral bevel gear case study.

EphA4 is a prognostic factor in gastric cancer

PubMed Central

2013-01-01

Background Erythropoietin-producing hepatocellular (Eph) receptor, consisting of a family of receptor tyrosine kinases, plays critical roles in tumour development and is considered an attractive target for cancer therapy. Methods Tumour samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy. The expressions of EphA2, EphA4, and ephrinA1 were evaluated immunohistochemically. Results High expressions of EphA2, EphA4, and ephrinA1 significantly correlated with variables related to tumour progression, including the depth of invasion, metastatic lymph nodes, pathological stage, and distant metastasis or recurrent disease. High expressions of EphA2, EphA4, and ephrinA1 were significantly associated with poorer disease-specific survival (DSS; p < 0.001, p < 0.001, p = 0.026). On multivariate analysis, EphA4 was an independent prognostic factor of DSS (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.1-4.8; p = 0.028), and EphA2 tended to be a prognostic factor (HR, 2.4; 95% CI, 1.0-5.8; p = 0.050). In stage II and III cancer, EphA4 and EphA2 were both significantly associated with shorter survival (p = 0.007 and 0.019), but only EphA2 was an independent prognostic factor (HR, 2.6; 95% CI, 1.1-6.3; p = 0.039). Conclusion EphA4 may play important roles in tumor progression and outcomes in patients with gastric cancer. PMID:23738943

Assessment of corticosteroid-induced alkaline phosphatase as a prognostic indicator in canine lymphoma.

PubMed

Wiedemann, A L; Charney, S C; Barger, A M; Schaeffer, D J; Kitchell, B E

2005-04-01

To examine the incidence of elevated corticosteroid-induced alkaline phosphatase (sALP) in dogs with lymphoma and to determine if sALP is a reliable prognostic indicator in canine lymphoma. The medical records of 62 canine lymphoma patients treated with a combination chemotherapy protocol from 1994 to 2003 at the University of Illinois Veterinary Teaching Hospital were examined. Variables assessed with respect to response rate and remission duration included age, bodyweight, sex, breed, World Health Organization stage (I to V), substage (a or b), pretreatment administration of corticosteroid, and serum levels of alkaline phosphatase, sALP and alanine aminotransferase. sALP was not statistically significant with respect to response rate or duration of remission, nor was preinduction glucocorticoid administration. Stage was significant with respect to achieving remission. It was found that sALP is not a useful prognostic indicator for response rate and remission duration in dogs with lymphoma.

Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue.

PubMed

Nielsen, H J; Hansen, U; Christensen, I J; Reimert, C M; Brünner, N; Moesgaard, F

1999-12-01

Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours, but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification. In the present study, the prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed. Intra-operative tumour tissue samples from 584 patients undergoing elective surgery for colorectal cancer were included. None of the patients received pre- or post-operative adjuvant chemotherapy. Tissue blocks were cut from the periphery of the tumours and embedded in paraffin. All blocks included both tumour tissue and normal bowel tissue. Serial sections of 4 microm were analysed for tumour tissue inflammatory cell infiltration using a computer- and video-assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used to dichotomize the cell counts with respect to survival. The median observation period was 61 (49-75) months. In a multivariate analysis including Dukes' stage, gender, age, peri-operative blood transfusion, tumour location, and counts of specific inflammatory cells, only advanced Dukes' stage ( p< 0.0001), high age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth. Copyright 1999 John Wiley & Sons, Ltd.

Towards Prognostics of Electrolytic Capacitors

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Kulkarni, Chetan; Biswas, Gautam; Goegel, Kai

2011-01-01

A remaining useful life prediction algorithm and degradation model for electrolytic capacitors is presented. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management research. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. In particular, experimental results of an accelerated aging test under electrical stresses are presented. The capacitors used in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors.

A primary tumor of mixed histological type is a novel poor prognostic factor for patients undergoing resection of liver metastasis from gastric cancer.

PubMed

Ikari, Naoki; Taniguchi, Kiyoaki; Serizawa, Akiko; Yamada, Takuji; Yamamoto, Masakazu; Furukawa, Toru

2017-05-01

Surgical resection can be an option for the treatment of metastatic liver tumors originating from gastric cancer; however, its prognostic impact is controversial. The aim of this study was to identify prognostic factors in patients with surgical resection of liver metastasis from gastric cancer. We retrospectively analyzed the clinicopathological features of 38 consecutive patients undergoing hepatectomy for metastatic tumors from gastric cancer in our institution between 1990 and 2014. The median overall survival of the patients was 28 months. The 5-year survival rate was 33.9%. Primary tumors of a mixed histological type, and residual tumors during the course of treatment were identified as significant independent poor prognostic factors. Histological evaluation of primary tumors may aid to identify patients suitable for undergoing surgical resection of liver metastasis from gastric cancer. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Prognostic significance of chemotherapy-induced necrosis in osteosarcoma patients receiving pasteurized autografts

PubMed Central

Joo, Min Wook; Kang, Yong Koo; Yoo, Chang-Young; Cha, Sung Ho

2017-01-01

Background Among various reconstruction methods after wide excision for osteosarcoma, pasteurized autograft is often preferred. While the whole area of the tumor can be assessed for chemotherapy-induced necrosis, one of the important prognostic factors, in other reconstructive techniques, only a portion removed from a wide-resection specimen is available when using pasteurized autograft method. The assessment, therefore, may be unreliable. We analyzed the prognostic significance of the chemotherapy-induced necrosis in osteosarcoma patients who underwent reconstruction with pasteurized autografts. Patients and methods We reviewed the records of osteosarcoma patients who underwent treatment in our institution from 1998 to 2013. Cases of reconstruction with pasteurized autografts were defined as the patient group, and the same number of patients who underwent other reconstruction methods served as controls. Chemotherapy-induced necrosis was evaluated for removed extra-osseous and curetted intramedullary tumor tissues. Results A total of 22 patients were identified; the median age was 15.5 years, and there were 12 males. The most common tumor location was the distal femur. The most common histological subtype was osteoblastic. Median size was 8.1 cm. Disease status was stage IIB in 13 patients and IIA in 9. Median follow-up was 76 months. No differences between the patient and control groups were observed in potential prognostic factors, overall survival, metastasis-free survival, or recurrence-free survival. Univariate analyses demonstrated that histological response was a significant prognostic factor for metastasis-free survival and also significant for recurrence-free survival. Conclusion Chemotherapy-induced necrosis grading, using only available tumor tissues, could be a prognostic factor for osteosarcoma patients receiving pasteurized autografts for reconstructive surgery. PMID:28196121

Identifying Psychosocial Variables That Predict Safer Sex Intentions in Adolescents and Young Adults

PubMed Central

Brüll, Phil; Ruiter, Robert A. C.; Wiers, Reinout W.; Kok, Gerjo

2016-01-01

Young people are especially vulnerable to sexually transmitted infections (STIs). The triad of deliberate and effective safer sex behavior encompasses condom use, combined with additional information about a partner’s sexual health, and the kind of sex acts usually performed. To identify psychosocial predictors of young people’s intentions to have safer sex, as related to this triad, we conducted an online study with 211 sexually active participants aged between 18 and 24 years. Predictors [i.e., perceived behavioral control (PBC), subjective norms, and intention] taken from Fishbein and Ajzen’s Reasoned Action Approach (RAA), were combined with more distal variables (e.g., behavioral inhibition, sensation seeking, parental monitoring, and knowledge about STIs). Beyond the highly predictive power of RAA variables, additional variance was explained by the number of instances of unprotected sexual intercourse (SI) during the last 12 months and reasons for using barrier protection during first SI. In particular, past condom non-use behavior moderated PBC related to intended condom use. Further, various distal variables showed significant univariate associations with intentions related to the three behaviors of interest. It may, therefore, be helpful to include measures of past behavior as well as certain additional distal variables in future safer sex programs designed to promote health-sustaining sexual behavior. PMID:27148520

Procalcitonin and albumin as prognostic biomarkers in elderly patients with a risk of bacterial infection.

PubMed

Higashikawa, Toshihiro; Okuro, Masashi; Ishigami, Keiichirou; Mae, Kunihiro; Sangen, Ryusho; Mizuno, Takurou; Usuda, Daisuke; Saito, Atushi; Kasamaki, Yuji; Fukuda, Akihiro; Saito, Hitoshi; Morimoto, Shigeto; Kanda, Tsugiyasu

2018-01-01

Aim This study was performed to investigate serum procalcitonin (PCT) and albumin (Alb) as prognostic biomarkers in elderly patients at risk of bacterial infection. Methods Serum PCT was measured in 270 hospitalized patients (mean age, 77.4 years) with suspected bacterial infection. The PCT-negative (<0.5 ng/mL) and PCT-positive (≥0.5 ng/mL) groups comprised 155 and 115 patients, respectively. Logistic regression analysis was performed with various clinical laboratory test values as independent variables and PCT positivity/negativity as the dependent variable. Results C-reactive protein (CRP) was the only independent variable significantly associated with PCT positivity/negativity. In the survival analysis, the 30-day in-hospital death rate was significantly higher in the PCT-positive than -negative group. Within the Alb-positive group (>2.5 g/dL), no significant difference in survival was observed between the PCT-positive and -negative groups. However, within the Alb-negative group (≤2.5 g/dL), the survival rate was significantly lower in the PCT-positive than -negative group. PCT was strongly associated with CRP and Alb, and having both PCT positivity and Alb negativity was a prognostic factor for elderly people at risk of bacterial infection. Conclusions Combined measurement of PCT with Alb is expected to be a valuable tool to assess prognosis in elderly people at risk of bacterial infection.

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

PubMed

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

2016-08-01

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

A potential prognostic long non-coding RNA signature to predict metastasis-free survival of breast cancer patients.

PubMed

Sun, Jie; Chen, Xihai; Wang, Zhenzhen; Guo, Maoni; Shi, Hongbo; Wang, Xiaojun; Cheng, Liang; Zhou, Meng

2015-11-09

Long non-coding RNAs (lncRNAs) have been implicated in a variety of biological processes, and dysregulated lncRNAs have demonstrated potential roles as biomarkers and therapeutic targets for cancer prognosis and treatment. In this study, by repurposing microarray probes, we analyzed lncRNA expression profiles of 916 breast cancer patients from the Gene Expression Omnibus (GEO). Nine lncRNAs were identified to be significantly associated with metastasis-free survival (MFS) in the training dataset of 254 patients using the Cox proportional hazards regression model. These nine lncRNAs were then combined to form a single prognostic signature for predicting metastatic risk in breast cancer patients that was able to classify patients in the training dataset into high- and low-risk subgroups with significantly different MFSs (median 2.4 years versus 3.0 years, log-rank test p < 0.001). This nine-lncRNA signature was similarly effective for prognosis in a testing dataset and two independent datasets. Further analysis showed that the predictive ability of the signature was independent of clinical variables, including age, ER status, ESR1 status and ERBB2 status. Our results indicated that lncRNA signature could be a useful prognostic marker to predict metastatic risk in breast cancer patients and may improve upon our understanding of the molecular mechanisms underlying breast cancer metastasis.

Electromechanical actuators affected by multiple failures: Prognostic method based on spectral analysis techniques

NASA Astrophysics Data System (ADS)

Belmonte, D.; Vedova, M. D. L. Dalla; Ferro, C.; Maggiore, P.

2017-06-01

The proposal of prognostic algorithms able to identify precursors of incipient failures of primary flight command electromechanical actuators (EMA) is beneficial for the anticipation of the incoming failure: an early and correct interpretation of the failure degradation pattern, in fact, can trig an early alert of the maintenance crew, who can properly schedule the servomechanism replacement. An innovative prognostic model-based approach, able to recognize the EMA progressive degradations before his anomalous behaviors become critical, is proposed: the Fault Detection and Identification (FDI) of the considered incipient failures is performed analyzing proper system operational parameters, able to put in evidence the corresponding degradation path, by means of a numerical algorithm based on spectral analysis techniques. Subsequently, these operational parameters will be correlated with the actual EMA health condition by means of failure maps created by a reference monitoring model-based algorithm. In this work, the proposed method has been tested in case of EMA affected by combined progressive failures: in particular, partial stator single phase turn to turn short-circuit and rotor static eccentricity are considered. In order to evaluate the prognostic method, a numerical test-bench has been conceived. Results show that the method exhibit adequate robustness and a high degree of confidence in the ability to early identify an eventual malfunctioning, minimizing the risk of fake alarms or unannounced failures.

Identifying optimal remotely-sensed variables for ecosystem monitoring in Colorado Plateau drylands

USGS Publications Warehouse

Poitras, Travis; Villarreal, Miguel; Waller, Eric K.; Nauman, Travis; Miller, Mark E.; Duniway, Michael C.

2018-01-01

Water-limited ecosystems often recover slowly following anthropogenic or natural disturbance. Multitemporal remote sensing can be used to monitor ecosystem recovery after disturbance; however, dryland vegetation cover can be challenging to accurately measure due to sparse cover and spectral confusion between soils and non-photosynthetic vegetation. With the goal of optimizing a monitoring approach for identifying both abrupt and gradual vegetation changes, we evaluated the ability of Landsat-derived spectral variables to characterize surface variability of vegetation cover and bare ground across a range of vegetation community types. Using three year composites of Landsat data, we modeled relationships between spectral information and field data collected at monitoring sites near Canyonlands National Park, UT. We also developed multiple regression models to assess improvement over single variables. We found that for all vegetation types, percent cover bare ground could be accurately modeled with single indices that included a combination of red and shortwave infrared bands, while near infrared-based vegetation indices like NDVI worked best for quantifying tree cover and total live vegetation cover in woodlands. We applied four models to characterize the spatial distribution of putative grassland ecological states across our study area, illustrating how this approach can be implemented to guide dryland ecosystem management.

DAPK1 as an independent prognostic marker in liver cancer.

PubMed

Li, Ling; Guo, Libin; Wang, Qingshui; Liu, Xiaolong; Zeng, Yongyi; Wen, Qing; Zhang, Shudong; Kwok, Hang Fai; Lin, Yao; Liu, Jingfeng

2017-01-01

The death-associated protein kinase 1 (DAPK1) can act as an oncogene or a tumor suppressor gene depending on the cellular context as well as external stimuli. Our study aims to investigate the prognostic significance of DAPK1 in liver cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was extracted from the Gene Expression Omnibus database in three independent liver cancer datasets while protein expression of DAPK1 was detected by immunohistochemistry in our Chinese liver cancer patient cohort. The associations between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were associated with shorter survival in a liver cancer patient cohort ( n  = 115;  p  = 0.041), while negative staining of DAPK1 protein was significantly correlated with shorter time to progression ( p  = 0.002) and overall survival ( p  = 0.02). DAPK1 was an independent prognostic marker for both time to progression and overall survival by multivariate analysis. Liver cancer with the b-catenin mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated under the b-catenin pathway. In addition, we also identified genes that are co-regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R, PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated, while SLC16A3 was significantly upregulated in liver cancer. By using connectivity mapping of these co-regulated genes, we have identified amcinonide and sulpiride as potential small molecules that could potentially reverse DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time that both DAPK1 mRNA and protein expression levels are important prognostic markers in liver cancer, and have identified genes that may contribute to DAPK1-mediated liver carcinogenesis.

Prognostic Analysis System and Methods of Operation

NASA Technical Reports Server (NTRS)

MacKey, Ryan M. E. (Inventor); Sneddon, Robert (Inventor)

2014-01-01

A prognostic analysis system and methods of operating the system are provided. In particular, a prognostic analysis system for the analysis of physical system health applicable to mechanical, electrical, chemical and optical systems and methods of operating the system are described herein.

Early Metabolome Profiling and Prognostic Value in Paraquat-Poisoned Patients: Based on Ultraperformance Liquid Chromatography Coupled To Quadrupole Time-of-Flight Mass Spectrometry.

PubMed

Hu, Lufeng; Hong, Guangliang; Tang, Yahui; Wang, Xianqin; Wen, Congcong; Lin, Feiyan; Lu, Zhongqiu

2017-12-18

Paraquat (PQ) has caused countless deaths throughout the world. There remains no effective treatment for PQ poisoning. Here we study the blood metabolome of PQ-poisoned patients using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). Patients were divided into groups according to blood PQ concentration. Healthy subjects served as controls. Metabolic features were statistically analyzed using multivariate pattern-recognition techniques to identify the most important metabolites. Selected metabolites were further compared with a series of clinical indexes to assess the prognostic value. PQ-poisoned patients showed substantial differences compared with healthy subjects. Based on variable of importance in the project (VIP) values and statistical analysis, 17 metabolites were selected and identified. These metabolites well-classified low PQ-poisoned patients, high PQ-poisoned patients, and healthy subjects, which was better than that of a complete blood count (CBC). Among the 17 metabolites, 20:3/18:1-PC (PC), LPA (0:0/16:0) (LPA), 19-oxo-deoxycorticosterone (19-oxo-DOC), and eicosapentaenoic acid (EPA) had prognostic value. In particular, EPA was the most sensitive one. Besides, the levels of EPA was correlated with LPA and 19-oxo-DOC. If EPA was excessively consumed, then prognosis was poor. In conclusion, the serum metabolome is substantially perturbed by PQ poisoning. EPA is the most important biomarker in early PQ poisoning.

Prognostic Value of Strain by Tissue Tracking Cardiac Magnetic Resonance After ST-Segment Elevation Myocardial Infarction.

PubMed

Gavara, Jose; Rodriguez-Palomares, Jose F; Valente, Filipa; Monmeneu, Jose V; Lopez-Lereu, Maria P; Bonanad, Clara; Ferreira-Gonzalez, Ignacio; Garcia Del Blanco, Bruno; Rodriguez-Garcia, Julian; Mutuberria, Maria; de Dios, Elena; Rios-Navarro, Cesar; Perez-Sole, Nerea; Racugno, Paolo; Paya, Ana; Minana, Gema; Canoves, Joaquim; Pellicer, Mauricio; Lopez-Fornas, Francisco J; Barrabes, Jose; Evangelista, Arturo; Nunez, Julio; Chorro, Francisco J; Garcia-Dorado, David; Bodi, Vicente

2017-12-08

The aim of this study was to evaluate the prognostic value of strain as assessed by tissue tracking (TT) cardiac magnetic resonance (CMR) soon after ST-segment elevation myocardial infarction (STEMI). The prognostic value of myocardial strain as assessed post-STEMI by TT-CMR is unknown. The authors studied the prognostic value of TT-CMR in 323 patients who underwent CMR 1 week post-STEMI. Global (average of peak segmental values [%]) and segmental (number of altered segments) longitudinal (LS), circumferential, and radial strain were assessed using TT-CMR. Global and segmental strain cutoff values were derived from 32 control patients. CMR-derived left ventricular ejection fraction, microvascular obstruction, and infarct size were determined. Results were validated in an external cohort of 190 STEMI patients. During a median follow-up of 1,085 days, 54 first major adverse cardiac events (MACE), which included 10 cardiac deaths, 25 readmissions for heart failure, and 19 readmissions for reinfarction were documented. MACE was associated with more severe abnormalities in all strain indexes (p < 0.001), although only global LS was an independent predictor (p < 0.001). The MACE rate was higher in patients with a global LS of ≥-11% (22% vs. 9%; p = 0.001). After adjustment for baseline and CMR variables, global LS (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.11 to 1.32; p < 0.001) was associated with MACE. In the external validation cohort, a global LS ≥-11% was seen in a higher proportion of patients with MACE (34% vs. 9%; p < 0.001). Global LS predicted MACE after adjustment for baseline and CMR variables (HR: 1.18; 95% CI: 1.04 to 1.33; p = 0.008). The addition of global LS to the multivariate models, including baseline and CMR variables, did not significantly improve the categorical net reclassification improvement index in either the study group (-0.015; p = 0.7) or in the external validation cohort (-0.019; p = 0.9). TT-CMR provided

Identifying environmental variables explaining genotype-by-environment interaction for body weight of rainbow trout (Onchorynchus mykiss): reaction norm and factor analytic models.

PubMed

Sae-Lim, Panya; Komen, Hans; Kause, Antti; Mulder, Han A

2014-02-26

Identifying the relevant environmental variables that cause GxE interaction is often difficult when they cannot be experimentally manipulated. Two statistical approaches can be applied to address this question. When data on candidate environmental variables are available, GxE interaction can be quantified as a function of specific environmental variables using a reaction norm model. Alternatively, a factor analytic model can be used to identify the latent common factor that explains GxE interaction. This factor can be correlated with known environmental variables to identify those that are relevant. Previously, we reported a significant GxE interaction for body weight at harvest in rainbow trout reared on three continents. Here we explore their possible causes. Reaction norm and factor analytic models were used to identify which environmental variables (age at harvest, water temperature, oxygen, and photoperiod) may have caused the observed GxE interaction. Data on body weight at harvest was recorded on 8976 offspring reared in various locations: (1) a breeding environment in the USA (nucleus), (2) a recirculating aquaculture system in the Freshwater Institute in West Virginia, USA, (3) a high-altitude farm in Peru, and (4) a low-water temperature farm in Germany. Akaike and Bayesian information criteria were used to compare models. The combination of days to harvest multiplied with daily temperature (Day*Degree) and photoperiod were identified by the reaction norm model as the environmental variables responsible for the GxE interaction. The latent common factor that was identified by the factor analytic model showed the highest correlation with Day*Degree. Day*Degree and photoperiod were the environmental variables that differed most between Peru and other environments. Akaike and Bayesian information criteria indicated that the factor analytical model was more parsimonious than the reaction norm model. Day*Degree and photoperiod were identified as environmental

Identifying environmental variables explaining genotype-by-environment interaction for body weight of rainbow trout (Onchorynchus mykiss): reaction norm and factor analytic models

PubMed Central

2014-01-01

Background Identifying the relevant environmental variables that cause GxE interaction is often difficult when they cannot be experimentally manipulated. Two statistical approaches can be applied to address this question. When data on candidate environmental variables are available, GxE interaction can be quantified as a function of specific environmental variables using a reaction norm model. Alternatively, a factor analytic model can be used to identify the latent common factor that explains GxE interaction. This factor can be correlated with known environmental variables to identify those that are relevant. Previously, we reported a significant GxE interaction for body weight at harvest in rainbow trout reared on three continents. Here we explore their possible causes. Methods Reaction norm and factor analytic models were used to identify which environmental variables (age at harvest, water temperature, oxygen, and photoperiod) may have caused the observed GxE interaction. Data on body weight at harvest was recorded on 8976 offspring reared in various locations: (1) a breeding environment in the USA (nucleus), (2) a recirculating aquaculture system in the Freshwater Institute in West Virginia, USA, (3) a high-altitude farm in Peru, and (4) a low-water temperature farm in Germany. Akaike and Bayesian information criteria were used to compare models. Results The combination of days to harvest multiplied with daily temperature (Day*Degree) and photoperiod were identified by the reaction norm model as the environmental variables responsible for the GxE interaction. The latent common factor that was identified by the factor analytic model showed the highest correlation with Day*Degree. Day*Degree and photoperiod were the environmental variables that differed most between Peru and other environments. Akaike and Bayesian information criteria indicated that the factor analytical model was more parsimonious than the reaction norm model. Conclusions Day*Degree and

Prognostics of Power MOSFET

NASA Technical Reports Server (NTRS)

Celaya, Jose Ramon; Saxena, Abhinav; Vashchenko, Vladislay; Saha, Sankalita; Goebel, Kai Frank

2011-01-01

This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and Gaussian process regression to perform prognostics. The approach is validated with experiments on 100V power MOSFETs. The failure mechanism for the stress conditions is determined to be die-attachment degradation. Change in ON-state resistance is used as a precursor of failure due to its dependence on junction temperature. The experimental data is augmented with a finite element analysis simulation that is based on a two-transistor model. The simulation assists in the interpretation of the degradation phenomena and SOA (safe operation area) change.

Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression.

PubMed

Matthews, Christine; Catherwood, Mark A; Morris, T C M; Kettle, Paul J; Drake, Mary B; Gilmore, William S; Alexander, H Denis

2006-10-01

Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients. Furthermore, the use of serum TK measurement to identify subcategories of disease within those defined by IgV(H) mutational status, gene usage and chromosomal aberrations was investigated. Ninety-one CLL patients were enrolled. Serum TK levels were measured using a radioenzyme assay. IgV(H) mutational status and V(H) gene usage were determined using BIOMED-2 primers and protocol. Recurring chromosomal abnormalities were detected by interphase fluorescent in situ hybridisation (FISH). Flow cytometry and reverse transcriptase polymerase chain reaction (RT-PCR) determined CD38 and Zap-70 expression, respectively. Significantly higher serum TK levels were found in IgV(H) unmutated, compared with IgV(H) mutated, patients (P < 0.001). Elevated TK levels were also found in patients with CD38 and Zap-70 positivity (P = 0.004, P < 0.001, respectively), short lymphocyte doubling time (LDT) (P = 0.044) and poor or intermediate prognosis chromosomal aberrations (P < 0.001). A TK level of >8.5 U/L best identified patients with progressive disease. Elevated TK levels could identify patients categorised, at diagnosis, into good prognosis subgroups by the various biological markers (mutated IgV(H), good prognosis chromosomal aberrations, Zap-70(-) and CD38(-)) who subsequently showed disease progression. Additionally, patients with V(H)3-21 gene usage showed high TK levels, irrespective of mutational status, and serum TK measurement retained predictive power as disease progressed in all subcategories studied.

Evaluating Algorithm Performance Metrics Tailored for Prognostics

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2009-01-01

Prognostics has taken a center stage in Condition Based Maintenance (CBM) where it is desired to estimate Remaining Useful Life (RUL) of the system so that remedial measures may be taken in advance to avoid catastrophic events or unwanted downtimes. Validation of such predictions is an important but difficult proposition and a lack of appropriate evaluation methods renders prognostics meaningless. Evaluation methods currently used in the research community are not standardized and in many cases do not sufficiently assess key performance aspects expected out of a prognostics algorithm. In this paper we introduce several new evaluation metrics tailored for prognostics and show that they can effectively evaluate various algorithms as compared to other conventional metrics. Specifically four algorithms namely; Relevance Vector Machine (RVM), Gaussian Process Regression (GPR), Artificial Neural Network (ANN), and Polynomial Regression (PR) are compared. These algorithms vary in complexity and their ability to manage uncertainty around predicted estimates. Results show that the new metrics rank these algorithms in different manner and depending on the requirements and constraints suitable metrics may be chosen. Beyond these results, these metrics offer ideas about how metrics suitable to prognostics may be designed so that the evaluation procedure can be standardized. 1

The evolving field of prognostication and risk stratification in MDS: Recent developments and future directions.

PubMed

Lee, Eun-Ju; Podoltsev, Nikolai; Gore, Steven D; Zeidan, Amer M

2016-01-01

The clinical course of patients with myelodysplastic syndromes (MDS) is characterized by wide variability reflecting the underlying genetic and biological heterogeneity of the disease. Accurate prediction of outcomes for individual patients is an integral part of the evidence-based risk/benefit calculations that are necessary for tailoring the aggressiveness of therapeutic interventions. While several prognostication tools have been developed and validated for risk stratification, each of these systems has limitations. The recent progress in genomic sequencing techniques has led to discoveries of recurrent molecular mutations in MDS patients with independent impact on relevant clinical outcomes. Reliable assays of these mutations have already entered the clinic and efforts are currently ongoing to formally incorporate mutational analysis into the existing clinicopathologic risk stratification tools. Additionally, mutational analysis holds promise for going beyond prognostication to therapeutic selection and individualized treatment-specific prediction of outcomes; abilities that would revolutionize MDS patient care. Despite these exciting developments, the best way of incorporating molecular testing for use in prognostication and prediction of outcomes in clinical practice remains undefined and further research is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Prognostic factors after cardiac arrest. Usefulness of early video-electroencephalogram].

PubMed

Arméstar, Fernando; Becerra Cuñat, Juan Luis; León Chan, Yariela; Mesalles Sanjuan, Eduard; Moreno, José Antonio; Jiménez González, Marta; Roca, Josep

2015-05-08

Predictors of unfavorable outcome in patients after cardiopulmonary arrest (CPA) are important to make decisions about the limitation of therapeutic efforts. The aim was to analyze the clinical variables in the prognosis of patients recovered after CPA. Retrospective study on comatose patients with recovered CPA. The variables were: age, sex, Glasgow Coma Score (GCS), pupillary light reflex, other variables related to CPA (cause, duration, witnessed or not witnessed), myoclonic status and electroencephalographic (EEG) patterns. Fifty patients were studied. The variables associated with mortality were the absence of pupillary light reflex (hazard ratio [HR] 0.277, 95% confidence interval [95% CI] 0.103-0.741, P=.01), a low GCS (HR 0.701, 95% CI 0.542-0.908, P=.007) and myoclonic state (HR 0.38, 95% CI 0.176-0.854, P=.01). We evaluated the EEG patterns in 22 patients. No statistical significance was observed. The absence of pupillary light reflex, a low GCS and myoclonic state are prognostic factors in patients recovered after a CPA. The EEG patterns showed a nonsignificant association with prognosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Low Tumor Infiltrating Mast Cell Density Confers Prognostic Benefit and Reflects Immunoactivation in Colorectal Cancer.

PubMed

Mao, Yihao; Feng, Qingyang; Zheng, Peng; Yang, Liangliang; Zhu, Dexiang; Chang, Wenju; Ji, Meiling; He, Guodong; Xu, Jianmin

2018-06-06

The role of mast cells (MCs) in colorectal cancer (CRC) progression was controversial. Thus, this study was designed to evaluate the prognostic value of MCs as well as their correlation with immune microenvironment. A retrospective cohort of CRC patients of stage I-IV was enrolled in this study. 854 consecutive patients were divided into training set (427 patients) and validation set (427 patients) randomly. The findings were further validated in a GEO cohort, GSE39582 (556 patients). The mast cell density (MCD) was measured by immunohistochemical staining of tryptase or by CIBERSORT algorithm. Low MCD predicted prolonged overall survival (OS) in training and validation set. Moreover, MCD was identified as an independent prognostic indicator in both sets. Better stratification for CRC prognosis can be achieved by building a MCD based nomogram. The prognostic role of MCD was further validated in GSE39582. In addition, MCD predicted improved survival in stage II and III CRC patients receiving adjuvant chemotherapy (ACT). Multiple immune pathways were enriched in low MCD group while cytokines/chemokines promoting anti-tumor immunity were highly expressed in such group. Furthermore, MCD was negatively correlated with CD8+ T cells infiltration. In conclusion, MCD was identified as an independent prognostic factor, as well as a potential biomarker for ACT benefit in stage II and III CRC. Better stratification of CRC prognosis could be achieved by building a MCD based nomogram. Moreover, immunoactivation in low MCD tumors may contributed to improved prognosis. This article is protected by copyright. All rights reserved. © 2018 UICC.

Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis.

PubMed

Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

2017-01-01

The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83-2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59-2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76-2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction.

Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis

PubMed Central

Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

2017-01-01

The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83–2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59–2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76–2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction. PMID:28182725

Is elevated Red cell distribution width a prognostic predictor in adult patients with community acquired Pneumonia?

PubMed Central

2014-01-01

Background Community acquired pneumonia (CAP) is a major cause of morbidity and mortality. We recently demonstrated that among young patients (<60 years old) with CAP, elevated red blood cell distribution width (RDW) level on admission was associated with significant higher rates of mortality and severe morbidity. We aimed to investigate the prognostic predictive value of RDW among CAP patients in general population of internal wards. Methods The cohort included patients of 18 years old or older who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between January 1, 2005 and December 31, 2010. Patients were retrospectively analyzed for risk factors for a primary endpoint of 90-day mortality. Secondary endpoint was defined as complicated hospitalization (defined as at least one of the following: In- hospital mortality, length of stay of at least 10 days or ICU admission). Binary logistic regression analysis was used for the calculation of the odds ratios (OR) and p values in univariate and multivariate analysis to identify association between patient characteristic, 90-day mortality and complicated hospitalization. Results The cohort included 3815 patients. In univariate analysis, patients with co-morbid conditions tended to have a complicated course of CAP. In multivariate regression analysis, variables associated with an increased risk of 90-day mortality included age > 70 years, high Charlson comorbidity index (>2), Hb < 10 mg/dl, Na <130 meq/l, blood urea nitrogen (BUN) >30 mg/dl, systolic blood pressure < 90 mmHg and elevated RDW >15%. Variables associated with complicated hospitalization included high Charlson comorbidity index, BUN > 30 mg/dl, hemoglobin < 10 g/dl, heart rate >124 bpm, systolic blood pressure < 90 mmHg and elevated RDW. Mortality rate and complicated hospitalization were significantly higher among patients with increased RDW regardless of the white blood cell

Telomere length is an independent prognostic marker in MDS but not in de novo AML.

PubMed

Williams, Jenna; Heppel, Nicole H; Britt-Compton, Bethan; Grimstead, Julia W; Jones, Rhiannon E; Tauro, Sudhir; Bowen, David T; Knapper, Steven; Groves, Michael; Hills, Robert K; Pepper, Chris; Baird, Duncan M; Fegan, Chris

2017-07-01

Telomere dysfunction is implicated in the generation of large-scale genomic rearrangements that drive progression to malignancy. In this study we used high-resolution single telomere length analysis (STELA) to examine the potential role of telomere dysfunction in 80 myelodysplastic syndrome (MDS) and 95 de novo acute myeloid leukaemia (AML) patients. Despite the MDS cohort being older, they had significantly longer telomeres than the AML cohort (P < 0·0001) where telomere length was also significantly shorter in younger AML patients (age <60 years) (P = 0·02) and in FLT3 internal tandem duplication-mutated AML patients (P = 0·03). Using a previously determined telomere length threshold for telomere dysfunction (3·81 kb) did not provide prognostic resolution in AML [Hazard ratio (HR) = 0·68, P = 0·2]. In contrast, the same length threshold was highly prognostic for overall survival in the MDS cohort (HR = 5·0, P < 0·0001). Furthermore, this telomere length threshold was an independent parameter in multivariate analysis when adjusted for age, gender, cytogenetic risk group, number of cytopenias and International Prognostic Scoring System (IPSS) score (HR = 2·27, P < 0·0001). Therefore, telomere length should be assessed in a larger prospective study to confirm its prognostic role in MDS with a view to integrating this variable into a revised IPSS. © 2017 John Wiley & Sons Ltd.

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma.

PubMed

Mutz, M; Boudreaux, B; Kearney, M; Stroda, K; Gaunt, S; Shiomitsu, K

2015-12-01

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance. © 2013 John Wiley & Sons Ltd.

Validation and Development of a Modified Breast Graded Prognostic Assessment As a Tool for Survival in Patients With Breast Cancer and Brain Metastases.

PubMed

Subbiah, Ishwaria M; Lei, Xiudong; Weinberg, Jeffrey S; Sulman, Erik P; Chavez-MacGregor, Mariana; Tripathy, Debu; Gupta, Rohan; Varma, Ankur; Chouhan, Jay; Guevarra, Richard P; Valero, Vicente; Gilbert, Mark R; Gonzalez-Angulo, Ana M

2015-07-10

Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P < .001). In multivariable analysis of the breast-GPA and number of brain metastases (> three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001). The modified breast-GPA incorporates four simple clinical parameters of high prognostic significance. This index has an immediate role in the clinic as a formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials. © 2015 by American Society of Clinical Oncology.

Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib.

PubMed

Seifert, Heike; Fisher, Rosalie; Martin-Liberal, Juan; Edmonds, Kim; Hughes, Peta; Khabra, Komel; Gore, Martin; Larkin, James

2016-04-01

The BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials.

Serum C-reactive protein (CRP) as a simple and independent prognostic factor in extranodal natural killer/T-cell lymphoma, nasal type.

PubMed

Li, Ya-Jun; Li, Zhi-Ming; Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.

Prevalence and prognostic value of exercise-induced ventricular arrhythmias.

PubMed

Partington, Sara; Myers, Jonathan; Cho, Shaun; Froelicher, Victor; Chun, Sung

2003-01-01

The purpose of this study was to determine the prevalence and prognostic significance of exercise-induced ventricular arrhythmias (EIVAs) in patients referred for exercise testing, considering the arrhythmic substrate and exercise-induced ischemia. EIVAs are frequently observed during exercise testing, but their prognostic significance is uncertain. The design of this study was a retrospective analysis of prospectively collected data, and it took place in 2 university-affiliated Veterans Affairs Medical Centers. Patients comprised 6213 consecutive males referred for exercise tests. We measured clinical exercise test responses and all-cause mortality after a mean follow-up of 6 +/- 4 years. EIVAs were defined as frequent premature ventricular contractions (PVCs) constituting >10% of all ventricular depolarizations during any 30 second electrocardiogram recording, or a run of > or =3 consecutive PVCs during exercise or recovery. A total of 1256 patients (20%) died during follow-up. EIVAs occurred in 503 patients (8%); the prevalence of EIVAs increased in older patients and in those with cardiopulmonary disease, resting PVCs, and ischemia during exercise. EIVAs were associated with mortality irrespective of the presence of cardiopulmonary disease or exercise-induced ischemia. In those without cardiopulmonary disease, mortality differed more so later in follow up than earlier. In those without resting PVCs, EIVAs were also predictive of mortality, but in those with resting PVCs, poorer prognosis was not worsened by the presence of EIVAs. Exercise induced ischemia does not affect the prognostic value of EIVAs, whereas the arrhythmic substrate does. EIVAs and resting PVCs are both independent predictors of mortality after consideration of other clinical and exercise-test variables. These findings are of limited clinical significance because of the modest change in risk and the lack of any established intervention. However, they explain some of the previous controversy

Prognostic Factors After Extraneural Metastasis of Medulloblastoma

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

Mazloom, Ali; Zangeneh, Azy H.; Paulino, Arnold C., E-mail: apaulino@tmhs.or

2010-09-01

Purpose: To review the existing literature regarding the characteristics, prognostic factors, treatment, and survival of patients with medulloblastoma, who develop extraneural metastasis (ENM). Methods and Materials: A PubMed search of English language articles from 1961 to 2007 was performed, yielding 47 articles reporting on 119 patients. Factors analyzed included age, time interval to development of ENM, ENM location, central nervous system (CNS) involvement, treatment, and outcome. Results: Sites of ENM included bone in 84% of patients, bone marrow in 27% of patients, lymph nodes in 15% of patients, lung in 6% of patients, and liver in 6% of patients. Medianmore » survival was 8 months after diagnosis of ENM. The 1-, 2-, and 5-year overall survival (OS) rates after diagnosis of ENM were 41.9%, 31.0%, and 26.0%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates after diagnosis of ENM were 34.5%, 23.2%, and 13.4%, respectively. For patients without CNS involvement at the time of ENM diagnosis, the 1-, 2-, and 5-year OS rates for those treated with and without radiotherapy (RT) were 82.4%, 64.8%, and 64.8% vs. 51.0%, 36.6%, and 30.5%, respectively (p = 0.03, log-rank test). RT did not significantly improve OS or PFS rates for those with CNS involvement. Concurrent CNS involvement, ENM in the lung or liver, a time interval of <18 months to development of ENM, and a patient age of <16 years at ENM diagnosis were found to be negative prognostic factors for both OS and PFS. Conclusions: Several prognostic factors were identified for patients with ENM from medulloblastoma. Patients without concurrent CNS involvement, who received RT after ENM diagnosis had an OS and PFS benefit compared to those who did not receive RT.« less

Prognostic Factors for Persistent Leg-Pain in Patients Hospitalized With Acute Sciatica.

PubMed

Fjeld, Olaf; Grotle, Margreth; Siewers, Vibeke; Pedersen, Linda M; Nilsen, Kristian Bernhard; Zwart, John-Anker

2017-03-01

Prospective cohort study. To identify potential prognostic factors for persistent leg-pain at 12 months among patients hospitalized with acute severe sciatica. The long-term outcome for patients admitted to hospital with sciatica is generally unfavorable. Results concerning prognostic factors for persistent sciatica are limited and conflicting. A total of 210 patients acutely admitted to hospital for either surgical or nonsurgical treatment of sciatica were consecutively recruited and received a thorough clinical and radiographic examination in addition to responding to a comprehensive questionnaire. Follow-up assessments were done at 6 weeks, 6 months, and 12 months. Potential prognostic factors were measured at baseline and at 6 weeks. The impact of these factors on leg-pain was analyzed by multiple linear regression modeling. A total of 151 patients completed the entire study, 93 receiving nonrandomized surgical treatment. The final multivariate models showed that the following factors were significantly associated with leg-pain at 12 months: high psychosocial risk according to the Örebro Musculosceletal Pain Questionnaire (unstandardized beta coefficient 1.55, 95% confidence interval [CI] 0.72-2.38, P < 0.001), not receiving surgical treatment (1.11, 95% CI 0.29-1.93, P = 0.01), not actively employed upon admission (1.47, 95% CI 0.63-2.31, P < 0.01), and self-reported leg-pain recorded 6 weeks posthospital admission (0.49, 95% CI 0.34-0.63, P < 0.001). Interaction analysis showed that the Örebro Musculosceletal Pain Questionnaire had significant prognostic value only on the nonsurgically treated patients (3.26, 95% CI 1.89-4.63, P < 0.001). The results suggest that a psychosocial screening tool and the implementation of a 6-week postadmission follow-up has prognostic value in the hospital management of severe sciatica. 2.

Estimate variable importance for recurrent event outcomes with an application to identify hypoglycemia risk factors.

PubMed

Duan, Ran; Fu, Haoda

2015-08-30

Recurrent event data are an important data type for medical research. In particular, many safety endpoints are recurrent outcomes, such as hypoglycemic events. For such a situation, it is important to identify the factors causing these events and rank these factors by their importance. Traditional model selection methods are not able to provide variable importance in this context. Methods that are able to evaluate the variable importance, such as gradient boosting and random forest algorithms, cannot directly be applied to recurrent events data. In this paper, we propose a two-step method that enables us to evaluate the variable importance for recurrent events data. We evaluated the performance of our proposed method by simulations and applied it to a data set from a diabetes study. Copyright © 2015 John Wiley & Sons, Ltd.

Joint System Prognostics For Increased Efficiency And Risk Mitigation In Advanced Nuclear Reactor Instrumentation and Control

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

Donald D. Dudenhoeffer; Tuan Q. Tran; Ronald L. Boring

2006-08-01

The science of prognostics is analogous to a doctor who, based on a set of symptoms and patient tests, assesses a probable cause, the risk to the patient, and a course of action for recovery. While traditional prognostics research has focused on the aspect of hydraulic and mechanical systems and associated failures, this project will take a joint view in focusing not only on the digital I&C aspect of reliability and risk, but also on the risks associated with the human element. Model development will not only include an approximation of the control system physical degradation but also on humanmore » performance degradation. Thus the goal of the prognostic system is to evaluate control room operation; to identify and potentially take action when performance degradation reduces plant efficiency, reliability or safety.« less

Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis.

PubMed

Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro; Romero, Alberto Omar; Machiavelli, Mario Raúl; Pérez, Juan Eduardo; Leone, Julieta; Leone, José Pablo

2017-02-01

To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM). We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM. We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2- tumors, triple-negative and HR-/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases. There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

Prognostic Significance of Interleukin-34 (IL-34) in Patients With Chronic Heart Failure With or Without Renal Insufficiency.

PubMed

Tao, Rong; Fan, Qin; Zhang, Hang; Xie, Hongyang; Lu, Lin; Gu, Gang; Wang, Fang; Xi, Rui; Hu, Jian; Chen, Qiujing; Niu, Wenquan; Shen, Weifeng; Zhang, Ruiyan; Yan, Xiaoxiang

2017-04-01

Renal dysfunction, commonly associated with cardiac dysfunction, has predictive value for adverse long-term outcomes in heart failure (HF). We previously identified a novel renal biomarker, interleukin-34 (IL-34), elevated in HF patients and associated with kidney dysfunction and coronary artery disease during HF. However, the prognostic value of IL-34 in HF remains unclear, so that the present study aimed to determine it. This prospective, observational study included 510 consecutive HF patients with their serum IL-34 as well as other variables measured at baseline, and they were followed up for 2 years. The primary end point was a composite of cardiovascular death or a first HF hospitalization, with cardiovascular death, HF hospitalization, and all-cause mortality as secondary outcomes. There was a significant and gradual increase in risk as IL-34 increased, determined by log-rank tests with Kaplan-Meier curves. Serum IL-34 was also a significant prognostic predictor of the primary end point (1.301 [1.115-1.518]; P =0.001), cardiovascular death (1.347 [1.096-1.655]; P =0.005), HF hospitalization (1.234 [1.018-1.494]; P =0.032), and all-cause mortality (1.343 [1.115-1.618]; P =0.002) in HF as per SD increase in the log IL-34 level after adjusting for age, sex, traditional risk factors, and N-terminal pro-brain natriuretic peptide. Especially, IL-34 had a more-significant prognostic value in HF patients with kidney impairment than those without. IL-34 is a significant predictor of cardiovascular death, HF hospitalization, and all-cause mortality in chronic HF, especially when concomitant with renal dysfunction. Serum IL-34 measurement may provide new insights linking kidney impairment to poor HF outcomes beyond other renal markers. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

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

Freedland, Stephen J., E-mail: steve.freedland@duke.edu; Department of Surgery; Department of Pathology, Duke University School of Medicine, Durham, North Carolina

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-upmore » for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.« less

Using variable rate models to identify genes under selection in sequence pairs: their validity and limitations for EST sequences.

PubMed

Church, Sheri A; Livingstone, Kevin; Lai, Zhao; Kozik, Alexander; Knapp, Steven J; Michelmore, Richard W; Rieseberg, Loren H

2007-02-01

Using likelihood-based variable selection models, we determined if positive selection was acting on 523 EST sequence pairs from two lineages of sunflower and lettuce. Variable rate models are generally not used for comparisons of sequence pairs due to the limited information and the inaccuracy of estimates of specific substitution rates. However, previous studies have shown that the likelihood ratio test (LRT) is reliable for detecting positive selection, even with low numbers of sequences. These analyses identified 56 genes that show a signature of selection, of which 75% were not identified by simpler models that average selection across codons. Subsequent mapping studies in sunflower show four of five of the positively selected genes identified by these methods mapped to domestication QTLs. We discuss the validity and limitations of using variable rate models for comparisons of sequence pairs, as well as the limitations of using ESTs for identification of positively selected genes.

Independent and incremental prognostic value of Doppler-derived left ventricular total isovolumic time in patients with systolic heart failure.

PubMed

Bajraktari, Gani; Dini, Frank Lloyd; Fontanive, Paolo; Elezi, Shpend; Berisha, Venera; Napoli, Anna Maria; Ciuti, Manrico; Henein, Michael

2011-05-05

A prolonged total isovolumic time (T-IVT) has been shown to be associated with worsening survival in patients submitted to coronary artery surgery. However, it is not known whether it has prognostic significance in patients with chronic systolic heart failure (HF). To determine the prognostic value of T-IVT in comparison with other clinical, biochemical and echocardiographic variables in patients with chronic systolic HF. Patients (n=107; age 68±12 years, 25% women) with chronic systolic HF, left ventricular ejection fraction (EF)<45%, and sinus rhythm, underwent a complete Doppler echocardiographic study, that included tissue Doppler long axis velocities and total isovolumic time (T-IVT), determined as [60-(total ejection time+total filling time)]. Plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) was also measured. The associations of dichotomous variables selected according to the Receiver Operator Characteristic analysis were assessed using the Cox proportional hazard model. Follow-up period was 37±18 months. Multivariate predictors of events were T-IVT≥12.3% s/min, mean E/Em ratio≥10, log NT-pro-BNP levels≥2.47 pg/ml and LV EF≤32.5%. On Kaplan-Meier analysis, patients with prolonged T-IVT, high mean E/Em ratio, increased NT-pro-BNP levels and decreased LV EF had a worse outcome compared with those without. The addition of T-IVT and NT-pro-BNP to conventional clinical and echocardiographic variables significantly improved the chi-square for the prediction of the outcome from 33.1 to 38.0, (P<0.001). Prolonged T-IVT added to the prognostic stratification of patients with systolic HF. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Rate of Decline of Ferritin in Patients with Hemophagocytic Lymphohistiocytosis as a Prognostic Variable for Mortality

PubMed Central

Lin, Tiffany F.; Ferlic-Stark, Laura L.; Allen, Carl E.; Kozinetz, Claudia A.; McClain, Kenneth L.

2012-01-01

Hemophagocytic lymphohistiocytosis (HLH) is difficult to diagnose and treat. Highly elevated ferritin is strongly associated with HLH and levels may provide a prognostic marker. A comprehensive review of ferritin data from our patients during treatment was analyzed with respect to mortality. A patient was 17 times more likely to die when percent ferritin decrease was less than 50% as compared to a 96% or greater decrease as indicated with multivariate logistic modeling. Higher maximum ferritin levels in the first 3 weeks also contributed to the odds of death (OR=5.6;90%CI=1.2-24.9). Regular ferritin measurements may be useful predicting outcomes in HLH patients. PMID:20842751

Can prognostic indicators be identified in a fetus with an encephalocele?

PubMed

Bannister, C M; Russell, S A; Rimmer, S; Thorne, J A; Hellings, S

2000-12-01

Encephaloceles, like other congenital malformations of the brain diagnosable in utero, can be either complicated (there being an associated chromosomal abnormality, abnormalities in the remainder of the central nervous system (CNS) and/or other organs), or isolated (no abnormalities in the chromosomes, the remainder of the CNS or other organs). Complicated cases invariably have a poor prognosis but amongst those with isolated lesions the outcome is variable with some affected children having poor mental and physical development but others who are only mildly or moderately disabled. To be able to make an informed decision about how to manage their pregnancy parents need to know what the prognosis is likely to be for their fetus with an encephalocele. To see if the necessary information could be reliably gathered by prenatal assessment of affected fetuses, a review was carried out of the medical records and ultrasound scans of 31 fetuses with encephaloceles referred to the Fetal Management Unit at St. Mary's Hospital in Manchester between January 1991 and December 1997. Eighteen of the cohort were classified as having a complicated encephalocele. Thirteen of the pregnancies were terminated; there were three intrauterine deaths, and one neonatal death. There is only one surviving child who is severely disabled. Thirteen fetuses were classified as having isolated encephaloceles, six had a mass of neural tissue in the encephalocele sac and were terminated, one died in utero and six had a cystic lesion or only a nubbin and have survived with few or no abnormalities. This study has shown that it is possible to identify fetuses with an encephalocele with a favourable outcome.

BCL-2 system analysis identifies high-risk colorectal cancer patients.

PubMed

Lindner, Andreas U; Salvucci, Manuela; Morgan, Clare; Monsefi, Naser; Resler, Alexa J; Cremona, Mattia; Curry, Sarah; Toomey, Sinead; O'Byrne, Robert; Bacon, Orna; Stühler, Michael; Flanagan, Lorna; Wilson, Richard; Johnston, Patrick G; Salto-Tellez, Manuel; Camilleri-Broët, Sophie; McNamara, Deborah A; Kay, Elaine W; Hennessy, Bryan T; Laurent-Puig, Pierre; Van Schaeybroeck, Sandra; Prehn, Jochen H M

2017-12-01

The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project. High-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories. BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling. DR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors. 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/.

Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI) in Patients with Small Cell Lung Cancer_ Comparison with Original ALI.

PubMed

Kim, Eun Young; Kim, Nambeom; Kim, Young Saing; Seo, Ja-Young; Park, Inkeun; Ahn, Hee Kyung; Jeong, Yu Mi; Kim, Jeong Ho

2016-01-01

Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI. L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable. Patients with low ALI (cut-off, 31.1, n = 94) had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p < 0.001), and patients with low mALI (cut-off 67.7, n = 94) had shorter OS than patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001). There was no significant difference in estimates of median survival time between low ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z = 0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p < 0.001), supportive care only (HR, 7.86, p < 0.001), and elevated LDH (HR, 1.45, p = 0.037). Furthermore, goodness of fit of this prognostic model was not significantly increased by adding mALI as an extra variable (LR difference = 2.220, p = 0.136). The present study confirms mALI using CT-determined L3MI has no additional prognostic value beyond original ALI using BMI. ALI

Prognostic factors of a favorable outcome following a supervised exercise program for soldiers with sub-acute and chronic low back pain.

PubMed

Perron, Marc; Gendron, Chantal; Langevin, Pierre; Leblond, Jean; Roos, Marianne; Roy, Jean-Sébastien

2018-04-02

Low back pain (LBP) encompasses heterogeneous patients unlikely to respond to a unique treatment. Identifying sub-groups of LBP may help to improve treatment outcomes. This is a hypothesis-setting study designed to create a clinical prediction rule (CPR) that will predict favorable outcomes in soldiers with sub-acute and chronic LBP participating in a multi-station exercise program. Military members with LBP participated in a supervised program comprising 7 stations each consisting of exercises of increasing difficulty. Demographic, impairment and disability data were collected at baseline. The modified Oswestry Disability Index (ODI) was administered at baseline and following the 6-week program. An improvement of 50% in the initial ODI score was considered the reference standard to determine a favorable outcome. Univariate associations with favorable outcome were tested using chi-square or paired t-tests. Variables that showed between-group (favorable/unfavorable) differences were entered into a logistic regression after determining the sampling adequacy. Finally, continuous variables were dichotomized and the sensitivity, specificity and positive and negative likelihood ratios were determined for the model and for each variable. A sample of 85 participants was included in analyses. Five variables contributed to prediction of a favorable outcome: no pain in lying down (p = 0.017), no use of antidepressants (p = 0.061), FABQ work score < 22.5 (p = 0.061), fewer than 5 physiotherapy sessions before entering the program (p = 0.144) and less than 6 months' work restriction (p = 0.161). This model yielded a sensitivity of 0.78, specificity of 0.80, LR+ of 3.88, and LR- of 0.28. A 77.5% probability of favorable outcome can be predicted by the presence of more than three of the five variables, while an 80% probability of unfavorable outcome can be expected if only three or fewer variables are present. The use of prognostic factors may guide

Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma

PubMed Central

Pang, Qing; Zhang, Ling-Qiang; Wang, Rui-Tao; Bi, Jian-Bin; Zhang, Jing-Yao; Qu, Kai; Liu, Su-Shun; Song, Si-Dong; Xu, Xin-Sen; Wang, Zhi-Xin; Liu, Chang

2015-01-01

AIM: To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio (PLR) in patients with gallbladder carcinoma (GBC). METHODS: Clinical data of 316 surgical GBC patients were analyzed retrospectively, and preoperative serum platelet and lymphocyte counts were used to calculate the PLR. The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic (ROC) curve. The primary outcome was overall survival, which was estimated by the Kaplan-Meier method. The log-rank test was used to compare the differences in survival. Then, we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients. RESULTS: For the PLR, the area under the ROC curve was 0.620 (95%CI: 0.542-0.698, P = 0.040) in detecting death. The cut-off value for the PLR was determined to be 117.7, with 73.6% sensitivity and 53.2% specificity. The PLR was found to be significantly positively correlated with CA125 serum level, tumor-node-metastasis (TNM) stage, and tumor differentiation. Univariate analysis identified carcinoembryonic antigen (CEA), CA125 and CA199 levels, PLR, TNM stage, and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data. Multivariate analysis showed that CA125 > 35 U/mL, CA199 > 39 U/mL, PLR ≥ 117.7, and TNM stage IV were independently associated with poor survival in GBC. When expressed as a continuous variable, the PLR was still an independent predictor for survival, with a hazard ratio of 1.018 (95%CI: 1.001-1.037 per 10-unit increase, P = 0.043). CONCLUSION: The PLR could be used as a simple, inexpensive, and valuable tool for predicting the prognosis of GBC patients. PMID:26074706

Identification and validation of novel prognostic markers in Renal Cell Carcinoma.

PubMed

Rabjerg, Maj

2017-10-01

Kidney cancer (Renal Cell Carcinoma (RCC)) is one of the most deadly malignancies due to frequent late diagnosis and poor treatment options. Histologically, RCC embraces a wide variety of different subtypes with the clear cell variant (ccRCC) being the most common, accounting for 75-90% of all RCCs. At present, the surveillance protocols for follow-up of RCC patients after radical nephrectomy are based on the American Joint Committee on Cancers (AJCC) pathological tumor-node-metastasis (TNM) classification system. Other comprehensive staging modalities have emerged and have been implemented in an attempt to improve prognostication by combining other pathological and clinical variables, including Fuhrman nuclear grade and Leibovich score. However, even early stage tumors remain at risk of metastatic progression after surgical resection and 20-40% of patients undergoing nephrectomy for clinically localized RCC will develop a recurrence. Identifying this high-risk group of RCC patients remains a challenge. Hence, novel molecular prognostic biomarkers are needed to better predict clinical outcomes. An intensive search within this field has been ongoing in the past few years, and the three main predictive and prognostic markers validated in RCC are Von Hippel Lindau (VHL), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CAIX). Nonetheless, the use of these is still debated and none of them have yet been implemented in clinical routine. RCC is resistant to conventional oncological therapies, such as chemotherapy and radiation. The availability of novel targeted therapies directed against tumorigenic and angiogenic pathways have increased over the last years, and the outcome of patients with advanced RCC has significantly improved as a consequence. Unfortunately, all patients eventually become resistant. Thus, the development of novel targeted therapies is of great importance. The aim of this thesis was therefore to contribute in the search for novel

A Discussion on Uncertainty Representation and Interpretation in Model-Based Prognostics Algorithms based on Kalman Filter Estimation Applied to Prognostics of Electronics Components

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Saxen, Abhinav; Goebel, Kai

2012-01-01

This article discusses several aspects of uncertainty representation and management for model-based prognostics methodologies based on our experience with Kalman Filters when applied to prognostics for electronics components. In particular, it explores the implications of modeling remaining useful life prediction as a stochastic process and how it relates to uncertainty representation, management, and the role of prognostics in decision-making. A distinction between the interpretations of estimated remaining useful life probability density function and the true remaining useful life probability density function is explained and a cautionary argument is provided against mixing interpretations for the two while considering prognostics in making critical decisions.

Intelligent approach to prognostic enhancements of diagnostic systems

NASA Astrophysics Data System (ADS)

Vachtsevanos, George; Wang, Peng; Khiripet, Noppadon; Thakker, Ash; Galie, Thomas R.

2001-07-01

This paper introduces a novel methodology to prognostics based on a dynamic wavelet neural network construct and notions from the virtual sensor area. This research has been motivated and supported by the U.S. Navy's active interest in integrating advanced diagnostic and prognostic algorithms in existing Naval digital control and monitoring systems. A rudimentary diagnostic platform is assumed to be available providing timely information about incipient or impending failure conditions. We focus on the development of a prognostic algorithm capable of predicting accurately and reliably the remaining useful lifetime of a failing machine or component. The prognostic module consists of a virtual sensor and a dynamic wavelet neural network as the predictor. The virtual sensor employs process data to map real measurements into difficult to monitor fault quantities. The prognosticator uses a dynamic wavelet neural network as a nonlinear predictor. Means to manage uncertainty and performance metrics are suggested for comparison purposes. An interface to an available shipboard Integrated Condition Assessment System is described and applications to shipboard equipment are discussed. Typical results from pump failures are presented to illustrate the effectiveness of the methodology.

Value of coronary computed tomography as a prognostic tool.

PubMed

Contractor, Tahmeed; Parekh, Maansi; Ahmed, Shameer; Martinez, Matthew W

2012-08-01

Coronary computed tomography angiography (CCTA) has become an important part of our armamentarium for noninvasive diagnosis of coronary artery disease (CAD). Emerging technologies have produced lower radiation dose, improved spatial and temporal resolution, as well as information about coronary physiology. Although the prognostic role of coronary artery calcium scoring is known, similar evidence for CCTA has only recently emerged. Initial, small studies in various patient populations have indicated that CCTA-identified CAD may have a prognostic value. These findings were confirmed in a recent analysis of the international, prospective Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) registry. An incremental increase in mortality was found with a worse severity of CAD on a per-patient, per-vessel, and per-segment basis. In addition, age-, sex-, and ethnicity-based differences in mortality were also found. Whether changing our management algorithms based on these findings will affect outcomes is unclear. Large prospective studies utilizing targeted management strategies for obstructive and nonobstructive CAD are required to incorporate these recent findings into our daily practice. © 2012 Wiley Periodicals, Inc.

A Model-Based Prognostics Approach Applied to Pneumatic Valves

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Goebel, Kai

2011-01-01

Within the area of systems health management, the task of prognostics centers on predicting when components will fail. Model-based prognostics exploits domain knowledge of the system, its components, and how they fail by casting the underlying physical phenomena in a physics-based model that is derived from first principles. Uncertainty cannot be avoided in prediction, therefore, algorithms are employed that help in managing these uncertainties. The particle filtering algorithm has become a popular choice for model-based prognostics due to its wide applicability, ease of implementation, and support for uncertainty management. We develop a general model-based prognostics methodology within a robust probabilistic framework using particle filters. As a case study, we consider a pneumatic valve from the Space Shuttle cryogenic refueling system. We develop a detailed physics-based model of the pneumatic valve, and perform comprehensive simulation experiments to illustrate our prognostics approach and evaluate its effectiveness and robustness. The approach is demonstrated using historical pneumatic valve data from the refueling system.

A Prognostic Indicator for Patients Hospitalized with Heart Failure.

PubMed

Snow, Richard; Vogel, Karen; Vanderhoff, Bruce; Kelch, Benjamin P; Ferris, Frank D

2016-12-01

Current methods for identifying patients at risk of dying within six months suffer from clinician biases resulting in underestimation of this risk. As a result, patients who are potentially eligible for hospice and palliative care services frequently do not benefit from these services until they are very close to the end of their lives. To develop a prospective prognostic indicator based on actual survival within Centers for Medicare and Medicaid Services (CMS) claims data that identifies patients with congestive heart failure (CHF) who are at risk of six-month mortality. CMS claims data from January 1, 2008 to June 30, 2009 were reviewed to find the first hospitalization for CHF patients with episode of care diagnosis-related groups (DRGs) 291, 292, and 293. Univariate and multivariable analyses were used to determine the associations between demographic and clinical factors and six-month mortality. The resulting model was evaluated for discrimination and calibration. The resulting prospective prognostic model demonstrated fair discrimination with an ROC of 0.71 and good calibration with a Hosmer-Lemshow statistic of 0.98. Across all DRGs, 5% of discharged patients had a six-month mortality risk of greater than 50%. This prospective approach appears to provide a method to identify patients with CHF who would potentially benefit from a clinical evaluation for referral to hospice care or for a palliative care consult due to high predicted risk of dying within 180 days after discharge from a hospital. This approach can provide a model to match at-risk patients with evidenced-based care in a more consistent manner. This method of identifying patients at risk needs further prospective evaluation to see if it has value for clinicians, increases referrals to hospice and palliative care services, and benefits patients and families.

Prognostic factors for return to work in patients with sciatica.

PubMed

Grøvle, Lars; Haugen, Anne J; Keller, Anne; Ntvig, Bård; Brox, Jens I; Grotle, Margreth

2013-12-01

Little is known about the prognostic factors for work-related outcomes of sciatica caused by disc herniation. To identify the prognostic factors for return to work (RTW) during a 2-year follow-up among sciatica patients referred to secondary care. Multicenter prospective cohort study including 466 patients. Administrative data from the National Sickness Benefit Register were accessed for 227 patients. Two samples were used. Sample A comprised patients who at the time of inclusion in the cohort reported being on partial sick leave or complete sick leave or were undergoing rehabilitation because of back pain/sciatica. Sample B comprised patients who, according to the sickness benefit register, at the time of inclusion received sickness benefits or rehabilitation allowances because of back pain/sciatica. In Sample A, the outcome was self-reported return to full-time work at the 2-year follow-up. In Sample B, the outcome was time to first sustained RTW, defined as the first period of more than 60 days without receiving benefits from the register. Significant baseline predictors of self-reported RTW at 2 years (Analysis A) were identified by multivariate logistic regression. Significant predictors of time to sustained RTW (Analysis B) were identified by multivariate Cox proportional hazard modeling. Both analyses included adjustment for age and sex. To assess the effect of surgery on the probability of RTW, analyses similar to A and B were performed, including the variable surgery (yes/no). One-fourth of the patients were still out of work at the 2-year follow-up. In Sample A (n=237), younger age, better general health, lower baseline sciatica bothersomeness, less fear-avoidance work, and a negative straight-leg-raising test result were significantly associated with a higher probability of RTW at the 2-year follow-up. Surgery was not significantly associated with the outcome. In Sample B (n=125), history of sciatica, duration of the current sciatica episode more than 3

Type 2 diabetes is an independent negative prognostic factor in patients undergoing surgical resection of a WHO grade I meningioma.

PubMed

Nayeri, Arash; Chotai, Silky; Prablek, Marc A; Brinson, Philip R; Douleh, Diana G; Weaver, Kyle D; Thompson, Reid C; Chambless, Lola

2016-10-01

In recent years, there has been increased recognition of the relationship between type 2 diabetes mellitus (DM) and poor outcomes following a variety of surgical procedures. We sought to study the role of type 2 DM as a prognostic factor affecting the long-term survival of patients undergoing surgical resection of a WHO Grade I meningioma. We conducted a retrospective cohort study on 196 patients who had a WHO Grade I meningioma resected at our institution between 2001 and 2013. The medical record was reviewed to identify a pre-existing diagnosis of type 2 DM. Patient mortality was reviewed by medical record and Social Security Death Index (SSDI). Variables associated with survival in a univariate analysis were included in the multivariate Cox model if P<0.10. Variables with probability values >0.05 were then removed from the multivariate model in a step-wise fashion. 33 (17%) patients had pre-existing diagnoses of type 2 DM prior to clinical presentation. Mean survival time in diabetic patients was 52.1 months compared to 160.9 months in non-diabetics. The decreased survival rate and time in patients with type 2 DM were found to be statistically significant (p=0.008 and p<0.0001, respectively). In a multivariate Cox analysis, a pre-existing history of type 2 DM was independently associated with decreased survival following the resection of a WHO Grade I meningioma (HR=2.6, p=0.045). A pre-existing diagnosis of type 2 DM is an independent negative prognostic indicator following the resection of a WHO Grade I meningioma. Copyright © 2016 Elsevier B.V. All rights reserved.

Prognostic and survival analysis of 837 Chinese colorectal cancer patients.

PubMed

Yuan, Ying; Li, Mo-Dan; Hu, Han-Guang; Dong, Cai-Xia; Chen, Jia-Qi; Li, Xiao-Fen; Li, Jing-Jing; Shen, Hong

2013-05-07

To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined as P < 0.05. The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage III CRC (P < 0.0001). We divided 341 stage III patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups: LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM

A new extranodal scoring system based on the prognostically relevant extranodal sites in diffuse large B-cell lymphoma, not otherwise specified treated with chemoimmunotherapy.

PubMed

Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

2016-08-01

Extranodal involvement is a well-known prognostic factor in patients with diffuse large B-cell lymphomas (DLBCL). Nevertheless, the prognostic impact of the extranodal scoring system included in the conventional international prognostic index (IPI) has been questioned in an era where rituximab treatment has become widespread. We investigated the prognostic impacts of individual sites of extranodal involvement in 761 patients with DLBCL who received rituximab-based chemoimmunotherapy. Subsequently, we established a new extranodal scoring system based on extranodal sites, showing significant prognostic correlation, and compared this system with conventional scoring systems, such as the IPI and the National Comprehensive Cancer Network-IPI (NCCN-IPI). An internal validation procedure, using bootstrapped samples, was also performed for both univariate and multivariate models. Using multivariate analysis with a backward variable selection, we found nine extranodal sites (the liver, lung, spleen, central nervous system, bone marrow, kidney, skin, adrenal glands, and peritoneum) that remained significant for use in the final model. Our newly established extranodal scoring system, based on these sites, was better correlated with patient survival than standard scoring systems, such as the IPI and the NCCN-IPI. Internal validation by bootstrapping demonstrated an improvement in model performance of our modified extranodal scoring system. Our new extranodal scoring system, based on the prognostically relevant sites, may improve the performance of conventional prognostic models of DLBCL in the rituximab era and warrants further external validation using large study populations.

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

PubMed

Jin, Zhaohui; Hartgers, Mindy L; Sanhueza, Cristobal T; Shubert, Christopher R; Alberts, Steven R; Truty, Mark J; Muppa, Prasuna; Nagorney, David M; Smyrk, Thomas C; Hassan, Mohamed; Mahipal, Amit

2018-05-01

Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification in stage IB lung adenocarcinoma.

PubMed

Xu, C-h; Wang, W; Wei, Y; Hu, H-d; Zou, J; Yan, J; Yu, L-k; Yang, R-s; Wang, Y

2015-10-01

Patients with pathological stage IB lung adenocarcinoma have a variable prognosis, even if received the same treatment. This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage IB lung adenocarcinoma. We identified 276 patients with pathological stage IB adenocarcinoma who had undergone surgical resection at the Nanjing Chest Hospital between 2005 and 2010. The histological subtypes of all patients were classified according to the 2011 IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the IASLC/ATS/ERS classification and patients' prognosis. Two hundred and seventy-six patients with pathological stage IB adenocarcinoma had an 86.2% 5-year overall survival (OS) and 80.4% 5-year disease-free survival (DFS). Patients with micropapillary and solid predominant tumors had a significantly worse OS and DFS as compared to those with other subtypes predominant tumors (p = 0.003 and 0.001). Multivariate analysis revealed that the new classification was an independent prognostic factor for both OS and DFS of pathological stage IB adenocarcinoma (p = 0.009 and 0.003). Our study revealed that the new IASLC/ATS/ERS classification was an independent prognostic factor of pathological stage IB adenocarcinoma. This new classification is valuable of screening out high risk patients to receive postoperative adjuvant therapy. Copyright © 2015. Published by Elsevier Ltd.

[Chronic obstructive pulmonary disease: 2. Short-term prognostic scores for acute exacerbations].

PubMed

Junod, Alain F

2014-01-22

The chronic obstructive pulmonary disease or COPD is a slowly progressive disease whose course is frequently the subject of acute episodes, of variable severity, although, in general, reversible, called acute exacerbations. In the past five years (between 2008 and 2013), seven prognostic scores have been published to try to assess the short-term risk of these acute exacerbations. Their components and characteristics are analysed and commented upon. An Internet program with a detailed compilation of the main features of these scores (www.medhyg.ch/scoredoc) supplements this review.

Remote Structural Health Monitoring and Advanced Prognostics of Wind Turbines

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

Douglas Brown; Bernard Laskowski

The prospect of substantial investment in wind energy generation represents a significant capital investment strategy. In order to maximize the life-cycle of wind turbines, associated rotors, gears, and structural towers, a capability to detect and predict (prognostics) the onset of mechanical faults at a sufficiently early stage for maintenance actions to be planned would significantly reduce both maintenance and operational costs. Advancement towards this effort has been made through the development of anomaly detection, fault detection and fault diagnosis routines to identify selected fault modes of a wind turbine based on available sensor data preceding an unscheduled emergency shutdown. Themore » anomaly detection approach employs spectral techniques to find an approximation of the data using a combination of attributes that capture the bulk of variability in the data. Fault detection and diagnosis (FDD) is performed using a neural network-based classifier trained from baseline and fault data recorded during known failure conditions. The approach has been evaluated for known baseline conditions and three selected failure modes: pitch rate failure, low oil pressure failure and a gearbox gear-tooth failure. Experimental results demonstrate the approach can distinguish between these failure modes and normal baseline behavior within a specified statistical accuracy.« less

Predicting stabilizing treatment outcomes for complex posttraumatic stress disorder and dissociative identity disorder: an expertise-based prognostic model.

PubMed

Baars, Erik W; van der Hart, Onno; Nijenhuis, Ellert R S; Chu, James A; Glas, Gerrit; Draijer, Nel

2011-01-01

The purpose of this study was to develop an expertise-based prognostic model for the treatment of complex posttraumatic stress disorder (PTSD) and dissociative identity disorder (DID). We developed a survey in 2 rounds: In the first round we surveyed 42 experienced therapists (22 DID and 20 complex PTSD therapists), and in the second round we surveyed a subset of 22 of the 42 therapists (13 DID and 9 complex PTSD therapists). First, we drew on therapists' knowledge of prognostic factors for stabilization-oriented treatment of complex PTSD and DID. Second, therapists prioritized a list of prognostic factors by estimating the size of each variable's prognostic effect; we clustered these factors according to content and named the clusters. Next, concept mapping methodology and statistical analyses (including principal components analyses) were used to transform individual judgments into weighted group judgments for clusters of items. A prognostic model, based on consensually determined estimates of effect sizes, of 8 clusters containing 51 factors for both complex PTSD and DID was formed. It includes the clusters lack of motivation, lack of healthy relationships, lack of healthy therapeutic relationships, lack of other internal and external resources, serious Axis I comorbidity, serious Axis II comorbidity, poor attachment, and self-destruction. In addition, a set of 5 DID-specific items was constructed. The model is supportive of the current phase-oriented treatment model, emphasizing the strengthening of the therapeutic relationship and the patient's resources in the initial stabilization phase. Further research is needed to test the model's statistical and clinical validity.

[PROGNOSTIC MODELS IN MODERN MANAGEMENT OF VULVAR CANCER].

PubMed

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

2016-01-01

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

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

PubMed

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

2016-10-12

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

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.

Luteinizing Hormone and Testosterone Levels during Acute Phase of Severe Traumatic Brain Injury: Prognostic Implications for Adult Male Patients

PubMed Central

Hohl, Alexandre; Zanela, Fernando Areas; Ghisi, Gabriela; Ronsoni, Marcelo Fernando; Diaz, Alexandre Paim; Schwarzbold, Marcelo Liborio; Dafre, Alcir Luiz; Reddi, Benjamin; Lin, Kátia; Pizzol, Felipe Dal; Walz, Roger

2018-01-01

Traumatic brain injury (TBI) is a worldwide core public health problem affecting mostly young male subjects. An alarming increase in incidence has turned TBI into a leading cause of morbidity and mortality in young adults as well as a tremendous resource burden on the health and welfare sector. Hormone dysfunction is highly prevalent during the acute phase of severe TBI. In particular, investigation of the luteinizing hormone (LH) and testosterone levels during the acute phase of severe TBI in male has identified a high incidence of low testosterone levels in male patients (36.5–100%) but the prognostic significance of which remains controversial. Two independent studies showed that normal or elevated levels of LH levels earlier during hospitalization are significantly associated with higher mortality/morbidity. The association between LH levels and prognosis was independent of other predictive variables such as neuroimaging, admission Glasgow coma scale, and pupillary reaction. The possible mechanisms underlying this association and further research directions in this field are discussed. Overall, current data suggest that LH levels during the acute phase of TBI might contribute to accurate prognostication and further prospective multicentric studies are required to develop more sophisticated predictive models incorporating biomarkers such as LH in the quest for accurate outcome prediction following TBI. Moreover, the potential therapeutic benefits of modulating LH during the acute phase of TBI warrant investigation. PMID:29487565

Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide).

PubMed

Pandith, Arshad A; Qasim, Iqbal; Zahoor, Wani; Shah, Parveen; Bhat, Abdul R; Sanadhya, Dheera; Shah, Zafar A; Naikoo, Niyaz A

2018-04-30

O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Methylation status of MGMT and loss of protein expression showed a very high concordant association with better survival and progression free survival (PFS) (p < 0.0001). Multivariate Cox regression analysis showed both MGMT methylation and loss of protein as significant independent prognostic factors in glioma patients with respect to lower Hazard Ratio (HR) for better OS and PFS) [p < 0.05]. Interestingly concordant MGMT methylation and lack of protein showed better response in TMZ therapy treated patient subgroups with HR of 2.02 and 0.76 (p < 0.05). We found the merits of prognostication of MGMT parameters, methylation as well as loss of its protein as predictive factors for favorable outcome in terms of better survival for TMZ therapy.

Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer

PubMed Central

Enzinger, Andrea C.; Zhang, Baohui; Schrag, Deborah; Prigerson, Holly G.

2015-01-01

Purpose To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. Patients and Methods This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Results Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Conclusion Prognostic disclosures are associated with more realistic

Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer.

PubMed

Enzinger, Andrea C; Zhang, Baohui; Schrag, Deborah; Prigerson, Holly G

2015-11-10

To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Prognostic disclosures are associated with more realistic patient expectations of LE, without decrements to

Prognostic markers for colorectal cancer: estimating ploidy and stroma

PubMed Central

Danielsen, H E; Hveem, T S; Domingo, E; Pradhan, M; Kleppe, A; Syvertsen, R A; Kostolomov, I; Nesheim, J A; Askautrud, H A; Nesbakken, A; Lothe, R A; Svindland, A; Shepherd, N; Novelli, M; Johnstone, E; Tomlinson, I; Kerr, R; Kerr, D J

2018-01-01

Abstract Background We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC). Patients and methods DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point. Results Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13–2.77) and HR = 2.95 (95% CI: 1.73–5.03), P < 0.001]. Conclusion A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals. PMID:29293881

A novel protein-based prognostic signature improves risk stratification to guide clinical management in early lung adenocarcinoma patients.

PubMed

Martínez-Terroba, Elena; Behrens, Carmen; de Miguel, Fernando J; Agorreta, Jackeline; Monsó, Eduard; Millares, Laura; Sainz, Cristina; Mesa-Guzman, Miguel; Pérez-Gracia, Jose Luis; Lozano, María Dolores; Zulueta, Javier J; Pio, Ruben; Wistuba, Ignacio I; Montuenga, Luis M; Pajares, María J

2018-05-13

Each of the pathological stages (I-IIIa) in which surgically resected non-small cell lung cancer patients are classified conceals hidden biological heterogeneity, manifested in heterogeneous outcomes within each stage. Thus, the finding of robust and precise molecular classifiers to assess individual patient risk is an unmet medical need. Here we identified and validated the clinical utility of a new prognostic signature based on three proteins (BRCA1, QKI and SLC2A1) to stratify early lung adenocarcinoma patients according to their risk of recurrence or death. Patients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (8 th edition, 2018). A test cohort (n=239) was used to assess the value of this new prognostic index (PI) based on the three proteins. The prognostic signature was developed by Cox regression following stringent statistical criteria (TRIPOD: Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis). The model resulted in a highly significant predictor of five-year outcome for disease-free survival (P<0.001) and overall survival (P<0.001). The prognostic ability of the model was externally validated in an independent multi-institutional cohort of patients (n=114, P=0.021). We also demonstrated that this molecular classifier adds relevant information to the gold standard TNM-based pathological staging with a highly significant improvement of likelihood ratio. We subsequently developed a combined prognostic index (CPI) including both the molecular and the pathological data which improved the risk stratification in both cohorts (P≤0.001). Moreover, the signature may help to select stage I-IIA patients who might benefit from adjuvant chemotherapy. In summary, this protein-based signature accurately identifies those patients with high risk of recurrence and death, and adds further prognostic information to the TNM-based clinical staging, even applying the

Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma.

PubMed

Steponaitis, Giedrius; Kazlauskas, Arunas; Skiriute, Daina; Valiulyte, Indre; Skauminas, Kestutis; Tamasauskas, Arimantas; Vaitkiene, Paulina

2016-11-01

Astrocytomas are one of the most common brain tumours; however, the current methods used to characterize these tumours are inadequate. The establishment of molecular markers may identify variables required to improve tumour characterization and subtyping, and may aid to specify targets for improved treatment with essential prognostic value for patient survival. One such candidate is testin (TES), which was reported to have prognostic value for glioblastoma patients. However, the role of TES protein in gliomagenesis is currently unknown. In the present study, the methylation status of the TES promoter was investigated in post-operative astrocytoma tumours of different malignancy grade, and its association with the survival of astrocytoma patients was evaluated. In addition, the expression of TES protein was investigated in the same set of astrocytoma tumours tissue, and the association of protein expression with glioma patients survival was evaluated. The methylation status of TES was assessed by methylation-specific polymerase chain reaction in 138 different grade astrocytoma samples. Western blot analysis was used to characterize the expression pattern of TES in 86 different grade astrocytoma specimens: 13 of pathological grade I, 31 of pathological grade II, 17 of pathological grade III and 25 of pathological grade IV (glioblastoma). Statistical analyses were conducted to investigate the association between tumour molecular pattern, patient clinical variables and overall survival. The methylation analysis of the TES promoter exhibited a distinct profile between astrocytomas of different malignancy grade (P<0.001). Furthermore, gene promoter methylation was significantly associated with patients' age, survival and pathological grade (P<0.001). The protein expression level of TES was significantly lower in glioblastoma (grade IV astrocytoma) than in lower grade (II-III) astrocytoma tissue (P=0.028 and P=0.04, respectively). Additionally, short overall survival of

Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma

PubMed Central