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Sample records for adverse prognostic parameters

  1. A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention

    PubMed Central

    Yuan, Min-Jie; Pan, Ye-Sheng; Hu, Wei-Guo; Lu, Zhi-Gang; Zhang, Qing-Yong; Huang, Dong; Huang, Xiao-Li; Wei, Meng; Li, Jing-Bo

    2015-01-01

    The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness. PMID:26885226

  2. A prognostic model for short term adverse events in normotensive patients with pulmonary embolism.

    PubMed

    Agterof, Mariette J; Schutgens, Roger E G; Moumli, Noureddine; Eijkemans, M J C; van der Griend, René; Tromp, Ellen A M; Biesma, Douwe H

    2011-08-01

    Risk stratification of patients with PE has gained interest in terms of the identification of patients in whom treatment on an outpatient base can be considered. Previous studies are of limited value due to their focus on adverse clinical events within several months after diagnosis of PE. We developed a prognostic model, based on easily accessible, clinical, and laboratory parameters, to predict adverse events during the first 10 days after the diagnosis of acute PE. We have analyzed the data of 210 outpatients with confirmed PE. Collected data included medical history, pulse rate, blood pressure, NT-proBNP, and D-dimer concentrations. The primary outcome was the occurrence of adverse clinical events in a 10 day follow-up period. Our final prognostic model to predict short-term adverse events consists of NT-proBNP levels, D-dimer concentrations, pulse rate, and the occurrence of active malignancy; the total score ranges from 0 to 37 points. Patients with a low score (no active malignancy, pulse rate <90 bpm, NT-proBNP <500 pg/ml, and D-dimer <3,000 μg/l FEU) have a 10-day adverse event risk <1.5%. This risk increases to over 30% in patients with a maximum score, based on high pulse rate, D-dimer concentrations, and NT-proBNP levels. Our prognostic model, once prospectively validated in an independent sample of patients, can be used in the early risk stratification of PE to estimate the risk of adverse events and to differentiate between candidates for in- or out- hospital treatment. PMID:21630313

  3. A Health Care Worker with Ebola Virus Disease and Adverse Prognostic Factors Treated in Sierra Leone.

    PubMed

    O'Shea, Matthew K; Clay, Katherine A; Craig, Darren G; Moore, Alastair J; Lewis, Stephen; Espina, Melanie; Praught, Jeff; Horne, Simon; Kao, Raymond; Johnston, Andrew M

    2016-04-01

    We describe the management of a Sierra Leonean health care worker with severe Ebola virus disease complicated by diarrhea, significant electrolyte disturbances, and falciparum malaria coinfection. With additional resources and staffing, high quality care can be provided to patients with Ebola infection and adverse prognostic factors in west Africa. PMID:26903609

  4. Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors

    PubMed Central

    Hamzić-Mehmedbašić, Aida; Rašić, Senija; Balavac, Merima; Rebić, Damir; Delić-Šarac, Marina; Durak-Nalbantić, Azra

    2016-01-01

    Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome. PMID:27471736

  5. Prognostic significance of adverse events in patients with hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Granito, Alessandro; Marinelli, Sara; Negrini, Giulia; Menetti, Saverio; Benevento, Francesca; Bolondi, Luigi

    2016-01-01

    Sorafenib is the standard treatment for patients with hepatocellular carcinoma (HCC) with advanced stage disease. Although its effectiveness has been demonstrated by randomized clinical trials and confirmed by field practice studies, reliable markers predicting therapeutic response have not yet been identified. Like other tyrosine kinase inhibitors, treatment with sorafenib is burdened by the development of adverse effects, the most frequent being cutaneous toxicity, diarrhoea, arterial hypertension and fatigue. In recent years, several studies have analysed the correlation between off-target effects and sorafenib efficacy in patients with HCC. In this review, an overview of the studies assessing the prognostic significance of sorafenib-related adverse events is provided. PMID:26929785

  6. Construction and analysis of multi-parameter prognostic models for melanoma outcome

    PubMed Central

    Gould Rothberg, Bonnie E.; Rimm, David L.

    2014-01-01

    Summary The outcome of Stage II melanoma is uncertain. Despite that 10-year melanoma-specific survival can approach 50% following curative-intent wide local excision and negative sentinel lymph node biopsy, the adverse risk-benefit ratio of interferon-based adjuvant regimens precludes their use in most patients. The discovery and translation of protein-based prognostic biomarkers into the clinic offers the promise for residual risk stratification of Stage II melanoma patients beyond conventional clinicopathologic criteria to identify an additional subset of patients who, based upon tumor molecular profiles, might also derive benefit from adjuvant regimens. Despite incorporation of Ki-67 assays into clinical practice, systematic review of REMARK-compliant, immunostain-based prognostic biomarker assays in melanoma suggests that residual risk of recurrence might be best explained by a composite score derived from a small panel of proteins representing independent features of melanoma biology. Reflecting this trend, to date, 5 such multi-parameter melanoma prognostic models have been published. Here, we review these 5 models and provide detailed protocols for discovering and validating multi-parameter models including: appropriate cohort recruitment strategies, comprehensive laboratory protocols supporting fully quantitative chromogenic or fluorescent immunostaining platforms, statistical approaches to create composite prognostic indices recommended steps for model validation in independent cohorts. PMID:24258982

  7. CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer

    PubMed Central

    Yoshida, Kazumichi; Tsujimoto, Hironori; Matsumura, Kouji; Kinoshita, Manabu; Takahata, Risa; Matsumoto, Yusuke; Hiraki, Shuichi; Ono, Satoshi; Seki, Shuhji; Yamamoto, Junji; Hase, Kazuo

    2015-01-01

    CD47 is an antiphagocytic molecule that acts via ligation to signal regulatory protein alpha on phagocytes; its enhanced expression and therapeutic targeting have recently been reported for several malignancies. However, CD47 expression in gastric cancer is not well documented. Immunohistochemical expression of CD47 in surgical specimens was investigated. Expression of CD47 and CD44, a known gastric cancer stem cell marker, were investigated in gastric cancer cell lines by flow cytometry. MKN45 and MKN74 gastric cancer cells were sorted by fluorescence-activated cell sorting according to CD44 and CD47 expression levels, and their in vitro proliferation, spheroid-forming capacity, and in vivo tumorigenicity were studied. In vitro phagocytosis of cancer cells by human macrophages in the presence of a CD47 blocking monoclonal antibody (B6H12) and the survival of immunodeficient mice intraperitoneally engrafted with MKN45 cells and B6H12 were compared to experiments using control antibodies. Immunohistochemistry of the clinical specimens indicated that CD47 was positive in 57 out of 115 cases, and its positivity was an independent adverse prognostic factor. Approximately 90% of the MKN45 and MKN74 cells expressed CD47 and CD44. CD47hi gastric cancer cells showed significantly higher proliferation and spheroid colony formation than CD47lo, and CD44hiCD47hi cells showed the highest proliferation in vitro and tumorigenicity in vivo. B6H12 significantly enhanced in vitro phagocytosis of cancer cells by human macrophages and prolonged the survival of intraperitoneal cancer dissemination in mice compared to control antibodies. In conclusion, CD47 is an adverse prognostic factor and promising therapeutic target in gastric cancer. PMID:26077800

  8. Prognostic Parameters and Spinal Metastases: A Research Study

    PubMed Central

    Daniel, Jefferson W.; Veiga, José C. E.

    2014-01-01

    Object To identify pre-operative prognostic parameters for survival in patients with spinal epidural neoplastic metastasis when the primary tumour is unknown. Methods This study was a retrospective chart review of patients who underwent surgery for spinal epidural neoplastic metastases between February 1997 and January 2011. The inclusion criteria were as follows: known post-operative survival period, a Karnofsky Performance Score equal to or greater than 30 points and a post-operative neoplastic metastasis histological type. The Kaplan-Meier method was used to estimate post-operative survival, and the Log-Rank test was used for statistical inference. Results A total of 52 patients who underwent 52 surgical procedures were identified. The mean age at the time of spinal surgery was 53.92 years (std. deviation, 19.09). The median survival after surgery was 70 days (95% CI 49.97–90.02), and post-operative mortality occurred within 6 months in 38 (73.07%) patients. Lung cancer, prostate cancer, myeloma and lymphoma, the 4 most common primary tumour types, affected 32 (61.53%) patients. The three identified prognostic parameters were the following: pre-operative walking incapacity (American Spinal Injury Association, A and B), present in 86.53% of the patients (p-value = 0.107); special care dependency (Karnofsky Performance Score, 10–40 points), present in 90.38% of the patients (p-value = 0.322); and vertebral epidural neoplastic metastases that were in contact with the thecal sac (Weinstein-Boriani-Biagini, sector D), present in 94.23% of the patients (p-value = 0.643). When the three secondary prognostic parameters were combined, the mean post-operative survival was 45 days; when at least one was present, the survival was 82 days (p-value = 0.175). Conclusions Walking incapacity, special care dependency and contact between the neoplastic metastases and the thecal sac can help determine the ultimate survival of this patient population and

  9. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

    SciTech Connect

    Mestre, Francisco; Gutiérrez, Antonio; Rodriguez, Jose; Ramos, Rafael; Garcia, Juan Fernando; Martinez-Serra, Jordi; Casasus, Marta; Nicolau, Cristina; Bento, Leyre; Herraez, Ines; Lopez-Perezagua, Paloma; Daumal, Jaime; Besalduch, Joan

    2015-05-01

    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.

  10. Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

    PubMed Central

    Lee, Nuri; Lee, Hyewon; Moon, Soo Young; Sohn, Ji Yeon; Hwang, Sang Mee; Yoon, Ok Jin; Youn, Hye Sun

    2015-01-01

    Background Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. Methods The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). Results Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). Conclusions Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM. PMID:26354343

  11. Prognostics

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.

    2013-01-01

    Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.

  12. Serum alpha-fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance.

    PubMed Central

    de Wit, R.; Collette, L.; Sylvester, R.; de Mulder, P. H.; Sleijfer, D. T.; ten Bokkel Huinink, W. W.; Kaye, S. B.; van Oosterom, A. T.; Boven, E.; Stoter, G.

    1998-01-01

    It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a cohort of patients treated with cisplatin combination chemotherapy between 1983 and 1991. A total of 669 patients were studied. Of 352 patients who had an elevated AFP at the start of treatment and for whom we had data at both day 1 and day 8, 101 (29%) had a surge. Of 317 patients for whom we had data for HCG, 80 patients (25%) had a surge. It was found that an AFP surge was a strong adverse prognostic factor for progression [hazard ratio (HR) 2.28, P=0.005]. There was no statistically significant difference in survival (HR 1.65, P=0.13). There was no prognostic significance of a HCG surge, either for progression or for survival. To investigate whether a surge was an independent prognostic factor for progression and survival, multivariate Cox regression models were fitted using the independent prognostic factors for progression and survival and the surge/decline variable. An AFP surge was retained in the final model for progression. A HCG surge was of no prognostic importance for progression or survival. We conclude that an AFP surge has an adverse prognostic significance, independent of pretreatment characteristics. PMID:9823978

  13. The amplification of 1q21 is an adverse prognostic factor in patients with multiple myeloma in a Chinese population

    PubMed Central

    Yu, Wenjun; Guo, Rui; Qu, Xiaoyan; Qiu, Hairong; Li, Jianyong; Zhang, Run; Chen, Lijuan

    2016-01-01

    The prognostic heterogeneity of multiple myeloma (MM) is largely due to different genetic abnormalities. Cytogenetic analysis has revealed that most of MM harbor chromosome aberrations. Amplification of 1q21 is one of the most common chromosomal aberrations. Interphase fluorescence in situ hybridization was applied to detect the 1q21 amplification in 86 Chinese patients with newly diagnosed MM. Amp(1q21) was found in totally 40 of 86 (46.5%) cases, among which 29 with three copies of 1q21 and eleven with at least four copies of 1q21. Further analysis revealed a significant difference of overall survival and progression-free survival among the three arms (P<0.05). Bortezomib could not significantly improve the overall survival for patients with 1q21 amplification (P>0.05). These findings suggest that 1q21 amplification with four copies or more is prognostic factor for adverse outcomes of MM patients. Furthermore, chromosome 1q21 gains predicted a poor overall survival even in those receiving bortezomib-based regimens. PMID:26834489

  14. Prognostic Utility of Neutrophil-to-Lymphocyte Ratio on Adverse Clinical Outcomes in Patients with Severe Calcific Aortic Stenosis

    PubMed Central

    Cho, Kyoung Im; Cho, Sang Hoon; Her, Ae-Young; Singh, Gillian Balbir; Shin, Eun-Seok

    2016-01-01

    Background Inflammation is an important factor in the pathogenesis of calcific aortic stenosis (AS). We aimed to evaluate the association between an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) and major adverse cardiovascular events (MACE) in patients with severe calcific AS. Methods A total of 336 patients with isolated severe calcific AS newly diagnosed between 2010 and 2015 were enrolled in this study. Using Cox proportional hazards (PH) regression models, we investigated the prognostic value of NLR adjusted for baseline covariates including logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE-I) and undergoing aortic valve replacement (AVR). We also evaluated the clinical relevance of NLR risk groups (divided into low, intermediate, high risk) as categorized by NLR cutoff values. MACE was defined as a composite of all-cause mortality, cardiac death and non-fatal myocardial infarction during the follow-up period. Results The inflammatory marker NLR was an independent prognostic factor most significantly associated with MACE [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.04–1.09; p-value <0.001]. The goodness-of-fit and discriminability of the model including EuroSCORE-I and AVR (loglikelihood difference, 15.49; p-value <0.001; c-index difference, 0.035; p-value = 0.03) were significantly improved when NLR was incorporated into the model. The estimated Kaplan-Meier survival rates at 5 years for the NLR risk groups were 84.6% for the low risk group (NLR ≤ 2), 67.7% for the intermediate risk group (2 < NLR ≤ 9), and 42.6% for the high risk group (NLR > 9), respectively. Conclusion The findings of the present study demonstrate the potential utility of NLR in risk stratification of patients with severe calcific AS. PMID:27548384

  15. Prognostic significance of neoplastic cell proliferation parameters in human haematological malignancies.

    PubMed

    Kotelnikov, V M

    1990-01-01

    High percentage of neoplastic cells in S, G2 and M phases of cell cycle is unfavourable prognostic sign in human haematological malignancies. In chronic leukaemias (CML and CLL) it is true for peripheral blood leukaemic cells, in non-Hodgkin lymphomas--for lymph node cells, in multiple myeloma--for bone marrow plasma cells. In acute leukaemia results are controversial: some authors found a correlation between proliferation parameters of bone marrow blast cells while others did not. These parameters correlate positively with the rate of complete remission and negatively with its duration. It is concluded that proliferation parameters of neoplastic cells may be used for individual prognosis in patients with haematological tumours especially in combination with other biological and clinical prognostic markers. PMID:1703108

  16. Excellent reliability for MRI grading and prognostic parameters in acute hamstring injuries

    PubMed Central

    Hamilton, B; Whiteley, R; Almusa, E; Roger, B; Geertsema, C; Tol, Johannes L

    2014-01-01

    Background Categorical grading and other measurable MRI parameters are frequently utilised for predicting the outcome of hamstring injuries. However, the reliability and smallest detectable difference (SDD) have not been previously evaluated. It therefore remains unclear if the variability in previously reported results reflects reporting variation or actual injury status. Methods 25 hamstring injuries were scored by two experienced radiologists using the Peetrons grading and specific prognostic MRI parameters: distance from ischial tuberosity (cm), extent (cranio to caudal, anterior to posterior, medial to lateral; (cm)), maximum cross-sectional area (%), volume (cm3) of the oedema. The interobserver and intraobserver reliability was calculated along with the SDDs for each scale variable. Results There were 3 Grade 0 (12%), 11 grade 1 (44%), 9 grade 2 (36%) and 2 grade 3 (8%) injuries. Cronbach's α values for grading were 1.00 (inter) and 0.96 (intra), respectively. The intraclass correlation coefficients for the prognostic MRI parameters were between 0.77 and 1.0. The SDDs varied between each parameter. Conclusions Excellent interobserver and intraobserver reliability was found for grading and prognostic MRI parameters in acute hamstring injuries. In daily practice and research, we can be confident that scoring hamstring injuries by experienced radiologists is reproducible. The documented SDDs allow meaningful clinical inferences to be made when assessing observed and reported changes in MRI status. PMID:24037670

  17. Fluorescence parameters of leaves of trees and shrubs during period of adverse weather conditions in Krasnoyarsk

    NASA Astrophysics Data System (ADS)

    Zavorueva, E. N.; Zavoruev, V. V.

    2015-11-01

    The effect of adverse weather conditions (AWC) on the fluorescence parameters of leaves Prinsepia sinensis, Amelanchier florida, Crataegus chlorocarca is obtained. However, significant changes in the fluorescence of the leaves of Acer negundo, Betula pendula under AWC were not observed.

  18. Methylation of CTNNA1 promoter: frequent but not an adverse prognostic factor in acute myeloid leukemia.

    PubMed

    Chen, Xing-xing; Lin, Jiang; Qian, Jun; Qian, Wei; Yang, Jing; Ma, Ji-chun; Deng, Zhao-qun; An, Cui; Tang, Chun-yan; Qian, Zhen; Liu, Qing

    2014-05-01

    The reduced expression of CTNNA1 gene, a putative tumor suppressor gene, has been found in several cancers including acute myeloid leukemia (AML). CTNNA1 expression is regulated by methylation and histone deacetylation. However, the clinical significance of CTNNA1 methylation in AML is rarely known. The present study was aimed to investigate the methylation status of CTNNA1 promoter region using methylation-specific PCR (MSP) and its clinical relevance in Chinese AML patients. Patients with CTNNA1 hypermethylation had significantly lower level of CTNNA1 transcript than those without CTNNA1 hypermethylation (P=0.031). The relationship of CTNNA1 methylation with clinical parameters was evaluated. Aberrant hypermethylation of CTNNA1 gene was found in 23.9% (37/155) AML cases. The status of CTNNA1 methylation was not correlated with the mutations of seven genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, N/K-RAS and C/EBPA). There was no significant difference in the rates of complete remission (CR) between patients with and without CTNNA1 methylation. Although the overall survival (OS) time of the CTNNA1-methylated AML was shorter than that of CTNNA1-unmethylated group (6 months vs 9 months), the difference was not statistically significant (P=0.681). Our data suggest that CTNNA1 methylation is a recurrent event but has no influence on prognosis in AML. PMID:24685333

  19. Prognostic significance of volume-based PET parameters in cancer patients.

    PubMed

    Moon, Seung Hwan; Hyun, Seung Hyup; Choi, Joon Young

    2013-01-01

    Accurate prediction of cancer prognosis before the start of treatment is important since these predictions often affect the choice of treatment. Prognosis is usually based on anatomical staging and other clinical factors. However, the conventional system is not sufficient to accurately and reliably determine prognosis. Metabolic parameters measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) have the potential to provide valuable information regarding prognosis and treatment response evaluation in cancer patients. Among these parameters, volume-based PET parameters such as metabolic tumor volume and total lesion glycolysis are especially promising. However, the measurement of these parameters is significantly affected by the imaging methodology and specific image characteristics, and a standard method for these parameters has not been established. This review introduces volume-based PET parameters as potential prognostic indicators, and highlights methodological considerations for measurement, potential implications, and prospects for further studies. PMID:23323025

  20. Up-regulation of PKM2 promote malignancy and related to adverse prognostic risk factor in human gallbladder cancer

    PubMed Central

    Lu, Wei; Cao, Yang; Zhang, Yijian; Li, Sheng; Gao, Jian; Wang, Xu-An; Mu, Jiasheng; Hu, Yun-Ping; Jiang, Lin; Dong, Ping; Gong, Wei; Liu, Yingbin

    2016-01-01

    Recently, pyruvate kinase M2 (PKM2) has been implicated in the progression of certain cancers and might play pivotal roles in the formation of malignancy. However, the role of PKM2 in gallbladder cancer had not been well investigated. This study analyzed associations between PKM2 expression status with various clinical and pathologic parameters in a large cohort of gallbladder cancer (GBC) patients from a long term follow up results. The expression level of pyruvate kinase isotypes in GBC tissues and their adjacent normal gallbladder tissues were estimated by qRT-PCR and Western blot. PKM2 mRNA level were significantly high in gallbladder cancer tissues than in adjacent noncancerous tissues (P < 0.001). High expression of the PKM2 was detected in 55.71% paraffin-embedded GBC tissue. The high PKM2 expression was independently associated with poorer overall survival in patients with GBC (median survival 11.9 vs 30.1 months; hazard ratio 2.79; 95% CI = 1.18 to 6.55; P = 0.02). These findings indicated elevated expression of PKM2 is a prognostic factor for poor GBC clinical outcomes, implied involving of PKM2 in GBC progression. PMID:27283076

  1. Heterogeneous chromosome 12p deletion is an independent adverse prognostic factor and resistant to bortezomib-based therapy in multiple myeloma

    PubMed Central

    Li, Fei; Xu, Yan; Deng, Ping; Yang, Ye; Sui, Weiwei; Jin, Fengyan; Hao, Mu; Li, Zengjun; Zang, Meirong; Zhou, Dehui; Gu, Zhimin; Ru, Kun; Wang, Jianxiang; Cheng, Tao; Qiu, Lugui

    2015-01-01

    The deletion of 12p (del(12p)) has been described as a novel negative prognostic marker in multiple myeloma (MM) and has gained increasing attention in recent years. However, its impact on MM is still controversial. In this study, we comprehensively evaluated the clinical impact of 12p13 deletion using fluorescence in situ hybridization (FISH) on 275 newly diagnosed MM cases treated in a prospective, non-randomized clinical trial (BDH 2008/02). The results showed that deletion of 12p13 was detected in 10.5% of newly diagnosed cases and associated with multiple indicators for high tumor burden including ISS III, BM plasmacytosis larger than 50%, and renal lesion. Moreover, the cases with 12p13 deletion typically had higher incidence of del(17p), IGH translocation and t(4;14). Patients with del(12p) conferred significantly adverse prognosis for PFS and OS, even in patients subjected to bortezomib-based therapy. When adjusted to the established prognostic variables including del(13q), del(17p), t(4;14), amp(1q21), ISS stage and LDH, del(12p13) remained the powerful independent adverse factor for PFS (P = 0.007) and OS (P = 0.032). In addition, del(12p13) combined with high β2-MG, high LDH and bone lesion can further identify subpopulations with high-risk features. Our results strongly supported that del(12p13) can be used as a valuable prognostic marker in MM. PMID:25831238

  2. Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: A prospective and single-arm study.

    PubMed

    Pan, Zhenyu; Yang, Guozi; He, Hua; Zhao, Gang; Yuan, Tingting; Li, Yu; Shi, Weiyan; Gao, Pengxiang; Dong, Lihua; Li, Yunqian

    2016-10-15

    The prognosis of leptomeningeal metastasis (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. In this phase II clinical trial, we evaluated the efficacy and safety of intrathecal chemotherapy (IC) combined with concomitant involved-field radiotherapy (IF-RT) for treating LM from solid tumors with adverse prognostic factors. Fifty-nine patients with LM from various solid tumors were enrolled between May 2010 and December 2014. Concurrent therapy consisted of concomitant IC (methotrexate 12.5-15 mg and dexamethasone 5 mg, weekly) and IF-RT (whole brain and/or spinal canal RT, 40 Gy/20f). For patients with low Karnofsky performance status (KPS) score and radiotherapy intolerance, induction IC (1-3 times) was given before concurrent therapy. Thirty-eight patients (64.4%) received subsequent treatments. All patients were followed up at least 6 months after LM diagnosis or until death. Primary endpoint evaluated was clinical response rate. Secondary endpoints were overall survival (OS) and safety. The pathological types included lung cancer (n = 42), breast cancer (n = 11) and others (n = 6). Median KPS score was 40 (range 20-70). Fifty-one patients (86.4%) completed concurrent therapy. The overall response rate was 86.4% (51/59). OS ranged from 0.4 to 36.7 months (median 6.5 months), and 1-year-survival rate was 21.3%. Treatment-related adverse events mainly included acute meningitis, chronic-delayed encephalopathy, radiculitis, myelosuppression and mucositis. Twelve patients (20.3%) had grade III-V toxic reactions. We concluded that IC combined with concomitant IF-RT, with significant efficacy and acceptable toxicity, may be an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors. LM, in which cancer cells spread to membranes enveloping the brain and spinal cord, is a devastating complication of solid cancers. Existing LM therapies center on IC. In this prospective

  3. Different Mid-Term Prognostic Predictors of Major Adverse Events in Diabetic and Nondiabetic Peripheral Artery Disease Presenting With Critical Limb Ischemia.

    PubMed

    Liang, Kae-Woei; Kuo, Hsun-Nan; Lee, Wen-Lieng; Liu, Tsun-Jui; Lin, Wei-Wen; Tsao, Chen-Rong; Ting, Chih-Tai; Wang, Kuo-Yang

    2016-03-01

    We compared midterm prognostic predictors of peripheral artery disease (PAD) with or without diabetes mellitus (DM) presenting with critical lower limb ischemia (CLI). A total of 172 patients with PAD (109 DM; 63 non-DM) were enrolled. The major adverse events (MAEs) were death or amputation. The diabetic group had a higher MAE rate (39% vs 22%, P = .042) with a mean follow-up duration of 30 ± 19 months. In a multivariate binary logistic regression analysis, revascularization (odds ratio = 0.289, P = .006) and higher serum cholesterol (odds ratio=0.988, P = .027) predicted a lower MAE rate in the DM group. In contrast, the presence of severe chronic kidney disease (stage 4 or 5, odds ratio = 5.238, P = .025) was a positive predictor of MAEs in the nondiabetic group. In conclusion, the prognostic predictors of MAE in diabetic and nondiabetic patients with PAD and CLI were different. PMID:23389094

  4. Prognostic parameters in uveal melanoma and their association with BAP1 expression

    PubMed Central

    van Essen, T Huibertus; van Pelt, Sake I; Versluis, Mieke; Bronkhorst, Inge HG; van Duinen, Sjoerd G; Marinkovic, Marina; Kroes, Wilma GM; Ruivenkamp, Claudia AL; Shukla, Shruti; de Klein, Annelies; Kiliç, Emine; Harbour, J William; Luyten, Gregorius PM; van der Velden, Pieter A; Verdijk, Rob M; Jager, Martine J

    2016-01-01

    Aim To determine whether BAP1 gene and protein expression associates with different prognostic parameters in uveal melanoma and whether BAP1 expression correctly identifies patients as being at risk for metastases, following enucleation of the primary tumour. Methods Thirty cases of uveal melanoma obtained by enucleation between 1999 and 2004 were analysed for a variety of prognostic markers, including histological characteristics, chromosome aberrations obtained by fluorescence in situ hybridisation (FISH) and single nucleotide polymorphism (SNP) analysis and gene expression profiling. These parameters were compared with BAP1 gene expression and BAP1 immunostaining. Results The presence of monosomy of chromosome 3 as identified by the different chromosome 3 tests showed significantly increased HRs (FISH on isolated nuclei cut-off 30%: HR 11.6, p=0.002; SNP analysis: HR 20.3, p=0.004) for death due to metastasis. The gene expression profile class 2, based on the 15-gene expression profile, similarly provided a significantly increased HR for a poor outcome (HR 8.5, p=0.005). Lower BAP1 gene expression and negative BAP1 immunostaining (50% of 28 tumours were immunonegative) were both associated with these markers for prognostication: FISH cut-off 30% monosomy 3 (BAP1 gene expression: p=0.037; BAP1 immunostaining: p=0.001), SNP-monosomy 3 (BAP1 gene expression: p=0.008; BAP1 immunostaining: p=0.002) and class 2 profile (BAP1 gene expression: p<0.001; BAP1 immunostaining: p=0.001) and were themselves associated with an increased risk of death due to metastasis (BAP1 gene expression dichotomised: HR 8.7, p=0.006; BAP1 immunostaining: HR 4.0, p=0.010). Conclusions Loss of BAP1 expression associated well with all of the methods currently used for prognostication and was itself predictive of death due to metastasis in uveal melanoma after enucleation, thereby emphasising the importance of further research on the role of BAP1 in uveal melanoma. PMID:25147369

  5. Hematological Parameters Improve Prediction of Mortality and Secondary Adverse Events in Coronary Angiography Patients

    PubMed Central

    Gijsberts, Crystel M.; den Ruijter, Hester M.; de Kleijn, Dominique P.V.; Huisman, Albert; ten Berg, Maarten J.; van Wijk, Richard H.A.; Asselbergs, Folkert W.; Voskuil, Michiel; Pasterkamp, Gerard; van Solinge, Wouter W.; Hoefer, Imo E.

    2015-01-01

    Abstract Prediction of primary cardiovascular events has been thoroughly investigated since the landmark Framingham risk score was introduced. However, prediction of secondary events after initial events of coronary artery disease (CAD) poses a new challenge. In a cohort of coronary angiography patients (n = 1760), we examined readily available hematological parameters from the UPOD (Utrecht Patient Oriented Database) and their addition to prediction of secondary cardiovascular events. Backward stepwise multivariable Cox regression analysis was used to test their ability to predict death and major adverse cardiovascular events (MACE). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) measures were calculated for the hematological parameters on top of traditional risk factors to assess prediction improvement. Panels of 3 to 8 hematological parameters significantly improved prediction of death and adverse events. The IDIs ranged from 0.02 to 0.07 (all P < 0.001) among outcome measures and the cNRIs from 0.11 to 0.40 (P < 0.001 in 5 of 6 outcome measures). In the hematological panels red cell distribution width (RDW) appeared most often. The multivariable adjusted hazard ratio of RDW per 1 standard deviation (SD) increase for MACE was 1.19 [1.08–1.32], P < 0.001. Routinely measured hematological parameters significantly improved prediction of mortality and adverse events in coronary angiography patients. Accurately indicating high-risk patients is of paramount importance in clinical decision-making. PMID:26559287

  6. Proposal for a Standardized Pathology Report of Gastroenteropancreatic Neuroendocrine Tumors: Prognostic Significance of Pathological Parameters

    PubMed Central

    Cho, Mee-Yon; Jin, So Young; Kim, Hyunki; Jung, Eun Sun; Kim, Mi-Jung; Kim, Kyoung-Mee; Kim, Woo Ho; Kim, Joon Mee; Kang, Yun Kyung; Choi, Joon Hyuk; Kang, Dae Young; Kim, Youn Wha; Choi, Eun Hee

    2013-01-01

    Background There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients. Methods We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report. Results Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms. Conclusions A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET. PMID:23837015

  7. Prognostic factors in anal squamous carcinoma: a multivariate analysis of clinical, pathological and flow cytometric parameters in 235 cases.

    PubMed

    Shepherd, N A; Scholefield, J H; Love, S B; England, J; Northover, J M

    1990-06-01

    Clinical, pathological and flow cytometric parameters have been analysed by univariate and multivariate analysis to define those parameters of important prognostic influence in 235 cases of surgically treated squamous carcinoma of the anus and perianal skin. Patients had been treated by anorectal excision (166 patients) or by local excision (69). Analyses were carried out on five data sets--the two surgical subgroups, two groups distinguished by site of tumour and on all 235 patients. Univariate analysis showed many parameters to be of prognostic influence, although histological typing of tumours into the more common histological subtypes was of no prognostic value. Parameters of independent prognostic significance in multivariate analysis were those indicating depth of spread, inguinal lymph node involvement and DNA-ploidy. In this study the subdivision of the rarer types of anal canal tumour, such as mucoepidermoid carcinoma, microcystic squamous carcinoma and small cell anaplastic carcinoma, was relevant confirming that these tumours have a poor prognosis. It is now felt that surgery should not be employed as primary treatment in most cases of anal cancer and the results of this study have to be interpreted with caution when applied to patients treated with radiotherapy with or without chemotherapy. Nevertheless, our findings suggest that the most useful prognostic information can be gleaned from accurate clinical staging and an assessment of DNA-ploidy status. PMID:2376397

  8. Hypoxia-inducible factor 1 alpha in high-risk breast cancer: an independent prognostic parameter?

    PubMed Central

    Gruber, Günther; Greiner, Richard H; Hlushchuk, Ruslan; Aebersold, Daniel M; Altermatt, Hans J; Berclaz, Gilles; Djonov, Valentin

    2004-01-01

    Background Hypoxia-inducible factor 1 alpha (hif-1α) furnishes tumor cells with the means of adapting to stress parameters like tumor hypoxia and promotes critical steps in tumor progression and aggressiveness. We investigated the role of hif-1α expression in patients with node-positive breast cancer. Methods Tumor samples from 77 patients were available for immunohistochemistry. The impact of hif-1α immunoreactivity on survival endpoints was determined by univariate and multivariate analyses, and correlations to clinicopathological characteristics were determined by cross-tabulations. Results hif-1α was expressed in 56% (n = 43/77) of the patients. Its expression correlated with progesterone receptor negativity (P = 0.002). The Kaplan–Meier curves revealed significantly shorter distant metastasis-free survival (DMFS) (P = 0.04, log-rank) and disease-free survival (DFS) (P = 0.04, log-rank) in patients with increased hif-1α expression. The difference in overall survival (OS) did not attain statistical significance (5-year OS, 66% without hif-1α expression and 55% with hif-1α expression; P = 0.21). The multivariate analysis failed to reveal an independent prognostic value for hif-1α expression in the whole patient group. The only significant parameter for all endpoints was the T stage (T3/T4 versus T1/T2: DMFS, relative risk = 3.16, P = 0.01; DFS, relative risk = 2.57, P = 0.03; OS, relative risk = 3.03, P = 0.03). Restricting the univariate and multivariate analyses to T1/T2 tumors, hif-1α expression was a significant parameter for DFS and DMFS. Conclusions hif-1α is expressed in the majority of patients with node-positive breast cancer. It can serve as a prognostic marker for an unfavorable outcome in those with T1/T2 tumors and positive axillary lymph nodes. PMID:15084243

  9. Adverse Pregnancy Outcomes: Opportunity for Analysis of Biospecimens and Co-development of Prognostics | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Pregnancy and Perinatology Branch seeks partners interested in collaborative research to: (i) evaluate data and samples taken from women for potential biomarkers indicative for adverse pregnancy outcomes and (ii) co-develop diagnostic kits useful as predictors of adverse pregnancy outcomes.

  10. MAGE-A3 expression is an adverse prognostic factor in diffuse large B-cell lymphoma.

    PubMed

    Olarte, Irma; Martinez, Adolfo; Ramos-Peñafiel, Christian; Castellanos-Sinco, Humberto; Zamora, Jorge; Collazo-Jaloma, Juan; Gutiérrez, Mario; Gutiérrez-Kobeh, Laila; Chavez-Olmos, Pedro; Manzanilla, Hugo; Garrido-Guerrero, Efraín; Ordoñez-Razo, Rosa M; Miranda, Enrique I

    2011-11-01

    This study evaluates the prognostic value of MAGE-A3 expression in 28 diffuse large B-cell lymphoma (DLBCL) patients. A significant association was observed between MAGE-A3 expressions, assessed by quantitative real-time RT-polymerase chain reaction (PCR), with advanced stages of disease (P < 0.05). Elevated serum lactate dehydrogenase (LDH) levels and International Prognostic Index (IPI) score were significantly higher in MAGE-A3-positive patients (P = 0.025 and P = 0.004, respectively). Expression of MAGE-A3 was associated with poor response to treatment and a significantly shorter overall survival (P < 0.001). Our data address new information in the association of MAGE-A3 expression and poor prognosis in DLBCL patients. PMID:22183072

  11. Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma

    PubMed Central

    Karakhanova, S; Ryschich, E; Mosl, B; Harig, S; Jäger, D; Schmidt, J; Hartwig, W; Werner, J; Bazhin, A V

    2015-01-01

    Background: Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma from the CapRI trial did not show any benefit of interferon-α in addition to a 5-fluorouracil (5FU)-based treatment. The aim of this study was to identify immunological parameters in patients from this trial to be used for predictive and/or prognostic purposes. Methods: The following methods were used: tumour immunohistology, FACS analyses, cytokine measurement, as well as cytotoxicity and ELIspot. Immunological parameters were correlated with patients' survival using the Kaplan–Meier method. Results: Irrespective of therapy type, high lymphocyte accumulation in tumours and frequencies of NK cells and effector (eff) CD8+ T cells in peripheral blood of the patients were associated with patients' survival. Amount of CD3+ and effector-memory CD8+ blood lymphocytes, expression of CD152 and interleukin (IL)-2 serum level showed a predictive value for chemoradioimmunotherapy. Tumoural accumulation of CD3+ and CD8+ cells was predictive for outcome of chemotherapy alone. Besides, we identified the frequencies of CD3+ lymphocytes, effCD8+ T cells and NK cells in the peripheral blood of the patients, and IL-10 amount in serum, to be predictive values for 5FU-based chemotherapy. Conclusions: Immunological parameters, identified in this trial as possible markers, may be of interest in personalized medicine towards the improvement of the treatment and prognosis of pancreatic carcinoma patients. PMID:25742476

  12. Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis

    PubMed Central

    Bruha, Radan; Jachymova, Marie; Petrtyl, Jaromir; Dvorak, Karel; Lenicek, Martin; Urbanek, Petr; Svestka, Tomislav; Vitek, Libor

    2016-01-01

    AIM: To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value. METHODS: A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals. RESULTS: The mean value of HVPG was 16.18 ± 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P < 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG > 10 mmHg and 65% for those with HVPG ≤ 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68). CONCLUSION: Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival. PMID:27022226

  13. Microenvironmental remodeling as a parameter and prognostic factor of heterogeneous leukemogenesis in acute myelogenous leukemia.

    PubMed

    Kim, Jin-A; Shim, Jae-Seung; Lee, Ga-Young; Yim, Hyeon Woo; Kim, Tae-Min; Kim, Myungshin; Leem, Sun-Hee; Lee, Jong-Wook; Min, Chang-Ki; Oh, Il-Hoan

    2015-06-01

    Acute myelogenous leukemia (AML) is a heterogeneous disorder characterized by clonal proliferation of stem cell-like blasts in bone marrow (BM); however, their unique cellular interaction within the BM microenvironment and its functional significance remain unclear. Here, we assessed the BM microenvironment of AML patients and demonstrate that the leukemia stem cells induce a change in the transcriptional programming of the normal mesenchymal stromal cells (MSC). The modified leukemic niche alters the expressions of cross-talk molecules (i.e., CXCL12 and JAG1) in MSCs to provide a distinct cross-talk between normal and leukemia cells, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemoresistance. Of note, AML patients exhibited distinct heterogeneity in the alteration of mesenchymal stroma in BM. The distinct pattern of stromal changes in leukemic BM at initial diagnosis was associated with a heterogeneous posttreatment clinical course with respect to the maintenance of complete remission for 5 to 8 years and early or late relapse. Thus, remodeling of mesenchymal niche by leukemia cells is an intrinsic self-reinforcing process of leukemogenesis that can be a parameter for the heterogeneity in the clinical course of leukemia and hence serve as a potential prognostic factor. PMID:25791383

  14. Prognostic value of parameters derived from white blood cell and differential counts in patients receiving palliative radiotherapy

    PubMed Central

    Saito, Tetsuo; Toya, Ryo; Matsuyama, Tomohiko; Semba, Akiko; Matsuyama, Keiya; Oya, Natsuo

    2016-01-01

    The aim of the present study was to identify white blood cell (WBC) parameters with high prognostic value for the survival of patients receiving palliative radiotherapy. The prognostic value of seven parameters derived from WBC and differential counts was retrospectively evaluated in patients who underwent palliative radiotherapy between October, 2010 and June, 2013. The analyzed parameters were the total WBC count, the absolute and relative lymphocyte count, the absolute and relative neutrophil count, and the neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratios. Following univariate analysis, multivariate Cox regression analysis was performed to adjust for gender, age, disease type, previous chemotherapy, previous radiotherapy and the levels of albumin and lactate dehydrogenase. A total of 220 patients with a median survival of 4.7 months were identified. All seven parameters were found to be statistically significant predictors of survival on univariate Cox regression analysis (P<0.05). Of these parameters, the low relative lymphocyte and high relative neutrophil counts were consistent predictors of poor survival in patients who received chemotherapy within 1 month prior to blood sampling (n=68) and in patients who received steroid treatment at the time of sampling (n=49). Multivariate Cox regression analysis revealed that the relative lymphocyte and neutrophil counts were independent predictors of survival in all 220 patients (P<0.05). In conclusion, relative lymphocyte and neutrophil counts were of high prognostic value for the survival of patients receiving palliative radiotherapy, even in those receiving medications that affect WBC and differential counts. PMID:27602221

  15. The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters.

    PubMed

    Delahunt, Brett; Cheville, John C; Martignoni, Guido; Humphrey, Peter A; Magi-Galluzzi, Cristina; McKenney, Jesse; Egevad, Lars; Algaba, Ferran; Moch, Holger; Grignon, David J; Montironi, Rodolfo; Srigley, John R

    2013-10-01

    The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome. For tumors showing sarcomatoid or rhabdoid differentiation, there was consensus that a minimum proportion of tumor was not required for diagnostic purposes. It was also agreed upon that the underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it was further agreed upon that if the underlying carcinoma subtype was absent the tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid component. Tumor necrosis was considered to have prognostic significance, with assessment based on macroscopic and microscopic examination of the tumor. It was recommended that for clear cell RCC the amount of necrosis should be quantified. There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed upon that chromophobe RCC should not be graded. There was consensus that microvascular invasion should not be included as a staging criterion for RCC. PMID:24025520

  16. Tumor Epression of Major Vault Protein is an Adverse Prognostic Factor for Radiotherapy Outcome in Oropharyngeal Carcinoma

    SciTech Connect

    Silva, Priyamal; West, Catharine M.; Slevin, Nick F.R.C.R.; Valentine, Helen; Ryder, W. David J. Grad. I.S.; Hampson, Lynne; Bibi, Rufzan; Sloan, Philip; Thakker, Nalin; Homer, Jarrod; Hampson, Ian

    2007-09-01

    Purpose: Vaults are multi-subunit structures that may be involved in nucleo-cytoplasmic transport, with the major vault protein (MVP or lung resistance-related protein [LRP]) being the main component. The MVP gene is located on chromosome 16 close to the multidrug resistance-associated protein and protein kinase c-{beta} genes. The role of MVP in cancer drug resistance has been demonstrated in various cell lines as well as in ovarian carcinomas and acute myeloid leukemia, but nothing is known about its possible role in radiation resistance. Our aim was to examine this in head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Archived biopsy material was obtained for 78 patients with squamous cell carcinoma of the oropharynx who received primary radiotherapy with curative intent. Immunohistochemistry was used to detect MVP expression. Locoregional failure and cancer-specific survival were estimated using cumulative incidence and Cox multivariate analyses. Results: In a univariate and multivariate analysis, MVP expression was strongly associated with both locoregional failure and cancer-specific survival. After adjustment for disease site, stage, grade, anemia, smoking, alcohol, gender, and age, the estimated hazard ratio for high MVP (2/3) compared with low (0/1) was 4.98 (95% confidence interval, 2.17-11.42; p 0.0002) for locoregional failure and 4.28 (95% confidence interval, 1.85-9.95; p = 0.001) for cancer-specific mortality. Conclusion: These data are the first to show that MVP may be a useful prognostic marker associated with radiotherapy resistance in a subgroup of patients with HNSCC.

  17. Are neutrophil/lymphocyte ratio and platelet/lymphocyte ratio reliable parameters as prognostic indicators in malignant mesothelioma?

    PubMed Central

    Tural Onur, Seda; Sokucu, Sinem Nedime; Dalar, Levent; Iliaz, Sinem; Kara, Kaan; Buyukkale, Songül; Altin, Sedat

    2016-01-01

    Background Malignant mesothelioma (MM) is an aggressive asbestos-related pleural tumor. The incidence is increasing with intensive use of asbestos in developing countries. We need an easily accessible, inexpensive, and reliable method for determining the low survival time prognosis of this tumor. The aim of our study was to investigate the viability of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) as prognostic indicators in MM. Patients and methods Thirty-six patients with MM, whose histopathologic diagnosis and follow-up were performed by our clinic and whose complete archive data were accessible, were included in this retrospective study. The patients’ histopathologic disease types and stages, complete blood count parameters at diagnosis, and survival were recorded. Results Eighteen of the patients with MM were male and the remaining 18 of them were female; the average follow-up period was 24.83±3.61 months. The PLR levels of the patients were statistically significant (P<0.05). The NLR and PLR area under the receiver operating characteristic curve values were 0.559 and 0.749, respectively (P=0.631 and P=0.044, respectively). Conclusion PLR was a significant prognostic indicator of MM at diagnosis on complete blood count parameters; however, NLR was not a significant prognostic indicator. A large number of prospective studies are needed to prove the reliability of the parameters. PMID:27217757

  18. The adverse prognostic hallmarks in identical twins with Langerhans cell histiocytosis: a clinical report and literature review.

    PubMed

    Chai, Damin; Tao, Yisheng; Bao, Zhengqi; Yang, Li; Feng, Zhenzhong; Ma, Li; Liang, Limei; Zhou, Xinwen

    2013-01-01

    Langerhans cell histiocytosis (LCH) is characterized by uncontrolled proliferation of Langerhans cells accompanying eosinophils. It often attacks children under 10 years of age. LCH in identical twins is very rare and its prognosis is different. Here we report identical-twin sisters with LCH. Computed tomography (CT) revealed osteolytic change in each twin's skull, and the elder exhibited poor eyesight. There were massive histiocyte-like cells surrounded by eosinophils in pathologic specimen of the abnormal lesions, which is typical pathologic finding in LCH. These pathologic cells were positive for S-100 and the cell surface protein CD1 antigen (CD1α), the known markers of LCH. After treating them with surgery, no symptoms were seen in the younger until now. While the older was found another soft mass (about 2.0 cm in diameter) in the left temporal area 18 months later. The same treatment was given to the older after admission, and she is healthy to date. To explore the relationship between hallmarks and the prognosis of identical-twin patients with LCH, we retrieved the 16 literatures (16 identical-twin pairs, 31 patients) listed in PubMed during the past 60 years. The data revealed all those patients who have disseminated to the bone marrow, spleen and liver with symptoms of fever and hepatosplenomegaly exhibited worse prognosis (9 out of the 31 patients). The other identical-twin subjects without infiltration of those organs recovered well. In conclusion, this study reveals the adverse hallmarks of prognosis in identical-twin patients with LCH by reviewing relevant literatures. PMID:23924960

  19. Exploratory Study of the Prognostic Value of Microenvironmental Parameters During Fractionated Irradiation in Human Squamous Cell Carcinoma Xenografts

    SciTech Connect

    Yaromina, Ala; Kroeber, Theresa; Meinzer, Andreas; Boeke, Simon; Thames, Howard; Baumann, Michael; Zips, Daniel

    2011-07-15

    Purpose: To explore the prognostic value of microenvironmental parameters for local tumor control determined before and during fractionated irradiation. Methods and Materials: Six human squamous cell carcinoma (hSCC) lines were transplanted subcutaneously into the right hind leg of nude mice. Tumors were irradiated with 30 fractions within 6 weeks. Local tumor control was determined 120 days after irradiation. Radiation response was quantified as dose to cure 50% of tumors (TCD{sub 50}). In parallel, untreated and irradiated tumors were excised after injection of pimonidazole (hypoxia marker) and Hoechst 33342 (perfusion marker) for histological evaluation. Results: Pimonidazole hypoxia decreased during fractionated irradiation in the majority of tumor lines. Fraction of perfused vessels and vascular area showed modest changes during fractionated irradiation. Histological parameters before treatment and after three and five fractions did not significantly correlate with TCD{sub 50} after irradiation with 30 fractions within 6 weeks (p > 0.05). Hypoxic volume and perfused vessels after 10 fractions showed a significant association with local tumor control after fractionated irradiation (p = 0.018 and p = 0.019, respectively). None of these parameters remained statistically significant when the p value was adjusted for multiple comparisons. Conclusions: The results from this exploratory study suggest that determination of microenvironmental parameters during treatment provides better prognostic information for the outcome after fractionated radiotherapy than pretreatment parameters, which warrants further investigation and confirmation in experimental and clinical studies.

  20. Maternal hypothyroxinaemia in pregnancy is associated with obesity and adverse maternal metabolic parameters

    PubMed Central

    Knight, Bridget A; Shields, Beverley M; Hattersley, Andrew T; Vaidya, Bijay

    2016-01-01

    Objective Subclinical hypothyroidism and isolated hypothyroxinaemia in pregnancy have been associated with an increased risk of gestational diabetes. We aimed to ascertain if these women have a worse metabolic phenotype than euthyroid pregnant women. Design, subjects and methods We recruited 956 healthy Caucasian women with singleton, non-diabetic pregnancies from routine antenatal clinics. Detailed anthropometric measurements (including BMI and skinfold thickness) and fasting blood samples (for TSH, free thyroxine (FT4), free triiodothyronine (FT3), HbA1c, lipid profile, plasma glucose and insulin resistance (HOMA-IR) analysis) were obtained at 28 weeks gestation. Results In comparison to euthyroid women (n=741), women with isolated hypothyroxinaemia (n=82) had significantly increased BMI (29.5 vs 27.5 kg/m2, P<0.001), sum of skinfolds (57.5 vs 51.3 mm, P=0.002), fasting plasma glucose (4.5 vs 4.3 mmol/l, P=0.01), triglycerides (2.3 vs 2.0 mmol/l, P<0.001) and HOMA-IR (2.0 vs 1.3, P=0.001). Metabolic parameters in women with subclinical hypothyroidism (n=133) were similar to those in euthyroid women. Maternal FT4 was negatively associated with BMI (r=−0.22), HbA1c (r=−0.14), triglycerides (r=−0.17), HOMA-IR (r=−0.15) but not total/HDL cholesterol ratio (r=−0.03). Maternal FT3:FT4 ratio was positively associated with BMI (r=0.4), HbA1c (r=0.21), triglycerides (r=0.2), HOMA–IR (r=0.33) and total/HDL cholesterol ratio (r=0.07). TSH was not associated with the metabolic parameters assessed. Conclusions Isolated hypothyroxinaemia, but not subclinical hypothyroidism, is associated with adverse metabolic phenotype in pregnancy, as is decreasing maternal FT4 and increasing FT3:FT4 ratio. These associations may be a reflection of changes in the thyroid hormone levels secondary to increase in BMI rather than changes in thyroid hormone levels affecting body weight and related metabolic parameters. PMID:26586839

  1. Vascular Endothelial Growth Factor as a Prognostic Parameter in Subjects with “Plateau Red Face”

    PubMed Central

    Ma, Lan; Chen, Ying; Jin, Guoen; Yang, Yingzhong; Ga, Qin

    2015-01-01

    Abstract Ma, Lan, Ying Chen, Guoen Jin, Yingzhong Yang, Qin Ga, and Ri-Li Ge. Vascular endothelial growth factor as a prognostic parameter in subjects with “plateau red face.” High Alt Med Biol 16:147–153, 2015.—Some individuals living at high altitude on the Qinghai Plateau in China develop a red face called “ Plateau Red Face” (PRF). It is characterized by telangiectasia of the cheeks, which become a unique ruddy color. It is more common in young females than males, subjects who have polycythemia are more susceptible to PRF, and its pathogenesis is unknown. The aim of this study was to investigate associations between PRF and levels of vascular endothelial growth factor (VEGF). Methods: A total of 158 subjects (82 male and 76 female) residing at 4300 m and 140 subjects (73 male and 67 female) residing at 2260 m on the Qinghai Plateau, China, participated in this study. The determination and magnitude of PRF is evaluated by the dilation of veins on the face in the Qinghai chronic mountain sickness(CMS) score, established during the World Congress in 2004. Arterial O2 saturation (Sao2), hemoglobin (Hb) concentration, pulmonary function tests, and serum concentration of VEGF (by ELISA) were measured in all participants. Results: The occurrence of PRF was 32.9% (52/158) among subjects living at 4300 m and 15.7% (22/140) among those living at 2260 m. The levels of VEGF in PRF and non-PRF subjects were 399.9±115.6 pg/mL and 270.7±78.1 pg/mL, respectively (p<0.001) at 4300 m, and 244.4±109.0 pg/mL and 135.6±65.3 pg/mL, respectively (p<0.01) at 2260 m. However, comparing the levels of VEGF between the genders and ethnic groups at the same altitude, there were no significant differences between male and female both in Xining (p=0.12) and Maduo (p=0.18). There was also no significant difference between Tibetan and Han nationality in Xining (p=0.71), but In Maduo, the levels of VEGF in Han (351.70±122.62 pg/mL) were higher than that of

  2. Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the children’s oncology group

    PubMed Central

    Hamilton, Ronald L.; Murdoch, Geoffrey H.; Burger, Peter C.; Brat, Daniel J.; Rosenblum, Marc K.; Nikiforova, Marina N.; Holmes, Emiko J.; Zhou, Tianni; Cohen, Kenneth J.; Jakacki, Regina I.

    2010-01-01

    Aberrant activation of Akt is a common finding in adult malignant gliomas, resulting in most cases from mutations or deletions involving PTEN, which allows constitutive Akt phosphorylation. In contrast, we have previously reported that pediatric malignant gliomas, which are morphologically similar to lesions arising in adults, have a substantially lower incidence of genomic alterations of PTEN. The objective of this study was to determine whether Akt activation was also an uncommon finding in childhood malignant gliomas and whether this feature was associated with survival. To address this issue, we examined the frequency of Akt activation, determined by overexpression of the activated phosphorylated form of Akt (Se473) on immunohistochemical analysis, in a series of 53 childhood malignant gliomas obtained from newly diagnosed patients treated on the Children’s Oncology Group ACNS0126 and 0423 studies. The relationship between Akt activation and p53 over-expression, MIB1 labeling, and tumor histology was evaluated. The association between Akt activation and survival was also assessed. Overexpression of activated Akt was observed in 42 of 53 tumors, far in excess of the frequency of PTEN mutations we have previously observed. There was no association between Akt activation and either histology, p53 overexpression, or MIB1 proliferation indices. Although tumors that lacked Akt overexpression had a trend toward more favorable event-free survival and overall survival (p = 0.06), this association reflected that non-overexpressing tumors were significantly more likely to have undergone extensive tumor removal, which was independently associated with outcome. Activation of Akt is a common finding in pediatric malignant gliomas, although it remains uncertain whether this is an independent adverse prognostic factor. In view of the frequency of Akt activation, the evaluation of molecularly targeted therapies that inhibit this pathway warrants consideration for these tumors

  3. LOX expression in primary nasopharyngeal carcinoma: correlation with prognostic parameters and outcome

    PubMed Central

    Tang, Ling-Quan; Chen, Qiu-Yan; Shao, Jian-Yong; Mai, Hai-Qiang

    2016-01-01

    Lysyl oxidase (LOX) is an extracellular matrix-remodeling enzyme that plays important roles in tumor development and progression. To evaluate the prognostic value of LOX levels in primary nasopharyngeal carcinoma, we performed an immunohistochemical analysis using 233 tissue biopsy specimens from as many patients. We found that the extent of immunohistochemical LOX staining correlated inversely with the clinicopathological features and survival. High LOX expression correlated with decreases in 5-year survival, overall survival, distant metastasis-free survival and disease-free survival (p < 0.05). Cox regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5-year mortality for all patients (hazard ratio [HR], 1.670; 95% confidence interval [95% CI], 1.033–2.701 [p < .005]). Higher LOX expression was also an independent predictor of poor prognosis in patients with nasopharyngeal carcinoma. These findings suggest LOX may be a new biomarker predictive of NPC prognosis and may also be a useful treatment target. PMID:26882568

  4. Prospective Cohort Study Evaluating the Prognostic Value of Simple EEG Parameters in Postanoxic Coma.

    PubMed

    Azabou, Eric; Fischer, Catherine; Mauguiere, François; Vaugier, Isabelle; Annane, Djillali; Sharshar, Tarek; Lofaso, Fréderic

    2016-01-01

    We prospectively studied early bedside standard EEG characteristics in 61 acute postanoxic coma patients. Five simple EEG features, namely, isoelectric, discontinuous, nonreactive to intense auditory and nociceptive stimuli, dominant delta frequency, and occurrence of paroxysms were classified yes or no. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) of each of these variables for predicting an unfavorable outcome, defined as death, persistent vegetative state, minimally conscious state, or severe neurological disability, as assessed 1 year after coma onset were computed as well as Synek's score. The outcome was unfavorable in 56 (91.8%) patients. Sensitivity, specificity, PPV, NPV, and AUC of nonreactive EEG for predicting an unfavorable outcome were 84%, 80%, 98%, 31%, and 0.82, respectively; and were all very close to the ones of Synek score>3, which were 82%, 80%, 98%, 29%, and 0.81, respectively. Specificities for predicting an unfavorable outcome were 100% for isoelectric, discontinuous, or dominant delta activity EEG. These 3 last features were constantly associated to unfavorable outcome. Absent EEG reactivity strongly predicted an unfavorable outcome in postanoxic coma, and performed as accurate as a Synek score>3. Analyzing characteristics of some simple EEG features may easily help nonneurophysiologist physicians to investigate prognostic issue of postanoxic coma patient. In this study (a) discontinuous, isoelectric, or delta-dominant EEG were constantly associated with unfavorable outcome and (b) nonreactive EEG performed prognostic as accurate as a Synek score>3. PMID:26545818

  5. The prognostic value of a new tissue Doppler parameter in patients with heart failure.

    PubMed

    Mornoş, Cristian; Petrescu, Lucian; Ionac, Adina; Cozma, Dragoş

    2014-01-01

    It has been shown a good accuracy to predict high left ventricular end-diastolic pressure for a value >1.6 of a new tissue Doppler index, E/(E' × S'), including the ratio between early diastolic transmitral and mitral annulus velocity (E/E'), and the systolic mitral annulus velocity (S'). Our aim was to evaluate the prognostic value of E/(E' × S') > 1.6 in patients with heart failure (HF). Echocardiography was performed in 345 consecutive hospitalized patients with HF, in sinus rhythm, at hospital discharge and after 1 month. Worsening of E/(E' × S') was defined as any increase of baseline value. The primary end point consisted of cardiac death or readmission due to HF worsening in long term follow-up. At discharge, 153 patients (44.3%) presented E/(E' × S') ≤ 1.6 (group I) while 192 patients (55.7%) presented E/(E' × S') > 1.6 (group II). During the follow-up period (35.1 ± 8.7 months) the first cardiac event was cardiac death in 11 patients (3.1%) and readmission for HF in 179 patients (51.9%). The composite end point was significantly higher in group II than in group I (163 events, 84.9 % vs. 27 events, 17.6%, p < 0.001). By multivariate Cox regression analysis, E/(E' × S') > 1.6 was the best independent predictor of cardiac events (hazard ratio = 4.46, 95% CI = 2.44-8.13, p = 0.001). Patients with E/(E' × S') > 1.6 at discharge and its worsening after 1 month have presented the worst prognosis (all p < 0.05). In patients with HF, E/(E' × S') > 1.6 at hospital discharge is a powerful predictor of clinical outcome particularly if it is associated with worsening. PMID:24043477

  6. Prognostic value of gasometric parameters of carbon dioxide in resuscitation of septic patients. A bibliography review.

    PubMed

    Lamsfus-Prieto, J Á; de Castro-Fernández, R; Hernández-García, A M; Marcano-Rodriguez, G

    2016-04-01

    The anaerobic metabolism is the cornerstone in physiopathology of septic shock. Nowadays we have both the central or mixed venous oxygen saturation and lactate levels to monitoring the metabolism in septic patients. Some studies have shown that normalization of systemic hemodynamic and oxygen metabolism variables not prevent progression to multiorgan damage and death. Recently has been proposed the venous-to-arterial carbon dioxide difference (ΔpvaCO2) as an alternative marker of tissue hypoperfusion, like Cardiac Index. High ΔpvaCO2 predicts adverse outcomes. Also has been proposed both, the ratio between the ΔpvaCO2 and arterial-to-venous oxygen content difference (ΔCavO2): ΔpvaCO2/ΔCavO2; and, the ratio between venous-to-arterial carbon dioxide difference (ΔCvaCO2) and ΔCavO2: ΔCvaCO2/ΔCavO2, as markers of anaerobic metabolism. Both of high ratios are related to high levels of lactate and worse prognosis. Therefore in patients with sepsis the combination of markers of resuscitation could be important to improve the outcomes. PMID:26775123

  7. Prognostic implications of cardiac scintigraphic parameters obtained in the early phase of acute myocardial infarction

    SciTech Connect

    Suzuki, A.; Matsushima, H.; Satoh, A.; Hayashi, H.; Sotobata, I.

    1988-06-01

    A cohort of 76 patients with acute myocardial infarction was studied with infarct-avid scan, radionuclide ventriculography, and thallium-201 myocardial perfusion scintigraphy. Infarct area, left ventricular ejection fraction, and defect score were calculated as radionuclide indices of the extent of myocardial infarction. The correlation was studied between these indices and cardiac events (death, congestive heart failure, postinfarction angina, and recurrence of myocardial infarction) in the first postinfarction year. High-risk patients (nonsurvivors and patients who developed heart failure) had a larger infarct area, a lower left ventricular ejection fraction, and a larger defect score than the others. Univariate linear discriminant analysis was done to determine the optimal threshold of these parameters for distinguishing high-risk patients from others. Radionuclide parameters obtained in the early phase of acute myocardial infarction were useful for detecting both patients with grave complications and those with poor late prognosis during a mean follow-up period of 2.6 years.

  8. Prognostic significance of heart rate turbulence parameters in patients with chronic heart failure

    PubMed Central

    2014-01-01

    Background This study is aimed to evaluate the clinical significance of heart rate turbulence (HRT) parameters in predicting the prognosis in patients with chronic heart failure (CHF). Methods From June 2011 to December 2012, a total of 104 CHF patients and 30 healthy controls were enrolled in this study. We obtained a 24-hour Holter ECG recording to assess the HRT parameters, included turbulence onset (TO), turbulence slope (TS), standard deviation of N-N intervals (SDNN), and resting heart rate (RHR). The relationships between HRT parameters and the prognosis of CHF patients were determined. Results The assessment follow-up period lasted until January 31, 2013. The overall mortality of CHF patients was 9.6% (10/104). Our results revealed that CHF patients had higher levels of TO than those of healthy subjects, but the TS levels of CHF patients were lower than that of the control group. CHF patients with NYHA grade IV had higher HRT1/2 rate than those with NYHA grade II/III. There were statistical differences in TS, LVEF, SDNN and RHR between the non-deteriorating group and the non-survivor group. Significant differences in TS among the three groups were also found. Furthermore, CHF patients in the non-survivor group had lower levels of TS than those in the deteriorating group. Correlation analyses indicated that TO negatively correlate with SDNN, while TS positively correlated with SDNN and left ventricular ejection fraction (LVEF). We also observed negative correlations between TS and left ventricular end-diastolic cavity dimension (LVEDD), RHR, homocysteine (Hcy) and C-reactive protein (CRP). Multivariate Cox regression analysis further confirmed that LVEF (≤30%), HRT2, SDNN and RHR were independent risk factors which can indicate poor prognosis in CHF patients. Conclusions Our findings indicate that HRT may have good clinical predictive value in patients with CHF. Thus, quantifying HRT parameters could be a useful tool for predicting mortality in CHF

  9. Assessment on the adverse effects of Aminoglycosides and Flouroquinolone on sperm parameters and male reproductive tissue: A systematic review

    PubMed Central

    Khaki, Arash

    2015-01-01

    Background: Antibiotic therapies used in treatment of many diseases have adverse effects on fertility. This review analyzes previous comparative studies that surveyed the effects of two common groups of antibiotics on male fertility. Objective: To evaluate histo-pathological effects of fluoroquinolones and aminoglycosides on sperm parameters and male reproductive tissue. Materials and Methods: Articles about the effects of aminoglycosides and fluoroquinolones on male infertility, sperm parameters, male reproductive tissue, and spermatogenesis in English and Persian languages published on Google Scholar and PubMed databases from January 2000 to December 2013 were assessed. Randomized controlled trials (RCTs) assessing the effects of aminoglycosides or fluoroquinolones on sperm parameters, artificial insemination, and male reproductive tract or RCTs comparing aminoglycosides vs. fluoroquinolones were eligible for inclusion. For ascertaining the reliability of study, data were extracted independently and in duplicate by two investigators. Results: Sperm viability was decreased significantly with streptomycin, gentamicin, and neomycin (p<0.001). Sperm motility was decreased significantly with gentamicin and neomycin (p<0.05). Total sperm count was significantly decreased with ofloxacin, gentamicin, streptomycin, and neomycin (p<0.022). There was significant decrease in post-thawing motility with low dose and high dose of ciprofloxacin. Testis weight was decreased with gentamicin and ofloxacin significantly (p<0.011). There was significant decrease in seminal vesicle weight with gentamicin, neomycin, and ofloxacin (p<0.022). Furthermore, changes in epididymis weight, percentage of total apoptotic cells, and diameter of seminiferous tubule were significant with all drugs including streptomycin, gentamicin, neomycin, and ofloxacin (p<0.05). Conclusion: Streptomycin has less negative effects on cell’s apoptosis and sperm parameters as compared to other drugs. Gentamicin

  10. [Clinical course and prognostic significance of immunological and functional parameters after severe trauma].

    PubMed

    Lendemans, S; Kreuzfelder, E; Waydhas, C; Nast-Kolb, D; Flohé, S

    2004-03-01

    Generalized severe trauma leads to an increased incidence of SIRS, sepsis, and MOF. The aim of this prospective study was to investigate the immunological parameters in terms of their predictive value for multiple organ failure (MOF).HLA-DR expression on peripheral monocytes was analyzed by flow cytometry, the ex vivo endotoxin-stimulated TNFalpha synthesis of whole blood, and the serum levels of IL-6, IL-10, procalcitonin (PCT), and CRP were analyzed by ELISA in 16 severely injured patients with an ISS >25. Initially after trauma elevated serum levels of IL-6, IL-10, and PCT were found, while TNFalpha-producing capacity and HLA-DR expression on monocytes decreased. In patients with MOF a further decrease of HLA-DR expression on days 3-4 after injury was observed accompanied by elevated levels of IL-10 at this time point. However, the TNFalpha-producing capacity was even enhanced in patients with MOF in the 2nd week after trauma. Later PCT levels were also higher in patients with MOF.Monitoring of immunological parameters after severe injury is useful to identify mediator constellations that are associated with the development and clinical course of MOF even in extremely injured patients. PMID:14999368

  11. Prognostic Judgment at Post-Surgery by Biochemical Parameters in Beef Cattle with Left Displaced Abomasum

    PubMed Central

    ICHIJO, Toshihiro; SATOH, Hiroshi; YOSHIDA, Yuki; MURAYAMA, Isao; TAGUCHI, Kiyoshi; SATO, Shigeru

    2014-01-01

    ABSTRACT We examined whether the postoperative prognosis of beef cattle with left displaced abomasum (LDA) can be estimated from changes in laboratory parameters. Preoperatively, beef cattle with LDA showed increases in plasma glucose with decreased serum insulin in the glucose tolerance test compared to non-LDA cattle. Postoperatively, the cattle with LDA were retrospectively divided into two groups, good and bad prognoses. Although plasma glucose concentrations significantly increased either pre- or postoperatively, no difference was noted between the good and bad prognosis groups. Serum insulin concentrations in the bad prognosis group significantly decreased, compared to those in the good prognosis group. These findings suggest that beef cattle with LDA elicit disturbed glucose metabolite pre- and postoperatively, and serum insulin levels may predict their prognoses after surgery. PMID:24998331

  12. Bronchodilator response in adults with bronchiectasis: correlation with clinical parameters and prognostic implications

    PubMed Central

    Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Li, Hui-Min; Yuan, Jing-Jing; Zheng, Jin-Ping

    2016-01-01

    Background Bronchial dilation testing is an important tool to assess airway reversibility in adults with bronchiectasis. This study aims to investigate the association of bronchodilator response (BDR) and clinical parameters in bronchiectasis, and the utility of BDR to indicate lung function decline and risks of bronchiectasis exacerbations (BEs). Methods We recruited 129 patients with clinically stable bronchiectasis. Baseline measurements included assessment of sputum inflammation and matrix metalloproteinase-8 and -9, sputum bacterial culture, spirometry, bronchial dilation test (for baseline FEV1 less than 80% predicted only) and chest high-resolution computed tomography (HRCT). Bronchiectasis patients were followed-up for 1 year to determine the incidence of BEs and lung function trajectories. Significant BDR was defined as FEV1 improvement from pre-dose value by at least 200 mL and 12%. Clinical trial registry No.: NCT01761214; URL: www.clinicaltrials.gov. Results BDR was negatively correlated with baseline FEV1 percentage predicted, but not blood or sputum eosinophil count. Significant BDR was not associated with greater proportion of never-smokers, poorer past history, greater HRCT scores, poorer diffusing capacity or increased sputum matrix metalloproteinases (all P>0.05). There was a trend towards higher bronchiectasis severity index (BSI) and greater proportion of patients with Pseudomonas aeruginosa isolation or infection. Significant BDR at baseline was linked to poorer spirometry, but not more rapid lung function decline, throughout follow-up. Patients with significant BDR demonstrated non-significantly lower risks of experiencing the first BEs than those without (P=0.09 for log-rank test). Conclusions Significant BDR is associated with poorer lung function compared with non-significant BDR. Whether BDR predicts future risks of BEs needs to be tested in a larger cohort. PMID:26904207

  13. Investigation of landslide potential parameters on Zonguldak-Ereğli Highway and adverse effects of landslides in the region.

    PubMed

    Can, Eray

    2014-04-01

    Landslides are natural phenomena in the same class of natural disasters as earthquakes, floods, hurricanes, erosion, and volcanic eruptions that adversely affect human lives and property. Owing to their widespread occurrence, landslides are easily visible and able to be partially understood by people witnessing them. Nevertheless, to comprehend the detail of their formation and determine their potential, it is necessary to undertake geodetic, geological, and geophysical measurements in regions prone to landslides. By analyzing these measurements, it is possible to better ascertain those regions predisposed to landslides and thus provide the means to prevent loss of life and property. The city of Zonguldak, situated in the Western Black Sea region of Turkey, has a high occurrence of landslides owing to its harsh topography with rugged and steep slopes and rainfall in almost every season. Furthermore, the diurnal temperature ranging up to 10 °C in all seasons, especially in winter, plays a crucial role in rock disintegration in this region. Other factors damage ground composition and trigger landslides, such as underground mining operations, road construction that collapses rocky hills using explosives, and excavation works in steep terrain for building construction. This study gives a detailed account of the causes and adverse effects of landslides and their parameters through examples of landslide occurrences in the region, together with the results and analyses of two periods of geodetic measurements conducted on the Zonguldak-Ereğli Highway in Ilıksu district. PMID:24338097

  14. The prognostic value of haemodynamic parameters in the recovery phase of an exercise test. The Finnish Cardiovascular Study.

    PubMed

    Nieminen, T; Leino, J; Maanoja, J; Nikus, K; Viik, J; Lehtimäki, T; Kööbi, T; Lehtinen, R; Niemelä, K; Turjanmaa, V; Kähönen, M

    2008-08-01

    We tested the hypothesis that the change from the peak to recovery values of systolic arterial pressure (SAP recovery) and rate-pressure product (RPP recovery) can be used to predict all-cause and cardiovascular mortality, as well as sudden cardiac death (SCD) in patients referred to a clinical exercise stress test. As a part of the Finnish Cardiovascular Study (FINCAVAS), consecutive patients (n=2029; mean age+/-SD=57+/-13 years; 1290 men and 739 women) with a clinically indicated exercise test using a bicycle ergometer were included in the present study. Capacities of attenuated SAP recovery, RPP recovery and heart rate recovery (HRR) to stratify the risk of death were estimated. During a follow-up (mean+/-s.d.) of 47+/-13 months, 122 patients died; 58 of the deaths were cardiovascular and 33 were SCD. In Cox regression analysis after adjustment for the peak level of the variable under assessment, age, sex, use of beta-blockers, previous myocardial infarction and other common coronary risk factors, the hazard ratio of the continuous variable RPP recovery (in units 1000 mm Hg x b.p.m.) was 0.85 (95% CI: 0.73-0.98) for SCD, 0.87 (0.78-0.97) for cardiovascular mortality, and 0.87 (0.81 to 0.94) for all-cause mortality. SAP recovery was not a predictor of mortality. The relative risks of having HRR below 18 b.p.m., a widely used cutoff point, were as follows: for SCD 1.28 (0.59-2.81, ns), for cardiovascular mortality 2.39 (1.34-4.26) and for all-cause mortality 2.40 (1.61-3.58). In conclusion, as a readily available parameter, RPP recovery is a promising candidate for a prognostic marker. PMID:18509348

  15. Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia.

    PubMed

    Ravandi, Farhad; Jorgensen, Jeffrey L; O'Brien, Susan M; Jabbour, Elias; Thomas, Deborah A; Borthakur, Gautam; Garris, Rebecca; Huang, Xuelin; Garcia-Manero, Guillermo; Burger, Jan A; Ferrajoli, Alessandra; Wierda, William; Kadia, Tapan; Jain, Nitin; Wang, Sa A; Konoplev, Sergei; Kebriaei, Partow; Champlin, Richard E; McCue, Deborah; Estrov, Zeev; Cortes, Jorge E; Kantarjian, Hagop M

    2016-02-01

    The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9·35 × 10(9) /l (range, 0·4-658·1 ×1 0(9) /l). MRD by MFC was initially assessed with a sensitivity of 0·01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·004 and P = 0·03, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P = 0·004 and P < 0·0001, respectively) and OS (P = 0·004 and P < 0·0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P < 0·05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL. PMID:26492205

  16. Late prognostic value of scintigraphic parameters of acute myocardial infarction size in complicated myocardial infarction without heart failure

    SciTech Connect

    Botvinick, E.H.; Perez-Gonzalez, J.F.; Dunn, R.; Ports, T.; Chatterjee, K.; Parmley, W.

    1983-04-01

    Perfusion scintigraphy with thallium-201, infarct scintigraphy with technetium-99m pyrophosphate (TcPYP), and equilibrium blood pool scintigraphy were performed during the initial hospitalization for acute myocardial infarction (MI) in 25 patients without evidence of heart failure who presented with advanced electrocardiographic rhythm and conduction disturbances requiring treatment. Scintigraphic findings during short-term hospitalization were related to the late clinical follow-up performed an average of 14 months later, where patients were grouped as asymptomatic, 8 patients; symptomatic, 9 patients; and deceased, 8 patients. Quantitation of perfusion abnormalities, TcPYP image abnormalities, and left ventricular ejection fraction (EF) revealed that the deceased group had significantly larger TcPYP abnormalities (36 +/- 20 cm2), absolute perfusion abnormalities (32 +/- 16 cm2), and perfusion abnormalities expressed as a percentage of the projected left ventricular area (42 +/- 8%) than the asymptomatic group (13 +/- 8 cm2, 14 +/- 6 cm2, and 20 +/- 9%; p less than 0.05, p greater than 0.05, and p less than 0.01, respectively). The percent perfusion abnormality was significantly larger in the deceased group (42 +/- 8%, p less than 0.01) than in either the symptomatic group (35 +/- 13%, p less than 0.01) or the asymptomatic group (20 +/- 9%), and this parameter in the symptomatic group also differed from that in the asymptomatic group (p less than 0.01). The study indicates that patients with rhythm and conduction disturbances and without congestive heart failure during acute MI may follow an uncomplicated or a complicated late clinical course. Early scintigraphic measurements of MI and perfusion correlate well with this outcome; however, EF could not differentiate among prognostic subgroups.

  17. The number of tumor-free axillary lymph nodes removed as a prognostic parameter for node-negative breast cancer

    PubMed Central

    Gao, Fei; He, Ni; Wu, Pei-Hong

    2014-01-01

    Recently, there has been controversy about the relationship between the number of lymph nodes removed and survival of patients diagnosed with lymph node-negative breast cancer. To assess this relationship, 603 cases of lymph node-negative breast cancer with a median of 126 months of follow-up data were studied. Patients were stratified into two groups (Group A, 10 or fewer tumor-free lymph nodes removed; Group B, more than 10 tumor-free lymph nodes removed). The number of tumor-free lymph nodes in ipsilateral axillary resections as well as 5 other disease parameters were analyzed for prognostic value. Our results revealed that the risk of death from breast cancer was significantly associated with patient age, marital status, histologic grade, tumor size, and adjuvant therapy. The 5- and 10-year survival rates for patients with 10 or fewer tumor-free lymph nodes removed was 88.0% and 66.4%, respectively, compared with 69.2% and 51.1%, respectively, for patients with more than 10 tumor-free lymph nodes removed. For patients with 10 or fewer tumor-free lymph nodes removed, the adjusted hazard ratio (HR) for risk of death from breast cancer was 0.579 (95% confidence interval, 0.492-0.687, P < 0.001), independent of patient age, marital status, histologic grade, tumor size, and adjuvant therapy. Our study suggests that the number of tumor-free lymph nodes removed is an independent predictor in cases of lymph node-negative breast cancer. PMID:25322865

  18. Prognostic value of volumetric metabolic parameters measured by [18F]Fluorodeoxyglucose-positron emission tomography/computed tomography in patients with small cell lung cancer

    PubMed Central

    2014-01-01

    Background We evaluated the prognostic value of volume-based metabolic positron emission tomography (PET) parameters in patients with small cell lung cancer (SCLC) compared with other factors. Methods The subjects were 202 patients with pathologically proven SCLC who underwent pretreatment 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT). Volumetric metabolic parameters of intrathoracic malignant hypermetabolic lesions, including maximum and average standardized uptake value, sum of metabolic tumor volume (MTV), and sum of total lesion glycolysis (TLG) were measured. Results 164 patients had died during follow-up (median 17.4 months) and median overall survival was 14 months. On univariate survival analysis, age, stage, treatment modality, sum of MTV (cutoff = 100 cm3), and sum of TLG (cutoff = 555) were significant predictors of survival. There was a very high correlation between the sum of MTV and the sum of TLG (r = 0.963, P < 0.001). On multivariate survival analysis, age (HR = 1.04, P < 0.001), stage (HR = 2.442, P < 0.001), and sum of MTV (HR = 1.662, P = 0.002) were independent prognostic factors. On subgroup analysis based on limited disease (LD) and extensive disease (ED), sum of MTV and sum of TLG were significant prognostic factors only in LD. Conclusion Both sum of MTV and sum of TLG of intrathoracic malignant hypermetabolic lesions are important independent prognostic factors for survival in patients with SCLC, in addition to age and clinical stage. However, it may be more useful in limited disease rather than in extensive disease. PMID:25609313

  19. The E3 ubiquitin ligase EDD is an adverse prognostic factor for serous epithelial ovarian cancer and modulates cisplatin resistance in vitro.

    PubMed

    O'Brien, P M; Davies, M J; Scurry, J P; Smith, A N; Barton, C A; Henderson, M J; Saunders, D N; Gloss, B S; Patterson, K I; Clancy, J L; Heinzelmann-Schwarz, V A; Murali, Rajmohan; Scolyer, R A; Zeng, Y; Williams, E D; Scurr, L; Defazio, A; Quinn, D I; Watts, C K W; Hacker, N F; Henshall, S M; Sutherland, R L

    2008-03-25

    Despite a high initial response rate to first-line platinum/paclitaxel chemotherapy, most women with epithelial ovarian cancer relapse with recurrent disease that becomes refractory to further cytotoxic treatment. We have previously shown that the E3 ubiquitin ligase, EDD, a regulator of DNA damage responses, is amplified and overexpressed in serous ovarian carcinoma. Given that DNA damage pathways are linked to platinum resistance, the aim of this study was to determine if EDD expression was associated with disease recurrence and platinum sensitivity in serous ovarian cancer. High nuclear EDD expression, as determined by immunohistochemistry in a cohort of 151 women with serous ovarian carcinoma, was associated with an approximately two-fold increased risk of disease recurrence and death in patients who initially responded to first-line chemotherapy, independently of disease stage and suboptimal debulking. Although EDD expression was not directly correlated with relative cisplatin sensitivity of ovarian cancer cell lines, sensitivity to cisplatin was partially restored in platinum-resistant A2780-cp70 ovarian cancer cells following siRNA-mediated knockdown of EDD expression. These results identify EDD as a new independent prognostic marker for outcome in serous ovarian cancer, and suggest that pathways involving EDD, including DNA damage responses, may represent new therapeutic targets for chemoresistant ovarian cancer. PMID:18349819

  20. Upregulation of Trefoil Factor 3 (TFF3) After Rectal Cancer Chemoradiotherapy Is an Adverse Prognostic Factor and a Potential Therapeutic Target

    SciTech Connect

    Casado, Enrique; Moreno Garcia, Victor; Sanchez, Jose Javier; Gomez del Pulgar, Maria Teresa; Feliu, Jaime; Maurel, Joan; Castelo, Beatriz; Moreno Rubio, Juan; Lopez, Rocio A.B.; Garcia-Cabezas, Miguel Angel; Burgos, Emilio; and others

    2012-12-01

    Purpose: Management of locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiotherapy (CRT) with fluoropyrimidines, followed by total mesorectal excision. We sought to evaluate the expression of selected genes, some of which were derived from a previous undirected SAGE (serial analysis of gene expression)-based approach, before and after CRT, to identify mechanisms of resistance. Methods: This retrospective cohort study included 129 consecutive patients. Quantitative polymerase chain reaction of 53 candidate genes was performed on the biopsy specimen before treatment and on the surgical specimen after CRT. A paired-samples t test was performed to determine genes that were significantly changed after CRT. The result was correlated with patients' disease-free survival. Results: Twenty-two genes were significantly upregulated, and two were significantly downregulated. Several of the upregulated genes have roles in cell cycle control; these include CCNB1IP1, RCC1, EEF2, CDKN1, TFF3, and BCL2. The upregulation of TFF3 was associated with worse disease-free survival on multivariate analyses (hazard ratio, 2.64; P=.027). Patients whose surgical specimens immunohistochemically showed secretion of TFF3 into the lumen of the tumoral microglands had a higher risk of relapse (hazard ratio, 2.51; P=.014). In vitro experiments showed that DLD-1 cells stably transfected with TFF3 were significantly less sensitive to 5-fluorouracil and showed upregulation of genes involved in the transcriptional machinery and in resistance to apoptosis. Conclusion: Upregulation of TFF3 after CRT for RC is associated with a higher risk of relapse. The physiological role of TFF3 in restoring the mucosa during CRT could be interfering with treatment efficacy. Our results could reveal not only a novel RC prognostic marker but also a therapeutic target.

  1. Prognostic significance of geriatric assessment in combination with laboratory parameters in elderly patients with aggressive non-Hodgkin lymphoma.

    PubMed

    Aaldriks, Ab A; Giltay, Erik J; Nortier, Johan W R; van der Geest, Lydia G M; Tanis, Bea C; Ypma, Paula; le Cessie, Saskia; Maartense, Ed

    2015-04-01

    The age-adjusted International Prognostic Index (IPI) is an important prognostic factor for patients with non-Hodgkin lymphoma (NHL). We investigated whether a geriatric assessment (GA) is of additional prognostic value in NHL. In this prospective cohort study of 44 patients aged 70 years or older with NHL receiving rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), a GA was administered before the start of chemotherapy. GA was composed of the Mini Nutritional Assessment (MNA), Groningen Frailty Indicator (GFI), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Mini Mental State Examination (MMSE) and levels of albumin, creatinine, lactate dehydrogenase (LDH) and hemoglobin. Multivariate analyses were performed using logistic regression and the Cox regression model. After adjustment for sex, age, comorbidity and univariate laboratory values with p ≤ 0.1, abnormal MNA and GFI scores and low hemoglobin level were associated with not being able to complete the intended chemotherapy: odds ratio (OR) 8.29 (95% confidence interval [CI]: 1.24-55.6; p = 0.03), 9.17 (95% CI: 1.51-55.8; p = 0.02) and 5.41 (95% CI: 0.99-29.8; p = 0.05), respectively. Adjusted for sex, age, comorbidity, age-adjusted IPI and univariate laboratory values with p ≤ 0.1, frailty by GFI and low hemoglobin were associated with worse survival, with a hazard ratio (HR) of mortality of 2.55 (95% CI: 1.07-6.10; p = 0.04) and 4.90 (95% CI: 1.76-13.7; p = 0.002), respectively. We conclude that (risk of) malnutrition, measured with the MNA, frailty, measured with the GFI, and low hemoglobin level had additional predictive value for early treatment withdrawal, and GFI and hemoglobin were, independent of the age-adjusted IPI, predictive for an increased mortality risk. PMID:24956143

  2. Recurrent Amplification at 13q34 Targets at CUL4A, IRS2, and TFDP1 As an Independent Adverse Prognosticator in Intrahepatic Cholangiocarcinoma

    PubMed Central

    Weng, Shao-Wen; Wei, Yu-Ching; Eng, Hock-Liew; Huang, Wan-Ting

    2015-01-01

    Amplification of genes at 13q34 has been reported to be associated with tumor proliferation and progression in diverse types of cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA) has yet to be explored. We examined two iCCA cell lines and 86 cases of intrahepatic cholangiocarcinoma to analyze copy number of three target genes, including cullin 4A (CUL4A), insulin receptor substrate 2 (IRS2), and transcription factor Dp-1 (TFDP1) at 13q34 by quantitative real-time polymerase chain reaction. The cell lines and all tumor samples were used to test the relationship between copy number (CN) alterations and protein expression by western blotting and immunohistochemical assays, respectively. IRS2 was introduced, and each target gene was silenced in cell lines. The mobility potential of cells was compared in the basal condition and after manipulation using cell migration and invasion assays. CN alterations correlated with protein expression levels. The SNU1079 cell line containing deletions of the target genes demonstrated decreased protein expression levels and significantly lower numbers of migratory and invasive cells, as opposed to the RBE cell line, which does not contain CN alterations. Overexpression of IRS2 by introducing IRS2 in SUN1079 cells increased the mobility potential. In contrast, silencing each target gene showed a trend or statistical significance toward inhibition of migratory and invasive capacities in RBE cells. In tumor samples, the amplification of each of these genes was associated with poor disease-free survival. Twelve cases (13.9%) demonstrated copy numbers > 4 for all three genes tested (CUL4A, IRS2, and TFDP1), and showed a significant difference in disease-free survival by both univariate and multivariate survival analyses (hazard ratio, 2.69; 95% confidence interval, 1.23 to 5.88; P = 0.013). Our data demonstrate that amplification of genes at 13q34 plays an oncogenic role in iCCA featuring adverse disease-free survival

  3. Prognostic Impact of Cytogenetic Abnormalities in Multiple Myeloma

    PubMed Central

    Jian, Yuan; Chen, Xiaolei; Zhou, Huixing; Zhu, Wanqiu; Liu, Nian; Geng, Chuanying; Chen, Wenming

    2016-01-01

    Abstract The identification of specific cytogenetic abnormalities by interphase fluorescence in situ hybridization (i-FISH) has become a routine procedure for prognostic stratification of multiple myeloma (MM) patients. In this study, the prognostic significance of cytogenetic abnormalities detected by interphase fluorescence in situ hybridization (iFISH) in 229 newly diagnosed multiple myeloma patients was retrospectively analyzed. Results showed that del (17p), t(4;14), and 1q21 gain were adverse predictors of progression-free survival (PFS). Patients who carried these cytogenetic abnormalities were more likely to have more adverse biological parameters and lower response rate. Multivariate analysis showed that del (17p), t(4;14), and 1q21 gain were statistically independent predictors of PFS, whereas del (17p) was also adverse predictor of overall survival. Multiple coexisting cytogenetic abnormalities also had a negative correlation with PFS. Bortezomib-based therapy could improve the rate and depth of response in patients with t(4;14) translocation and 1q21 gain. Autologous stem cell transplantation could improve, but not overcome the adverse prognostic effect of high-risk cytogenetic abnormalities. These results demonstrate that MM patients with iFISH abnormalities, especially del (17p), are more likely to have a poor prognosis. PMID:27175647

  4. Monosomal karyotype as an adverse prognostic factor in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem-cell transplantation in first complete remission: a retrospective survey on behalf of the ALWP of the EBMT

    PubMed Central

    Brands-Nijenhuis, Angelique V.M.; Labopin, Myriam; Schouten, Harry C.; Volin, Liisa; Socié, Gérard; Cornelissen, Jan J.; Huynh, Anne; Ljungman, Per; Malard, Florent; Esteve, Jordi; Nagler, Arnon; Mohty, Mohamad

    2016-01-01

    Despite the overall benefit from allogeneic hematopoietic stem cell transplantation observed in patients with poor cytogenetic risk acute myeloid leukemia in first complete remission, the precise effect of this procedure for different poor-risk subtypes has not been fully analyzed. This retrospective analysis was performed to investigate whether allogeneic hematopoietic stem cell transplantation performed in first complete remission in patients with monosomal karyotype can overcome the adverse prognosis associated with these patients. Of the 4635 patients included in the study, 189 (4%) harbored a monosomal karyotype. The presence of a monosomal karyotype was associated with a worse outcome, with an inferior leukemia-free survival and overall survival (5-year leukemia-free survival and overall survival: 24±3% and 26±3% vs. 53±1% and 57±1% in monosomal-karyotype and non-monosomal-karyotype, respectively; P<0.0001) and higher relapse risk after transplantation (cumulative incidence of relapse at 5 years: 56±4% in monosomal-karyotype vs. 28±1% in non-monosomal-karyotype; P<0.0001). The adverse negative impact of monosomal karyotype cytogenetics was confirmed in the entire cohort in a multivariate analysis [Hazard Ratio (HR): 1.88, 95% Confidence Interval (CI):1.29–2.73, P=0.001 for relapse incidence; HR:1.71, 95%CI:1.27–2.32, P<0.0001 for leukemia-free survival; HR:1.81, 95%CI:1.32–2.48, P=0.0002 for overall survival], and was independent of the presence of other poor-risk cytogenetic subtypes. In summary, monosomal karyotype arises as a strong negative prognostic feature in acute myeloid leukemia also in patients who undergo allogeneic hematopoietic stem cell transplantation in first complete remission, stressing the need to develop additional pre- and post-transplantation strategies aimed at improving overall results. Nonetheless, allogeneic hematopoietic stem cell transplantation in early phase is currently the best therapy for this very poor-risk acute

  5. Analysis of prognostic factors and comparison of prognostic scores in peripheral T cell lymphoma, not otherwise specified: a single-institution study of 105 Chinese patients.

    PubMed

    Xu, Pengpeng; Yu, Dong; Wang, Li; Shen, Yang; Shen, Zhixiang; Zhao, Weili

    2015-02-01

    Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous subtype of non-Hodgkin's lymphoma. This study aims to better define the prognostic factors and compare the predictive value of the prognostic scores in Chinese patients with PTCL-NOS. One hundred and five patients diagnosed as PTCL-NOS from our institution were retrospectively studied and grouped according to four previously described prognostic scores [International Prognostic Index (IPI), Prognostic Index for PTCL-NOS (PIT), modified PIT (m-PIT), and International PTCL Project (IPTCLP)]. In addition to clinical parameters, peripheral lymphopenia and thrombocytopenia, serum Epstein-Barr virus positivity, and tumor Ki-67 were significantly associated with poor disease outcome. Multivariate analysis revealed that age >60 years, poor performance status, elevated lactic dehydrogenase, and bone marrow involvement were independent adverse variables for survival. All prognostic scores were successful for survival estimation. Risk subgroups in IPI and PIT could be further discriminated by platelet count (IPTCLP factor) and Ki-67 (m-PIT factor), respectively. Together, patient- and tumor-specific characteristics may be incorporated in risk stratification of PTCL-NOS patients. The prognostic scores could be mutually active to improve their predictive value of disease outcome. PMID:25193354

  6. Looking for prognosticators in ovine anaplasmosis: discriminant analysis of clinical and haematological parameters in lambs belonging to differently susceptible breeds experimentally infected with Anaplasma ovis

    PubMed Central

    2013-01-01

    Background A study was carried out to evaluate the response of different native sheep breeds to experimental infection with Anaplasma ovis, the most prevalent sheep tick-borne pathogen in Apulia (Southern Italy). Thirty-four lambs belonging to a Northern European breed (Suffolk) and two Southern Italian breeds (Comisana and Altamurana) were infected. Eleven clinical as well as haematological parameters were monitored at different temporal resolutions on the same subjects before and after the infection, resulting in a data set of 435 observations. The present work, aiming to further the research, presents the results of a multivariate analysis carried out to identify which parameters out of the eleven considered are the most reliable parameters to be considered as markers of the disease phenotype as well as prognosticators of practical clinical importance. Results Data were analysed by discriminant analysis. Out of the eleven considered variables (red blood cells, packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin content, haemoglobin concentration, white blood cells, neutrophils, leukocytes, platelets, rectal temperature), only seven were included in the step-wise model since significantly increasing the Mahlanobis distance between the two closest groups. Both discriminant functions resulted to be highly significant (P < 0.0001) and the percentage of variation accounted for by the first discriminant function was 63.6% of the variance in the grouping variable. Conclusions Taken together, the observed results stress the marked differentiation among the three breeds in terms of physio-pathological phenotypes indicating packed cell volume and red blood cell count as the most informative parameters in the routine clinical practice for A. ovis infection in sheep. PMID:24053615

  7. Determination of a New Parameter, Elevated Epiretinal Membrane, by En Face OCT as a Prognostic Factor for Pars Plana Vitrectomy and Safer Epiretinal Membrane Peeling

    PubMed Central

    Pavlidis, Mitrofanis; Georgalas, Ilias; Körber, Norbert

    2015-01-01

    Purpose. To evaluate the significance of the area of epiretinal membrane (EM) that is not in contact with the retinal structure as a preoperative parameter for safer grasping of the EM and a prognostic factor for visual improvement/outcome. Methods. This prospective observational study included 73 consecutive patients (80 eyes) who underwent pars plana vitrectomy (PPV) and EM peeling. Corrected distance visual acuity (CDVA) and central foveal thickness (CFT) were evaluated preoperatively and at 12 months postoperatively. The number of initial peeling grasps was recorded in the operation protocol. The elevated EM portion was identified by en face optical coherence tomography (OCT) and processed digitally to calculate its area. Results. Surgery was found to significantly improve CDVA and decrease CFT. CDVA improvement correlated with elevated EM, preoperative CFT, and the number of grasping attempts. Conclusion. The detection of elevated EM via en face OCT could assist safer grasping of the EM and indicate the potential for visual outcome improvement after PPV and EM peeling. PMID:26504597

  8. Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

    SciTech Connect

    Fietkau, Rainer . E-mail: rainer.fietkau@med.uni-rostock.de; Roedel, Claus; Hohenberger, Werner; Raab, Rudolf; Hess, Clemens; Liersch, Torsten; Becker, Heinz; Wittekind, Christian; Hutter, Matthias; Hager, Eva; Karstens, Johann; Ewald, Hermann; Christen, Norbert; Jagoditsch, Michael; Martus, Peter; Sauer, Rolf

    2007-03-15

    Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.

  9. Comparison of the Prognostic Value of F-18 Pet Metabolic Parameters of Primary Tumors and Regional Lymph Nodes in Patients with Locally Advanced Cervical Cancer Who Are Treated with Concurrent Chemoradiotherapy

    PubMed Central

    Chong, Gun Oh; Jeong, Shin Young; Park, Shin-Hyung; Lee, Yoon Hee; Lee, Sang-Woo; Hong, Dae Gy; Kim, Jae-Chul; Lee, Yoon Soon; Cho, Young Lae

    2015-01-01

    Objective This study investigated the metabolic parameters of primary tumors and regional lymph nodes, as measured by pre-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) to compare the prognostic value for the prediction of tumor recurrence. This study also identified the most powerful parameter in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy. Methods Fifty-six patients who were diagnosed with cervical cancer with pelvic and/or paraaortic lymph node metastasis were enrolled in this study. Metabolic parameters including the maximum standardized uptake value (SUVmax), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors and lymph nodes were measured by pre-treatment F-18 FDG PET/CT. Univariate and multivariate analyses for disease-free survival (DFS) were performed using the clinical and metabolic parameters. Results The metabolic parameters of the primary tumors were not associated with DFS. However, DFS was significantly longer in patients with low values of nodal metabolic parameters than in those with high values of nodal metabolic parameters. A univariate analysis revealed that nodal metabolic parameters (SUVmax, MTV and TLG), paraaortic lymph node metastasis, and post-treatment response correlated significantly with DFS. Among these parameters, nodal SUVmax (hazard ratio [HR], 4.158; 95% confidence interval [CI], 1.1–22.7; p = 0.041) and post-treatment response (HR, 7.162; 95% CI, 1.5–11.3; p = 0.007) were found to be determinants of DFS according to a multivariate analysis. Only nodal SUVmax was an independent pre-treatment prognostic factor for DFS, and the optimal cutoff for nodal SUVmax to predict progression was 4.7. Conclusion Nodal SUVmax according to pre-treatment F-18 FDG PET/CT may be a prognostic biomarker for the prediction of disease recurrence in patients with locally advanced cervical cancer. PMID:26368542

  10. Prognostic Value of Baseline 18F-FDG PET/CT Functional Parameters in Patients with Advanced Lung Adenocarcinoma Stratified by EGFR Mutation Status

    PubMed Central

    Wang, Dalong; Zhang, Minghui; Gao, Xuan; Yu, Lijuan

    2016-01-01

    The study objective was to retrospectively analyze the metabolic variables derived from 18 F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) as predictors of progression-free survival (PFS) and overall survival (OS) in advanced lung adenocarcinoma stratified by epidermal growth factor receptor (EGFR) mutation status. A total of 176 patients (91, EGFR mutation; 85, wild-type EGFR) who underwent 18F-FDG PET/CT before treatment were enrolled. The main 18F-FDG PET/CT-derived variables: primary tumor maximum standardized uptake value (SUVmaxT), primary tumor total lesion glycolysis (TLGT), the maximum SUVmax of all selected lesions in whole body determined using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria (SUVmaxWBR), and whole-body total TLG determined using the RECIST 1.1 criteria (TLGWBR) were measured. Survival analysis regarding TLGWBR, and other factors in advanced lung adenocarcinoma patients stratified using EGFR mutation status, were evaluated. The results indicated that high TLGWBR (≥259.85), EGFR wild-type, and high serum LDH were independent predictors of worse PFS and OS in all patients with advanced lung adenocarcinoma. Among patients with wild-type EGFR, only TLGWBR retained significance as an independent predictor of both PFS and OS. Among patients with the EGFR mutation, high serum LDH level was an independent predictor of worse PFS and OS, and high TLGWBR (≥259.85) was an independent predictor of worse PFS but not worse OS. In conclusion, TLGWBR is a promising parameter for prognostic stratification of patients with advanced lung adenocarcinoma and EGFR status; however, it cannot be used to further stratify the risk of worse OS for patients with the EGFR mutation. Further prospective studies are needed to validate our findings. PMID:27336755

  11. Estimating human-equivalent no observed adverse-effect levels for VOCs (volatile organic compounds) based on minimal knowledge of physiological parameters. Technical paper

    SciTech Connect

    Overton, J.H.; Jarabek, A.M.

    1989-01-01

    The U.S. EPA advocates the assessment of health-effects data and calculation of inhaled reference doses as benchmark values for gauging systemic toxicity to inhaled gases. The assessment often requires an inter- or intra-species dose extrapolation from no observed adverse effect level (NOAEL) exposure concentrations in animals to human equivalent NOAEL exposure concentrations. To achieve this, a dosimetric extrapolation procedure was developed based on the form or type of equations that describe the uptake and disposition of inhaled volatile organic compounds (VOCs) in physiologically-based pharmacokinetic (PB-PK) models. The procedure assumes allometric scaling of most physiological parameters and that the value of the time-integrated human arterial-blood concentration must be limited to no more than to that of experimental animals. The scaling assumption replaces the need for most parameter values and allows the derivation of a simple formula for dose extrapolation of VOCs that gives equivalent or more-conservative exposure concentrations values than those that would be obtained using a PB-PK model in which scaling was assumed.

  12. Earliest Bedside Assessment of Hemodynamic Parameters and Cardiac Biomarkers: Their Role as Predictors of Adverse Outcome in Patients with Septic Shock

    PubMed Central

    Sasko, Benjamin; Butz, Thomas; Prull, Magnus Wilhelm; Liebeton, Jeanette; Christ, Martin; Trappe, Hans-Joachim

    2015-01-01

    Background: Early assessment and aggressive hemodynamic treatment have been shown to increase the survival of patients in septic shock. Current and past sepsis guidelines recommend a resuscitation protocol including central venous pressure (CVP), mean arterial blood pressure (MAP), urine output and central venous oxygen saturation (ScvO2) for resuscitation within the first six hours. Currently, the established severity score systems like APACHE II score, SOFA score or SAPS II score predict the outcome of critically ill patients on the bases of variables obtained only after the first 24 hours. The present study aims to evaluate the risk of short-term mortality for patients with septic shock by the earliest possible assessment of hemodynamic parameters and cardiac biomarkers as well as their role for the prediction of the adverse outcome. Methods: 52 consecutive patients treated for septic shock in the intensive care unit of one centre (Marien Hospital Herne, Ruhr University Bochum, Germany) were prospectively enrolled in this study. Hemodynamic parameters (MAP, CVP, ScvO2, left ventricular ejection fraction, Hematocrit) and cardiac biomarkers (Troponin I) at the ICU admission were evaluated in regard to their influence on mortality. The primary endpoint was all-cause mortality within 28 days after the admission. Results: A total of 52 patients (31 male, 21 female) with a mean age of 71.4±8.5 years and a mean APACHE II score of 37.0±7.6 were enrolled in the study. 28 patients reached the primary endpoint (mortality 54%). Patients presenting with hypotension (MAP <65 mmHg) at ICU admission had significantly higher rates of 28-day mortality as compared with the group of patients without hypotension (28-day mortality rate 74 % vs. 32 %, p<0.01). Furthermore, the patients in the hypotension present group had significantly higher lactate concentration (p=0.002), higher serum creatinin (p=0.04), higher NTproBNP (p=0.03) and after the first 24 hours higher APACHE II

  13. A magnetic resonance imaging-based prognostic scoring system to predict outcome in transplant-eligible patients with multiple myeloma

    PubMed Central

    Mai, Elias K.; Hielscher, Thomas; Kloth, Jost K.; Merz, Maximilian; Shah, Sofia; Raab, Marc S.; Hillengass, Michaela; Wagner, Barbara; Jauch, Anna; Hose, Dirk; Weber, Marc-André; Delorme, Stefan; Goldschmidt, Hartmut; Hillengass, Jens

    2015-01-01

    Diffuse and focal bone marrow infiltration patterns detected by magnetic resonance imaging have been shown to be of prognostic significance in all stages of monoclonal plasma cell disorders and have, therefore, been incorporated into the definition of the disease. The aim of this retrospective analysis was to develop a rapidly evaluable prognostic scoring system, incorporating the most significant information acquired from magnetic resonance imaging. Therefore, the impact of bone marrow infiltration patterns on progression-free and overall survival in 161 transplant-eligible myeloma patients was evaluated. Compared to salt and pepper/minimal diffuse infiltration, moderate/severe diffuse infiltration had a negative prognostic impact on both progression-free survival (P<0.001) and overall survival (P=0.003). More than 25 focal lesions on whole-body magnetic resonance imaging or more than seven on axial magnetic resonance imaging were associated with an adverse prognosis (progression-free survival: P=0.001/0.003 and overall survival: P=0.04/0.02). A magnetic resonance imaging-based prognostic scoring system, combining grouped diffuse and focal infiltration patterns, was formulated and is applicable to whole-body as well as axial magnetic resonance imaging. The score identified high-risk patients with median progression-free and overall survival of 23.4 and 55.9 months, respectively (whole-body-based). Multivariate analyses demonstrated that the magnetic resonance imaging-based prognostic score stage III (high-risk) and adverse cytogenetics are independent prognostic factors for both progression-free and overall survival (whole-body-based, progression-free survival: hazard ratio=3.65, P<0.001; overall survival: hazard ratio=5.19, P=0.005). In conclusion, we suggest a magnetic resonance imaging-based prognostic scoring system which is a robust, easy to assess and interpret parameter summarizing significant magnetic resonance imaging findings in transplant

  14. Prognostic significance of clinical parameters and biological markers in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy.

    PubMed

    Homma, A; Furuta, Y; Oridate, N; Nakano, Y; Kohashi, G; Yagi, K; Nagahashi, T; Yagi, K; Nagahashi, T; Fukuda, S; Inoue, K; Inuyama, Y

    1999-04-01

    Concurrent chemoradiotherapy is reported to have a fair clinical outcome with organ preservation for patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to determine whether biological markers are related to proliferative activity or apoptosis of tumor cells and whether clinical factors are associated with a clinical outcome in SCCHN patients treated with concurrent chemoradiotherapy. Immunostaining with antibodies specific for p53, bcl-2, bax, and MIB-1 was performed to evaluate expression of these proteins in formalin-fixed, paraffin-embedded specimens of 111 SCCHN patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m2, four to six times every week; total radiation therapy dose of 40-65 Gy over 4-6.5 weeks). Multivariate analysis indicated that nodal status was a significant indicator of overall survival (OS; P = 0.001) and locoregional control (LRC; P = 0.002). In a univariate analysis, patients with a low MIB-1-positive index (< 40%) had better OS than those with a high MIB-1-positive index (> or = 40%; P = 0.013), although the difference was not statistically significant in a multivariate analysis (P = 0.060). Patients with bcl-2-positive tumors had better LRC than those with bcl-2-negative tumors, based on a multivariate analysis (P = 0.017). No statistically significant association was found between p53 or bax expression and clinical outcome. These results indicate that nodal status is the major prognostic factor in SCCHN patients treated with concurrent chemoradiotherapy. In addition, our findings suggest that bcl-2 positivity is associated with better LRC and that the proliferative activity of tumor cells might be prognostic for OS. PMID:10213215

  15. Banking of fresh-frozen prostate tissue using the alternate mirror image protocol: methods, validation, and impact on the pathological prognostic parameters in radical prostatectomy.

    PubMed

    Brimo, Fadi; Sircar, Kanishka; Chevalier, Simone; Saad, Fred; Lacombe, Louis; Têtu, Bernard; Scarlata, Eleanora; Aprikian, Armen

    2012-12-01

    We evaluated the value of the 'alternative slices mirror image method' used in prostate tissue banking in terms of predicting the sampling of cancerous tissue while preserving the pathological prognostic information. The concordance of diagnosis between banked sections and their mirror image paraffin- sections was studied using 50 cases corresponding to 400 H&E sections taken from 400 banked frozen blocks (two presumed benign and two presumed cancer for each case). The mean number of paraffin blocks in each case was 21. On average 29% of the prostate gland was banked and banked tissue contained cancer in 47 cases (94%). There was no difference between the concordant and discordant groups in terms of the final Gleason score, pathological stage, prostate size, number of banked blocks and the percentage of the prostate submitted for banking. However, concordant cases had larger foci of cancer in the mirror image paraffin block (P = 0.0088). In addition, the surgical margins sections which are not banked using this method provided important information about the pathological stage, surgical margins status and the final Gleason score in 2.6, 2.6, and 1.3% of cases, respectively. The 'alternative slices mirror image method' is a straightforward method that is highly efficient in banking prostatic cancerous tissue. Overall, tumor volume and especially size of tumor foci in the image paraffin block are the most important factors in dictating the success rate of banking frozen cancerous tissue. Including 'surgical margins' sections for histology provides additional important prognostic information in a minority of cases. PMID:22200970

  16. Tumor cell nuclear diameter and CD30 expression as potential prognostic parameter in patients with extranodal NK/T-cell lymphoma, nasal type.

    PubMed

    Hong, Junshik; Park, Sanghui; Baek, Hae Lim; Jung, Joo Hyun; Kang, Il Gyu; Sym, Sun Jin; Park, Jinny; Ahn, Jeong Yeal; Cho, Eun Kyung; Kim, Seon Tae; Shin, Dong Bok; Lee, Jae Hoon

    2012-01-01

    Extranodal natural killer/T-cell lymphoma, nasal type (nasal ENKTL) is a distinct clinicopathologic entity of lymphoid tumors with variable size and differentiation of tumor cells. Nasal ENKTL is related to infection of the tumor cells with Epstein-Barr virus (EBV) and virtually all cases contain monoclonal episomal EBV DNA and detectable EBV encoded small nuclear RNAs (EBERs). Several clinical factors are known for their relation to the prognosis, but histopathologic prognostic factors of nasal ENKTL have not yet been well established. We evaluated the prognostic value of the longest nuclear diameter of EBER+ tumor cells (NDTC) along with the result of CD30 expression. Twenty two patients with newly diagnosed nasal ENKTL were evaluated regarding clinicopathologic characteristics. NDTC was measured using a computerized image analysis system. The results were expressed as the mean diameter of ≥ 50 cells in a patient. Median of the mean NDTC of the patients was 7.32 μm (5.15-11.27). Patients with larger mean NDTC (≥ 7.35 μm) had a poorer event-free survival (EFS) than those with smaller mean NDTC (<7.35 μm; p = 0.024) and had a tendency of inferior overall survival (OS) (p = 0.08). Patients with CD30 expression had a inferior EFS (p = 0.018) and OS (p = 0.011) compared those without CD30 expression. The NDTC of EBV infected tumor cell and CD30 expression had relation to survival in the current exploratory analysis. PMID:23119111

  17. Prognostic factors and classification in multiple myeloma.

    PubMed Central

    San Miguel, J. F.; Sànchez, J.; Gonzalez, M.

    1989-01-01

    Analyses of prognostic factors have allowed the design of staging systems in different haematological disorders. In a series of 220 patients with multiple myeloma, univariate analysis showed that nine parameters had a significant adverse effect on survival; poor performance status (Karnowsky scaling system less than 70%), infections before diagnosis, renal impairment (assessed either by creatinine clearance greater than 2 mg dl-1 or urea greater than 40 mg dl-1), serum calcium (greater than 10 mg dl-1), severe anaemia (less than 8.5 g dl-1), the presence of Bence-Jones proteinuria, failure to achieve complete remission, more than 40% plasma cells in bone marrow and a low paraprotein index (monoclonal component/% plasma cells: P less than 0.09). In addition, this index correlated significantly with all the other prognostic factors except performance status. The best combination of disease characteristics selected by means of the Cox regression proportional hazards method were performance status and creatinine levels. Additionally, by factor analysis of principal components we obtained a regression equation that included creatinine levels, haemoglobin, performance status and paraprotein index. Using this it was possible to separate the series of patients into three risk categories: A (65 patients), B (69 patients) and C (65 patients) with a median survival of 41, 24 and 12 months, respectively. The model provided similar results to those of the British Medical Research Council, whereas the staging systems proposed by Durie and Salmon, Merlin et al. and Carbone et al. had a lower discriminant value in our series. PMID:2757917

  18. Adverse Interaction between Capecitabine and Warfarin Resulting in Altered Coagulation Parameters: A Review of the Literature Starting from a Case Report.

    PubMed

    Giunta, Giovanni

    2010-01-01

    Capecitabine is an orally active prodrug of fluorouracil and is extensively used as an antineoplastic agent. It is converted to 5-Fluorouracil in the liver and tumor tissues. Warfarin is an anticoagulant agent for preventing and treating venous and arterial thrombosis and embolism and is metabolized by cytochrome P450 isoenzymes in the liver. Preclinical in vitro studies using human liver microsomes report no inhibitory effects between capecitabine and substrates of cytochrome P. However, the concomitant administration of capecitabine and warfarin resulted in INR elevation in the cases previously reported in the literature. The exact mechanism of this interaction is unknown but may be related to downregulation of cytochrome P450 2C9 by capecitabine or its metabolites. We report on the possible adverse interaction between capecitabine and warfarin in a patient with metastatic breast cancer and critically review the existing literature on this topic. Physicians should be aware of adverse reactions arising from the combined use of capecitabine and warfarin. In the light of the current data, INR levels should be closely monitored in patients using these drugs together. PMID:20671989

  19. Regional Longitudinal Myocardial Deformation Provides Incremental Prognostic Information in Patients with ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Jensen, Jan Skov; Pedersen, Sune H.; Galatius, Søren; Fritz-Hansen, Thomas; Bech, Jan; Olsen, Flemming Javier; Mogelvang, Rasmus

    2016-01-01

    Background Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognosticator to conventional echocardiographic measures in patients after myocardial infarction (MI). The aim of this study was to evaluate the prognostic value of regional longitudinal myocardial deformation in comparison to GLS, conventional echocardiography and clinical information. Method In total 391 patients were admitted with ST-Segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention and subsequently examined by echocardiography. All patients were examined by tissue Doppler imaging (TDI) and two-dimensional strain echocardiography (2DSE). Results During a median-follow-up of 5.3 (IQR 2.5–6.1) years the primary endpoint (death, heart failure or a new MI) was reached by 145 (38.9%) patients. After adjustment for significant confounders (including conventional echocardiographic parameters) and culprit lesion, reduced longitudinal performance in the anterior septal and inferior myocardial regions (but not GLS) remained independent predictors of the combined outcome. Furthermore, inferior myocardial longitudinal deformation provided incremental prognostic information to clinical and conventional echocardiographic information (Harrell's c-statistics: 0.63 vs. 0.67, p = 0.032). In addition, impaired longitudinal deformation outside the culprit lesion perfusion region was significantly associated with an adverse outcome (p<0.05 for all deformation parameters). Conclusion Regional longitudinal myocardial deformation measures, regardless if determined by TDI or 2DSE, are superior prognosticators to GLS. In addition, impaired longitudinal deformation in the inferior myocardial segment provides prognostic information over and above clinical and conventional echocardiographic risk factors. Furthermore, impaired longitudinal deformation outside the culprit lesion perfusion region seems to be a paramount marker of adverse

  20. 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.

  1. Vehicle Integrated Prognostic Reasoner (VIPR) Final Report

    NASA Technical Reports Server (NTRS)

    Bharadwaj, Raj; Mylaraswamy, Dinkar; Cornhill, Dennis; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

    2013-01-01

    A systems view is necessary to detect, diagnose, predict, and mitigate adverse events during the flight of an aircraft. While most aircraft subsystems look for simple threshold exceedances and report them to a central maintenance computer, the vehicle integrated prognostic reasoner (VIPR) proactively generates evidence and takes an active role in aircraft-level health assessment. Establishing the technical feasibility and a design trade-space for this next-generation vehicle-level reasoning system (VLRS) is the focus of our work.

  2. 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. PMID:24782120

  3. The prognostic value of functional and anatomical parameters for the selection of patients receiving yttrium-90 microspheres for the treatment of liver cancer

    NASA Astrophysics Data System (ADS)

    Mesoloras, Geraldine

    Yttrium-90 (90Y) microsphere therapy is being utilized as a treatment option for patients with primary and metastatic liver cancer due to its ability to target tumors within the liver. The success of this treatment is dependent on many factors, including the extent and type of disease and the nature of prior treatments received. Metabolic activity, as determined by PET imaging, may correlate with the number of viable cancer cells and reflect changes in viable cancer cell volume. However, contouring of PET images by hand is labor intensive and introduces an element of irreproducibility into the determination of functional target/tumor volume (FTV). A computer-assisted method to aid in the automatic contouring of FTV has the potential to substantially improve treatment individualization and outcome assessment. Commercial software to determine FTV in FDG-avid primary and metastatic liver tumors has been evaluated and optimized. Volumes determined using the automated technique were compared to those from manually drawn contours identified using the same cutoff in the standard uptake value (SUV). The reproducibility of FTV is improved through the introduction of an optimal threshold value determined from phantom experiments. Application of the optimal threshold value from the phantom experiments to patient scans was in good agreement with hand-drawn determinations of the FTV. It is concluded that computer-assisted contouring of the FTV for primary and metastatic liver tumors improves reproducibility and increases accuracy, especially when combined with the selection of an optimal SUV threshold determined from phantom experiments. A method to link the pre-treatment assessment of functional (PET based) and anatomical (CT based) parameters to post-treatment survival and time to progression was evaluated in 22 patients with colorectal cancer liver metastases treated using 90Y microspheres and chemotherapy. The values for pre-treatment parameters that were the best

  4. [PROGNOSTIC VALUE OF SOME HEMOSTASIS-RELATED, HOMOCYSTEINE, HIGH SENSITIVE C R P AND MULTIDETECTOR COMPUTED TOMOGRAPHY PARAMETERS IN PULMONARY EMBOLISM].

    PubMed

    Todua, F; Akhvlediani, M; Vorobiova, E; Baramidze, A; Tsivtsivadze, G; Gachechiladze, D

    2016-05-01

    Nowadays, an arsenal of diagnostic methods is used in diagnosis of pulmonary embolism, which includes x-ray, angiography, perfusion-ventilation scintigraphy, CT and magnetic resonance imaging, Doppler and laboratory studies. Purpose of our study was to evaluate the diagnostic significance of determination of some parameters of hemostasis (D-dimer, Soluble fibrinmonomer complexes, fibrinogen), homocysteine, hs-CRP and multidetector computed tomography in suspected pulmonary embolism. We have examined 54 patients -31 men and 23 women, aged 18 to 76 years, with characteristics of pulmonary embolism. According to our data, Multidetector computed tomography angiopulmonography , measuring D-dimer, fibrinogen and related hyperhomocysteinemia with increased level of hs-CRP may serve as binding, diagnostically significant laboratory markers in the diagnosis and treatment efficacy of pulmonary thromboembolism. PMID:27348165

  5. 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.

  6. Prognostic factors in lupus nephritis.

    PubMed

    Mok, C C

    2005-01-01

    Systemic lupus erythematosus (SLE) is a heterogeneous disorder and its renal manifestations are protean. The course and prognosis of lupus nephritis is dependent on a large number of demographic, histopathological, serological, racial, socioeconomic and time dependent factors. Moreover, the initial and maintenance therapeutic regimens may also influence the long term renal outcome. This article reviews the important prognostic factors that have been reported in literature. The management strategy of lupus nephritis should be individualized and based on a composite of these parameters. PMID:15732286

  7. Prognostic Evaluation of Nasopharyngeal Carcinoma with Bone-Only Metastasis after Therapy

    PubMed Central

    Lu, Tianzhu; Guo, Qiaojuan; Cui, Xiaofei; Chen, Zhuhong; Lin, Shaojun; Xu, Luying; Lin, Jin; Zong, Jingfeng

    2016-01-01

    Purpose To evaluate the prognosis of nasopharyngeal carcinoma (NPC) patients who developed bone-only metastasis after primary treatment and the stratification of these patients into different risk groups based on independent prognostic factors. Materials and Methods Eighty NPC patients who developed bone-only metastasis after definitive radiotherapy from October 2005 to December 2010 were enrolled. All these patients received palliative treatment for bone metastasis, including chemotherapy and/or radiotherapy. Clinical features, treatment modality, and laboratory parameters were examined with univariate and multivariate analyses. Results The median follow-up time was 15.5 months (range, 2–67 months) for the whole cohort. The median overall metastatic survival (OMS) time and the 2-year estimate OMS rate were 26.5 months and 52%, respectively. Multivariate analysis indicated that patients with short metastases-free interval, multiple bone metastases sites, high serum lactic dehydrogenase levels, and treated with radiotherapy or chemotherapy alone had significantly worse outcomes. Patients were stratified into three different risk groups based on the number of adverse factors present. The OMS curves of the three groups were all significantly different (p<0.001). Conclusion Severl prognostic factors were found to be associated with worse outcomes. According to the number of adverse factors present, bone-only metastasis patients can be stratified into three risk groups with significantly different prognoses. Such grouping may help in improving the design of clinical trials and in guiding individualized treatment for NPC patients with bone-only metastasis. PMID:27189275

  8. An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies

    PubMed Central

    Padron, E; Garcia-Manero, G; Patnaik, M M; Itzykson, R; Lasho, T; Nazha, A; Rampal, R K; Sanchez, M E; Jabbour, E; Al Ali, N H; Thompson, Z; Colla, S; Fenaux, P; Kantarjian, H M; Killick, S; Sekeres, M A; List, A F; Onida, F; Komrokji, R S; Tefferi, A; Solary, E

    2015-01-01

    Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication. PMID:26230957

  9. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  10. The prognostic value of high sensitivity troponin T 7 weeks after an acute coronary syndrome

    PubMed Central

    Kao, Michelle P C; Dow, Ellie; Lang, Chim; Struthers, Allan

    2012-01-01

    Objective The role of high sensitivity troponin T (hs-TnT) in the convalescence phase after an acute coronary syndrome (ACS) is unknown. The authors aim to assess the prognostic utility of a single hs-TnT level at 7-week post-ACS. Second, the authors evaluated whether any serial changes in hs-TnT between the index admission and 7 weeks post-ACS had any link with the prognosis. Third, the authors assessed whether the prognostic utility of hs-TnT is independent of various echocardiographic abnormalities. Methods The authors measured hs-TnT levels in 326 consecutive patients at 7 weeks after an ACS event. The composite end point of death from any cause or acute myocardial infarction was evaluated over a median duration of 30 months. Results A high 7-week hs-TnT (>14 ng/l) predicted adverse clinical outcomes independent of conventional risk factors, left ventricular dysfunction and left ventricular hypertrophy on echocardiography (adjusted RR: 2.69 (95% CI 1.45 to 5.00)). Patients with persistent hs-TnT elevation at 7 weeks were also at an increased risk of cardiovascular events compared with those with an initial high hs-TnT which then normalised (unadjusted RR 3.39 (95% CI 2.02 to 5.68)). Conclusion The authors have demonstrated the prognostic utility of a single 7-week hs-TnT measurement in routine ACS patients and that it could be used to assist medium term risk stratification in this patient cohort. In addition, the authors also showed that hs-TnT predicted long-term adverse prognosis independent of various echo parameters. Future studies should evaluate whether tailoring specific treatment interventions to higher risk individuals as identified by an elevated hs-TnT during the convalescence phase of ACS would improve clinical outcomes. PMID:22689713

  11. 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.

  12. Exercise hypertension: an adverse prognosis?

    PubMed

    Smith, Ryan G; Rubin, Stanley A; Ellestad, Myrvin H

    2009-01-01

    We sought to clarify the prognostic importance of an "exaggerated" or "hypertensive" systolic blood pressure response to exercise during an exercise test. Studies evaluating the prognosis for cardiovascular events and cardiovascular mortality in those with hypertension during exercise testing were systematically reviewed. Fourteen studies were identified. Six studies were of healthy volunteers or hypertensives. Eight studies were in subjects with known or suspected heart disease. Without established heart disease, exercise hypertension predicted cardiovascular events and cardiovascular death. However, two of the six studies included a multivariate analysis; both demonstrated no independent association. Studies in subjects with known or suspected heart disease demonstrated that exercise hypertension predicted fewer cardiac events and lesser mortality or, after multivariate adjustment, no associated risk. In a healthy population, a higher exercise blood pressure may indicate hypertension or prehypertension, instead of normal vascular function, and an associated long-term adverse prognosis. In a population with a high burden of heart disease, the highest risk subjects with the most extensive cardiac disease may not be capable of generating pressure or workload to allow the manifestation of exercise systolic hypertension. By comparison, therefore, those with exercise hypertension have a better prognosis. PMID:20409979

  13. Requirements Flowdown for Prognostics and Health Management

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

    Prognostics and Health Management (PHM) principles have considerable promise to change the game of lifecycle cost of engineering systems at high safety levels by providing a reliable estimate of future system states. This estimate is a key for planning and decision making in an operational setting. While technology solutions have made considerable advances, the tie-in into the systems engineering process is lagging behind, which delays fielding of PHM-enabled systems. The derivation of specifications from high level requirements for algorithm performance to ensure quality predictions is not well developed. From an engineering perspective some key parameters driving the requirements for prognostics performance include: (1) maximum allowable Probability of Failure (PoF) of the prognostic system to bound the risk of losing an asset, (2) tolerable limits on proactive maintenance to minimize missed opportunity of asset usage, (3) lead time to specify the amount of advanced warning needed for actionable decisions, and (4) required confidence to specify when prognosis is sufficiently good to be used. This paper takes a systems engineering view towards the requirements specification process and presents a method for the flowdown process. A case study based on an electric Unmanned Aerial Vehicle (e-UAV) scenario demonstrates how top level requirements for performance, cost, and safety flow down to the health management level and specify quantitative requirements for prognostic algorithm performance.

  14. Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia

    PubMed Central

    Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

    2013-01-01

    Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. This trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374. PMID:23065509

  15. The Prognostic Significance of the Hedgehog Signaling Pathway in Colorectal Cancer.

    PubMed

    Papadopoulos, Vassilis; Tsapakidis, Konstantinos; Riobo Del Galdo, Natalia A; Papandreou, Christos N; Del Galdo, Francesco; Anthoney, Alan; Sakellaridis, Nikos; Dimas, Konstantinos; Kamposioras, Konstantinos

    2016-06-01

    Despite significant advances in the management of colorectal cancer (CRC) the identification of new prognostic biomarkers continues to be a challenge. Since its initial discovery, the role of the Hedgehog (Hh) signaling pathway in carcinogenesis has been extensively studied. We herein review and comment on the prognostic significance of the Hh signaling pathway in CRC. The differential expression of Hh pathway components between malignant and nonmalignant conditions as well as correlation of Hh activation markers with various clinicopathological parameters and the effect on disease-free survival, overall survival, and disease recurrence in patients with CRC is summarized and discussed. According to the studies reviewed herein the activation of the Hh pathway seems to be correlated with adverse clinicopathological features and worse survival. However, to date study results show significant variability with regard to the effect on outcomes. Such results need to be interpreted carefully and emphasize the need for further well designed studies to characterize the actual influence of the Hh pathway in CRC prognosis. PMID:27032873

  16. Prognostic impact of persistent cytogenetic abnormalities at complete remission in adult patients with acute lymphoblastic leukemia.

    PubMed

    Short, Nicholas J; Kantarjian, Hagop M; Jabbour, Elias J; O'Brien, Susan M; Faderl, Stefan; Burger, Jan A; Garris, Rebecca; Qiao, Wei; Huang, Xuelin; Jain, Nitin; Konopleva, Marina; Kadia, Tapan M; Daver, Naval; Borthakur, Gautam; Cortes, Jorge E; Ravandi, Farhad

    2016-06-01

    In acute myelogenous leukemia, the persistent detection of abnormal cytogenetics at complete remission (ACCR) is associated with inferior outcomes. However, the prognostic significance of ACCR in adult patients with acute lymphoblastic leukemia (ALL) is unknown. We evaluated 272 adult patients with ALL and abnormal cytogenetics at baseline who were treated with frontline induction chemotherapy, achieved complete remission (CR) and had cytogenetic analysis performed at the time of CR. ACCR was observed in 26 patients (9.6%). Median relapse-free survival was 22 months (95% CI, 12 months to not reached) for patients with ACCR vs. 48 months (range, 30-125 months) in patients with normal cytogenetics at CR (NCCR; P = 0.31). Median overall survival also did not differ significantly between the ACCR (99 months [range, 17 months to not reached]) and NCCR groups (67 months [range, 47 months to not reached], P = 0.86). The specificity of ACCR for minimal residual disease (MRD) positivity by multi-parameter flow cytometry (MFC) was 43%, and there was overall poor correlation between these two methods for the detection of residual disease. When patients were stratified by MRD status, the presence or absence of persistent cytogenetic abnormalities at CR did not add additional prognostic information. This study suggests that there is poor association between MRD assessment by MFC and the presence or absence of cytogenetic abnormalities at CR in adult patients with ALL. ACCR was not associated with adverse outcomes in ALL and did not add additional prognostic information when MRD status by MFC was known. PMID:26800008

  17. Adverse reactions to sulfites

    PubMed Central

    Yang, William H.; Purchase, Emerson C.R.

    1985-01-01

    Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be sulfite-related has occurred. The exact mechanism of sulfite-induced reactions is unknown. Practising physicians should be aware of the clinical manifestations of sulfite-related adverse reactions as well as which foods and pharmaceuticals contain sulfites. Cases should be reported to health officials and proper advice given to the victims to prevent further exposure to sulfites. The food industry, including beer and wine manufacturers, and the pharmaceutical industry should consider using alternative preservatives. In the interim, they should list any sulfites in their products. PMID:4052897

  18. A prognostic model based on pretreatment platelet lymphocyte ratio for stage IE/IIE upper aerodigestive tract extranodal NK/T cell lymphoma, nasal type.

    PubMed

    Wang, Ke-feng; Chang, Bo-yang; Chen, Xiao-qin; Liu, Pan-pan; Wuxiao, Zhi-jun; Wang, Zhi-hui; Li, Su; Jiang, Wen-qi; Xia, Zhong-jun

    2014-12-01

    Patients with stage IE/IIE natural killer T (NK/T) cell lymphomas have discrepant survival outcome. This study aims to establish a prognostic model based on the pretreatment platelet lymphocyte ratio (PLR) specifically for localized extranodal NK/T cell lymphoma to guide the therapy. We retrospectively analyzed the data of 252 patients with early-stage upper aerodigestive tract NK/T cell lymphoma. The 5-year overall survival rate in 252 patients was 67.1%. Prognostic factors for survival were female (P = 0.025; relative risk, 0.51; 95% CI 0.28-0.92), older age (P = 0.000; relative risk, 3.34; 95% CI 1.94-5.75), stage II(P = 0.020; relative risk, 1.79; 95% CI 1.10-2.91), lactate dehydrogenase (LDH) level (P = 0.009; relative risk, 2.00; 95% CI 1.19-3.35), and PLR (P = 0.020; relative risk, 1.77; 95% CI 1.10-2.87). Based on these five parameters, we identified three different risk groups: group 1(106 cases, 43.4%), no or one adverse factor; group 2(85 cases, 34.8%), two factors; group 3(53 cases, 21.7%), three to five factors. Five-year overall survival was 83.3% for group 1, 62.2% for group 2, and 43.1% for group 3 (P = 0.000). Compared with International Prognostic Index and Korean Prognostic Index, the new model has a better prognostic discrimination for the patients of stage IE/IIE upper aerodigestive tract NK/T cell lymphoma. The PLR-based prognosis model is useful to stratify patients with localized extranodal NK/T cell lymphoma into different risk groups and guide the treatment modalities selection. PMID:25377661

  19. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  20. Lifecycle Prognostics Architecture for Selected High-Cost Active Components

    SciTech Connect

    N. Lybeck; B. Pham; M. Tawfik; J. B. Coble; R. M. Meyer; P. Ramuhalli; L. J. Bond

    2011-08-01

    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, 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 operations and

  1. Cutaneous adverse reactions specific to epidermal growth factor receptor inhibitors

    PubMed Central

    Lupu, I; Voiculescu, VM; Bacalbasa, N; Prie, BE; Cojocaru, I; Giurcaneanu, C

    2015-01-01

    Classical antineoplastic therapy is encumbered by extensively studied adverse reactions, most often of systemic nature. The emergence of new generations of anticancer treatments, including epidermal growth factor receptor inhibitors, besides improving the response to treatment and the survival rate, is accompanied by the occurrence of new specific side effects, incompletely studied. These side effects are most often cutaneous (hand foot syndrome, acneiform reactions), and in some cases are extremely severe, requiring dose reduction or drug discontinuation. The prevention of the cutaneous adverse effects and their treatment require a close collaboration between the oncologist and the dermatologist. The occurrence of some of these skin adverse effects may be a favorable prognostic factor for the response to the cancer treatment and the overall survival. Abbreviations: EGFR = epidermal growth factor receptors; EGFRI = epidermal growth factor receptors inhibitors PMID:26361513

  2. The Practicability of a Novel Prognostic Index (PI) Model and Comparison with Nottingham Prognostic Index (NPI) in Stage I–III Breast Cancer Patients Undergoing Surgical Treatment

    PubMed Central

    Li, Shuaijie; Huang, Xiaojia; Yang, Lu; Xiao, Xiangsheng; Xie, Xiaoming

    2015-01-01

    Background Previous studies have indicated the prognostic value of various laboratory parameters in cancer patients. This study was to establish a prognostic index (PI) model for breast cancer patients based on the potential prognostic factors. Methods A retrospective study of 1661 breast cancer patients who underwent surgical treatment between January 2002 and December 2008 at Sun Yat-sen University Cancer Center was conducted. Multivariate analysis (Cox regression model) was performed to determine the independent prognostic factors and a prognostic index (PI) model was devised based on these factors. Survival analyses were used to estimate the prognostic value of PI, and the discriminatory ability of PI was compared with Nottingham Prognostic Index (NPI) by evaluating the area under the receiver operating characteristics curves (AUC). Results The mean survival time of all participants was 123.6 months. The preoperative globulin >30.0g/L, triglyceride >1.10mmol/L and fibrinogen >2.83g/L were identified as risk factors for shorter cancer-specific survival. The novel prognostic index model was established and enrolled patients were classified as low- (1168 patients, 70.3%), moderate- (410 patients, 24.7%) and high-risk groups (83 patients, 5.0%), respectively. Compared with the low-risk group, higher risks of poor clinical outcome were indicated in the moderate-risk group [Hazard ratio (HR): 1.513, 95% confidence interval (CI): 1.169–1.959, p = 0.002] and high-risk group (HR: 2.481, 95%CI: 1.653–3.724, p< 0.001). Conclusions The prognostic index based on three laboratory parameters was a novel and practicable prognostic tool. It may serve as complement to help predict postoperative survival in breast cancer patients. PMID:26600129

  3. 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.

  4. [Adverse reaction of pseudoephedrine].

    PubMed

    López Lois, G; Gómez Carrasco, J A; García de Frías, E

    2005-04-01

    We present a case of a 7 years old girl who developed an episode of myoclonic movements and tremors after being medicated with a not well quantified amount of a pseudoephedrine/antihistamine combination. We want to highlight the potential toxicity of pseudoephedrine, usually administered as part of cold-syrup preparations which are used for symptomatic treatment of upper respiratory tract cough and congestion associated with the common cold and allergic rhinitis. Although these products are generally considered to be safe either by physicians and parents, we can't underestimate the potential adverse events and toxic effects that can occur when administering these medications. PMID:15826569

  5. Screening for adverse events.

    PubMed

    Karson, A S; Bates, D W

    1999-02-01

    Adverse events (AEs) in medical patients are common, costly, and often preventable. Development of quality improvement programs to decrease the number and impact of AEs demands effective methods for screening for AEs on a routine basis. Here we describe the impact, types, and potential causes of AEs and review various techniques for identifying AEs. We evaluate the use of generic screening criteria in detail and describe a recent study of the sensitivity and specificity of individual generic screening criteria and combinations of these criteria. In general, the most sensitive screens were the least specific and no small sub-set of screens identified a large percentage of adverse events. Combinations of screens that were limited to administrative data were the least expensive, but none were particularly sensitive, although in practice they might be effective since routine screening is currently rarely done. As computer systems increase in sophistication sensitivity will improve. We also discuss recent studies that suggest that programs that screen for and identify AEs can be useful in reducing AE rates. While tools for identifying AEs have strengths and weaknesses, they can play an important role in organizations' quality improvement portfolios. PMID:10468381

  6. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421544

  7. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions. PMID:25458866

  8. Heart failure prognostic model.

    PubMed

    Axente, L; Sinescu, C; Bazacliu, G

    2011-05-15

    Heart failure (HF) is a common, costly, disabling and deadly syndrome. Heart failure is a progressive disease characterized by high prevalence in society, significantly reducing physical and mental health, frequent hospitalization and high mortality (50% of the patients survive up to 4 years after the diagnosis, the annual mortality varying from 5% to 75%). The purpose of this study is to develop a prognostic model with easily obtainable variables for patients with heart failure. METHODS AND RESULTS. Our lot included 101 non-consecutive hospitalized patients with heart failure diagnosis. It included 49.5% women having the average age of 71.23 years (starting from 40 up to 91 years old) and the roughly estimated period for monitoring was 35.1 months (5-65 months). Survival data were available for all patients and the median survival duration was of 44.0 months. A large number of variables (demographic, etiologic, co morbidity, clinical, echocardiograph, ECG, laboratory and medication) were evaluated. We performed a complex statistical analysis, studying: survival curve, cumulative hazard, hazard function, lifetime distribution and density function, meaning residual life time, Ln S (t) vs. t and Ln(H) t vs. Ln (t). The Cox multiple regression model was used in order to determine the major factors that allow the forecasting survival and their regression coefficients: age (0.0369), systolic blood pressure (-0.0219), potassium (0.0570), sex (-0.3124) and the acute myocardial infarction (0.2662). DISCUSSION. Our model easily incorporates obtainable variables that may be available in any hospital, accurately predicting survival of the heart failure patients and enables risk stratification in a few hours after the patients' presentation. Our model is derived from a sample of patients hospitalized in an emergency department of cardiology, some with major life-altering co morbidities. The benefit of being aware of the prognosis of these patients with high risk is extremely

  9. Heart failure prognostic model

    PubMed Central

    Axente, L; Sinescu, C; Bazacliu, G

    2011-01-01

    Heart failure (HF) is a common, costly, disabling and deadly syndrome. Heart failure is a progressive disease characterized by high prevalence in society, significantly reducing physical and mental health, frequent hospitalization and high mortality (50% of the patients survive up to 4 years after the diagnosis, the annual mortality varying from 5% to 75%). The purpose of this study is to develop a prognostic model with easily obtainable variables for patients with heart failure. Methods and Results. Our lot included 101 non–consecutive hospitalized patients with heart failure diagnosis. It included 49,5% women having the average age of 71.23 years (starting from 40 up to 91 years old) and the roughly estimated period for monitoring was 35.1 months (5–65 months). Survival data were available for all patients and the median survival duration was of 44.0 months. A large number of variables (demographic, etiologic, co morbidity, clinical, echocardiograph, ECG, laboratory and medication) were evaluated. We performed a complex statistical analysis, studying: survival curve, cumulative hazard, hazard function, lifetime distribution and density function, meaning residual life time, Ln S (t) vs. t and Ln(H) t vs. Ln (t). The Cox multiple regression model was used in order to determine the major factors that allow the forecasting survival and their regression coefficients: age (0.0369), systolic blood pressure (–0.0219), potassium (0.0570), sex (–0.3124) and the acute myocardial infarction (0.2662). Discussion. Our model easily incorporates obtainable variables that may be available in any hospital, accurately predicting survival of the heart failure patients and enables risk stratification in a few hours after the patients' presentation. Our model is derived from a sample of patients hospitalized in an emergency department of cardiology, some with major life–altering co morbidities. The benefit of being aware of the prognosis of these patients with high risk is

  10. The Glasgow Prognostic Score (GPS) as a novel and significant predictor of extranodal natural killer/T-cell lymphoma, nasal type.

    PubMed

    Li, Ya-Jun; Jiang, Wen-Qi; Huang, Jia-Jia; Xia, Zhong-Jun; Huang, Hui-Qiang; Li, Zhi-Ming

    2013-05-01

    The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score including C-reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T-cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T-cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more 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 high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low-risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL. PMID:23423859

  11. 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.

  12. Prognostic Significance of Tumor Hypoxia Inducible Factor-1{alpha} Expression for Outcome After Radiotherapy in Oropharyngeal Cancer

    SciTech Connect

    Silva, Priyamal; Slevin, Nick J.; Sloan, Philip; Valentine, Helen; Cresswell, Jo; Ryder, David; Price, Patricia; Homer, Jarrod J.; West, Catharine

    2008-12-01

    Purpose: Head-and-neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of patients in terms of subsite, treatment, and biology. Currently most management decisions are based on clinical parameters with little appreciation of patient differences in underlying tumor biology. We investigated the prognostic significance of clinicopathologic features and tumor hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) expression in a homogeneous series of patients who underwent radiotherapy. Methods and Materials: An audit identified 133 consecutive patients with histologically proven squamous cell carcinoma of the tonsil or tongue base. All patients received primary radiotherapy between 1996 and 2001. Tumor HIF-1{alpha} expression was examined in 79 patients. Results: Features associated with poor locoregional control were low Hb level (p = 0.05) and advancing T (p = 0.008), N (p = 0.03), and disease (p = 0.008) stage. HIF-1{alpha} expression was a more significant adverse prognostic factor in the tonsil (hazard ratio [HR], 23.1; 95% confidence interval [CI]. 3.04-176.7) than the tongue-base tumor (HR, 2.86; 95% CI, 1.14-7.19) group (p = 0.03, test for interaction). High tumor HIF-1{alpha} expression was associated with low blood Hb levels (p = 0.03). In a multivariate analysis HIF-1{alpha} expression retained prognostic significance for locoregional control (HR, 7.10; 95% CI, 3.07-16.43) and cancer-specific survival (HR, 9.19; 95% CI, 3.90-21.6). Conclusions: There are significant differences in radiation therapy outcome within a homogeneous subsite of the oropharynx related to molecular marker expression. The work highlights the importance of studying homogeneous groups of patients in HNSCC, and the complex interrelationships between tumor biology and clinicopathologic factors. The establishment of tumor-type specific markers would represent a major advance in this area.

  13. Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders

    PubMed Central

    Chang, I-Wei; Li, Chien-Feng; Lin, Victor Chia-Hsiang; He, Hong-Lin; Liang, Per-In; Wu, Wen-Jeng; Li, Ching-Chia; Huang, Chun-Nung

    2016-01-01

    Purpose: Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By data mining a published dataset of UC of bladder (UCB) transcriptome (GSE31684) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that THBS2 was the most significantly upregulated gene among those related to structural molecule activity (GO:0005198). Therefore, we evaluated the clinical significance and prognostic impact of thrombospondin-2 (THBS2) protein, A.K.A. TSP2, which encoded by THBS2 gene. Materials and Methods: THBS2 immunostaining was performed in 340 UCs of upper urinary tract (UC-UUTs) and 295 UCBs; subsequently, both groups were dichotomized into high- and low-expression subgroups. Moreover, statistical analyses were performed to correlate the association between THBS2 expression and clinicopathological parameters with two survival indexes: disease-specific survival (DSS) and metastasis-free survival (MeFS). Results: High THBS2 immunoexpression was significantly associated with advanced primary tumor status, nodal metastasis, and vascular invasion in both UC-UUT and UCB groups (all P ≤ .001). In addition, THBS2 overexpression was linked to adverse DSS and MeFS in univariate analyses and served as an independent prognosticator indicating poor outcomes in both groups in multivariate analyses. Conclusion: THBS2 may play a crucial role in UC progression and may be a novel prognostic marker. Additional investigations to elucidate the molecular pathway are necessary for developing potential THBS2-targeted therapies for UCs. PMID:27471570

  14. Lipoprotein lipase expression is a novel prognostic factor in B-cell chronic lymphocytic leukemia.

    PubMed

    Nückel, Holger; Hüttmann, Andreas; Klein-Hitpass, Ludger; Schroers, Roland; Führer, Anja; Sellmann, Ludger; Dührsen, Ulrich; Dürig, Jan

    2006-06-01

    B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course. Recent studies have shown that expression of lipoprotein lipase (LPL) and ADAM29 may serve as novel prognostic markers in B-CLL. To investigate the prognostic value of these genes, we quantified their expression in peripheral blood mononuclear cells using quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) in a cohort of 133 B-CLL patients and correlated the results with clinical outcome, and other known prognostic factors. LPL, ADAM29, LPL and ADAM29 ratios, as well as CD38 and ZAP-70 protein expression determined by multiparameter flow cytometry, were predictive of treatment-free survival. Multivariate Cox regression analysis identified LPL, ADAM29 and CD38 as independent prognostic markers. Evaluation of several disease characteristics in association with the LPL expression status of the patients' B-CLL cells showed highly significant differences for CD38 and ZAP-70 expression, suggesting a correlation of LPL expression with these established adverse prognostic factors. Sequential RQ-PCR analyses in a subset of 22 patients revealed that LPL mRNA expression was relatively stable in the majority of patients, whereas ADAM29 expression levels varied substantially over time. Furthermore, in a subgroup analysis, LPL provided prognostic information in both early stage (Binet A) and patients with more advanced disease (Binet B and C). Conversely, high ADAM29 expression was predictive of a long treatment-free interval in Binet stage A but did not retain its prognostic significance in Binet B and C patients. The LPL/ADAM29 expression ratio was not found to be an independent prognostic factor and did not offer any advantages over the use of LPL alone. Collectively, our data confirm a role for LPL as a novel prognostic indicator in B-CLL. PMID:16840197

  15. Particle filter based hybrid prognostics for health monitoring of uncertain systems in bond graph framework

    NASA Astrophysics Data System (ADS)

    Jha, Mayank Shekhar; Dauphin-Tanguy, G.; Ould-Bouamama, B.

    2016-06-01

    The paper's main objective is to address the problem of health monitoring of system parameters in Bond Graph (BG) modeling framework, by exploiting its structural and causal properties. The system in feedback control loop is considered uncertain globally. Parametric uncertainty is modeled in interval form. The system parameter is undergoing degradation (prognostic candidate) and its degradation model is assumed to be known a priori. The detection of degradation commencement is done in a passive manner which involves interval valued robust adaptive thresholds over the nominal part of the uncertain BG-derived interval valued analytical redundancy relations (I-ARRs). The latter forms an efficient diagnostic module. The prognostics problem is cast as joint state-parameter estimation problem, a hybrid prognostic approach, wherein the fault model is constructed by considering the statistical degradation model of the system parameter (prognostic candidate). The observation equation is constructed from nominal part of the I-ARR. Using particle filter (PF) algorithms; the estimation of state of health (state of prognostic candidate) and associated hidden time-varying degradation progression parameters is achieved in probabilistic terms. A simplified variance adaptation scheme is proposed. Associated uncertainties which arise out of noisy measurements, parametric degradation process, environmental conditions etc. are effectively managed by PF. This allows the production of effective predictions of the remaining useful life of the prognostic candidate with suitable confidence bounds. The effectiveness of the novel methodology is demonstrated through simulations and experiments on a mechatronic system.

  16. Multiple Damage Progression Paths in Model-Based Prognostics

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew; Goebel, Kai Frank

    2011-01-01

    Model-based prognostics approaches employ domain knowledge about a system, its components, and how they fail through the use of physics-based models. Component wear is driven by several different degradation phenomena, each resulting in their own damage progression path, overlapping to contribute to the overall degradation of the component. We develop a model-based prognostics methodology using particle filters, in which the problem of characterizing multiple damage progression paths is cast as a joint state-parameter estimation problem. The estimate is represented as a probability distribution, allowing the prediction of end of life and remaining useful life within a probabilistic framework that supports uncertainty management. We also develop a novel variance control mechanism that maintains an uncertainty bound around the hidden parameters to limit the amount of estimation uncertainty and, consequently, reduce prediction uncertainty. We construct a detailed physics-based model of a centrifugal pump, to which we apply our model-based prognostics algorithms. We illustrate the operation of the prognostic solution with a number of simulation-based experiments and demonstrate the performance of the chosen approach when multiple damage mechanisms are active

  17. Raman Spectroscopic Measurements of Dermal Carotenoids in Breast Cancer Operated Patients Provide Evidence for the Positive Impact of a Dietary Regimen Rich in Fruit and Vegetables on Body Oxidative Stress and BC Prognostic Anthropometric Parameters: A Five-Year Study

    PubMed Central

    Perrone, A.; Pintaudi, A. M.; Traina, A.; Carruba, G.; Attanzio, A.; Gentile, C.; Tesoriere, L.; Livrea, M. A.

    2016-01-01

    Dermal carotenoids are a feasible marker of the body antioxidative network and may reveal a moderate to severe imbalance of the redox status, thereby providing indication of individual oxidative stress. In this work noninvasive Resonance Raman Spectroscopy (RRS) measurements of skin carotenoids (skin carotenoid score (SCS)) were used to provide indications of individual oxidative stress, each year for five years, in 71 breast cancer (BC) patients at high risk of recurrence. Patients' SCS has been correlated with parameters relevant to BC risk, waist circumference (WC), and body mass index (BMI), in the aim of monitoring the effect of a dietary regimen intended to positively affect BC risk factors. The RRS methodological approach in BC patients appeared from positive correlation between patients' SCS and blood level of lycopene. The level of skin carotenoids was inversely correlated with the patients' WC and BMI. At the end of the 5 y observation BC patients exhibited a significant reduction of WC and BMI and increase of SCS, when strictly adhering to the dietary regimen. In conclusion, noninvasive measurements of skin carotenoids can (i) reveal an oxidative stress condition correlated with parameters of BC risk and (ii) monitor dietary-related variations in BC patients. PMID:27213029

  18. Raman Spectroscopic Measurements of Dermal Carotenoids in Breast Cancer Operated Patients Provide Evidence for the Positive Impact of a Dietary Regimen Rich in Fruit and Vegetables on Body Oxidative Stress and BC Prognostic Anthropometric Parameters: A Five-Year Study.

    PubMed

    Perrone, A; Pintaudi, A M; Traina, A; Carruba, G; Attanzio, A; Gentile, C; Tesoriere, L; Livrea, M A

    2016-01-01

    Dermal carotenoids are a feasible marker of the body antioxidative network and may reveal a moderate to severe imbalance of the redox status, thereby providing indication of individual oxidative stress. In this work noninvasive Resonance Raman Spectroscopy (RRS) measurements of skin carotenoids (skin carotenoid score (SCS)) were used to provide indications of individual oxidative stress, each year for five years, in 71 breast cancer (BC) patients at high risk of recurrence. Patients' SCS has been correlated with parameters relevant to BC risk, waist circumference (WC), and body mass index (BMI), in the aim of monitoring the effect of a dietary regimen intended to positively affect BC risk factors. The RRS methodological approach in BC patients appeared from positive correlation between patients' SCS and blood level of lycopene. The level of skin carotenoids was inversely correlated with the patients' WC and BMI. At the end of the 5 y observation BC patients exhibited a significant reduction of WC and BMI and increase of SCS, when strictly adhering to the dietary regimen. In conclusion, noninvasive measurements of skin carotenoids can (i) reveal an oxidative stress condition correlated with parameters of BC risk and (ii) monitor dietary-related variations in BC patients. PMID:27213029

  19. Adverse antibiotic drug interactions.

    PubMed

    Bint, A J; Burtt, I

    1980-07-01

    There is enormous potential for drug interactions in patients who, today, often receive many drugs. Antibiotics are prominent amongst the groups of drugs commonly prescribed. Many interactions take place at the absorption stage. Antacids and antidiarrhoeal preparations, in particular, can delay and reduce the absorption of antibiotics such as tetracyclines and clindamycin, by combining with them in the gastrointestinal tract to form chelates or complexes. Other drugs can affect gastric motility, which in turn often controls the rate at which antibiotics are absorbed. Some broad spectrum antibiotics can alter the bacterial flora of the gut which may be related to malabsorption states. The potentiation of toxic side effects of one drug by another is a common type of interaction. Antibiotics which are implicated in this type of interaction are those which themselves possess some toxicity such as aminoglycosides, some cephalosporins, tetracyclines and colistin. Some of the most important adverse interactions with antibiotics are those which involve other drugs which have a low toxicity/efficacy ratio. These include anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbitone and oral antidiabetic drugs like tolbutamide. Risk of interaction arises when the metabolism of these drugs is inhibited by liver microsomal enzyme inhibitors such as some sulphonamides and chloramphenicol, or is enhanced by enzyme inducers such as rifampicin. PMID:6995091

  20. ADVERSE CUTANEOUS DRUG REACTION

    PubMed Central

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR. PMID:19967009

  1. Prognostic and Clinicopathological Value of Programmed Death Ligand-1 in Breast Cancer: A Meta-Analysis

    PubMed Central

    Liu, Zeming; Maimaiti, Yusufu; Wang, Shan; Yin, Xingjie; Liu, Chunping

    2016-01-01

    Recently, the interest in programmed death ligand-1 (PD-L1) as a prognostic marker in several types of malignant tumors has increased. In the present meta-analysis, we aimed to explore the prognostic and clinicopathological value of PD-L1 in breast cancer. We searched Medline/PubMed, Web of Science, EMBASE, the Cochrane Library databases, and grey literature from inception until January 20, 2016. Studies concerning breast cancer that focused on PD-L1 expression and studies reporting survival data were included; two authors independently performed the data extraction. The pooled risk ratio (RR) and 95% confidence interval (CI) were assessed to determine the association between the clinicopathological parameters of patients and PD-L1 expression. Five studies involving 2061 patients were included in this meta-analysis. The results indicated that positive/higher PD-L1 expression was a negative predictor for breast cancer, with an RR of 1.64 (95% CI, 1.14–2.34) for the total mortality risk and an RR of 2.53 (95% CI, 1.78–3.59) for the mortality risk 10 years after surgery. Moreover, positive/higher PD-L1 expression was significantly associated with positive lymph node metastasis (RR, 1.33; 95% CI, 1.04–1.70), poor nuclear grade (RR, 1.24; 95% CI, 1.07–1.43), and negative estrogen receptor status (RR, 2.45; 95% CI, 1.31–4.60) in breast cancer patients. Our findings suggest that PD-L1 can serve as a significant biomarker for poor prognosis and the adverse clinicopathologic features of breast cancer and could facilitate the better management of individual patients. PMID:27227453

  2. Prognostic features and therapeutical approaches in B-cell chronic lymphocytic leukemia: an update.

    PubMed

    Molica, S; De Rossi, G; Luciani, M; Levato, D

    1995-01-01

    In the past few decades important progress has been made in the understanding of chronic lymphocytic leukemia (CLL). Indeed, systematic studies of natural history and prognostic factors have made it possible to predict the outcome of disease. Although clinical stage (i.e. Rai and Binet stages) is the strongest predictor of survival, additional prognostic parameters, including patterns of bone marrow (BM) infiltration, lymphocyte doubling time (LDT), immunophenotype and cytogenetics, have now been identified. Furthermore, criteria of smoldering CLL (i.e. stage A, low lymphocyte count, non-diffuse BM histology, relatively high hemoglobin level, LDT > 12 months) allow identification of a subgroup of patients with indolent course and good prognosis for whom treatment should be delayed, unless progression occurs. Recent meta-analysis of clinical trials has demonstrated no survival advantage for immediate versus referred treatment in low clinical stages. The same considerations apply when comparing combination versus single-drug regimens. Purine analogues like fludarabine, 2'-chlorodeoxyadenosine and 2'-deoxycoformicin are active in CLL. Data on these drugs come from uncontrolled clinical trials; randomized studies are in progress. In addition, some issues concerning the relationship between response and survival, cross-resistance between purine analogues and eradication of the CLL clone, remain still unresolved. There are also increasing data on bone marrow transplants in CLL, although the high treatment-related mortality suggests that this procedure may have some benefit only in selected refractory young CLL patients with adverse features. This review will focus on recent progress in the prognosis and therapy of CLL. Issues that remain controversial will be a matter of discussion. PMID:7628755

  3. 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

  4. 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

  5. Prognostic biomarkers in acute coronary syndrome.

    PubMed

    Salvagno, Gian Luca; Pavan, Chiara

    2016-07-01

    The acute coronary syndrome (ACS) is a leading cause of death around the globe. Beside a still high mortality rate, additional complications of ACS include arrhythmias, left ventricular mural thrombus, cardiac fibrosis, heart failure (HF), cardiogenic shock, mitral valve dysfunction, aneurysms, up to cardiac rupture. Despite many prognostic tools have been developed over the past decades, efforts are still ongoing to identify reliable and predictive biomarkers, which may help predict the prognosis of these patients and especially the risk of HF. Recent evidence suggests that the value of a discrete number of biomarkers of myocardial fibrosis, namely the soluble form of suppression of tumorigenicity 2 (sST2) and galectin-3 (GAL-3), may be predictive of HF and death in patients with ACS. Interestingly, the already promising predictive value of these biomarkers when measured alone was shown to be consistently magnified when combined with other and well-established cardiac biomarkers such natriuretic peptides and cardiac troponins. This article is hence aimed to review the current knowledge about cardiac biomarkers of fibrosis and adverse remodeling. PMID:27500159

  6. Prognostic biomarkers in acute coronary syndrome

    PubMed Central

    Pavan, Chiara

    2016-01-01

    The acute coronary syndrome (ACS) is a leading cause of death around the globe. Beside a still high mortality rate, additional complications of ACS include arrhythmias, left ventricular mural thrombus, cardiac fibrosis, heart failure (HF), cardiogenic shock, mitral valve dysfunction, aneurysms, up to cardiac rupture. Despite many prognostic tools have been developed over the past decades, efforts are still ongoing to identify reliable and predictive biomarkers, which may help predict the prognosis of these patients and especially the risk of HF. Recent evidence suggests that the value of a discrete number of biomarkers of myocardial fibrosis, namely the soluble form of suppression of tumorigenicity 2 (sST2) and galectin-3 (GAL-3), may be predictive of HF and death in patients with ACS. Interestingly, the already promising predictive value of these biomarkers when measured alone was shown to be consistently magnified when combined with other and well-established cardiac biomarkers such natriuretic peptides and cardiac troponins. This article is hence aimed to review the current knowledge about cardiac biomarkers of fibrosis and adverse remodeling. PMID:27500159

  7. Sensor Systems for Prognostics and Health Management

    PubMed Central

    Cheng, Shunfeng; Azarian, Michael H.; Pecht, Michael G.

    2010-01-01

    Prognostics and health management (PHM) is an enabling discipline consisting of technologies and methods to assess the reliability of a product in its actual life cycle conditions to determine the advent of failure and mitigate system risk. Sensor systems are needed for PHM to monitor environmental, operational, and performance-related characteristics. The gathered data can be analyzed to assess product health and predict remaining life. In this paper, the considerations for sensor system selection for PHM applications, including the parameters to be measured, the performance needs, the electrical and physical attributes, reliability, and cost of the sensor system, are discussed. The state-of-the-art sensor systems for PHM and the emerging trends in technologies of sensor systems for PHM are presented. PMID:22219686

  8. 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

  9. Vehicle Integrated Prognostic Reasoner (VIPR) 2010 Annual Final Report

    NASA Technical Reports Server (NTRS)

    Hadden, George D.; Mylaraswamy, Dinkar; Schimmel, Craig; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

    2011-01-01

    Honeywell's Central Maintenance Computer Function (CMCF) and Aircraft Condition Monitoring Function (ACMF) represent the state-of-the art in integrated vehicle health management (IVHM). Underlying these technologies is a fault propagation modeling system that provides nose-to-tail coverage and root cause diagnostics. The Vehicle Integrated Prognostic Reasoner (VIPR) extends this technology to interpret evidence generated by advanced diagnostic and prognostic monitors provided by component suppliers to detect, isolate, and predict adverse events that affect flight safety. This report describes year one work that included defining the architecture and communication protocols and establishing the user requirements for such a system. Based on these and a set of ConOps scenarios, we designed and implemented a demonstration of communication pathways and associated three-tiered health management architecture. A series of scripted scenarios showed how VIPR would detect adverse events before they escalate as safety incidents through a combination of advanced reasoning and additional aircraft data collected from an aircraft condition monitoring system. Demonstrating VIPR capability for cases recorded in the ASIAS database and cross linking them with historical aircraft data is planned for year two.

  10. Prognostic Value of Protease Activated Receptor-1 in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Hagag, Adel A.; Nosair, Nahla A.; Ghaith, Fatma M.; Elshenawy, Eman H.

    2014-01-01

    Background Acute Lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that proliferate and replace the normal hematopoietic cells of the bone marrow. Protease-activated receptors (PARs) comprise a family of trans-membrane G-protein coupled receptors. Protease-activated receptor 1 (PAR-1) is a typical member of this family of receptors that mediate cellular responses to thrombin and related proteases. PAR1 is expressed by a wide range of tumor cells and can promote tumor growth, invasion and metastasis. The aim of this work was to study the role of PAR-1 expression in newly diagnosed ALL patients. Patients and methods This study was conducted on 44 children with newly diagnosed ALL who were admitted to Hematology Unit, Pediatric department, Tanta University Hospital including 24 males and 20 females with their age ranged from 4–17 years and their mean age value of 9.06±3.26. All patients were subjected to complete history taking, thorough clinical examination, bone marrow aspiration and flow cytometric analysis for detection of PAR-1 expression by malignant cells. Results PAR-1 was positive in 18 cases (41%) and negative in 26 cases (59%) of studied patients. This study showed no significant relation between PAR-1 expression and age, sex and most of the clinical data including hepatomegaly, splenomegaly and purpura while generalized lymphadenopathy was significantly higher in PAR-1 positive group. PAR-1 positive expression was associated with some bad prognostic laboratory parameters including higher hemoglobin, higher white blood cells, higher peripheral blood and bone marrow blast cells, higher serum LDH and lower platelets count. No significant association was detected between PAR-1 expression and immunophenotyping. There were significantly higher remission rates in PAR-1 negative group and significantly higher relapse and death rates in PAR-1 positive group. Conclusion From this study, it could be concluded that PAR-1 expression

  11. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  12. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence. PMID:23850228

  13. Prognostics of Power Electronics, Methods and Validation Experiments

    NASA Technical Reports Server (NTRS)

    Kulkarni, Chetan S.; Celaya, Jose R.; Biswas, Gautam; Goebel, Kai

    2012-01-01

    Abstract Failure of electronic devices is a concern for future electric aircrafts that will see an increase of electronics to drive and control safety-critical equipment throughout the aircraft. As a result, investigation of precursors to failure in electronics and prediction of remaining life of electronic components is of key importance. DC-DC power converters are power electronics systems employed typically as sourcing elements for avionics equipment. Current research efforts in prognostics for these power systems focuses on the identification of failure mechanisms and the development of accelerated aging methodologies and systems to accelerate the aging process of test devices, while continuously measuring key electrical and thermal parameters. Preliminary model-based prognostics algorithms have been developed making use of empirical degradation models and physics-inspired degradation model with focus on key components like electrolytic capacitors and power MOSFETs (metal-oxide-semiconductor-field-effect-transistor). This paper presents current results on the development of validation methods for prognostics algorithms of power electrolytic capacitors. Particularly, in the use of accelerated aging systems for algorithm validation. Validation of prognostics algorithms present difficulties in practice due to the lack of run-to-failure experiments in deployed systems. By using accelerated experiments, we circumvent this problem in order to define initial validation activities.

  14. Prognostics for Ground Support Systems: Case Study on Pneumatic Valves

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew; Goebel, Kai

    2011-01-01

    Prognostics technologies determine the health (or damage) state of a component or sub-system, and make end of life (EOL) and remaining useful life (RUL) predictions. Such information enables system operators to make informed maintenance decisions and streamline operational and mission-level activities. We develop a model-based prognostics methodology for pneumatic valves used in ground support equipment for cryogenic propellant loading operations. These valves are used to control the flow of propellant, so failures may have a significant impact on launch availability. Therefore, correctly predicting when valves will fail enables timely maintenance that avoids launch delays and aborts. The approach utilizes mathematical models describing the underlying physics of valve degradation, and, employing the particle filtering algorithm for joint state-parameter estimation, determines the health state of the valve and the rate of damage progression, from which EOL and RUL predictions are made. We develop a prototype user interface for valve prognostics, and demonstrate the prognostics approach using historical pneumatic valve data from the Space Shuttle refueling system.

  15. Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients

    PubMed Central

    Pilanci, Kezban N.; Avcı, Nilüfer; Yıldız, İbrahim; Alço, Gül; Demirhan, Özkan; Köksal, Ülkühan I.; Elbüken, Filiz; Tecimer, Coskun; Demir, Gökhan

    2016-01-01

    Aim of the study Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12–61) and 19 months (5–45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. Conclusions As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients. PMID:27358594

  16. Towards Prognostics for Electronics Components

    NASA Technical Reports Server (NTRS)

    Saha, Bhaskar; Celaya, Jose R.; Wysocki, Philip F.; Goebel, Kai F.

    2013-01-01

    Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is becoming a very important research field as a result of the need to provide aircraft systems with system level health management information. This paper focuses on a prognostics application for electronics components within avionics systems, and in particular its application to an Isolated Gate Bipolar Transistor (IGBT). This application utilizes the remaining useful life prediction, accomplished by employing the particle filter framework, leveraging data from accelerated aging tests on IGBTs. These tests induced thermal-electrical overstresses by applying thermal cycling to the IGBT devices. In-situ state monitoring, including measurements of steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

  17. Neurological prognostication after cardiac arrest

    PubMed Central

    Sandroni, Claudio; Geocadin, Romergryko G.

    2016-01-01

    Purpose of review Prediction of neurological prognosis in patients who are comatose after successful resuscitation from cardiac arrest remains difficult. Previous guidelines recommended ocular reflexes, somatosensory evoked potentials and serum biomarkers for predicting poor outcome within 72h from cardiac arrest. However, these guidelines were based on patients not treated with targeted temperature management and did not appropriately address important biases in literature. Recent findings Recent evidence reviews detected important limitations in prognostication studies, such as low precision and, most importantly, lack of blinding, which may have caused a self-fulfilling prophecy and overestimated the specificity of index tests. Maintenance of targeted temperature using sedatives and muscle relaxants may interfere with clinical examination, making assessment of neurological status before 72 h or more after cardiac arrest unreliable. Summary No index predicts poor neurological outcome after cardiac arrest with absolute certainty. Prognostic evaluation should start not earlier than 72 h after ROSC and only after major confounders have been excluded so that reliable clinical examination can be made. Multimodality appears to be the most reasonable approach for prognostication after cardiac arrest. PMID:25922894

  18. Prognostic factors and treatment results of pediatric Hodgkin's lymphoma: A single center experience.

    PubMed

    Büyükkapu-Bay, Sema; Çorapçıoğlu, Funda; Aksu, Görkem; Anık, Yonca; Demir, Hakan; Erçin, Cengiz

    2015-01-01

    The aim of this study was to assess the demographic, clinic data, prognostic factors and treatment/follow-up results of children who were diagnosed with Hodgkin lymphoma and followed in our center of Pediatric Oncology, Kocaeli University Medical Faculty, Kocaeli, Turkey, for 10 years. This retrospective study evaluated 41 patients with Hodgkin lymphoma who were younger than 18 years-old. All patients were treated with risked adapted ABVD (Adriamycin, Bleomycin, Vincristine, Dacarbazine) chemotherapy and also received involved field radiotherapy. Thirty-two patients (78%) were males and 9 (22%) were females, with a mean age of 10.7±4.0 years. The histopathological diagnosis was mixed cellular type in 51.2% of the patients. B symptoms (unexplained fever, unexplained weight loss, drenching night sweats) were present in 53.7% of the patients and 36.6% of the patients were at advanced stage at the time of the diagnosis. The 3-year overall and event-free survival rates were 88% and 5-year overall and event-free survival rates were 88%, 78%. Age, stage, treatment risk groups, presence of B symptoms and hematological parameters had no significant effect on overall and event-free survival in univariate analysis while bulky disease was the only significant factor on overall survival. Our treatment policy was succesful regarding the similar survival rates in the treatment risk groups, however novel treatment strategies adopting the early response with the reduction of adverse effects are planned in the near future. PMID:27186698

  19. Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications

    PubMed Central

    2013-01-01

    Background Cancer–testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors. Methods The reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival. Results Expression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively). Conclusions Our findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies. PMID:23731661

  20. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction.

    PubMed

    Liao, Wen-I; Lin, Chin-Sheng; Lee, Chien-Hsing; Wu, Ya-Chieh; Chang, Wei-Chou; Hsu, Chin-Wang; Wang, Jen-Chun; Tsai, Shih-Hung

    2016-01-01

    Acute hyperglycemia is a frequent finding in patients presenting to the emergency department (ED) with acute myocardial infarction (AMI). The prognostic role of hyperglycemia in diabetic patients with AMI remains controversial. We retrospectively reviewed patients' medical records to obtain demographic data, clinical presentation, major adverse cardiac events (MACEs), several clinical scores and laboratory data, including the plasma glucose level at initial presentation and HbA1c levels. The glycemic gap, which represents changes in serum glucose levels during the index event, was calculated from the glucose level upon ED admission minus the HbA1c-derived average glucose (ADAG). We enrolled 331 patients after the review of medical records. An elevated glycemic gap between admission serum glucose levels and ADAG were associated with an increased risk of mortality in patients. The glycemic gap showed superior discriminative power regarding the development of MACEs when compared with the admission glucose level. The calculation of the glycemic gap may increase the discriminative powers of established clinical scoring systems in diabetic patients presenting to the ED with AMI. In conclusion, the glycemic gap could be used as an adjunct parameter to assess the severity and prognosis of diabetic patients presenting with AMI. However, the usefulness of the glycemic gap should be further explored in prospective longitudinal studies. PMID:27291987

  1. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction

    PubMed Central

    Liao, Wen-I; Lin, Chin-Sheng; Lee, Chien-Hsing; Wu, Ya-Chieh; Chang, Wei-Chou; Hsu, Chin-Wang; Wang, Jen-Chun; Tsai, Shih-Hung

    2016-01-01

    Acute hyperglycemia is a frequent finding in patients presenting to the emergency department (ED) with acute myocardial infarction (AMI). The prognostic role of hyperglycemia in diabetic patients with AMI remains controversial. We retrospectively reviewed patients’ medical records to obtain demographic data, clinical presentation, major adverse cardiac events (MACEs), several clinical scores and laboratory data, including the plasma glucose level at initial presentation and HbA1c levels. The glycemic gap, which represents changes in serum glucose levels during the index event, was calculated from the glucose level upon ED admission minus the HbA1c-derived average glucose (ADAG). We enrolled 331 patients after the review of medical records. An elevated glycemic gap between admission serum glucose levels and ADAG were associated with an increased risk of mortality in patients. The glycemic gap showed superior discriminative power regarding the development of MACEs when compared with the admission glucose level. The calculation of the glycemic gap may increase the discriminative powers of established clinical scoring systems in diabetic patients presenting to the ED with AMI. In conclusion, the glycemic gap could be used as an adjunct parameter to assess the severity and prognosis of diabetic patients presenting with AMI. However, the usefulness of the glycemic gap should be further explored in prospective longitudinal studies. PMID:27291987

  2. Dectin-1 predicts adverse postoperative prognosis of patients with clear cell renal cell carcinoma.

    PubMed

    Xia, Yu; Liu, Li; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

    2016-01-01

    Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P < 0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients' survival together with other clinical parameters (P < 0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients' RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P < 0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments. PMID:27600310

  3. Dectin-1 predicts adverse postoperative prognosis of patients with clear cell renal cell carcinoma

    PubMed Central

    Xia, Yu; Liu, Li; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

    2016-01-01

    Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P < 0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients’ survival together with other clinical parameters (P < 0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients’ RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P < 0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments. PMID:27600310

  4. Minimally invasive follicular thyroid carcinomas: prognostic factors.

    PubMed

    Stenson, Gustav; Nilsson, Inga-Lena; Mu, Ninni; Larsson, Catharina; Lundgren, Catharina Ihre; Juhlin, C Christofer; Höög, Anders; Zedenius, Jan

    2016-08-01

    Although minimally invasive follicular thyroid carcinoma (MI-FTC) is regarded as an indolent tumour, treatment strategies remain controversial. Our aim was to investigate the outcome for patients with MI-FTC and to identify prognostic parameters to facilitate adequate treatment and follow-up. This retrospective follow-up study involved all cases of MI-FTC operated at the Karolinska University Hospital between 1986 and 2009. Outcome was analysed using death from MI-FTC as endpoint. Fifty-eight patients (41 women and 17 men) with MI-FTC were identified. The median follow-up time was 140 (range 21-308) months. Vascular invasion was observed in 36 cases and was associated with larger tumour size [median 40 (20-76) compared with 24 (10-80) mm for patients with capsular invasion only (P = 0.001)] and older patients [54 (20-92) vs. 44 (11-77) years; P = 0.019]. Patients with vascular invasion were more often treated with thyroidectomy (21/36 compared to 7/22 with capsular invasion only; P = 0.045). Five patients died from metastatic disease of FTC after a median follow-up of 114 (range 41-193) months; all were older than 50 years (51-72) at the time of the initial surgery; vascular invasion was present in all tumours and all but one were treated with thyroidectomy. Univariate analysis identified combined capsular and vascular invasion (P = 0.034), age at surgery ≥50 years (P = 0.023) and male gender (P = 0.005) as related to risk of death from MI-FTC. MI-FTC should not be considered a purely indolent disease. Age at diagnosis and the existence of combined capsular and vascular invasion were identified as important prognostic factors. PMID:26858184

  5. Accelerated Aging in Electrolytic Capacitors for Prognostics

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Kulkarni, Chetan; Saha, Sankalita; Biswas, Gautam; Goebel, Kai Frank

    2012-01-01

    The focus of this work is the analysis of different degradation phenomena based on thermal overstress and electrical overstress accelerated aging systems and the use of accelerated aging techniques for prognostics algorithm development. Results on thermal overstress and electrical overstress experiments are presented. In addition, preliminary results toward the development of physics-based degradation models are presented focusing on the electrolyte evaporation failure mechanism. An empirical degradation model based on percentage capacitance loss under electrical overstress is presented and used in: (i) a Bayesian-based implementation of model-based prognostics using a discrete Kalman filter for health state estimation, and (ii) a dynamic system representation of the degradation model for forecasting and remaining useful life (RUL) estimation. A leave-one-out validation methodology is used to assess the validity of the methodology under the small sample size constrain. The results observed on the RUL estimation are consistent through the validation tests comparing relative accuracy and prediction error. It has been observed that the inaccuracy of the model to represent the change in degradation behavior observed at the end of the test data is consistent throughout the validation tests, indicating the need of a more detailed degradation model or the use of an algorithm that could estimate model parameters on-line. Based on the observed degradation process under different stress intensity with rest periods, the need for more sophisticated degradation models is further supported. The current degradation model does not represent the capacitance recovery over rest periods following an accelerated aging stress period.

  6. Adverse possession of subsurface minerals

    SciTech Connect

    Bowles, P.N.

    1983-01-01

    Concepts applicable to adverse possession of subsurface minerals are generally the same as those that apply to adverse possession of all real estate. However, special requirements must be satisfied in order to perfect title to subsurface minerals by adverse possession, particularly when there has been a severance of the true title between surface and subsurface minerals. In those jurisdictions where senior and junior grants came from the state or commonwealth covering the same or some of the same land and in those areas where descriptions of land were vague or not carefully drawn, adverse possession serves to solidify land and mineral ownership. There may be some public, social, and economic justification in rewarding, with good title, those who take possession and use real estate for its intended use, including the extraction of subsurface minerals. 96 refernces.

  7. Clinical features, outcome and prognostic factors of 87 patients with angioimmunoblastic T cell lymphoma in Taiwan.

    PubMed

    Kao, Hsiao-Wen; Lin, Tung-Liang; Shih, Lee-Yung; Dunn, Po; Kuo, Ming-Chung; Hung, Yu-Shin; Wu, Jin-Hou; Tang, Tzung-Chih; Chang, Hung; Kuo, Tseng-Tong; Ou, Che-Wei; Wang, Po-Nan

    2016-08-01

    We retrospectively analyzed 87 patients with angioimmunoblastic T cell lymphoma (AITL) in Taiwan. The median age was 68 (range 18-89) years. Of these patients, 74 % was at an advanced stage. The most common extra-nodal site involved was bone marrow (36 %). Of these patients, 77 % were International Prognostic Index (IPI) >1 and 79 % had a prognostic index for peripheral T-cell lymphoma (PIT) >1. Of 75 patients who received systemic chemotherapy, the complete remission rate was 60 %, the relapse rate was 47 %, and the 2-year progression-free survival rate was 37.4 %. The 2-year overall survival (OS) rate for all patients was 51.9 %. By multivariate analysis, bone marrow involvement (P < 0.001) and ECOG >1 (P = 0.007) were independent adverse factors for OS. A simplified prognostic index efficiently stratified patients into the following three groups: 2-year OS rates 79.8 % (0 factor), 28.3 % (1 factor), and 10.2 % (2 factors) by using bone marrow involvement and ECOG >1 (P < 0.001). In conclusion, AITL patients were older and had poorer prognosis in Taiwan. Bone marrow involvement, EOCG >1, IPI >1 and PIT >1 had adverse impact on OS. The usefulness of this simplified prognostic index needs further validation. PMID:27095042

  8. 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.

  9. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  10. Prognostic value of procalcitonin in hospitalized patients with lower respiratory tract infections

    PubMed Central

    Nobre, Vandack; Borges, Isabela

    2016-01-01

    Lower respiratory tract infections are common and potentially lethal conditions and are a major cause of inadequate antibiotic prescriptions. Characterization of disease severity and prognostic prediction in affected patients can aid disease management and can increase accuracy in determining the need for and place of hospitalization. The inclusion of biomarkers, particularly procalcitonin, in the decision taken process is a promising strategy. This study aims to present a narrative review of the potential applications and limitations of procalcitonin as a prognostic marker in hospitalized patients with lower respiratory tract infections. The studies on this topic are heterogeneous with respect to procalcitonin measurement techniques, cutoff values, clinical settings, and disease severity. The results show that procalcitonin delivers moderate performance for prognostic prediction in patients with lower respiratory tract infections; its predictive performance was not higher than that of classical methods, and knowledge of procalcitonin levels is most useful when interpreted together with other clinical and laboratory results. Overall, repeated measurement of the procalcitonin levels during the first days of treatment provides more prognostic information than a single measurement; however, information on the cost-effectiveness of this procedure in intensive care patients is lacking. The results of studies that evaluated the prognostic value of initial procalcitonin levels in patients with community-acquired pneumonia are more consistent and have greater potential for practical application; in this case, low procalcitonin levels identify those patients with a low risk of adverse outcomes. PMID:27305038

  11. Hybrid Bearing Prognostic Test Rig

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Certo, Joseph M.; Handschuh, Robert F.; Dimofte, Florin

    2005-01-01

    The NASA Glenn Research Center has developed a new Hybrid Bearing Prognostic Test Rig to evaluate the performance of sensors and algorithms in predicting failures of rolling element bearings for aeronautics and space applications. The failure progression of both conventional and hybrid (ceramic rolling elements, metal races) bearings can be tested from fault initiation to total failure. The effects of different lubricants on bearing life can also be evaluated. Test conditions monitored and recorded during the test include load, oil temperature, vibration, and oil debris. New diagnostic research instrumentation will also be evaluated for hybrid bearing damage detection. This paper summarizes the capabilities of this new test rig.

  12. Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma

    PubMed Central

    Ok, Chi Young; Tzankov, Alexandar; Manyam, Ganiraju C.; Sun, Ruifan; Visco, Carlo; Zhang, Mingzhi; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Møller, Michael B.; Wang, Jinfeng; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Pham, Lan V.; Medeiros, L. Jeffrey; Young, Ken H.

    2015-01-01

    Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-κB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2− activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-κB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications. PMID:26324762

  13. 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.

  14. 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

  15. TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis.

    PubMed

    Loghavi, Sanam; Al-Ibraheemi, Alyaa; Zuo, Zhuang; Garcia-Manero, Guillermo; Yabe, Mariko; Wang, Sa A; Kantarjian, Hagop M; Yin, Cameron C; Miranda, Roberto N; Luthra, Raja; Medeiros, L Jeffrey; Bueso-Ramos, Carlos E; Khoury, Joseph D

    2015-10-01

    Bone marrow (BM) fibrosis is associated with poor prognosis in patients with de novo myelodysplastic syndromes (MDS). TP53 mutations and TP53 (p53) overexpression in MDS are also associated with poor patient outcomes. The prevalence and significance of TP53 mutations and TP53 overexpression in MDS with fibrosis are unknown. We studied 67 patients with de novo MDS demonstrating moderate to severe reticulin fibrosis (MDS-F). Expression of TP53 was evaluated in BM core biopsy specimens using dual-colour CD34/TP53 immunohistochemistry with computer-assisted image analysis. Mutation analysis was performed using next-generation sequencing, or Sanger sequencing methods. TP53 mutations were present in 47·1% of cases. TP53 mutation was significantly associated with TP53 expression (P = 0·0294). High levels of TP53 expression (3 +  in ≥10% cells) were associated with higher BM blast counts (P = 0·0149); alterations of chromosomes 5 (P = 0·0009) or 7 (P = 0·0141); complex karyotype (P = 0·0002); high- and very-high risk IPSS-R groups (P = 0·009); and TP53 mutations (P = 0·0003). High TP53 expression independently predicted shorter overall survival (OS) by multivariate analysis (P = <0·001). Expression of TP53 by CD34-positive cells was associated with shorter OS and leukaemia-free survival (P = 0·0428). TP53 overexpression is a predictor of poor outcome in patients with MDS-F. PMID:26123119

  16. Biologics in dermatology: adverse effects.

    PubMed

    Sehgal, Virendra N; Pandhi, Deepika; Khurana, Ananta

    2015-12-01

    Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner. PMID:26147909

  17. Acute pancreatitis: prognostic value of CT

    SciTech Connect

    Balthazar, E.J.; Ranson, J.H.C.; Naidich, D.P.; Megibow, A.J.; Caccavale, R.; Cooper, M.M.

    1985-09-01

    In 83 patients with acute pancreatitis, the initial computed tomographic (CT) examinations were classified by degree of disease severity (grades A-E) and were correlated with the clinical follow-up, objective prognostic signs, and complications and death. The length of hospitalization correlated well with the severity of the initial CT findings. Abscesses occurred in 21.6% of the entire group, compared with 60.0% of grade E patients. Pleural effusions were also more common in grade E patients. Abscesses were seen in 80.0% of patients with six to eight prognostic signs, compared with 12.5% of those with zero to two. The use of prognostic signs with initial CT findings results in improved prognostic accuracy. Early CT examination of patients with acute pancreatitis is a useful prognostic indicator of morbidity and mortality.

  18. 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.

  19. Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors.

    PubMed

    Moschetta, Marina Gobbe; Maschio, Larissa Bazela; Jardim-Perassi, Bruna Victorasso; Gelaleti, Gabriela Bottaro; Lopes, Juliana Ramos; Leonel, Camila; Gonçalves, Naiane Do Nascimento; Ferreira, Lívia Carvalho; Martins, Gustavo Rodrigues; Borin, Thaiz Ferraz; Zuccari, Debora Aparecida Pires De Campos

    2015-05-01

    Mammary tumors are the most common type of tumor in dogs, with approximately half of these tumors being malignant. Hypoxia, characterized by oxygen levels below normal, is a known adverse factor to cancer treatment. The hypoxia-inducible factor 1α (HIF-1α) is a central regulator of the pathophysiological response of mammalian cells to low oxygen levels. HIF-1α activates the transcription of vascular endothelial growth factor (VEGF), which in turn promotes angiogenesis through its ability to stimulate the growth, migration and invasion of endothelial cells to form new blood vessels, contributing to tumor progression. In this study, we evaluated the serum concentration and gene expression of VEGF and HIF-1α linking them with clinicopathological parameters and survival of dogs with mammary tumors in order to infer the possible prognostic value of these factors. We collected blood and tumor fragments of 24 female dogs with malignant mammary tumors (study group) and 26 non-affected female dogs (control group) to verify the gene expression of VEGF and HIF-1α by quantitative real-time PCR (qPCR) and the serum levels by ELISA (enzyme-linked immunosorbent). The results showed high serum levels of VEGF in the study group and its correlation between abundant vascularization, lymph node involvement, metastasis, death rate and low survival (p<0.05). The serum percentage of HIF-1α in female dogs with mammary neoplasia was lower than that in the control group and higher in female dogs with tumor metastasis and history of tumor recurrence (p<0.05). Regarding gene expression, there was a gene overexpression of VEGFA in female dogs with poor outcome, in contrast to the gene underexpression of HIF-1A. Taken together, these results suggested that VEGF is important in tumor progression and can be used as a potential prognostic marker in the clinic and may be useful in predicting tumor progression in dogs with mammary neoplasia. PMID:25779537

  20. Prognostic value of MET, cyclin D1 and MET gene copy number in non-small cell lung cancer

    PubMed Central

    Sun, Wenze; Song, Liping; Ai, Ting; Zhang, Yingbing; Gao, Ying; Cui, Jie

    2013-01-01

    The aim of this study was to analyze the correlation of the expression of MET and cyclin D1 and MET gene copy number in non-small cell lung cancer (NSCLC) tissues and patient clinicopathologic characteristics and survival. Sixty-one NSCLC tissue specimens were included in the study. The expression of MET and cyclin D1 was evaluated by immunohistochemistry and MET gene copy number was assessed by quantitative real-time polymerase chain reaction (Q-PCR). Positive expression of MET and cyclin D1 protein and increased MET gene copy number occurred in 59.0%, 59.0% and 18.0% of 61 NSCLC tissues, respectively. MET-positivity correlated with poor differentiation (P = 0.009). Increased MET gene copy number was significantly associated with lymph node metastasis (P = 0.004) and advanced tumor stage (P = 0.048), while the expression of cyclin D1 was not associated with any clinicopathologic parameters. There was a significant correlation between the expression of MET and MET gene copy number (P = 0.002). Additionally, the expression of cyclin D1 had a significant association with the expression of MET as well as MET gene copy number (P = 0.002 and P = 0.017, respectively). MET-positivity and increased MET gene copy number were significantly associated with poor overall survival (P = 0.003 and P < 0.001, respectively) in univariate analysis. Multivariate Cox proportional hazard analysis confirmed that the expression of MET and MET gene copy number were prognostic indicators of NSCLC (P = 0.003 and P = 0.001, respectively). The overexpression of MET and the increased MET gene copy number might be adverse prognostic factors for NSCLC patients. The activation of the MET/cyclin D1 signaling pathway may contribute to carcinogenesis and the development of NSCLC, and may represent a target for therapy. PMID:23720678

  1. Local dynamics of heart rate: detection and prognostic implications.

    PubMed

    Moss, Travis J; Lake, Douglas E; Moorman, J Randall

    2014-10-01

    The original observation that reduced heart rate variability (HRV) confers poor prognosis after myocardial infarction has been followed by many studies of heart rate dynamics. We tested the hypothesis that an entropy-based local dynamics measure gave prognostic information in ambulatory patients undergoing 24-h electrocardiography. In this context, entropy is the probability that short templates will find matches in the time series. We studied RR interval time series from 24-h Holter monitors of 1564 consecutive patients over age 39. We generated histograms of the count of templates as a function of the number of templates matches in short RR interval time series, and found characteristic appearance of histograms for atrial fibrillation, sinus rhythm with normal HRV, and sinus rhythm with reduced HRV and premature ventricular contractions (PVCs). We developed statistical models to detect the abnormal dynamic phenotype of reduced HRV with PVCs and fashioned a local dynamics score (LDs) that, after controlling for age, added more prognostic information than other standard risk factors and common HRV metrics, including, to our surprise, the PVC count and the HRV of normal-to-normal intervals. Addition of the LDs to a predictive model using standard risk factors significantly increased the ROC area and the net reclassification improvement was 27%. We conclude that abnormal local dynamics of heart rate confer adverse prognosis in patients undergoing 24-h ambulatory electrocardiography. PMID:25229393

  2. Cancer of the glottis: prognostic factors in radiation therapy

    SciTech Connect

    Mantravadi, R.V.; Liebner, E.J.; Haas, R.E.; Skolnik, E.M.; Applebaum, E.L.

    1983-10-01

    The authors conducted a multivariate analysis of the prognostic factors in 96 patients with early glottic cancer treated by radiation therapy. Of these, 73 had T1 and 23 had T2 tumor. The primary tumor was controlled in 82% of T1 and 74% of T2 lesions. Actuarial five-year survival rates were 87% for T1 and 74% for T2. Carcinoma of the anterior commissure associated with bilateral vocal cord involvement, subglottic tumor extension, persistent or recurrent laryngeal edema, and impaired cord mobility was found to adversely influence the prognosis. The data suggest that irradiation is the treatment of choice for glottic cancer limited to the vocal cords or with minimal extension to the anterior commissure or supraglottic larynx.

  3. Cancer of the glottis: prognostic factors in radiation therapy

    SciTech Connect

    Mantravadi, R.V.P.; Liebner, E.J.; Haas, R.E.; Skolnik, E.M.; Applebaum, E.L.

    1983-10-01

    The authors conducted a multivariate analysis of the prognostic factors in 96 patients with early glottic cancer treated by radiation therapy. Of these, 73 had T/sub 1/ and 23 had T/sub 2/ tumor. The primary tumor was controlled in 82% of T/sub 1/ amd 74% for T/sub 2/. Carcinoma of the anterior commissure associated with bilateral vocal cord involvement, subglottic tumor extension, persistent or recurrent laryngeal edema, and impaired cord mobility was found to adversely influence the prognosis. The data suggest that irradiation is the treatment of choice for glottic cancer limited to the vocal cords or with minimal extension to the anterior commissure or gupraglottic larynx.

  4. Development and Validation of a Lifecycle-based Prognostics Architecture with Test Bed Validation

    SciTech Connect

    Hines, J. Wesley; Upadhyaya, Belle; Sharp, Michael; Ramuhalli, Pradeep; Jeffries, Brien; Nam, Alan; Strong, Eric; Tong, Matthew; Welz, Zachary; Barbieri, Federico; Langford, Seth; Meinweiser, Gregory; Weeks, Matthew

    2014-11-06

    RUL predictions, with as little uncertainty as possible. From a reliability and maintenance standpoint, there would be improved safety by avoiding all failures. Calculated risk would decrease, saving money by avoiding unnecessary maintenance. One major bottleneck for data-driven prognostics is the availability of run-to-failure degradation data. Without enough degradation data leading to failure, prognostic models can yield RUL distributions with large uncertainty or mathematically unsound predictions. To address these issues a "Lifecycle Prognostics" method was developed to create RUL distributions from Beginning of Life (BOL) to End of Life (EOL). This employs established Type I, II, and III prognostic methods, and Bayesian transitioning between each Type. Bayesian methods, as opposed to classical frequency statistics, show how an expected value, a priori, changes with new data to form a posterior distribution. For example, when you purchase a component you have a prior belief, or estimation, of how long it will operate before failing. As you operate it, you may collect information related to its condition that will allow you to update your estimated failure time. Bayesian methods are best used when limited data are available. The use of a prior also means that information is conserved when new data are available. The weightings of the prior belief and information contained in the sampled data are dependent on the variance (uncertainty) of the prior, the variance (uncertainty) of the data, and the amount of measured data (number of samples). If the variance of the prior is small compared to the uncertainty of the data, the prior will be weighed more heavily. However, as more data are collected, the data will be weighted more heavily and will eventually swamp out the prior in calculating the posterior distribution of model parameters. Fundamentally Bayesian analysis updates a prior belief with new data to get a posterior belief. The general approach to applying the

  5. Periodic acid-Schiff-positive loops and networks as a prognostic factor in oral mucosal melanoma.

    PubMed

    Song, Hao; Jing, Guangping; Wang, Lizhen; Guo, Wei; Ren, Guoxin

    2016-04-01

    The prognostic factors of oral mucosal melanoma (OMM), a rare and aggressive neoplasm, remain to be determined. The aim of this study is to investigate the prognostic significance of vasculogenic mimicry in OMM. The clinical data of 62 patients with primary OMM treated in Shanghai Ninth People's Hospital from April 2007 to April 2012 were retrieved and analyzed retrospectively. Staining of periodic acid-Schiff (PAS) and CD31 immunohistochemistry were performed to evaluate the prognostic value of PAS-positive patterns, blood lakes, and microvascular density. PAS-positive loops and networks (P<0.001) as well as blood lakes (P=0.040) were found to be predictors of overall survival (OS). The presence of PAS-positive loops and networks was an independent prognostic factor of poor OS in multivariate analysis (P=0.002). Although the presence of PAS-positive loops and networks was associated with hematogenous metastasis (P=0.041) and lymphogenous metastasis (P=0.041), it was not an independent predictor of both types of metastasis in multivariate analysis. Microvascular density was not associated with OS (P=0.627) and metastasis of OMM patients. PAS-positive loops and networks have a significant prognostic value in OMM. Detection of PAS-positive patterns may lead to better staging and serve as a prognostic parameter of OMM. PMID:26636907

  6. Adversity and advancing nursing knowledge.

    PubMed

    Reed, Pamela G

    2008-04-01

    This column reports the theme of adversity addressed in reference to theoretical and metatheoretical considerations for advancing nursing knowledge. The development and content of three classic nursing theories are presented by Neuman representatives, and by theorists King and Roy. Topics for continued dialogue are identified as derived from the interface between philosophy of science issues and these theories. PMID:18378823

  7. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  8. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  9. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  10. Model Adaptation for Prognostics in a Particle Filtering Framework

    NASA Technical Reports Server (NTRS)

    Saha, Bhaskar; Goebel, Kai Frank

    2011-01-01

    One of the key motivating factors for using particle filters for prognostics is the ability to include model parameters as part of the state vector to be estimated. This performs model adaptation in conjunction with state tracking, and thus, produces a tuned model that can used for long term predictions. This feature of particle filters works in most part due to the fact that they are not subject to the "curse of dimensionality", i.e. the exponential growth of computational complexity with state dimension. However, in practice, this property holds for "well-designed" particle filters only as dimensionality increases. This paper explores the notion of wellness of design in the context of predicting remaining useful life for individual discharge cycles of Li-ion batteries. Prognostic metrics are used to analyze the tradeoff between different model designs and prediction performance. Results demonstrate how sensitivity analysis may be used to arrive at a well-designed prognostic model that can take advantage of the model adaptation properties of a particle filter.

  11. [Prognostic and predictive factors in epithelial ovarian cancer].

    PubMed

    Boudou-Rouquette, P; Pautier, P; Morice, P; Lhommé, C

    2009-04-01

    Even if prognosis of epithelial ovarian cancer remains very bad, survival and response to treatment are variable according to the patients. Determination of new prognostic markers helps us to adapt therapeutics for each patient and is necessary for the elaboration and the interpretation of clinical research studies. Many prognostic factors related to the tumor, the patient or the treatment, have been evaluated. The goal of this work is to review these parameters. So far, the most powerful variables are volume of residual disease after cytoreductive surgery, FIGO tumor stage, histologic type and grade of differentiation. The progress and accessibility to novel technologies applied to biology will make possible in the future the assessment of new prognostic profiles-based on genetic and/or proteomic tumor characteristics. The future also relies on the identification of predictive factors of response to treatment, but force is to note that on the last hundred publications testing predictive factors (p53, HER2, Topo-2-alpha, BRCA...), none have modified today our clinical practices. PMID:19357017

  12. Prognostic factors in histiocytosis X.

    PubMed

    Lahey, M E

    1981-01-01

    It is now clear that the prognosis in children with histiocytosis X has improved considerable over the past few years. To be sure, patients with solitary lesions have an excellent prognosis. Whereas the outlook for patients with significant visceral involvement is not as good as those with bone lesions only, the outlook is by no means hopeless, as was once thought. A number of prognostic factors have been reviewed here. The most significant of these factors at the present time would appear to be age of onset of the disease, extent of involvement, the rapidity of progression of the disease, and, in particular, the presence or absence of dysfunction of such crucial organ systems as liver, lung, and hemopoietic system. Further studies of the significance of histologic features and immunologic findings are clearly needed to further our understanding of this disorder. PMID:6972178

  13. A Physics-Based Modeling Framework for Prognostic Studies

    NASA Technical Reports Server (NTRS)

    Kulkarni, Chetan S.

    2014-01-01

    Prognostics and Health Management (PHM) methodologies have emerged as one of the key enablers for achieving efficient system level maintenance as part of a busy operations schedule, and lowering overall life cycle costs. PHM is also emerging as a high-priority issue in critical applications, where the focus is on conducting fundamental research in the field of integrated systems health management. The term diagnostics relates to the ability to detect and isolate faults or failures in a system. Prognostics on the other hand is the process of predicting health condition and remaining useful life based on current state, previous conditions and future operating conditions. PHM methods combine sensing, data collection, interpretation of environmental, operational, and performance related parameters to indicate systems health under its actual application conditions. The development of prognostics methodologies for the electronics field has become more important as more electrical systems are being used to replace traditional systems in several applications in the aeronautics, maritime, and automotive fields. The development of prognostics methods for electronics presents several challenges due to the great variety of components used in a system, a continuous development of new electronics technologies, and a general lack of understanding of how electronics fail. Similarly with electric unmanned aerial vehicles, electrichybrid cars, and commercial passenger aircraft, we are witnessing a drastic increase in the usage of batteries to power vehicles. However, for battery-powered vehicles to operate at maximum efficiency and reliability, it becomes crucial to both monitor battery health and performance and to predict end of discharge (EOD) and end of useful life (EOL) events. We develop an electrochemistry-based model of Li-ion batteries that capture the significant electrochemical processes, are computationally efficient, capture the effects of aging, and are of suitable

  14. The prognostic role of desmoplastic stroma in pancreatic ductal adenocarcinoma

    PubMed Central

    Soonawalla, Zahir; Liu, Stanley; O'Neill, Eric; Mukherjee, Somnath; McKenna, W. Gillies; Muschel, Ruth; Fokas, Emmanouil

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic stroma. We examined the prognostic value of stroma density and activity in patients with resectable PDAC treated with surgery and adjuvant gemcitabine-based chemotherapy. FFPE-tissue from the pancreatectomy of 145 patients was immunohistochemically stained for haematoxylin-eosin and Masson's trichrome to assess stroma density, and alpha-smooth muscle actin (αSMA) expression for activated pancreatic stellate cells. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS). After a mean follow-up of 20 months (range, 2–69 months), the median OS was 21 months and the 3-year OS was 35.7%. In multivariate analysis, highly-dense stroma was an independent prognostic parameter for OS (p = 0.001), PFS (p = 0.007), LPFS (p = 0.001) and DMFS (p = 0.002), while αSMA expression lacked significance. Interestingly, highly-dense stroma retained significance for the four clinical endpoints only in early (pT1–2) but not late (pT3–4) stage tumors. Additionally, late pT-stage (pT3–4), the presence of lymph node metastases (pN+ vs pN0), perineural/neural invasion and administration of adjuvant chemotherapy also correlated with prognosis in multivariate analysis. Altogether, stroma density constitutes an independent prognostic marker in PDAC patients treated with adjuvant chemotherapy. Our findings highlight the dynamic complexity of desmoplasia and indicate that highly-dense stroma is correlated with better outcome. Further validation of the prognostic value of stroma as a biomarker and its role in PDAC patients after adjuvant chemotherapy is warranted and will be performed in a prospective study. PMID:26716653

  15. Prognostic value of perioperative leukocyte count in resectable gastric cancer

    PubMed Central

    Chen, Xiao-Feng; Qian, Jing; Pei, Dong; Zhou, Chen; Røe, Oluf Dimitri; Zhu, Fang; He, Shao-Hua; Qian, Ying-Ying; Zhou, Yue; Xu, Jun; Xu, Jin; Li, Xiao; Ping, Guo-Qiang; Liu, Yi-Qian; Wang, Ping; Guo, Ren-Hua; Shu, Yong-Qian

    2016-01-01

    AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer. METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors. RESULTS: The mean white blood cell count (WBC) significantly decreased after surgery, and 107/614 (17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC < 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio (HR) = 1.602, 95% confidence interval (CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, pTNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p-leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia (27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer. PMID:26973420

  16. CD163 and c-Met expression in the lymph node and the correlations between elevated levels of serum free light chain and the different clinicopathological parameters of advanced classical Hodgkin's lymphoma

    PubMed Central

    Bedewy, Magdy; El-Maghraby, Shereen

    2013-01-01

    Background Advances in the understanding of Hodgkin's lymphoma (HL) show various functions of infiltrating immune cells and cytokines in relation to clinical outcomes. The expression of CD163 and c-Met has been suggested to have a role in lymphoid malignancy. Thus, we evaluated the expressions of CD163, c-Met, and serum free light chain (sFLC) in relation to the clinicopathological features of patients with advanced classical HL (cHL). Methods We assessed the expression of CD163 and c-Met in 34 patients with cHL through immunohistochemistry on the lymph node biopsy sections and the levels of pretreatment sFLC were estimated using ELISA. Results High CD163 expression correlated with increased age, B symptoms, International Prognostic Score (IPS) ≥3, mixed cellularity subtype, and low response to treatment. Further, high c-Met expression correlated with increased age at diagnosis, leukocytosis, B symptoms, and lower chance to achieve complete remission. The sFLC levels correlated with increased age at diagnosis, lymphopenia, IPS ≥3, B symptoms, and lower complete remission rates. Conclusion In advanced cHL, increased expression of CD163 and c-Met showed a significant association with adverse prognostic parameters and poor response to treatment. Pretreatment high sFLC level also correlated with poor risk factors, suggesting its use as a candidate prognostic marker. A comprehensive approach for prognostic markers might represent a step towards developing a tailored therapeutic approach for HL. PMID:23826581

  17. 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.

  18. Cardiovascular adverse effects of phenytoin.

    PubMed

    Guldiken, B; Rémi, J; Noachtar, Soheyl

    2016-05-01

    Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. One of its main advantages over benzodiazepines is the less sedative effect. However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs. In this study, we aimed to review the studies which evaluated the safety of phenytoin with respect to cardiovascular adverse effects. The original clinical trials and case reports listed in PUBMED in English language between the years of 1946-2014 were evaluated. As the key words, "phenytoin, diphenylhydantoin, epilepsy, seizure, cardiac toxicity, asystole, arrhythmia, respiratory arrest, hypotension, death" were used. Thirty-two clinical trials and ten case reports were identified. In the case reports, a rapid infusion rate (>50 mg/min) of phenytoin appeared as the major cause of increased mortality. In contrast, no serious cardiovascular adverse effects leading to death were met in the clinical trials which applied the recommended infusion rate and dosages. An infusion rate of 50 mg/min was reported to be safe for young patients. For old patients and patients with a cardiovascular co-morbidity, a slower infusion rate was recommended with a careful follow-up of heart rhythm and blood pressure. No cardiovascular adverse effect was reported in oral phenytoin overdoses except one case with a very high serum phenytoin level and hypoalbuminemia. Phenytoin is an effective and well tolerated drug in the treatment of epilepsy. Intravenous phenytoin is safe when given at recommended infusion rates and doses. PMID:26645393

  19. [Adverse events of psychotropic drugs].

    PubMed

    Watanabe, Koichiro; Kikuchi, Toshiaki

    2014-01-01

    The authors discuss adverse events which are often missed but clinicians should pay attention to in order to preserve patients'quality of life(QOL). Among mood stabilizers, lithium may cause a urinary volume increase, hyperparathyroidism, and serum calcium elevation; sodium valproate possibly increases androgenic hormone levels and the risk of polycystic ovary syndrome (PCOS) as well as hypothyroidism. Moreover, in addition to teratogenesis, it has been reported that fetal exposure to a higher dose of valproate is associated with a lower intelligence quotient and higher incidence of autism spectrum disorders in children. Antidepressants with a higher affinity for serotonin transporters might induce gastrointestinal bleeding, and some antidepressants cause sexual dysfunction more frequently than others. Activation syndrome is still a key side effect which should be noted. Regarding the adverse events of antipsychotics, subjective side effects unpleasant to patients such as dysphoria and a lower subjective well-being should not be overlooked. We clinicians have to cope with adverse events worsening the QOL of patients with psychiatric disorders and, therefore, we need to adopt appropriate counter-measures. PMID:24864567

  20. The Prognostic Value of Circulating Cell-Free DNA in Colorectal Cancer: A Meta-Analysis

    PubMed Central

    Basnet, Shiva; Zhang, Zhen-yu; Liao, Wen-qiang; Li, Shu-heng; Li, Ping-shu; Ge, Hai-yan

    2016-01-01

    Background: Circulating cell-free DNA (cfDNA) is a promising candidate biomarker for detection, monitoring and survival prediction of colorectal cancer (CRC). However, its prognostic significance for patients with CRC remains controversial. To derive a precise estimation of the prognostic significance of cfDNA, a meta-analysis was performed. Methods: We made a systematic search in data base of the Science Citation Index Embase and Pubmed for studies reporting prognostic data of cfDNA in CRC patients. The data of cfDNA on recurrences-free survival (RFS) and overall survival (OS) were extracted and measured in hazard rates (HRs) and 95% confident intervals (CIs). Subgroup analyses were carried out as well. Finally, the meta-analysis is accompanied with nine studies including 19 subunits. Results: The pooled HRs with 95% CIs revealed strong associations between cfDNA and RFS (HR [95%CI]=2.78[2.08-3.72], I2=32.23%, n=7) along with OS (HR [95%CI]=3.03[2.51-3.66], I2=29.24%, n=12) in patients with CRC. Entire subgroup analyses indicated strong prognostic value of cfDNA irrespective tumor stage, study size, tumor markers, detection methods and marker origin. Conclusions: All the results exhibits that appearance of cfDNA in blood is an indicator for adverse RFS and OS in CRC patients. PMID:27326254

  1. 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.

  2. 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.

  3. 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.

  4. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM).

    PubMed

    Della Porta, M G; Tuechler, H; Malcovati, L; Schanz, J; Sanz, G; Garcia-Manero, G; Solé, F; Bennett, J M; Bowen, D; Fenaux, P; Dreyfus, F; Kantarjian, H; Kuendgen, A; Levis, A; Cermak, J; Fonatsch, C; Le Beau, M M; Slovak, M L; Krieger, O; Luebbert, M; Maciejewski, J; Magalhaes, S M M; Miyazaki, Y; Pfeilstöcker, M; Sekeres, M A; Sperr, W R; Stauder, R; Tauro, S; Valent, P; Vallespi, T; van de Loosdrecht, A A; Germing, U; Haase, D; Greenberg, P L; Cazzola, M

    2015-07-01

    A risk-adapted treatment strategy is mandatory for myelodysplastic syndromes (MDS). We refined the World Health Organization (WHO)-classification-based Prognostic Scoring System (WPSS) by determining the impact of the newer clinical and cytogenetic features, and we compared its prognostic power to that of the revised International Prognostic Scoring System (IPSS-R). A population of 5326 untreated MDS was considered. We analyzed single WPSS parameters and confirmed that the WHO classification and severe anemia provide important prognostic information in MDS. A strong correlation was found between the WPSS including the new cytogenetic risk stratification and WPSS adopting original criteria. We then compared WPSS with the IPSS-R prognostic system. A highly significant correlation was found between the WPSS and IPSS-R risk classifications. Discrepancies did occur among lower-risk patients in whom the number of dysplastic hematopoietic lineages as assessed by morphology did not reflect the severity of peripheral blood cytopenias and/or increased marrow blast count. Moreover, severe anemia has higher prognostic weight in the WPSS versus IPSS-R model. Overall, both systems well represent the prognostic risk of MDS patients defined by WHO morphologic criteria. This study provides relevant in formation for the implementation of risk-adapted strategies in MDS. PMID:25721895

  5. Detecting Adverse Events Using Information Technology

    PubMed Central

    Bates, David W.; Evans, R. Scott; Murff, Harvey; Stetson, Peter D.; Pizziferri, Lisa; Hripcsak, George

    2003-01-01

    Context: Although patient safety is a major problem, most health care organizations rely on spontaneous reporting, which detects only a small minority of adverse events. As a result, problems with safety have remained hidden. Chart review can detect adverse events in research settings, but it is too expensive for routine use. Information technology techniques can detect some adverse events in a timely and cost-effective way, in some cases early enough to prevent patient harm. Objective: To review methodologies of detecting adverse events using information technology, reports of studies that used these techniques to detect adverse events, and study results for specific types of adverse events. Design: Structured review. Methodology: English-language studies that reported using information technology to detect adverse events were identified using standard techniques. Only studies that contained original data were included. Main Outcome Measures: Adverse events, with specific focus on nosocomial infections, adverse drug events, and injurious falls. Results: Tools such as event monitoring and natural language processing can inexpensively detect certain types of adverse events in clinical databases. These approaches already work well for some types of adverse events, including adverse drug events and nosocomial infections, and are in routine use in a few hospitals. In addition, it appears likely that these techniques will be adaptable in ways that allow detection of a broad array of adverse events, especially as more medical information becomes computerized. Conclusion: Computerized detection of adverse events will soon be practical on a widespread basis. PMID:12595401

  6. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID:27357302

  7. Adverse Effects of Electroconvulsive Therapy.

    PubMed

    Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

    2016-09-01

    Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. PMID:27514303

  8. Development and cross-validation of prognostic models to assess the treatment effect of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients.

    PubMed

    Mou, Wenjun; Liu, Zhaoqi; Luo, Yuan; Zou, Meng; Ren, Chao; Zhang, Chunyan; Wen, Xinyu; Wang, Yong; Tian, Yaping

    2014-09-01

    Better understanding of the treatment effect of cisplatin/pemetrexed chemotherapy on lung adenocarcinoma patients is needed to facilitate chemotherapy planning and patient care. In this retrospective study, we will develop prognostic models by the cross-validation method using clinical and serum factors to predict outcomes of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients. Lung adenocarcinoma patients admitted between 2008 and 2013 were enrolled. 29 serum parameters of laboratory tests and 14 clinical factors were analyzed to develop the prognostic models. First, the stepwise selection and five-fold cross-validation were performed to identify candidate prognostic factors. Then a classification of all patients based on the number of metastatic sites resulted in four distinct subsets. In each subset, a prognostic model was fitted with the most accurate prognostic factors from the candidate prognostic factors. Categorical survival prediction was estimated using a log-rank test and visualized with Kaplan-Meier method. 227 lung adenocarcinoma patients were enrolled. Twenty candidate prognostic factors evaluated using the five-fold cross-validation method were total protein, total bilirubin, direct bilirubin, creatine kinase, age, smoking index, neuron-specific enolase, bone metastasis, total triglyceride, albumin, gender, uric acid, CYFRA21-1, lymph node metastasis, liver metastasis, lactate dehydrogenase, CA153, peritoneal metastasis, CA125, and CA199. From these 20 candidate prognostic factors, the multivariate Cox proportional hazard model with the highest prognostic accuracy in each subset was identified by the stepwise forward selection method, which generated significant prognostic stratifications in Kaplan-Meier survival analyses (all log-rank p < 0.01). Generally, the prognostic models using five-fold cross-validation achieve a good prediction performance. The prognostic models can be administered safely to lung adenocarcinoma patients treated

  9. The Prognostic Value of C-Reactive Protein Serum Levels in Patients with Uterine Leiomyosarcoma

    PubMed Central

    Schwameis, Richard; Grimm, Christoph; Petru, Edgar; Natter, Camilla; Staudigl, Christine; Lamm, Wolfgang; Koelbl, Heinz; Krainer, Michael; Brodowicz, Thomas; Reinthaller, Alexander; Polterauer, Stephan

    2015-01-01

    Objective C-reactive protein (CRP) has previously been shown to serve as a prognostic parameter in women with gynecologic malignancies. Due to the lack of valid prognostic markers for uterine leiomyosarcoma (ULMS) this study set out to investigate the value of pre-treatment CRP serum levels as prognostic parameter. Methods Data of women with ULMS were extracted from databases of three Austrian centres for gynaecologic oncology. Pre-treatment CRP serum levels were measured and correlated with clinico-pathological parameters. Univariate and multivariable survival analyses were performed. Results In total, 53 patients with ULMS were included into the analysis. Mean (SD) CRP serum level was 3.46 mg/dL (3.96). Solely, an association between pre-treatment CRP serum levels and tumor size (p = 0.04) but no other clinic-pathologic parameter such as tumor stage (p = 0.16), or histological grade (p = 0.07), was observed. Univariate and multivariable survival analyses revealed that CRP serum levels (HR 2.7 [1.1–7.2], p = 0.037) and tumor stage (HR 6.1 [1.9–19.5], p = 0.002) were the only independent prognostic factors for overall survival (OS) in patients with ULMS. Patients with high pre-treatment CRP serum levels showed impaired OS compared to women with low levels (5-year-OS rates: 22.6% and 52.3%, p = 0.007). Conclusion High pre-treatment CRP serum levels were independently associated with impaired prognosis in women with ULMS and might serve as a prognostic parameter in these patients. PMID:26248232

  10. Prognostic Disclosures to Children: A Historical Perspective

    PubMed Central

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

    2016-01-01

    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. Prior to 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 four 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 four 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. PMID:27561728

  11. 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. PMID:27561728

  12. Adverse drug reactions in dermatology.

    PubMed

    Ferner, R E

    2015-03-01

    Adverse drug reactions (ADRs) - that is, unintended and harmful responses to medicines - are important to dermatologists because many present with cutaneous signs and because dermatological treatments can cause serious ADRs. The detection of ADRs to new drugs is often delayed because they have a long latency or are rare or unexpected. This means that ADRs to newer agents emerge only slowly after marketing. ADRs are part of the differential diagnosis of unusual rashes. A good drug history that includes details of drug dose, time-course of the reaction and factors that may make the patient more susceptible, will help. For example, Stevens-Johnson syndrome with abacavir is much commoner in patients with HLA-B*5701, and has a characteristic time course. Newer agents have brought newer reactions; for example, acneiform rashes associated with epidermal growth factor receptor inhibitors such as erlotinib. Older systemic agents used to treat skin disease, including corticosteroids and methotrexate, cause important ADRs. The adverse effects of newer biological agents used in dermatology are becoming clearer; for example, hypersensitivity reactions or loss of efficacy from antibody formation and progressive multifocal leucoencephalopathy due to reactivation of latent JC (John Cunningham) virus infections during efalizumab treatment. Unusual or serious harm from medicines, including ADRs, medication errors and overdose, should be reported. The UK Yellow Card scheme is online, and patients can report their own ADRs. PMID:25622648

  13. [Recipients adverse reactions: guidance supports].

    PubMed

    Bazin, A

    2010-12-01

    Since 1994, adverse effects of transfusion transmitted to the French haemovigilance network are registered on "e-fit", the database of the French agency for the safety of health products (Afssaps). In order to improve their analysis, guidance supports have been made by Afssaps working groups. Each support deals with a blood transfusion side effect and is composed of five parts including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules of filing the notification form on e-fit. The major characteristics of sheets published or soon-to-be published are presented: transfusion-related acute lung injury, transfusion-transmitted bacterial infection, non-haemolytic febrile reaction, allergic reaction, transfusion-associated circulatory overload, hypotensive transfusion reaction, alloimmunization, erythrocyte incompatibility reaction and hemosiderosis. These new supports give relevant guidelines allowing a better analysis and evaluation of recipients' adverse reactions, particularly their diagnosis, gravity and accountability. They could also initiate studies in European and international haemovigilance and transfusion networks. PMID:21051267

  14. Adverse effects of plasma transfusion.

    PubMed

    Pandey, Suchitra; Vyas, Girish N

    2012-05-01

    Plasma utilization has increased over the past two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions after infusion of fresh-frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: 1) transfusion-related acute lung injury, 2) transfusion-associated circulatory overload, and 3) allergic and/or anaphylactic reactions. Other less common risks include 1) transmission of infections, 2) febrile nonhemolytic transfusion reactions, 3) red blood cell alloimmunization, and 4) hemolytic transfusion reactions. The effects of pathogen inactivation or reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. PMID:22578374

  15. Prognostic value of plasma biomarkers in patients with acute coronary syndrome: a review of advances in the past decade.

    PubMed

    Cao, Richard Y; Zheng, Hongchao; Guo, Junjun; Redfearn, Damian P

    2016-05-01

    Acute coronary syndrome (ACS), especially myocardial infarction, commonly known as a heart attack, is a serious life-threatening cardiovascular disease. Despite dramatic therapeutic advances, there have still been more than 20% patients with ACS suffering recurrent adverse cardiovascular events 3 years after disease onset. Therefore, the aim to prevent cardiac death caused by the heart attack remains challenging. Plasma biomarkers, originally developed to complement clinical assessment and electrocardiographic examination for the diagnosis of ACS, have been reported to play important prognostic roles in predicting adverse outcomes. These biomarkers mirror different pathophysiological mechanisms in association with ACS. In this review, we focus on advances of prognostic biomarkers in the past decade for short- and long-term risk assessment and management of patients with ACS. PMID:27089223

  16. Tissue polypeptide antigen in tumor cytosol: a new prognostic indicator in primary breast cancer.

    PubMed

    Gion, M; Mione, R; Gatti, C; Dittadi, R; Leon, A; Castiglioni, C; Nascimben, O; Bruscagnin, G

    1990-11-01

    The assessment of the risk of relapse is a critical need in the management strategy of breast cancer patients. To date, the most reliable prognostic factor is axillary nodal status. Several other pathological and biological parameters are currently under evaluation. Since 1982 we have been studying the prognostic role of several tumor markers in breast cancer cytosol. Elevated cytosol concentrations of tissue polypeptide antigen (TPA) have been found to have a highly significant direct correlation with both prolonged relapse-free interval (RFI) and higher survival rate. The information provided by cytosol TPA was independent of both axillary nodal status and steroid receptor content. In patients with a low risk of relapse (no axillary metastases, estrogen and progesterone receptor positive), cytosol TPA was still a significant prognostic indicator. PMID:1965704

  17. ARID1A expression in early stage colorectal adenocarcinoma: an exploration of its prognostic significance.

    PubMed

    Lee, Lik Hang; Sadot, Eran; Ivelja, Sinisa; Vakiani, Efsevia; Hechtman, Jaclyn F; Sevinsky, Christopher J; Klimstra, David S; Ginty, Fiona; Shia, Jinru

    2016-07-01

    ARID1A is a chromatin remodeling gene that is mutated in a number of cancers including colorectal carcinoma (CRC). Loss of ARID1A has been associated with an adverse outcome in some types of cancer. However, literature data have not been consistent. Major limitations of some outcome studies include small sample size and heterogeneous patient population. In this study, we evaluated the prognostic value of ARID1A in a homogeneous group of early stage CRC patients, a population where prognostic markers are particularly relevant. We collected a retrospective series of 578 stage I or II CRCs. All patients underwent surgery with curative intent and without neoadjuvant or adjuvant therapy. ARID1A expression was analyzed by immunohistochemistry using tissue microarray. We found ARID1A loss in 49 of 552 analyzable tumors (8.9%). Compared with the ARID1A-retained group, cases with ARID1A loss were associated with female sex (P<.001), mismatch-repair protein deficiency (P<.001), poor differentiation (P<.001), lymphovascular invasion (P=.001), and higher pT stage (P=.047). However, at a median follow-up of 49months, ARID1A loss did not correlate with overall, disease-specific, or recurrence-free survival. This is the first systematic analysis to evaluate the prognostic significance of ARID1A in stage I/II CRCs, and our data indicate that ARID1A loss lacks prognostic significance in this population despite its association with other adverse features. Such data are clinically relevant, as efforts are ongoing in identifying markers that can detect the small but significant subset of early stage CRCs that will have a poor outcome. PMID:26980037

  18. "Adversative Conjunction": The Poetics of Linguistic Opposition.

    ERIC Educational Resources Information Center

    Wallerstein, Nicholas

    1992-01-01

    The general use of adversative conjunction in (primarily) English and U.S. poetry is outlined. The contention is that the adversative is not merely a grammatical convenience but sometimes a highly functional tool of rhetorical strategy. (36 references) (LB)

  19. Prognostic Significance of Ascites and Serum Sodium in Patients with Low Meld Scores

    PubMed Central

    Prohic, Dzanela; Mesihovic, Rusmir; Vanis, Nenad; Puhalovic, Amra

    2016-01-01

    Objective: to determine ascites and serum sodium significance in short term mortality prediction in patients with advanced liver cirrhosis. Methods: a cohort of 115 cirrhotic patients referred to our Department were followed up for 6 months in non-transplant settings. The c index equivalent to the area under the receiver operating curve (ROC) was calculated and compared to estimate the short-term prognostic accuracy of the following parameters: ascites, serum sodium and MELD score. Results: in patients with a MELD score less than 21, ascites and low serum sodium (c index 0,687, p<0 0,001 and 0,748, p<0,001 respectively) showed better prognostic accuracy and were independent predictors of mortality. For MELD scores above 21, only MELD was an independent mortality prognostic factor (c index 0,710, p<0,001). Conclusion: in our study, sample ascites and low serum sodium help identify patients with advanced liver disease who are at high risk of mortality despite low MELD scores. These parameters should be considered as additional prognostic parameters that could improve available treatment options and outcomes in this group of patients. PMID:26980932

  20. Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

    PubMed

    Riley, Richard D; Elia, Eleni G; Malin, Gemma; Hemming, Karla; Price, Malcolm P

    2015-07-30

    A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points). PMID:25924725

  1. Prognostic DNA Methylation Markers for Prostate Cancer

    PubMed Central

    Strand, Siri H.; Orntoft, Torben F.; Sorensen, Karina D.

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  2. Prognostic DNA methylation markers for prostate cancer.

    PubMed

    Strand, Siri H; Orntoft, Torben F; Sorensen, Karina D

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  3. 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

  4. 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.

  5. Prognostic value of preoperative inflammatory response biomarkers in patients with sarcomatoid renal cell carcinoma and the establishment of a nomogram

    PubMed Central

    Gu, Liangyou; Ma, Xin; Li, Hongzhao; Chen, Luyao; Xie, Yongpeng; Zhao, Chaofei; Luo, Guoxiong; Zhang, Xu

    2016-01-01

    To examine the prognostic role of inflammatory response biomarkers in sarcomatoid renal cell carcinoma (sRCC). From January 2004 to May 2015, 103 patients with sRCC were enrolled in this study. Preoperative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the prognostic value of this four markers using Kaplan-Meier method and Cox regression models. Additionally, a nomogram was established to predict the prognosis of sRCC patients. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), nevertheless, elevated LMR showed an adverse effect on reduced OS. Multivariate analysis revealed that NLR (HR = 4.07, 95% CI = 1.50–11.00, P = 0.006) retained as independent factor. Incorporation of the NLR into a prognostic model including T stage, M stage, tumor necrosis and percentage of sarcomatoid generated a nomogram, which accurately predicted OS for sRCC patients. Preoperative NLR may serve as a potential prognostic biomarker in patients with sRCC and may help with clinical decisions about treatment intervention in clinical practice. The proposed nomogram can be used for the prediction of OS in patients with sRCC. PMID:27035802

  6. Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas.

    PubMed

    Grange, Florent; Petrella, Tony; Beylot-Barry, Marie; Joly, Pascal; D'Incan, Michel; Delaunay, Michele; Machet, Laurent; Avril, Marie-Francoise; Dalac, Sophie; Bernard, Philippe; Carlotti, Agnes; Esteve, Eric; Vergier, Beatrice; Dechelotte, Pierre; Cassagnau, Elisabeth; Courville, Philippe; Saiag, Philippe; Laroche, Liliane; Bagot, Martine; Wechsler, Janine

    2004-05-15

    Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions. PMID:14726400

  7. Prognostic and Safety Roles in Laparoscopic Versus Abdominal Radical Hysterectomy in Cervical Cancer: A Meta-analysis

    PubMed Central

    Cao, Tiefeng; Feng, Yanling; Huang, Qidan; Wan, Ting

    2015-01-01

    Abstract Objective: Studies comparing the prognostic results between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in cervical cancer reported contradictory results. We aimed to evaluate the prognostic and safety roles of LRH by pooling studies in a meta-analysis. Materials and Methods: Original articles were searched in PubMed, EMBASE, and the Cochrane Library. The survival results (5-year disease-free survival [DFS], 5-year overall survival [OS], and recurrence rate [RR]), safety parameters (intra-, peri-, and postoperative complication rates and postoperative bowel or bladder recovery days), efficiency parameters (pelvic/para-aortic lymph nodes removed), and other parameters (operative time, estimated blood loss, and hospital of stay) between the two approaches were reviewed. Results: For the 2922 cases identified, DFS, OS, and RR did not differ in balanced prognostic factors, including lymph node metastasis, Stage IIB or above, non–squamous cancer histology, grade G3, lymphovascular space invasion, tumor size ≥4 cm, and positive parametrial and vaginal margin rates. Meanwhile, LRH was associated with higher complication rates and a shorter time to the recovery of bowel or bladder function than for ARH. The number of removed pelvic or para-aortic lymph nodes did not significantly differ. Other parameters showed LRH was associated with a longer operative time, less blood loss, and a shorter length of hospital stay. The survival and prognostic results did not differ in balanced prognostic factors. Conclusions: LRH is safe and has lower operative complication rates than ARH. PMID:26584414

  8. Fiber optics in adverse environments

    SciTech Connect

    Lyous, P.B.

    1982-01-01

    Radiation effects in optical fibers are considered, taking into account recent progress in the investigation of radiation resistant optical fibers, radiation damage in optical fibers, radiation-induced transient absorption in optical fibers, X-ray-induced transient attenuation at low temperatures in polymer clad silica (PCS) fibers, optical fiber composition and radiation hardness, the response of irradiated optical waveguides at low temperatures, and the effect of ionizing radiation on fiber-optic waveguides. Other topics explored are related to environmental effects on components of fiber optic systems, and radiation detection systems using optical fibers. Fiber optic systems in adverse environments are also discussed, giving attention to the survivability of Army fiber optics systems, space application of fiber optics systems, fiber optic wavelength multiplexing for civil aviation applications, a new fiber optic data bus topology, fiber optics for aircraft engine/inlet control, and application of fiber optics in high voltage substations.

  9. Adverse reactions to food additives.

    PubMed

    Simon, R A

    1986-01-01

    There are thousands of agents that are intentionally added to the food that we consume. These include preservatives, stabilizers, conditioners, thickeners, colorings, flavorings, sweeteners, antioxidants, etc. etc. Yet only a surprisingly small number have been associated with hypersensitivity reactions. Amongst all the additives, FD&C dyes have been most frequently associated with adverse reactions. Tartrazine is the most notorious of them all; however, critical review of the medical literature and current Scripps Clinic studies would indicate that tartrazine has been confirmed to be at best only occasionally associated with flares of urticaria or asthma. There is no convincing evidence in the literature of reactivity to the other azo or nonazo dyes. This can also be said of BHA/BHT, nitrites/nitrates and sorbates. Parabens have been shown to elicit IgE mediated hypersensitivity reactions when used as pharmaceutical preservatives; however, as with the other additives noted above, ingested parabens have only occasionally been associated with adverse reactions. MSG, the cause of the 'Chinese restaurant syndrome' has only been linked to asthma in one report. Sulfiting agents used primarily as food fresheners and to control microbial growth in fermented beverages have been established as the cause of any where from mild to severe and even fatal reactions in at least 5% of the asthmatic population. Other reactions reported to follow sulfite ingestion include anaphylaxis, gastro intestinal complaints and dermatological eruptions. The prevalence of these non asthmatic reactions is unknown. The mechanism of sulfite sensitive asthma is also unknown but most likely involves hyperreactivity to inhale SO2 in the great majority of cases; however, there are reports of IgE mediated reactions and other sulfite sensitive asthmatics have been found with low levels of sulfite oxidase; necessary to oxidize endogenous sulfite to sulfate. PMID:3302664

  10. Prognostic impact of bone marrow fibrosis in primary myelofibrosis. A study of the AGIMM group on 490 patients.

    PubMed

    Guglielmelli, Paola; Rotunno, Giada; Pacilli, Annalisa; Rumi, Elisa; Rosti, Vittorio; Delaini, Federica; Maffioli, Margherita; Fanelli, Tiziana; Pancrazzi, Alessandro; Pieri, Lisa; Fjerza, Rajmonda; Pietra, Daniela; Cilloni, Daniela; Sant'Antonio, Emanuela; Salmoiraghi, Silvia; Passamonti, Francesco; Rambaldi, Alessandro; Barosi, Giovanni; Barbui, Tiziano; Cazzola, Mario; Vannucchi, Alessandro M

    2016-09-01

    The prognostic significance of bone marrow (BM) fibrosis grade in patients with primary myelofibrosis (PMF) is still debated. A fibrosis grade greater than 1 was shown to associate with higher risk of death, and addition of fibrosis grade to IPSS score resulted in a more accurate prediction of survival. The aim of this study was to analyze the prognostic impact of BM fibrosis in 490 patients with PMF, evaluated at diagnosis, molecularly annotated and with extensive follow-up information. We found that fibrosis grade 2 and greater on a 0-3 scale was associated with clinical characteristics indicative of a more advanced disease, such as anemia, leukopenia, thrombocytopenia, constitutional symptoms, larger splenomegaly and a higher IPSS risk category. Patients with higher grade of fibrosis were also more likely to have additional somatic mutations in ASXL1 and EZH2, that are prognostically adverse. Median survival was significantly reduced in patients with grade 2 and 3 fibrosis as compared with grade 1; this effect was maintained when analysis was restricted to younger patients. In multivariate analysis, fibrosis grade independently predicted for survival regardless of IPSS variables and mutational status; the adverse impact of fibrosis was noticeable especially in lower IPSS risk categories. Overall, results indicate that higher grades of fibrosis correlate with unique clinical and molecular aspects and represent an independent adverse variable in patients with PMF; these observations deserve confirmation in prospectively designed series of patients. Am. J. Hematol. 91:918-922, 2016. © 2016 Wiley Periodicals, Inc. PMID:27264006

  11. Adverse events in healthcare: learning from mistakes.

    PubMed

    Rafter, N; Hickey, A; Condell, S; Conroy, R; O'Connor, P; Vaughan, D; Williams, D

    2015-04-01

    Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety. PMID:25078411

  12. Prognostic Factors in Childhood Leukemia (ALL or AML)

    MedlinePlus

    ... for childhood leukemias Prognostic factors in childhood leukemia (ALL or AML) Certain factors that can affect a ... myelogenous leukemia (AML). Prognostic factors for children with ALL Children with ALL are often divided into risk ...

  13. A new prognostic index of severity of intellectual disabilities in Cornelia de Lange syndrome.

    PubMed

    Cereda, Anna; Mariani, Milena; Rebora, Paola; Sajeva, Anna; Ajmone, Paola Francesca; Gervasini, Cristina; Russo, Silvia; Kullmann, Gaia; Valsecchi, Grazia; Selicorni, Angelo

    2016-06-01

    Cornelia de Lange syndrome is a well-known multiple congenital anomalies/intellectual disability syndrome with genetic heterogeneity and wide clinical variability, regarding the severity of both the intellectual disabilities and the physical features, not completely explained by the genotype-phenotype correlations known to date. The aim of the study was the identification of prognostic features, ascertainable precociously in the patient's life, of a better intellectual outcome and the development of a new prognostic index of severity of intellectual disability in CdLS patients. In 66 italian CdLS patients aged 8 years or more, we evaluated the association of the degree of intellectual disability with various clinical parameters ascertainable before 6 months of life and with the molecular data by the application of cumulative regression logistic model. Based on these results and on the previously known genotype-phenotype correlations, we selected seven parameters to be used in a multivariate cumulative regression logistic model to develop a prognostic index of severity of intellectual disability. The probability of a mild ID increases with the reducing final score less than two, the probability of a severe ID increases with the increasing final score more than three. This prognostic index allows to define, precociously in the life of a baby, the probability of a better or worse intellectual outcome in CdLS patients. © 2016 Wiley Periodicals, Inc. PMID:27148700

  14. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    PubMed Central

    Chen, Ying; Zhang, Lei; Liu, Wenxin; Liu, Xiangyu

    2015-01-01

    Tumor-stroma ratio (TSR) has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC) and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P < 0.001). The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%), LN metastasis (51.93% versus 27.25%), and recurrence (34.27% versus 6.82%). Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months) and overall survival (50 versus 58 months), respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC. PMID:26609529

  15. Leptomeningeal metastasis: survival and prognostic factors in 155 patients.

    PubMed

    Herrlinger, Ulrich; Förschler, Heike; Küker, Wilhelm; Meyermann, Richard; Bamberg, Michael; Dichgans, Johannes; Weller, Michael

    2004-08-30

    In this single-center retrospective study, 155 consecutive patients with leptomeningeal metastasis (LM) were analyzed for the prognostic role of patient- and therapy-related variables. Ten percent of the patients received radiotherapy alone, 32% had chemotherapy alone, 31% received radiochemotherapy, 17% had supportive therapy only, and 10% were not evaluable for therapy. Chemotherapy was systemic (17%), combined systemic and intrathecal (10%), or intrathecal only (35%). Clinical improvement was noted in 41% of the patients. Overall median survival time (MST) was 4.8 months. Survival varied considerably depending on the type of primary tumor in this largest published cohort of LM patients. Univariate Cox regression analysis revealed that age >60 and elevated cerebrospinal fluid (CSF) albumin or lactate levels were therapy-independent predictors of poor survival in the entire cohort as well as in the subgroup of patients with systemic primary tumors (n=105). The assessment of three therapy-independent parameters allows to group LM patients into groups of low, intermediate, and high risk of poor survival. Moreover, the application of systemic chemotherapy was a positive prognostic factor in patients with subarachnoid lesions detected by neuroimaging (RR 1.94, p=0.001) or with extra-CNS tumor deposits (RR 1.52, p=0.05). The results of this study suggest that systemic chemotherapy alone or in combination with other therapeutic modalities may improve outcome in patients with subarachnoid tumor cell deposits detectable by neuroimaging. PMID:15337619

  16. Posterior urethral valve: Prognostic factors and renal outcome

    PubMed Central

    Bhadoo, Divya; Bajpai, Minu; Panda, Shasanka Shekhar

    2014-01-01

    Objective: The aim was to study the outcome of posterior urethral valve (PUV) cases treated by stepladder protocol and the prognostic factors affecting the outcome. Materials and Methods: Hospital records of all PUV patients treated by stepladder protocol between January 1992 and December 2013 were reviewed. The studied parameters were: Age at presentation, serum creatinine, types of surgical intervention, vesicoureteral reflux (VUR) on initial voiding cystourethrogram (VCUG), renal cortical scars, plasma renin activity (PRA), and glomerular filtration rate (GFR). Results: Of 396 PUV patients treated during the study period, 152 satisfied study criteria. The age at presentation ranged from 2 days to 15 years (mean 31.3 months). The mean follow-up period was 5 years (range: 2-18 years). Primary endoscopic valve ablation was the most common initial procedure. Chronic renal failure was seen in 42.7% patients at the last follow-up. Serum creatinine at presentation, initial PRA levels, initial GFR, and PRA levels at last follow-up were significant predictors of final renal outcome. Age at presentation (<1 vs. >1 year), presence/absence of VUR on initial VCUG and renal cortical scars had no significant correlation with ultimate renal function. Conclusion: Our study confirms the high prognostic significance of initial serum creatinine, PRA levels and GFR in cases with PUV. PRA also holds promise in long-term follow-up of these patients as a marker of progressive renal damage. PMID:25197189

  17. Prognostic role of sex steroid receptors in pancreatic adenocarcinoma.

    PubMed

    Georgiadou, Despoina; Sergentanis, Theodoros N; Sakellariou, Stratigoula; Vlachodimitropoulos, Dimitris; Psaltopoulou, Theodora; Lazaris, Andreas C; Gounaris, Antonia; Zografos, George C

    2016-01-01

    From the available literature, it is unclear what proportion of pancreatic adenocarcinomas express estrogen receptors (ERα, ERβ), progesterone receptors (PR), and androgen receptors (AR), and if any of these markers have prognostic significance. We aimed to assess (1) the expression and (2) the correlation of the aforementioned markers with clinicopathological parameters and prognosis in patients with pancreatic adenocarcinoma. During a five-year period, 60 patients with pancreatic ductal adenocarcinoma underwent surgical resection at a single institution. Immunohistochemical stains of the studied markers were quantified by Image analysis system. ERα expression was positively associated with PR expression. Moreover, ERβ was inversely associated with the presence of metastases, whereas no significant associations implicated AR. As far as the prognostic significance of the studied receptors is concerned, higher ERα expression correlated with poorer survival at the univariate analysis, but the finding dissipated at the multivariate approach. No significant associations with overall survival were noted regarding the other receptors. The role of sex hormone receptors in the survival from pancreatic adenocarcinoma seems rather limited. Further prospective studies assessing those receptors should ideally be designed in order to confirm our results and possibly outline additional correlations between other steroid receptors and features of pancreatic adenocarcinoma. PMID:26652605

  18. OAE: The Ontology of Adverse Events

    PubMed Central

    2014-01-01

    Background A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. Description The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. Conclusion OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of

  19. Remote sensing data assimilation for a prognostic phenology model

    SciTech Connect

    Thornton, Peter E; Stockli, Reto

    2008-01-01

    Predicting the global carbon and water cycle requires a realistic representation of vegetation phenology in climate models. However most prognostic phenology models are not yet suited for global applications, and diagnostic satellite data can be uncertain and lack predictive power. We present a framework for data assimilation of Fraction of Photosynthetically Active Radiation absorbed by vegetation (FPAR) and Leaf Area Index (LAI) from the MODerate Resolution Imaging Spectroradiometer (MODIS) to constrain empirical temperature, light, moisture and structural vegetation parameters of a prognostic phenology model. We find that data assimilation better constrains structural vegetation parameters than climate control parameters. Improvements are largest for drought-deciduous ecosystems where correlation of predicted versus satellite-observed FPAR and LAI increases from negative to 0.7-0.8. Data assimilation effectively overcomes the cloud- and aerosol-related deficiencies of satellite data sets in tropical areas. Validation with a 49-year-long phenology data set reveals that the temperature-driven start of season (SOS) is light limited in warm years. The model has substantial skill (R = 0.73) to reproduce SOS inter-annual and decadal variability. Predicted SOS shows a higher inter-annual variability with a negative bias of 5-20 days compared to species-level SOS. It is however accurate to within 1-2 days compared to SOS derived from net ecosystem exchange (NEE) measurements at a FLUXNET tower. The model only has weak skill to predict end of season (EOS). Use of remote sensing data assimilation for phenology model development is encouraged but validation should be extended with phenology data sets covering mediterranean, tropical and arctic ecosystems.

  20. Complement Component 1, s Subcomponent Overexpression is an Independent Poor Prognostic Indicator in Patients with Urothelial Carcinomas of the Upper Urinary Tract and Urinary Bladder

    PubMed Central

    Chang, I-Wei; Lin, Victor Chia-Hsiang; Wu, Wen-Jen; Liang, Peir-In; Li, Wei-Ming; Yeh, Bi-Wen; He, Hong-Lin; Liao, Alex Chien-Hwa; Chan, Ti-Chun; Li, Chien-Feng

    2016-01-01

    Purpose: Urothelial carcinoma of the urinary bladder and upper tract is prevalent. By subjecting a documented transcriptome data set of urothelial carcinoma of bladder (GSE31684) to data mining and focusing on genes linked to peptidase activity (GO:0008233), we recognized C1S as the most significantly upregulated gene related to an advanced tumor status and metastasis. We subsequently analyzed the association of both C1S mRNA and its encoded protein expression with the clinical and pathological significance. Materials and Methods: We used real-time reverse transcription polymerase chain reaction to detect C1S transcription levels in 20 cases each of urothelial carcinoma of bladder and upper tract. An immunohistochemical stain was conducted to determine C1s protein expression levels in patients with urothelial carcinoma of upper tract (n = 340) and urinary bladder (n = 295). Furthermore, we examined the correlation of C1s expression with clinicopathological characteristics, disease-specific survival, and metastasis-free survival. Results: C1S transcription levels were significantly high in patients with advanced-stage tumors of both groups (all P < .05). Immunohistochemical analysis revealed that C1s expression levels were significantly associated with adverse clinicopathological parameters in both groups of urothelial carcinoma (all P < .05). C1s overexpression predicted poor disease-specific and metastasis-free survival rates for both urothelial carcinoma groups in the univariate analysis, and it was also an independent prognostic factor in the multivariate analysis (all P < .05). Conclusions: C1s may play a pivotal role in urothelial carcinoma progress and can represent a vital prognostic marker and a promising new therapeutic target in urothelial carcinoma. PMID:27471555

  1. Advanced Ground Systems Maintenance Prognostics Project

    NASA Technical Reports Server (NTRS)

    Harp, Janicce Leshay

    2014-01-01

    The project implements prognostics capabilities to predict when a component, system or subsystem will no longer meet desired functional or performance criteria, called the "end of life." The capability also provides an assessment of the "remaining useful life" of a hardware component.

  2. Prognostic Analysis of the Tactical Quiet Generator

    SciTech Connect

    Hively, Lee M

    2008-09-01

    The U.S. Army needs prognostic analysis of mission-critical equipment to enable condition-based maintenance before failure. ORNL has developed and patented prognostic technology that quantifies condition change from noisy, multi-channel, time-serial data. This report describes an initial application of ORNL's prognostic technology to the Army's Tactical Quiet Generator (TQG), which is designed to operate continuously at 10 kW. Less-than-full power operation causes unburned fuel to accumulate on internal components, thereby degrading operation and eventually leading to failure. The first objective of this work was identification of easily-acquired, process-indicative data. Two types of appropriate data were identified, namely output-electrical current and voltage, plus tri-axial acceleration (vibration). The second objective of this work was data quality analysis to avoid the garbage-in-garbage-out syndrome. Quality analysis identified more than 10% of the current data as having consecutive values that are constant, or that saturate at an extreme value. Consequently, the electrical data were not analyzed further. The third objective was condition-change analysis to indicate operational stress under non-ideal operation and machine degradation in proportion to the operational stress. Application of ORNL's novel phase-space dissimilarity measures to the vibration power quantified the rising operational stress in direct proportion to the less-than-full-load power. We conclude that ORNL's technology is an excellent candidate to meet the U.S. Army's need for equipment prognostication.

  3. Multidisciplinary Prognostication Using the Palliative Prognostic Score in an Australian Cancer Center

    PubMed Central

    Mendis, Ruwani; Soo, Wee-Kheng; Zannino, Diana; Michael, Natasha; Spruyt, Odette

    2015-01-01

    CONTEXT Accurate prognostication is important in oncology and palliative care. A multidisciplinary approach to prognostication provides a novel approach, but its accuracy and application is poorly researched. In this study, we describe and analyze our experience of multidisciplinary prognostication in palliative care patients with cancer. OBJECTIVES To assess our accuracy of prognostication using multidisciplinary team prediction of survival (MTPS) alone and within the Palliative Prognostic (PaP) Score. METHODS This retrospective study included all new patients referred to a palliative care consultation service in a tertiary cancer center between January 2010 and December 2011. Initial assessment data for 421 inpatients and 223 outpatients were analyzed according to inpatient and outpatient groups to evaluate the accuracy of prognostication using MTPS alone and within the PaP score (MTPS-PaP) and their correlation with overall survival. RESULTS Inpatients with MTPS-PaP group A, B, and C had a median survival of 10.9, 3.4, and 0.7 weeks, respectively, and a 30-day survival probability of 81%, 40%, and 10%, respectively. Outpatients with MTPS-PaP group A and B had a median survival of 17.3 and 5.1 weeks, respectively, and a 30-day survival probability of 94% and 50%, respectively. MTPS overestimated survival by a factor of 1.5 for inpatients and 1.2 for outpatients. The MTPS-PaP score correlated better than MTPS alone with overall survival. CONCLUSION This study suggests that a multidisciplinary team approach to prognostication within routine clinical practice is possible and may substitute for single clinician prediction of survival within the PaP score without detracting from its accuracy. Multidisciplinary team prognostication can assist treating teams to recognize and articulate prognosis, facilitate treatment decisions, and plan end-of-life care appropriately. PaP was less useful in the outpatient setting, given the longer survival interval of the outpatient

  4. Beta-2 microglobulin and lactate dehydrogenase levels are useful prognostic markers in early stage primary gastric lymphoma.

    PubMed

    Avilés, A; Narváez, B R

    1998-10-01

    The optimal management of primary gastric lymphoma (PGL) remains undecided because a definitive classification for therapeutic decision is not available. The International Index Project has proved to be useful in patients with nodal disease, but in extranodal presentation it has not been tested. We reviewed 297 patients with early stage PGL. They were initially classified according to the prognostic features of the International Index Project. No influence on duration of time to treatment failure (TTF) or overall survival was observed. For this reason we developed a logistical model to identify prognostic factors in patients with early stage PGL. Levels of beta-2 microglobulin and lactic dehydrogenase were observed to have prognostic significance in both univariate and multivariate analysis. With these parameters we constructed a logistical model to identify patients at low risk (TTF = 76%; at 7 years overall survival was 96%), statistically different to patients at high risk (TTF = 34% and overall survival = 22%). The number of patients at intermediate risk were too small to compare with the other groups. Because pathological or other clinical or laboratory prognostic features cannot help in the identification of a prognostic model, we propose that the use beta-2 microglobulin and lactic dehydrogenase can define different groups at risk and develop a prognostic system to define the best therapeutic approach in this patients. PMID:9807677

  5. Expression and prognostic relevance of MET and phospho-BAD in non-small cell lung cancer

    PubMed Central

    Sun, Wenze; Ai, Ting; Gao, Ying; Zhang, Yingbing; Cui, Jie; Song, Liping

    2013-01-01

    Background MET is involved in the progression of several types of human cancers, while phospho-BAD(Ser-136) is a key molecule in apoptosis and might be regulated by MET. The aim of this study was to investigate the correlation between altered expression of MET and phospho-BAD in non-small cell lung cancer (NSCLC) and their association with clinicopathologic parameters and overall survival. Methods MET and phospho-BAD(Ser-136) proteins were evaluated by immunohistochemical analysis in 183 paraffin-embedded specimens and were also assessed by Western blotting analysis in 12 frozen tumor tissue samples, which were representative examples of immunohistochemical staining. Results Positive expression of MET and phospho-BAD(Ser-136) occurred in 67.2% and 49.2% of the 183 cases of NSCLC, respectively. However, neither MET expression nor phospho-BAD(Ser-136) expression was associated with any clinicopathologic parameter. A significant correlation was found between MET and phospho-BAD(Ser-136) expression levels evaluated by immunohistochemistry (r = 0.268, P < 0.001). Overexpression of MET was significantly associated with shortened overall survival in univariate analysis (P < 0.001). Moreover, patients with a MET+/phospho-BAD(Ser-136)+ phenotype had a poorer prognosis than others (P < 0.001). Multivariate Cox proportional hazard analysis confirmed that MET expression is a prognostic factor for NSCLC. Conclusion MET expression might be correlated with phospho-BAD(Ser-136) expression, and may be an adverse predictor for NSCLC. Activation of the MET/phospho-BAD(Ser-136) signaling pathway might play a role in the development and progression of NSCLC. PMID:24092988

  6. Low health-related quality of life is a predictor of major adverse cardiovascular events in patients with chronic nonischemic heart failure

    PubMed Central

    Zakliczyński, Michał; Owczarek, Aleksander; Partyka, Robert; Mościński, Mateusz; Pudlo, Robert; Kaczmarczyk, Marcin; Zembala, Marian; Poloński, Lech

    2014-01-01

    Introduction The need to indentify patients with chronic heart failure (CHF) at a higher risk of major adverse cardiovascular events (MACEs) has become increasingly important; therefore, new parameters, such as health-related quality of life (HRQoL), are gaining ground. The aim of this study The aim of this study was to determine the risk factors for MACEs, with a special emphasis on HRQoL in chronic non-ischemic heart failure (NIHF) patients. Material and methods This prospective study enrolled 271 hospitalized patients with heart failure symptoms (NYHA II and III), without neoplastic disease, diabetes, hepatic cirrhosis or chronic kidney disease, who had been receiving optimal medical treatment. In all the patients, laboratory examinations, electrocardiography, echocardiography, a 6-minute walking test, invasive right heart pressure measurements and coronary angiography were performed. HRQoL assessment was conducted with the Short-Form Health Survey (SF-36). Clinical observation commenced on admission to the hospital and lasted 3 years. Data concerning MACE incidence (death, transplantation, circulatory support, hospitalization) were obtained during outpatient visits. Results The final analysis enrolled 202 patients, while 17 patients were lost to follow up. The MACE incidence was 42.1%. Major adverse cardiovascular events risk factors in multiple factor analysis were: alkaline phosphatase (hazard ratio [HR] = 1.01; p < 0.05); right ventricular end-diastolic diameter (HR = 1.08; p < 0.001); hsCRP (HR = 1.04; p < 0.05); and the following HRQoL indices: Bodily Pain (HR = 0.98; p < 0.05) and Mental Health (HR = 0.97; p < 0.01). Conclusions Low values for HRQoL parameters (Bodily Pain and Mental Health), right ventricular end-diastolic diameter, serum concentration of hsCRP and alkaline phosphatase are prognostic factors in NIHF patients. PMID:26336436

  7. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis

    PubMed Central

    2012-01-01

    Background Prognostic assessment is important for the management of patients with acute pulmonary embolism (APE). Pulmonary Embolism Severity Index (PESI) and simple PESI (sPESI) are new emerged prognostic assessment tools for APE. The aim of this meta-analysis is to assess the accuracy of the PESI and the sPESI to predict prognostic outcomes (all-cause and PE-related mortality, serious adverse events) in APE patients, and compare between these two PESIs. Methods MEDLINE and EMBASE database were searched up to June 2012 using the terms “Pulmonary Embolism Severity Index” and “pulmonary embolism”. Summary odds ratio (OR) with 95% confidence intervals (CIs) for prognostic outcomes in low risk PESI versus high risk PESI were calculated. Summary receiver operating characteristic curve (SROC) used to estimate overall predicting accuracies of prognostic outcomes. Results Twenty-one studies were included in this meta-analysis. The results showed low-risk PESI was significantly associated with lower all-cause mortality (OR 0.13; 95% CI 0.12 to 0.15), PE-related mortality (OR 0.09; 95% CI 0.05 to 0.17) and serious adverse events (OR 0.34; 95% CI 0.29 to 0.41), with no homogeneity across studies. In sPESI subgroup, the OR of all-cause mortality, PE-related mortality, and serious adverse events was 0.10 (95% CI 0.08 to 0.14), 0.09 (95% CI 0.03 to 0.26) and 0.40 (95% CI 0.31 to 0.51), respectively; while in PESI subgroup, the OR was 0.14 (95% CI 0.13 to 0.16), 0.09 (95% CI 0.04 to 0.21), and 0.30 (95% CI 0.23 to 0.38), respectively. For accuracy analysis, the pooled sensitivity, the pooled specificity, and the overall weighted AUC for PESI predicting all-cause mortality was 0.909 (95% CI: 0.900 to 0.916), 0.411 (95% CI: 0.407 to 0.415), and 0.7853±0.0058, respectively; for PE-related mortality, it was 0.953 (95% CI: 0.913 to 0.978), 0.374 (95% CI: 0.360 to 0.388), and 0.8218±0.0349, respectively; for serious adverse events, it was 0.821 (95% CI: 0.795 to 0.845), 0

  8. bc-GenExMiner: an easy-to-use online platform for gene prognostic analyses in breast cancer.

    PubMed

    Jézéquel, Pascal; Campone, Mario; Gouraud, Wilfried; Guérin-Charbonnel, Catherine; Leux, Christophe; Ricolleau, Gabriel; Campion, Loïc

    2012-02-01

    Gene prognostic meta-analyses should benefit from breast tumour genomic data obtained during the last decade. The aim was to develop a user-friendly, web-based application, based on DNA microarrays results, called "breast cancer Gene-Expression Miner" (bc-GenExMiner) to improve gene prognostic analysis performance by using the same bioinformatics process. bc-GenExMiner was developed as a web-based tool including a MySQL relational database. Survival analyses are performed with R statistical software and packages. Molecular subtyping was performed by means of three single sample predictors (SSPs) and three subtype clustering models (SCMs). Twenty-one public data sets have been included. Among the 3,414 recovered breast cancer patients, 1,209 experienced a pejorative event. Molecular subtyping by means of three SSPs and three SCMs was performed for 3,063 patients. Furthermore, three robust lists of stable subtyped patients were built to maximize reliability of molecular assignment. Gene prognostic analyses are done by means of univariate Cox proportional hazards model and may be conducted on cohorts split by nodal (N), oestrogen receptor (ER), or molecular subtype status. To evaluate independent prognostic impact of genes relative to Nottingham Prognostic Index and Adjuvant! Online, adjusted Cox proportional hazards models are performed. bc-GenExMiner allows researchers without specific computation skills to easily and quickly evaluate the in vivo prognostic role of genes in breast cancer by means of Cox proportional hazards model on large pooled cohorts, which may be split according to different prognostic parameters: N, ER, and molecular subtype. Prognostic analyses by molecular subtype may also be performed in three robust molecular subtype classifications. PMID:21452023

  9. The Biochemical Prognostic Factors of Subclinical Hypothyroidism

    PubMed Central

    Lee, Myung Won; Shin, Dong Yeob; Kim, Kwang Joon; Hwang, Sena

    2014-01-01

    Background Patients with subclinical hypothyroidism (SHT) are common in clinical practice. However, the clinical significance of SHT, including prognosis, has not been established. Further clarifying SHT will be critical in devising a management plan and treatment guidelines for SHT patients. Thus, the aim of this study was to investigate the prognostic factors of SHT. Methods We reviewed the medical records of Korean patients who visited the endocrinology outpatient clinic of Severance Hospital from January 2008 to September 2012. Newly-diagnosed patients with SHT were selected and reviewed retrospectively. We compared two groups: the SHT maintenance group and the spontaneous improvement group. Results The SHT maintenance group and the spontaneous improvement group had initial thyroid-stimulating hormone (TSH) levels that were significantly different (P=0.035). In subanalysis for subjects with TSH levels between 5 to 10 µIU/mL, the spontaneous improvement group showed significantly lower antithyroid peroxidase antibody (anti-TPO-Ab) titer than the SHT maintenance group (P=0.039). Regarding lipid profiles, only triglyceride level, unlike total cholesterol and low density lipoprotein cholesterol, was related to TSH level, which is correlated with the severity of SHT. Diffuse thyroiditis on ultrasonography only contributed to the severity of SHT, not to the prognosis. High sensitivity C-reactive protein and urine iodine excretion, generally regarded as possible prognostic factors, did not show any significant relation with the prognosis and severity of SHT. Conclusion Only initial TSH level was a definite prognostic factor of SHT. TPO-Ab titer was also a helpful prognostic factor for SHT in cases with mildly elevated TSH. Other than TSH and TPO-Ab, we were unable to validate biochemical prognostic factors in this retrospective study for Korean SHT patients. PMID:25031888

  10. Severe cutaneous adverse drug reactions.

    PubMed

    Chung, Wen-Hung; Wang, Chuang-Wei; Dao, Ro-Lan

    2016-07-01

    The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T-cell receptor (TCR): (i) the "hapten/prohapten" theory; (ii) the "p-i concept"; (iii) the "altered peptide repertoire"; and (iv) the "altered TCR repertoire". The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA-B*15:02 for carbamazepine-induced SJS/TEN and HLA-B*58:01 for allopurinol-induced SCAR), involvement of specific TCR, induction of T-cell-mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T-helper 1/2-associated cytokines) and cell death mechanism (e.g. miR-18a-5p-induced apoptosis; annexin A1 and formyl peptide receptor 1-induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin-induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved. PMID:27154258

  11. Differential Prognostic Value of Coronary Computed Tomography Angiography in Relation to Exercise Electrocardiography in Asymptomatic Subjects

    PubMed Central

    Lee, Sang-Eun; Cho, Iksung; Hong, Geu-Ru; Sung, Ji Min; Cho, In-Jeong; Shim, Chi Young; Choi, Byoung Wook; Chung, Namsik

    2015-01-01

    Background To explore the prognostic performance of coronary computed tomography angiography (CCTA) and exercise electrocardiography (XECG) in asymptomatic subjects. Methods We retrospectively enrolled 812 (59 ± 9 years, 60.8% male) asymptomatic subjects who underwent CCTA and XECG concurrently from 2003 through 2009. Subjects were followed-up for major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, unstable angina, and revascularization after 90 days from index CCTA. Results The prevalence of occult coronary artery disease (CAD) detected by CCTA was 17.5% and 120 subjects (14.8%) had positive XECG. During a mean follow-up of 37 ± 16 months, nine subjects experienced MACE. In multivariable Cox-regression analysis, only the presence of CAD by CCTA independently predicted future MACE (p = 0.002). Moreover, CAD by CCTA improved the predictive value when added to a clinical risk factor model using the likelihood ratio test (p < 0.001). Notably, the prognostic value of CCTA persisted in the moderate-to-high-risk group as classified by the Duke treadmill score (p = 0.040), but not in the low-risk group (p = 0.991). Conclusion CCTA provides incremental prognostic benefit over and above XECG in an asymptomatic population, especially for those in a moderate-to-high-risk group as classified by the Duke treadmill score. Risk stratification using XECG may prove valuable for identifying asymptomatic subjects who can benefit from CCTA. PMID:26755933

  12. The Prognostic Value of Amplitude-Integrated EEG in Full-Term Neonates with Seizures

    PubMed Central

    Liu, Lili; Hou, Xinlin; Sun, Guoyu; Li, Lei; Liu, Yunzhe; Zhou, Congle; Gu, Ruolei; Luo, Yuejia

    2013-01-01

    Neonatal seizures pose a high risk for adverse outcome in survived infants. While the prognostic value of amplitude-integrated electroencephalogram (aEEG) is well established in neonates with encephalopathy and asphyxia, neonatal seizure studies focusing on the direct correlation between early aEEG measurement and subsequent neurologic outcome are scarce. In this study, the prognostic value of aEEG features was systematically analyzed in 143 full-term neonates to identify prognostic indicators of neurodevelopmental outcome. Neonatal aEEG features of background pattern, cyclicity, and seizure activity, as well as the etiology of neonatal seizures, were significantly associated with neurodevelopmental outcome at one year of age. aEEG background pattern was highly associated with neurologic outcomes (χ2 = 116.9), followed by aEEG cyclicity (χ2 = 87.2) and seizure etiology (χ2 = 79.3). Multiple linear regression showed that the four predictors explained 71.2% of the variation in neurological outcome, with standardized β coefficients of 0.44, 0.24, 0.22, and 0.14 for the predictors of aEEG background pattern, cyclicity, etiology, and aEEG seizure activity, respectively. This clinically applicable scoring system based on etiology and three aEEG indices would allow pediatricians to assess the risk for neurodevelopmental impairment and facilitate an early intervention in newborns developing seizures. PMID:24236076

  13. 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

  14. 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.

  15. Visceral adipose tissue is prognostic for survival of diffuse large B cell lymphoma treated with frontline R-CHOP.

    PubMed

    Shin, Dong-Yeop; Kim, Areumnuri; Byun, Byung Hyun; Moon, Hansol; Kim, Soyeun; Ko, Young-Jin; Kim, Min-Jung; Lee, Hyo-Rak; Kang, Hye-Jin; Na, Im Il; Park, Sunhoo; Lee, Seung Sook; Yang, Sung-Hyun

    2016-02-01

    The potential role of visceral adipose tissue (VAT) as a prognostic factor in patients with diffuse large B cell lymphoma (DLBCL) treated with frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy was explored. Total adipose tissue and VAT were measured by analyzing positron emission tomography (PET)/computed tomography (CT) images obtained during the initial staging of patients with DLBCL. The VAT ratio was calculated as follows: VAT ratio = VAT area/total adipose tissue area. Body mass index (BMI), sex, and International Prognostic Index (IPI) were also incorporated as co-variates in the final model of multivariate Cox regression analysis for survival. A total of 156 patients with DLBCL, who were treated with frontline R-CHOP, were enrolled in our study. The median patient age was 61 years, and 81 patients were male (51.9 %). The median cycle of R-CHOP was six. The IPI risk group was a strong prognostic factor for progression-free survival (PFS) and overall survival (OS) (p < 0.001). Obese BMIs were an independent prognostic factor for PFS, but not for OS in multivariate analyses, compared to patients with normal BMIs (HR = 0.43, 95 % CI = 0.19-0.98, and p = 0.046 for PFS). A high VAT ratio (third tertile) was an independent adverse prognostic factor for PFS and OS in multivariate analyses (HR = 2.87 and 2.66, 95 % CI = 1.30-6.32 and 1.30-5.44, and p = 0.009 and 0.007 for PFS and OS, respectively). VAT ratio was an independent prognostic factor for patients with DLBCL treated with first-line R-CHOP; thus, additional large prospective studies are warranted. PMID:26658607

  16. CD69 is independently prognostic in chronic lymphocytic leukemia: a comprehensive clinical and biological profiling study

    PubMed Central

    Del Poeta, Giovanni; Del Principe, Maria Ilaria; Zucchetto, Antonella; Luciano, Fabrizio; Buccisano, Francesco; Maria Rossi, Francesca; Bruno, Antonio; Biagi, Annalisa; Bulian, Pietro; Maurillo, Luca; Neri, Benedetta; Bomben, Riccardo; Simotti, Cristina; Coletta, Angela Maria; Dal Bo, Michele; de Fabritiis, Paolo; Venditti, Adriano; Gattei, Valter; Amadori, Sergio

    2012-01-01

    Background CD69 is expressed in several hemopoietic cells and is an early activation marker in chronic lymphocytic leukemia. Chronic lymphocytic leukemia is a clinically heterogeneous disease which needs novel prognostic parameters which can be easily and efficiently managed. Design and Methods We investigated CD69 by flow cytometry in a series of 417 patients affected by chronic lymphocytic leukemia and compared this to other biological and clinical prognosticators. Results CD69 was associated with Rai stages (P=0.00002), β2-microglobulin (P=0.0005) and soluble CD23 (P<0.0001). CD69 and ZAP-70 (P=0.018) or CD38 (P=0.00015) or immunoglobulin variable heavy chain gene mutations (P=0.0005) were also significantly correlated. Clinically, CD69 positive chronic lymphocytic leukemias received chemotherapy more frequently (74%; P<0.0001), and presented a shorter duration of response after fludarabine plus rituximab (P=0.010) as well as shorter progression free survival and overall survival (P<0.0001). CD69 demonstrated true additive prognostic properties, since the CD69+ plus ZAP-70+ or CD38+ or immunoglobulin variable heavy chain gene unmutated patients had the worst progression free survival and overall survival (P<0.0001). Interestingly, low CD69 expression was necessary to correctly prognosticate the longer progression free survival of patients with a low tumor burden of β2-microglobulin (P=0.002), of soluble CD23 (P=0.020), or of Rai stages 0-I (P=0.005). CD69 was confirmed to be an independent prognostic factor in multivariate analysis of progression free survival (P=0.017) and overall survival (P=0.039). Conclusions Our data indicate that CD69 is significantly correlated with poor clinical and biological prognostic factors and is confirmed to be an independent disease prognosticator. This supports its introduction in a routine laboratory assessment and, possibly, in a prognostic scoring system for chronic lymphocytic leukemia, after an adequate standardization

  17. Clinicopathological prognostic and theranostic markers in pituitary tumors.

    PubMed

    Vasiljevic, Alexandre; Jouanneau, Emmanuel; Trouillas, Jacqueline; Raverot, Gérald

    2016-09-01

    More than just the confirmation of an endocrinological diagnosis, the pathological analysis of pituitary endocrine tumors may contribute to bring crucial information in prognosis as well as useful insights in therapeutic management. Taken individually, parameters such as histopathological subtyping, Ki-67-labelling or P53 immunoexpression cannot accurately predict the outcome of patients affected by such tumors. Conversely, "mixed" classification integrating invasion assessment by imaging to histopathological diagnosis may give critical prognostic information and help the clinician in identifying those aggressive tumors that will require a careful follow-up and a more vigorous postoperative treatment. Analysis of theranostic factors such as O6-methylguanine-DNA methyl-transferase or somatostatin receptor expression may guide the choice of postoperative treatment. PMID:26940458

  18. Left Atrial Volume and Adverse Cardiovascular Outcomes in Unselected Patients with and without CKD

    PubMed Central

    Hee, Leia; Nguyen, Tuan; Whatmough, Melinda; Descallar, Joseph; Chen, Jack; Kapila, Shruti; French, John K.

    2014-01-01

    Background and objectives Patients with CKD have increased cardiovascular morbidity and mortality. This study investigated the prognostic value of common clinical echocardiographic parameters. Design, setting, participants, & measurements There were 289 unselected consecutive patients who had a transthoracic echocardiogram between January and June 2003. Patients with stage 3 or 4 CKD (n=49) were compared with those with eGFR≥60 ml/min per 1.73 m2, n=240). Left ventricular volume, ejection fraction and mass, left atrial volume, and function parameters were measured. The primary endpoint, determined a priori, was a composite of cardiac death, myocardial infarction, and congestive cardiac failure. Results Patients were followed for a median 5.6 years. The incidence of the primary endpoint was higher in patients with CKD (29% versus 12%, P=0.001), who were older and had a higher prevalence of hypertension and ischemic heart disease. Indexed left ventricular mass (LVMI) and left atrial volume (LAVI) were higher in patients with CKD. Furthermore, patients with LAVI>32 ml/m2 had significantly lower event-free survival than patients with normal (<28 ml/m2) or mildly dilated LAVI (28–32 ml/m2) (P<0.001). Multivariate analysis showed that age (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.08 to 1.31; P=0.001) and LVMI (OR, 3.66; 95% CI, 2.47 to 5.41; P<0.001) were independently associated with LAVI>32 ml/m2. Multivariate Cox regression analysis demonstrated that CKD (hazard ratio [HR], 1.13; 95% CI, 1.01 to 1.26; P=0.04), hypertension (HR, 2.18; 95% CI, 1.05 to 4.54; P=0.04), and a larger LAVI (HR, 1.35; 95% CI, 1.02 to 1.77; P=0.04) were independent predictors of the primary endpoint. Conclusions Patients with CKD were at higher risk for cardiovascular events. LAVI was significantly larger in the CKD group and was a predictor of adverse cardiac events. PMID:24923578

  19. [Acute adverse effects of dialysis].

    PubMed

    Opatrný, K

    2003-02-01

    Adverse reactions to dialyzers are a not very frequent, but because of the serious, sometimes fatal course, a dreaded complication of haemodialysis treatment. Most important among these reactions are hypersensitive reactions (anaphylactoid, reaction type A to dialyzer), which develop as a rule within the 10th minute of the procedure, and the reaction caused by the action of perfluorohydrocarbon which develop hours after onset or even completion of haemodialysis. Explanation of the development of hypersensitive reactions (HSR) by complement activation and formation of anaphylatoxins C3a and C5a during contact of blood with the bioincompatible dialysis membrane has been abandoned. Evidence of the etiological role of ethylene oxide (ETO) in the development of HSR influenced the selection of materials for the production of dialyzers and sterilization during manufacture, it emphasized the importance of rinsing of the dialyzer in the dialysis centre and led to the wide application of alternative methods of sterilization by gamma radiation and steam. HSR may be also caused by overproduction of bradykinin and inhibition of its degradation or degradation of its metabolites. Excessive bradykinin production caused by dialysis membranes with a negative charge is potentiated e.g. by a lower pH and increased plasma dilution in the initial stage of haemodialysis. Inhibition of bradykinin degradation develops during treatment with angiotensin converting enzyme inhibitors (ACEI). In prevention of HSR associated with bradykinin in addition to elimination of a combination of a negatively charged dialysis membrane and ACEI treatment a part is played also by rinsing of the dialyzer before haemodialysis with a bicarbonate solution and the modification of the membrane surface (implemented by the manufacturer) which reduces its negative charge. The first reaction to the dialyzer in conjunction with perfluorohydrocarbon (PF-5070), used in production of some dialyzers for testing the

  20. Prognostic significance of preoperative fibrinogen in patients with colon cancer

    PubMed Central

    Sun, Zhen-Qiang; Han, Xiao-Na; Wang, Hai-Jiang; Tang, Yong; Zhao, Ze-Liang; Qu, Yan-Li; Xu, Rui-Wei; Liu, Yan-Yan; Yu, Xian-Bo

    2014-01-01

    AIM: To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients. METHODS: A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1st 2005 to June 1st 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P < 0.05). In contrast, there was no significant difference between OS and DFS in stage I patients with low or high fibrinogen levels. Cox regression analysis indicated preoperative fibrinogen levels, TNM stage, mGPS score, CEA, and

  1. Towards Prognostics of Power MOSFETs: Accelerated Aging and Precursors of Failure

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Saxena, Abhinav; Wysocki, Philip; Saha, Sankalita; Goebel, Kai

    2010-01-01

    This paper presents research results dealing with power MOSFETs (metal oxide semiconductor field effect transistor) within the prognostics and health management of electronics. Experimental results are presented for the identification of the on-resistance as a precursor to failure of devices with die-attach degradation as a failure mechanism. Devices are aged under power cycling in order to trigger die-attach damage. In situ measurements of key electrical and thermal parameters are collected throughout the aging process and further used for analysis and computation of the on-resistance parameter. Experimental results show that the devices experience die-attach damage and that the on-resistance captures the degradation process in such a way that it could be used for the development of prognostics algorithms (data-driven or physics-based).

  2. Serum LAMC2 enhances the prognostic value of a multi-parametric panel in non-small cell lung cancer

    PubMed Central

    Korbakis, D; Dimitromanolakis, A; Prassas, I; Davis, G J; Barber, E; Reckamp, K L; Blasutig, I; Diamandis, E P

    2015-01-01

    Background: Non-small cell lung cancer (NSCLC) lacks reliable serological biomarkers for predicting patients' survival and response to treatment. The present study examined the capability of serum LAMC2 and four known tumour markers for disease prognosis and patients' risk stratification. Methods: LAMC2, CA 125, CEA, CYFRA 21-1 and SCC levels were retrospectively measured in sera obtained from 127 patients diagnosed with NSCLC by commercial immunoassays. Prognostic performance of the markers was compared with established clinical parameters and multivariate models were constructed to assess the prognostic complementarity of variables. Results: LAMC2 showed significant prognostic ability for overall survival (hazards ratio: 1.607, 95% confidence interval: 1.268–2.037, P<0.0001) in the full cohort. LAMC2 and CYFRA 21-1 combination enhanced prognostic models based on common clinical parameters (c-index: 0.81 vs 0.72, P=0.00018), further enabling stratification of patients into clear risk groups. A bootstrap-based cross-validation analysis was supportive of our findings. Combination of LAMC2 and CA 125 showed similar performance. Conclusions: Our preliminary study proposes LAMC2 as a novel NSCLC prognostic factor. LAMC2 combined with CA 125 and CYFRA 21-1 could aid in clinical prediction of NSCLC patients' overall survival and inform clinical practice. Larger studies are necessary to unravel LAMC2's full potential as a new NSCLC biomarker. PMID:26180921

  3. Strategic approaches to adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

  4. Adverse Drug Reactions in Dental Practice

    PubMed Central

    Becker, Daniel E.

    2014-01-01

    Adverse reactions may occur with any of the medications prescribed or administered in dental practice. Most of these reactions are somewhat predictable based on the pharmacodynamic properties of the drug. Others, such as allergic and pseudoallergic reactions, are less common and unrelated to normal drug action. This article will review the most common adverse reactions that are unrelated to drug allergy. PMID:24697823

  5. Effect of wettability on adverse mobility immiscible floods

    SciTech Connect

    Vives, M.T.; Chang, Y.C.; Mohanty, K.K.

    1995-12-31

    Many immiscible displacements in reservoirs occur at adverse mobility. Effect of wettability on these displacements is not well understood and often ignored in reservoir simulation. Recent macroscopic theories of viscous fingering treat adverse immiscible flows similar to miscible flows, the mixing in the fingered region being controlled by a Todd-Longstaff-type functional form. The wettability of the medium is taken into account only through the use of appropriate relative permeabilities. The goal of this paper is to understand the macroscopic bypassing in adverse mobility immiscible floods. Immiscible displacements are conducted in a quarter 5-spot model in both drainage and imbibition modes at similar effective mobility ratios and viscous-to-gravity numbers. The level of bypassing and gravity override is visualized and measured. Tertiary water-alternating-gas (WAG) displacements are also conducted at various WAG ratios and viscosity ratios. Fractional flow analysis and numerical simulation are used to understand these displacements. Experiments show that macroscopic viscous fingering is present in adverse viscosity immiscible displacements where no saturation shock is expected from 1-D fractional flow theory. Bypassing due to both fingering and gravity override is higher in the drainage mode than in the imbibition mode, with other key parameters being the same. Optimum WAG ratio in water-wet rock is a function of oil/solvent viscosity ratio. The macroscopic flow theory needs to include capillarity and viscous fingering to match these experimental findings.

  6. Diffuse large B-cell lymphoma of the breast: prognostic factors and treatment outcomes

    PubMed Central

    Sun, Yao; Joks, Monika; Xu, Li-Ming; Chen, Xiu-Li; Qian, Dong; You, Jin-Qiang; Yuan, Zhi-Yong

    2016-01-01

    Background The breast is a rare site of extranodal involvement of diffuse large B-cell lymphoma (DLBCL). We aimed to assess the clinical characteristics, prognostic factors, and treatment outcomes of breast DLBCL. Patients and methods We retrospectively analyzed 113 patients (from our institution and the literature) between 1973 and 2014. The primary end point was overall survival (OS). Kaplan–Meier OS curves were compared with the log-rank test. Cox regression analysis was applied to determine the prognostic factors for OS, progression-free survival (PFS), local control (LC), and cause-specific survival (CSS). Results A total of 113 patients were included in the study: 42 cases from our hospital and 71 cases from 12 publications. The median age at diagnosis was 58 years. With a median follow-up time of 39.2 months, the estimated 5-year OS, PFS, LC, and CSS were 71.4%, 58.8%, 75.6%, and 74.9%, respectively. In multivariate analysis, more than four cycles of chemotherapy, having localized cancer, lumpectomy with or without axillary lymph node (ALN) dissection, and low to low-to-intermediate International Prognostic Index were favorable factors for OS. For PFS, significant prognostic factors were rituximab use, B symptoms, and tumor size. As for the local group, lumpectomy with or without ALN dissection and more than four cycles of chemotherapy were favorable factors for OS. Tumor size >4 cm and nonuse of rituximab were adverse factors for PFS. Twenty-one patients (18.6%) developed local relapse and 33 (29.2%) developed systemic relapse. Eight patients had central nervous system relapse (7.3%). Conclusion Our results reveal that local and extended staging criteria can reflect the different prognosis and treatment outcomes of breast DLBCL. Rituximab use, lumpectomy, and more than four cycles of chemotherapy are recommended as a treatment regimen. However, further study is warranted to validate our data. PMID:27103833

  7. Evolving transcriptomic fingerprint based on genome‐wide data as prognostic tools in prostate cancer

    PubMed Central

    Schliekelman, Mark; Shin, Heesun; Erho, Nicholas; Davicioni, Elai

    2015-01-01

    Background Information Prostate cancer (PCa) is a common disease but only a small subset of patients are at risk of developing metastasis and lethal disease, and identifying which patients will progress is challenging because of the heterogeneity underlying tumour progression. Understanding this heterogeneity at the molecular level and the resulting clinical impact is a critical step necessary for risk stratification. Defining genomic fingerprint elucidates molecular variation and may improve PCa risk stratification, providing more accurate prognostic information of tumour aggressiveness (or lethality) for prognostic biomarker development. Therefore, we explored transcriptomic differences between patients with indolent disease outcome and patients who developed metastasis post‐radical prostatectomy using genome‐wide expression data in the post radical prostatectomy clinical space before metastatic spread. Results Based on differential expression analysis, patients with adverse pathological findings who are at higher risk of developing metastasis have a distinct transcriptomic fingerprint that can be detected on surgically removed prostate specimens several years before metastasis detection. Nearly half of the transcriptomic fingerprint features were non‐coding RNA highlighting their pivotal role in PCa progression. Protein‐coding RNA features in the fingerprint are involved in multiple pathways including cell cycle, chromosome structure maintenance and cytoskeleton organisation. The metastatic transcriptomic fingerprint was determined in independent cohorts verifying the association between the fingerprint and metastatic patients. Further, the fingerprint was confirmed in metastasis lesions demonstrating that the fingerprint represents early metastatic transcriptomic changes, suggesting its utility as a prognostic tool to predict metastasis and provide clinical value in the early radical prostatectomy setting. Conclusions Here, we show that transcriptomic

  8. The Predictive Value of Scores Used in Intensive Care Unit for Burn Patients Prognostic

    PubMed Central

    NOVAC, M.; DRAGOESCU, ALICE; STANCULESCU, ANDREEA; DUCA, LUCICA; CERNEA, DANIELA

    2014-01-01

    Purpose: Statistical evaluation of the prognosis of burned patients based on the analysis of prognostic scores as quickly and easily obtainable that track the evolution of burned patient in ICU. Material / Methods: The prospective study included 92 patients were performed with severe burns on 35-67% body surface large area, aiming to establish a cut-off score for each studied and statistically significant prognostic parameter for assessing the risk of mortality. The control group was represented by 20 patients with burns on the body surface of <10%. Results: The death rate was not statistically significant on burned (p> 0.05) sex (male / female), but we had p <0.001 when we referred to the total body surface area, and p <0.05 when we took into account the degree burns, acute respiratory distress syndrome and age. For each index / prognostic score studied by making ROC curve when they take different values, we set a cut-off. Quantification of variables by calculating the area under the ROC curve (AUC), sensitivity and sensitivity, positive predictive value (PPV) and negative predictive value (NPV), allowed a better appreciation of these prognostic scores. Conclusions: These systems applicable to the burned patient scores, making a cut-off of each index / mortality probability score, he can manifest usefulness in medical decision making process and strategy to reduce the risk of death in patients with severe burns. PMID:26793322

  9. Nurses must report adverse drug reactions.

    PubMed

    Griffith, Richard

    There is renewed determination throughout the European Union (EU) to reduce the economic cost and high death rate associated with adverse drug reactions through better pharmacovigilance. Timely reporting and sharing of information concerning adverse drug reactions is vital to the success of this initiative. In the UK, the reporting of serious adverse drug reactions is facilitated by the Yellow Card Scheme, yet despite being well placed to monitor the effect of medicines on patients, nurses do not make full use of the scheme. This article sets out the impact of adverse drug reactions in the EU and argues that it is essential that nurses must be at the vanguard of adverse reaction reporting if the EU's pharmacovigilance initiative is to be a success. PMID:23905231

  10. Adulthood personality correlates of childhood adversity

    PubMed Central

    Carver, Charles S.; Johnson, Sheri L.; McCullough, Michael E.; Forster, Daniel E.; Joormann, Jutta

    2014-01-01

    Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, which we termed anger/aggression, extrinsic focus, agreeableness, and engagement. Results: Controlling for concurrent depressive symptoms and gender, higher levels of reported childhood adversity related to lower agreeableness and to higher anger/aggression and extrinsic focus. Conclusions: Findings suggest that early adversity is linked to personality variables relevant to the building of social connection. PMID:25484874

  11. Understanding adverse events: human factors.

    PubMed Central

    Reason, J

    1995-01-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  12. Platelet to lymphocyte ratio as a prognostic marker in primary percutaneous coronary intervention.

    PubMed

    Ayça, Burak; Akin, Fatih; Çelik, Ömer; Yüksel, Yasin; Öztürk, Derya; Tekiner, Fatih; Çetin, Şükrü; Okuyan, Ertuğrul; Dinçkal M, Hakan

    2015-01-01

    We assessed the prognostic value of the platelet to lymphocyte ratio (PLR) in primary percutaneous coronary intervention (pPCI). Patients (n = 440) with acute myocardial infarction (AMI) who underwent pPCI were divided into 2 groups: low PLR (<137) and high PLR (>137). "Thrombolysis In Myocardial Infarction" (TIMI) flow grades and Syntax scores (SXS) were calculated from initial angiograms. In-hospital mortality rate and cardiac adverse events were obtained from medical records. Patients with high PLR had more no-reflow, higher SXS and higher mortality rate (p < 0.001, p < 0.001 and p = 0.008, respectively). In receiver operating characteristic curve analysis, high PLR predicted development of no-reflow (specificity 71% and sensitivity 85%), SXS>22 (specificity 52% and sensitivity 61%) and adverse events (specificity 67% and sensitivity 63%). In multivariate regression analysis, PLR was an independent risk factor for no-reflow, SXS>22 and in-hospital adverse events. In addition to PLR, we present the relationship between mean platelet volume, red cell distribution width and neutrophil to lymphocyte ratio and no-reflow, SXS and in-hospital adverse events. PMID:25350375

  13. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Aust, Stefanie; Knogler, Thomas; Pils, Dietmar; Obermayr, Eva; Reinthaller, Alexander; Zahn, Lisa; Radlgruber, Ilja; Mayerhoefer, Marius Erik; Grimm, Christoph; Polterauer, Stephan

    2015-01-01

    Objective Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC). Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs) ascertained by pre-operative computed tomography (CT). Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients. Methods We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient’s outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis. Results Muscle attenuation (MA)—a well established BCM parameter—is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028). Low MA—reflecting a state of cachexia—is also associated with residual tumor after cytoreductive surgery (p = 0.046) and with an unfavorable performance status (p = 0.015). Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively). Conclusion MA—ascertained by routine pre-operative CT—is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA. PMID:26457674

  14. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

    Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

  15. Assessing calibration of prognostic risk scores.

    PubMed

    Crowson, Cynthia S; Atkinson, Elizabeth J; Therneau, Terry M

    2016-08-01

    Current methods used to assess calibration are limited, particularly in the assessment of prognostic models. Methods for testing and visualizing calibration (e.g. the Hosmer-Lemeshow test and calibration slope) have been well thought out in the binary regression setting. However, extension of these methods to Cox models is less well known and could be improved. We describe a model-based framework for the assessment of calibration in the binary setting that provides natural extensions to the survival data setting. We show that Poisson regression models can be used to easily assess calibration in prognostic models. In addition, we show that a calibration test suggested for use in survival data has poor performance. Finally, we apply these methods to the problem of external validation of a risk score developed for the general population when assessed in a special patient population (i.e. patients with particular comorbidities, such as rheumatoid arthritis). PMID:23907781

  16. Prognostics for Electronics Components of Avionics Systems

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Saha, Bhaskar; Wysocki, Philip F.; Goebel, Kai F.

    2009-01-01

    Electronics components have and increasingly critical role in avionics systems and for the development of future aircraft systems. Prognostics of such components is becoming a very important research filed as a result of the need to provide aircraft systems with system level health management. This paper reports on a prognostics application for electronics components of avionics systems, in particular, its application to the Isolated Gate Bipolar Transistor (IGBT). The remaining useful life prediction for the IGBT is based on the particle filter framework, leveraging data from an accelerated aging tests on IGBTs. The accelerated aging test provided thermal-electrical overstress by applying thermal cycling to the device. In-situ state monitoring, including measurements of the steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

  17. [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. PMID:25726309

  18. Prognostic Value of Colorectal Cancer Biomarkers

    PubMed Central

    Bianchi, Paolo; Laghi, Luigi; Delconte, Gabriele; Malesci, Alberto

    2011-01-01

    Despite the large amount of data in cancer biology and many studies into the likely survival of colorectal cancer (CRC) patients, knowledge regarding the issue of CRC prognostic biomarkers remains poor. The Tumor-Node-Metastasis (TNM) staging system continues to be the most powerful and reliable predictor of the clinical outcome of CRC patients. The exponential increase of knowledge in the field of molecular genetics has lead to the identification of specific alterations involved in the malignant progression. Many of these genetic alterations were proposed as biomarkers which could be used in clinical practice to estimate CRC prognosis. Recently there has been an explosive increase in the number of putative biomarkers able to predict the response to specific adjuvant treatment. In this review we explore and summarize data concerning prognostic and predictive biomarkers and we attempt to shed light on recent research that could lead to the emergence of new biomarkers in CRC. PMID:24212797

  19. Stage-specific prognostic biomarkers in melanoma.

    PubMed

    Cheng, Yabin; Lu, Jing; Chen, Guangdi; Ardekani, Gholamreza Safaee; Rotte, Anand; Martinka, Magdalena; Xu, Xuezhu; McElwee, Kevin J; Zhang, Guohong; Zhou, Youwen

    2015-02-28

    The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression. Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients). Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities. PMID:25784655

  20. 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.

  1. Prognostic significance of QRS duration and morphology.

    PubMed

    Brenyo, Andrew; Zaręba, Wojciech

    2011-01-01

    QRS duration and morphology, evaluated via a standard 12-lead electrocardiogram (ECG), represent an opportunity to derive useful prognostic information regarding the risk of subsequent cardiac events or therapeutic outcomes. Prolonged QRS duration, and the presence of intraventricular conduction abnormalities, usually indicate the presence of changes in the myocardium due to underlying heart disease. Prolonged QRS duration is often associated with depressed ejection fraction or enlarged left ventricular volumes, but several studies have demonstrated that this simple ECG measure provides independent prognostic value, after adjusting for relevant clinical covariates. Post-infarction patients with prolonged QRS duration have a significantly increased risk of mortality, although data associating QRS prolongation specifically with sudden death is less supportive. In non-ischemic cardiomyopathy, there is no evidence that QRS duration has prognostic significance in predicting mortality or sudden death. Prolonged QRS duration, and especially presence of left bundle branch block, seems to predict a benefit from cardiac resynchronization therapy in both ischemic and non-ischemic cardiomyopathy patients. Therefore, QRS duration and morphology should not only be considered a predictor of death or sudden death in patients after myocardial infarction, and in those suspected of coronary artery disease, but also as a predictor of benefit from cardiac resynchronization therapy in patients with heart failure, whether of an ischemic or non-ischemic origin. PMID:21305480

  2. New prognostic biomarkers in multiple myeloma.

    PubMed

    Szudy-Szczyrek, Aneta; Szczyrek, Michał; Soroka-Wojtaszko, Maria; Hus, Marek

    2016-01-01

    Multiple myeloma is a malignant neoplastic disease, characterized by uncontrolled proliferation and accumulation of plasma cells in the bone marrow, which is usually connected with production of a monoclonal protein. It is the second most common hematologic malignancy. It constitutes approximately 1% of all cancers and 10% of hematological malignancies. Despite the huge progress that has been made in the treatment of multiple myeloma in the past 30 years including the introduction of new immunomodulatory drugs and proteasome inhibitors, it is still an incurable disease. According to current data, the five-year survival rate is 45%. Multiple myeloma is a very heterogeneous disease with a very diverse clinical course, which is expressed by differences in effectiveness of therapeutic strategies and ability to develop chemoresistance. This diversity implies the need to define risk stratification factors that would help to create personalized and optimized therapy and thereby improve treatment outcomes. Prognostic markers that aim to objectively evaluate the risk of a poor outcome, relapse and the patient's overall outcome are useful for this purpose. The existing, widely used prognostic classifications, such as the Salmon-Durie classification or ISS, do not allow for individualization of treatment. As a result of the development of diagnostic techniques, especially cytogenetics and molecular biology, we were able to discover a lot of new, more sensitive and specific prognostic factors. The paper presents recent reports on the role of molecular, cytogenetic and biochemical alterations in pathogenesis and prognosis of the disease. PMID:27463592

  3. Prognostic factors in neuroendocrine cervical carcinoma

    PubMed Central

    Lee, Da Yong; Chong, Chul; Kim, Jae Weon; Park, Noh Hyun; Song, Yong Sang; Park, Sang Yoon

    2016-01-01

    Objective To evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine cervical carcinoma (NECC). Methods The records of 61 patients with NECC diagnosed between 2000 and 2014 at Seoul National University Hospital and the National Cancer Center were retrospectively reviewed. Kaplan-Meier and Cox regression methods were used for analyses. Results Of the 61 patients, 67.2% were diagnosed at early stage (I to IIA) with a median age of 49 years. Of those, 78% underwent surgery and 75.6% received postoperative adjuvant treatment. For patients diagnosed at advanced stage, 60.0% received chemotherapy only and 25.0% received concurrent chemoradiation therapy. In the univariate analysis, advanced stage (77 vs. 40 months, P=0.013), tumor size ≥2 cm (133 vs. 47 months, P=0.002) and mixed tumor (101 vs. 34 months, P=0.004) were shown to be poor prognostic factors. In the multivariate analysis, tumor stage, tumor size and tumor homology were shown to be independent prognostic factors for overall survival. Of the total, 39.3% of the patients experienced recurrence, and 54.1% of the patients had metastasis. Of the patients diagnosed at early stage, 51.2% experienced recurrence. Conclusion Tumor stage, tumor size and tumor homology were found to be independent prognostic factors in patients with NECC. Even in patients diagnosed at early stage, recurrence and distant metastasis were frequently observed. PMID:27004202

  4. A new cardiopulmonary exercise testing prognosticating algorithm for heart failure patients treated with beta-blockers.

    PubMed

    Corrà, Ugo; Mezzani, Alessandro; Giordano, Andrea; Caruso, Roberto; Giannuzzi, Pantaleo

    2012-04-01

    In 2004, a cardiopulmonary exercise testing (CPET) prognosticating algorithm for heart failure (HF) patients was proposed. The algorithm employed a stepwise assessment of peak oxygen consumption (VO2), slope of regression relating minute ventilation to carbon dioxide output (VE/VCO2) and peak respiratory exchange ratio (RER), and was proposed as an alternative to the traditional strategy of using a single CPET parameter to describe prognosis. Since its initial proposal, the prognosticating algorithm has not been reassessed, although a re-evaluation is in order given the fact that new HF therapies, such as beta-blocker therapy, have significantly improved survival in HF. The present review, based on a critical examination of CPET outcome studies in HF patients regularly treated with beta-blockers, suggests a new prognosticating algorithm. The algorithm comprises four CPET parameters: peak RER, exertional oscillatory ventilation (EOV), peak VO2 and peak systolic blood pressure (SBP). Compared to previous proposals, the present preliminary attempt includes EOV instead of VE/VCO2 slope as ventilatory CPET parameter, and peak SBP as hemodynamic-derived index. PMID:21450608

  5. Evaluation of Uric Acid as a Prognostic Blood-Based Marker in a Large Cohort of Pancreatic Cancer Patients

    PubMed Central

    Stotz, Michael; Szkandera, Joanna; Seidel, Julia; Stojakovic, Tatjana; Samonigg, Hellmut; Reitz, Daniel; Gary, Thomas; Kornprat, Peter; Schaberl-Moser, Renate; Hoefler, Gerald; Gerger, Armin; Pichler, Martin

    2014-01-01

    Background Recently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC. Patients and Methods Data from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated. Results None of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus ≥5.1 mg/dl, p = 0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR = 1.373%; CI = 1.077–1.751; p = 0.011). Conclusion In conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management. PMID:25133546

  6. Collateral Adverse Outcomes After Lumbar Spine Surgery.

    PubMed

    Daniels, Alan H; Gundle, Kenneth; Hart, Robert A

    2016-01-01

    Collateral adverse outcomes are the expected or unavoidable results of a procedure that is performed in a standard manner and typically experienced by the patient. Collateral adverse outcomes do not result from errors, nor are they rare. Collateral adverse outcomes occur as the direct result of a surgical procedure and must be accepted as a trade-off to attain the intended benefits of the surgical procedure. As such, collateral adverse outcomes do not fit into the traditional definition of a complication or adverse event. Examples of collateral adverse outcomes after lumbar spine arthrodesis include lumbar stiffness, postoperative psychological stress, postoperative pain, peri-incisional numbness, paraspinal muscle denervation, and adjacent-level degeneration. Ideally, a comparison of interventions for the treatment of a clinical condition should include information on both the negative consequences (expected and unexpected) and potential benefits of the treatment options. The objective evaluation and reporting of collateral adverse outcomes will provide surgeons with a more complete picture of invasive interventions and, thus, the improved ability to assess alternative treatment options. PMID:27049197

  7. Adverse event recording post hip fracture surgery.

    PubMed

    Doody, K; Mohamed, K M S; Butler, A; Street, J; Lenehan, B

    2013-01-01

    Accurate recording of adverse events post hip fracture surgery is vital for planning and allocating resources. The purpose of this study was to compare adverse events recorded prospectively at point of care with adverse recorded by the Hospital In-Patient Enquiry (HIPE) System. The study examined a two month period from August to September 2011 at University Hospital Limerick. Out of a sample size of 39, there were 7 males (17.9%) and 32 females (82.1%) with an age range of between 53 and 98 years. The mean age was 80.5 years. 55 adverse events were recorded, in contrast to the HIPE record of 13 (23.6%) adverse events. The most common complications included constipation 10 (18.2%), anaemia 8 (14.5%), urinary retention 8 (14.50%), pneumonia 5 (9.1%) and delirium 5 (9.1%). Of the female cohort, 24 (68.8%) suffered an adverse event, while only 4 (57%) males suffered an adverse event. PMID:24579408

  8. Sun exposure and melanoma prognostic factors

    PubMed Central

    GANDINI, SARA; MONTELLA, MAURIZIO; AYALA, FABRIZIO; BENEDETTO, LUCIA; ROSSI, CARLO RICCARDO; VECCHIATO, ANTONELLA; CORRADIN, MARIA TERESA; DE GIORGI, VINCENZO; QUEIROLO, PAOLA; ZANNETTI, GUIDO; GIUDICE, GIUSEPPE; BORRONI, GIOVANNI; FORCIGNANÒ, ROSACHIARA; PERIS, KETTY; TOSTI, GIULIO; TESTORI, ALESSANDRO; TREVISAN, GIUSTO; SPAGNOLO, FRANCESCO; ASCIERTO, PAOLO A.

    2016-01-01

    Previous studies have reported an association between sun exposure and the increased survival of patients with cutaneous melanoma (CM). The present study analyzed the association between ultraviolet (UV) light exposure and various prognostic factors in the Italian Clinical National Melanoma Registry. Clinical and sociodemographic features were collected, as well as information concerning sunbed exposure and holidays with sun exposure. Analyses were performed to investigate the association between exposure to UV and melanoma prognostic factors. Between December 2010 and December 2013, information was obtained on 2,738 melanoma patients from 38 geographically representative Italian sites. A total of 49% of the patients were >55 years old, 51% were men, 50% lived in the north of Italy and 57% possessed a high level of education (at least high school). A total of 8 patients had a family history of melanoma and 56% had a fair phenotype (Fitzpatrick skin type I or II). Of the total patients, 29% had been diagnosed with melanoma by a dermatologist; 29% of patients presented with a very thick melanoma (Breslow thickness, >2 mm) and 25% with an ulcerated melanoma. In total, 1% of patients had distant metastases and 13% exhibited lymph node involvement. Holidays with sun exposure 5 years prior to CM diagnosis were significantly associated with positive prognostic factors, including lower Breslow thickness (P<0.001) and absence of ulceration (P=0.009), following multiple adjustments for factors such as sociodemographic status, speciality of doctor performing the diagnosis and season of diagnosis. Sunbed exposure and sun exposure during peak hours of sunlight were not significantly associated with Breslow thickness and ulceration. Holidays with sun exposure were associated with favorable CM prognostic factors, whereas no association was identified between sunbed use and sun exposure during peak hours of sunlight with favorable CM prognostic factors. However, the results of the

  9. Usefulness of Geriatric Nutritional Risk Index for Assessing Nutritional Status and Its Prognostic Impact in Patients Aged ≥65 Years With Acute Heart Failure.

    PubMed

    Honda, Yasuyuki; Nagai, Toshiyuki; Iwakami, Naotsugu; Sugano, Yasuo; Honda, Satoshi; Okada, Atsushi; Asaumi, Yasuhide; Aiba, Takeshi; Noguchi, Teruo; Kusano, Kengo; Ogawa, Hisao; Yasuda, Satoshi; Anzai, Toshihisa

    2016-08-15

    Malnutrition is becoming one of the most important determinants of worse clinical outcomes in patients with acute heart failure (AHF). However, appropriate tools for evaluating the nutritional status in patients aged ≥65 years with AHF remain unclear. We examined 490 consecutive patients aged ≥65 years with AHF. They were divided into 2 groups according to Geriatric Nutritional Risk Index (GNRI; cut-off value = 92). During a median period of 189 days, the mortality rate was significantly higher in the lower GNRI group than the higher GNRI group (p <0.001). In multivariate analyses, lower GNRI was an independent determinant of adverse events (HR 0.92, 95% CI 0.88 to 0.95, p <0.001). The GNRI showed the best prognostic value (C-statistic: 0.70) among other nutritional indexes. Adding GNRI to an existing outcome prediction model for mortality in AHF significantly increased the C-statistic from 0.68 to 0.74 (p = 0.017). The net reclassification improvement afforded by GNRI was 60% overall, 27% for events, and 33% for nonevents (p <0.001). In conclusion, lower GNRI on admission was independently associated with worse clinical outcomes in patients aged ≥65 years with AHF, and it was superior to other nutritional parameters. Furthermore, the assessment of nutritional status using GNRI is very helpful for risk stratification. PMID:27324158

  10. Learning from adverse incidents involving medical devices.

    PubMed

    Amoore, John; Ingram, Paula

    While an adverse event involving a medical device is often ascribed to either user error or device failure, the causes are typically multifactorial. A number of incidents involving medical devices are explored using this approach to investigate the various causes of the incident and the protective barriers that minimised or prevented adverse consequences. User factors, including mistakes, omissions and lack of training, conspired with background factors--device controls and device design, storage conditions, hidden device damage and physical layout of equipment when in use--to cause the adverse events. Protective barriers that prevented or minimised the consequences included staff vigilance, operating procedures and alarms. PMID:12715578

  11. Prognostic significance of pleural or pericardial effusion and the implication of optimal treatment in primary mediastinal large B-cell lymphoma: a multicenter retrospective study in Japan

    PubMed Central

    Aoki, Tomohiro; Izutsu, Koji; Suzuki, Ritsuro; Nakaseko, Chiaki; Arima, Hiroshi; Shimada, Kazuyuki; Tomita, Akihiro; Sasaki, Makoto; Takizawa, Jun; Mitani, Kinuko; Igarashi, Tadahiko; Maeda, Yoshinobu; Fukuhara, Noriko; Ishida, Fumihiro; Niitsu, Nozomi; Ohmachi, Ken; Takasaki, Hirotaka; Nakamura, Naoya; Kinoshita, Tomohiro; Nakamura, Shigeo; Ogura, Michinori

    2014-01-01

    The prognosis of patients with primary mediastinal large B-cell lymphoma has improved over recent years. However, the optimal treatment strategy including the role of radiotherapy remains unknown. We retrospectively analyzed the clinical outcomes of 345 patients with newly diagnosed primary mediastinal large B-cell lymphoma in Japan. With a median follow up of 48 months, the overall survival at four years for patients treated with R-CHOP (n=187), CHOP (n=44), DA-EPOCH-R (n=9), 2nd- or 3rd-generation regimens, and chemotherapy followed by autologous stem cell transplantation were 90%, 67%, 100%, 91% and 92%, respectively. Focusing on patients treated with R-CHOP, a higher International Prognostic Index score and the presence of pleural or pericardial effusion were identified as adverse prognostic factors for overall survival in patients treated with R-CHOP without consolidative radiotherapy (IPI: hazard ratio 4.23, 95% confidence interval 1.48–12.13, P=0.007; effusion: hazard ratio 4.93, 95% confidence interval 1.37–17.69, P=0.015). Combined with the International Prognostic Index score and the presence of pleural or pericardial effusion for the stratification of patients treated with R-CHOP without radiotherapy, patients with lower International Prognostic Index score and the absence of effusion comprised approximately one-half of these patients and could be identified as curable patients (95% overall survival at 4 years). The DA-EPOCH-R regimen might overcome the effect of these adverse prognostic factors. Our simple indicators of International Prognostic Index score and the presence of pleural or pericardial effusion could stratify patients with primary mediastinal large B-cell lymphoma and help guide selection of treatment. PMID:25216682

  12. Particle filter-based prognostics: Review, discussion and perspectives

    NASA Astrophysics Data System (ADS)

    Jouin, Marine; Gouriveau, Rafael; Hissel, Daniel; Péra, Marie-Cécile; Zerhouni, Noureddine

    2016-05-01

    Particle filters are of great concern in a large variety of engineering fields such as robotics, statistics or automatics. Recently, it has developed among Prognostics and Health Management (PHM) applications for diagnostics and prognostics. According to some authors, it has ever become a state-of-the-art technique for prognostics. Nowadays, around 50 papers dealing with prognostics based on particle filters can be found in the literature. However, no comprehensive review has been proposed on the subject until now. This paper aims at analyzing the way particle filters are used in that context. The development of the tool in the prognostics' field is discussed before entering the details of its practical use and implementation. Current issues are identified, analyzed and some solutions or work trails are proposed. All this aims at highlighting future perspectives as well as helping new users to start with particle filters in the goal of prognostics.

  13. Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin’s lymphoma: identification of prognostic factors predicting outcome

    PubMed Central

    Robinson, Stephen P.; Sureda, Anna; Canals, Carmen; Russell, Nigel; Caballero, Dolores; Bacigalupo, Andrea; Iriondo, Arturo; Cook, Gordon; Pettitt, Andrew; Socie, Gerard; Bonifazi, Francesca; Bosi, Alberto; Michallet, Mauricette; Liakopoulou, Effie; Maertens, Johan; Passweg, Jakob; Clarke, Fiona; Martino, Rodrigo; Schmitz, Norbert

    2009-01-01

    Background The role of reduced intensity conditioning allogeneic stem transplantation (RICalloSCT) in the management of patients with Hodgkin’s lymphoma remains controversial. Design and Methods To further define its role we have conducted a retrospective analysis of 285 patients with HL who underwent a RICalloSCT in order to identify prognostic factors that predict outcome. Eighty percent of patients had undergone a prior autologous stem cell transplantation and 25% had refractory disease at transplant. Results Non-relapse mortality was associated with chemorefractory disease, poor performance status, age >45 and transplantation before 2002. For patients with no risk factors the 3-year non-relapse mortality rate was 12.5% compared to 46.2% for patients with 2 or more risk factors. The use of an unrelated donor had no adverse effect on the non-relapse mortality. Acute graft versus host disease (aGVHD) grades II–IV developed in 30% and chronic GVHD in 42%. The development of cGVHD was associated with a lower relapse rate. The disease progression rate at one and five years was 41% and 58.7% respectively and was associated with chemorefractory disease and extent of prior therapy. Donor lymphocyte infusions were administered to 64 patients for active disease of whom 32% showed a clinical response. Eight out of 18 patients receiving donor lymphocyte infusions alone had clinical responses. Progression-free and overall survival were both associated with performance status and disease status at transplant. Patients with neither risk factor had a 3-year PFS and overall survival of 42% and 56% respectively compared to 8% and 25% for patients with one or more risk factors. Relapse within six months of a prior autologous transplant was associated with a higher relapse rate and a lower progression-free. Conclusions This analysis identifies important clinical parameters that may be useful in predicting the outcome of RICaIICalloSCT in Hodgkin’s lymphoma. PMID:19066328

  14. Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer.

    PubMed Central

    Solomayer, E. F.; Diel, I. J.; Wallwiener, D.; Bode, S.; Meyberg, G.; Sillem, M.; Gollan, C.; Kramer, M. D.; Krainick, U.; Bastert, G.

    1997-01-01

    Patients with an elevated level of urokinase plasminogen activator (uPA) in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: 2E11, which detects TAG 12--a tumour-associated glycoprotein typically expressed by almost all breast cancer cells--and the anti-uPA antibody HD-UK9. Thirty-five of the 2E11-positive women (n = 132, 47%) developed metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Patients with uPA-positive cells in bone marrow (n = 98, 35%) had a significantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patients positive for both markers (29.5 months), followed by those who were uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant systemic therapy. For the first time, it was possible to evaluate an important qualitative parameter involved in the process of breast cancer metastases. Images Figure 1 PMID:9310251

  15. Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer.

    PubMed

    Green, Andrew R; Soria, D; Powe, D G; Nolan, C C; Aleskandarany, M; Szász, M A; Tőkés, A M; Ball, G R; Garibaldi, J M; Rakha, E A; Kulka, J; Ellis, I O

    2016-05-01

    The Nottingham prognostic index plus (NPI+) is based on the assessment of biological class combined with established clinicopathologic prognostic variables providing improved patient outcome stratification for breast cancer superior to the traditional NPI. This study aimed to determine prognostic capability of the NPI+ in predicting risk of development of distant disease. A well-characterised series of 1073 primary early-stage BC cases treated in Nottingham and 251 cases from Budapest were immunohistochemically assessed for cytokeratin (Ck)5/6, Ck18, EGFR, oestrogen receptor (ER), progesterone receptor, HER2, HER3, HER4, Mucin 1 and p53 expression. NPI+ biological class and prognostic scores were assigned using individual algorithms for each biological class incorporating clinicopathologic parameters and investigated in terms of prediction of distant metastases-free survival (MFS). The NPI+ identified distinct prognostic groups (PG) within each molecular class which were predictive of MFS providing improved patient outcome stratification superior to the traditional NPI. NPI+ PGs, between series, were comparable in predicting patient outcome between series in luminal A, basal p53 altered and HER2+/ER+ (p > 0.01) tumours. The low-risk groups were similarly validated in luminal B, luminal N, basal p53 normal tumours (p > 0.01). Due to small patient numbers the remaining PGs could not be validated. NPI+ was additionally able to predict a higher risk of metastases at certain distant sites. This study may indicate the NPI+ as a useful tool in predicting the risk of metastases. The NPI+ provides accurate risk stratification allowing improved individualised clinical decision making for breast cancer. PMID:27116185

  16. Assessing the influence of treating therapist and patient prognostic factors on recovery from axial pain

    PubMed Central

    Simon, Corey B; Stryker, Sandra E; George, Steven Z

    2013-01-01

    . Future analyses should consider intrinsic therapist factors (beliefs, equipoise), specific treatment parameters (dosage, type), and other patient prognostic factors (psychological, age, expectation, satisfaction) to further elucidate the influence of therapist effects. PMID:24421631

  17. Prognostic impact of atrial fibrillation on clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease

    PubMed Central

    Patel, Nileshkumar J; Patel, Aashay; Agnihotri, Kanishk; Pau, Dhaval; Patel, Samir; Thakkar, Badal; Nalluri, Nikhil; Asti, Deepak; Kanotra, Ritesh; Kadavath, Sabeeda; Arora, Shilpkumar; Patel, Nilay; Patel, Achint; Sheikh, Azfar; Patel, Neil; Badheka, Apurva O; Deshmukh, Abhishek; Paydak, Hakan; Viles-Gonzalez, Juan

    2015-01-01

    Atrial fibrillation (AF) is the most common type of sustained arrhythmia, which is now on course to reach epidemic proportions in the elderly population. AF is a commonly encountered comorbidity in patients with cardiac and major non-cardiac diseases. Morbidity and mortality associated with AF makes it a major healthcare burden. The objective of our article is to determine the prognostic impact of AF on acute coronary syndromes, heart failure and chronic kidney disease. Multiple studies have been conducted to determine if AF has an independent role in the overall mortality of such patients. Our review suggests that AF has an independent adverse prognostic impact on the clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease. PMID:26225200

  18. Expression and prognostic significance of apolipoprotein D in breast cancer.

    PubMed Central

    Díez-Itza, I.; Vizoso, F.; Merino, A. M.; Sánchez, L. M.; Tolivia, J.; Fernández, J.; Ruibal, A.; López-Otín, C.

    1994-01-01

    Apolipoprotein D (apo D) is a glycoprotein involved in the human plasma lipid transport system and present at large amounts in cyst fluid from women with gross cystic disease of the breast. Apo D expression in breast carcinomas was examined by immunoperoxidase staining of a series of 163 tumors. A total of 60 (36.8%) tumors were negative for apo D immunostaining, 28 (17.2%) carcinomas were weakly positive, 33 (20.2%) were moderately stained, whereas the remaining 42 (25.8%) tumors were strongly stained with the specific antibodies. No significant correlation was found between apo D content and tumor size, lymph node involvement, or biochemical parameters such as estrogen receptors, cathepsin D, or pS2 protein. However, the finding of a significant association between apo D and menopausal status of patients or differentiation grade of tumors, with apo D values being lower in tumors from premenopausal women or in poorly differentiated carcinomas, suggested a potential value of this glycoprotein as a prognostic factor in breast cancer. Preliminary analysis of relapse-free survival and overall survival in a subgroup of 152 women with a mean follow-up of 42 months confirmed that low apo D values were significantly associated to a shorter relapse-free survival and poorer survival. According to these data, we propose that apo D in combination with other well-established prognostic factors may contribute to more accurately identify subgroups of breast cancer patients with low or high risk for relapse and death. Images Figure 1 Figure 2 Figure 3 PMID:8311115

  19. Prognostic Value of Posteromedial Cortex Deactivation in Mild Cognitive Impairment

    PubMed Central

    Petrella, Jeffrey R.; Prince, Steven E.; Wang, Lihong; Hellegers, Caroline; Doraiswamy, P. Murali

    2007-01-01

    Background Normal subjects deactivate specific brain regions, notably the posteromedial cortex (PMC), during many tasks. Recent cross-sectional functional magnetic resonance imaging (fMRI) data suggests that deactivation during memory tasks is impaired in Alzheimer's disease (AD). The goal of this study was to prospectively determine the prognostic significance of PMC deactivation in mild cognitive impairment (MCI). Methodology/Principal Findings 75 subjects (34 MCI, 13 AD subjects and 28 controls) underwent baseline fMRI scanning during encoding of novel and familiar face-name pairs. MCI subjects were followed longitudinally to determine conversion to AD. Regression and analysis of covariance models were used to assess the effect of PMC activation/deactivation on conversion to dementia as well as in the longitudinal change in dementia measures. At longitudinal follow up of up to 3.5 years (mean 2.5±0.79 years), 11 MCI subjects converted to AD. The proportion of deactivators was significantly different across all groups: controls (79%), MCI-Nonconverters (73%), MCI-converters (45%), and AD (23%) (p<0.05). Mean PMC activation magnitude parameter estimates, at baseline, were negative in the control (−0.57±0.12) and MCI-Nonconverter (−0.33±0.14) groups, and positive in the MCI-Converter (0.37±0.40) and AD (0.92±0.30) groups. The effect of diagnosis on PMC deactivation remained significant after adjusting for age, education and baseline Mini-Mental State Exam (p<0.05). Baseline PMC activation magnitude was correlated with change in dementia ratings from baseline. Conclusion Loss of physiological functional deactivation in the PMC may have prognostic value in preclinical AD, and could aid in profiling subgroups of MCI subjects at greatest risk for progressive cognitive decline. PMID:17971867

  20. Microvessel density is a prognostic marker of human gastric cancer

    PubMed Central

    Zhao, Hong-Chuan; Qin, Rong; Chen, Xiao-Xin; Sheng, Xia; Wu, Ji-Feng; Wang, Dao-Bin; Chen, Gui-Hua

    2006-01-01

    AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis. METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohistochemical staining. To assess tumor angiogenesis, MVD was determined by immunohistochemical staining of endothelial protein factor VIII-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2 and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer. PMID:17171787

  1. Physics-based prognostic modelling of filter clogging phenomena

    NASA Astrophysics Data System (ADS)

    Eker, Omer F.; Camci, Fatih; Jennions, Ian K.

    2016-06-01

    In industry, contaminant filtration is a common process to achieve a desired level of purification, since contaminants in liquids such as fuel may lead to performance drop and rapid wear propagation. Generally, clogging of filter phenomena is the primary failure mode leading to the replacement or cleansing of filter. Cascading failures and weak performance of the system are the unfortunate outcomes due to a clogged filter. Even though filtration and clogging phenomena and their effects of several observable parameters have been studied for quite some time in the literature, progression of clogging and its use for prognostics purposes have not been addressed yet. In this work, a physics based clogging progression model is presented. The proposed model that bases on a well-known pressure drop equation is able to model three phases of the clogging phenomena, last of which has not been modelled in the literature yet. In addition, the presented model is integrated with particle filters to predict the future clogging levels and to estimate the remaining useful life of fuel filters. The presented model has been implemented on the data collected from an experimental rig in the lab environment. In the rig, pressure drop across the filter, flow rate, and filter mesh images are recorded throughout the accelerated degradation experiments. The presented physics based model has been applied to the data obtained from the rig. The remaining useful lives of the filters used in the experimental rig have been reported in the paper. The results show that the presented methodology provides significantly accurate and precise prognostic results.

  2. Adverse Outcome Pathways: From Definition to Application

    EPA Science Inventory

    A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...

  3. Adverse cutaneous drug eruptions: current understanding.

    PubMed

    Hoetzenecker, W; Nägeli, M; Mehra, E T; Jensen, A N; Saulite, I; Schmid-Grendelmeier, P; Guenova, E; Cozzio, A; French, L E

    2016-01-01

    Adverse cutaneous drug reactions are recognized as being major health problems worldwide causing considerable costs for health care systems. Most adverse cutaneous drug reactions follow a benign course; however, up to 2% of all adverse cutaneous drug eruptions are severe and life-threatening. These include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Physicians should be aware of specific red flags to rapidly identify these severe cutaneous drug eruptions and initiate appropriate treatment. Besides significant progress in clinical classification and treatment, recent studies have greatly enhanced our understanding in the pathophysiology of adverse cutaneous drug reactions. Genetic susceptibilities to certain drugs have been identified in SJS/TEN patients, viral reactivation in DRESS has been elucidated, and the discovery of tissue resident memory T cells helps to better understand the recurrent site-specific inflammation in patients with fixed drug eruption. PMID:26553194

  4. Childhood adversities and psychosis: evidence, challenges, implications

    PubMed Central

    Morgan, Craig; Gayer‐Anderson, Charlotte

    2016-01-01

    There is a substantial body of research reporting evidence of associations between various forms of childhood adversity and psychosis, across the spectrum from experiences to disorder. This has been extended, more recently, to include studies of cumulative effects, of interactions with other factors, of specific effects, and of putative biological and psychological mechanisms. In this paper we evaluate this research and highlight the remaining methodological issues and gaps that temper, but do not dismiss, conclusions about the causal role of childhood adversity. We also consider the emerging work on cumulative, synergistic, and specific effects and on mechanisms; and discuss the broader implications of this line of research for our understanding of psychosis. We conclude that the current balance of evidence is that childhood adversities – particularly exposure to multiple adversities involving hostility and threat – do, in some people, contribute to the onset of psychotic experiences and psychotic disorders. PMID:27265690

  5. RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

    EPA Science Inventory

    INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...

  6. Attention-deficit/hyperactivity disorder and adverse health outcomes in adults.

    PubMed

    Spencer, Thomas J; Faraone, Stephen V; Tarko, Laura; McDermott, Katie; Biederman, Joseph

    2014-10-01

    Whereas the adverse impact of attention-deficit/hyperactivity disorder (ADHD) on emotional and psychosocial well-being has been well investigated, its impact on physical health has not. The main aim of this study was to assess the impact of ADHD on lifestyle behaviors and measures of adverse health risk indicators. Subjects were 100 untreated adults with ADHD and 100 adults without ADHD of similar age and sex. Unhealthy lifestyle indicators included assessments of bad health habits, frequency of visits to healthcare providers, and follow through with recommended prophylactic tests. Assessments of adverse health risk indicators included measurements of cardiovascular and metabolic parameters, weight, body mass index, and waist circumference. No differences were identified in health habits between subjects with and without ADHD, but robust differences were found in a wide range of adverse health risk indicators. ADHD is associated with an adverse impact in health risk indicators well known to be associated with high morbidity and mortality. PMID:25211634

  7. Prognosis and prognostic factors of retinal infarction: a prospective cohort study.

    PubMed Central

    Hankey, G J; Slattery, J M; Warlow, C P

    1991-01-01

    OBJECTIVE--To determine the prognosis and adverse prognostic factors in patients with retinal infarction due to presumed atheromatous thromboembolism or cardiogenic embolism. DESIGN--Prospective cohort study. SETTING--University hospital departments of clinical neurology. PATIENTS--99 patients with retinal infarction, without prior stroke, referred to a single neurologist between 1976 and 1986 and evaluated and followed up prospectively until death or the end of 1986 (mean follow up 4.2 years). INTERVENTIONS--Cerebral angiography (55 patients), aspirin treatment (37), oral anticoagulant treatment (eight), carotid endarterectomy (13), cardiac surgery (six), and peripheral vascular surgery (two). MAIN OUTCOME MEASURES--Death, stroke, coronary events, contralateral retinal infarction; survival analysis confined to 98 patients with retinal infarction due to presumed artheromatous thromboembolism or cardiogenic embolism (one patient with giant cell arteries excluded), and Cox's proportional hazards regression analysis, including age as a prognostic factor. RESULTS--During follow up 29 patients died (21 of vascular causes and eight of non-vascular or unknown causes), 10 had a first ever stroke, 19 had a coronary event, and only one developed contralateral retinal infarction. A coronary event accounted for more than half (59%) of the deaths whereas stroke was the cause of only one death (3%). Over the first five years after retinal infarction the actuarial average absolute risk of death was 8% per year; of stroke 2.5% per year (7.4% in the first year); of coronary events 5.3% per year, exceeding that of stroke; and of stroke, myocardial infarction, or vascular death 7.4% per year. Prognostic factors associated with an increased risk of death were increasing age, peripheral vascular disease, cardiomegaly, and carotid bruit. Adverse prognostic factors for serious vascular events were increasing age and carotid bruit for stroke, and increasing age, cardiomegaly, and carotid

  8. Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

    2016-01-01

    Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

  9. Prognostic Factors After Extraneural Metastasis of Medulloblastoma

    SciTech Connect

    Mazloom, Ali; Zangeneh, Azy H.; Paulino, Arnold C.

    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. Median 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.

  10. Prognostic Factors in Cholinesterase Inhibitor Poisoning

    PubMed Central

    Sun, In O; Yoon, Hyun Ju; Lee, Kwang Young

    2015-01-01

    Background Organophosphates and carbamates are insecticides that are associated with high human mortality. The purpose of this study is to investigate the prognostic factors affecting survival in patients with cholinesterase inhibitor (CI) poisoning. Material/Methods This study included 92 patients with CI poisoning in the period from January 2005 to August 2013. We divided these patients into 2 groups (survivors vs. non-survivors), compared their clinical characteristics, and analyzed the predictors of survival. Results The mean age of the included patients was 56 years (range, 16–88). The patients included 57 (62%) men and 35 (38%) women. When we compared clinical characteristics between the survivor group (n=81, 88%) and non-survivor group (n=11, 12%), there were no differences in renal function, pancreatic enzymes, or serum cholinesterase level, except for serum bicarbonate level and APACHE II score. The serum bicarbonate level was lower in non-survivors than in survivors (12.45±2.84 vs. 18.36±4.73, P<0.01). The serum APACHE II score was higher in non-survivors than in survivors (24.36±5.22 vs. 12.07±6.67, P<0.01). The development of pneumonia during hospitalization was higher in non-survivors than in survivors (n=9, 82% vs. n=31, 38%, P<0.01). In multiple logistic regression analysis, serum bicarbonate concentration, APACHE II score, and pneumonia during hospitalization were the important prognostic factors in patients with CI poisoning. Conclusions Serum bicarbonate and APACHE II score are useful prognostic factors in patients with CI poisoning. Furthermore, pneumonia during hospitalization was also important in predicting prognosis in patients with CI poisoning. Therefore, prevention and active treatment of pneumonia is important in the management of patients with CI poisoning. PMID:26411989

  11. Molecular predictive and prognostic factors in ependymoma.

    PubMed

    Benson, Rony; Mallick, Supriya; Julka, Pramod K; Rath, Goura K

    2016-01-01

    An ependymoma is an uncommon glial tumor, which arises from different parts of the neuroaxis. Considerable variation in presentation and survival in tumors in different locations after an optimum treatment indicates inherent molecular and genetic differences in tumorigenesis between them. A number of genetic aberrations have been identified to distinctly characterize different subgroups of ependymomas that include a posterior fossa tumor, a supratentorial tumor, and a pediatric tumor. These different groups have substantial genetic alterations, and also distinct demography, clinical characteristics, and prognosis. This article is intended to review the diverse molecular and genetic aberrations that may be helpful in prognostication and prediction of survival in patients suffering from an ependymoma. PMID:26954807

  12. Prognostic Factors in Sudden Sensorineural Hearing Loss

    PubMed Central

    Atay, Gamze; Kayahan, Bahar; çınar, Betül çiçek; Saraç, Sarp; Sennaroğlu, Levent

    2016-01-01

    Background: Sudden sensorineural hearing loss (SSNHL) is still a complex and challenging process which requires clinical evidence regarding its etiology, treatment and prognostic factors. Therefore, determination of prognostic factors might aid in the selection of proper treatment modality. Aims: The aim of this study is to analyze whether there is correlation between SSNHL outcomes and (1) systemic steroid therapy, (2) time gap between onset of symptoms and initiation of therapy and (3) audiological pattern of hearing loss. Study Design: Retrospective chart review. Methods: Patients diagnosed at our clinic with SSNHL between May 2005 and December 2011 were reviewed. A detailed history of demographic features, side of hearing loss, previous SSNHL and/or ear surgery, recent upper respiratory tract infection, season of admission, duration of symptoms before admission and the presence of co-morbid diseases was obtained. Radiological and audiological evaluations were recorded and treatment protocol was assessed to determine whether systemic steroids were administered or not. Treatment started ≤5 days was regarded as “early” and >5 days as “delayed”. Initial audiological configurations were grouped as “upward sloping”, “downward sloping”, “flat” and “profound” hearing loss. Significant recovery was defined as thresholds improved to the same level with the unaffected ear or improved ≥30 dB on average. Slight recovery was hearing improvement between 10–30dB on average. Hearing recovery less than 10 dB was accepted as unchanged. Results: Among the 181 patients who met the inclusion criteria, systemic steroid was administered to 122 patients (67.4%), whereas 59 (32.6%) patients did not have steroids. It was found that steroid administration did not have any statistically significant effect in either recovered or unchanged hearing groups. Early treatment was achieved in 105 patients (58%) and 76 patients (42%) had delayed treatment. Recovery

  13. Cellular prognostic markers in hepatocellular carcinoma.

    PubMed

    Buonaguro, Luigi; Tagliamonte, Maria; Petrizzo, Annacarmen; Damiano, Elvira; Tornesello, Maria Lina; Buonaguro, Franco M

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the five big killers worldwide and is frequently associated with chronic hepatitis B and C virus (HBV and HCV) infections. Tumor microenvironment consists of a complex network of cells and factors that plays a key role in the tumor progression and prognosis. This is true also for HCC. Several studies have shown strikingly strong correlation between HCC clinical prognosis and intratumoral infiltration of cells affecting tumor growth, invasion, angiogenesis and metastasis. None of such cells is yet validated for routine diagnostic and prognostic assessment. The present review aims at providing a state-of-the-art of such studies. PMID:26043213

  14. Machine Learning Approach to Extract Diagnostic and Prognostic Thresholds: Application in Prognosis of Cardiovascular Mortality

    PubMed Central

    Mena, Luis J.; Orozco, Eber E.; Felix, Vanessa G.; Ostos, Rodolfo; Melgarejo, Jesus; Maestre, Gladys E.

    2012-01-01

    Machine learning has become a powerful tool for analysing medical domains, assessing the importance of clinical parameters, and extracting medical knowledge for outcomes research. In this paper, we present a machine learning method for extracting diagnostic and prognostic thresholds, based on a symbolic classification algorithm called REMED. We evaluated the performance of our method by determining new prognostic thresholds for well-known and potential cardiovascular risk factors that are used to support medical decisions in the prognosis of fatal cardiovascular diseases. Our approach predicted 36% of cardiovascular deaths with 80% specificity and 75% general accuracy. The new method provides an innovative approach that might be useful to support decisions about medical diagnoses and prognoses. PMID:22924062

  15. Incorporating adverse event relatedness into dose-finding clinical trial designs.

    PubMed

    Darssan, Darsy; Thompson, Mery H; Pettitt, Anthony N

    2014-03-30

    Dose-finding designs estimate the dose level of a drug based on observed adverse events. Relatedness of the adverse event to the drug has been generally ignored in all proposed design methodologies. These designs assume that the adverse events observed during a trial are definitely related to the drug, which can lead to flawed dose-level estimation. We incorporate adverse event relatedness into the so-called continual reassessment method. Adverse events that have 'doubtful' or 'possible' relationships to the drug are modelled using a two-parameter logistic model with an additive probability mass. Adverse events 'probably' or 'definitely' related to the drug are modelled using a cumulative logistic model. To search for the maximum tolerated dose, we use the maximum estimated toxicity probability of these two adverse event relatedness categories. We conduct a simulation study that illustrates the characteristics of the design under various scenarios. This article demonstrates that adverse event relatedness is important for improved dose estimation. It opens up further research pathways into continual reassessment design methodologies. PMID:24122859

  16. Prognostic significance of NQO1 expression in intrahepatic cholangiocarcinoma

    PubMed Central

    Wakai, Toshifumi; Shirai, Yoshio; Sakata, Jun; Matsuda, Yasunobu; Korit, Pavel V; Takamura, Masaaki; Ajioka, Yoichi; Hatakeyama, Katsuyoshi

    2011-01-01

    This study aimed to evaluate the association between the immunohistochemical expression of NAD(P) H:quinone oxidoreductase-1 (NQO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in resected specimens of intrahepatic cholangiocarcinoma (ICC) and to elucidate the prognostic value of NQO1 and Nrf2 expression. A retrospective analysis was conducted of 34 consecutive patients who underwent surgical resection for ICC. Immunohistochemistry of the resected specimens was conducted using each of the following primary monoclonal antibodies against NQO1 and Nrf2. Of the 34 patients, 23 were classified as having tumors with NQO1-positive expression and 11 had tumors with loss of NQO1 expression, whereas 22 patients had tumors with Nrf2-positive expression and 12 had tumors with loss of Nrf2 expression. NQO1 expression showed a positive association with Nrf2 expression (p=0.005). Loss of NQO1 expression was more frequent in tumor specimens that were moderately or poorly differentiated (11/26; 42%) than in well-differentiated tumors (0/8; 0%; p=0.034). Post-resection survival was significantly worse in patients with tumors with loss of NQO1 expression than in patients with NQO1-positive tumors (cumulative 5 -year survival rate of 0% and 51%, respectively; p=0.005). Nrf2 expression was not associated with survival after resection (p=0.287). The Cox proportional hazards regression analysis revealed that lymph node involvement (p<0.001) and loss of NQO1 expression (p<0.001) had an independent adverse effect on survival. Loss of NQO1 expression reflects dedifferentiation and thus indicates a poor prognosis for patients undergoing resection for ICC. PMID:21577322

  17. A turbulence model for nonequilibrium adverse pressure gradient flows

    NASA Technical Reports Server (NTRS)

    Horstman, C. C.

    1976-01-01

    This paper presents a method for calculating compressible adverse pressure gradient boundary layers by using an algebraic eddy viscosity turbulence model that has been modified for variable pressure gradient and turbulence memory effects. The pressure gradient corrections are based on previous incompressible data correlations. Several methods for including the effects of turbulence memory are evaluated. A new lag model, which gives good agreement with available experimental data, is developed. Finally, a correlation is developed for the lag length parameter employed in the model as a function of the known experimental flow variables.

  18. Adverse Selection and an Individual Mandate: When Theory Meets Practice*

    PubMed Central

    Hackmann, Martin B.; Kolstad, Jonathan T.; Kowalski, Amanda E.

    2014-01-01

    We develop a model of selection that incorporates a key element of recent health reforms: an individual mandate. Using data from Massachusetts, we estimate the parameters of the model. In the individual market for health insurance, we find that premiums and average costs decreased significantly in response to the individual mandate. We find an annual welfare gain of 4.1% per person or $51.1 million annually in Massachusetts as a result of the reduction in adverse selection. We also find smaller post-reform markups. PMID:25914412

  19. Prognostic factors in pediatric high-grade astrocytoma: the importance of accurate pathologic diagnosis.

    PubMed

    Hales, Russell K; Shokek, Ori; Burger, Peter C; Paynter, Nina P; Chaichana, Kaisorn L; Quiñones-Hinojosa, Alfredo; Jallo, George I; Cohen, Kenneth J; Song, Danny Y; Carson, Benjamin S; Wharam, Moody D

    2010-08-01

    To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis

  20. Adverse drug reactions and safety considerations of NSAIDs: clinical analysis.

    PubMed

    Bahadur, Shiv; Keshri, Lav; Pathak, Kamla

    2011-11-01

    NSAIDs are the most frequently used drugs for treatment, in Europe and the United States, accounting for approximately 5% of all prescriptions. Moreover, the use of NSAIDs is increasing because these constitute the first-line drug therapy for a wide range of rheumatic conditions. This increase is in part the result of the increasing population of elderly patients, who constitute the group of patients with greatest demand for these agents. There are many types of NSAIDs that vary in potency, action and potential side effects. Thus various efforts have been made to determine the safety considerations including adverse drug effects, duration of drug therapy, drug interactions, precautions and other drugs applied to reduce side effects. Researchers have introduced some novel techniques to diagnose NSAIDs related adverse effects on the gastrointestinal mucosa. The researchers dealing with the development of drug delivery system for these drugs should aim at designing a therapeutically efficacious dosage form with reduced side/adverse effects. Thus an effort has been made in this review to deal with the safety parameters of various NSAIDs with a special emphasis on preclinical and clinical safety analysis and various attempts to minimize the side effects by structural modification or by drug delivery system. PMID:22424538

  1. Prediction of surgical outcome in compressive cervical myelopathy: A novel clinicoradiological prognostic score

    PubMed Central

    Aggarwal, Rishi Anil; Srivastava, Sudhir Kumar; Bhosale, Sunil Krishna; Nemade, Pradip Sharad

    2016-01-01

    Context: Preoperative severity of myelopathy, age, and duration of symptoms have been shown to be highly predictive of the outcome in compressive cervical myelopathy (CCM). The role of radiological parameters is still controversial. Aims: Define the prognostic factors in CCM and formulate a prognostic score to predict the outcome following surgery in CCM. Settings and Design: Retrospective. Materials and Methods: This study included 78 consecutive patients with CCM treated surgically. The modified Japanese Orthopaedic Association (mJOA) scale was used to quantify severity of myelopathy at admission and at 12-month follow-up. The outcome was defined as good if the patient had mJOA score ≥16 and poor if the score was <16. Age, sex, duration of symptoms, comorbidities, intrinsic hand muscle wasting (IHMW), diagnosis, surgical technique, Torg ratio, instability on dynamic radiographs, and magnetic resonance imaging (MRI) signal intensity changes were assessed. Statistics: Statistical Package for the Social Sciences (SPSS) (version 20.0) was used for statistical analysis. The association was assessed amongst variables using logistic regression analysis. Parameters having a statistically significant correlation with the outcome were included in formulating a prognostic score. Results: Severity of myelopathy, IHMW, age, duration, diabetes, and instability on radiographs were predictive of the outcome with a P value <0.01. Genders, diagnosis, surgical procedure, Torg ratio, and intensity changes on MRI were not significantly related to the outcome. A 8-point scoring system was devised incorporating the significant clinicoradiological parameters, and it was found that nearly all patients (97.82%) with a score below 5 had good outcome and all patients (100%) with a score above 5 had poor outcome. The outcome is difficult to predict with a score of 5. Conclusions: Clinical parameters are better predictors of the outcome as compared to radiological findings, following

  2. Prognostic value of troponins in acute nonmassive pulmonary embolism: A meta-analysis.

    PubMed

    Bajaj, Anurag; Saleeb, Michael; Rathor, Parul; Sehgal, Vishal; Kabak, Besher; Hosur, Srikanth

    2015-01-01

    The objective of our meta-analysis is to update the evidence on the prognostic value of elevated troponin levels in patient with acute normotensive pulmonary embolism (PE). We did a systematic literature review of database, including Pubmed, EMBASE, and Cochrane. Studies were included if those were done on normotensive patients with acute PE and serum troponin assay was done. The primary end point was short term all cause mortality. The secondary end points were short term PE related mortality and serious adverse events. Elevated troponin levels were significantly associated with the increased risk for short term mortality (odds ratio [OR], 4.80; 95% CI, 3.25-7.08, I(2) = 54%), PE related mortality (OR, 3.80; 95% CI, 2.74-5.27, I(2) = 0%) and serious adverse events (OR, 3.65; 95% CI, 2.41-5.53, I(2) = 47%). Our study suggests that elevated levels of troponin identify a subgroup of patients with increased risk for short term mortality and serious adverse events. PMID:25976228

  3. Gender Differences in Community-acquired Meningitis in Adults: Clinical Presentations and Prognostic Factors

    PubMed Central

    Dharmarajan, Lavanya; Salazar, Lucrecia; Hasbun, Rodrigo

    2016-01-01

    Community-acquired meningitis is a serious disease that is associated with high morbidity and mortality. The purpose of this study was to investigate the gender differences involved with the clinical presentations of and prognostic factors for this disease. We conducted a retrospective study of 619 adults diagnosed with community-acquired meningitis in Houston, Texas, who were hospitalized between 2005 and 2010. Patients were categorized as male or female. Those who were evaluated to have a Glasgow Outcome Scale score of four or less were classified to have an adverse clinical outcome. Males consisted of 47.2% (292/619) of the total cohort, and more often presented with coexisting medical conditions, fever, abnormal microbiology results, and abnormalities on head computed tomography. Females more often presented with nuchal rigidity. On logistic regression, fever, CSF glucose <45 mg/dL, and an abnormal neurological examination were predictors of an adverse outcome in male patients, while age greater than 60 years and an abnormal neurological examination were associated with a poor prognosis in female patients. Thus, community-acquired meningitis in males differs significantly from females in regards to comorbidities, presenting symptoms and signs, abnormal laboratory and imaging analysis, and predictors of adverse clinical outcomes. PMID:27500284

  4. Echocardiography and pulmonary embolism severity index have independent prognostic roles in pulmonary embolism.

    PubMed

    Sanchez, Olivier; Trinquart, Ludovic; Planquette, Benjamin; Couturaud, Francis; Verschuren, Franck; Caille, Vincent; Meneveau, Nicolas; Pacouret, Gérard; Roy, Pierre-Marie; Righini, Marc; Perrier, Arnaud; Bertoletti, Laurent; Parent, Florence; Lorut, Christine; Meyer, Guy

    2013-09-01

    We analysed a cohort of patients with normotensive pulmonary embolism (PE) in order to assess whether combining echocardiography and biomarkers with the pulmonary embolism severity index (PESI) improves the risk stratification in comparison to the PESI alone. The PESI was calculated in normotensive patients with PE who also underwent echocardiography and assays of cardiac troponin I and brain natriuretic peptide. 30-day adverse outcome was defined as death, recurrent PE or shock. 529 patients were included, 25 (4.7%, 95% CI 3.2-6.9%) had at least one outcome event. The proportion of patients with adverse events increased from 2.1% in PESI class I-II to 8.4% in PESI class III-IV, and to 14.3% in PESI class V (p<0.001). In PESI class I-II, the rate of outcome events was significantly higher in patients with abnormal values of biomarkers or right ventricular dilatation. In multivariate analysis, the PESI (class III-IV versus I-II, OR 3.1, 95% CI 1.2-8.3; class V versus I-II, OR 5.5, 95% CI 1.5-25.5 and echocardiography (right ventricular/left ventricular ratio, OR (for an increase of 0.1) 1.3, 95% CI 1.1-1.5) were independent predictors of an adverse outcome. In patients with normotensive PE, biomarkers and echocardiography provided additional prognostic information to the PESI. PMID:23258789

  5. Adverse events temporally associated with meningococcal vaccines.

    PubMed Central

    Yergeau, A; Alain, L; Pless, R; Robert, Y

    1996-01-01

    OBJECTIVE: To determine the incidence of severe adverse events temporally associated with meningococcal vaccines administered as part of a mass vaccination program. DESIGN: Retrospective descriptive study of events reported to a passive provincial surveillance system. SETTING: The province of Quebec. PARTICIPANTS: The 1,198,751 individuals aged 6 months to 20 years who were vaccinated against meningococcal disease between Dec. 27, 1992, and Mar. 31, 1993. OUTCOME MEASURES: Total numbers and rates of severe adverse events, including allergic reactions, anaphylactic reactions, neurological events (other than abnormal crying and screaming) and other serious or unusual events. RESULTS: A total of 118 reports of severe adverse events were selected from the surveillance system. The most frequent were allergic reactions (9.2 per 100,000 doses). Few anaphylactic or neurologic reactions were reported (0.1 and 0.5 per 100,000 doses respectively). There were no reports of sequelae or of encephalopathy, meningitis or encephalitis. CONCLUSION: Meningococcal vaccines seem to be associated with fewer adverse events than have previously been reported. Existing surveillance programs are useful for determining the incidence of adverse events temporally associated with vaccines. PMID:8630839

  6. The complement system and adverse pregnancy outcomes.

    PubMed

    Regal, Jean F; Gilbert, Jeffrey S; Burwick, Richard M

    2015-09-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the fetal allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

  7. Prognostic factors in canine mammary cancer.

    PubMed

    Misdorp, W; Hart, A A

    1976-04-01

    From a follow-up study of dogs surgically treated for mammary cancer, ten characteristics were analyzed statistically with special reference to their association with prognosis (expressed as survival for 2 years). The interrelations among five of the characteristics were also tested. The histologic type (descending range in malignancy: sarcomas greater than simple carcinomas greater than complex carcinomas), mode of growth (highly infiltrating greater than moderately infiltrating greater than expansive), clinical stage of complex carcinomas (large tumors and/or tumors involving the skin or underlying tissue greater than small, well-defined tumors), and size (greater than 15 cm greater than 11-15 cm greater than 5-10 cm greater than 0-5 cm) were of definite prognostic importance. The histologic grade was of possible prognostic importance. Localization, type of surgical therapy (mastectomy, block-dissection), growth in lymph vessels, involvement of regional lymph nodes, and duration of symptoms before treatment were not important to prognosis. A comparison between the factors associated with the prognosis of canine and human mammary cancer showed many similarities. However, the involvement of regional lymph nodes, important in women, was not so in bitches. PMID:1255797

  8. Advanced Ground Systems Maintenance Prognostics Project

    NASA Technical Reports Server (NTRS)

    Perotti, Jose M.

    2015-01-01

    The project implements prognostics capabilities to predict when a component system or subsystem will no longer meet desired functional or performance criteria, called the end of life. The capability also provides an assessment of the remaining useful life of a hardware component. The project enables the delivery of system health advisories to ground system operators. This project will use modeling techniques and algorithms to assess components' health andpredict remaining life for such components. The prognostics capability being developed will beused:during the design phase and during pre/post operations to conduct planning and analysis ofsystem design, maintenance & logistics plans, and system/mission operations plansduring real-time operations to monitor changes to components' health and assess their impacton operations.This capability will be interfaced to Ground Operations' command and control system as a part ofthe AGSM project to help assure system availability and mission success. The initial modelingeffort for this capability will be developed for Liquid Oxygen ground loading applications.

  9. Prognostics Applied to Electric Propulsion UAV

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Saha, Bhaskar

    2013-01-01

    Health management plays an important role in operations of UAV. If there is equipment malfunction on critical components, safe operation of the UAV might possibly be compromised. A technology with particular promise in this arena is equipment prognostics. This technology provides a state assessment of the health of components of interest and, if a degraded state has been found, it estimates how long it will take before the equipment will reach a failure threshold, conditional on assumptions about future operating conditions and future environmental conditions. This chapter explores the technical underpinnings of how to perform prognostics and shows an implementation on the propulsion of an electric UAV. A particle filter is shown as the method of choice in performing state assessment and predicting future degradation. The method is then applied to the batteries that provide power to the propeller motors. An accurate run-time battery life prediction algorithm is of critical importance to ensure the safe operation of the vehicle if one wants to maximize in-air time. Current reliability based techniques turn out to be insufficient to manage the use of such batteries where loads vary frequently in uncertain environments.

  10. Epidemiologic and Molecular Prognostic Review of Glioblastoma

    PubMed Central

    Thakkar, Jigisha P.; Dolecek, Therese A.; Horbinski, Craig; Ostrom, Quinn T.; Lightner, Donita D.; Barnholtz-Sloan, Jill S.; Villano, John L.

    2014-01-01

    Glioblastoma (GBM) is the most common and aggressive primary CNS malignancy with a median survival of 15 months. The average incidence rate (IR) of GBM is 3.19/100,000 population and the median age of diagnosis is 64 years. Incidence is higher in men and individuals of white race and non-Hispanic ethnicity. Many genetic and environmental factors have been studied in GBM but the majority are sporadic and no risk factor accounting for a large proportion of GBMs has been identified. However, several favorable clinical prognostic factors are identified including, younger age at diagnosis, cerebellar location, high performance status and maximal tumor resection. GBMs comprise of primary and secondary subtypes which evolve through different genetic pathways, affect patients at different ages and have differences in outcomes. We report the current epidemiology of GBM with new data from the Central Brain Tumor Registry of the United States (CBTRUS) 2006–2010 as well as demonstrate and discuss trends in incidence and survival. We also provide a concise review on molecular markers in GBM that have helped distinguish biologically similar subtypes of GBM and have prognostic and predictive value. PMID:25053711

  11. 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

  12. Vascular grading of angiogenesis: prognostic significance in breast cancer

    PubMed Central

    Hansen, S; Grabau, D A; Sørensen, F B; Bak, M; Vach, W; Rose, C

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers was moderately reproduced (κ = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all patients (P< 0.0001), node-negative patients (P< 0.0001) and node-positive patients (P< 0.0001). Cox multivariate regression analysis showed that vascular grading contributed with independent prognostic value in all patients (P< 0.0001). A prognostic index including the vascular grade had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer. © 2000 Cancer Research Campaign PMID:10646886

  13. Early Life Adversity and Adult Biological Risk Profiles

    PubMed Central

    Friedman, Esther M.; Karlamangla, Arun S.; Gruenewald, Tara; Koretz, Brandon; Seeman, Teresa E.

    2015-01-01

    Objectives To determine whether there is a relationship between early life adversity (ELA) and biological parameters known to predict health risks and to examine the extent to which circumstances in midlife mediate this relationship. Methods We analyzed data on 1,180 respondents from the biomarker subsample of the second wave of the National Survey of Midlife Development in the United States (MIDUS) study. ELA assessments were based on childhood socioeconomic disadvantage (i.e. on welfare, perceived low income, less-educated parents) and other stressors (e.g., parental death, parental divorce, and parental physical abuse). The outcome variable was cumulative allostatic load (AL), a marker of biological risk. We also incorporate information on adult circumstances, including: education, social relationships, and health behaviors. Results Childhood socioeconomic adversity was associated with increased AL (B=0.094, SE=0.041) and physical abuse (B=0.263, SE=0.091), with non-significant associations for parental divorce and death. Adult education mediated the relationship between socioeconomic ELA and cumulative allostatic load to the point of non-significance, with this factor alone explaining nearly 40% of the relationship. The association between childhood physical abuse and AL remained even after adjusting for adult educational attainments, social relationships, and health behaviors. These associations were most pronounced for secondary stress systems, including inflammation, cardiovascular function, and lipid metabolism. Conclusions The physiological consequences of early life socioeconomic adversity are attenuated by achieving high levels of schooling later on. The adverse consequences of childhood physical abuse, on the other hand, persist in multivariable adjusted analysis. PMID:25650548

  14. [Is obesity an adverse prognostic factor for pulmonary manifestations of influenza? Lesson from complicated disease course H1N1].

    PubMed

    Zoubková, Renata; Máca, Jan; Handlos, Petr; Rudinská, Lenka; Nytra, Ivana; Chýlek, Václav; Vavrošová, Jana

    2014-01-01

    Influenza viruses cause annual epidemics that occur at different times in both the northern and southern hemisphere. In cases of seasonal influenza these are usually mild forms of the disease, which rarely lead to death of the patient. Vulnerable groups include the elderly, the young or those with comorbidities, where the virus affects tens of thousands of victims around the world. Occasionally, however, large epidemics appear caused by a dangerous variant of a new virus, which is usually characterized by high contagiousness and pathogenicity (virulence). Consequently, it is often accompanied by a complicated disease course and associated with high mortality. In 2009, a viral pandemic disease marked pH1N1 2009 Influenza A appeared. Even though the initial predictions were far worse, the course of influenza caused by this virus was often complicated by acute respiratory failure in the form of acute respiratory distress syndrome (ARDS). This formed part of the wider multiple organ failure syndrome (MODS). This type of virus often infects younger age groups and is more contagious compared to the seasonal flu. In order to illustrate the complicated forms of viral infections pH1N1 2009 Influenza A we present three case studies which demonstrate complicated pulmonary manifestation, which take the primary form of ARDS. PMID:25561242

  15. Identifying Adverse Drug Events by Relational Learning

    PubMed Central

    Page, David; Costa, Vítor Santos; Natarajan, Sriraam; Barnard, Aubrey; Peissig, Peggy; Caldwell, Michael

    2013-01-01

    The pharmaceutical industry, consumer protection groups, users of medications and government oversight agencies are all strongly interested in identifying adverse reactions to drugs. While a clinical trial of a drug may use only a thousand patients, once a drug is released on the market it may be taken by millions of patients. As a result, in many cases adverse drug events (ADEs) are observed in the broader population that were not identified during clinical trials. Therefore, there is a need for continued, post-marketing surveillance of drugs to identify previously-unanticipated ADEs. This paper casts this problem as a reverse machine learning task, related to relational subgroup discovery and provides an initial evaluation of this approach based on experiments with an actual EMR/EHR and known adverse drug events. PMID:24955289

  16. Standardizing drug adverse event reporting data.

    PubMed

    Wang, Liwei; Jiang, Guoqian; Li, Dingcheng; Liu, Hongfang

    2013-01-01

    Normalizing data in the Adverse Event Reporting System (AERS), an FDA database, would improve the mining capacity of AERS for drug safety signal detection. In this study, we aim to normalize AERS and build a publicly available normalized Adverse drug events (ADE) data source.he drug information in AERS is normalized to RxNorm, a standard terminology source for medication. Drug class information is then obtained from the National Drug File - Reference Terminology (NDF-RT). Adverse drug events (ADE) are aggregated through mapping with the PT (Preferred Term) and SOC (System Organ Class) codes of MedDRA. Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). The AERS-DM could provide more perspectives to mine AERS database for drug safety signal detection and could be used by research community in the data mining field. PMID:23920875

  17. A revised inventory of Adverse Childhood Experiences.

    PubMed

    Finkelhor, David; Shattuck, Anne; Turner, Heather; Hamby, Sherry

    2015-10-01

    This study examines whether the items from the original Adverse Childhood Experiences (ACE) scale can be improved in their prediction of health outcomes by adding some additional widely recognized childhood adversities. The analyses come from the National Survey of Children's Exposure to Violence 2014, a telephone survey conducted from August 2013 through April 2014 with a nationally representative sample of 1,949 children and adolescents aged 10-17 and their caregivers who were asked about adversities, physical health conditions and mental health symptoms. The addition of measures of peer victimization, peer isolation/rejection, and community violence exposure added significantly to the prediction of mental health symptoms, and the addition of a measure of low socioeconomic status (SES) added significantly to the prediction of physical health problems. A revised version of the ACES scale is proposed. PMID:26259971

  18. Adverse health consequences of the Iraq War.

    PubMed

    Levy, Barry S; Sidel, Victor W

    2013-03-16

    The adverse health consequences of the Iraq War (2003-11) were profound. We conclude that at least 116,903 Iraqi non-combatants and more than 4800 coalition military personnel died over the 8-year course. Many Iraqi civilians were injured or became ill because of damage to the health-supporting infrastructure of the country, and about 5 million were displaced. More than 31,000 US military personnel were injured and a substantial percentage of those deployed suffered post-traumatic stress disorder, traumatic brain injury, and other neuropsychological disorders and their concomitant psychosocial problems. Many family members of military personnel had psychological problems. Further review of the adverse health consequences of this war could help to minimise the adverse health consequences of, and help to prevent, future wars. PMID:23499043

  19. Adverse events related to blood transfusion

    PubMed Central

    Sahu, Sandeep; Hemlata; Verma, Anupam

    2014-01-01

    The acute blood transfusion reactions are responsible for causing most serious adverse events. Awareness about various clinical features of acute and delayed transfusion reactions with an ability to assess the serious reactions on time can lead to a better prognosis. Evidence-based medicine has changed today's scenario of clinical practice to decrease adverse transfusion reactions. New evidence-based algorithms of transfusion and improved haemovigilance lead to avoidance of unnecessary transfusions perioperatively. The recognition of adverse events under anaesthesia is always challenging. The unnecessary blood transfusions can be avoided with better blood conservation techniques during surgery and with anaesthesia techniques that reduce blood loss. Better and newer blood screening methods have decreased the infectious complications to almost negligible levels. With universal leukoreduction of red blood cells (RBCs), selection of potential donors such as use of male donors only plasma and restriction of RBC storage, most of the non-infectious complications can be avoided. PMID:25535415

  20. Prognostic factors for sperm retrieval in non-obstructive azoospermia.

    PubMed

    Glina, Sidney; Vieira, Marcelo

    2013-01-01

    Testicular sperm retrieval techniques associated with intracytoplasmic sperm injection have changed the field of male infertility treatment and given many azoospermic men the chance to become biological fathers. Despite the current use of testicular sperm extraction, reliable clinical and laboratory prognostic factors of sperm recovery are still absent. The objective of this article was to review the prognostic factors and clinical use of sperm retrieval for men with non-obstructive azoospermia. The PubMed database was searched for the Medical Subject Headings (MeSH) terms azoospermia, sperm retrieval, and prognosis. Papers on obstructive azoospermia were excluded. The authors selected articles that reported successful sperm retrieval techniques involving clinical, laboratory, or parenchyma processing methods. The selected papers were reviewed, and the prognostic factors were discussed. No reliable positive prognostic factors guarantee sperm recovery for patients with non-obstructive azoospermia. The only negative prognostic factor is the presence of AZFa and AZFb microdeletions. PMID:23503961

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

    PubMed

    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

  2. Adverse Drug Reactions of the Lower Extremities.

    PubMed

    Adigun, Chris G

    2016-07-01

    Adverse drug reactions (ADRs) are a common cause of dermatologic consultation, involving 2 to 3 per 100 medical inpatients in the United States. Female patients are 1.3 to 1.5 times more likely to develop ADRs, except in children less than 3 years of age, among whom boys are more often affected. Certain drugs are more frequent causes, including aminopenicillins, trimethoprim-sulfamethoxazole, and nonsteroidal antiinflammatory drugs. Chemotherapeutic agents commonly cause adverse reactions to the skin and nails, with certain agents causing particular patterns of reactions. ADRs can involve any area of the skin; the appendages, including hair and nails; as well as mucosa. PMID:27215159

  3. Reduced impact of nodal metastases as a prognostic factor for tonsil cancer in the HPV era.

    PubMed

    Vila, Peter M; Stucken, Chaz L; Morris, Luc G T; Posner, Marshall R; Genden, Eric M; Boffetta, Paolo; Sikora, Andrew G

    2014-09-01

    Metastatic lymph nodes (LN) are an adverse prognostic factor in head and neck squamous cell carcinoma (SCC). In this study, we tested the hypothesis that nodal metastases have reduced impact on survival in tonsil cancer in the HPV-predominant era. Incidence and mortality data of tonsil and oral cavity SCC between 1988 and 2007 were obtained from the SEER database. Based on published literature, we considered cases of tonsil cancer from 1988 to 1997 as the pre-HPV cohort (N = 752), and 1998-2007 as the HPV-predominant cohort (N = 2,755). Comparing the two cohorts, Kaplan-Meier 5-year overall survival (OS) for tonsil SCC improved from 54.0 to 74.3 % (p < 0.0001), and cancer-specific survival (CSS) improved from 66.0 to 82.9 % (p < 0.0001). Stratifying by LN involvement showed improved OS in the HPV-predominant cohort with one (63.6 vs. 79.7 %, p < 0.0001), two to three (54.2 vs. 75.9 %, p < 0.0001), four to eight (40.3 vs. 68.9 %, p < 0.0001), and greater than eight positive nodes (25.5 vs. 41.9 %, p < 0.0001). While metastatic LNs still negatively affect prognosis, their impact on OPC survival has diminished in the HPV-predominant era. This finding provides a rationale for additional studies of the prognostic significance of LN metastases in OPC cohorts of defined HPV status, and supports the concept that HPV-related OPC is a disease distinct from "classical" OPC, with unique prognostic features. PMID:24190760

  4. Reduced Impact of Nodal Metastases as a Prognostic Factor for Tonsil Cancer in the HPV Era

    PubMed Central

    Vila, Peter M.; Stucken, Chaz L.; Morris, Luc G.T.; Posner, Marshall R.; Genden, Eric M.; Boffetta, Paolo; Sikora, Andrew G.

    2013-01-01

    Objective Metastatic lymph nodes (LN) are an adverse prognostic factor in head and neck squamous cell carcinoma (SCC). In this study, we tested the hypothesis that nodal metastases have reduced impact on survival in tonsil cancer in the HPV-predominant era. Methods Incidence and mortality data of tonsil and oral cavity SCC between 1988 and 2007 was obtained from the SEER database. Based on published literature, we considered cases of tonsil cancer from 1988–1997 the pre-HPV cohort (N=752), and 1998–2007 as the HPV-predominant cohort (N=2,755). Results Comparing the two cohorts, Kaplan-Meier five-year overall survival (OS) for tonsil SCC improved from 54.0% to 74.3% (p<0.0001), and cancer-specific survival (CSS) improved from 66.0 to 82.9% (p<0.0001). Stratifying by LN involvement showed improved OS in the HPV-predominant cohort with one (63.6 vs. 79.7%, p<0.0001), two to three (54.2 vs. 75.9%, P<0.0001), four to eight (40.3 vs. 68.9%, p<0.0001), and greater than eight positive nodes (25.5 vs. 41.9%, p<0.0001). Conclusion While metastatic LNs still negatively affect prognosis, their impact on OPC survival has diminished in the HPV-predominant era. This finding provides a rationale for additional studies of the prognostic significance of LN metastases in OPC cohorts of defined HPV status, and supports the concept that HPV-related OPC is a disease distinct from “classical” OPC, with unique prognostic features. PMID:24190760

  5. Prognostic Value of Perineural Invasion in Esophageal and Esophagogastric Junction Carcinoma: A Meta-Analysis

    PubMed Central

    Gao, Aiqin; Wang, Linlin; Li, Juan; Li, Hongyu; Han, Yali; Sun, Yuping

    2016-01-01

    Objective. Here we aimed to clarify the prognostic significance of perineural invasion (PNI) in esophageal and esophagogastric junction (EGJ) carcinoma. Methods. A comprehensive literature search for relevant reports published up to July 2015 was performed using Pubmed and Embase databases. The pooled HR and 95% CI for overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic value. The association of PNI with pathological characteristics was evaluated by OR and 95% CI. Results. A total of 13 cohorts were retrieved, covering 2770 patients treated by surgery. The cumulative analysis revealed a statistical correlation between PNI and poor OS (HR = 1.76, 95% CI: 1.54–2.20, and P < 0.00001), as well as poor DFS (HR = 1.96, 95% CI: 1.42–2.71, and P < 0.001). Moreover, analysis of 1475 patients showed improved PNI in T3 + T4 (OR = 0.39, 95% CI: 0.21–0.70, and P = 0.002), N+ (OR = 0.52, 95% CI: 0.40–0.69, and P < 0.00001), and G3 + G4 (OR = 0.66, 95% CI: 0.48–0.90, and P = 0.008) patients compared with T1 + T2, N−, and G1 + G2 ones, respectively. No significant heterogeneity was found between the studies. Conclusions. PNI is an adverse prognostic biomarker in esophageal and EGJ carcinoma. Moreover, PNI implies advanced T, N stage and poor cell differentiation. PMID:27051075

  6. Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers

    PubMed Central

    Aradottir, Margret; Reynisdottir, Sigridur T; Stefansson, Olafur A; Jonasson, Jon G; Sverrisdottir, Asgerdur; Tryggvadottir, Laufey; Eyfjord, Jorunn E

    2014-01-01

    Abstract Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild‐type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer‐specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23–40.6; p = 0.028). Poor breast cancer‐specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19–85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81–51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving

  7. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients.

    PubMed

    Guillevin, L; Lhote, F; Gayraud, M; Cohen, P; Jarrousse, B; Lortholary, O; Thibult, N; Casassus, P

    1996-01-01

    We undertook this study to determine the clinical, biologic, immunologic, and therapeutic factors associated with the prognoses of polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS). Three hundred forty-two patients (260 with PAN, 82 with CSS) followed from 1980 to 1993 were included in a prospective study on prognostic factors. Two hundred eighty-eight of these patients were included in the prospective studies on PAN and CSS. Items to be considered for analysis were collected at the time of diagnosis, during the acute phase of the disease. A survival curve was plotted for each clinical and biologic symptom observed in PAN or CSS. Each treatment arm of the prospective therapeutic trials was also tested: 1) prednisone (CS) + oral cyclophosphamide (CYC) + plasma exchanges (PE) versus CS E, 2) CS + PE versus CS, 3) CS + oral CY versus CS + pulse CY, 4) CS + pulse CY + PE versus CS + pulse CY in severe PAN and CSS, and 5) PE + antiviral agents after short-term CS in hepatitis B virus-related PAN. Of the parameters thus evaluated, the following had significant prognostic value and were responsible for higher mortality: proteinuria > 1 g/d (p < 0.0001; relative risk [RR] 3.6), renal insufficiency with serum creatinine > 1.58 mg/DL (p < 0.02; RR 1.86), GI tract involvement (p < 0.008. RR 2.83 for surgery). Cardiomyopathy and CNS involvement were associated with a RR of mortality of 2.18 and 1.76, respectively; these were not statistically significant. Similar survival rates were obtained with the prospectively tested therapies. The five-factors score (FFS) we established considered the prognostic factors creatinemia, proteinuria, cardiomyopathy, GI tract involvement, and CNS signs. Multivariate analysis showed that proteinuria (due to vascular or glomerular disease) and GI tract involvement were independent prognostic factors. When FFS = 0 (none of the 5 prognostic factors present), mortality at 5 years was 11.9%; when FFS = 1 (1 of the 5 factors present

  8. Adverse effects of common medications on male fertility.

    PubMed

    Samplaski, Mary K; Nangia, Ajay K

    2015-07-01

    An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility. PMID:26101108

  9. Incremental prognostic value of computed tomography in stroke: rationale and design of the IMPACTS study.

    PubMed

    Lee, Ji Won; Hur, Jin; Choi, Sang Il; Chun, Eun Ju; Kang, Joon-Won; Jin, Gong Yong; Kim, Eun Young; Yong, Hwan Seok; Kang, Eun-Ju; Han, Kyunghwa; Lee, Hoon-Suk; Choi, Byoung Wook

    2016-06-01

    This study was designed to determine the prognostic value of coronary computed tomography angiography (CCTA) in ischemic stroke patients and to identify any incremental risk stratification benefits of CCTA findings compared with coronary artery calcium scoring (CACS) and traditional Framingham risk scores (FRS) in ischemic stroke patients without chest pain. IMPACTS is a prospective, multicenter, observational cohort study in which at least seven centers in Korea will participate. All participants will be enrolled in this study after providing informed consent. Nine hundred total ischemic stroke patients without chest pain will be enrolled and will undergo CACS and CCTA. All participants will be followed-up for a minimum of 24 months to determine the endpoints. The primary endpoint will be occurrence of major adverse cardiovascular events (MACEs), defined as all-cause mortality, cardiovascular death, myocardial infarction, or cardiovascular events requiring hospitalization and revascularization either by percutaneous coronary intervention or by coronary artery bypass graft after 90 days of index testing during the follow-up period. Patient enrollment should be completed within 2.5 years. We plan to analyze and identify the CCTA predictors of MACEs. In addition, we will compare several models used to assess independent relationships between the variables and MACEs using a shared frailty model and therefore determine the incremental prognostic value of CCTA findings compared with either the CACS or FRS. The results of IMPACTS will provide valuable information for risk stratification with CCTA in ischemic stroke patients without chest pain. PMID:26910046

  10. The prognostic landscape of genes and infiltrating immune cells across human cancers

    PubMed Central

    Liu, Chih Long; Bratman, Scott V.; Feng, Weiguo; Kim, Dongkyoon; Nair, Viswam S.; Xu, Yue; Khuong, Amanda; Hoang, Chuong D.; Diehn, Maximilian; West, Robert B.; Plevritis, Sylvia K.; Alizadeh, Ash A.

    2016-01-01

    Molecular profiles of tumors and tumor-associated cells hold great promise as biomarkers of clinical outcomes. However, existing datasets are fragmented and difficult to analyze systematically. Here we present a pan-cancer resource and meta-analysis of expression signatures from ~18,000 human tumors with overall survival outcomes across 39 malignancies. Using this resource, we identified a FOXM1 regulatory network as a major predictor of adverse outcomes, and found that expression of favorably prognostic genes, including KLRB1, largely reflect tumor-associated leukocytes. By applying CIBERSORT, a computational approach for inferring leukocyte representation in bulk tumor transcriptomes, we identified complex associations between 22 distinct leukocyte subsets and cancer survival. For example, tumor-associated neutrophil and plasma cell signatures emerged as significant but opposite predictors of survival for diverse solid tumors, including breast and lung adenocarcinomas. This resource and associated analytical tools (http://precog.stanford.edu) may help delineate prognostic genes and leukocyte subsets within and across cancers, shed light on the impact of tumor heterogeneity on cancer outcomes, and discover biomarkers and therapeutic targets. PMID:26193342

  11. Prognostic role of FGFR1 amplification in early-stage non-small cell lung cancer

    PubMed Central

    Cihoric, N; Savic, S; Schneider, S; Ackermann, I; Bichsel-Naef, M; Schmid, R A; Lardinois, D; Gugger, M; Bubendorf, L; Zlobec, I; Tapia, C

    2014-01-01

    Background: Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data are available regarding prevalence, prognostic significance and clinico-pathological characteristics of FGFR1-amplified and early-stage non-small cell lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a large number of well-characterised early-stage NSCLC. Methods: FGFR1 gene status was evaluated using a commercially available fluorescent in situ hybridisation (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected, formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I–II. The FISH results were correlated with clinico-pathological features and overall survival (OS). Results: The prevalence of an FGFR1 amplification was 12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%). Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in patients with an FGFR1-amplified NSCLC. Conclusions: FGFR1 amplification is common in early-stage SCC of the lung and is an independent and adverse prognostic marker. Its potential role as a predictive marker for targeted therapies or adjuvant treatment needs further investigation. PMID:24853178

  12. The adverse outcome pathway knowledge base

    EPA Science Inventory

    The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

  13. Adverse Effects of Psychotropic Medications on Sleep.

    PubMed

    Doghramji, Karl; Jangro, William C

    2016-09-01

    Psychotropic medications such as antidepressants, antipsychotics, stimulants, and benzodiazepines are widely prescribed. Most of these medications are thought to exert their effects through modulation of various monoamines as well as interactions with receptors such as histamine and muscarinic cholinergic receptors. Through these interactions, psychotropics can also have a significant impact on sleep physiology, resulting in both beneficial and adverse effects on sleep. PMID:27514301

  14. Resilience in the Face of Adversity.

    ERIC Educational Resources Information Center

    Patterson, Jerry

    2001-01-01

    "Resilience" is the capacity for moving ahead under adverse circumstances. School superintendents are advised to stay upbeat and mindful of "both-and" opportunities; stay focused on what they care about; remain flexible and tolerant of ambiguity; be proactive, not reactive; and apply resilience-conserving strategies during tough times. (MLH)

  15. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

    Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options. PMID:25536126

  16. Helping Student Teachers Avoid Adverse Legal Actions.

    ERIC Educational Resources Information Center

    Peach, Larry; Reddick, Thomas L.

    1984-01-01

    Discusses five areas of the school environment lending themselves to the possibility of teacher and student teacher liability: negligence, malpractice, rights to privacy, field trips, and search of students and school property. Suggests specific guidelines for decreasing the possibility of adverse legal action. (NEC)

  17. Pharmacogenomics and adverse drug reactions in children

    PubMed Central

    Rieder, Michael J.; Carleton, Bruce

    2014-01-01

    Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. PMID:24795743

  18. [Analysis of Spontaneously Reported Adverse Events].

    PubMed

    Nakamura, Mitsuhiro

    2016-01-01

    Observational study is necessary for the evaluation of drug effectiveness in clinical practice. In recent years, the use of spontaneous reporting systems (SRS) for adverse drug reactions has increased and they have become an important resource for regulatory science. SRS, being the largest and most well-known databases worldwide, are one of the primary tools used for postmarketing surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance algorithms were used for signal detection, including the reporting odds ratio. An SRS is a passive reporting database and is therefore subject to numerous sources of selection bias, including overreporting, underreporting, and a lack of a denominator. Despite the inherent limitations of spontaneous reporting, SRS databases are a rich resource and data mining index that provide powerful means of identifying potential associations between drugs and their adverse effects. Our results, which are based on the evaluation of SRS databases, provide essential knowledge that could improve our understanding of clinical issues. PMID:27040337

  19. Adverse outcome pathway (AOP) development and evaluation

    EPA Science Inventory

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...

  20. Reducing Adverse Impact: One City's Efforts.

    ERIC Educational Resources Information Center

    Prewitt, Jeff

    Following a workshop on "Innovations in Employment Testing that Improve Validity and Reduce Adverse Impact," the City of Louisville (Kentucky) implemented a strategy to develop a comprehensive testing and recruiting program for police recruits. To improve candidate expectations and preparation, the following activities were undertaken: intense…

  1. Development of an On-board Failure Diagnostics and Prognostics System for Solid Rocket Booster

    NASA Technical Reports Server (NTRS)

    Smelyanskiy, Vadim N.; Luchinsky, Dmitry G.; Osipov, Vyatcheslav V.; Timucin, Dogan A.; Uckun, Serdar

    2009-01-01

    We develop a case breach model for the on-board fault diagnostics and prognostics system for subscale solid-rocket boosters (SRBs). The model development was motivated by recent ground firing tests, in which a deviation of measured time-traces from the predicted time-series was observed. A modified model takes into account the nozzle ablation, including the effect of roughness of the nozzle surface, the geometry of the fault, and erosion and burning of the walls of the hole in the metal case. The derived low-dimensional performance model (LDPM) of the fault can reproduce the observed time-series data very well. To verify the performance of the LDPM we build a FLUENT model of the case breach fault and demonstrate a good agreement between theoretical predictions based on the analytical solution of the model equations and the results of the FLUENT simulations. We then incorporate the derived LDPM into an inferential Bayesian framework and verify performance of the Bayesian algorithm for the diagnostics and prognostics of the case breach fault. It is shown that the obtained LDPM allows one to track parameters of the SRB during the flight in real time, to diagnose case breach fault, and to predict its values in the future. The application of the method to fault diagnostics and prognostics (FD&P) of other SRB faults modes is discussed.

  2. [Prognostic significance of syncope in patients with Wolff-Parkinson-White syndrome].

    PubMed

    Auricchio, A; Klein, H; Trappe, H J; Troester, J

    1990-12-01

    The prognostic value of syncope in symptomatic patients with Wolff-Parkinson-White syndrome (WPW) is unknown. Therefore, in order to evaluate the sensibility, specificity, positive and negative predictive value of syncope and compare those values with the one obtained for the shortest RR interval (less than or equal to 250 msec) as well as for the anterograde refractory period of the accessory pathway (less than 270 msec), we reviewed the clinical and electrophysiological data of 158 symptomatic patients with WPW. Fourty-eight patients (30%) reported at least one episode of syncope, and 24 out of 158 patients experienced an aborted sudden death, probably due to rapid conduction via the accessory pathway during atrial fibrillation. Syncope has poor sensibility but high specificity in recognizing an aborted sudden death. However, the syncope demonstrated it had a lower prognostic value when compared with other electrophysiological parameters in correctly identifying patients with a history of ventricular tachycardia and/or fibrillation. In conclusion, the data of this study propose the symptom "syncope" as a frequent event in the history of symptomatic patients with WPW referred to electrophysiological study. Generally its presence does not correctly identify patients who experienced an aborted sudden death. Furthermore, its prognostic value is significantly lower than a shorter RR interval (less than or equal to 250 msec) during atrial fibrillation and an anterograde effective refractory period less than 270 msec. PMID:2083811

  3. Genomic Instability: A Stronger Prognostic Marker Than Proliferation for Early Stage Luminal Breast Carcinomas

    PubMed Central

    Vincent-Salomon, Anne; Benhamo, Vanessa; Gravier, Eléonore; Rigaill, Guillem; Gruel, Nadège; Robin, Stéphane; de Rycke, Yann; Mariani, Odette; Pierron, Gaëlle; Gentien, David; Reyal, Fabien; Cottu, Paul; Fourquet, Alain; Rouzier, Roman; Sastre-Garau, Xavier; Delattre, Olivier

    2013-01-01

    Background The accurate prognosis definition to tailor treatment for early luminal invasive breast carcinoma patients remains challenging. Materials and Methods Two hundred fourteen early luminal breast carcinomas were genotyped with single nucleotide polymorphisms (SNPs) array to determine the number of chromosomal breakpoints as a marker of genomic instability. Proliferation was assessed by KI67 (immunohistochemistry) and genomic grade index (transcriptomic analysis). IHC3 (IHC4 score for HER2 negative tumors) was also determined. Results In the training set (109 cases), the optimal cut-off was 34 breakpoints with a specificity of 0.94 and a sensitivity of 0.57 (Area under the curve (AUC): 0.81[0.71; 0.91]). In the validation set (105 cases), the outcome of patients with > 34 breakpoints (11 events / 22 patients) was poorer (logrank test p < 0.001; Relative Risk (RR): 3.7 [1.73; 7.92]), than that of patients with < 34 breakpoints (19 events / 83 patients).Whereas genomic grade and KI67 had a significant prognostic value in univariate analysis in contrast to IHC3 that failed to have a statistical significant prognostic value in this series, the number of breakpoints remained the only significant parameter predictive of outcome (RR: 3.47, Confidence Interval (CI [1.29; 9.31], p = 0.014)) in multivariate analysis . Conclusion Genomic instability, defined herein as a high number of chromosomal breakpoints, in early stage luminal breast carcinoma is a stronger prognostic marker than proliferation. PMID:24143191

  4. Association of BMI-1 and p16 as prognostic factors for head and neck carcinomas.

    PubMed

    Lundberg, Marie; Renkonen, Suvi; Haglund, Caj; Mattila, Petri S; Leivo, Ilmo; Hagström, Jaana; Mäkitie, Antti A

    2016-05-01

    Conclusions BMI-1 is an upstream repressor of tumor suppressor p16 and their inverse expression patterns have been linked with patient survival in OPSCC. In this material only p16 remained a relevant prognostic marker in OPSCC. Objectives HNSCC tumors carry variable phenotypes and clinical outcomes depending on their anatomical location. In OPSCC, expression of tumor suppressor p16 is used as a surrogate marker of HPV infection and has prognostic value. There are no good prognostic biomarkers for HNSCC tumors of other anatomical locations. Aim To study the expression patterns of p16 and BMI-1 in not only oropharyngeal but also oral, hypopharyngeal, and laryngeal squamous cell carcinomas and to clarify their putative connections with clinical parameters, survival, and each other. Method Hospital records on 130 patients (59 OPSCC, 18 OSCC, 20 HPSCC, and 33 LSCC) diagnosed between 1997-2008 at the Helsinki University Hospital, Finland, were reviewed. BMI-1 and p16 expressions were studied by immunohistochemistry. Results Sixty-eight per cent of OPSCC expressed p16 and expression correlated with lower age, lower T- and higher N-category, and with improved OS and DFS. BMI-1 expression was most prevalent in OPSCC and LSCC, but had no clinical correlations. No correlation between p16 and BMI-1 expression was found. PMID:27052966

  5. Prognostic factors for ampullary adenocarcinomas: tumor stage, tumor histology, tumor location, immunohistochemistry and microsatellite instability.

    PubMed

    Sessa, Fausto; Furlan, Daniela; Zampatti, Clementina; Carnevali, Ileana; Franzi, Francesca; Capella, Carlo

    2007-09-01

    Prognostic factors for ampullary carcinomas (ACs) are poorly defined. Fifty three resected ACs were analyzed for CDX2, MUC1, MUC5AC, MUC6, MUC2, and for mismatch repair proteins (hMLH1, hMSH2, PMS2, hMSH6) using immunohistochemistry. Microsatellite instability (MSI) status was evaluated by fluorescently labeled PCR using an automated sequencer. Univariate and multivariate analysis was performed for clinicopathological, immunohistochemical and molecular parameters. CDX2 was found in 32 out of 53 (60%) ACs with a significantly higher frequency among intestinal ACs compared with biliopancreatic (BP) ACs. The MUC1, MUC5AC, MUC6, MUC2 apomucins were expressed in 75, 43, 39, and 28% of ACs, respectively, with a significantly higher coexpression of MUC1/MUC5AC in BP ACs. MSI and loss of expression of hMLH1/PMS2 or hMSH2/hMSH6 proteins were observed only in intestinal ACs. Factors significantly correlated with improved survival in the univariate analysis were: low stage, absence of lymph nodes metastases, negative surgical margins (R0 status), and presence of MSI. In the multivariate analysis, stage was the only independent prognostic factor of survival. We conclude that stage is the only independent prognostic factor of survival in the multivariate analysis, whereas histological criteria and the immunohistochemical expression of apomucins and CDX2 are helpful in the classification and understanding of the histogenesis of ACs. PMID:17653761

  6. [FACTORIAL ANALYSIS IN PROGNOSTICATION OF INFECTIOUS COMPLICATIONS AFTER SIMULTANT OPERATIVE INTERVENTIONS FOR BILIARY CALCULOUS DISEASE].

    PubMed

    Avad, Ahl Shyrafi Mokhammed; Lutsenko, R V; Malyk, S V

    2016-03-01

    Prognostication of postoperative complications, having a certain high risk of occurrence in surgical treatment of biliary calculous disease, using laparoscopic and open access, peculiarly while performing simultant operative interventions, may promote the treatment efficacy rising in such patients. A multifactorial disperse analysis, using Statistica 6 for Windows (StatSoft), was applied for prognostication of risk for the infectious complications occurrence while a simultant operative interventions conduction for biliary calculous disease. The indices, which, in accordance to the pathophysiological processes character, may influence the postoperative complications occurrence rate, were analyzed. During conduction of this procedure, a great quantity of the parameters, which were determined in the patients, were transformed to a lesser quantity of independent causes. In the one cause a several variables were cojoined, which, as a rule, correlate with each other closely. On a subsequent stage a sum of the points of the prognosis causes for the risk of the postoperative purulent complications occurrence, as the points sum for the status severity and the operative intervention severity, were calculated. A prognostical validity of the algorithm proposed was tested in clinical conditions, its significance was estimated. PMID:27514087

  7. Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia.

    PubMed

    Schnittger, S; Bacher, U; Kern, W; Alpermann, T; Haferlach, C; Haferlach, T

    2011-08-01

    High FLT3-ITD/wildtype (wt) load in FLT3-ITD-mutated AML has been associated with adverse impact on outcome in several studies. To clarify whether FLT3-ITD load as expressed as FLT3-ITD/wt ratio is also relevant in patients with NPM1 mutated AML, we assessed the FLT3-ITD mutation status and FLT3-ITD/wt ratio by fragment analysis in 638 NPM1mut AML (339 females; 299 males; 17.8-88.0 years), and analyzed its prognostic relevance in 355 patients. FLT3-ITD of various length and load were detected in 243/638 cases (38.1%). Median EFS (19.3 vs 9.7 months, P<0.001) and median 2-year survival rate (72.0 vs 52.7%, P=0.006) was better in FLT3wt (n=212 with available follow-up data) than FLT3-ITD (n=143). A higher FLT3-ITD/wt ratio as continuous variable was correlated with a shorter EFS (P=0.028). When patients were separated into subgroups according to the FLT3-ITD mutation load, only a FLT3-ITD/wt ratio 0.5 conferred an independent adverse impact on EFS and OS, and retained its prognostic significance also in multivariate analysis (P=0.009 for EFS, P=0.008 for OS). In conclusion, for risk estimation in NPM1 mutated AML not only the FLT3-ITD status, but also the FLT3-ITD load has to be taken into account. These data might contribute to clinical decision making in AML. PMID:21537333

  8. Prognostic role of MIR146A polymorphisms for cardiovascular events in atrial fibrillation.

    PubMed

    Roldán, Vanessa; Arroyo, Ana Belen; Salloum-Asfar, Sallam; Manzano-Fernández, Sergio; García-Barberá, Nuria; Marín, Francisco; Vicente, Vicente; González-Conejero, Rocío; Martínez, Constantino

    2014-10-01

    There are few biomarkers able to forecast new thrombotic events in patients with AF. In this framework, microRNAs have emerged as critical players in cardiovascular biology. In particular, miR-146a-5p is recognised as an important negative regulator of inflammation. This study aims to evaluate the prognostic role and biological effect of functional MIR146A polymorphisms, rs2431697 and rs2910164, in non-valvular atrial fibrillation (AF) patients under oral anticoagulation.We studied 901 patients with permanent/paroxysmal AF stabilized for at least six months. Patients were followed-up for two years and adverse cardiovascular events (ACE) were recorded. In vitro studies were performed in monocytes from healthy homozygous for the two genotypes of rs2431697. Rs2910164 had no association with ACE. However, multivariate analysis (adjusted by CHA2DS2-VASc score) revealed that rs2431697TT was associated with adverse cardiovascular events [HR: 1.64 (1.09-2.47); p=0.017]. The predictive value of usefulness of the CHA2DS2-VASc+IL6+rs2431697 for predicting ACE, was statistically better than that predicted by CHA2DS2-VASc+IL6. Functional studies showed that after 24 hours incubation, monocytes from CC individuals showed a 65 % increase in miR-146a-5p levels, while TT individuals only showed a 28 % increase. Indeed, after 24 hours of LPS activation, TT monocytes showed a higher increase in IL6 mRNA expression than CC (52 % vs 26 %). Our study established MIR146A rs2431697 as a prognostic biomarker for ACE in anticoagulated AF patients. These data suggest that TT individuals, when submitted to an inflammatory stress, may be prone to a highest pro-inflammatory state due, in part, to lower levels of miR-146a-5p. PMID:25008481

  9. Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Adamovich, Edward; Wallner, Kent E.

    2012-10-01

    Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate size for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.

  10. GFI1(36N) as a therapeutic and prognostic marker for myelodysplastic syndrome.

    PubMed

    Botezatu, Lacramioara; Michel, Lars C; Makishima, Hideki; Schroeder, Thomas; Germing, Ulrich; Haas, Rainer; van der Reijden, Bert; Marneth, Anne E; Bergevoet, Saskia M; Jansen, Joop H; Przychodzen, Bartlomiej; Wlodarski, Marcin; Niemeyer, Charlotte; Platzbecker, Uwe; Ehninger, Gerhard; Unnikrishnan, Ashwin; Beck, Dominik; Pimanda, John; Hellström-Lindberg, Eva; Malcovati, Luca; Boultwood, Jacqueline; Pellagatti, Andrea; Papaemmanuil, Elli; Le Coutre, Philipp; Kaeda, Jaspal; Opalka, Bertram; Möröy, Tarik; Dührsen, Ulrich; Maciejewski, Jaroslaw; Khandanpour, Cyrus

    2016-07-01

    Inherited gene variants play an important role in malignant diseases. The transcriptional repressor growth factor independence 1 (GFI1) regulates hematopoietic stem cell (HSC) self-renewal and differentiation. A single-nucleotide polymorphism of GFI1 (rs34631763) generates a protein with an asparagine (N) instead of a serine (S) at position 36 (GFI1(36N)) and has a prevalence of 3%-5% among Caucasians. Because GFI1 regulates myeloid development, we examined the role of GFI1(36N) on the course of MDS disease. To this end, we determined allele frequencies of GFI1(36N) in four independent MDS cohorts from the Netherlands and Belgium, Germany, the ICGC consortium, and the United States. The GFI1(36N) allele frequency in the 723 MDS patients genotyped ranged between 9% and 12%. GFI1(36N) was an independent adverse prognostic factor for overall survival, acute myeloid leukemia-free survival, and event-free survival in a univariate analysis. After adjustment for age, bone marrow blast percentage, IPSS score, mutational status, and cytogenetic findings, GFI1(36N) remained an independent adverse prognostic marker. GFI1(36S) homozygous patients exhibited a sustained response to treatment with hypomethylating agents, whereas GFI1(36N) patients had a poor sustained response to this therapy. Because allele status of GFI1(36N) is readily determined using basic molecular techniques, we propose inclusion of GFI1(36N) status in future prospective studies for MDS patients to better predict prognosis and guide therapeutic decisions. PMID:27080012

  11. Sudden Sensorineural Hearing Loss; Prognostic Factors

    PubMed Central

    Arjun, Dass; Neha, Goel; Surinder K, Singhal; Ravi, Kapoor

    2015-01-01

    Introduction: Sudden sensorineural hearing loss (SSNHL) is a frightening and frustrating symptom for the patient as well as the physician. Prognosis is affected by multiple factors including duration of hearing loss, presence of associated vertigo and tinnitus, and co-morbidities such as hypertension and diabetes. Materials and Methods: Forty subjects presenting to our department with features of sudden hearing loss were included in the study. Detailed otological history and examination, serial audiometric findings and course of disease were studied. Results: Subjects presenting late (in older age), having associated vertigo, hypertension and diabetes had a significantly lower rate of recovery. Conclusion: Only 60–65% of patients experiencing SSNHL recover within a period of 1 month; this rate is further affected by presence of multiple prognostic indicators. PMID:26568939

  12. Prognostic and predictive markers in pancreatic adenocarcinoma.

    PubMed

    Le, Nha; Sund, Malin; Vinci, Alessio

    2016-03-01

    Pancreatic ductal adenocarcinoma is characterized by a poor prognosis and a low median survival, despite improvements observed for many other solid tumours. Intensive research efforts have been undertaken during the last decades to discover new prognostic and treatment predictive biomarkers for pancreatic ductal adenocarcinoma. The mainstay of medical treatment for the disease has been the well-tolerated nucleoside analogue, gemcitabine. The only targeted agent currently used in pancreatic ductal adenocarcinoma patients is the epithelial growth factor receptor inhibitor erlotinib in combination with gemcitabine. Recently, treatment regimens such as a combination of fluorouracil-leucovorin-irinotecan-oxaliplatin (FOLFIRINOX) and the combination of nab-paclitaxel with gemcitabine have been introduced for metastatic pancreatic ductal adenocarcinoma. Although these treatment regimens significantly improve survival of patients, there are no good predictive biomarkers available that can be used to identify who would benefit most from them. Therefore, the search for predictive biomarkers that would facilitate personalization of chemotherapy is highly relevant. PMID:26769569

  13. Prognostic Significance of Imaging Myocardial Sympathetic Innervation.

    PubMed

    Malhotra, Saurabh; Fernandez, Stanley F; Fallavollita, James A; Canty, John M

    2015-08-01

    There has been a longstanding interest in understanding whether the presence of inhomogeneity in myocardial sympathetic innervation can predict patients at risk of sudden cardiac arrest from lethal ventricular arrhythmias. The advent of radiolabeled norepinephrine analogs has allowed this to be imaged in patients with ischemic and non-ischemic cardiomyopathy using single, photon emission computed tomography (SPECT) and positron emission tomography (PET). Several observational studies have demonstrated that globally elevated myocardial sympathetic tone (as reflected by reduced myocardial norepinephrine analog uptake) can predict composite cardiac end-points including total cardiovascular mortality. More recent studies have indicated that quantifying the extent of regional denervation can predict the risk of lethal ventricular arrhythmias and sudden cardiac death. This review will summarize our current understanding of the prognostic significance of altered myocardial sympathetic innervation. PMID:26087899

  14. Nonrhabdomyosarcomatous abdominopelvic sarcomas: Analysis of prognostic factors

    PubMed Central

    Iqbal, Nida; Shukla, Nootan K.; Deo, S. V. S.; Agarwala, Sandeep; Sharma, D. N.; Sharma, Meher C.; Bakhshi, Sameer

    2016-01-01

    Background: Data concerning treatment outcome and prognostic factors in sarcomas of abdomen and pelvis are sparse in literature. Methods and Results: Of 696 patients with nonrhabdomyosarcomatous soft tissue sarcoma registered at our center between June 2003 and December 2012, 112 (16%) patients of sarcomas arising from abdomen and pelvis were identified, of which 88 patients were analyzed for treatment outcome and prognostic factors. The median age was 40 years (range: 1–78 years) with a male: female ratio of 0.7:1. Twenty-one (24%) patients were metastatic at baseline. The most common tumor sites were retroperitoneum in 70% patients and abdominal wall in 18% patients. Leiomyosarcoma was the most common histological subtype in 36% patients followed by liposarcoma in 17% patients. Thirty-five (40%) patients had Grade III tumors. Forty-six (52%) patients underwent surgical resection. At a median follow-up of 43 months (range: 2–94 months), the 5-year event-free survival (EFS) and overall survival (OS) were 35% and 42%, with a median of 22 months and 43 months, respectively. Multivariate analysis identified male gender (P - 0.03, hazard ratio [HR] - 0.46, 95% confidence interval [CI] - 0.23–0.92), baseline metastatic disease (P - 0.01, HR - 2.98, 95% CI - 1.27–6.98) and Grade III tumors (P - 0.02, HR - 1.84, 95% CI - 1.08–3.13) as factors associated with poor EFS, whereas baseline metastatic disease (P < 0.001, HR - 5.45, 95% CI - 2.31–12.87) and unresectability (P - 0.01, HR - 2.72, 95% CI - 1.27–5.83) were associated with poor OS. Conclusion: This is a single-institutional study of patients with abdominopelvic sarcomas where gender was identified as a new factor affecting survival apart from baseline presentation, histologic grade, and surgical resection. PMID:27168708

  15. Prognostic factors in patients with intracerebral haematoma.

    PubMed Central

    Franke, C L; van Swieten, J C; Algra, A; van Gijn, J

    1992-01-01

    In a prospective study, the prognostic value of clinical characteristics in 157 consecutive patients with spontaneous supratentorial intracerebral haemorrhage were examined by means of multivariate analysis. Two days after the event 37 (24%) patients had died. Factors independently contributing to the prediction of two day mortality were pineal gland displacement on CT of 3 mm or more (p less than 0.001), blood glucose level on admission of 8.0 mmol/l or more (p = 0.01), eye and motor score on the Glasgow Coma Scale of eight out of 10 or less (p = 0.022) and haematoma volume of 40 cm3 or more (p = 0.037). Between the third day and one year after the event another 46 of the 120 two day survivors had died; the independent prognostic indicators for death during that period were: age 70 years or more (p less than 0.001) and severe handicap (Rankin grade five) on the third day (p less than 0.001). Functional independence (Rankin grade two or less) at one year was most common not only with the converse features of age less than 70 years (p less than 0.01) and Rankin grade four or less on the third day (p = 0.002), but also with an eye and motor score on the Glasgow Coma Scale of nine or 10 on the third day (p less than 0.001). The 120 patients with intracerebral haemorrhage who were still alive two days after the event were matched with 120 patients with cerebral infarction, according to age, level of consciousness on the third day after stroke (Glasgow Coma Scale) and handicap (Rankin grade). Survival and handicap after one year did not differ between these two groups. The conclusion drawn is that it is not the cause (intracerebral haemorrhage or cerebral infarction) but the extent of the brain lesion that determines the outcome in patients who survive the first two days. PMID:1527534

  16. Renal tumors: diagnostic and prognostic biomarkers.

    PubMed

    Tan, Puay Hoon; Cheng, Liang; Rioux-Leclercq, Nathalie; Merino, Maria J; Netto, George; Reuter, Victor E; Shen, Steven S; Grignon, David J; Montironi, Rodolfo; Egevad, Lars; Srigley, John R; Delahunt, Brett; Moch, Holger

    2013-10-01

    The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants' responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary. PMID:24025522

  17. Aldosterone predicts major adverse cardiovascular events in patients with acute myocardial infarction

    PubMed Central

    Yuyun, Matthew Fomonyuy; Jutla, Sandeep K; Quinn, Paulene A; Ng, Leong L

    2012-01-01

    Objective Aldosterone is associated with increased mortality in chronic heart failure patients and correlates with adverse outcomes after an acute myocardial infarction (AMI) in smaller cohorts. We evaluated the prognostic significance of plasma aldosterone in a large cohort of post-AMI patients in relation to major adverse cardiovascular events (MACE). Design A prospective cohort study. Setting University Hospitals of Leicester, UK. Patients Consecutive 955 patients admitted with AMI. Plasma aldosterone levels were measured in these patients. Main outcome measures During the 2 years follow-up, MACE which was a composite of all-cause mortality, myocardial reinfarction, and hospitalisation for heart failure as well as secondary endpoints (all-cause mortality and a combination of all-cause mortality and hospitalisation for heart failure), were ascertained. Results MACE occured in N=261, 27.3%, all-cause mortality (N=114, 11.9%) and a combination of all-cause mortality and hospitalisation for heart failure (N=176, 18.4%). Patients with MACE had significantly higher median levels of aldosterone than those without (1150.1 vs 950.4 pmol/l, p=0.0118). The multivariate adjusted HR (95% CI) for log aldosterone on MACE was 1.26 (1.01 to 1.56), p=0.041; all-cause mortality 1.60 (1.13 to 2.27), p=0.008; and combination of all-cause mortality and heart failure 1.50 (1.14 to 1.97), p=0.003. Conclusions The prognostic significance of aldosterone for a variety of endpoints in this large cohort of post-AMI patients is not new and adds to the findings by others. The magnitude of the increase in aldosterone secretion post infarction is higher than previously believed.

  18. Prognostic impact of stress testing in coronary artery disease

    SciTech Connect

    Severi, S.; Michelassi, C. )

    1991-05-01

    Observational data prospectively collected permit the examination of a complex set of decisions, including the decision not to perform any stress testing. Patients with or without previous myocardial infarction admitted for coronary evaluation and not submitted to any stress testing because of clinical reasons are at a higher risk for subsequent death. For prognostication, no test has been better validated than exercise electrocardiography: it can identify patients at low and high risk for future cardiac events among those without symptoms, with typical chest pain, and with previous myocardial infarction. In patients with triple-vessel disease, the results of exercise also allow those at low and high risk to be recognized. Both exercise radionuclide angiography and {sup 201}Tl scintigraphy (the latter in larger patient populations) have also demonstrated significant prognostic value on patients with or without previous myocardial infarction. Neither one has shown superiority to the other in prognostication. So far, they have been considered the only viable alternatives to exercise electrocardiography stress testing for diagnosis and prognostication. However, their costs limit their extensive application. Preliminary data suggest that intravenous dipyridamole echocardiography can be used for both diagnosis and prognostication of coronary artery disease; moreover, the prognostic information derived from dipyridamole echocardiography testing seems independent of and additive to that provided by exercise electrocardiography. Further prospective studies on larger patient populations are needed to better define the prognostic value of dipyridamole echocardiography testing.47 references.

  19. Prognostic value of the six-minute walk test in heart failure patients undergoing cardiac surgery: a literature review.

    PubMed

    Zielińska, Dominika; Bellwon, Jerzy; Rynkiewicz, Andrzej; Elkady, Mohamed Amr

    2013-01-01

    Background. The prognostic value of cardiopulmonary exercise testing (CPET) is known, but the predictive value of 6MWT in patients with heart failure (HF) and patients undergoing coronary artery bypass grafting (CABG) is not established yet. Objective. We conducted a systematic review exploring the prognostic value of 6MWT in HF patients undergoing cardiac surgery. The aim was to find out whether the change in the distance walked during follow-up visits was associated with prognosis. Data Source. We searched "PubMed" from January 1990 to December 2012 for any review articles or experimental studies investigating the prognostic value of 6MWT in HF patients and patients undergoing cardiac surgery. Results. 53 studies were included in the review, and they explored the role of 6MWT in cardiology, cardiac surgery, and rehabilitation. The results did not show the relation between the six-minute walk distance and adverse events after CABG. The predictive power of the distance walked for death in HF patients undergoing cardiac surgery was not found. It is not yet proved if the change in the six-minute walk distance is associated with prognosis. The predictive power of the six-minute walk distance for death in HF patients undergoing cardiac surgery remains unclear. PMID:23984074

  20. Prognostic significance of TP53 alterations in breast carcinoma.

    PubMed Central

    Andersen, T. I.; Holm, R.; Nesland, J. M.; Heimdal, K. R.; Ottestad, L.; Børresen, A. L.

    1993-01-01

    Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions. Immunohistochemistry demonstrated nuclear accumulation of p53 protein in 35 of 162 primary tumours (22%) and in four of 15 metastases (27%). TP53 mutation was strongly associated with nuclear accumulation of p53 protein. In total 42 of 163 primary tumours (26%) and 5 of 16 metastases (31%) were demonstrated to contain TP53 alterations (mutation and/or nuclear protein accumulation). TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival. Images Figure 1 Figure 2 PMID:8102535

  1. Prognostic significance of minichromosome maintenance proteins in breast cancer

    PubMed Central

    Kwok, Hang Fai; Zhang, Shu-Dong; McCrudden, Cian M; Yuen, Hiu-Fung; Ting, Kam-Po; Wen, Qing; Khoo, Ui-Soon; Chan, Kelvin Yuen-Kwong

    2015-01-01

    A role for the minichromosome maintenance (MCM) proteins in cancer initiation and progression is slowly emerging. Functioning as a complex to ensure a single chromosomal replication per cell cycle, the six family members have been implicated in several neoplastic disease states, including breast cancer. Our study aim to investigate the prognostic significance of these proteins in breast cancer. We studied the expression of MCMs in various datasets and the associations of the expression with clinicopathological parameters. When considered alone, high level MCM4 overexpression was only weakly associated with shorter survival in the combined breast cancer patient cohort (n = 1441, Hazard Ratio = 1.31; 95% Confidence Interval = 1.11-1.55; p = 0.001). On the other hand, when we studied all six components of the MCM complex, we found that overexpression of all MCMs was strongly associated with shorter survival in the same cohort (n = 1441, Hazard Ratio = 1.75; 95% Confidence Interval = 1.31-2.34; p < 0.001), suggesting these MCM proteins may cooperate to promote breast cancer progression. Indeed, their expressions were significantly correlated with each other in these cohorts. In addition, we found that increasing number of overexpressed MCMs was associated with negative ER status as well as treatment response. Together, our findings are reproducible in seven independent breast cancer cohorts, with 1441 patients, and suggest that MCM profiling could potentially be used to predict response to treatment and prognosis in breast cancer patients. PMID:25628920

  2. Synthesize battery degradation modes via a diagnostic and prognostic model

    NASA Astrophysics Data System (ADS)

    Dubarry, Matthieu; Truchot, Cyril; Liaw, Bor Yann

    2012-12-01

    Batteries are being used in increasingly complicated configurations with very demanding duty schedules. Such usage makes the use of batteries in multi-cell configurations to meet voltage, power, and energy demands in a very stressful manner. Thus, effective management and control of a battery system to allow efficient, reliable, and safe operation becomes vital, and diagnostic and prognostic tools are essential. Yet, developing these tools in practical applications is new to the industry, difficult and challenging. Here we present a novel mechanistic model that can enable battery diagnosis and prognosis. The model can simulate various “what-if” scenarios of battery degradation modes via a synthetic approach based on specific electrode behavior with proper adjustment of the loading ratio and the extent of degradation in and between the two electrodes. This approach is very different from the conventional empirical ones that correlate the cell parameters (such as impedance increases) with degradation in capacity or power fade to predict performance and life. This approach, with mechanistic understanding of battery degradation processes and failure mechanisms, offers unique high-fidelity simulation to address path dependence of the battery degradation.

  3. Prognostic value of DNA repair based stratification of hepatocellular carcinoma.

    PubMed

    Lin, Zhuo; Xu, Shi-Hao; Wang, Hai-Qing; Cai, Yi-Jing; Ying, Li; Song, Mei; Wang, Yu-Qun; Du, Shan-Jie; Shi, Ke-Qing; Zhou, Meng-Tao

    2016-01-01

    Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy. PMID:27174663

  4. Prognostic value of DNA repair based stratification of hepatocellular carcinoma

    PubMed Central

    Lin, Zhuo; Xu, Shi-Hao; Wang, Hai-Qing; Cai, Yi-Jing; Ying, Li; Song, Mei; Wang, Yu-Qun; Du, Shan-Jie; Shi, Ke-Qing; Zhou, Meng-Tao

    2016-01-01

    Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy. PMID:27174663

  5. Fault Diagnostics and Prognostics for Large Segmented SRMs

    NASA Technical Reports Server (NTRS)

    Luchinsky, Dmitry; Osipov, Viatcheslav V.; Smelyanskiy, Vadim N.; Timucin, Dogan A.; Uckun, Serdar; Hayashida, Ben; Watson, Michael; McMillin, Joshua; Shook, David; Johnson, Mont; Hyde, Scott

    2009-01-01

    We report progress in development of the fault diagnostic and prognostic (FD&P) system for large segmented solid rocket motors (SRMs). The model includes the following main components: (i) 1D dynamical model of internal ballistics of SRMs; (ii) surface regression model for the propellant taking into account erosive burning; (iii) model of the propellant geometry; (iv) model of the nozzle ablation; (v) model of a hole burning through in the SRM steel case. The model is verified by comparison of the spatially resolved time traces of the flow parameters obtained in simulations with the results of the simulations obtained using high-fidelity 2D FLUENT model (developed by the third party). To develop FD&P system of a case breach fault for a large segmented rocket we notice [1] that the stationary zero-dimensional approximation for the nozzle stagnation pressure is surprisingly accurate even when stagnation pressure varies significantly in time during burning tail-off. This was also found to be true for the case breach fault [2]. These results allow us to use the FD&P developed in our earlier research [3]-[6] by substituting head stagnation pressure with nozzle stagnation pressure. The axial corrections to the value of the side thrust due to the mass addition are taken into account by solving a system of ODEs in spatial dimension.

  6. The Prognostic Role of SOCS3 and A20 in Human Cholangiocarcinoma

    PubMed Central

    Wang, Yimin; Wan, Ming; Zhou, Qingxin; Wang, Hao; Wang, Zhidong; Zhong, Xiangyu; Zhang, Lei; Tai, Sheng; Cui, Yunfu

    2015-01-01

    As an antagonist of the JAK/STAT pathway, suppressor of cytokine signaling 3 (SOCS3) plays an integral role in shaping the inflammatory environment, tumorigenesis and disease progression in cholangiocarcinoma (CCA); however, its prognostic significance remains unclear. Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown. In this study, we investigated the expression of SOCS3 and A20 in human CCA tissues to assess the prognostic significance of these proteins. The expression of SOCS3 and A20 was initially detected by western blot in 22 cases of freshly frozen CCA tumors with corresponding peritumoral tissues and 22 control normal bile duct tissues. Then, these proteins were investigated in 86 CCA patients by immunohistochemistry (IHC) and were evaluated for their association with clinicopathological parameters in human CCA. The results indicated that SOCS3 expression was significantly lower in CCA tumor tissues than in corresponding peritumoral biliary tissues and normal bile duct tissues. Conversely, A20 was overexpressed in CCA tissues. Thus, an inverse correlation between the expression of SOCS3 and A20 was discovered. Furthermore, patients with low SOCS3 expression or high A20 expression showed a dramatically lower overall survival rate. These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate. However, only A20 showed a significant association with the tumor node metastasis (TNM) stage, while SOCS3 showed a significant association with tumor differentiation. Multivariate Cox analysis revealed that SOCS3 and A20 were independent prognostic indicators for overall survival in CCA. Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA. PMID:26485275

  7. Prognostic Impact of Time to Ipsilateral Breast Tumor Recurrence after Breast Conserving Surgery

    PubMed Central

    Gosset, Marie; Hamy, Anne-Sophie; Mallon, Peter; Delomenie, Myriam; Mouttet, Delphine; Pierga, Jean-Yves; Lae, Marick; Fourquet, Alain; Rouzier, Roman; Reyal, Fabien; Feron, Jean-Guillaume

    2016-01-01

    Background The poor prognosis of patients who experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) is established. A short time between primary cancer and IBTR is a prognostic factor but no clinically relevant threshold was determined. Classification of IBTR may help tailor treatment strategies. Purpose We determined a specific time frame, which differentiates IBTR into early and late recurrence, and identified prognostic factors for patients with IBTR at time of the recurrence. Methods We analyzed 2209 patients with IBTR after BCS. We applied the optimal cut-points method for survival data to determine the cut-off times to IBTR. A subgroup analysis was performed by hormone receptor (HR) status. Survival analyses were performed using a Cox proportional hazard model to determine clinical features associated with distant-disease-free survival (DDFS) after IBTR. We therefor built decision trees. Results On the 828 metastatic events observed, the majority occurred within the first 3 months after IBTR: 157 in the HR positive group, 98 in the HR negative group. We found different prognostic times to IBTR: 49 months in the HR positive group, 33 in the HR negative group. After multivariate analysis, time to IBTR was the first discriminant prognostic factor in both groups (HR 0.65 CI95% [0.54–0.79] and 0.42 [0.30–0.57] respectively). The other following variables were significantly correlated with the DDFS: the initial number of positive lymph nodes for both groups, the initial tumor size and grade for HR positive tumors. Conclusion A short interval time to IBTR is the strongest factor of poor prognosis and reflects occult distant disease. It would appear that prognosis after IBTR depends more on clinical and histological parameters than on surgical treatment. A prospective trial in a low-risk group of patients to validate the safety of salvage BCS instead of mastectomy in IBTR is needed. PMID:27494111

  8. Identification of prognostic factors in canine mammary malignant tumours: a multivariable survival study

    PubMed Central

    2013-01-01

    Background Although several histopathological and clinical features of canine mammary gland tumours have been widely studied from a prognostic standpoint, considerable variations in tumour individual biologic behaviour difficult the definition of accurate prognostic factors. It has been suggested that the malignant behaviour of tumours is the end result of several alterations in cellular physiology that culminate in tumour growth and spread. Accordingly, the aim of this study was to determine, using a multivariable model, the independent prognostic value of several immunohistochemically detected tumour-associated molecules, such as MMP-9 and uPA in stromal cells and Ki-67, TIMP-2 and VEGF in cancer cells. Results Eighty-five female dogs affected by spontaneous malignant mammary neoplasias were followed up for a 2-year post-operative period. In univariate analysis, tumour characteristics such as size, mode of growth, regional lymph node metastases, tumour cell MIB-1 LI and MMP-9 and uPA expressions in tumour-adjacent fibroblasts, were associated with both survival and disease-free intervals. Histological type and grade were related with overall survival while VEGF and TIMP-2 were not significantly associated with none of the outcome parameters. In multivariable analysis, only a MIB-1 labelling index higher than 40% and a stromal expression of MMP-9 higher than 50% retained significant relationships with poor overall and disease-free survival. Conclusions The results of this study indicate that MMP-9 and Ki-67 are independent prognostic markers of canine malignant mammary tumours. Furthermore, the high stromal expressions of uPA and MMP-9 in aggressive tumours suggest that these molecules are potential therapeutic targets in the post-operative treatment of canine mammary cancer. PMID:23289974

  9. Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

    PubMed Central

    Fabregat-Andrés, Óscar; Estornell-Erill, Jordi; Ridocci-Soriano, Francisco; Pérez-Boscá, José Leandro; García-González, Pilar; Payá-Serrano, Rafael; Morell, Salvador; Cortijo, Julio

    2016-01-01

    Background Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. Results 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). Conclusions In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF. PMID:26840055

  10. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  11. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  12. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  13. Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: a large case series study with a long-term follow-up.

    PubMed

    Bustreo, Sara; Osella-Abate, Simona; Cassoni, Paola; Donadio, Michela; Airoldi, Mario; Pedani, Fulvia; Papotti, Mauro; Sapino, Anna; Castellano, Isabella

    2016-06-01

    Although Ki67 index suffers from poor reproducibility, it is one of the most important prognostic markers used by oncologists to select the treatment of estrogen receptor (ER) positive breast cancer patients. In this study, we aim to establish the optimal Ki67 cut-offs for stratifying patient prognosis and to create a comprehensive prognostic index for clinical applications. A mono-institutional cohort of 1.577 human epidermal growth factor receptor 2 negative/ER+ breast cancer patients having complete clinical, histological, and follow-up data was collected. The 14 and 20 % Ki67 cut-offs were correlated to disease-free interval (DFI) and disease-specific survival (DSS). To create a comprehensive prognostic index, we used independent variables selected by uni/multivariate analyses. In terms of DFI and DSS, patients bearing tumors with Ki67 < 14 % proliferation index did not differ from those with Ki67 values between 14 and 20 %. Patients with tumor with Ki67 > 20 % showed the poorest prognosis. Moreover, to tumor size, the number of metastatic lymph nodes and Ki67 > 20 % was given a score value, varying depending on definite cut-offs and used to create a prognostic index, which was applied to the population. Patients with a prognostic index ≥3 were characterized by significant risk of relapse [DFI: Hazard Ratio (HR) = 4.74, p < 0.001] and death (DSS: HR = 5.03, p < 0.001). We confirm that the 20 % Ki67 cut-off is the best to stratify high-risk patients in luminal breast cancers, and we suggest to integrate it with other prognostic factors, to better stratify patients at risk of adverse outcome. PMID:27155668

  14. Prognostic models in acute pulmonary embolism: a systematic review and meta-analysis

    PubMed Central

    Elias, Antoine; Mallett, Susan; Daoud-Elias, Marie; Poggi, Jean-Noël; Clarke, Mike

    2016-01-01

    Objective To review the evidence for existing prognostic models in acute pulmonary embolism (PE) and determine how valid and useful they are for predicting patient outcomes. Design Systematic review and meta-analysis. Data sources OVID MEDLINE and EMBASE, and The Cochrane Library from inception to July 2014, and sources of grey literature. Eligibility criteria Studies aiming at constructing, validating, updating or studying the impact of prognostic models to predict all-cause death, PE-related death or venous thromboembolic events up to a 3-month follow-up in patients with an acute symptomatic PE. Data extraction Study characteristics and study quality using prognostic criteria. Studies were selected and data extracted by 2 reviewers. Data analysis Summary estimates (95% CI) for proportion of risk groups and event rates within risk groups, and accuracy. Results We included 71 studies (44 298 patients). Among them, 17 were model construction studies specific to PE prognosis. The most validated models were the PE Severity Index (PESI) and its simplified version (sPESI). The overall 30-day mortality rate was 2.3% (1.7% to 2.9%) in the low-risk group and 11.4% (9.9% to 13.1%) in the high-risk group for PESI (9 studies), and 1.5% (0.9% to 2.5%) in the low-risk group and 10.7% (8.8% to12.9%) in the high-risk group for sPESI (11 studies). PESI has proved clinically useful in an impact study. Shifting the cut-off or using novel and updated models specifically developed for normotensive PE improves the ability for identifying patients at lower risk for early death or adverse outcome (0.5–1%) and those at higher risk (up to 20–29% of event rate). Conclusions We provide evidence-based information about the validity and utility of the existing prognostic models in acute PE that may be helpful for identifying patients at low risk. Novel models seem attractive for the high-risk normotensive PE but need to be externally validated then be assessed in impact studies. PMID

  15. Adverse Reactions in Allogeneic Blood Donors: A Tertiary Care Experience from a Developing Country

    PubMed Central

    Sultan, Sadia; Baig, Mohammad Amjad; Irfan, Syed Mohammed; Ahmed, Syed Ijlal; Hasan, Syeda Faiza

    2016-01-01

    Objectives Fragmented blood transfusion services along with an unmotivated blood donation culture often leads to blood shortage. Donor retention is crucial to meet the increasing blood demand, and adverse donor reactions have a negative impact on donor return. The aim of this study was to estimate adverse donor reactions and identify any demographic association.   Methods We conducted a prospective study between January 2011 and December 2013. A total of 41,759 healthy donors were enrolled. Professionally trained donor attendants drew blood and all donors were observed during and following donation for possible adverse events for 20 minutes. Blood donors were asked to report if they suffered from any delayed adverse consequences.   Results Out of 41,759 blood donors, 537 (1.3%) experienced adverse reactions. The incidence was one in every 78 donations. The mean age of donors who experienced adverse events was 26.0±6.8 years, and all were male. Out of 537 donors, 429 (80%) developed vasovagal reaction (VVR), 133 (25%) had nausea, 63 (12%) fainted, 35 (6%) developed hyperventilation, 9 (2%) had delayed syncope, and 9 (2%) developed hematoma. Arterial prick, nerve injury, cardiac arrest, and seizures were not observed. Donors aged less than < 30 years and weighing < 70 kg were significantly associated with VVR, hyperventilation, and nausea (p < 0.005). Undergraduates and Urdu speaking donors also had a significant association with fainting and nausea, respectively (p < 0.05).   Conclusion The prevalence of adverse events was low at our tertiary center. A VVR was the predominant adverse reaction and was associated with age and weight. Our study highlights the importance of these parameters in the donation process. A well-trained and experienced phlebotomist and pre-evaluation counseling of blood donors could further minimize the adverse reactions. PMID:27168923

  16. Prognostic relevance of morphological classification models for myelodysplastic syndromes in an era of the revised International Prognostic Scoring System.

    PubMed

    van Spronsen, Margot F; Ossenkoppele, Gert J; Westers, Theresia M; van de Loosdrecht, Arjan A

    2016-03-01

    Numerous morphological classification models have been developed to organise the heterogeneous spectrum of myelodysplastic syndromes (MDS). While the 2008 update of the World Health Organisation (WHO) is the current standard, the publication of the revised International Prognostic Scoring System (IPSS-R) has illustrated the need for supplemental prognostic information. The aim of this study was to investigate whether morphological classification models for MDS - of both the French-American-British (FAB) group and WHO - provide reliable criteria for their classification into homogeneous and clinically relevant categories with prognostic relevance beyond the IPSS-R. We reclassified 238 MDS patients using each of the FAB, WHO 2001 and WHO 2008 criteria and studied classification categories in terms of clinical, haematological and cytogenetic features. Subsequently, we calculated prognostic scores using the IPSS-R and investigated whether the morphological classification models had significantly prognostic value in patients stratified by the IPSS-R and vice versa. By adopting the FAB, WHO 2001 and WHO 2008 classifications, MDS patients were organised into homogeneous categories with intrinsic prognostic information. However, whereas the morphological classification models showed no prognostic value beyond the IPSS-R, the IPSS-R had significant prognostic value beyond the FAB, WHO 2001 and WHO 2008 classifications. Even though morphological classification models for MDS might be clinically relevant from a prognostic point of view, their relevance in terms of risk stratification is evidently limited in light of the IPSS-R. Therefore, we suggest to stop the use of morphological classification models for MDS for risk stratification in routine clinical practice. PMID:26798967

  17. Glaucoma eye drops adverse skin reactions.

    PubMed

    Cantisani, Carmen; Ambrifi, Marina; Frascani, Federica; Fazia, Gilda; Paolino, Giovanni; Lisi, Roberto; Calvieri, Stefano

    2014-01-01

    The term "Glaucoma" is used to describe a number of diseases of the eye characterized by a particular form of optic nerve damage that is often associated with high intraocular pressure (IOP). The open-angle glaucoma is the most common form that is also referred to as chronic glaucoma. This is described as an optic neuropathy with multifactorial nature in which there is a loss of characteristics of the optic nerve fibers. Therapeutic options for the treatment of this disease are different, you can take advantage of eye drops, laser therapy and conventional surgery or more combined treatments. Medicated eye drops are the most common way to treat glaucoma. Although eye drops are widely used, adverse reactions are not frequently observed and described. In particular, the adverse skin reactions are not frequently described in the literature, but often seen in dermatologic clinic, we reported their skin reactions and possible alternative treatments described in literature and their patent applications. PMID:25487259

  18. Ruptured abdominal aortic aneurysms: review of 33 cases treated surgically and discussion of prognostic indicators.

    PubMed

    Sink, J D; Myers, R T; James, P M

    1976-05-01

    Over an eight-year peroid at NCBH, 33 patients were operated for ruptured abdominal aortic aneurysm. Factors associated with an increased mortality included preoperative blood urea nitrogen levels of more than 20 mg per cent, severe preoperative hypotension, duration of symptoms of less than 24 hours, free peritoneal rupture and blood transfusions of greater than 19 units. Preoperative hypotension was the most selective preoperative prognostic parameter. From a review of this and other reported series, it was concluded that reduced mortality from ruptured abdominal aortic aneurysm can best be achieved by prompt diagnosis followed by surgical treatment before cardiovascular collapse can occur. PMID:1267283

  19. [Prognostic value of the immunohistochemical expresion of protein Rb in epidermoid carcinoma of the larynx].

    PubMed

    García Lozano, M C; Orradre Romero, J L; Sánchez Carrión, S; Menéndez Loras, L M; Jiménez Antolín, J; Piris Pinilla, M A

    2005-01-01

    In this paper we carried out an immunohistochemical study of protein Rb (G3-245) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain) for a time of 5 years. In the cases with lymph node metastasis we also studied Rb expression at this level. Furthermore we have analysed the value of Rb expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between Rb expression and other clinic and pathologic parameters. PMID:15929589

  20. The diagnostic, predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer.

    PubMed

    Karabulut, S; Tas, F; Tastekin, D; Karabulut, M; Yasasever, C T; Ciftci, R; Güveli, M; Fayda, M; Vatansever, S; Serilmez, M; Disci, R; Aydıner, A

    2014-09-01

    The purpose of this study was to determine the clinical significance of vascular cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM) in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent assay (ELISA)). The median age at diagnosis was 48 years (range 29-80 years). Majority of the patients (71 %) had luminal subtype, and 38.5 % had metastatic disease. Twenty-nine (30 %) patients showed tumor progression, and 20 (21 %) patients died during follow-up. Median progression-free survival (PFS) and overall survival (OS) were 8.6 ± 1.7 and 35.5 ± 1.5 months, respectively. The baseline serum EpCAM levels of the patients were significantly higher than those of the controls (p < 0.001). There was no significant difference in the serum levels of VCAM-1 between the patients and controls (p = 0.47). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p > 0.05). Patients with HER-2-positive and triple-negative tumors had significantly poorer PFS (p = 0.04 and p = 0.001, respectively), while metastatic disease and chemotherapy unresponsiveness had significantly adverse effect on OS analysis (p < 0.001 and p < 0.001, respectively). Neither serum VCAM-1 levels nor serum EpCAM levels were identified to have a prognostic role on either PFS or OS (VCAM-1 p = 0.76 and p = 0.32; EpCAM p = 0.16 and p = 0.69, respectively). Even though any predictive or prognostic role could not be determined for both markers, serum levels of EpCAM were found to have diagnostic value in BC patients. PMID:24891186

  1. High resolution ECG-aided early prognostic model for comatose survivors of out of hospital cardiac arrest.

    PubMed

    Rauber, Martin; Štajer, Dušan; Noč, Marko; Schlegel, Todd T; Starc, Vito

    2015-01-01

    Out of hospital cardiac arrest (OHCA) has a high mortality despite modern treatment. Reliable early prognosis in OHCA could significantly improve clinical decision making. We explored prognostic utility of advanced ECG parameters, obtained from high-resolution ECG, in combination with clinical and OHCA-related parameters during treatment with mild induced hypothermia (MIH) and after rewarming in unconscious survivors of OHCA. Ninety-two patients during MIH and 66 after rewarming were included. During MIH, a score based on initial rhythm, QRS-upslope and systolic pressure resulted in an area under curve (AUC) of 0.82 and accuracy of 80% for survival. After rewarming, a score based on admission rhythm, sum of 12 lead QRS voltages, and mean lateral ST segment level in leads I and V6 resulted in an AUC of 0.88 and accuracy of 85% for survival. ECG can assist with early prognostication in unconscious survivors of OHCA during MIH and after rewarming. PMID:25911585

  2. Anaphylactoid and adverse reactions to radiocontrast agents.

    PubMed

    Hagan, John B

    2004-08-01

    Over the past 75 years, radiocontrast agents have provided numerous diagnostic and therapeutic advances. The benefits of these agents must be weighed against the potential risks for each individual undergoing radiologic tests. This summary is intended to be a guide for the allergy and immunology specialist to direct him or her to the current literature regarding adverse reactions to traditional and less commonly used radiologic contrast agents. PMID:15242724

  3. An Ss Model with Adverse Selection.

    ERIC Educational Resources Information Center

    House, Christopher L.; Leahy, John V.

    2004-01-01

    We present a model of the market for a used durable in which agents face fixed costs of adjustment, the magnitude of which depends on the degree of adverse selection in the secondary market. We find that, unlike typical models, the sS bands in our model contract as the variance of the shock increases. We also analyze a dynamic version of the model…

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

    SciTech Connect

    Kim, Jun-Sang; Kim, Jin-Man; Liang, Zhe Long; Jang, Ji Young; Kim, Sup; Huh, Gil Ja; Kim, Ki-Hwan; Cho, Moon-June

    2012-01-01

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

  5. Adverse effects of human immunoglobulin therapy.

    PubMed

    Stiehm, E Richard

    2013-07-01

    Human immunoglobulin (IG) is used for IgG replacement therapy in primary and secondary immunodeficiency, for prevention and treatment of certain infections, and as an immunomodulatory agent for autoimmune and inflammatory disorders. IG has a wide spectrum of antibodies to microbial and human antigens. Several high-titered IGs are also available enriched in antibodies to specific viruses or bacterial toxins. IG can be given intravenously (IGIV), intramuscularly (IGIM) or by subcutaneous infusions (SCIG). Local adverse reactions such as persistent pain, bruising, swelling and erythema are rare with IGIV infusions but common (75%) with SCIG infusions. By contrast, adverse systemic reactions are rare with SCIG infusions but common with IGIV infusions, occurring as often as 20% to 50% of patients and 5% to 15% of all IGIV infusions. Systemic adverse reactions can be immediate (60% of reactions) occurring within 6 hours of an infusion, delayed (40% of reactions) occurring 6 hours-1 week after an infusion, and late (less than 1% of reactions), occurring weeks and months after an infusion. Immediate systemic reactions such as head and body aches, chills and fever are usually mild and readily treatable. Immediate anaphylactic and anaphylactoid reactions are uncommon. The most common delayed systemic reaction is persistent headache. Less common but more serious delayed reactions include aseptic meningitis, renal failure, thromboembolism, and hemolytic reactions. Late reactions are uncommon but often severe, and include lung disease, enteritis, dermatologic disorders and infectious diseases. The types, incidence, causes, prevention, and management of these reactions are discussed. PMID:23835249

  6. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors. PMID:26070758

  7. Prognostic value of health-related quality of life for death risk stratification in patients with unresectable glioblastoma.

    PubMed

    Paquette, Brice; Vernerey, Dewi; Chauffert, Bruno; Dabakuyo, Sandrine; Feuvret, Loic; Taillandier, Luc; Frappaz, Didier; Taillia, Hervé; Schott, Roland; Ducray, François; Fabbro, Michel; Tennevet, Isabelle; Ghiringhelli, François; Guillamo, Jean-Sébastien; Durando, Xavier; Castera, Daniel; Frenay, Marc; Campello, Chantal; Dalban, Cécile; Skrzypski, Jérome; Chinot, Olivier; Anota, Amélie; Bonnetain, Franck

    2016-08-01

    Glioblastoma is the most common malignant brain tumor in adults. Baseline health-related quality of life (HRQoL) is a major subject of concern for these patients. We aimed to assess the independent prognostic value of HRQoL in unresectable glioblastoma (UGB) patients for death risk stratification. One hundred and thirty-four patients with UGB were enrolled from the TEMAVIR trial. HRQoL was evaluated at baseline using the EORTC QLQ-C30 and BN20 brain cancer module. Clinical and HRQoL parameters were evaluated in univariable and multivariable Cox analysis as prognostic factors for overall survival (OS). Performance assessment and internal validation of the final model were evaluated with Harrel's C-index, calibration plot, and bootstrap sample procedure. Two OS independent predictors were identified: future uncertainty and sensitivity deficit. The final model exhibited good calibration and acceptable discrimination (C statistic = 0.63). The internal validity of the model was verified with robust uncertainties around the hazard ratio. The prognostic score identified three groups of patients with distinctly different risk profiles with median OS estimated at 16.2, 9.2, and 4.5 months. We demonstrated the additional prognostic value of HRQoL in UGB for death risk stratification and provided a score that may help to guide clinical management and stratification in future clinical trials. PMID:27252150

  8. Accelerated Aging with Electrical Overstress and Prognostics for Power MOSFETs

    NASA Technical Reports Server (NTRS)

    Saha, Sankalita; Celaya, Jose Ramon; Vashchenko, Vladislav; Mahiuddin, Shompa; Goebel, Kai F.

    2011-01-01

    Power electronics play an increasingly important role in energy applications as part of their power converter circuits. Understanding the behavior of these devices, especially their failure modes as they age with nominal usage or sudden fault development is critical in ensuring efficiency. In this paper, a prognostics based health management of power MOSFETs undergoing accelerated aging through electrical overstress at the gate area is presented. Details of the accelerated aging methodology, modeling of the degradation process of the device and prognostics algorithm for prediction of the future state of health of the device are presented. Experiments with multiple devices demonstrate the performance of the model and the prognostics algorithm as well as the scope of application. Index Terms Power MOSFET, accelerated aging, prognostics

  9. Prognostic value of normal regadenoson stress perfusion cardiovascular magnetic resonance

    PubMed Central

    2013-01-01

    Background Regadenoson is a vasodilator stress agent that selectively activates the A2A receptor. Compared to adenosine, regadenoson is easier to administer and results in fewer side effects. Although extensively studied in patients undergoing nuclear perfusion imaging (MPI), its use for perfusion cardiovascular magnetic resonance (CMR) is not well described. The aim of this study was to determine the prognostic value of a normal regadenoson perfusion CMR in patients with known or suspected coronary artery disease. Methods Patients with known or suspected coronary artery disease were prospectively enrolled to receive perfusion CMR (Philips 1.5 T) with regadenoson. Three short-axis slices of the left ventricle (LV) were obtained during first pass of contrast using a hybrid GRE-EPI pulse sequence (0.075 mmol/kg Gadolinium-DTPA-BMA at 4 ml/sec). Imaging was performed 1 minute after injection of regadenoson (0.4 mg) and repeated 15 minutes after reversal of hyperemia with aminophylline (125 mg). Perfusion defects were documented if they persisted for ≥2 frames after peak enhancement of the LV cavity. CMR was considered abnormal if there was a resting wall motion abnormality, decreased LVEF (<40%), presence of LGE, or the presence of a perfusion defect during hyperemia. All patients were followed for a minimum of 1 year for major adverse cardiovascular event (MACE) defined as coronary revascularization, non-fatal myocardial infarction, and cardiovascular death. Results 149 patients were included in the final analysis. Perfusion defects were noted in 43/149 (29%) patients; 59/149 (40%) had any abnormality on CMR. During the mean follow-up period of 24 ± 9 months, 17/149 (11.4%) patients experienced MACE. The separation in the survival distributions for those with perfusion defects and those without perfusion defects was highly significant (log-rank p = 0.0001). When the absence of perfusion defects was added to the absence of other resting CMR

  10. Population-specific prognostic models are needed to stratify outcomes for African-Americans with diffuse large B-cell lymphoma.

    PubMed

    Chen, Qiushi; Ayer, Turgay; Nastoupil, Loretta J; Koff, Jean L; Staton, Ashley D; Chhatwal, Jagpreet; Flowers, Christopher R

    2016-04-01

    Diffuse large B-cell lymphoma (DLBCL) demonstrates significant racial differences in age of onset, stage, and survival. To examine whether population-specific models improve prediction of outcomes for African-American (AA) patients with DLBCL, we utilized Surveillance, Epidemiology, and End Results data and compared stratification by the international prognostic index (IPI) in general and AA populations. We also constructed and compared prognostic models for general and AA populations using multivariable logistic regression (LR) and artificial neural network approaches. While the IPI adequately stratified outcomes for the general population, it failed to separate AA DLBCL patients into distinct risk groups. Our AA LR model identified age ≥ 55 (odds ratio 0.45, [95% CI: 0.36, 0.56], male sex (0.75, [0.60, 0.93]), and stage III/IV disease (0.43, [0.34, 0.54]) as adverse predictors of 5-year survival for AA patients. In addition, general-population prognostic models were poorly calibrated for AAs with DLBCL, indicating a need for validated AA-specific prognostic models. PMID:26415108

  11. Diagnostic and Prognostic Models for Generator Step-Up Transformers

    SciTech Connect

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

    2014-09-01

    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 fault 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.

  12. Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma.

    PubMed

    Hillengass, Jens; Ritsch, Judith; Merz, Maximilian; Wagner, Barbara; Kunz, Christina; Hielscher, Thomas; Laue, Hendrik; Bäuerle, Tobias; Zechmann, Christian M; Ho, Anthony D; Schlemmer, Heinz-Peter; Goldschmidt, Hartmut; Moehler, Thomas M; Delorme, Stefan

    2016-07-01

    This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0·89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS. PMID:26991959

  13. Meningioma Genomics: Diagnostic, Prognostic, and Therapeutic Applications

    PubMed Central

    Bi, Wenya Linda; Zhang, Michael; Wu, Winona W.; Mei, Yu; Dunn, Ian F.

    2016-01-01

    There has been a recent revolution in our understanding of the genetic factors that drive meningioma, punctuating an equilibrium that has existed since Cushing’s germinal studies nearly a century ago. A growing appreciation that meningiomas share similar biologic features with other malignancies has allowed extrapolation of management strategies and lessons from intra-axial central nervous system neoplasms and systemic cancers to meningiomas. These features include a natural proclivity for invasion, frequent intratumoral heterogeneity, and correlation between biologic profile and clinical behavior. Next-generation sequencing has characterized recurrent somatic mutations in NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA, which are collectively present in ~80% of sporadic meningiomas. Genomic features of meningioma further associate with tumor location, histologic subtype, and possibly clinical behavior. Such genomic decryption, along with advances in targeted pharmacotherapy, provides a maturing integrated view of meningiomas. We review recent advances in meningioma genomics and probe their potential applications in diagnostic, therapeutic, and prognostic frontiers. PMID:27458586

  14. Prognostic value of sarcopenia in liver surgery.

    PubMed

    Cornet, M; Lim, C; Salloum, C; Lazzati, A; Compagnon, P; Pascal, G; Azoulay, D

    2015-11-01

    Current knowledge indicates that malnutrition increases the rate of post-operative complications, particularly respiratory and infectious, after major surgery. Almost all liver surgery is performed in patients with cancer, a factor that increases the risk of malnutrition. The primary risk factors for post-operative complications are pre-operative hypo-albuminemia and a body mass index less than 20 kg/m(2). To improve the prediction of complications in these patients, some teams have suggested measurement of muscle thickness by computed tomography. Muscular mass can thus be quantified by measuring the total surface of the psoas muscle or the total surface of all muscles (i.e. external and internal oblique, transverse, psoas and paravertebral muscles) seen on an axial CT slice at L3. As well, data exist suggesting that sarcopenia is an independent predictive factor of post-operative morbidity and poor long-term survival after resection for cancer. Nonetheless, the literature on the subject is limited, there are no standardized definitions for sarcopenia, and the need of special software to calculate the surfaces limits its usefulness. Lastly, there are little if any data concerning the nutritional or pharmacologic means to treat sarcopenia. This update, based on a literature review, deals with the value and the prognostic impact of sarcopenia in surgery for liver tumors. The current definition of sarcopenia, validated internationally, the methods of measurement, and the consequences of sarcopenia on the outcome of liver resections are detailed in this review. PMID:26476674

  15. Damage Propagation Modeling for Aircraft Engine Prognostics

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Goebel, Kai; Simon, Don; Eklund, Neil

    2008-01-01

    This paper describes how damage propagation can be modeled within the modules of aircraft gas turbine engines. To that end, response surfaces of all sensors are generated via a thermo-dynamical simulation model for the engine as a function of variations of flow and efficiency of the modules of interest. An exponential rate of change for flow and efficiency loss was imposed for each data set, starting at a randomly chosen initial deterioration set point. The rate of change of the flow and efficiency denotes an otherwise unspecified fault with increasingly worsening effect. The rates of change of the faults were constrained to an upper threshold but were otherwise chosen randomly. Damage propagation was allowed to continue until a failure criterion was reached. A health index was defined as the minimum of several superimposed operational margins at any given time instant and the failure criterion is reached when health index reaches zero. Output of the model was the time series (cycles) of sensed measurements typically available from aircraft gas turbine engines. The data generated were used as challenge data for the Prognostics and Health Management (PHM) data competition at PHM 08.

  16. Prognostication--the lost skill of medicine.

    PubMed

    Kellett, John

    2008-05-01

    Making a prognosis is one of the primary functions of the medical profession. At the end of the nineteenth century prognostication took up approximately ten percent of medical textbooks, by 1970 this had fallen to nearly zero. Given medical technology's awesome ability to prolong the process and suffering of dying today's patients need to know their prognosis in order to make choices about their treatment options. Whilst precise predictions of the future are obviously not possible, relatively simple mathematical modelling techniques can make reasonable estimates of likely outcomes for individual patients. The life expectancy of a patient of any age with any illness can be estimated provided the disease-specific mortality of the illness is known. Decision analysis or logistic regression models can then be used to determine the risks and benefits of various treatment options. A patient's prognosis does not just depend on their age and primary diagnosis, but also on the severity of their illness, their functional capacity both prior to and during the illness and the number of co-morbidities also suffered from. Several predictive instruments have been developed to help simplify the prediction of the outcome of individual patients. There are conflicting reports on how these models compare with doctors' intuition--whatever their strengths and weaknesses it is unlikely that they worsen clinical judgement. Therefore, all doctors should become familiar with them and use them appropriately. PMID:18395158

  17. Prognostic significance of metastatic lymph node ratio in squamous cell carcinoma of the cervix

    PubMed Central

    Li, Chen; Liu, Wenhui; Cheng, Yufeng

    2016-01-01

    Purpose Metastatic lymph node ratio (MLNR) was reported to be an important prognostic factor in several tumors. However, depth of primary tumor invasion is also important in cervical cancer prognostic analysis. In this study, the objective was to determine if MLNR can be used to define a high-risk category of patients with squamous cell carcinoma of the cervix (SCC). And we combined MLNR and depth of invasion to investigate whether prognosis of SCC can be predicted better. Patients and methods We performed a retrospective review of patients with SCC who underwent radical hysterectomy and pelvic lymphadenectomy at QiLu Hospital of Shandong University from January 2007 to December 2009. Prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified by univariate and multivariate analyses. Results One hundred and ninety-eight patients met the inclusion criteria and were included in the analysis. By cut-point survival analysis, MLNR cutoff was designed as 0.2. On multivariate analysis, an MLNR >0.2 was associated with a worse OS (hazard ratio [HR] =2.560, 95% CI 1.275–5.143, P=0.008) and DFS (HR =2.404, 95% CI 1.202–4.809, P=0.013). Depth of invasion cutoff was designed as invasion >1/2 cervix wall and was associated with a worse OS (HR =1.806, 95% CI 1.063–3.070, P=0.029) and DFS (HR =1.900, 95% CI 1.101–3.279, P=0.021). In addition, subgroup analysis revealed significant difference in OS and DFS rates between different MLNR categories within the same depth of invasion category (P<0.05), however, not between different depth of invasion categories within the same MLNR category (P>0.05). Conclusion MLNR may be used as the independent prognostic parameter in patients with SCC. Combined MLNR and depth of invasion can predict both OS and DFS better in SCC than one factor. Besides, MLNR appears to be a better prognostic value than depth of invasion for SCC. PMID:27382315

  18. Prognostic and Clinicopathological Significance of Survivin in Colorectal Cancer: A Meta-Analysis

    PubMed Central

    Krieg, Andreas; Werner, Thomas A.; Verde, Pablo E.; Stoecklein, Nikolas H.; Knoefel, Wolfram T.

    2013-01-01

    Survivin/BIRC5 is a potentially interesting prognostic marker and therapeutic target in colorectal cancer (CRC). However, the available data on survivin expression in CRC are heterogeneous. Thus, to clarify the prognostic relevance of survivin in patients with CRC and its association with clinicopathological parameters we performed a meta-analysis. We screened PubMed and EMBASE for those studies that investigated the prognostic value of survivin and its association with clinicopathological parameters in CRC. Data from eligible studies were extracted and included into the meta-analyses using a random effects model. Electronical literature search identified 15 studies including 1934 patients with CRC mostly detecting survivin by immunohistochemistry (IHC). Pooled hazard ratios of 11 studies that performed survival analysis revealed a positive correlation between survivin expression and poor prognosis (HR 1.93; 95% CI: 1.55–2.42; P<0.00001; I2 = 23%). Subgroup analyses with respect to the detection method, HR estimation, global quality score and the country of origin in which the study was conducted supported the stability of this observation. In addition, meta-analyses revealed a significant association between expression of survivin and the presence of lymph node metastases (OR: 0.37; 95% CI: 0.19–0.75; I2 = 61%) or blood vessel invasion (OR: 0.50; 95% CI: 0.28–0.90; I2 = 0%). Expression of survivin indicates poor prognosis and a pro-metastatic phenotype and may be useful in identifying a subgroup of patients that could benefit from a targeted therapy against survivin in CRC. PMID:23755220

  19. 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

  20. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma

    PubMed Central

    Shen, G H; Ghazizadeh, M; Kawanami, O; Shimizu, H; Jin, E; Araki, T; Sugisaki, Y

    2000-01-01

    The influence of vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) on prognosis and the relationship between VEGF expression and MVD in ovarian carcinoma are not well defined. We studied VEGF expression in parallel with MVD by immunohistochemistry in 94 ovarian tumours (64 malignant, 13 borderline, and 17 benign) and correlated the results with the clinicopathologic prognostic factors of the disease to clarify their significance in this disease. Assessment of VEGF mRNA isoforms by RT-PCR was also performed. Of the malignant, borderline, and benign ovarian tumours respectively, two (3%), four (31%) and 16 (94%) were negative, 31 (48%), seven (54%) and one (6%) had low expressions, and 31 (48%), two (15%) and none (0%) had high expressions of VEGF. There were significant associations between the VEGF expression and disease stage (P = 0.002), histologic grade (P = 0.0004), and patient outcome (P = 0.0002). MVD did not correlate significantly with the clinicopathologic parameters. Likewise, no correlation was found between MVD and VEGF expression. The survival of patients with high VEGF expression was significantly worse than that of patients with low and negative VEGF expression (P = 0.0004). Multivariate analysis revealed that disease stage and VEGF expression were significant and independent prognostic indicators of overall survival time (P = 0.008 and P = 0.006 respectively). These findings suggest that in conjunction with the established clinicopathologic prognostic parameters of ovarian carcinoma, VEGF expression may enhance the predictability of patients at high risk for tumour progression who are potential candidates for further aggressive therapy. © 2000 Cancer Research Campaign PMID:10901370

  1. Short-term prognostic factors in lumbar disc surgery: the low back prognostic score is of predictive value.

    PubMed

    Woertgen, C; Gliese, M; Rothoerl, R D; Holzschuh, M; Schlaier, J; Ullrich, O W; Brawanski, A

    1998-01-01

    In order to determine prognostic factors of lumbar disc surgery, we examined 107 patients who were conventionally operated on in a prospective, consecutive study. We analysed general data, the case history, the neurological examination at admission and all data from imaging examinations and therapy. In addition, all patients received a questionnaire based on the Low Back Outcome Score [9, 10]. The patients were re-examined after 2-8 months (103 days mean). According to their ratings on a pain grading scale, the patients were divided into a group with favorable and another with unfavorable results. These groups were analysed in relation to the patients' initial condition. At follow up, 88% of the patients had either completely recovered or their complaints had been relieved. According to the Low Back Outcome Score (LBOS), 64.5% went well. Used to evaluate the initial condition of the patients on admission the LBOS was able to predict favorable outcome in 68% and unfavorable outcome in 50%. To improve the prognostic value, we combined significant questions of the LBOS with the pain grading scale and significant prognostic factors to form a new prognostic score (Low Back Prognostic Score). With this new score we were able to predict a favorable outcome in 84% of our patients, and an unfavorable outcome in 71%. The Low Back Prognostic score seems to provide a sensitive method for predicting a favorable or unfavorable outcome for patients scheduled to undergo lumbar disc surgery. PMID:9577926

  2. Pharmacogenetics of idiosyncratic adverse drug reactions.

    PubMed

    Pirmohamed, Munir

    2010-01-01

    Idiosyncratic adverse drug reactions are unpredictable and thought to have an underlying genetic etiology. With the completion of the human genome and HapMap projects, together with the rapid advances in genotyping technologies, we have unprecedented capabilities in identifying genetic predisposing factors for these relatively rare, but serious, reactions. The main roadblock to this is the lack of sufficient numbers of well-characterized samples from patients with such reactions. This is now beginning to be solved through the formation of international consortia, including developing novel ways of identifying and recruiting patients affected by these reactions, both prospectively and retrospectively. This has been led by the research on abacavir hypersensitivity - its association with HLA-B*5701 forms the gold standard of how we need to identify associations and implement them in clinical practice. Strong genetic predisposing factors have also been identified for hypersensitivity reactions such as are associated with carbamazepine, allopurinol, flucloxacillin, and statin-induced myopathy. However, for most other idiosyncratic adverse drug reactions, the genetic effect sizes have been low to moderate, although this may partly be due to the fact that only small numbers have been investigated and limited genotyping strategies have been utilized. It may also indicate that genetic predisposition will be dependent on multiple genes, with complex interactions with environmental factors. Irrespective of the strength of the genetic associations identified with individual idiosyncratic adverse drug reactions, it is important to undertake functional investigations to provide insights into the mechanism(s) of how the drug interacts with the gene variant to lead to a phenotype, which can take a multitude of clinical forms with variable severity. Such investigations will be essential in preventing the burden caused by idiosyncratic reactions, both in healthcare and in industry

  3. Determinants of Adverse Events in Vascular Surgery

    PubMed Central

    Hernandez-Boussard, Tina; McDonald, Kathryn; Morton, John; Dalman, Ron L; Bech, Fritz R

    2016-01-01

    Background Patient safety is a national priority. Patient Safety Indicators (PSIs) monitor potential adverse events during hospital stays. Surgical specialty PSI benchmarks do not exist, which are needed to account for differences in the range of procedures performed, reasons for the procedure, and differences in patient characteristics. A comprehensive profile of adverse events in vascular surgery was created. Study Design The Nationwide Inpatient Sample was queried for 8 vascular procedures using ICD-9-CM codes from 2005–2009. Factors associated with PSI development were evaluated in univariate and multivariate analyses. Results A total of 1,412,703 patients underwent a vascular procedure and 5.2% developed a PSI. PSIs were more frequent in female, non-white patients with public payers (p<.01). Patients at mid and low volume hospitals had greater odds of developing a PSI (Odds Ratio [OR], 1.17; 95% Confidence Interval [CI], 1.10–1.23 and OR, 1.69; CI, 1.53–1.87). Amputations had highest PSI risk-adjusted rate (RAR) and carotid endarterectomy and endovascular abdominal aortic aneurysm (AAA) repair had lower RAR (p<.0001). PSI RAR increased linearly by severity of patient indication: claudicants (OR, 0.40, CI, 0.35–0.46), rest pain patients (OR, 0.78, CI 0.69–0.90), ulcer (OR: 1.20, CI: 1.07–1.34) and gangrene patients (OR:1.85, CI: 1.66–2.06). Conclusions Patient safety events in vascular surgery were high and varied by procedure, with amputations and open AAA having substantially more potential adverse events. PSIs were associated with black race, public payer, and procedure indication. It is important to note the overall higher rates of PSIs occurring in vascular patients and appropriately adjust benchmarks for this surgical specialty. PMID:22425449

  4. Adverse blood transfusion outcomes: establishing causation.

    PubMed

    Isbister, James P; Shander, Aryeh; Spahn, Donat R; Erhard, Jochen; Farmer, Shannon L; Hofmann, Axel

    2011-04-01

    The transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, "the blood supply is safer than ever," data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognized serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes related to immunomodulation and the storage lesion comes from observational studies, and a broad and critical analysis to evaluate causation is overdue. It is suggested in several circumstances that this cannot wait for the design, execution, and conduct of rigorous RCTs. We begin by examining the nature and definition of causation with relevant examples from transfusion medicine. Deductive deterministic methods may be applied to most of the well-accepted and understood serious hazards of transfusion, with modified Koch's postulates being fulfilled in most circumstances. On the other hand, when several possible interacting risk factors exist and RBC transfusions are associated with adverse clinical outcomes, establishing causation requires inferential probabilistic methodology. In the latter circumstances, the case for RBC transfusions being causal for adverse clinical outcomes can be strengthened by applying modified Bradford Hill criteria to the plethora of existing observational studies. This being the case, a greater precautionary approach to RBC transfusion is necessary and equipoise that justifying RCTs may become problematic. PMID:21345639

  5. Standardizing adverse drug event reporting data

    PubMed Central

    2014-01-01

    Background The Adverse Event Reporting System (AERS) is an FDA database providing rich information on voluntary reports of adverse drug events (ADEs). Normalizing data in the AERS would improve the mining capacity of the AERS for drug safety signal detection and promote semantic interoperability between the AERS and other data sources. In this study, we normalize the AERS and build a publicly available normalized ADE data source. The drug information in the AERS is normalized to RxNorm, a standard terminology source for medication, using a natural language processing medication extraction tool, MedEx. Drug class information is then obtained from the National Drug File-Reference Terminology (NDF-RT) using a greedy algorithm. Adverse events are aggregated through mapping with the Preferred Term (PT) and System Organ Class (SOC) codes of Medical Dictionary for Regulatory Activities (MedDRA). The performance of MedEx-based annotation was evaluated and case studies were performed to demonstrate the usefulness of our approaches. Results Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). In total, the AERS-DM contains 37,029,228 Drug-ADE records. Seventy-one percent (10,221/14,490) of normalized drug concepts in the AERS were classified to 9 classes in NDF-RT. The number of unique pairs is 4,639,613 between RxNorm concepts and MedDRA Preferred Term (PT) codes and 205,725 between RxNorm concepts and SOC codes after ADE aggregation. Conclusions We have built an open-source Drug-ADE knowledge resource with data being normalized and aggregated using standard biomedical ontologies. The data resource has the potential to assist the mining of ADE from AERS for the data mining research community. PMID:25157320

  6. [Haematological adverse effects caused by psychiatric drugs].

    PubMed

    Mazaira, Silvina

    2008-01-01

    Almost all clases of psychiatric drugs (typical and atypical antipsychotics, antidepressants, mood stabilizers, benzodiazepines) have been reported as possible causes of haematological toxicity. This is a review of the literature in which different clinical situations involving red blood cells, white blood cells, platelets and impaired coagulation are detailed and the drugs more frequently involved are listed. The haematological adverse reactions detailed here include: aplastic anemia, haemolitic anemia, leukopenia, agranulocytosis, leukocytosis, eosinophilia, thrombocytosis, thrombocytopenia, disordered platelet function and impaired coagulation. The haematologic toxicity profile of the drugs more frequently involved: lithium, clozapine, carbamazepine, valproic acid and SSRI antidepressants is mentioned. PMID:19424521

  7. [Adverse drug effects in the community pharmacy].

    PubMed

    Arnet, Isabelle; Seidling, Hanna M; Hersberger, Kurt E

    2015-12-01

    Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE. PMID:26654812

  8. [Injectable fillers: adverse reactions and their management].

    PubMed

    Rzany, B; Bachmann, F; Nast, A

    2013-02-01

    Injectable fillers are one of the corner stones of aesthetic medicine. In general they are safe to use. However, adverse reactions may occur. These reactions may be acute, subacute or delayed, e.g. after decades. It is important to know these reactions and to be prepared so that they can be adequately treated, in view of the clinical symptoms, the injected material and if applicable other diseases/treatments that might trigger these reactions. Last but not least, all reactions should be reported either to specialized registries or regulatory agencies. Only then we are able to learn more about these reactions and their best possible treatment. PMID:23407758

  9. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  10. Adverse Pregnancy Outcomes Following Motor Vehicle Crashes

    PubMed Central

    Vladutiu, Catherine J.; Marshall, Stephen W.; Poole, Charles; Casteel, Carri; Menard, M. Kathryn; Weiss, Harold B.

    2013-01-01

    Background Motor vehicle crashes are a leading cause of serious trauma during pregnancy, but little is known about their relationships with pregnancy outcomes. Purpose To estimate the association between motor vehicle crashes and adverse pregnancy outcomes. Methods A retrospective cohort study of 878,546 pregnant women, aged 16–46 years, who delivered a singleton infant in North Carolina (NC) from 2001 to 2008. Pregnant drivers in crashes were identified by probabilistic linkage of vital records and crash reports. Poisson regression modeled the association among crashes, vehicle safety features, and adverse pregnancy outcomes. Analyses were conducted in 2012. Results In 2001–2008, 2.9% of pregnant NC women were drivers in one or more crashes. After a single crash, compared to not being in a crash, pregnant drivers had slightly elevated rates of preterm birth (adjusted rate ratio, aRR=1.23, 95% CI=1.19, 1.28); placental abruption (aRR=1.34, 95% CI=1.15, 1.56); and premature rupture of the membranes (PROM; aRR=1.32, 95% CI=1.21, 1.43). Following a second or subsequent crash, pregnant drivers had more highly elevated rates of preterm birth (aRR=1.54, 95% CI=1.24, 1.90); stillbirth (aRR=4.82, 95% CI=2.85, 8.14); placental abruption (aRR=2.97, 95% CI=1.60, 5.53); and PROM (aRR=1.95, 95% CI=1.27, 2.99). Stillbirth rates were elevated following crashes involving unbelted pregnant drivers (aRR=2.77, 95% CI=1.22, 6.28) compared to belted pregnant drivers. Conclusions Crashes while driving during pregnancy were associated with elevated rates of adverse pregnancy outcomes, and multiple crashes were associated with even higher rates of adverse pregnancy outcomes. Crashes were especially harmful if drivers were unbelted. PMID:24139777

  11. Adverse environments and children's creativity development: transforming the notion of "success in adversity" in China.

    PubMed

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications for China's future as it brings together one of China's core cultural values-"success in adversity"-the importance of creativity, and very real social and economic needs. "Success in adversity" reflects the strongly held belief that individuals who suffer adverse environments can rise to excellence and success through persistence, effort, and creativity. In this article, we briefly explore the historical sources of this belief and how it is closely related to the Chinese conception of creativity. We then present some studies on the creativity of some of China's migrant children. Findings show that while migrant children as a group may not generally exhibit higher creativity than their urban peers as hypothesized, indications of resilience and creative potential suggest that the notion of success in adversity may contribute to the positive development of China's migrant children more substantially when it is informed by research and augmented by research-supported policy. PMID:25732020

  12. Clinicopathological and prognostic value of programmed death ligand-1 (PD-L1) in renal cell carcinoma: a meta-analysis

    PubMed Central

    Xu, Feng; Xu, Lingling; Wang, Qian; An, Guangyu; Feng, Guosheng; Liu, Fuquan

    2015-01-01

    Background: Recently, the association of immunological checkpoint marker programmed death ligand-1 (PD-L1) and the prognosis of various cancers has always been a research hotspot. The objective of this study is to assess the clinical value of PD-L1 as a novel prognostic biomarker of renal cell carcinoma (RCC). Methods: Medline/PubMed, EMBASE, the Cochrane Library databases and Grey literature were searched up to 30 March 2015 for eligible studies of the association between PD-L1 expression and cancer-specific survival (CSS) in RCC. The risk ratio (RR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and PDL1 expression. Results: Five studies involving 1073 patients were included in the meta-analysis. The pooled results showed that positive/higher PD-L1 expression was a negative predictor for CSS with RR of 2.90 (95% CI: 1.64-5.13; Pheterogeneity. ≤ 0.001). Additionally, increased PD-L1 was found to be significantly associated with large tumor size (OR = 2.28, 95% CI: 1.61-3.23; Pheterogeneity. = 0.645), high TNM stage (OR = 4.37, 95% CI: 2.99-6.39; Pheterogeneity. = 0.676), poor nuclear grade (OR = 7.58, 95% CI: 5.26-10.92; Pheterogeneity. = 0.203) and present tumor necrosis (OR = 6.77, 95% CI: 4.73-9.71; Pheterogeneity. = 0.111) in renal cell carcinoma patients. Conclusion: The meta-analysis suggested that PD-L1 could act as a significant biomarker in the worse prognosis and adverse clinicopathologic features of renal cell carcinoma. PMID:26628942

  13. A Systematic Review of Clinical Outcomes and Prognostic Factors for Patients Undergoing Surgery for Spinal Metastases Secondary to Breast Cancer

    PubMed Central

    Sciubba, Daniel M.; Goodwin, C. Rory; Yurter, Alp; Ju, Derek; Gokaslan, Ziya L.; Fisher, Charles; Rhines, Laurence D.; Fehlings, Michael G.; Fourney, Daryl R.; Mendel, Ehud; Laufer, Ilya; Bettegowda, Chetan; Patel, Shreyaskumar R.; Rampersaud, Y. Raja; Sahgal, Arjun; Reynolds, Jeremy; Chou, Dean; Weber, Michael H.; Clarke, Michelle J.

    2015-01-01

    Study Design  Review of the literature. Objective  Surgery and cement augmentation procedures are effective palliative treatment of symptomatic spinal metastases. Our objective is to systematically review the literature to describe the survival, prognostic factors, and clinical outcomes of surgery and cement augmentation procedures for breast cancer metastases to the spine. Methods  We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. Results  The median postoperative survival for metastatic breast cancer was 21.7 months (8.2 to 36 months), the mean rate of any pain improvement was 92.9% (76 to 100%), the mean rate of neurologic improvement was 63.8% (53 to 100%), the mean rate of neurologic decline was 4.1% (0 to 8%), and the local tumor control rate was 92.6% (89 to 100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included hormonal (estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2) receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. Conclusion  With respect to clinical outcomes, surgery consistently yielded neurologic improvements in patients presenting with a deficit with a minimal risk of worsening; however, negative prognostic factors associated with shorter survival following surgery include estrogen receptor/progesterone receptor negativity, HER2 negativity, and a short DFI. PMID:27433433

  14. Different Prognostic Implications of 18F-FDG PET Between Histological Subtypes in Patients With Cervical Cancer

    PubMed Central

    Rahman, Tasmiah; Tsujikawa, Tetsuya; Yamamoto, Makoto; Chino, Yoko; Shinagawa, Akiko; Kurokawa, Tetsuji; Tsuchida, Tatsuro; Kimura, Hirohiko; Yoshida, Yoshio; Okazawa, Hidehiko

    2016-01-01

    Abstract This study aimed to investigate whether the predictive values of intensity- and volume-based PET parameters are different between histological subtypes in patients with cervical cancer. Ninety patients, 65 with squamous cell carcinoma (SCC) and 25 with non-SCC (NSCC), who underwent pretreatment 18F-FDG PET/CT and pelvic MRI, were studied retrospectively. In addition to SUVmax and SUVmean, metabolic-tumor-volume (MTV) was determined by thresholding of 40% SUVmax and total-lesion-glycolysis (TLG) was calculated. Clinical factors and PET metabolic indices were compared between SCC and NSCC. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method with cut-offs determined by ROC analyses to stratify SCC and NSCC patients separately. Factors associated with survival were assessed with univariate and multivariate analyses using the Cox regression model. No significant differences were observed in clinical factors other than tumor size or 18F-FDG PET metabolic indices between SCC and NSCC. The Kaplan–Meier estimates of 2-year PFS and OS rates were 60% and 70% for SCC and 40% and 76% for NSCC, respectively. Multivariate analyses showed that MTV and TLG were the independent prognostic factors for PFS and OS in SCC; in contrast, SUVmax was the independent prognostic factor for PFS and OS in NSCC. Metabolic burden (MTV and TLG) could be beneficial for the prognostic prediction of cervical SCC patients; in contrast, metabolic intensity (SUVmax) could be beneficial for the prognostic prediction of NSCC patients. The different prognostic implications might be based on the differences of tissue integrity and histological heterogeneity between SCC and NSCC. PMID:26945427

  15. Prognostic Value of Coronary Computed Tomography Imaging in Patients at High Risk Without Symptoms of Coronary Artery Disease.

    PubMed

    Dedic, Admir; Ten Kate, Gert-Jan R; Roos, Cornelis J; Neefjes, Lisan A; de Graaf, Michiel A; Spronk, Angela; Delgado, Victoria; van Lennep, Jeanine E Roeters; Moelker, Adriaan; Ouhlous, Mohamed; Scholte, Arthur J H A; Boersma, Eric; Sijbrands, Eric J G; Nieman, Koen; Bax, Jeroen J; de Feijter, Pim J

    2016-03-01

    At present, traditional risk factors are used to guide cardiovascular management of asymptomatic subjects. Intensified surveillance may be warranted in those identified as high risk of developing cardiovascular disease (CVD). This study aims to determine the prognostic value of coronary computed tomography (CT) angiography (CCTA) next to the coronary artery calcium score (CACS) in patients at high CVD risk without symptoms suspect for coronary artery disease (CAD). A total of 665 patients at high risk (mean age 56 ± 9 years, 417 men), having at least one important CVD risk factor (diabetes mellitus, familial hypercholesterolemia, peripheral artery disease, or severe hypertension) or a calculated European systematic coronary risk evaluation of >10% were included from outpatient clinics at 2 academic centers. Follow-up was performed for the occurrence of adverse events including all-cause mortality, nonfatal myocardial infarction, unstable angina, or coronary revascularization. During a median follow-up of 3.0 (interquartile range 1.3 to 4.1) years, adverse events occurred in 40 subjects (6.0%). By multivariate analysis, adjusted for age, gender, and CACS, obstructive CAD on CCTA (≥50% luminal stenosis) was a significant predictor of adverse events (hazard ratio 5.9 [CI 1.3 to 26.1]). Addition of CCTA to age, gender, plus CACS, increased the C statistic from 0.81 to 0.84 and resulted in a total net reclassification index of 0.19 (p <0.01). In conclusion, CCTA has incremental prognostic value and risk reclassification benefit beyond CACS in patients without CAD symptoms but with high risk of developing CVD. PMID:26754124

  16. Preoperative radiotherapy for rectal adenocarcinoma: Which are strong prognostic factors?

    SciTech Connect

    Chapet, Olivier . E-mail: ochapet@med.umich.edu; Romestaing, Pascale; Mornex, Francoise; Souquet, Jean-Christophe; Favrel, Veronique; Ardiet, Jean-Michel; D'Hombres, Anne; Gerard, Jean-Pierre

    2005-04-01

    Purpose: This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors. Methods and Materials: Between 1985 and 1996, 297 patients were treated with preoperative radiotherapy (39 Gy in 13 fractions) and surgery for Stage T2-T4N0-N1M0 rectal adenocarcinoma. Pretreatment staging included a clinical examination and endorectal ultrasonography (EUS) since 1988. Clinical staging was performed by digital rectal examination and rigid proctoscopy. EUS was performed in 236 patients. Postoperative staging was performed by examination of the pathologic specimen. Results: The median follow-up was 49 months. The overall 5-year survival rate was 67%, with a local failure rate of 9%. The rate of sphincter preservation was 65%. The clinical examination findings were strong prognostic factor for both cT stage (p < 0.001) and cN stage (p < 0.006) but had poor specificity for cN stage (only 25 lymph nodes detected). In both univariate and multivariate analyses, EUS had a statistically significant prognostic value for uT (p < 0.014) but not for uN (p < 0.47) stage. In contrast, pT and pN stages were strong prognostic factors (p < 0.001 and p < 0.001, respectively). Conclusion: Pretreatment staging, including clinical examination and EUS, seemed accurate enough to present a high prognostic value for the T stage. EUS was insufficient to stage lymph node involvement. Owing to its lack of specificity, uN stage was not a reliable prognostic factor. An improvement in N staging is necessary and essential. Despite downstaging, postoperative staging remained a very strong prognostic factor for both T and N stages.

  17. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer.

    PubMed

    Kolin, David L; Sy, Keiyan; Rotondo, Fabio; Bassily, Mena N; Kovacs, Kalman; Brezden-Masley, Christine; Streutker, Catherine J; Yousef, George M

    2014-09-01

    The prognosis of patients following surgery for gastric cancer is often poor and is estimated using traditional clinicopathological parameters, which can be inaccurate predictors of future survival. Kallikreins are a group of serine proteases, which are differentially expressed in many human tumors and are being investigated as potential cancer biomarkers. This study assessed the prognostic utility of human tissue kallikrein-like peptidases 6 and 10 (KLK6 and KLK10) and correlated their expression with histopathological and clinical parameters in gastric cancer. We constructed a gastric tumor tissue microarray from 113 gastrectomy specimens and quantified KLK6 and KLK10 expression using immunohistochemistry. To overcome the problem of inter-observer variability and subjectivity in immunohistochemistry interpretation, a whole-slide scanned image of the tissue microarray was analyzed using an automated algorithm to quantify staining intensity. KLK6 expression was positively correlated with nodal involvement (p=0.002) and was predictive of advanced-stage disease (p<0.05). Kaplan-Meier survival curves revealed that tumors expressing high levels of KLK6 were significantly associated with significantly lower overall survival (p=0.04). KLK10 overexpression was also a predictor of advanced-stage disease (p<0.01), but was not significantly correlated with lymph node involvement or survival period. Our results show the potential ability of KLK6 as a prognostic marker for gastric cancer. PMID:25153389

  18. Current Pressure Transducer Application of Model-based Prognostics Using Steady State Conditions

    NASA Technical Reports Server (NTRS)

    Teubert, Christopher; Daigle, Matthew J.

    2014-01-01

    Prognostics is the process of predicting a system's future states, health degradation/wear, and remaining useful life (RUL). This information plays an important role in preventing failure, reducing downtime, scheduling maintenance, and improving system utility. Prognostics relies heavily on wear estimation. In some components, the sensors used to estimate wear may not be fast enough to capture brief transient states that are indicative of wear. For this reason it is beneficial to be capable of detecting and estimating the extent of component wear using steady-state measurements. This paper details a method for estimating component wear using steady-state measurements, describes how this is used to predict future states, and presents a case study of a current/pressure (I/P) Transducer. I/P Transducer nominal and off-nominal behaviors are characterized using a physics-based model, and validated against expected and observed component behavior. This model is used to map observed steady-state responses to corresponding fault parameter values in the form of a lookup table. This method was chosen because of its fast, efficient nature, and its ability to be applied to both linear and non-linear systems. Using measurements of the steady state output, and the lookup table, wear is estimated. A regression is used to estimate the wear propagation parameter and characterize the damage progression function, which are used to predict future states and the remaining useful life of the system.

  19. Prognostic significance of hematological profiles in melanoma patients.

    PubMed

    Gandini, Sara; Ferrucci, Pier Francesco; Botteri, Edoardo; Tosti, Giulio; Barberis, Massimo; Pala, Laura; Battaglia, Angelo; Clerici, Alessandra; Spadola, Giuseppe; Cocorocchio, Emilia; Martinoli, Chiara

    2016-10-01

    Cancer-related inflammation may play an important role in disease progression and patient outcome, and could be easily monitored through indirect parameters routinely evaluated at diagnosis. Here, we investigated if peripheral blood cells and the ratios of neutrophils to lymphocytes (NLR) and of lymphocytes to monocytes (LMR) as surrogate markers of cancer related inflammation are associated with disease progression and survival of melanoma patients at any stage of the disease. Records of 1,182 melanoma patients included in an Institutional tumor registry in the period 2000-2010, were reviewed. Among them, 584 patients with a cutaneous or unknown primary melanoma and available pre-operative blood tests were analyzed. Survival was estimated with the Kaplan-Meier method, and analyzed using Log-rank test, Cox regression and multivariate Cox proportional hazard models. We found that patients presenting with distant metastases had higher leukocytes, neutrophils and monocytes, and lower lymphocytes compared to Stage I-III patients. Furthermore, at a single-patient level, hematological profiles changed on disease progression from regional to distant metastatic, with significantly increased circulating leukocytes, neutrophils and monocytes, and decreased lymphocytes. Peripheral blood cell counts were not associated with survival of patients with a localized or regionally metastasized melanoma. Instead, in Stage IV patients, leukocytes (p = 0.001), neutrophils (p = 0.0002), monocytes (p = 0.002), NLR (p < 0.0001) and LMR (p = 0.005) were all significantly associated with survival, independently of other known prognostic factors. These results suggest that cellular components of peripheral blood do count for survival of patients with advanced melanoma. PMID:27252119

  20. Adverse Effects of Common Drugs: Adults.

    PubMed

    Lewis, Peter R; Karpa, Kelly Dowhower; Felix, Todd Matthew

    2015-09-01

    Although drugs can be an essential and lifesaving component of the care of adult patients, their use frequently is accompanied by adverse effects and life-threatening adverse drug reactions that can result in significant disability and mortality. The potential for drug-related severe morbidity and mortality is compounded during periods of hospitalization, when high-risk drugs such as anticoagulants or insulin are used, and when care in an intensive care unit is required. Patient factors in adults that can increase the risk of drug harms include immunosuppression, cognitive impairment, depression, alcoholism and other substance abuse disorders, chronic kidney disease, hepatic dysfunction, coagulopathies, limited English proficiency, institutional/nursing home care, and underinsurance or lack of insurance. Physician factors that can increase the risk of drug harms include inappropriate prescribing of drugs (including to pregnant and breastfeeding women), failure to appropriately discontinue/deprescribe drugs, insufficient drug reconciliation, failure to coordinate care among multiple prescribing clinicians, and failure to elicit and incorporate into health histories and clinical decision-making the widespread use of nonprescription drugs, herbal products, and dietary supplements. PMID:26375995

  1. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype. PMID:26919895

  2. Fingolimod-Associated Peripheral Vascular Adverse Effects.

    PubMed

    Russo, Margherita; Guarneri, Claudio; Mazzon, Emanuela; Sessa, Edoardo; Bramanti, Placido; Calabrò, Rocco Salvatore

    2015-10-01

    Fingolimod is the first oral disease-modifying drug approved for the treatment of multiple sclerosis. The drug is usually well tolerated, and common adverse effects include bradycardia, headache, influenza, diarrhea, back pain, increased liver enzyme levels, and cough. Fingolimod is thought to provide therapeutic benefit by preventing normal lymphocyte egress from lymphoid tissues, thus reducing the infiltration of autoaggressive lymphocytes into the central nervous system. However, because the drug acts on different sphingosine-1-phosphate receptors, it may induce several biological effects by influencing endothelial cell-cell adhesion, angiogenesis, vascular development, and cardiovascular function. We describe a patient with multiple sclerosis who, after 3 weeks of fingolimod administration, developed purplish blotches over the dorsal surface of the distal phalanges of the second and fifth digits and the middle phalanx of the fourth ray, itching, and edema on his left hand, without other evident clinical manifestations. When fingolimod therapy was discontinued, the clinical picture regressed within a few days but reappeared after a rechallenge test. Physicians should be aware of unexpected peripheral vascular adverse effects due to fingolimod use, and patients with vascular-based acropathies should be carefully screened and monitored when taking this drug. PMID:26349949

  3. Adverse Effects of Common Drugs: General Concepts.

    PubMed

    Karpa, Kelly Dowhower; Lewis, Peter R; Felix, Todd Matthew

    2015-09-01

    Adverse drug reactions (ADRs) contribute to substantial morbidity and mortality and add to rising health care costs. Many ADRs are preventable with appropriate prescribing and monitoring because they often occur as an extension of a drug's mechanism of action or known drug interactions. Patients at higher risk of ADRs include those at the extremes of age, those with multiple comorbidities, those taking multiple drugs, and patients admitted to intensive care units or experiencing transitions of care. Because the risk of ADRs becomes greater as the number of drugs and dietary supplements taken increases, it is imperative that prescribers be vigilant about the prescribing cascade and take steps to discontinue drugs that are likely to be more harmful than helpful. Pharmacists serve as important partners in clinical care environments by conducting comprehensive drug reviews, aiding in drug/dosage selection, and developing therapeutic monitoring plans. Although the potential exists for clinicians to use electronic health record systems to aid in clinical decision making through drug safety decision support tools, computer systems should never replace clinical judgment. Clinicians also are encouraged to report ADRs to the Food and Drug Administration Adverse Event Reporting System. PMID:26375993

  4. Translating Developmental Science to Address Childhood Adversity.

    PubMed

    Garner, Andrew S; Forkey, Heather; Szilagyi, Moira

    2015-01-01

    Demystifying child development is a defining element of pediatric care, and pediatricians have long appreciated the profound influences that families and communities have on both child development and life course trajectories. Dramatic advances in the basic sciences of development are beginning to reveal the biologic mechanisms underlying well-established associations between a spectrum of childhood adversities and less than optimal outcomes in health, education and economic productivity. Pediatricians are well positioned to translate this new knowledge into both practice and policy, but doing so will require unprecedented levels of collaboration with educators, social service providers, and policy makers. Pediatricians might recognize the negative impact of family-level adversities on child development, but developing an effective response will likely require the engagement of community partners. By developing collaborative, innovative ways to promote the safe, stable, and nurturing relationships that are biologic prerequisites for health, academic success, and economic productivity, family-centered pediatric medical homes will remain relevant in an era that increasingly values wellness and population health. PMID:26183002

  5. [The undesirable, psychologically adverse effects of screening].

    PubMed

    Döbrössy, Bence; Kovács, Attila; Budai, András; Cornides, Agnes; Döbrössy, Lajos

    2007-09-01

    The psychological adverse effects might play an important role in the non-compliance with the offered screening examination. The possible sources of them are three-fold: 1. The general human attitude, such as the rejection of health interventions, particularly those aiming at the prevention of eventual future health problems instead of handling existing complaints and symptoms at present; the screening can be seen as a "future-oriented" intervention. 2. The cultural image of cancer and the disbelief of its curability. 3. The subjective experiences in relation to the screening process. The providers have to do their best to eliminate these causes: by means of a) health education addressing people of various ages, social classes and cultural levels, promoting the understanding of the importance of disease prevention, and, changing their negative, defeatist attitude towards cancer; b) minimizing the psychological adverse effects of all kinds. This can be done by proper organisation of the screening process; optimizing the quality of work, and, provision of good quality of information and advice to the screenees before, during and after the screening. PMID:17766222

  6. Adverse Outcome Pathway Development II: Best Practices

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of “functional equivalence” can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  7. Ranking Adverse Drug Reactions With Crowdsourcing

    PubMed Central

    Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel

    2015-01-01

    Background There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective The intent of the study was to rank ADRs according to severity. Methods We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making. PMID:25800813

  8. Managing the adverse effects of radiation therapy.

    PubMed

    Berkey, Franklin J

    2010-08-15

    Nearly two thirds of patients with cancer will undergo radiation therapy as part of their treatment plan. Given the increased use of radiation therapy and the growing number of cancer survivors, family physicians will increasingly care for patients experiencing adverse effects of radiation. Selective serotonin reuptake inhibitors have been shown to significantly improve symptoms of depression in patients undergoing chemotherapy, although they have little effect on cancer-related fatigue. Radiation dermatitis is treated with topical steroids and emollient creams. Skin washing with a mild, unscented soap is acceptable. Cardiovascular disease is a well-established adverse effect in patients receiving radiation therapy, although there are no consensus recommendations for cardiovascular screening in this population. Radiation pneumonitis is treated with oral prednisone and pentoxifylline. Radiation esophagitis is treated with dietary modification, proton pump inhibitors, promotility agents, and viscous lidocaine. Radiation-induced emesis is ameliorated with 5-hydroxytryptamine3 receptor antagonists and steroids. Symptomatic treatments for chronic radiation cystitis include anticholinergic agents and phenazopyridine. Sexual dysfunction from radiation therapy includes erectile dysfunction and vaginal stenosis, which are treated with phosphodiesterase type 5 inhibitors and vaginal dilators, respectively. PMID:20704169

  9. Consumer reporting of adverse events following immunization

    PubMed Central

    Clothier, Hazel J; Selvaraj, Gowri; Easton, Mee Lee; Lewis, Georgina; Crawford, Nigel W; Buttery, Jim P

    2014-01-01

    Surveillance of adverse events following immunisation (AEFI) is an essential component of vaccine safety monitoring. The most commonly utilized passive surveillance systems rely predominantly on reporting by health care providers (HCP). We reviewed adverse event reports received in Victoria, Australia since surveillance commencement in July 2007, to June 2013 (6 years) to ascertain the contribution of consumer (vaccinee or their parent/guardian) reporting to vaccine safety monitoring and to inform future surveillance system development directions. Categorical data included were: reporter type; serious and non-serious AEFI category; and, vaccinee age group. Chi-square test and 2-sample test of proportions were used to compare categories; trend changes were assessed using linear regression. Consumer reporting increased over the 6 years, reaching 21% of reports received in 2013 (P <0.001), most commonly for children aged less than 7 years. Consumer reports were 5% more likely to describe serious AEFI than HCP (P = 0.018) and 10% more likely to result in specialist clinic attendance (P <0.001). Although online reporting increased to 32% of all report since its introduction in 2010, 85% of consumers continued to report by phone. Consumer reporting of AEFI is a valuable component of vaccine safety surveillance in addition to HCP reporting. Changes are required to AEFI reporting systems to implement efficient consumer AEFI reporting, but may be justified for their potential impact on signal detection sensitivity. PMID:25483686

  10. Prognostic value of legumain in uveal melanoma

    PubMed Central

    WU, TONG; SUN, LEI; WU, YING; XIANG, RONG; LI, YUWEI; RONG, WEINING; SUN, FENGYUAN; WANG, NINGLI

    2016-01-01

    The present study aimed to assess the expression of legumain in uveal melanoma (UM) cell lines and primary UM specimens, and to determine the possible association between legumain expression and clinical as well as pathological characteristics to reveal its impact on the prognosis of patients with UM. Records of primary UM cases treated at Beijing Tongren Hospital and Tianjin Eye Hospital between 1996 and 2005 were retrieved for analysis and a total of 82 patients with uveal melanoma were included in the study. The expression of legumain in the formalin-fixed and paraffin-embedded surgical specimens of these 82 patients was determined using immunohistochemical analysis. In addition, the expression of legumain was examined in two uveal melanoma cell lines using polymerase chain reaction and western blot analyses. The association of legumain expression with clinical/pathological characteristics was analyzed using the χ2 and Fisher's exact test. In addition, the impact of legumain on the prognosis of patients with uveal melanoma was examined. Upregulation of legumain was more predominant in the highly invasive uveal melanoma cell line MUM-2B compared with that in the MUM-2C with low invasiveness. Of 82 primary uveal melanoma tissues, 35 exhibited high expression of legumain, while the other 47 specimens exhibited low or negative expression of legumain. High legumain expression was primarily associated with local invasion of UM. Overall survival analysis revealed that the patients with high legumain expression exhibited poorer survival than patients with low/negative legumain expression. These findings suggested that upregulation of legumain is associated with malignant behavior of UM and that legumain may be used as an negative prognostic factor as well as a therapeutic target. PMID:26846877

  11. Reduced fractional shortening of right ventricular outflow tract is associated with adverse outcomes in patients with left ventricular dysfunction

    PubMed Central

    2013-01-01

    Background Recent studies suggest the significance of right ventricular (RV) function in the outcome in patients with left ventricular dysfunction (LVSD); however, global assessment of RV remains to be determined by echocardiogram because of its complex geometry. This study aimed to validate RV outflow tract fractional shortening (RVOT-FS) in the evaluation of RV function and its prognostic value in patients with LVSD. Methods This study included eighty-one patients (62 ± 17 years, mean ± SD, male 79%) with reduced LV ejection fraction (LVEF) (≤40%). Two-dimensional echocardiogram of the parasternal short axis view was obtained at the level of the aortic root, and RVOT-FS was calculated as the ratio of end-diastole minus end-systole dimension to end-diastole dimension. Results RVOT-FS ranged from 0.04 to 0.8 (0.3 ± 0.2, mean ± SD), and correlated with LVEF (r = 0.33, p = 0.0028), RV fractional area change (r = 0.37, p = 0.0008) and brain natriuretic peptide level (r = -0.38, p = 0.0005). In Cox multivariate regression analysis, RVOT-FS [hazard ratio (HR) 0.028, 95% confidence interval (CI): 0.002-0.397]; p = 0.008] and New York Heart Association functional class III-IV [HR 2.233, 95% CI: 1.048-4.761]; p = 0.037] were independent factors to predict the events. During a median follow-up period of 319 days (1 to 1862 days), patients with RVOT-FS ≥ 0.2 showed a higher event-free rate than those < 0.2 by Kaplan-Meier analysis (log-rank test, p = 0.0016). Conclusions Our data suggest that RVOT-FS is a simple parameter reflecting the severity of both ventricular function in patients with LVSD. In addition, RVOT-FS might be useful to predict adverse outcomes in such a patient population. PMID:23731725

  12. [Neutrophilia in the bronchoalveolar lavage of patients with AIDS and Pneumocystis carinii pneumonia. Reflections on its prognostic value in the Spanish setting].

    PubMed

    Sauleda, J; Gea, J; Aran, X; Gimferrer, E; Conangla, M; Broquetas, J M

    1994-04-01

    The prognostic value of neutrophilia (> 5%) in bronchoalveolar lavage (BAL) in our context is studied in 21 patients with AIDS and Pneumocystis carinii pneumonia. Neutrophilia does not seem to be a good prognostic indicator in our context. We have found this condition, with a mean of 6 +/- 4%, in only 33% of our sample. The sensitivity of this parameter with respect to risk of death was very low (25%), while specificity was moderate (65%). In contrast with what has been reported in studies done with Anglo-Saxon populations, neutrophilia in BAL is probably of little prognostic use in our context. This may be due to various factors, among them the type of population (most being intravenous drug users) and the therapeutic protocol (early empirical treatment). PMID:8025785

  13. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  14. Adverse Outcome Pathways – Tailoring Development to Support Use

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) represent an ideal framework for connecting high-throughput screening (HTS) data and other toxicity testing results to adverse outcomes of regulatory importance. The AOP Knowledgebase (AOP-KB) captures AOP information to facilitate the development,...

  15. Adverse Outcome Pathway (AOP) Network Development for Fatty Liver

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk re...

  16. Adverse outcome pathway (AOP) development I: Strategies and principles

    EPA Science Inventory

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

  17. Prognostic factors for a favorable outcome after varicocele repair in adolescents and adults

    PubMed Central

    Samplaski, Mary K; Jarvi, Keith A

    2016-01-01

    The effect of varicocele repair on male fertility remains controversial. It would be helpful to determined which men would benefit most from varicocele repair, and target repair efforts at those individuals. A detailed review of the literature on prognostic factors for varicocele repair was performed using the PubMed NLM database. We found that the best predictor of postvaricocelectomy semen parameters is the preoperative semen parameters. The greatest improvements in semen parameters were found in men with larger varicoceles. While there is controversy, higher testosterone, younger age and larger testis size, in some studies predict for improvements in semen parameters postvaricocelectomy. A nomogram has been developed to predict the postvaricocelectomy semen parameters based on the preoperative semen parameters, varicocele grade and the age of the man (www.fertilitytreatmentresults.com). Limited data consistently demonstrates the greatest improvements in DNA fragmentation rates in men with higher baseline DNA fragmentation rates. With respect to reproductive outcomes, higher baseline sperm density consistently predicts for natural pregnancy or assisted reproductive technology (ART) pregnancy rates. In addition, varicocele repair does seem to reduce the need for more invasive modalities of ART. In conclusion, we can now start to use specific parameters such as baseline semen quality, varicocele grade and patient age to predict post-repair semen quality and fertility potential following varicocelectomy. PMID:26732108

  18. Ki-67 index as a prognostic factor of subsequent lapatinib-based therapy in HER2-positive metastatic breast cancer with resistance to trastuzumab

    PubMed Central

    Bian, Li; Wang, Tao; Zhang, Shao-hua; Zhang, Hui-qiang; Guo, Yun-fei; Du, Ge; Li, Wang; Wu, Shi-kai; Song, San-tai; Jiang, Ze-fei

    2014-01-01

    Prognostic factor analysis has been conducted to determine whether the parameters of clinical data and biomarkers would predict differential progression-free survival (PFS) or overall survival (OS) from lapatinib-based therapy in patients with primary or acquired resistance to trastuzumab. Treatment with lapatinib plus capecitabine for HER2-positive metastatic breast cancer (MBC) with primary or acquired resistance to trastuzumab was analyzed retrospectively. Tumor biomarkers, which came from the biopsies before the starting of lapatinib therapy, were evaluated by immunohistochemistry (IHC). Prognostic factors related to PFS or OS of the lapatinib therapy were assessed by univariate and multivariate analysis. Ki-67 index and liver metastases were the significant prognostic factors for predicting PFS of subsequent lapatinib therapy in the univariate analysis and the multivariate analysis. The risk for disease progression in patients who had a Ki-67 index < 40% was 59% less than that in patients had Ki-67 ≥ 40 (HR = 0.41, 95% CI, 0.23–0.74, P = 0.003). TTP of prior trastuzumab therapy, liver metastases, and the number of metastatic sites were three independent prognostic factors of subsequent lapatinib therapy. Ki-67 index was the significant prognostic factors for predicting PFS of the subsequent second line targeted therapy in patients with trastuzumab resistance. PMID:24424115

  19. The prognostic relevance of flt3 and npm1 mutations on older patients treated intensively or non-intensively: a study of 1312 patients in the UK NCRI AML16 trial.

    PubMed

    Lazenby, M; Gilkes, A F; Marrin, C; Evans, A; Hills, R K; Burnett, A K

    2014-10-01

    Although the prognostic impact of mutations of FLT3 and NPM1 have been extensively studied in younger patients with acute myeloid leukaemia, less is known in older patients whether treated intensively or non-intensively, or in the context of existing prognostic scores. In 1312 patients 16 and 21%, respectively had an FLT3 and NPM1 mutation. An FLT3 mutation did not affect remission rate in intensively or non-intensively treated patients but was associated with an inferior survival. All patients with an NPM1c mutation had a significantly higher remission rate irrespective of treatment approach but survival was not improved, overall, or in any genotype except as in younger patients, in the FLT3 WT NPM1c mutant subgroup. When incorporated into an established multi-parameter prognostic risk score, the molecular information provided additional prognostic definition in 11% of patients. PMID:24573385

  20. Prognostic significance of modified Glasgow Prognostic Score in patients with non-metastatic clear cell renal cell carcinoma.

    PubMed

    Cho, Dae Sung; Kim, Sun Il; Choo, Seol Ho; Jang, Seok Heun; Ahn, Hyun Soo; Kim, Se Joong

    2016-06-01

    Objective The aim of this study was to evaluate the usefulness of the modified Glasgow Prognostic Score (mGPS) as a prognostic factor in patients with non-metastatic clear cell renal cell carcinoma (RCC). Materials and methods Between June 1994 and July 2012, 469 patients with RCC underwent radical or partial nephrectomy at two hospitals. Among these patients, 65 with non-clear cell type histology and 16 with lymph-node or distant metastasis were excluded. The medical records of the remaining 388 patients were retrospectively reviewed. The mGPS was calculated using a selective combination of C-reactive protein (CRP) and albumin as previously described. The prognostic significance of various clinicopathological variables including mGPS was analyzed using univariate and multivariate analyses. Results Of the total 388 patients, 40 patients (10.3%) developed local recurrence or distant metastasis and 18 patients (4.6%) died of disease during the follow-up period. The univariate analysis identified CRP, mGPS, thrombocytosis, T stage, Fuhrman's nuclear grade and lymphovascular invasion as significant prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS). The multivariate analysis indicated that mGPS (p < 0.001), T stage (p = 0.024) and lymphovascular invasion (p = 0.046) were independent prognostic factors for RFS, whereas mGPS (p = 0.001) was the only independent prognostic factor for CSS. Conclusions The mGPS is an independent prognostic factor for RFS and CSS in patients with non-metastatic clear cell RCC treated with radical or partial nephrectomy. These findings suggest that mGPS should be used for predicting recurrence or survival in patients undergoing nephrectomy for non-metastatic clear cell RCC. PMID:26878156

  1. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  2. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Adverse reaction file. 606.170 Section 606.170 Food... reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding... investigation of each reported adverse reaction shall be made. A written report of the investigation of...

  3. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. Link to an amendment published at 77 FR 18, Jan. 3, 2012. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding each unit of blood or blood...

  4. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  5. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  6. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  7. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  8. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  9. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  10. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  11. Adversity and Resilience: A Synthesis of International Research

    ERIC Educational Resources Information Center

    Noltemeyer, Amity L.; Bush, Kevin R.

    2013-01-01

    Children and adolescents worldwide experience a variety of adversities that have the potential to disrupt typical development. However, some of these individuals exhibit resilience, evidencing normal development in the face of adversity. Here we review research on these constructs of risk, adversity, and resilience; synthesize international…

  12. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  13. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Postmarketing reporting of adverse experiences. 600.80 Section 600.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Reporting of Adverse Experiences § 600.80 Postmarketing reporting of adverse experiences....

  14. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Postmarketing reporting of adverse experiences. 600.80 Section 600.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Reporting of Adverse Experiences § 600.80 Postmarketing reporting of adverse experiences....

  15. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Postmarketing reporting of adverse experiences. 600.80 Section 600.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Reporting of Adverse Experiences § 600.80 Postmarketing reporting of adverse experiences....

  16. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Postmarketing reporting of adverse experiences. 600.80 Section 600.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Reporting of Adverse Experiences § 600.80 Postmarketing reporting of adverse experiences....

  17. Systematic review and validation of prognostic models in liver transplantation.

    PubMed

    Jacob, Matthew; Lewsey, James D; Sharpin, Carlos; Gimson, Alexander; Rela, Mohammed; van der Meulen, Jan H P

    2005-07-01

    A model that can accurately predict post-liver transplant mortality would be useful for clinical decision making, would help to provide patients with prognostic information, and would facilitate fair comparisons of surgical performance between transplant units. A systematic review of the literature was carried out to assess the quality of the studies that developed and validated prognostic models for mortality after liver transplantation and to validate existing models in a large data set of patients transplanted in the United Kingdom (UK) and Ireland between March 1994 and September 2003. Five prognostic model papers were identified. The quality of the development and validation of all prognostic models was suboptimal according to an explicit assessment tool of the internal, external, and statistical validity, model evaluation, and practicality. The discriminatory ability of the identified models in the UK and Ireland data set was poor (area under the receiver operating characteristic curve always smaller than 0.7 for adult populations). Due to the poor quality of the reporting, the methodology used for the development of the model could not always be determined. In conclusion, these findings demonstrate that currently available prognostic models of mortality after liver transplantation can have only a limited role in clinical practice, audit, and research. PMID:15973726

  18. 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.

  19. Rotating machinery prognostics: State of the art, challenges and opportunities

    NASA Astrophysics Data System (ADS)

    Heng, Aiwina; Zhang, Sheng; Tan, Andy C. C.; Mathew, Joseph

    2009-04-01

    Machinery prognosis is the forecast of the remaining operational life, future condition, or probability of reliable operation of an equipment based on the acquired condition monitoring data. This approach to modern maintenance practice promises to reduce downtime, spares inventory, maintenance costs, and safety hazards. Given the significance of prognostics capabilities and the maturity of condition monitoring technology, there have been an increasing number of publications on rotating machinery prognostics in the past few years. These publications covered a wide spectrum of prognostics techniques. This review article first synthesises and places these individual pieces of information in context, while identifying their merits and weaknesses. It then discusses the identified challenges, and in doing so, alerts researchers to opportunities for conducting advanced research in the field. Current methods for predicting rotating machinery failures are summarised and classified as conventional reliability models, condition-based prognostics models and models integrating reliability and prognostics. Areas in need of development or improvement include the integration of condition monitoring and reliability, utilisation of incomplete trending data, consideration of effects from maintenance actions and variable operating conditions, derivation of the non-linear relationship between measured data and actual asset health, consideration of failure interactions, practicability of requirements and assumptions, as well as development of performance evaluation frameworks.

  20. An Algorithm for Creating Prognostic Systems for Cancer.

    PubMed

    Chen, Dechang; Wang, Huan; Sheng, Li; Hueman, Matthew T; Henson, Donald E; Schwartz, Arnold M; Patel, Jigar A

    2016-07-01

    The TNM staging system is universally used for classification of cancer. This system is limited since it uses only three factors (tumor size, extent of spread to lymph nodes, and status of distant metastasis) to generate stage groups. To provide a more accurate description of cancer and thus better patient care, additional factors or variables should be used to classify cancer. In this paper we propose a hierarchical clustering algorithm to develop prognostic systems that classify cancer according to multiple prognostic factors. This algorithm has many potential applications in augmenting the data currently obtained in a staging system by allowing more prognostic factors to be incorporated. The algorithm clusters combinations of prognostic factors that are formed using categories of factors. The dissimilarity between two combinations is determined by the area between two corresponding survival curves. Groups from cutting the dendrogram and survival curves of the individual groups define our prognostic systems that classify patients using survival outcomes. A demonstration of the proposed algorithm is given for patients with breast cancer from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. PMID:27189622

  1. Severe acute pancreatitis: Pathogenetic aspects and prognostic factors

    PubMed Central

    Mofleh, Ibrahim A Al

    2008-01-01

    Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis (SAP). An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as effective as multifactorial scoring systems (MFSS) at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen (BUN), creatinine, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis (PN), infected PN (IPN) and mortality. PMID:18205255

  2. External validation of a Cox prognostic model: principles and methods

    PubMed Central

    2013-01-01

    Background A prognostic model should not enter clinical practice unless it has been demonstrated that it performs a useful role. External validation denotes evaluation of model performance in a sample independent of that used to develop the model. Unlike for logistic regression models, external validation of Cox models is sparsely treated in the literature. Successful validation of a model means achieving satisfactory discrimination and calibration (prediction accuracy) in the validation sample. Validating Cox models is not straightforward because event probabilities are estimated relative to an unspecified baseline function. Methods We describe statistical approaches to external validation of a published Cox model according to the level of published information, specifically (1) the prognostic index only, (2) the prognostic index together with Kaplan-Meier curves for risk groups, and (3) the first two plus the baseline survival curve (the estimated survival function at the mean prognostic index across the sample). The most challenging task, requiring level 3 information, is assessing calibration, for which we suggest a method of approximating the baseline survival function. Results We apply the methods to two comparable datasets in primary breast cancer, treating one as derivation and the other as validation sample. Results are presented for discrimination and calibration. We demonstrate plots of survival probabilities that can assist model evaluation. Conclusions Our validation methods are applicable to a wide range of prognostic studies and provide researchers with a toolkit for external validation of a published Cox model. PMID:23496923

  3. Adverse weather impacts on arable cropping systems

    NASA Astrophysics Data System (ADS)

    Gobin, Anne

    2016-04-01

    Damages due to extreme or adverse weather strongly depend on crop type, crop stage, soil conditions and management. The impact is largest during the sensitive periods of the farming calendar, and requires a modelling approach to capture the interactions between the crop, its environment and the occurrence of the meteorological event. The hypothesis is that extreme and adverse weather events can be quantified and subsequently incorporated in current crop models. Since crop development is driven by thermal time and photoperiod, a regional crop model was used to examine the likely frequency, magnitude and impacts of frost, drought, heat stress and waterlogging in relation to the cropping season and crop sensitive stages. Risk profiles and associated return levels were obtained by fitting generalized extreme value distributions to block maxima for air humidity, water balance and temperature variables. The risk profiles were subsequently confronted with yields and yield losses for the major arable crops in Belgium, notably winter wheat, winter barley, winter oilseed rape, sugar beet, potato and maize at the field (farm records) to regional scale (statistics). The average daily vapour pressure deficit (VPD) and reference evapotranspiration (ET0) during the growing season is significantly lower (p < 0.001) and has a higher variability before 1988 than after 1988. Distribution patterns of VPD and ET0 have relevant impacts on crop yields. The response to rising temperatures depends on the crop's capability to condition its microenvironment. Crops short of water close their stomata, lose their evaporative cooling potential and ultimately become susceptible to heat stress. Effects of heat stress therefore have to be combined with moisture availability such as the precipitation deficit or the soil water balance. Risks of combined heat and moisture deficit stress appear during the summer. These risks are subsequently related to crop damage. The methodology of defining

  4. The characteristics and prognostic value of signet ring cell histology in gastric cancer: A retrospective cohort study of 2199 consecutive patients.

    PubMed

    Lu, Ming; Yang, Zuyao; Feng, Qi; Yu, Mei; Zhang, Yuelun; Mao, Chen; Shen, Lin; Tang, Jinling

    2016-07-01

    Although signet ring cell cancer (SRCC) has long been regarded as an adverse prognostic factor of gastric cancer, the findings of existing studies on this issue are inconsistent. We conducted a retrospective cohort study of 2199 consecutive patients with gastric cancer treated in a tertiary cancer hospital in Beijing, China, 1994 to 2013. The characteristics of SRCC and non-SRCC were compared. The prognostic effects of SRCC and other important clinicopathological factors on overall survival were evaluated by both univariate and multivariate Cox regression analyses and expressed as hazard ratio (HR) with 95% confidence interval (CI). SRCC accounted for 16.1% of gastric cancer, increasing from 6% to 20% over the last 2 decades, and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. SRCC (HR: 1.387, 95% CI: 1.177-1.634), stage (HR: 1.752, 95% CI: 1.458-2.106), surgery (palliative resection: HR: 0.712, 95% CI: 0.590-0.859; curative resection: HR: 0.490, 95% CI: 0.380-0.633), performance status (HR: 1.849, 95% CI: 1.553-2.201), and age (HR: 1.070, 95% CI: 1.001-1.143) were independent prognostic factors for gastric cancer, whereas time period of diagnosis, sex, and tumor location were not statistically significantly associated with overall survival. Subgroup analyses showed that the prognostic value of SRCC did not vary much with age, sex, performance status, stage, and surgery and chemotherapy status. As compared with non-SRCC, SRCC accounted for increasingly more of gastric cancer and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. It was an independent prognostic factor associated with worse survival in gastric cancer. PMID:27399088

  5. DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers.

    PubMed

    Abdel-Fatah, Tarek M A; Arora, Arvind; Moseley, Paul M; Perry, Christina; Rakha, Emad A; Green, Andrew R; Chan, Stephen Y T; Ellis, Ian O; Madhusudan, Srinivasan

    2015-09-01

    Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol β, FEN1, APE1, XRCC1, SMUG1, PARP1, BRCA1, ATR, ATM, DNA-PKcs, Chk1, Chk2, p53, and TOPO2. Multivariate Cox proportional hazards models (with backward stepwise exclusion of these factors, using a criterion of p < 0.05 for retention of factors in the model) were used to identify factors that were independently associated with clinical outcomes. XRCC1 (p = 0.002), pol β (p = 0.032) FEN1 (p = 0.001) and BRCA1 (p = 0.040) levels were independently associated with poor BCSS. Subsequently, DNA repair index prognostic (DRPI) scores for breast cancer specific survival (BCSS) were calculated and two prognostic groups (DRPI-PGs) were identified. Patients in prognostic group 2 (DRPI-PG2) have higher risk of death (p < 0.001). Furthermore, in DRPI-PG2 patients, exposure to anthracycline reduced the risk of death [(HR (95% CI) = 0.79 (0.64-0.98), p = 0.032) by 21-26%. In addition, DRPI-PG2 patients have adverse clinicopathological features including higher grade, lympho-vascular invasion, Her-2 positive phenotype, compared to those in DRPI-PG1 (p < 0.01). Receiver operating characteristic (ROC) curves indicated that the DRPI outperformed the currently used prognostic factors and adding DRPI to lymph node stage significantly improved their performance as a predictor for BCSS [p < 0.00001, area under curve (AUC) = 0.70]. BER strongly influences pathogenesis of ER- and TNBCs. The DRPI accurately predicts BCSS and can also serve as a valuable prognostic and predictive tool for TNBCs. PMID:26267318

  6. Tumor budding score based on 10 high-power fields is a promising basis for a standardized prognostic scoring system in stage II colorectal cancer.

    PubMed

    Horcic, Milo; Koelzer, Viktor H; Karamitopoulou, Eva; Terracciano, Luigi; Puppa, Giacomo; Zlobec, Inti; Lugli, Alessandro

    2013-05-01

    Tumor budding is recognized by the World Health Organization as an additional prognostic factor in colorectal cancer but remains unreported in diagnostic work due to the absence of a standardized scoring method. This study aims to assess the most prognostic and reproducible scoring systems for tumor budding in colorectal cancer. Tumor budding on pancytokeratin-stained whole tissue sections from 105 well-characterized stage II patients was scored by 3 observers using 7 methods: Hase, Nakamura, Ueno, Wang (conventional and rapid method), densest high-power field, and 10 densest high-power fields. The predictive value for clinicopathologic features, the prognostic significance, and interobserver variability of each scoring method was analyzed. Pancytokeratin staining allowed accurate evaluation of tumor buds. Interobserver agreement for 3 observers was excellent for densest high-power field (intraclass correlation coefficient, 0.83) and 10 densest high-power fields (intraclass correlation coefficient, 0.91). Agreement was moderate to substantial for the conventional Wang method (κ = 0.46-0.62) and moderate for the rapid method (κ = 0.46-0.58). For Nakamura, moderate agreement (κ = 0.41-0.52) was reached, whereas concordance was fair to moderate for Ueno (κ = 0.39-0.56) and Hase (κ = 0.29-0.51). The Hase, Ueno, densest high-power field, and 10 densest high-power field methods identified a significant association of tumor budding with tumor border configuration. In multivariate analysis, only tumor budding as evaluated in densest high-power field and 10 densest high-power fields had significant prognostic effects on patient survival (P < .01), with high prognostic accuracy over the full 10-year follow-up. Scoring tumor buds in 10 densest high-power fields is a promising method to identify stage II patients at high risk for recurrence in daily diagnostics; it is highly reproducible, accounts for heterogeneity, and has a strong predictive value for adverse outcome

  7. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

    PubMed

    Soukavong, Mick; Kim, Jungmee; Park, Kyounghoon; Yang, Bo Ram; Lee, Joongyub; Jin, Xue Mei; Park, Byung Joo

    2016-09-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  8. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database

    PubMed Central

    2016-01-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  9. Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia

    PubMed Central

    Patnaik, M M; Lasho, T L; Vijayvargiya, P; Finke, C M; Hanson, C A; Ketterling, R P; Gangat, N; Tefferi, A

    2016-01-01

    Mutations involving epigenetic regulators (TET2~60% and ASXL1~40%) and splicing components (SRSF2~50%) are frequent in chronic myelomonocytic leukemia (CMML). On a 27-gene targeted capture panel performed on 175 CMML patients (66% males, median age 70 years), common mutations included: TET2 46%, ASXL1 47%, SRSF2 45% and SETBP1 19%. A total of 172 (98%) patients had at least one mutation, 21 (12%) had 2, 24 (14%) had 3 and 30 (17%) had >3 mutations. In a univariate analysis, the presence of ASXL1 mutations (P=0.02) and the absence of TET2 mutations (P=0.03), adversely impacted survival; while the number of concurrent mutations had no impact (P=0.3). In a multivariable analysis that included hemoglobin, platelet count, absolute monocyte count and circulating immature myeloid cells (Mayo model), the presence of ASXL1 mutations (P=0.01) and absence of TET2 mutations (P=0.003) retained prognostic significance. Patients were stratified into four categories: ASXL1wt/TET2wt (n=56), ASXL1mut/TET2wt (n=31), ASXL1mut/TET2mut (n=50) and ASXL1wt/TET2mut (n=38). Survival data demonstrated a significant difference in favor of ASXL1wt/TET2mut (38 months; P=0.016), compared with those with ASXL1wt/TET2wt (19 months), ASXL1mut/TET2wt (21 months) and ASXL1mut/TET2mut (16 months) (P=0.3). We confirm the negative prognostic impact imparted by ASXL1 mutations and suggest a favorable impact from TET2 mutations in the absence of ASXL1 mutations. PMID:26771811

  10. NDRG4 stratifies the prognostic value of body mass index in colorectal cancer.

    PubMed

    Zheng, Jianyong; Li, Yunming; Zhu, Shaojun; Li, Jipeng; Zhao, Qingchuan; Ji, Gang; Wang, Weizhong; Chu, Dake

    2016-01-12

    NDRG4 is a novel candidate tumor suppressor and can inhibit PI3K/AKT signal which is related with energy balance and related carcinogenesis. In the present study, we investigated whether NDRG4 status could modify the association of obesity with clinical outcome of colorectal cancer. For this purpose, a hospital-based prospective study cohort of 226 colorectal cancer patients was involved. NDRG4 mRNA levels were determined by real-time PCR. Association of NDRG4 mRNA expression with disease-free and overall survival was studied first. Then, the association of obesity with clinical outcome was determined according to NDRG4 level. Multivariate Cox proportional hazards model was used to compute hazard ratio, adjusting for covariates including microsatellite instability, KRAS, BRAF and PIK3CA mutation. Results showed that NDRG4 mRNA expression was decreased in tumor specimens and significantly correlated with tumor differentiation, invasion and metastasis. Patients with tumor of reduced NDRG4 mRNA level had unfavorable disease-free and overall survival. Obesity was found to be adversely associated with disease-free and overall survival in tumors with reduced NDRG4 level, not in preserved NDRG4 level group, in both univariate and multivariate analysis. These data provided the first evidence that NDRG4 level in colorectal cancer could effectively stratify the prognostic value of obesity, which would better the understanding of the prognostic role of obesity in colorectal cancer. Our results also support the notion that the host-tumor interactions in colorectal cancer might influence tumor aggressiveness. PMID:26515606

  11. NDRG4 stratifies the prognostic value of body mass index in colorectal cancer

    PubMed Central

    Zheng, Jianyong; Li, Yunming; Zhu, Shaojun; Li, Jipeng; Zhao, Qingchuan; Ji, Gang; Wang, Weizhong; Chu, Dake

    2016-01-01

    NDRG4 is a novel candidate tumor suppressor and can inhibit PI3K/AKT signal which is related with energy balance and related carcinogenesis. In the present study, we investigated whether NDRG4 status could modify the association of obesity with clinical outcome of colorectal cancer. For this purpose, a hospital-based prospective study cohort of 226 colorectal cancer patients was involved. NDRG4 mRNA levels were determined by real-time PCR. Association of NDRG4 mRNA expression with disease-free and overall survival was studied first. Then, the association of obesity with clinical outcome was determined according to NDRG4 level. Multivariate Cox proportional hazards model was used to compute hazard ratio, adjusting for covariates including microsatellite instability, KRAS, BRAF and PIK3CA mutation. Results showed that NDRG4 mRNA expression was decreased in tumor specimens and significantly correlated with tumor differentiation, invasion and metastasis. Patients with tumor of reduced NDRG4 mRNA level had unfavorable disease-free and overall survival. Obesity was found to be adversely associated with disease-free and overall survival in tumors with reduced NDRG4 level, not in preserved NDRG4 level group, in both univariate and multivariate analysis. These data provided the first evidence that NDRG4 level in colorectal cancer could effectively stratify the prognostic value of obesity, which would better the understanding of the prognostic role of obesity in colorectal cancer. Our results also support the notion that the host-tumor interactions in colorectal cancer might influence tumor aggressiveness. PMID:26515606

  12. FOXM1 expression in rhabdomyosarcoma: a novel prognostic factor and therapeutic target.

    PubMed

    Kuda, Masaaki; Kohashi, Kenichi; Yamada, Yuichi; Maekawa, Akira; Kinoshita, Yoshiaki; Nakatsura, Tetsuya; Iwamoto, Yukihide; Taguchi, Tomoaki; Oda, Yoshinao

    2016-04-01

    The transcription factor Forkhead box M1 (FOXM1) is known to play critical roles in the development and progression of various types of cancer, but the clinical significance of FOXM1 expression in rhabdomyosarcoma (RMS) is unknown. This study aimed to determine the role of FOXM1 in RMS. We investigated the expression levels of FOXM1 and vascular endothelial growth factor (VEGF) and angiogenesis in a large series of RMS clinical cases using immunohistochemistry (n = 92), and we performed clinicopathologic and prognostic analyses. In vitro studies were conducted to examine the effect of FOXM1 knock-down on VEGF expression, cell proliferation, migration, and invasion in embryonal RMS (ERMS) and alveolar RMS (ARMS) cell lines, using small interference RNA (siRNA). High FOXM1 expression was significantly increased in the cases of ARMS, which has an adverse prognosis compared to ERMS (p = 0.0310). The ERMS patients with high FOXM1 expression (n = 25) had a significantly shorter survival than those with low FOXM1 expression (n = 24; p = 0.0310). FOXM1 expression was statistically correlated with VEGF expression in ERMS at the protein level as shown by immunohistochemistry and at the mRNA level by RT-PCR. The in vitro study demonstrated that VEGF mRNA levels were decreased in the FOXM1 siRNA-transfected ERMS and ARMS cells. FOXM1 knock-down resulted in a significant decrease of cell proliferation and migration in all four RMS cell lines and invasion in three of the four cell lines. Our results indicate that FOXM1 overexpression may be a prognostic factor of RMS and that FOXM1 may be a promising therapeutic target for the inhibition of RMS progression. PMID:26553361

  13. Alexithymia as a prognostic risk factor for health problems: a brief review of epidemiological studies

    PubMed Central

    2012-01-01

    The number of articles on alexithymia has been steadily increasing since the word “alexithymia” was coined in the 1970s to denote a common characteristic that is observed among classic psychosomatic patients in whom therapy was unsuccessful. Alexithymia, a disorder of affect regulation, has been suggested to be broadly associated with various mental and physical health problems. However, most available evidence is based on anecdotal reports or cross-sectional observations. To clarify the predictive value of alexithymia for health problems, a systematic review of prospective studies was conducted. A search of the PubMed database identified 1,507 articles on “alexithymia” that were published by July 31, 2011. Among them, only 7 studies examined the developmental risks of alexithymia for health problems among nonclinical populations and 38 studies examined the prognostic value of alexithymia among clinical populations. Approximately half of the studies reported statistically significant adverse effects, while 5 studies demonstrated favorable effects of alexithymia on health outcomes; four of them were associated with surgical interventions and two involved cancer patients. The studies that showed insignificant results tended to have a small sample size. In conclusion, epidemiological evidence regarding alexithymia as a prognostic risk factor for health problems remains un-established. Even though alexithymia is considered to be an unfavorable characteristic for disease control and health promotion overall, some beneficial aspects are suggested. More prospective studies with sufficient sample sizes and follow-up period, especially those involving life course analyses, are needed to confirm the contribution of alexithymia to health problems. PMID:23244192

  14. Early Childhood Adversity and Pregnancy Outcomes

    PubMed Central

    Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

    2016-01-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  15. Early Childhood Adversity and Pregnancy Outcomes.

    PubMed

    Smith, Megan V; Gotman, Nathan; Yonkers, Kimberly A

    2016-04-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers' delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  16. Adverse reactions to the sulphite additives

    PubMed Central

    Misso, Neil LA

    2012-01-01

    Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. Most studies report a prevalence of sulphite sensitivity of 3 to 10% among asthmatic subjects who ingest these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. Although a number of potential mechanisms have been proposed, the precise mechanisms underlying sulphite sensitivity remain unclear. PMID:24834193

  17. Management of adverse effects of mood stabilizers.