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Sample records for adverse prognostic indicator

  1. 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

  2. Prognostic Indicators for Ebola Patient Survival.

    PubMed

    Crowe, Samuel J; Maenner, Matthew J; Kuah, Solomon; Erickson, Bobbie Rae; Coffee, Megan; Knust, Barbara; Klena, John; Foday, Joyce; Hertz, Darren; Hermans, Veerle; Achar, Jay; Caleo, Grazia M; Van Herp, Michel; Albariño, César G; Amman, Brian; Basile, Alison Jane; Bearden, Scott; Belser, Jessica A; Bergeron, Eric; Blau, Dianna; Brault, Aaron C; Campbell, Shelley; Flint, Mike; Gibbons, Aridth; Goodman, Christin; McMullan, Laura; Paddock, Christopher; Russell, Brandy; Salzer, Johanna S; Sanchez, Angela; Sealy, Tara; Wang, David; Saffa, Gbessay; Turay, Alhajie; Nichol, Stuart T; Towner, Jonathan S

    2016-02-01

    To determine whether 2 readily available indicators predicted survival among patients with Ebola virus disease in Sierra Leone, we evaluated information for 216 of the 227 patients in Bo District during a 4-month period. The indicators were time from symptom onset to healthcare facility admission and quantitative real-time reverse transcription PCR cycle threshold (Ct), a surrogate for viral load, in first Ebola virus-positive blood sample tested. Of these patients, 151 were alive when detected and had reported healthcare facility admission dates and Ct values available. Time from symptom onset to healthcare facility admission was not associated with survival, but viral load in the first Ebola virus-positive blood sample was inversely associated with survival: 52 (87%) of 60 patients with a Ct of >24 survived and 20 (22%) of 91 with a Ct of <24 survived. Ct values may be useful for clinicians making treatment decisions or managing patient or family expectations.

  3. Tumor budding is an independent adverse prognostic factor in pancreatic ductal adenocarcinoma.

    PubMed

    O'Connor, Kate; Li-Chang, Hector H; Kalloger, Steven E; Peixoto, Renata D; Webber, Douglas L; Owen, David A; Driman, David K; Kirsch, Richard; Serra, Stefano; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-04-01

    Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of <5 cells. The presence of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.

  4. 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

  5. Identification of novel prognostic indicators in burned patients.

    PubMed

    Peterson, V M; Murphy, J R; Haddix, T; Ford, P; Anderson, S J; Bartle, E J

    1988-05-01

    The size and depth of burn and patient age are useful early prognostic indicators in burned patients, but have limited value in predicting which patients in a given cohort are likely to die. The objective of this study was to identify additional variables in the first 10 days of burn injury which could better predict patient outcome. Variables consisting of demographic information, routine laboratory data, and clinical observations on 89 burned patients (63 survivors and 26 nonsurvivors) were analyzed. Compared to survivors, nonsurvivors had significantly larger burns (58 +/- 23% vs. 37 +/- 17%; p less than 0.0002) and a higher incidence of Gram-negative septicemia (20 of 26 [77%] vs. 24 of 63 [38%]; p less than 0.001). Potential prognostic variables were subjected to multivariate logistic regression analysis for each of the first 10 days following burn injury in order to identify a combination of parameters which predicted patient outcome. The regression analyses revealed that, as previously demonstrated, patient age and burn size were significant predictors of mortality on admission and throughout the first 10 days postburn. In addition, absolute monocyte count (AMC), absolute lymphocyte count (ALC), maximum daily temperature (Tmax), and BUN were also significant predictors (p less than 0.05). These data indicate that logistic regression models can identify simple prognostic variables in burned patients which may improve clinicians' ability to identify high-risk patients early in the course of their burn injuries.

  6. Prognostic indications of the failure to treat amoebic liver abscesses

    PubMed Central

    Sánchez-Aguilar, Martín; Morán-Mendoza, Onofre; Herrera-Hernández, Miguel F; Hernández-Sierra, Juan Francisco; Mandeville, Peter B; Tapia-Pérez, J Humberto; Sánchez-Reyna, Martín; Sánchez-Rodríguez, José Juan; Gordillo-Moscoso, Antonio

    2012-01-01

    Objectives To identify the variables that predict the failure to treat amoebic liver abscesses. Methods We prospectively carried out a case–control study on a cohort of patients who had been diagnosed with amoebic liver abscesses using clinical, ultrasonic, and serologic methods. Patients with pyogenic abscesses, negative ELISA tests for amoebiasis, immunosuppression status, or previous abdominal surgery were excluded. All patients received metronidazole, and those who demonstrated 4 days of unfavorable clinical responses received percutaneous or surgical draining of the abscess. Demographic, laboratory, and ultrasonographic characteristics were assessed as prognostic indications of failure. Results Of 40 patients with amoebic liver abscess, 24 (mean age: 36.7±11.2 years) responded to medical treatment and 16 (41.8±11.6 years) required drainage, including 14 patients who underwent percutaneous drainage and two patients who required surgery. The albumin level, abscess volume, abscess diameter, and alkaline phosphatase level were all statistically significant (P<0.05) on the bivariate analysis. The highest (>99%) sensitivity and negative predictive value were observed for an abscess volume >500 ml and diameter >10 cm, while the best specificity and positive predictive value were achieved with the combination of low serum albumin level, high alkaline phosphatase level, and large abscess volume or diameter. Conclusions The prognostic indications of the failure to treat amoebic liver abscesses include low albumin, high alkaline phosphatase, and large abscess volume or diameter. The combination of these variables is a useful and easy tool for determining appropriate therapy. PMID:23265424

  7. Clinicopathological classification and traditional prognostic indicators of breast cancer

    PubMed Central

    Li, Jiehua; Chen, Zhibai; Su, Ka; Zeng, Jian

    2015-01-01

    Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. The objective of this study is to evaluate the value of molecular subtypes in breast cancer management according to a retrospective analysis of breast carcinoma molecular subtypes, histopathological grade, and TNM stage. A retrospective study of 475 paraffin-embedded tissues of breast cancer samples from the First Affiliated Hospital of Guangxi Medical University was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The differences of molecular subtypes of breast cancers in regard to TNM staging and pathological grade were analyzed using χ2 tests. Values of P<0.05 were considered statistically significant. The frequency of luminal A, luminal B, HER2-positive luminal B, triple negative and non-luminal HER2-positive subtypes were: 35.5%, 22.5%, 13.1%, 15.2% and 13.7%, respectively. Among the five subtypes of breast cancer, the distribution of pathological grades showed a significant difference (P<0.001). There were significant differences in the distribution of TNM staging among the five subtypes of breast cancer (P<0.001). In addition to traditional prognostic indicators such as TNM staging and pathological grade, molecular subtype may aid clinical practice and research into breast cancer. Different molecular subtypes will lead to different prognosis and therapeutic option. Molecular subtyping is essential for breast cancer management. PMID:26339424

  8. 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.

  9. Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia

    PubMed Central

    Qiu, Yi Hua; Zhang, Nianxiang; Singh, Neera; Faderl, Stefan; Ferrajoli, Alessandra; York, Heather; Qutub, Amina A.; Coombes, Kevin R.; Watson, Dennis K.

    2011-01-01

    Friend leukemia virus integration 1 (FLI1), an Ets transcription factor family member, is linked to acute myelogenous leukemia (AML) by chromosomal events at the FLI1 locus, but the biologic impact of FLI1 expression on AML is unknown. FLI1 protein expression was measured in 511 newly diagnosed AML patients. Expression was similar in peripheral blood (PB) and BM and higher at diagnosis than at relapse (P = .02). Compared with normal CD34+ cells, expression in AML was above or below normal in 32% and 5% of patients, respectively. Levels were negatively correlated with an antecedent hematologic disorder (P = .002) but not with age or cytogenetics. Mutated NPM1 (P = .0007) or FLT3-ITD (P < .02) had higher expression. FLI1 levels were negatively correlated with 10 of 195 proteins associated with proliferation and stromal interaction, and positively correlated (R > 0.3) with 19 others. The FLI1 level was not predictive of remission attainment, but patients with low or high FLI1 expression had shorter remission duration (22.6 and 40.3 vs 51.1 weeks, respectively; P = .01) and overall survival (45.2 and 35.4 vs 59.4 weeks, respectively; P = .03). High FLI1 levels were adverse in univariate and multivariate analysis. FLI1 expression is frequently abnormal and prognostically adverse in AML. FLI1 and/or its response genes may be therapeutically targetable to interfere with AML cell biology. PMID:21917756

  10. Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia.

    PubMed

    Kornblau, Steven M; Qiu, Yi Hua; Zhang, Nianxiang; Singh, Neera; Faderl, Stefan; Ferrajoli, Alessandra; York, Heather; Qutub, Amina A; Coombes, Kevin R; Watson, Dennis K

    2011-11-17

    Friend leukemia virus integration 1 (FLI1), an Ets transcription factor family member, is linked to acute myelogenous leukemia (AML) by chromosomal events at the FLI1 locus, but the biologic impact of FLI1 expression on AML is unknown. FLI1 protein expression was measured in 511 newly diagnosed AML patients. Expression was similar in peripheral blood (PB) and BM and higher at diagnosis than at relapse (P = .02). Compared with normal CD34(+) cells, expression in AML was above or below normal in 32% and 5% of patients, respectively. Levels were negatively correlated with an antecedent hematologic disorder (P = .002) but not with age or cytogenetics. Mutated NPM1 (P = .0007) or FLT3-ITD (P < .02) had higher expression. FLI1 levels were negatively correlated with 10 of 195 proteins associated with proliferation and stromal interaction, and positively correlated (R > 0.3) with 19 others. The FLI1 level was not predictive of remission attainment, but patients with low or high FLI1 expression had shorter remission duration (22.6 and 40.3 vs 51.1 weeks, respectively; P = .01) and overall survival (45.2 and 35.4 vs 59.4 weeks, respectively; P = .03). High FLI1 levels were adverse in univariate and multivariate analysis. FLI1 expression is frequently abnormal and prognostically adverse in AML. FLI1 and/or its response genes may be therapeutically targetable to interfere with AML cell biology.

  11. Tetraspanin CD81 is an adverse prognostic marker in acute myeloid leukemia

    PubMed Central

    Roumier, Christophe; Peyrouze, Pauline; Gonzales, Fanny; Berthon, Céline; Quesnel, Bruno; Preudhomme, Claude; Behal, Hélène; Duhamel, Alain; Roche-Lestienne, Catherine; Cheok, Meyling

    2016-01-01

    CD81 is a cell surface protein which belongs to the tetraspanin family. While in multiple myeloma its expression on plasma cells is associated with worse prognosis, this has not yet been explored in acute myeloid leukemia (AML). We measured membrane expression of CD81 on AML cells at diagnosis, evaluated its association with AML characteristics and its influence on patient outcome after intensive chemotherapy in a cohort of 134 patients. CD81 was detected in 92/134 (69%) patients. Patients with AML expressing CD81 had elevated leukocyte count (P=0.02) and were more likely classified as intermediate or adverse-risk by cytogenetics (P<0.001). CD81 expression had a negative impact on survival (event-free survival, overall survival and relapse-free survival) in univariate (P<0.001) and in multivariate analyses (P=0.003, 0.002 and <0.001, respectively). CD81 has a negative impact on OS in patients with NPM1 mutation (P=0.01) and in patients ELN-favorable (P=0.002). In conclusion, this cell surface marker may be a new prognostic marker for diagnostic risk classification and a potential therapeutic target for drug development in AML. PMID:27566555

  12. Platelet activation risk index as a prognostic thrombosis indicator

    PubMed Central

    Zlobina, K. E.; Guria, G. Th.

    2016-01-01

    Platelet activation in blood flow under high, overcritical shear rates is initiated by Von Willebrand factor. Despite the large amount of experimental data that have been obtained, the value of the critical shear rate, above which von Willebrand factor starts to activate platelets, is still controversial. Here, we recommend a theoretical approach to elucidate how the critical blood shear rate is dependent on von Willebrand factor size. We derived a diagram of platelet activation according to the shear rate and von Willebrand factor multimer size. We succeeded in deriving an explicit formula for the dependence of the critical shear rate on von Willebrand factor molecule size. The platelet activation risk index was introduced. This index is dependent on the flow conditions, number of monomers in von Willebrand factor, and platelet sensitivity. Probable medical applications of the platelet activation risk index as a universal prognostic index are discussed. PMID:27461235

  13. Tumour biomarkers: homeostasis as a novel prognostic indicator

    PubMed Central

    Falco, Michela; Palma, Giuseppe; Rea, Domenica; De Biase, Davide; Scala, Stefania; D'Aiuto, Massimiliano; Facchini, Gaetano; Perdonà, Sisto; Barbieri, Antonio

    2016-01-01

    The term ‘personalized medicine’ refers to a medical procedure that consists in the grouping of patients based on their predicted individual response to therapy or risk of disease. In oncologic patients, a ‘tailored’ therapeutic approach may potentially improve their survival and well-being by not only reducing the tumour, but also enhancing therapeutic response and minimizing the adverse effects. Diagnostic tests are often used to select appropriate and optimal therapies that rely both on patient genome and other molecular/cellular analysis. Several studies have shown that lifestyle and environmental factors can influence the epigenome and that epigenetic events may be involved in carcinogenesis. Thus, in addition to traditional biomarkers, epigenetic factors are raising considerable interest, because they could potentially be used as an excellent tool for cancer diagnosis and prognosis. In this review, we summarize the role of conventional cancer genetic biomarkers and their association with epigenomics. Furthermore, we will focus on the so-called ‘homeostatic biomarkers’ that result from the physiological response to cancer, emphasizing the concept that an altered ‘new’ homeostasis influence not only tumour environment, but also the whole organism. PMID:27927793

  14. Enzymes approved for human therapy: indications, mechanisms and adverse effects.

    PubMed

    Baldo, Brian A

    2015-02-01

    Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

  15. Ropinirole: new indication. Restless legs: disproportionate adverse effects.

    PubMed

    2006-10-01

    (1) The restless legs syndrome consists of unpleasant sensory and motor symptoms of varying intensity in the lower limbs. Symptoms occur at rest, seated or lying down, are more intense in the evening and at night, and are relieved by moving the limb. This syndrome does not cause serious physical complications. When sleep disturbances occur, non drug methods should be tried first. (2) Ropinirole is a dopaminergic agonist initially marketed for the treatment of Parkinson's disease. It is the first drug to be approved for restless legs syndrome in France. (3) Three double-blind randomised placebo-controlled trials with similar designs showed minimal differences on a composite rating scale. After 12 weeks of treatment, ropinirole led to an improvement of about 3 points on a 40-point scale compared with placebo. (4) A 12-week double-blind randomised controlled trial and including patients who had "responded" to ropinirole showed a lower relapse rate in the group that continued to use ropinirole (32.6%) instead of switching to placebo (57.8%). However, we do not know if this was because of continued drug efficacy or a rebound effect in the placebo group. (5) The adverse effects of ropinirole in patients with restless legs syndrome had already been observed in the treatment of Parkinson's disease, and included nausea, vomiting, drowsiness, a sudden urge to sleep, syncope, hypotension, and hallucinations. (6) An increase in the severity of restless legs symptoms, typically seen with levodopa, was not evaluated in clinical trials of ropinirole. Some cases have nevertheless been reported. They describe the appearance of symptoms increasingly early in the evening, then in the afternoon, or as a rebound effect in the morning or the latter part of the night. Their intensity increases and can affect other parts of the body. (7) In practice, ropinirole has a negative risk-benefit balance in restless legs syndrome, which is a minor health disorder.

  16. Indications for frontolateral laryngectomy and prognostic factors of failure.

    PubMed

    Fiorella, R; Di Nicola, V; Mangiatordi, F; Fiorella, M L

    1999-01-01

    The aim of this study was a retrospective analysis of the oncological results in a group of patients treated by frontolateral laryngectomy using clinical and histopathological correlations in order to review the indications for surgery. In all, 150 patients underwent frontolateral laryngectomy as described by Leroux-Robert. All were staged according to the 1992 UICC TNM classification. Factors examined were clinical T, histopathological T, tumor infiltration of the anterior commissure and the vocal cord muscle, survival without disease and the percentage of local relapses. Twenty-one patients had local relapses (14%), while four patients developed second primary tumors (2.7%). Among the different correlations examined, microscopic infiltration of the anterior commissure was related to a greater number of local relapses (25.5% vs 5%) and a 55% survival with with no evidence of disease (NED). The crude 5-year NED survival was 66% and was influenced by second primary tumors and metastases (7.4%) and non-oncological diseases (14.6%). These data show the need for a re-evaluation of the indications for frontolateral laryngectomy because subtotal reconstructive laryngectomy could be performed more safely in the more advanced cases. In contrast, cases with more limited tumors might be better treated by laser for a more functional and cost-beneficial result.

  17. 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.

  18. 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

  19. The Impact of Various Platelet Indices as Prognostic Markers of Septic Shock

    PubMed Central

    Yu, Xuezhong; Guo, Shigong; Ji, Xu; Sun, Tongwen; Lan, Chao; Lavergne, Valery; Ghannoum, Marc; Li, Li

    2014-01-01

    Introduction Platelet indices, including mean platelet volume (MPV), are readily available blood tests, although their prognostic value in patients with septic shock has not been fully explored. Current evidence has found contradictory results. This study aims to explore the behavior of platelet indices in septic shock and their clinical prognostic value. Methods Charts of septic shock patients from January to December 2012 in a tertiary medical center in Northern China were reviewed retrospectively. Platelet indices were recorded during the first five consecutive days after admission, as well as the penultimate and the last day of hospital stay. The data were compared between surviving and non-surviving patients. Results A total of 124 septic shock patients were enrolled. Thirty-six of the patients survived and 88 of them expired. MPV in the non-survivor group was higher than that of the survivor group, especially on the last day. PDW and PLCR showed increased trends, while PCT and PLT decreased in the non-survivor group. Among the PLT indices, MPV had the highest area under the receiver operating characteristic curve (0.81) with a precision rate of 75.6% at a cut-off of 10.5.Compared with other more usual septic shock prognostic markers, MPV is second only to lactate for the highest area under the curve. Conclusion A statistically significant difference was seen between survivors and non-survivors for platelet indices which make them easily available and useful prognostic markers for patients in septic shock. PMID:25118886

  20. 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.

  1. 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

  2. Prognostic value of echocardiographic indicators of left ventricular systolic function in asymptomatic dialysis patients.

    PubMed

    Zoccali, Carmine; Benedetto, Francesco A; Mallamaci, Francesca; Tripepi, Giovanni; Giacone, Giuseppe; Cataliotti, Alessandro; Seminara, Giuseppe; Stancanelli, Benedetta; Malatino, Lorenzo S

    2004-04-01

    Patients with end-stage renal disease (ESRD) are at high risk for heart failure, but the prevalence and the prognostic value of asymptomatic systolic dysfunction in these patients are unknown. In this prospective cohort study, the authors have therefore assessed by echocardiography the prevalence and the prognostic value of systolic function as estimated by ejection fraction (EF), fractional shortening at endocardial level (endoFS), and at midwall (mwFS), in a cohort of 254 asymptomatic dialysis patients. Systolic dysfunction had a prevalence rate of 26% by endoFS and of 48% by mwFS. During the follow-up period, 125 patients had one or more fatal and nonfatal CV events. On multivariate COX regression analysis, the three LV systolic function indicators were independently associated with incident fatal and nonfatal CV events, and there were no differences in the predictive power of these indicators (P > 0.30). The prediction power of LV function indicators was largely independent of traditional and novel risk factors in ESRD such as C-reactive protein and asymmetric dimethyl arginine (ADMA). ADMA was significantly related with LV function indicators as well as with mortality and incident CV events, but these links were much reduced (P = NS) in models including LV function indicators. Of note, the risk of CV events was minimal in patients with normal LV mass and function, intermediate in patients with either LVH or systolic dysfunction, and maximal in patients displaying both alterations. The study of myocardial contractility by echocardiography provides prognostic information independently of LV mass and other risk factors in ESRD. Risk stratification by simple systolic function parameters may prove useful in secondary prevention strategies in these patients.

  3. Loss of RUNX3 expression is an independent adverse prognostic factor in diffuse large B-cell lymphoma.

    PubMed

    Duncan, Virginia E; Ping, Zheng; Varambally, Sooryanarayana; Peker, Deniz

    2017-01-01

    Runt-related transcription factor-3 (RUNX3) is an apoptotic factor correlated with tumorigenesis and cancer progression. Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been shown to mediate silencing of RUNX3. We investigated RUNX3 and EZH2 expression in diffuse large B-cell lymphoma (DLBCL). A chart review was conducted and tissue-microarray (TMA) was constructed using archived tissue from 83 DLBCL cases. RUNX3 and EZH2 protein expression was correlated with immunophenotypic subtypes and survival. Loss of RUNX3 was observed in 20 cases; EZH2 expression was observed in 59 cases. RUNX3-negative tumors had significantly lower overall and recurrence-free survival (log-rank test, p < 0.0001 for each). No correlation was found between RUNX3 and EZH2 staining (r = 0.14; p = 0.2). Results suggest a role for the RUNX3 gene in the pathogenesis of DLBCL. Loss of RUNX3 expression strongly correlated with adverse prognosis, independent of subtype. Further studies are warranted to elucidate the biology and prognostic utility of RUNX3 in DLBCL.

  4. Checkpoint kinase 1 expression is an adverse prognostic marker and therapeutic target in MYC-driven medulloblastoma

    PubMed Central

    Shah, Monil; Mulcahy Levy, Jean M.; Griesinger, Andrea M.; Alimova, Irina; Harris, Peter S.; Birks, Diane K.; Donson, Andrew M.; Davidson, Nathan; Remke, Marc; Taylor, Michael D.; Handler, Michael H.; Foreman, Nicholas K.; Venkataraman, Sujatha; Vibhakar, Rajeev

    2016-01-01

    Checkpoint kinase 1 (CHK1) is an integral component of the cell cycle as well as the DNA Damage Response (DDR) pathway. Previous work has demonstrated the effectiveness of inhibiting CHK1 with small-molecule inhibitors, but the role of CHK1 mediated DDR in medulloblastoma is unknown. CHK1, both at the mRNA and protein level, is highly expressed in medulloblastoma and elevated CHK1 expression in Group3 medulloblastoma is an adverse prognostic marker. CHK1 inhibition with the small-molecule drug AZD7762, results in decreased cell growth, increased DNA damage and cell apoptosis. Furthermore, AZD7762 acts in synergy with cisplatin in reducing cell proliferation in medulloblastoma. Similar phenotypic changes were observed with another CHK1 inhibitor, PF477736, as well as genetic knockdown using siRNA against CHK1. Treatments with small-molecule inhibitors of CHK1 profoundly modulated the expression of both upstream and downstream target proteins within the CHK1 signaling pathways. This suggests the presence of a feedback loop in activating CHK1. Overall, our results demonstrate that small-molecule inhibition of CHK1 in combination with, cisplatin, is more advantageous than either treatment alone, especially for Group 3 medulloblastoma, and therefore this combined therapeutic approach serves as an avenue for further investigation. PMID:27449089

  5. Time factor as a prognostic indicator on the Bender-Gestalt test.

    PubMed

    Sahay, M; Singh, M V

    1975-10-01

    Z-scores from Bender-Gestalt records of 62 psychiatric in- and outpatients were computed. The patients were put on active treatment, and a psychiatric rating was done to evaluate therapeutic recovery after a period of 19 to 24 months. These patients were grouped into three categories, i.e., patients with low Z-scores and good therapeutic recovery; patients with high Z-scores and poor therapeutic recovery; patients with low Z-scores who still showed poor response to treatment. Total time taken by each patient to reprduce the BG designs was noted as well. Results indicate that Z-score was a significant prognostic indicator for schizophrenics, affective psychotics, organic psychotics and patients who were suffering from anxiety and conversion reactions, but not for obsessive compulsive neurotics. Time taken for BG reproductions proved to be an important prognostic indicator, as patients who did not respond satisfactorily to the treatment took significantly more time than those who responded well to treatment. Hence, time taken by the patients for BG reproductions also needs to be considered when any predictions are made with regard to therapeutic outcome.

  6. Monoacylglycerol Lipase: A Novel Potential Therapeutic Target and Prognostic Indicator for Hepatocellular Carcinoma

    PubMed Central

    Zhang, Junyong; Liu, Zuojin; Lian, Zhengrong; Liao, Rui; Chen, Yi; Qin, Yi; Wang, Jinlong; Jiang, Qing; Wang, Xiaobo; Gong, Jianping

    2016-01-01

    Monoacylglycerol lipase (MAGL) is a key enzyme in lipid metabolism that is demonstrated to be involved in tumor progression through both energy supply of fatty acid (FA) oxidation and enhancing cancer cell malignance. The aim of this study was to investigate whether MAGL could be a potential therapeutic target and prognostic indicator for hepatocellular carcinoma (HCC). To evaluate the relationship between MAGL levels and clinical characteristics, a tissue microarray (TMA) of 353 human HCC samples was performed. MAGL levels in HCC samples were closely linked to the degree of malignancy and patient prognosis. RNA interference, specific pharmacological inhibitor JZL-184 and gene knock-in of MAGL were utilized to investigate the effects of MAGL on HCC cell proliferation, apoptosis, and invasion. MAGL played important roles in both proliferation and invasion of HCC cells through mechanisms that involved prostaglandin E2 (PGE2) and lysophosphatidic acid (LPA). JZL-184 administration significantly inhibited tumor growth in mice. Furthermore, we confirmed that promoter methylation of large tumor suppressor kinase 1 (LATS1) resulted in dysfunction of the Hippo signal pathway, which induced overexpression of MAGL in HCC. These results indicate that MAGL could be a potentially novel therapeutic target and prognostic indicator for HCC. PMID:27767105

  7. Optimal management of pulmonary arterial hypertension: prognostic indicators to determine treatment course

    PubMed Central

    Baldi, Fabiana; Fuso, Leonello; Arrighi, Eugenio; Valente, Salvatore

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a rapidly progressive pulmonary vascular disease with a multifactorial etiopathogenesis that can result in right-sided heart failure and death. A number of studies indicate that an early therapeutic intervention yields better results on disease progression as compared to delayed treatment. In this review, we will analyze treatment strategies that may be used for monitoring disease progression and for guiding treatment decisions. Several factors (ie, symptoms, functional class, exercise capacity as assessed by a walking test and cardiopulmonary stress testing, hemodynamic parameters, cardiac magnetic resonance imaging, and plasma levels of biochemical markers) have been prognostic of survival. These indicators may be used both at the time of diagnosis and during treatment follow-up. No resolutive therapy is currently available for PAH; however, in the last decade, the advent of specific pharmacological treatments has given new hope to patients suffering from this debilitating disease with a poor prognosis. Combination drug therapies offer increased benefits over monotherapy, and current guidelines recommend a sequential “add on” design approach for patients in functional class II–IV. The goal-oriented “treat to target” therapy sets the timing for treatment escalation in case of inadequate response to currently known prognostic indicators. To date, further longitudinal studies should be urgently conducted to identify new goals that may improve therapeutic strategies in order to optimize personalized treatment in PAH patients. PMID:25328398

  8. CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer

    PubMed Central

    2012-01-01

    Introduction Tumor infiltrating lymphocytes may indicate an immune response to cancer development, but their significance remains controversial in breast cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte infiltration in a large cohort of invasive early stage breast cancers, and to evaluate its prognostic effect in different breast cancer intrinsic subtypes. Methods Immunohistochemistry for CD8 staining was performed on tissue microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes were counted as intratumoral when in direct contact with tumor cells, and as stromal in adjacent locations. Kaplan-Meier functions and Cox proportional hazards regression models were applied to examine the associations between tumor infiltrating lymphocytes and breast cancer specific survival. Results Among 3403 cases for which immunohistochemical results were obtained, CD8+ tumor infiltrating lymphocytes were identified in an intratumoral pattern in 32% and stromal pattern in 61% of the cases. In the whole cohort, the presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival. Multivariate analysis indicated that the favorable prognostic effect of CD8+ tumor infiltrating lymphocytes was significant only in the core basal intrinsic subgroup (Hazard ratio, HR = 0.35, 95% CI = 0.23-0.54). No association with improved survival was present in those triple negative breast cancers that lack expression of basal markers (HR = 0.99, 95% CI = 0.48-2.04) nor in the other intrinsic subtypes. Conclusions CD8+ tumor infiltrating lymphocytes are an independent prognostic factor associated with better patient survival in basal-like breast cancer, but not in non-basal triple negative breast cancers nor in other intrinsic

  9. SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer

    PubMed Central

    Sun, Hui-Min; Mi, Yu-Shuai; Yu, Fu-Dong; Han, Yang; Liu, Xi-Sheng; Lu, Su; Zhang, Yu; Zhao, Sen-Lin; Ye, Ling; Liu, Ting-Ting; Yang, Dao-Hua; Sun, Xiao-Feng; Qin, Xue-Bin; Zhou, Zong-Guang; Tang, Hua-Mei; Peng, Zhi-Hai

    2016-01-01

    Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC. PMID:27648355

  10. The Use of Three Long Non-Coding RNAs as Potential Prognostic Indicators of Astrocytoma.

    PubMed

    Zhi, Feng; Wang, Qiang; Xue, Lian; Shao, Naiyuan; Wang, Rong; Deng, Danni; Wang, Suinuan; Xia, Xiwei; Yang, Yilin

    2015-01-01

    Long noncoding RNAs (lncRNAs) are pervasively transcribed and play a key role in tumorigenesis. The aim of the study was to determine the lncRNA expression profile in astrocytomas and to assess its potential clinical value. We performed a three-step analysis to establish the lncRNA profile for astrocytoma: a) the lncRNA expression was examined on 3 astrocytomas as well as 3 NATs (normal adjacent tissues) using the lncRNA microarray; b) the top-hits were validated in 40 astrocytomas (WHO grade II-IV) by quantitative real time-PCR (qRT-PCR); c) the hits with significant differences were re-evaluated using qRT-PCR in 90 astrocytomas. Finally, 7 lncRNAs were found to have a significantly different expression profile in astrocytoma samples compared to the NAT samples. Unsupervised clustering analysis further revealed the potential of the 7-lncRNA profile to differentiate between tumors and NAT samples. The upregulation of ENST00000545440 and NR_002809 was associated with advanced clinical stages of astrocytoma. Using Kaplan-Meier survival analysis, we showed that the low expression of BC002811 or XLOC_010967, or the high expression of NR_002809 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors. Our results indicate that the lncRNA profile may be a potential prognostic biomarker for the prediction of post-surgical outcomes.

  11. Feline mediastinal lymphoma: a retrospective study of signalment, retroviral status, response to chemotherapy and prognostic indicators.

    PubMed

    Fabrizio, Francesca; Calam, Amy E; Dobson, Jane M; Middleton, Stephanie A; Murphy, Sue; Taylor, Samantha S; Schwartz, Anita; Stell, Anneliese J

    2014-08-01

    Historically, feline mediastinal lymphoma has been associated with young age, positive feline leukaemia virus (FeLV) status, Siamese breed and short survival times. Recent studies following widespread FeLV vaccination in the UK are lacking. The aim of this retrospective multi-institutional study was to re-evaluate the signalment, retroviral status, response to chemotherapy, survival and prognostic indicators in feline mediastinal lymphoma cases in the post-vaccination era. Records of cats with clinical signs associated with a mediastinal mass and cytologically/histologically confirmed lymphoma were reviewed from five UK referral centres (1998-2010). Treatment response, survival and prognostic indicators were assessed in treated cats with follow-up data. Fifty-five cases were reviewed. The median age was 3 years (range, 0.5-12 years); 12 cats (21.8%) were Siamese; and the male to female ratio was 3.2:1.0. Five cats were FeLV-positive and two were feline immunodeficiency-positive. Chemotherapy response and survival was evaluated in 38 cats. Overall response was 94.7%; complete (CR) and partial response (PR) rates did not differ significantly between protocols: COP (cyclophosphamide, vincristine, prednisone) (n = 26, CR 61.5%, PR 34.0%); Madison-Wisconsin (MW) (n = 12, CR 66.7%, PR 25.0%). Overall median survival was 373 days (range, 20-2015 days) (COP 484 days [range, 20-980 days]; MW 211 days [range, 24-2015 days] [P = 0.892]). Cats achieving CR survived longer (980 days vs 42 days for PR; P = 0.032). Age, breed, sex, location (mediastinal vs mediastinal plus other sites), retroviral status and glucocorticoid pretreatment did not affect response or survival. Feline mediastinal lymphoma cases frequently responded to chemotherapy with durable survival times, particularly in cats achieving CR. The prevalence of FeLV-antigenaemic cats was low; males and young Siamese cats appeared to be over-represented.

  12. Comparison of prognostic indices in patients who undergo melanoma brain metastasis radiosurgery.

    PubMed

    Kano, Hideyuki; Morales-Restrepo, Alejandro; Iyer, Aditya; Weiner, Gregory M; Mousavi, Seyed H; Kirkwood, John M; Tarhini, Ahmad A; Flickinger, John C; Lunsford, L Dade

    2017-01-20

    OBJECTIVE The goal of this study was to use 4 prognostic indices to compare survival times of patients who underwent Gamma Knife stereotactic radiosurgery (SRS) to treat melanoma brain metastases. METHODS The authors analyzed 422 consecutive patients (1440 brain metastases) who underwent Gamma Knife SRS. The median total brain tumor volume was 4.7 cm(3) (range 0.3-69.3 cm(3)), and the median number of metastases was 2 (range 1-32). One hundred thirty-two patients underwent whole-brain radiation therapy. Survival times were compared using recursive partitioning analysis (RPA), the Score Index for Radiosurgery (SIR), the Basic Score for Brain Metastases (BSBM), and the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA). RESULTS The overall survival times after SRS were compared. With the RPA index, survival times were 2.6 months (Class III, n = 27), 5.5 months (Class II, n = 348), and 13.0 months (Class I, n = 47). With the DS-GPA index, survival times were 2.8 months (Scores 0-1, n = 67), 4.2 months (Scores 1.5-2.0, n = 143), 6.6 months (Scores 2.5-3.0, n = 111), and 9.4 months (Scores 3.5-4.0, n = 101). With the SIR, survival times were 3.2 months (Scores 0-3, n = 56), 5.8 months (Scores 4-7, n = 319), and 12.7 months (Scores 8-10, n = 47). With the BSBM index, survival times were 2.6 months (BSBM0, n = 47), 5.4 months (BSBM1, n = 282), 11.0 months (BSBM2, n = 86), and 8.8 months (BSBM3, n = 7). The DS-GPA index was the most balanced by case numbers in each class and provided the overall best prognostic index for overall survival. CONCLUSIONS The DS-GPA index proved most balanced and predictive of survival for patients with melanoma who underwent SRS as part of management for brain metastases. Patients whose DS-GPA score was ≥ 2.5 had predictably improved survival times after SRS.

  13. 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

  14. Dual specificity phosphatase 5 is a novel prognostic indicator for patients with advanced colorectal cancer

    PubMed Central

    Yan, Xuebing; Liu, Liguo; Li, Hao; Huang, Linsheng; Yin, Mingming; Pan, Cheng; Qin, Huanlong; Jin, Zhiming

    2016-01-01

    Dual specificity phosphatase 5 (DUSP5) is a negative regulator of Mitogen-activated protein kinase (MAPK) signaling pathway and has recently been identified as a tumor suppressor in several human malignancies. However, its clinical significance in colorectal cancer (CRC) remains unclear. In this study, we aimed to investigate the potential utility of DUSP5 as a novel biomarker for progression indication and chemotherapy benefit in CRC patients. Through quantitative real time-polymerase chain reaction and western blot, we determined that DUSP5 expression is dramatically lower in CRC tissues than that in matched normal tissues. The statistical analysis based on immunohistochemistry revealed that DUSP5 expression is significantly correlated with tumor differentiation, TNM stage, lymph node metastasis and distant metastasis. For the whole study cohort, patients with high DUSP5 expression had a better CRC-specific and disease-free survival than those with low DUSP5 expression and DUSP5 expression is an independent prognostic factor for patient survival. In subgroup analysis, DUSP5 has no prognostic significance in low-risk stage II patients, but could predict treatment response in high-risk stage II and stage III/IV patients who received standard FOLFOX chemotherapy scheme. Finally, the correlation analysis suggested that DUSP5 expression is associated with Epithelial-to-Mesenchymal Transition (EMT) phenotype in CRC tissues, suggesting that downregulated DUSP5 may contribute to poor prognosis partly by involving EMT. Taken together, our study proposes that DUSP5 is a promising biomarker for predicting CRC progression and advanced patients with high DUSP5 expression appear to benefit from standard FOLFOX chemotherapy scheme. PMID:27822421

  15. Predicting ADHD by Assessment of Rutter’s Indicators of Adversity in Infancy

    PubMed Central

    Østergaard, Søren D.; Larsen, Janne T.; Wilens, Timothy E.; Mortensen, Preben B.; Agerbo, Esben; Mors, Ole; Petersen, Liselotte

    2016-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with early onset. ADHD is associated with significant morbidity and mortality, partly due to delayed diagnosis. Identification of children at high risk for developing ADHD could lead to earlier diagnosis and potentially change the negative trajectory of the illness for the better. Since early psychosocial adversity is considered to be a likely etiological risk factor for ADHD, markers of this construct may be useful for early identification of children at high risk. Therefore, we sought to investigate whether Rutter’s indicators of adversity (low social class, severe marital discord, large family size, paternal criminality, maternal mental disorder, and placement in out-of-home care) assessed in infancy could serve as early predictors for the development of ADHD. Methods and Findings Using data from the Danish nationwide population-based registers, we established a cohort consisting of all 994,407 children born in Denmark between January 1st 1993 and December 31st 2011 and extracted dichotomous values for the six Rutter’s indicators of adversity at age 0–12 months (infancy) for each cohort member. The cohort members were followed from their second birthday and the association between the sum of Rutter’s indicators of adversity (RIA-score) in infancy and subsequent development of ADHD was estimated by means of Cox regression. Also, the number needed to screen (NNS) to detect one case of ADHD based on the RIA-scores in infancy was calculated. During follow-up (9.6 million person-years), 15,857 males and 5,663 females from the cohort developed ADHD. For both males and females, there was a marked dose-response relationship between RIA-scores assessed in infancy and the risk for developing ADHD. The hazard ratios for ADHD were 11.0 (95%CI: 8.2–14.7) and 11.4 (95%CI: 7.1–18.3) respectively, for males and females with RIA-scores of 5–6, compared to males and

  16. Senescence marker protein 30 (SMP30) serves as a potential prognostic indicator in hepatocellular carcinoma

    PubMed Central

    Mo, Zhijing; Zheng, Shunxin; Lv, Zhilue; Zhuang, Yuan; Lan, Xiuwan; Wang, Feng; Lu, Xiaoling; Zhao, Yongxiang; Zhou, Sufang

    2016-01-01

    Senescence marker protein 30 (SMP30) has been identified as a tumor-related molecule of hepatocellular carcinoma (HCC). Its clinical significance and underlying mechanisms in HCC tissues, however, remain largely unexplored. We have demonstrated a preferentially expressed SMP30 in normal liver using a tissue microarray. By employing real-time quantitative PCR, two tissue microarrays and Oncomine database analysis, we have also shown that the SMP30 in HCC tissues has significantly reduced when compared with that in paired adjacent non-tumor tissues (P = 0.0037). The reduced expression of SMP30 is very noticeably related to larger tumor size (P = 0.012), enhanced TNM (P = 0.009) and worse survival (P < 0.0001) in HCC patients. The analyses using Cox regression have indicated that the decreased SMP30 expression is an independent risk to the reduced overall survival rate of HCC patients (P = 0.001), and the down-regulation of SMP30 in HCC might be mediated by DNA methylation. Moreover, genes co-expressed with SMP30 may affect the prognosis through apoptotic process, biological adhesion and blood coagulation by PANTHER analyses. Our studies have indicated that the SMP30 may serve as a candidate of HCC clinical prognostic marker and a potential therapeutic target. PMID:27991558

  17. Imaging After GliaSite Brachytherapy: Prognostic MRI Indicators of Disease Control and Recurrence

    SciTech Connect

    Kleinberg, Lawrence; Yoon, Geoffrey; Weingart, John D.; Parisi, Michele; Olivi, Alessandro; Detorie, Nicholas A.; Chan, Timothy A.

    2009-12-01

    Purpose: In this study, we analyzed the magnetic resonance imaging (MRI) changes in patients after GliaSite treatment and characterized the prognostic MRI indicators in these patients. Methods and Materials: A total of 25 patients with recurrent glioblastoma multiforme were treated with the GliaSite Radiation Therapy System. Patients at the Johns Hopkins Hospital with recurrent glioblastoma multiforme underwent surgical resection followed by GliaSite balloon implantation. Available MRI scans for 20 patients were obtained throughout the post-GliaSite treatment course. These were reviewed and analyzed for prognostic significance. Results: After GliaSite treatment, all patients developed some degree of T{sub 1}-weighted contrast and T{sub 2}-weighted hyperintensity around the resection cavity. The development of enhancement on T{sub 1}-weighted contrast-enhanced imaging and the size of these lesions, in the absence of increasing T{sub 2}-weighted hyperintensity, before clinical progression was not associated with decreased survival. Patients with T{sub 1}-weighted enhancement >1 cm had a median survival of 13.6 months and those with T{sub 1}-weighted lesions <=1 cm had a median survival of 8.5 months (p = .014). In contrast, the development of larger areas of T{sub 2}-weighted hyperintensity surrounding the resection cavity was significantly associated with poorer survival (p = .027). Conclusion: After GliaSite treatment, characteristic T{sub 1}- and T{sub 2}-weighted changes are seen on MRI. Greater T{sub 1}-weighted changes in the absence of increasing edema appears not to indicate disease progression; however, greater T{sub 2}-weighted changes were associated with decreased survival. These findings suggest that T{sub 1}-weighted enhancement in the absence of concomitant edema after GliaSite treatment might represent pseudoprogression. Conversely, increasing T{sub 2}-weighted hyperintensity might reflect infiltrative disease progression. These results provide a

  18. Economic Adversity and Children’s Sleep Problems: Multiple Indicators and Moderation of Effects

    PubMed Central

    El-Sheikh, Mona; Bagley, Erika J.; Keiley, Margaret; Elmore-Staton, Lori; Chen, Edith; Buckhalt, Joseph A.

    2014-01-01

    Objective Toward explicating relations between economic adversity and children’s sleep, we examined associations between multiple indicators of socioeconomic status (SES)/adversity and children’s objectively and subjectively derived sleep parameters; ethnicity was examined as potential moderator. Methods Participants were 276 third- and fourth-grade children and their families (133 girls; M age = 9.44 years; SD = .71): 66% European American (EA) and 34% African American (AA). Four SES indicators were used: income-to-needs ratio, perceived economic well-being, maternal education, and community poverty. Children wore actigraphs for 7 nights and completed a self-report measure to assess sleep problems. Results Objectively and subjectively assessed sleep parameters were related to different SES indicators, and overall worse sleep was evident for children from lower SES homes. Specifically, children from homes with lower income-to-needs ratios had higher levels of reported sleep/wake problems. Parental perceived economic well-being was associated with shorter sleep minutes and greater variability in sleep onset for children. Lower mother’s education was associated with lower sleep efficiency. Children who attended Title 1 schools had shorter sleep minutes. Ethnicity was a significant moderator of effects in the link between some SES indicators and children’s sleep. AA children’s sleep was more negatively affected by income-to-needs ratio and mother’s education than was the sleep of EA children. Conclusions The results advocate for the importance of specifying particular SES and sleep variables used because they may affect the ability to detect associations between sleep and economic adversity. PMID:23148451

  19. Using Temporal Patterns in Medical Records to Discern Adverse Drug Events from Indications

    PubMed Central

    Liu, Yi; LePendu, Paea; Iyer, Srinivasan; Shah, Nigam H.

    2012-01-01

    Researchers estimate that electronic health record systems record roughly 2-million ambulatory adverse drug events and that patients suffer from adverse drug events in roughly 30% of hospital stays. Some have used structured databases of patient medical records and health insurance claims recently—going beyond the current paradigm of using spontaneous reporting systems like AERS—to detect drug-safety signals. However, most efforts do not use the free-text from clinical notes in monitoring for drug-safety signals. We hypothesize that drug–disease co-occurrences, extracted from ontology-based annotations of the clinical notes, can be examined for statistical enrichment and used for drug safety surveillance. When analyzing such co-occurrences of drugs and diseases, one major challenge is to differentiate whether the disease in a drug–disease pair represents an indication or an adverse event. We demonstrate that it is possible to make this distinction by combining the frequency distribution of the drug, the disease, and the drug-disease pair as well as the temporal ordering of the drugs and diseases in each pair across more than one million patients. PMID:22779050

  20. CHKA mediates the poor prognosis of lung adenocarcinoma and acts as a prognostic indicator

    PubMed Central

    Zhang, Li; Chen, Ping; Yang, Shen; Li, Guodong; Bao, Wentao; Wu, Peng; Jiang, Shujuan

    2016-01-01

    Choline kinase α (CHKA), the enzyme that converts choline to phosphocholine, has been studied in human carcinogenesis widely. However, the expression and underlying clinicopathological characteristics of CHKA in lung adenocarcinoma remains elusive. In the present study, a tissue microarray of 119 pairs of lung adenocarcinoma samples and corresponding adjacent normal mucosae was used to analysis CHKA expression by immunohistochemistry, and CHKA was observed to exhibit enhanced expression in lung adenocarcinoma tissues. Elevated CHKA expression in lung adenocarcinoma tissues at the gene and protein level was observed. The levels of CHKA expression were closely associated with the poor prognosis status of lung adenocarcinoma patients. Furthermore, certain clinicopathological characteristics such as tumor diameter and differentiation were observed to be significant in those lung adenocarcinoma patients who displayed enhanced CHKA expression. The analysis of CHKA expression could provide a more precise way to predict the prognosis of lung adenocarcinoma patients. Collectively, the present study revealed a novel biomarker in lung adenocarcinoma, and indicated that CHKA may be a promising prognostic marker and therapeutic target for lung adenocarcinoma. PMID:27588131

  1. [Diagnostic and prognostic value of humoral immune status indices for alimentary system diseases].

    PubMed

    Tsaregorodtseva, T M; Serova, T I

    2007-01-01

    The paper describes the results of studying the immune status of 1,960 patients with stomach, pancreas, liver, gall bladder, small and large intestine disorders, who were treated in the Central Research Institute of Gastroenterology. The results of the study demonstrate that alimentary system diseases are concomitant with changes in the functional activity of the immune system and development of the systemic immune response aimed at the neutralization and elimination of pathogenic agents. Impaired regulatory and efferent lymphocyte capacities, increased synthesis of cytokines, immunoglobulins, heterologous (anti-viral, anti-bacterial or antigliadin), autologous (to parietal cells, microsome mitochondria, tissue transglutaminase) antibodies, formation of immune complexes, autoimmune reactions and secondary immunodeficiency are specific immune mechanisms of the pathological process development, its synchronization and progression in patients with alimentary system diseases. Changes in the immunological status indices are expressed in varying degree depending on the organ involved, etiological factor, clinical course and stage of the disease, as well as treatment used. The immunological status indices have maximal values in cases of chronic hepatitis, hepatic cirrhosis, peptic or duodenal ulcer, cholelithiasis, chronic pancreatitis, gluten-sensitive enteropathy and minimal values in cases of chronic gastritis, gastroesophageal disease, steatohepatitis and irritable bowel syndrome. These data are sufficient for developing an algorithm of immune diagnostics for a number of alimentary system diseases. The study of immune status indices is of great diagnostic and prognostic value as it defines the etiological factor, intensity of inflammatory, infectious and autoimmune processes as well as disease stage and activity, its forecast and the efficacy of treatment of alimentary system diseases.

  2. C-reactive protein is a prognostic indicator in patients with perihilar cholangiocarcinoma

    PubMed Central

    Gerhardt, Thomas; Milz, Sabine; Schepke, Michael; Feldmann, Georg; Wolff, Martin; Sauerbruch, Tilman; Dumoulin, Franz Ludwig

    2006-01-01

    AIM: To evaluate prognostic indicators for the outcome of patients with perihilar extrahepatic cholangiocarcinoma in an unselected cohort. METHODS: We retrospectively analyzed 98 patients with perihilar cholangiocarcinoma. Twenty-three patients (23.5%) underwent tumor resection. Patients with non-resectable tumors underwent either transpapillary or percutaneous transhepatic biliary drainage. Additionally, 32 patients (32.7%) received photodynamic therapy (PDT) and 18 patients (18.4%) systemic chemotherapy. Predefined variables at the time of diagnosis and characteristics considering the mode of treatment were entered into a Cox’s proportional hazards model. Included in the analysis were age, tumor stage following the modified Bismuth-Corlette classification, bilirubin, prothrombin time (PT), C-reactive protein (CRP), carbohydrate antigen 19-9 (CA19-9), history of weight loss, surgical resection, chemotherapy and PDT. RESULTS: The Kaplan-Meier estimate of overall median survival was 10.5 (95%CI: 8.4-12.6) mo. In the univariate analysis, low Bismuth stage, low CRP and surgical resection correlated significantly with better survival. In the multivariate analysis, only CRP (P = 0.005) and surgical resection (P = 0.029) were found to be independently predictive of survival in the cohort. Receiver operating characteristic (ROC) analysis identified a CRP level of 11.75 mg/L as the value associated with the highest sensitivity and specificity predicting a survival > 5 mo. Applying Kaplan-Meier analysis, patients with a CRP < 12 mg/L at the time of diagnosis had a significantly longer median survival than patients with higher values (16.2 vs 7.6 mo; P = 0.009). CONCLUSION: This retrospective analysis identified CRP level at the time of diagnosis as a novel indicator for the prognosis of patients with perihilar cholangiocarcinoma. It should be evaluated in future prospective trials on this entity. PMID:17006987

  3. Adverse prognostic impact of TGFB1 T869C polymorphism in non-small-cell lung cancer

    PubMed Central

    Sang, Yulan; Bi, Xin; Liu, Yan; Zhang, Wei; Wang, Dongjie

    2017-01-01

    Previously, several polymorphisms in TGFB1 have been identified in non-small-cell lung cancer (NSCLC), and the variants, C-509T, T869C, and G915C, have been demonstrated to associate with higher circulating levels of TGF-β1. However, little is known about the prognostic value of TGF-β1 polymorphisms in cancers. In this study, by genotyping the TGF-β1 T869C polymorphism in a total of 261 patients with NSCLC using DNA from blood lymphocytes, we first found that NSCLC patients, especially those with allele C carriers, had significantly higher serum TGF-β1 levels than healthy individuals. By using chi-square (χ2) test and Fisher’s exact test, we noticed that TC/CC genotypes were positively correlated with smoking, clinical TNM stage, lymph node, and distant metastasis in NSCLC patients. Kaplan–Meier analysis showed that patients with TT genotype had a better overall survival than the allele C carriers (TC + CC). Finally, multivariate analysis confirmed histology, lymph node, and distant metastasis but not T869C polymorphism as independent prognostic factors for NSCLC. Taken together, our data, as a proof of principle, suggest that T869C polymorphism in TGFB1 may act as a genetic modifier in NSCLC progression and a promising prognostic marker of survival in NSCLC patients. PMID:28331344

  4. Validation of prognostic indices in Egyptian Budd-Chiari syndrome patients: A single-center study

    PubMed Central

    Sakr, Mohammad; Abdelhakam, Sara M; Elsayed, Soheir A; Allam, Enas H; Farid, Amir M; Abdelmoaty, Waleed; Hassan, Azza M; Shaker, Mohamed; El-Gharib, Mohamed; Eldorry, Ahmed

    2017-01-01

    AIM To compare predictive ability of Budd-Chiari syndrome (BCS) prognostic indices (PIs) for one-year survival and Transjugular intrahepatic portosystemic shunt (TIPS) patency. METHODS This retrospective study enrolled 194 Egyptian patients with primary BCS who presented to the Budd-Chiari Study Group of Ain Shams University Hospital. Calculation of the available PIs was performed using Child-Pugh and model for end-stage liver disease scores, BCS-specific PIs (Clichy, New Clichy and Rotterdam) for all patients, and BCS-TIPS PI only for patients who underwent TIPS. The overall one-year survival rate and the one-year shunt patency rate for TIPS were reported. RESULTS The overall one-year survival rate was 69.6%, and the New Clichy PI revealed the best validity for its prediction at a cut-off value of 3.75, with sensitivity and specificity of 78% and 73.3%, respectively [area under receiver operating characteristic curve (AUC) = 0.806]. The one-year survival rate post-TIPS was 89.7%, and the BCS-TIPS score demonstrated validity for its prediction at a cut-off value of 3.92 (sensitivity and specificity were 71.4% and 64.5%, respectively) (AUC = 0.715). Logistic regression analysis revealed that the New Clichy PI (P = 0.030), high serum total bilirubin (P = 0.047) and low albumin (P < 0.001) were independent factors for predicting mortality within one year. The one-year shunt patency rate in TIPS was 80.2%, and none of the PIs exhibited significant validity for its prediction. CONCLUSION The New Clichy score could independently predict the one-year survival in Egyptian BCS patients. PMID:28216969

  5. Are salivary amylase and pH – Prognostic indicators of cancers?

    PubMed Central

    Ramya, Atmakuri Shanmukha; Uppala, Divya; Majumdar, Sumit; Surekha, Ch.; Deepak, K.G.K.

    2015-01-01

    Background Saliva, “Mirror of body's health” has long been of particular interest as a substitute for blood for disease diagnosis and monitoring. The radiation effects on salivary glands are of particular interest in which salivary amylase is a good indicator of salivary glands function. Thus, estimation of these parameters represents a reasonable approach in evaluation of patient's risk for disease occurrence, intensity and prognosis. Aim of study To evaluate and compare the pH and amylase levels in saliva of cancer patients prior to treatment, patients during treatment. Materials and methods Saliva samples of 90 individuals were taken which were divided into 3 groups - 30 individuals without cancer, 30 cancer patients prior treatment and 30 cancer patients during treatment. Materials used were pH strips and pH meter, Salivary Amylase assay. Results Statistical analysis – ANOVA with post-hoc Tukey's test. 1) Significant decrease in salivary amylase levels – in cancer patients, during treatment when compared to others. 2) Significant decrease in salivary pH levels in newly diagnosed cancer patients prior to treatment. Conclusion To conclude, pH strips and pH meter showed to be a useful tool in the measurement of pH of saliva in individuals with and without cancer. This study showed that cancer patients without treatment have a lower pH of saliva. Treatment increased the pH of the saliva to a more alkaline level whereas amylase levels decreased in those subjects. Therefore those parameters can be an area of further research with an increased sample size, which in-turn may help in opening the doors for new dimension in non invasive prognostic markers. PMID:26258019

  6. Prognostic Indicators of Surgery for Esophageal Cancer: A 5 Year Experience

    PubMed Central

    Khan, Nadim; Bangash, Adil; Sadiq, Muzaffaruddin

    2010-01-01

    Background/Aim: To assess the prognostic indicators preoperatively presenting and influencing the mortality rate following esophagectomy for esophageal cancer. Materials and Methods: This study was a retrospective cohort study, conducted at the Department of Surgery, Lady Reading Hospital, Peshawar, from 1 January 2003 till 31 December 2008. Group 1 included patients who had undergone sub-total esophagectomy and were alive at completion of 12 months; whereas Group 2 included those patients who died by the completion of 12 months. Data were recollected from the Data Bank. A list of variables common to all patients from both groups was categorized and subsequently all data related to each individual patient were placed and analyzed on the version 13.0 of SPSSR for Windows. Results: Significant findings of a lower mean level of serum albumin from Group 2 were observed, whereas serum transferrin levels, also found lower in Group 2, were not statistically significant. Findings of serum pre-albumin, with a mean value of 16.12 mg/dl (P<0.05) and Geansler’s index for the evaluation of the presence of obstructive pulmonary disease prior to surgery showed a lower reading of mean ratio in Group 2. Anastamotic leak was not a common finding in the entire study. In most cases, the choice of conduit was the remodeled stomach. Nine patients from Group 2 were observed with evident leak on the fifth to seventh post-operative day following contrast swallow studies. This was statistically insignificant (P = 0.051) on multivariate analysis. Conclusion: Pre-operative variables including weight loss, low serum albumin and pre-albumin, Geansler’s index, postoperative chylothorax, pleural effusion, and hospital stay, are predictive of mortality in patients who undergo esophagectomy for esophageal cancer. PMID:20871187

  7. Family Type as a Prognostic Indicator of Rehabilitation Outcome with Post-Hospitalized Male Schizophrenics

    ERIC Educational Resources Information Center

    Beres, Barbara Oliver; Frumkin, Robert M.

    1973-01-01

    A study of 65 male schizophrenic patients at the Bureau of Vocational Rehabilitation Unit, Cleveland Psychiatric Institute, Cleveland, Ohio revealed that family type (conjugal settings, parental settings, living alone) is found to to be a valuable prognosticator of rehabilitation outcome among post-hospitalized schizophrenics. (EA)

  8. 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

  9. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas

    PubMed Central

    Hatanpaa, Kimmo J.; Foong, Chan; Raisanen, Jack M.; Oliver, Dwight; Hiemenz, Matthew C.; Burns, Dennis K.; White, Charles L.; Whitworth, L. Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A.; Fink, Karen; Maher, Elizabeth A.; Bachoo, Robert M.

    2015-01-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n=50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p=0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III). PMID:24519516

  10. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas.

    PubMed

    Hatanpaa, Kimmo J; Hu, Tianshen; Vemireddy, Vamsidhara; Foong, Chan; Raisanen, Jack M; Oliver, Dwight; Hiemenz, Matthew C; Burns, Dennis K; White, Charles L; Whitworth, L Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A; Fink, Karen; Maher, Elizabeth A; Bachoo, Robert M

    2014-03-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n = 50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p = 0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III).

  11. CD38+ CD58- is an independent adverse prognostic factor in paediatric Philadelphia chromosome negative B cell acute lymphoblastic leukaemia patients.

    PubMed

    Li, Xu-Mian; Zhang, Le-Ping; Wang, Ya-Zhe; Lu, Ai-Dong; Chang, Yan; Zhu, Hong-Hu; Qin, Ya-Zhen; Lai, Yue-Yun; Kong, Yuan; Huang, Xiao-Jun; Liu, Yan-Rong

    2016-04-01

    To explore new risk predictors for a high risk of relapse in Philadelphia chromosome negative (Ph-) B cell acute lymphoblastic leukaemia (B-ALL) patients, 196 paediatric Ph- B-ALL patients (≤ 18 years) were retrospectively analysed. We mainly focus on investigating the prognostic value of CD38 and CD58 expression in leukemic blasts in these patients by four colour flow cytometry. The CD38+ CD58- group (n=16) had a higher relapse rate, a shorter 3-year event-free survival (EFS) and overall survival (OS) than the CD38+ CD58+ group (n=157; 31.3% vs 10.2%, P=0.04; 52.4% vs 92.3%, P<0.01; 32.5% vs 91.0%, P=0.01); CD38+ CD58- was an independent adverse prognostic predictor for relapse (hazard ratio [HR], 0.203; 95%CI, 0.063-0.656; P=0.01), 3-year EFS (HR, 0.091; 95%CI, 0.023-0.355; P<0.01) and OS (HR, 0.102; 95%CI, 0.026-0.3971; P<0.01) in this cohort, as determined by Cox multivariate analysis. We identified, for the first time, a higher risk population of paediatric Ph- B-ALL patients with CD38+ CD58- who had a higher relapse risk and a shorter survival. Our results may allow better risk stratification and individualized treatment.

  12. Biochemical prognostic indicators for pancreatic neuroendocrine tumors and small bowel neuroendocrine tumors

    PubMed Central

    Cavaness, Keith; Celinski, Scott; Preskitt, John

    2014-01-01

    Pancreatic neuroendocrine tumors (PNETs) and small bowel neuroendocrine tumors (SBNETs) are rare tumors that are frequently diagnosed late in the course of the disease. Several biomarkers have been proposed in the literature as prognostic factors for patients with these tumors. This article discusses a recent publication in Annals of Surgical Oncology from the University of Iowa analyzing the effect of different biomarkers on survival in patients with PNETs and SBNETs. PMID:25493250

  13. Alpha-SM actin expression as prognostic indicator in IgA nephropathy (Berger's disease).

    PubMed

    Pastorello, M T; Costa, R S; Ravinal, R C; Coimbra, M; dos Reis, M A; Dantas, M

    2005-01-01

    Recent studies have demonstrated that alpha-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of alpha-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger's disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, Brazil, was studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to alpha-SM actin. Our data showed that alpha-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy.

  14. Capacitance of Membrane As a Prognostic Indicator of Survival in Head and Neck Cancer

    PubMed Central

    Małecka-Massalska, Teresa; Mlak, Radosław; Smoleń, Agata; Brzozowska, Anna; Surtel, Wojciech; Morshed, Kamal

    2016-01-01

    Background Evaluation of prognostic value of capacitance of membrane (Cm), parameter measured by bioelectrical impedance (BIA) as an alternative to known clinical factors in patients with Head and Neck Cancer (HNC). Methods A cohort of 75 stage IIIB and IV HNC patients treated in Department of Otolaryngology, Head and Neck Surgery, Medical University of Lublin, Poland were prospectively evaluated. Cm measurements were performed in all patients using a bioelectrical impedance analyzer that was set on a frequency of 50 kHz. Results of Cm measurements were presented in nF. Survival differences were estimated using Kaplan–Meier method. Results Significantly higher Cm median was noted in well-nourished(n = 45) compared to malnourished (n = 30) patients (1.41 vs 1.01 respectively; p = 0.0009). Established in ROC curves analysis cut-off value (0.743) was characterized by 98% specificity and 37% sensitivity in the detection of malnutrition. Median overall survival (mOS) in the cohort was 32months. At the time of analysis deaths were recorded in 47 cases (62.7%). In patients who had Cm below the level of 0.743 risk of OS shortening was significantly higher than in other patients (12.1 and 43.4 months respectively; HR = 8.47, 95%CI: 2.91–24.66; χ2 = 15.38, p = 0.0001). Conclusion Cm is a strong, independent prognostic factor in head and neck cancer. PMID:27802349

  15. 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.

  16. PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters.

    PubMed

    Catasus, Lluis; Gallardo, Alberto; Cuatrecasas, Miriam; Prat, Jaime

    2008-02-01

    Mutations of the oncogene PIK3CA occur frequently in endometrial carcinomas, but their prognostic significance is unclear. To determine the clinicopathological and molecular implications of these mutations, PIK3CA status was investigated in 109 endometrial (102 endometrioid and 7 mixed) carcinomas and the results were compared with clinicopathological parameters associated with prognosis. Tumors were also investigated for microsatellite instability and PTEN, beta-catenin gene (CTNNB1), K-RAS, and B-RAF mutations. We found 35 PIK3CA somatic missense mutations in 32 (29%) endometrial carcinomas. Eighteen mutations occurred in exon 20 (kinase domain), and 17 in exon 9 (helical domain). Almost all mutated tumors were pure endometrioid adenocarcinomas. All tumors with PIK3CA mutations exhibited myometrial invasion (P=0.032). Lymphovascular invasion was found more frequently in mutated (28%) than nonmutated carcinomas (18%). Histological grade varied significantly according to the location of the PIK3CA mutations whether in exon 9 or exon 20 (P=0.033). The frequency of exon 9 mutations was higher in grade 1 carcinomas (57%) than in grade 2 (29%) or grade 3 (14%) tumors. Conversely, mutations in exon 20 were more common in grade 3 (60%) than in grade 2 (20%) or grade 1 (20%) carcinomas. None of the tumors confined to the endometrium (stage IA) had PIK3CA mutations. Furthermore, whereas 64% of adenocarcinomas with exon 9 mutations had invaded < or =(1/2) of the myometrial thickness (stage IB), 73% of tumors with exon 20 mutations had either deeper myometrial invasion (stage IC) or cervical involvement (stage II) (P=0.045). PIK3CA mutations coexisted with microsatellite instability and mutations in PTEN, CTNNB1, K-RAS, and B-RAF genes. These results favor that PIK3CA mutations are associated with myometrial invasion and, moreover, that tumors harboring PIK3CA mutations in exon 20 are frequently high-grade, deeply invasive endometrial carcinomas that tend to exhibit

  17. Prognostic value of depression, anxiety, and anger in hospitalized cardiovascular disease patients for predicting adverse cardiac outcomes.

    PubMed

    Nakamura, Shunichi; Kato, Koji; Yoshida, Asuka; Fukuma, Nagaharu; Okumura, Yasuyuki; Ito, Hiroto; Mizuno, Kyoichi

    2013-05-15

    Although attention has recently been focused on the role of psychosocial factors in patients with cardiovascular disease (CVD), the factors that have the greatest influence on prognosis have not yet been elucidated. The aim of this study was to evaluate the effects of depression, anxiety, and anger on the prognosis of patients with CVD. Four hundred fourteen consecutive patients hospitalized with CVD were prospectively enrolled. Depression was evaluated using the Patient Health Questionnaire, anxiety using the Generalized Anxiety Disorder Questionnaire, and anger using the Spielberger Trait Anger Scale. Cox proportional-hazards regression was used to examine the individual effects of depression, anxiety, and anger on a combined primary end point of cardiac death or cardiac hospitalization and on a combined secondary end point of all-cause death or hospitalization during follow-up (median 14.2 months). Multivariate analysis showed that depression was a significant risk factor for cardiovascular hospitalization or death after adjusting for cardiac risk factors and other psychosocial factors (hazard ratio 2.62, p = 0.02), whereas anxiety was not significantly associated with cardiovascular hospitalization or death after adjustment (hazard ratio 2.35, p = 0.10). Anger was associated with a low rate of cardiovascular hospitalization or death (hazard ratio 0.34, p <0.01). In conclusion, depression in hospitalized patients with CVD is a stronger independent risk factor for adverse cardiac events than either anxiety or anger. Anger may help prevent adverse outcomes. Routine screening for depression should therefore be performed in patients with CVD, and the potential effects of anger in clinical practice should be reconsidered.

  18. Preoperative computerized dynamic posturography as a prognostic indicator of balance function in patients with acoustic neuroma.

    PubMed

    Bergson, Eric; Sataloff, Robert T

    2005-03-01

    We conducted a study to determine the prognostic reliability of preoperative computerized dynamic posturography (CDP) in patients undergoing surgical excision of an acoustic neuroma. Our goal was to determine the correlation between objective preoperative assessments of balance function and subjective postoperative patient self-assessments. To that end, we retrospectively reviewed the records of 21 adults who had undergone preoperative CDP, and we subsequently obtained their subjective assessments of balance function by follow-up telephone surveys at least 1 year postoperatively. We conclude that although CDP has proven to be useful in many aspects of balance evaluation, it did not appear to be a valuable predictor of subjective postoperative balance function in these patients.

  19. Immunohistochemical expression of epithelial and stromal immunomodulatory signalling molecules is a prognostic indicator in breast cancer

    PubMed Central

    2012-01-01

    Background The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells. Methods On immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity. Results The expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both P < 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (P = 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both P < 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (P < 0.001), whereas in the metastases the expression was highest in tumor cell areas (P < 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (P < 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality. Conclusions Stromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer. PMID:22353218

  20. Phosphohistone-H3 (PHH3) is prognostic relevant in Merkel cell carcinomas but Merkel cell polyomavirus is a more powerful prognostic factor than AJCC clinical stage, PHH3, Ki-67 or mitotic indices.

    PubMed

    Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kato, Masako; Nagata, Keiko; Murakami, Ichiro; Hayashi, Kazuhiko

    2015-08-01

    Merkel cell carcinomas (MCCs) associated with Merkel cell polyomavirus (MCPyV) have better prognosis than those without MCPyV. The relationship between mitotic index (MI) and MCC outcome has remained elusive because of the difficulty in differentiating mitotic cells from apoptotic ones. We evaluated the role of phosphohistone-H3 (PHH3) (Ser10), a new mitotic count biomarker, in MCPyV-positive or -negative MCC patients, and assessed its prognostic value in comparison to Ki-67 labeling index or MI using hematoxylin and eosin (HE) staining. We compared the prognostic value of PHH3 mitotic index with that of MI by HE in 19 MCPyV-positive and 9 MCPyV-negative MCC patients. PHH3-positive immunoreactivity was mostly observed in mitotic figures. Multivariate analysis significantly showed that MCPyV status (HR, 0.004; 95% CI 0.0003-0.058) and the American Joint Committee of Cancer (AJCC) stage (HR, 5.02; 95% CI 1.23-20.51) were observed as significantly independent prognostic factors for OS. PHH3-positive cell counts/10 HPF was a slightly significant independent prognostic factor for OS (HR, 4.96; 95% CI 0.93-26.55). PHH3-positive MI and MCPyV status in MCC patients are useful in prognostication, although MCPyV-infection is a more powerful prognostic factor in MCCs than the AJCC scheme on proliferation or mitotic indices.

  1. Systemic immune-inflammation index (SII) is a useful prognostic indicator for patients with squamous cell carcinoma of the esophagus

    PubMed Central

    Feng, Ji-Feng; Chen, Sheng; Yang, Xun

    2017-01-01

    Abstract The aim of the study was to determine the prognostic role of systemic immune-inflammation index (SII) in patients with esophageal squamous cell carcinoma (ESCC). A total of 298 ESCC patients were enrolled in the current retrospective study. The SII was calculated by the formula: neutrophil × platelet/lymphocyte. The optimal cut-off value was calculated by the Cutoff Finder. Univariate and multivariate analyses were evaluated for cancer-specific survival (CSS). Additional, we also established a nomogram model to predict the prognosis for patients with ESCC. The optimal cut-off value was 410 × 109/L for SII. Patients with SII ≤ 410 (×109/L) had a significantly better 5-year CSS than patients with SII > 410 (×109/L) (51.9% vs 24.0%, P < 0.001). Multivariate analyses revealed that SII was a significant independent predictive indicator (P = 0.027). A nomogram could be more accuracy for CSS for patients with ESCC (c-index: 0.68). The SII is a useful independent prognostic indicator for patients with resectable ESCC. PMID:28121932

  2. 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.

  3. Bioelectrical impedance phase angle as a prognostic indicator of survival in head-and-neck cancer

    PubMed Central

    Władysiuk, M.S.; Mlak, R.; Morshed, K.; Surtel, W.; Brzozowska, A.; Małecka-Massalska, T.

    2016-01-01

    Background Phase angle could be an alternative to subjective global assessment for the assessment of nutrition status in patients with head-and-neck cancer. Methods We prospectively evaluated a cohort of 75 stage iiib and iv head-and-neck patients treated at the Otolaryngology Department, Head and Neck Surgery, Medical University of Lublin, Poland. Bioelectrical impedance analysis was performed in all patients using an analyzer that operated at 50 kHz. The phase angle was calculated as reactance divided by resistance (Xc/R) and expressed in degrees. The Kaplan–Meier method was used to calculate survival. Results Median overall survival in the cohort was 32.0 months. At the time of analysis, 47 deaths had been recorded in the cohort (62.7%). The risk of shortened overall survival was significantly higher in patients whose phase angle was less than 4.733 degrees than in the remaining patients (19.6 months vs. 45 months, p = 0.0489; chi-square: 3.88; hazard ratio: 1.8856; 95% confidence interval: 1.0031 to 3.5446). Conclusions Phase angle might be prognostic of survival in patients with advanced head-and-neck cancer. Further investigation in a larger population is required to confirm our results. PMID:27803609

  4. Dialysate bacterial endotoxin as a prognostic indicator of peritoneal dialysis related peritonitis.

    PubMed

    Szeto, Cheuk-Chun; Lai, Ka-Bik; Chow, Kai-Ming; Kwan, Bonnie Ching-Ha; Law, Man-Ching; Pang, Wing-Fai; Ma, Terry King-Wing; Leung, Chi-Bon; Li, Philip Kam-Tao

    2016-12-01

    Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our present study is to explore the prognostic value of endotoxin level in PD effluent for the prediction of treatment failure in PD-related peritonitis. We studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected every 5 days for endotoxin level and leukocyte count. Patients were followed for relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary treatment failure; 41 (12.6%) developed relapsing, 19 (5.8%) had recurrent, and 22 (6.8%) had repeat episodes. Endotoxin was detectable in the PDE of 19 episodes (24.4%) caused by Gram negative organisms, 4 episodes (6.8%) of mixed bacterial growth, and none of the culture negative episodes or those by Gram positive organisms. For episodes caused by Gram negative bacteria, a detectable endotoxin level in PDE on day 5 had a sensitivity and specificity of 66.7% and 83.3%, respectively, for predicting primary treatment failure. In contrast, PDE leukocyte count > 1000 per mm3 on day 5 had a sensitivity and specificity of 88.9% and 89.1%, respectively; the addition of PDE endotoxin assay did not improve the sensitivity or specificity. We conclude that detectable endotoxin in PDE 5 days after antibiotic therapy might predict primary treatment failure in peritonitis episodes caused by Gram negative organisms. However, the sensitivity and specificity of PDE endotoxin assay was inferior to PDE leukocyte count.

  5. Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

    PubMed Central

    Bovenzi, Cory D.; Hamilton, James; Tassone, Patrick; Johnson, Jennifer; Cognetti, David M.; Luginbuhl, Adam; Keane, William M.; Zhan, Tingting; Tuluc, Madalina; Bar-Ad, Voichita; Martinez-Outschoorn, Ubaldo; Curry, Joseph M.

    2015-01-01

    Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p < 0.001 for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p < 0.0001 for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations. PMID:26779534

  6. The expressions of MIF and CXCR4 protein in tumor microenvironment are adverse prognostic factors in patients with esophageal squamous cell carcinoma

    PubMed Central

    2013-01-01

    Background Tumor-derived cytokines and their receptors usually take important roles in the disease progression and prognosis of cancer patients. In this survey, we aimed to detect the expression levels of MIF and CXCR4 in different cell populations of tumor microenvironments and their association with survivals of patients with esophageal squamous cell carcinoma (ESCC). Methods MIF and CXCR4 levels were measured by immunochemistry in tumor specimens from 136 resected ESCC. Correlation analyses and independent prognostic outcomes were determined using Pearson’s chi-square test and Cox regression analysis. Results The expression of CXCR4 in tumor cells was positively associated with tumor status (P = 0.045) and clinical stage (P = 0.044); whereas the expression of CXCR4 in tumor-infiltrating lymphocytes (TILs) and the expression of MIF in tumor cells and in TILs were not associated with clinical parameters of ESCC patients. High MIF expression in tumor cells or in TILs or high CXCR4 expression in tumor cells was significantly related to poor survival of ESCC patients (P < 0.05). Multivariate analysis showed that the expression of MIF or CXCR4 in tumor cells and the expression of MIF in TILs were adverse independent factors for disease-free survival (DFS) and overall survival (OS) in the whole cohort of patients (P < 0.05). Furthermore, the expression of MIF and CXCR4 in tumor cells were independent factors for reduced DFS and OS in metastatic/recurrent ESCC patients (P < 0.05). Interestingly, the expressions of MIF and CXCR4 in tumor cells and in TILs were significantly positively correlated (P < 0.05), and the combined MIF and CXCR4 expression in tumor cells was an independent adverse predictive factor for DFS and OS (P < 0.05). Conclusion The expressions of MIF and CXCR4 proteins in tumor cells and TILs have different clinically predictive values in ESCC. PMID:23497377

  7. Prevalence and Predictors of Adverse Events in Older Surgical Patients: Impact of the Present on Admission Indicator

    ERIC Educational Resources Information Center

    Kim, Hongsoo; Capezuti, Elizabeth; Kovner, Christine; Zhao, Zhonglin; Boockvar, Kenneth

    2010-01-01

    Purpose of the Study: To examine the effects of the present on admission (POA) indicator on the prevalence of and factors associated with postsurgical adverse events in older patients. Design and Methods: This is a secondary data analysis of 82,898 surgical patients aged 65 years or older in 252 acute care hospitals in California in 2004. Four…

  8. Clinical characteristics and prognostic indicators for metastatic melanoma: data from 446 patients in north China.

    PubMed

    Hao, Mengze; Zhao, Gang; Du, Xiaoling; Yang, Yun; Yang, Jilong

    2016-08-01

    Melanoma is an extremely rare tumor in Asia. This retrospective study aimed to identify the clinical characteristics and prognostic factors of metastatic melanoma patients at Tianjin Medical University Cancer Hospital over the last 30 years. Survival analysis was performed with Kaplan-Meier, log-rank test, and multivariate Cox regression method using SPSS 19.0 software. The 1-, 2-, and 5-year survival rates of metastatic melanoma patients were 52, 32, and 16 %, respectively. Median overall survival (OS) was 13.5 months, median progression-free survival (PFS) 9.0 months, and median disease-free survival 20.3 months. Furthermore, patients with a single metastatic site achieved better OS and PFS than those with two or more metastatic lesions (OS 21.6 vs. 8.9 months, P < 0.001; PFS 11.3 vs. 7.1 months, P < 0.001). Survival times of patients with visceral metastases were the shortest (OS 8.5 months; PFS 7.5 months). Specifically, patients with primary mucosal lesions had a worse OS (9.7 months) and PFS (6.8 months) than those with acral (19.2 and 15.6 months, respectively) or non-acral primary lesions (11.8 and 11.1 months, respectively). The treatment of advanced melanoma was unitary, and prognoses of patients with metastatic melanoma in China were poor. Visceral metastasis, multiple metastatic sites, and primary mucosal lesions were significant predictors of survival of patients with metastatic melanoma. Those with primary mucosal lesions had significantly worse survivals than those with primary cutaneous lesions. More active involvement in clinical studies and more feedback on various treatment options are required.

  9. An evaluation of serial bone imaging in carcinoma of the breast: Prognostic indicators

    SciTech Connect

    Spencer, R.P.; Garg, A.; Pinch, P.; Mathur, B.; Karimeddini, M.

    1984-01-01

    Studies have appeared on the use of bone imaging for initial staging of patients with carcinoma of the breast (COB). Less well evaluated has been the role played by bone scans in serially following those with COB, and in determining which findings have prognostic significance. The authors have had the opportunity to follow a population of patients with COB, by means of Tc-99m-phosphate images. Of 134 patients who died of their disease, 105 (78.4%) had a positive bone scan just prior to the terminal event. A more detailed study was made of those who had been studied at intervals of about 6 months and met 3 criteria. 1) Histologically diagnosed carcinoma of the breast. 2) No unrelated malignancy (second primary) known. 3) Two or more bone scans at least one year apart. Of 102 women in this group and still living, 33 had an abnormal bone scan, while 69 presented with an initially normal study. Of these, 47 stayed normal, while 22 showed lesions at a later date. A Kaplan-Meier type plot was made, comparing the living group with those who died. The most noticeable difference was that many of those who died had the bone scan turn positive within 6 months, while none of the survivors had such a finding (follow-up for 5 years in some cases). A plot of percent positive versus time suggests that some patients bear a metastatic burden that is initially undetected, but shortly becomes positive. The analysis has been extended to which bones are involved (vertebrae most frequent) and the presence of ancillary findings such as lymphedema.

  10. Glasgow Prognostic Score (GPS) can be a useful indicator to determine prognosis of patients with colorectal carcinoma.

    PubMed

    Nozoe, Tadahiro; Matono, Rumi; Ijichi, Hideki; Ohga, Takefumi; Ezaki, Takahiro

    2014-01-01

    The Glasgow Prognostic Score (GPS), an inflammation-based score, has been used to predict the biologic behavior of malignant tumors. The aim of the current study was to elucidate a further significance of GPS in colorectal carcinoma. Correlation of GPS and modified GPS (mGPS), which are composed of combined score provided for serum elevation of C-reactive protein and hypoalbuminemia examined before surgical treatment, with clinicopathologic features was investigated in 272 patients with colorectal carcinoma. Survival of GPS 1 patients was significantly worse than that of GPS 0 patients (P= 0.009), and survival of GPS 2 patients was significantly worse than that of GPS 1 patients (P < 0.0001). Similarly, survival of mGPS 1 patients was significantly worse than that of mGPS 0 patients (P = 0.009), and survival of mGPS 2 patients was significantly worse than that of mGPS 1 patients (P = 0.0006). Multivariate analysis demonstrated that GPS (P < 0.0001) as well as tumor stage (P= 0.004) and venous invasion (P = 0.011) were factors independently associated with worse prognosis. Both GPS and mGPS could classify outcome of patients with a clear stratification, and could be applied as prognostic indicators in colorectal carcinoma.

  11. p53 exon 5 mutations as a prognostic indicator of shortened survival in non-small-cell lung cancer.

    PubMed Central

    Vega, F. J.; Iniesta, P.; Caldés, T.; Sanchez, A.; López, J. A.; de Juan, C.; Diaz-Rubio, E.; Torres, A.; Balibrea, J. L.; Benito, M.

    1997-01-01

    Inactivation of the tumour-suppressor gene p53 has been described as one of the most common molecular changes found in lung tumours. Our purpose was to study the prognostic value of p53 alterations and to determine whether some specific mutation type in the p53 gene could be associated with poor clinical evolution in non-small-cell lung cancer (NSCLC) patients. To this end, we studied 81 resected primary NSCLCs in order to detect p53 alterations. p53 protein accumulation was analysed using immunohistochemistry methods; p53 gene mutations in exons 5-9 were studied using polymerase chain reaction-single-strand conformation polymorphism and sequencing techniques. p53 protein was immunodetected in 46.9% of lung carcinomas and 44.7% of p53-immunopositive tumours showed p53 mutations. Survival analysis was performed on 62 patients. No survival differences were found for patients with or without p53 immunopositivity. A shorter survival was found in patients with underlying p53 gene mutations, mainly in patients with squamous cell lung tumours; the worst prognosis was found when mutations were located in exon 5 (P = 0.007). In conclusion, the location of p53 mutations might be considered as a prognostic indicator for the evaluation of poor clinical evolution in NSCLC patients. Images Figure 1 PMID:9218731

  12. p53 exon 5 mutations as a prognostic indicator of shortened survival in non-small-cell lung cancer.

    PubMed

    Vega, F J; Iniesta, P; Caldés, T; Sanchez, A; López, J A; de Juan, C; Diaz-Rubio, E; Torres, A; Balibrea, J L; Benito, M

    1997-01-01

    Inactivation of the tumour-suppressor gene p53 has been described as one of the most common molecular changes found in lung tumours. Our purpose was to study the prognostic value of p53 alterations and to determine whether some specific mutation type in the p53 gene could be associated with poor clinical evolution in non-small-cell lung cancer (NSCLC) patients. To this end, we studied 81 resected primary NSCLCs in order to detect p53 alterations. p53 protein accumulation was analysed using immunohistochemistry methods; p53 gene mutations in exons 5-9 were studied using polymerase chain reaction-single-strand conformation polymorphism and sequencing techniques. p53 protein was immunodetected in 46.9% of lung carcinomas and 44.7% of p53-immunopositive tumours showed p53 mutations. Survival analysis was performed on 62 patients. No survival differences were found for patients with or without p53 immunopositivity. A shorter survival was found in patients with underlying p53 gene mutations, mainly in patients with squamous cell lung tumours; the worst prognosis was found when mutations were located in exon 5 (P = 0.007). In conclusion, the location of p53 mutations might be considered as a prognostic indicator for the evaluation of poor clinical evolution in NSCLC patients.

  13. Downward percentile-crossing as an indicator of an adverse prenatal environment

    PubMed Central

    Lampl, Michelle; Gotsch, Francesca; Kusanovic, Juan Pedro; Espinoza, Jimmy; Goncalves, Luis; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A.; Romero, Roberto

    2011-01-01

    Background Postnatal health sequelae associated with low birth weight have been attributed to ‘poor fetal growth’ from inferred adverse prenatal environments; risks augmented by infant growth rates. Identifying prenatal growth-restricting events is essential to clarify pathways and mechanisms of fetal growth. Aim The specific aim of this investigation was to examine whether an episode of preterm labor may compromise fetal growth. Subjects and methods Fetal size at the end of the second trimester and birth were compared among a sample of women with uncomplicated pregnancies (n=3167) and those who experienced preterm labor (<37 weeks) and subsequently delivered at term (>=37 weeks, n=147). Fetal weight was estimated from ultrasound measures and changes in weight standard scores across the third trimester investigated significant centile-crossing (> 0.67 standard deviation score change). Results Fetuses delivered at term after an episode of preterm labor were smaller at birth relative to their peers than at the end of the second trimester, and were 47% more likely to experience clinically significant downward centile crossing (p<0.05) than their peers (OR 1.47, 95% CI 1.04-2.07) Conclusion An episode of preterm labor may signal an adverse prenatal environment for term-delivered neonates. Epidemiologically silent events in the natural history of pregnancy are an understudied source of fetal growth compromise as inferred by small birth size among peers. PMID:18821324

  14. A New Prognostic Index and Comparison to Three Other Indices for Patients With Brain Metastases: An Analysis of 1,960 Patients in the RTOG Database

    SciTech Connect

    Sperduto, Paul W. Berkey, Brian M.S.; Gaspar, Laurie E.; Mehta, Minesh; Curran, Walter

    2008-02-01

    Purpose: The purpose of this study is to introduce a new prognostic index for patients with brain metastases and compare it with three published indices. Treatment for brain metastases varies widely. A sound prognostic index is thus important to guide both clinical decision making and outcomes research. Methods and Materials: A new index was developed because of limitations in the three existing indices and new data (Radiation Therapy Oncology Group 9508) are available since the others were developed. All four indices were compared using the Radiation Therapy Oncology Group database of 1,960 patients with brain metastases from five randomized trials. The ability of the four indices to distinguish its separate classes was determined statistically. Advantages and disadvantages of each index are discussed. Results: Recursive partitioning analysis (RPA) and the new Graded Prognostic Assessment (GPA) had the most statistically significant differences between classes (p < 0.001 for all classes). Conclusions: The new index, the GPA, is as prognostic as the RPA and more prognostic than the other indices. The GPA is the least subjective, most quantitative and easiest to use of the four indices. Future clinical trials should compare the GPA with the RPA to prospectively validate these findings.

  15. Surgical Indications of Exploring Optic Canal and Visual Prognostic Factors in Neurosurgical Treatment of Tuberculum Sellae Meningiomas

    PubMed Central

    Liu, Hao-Cheng; Qiu, E; Zhang, Jia-Liang; Kang, Jun; Li, Yong; Li, Yong; Jiang, Li-Bin; Fu, Ji-Di

    2015-01-01

    Background: Tuberculum sellae meningiomas (TSMs) present a special symptom because of the adherence and compression to the optic nerve, optic artery, and the chiasm. A significant number of patients with TSMs appear visual deficits. This study aimed to investigate the surgical indications of exploring the optic canal and visual prognostic factors in the neurosurgical treatment of TSMs. Methods: Totally 21 patients with TSM, who were operated from September 2007 to August 2011 in the Department of Neurosurgery, Tongren Hospital were enrolled in this study. Results of orbital computed tomography (CT) and magnetic resonance imaging (MRI), visual acuity, Goldmann visual field test, orbital color Doppler flow imaging (CDI) test in these patients were retrospectively analyzed. Results: Visual deficit and optic canal involvement (OCI) were detected in all the 21 patients. Fourteen patients had bone proliferation within the area of the optic canal. After the operation, visual outcomes were improved in 13 patients, unchanged in 7 patients, and deteriorated in 1 patient. All the 21 patients performed orbital CDI test preoperatively, the results showed that if the peak systolic velocity (PSV) of central retinal artery (CRA) value was ≤8 cm/s, the visual outcome would be better. Conclusions: The surgical indications of exploring optic canal in TSM cases included: (1) The neuroimaging evidences of OCI (CT and/or MRI); (2) PSV of CRA in orbital CDI test was ≤8 cm/s; (3) visual acuity was below 0.1; (4) visual field deficit. The PSV of CRA in CDI test could be a prognostic factor for visual outcomes of TSMs. PMID:26315077

  16. Relation between tumor FDG uptake and hematologic prognostic indicators in stage I lung cancer patients following curative resection

    PubMed Central

    Jeong, Eugene; Hyun, Seung Hyup; Moon, Seung Hwan; Cho, Young Seok; Kim, Byung-Tae; Lee, Kyung-Han

    2017-01-01

    Abstract Hematologic parameters of systemic inflammation are receiving attention as promising prognostic indicators in cancer patients. Here, we investigated the relation and compared the prognostic values of circulating blood cell-based parameters and tumor 18F-fluoro-2-deoxyglucose (FDG) uptake in patients with stage I nonsmall cell lung cancers (NSCLC). Subjects were 1034 patients with newly diagnosed stage I NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) followed by curative resection. Total white blood cell (WBC) count, absolute neutrophil, lymphocyte and platelet counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were obtained. Tumor FDG uptake was measured as SUVmax. WBC, neutrophil and lymphocyte counts, and NLR demonstrated weak but significant correlation to tumor SUVmax. Using the upper quartile as cutoff, patients with high tumor SUVmax had significantly higher WBC, neutrophil and lymphocyte counts, and greater NLR. There were 144 recurrences (13.9%) over a median follow-up of 29.5 months. On Cox proportional hazards regression analysis, WBC count, tumor SUVmax, age, gender, smoking, cell type, and tumor stage were significant univariate prognostic factors. On multivariate analysis, high tumor SUVmax (HR = 2.22; 95% CI, 1.52–3.25; P < 0.001), tumor stage 1B (HR = 2.11; 95% CI, 1.47–3.01; P < 0.001), and old age (HR = 1.03; 95% CI, 1.01–1.05; P = 0.002) were significant independent predictors of poor survival. Finally, high tumor SUVmax remained a significant predictor of prognosis in both low and WBC count groups. Circulating blood counts showed significant correlation to tumor FDG uptake in early stage NSCLC. WBC count was a significant univariate variable, but tumor FDG uptake was a superior and independent predictor of outcome. Hence, tumor FDG uptake effectively stratified prognosis in patients with low as well as high WBC count. PMID:28151879

  17. In Vivo Assessment of Pulmonary Arterial Wall Fibrosis by Intravascular Optical Coherence Tomography in Pulmonary Arterial Hypertension: A New Prognostic Marker of Adverse Clinical Follow-Up§

    PubMed Central

    Domingo, Enric; Grignola, Juan C; Aguilar, Rio; Montero, María Angeles; Arredondo, Christian; Vázquez, Manuel; López-Messeguer, Manuel; Bravo, Carlos; Bouteldja, Nadia; Hidalgo, Cristina; Roman, Antonio

    2013-01-01

    Background: The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hypertension (PAH) with clinical follow-up. Histology of PA specimens is also performed. Methods: 19 patients, aged 54±16 (4 men), functional class II-III were studied with right heart catheterization, PA Intravascular Ultrasound and optical coherence tomography (OCT) in inferior lobe segment. PA wall fibrosis was obtained by OCT ( area of fibrosis/PA cross sectional area × 100). Patients follow-up was blind to OCT. Events were defined as mortality, lung transplantation, need of intravenous prostaglandins or onset of right ventricular failure. Results: OCT measurements showed high intra- and interobserver agreement. There was a good correlation between OCT and histology in PA fibrosis from explanted lungs. Area of fibrosis was 1.4±0.8 mm2, % fibrosis was 22.3±8. Follow-up was 3.5 years (2.5-4.5). OCT %Fib was significantly correlated with PA capacitance (r=-0.536) and with pulmonary vascular rsistance (r=0.55). Patients were divided according to the median value of PA fibrosis. There were 10 patients with a high (≥ 22%) and 9 with a low fibrosis (<22%). Events occurred in 6 (1 death, 1 lung transplantation, 2 intravenous prostaglandins, 2 right heart failure) out of 10 patients with high and in 0 out of 9 patients with low fibrosis (p<0.01). Conclusions: In PAH, the severity of PA remodeling assessed by OCT wall fibrosis was significantly predictive of severely unfavorable clinical outcome. In vivo assessment of pulmonary arterial wall fibrosis by intravascular OCT in PAH is a promising new prognostic marker of adverse clinical outcome. PMID:23730366

  18. Coagulation factor V and VIII/V ratio as predictors of outcome in paracetamol induced fulminant hepatic failure: relation to other prognostic indicators.

    PubMed Central

    Pereira, L M; Langley, P G; Hayllar, K M; Tredger, J M; Williams, R

    1992-01-01

    The value of coagulation factor V and VIII/V levels as prognostic indicators was assessed in 27 patients with fulminant hepatic failure and compared with other predictive indices. Admission factor V levels were significantly reduced in 22 patients with paracetamol induced hepatic failure compared with a healthy control group (median 9.5% v 103%, respectively; p less than 0.001) and with lower values in non-A non-B hepatitis (median 2.7%). Values in the seven patients who died after paracetamol overdose, considered together with the four who underwent liver transplantation (group median 5.1%), were significantly lower than in the 11 who survived (median 11.8%; p less than 0.01). Median admission factor VIII was higher in those who died or received a transplant than in those who survived (298% v 162%; p less than 0.05), with both results higher than in healthy volunteers (median 104%; p less than 0.01) but lower than in non-A non-B hepatitis (median 340%). The ratio of factor VIII/V on admission was less than 30 in all patients who survived paracetamol overdose (median 17) with corresponding values greater than 30 in 10 of 11 of those who died (median 39). A factor V result less than or equal to 10% on admission predicted an adverse outcome in 10 of 11 fatal cases, a 91% sensitivity which was greater than for the previously defined indicator of an arterial blood pH less than 7.30 on admission (sensitivity 82%). Prothrombin time at admission or on day 4 did not usefully predict outcome in our series. Predictive accuracy was 73% and 82% for factor V and admission acidosis respectively and 95% for factor V in conjunction with admission coma grade III or IV and factor VIII (ratio > 30). These criteria may be useful in selecting patients with paracetamol induced fulminant hepatic failure for transplantation. PMID:1740285

  19. Using patient safety indicators to estimate the impact of potential adverse events on outcomes.

    PubMed

    Rivard, Peter E; Luther, Stephen L; Christiansen, Cindy L; Shibei Zhao; Loveland, Susan; Elixhauser, Anne; Romano, Patrick S; Rosen, Amy K

    2008-02-01

    The authors estimated the impact of potentially preventable patient safety events, identified by Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSIs), on patient outcomes: mortality, length of stay (LOS), and cost. The PSIs were applied to all acute inpatient hospitalizations at Veterans Health Administration (VA) facilities in fiscal 2001. Two methods-regression analysis and multivariable case matching- were used independently to control for patient and facility characteristics while predicting the effect of the PSI on each outcome. The authors found statistically significant (p < .0001) excess mortality, LOS, and cost in all groups with PSIs. The magnitude of the excess varied considerably across the PSIs. These VA findings are similar to those from a previously published study of nonfederal hospitals, despite differences between VA and non-VA systems. This study contributes to the literature measuring outcomes of medical errors and provides evidence that AHRQ PSIs may be useful indicators for comparison across delivery systems.

  20. Is human saliva an indicator of the adverse health effects of using mobile phones?

    PubMed

    Hamzany, Yaniv; Feinmesser, Raphael; Shpitzer, Thomas; Mizrachi, Aviram; Hilly, Ohad; Hod, Roy; Bahar, Gideon; Otradnov, Irina; Gavish, Moshe; Nagler, Rafael M

    2013-02-20

    Increasing use of mobile phones creates growing concerns regarding harmful effects of radiofrequency nonionizing electromagnetic radiation on human tissues located close to the ear, where phones are commonly held for long periods of time. We studied 20 subjects in the mobile-phone group who had a mean duration of mobile phone use of 12.5 years (range 8-15) and a mean time use of 29.6 h per month (range 8-100). Deaf individuals served as controls. We compared salivary outcomes (secretion, oxidative damage indices, flow rate, and composition) between mobile phone users and nonusers. We report a significant increase in all salivary oxidative stress indices studied in mobile phone users. Salivary flow, total protein, albumin, and amylase activity were decreased in mobile phone users. These observations lead to the hypothesis that the use of mobile phones may cause oxidative stress and modify salivary function.

  1. Acute liver failure due to zinc phosphide containing rodenticide poisoning: Clinical features and prognostic indicators of need for liver transplantation.

    PubMed

    Saraf, Vivek; Pande, Supriya; Gopalakrishnan, Unnikrishnan; Balakrishnan, Dinesh; Menon, Ramachandran N; Sudheer, O V; Dhar, Puneet; Sudhindran, S

    2015-07-01

    Zinc phosphide (ZnP) containing rodenticide poisoning is a recognized cause of acute liver failure (ALF) in India. When standard conservative measures fail, the sole option is liver transplantation. Records of 41 patients admitted to a single centre with ZnP-induced ALF were reviewed to identify prognostic indicators for requirement of liver transplantation. Patients were analyzed in two groups: group I (n = 22) consisted of patients who either underwent a liver transplant (n = 14) or died without a transplant (n = 8); group II (n = 19) comprised those who survived without liver transplantation. International normalized ratio (INR) in group I was 9 compared to 3 in group II (p < 0.001). Encephalopathy occurred only in group I. Model for End-Stage Liver Disease (MELD) score in group I was 41 compared to 24 in group II (p < 0.001). MELD score of 36 (sensitivity of 86.7 %, specificity of 90 %) or a combination of INR of 6 and encephalopathy (sensitivity of 100 %, specificity of 83 %) were the best indicators of mortality. Such patients should undergo urgent liver transplantation.

  2. [Pulse pressure as a prognostic indicator of organ damage in patients with essential hypertension].

    PubMed

    Jołda-Mydłowska, Beata; Kobusiak-Prokopowicz, Małgorzata; Sławuta, Agnieszka; Witkowska, Maria

    2004-05-01

    Pulse pressure (PP), defined as systolic blood pressure minus diastolic blood pressure, plays an important role as a risk factor for cardiovascular events. Pulse pressure is pulsatile component of blood pressure. A widened pulse pressure reflects increased stiffness of the large arteries. The aim of the study was to evaluate the association between pulse pressure and organ damage in essential hypertension. We examined 60 subjects, 34 women aged 59 +/- 13 years and 26 men aged 48 +/- 17 years with primary hypertension. In every subject we performed 24-hour automatic blood pressure measurement and echocardiography, abdominal ultrasonography, funduscopy, chest x-ray. We measured sodium potassium, creatinine level in serum and in urine, creatinine clearance and microalbuminuria. Pulse pressure is proportional to the stage of hypertension. A dimension of the aorta parallels with measures of blood pressure. The strong correlation between pulse pressure and damage in funduscopy can indicate, that complication in fundus of the eye are dependent more than the level of a pressure. The significantly higher sodium level in serum and the positive correlation between natremia, natriuresis and pulse pressure proves the role of natrium in pathophysiology of hypertension.

  3. RNA sequencing reveals differentially expressed genes as potential diagnostic and prognostic indicators of gallbladder carcinoma

    PubMed Central

    Jiang, Mingming; Fang, Meng; Ji, Jun; Wang, Aihua; Wang, Mengmeng; Jiang, Xiaoqing; Gao, Chunfang

    2015-01-01

    Gallbladder carcinoma (GBC) is a rare tumor with a dismal survival rate overall. Hence, there is an urgent need for exploring more specific and sensitive biomarkers for the diagnosis and treatment of GBC. At first, amplified total RNAs from two paired GBC tumors and adjacent non-tumorous tissues (ANTTs) were subjected to RNA sequencing. 161 genes were identified differentially expressed between tumors and ANTTs. Functional enrichment analysis indicated that the up-regulated genes in tumor were primarily associated with signaling molecules and enzyme modulators, and mainly involved in cell cycles and pathways in cancer. Twelve differentially expressed genes (DEGs) were further confirmed in another independent cohort of 35 GBC patients. Expression levels of BIRC5, TK1, TNNT1 and MMP9 were found to be positively related to postoperative relapse. There was also a significant correlation between BIRC5 expression and tumor-node-metastasis (TNM) stage. Besides, we observed a positive correlation between serum CA19–9 concentration and the expression levels of TNNT1, MMP9 and CLIC3. Survival analysis revealed that GBC patients with high TK1 and MMP9 expression levels had worse prognosis. These identified DEGs might not only be promising biomarkers for GBC diagnosis and prognosis, but also expedite the discovery of novel therapeutic strategies. PMID:25970782

  4. Nutritional indicators of adverse pregnancy outcomes and mother-to-child transmission of HIV among HIV-infected women2

    PubMed Central

    Mehta, Saurabh; Manji, Karim P; Young, Alicia M; Brown, Elizabeth R; Chasela, Charles; Taha, Taha E; Read, Jennifer S; Goldenberg, Robert L; Fawzi, Wafaie W

    2008-01-01

    Background Poor nutrition may be associated with mother-to-child transmission (MTCT) of HIV and other adverse pregnancy outcomes. Objective The objective was to examine the relation of nutritional indicators with adverse pregnancy outcomes among HIV-infected women in Tanzania, Zambia, and Malawi. Design Body mass index (BMI; in kg/m2) and hemoglobin concentrations at enrollment and weight change during pregnancy were prospectively related to fetal loss, neonatal death, low birth weight, preterm birth, and MTCT of HIV. Results In a multivariate analysis, having a BMI < 21.8 was significantly associated with preterm birth [odds ratio (OR): 1.82; 95% CI: 1.34, 2.46] and low birth weight (OR: 2.09; 95% CI: 1.41, 3.08). A U-shaped relation between weight change during pregnancy and preterm birth was observed. Severe anemia was significantly associated with fetal loss or stillbirth (OR: 3.67; 95% CI: 1.16, 11.66), preterm birth (OR: 2.08; 95% CI: 1.39, 3.10), low birth weight (OR: 1.76; 95% CI: 1.07, 2.90), and MTCT of HIV by the time of birth (OR: 2.26; 95% CI: 1.18, 4.34) and by 4−6 wk among those negative at birth (OR: 2.33; 95% CI: 1.15, 4.73). Conclusions Anemia, poor weight gain during pregnancy, and low BMI in HIV-infected pregnant women are associated with increased risks of adverse infant outcomes and MTCT of HIV. Interventions that reduce the risk of wasting or anemia during pregnancy should be evaluated to determine their possible effect on the incidence of adverse pregnancy outcomes and MTCT of HIV. PMID:18541551

  5. Which Anthropometric Indicators Identify a Pregnant Woman as Acutely Malnourished and Predict Adverse Birth Outcomes in the Humanitarian Context?

    PubMed Central

    Ververs, Mija-tesse; Antierens, Annick; Sackl, Anita; Staderini, Nelly; Captier, Valerie

    2013-01-01

    Currently there is no consensus on how to identify pregnant women as acutely malnourished and when to enroll them in nutritional programmes. Médecins Sans Frontières Switzerland undertook a literature review with the purpose of determining values of anthropometric indicators for acute malnutrition that are associated with adverse birth outcomes (such as low birth weight (LBW)), pre-term birth and intra-uterine growth retardation (IUGR). A literature search in PUBMED was done covering 1 January 1995 to 12 September 2012 with the key terms maternal anthropometry and pregnancy. The review focused on the humanitarian context. Mid-upper-arm circumference (MUAC) was identified as the preferential indicator of choice because of its relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings) and it does not require prior knowledge of gestational age. The MUAC values below which most adverse effects were identified were <22 and <23 cm. A conservative cut-off of <23 cm is recommended to include most pregnant women at risk of LBW for their infants in the African and Asian contexts. PMID:23787989

  6. 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.

  7. A study of different indicators of Maillard reaction with whey proteins and different carbohydrates under adverse storage conditions.

    PubMed

    Leiva, Graciela E; Naranjo, Gabriela B; Malec, Laura S

    2017-01-15

    This study examined different indicators of each stage of Maillard reaction under adverse storage conditions in a system with whey proteins and lactose or glucose. The analysis of lysine loss by the o-phthaldialdehyde method can be considered a good indicator of the early stage, showing considerable differences in reactivity when systems with mono and disaccharides were analyzed. Capillary electrophoresis proved to be a sensitive method for evaluating the extent of glycosylation of the native proteins, providing valuable information when the loss of lysine was not significant. The estimation of the Amadori compound from the determination of total 5-hydroxymethyl-2-furfuraldehyde would have correlate well with reactive lysine content if the advanced stages of the reaction had not been reached. For assessing the occurrence of the intermediate and final stages, the measurement of free 5-hydroxymethyl-2-furfuraldehyde and color, proved not to be suitable for storage conditions.

  8. Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

    PubMed Central

    Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2010-01-01

    Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

  9. Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts

    PubMed Central

    Usha, Lydia; Tabesh, Bita; Morrison, Larry E; Rao, Ruta D; Jacobson, Kris; Zhu, April; Basu, Sanjib; Coon, John S

    2008-01-01

    Background Amplification of the ERBB2 (Her-2/neu) oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for topoisomerase II alpha (TOP2A), a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy. Methods and patients Archival tissue samples from 63 breast cancer patients with ERBB2 amplification, stages 0–IV, were previously analyzed with FISH probes for genes located near ERBB2. In the present study, the clinical outcome data were determined for all patients presenting at stages I–III for whom adequate clinical follow up was available. Results Four amplicon patterns (Classes) were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted TOP2A had 67% (6/9) cases with recurrence, whereas the other three classes combined had only 12% (3/25) cases (p-value = 0.004) at the time of last follow-up. TOP2A deletion was also significantly associated with time to recurrence (p-value = 0.0002). After adjusting for age in Cox regression analysis, the association between TOP2A deletion and time to recurrence remains strongly significant (p-value = 0.002) whereas the association with survival is marginally significant (p-value = 0.06). Conclusion TOP2A deletion is associated with poor prognosis in ERBB2-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study. PMID:18702822

  10. Expression of Interleukin-8, Interleukin-10 and Epstein-Barr Viral-Load as Prognostic Indicator in Nasopharyngeal Carcinoma

    PubMed Central

    Savitri, Eka; Haryana, Mubarika Sofia

    2015-01-01

    Interleukin-8 (IL-8) is angiogeneic chemokine that plays a potential role in both development and progression of many human malignancies including nasopharyngeal carcinoma (NPC). Epstein- Barr virus (EBV) is recognized to be an important etiologic agent of NPC as the viral gene products are frequently detected in NPC tissue along with the elevation of antibody titre to the viral protein (VCA-p18+ EBNA1) of IgA in the majority of patients. Elevated plasma of Viral Load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the level of certain interleukins (IL-8 and IL-10) has also been implicated in NPC progression. The study aimed to investigate the correlations between plasma Viral Load and the level of interleukin (IL-8) and Interleukin (IL-10) in relating these parameters to the stages of NPC. In addition of Viral Load (VCA-p18+EBNA1) IgA, Interleukin-8 and Interleukin-10 before and after therapy will be investigated to seek the possible marker for disease progression. A total of 39 NPC patients and 29 healthy control individuals enrolled in this study. Plasma Viral Load was quantified using real-time quantitative PCR. The Level of plasma interleukins both IL-8 and IL-10 were analyzed using ELISA methods. Results indicated there was a significant decrease in viral load was detected in plasma of NPC patients following therapy. Plasma of viral load was shown to be a good prognosticator for disease progression. There were positive correlation between plasma of viral load and IL-8. These non invasive parameters expressed in blood, could be substitutes of viral load using brushing method, which is invasive. In conclusion that: Viral Load, (VCA-p18+EBNA1) IgA and IL-8 levels are promising markers for the presence of NPC and progression of the disease. PMID:25948470

  11. Biopsychosocial studies on cutaneous malignant melanoma: psychosocial factors associated with prognostic indicators, progression, psychophysiology and tumor-host response.

    PubMed

    Temoshok, L

    1985-01-01

    A series of seven studies investigating biopsychosocial aspects of cutaneous malignant melanoma were conducted by a multidisciplinary group of researchers at the University of California, San Francisco. Two studies investigated the relationship of variables derived from a videotaped psychosocial interview and from self-report measures, and two histopathologic indicators: tumor thickness and level of invasion. Associations of psychosocial variables to prognostic indicators were stronger within the younger vs the older subject group. In a multiple regression analysis, patient delay in seeking medical attention emerged as the most significant variable predicting tumor thickness. A study of factors related to patient delay found longer delays in patients who had lesions on the back, less previous knowledge of melanoma, less understanding of its treatment and less minimization of its seriousness. Another study compared the repressive coping reactions--defined as the discrepancy between reported anxiety and that reflected in electrodermal activity--in melanoma patients, cardiovascular disease patients and disease-free controls. The melanoma group was significantly more 'repressed' on the combined self-report/physiological measure, as well as on other self-report measures of repressiveness. In order to investigate the relationship of psychosocial factors to more disease-relevant physiological variables, the next study focused on two clinical variables significantly predictive of disease outcome:mitotic rate of the tumor and lymphocytes at tumor site. Emotional expression of sadness and anger, rated from the videotaped interviews, was positively correlated with tumor-specific host-response factors and negatively correlated with mitotic rate. In another study, subjects who had died or had disease progression were matched on the basis of tumor and demographic characteristics with subjects who had no evidence of disease by follow-up. The unfavorable outcome group had higher

  12. An independent evaluation of the potential clinical usefulness of proposed CA-125 indices previously shown to be of prognostic significance in epithelial ovarian cancer.

    PubMed Central

    Cruickshank, D. J.; Paul, J.; Lewis, C. R.; McAllister, E. J.; Kaye, S. B.

    1992-01-01

    CA-125 levels were assessed prior to each of the first three cycles of chemotherapy, in 81 patients with epithelial ovarian cancer receiving first-line chemotherapy. All patients have at least 1 year's follow-up. Thirty-nine patients (48%) have progressed clinically or have died within 1 year of treatment (treatment 'failures'). Three CA-125 indices previously shown to be of prognostic value are assessed for their ability to pick-out these 'failures'. When the indices examined are modified to obtain a specificity for picking out failures just exceeding 90%, the maximum sensitivity obtained was 46%. The use of CA-125 for clinical decision making in ovarian cancer requires further investigation to determine and validate a prognostic index with acceptable sensitivity and specificity, and to determine the clinical impact of treatment decisions made using such an index. PMID:1562469

  13. Dysregulation of MALAT1 and miR-619-5p as a prognostic indicator in advanced colorectal carcinoma

    PubMed Central

    Qiu, Gu; Zhang, Xiu-Bing; Zhang, Shu-Qing; Liu, Pei-Long; Wu, Wei; Zhang, Jin-Ye; Dai, Shi-Rong

    2016-01-01

    R-619-5p have potential for the molecular diagnosis of CRC patients, and combined assaying of MALAT1 and miR-619-5p may improve the accuracy of the diagnosis of CRC and act as a good prognostic indicator in CRC patients. PMID:28101234

  14. The Checkpoint Immunotherapy Revolution: What Started as a Trickle Has Become a Flood, Despite Some Daunting Adverse Effects; New Drugs, Indications, and Combinations Continue to Emerge.

    PubMed

    Alexander, Walter

    2016-03-01

    What started as a trickle of new agents that help the body's immune system fight cancer has now become a flood, despite some daunting adverse effects. This report discusses the new drugs, indications, and combinations that continue to emerge.

  15. Histological vascular invasion is a novel prognostic indicator in extranodal natural killer/T-cell lymphoma, nasal type

    PubMed Central

    Wang, Hua; Li, Pengfei; Zhang, Xinke; Xia, Zhongjun; Lu, Yue; Huang, Huiqiang

    2016-01-01

    Extranodal natural killer (NK)/T-cell lymphoma, (ENKTL), nasal type, is an aggressive lymphoma with no validated prognostic parameters, to date. In the present study, vascular invasion by this tumor was retrospectively analyzed in 214 patients with untreated ENKTL to evaluate its association with clinical features, treatment response and prognosis. Histological vascular invasion by the tumor was confirmed in 32.7% of patients with ENKTL. The presence of vascular invasion significantly correlated with poor performance status, B symptoms, extranodal involved sites, advanced stage, elevated serum lactate dehydrogenase, D-dimer and cluster of differentiation 68+ tumor-associated macrophages. Upon treatment termination, the complete remission (CR) rate and overall response rate were significantly lower for the vascular invasion group compared with the non-vascular invasion group. Furthermore, vascular invasion resulted in significantly reduced 5-year progression-free survival (PFS; 21.8 vs. 60.1%) and overall survival (OS; 36.8 vs. 77.0%) rates. Using the multivariate Cox regression model, vascular invasion, stage III/IV and CR after chemotherapy were independent prognostic factors for OS and PFS. Thus, histological vascular invasion by the tumor affected the response to treatment, and was also an independent prognostic factor for OS and PFS in ENKTL, nasal type, suggesting a role for vascular invasion in disease progression. PMID:27446357

  16. Microvascular invasion as a prognostic indicator in renal cell carcinoma: a systematic review and meta-analysis

    PubMed Central

    Huang, Hai; Pan, Xiu-Wu; Huang, Yi; Xu, Dan-Feng; Cui, Xin-Gang; Li, Lin; Hong, Yi; Chen, Lu; Gao, Yi; Yin, Lei

    2015-01-01

    Microvascular invasion (MVI), an omen of potential hematogenous spread of tumor cells, has been identified as an accepted risk factor for poor prognosis in some solid tumors. But its prognostic value in renal cell carcinoma (RCC) remains disputable. In order to address this question rigorously, we performed a systematical review of the published literature on MVI and RCC prognosis. According to the PRISMA statement, we searched PubMed, Web of science, and Cochrane Library database and identified 33 cohort articles that met the eligibility criteria and involved 14,946 patients (48-2596 per study) in this meta-analysis. Using the random effects model, the association between MVI and four generally recognized end points were estimated, including cancer-specific survival (CSS), recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS). The presence of MVI was detected in 14.4% of the pathological specimens. A higher incidence of MVI was associated with some acknowledged prognostic risk factors such as higher pathological TNM stages and higher tumor grades. Statistical significance of the combined hazard ratio (HR) was detected for CSS (HR, 2.090; 95% CI, 1.530-2.857), RFS (HR = 2.749; 95% CI, 1.974-3.828), MFS (HR = 1.621; 95% CI, 1.095-2.400). However, the association between MVI and worse overall survival did not address statistical significance (HR = 1.371; 95% CI, 0.978-1.923). These findings suggest that the presence of MVI has a detrimental effect on clinicopathological features of RCC and could serve as a poor prognostic factor for patient with RCC. PMID:26379872

  17. Colon cancer and gene alterations: their immunological implications and suggestions for prognostic indices and improvements in biotherapy.

    PubMed

    Contasta, Ida; Pellegrini, Patrizia; Berghella, Anna Maria; Del Beato, Tiziana; Adorno, Domenico

    2006-10-01

    Studies have shown that changes occur in c-Ki-ras, p53, and Bcl2 gene structure and function during the various stages of human colon carcinogenesis. Alterations of these genes are responsible for the establishment of a state of continuous stimulus for cell division and apoptotic inhibition at physiological and pharmacological levels. This paper focuses on the results of our research aimed at investigating how these gene alterations influence tumoral mechanisms on an immunological level and how immunological parameters can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma. Overall, our data suggest that an alteration in the c-Ki-ras gene results in a switch to a suppressive type of immune response, determining an impairment of immune cell activation at both antigen- presenting-cell and T-cell levels. c-Ki-ras gene mutations, p53 deletions, and Bc12 expression, on the other hand, can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma. The p53 oncogene does not appear to impair patients' immunological response further. In conclusion, an evaluation of c-Ki-ras, rather than p53 gene alterations, would seem to be more relevant in colon cancer prevention programs and biotherapy improvement.

  18. Canine distemper virus antigen detection in external epithelia of recently vaccinated, sick dogs by fluorescence microscopy is a valuable prognostic indicator.

    PubMed

    Kapil, Sanjay; Neel, Tina

    2015-02-01

    Currently, there are no reliable predictors of the clinical outcomes of domesticated dogs that have been recently vaccinated against canine distemper virus (CDV) and develop respiratory disease. In this study, vaccinated dogs from Oklahoma City that were showing clinical signs of respiratory disease were evaluated for CDV antigen using a direct fluorescent antibody test (FAT). Clinical outcomes after standard symptomatic therapy for respiratory disease were recorded, and a statistical analysis of the results was performed. We present our study showing that CDV FAT results were predictive of clinical recovery (prognostic indicator, prospects of clinical recovery) among vaccinated dogs showing clinical signs of respiratory disease. Negative CDV FAT results equated to 80% chances of recovery after symptomatic therapy, compared to 55% chances of recovery when the CDV FAT results were positive. Based on the results of this study, we show that veterinarians can make better informed decisions about the clinical outcomes of suspected CDV cases, with 2-h turnaround times, by using the CDV FAT. Thus, antemortem examination with the CDV FAT on external epithelia of recently vaccinated, sick dogs is a clinically useful diagnostic test and valuable prognostic indicator for veterinarians. Application of the CDV FAT to these samples avoids unnecessary euthanasia of dogs with suspected CDV.

  19. Circulating Tumor Cells Detected by RT-PCR for CK-20 before Surgery Indicate Worse Prognostic Impact in Triple-Negative and HER2 Subtype Breast Cancer

    PubMed Central

    Hwang, Seong Bae; Lee, Hye Yoon; Kim, Hoon Yub

    2012-01-01

    Purpose Circulating tumor cells (CTC) clearly correlate with unfavorable outcomes for patients with metastatic breast cancer, but the long-term prognostic implications of CTC for molecular subtypes of operable breast cancer are not yet known. We explored the relationships between previously established prognostic factors and CTC in operable breast cancer, and the significance of CTC by breast cancer molecular subtype. Methods We retrospectively evaluated 166 patients with operable breast cancer (stage I-IIIA) diagnosed from April 1997 to May 2003. CTC were detected using cytokeratin-20 (CK-20) mRNA expression in peripheral blood samples that were collected just prior to surgery under general anesthesia. Clinicopathological characteristics of the cancer were analyzed according to CTC status. Metastasis-free survival (MFS) and overall survival (OS) were analyzed according to CTC status and breast cancer molecular subtype. Results CK-20 mRNA-positive CTC was detected in 37 of 166 patients (22.3%) and was not correlated with any previous clinical factors in univariate analysis (p>0.05). After a median follow-up of 100 months, the patients with CK-20 mRNA-positive CTC had less favorable outcomes in terms of MFS and OS than those without detectable CTC (log-rank p<0.05). Among molecular subtypes of operable breast cancer, the patients with CK-20 mRNA-positive CTC had shorter MFS and OS in triple negative and human epidermal growth factor 2 (HER2) breast cancer subtype (log-rank, p<0.05). Conclusion CK-20 mRNA-positive CTC may lend insight into tumor progression as a prognostic indicator especially in the triple negative and HER2 subtypes of operable breast cancer. PMID:22493626

  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 indices among hypertensive heart failure patients in Nigeria: the roles of 24-hour Holter electrocardiography and 6-minute walk test

    PubMed Central

    Mene-Afejuku, Tuoyo O; Balogun, Michael O; Akintomide, Anthony O; Adebayo, Rasaaq A

    2017-01-01

    Background Hypertensive heart failure (HHF) is associated with a poor prognosis. There is paucity of data in Nigeria on prognosis among HHF patients elucidating the role of 24-hour Holter electrocardiogram (ECG) in concert with other risk factors. Objective The aim of this study was to determine the prognostic utility of 24-hour Holter ECG, the 6-minute walk test (6-MWT), echocardiography, clinical and laboratory parameters among HHF patients. Methods A total of 113 HHF patients were recruited and followed up for 6 months. Thirteen of these patients were lost to follow-up, and as a result only 100 HHF patients were analyzed. All the patients underwent baseline laboratory tests, echocardiography, 24-hour Holter ECG and the 6-MWT. HHF patients were analyzed as “mortality vs alive” and as “events vs no-events” based on the outcome at the end of 6 months. Events was defined as HHF patients who were rehospitalized for heart failure (HF), had prolonged hospital stay or died. No-events group was defined as HHF patients who did not meet the criteria for the events group. Results HHF patients in the mortality group (n = 7) had significantly higher serum urea (5.71 ± 2.07 mmol/L vs 3.93 ± 1.45 mmol/L, p = 0.003) than that in those alive. After logistic regression, high serum urea conferred increased mortality risk (p = 0.035). Significant premature ventricular complexes (PVCs) on 24-hour Holter ECG following logistic regression were also significantly higher (p = 0.015) in the mortality group than in the “alive” group (n = 93) at the end of the 6-month follow-up period. The 6-minute walk distance (6-MWD) was least among the HHF patients who died (167.26 m ± 85.24 m). However, following logistic regression, the 6-MWT was not significant (p = 0.777) for predicting adverse outcomes among HHF patients. Patients in the events group (n = 41) had significantly higher New York Heart Association (NYHA) class (p = 0.001), Holter-detected ventricular tachycardia (VT; p

  2. Multicentric survey on dose reduction/interruption of cancer drug therapy in 12.472 patients: indicators of suspected adverse reactions.

    PubMed

    Casadei Gardini, Andrea; Tenti, Elena; Masini, Carla; Nanni, Oriana; Scarpi, Emanuela; Valgiusti, Martina; Restuccia, Silvia; Gallani, Maria Laura; Palazzini, Simonetta; Bianchini, Erica; Menozzi, Silvia; Maugeri, Antonio; Amadori, Dino; Minguzzi, Martina; Frassineti, Giovanni Luca

    2016-06-28

    Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012.Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events.

  3. PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients

    PubMed Central

    Lotan, Tamara L.; Gurel, Bora; Sutcliffe, Siobhan; Esopi, David; Liu, Wennuan; Xu, Jianfeng; Hicks, Jessica L.; Park, Ben H.; Humphreys, Elizabeth; Partin, Alan W.; Han, Misop; Netto, George J.; Isaacs, William B.; De Marzo, Angelo M.

    2011-01-01

    Purpose Analytically validated assays to interrogate biomarker status in clinical samples are crucial for personalized medicine. PTEN is a tumor suppressor commonly inactivated in prostate cancer that has been mechanistically linked to disease aggressiveness. Though deletion of PTEN, as detected by cumbersome fluorescence in situ hybridization (FISH) spot counting assays, is associated with poor prognosis, few studies have validated immunohistochemical (IHC) assays to determine whether loss of PTEN protein is associated with unfavorable disease. Experimental Design PTEN IHC was validated by employing formalin fixed and paraffin embedded isogenic human cell lines containing or lacking intact PTEN alleles. PTEN IHC was 100% sensitive and 97.8% specific for detecting genomic alterations in 58 additional cell lines. PTEN protein loss was then assessed on 376 prostate tumor samples, and PTEN FISH or high resolution SNP microarray analysis was performed on a subset of these cases. Results PTEN protein loss, as assessed as a dichotomous IHC variable, was highly reproducible, correlated strongly with adverse pathologic features (e.g. Gleason score and pathological stage), detected between 75% and 86% of cases with PTEN genomic loss, and was found at times in the absence of apparent genomic loss. In a cohort of 217 high risk surgically treated patients, PTEN protein loss was associated with decreased time to metastasis. Conclusions These studies validate a simple method to interrogate PTEN status in clinical specimens and support the utility of this test in future multi-center studies, clinical trials and ultimately perhaps for routine clinical care. PMID:21878536

  4. Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals

    PubMed Central

    Min, James K.; Labounty, Troy M.; Gomez, Millie J.; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Filippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Cheng, Victor; Chinnaiyan, Kavitha M.; Chow, Benjamin; Cury, Ricardo; Delago, Augustin; Dunning, Allison; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Jorg; Kaufmann, Philipp; Kim, Yong-Jin; Leipsic, Jonathon; Lin, Fay Y.; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J.; Villines, Todd C.; Berman, Daniel S.

    2015-01-01

    Background Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored. Methods From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1–49%, 50–69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) – inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) – and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification. Results Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61–3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75–3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09–1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18–2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29–2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05–1.18, p < 0.001) were associated with increased risk of

  5. Arm function after stroke. An evaluation of grip strength as a measure of recovery and a prognostic indicator.

    PubMed Central

    Sunderland, A; Tinson, D; Bradley, L; Hewer, R L

    1989-01-01

    The value of strength of voluntary grip as an indicator of recovery of arm function was assessed by testing 38 recent stroke patients using a sensitive electronic dynamometer, and comparing the results with those from five other arm movement and function tests (Motricity Index, Motor Club Assessment, Nine Hole Peg Test, and Frenchay Arm Test). This procedure allowed measurement of grip in a large proportion of patients, and strength correlated highly with performance on the other tests. Measuring grip over a six month follow up period was a sensitive method of charting intrinsic neurological recovery. The presence of voluntary grip at one month indicates that there will be some functional recovery at six months. PMID:2592969

  6. Are CSF Biomarkers Useful as Prognostic Indicators in Diagnostically Unresolved Cognitively Impaired Patients in a Normal Clinical Setting

    PubMed Central

    Schjønning Nielsen, Malene; Simonsen, Anja Hviid; Siersma, Volkert; Hasselbalch, Steen Gregers; Høgh, Peter

    2016-01-01

    Background Despite an extensive evaluation program, patients may remain diagnostically unresolved with regard to the etiology of their cognitive dysfunction. Cerebrospinal fluid neuroinflammation and Alzheimer disease (AD) biomarkers may act as indicators of neurodegenerative disorders in diagnostically unresolved patients. Methods Data on 348 patients were retrospectively evaluated. All participants had a standardized diagnostic workup and follow-up in a memory clinic. Results Aβ42 levels and Aβ42/p-tau ratios were reduced and levels of t-tau and p-tau as well as the t-tau × p-tau/Aβ42 ratio were elevated in diagnostically unresolved patients who clinically progressed, compared to a stable group. No differences in neuroinflammatory parameters were found. Conclusion AD biomarkers - in particular the Aβ42/p-tau ratio, but not neuroinflammatory parameters - predicted clinical progression, regardless of etiology. PMID:27843444

  7. Nonenhancing peritumoral hyperintense lesion on diffusion-weighted imaging in glioblastoma: a novel diagnostic and specific prognostic indicator.

    PubMed

    Kolakshyapati, Manish; Adhikari, Rupendra B; Karlowee, Vega; Takayasu, Takeshi; Nosaka, Ryo; Amatya, Vishwa J; Takeshima, Yukio; Akiyama, Yuji; Sugiyama, Kazuhiko; Kurisu, Kaoru; Yamasaki, Fumiyuki

    2017-03-31

    .0001) and poor prognosis (p = 0.0007). CONCLUSIONS The presence of Definite-NePDHL is very specific for glioblastoma and indicates poor prognosis. Definite-NePDHL is a significant indicator of early local and distant/dissemination recurrence in patients with glioblastoma. Studying peritumoral DWI and high-b-value DWI is useful for tumor differentiation.

  8. Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival

    PubMed Central

    Li, Z; Yamada, S; Inenaga, S; Imamura, T; Wu, Y; Wang, K-Y; Shimajiri, S; Nakano, R; Izumi, H; Kohno, K; Sasaguri, Y

    2011-01-01

    Background: The family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) is responsible for the altered glycosylation in cancer. The purpose of our study was to investigate the clinical significance of two isoforms, GalNAc-T6 and -T3, and their correlation with the prognosis of pancreatic cancer. Methods: Immunohistochemistry was used to analyse GalNAc-T6 and -T3 expressions in 70 clinicopathologically characterised pancreatic cancer cases. Results: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively. A close relationship was noted between GalNAc-T6 positive expression and pathological well/moderate differentiated type (P=0.001), small tumour size (P=0.044), absence of vascular invasion (P=0.009), and low stage of the American Joint Committee on Cancer systems (P=0.043). The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features. Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356). Conclusion: Both GalNAc-T6 and -T3 expressions correlated significantly with tumour differentiation, whereas only GalNAc-T6 expression predicted prognosis in pancreatic cancer. PMID:21587259

  9. Part 3. Modeling of Multipollutant Profiles and Spatially Varying Health Effects with Applications to Indicators of Adverse Birth Outcomes.

    PubMed

    Molitor, John; Coker, Eric; Jerrett, Michael; Ritz, Beate; Li, Arthur

    2016-04-01

    obtained by the estimation process generally yields smaller standard errors while inconsistent clustering is generally associated with larger errors. These multivariate methods are applied to a range of different problems related to air pollution exposures, namely an association of multipollutant profiles with indicators of poverty and to an assessment of the association between measures of various air pollutants, patterns of socioeconomic status (SES), and birth outcomes. All of these studies involve an examination of regional-level exposures, at the census tract (CT) and census block group (CBG) levels, and individual-level outcomes throughout Los Angeles (LA) County. Results indicate that effects of pollutants vary spatially and vary in a complex interconnected manner that cannot be discerned using standard additive line ar models. Results obtaine d from these studies can be used to efficiently use limited resources to inform policies in targeting are as where air pollution reductions result in maximum health benefits.

  10. High-Flow Nasal Cannula Oxygen Therapy in Adults: Physiological Benefits, Indication, Clinical Benefits, and Adverse Effects.

    PubMed

    Nishimura, Masaji

    2016-04-01

    High-flow nasal cannula (HFNC) oxygen therapy is carried out using an air/oxygen blender, active humidifier, single heated tube, and nasal cannula. Able to deliver adequately heated and humidified medical gas at flows up to 60 L/min, it is considered to have a number of physiological advantages compared with other standard oxygen therapies, including reduced anatomical dead space, PEEP, constant F(IO2), and good humidification. Although few large randomized clinical trials have been performed, HFNC has been gaining attention as an alternative respiratory support for critically ill patients. Published data are mostly available for neonates. For critically ill adults, however, evidence is uneven because the reports cover various subjects with diverse underlying conditions, such as hypoxemic respiratory failure, exacerbation of COPD, postextubation, preintubation oxygenation, sleep apnea, acute heart failure, and conditions entailing do-not-intubate orders. Even so, across the diversity, many published reports suggest that HFNC decreases breathing frequency and work of breathing and reduces the need for respiratory support escalation. Some important issues remain to be resolved, such as definitive indications for HFNC and criteria for timing the starting and stopping of HFNC and for escalating treatment. Despite these issues, HFNC has emerged as an innovative and effective modality for early treatment of adults with respiratory failure with diverse underlying diseases.

  11. Bio-pathologic characteristics related to chromosome 11 aneusomy and cyclin D1 gene status in surgically resected stage I and II breast cancer: Identification of an adverse prognostic profile.

    PubMed

    Mottolese, Marcella; Orlandi, Giulia; Sperduti, Isabella; Merola, Roberta; Buglioni, Simonetta; Di Benedetto, Anna; Pinnarò, Paola; Perracchio, Letizia; Venturo, Irene; Cognetti, Francesco; Cianciulli, AnnaMaria

    2007-02-01

    We aimed at developing a more detailed understanding of cyclin D1 in early stage human breast cancer and defining the biologic profiles with different prognostic value correlating cyclin D1 gene amplification and chromosome 11 aneusomy with bio-pathologic variables of known clinical importance. Cyclin D1 gene amplification and chromosome 11 aneusomy were investigated using fluorescence in situ hybridization whereas cyclin D1, PgR, HER-2, Bcl2, p53, and Ki-67 expressions were analyzed by immunohistochemistry in 121 stage I or II breast cancer patients uniformly treated with cyclophosphamide/metotrexate/5-fluorouracil-based chemotherapy. Cyclin D1 was amplified in 6.6% and overexpressed in 32.2% of cases. Amplification was not associated with any selected bio-pathologic variables, whereas the chromosome 11 aneusomy level significantly increased in tumors with higher histologic grade (P < 0.01), higher tumor size (P < 0.003), p53 nuclear accumulation (P < 0.04), and ERalpha negativity (P < 0.049). Multiple correspondence analysis showed 4 different biologic tumor profiles. The first, characterized by high Ki-67 score, p53+, cyclin D1+, HER-2+, aneusomy level > 30%, ratio (cyclin D1 gene/CEP11) > 2, was associated with tumor relapse defining the most unfavorable biologic profile. Kaplan-Meier's method showed significantly shorter disease-free survival in patients with at least 3 variables positive out of the 6 detected by multiple correspondence analysis. In multivariate analysis, the identified biologic profile emerged as the only significant prognostic indicator. Our findings are of particular clinical interest for early stage breast cancer patients, because the assessment of biologic factors predictive of tumor aggressiveness may influence postoperative therapeutic strategies.

  12. Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging versus Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events: The CORE320 Multicenter Study.

    PubMed

    Chen, Marcus Y; Rochitte, Carlos E; Arbab-Zadeh, Armin; Dewey, Marc; George, Richard T; Miller, Julie M; Niinuma, Hiroyuki; Yoshioka, Kunihiro; Kitagawa, Kakuya; Sakuma, Hajime; Laham, Roger; Vavere, Andrea L; Cerci, Rodrigo J; Mehra, Vishal C; Nomura, Cesar; Kofoed, Klaus F; Jinzaki, Masahiro; Kuribayashi, Sachio; Scholte, Arthur J; Laule, Michael; Tan, Swee Yaw; Hoe, John; Paul, Narinder; Rybicki, Frank J; Brinker, Jeffrey A; Arai, Andrew E; Matheson, Matthew B; Cox, Christopher; Clouse, Melvin E; Di Carli, Marcelo F; Lima, João A C

    2017-03-14

    Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study. All images were analyzed in blinded independent core laboratories, and a panel of physicians adjudicated all adverse events. MACE was defined as revascularization (>30 days after index ICA), myocardial infarction, or cardiac death; hospitalization for chest pain or congestive heart failure; or arrhythmia. Late MACE was defined similarly, except for patients who underwent revascularization within the first 182 days after ICA, who were excluded. Comparisons of 2-year survival (time to MACE) used standard Kaplan-Meier curves and restricted mean survival times bootstrapped with 2000 replicates. Results An MACE (49 revascularizations, five myocardial infarctions, one cardiac death, nine hospitalizations for chest pain or congestive heart failure, and one arrhythmia) occurred in 51 of 379 patients (13.5%). The 2-year MACE-free rates for combined CT angiography and CT perfusion findings were 94% negative for coronary artery disease (CAD) versus 82% positive for CAD and were similar to combined ICA and single photon emission CT findings (93% negative for CAD vs 77% positive for CAD, P < .001 for both). Event-free rates for CT angiography and CT perfusion versus ICA and single photon emission CT for either positive or negative results were not

  13. Patterns of Reef Ecosystem Recovery Indicate That Adverse Early Triassic Ocean Conditions Extended into Middle Triassic Time

    NASA Astrophysics Data System (ADS)

    Kelley, B. M.; Yu, M.; Lehrmann, D. J.; Jost, A. B.; Lau, K. V.; Li, X.; Schaal, E. K.; Payne, J.

    2013-12-01

    The pattern of reef ecosystem recovery from the end-Permian extinction is poorly constrained due to the limited stratigraphic, spatial, and geographic range of reef buildups in Early Triassic and Anisian (early Middle Triassic) strata. In this study, we combined field studies and petrographic analysis to examine the pattern of reef evolution in latest Permian to Late Triassic carbonate platforms in the Nanpanjiang Basin of South China, an area of extensive shallow-water carbonate deposition in the tropical eastern Tethys. We find that early Mesozoic reef recovery in the eastern Tethys was a five-step process: (1) in the immediate aftermath of extinction, calcimicrobial biostromes (P/T boundary microbialites) developed in shallow-water platform settings; (2) in late Induan time, biohermal stromatolites developed in platform interior settings; (3) in latest Spathian time, large-scale Tubiphytes, microbial, and cement reefs lacking skeletal metazoans initiated on the margins and steep upper slopes of carbonate platforms, signaling the return of reefs to platform-margin settings; (4) in the Aegean or Bithynian (early Anisian), diminutive (mm-scale) calcareous sponges and calcareous algae appeared in the Tubiphytes reef, marking the reappearance of skeletal metazoans and calcareous algae to reefs in the eastern Tethys; and (5) in the late Anisian, the appearance of scleractinian corals coincided with increased abundance, size, and diversity of metazoan and algal reef builders. Early Mesozoic reefs of the eastern Tethys were dominated by microbes, Tubiphytes, and early-marine cements until the late Anisian, several million years into the Middle Triassic. The appearance of small metazoan buildups in Early Triassic strata in other parts of the world indicates that potential reef-building organisms were present much earlier. The limited stratigraphic range of those buildups, however, reinforces the interpretation that episodic environmental disturbances such as euxinia

  14. Body mass index, airflow obstruction and dyspnea and body mass index, airflow obstruction, dyspnea scores, age and pack years-predictive properties of new multidimensional prognostic indices of chronic obstructive pulmonary disease in primary care

    PubMed Central

    Ansari, Khalid; Keaney, Niall; Kay, Andrea; Price, Monica; Munby, Joan; Billett, Andrew; Haggerty, Sharon; Taylor, Ian K.; Al Otaibi, Hajed

    2016-01-01

    BACKGROUND: The assessment of the severity of chronic obstructive pulmonary disease (COPD) should involve a multidimensional approach that is now clearly shown to be better than using spirometric impairment alone. The aim of this study is to validate and compare novel tools without an exercise test and to extend prognostic value to patients with less severe impairment of Forced expiratory volume 1 s. METHODS: A prospective, observational, primary care cohort study identified 458 eligible patients recruited from the primary care clinics in the northeast of England in 1999–2002. A new prognostic indicator – body mass index, airflow obstruction and dyspnea (BOD) together with the conventional prognostic indices age, dyspnea and airflow obstruction (ADO), global initiative for chronic obstructive lung disease (GOLD) and new GOLD matrix were studied. We also sought to improve prognostication of BOD by adding age (A) and smoking history as pack years (S) to validate BODS (BOD with smoking history) and BODAS (BOD with smoking history and age) as prognostic tools and the predictive power of each was analyzed. RESULTS: The survival of the 458 patients was assessed after a median of 10 years when the mortality was found to be 33.6%. The novel indices BOD, BODS, and BODAS were significantly predictive for all-cause mortality in our cohort. Furthermore with ROC analysis the C statistics for BOD, BODS, and BODAS were 0.62, 0.66, and 0.72, respectively (P < 0.001 for each), whereas ADO and GOLD stages had a C statistic of 0.70 (P < 0.001) and 0.56 (P < 0.02), respectively. GOLD Matrix was not significant in this cohort. CONCLUSION: BOD, BODS, and BODAS scores are validated predictors of all-cause mortality in a primary care cohort with COPD. PMID:27803752

  15. Lactate dehydrogenase is a prognostic indicator in patients with hepatocellular carcinoma treated by sorafenib: results from the real life practice in HBV endemic area

    PubMed Central

    Li, Mu-xing; Zhao, Hong; Bi, Xin-yu; Li, Zhi-yu; Yao, Xue-song; Li, Huai; Huang, Zhen; Han, Yue; Zhou, Jian-guo; Zhao, Jian-jun; Zhang, Ye-fan; Zhao, Dong-bin; Cai, Jian-qiang

    2016-01-01

    Purpose Lactate dehydrogenase (LDH), which was an indirect marker of hypoxia, was a potentially prognostic factor in several malignancies. There is a lack of evidence about the prognostic value of serum LDH level in patients with hepatocellular carcinoma (HCC) receiving sorafenib treatment from hepatitis B virus endemic areas. Materials and Methods A total of 119 HBV-related HCC patients treated by sorafenib from a Chinese center were included into the study. They were categorized into 2 groups according to the cut-off value of pre-treatment LDH, which was determined by the time dependent receiver operating characteristics (ROC) curve for the overall survival. The prognostic value of LDH was evaluated. The relationships between LDH and other clinicopathological factors were also assessed. Results The cut-off value was 221 U/L. With a median follow up of 15 (range, 3-73) months, 91 patients reached the endpoint. Multivariate analysis proved that pre-treatment serum LDH level was an independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). For patients whose pre-treatment LDH ≥ 221 U/L, increased LDH value after 3 months of sorafenib treatment predicted inferior OS and PFS. And patients with elevated pre-treatment LDH level predisposed to be featured with lower serum albumin, presence of macroscopic vascular invasion, advanced Child-Pugh class, advanced T category, higher AFP, and higher serum total bilirubin. Conclusions Serum LDH level was a potentially prognostic factor in HCC patients treated by sorafenib in HBV endemic area. More relevant studies with reasonable study design are needed to further strengthen its prognostic value. PMID:27880930

  16. Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer

    PubMed Central

    Mir, Rashid; Gandhi, Gauri; Ray, Prakash Chandra

    2016-01-01

    MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan—Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC. PMID:27092777

  17. Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer.

    PubMed

    Zuberi, Mariyam; Khan, Imran; Mir, Rashid; Gandhi, Gauri; Ray, Prakash Chandra; Saxena, Alpana

    2016-01-01

    MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan-Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

  18. Human epididymis protein 4 expression positively correlated with miR-21 and served as a prognostic indicator in ovarian cancer.

    PubMed

    Chen, Yong; Chen, Qingquan; Liu, Qicai; Gao, Feng

    2016-06-01

    Ovarian cancer is the most common cause of gynecological malignancy-related mortality. Human epididymis protein 4 (HE4) is a useful biomarker for ovarian cancer when either used alone or in combination with carbohydrate antigen 125 (CA125). What is more, aberrant expression of microRNA-21 (miR-21) has been shown to be involved in oncogenesis, but the relationship between miR-21 and HE4 in ovarian cancer is not clear. Tumor and adjacent tumor tissues from 43 patients with ovarian cancer were examined. Real-time polymerase chain reaction (RT-PCR) was used to detect the expression of HE4 in the carcinoma and adjacent tissues. The associations between HE4 and tumor biological characters were discussed. TaqMan(®) MicroRNA (miRNA) assays were employed to detect the expression of miR-21 in the ovarian carcinoma. In ovarian cancer, the expression of HE4 messenger RNA (mRNA) in cancer tissues was higher than adjacent tumor tissues (P < 0.0001), which was 1.299-fold of adjacent tumor tissues. And, the expression of miR-21 was also up-regulated which was significantly different in the ovarian cancer (the positive rate was 76.74 %). There was a significantly positive correlation between miR-21 and HE4 expression (r = 0.283 and P = 0.066 for HE4 mRNA, r = 0.663 and P < 0.0001 for serum HE4). There was also a significant correlation between miR-21 and tumor grade (r = 0.608, P < 0.0001). Significantly, patients with recent recurrence (less than 6 months, n = 17) have a higher miR-21 expression than those with no recent recurrence. Therefore, HE4 and miR-21 may play an important role in the development and progression of ovarian cancer and they may serve as prognostic indicators in ovarian cancer.

  19. Coalesced Multicentric Analysis of 2,351 Patients With Myelodysplastic Syndromes Indicates an Underestimation of Poor-Risk Cytogenetics of Myelodysplastic Syndromes in the International Prognostic Scoring System

    PubMed Central

    Schanz, Julie; Steidl, Christian; Fonatsch, Christa; Pfeilstöcker, Michael; Nösslinger, Thomas; Tuechler, Heinz; Valent, Peter; Hildebrandt, Barbara; Giagounidis, Aristoteles; Aul, Carlo; Lübbert, Michael; Stauder, Reinhard; Krieger, Otto; Garcia-Manero, Guillermo; Kantarjian, Hagop; Germing, Ulrich; Haase, Detlef; Estey, Elihu

    2011-01-01

    Purpose The International Prognostic Scoring System (IPSS) remains the most commonly used system for risk classification in myelodysplastic syndromes (MDSs). The IPSS gives more weight to blast count than to cytogenetics. However, previous publications suggested that cytogenetics are underweighted in the IPSS. Here we investigate the prognostic impact of cytogenetic subgroups compared with that of bone marrow blast count in a large, multicentric, international patient cohort. Patients and Methods In total, 2,351 patients with MDS who have records in the German-Austrian and the MD Anderson Cancer Center databases were included and analyzed in univariate and multivariate models regarding overall survival and risk of transformation to acute myeloid leukemia (AML). The data were analyzed separately for patients treated with supportive care without specific therapy, with AML-like chemotherapy, or with other therapy regimens (low-dose chemotherapy, demethylating agents, immune modulating agents, valproic acid, and cyclosporine). Results The prognostic impact of poor-risk cytogenetic findings (as defined by the IPSS classification) on overall survival was as unfavorable as an increased (> 20%) blast count. The hazard ratio (compared with an abnormal karyotype or a bone marrow blast count < 5%) was 3.3 for poor-risk cytogenetics, 4.8 for complex abnormalities harboring chromosomes 5 and/or 7, and 3.1 for a blast count of 21% to 30% (P < .01 for all categories). The predictive power of the IPSS cytogenetic subgroups was unaffected by type of therapy given. Conclusion The independent prognostic impact of poor-risk cytogenetics on overall survival is equivalent to the impact of high blast counts. This finding should be considered in the upcoming revision of the IPSS. PMID:21519021

  20. Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma

    PubMed Central

    2014-01-01

    Background New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes. Methods CTCs were captured by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled prospectively and CTC counts performed at baseline (prior to treatment), during and after treatment. Results Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival. However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy. A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients. Conclusions Measuring changes in CTC numbers during treatment is useful for monitoring therapy response in melanoma patients and for providing prognostic information relating to overall survival. Further studies with larger sample sizes are required to confirm the utility of CTC quantification as a companion diagnostic for metastatic melanoma treatment. PMID:24915896

  1. High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers

    PubMed Central

    Peng, Li; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui

    2017-01-01

    Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients. PMID:27926484

  2. MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer

    PubMed Central

    Xu, Xin; Zhang, Yun; Jasper, Jeff; Lykken, Erik; Alexander, Peter B.; Markowitz, Geoffrey J.; McDonnell, Donald P.; Li, Qi-Jing; Wang, Xiao-Fan

    2016-01-01

    Triple-negative breast cancer (TNBC) presents a major challenge in the clinic due to its lack of reliable prognostic markers and targeted therapies. Accumulating evidence strongly supports the notion that microRNAs (miRNAs) are involved in tumorigenesis and could serve as biomarkers for diagnostic purposes. To identify miRNAs that functionally suppress metastasis of TNBC, we employed a concerted approach with selecting miRNAs that display differential expression profiles from bioinformatic analyses of breast cancer patient databases and validating top candidates with functional assays using breast cancer cell lines and mouse models. We have found that miR-148a exhibits properties as a tumor suppressor as its expression is inversely correlated with the ability of both human and mouse breast cancer cells to colonize the lung in mouse xenograft tumor models. Mechanistically, miR-148a appears to suppress the extravasation process of cancer cells, likely by targeting two genes WNT1 and NRP1 in a cell non-autonomous manner. Importantly, lower expression of miR-148a is detected in higher-grade tumor samples and correlated with increased likelihood to develop metastases and poor prognosis in subsets of breast cancer patients, particularly those with TNBC. Thus, miR-148a is functionally defined as a suppressor of breast cancer metastasis and may serve as a prognostic biomarker for this disease. PMID:26967387

  3. Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy.

    PubMed

    Ji, W H; Jiang, Y H; Ji, Y L; Li, B; Mao, W M

    2016-07-01

    prechemotherapy platelet to lymphocyte ratio ≤30 to preoperative platelet to lymphocyte ratio ≤130 group. In conclusions, prechemotherapy neutrophil to lymphocyte ratio is an independent prognostic factor for OS in patients with advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy, and, as an adverse prognostic predictor, increased prechemotherapy neutrophil to lymphocyte ratio is superior to platelet to lymphocyte ratio. Maintaining a low neutrophil to lymphocyte ratio and platelet to lymphocyte ratio throughout treatment is a predictor of better OS.

  4. Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy

    SciTech Connect

    Chan, Alexander K.P. . E-mail: alexc@cancerboard.ab.ca; Wong, Alfred; Jenken, Daryl; Heine, John; Buie, Donald; Johnson, Douglas

    2005-03-01

    Purpose: To evaluate the prognostic value of the posttreatment TNM stage as a predictor of outcome in locally advanced rectal cancers treated with preoperative chemotherapy and radiotherapy. Methods and materials: Between 1993 and 2000, 128 patients with tethered (103) or fixed (25) rectal cancers were treated with 50 Gy preoperative pelvic radiotherapy and two cycles of concurrent 5-fluorouracil infusion (20 mg/kg/d) and leucovorin (200 mg/m{sup 2}/d) chemotherapy on Days 1-4 and 22-25 and a single bolus mitomycin C injection (8 mg/m{sup 2}) on Day 1. Of the 128 patients, 111 had Stage T3 and 17 Stage T4 according to the rectal ultrasound or CT findings and clinical evaluation. All 128 patients underwent surgery 8 weeks after chemoradiotherapy. Postoperatively, the disease stage was determined according to the surgical and pathologic findings using the American Joint Committee on Cancer TNM staging system. Results: Of the 128 patients, 32 had postchemoradiotherapy (pCR) Stage 0 (T0N0M0), 37 pCR Stage I, 26 pCR Stage II, 28 pCR Stage III, and 5 pCR Stage IV disease. Of the 128 patients, 79 had pCR Stage T0-T2, 35 pCR Stage T3, and 14 pCR Stage T4. The rate of T stage downstaging was 66% (84 of 128). Of the 128 patients, 25% achieved a pathologic complete response, and 31 (24%) had positive nodal disease. Lymphovascular or perineural invasion was found in 13 patients (10%). The 5-year disease-specific survival rate was 97% for pCR Stage 0, 88% for pCR Stage I, 74% for pCR Stage II, 44% for pCR Stage III, and 0% for pCR Stage IV (p = 0.0000059). The 5-year relapse-free survival rate was 97% for pCR Stage 0, 80% for pCR Stage I, 72% for pCR Stage II, 42% for pCR Stage III, and 0% for pCR Stage IV (p < 0.000001). In univariate analysis, the pretreatment tumor status (fixed vs. tethered tumors), the pCR TNM stage, T stage downstaging, pathologic T4 tumors, node-positive disease after chemoradiotherapy, and lymphovascular or perineural invasion were statistically

  5. Overexpression of ANXA3 is an independent prognostic indicator in gastric cancer and its depletion suppresses cell proliferation and tumor growth

    PubMed Central

    Wang, Ke; Li, Jiansheng

    2016-01-01

    Background Gastric cancer (GC) is one of the most common malignancies worldwide. Tumour metastasis is one of the leading causes of death in GC patients. This study aims to investigate the significance of ANXA3 expression and the mechanism by which ANXA3 is involved in the epithelial–mensenchymal transition (EMT) of gastric cancer cells. Results Our results confirmed that ANXA3 was high expression at the mRNA and protein level in GC cancer tissues and the majority of GC cell lines. In clinicopathological analysis, we found that increased expression of ANXA3 in tumors was closely associated with a poor prognosis. Xogenous ANXA3 transduction promoted proliferation, clone formation, migration, and invasion. Small interfering RNA silencing of ANXA3 inhibited these processes. Silence of ANXA3 inhibited tumorigenicity in vivo. Additionally, ANXA3 expression is associated with the epithelial–mesenchymal transition. Methods Firstly, we investigated the ANXA3 expression on mRNA and protein level with RT-PCR and Western blot. Secondly, 183 GC patients tissues were used the to evaluate the clinicopathological characteristics and prognosis through immunohistochemistry. Furthermore, The functions of ANXA3 were analyzed in the cell proliferation, Colony Formation, migration, invasion and apoptosis of GC cell lines. Conclusions Our research suggests that ANXA3 plays important roles in gastric cancer carcinogenesis and metastasis, and provides a valuable prognostic marker and potential target for treatment of gastric cancer patients. PMID:27894078

  6. Identification of novel prognostic indicators for triple-negative breast cancer patients through integrative analysis of cancer genomics data and protein interactome data

    PubMed Central

    Zhao, Hengqiang; Yang, Lei; Su, Fei; Zhou, Ming-Ming; Han, Junwei; Sobie, Eric A.; Walsh, Martin J.

    2016-01-01

    Triple negative breast cancers (TNBCs) are highly heterogeneous and aggressive without targeted treatment. Here, we aim to systematically dissect TNBCs from a prognosis point of view by building a subnetwork atlas for TNBC prognosis through integrating multi-dimensional cancer genomics data from The Cancer Genome Atlas (TCGA) project and the interactome data from three different interaction networks. The subnetworks are represented as the protein-protein interaction modules perturbed by multiple genetic and epigenetic interacting mechanisms contributing to patient survival. Predictive power of these subnetwork-derived prognostic models is evaluated using Monte Carlo cross-validation and the concordance index (C-index). We uncover subnetwork biomarkers of low oncogenic GTPase activity, low ubiquitin/proteasome degradation, effective protection from oxidative damage, and tightly immune response are linked to better prognosis. Such a systematic approach to integrate massive amount of cancer genomics data into clinical practice for TNBC prognosis can effectively dissect the molecular mechanisms underlying TNBC patient outcomes and provide potential opportunities to optimize treatment and develop therapeutics. PMID:27690302

  7. [Prognostic significance of local and systemic indicators of lipid peroxidation and antioxidant system in perforating wounds of the eyes and their time course during local antioxidant treatment].

    PubMed

    Arkhipova, L T; Dolgova, I G

    2001-01-01

    Lipid peroxidation parameters malonic dialdehyde (MDA) and dienic conjugates (DC) and antioxidant defense (AOD) values superoxide dismutase (SOD), catalase, alpha-tocopherol were measured in the blood neutrophils and lacrimal fluid of 66 patients on days 1-2, 7-8, 14-15, and 21-22 after perforating wound of first, second, third, and fourth degree of severity according to P, 1. Lebekhov and in repeated injury, and the time course of these parameters during local treatment with therapeutic films with emoxipin and emoxipin + piridoxine was evaluated. A stable increase of MDA and DC levels in blood neutrophils, decrease of catalase, SOD, and alpha-tocopherol levels in blood neutrophils, and decrease of catalase enzymes and SOD activities in the lacrimal fluid of injured eye starting from days 7-8 are prognostically unfavorable signs. These data prompt the use of local and systemic treatment with antioxidants (emoxipin, tocopherol, etc.) in perforating wounds starting from the first days after the injury. Good clinical and antioxidant effect was observed after treatment with ocular therapeutic films with emoxipin and piridoxine.

  8. MELD-Na as a prognostic indicator of 30- and 90-day mortality in patients with end-stage liver disease after creation of transjugular intrahepatic portosystemic shunt.

    PubMed

    Ahmed, Rezwan; Santhanam, Prasanna; Rayyan, Yaser

    2015-10-01

    Previous studies have shown that the Model for End-Stage Liver Disease (MELD) score is superior to other liver disease scoring systems to establish optimal candidates for transjugular intrahepatic portosystemic shunt (TIPS) procedure and liver transplantation. Our aim was to compare MELD-Na score with MELD score as a predictor of 30-day as well as 90-day mortality for individuals with end-stage liver disease (ESLD) after creation of TIPS. We performed a chart review on cirrhotic patients who underwent TIPS procedure and documented presence and severity of ascites and hepatic encephalopathy, patient laboratory values, and results from TIPS procedures. We compared continuous variables by Student's t-test for independent samples and categorical variables by χ-test(s). In non-normal distributions, a nonparametric test was used. We performed a logistic regression to determine the effects of several variables and analyzed variable predictors of likelihood of death within 30 and 90 days of TIPS procedure. Of the six predictor variables, only MELD-Na score was a statistically significant predictor of 30- and 90-day mortality following TIPS procedure for ESLD (P=0.028). For each one point increase in MELD-Na score, the odds of death increased by 1.15 times [95% confidence interval (1.02-1.30), P=0.28]. Since hyponatremia may be associated with poor prognostic features of overall health, its incorporation into the MELD scoring system to predict mortality in ESLD after creation of TIPS serves a useful purpose. Our single-center experience suggests that the MELD-Na score is the most effective predictor of survival after TIPS creation.

  9. Identifying patients with advanced chronic conditions for a progressive palliative care approach: a cross-sectional study of prognostic indicators related to end-of-life trajectories

    PubMed Central

    Amblàs-Novellas, J; Murray, S A; Espaulella, J; Martinez-Muñoz, M; Blay, C; Gómez-Batiste, X

    2016-01-01

    Objectives 2 innovative concepts have lately been developed to radically improve the care of patients with advanced chronic conditions (PACC): early identification of palliative care (PC) needs and the 3 end-of-life trajectories in chronic illnesses (acute, intermittent and gradual dwindling). It is not clear (1) what indicators work best for this early identification and (2) if specific clinical indicators exist for each of these trajectories. The objectives of this study are to explore these 2 issues. Setting 3 primary care services, an acute care hospital, an intermediate care centre and 4 nursing homes in a mixed urban–rural district in Barcelona, Spain. Participants 782 patients (61.5% women) with a positive NECPAL CCOMS-ICO test, indicating they might benefit from a PC approach. Outcome measures The characteristics and distribution of the indicators of the NECPAL CCOMS-ICO tool are analysed with respect to the 3 trajectories and have been arranged by domain (functional, nutritional and cognitive status, emotional problems, geriatric syndromes, social vulnerability and others) and according to their static (severity) and dynamic (progression) properties. Results The common indicators associated with early end-of-life identification are functional (44.3%) and nutritional (30.7%) progression, emotional distress (21.9%) and geriatric syndromes (15.7% delirium, 11.2% falls). The rest of the indicators showed differences in the associations per illness trajectories (p<0.05). 48.2% of the total cohort was identified as advanced frailty patients with no advanced disease criteria. Conclusions Dynamic indicators are present in the 3 trajectories and are especially useful to identify PACC for a progressive PC approach purpose. Most of the other indicators are typically associated with a specific trajectory. These findings can help clinicians improve the identification of patients for a palliative approach. PMID:27645556

  10. Lipoprotein Lipase as a Prognostic Marker in Chronic Lymphocytic Leukemia.

    PubMed

    Mátrai, Zoltán; Andrikovics, Hajnalka; Szilvási, Anikó; Bors, András; Kozma, András; Ádám, Emma; Halm, Gabriella; Karászi, Éva; Tordai, Attila; Masszi, Tamás

    2017-01-01

    The marked clinical heterogeneity of CLL makes early prognosis assessment important. Lipoprotein lipase (LPL) has been shown to confer adverse prognosis in CLL, recent data indicating it might also contribute to CLL cell survival and metabolism. We determined LPL mRNA expression in unselected peripheral blood of 84 CLL patients by RT PCR. Results were correlated with other prognostic markers and outcome. 30/84 (40 %) of cases were LPL positive based on the cutoff established by ROC analysis. In LPL positive patients significantly shorter median survival (136 vs 258 months, p < 0.0001) and time to first treatment intervals (36 vs 144 months, p < 0.002) were documented. LPL values correlated with male gender, higher stages, more treatment requirement, CD38 positivity and unmutated IgVH genes. Among cases with 13q deletion, LPL positivity identified a subcohort with poor outcome (median survival 108 months vs NR, p < 0.0001). In multivariate analysis, cytogenetic aberrations and LPL had significant impact on survival. Our results confirm that LPL is a strong predictor of outcome in CLL, able to improve prognostic accuracy in good risk cytogenetic subgroups. The relationship between its prognostic and functional role in CLL needs to be explored further.

  11. Definition of Time Induction of Self-Ignition of the Substance on the Prognostic Extrapolation Depending on the Basis of Indicators Fire and Explosion Hazard

    NASA Astrophysics Data System (ADS)

    Sechin, A.; Kyrmakova, O.; Osipenko, S.

    2016-01-01

    In this article the research directed on development of a technique of definition of time of induction of the self-ignition of substances and materials which is an indicator of the beginning of development of an emergency is conducted. The experiment consisting in supervision over process of self-ignition of coal and oil deposits was the basis for research. On the basis of experimental data the curve expressing analytic - expected dependence of size of temperature of ignition on induction time was constructed. Proceeding from graphical representation of process, functional dependence of time of induction on a temperature indicator was received: y = 16920 • x0 537. By means of known indicators of such substances as bitumen oil oxidized (the combustible solid substance received by oxidation of residual product of oil refining) and tar oil (the combustible solid substance which is residual product of oil refining) and the received algorithm, verification of reliability of the received dependence and a technique of definition of time of induction of spontaneous ignition of deposits of oil in general was carried out. The practical importance of the conducted research is that having data on time of induction of process of self-ignition, by means of preventive measures becomes possible to avoid and prevent accidents in oil and oil processing branches, at the same time loss of property and loss of human life.

  12. Peripheral blood lymphocyte-to-monocyte ratio as a prognostic factor in advanced epithelial ovarian cancer: a multicenter retrospective study

    PubMed Central

    Zhu, Jia-yu; Liu, Cheng-cheng; Wang, Liang; Zhong, Mei; Tang, Hai-lin; Wang, Hua

    2017-01-01

    The lymphocyte-to-monocyte ratio (LMR), as a surrogate marker of systemic inflammation, has been found to be a novel prognostic indicator in various malignancies. Data from 672 advanced epithelial ovarian cancer (EOC) patients treated with neoadjuvant chemotherapy (NAC) followed by debulking surgery were analyzed, and the prognostic value of LMR were evaluated. The optimal cutoff point of LMR in prediction of survival was defined as 3.45 through receiver operating characteristics curve analysis. Patients with low LMR (≤3.45) at diagnosis tended to have more adverse clinical features, such as higher histological grade, chemotherapy resistance, and residual tumor >1cm after debulking surgery. No significant correlation was found between LMR level and age and histological type. Moreover, after NAC, the complete remission (CR) rate for the low-LMR group was lower than those for the high-LMR group (P<0.05). Patients with low LMR had poorer progression-free survival (PFS; P<0.001) and overall survival (OS; P<0.001). Multivariate analysis revealed that low LMR was an independent adverse predictor for PFS and OS. Results indicated that low LMR at diagnosis is a novel independent prognostic factor for advanced EOC. However, prospective study is needed to validate this prognostic factor and biological studies should further investigate the mechanisms underlying the correlation between low LMR and poor prognosis in advanced EOC.

  13. Household Food Insecurity Is Associated with Adverse Mental Health Indicators and Lower Quality of Life among Koreans: Results from the Korea National Health and Nutrition Examination Survey 2012–2013

    PubMed Central

    Chung, Hye-Kyung; Kim, Oh Yoen; Kwak, So Young; Cho, Yoonsu; Lee, Kyong Won; Shin, Min-Jeong

    2016-01-01

    Food insecurity is an ongoing public health issue and contributes to mental health status. We investigated whether food insecurity is associated with inadequate nutrient intake and whether it affects mental health indicators (perceived stress/experience of depressive symptom/suicidal ideation) and quality of life (QOL) among Koreans (n = 5862, 20–64 years) using data from the Korea National Health and Nutritional Examination Survey (2012–2013). Household food security status was categorized as “food-secure household”, “food-insecure household without hunger”, and “food-insecure household with hunger”. Data on food insecurity, sociodemographic factors, nutrient intake, mental health indicators, and QOL were used. A logistic regression model was conducted to determine odds ratios (ORs) for psychological health. A greater proportion of food-insecure participants were nutritionally deficient compared with expectations of the 2015 Korean Dietary Reference Intakes. These deficiencies were generally higher in both “food-insecure household” groups. Both “food-insecure household” groups, particularly the “food-insecure household with hunger” group showed significantly adverse mental health status (ORs: 1.52–3.83) and lower QOL (ORs: 1.49–3.92) than did the “food-secure household” group before and after adjusting for sex, age, education, household income, smoking/alcohol consumption, physical activity, marital status, and receiving food assistance. In conclusion, food insecurity may be significantly associated with adverse mental health indicators and decreased QOL in young/middle-aged Koreans. PMID:27999277

  14. Household Food Insecurity Is Associated with Adverse Mental Health Indicators and Lower Quality of Life among Koreans: Results from the Korea National Health and Nutrition Examination Survey 2012-2013.

    PubMed

    Chung, Hye-Kyung; Kim, Oh Yoen; Kwak, So Young; Cho, Yoonsu; Lee, Kyong Won; Shin, Min-Jeong

    2016-12-16

    Food insecurity is an ongoing public health issue and contributes to mental health status. We investigated whether food insecurity is associated with inadequate nutrient intake and whether it affects mental health indicators (perceived stress/experience of depressive symptom/suicidal ideation) and quality of life (QOL) among Koreans (n = 5862, 20-64 years) using data from the Korea National Health and Nutritional Examination Survey (2012-2013). Household food security status was categorized as "food-secure household", "food-insecure household without hunger", and "food-insecure household with hunger". Data on food insecurity, sociodemographic factors, nutrient intake, mental health indicators, and QOL were used. A logistic regression model was conducted to determine odds ratios (ORs) for psychological health. A greater proportion of food-insecure participants were nutritionally deficient compared with expectations of the 2015 Korean Dietary Reference Intakes. These deficiencies were generally higher in both "food-insecure household" groups. Both "food-insecure household" groups, particularly the "food-insecure household with hunger" group showed significantly adverse mental health status (ORs: 1.52-3.83) and lower QOL (ORs: 1.49-3.92) than did the "food-secure household" group before and after adjusting for sex, age, education, household income, smoking/alcohol consumption, physical activity, marital status, and receiving food assistance. In conclusion, food insecurity may be significantly associated with adverse mental health indicators and decreased QOL in young/middle-aged Koreans.

  15. Prognostic utility of coronary computed tomographic angiography

    PubMed Central

    Otaki, Yuka; Berman, Daniel S.; Min, James K.

    2013-01-01

    Coronary computed tomographic angiography (CCTA) employing CT scanners of 64-detector rows or greater represents a noninvasive method that enables accurate detection and exclusion of anatomically obstructive coronary artery disease (CAD), providing excellent diagnostic information when compared to invasive angiography. There are numerous potential advantages of CCTA beyond simply luminal stenosis assessment including quantification of atherosclerotic plaque volume as well as assessment of plaque composition, extent, location and distribution. In recent years, an array of studies has evaluated the prognostic utility of CCTA findings of CAD for the prediction of major adverse cardiac events, all-cause death and plaque instability. This prognostic information enhances risk stratification and, if properly acted upon, may improve medical therapy and/or behavioral changes that may enhance event-free survival. The goal of the present article is to summarize the current status of the prognostic utility of CCTA findings of CAD. PMID:23809386

  16. 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.

  17. Predictive and prognostic value of preoperative serum tumor markers in resectable adenosqamous lung carcinoma

    PubMed Central

    Yue, Dongsheng; Li, Kai; Jiang, Richeng

    2016-01-01

    Background Adenosquamous carcinoma is a rare and aggressive form of lung cancer. The prognostic and predictive value of preoperative serum tumor markers and frequency of EGFR mutations in adenosquamous lung carcinoma are unclear. Methods We retrospectively analyzed data and samples collected from 106 radically resected adenosquamous lung carcinoma patients with pathological stage I-IIIA between 2008 and 2013. Correlations between serum tumor marker levels and EGFR mutations as well as survival parameters were analyzed and prognostic factors were identified. Results Of the 106 adenosquamous lung carcinoma patients, 29 (27.4%) harbored EGFR mutations. By univariate analysis, advanced clinical stage (P = 0.009 for disease-free survival [DFS]; P = 0.046 for overall survival [OS]), larger tumor size (P = 0.001 for DFS; P = 0.002 for OS), regional lymph node metastasis (P = 0.024 for DFS; P = 0.030 for OS), higher NSE level (P = 0.002 for DFS; P < 0.001 for OS), and higher TMI (tumor marker index) (P = 0.009 for OS) were significantly correlated with a worse prognosis. By multivariate analysis, NSE (P = 0.014) was confirmed as independent predictor for DFS, while NSE (P = 0.001) and TMI (P = 0.038) were independent prognostic factors for OS. Conclusion Adenosquamous lung carcinoma is an aggressive malignancy with relatively high EGFR mutation frequency. Elevated preoperative NSE level and TMI are adverse predictive and prognostic indicators. PMID:27623437

  18. 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.

  19. 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.

  20. Prognostic factors in cancer.

    PubMed

    Gospodarowicz, Mary; O'Sullivan, Brian

    2003-01-01

    Diagnosis, prognosis, and treatment are the three core elements of the art of medicine. Modern medicine pays more attention to diagnosis and treatment but prognosis has been a part of the practice of medicine much longer than diagnosis. Cancer is a heterogeneous group of disease characterized by growth, invasion and metastasis. To plan the management of an individual cancer patient, the fundamental knowledge base includes the site of origin of the cancer, its morphologic type, and the prognostic factors specific to that particular patient and cancer. Most prognostic factors literature describes those factors that directly relate to the tumor itself. However, many other factors, not directly related to the tumor, also affect the outcome. To comprehensively represent these factors we propose three broad groupings of prognostic factors: 'tumor'-related prognostic factors, 'host'-related prognostic factors, and 'environment'-related prognostic factors. Some prognostic factors are essential to decisions about the goals and choice treatment, while others are less relevant for these purposes. To guide the use of various prognostic factors we have proposed a grouping of factors based on their relevance in everyday practice; these comprise 'essential,' 'additional,' and 'new and promising factors.' The availability of a comprehensive classification of prognostic factors assures an ordered and deliberate approach to the subject and provide safeguard against skewed approaches that may ignore large parts of the field. The current attention to tumor factors has diminished the importance of 'patient' (i.e., 'host'), and almost completely overshadows the importance of the 'environment'. This ignores the fact that the latter presents the greatest potential for immediate impact. The acceptance of a generic prognostic factor classification would facilitate communication and education about this most important subject in oncology.

  1. Cytogenetic Alterations in Multiple Myeloma: Prognostic Significance and the Choice of Frontline Therapy.

    PubMed

    Stella, Flavia; Pedrazzini, Estela; Agazzoni, Mara; Ballester, Oscar; Slavutsky, Irma

    2015-01-01

    Multiple myeloma tumor cells demonstrate multiple and often complex genetic lesions as evaluated by standard cytogenetic/FISH studies. Over the past decade, specific abnormalities have been associated with standard or high-risk clinical behavior and they have become strong prognostic indicators. Further, as evidenced by recent randomized clinical trials, the choice of front-line therapy (transplant vs. no transplant, inclusion of novel drugs such as bortezomib, thalidomide, and lenalidomide) may be able to overcome the adverse effect of high-risk genetic lesions.

  2. 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

  3. 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 ...

  4. 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.

  5. Significance Analysis of Prognostic Signatures

    PubMed Central

    Beck, Andrew H.; Knoblauch, Nicholas W.; Hefti, Marco M.; Kaplan, Jennifer; Schnitt, Stuart J.; Culhane, Aedin C.; Schroeder, Markus S.; Risch, Thomas; Quackenbush, John; Haibe-Kains, Benjamin

    2013-01-01

    A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that “random” gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated

  6. 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.

  7. Littoral Refractivity Prognostic Advancement

    DTIC Science & Technology

    2009-09-30

    situational awareness of the 3D radio-frequency (RF) propagation environment and a quantitative diagnostic and prognostic capability for assessing sub- and...Rev. 8-98) Prescribed by ANSI Std Z39-18 2 with the benchmark showing the quantitative improvement with each stage of model development...grid point. Modified the NSWCDD littoral clutter model ( LCM ) to accept COAMPS® derived refractivity fields. Analyzed the impact on ducting of

  8. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    PubMed

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values < 0.05). For every reduction of 5% in left ventricular ejection fraction induced by mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  9. Prognostic value of preoperative serum lactate dehydrogenase levels for resectable gastric cancer and prognostic nomograms

    PubMed Central

    Zhou, Yi-Xin; Wang, Feng; Zhang, Dong-Sheng; Wang, Feng-Hua; Li, Yu-Hong; Xu, Rui-Hua

    2016-01-01

    The present study aimed to evaluate the prognostic significance of preoperative serum lactate dehydrogenase (SLDH) levels for resected gastric cancer and construct prognostic nomograms for risk prediction. The study cohort consisted of 619 patients with D2-resected gastric cancer. The relationship of SLDH levels with clinicopathological features and clinical outcomes was evaluated. Prognostic nomograms were created using identified prognosticators to predict 3-year overall survival (OS) and 3-year disease-free survival (DFS), and bootstrap validation was performed. High SLDH levels were correlated with old age but not depth of invasion or lymph node metastasis. When assessed as a continuous variable, high SLDH levels were independently associated with poor OS and DFS. Internal validation of the developed nomograms revealed good predictive accuracy (bootstrap-corrected concordance indices: 0.77 and 0.75, respectively for prediction of OS and DFS). The preoperative SLDH levels, an identified unfavorable prognosticator, were incorporated into nomograms along with other clinicopathological features to refine the prediction of clinical outcomes for patients with D2-resected gastric cancer. PMID:27223065

  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

    2016-01-01

    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.

  11. [Pain as adverse drug reaction].

    PubMed

    Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard

    2012-09-01

    We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics.

  12. 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

  13. Prognostic Scores for Acute Pulmonary Embolism.

    PubMed

    Morillo, Raquel; Moores, Lisa; Jiménez, David

    2017-02-06

    Rapid and accurate risk stratification is critical in determining the optimal treatment strategy for patients with acute pulmonary embolism (PE). Early identification of patients with normal blood pressure and a favorable prognosis (low-risk PE) might select a subset of patients for outpatient treatment, which is associated with reduced cost and improved patient satisfaction, and has been shown to be effective and safe. Alternatively, identification of normotensive patients deemed as having a high risk for PE-related adverse clinical events (intermediate-high-risk PE) might select a subset of patients for close observation and consideration of escalation of therapy. Clinical prognostic scores have been gaining importance in the classification of patients into these categories. They should be derived and validated following strict methodological standards, and their use in clinical practice should be encouraged.

  14. D-Dimer elevation and adverse outcomes.

    PubMed

    Halaby, Rim; Popma, Christopher J; Cohen, Ander; Chi, Gerald; Zacarkim, Marcelo Rodrigues; Romero, Gonzalo; Goldhaber, Samuel Z; Hull, Russell; Hernandez, Adrian; Mentz, Robert; Harrington, Robert; Lip, Gregory; Peacock, Frank; Welker, James; Martin-Loeches, Ignacio; Daaboul, Yazan; Korjian, Serge; Gibson, C Michael

    2015-01-01

    D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.

  15. 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…

  16. Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Lee, Yi-Ying; Chao, Tung-Bo; Sheu, Ming-Jen; Tian, Yu-Feng; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Lin, Ching-Yih; Li, Chien-Feng

    2016-01-01

    Background: Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC. Methods: We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates. Results: GAD1 overexpression was significantly associated with an increase in the primary tumor status (p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.002) and was a univariate predictor of adverse outcomes of DSS (p = 0.002), DMeFS (p < 0.0001), and LRFS (p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS (p = 0.004, hazard ratio = 2.234), DMeFS (p < 0.001, hazard ratio = 4.218), and LRFS (p = 0.013, hazard ratio = 2.441) rates. Conclusions: Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities. PMID:27698909

  17. Prognostic Biomarkers in Ovarian Cancer

    PubMed Central

    Huang, Jie; Hu, Wei; Sood, Anil K

    2014-01-01

    Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy despite several decades of progress in diagnosis and treatment. Taking advantage of the robust development of discovery and utility of prognostic biomarkers, clinicians and researchers are developing personalized and targeted treatment strategies. This review encompasses recently discovered biomarkers of ovarian cancer, the utility of published prognostic biomarkers for EOC (especially biomarkers related to angiogenesis and key signaling pathways), and their integration into clinical practice. PMID:22045356

  18. A Prognostic Model for Patients with Triple-Negative Breast Cancer: Importance of the Modified Nottingham Prognostic Index and Age

    PubMed Central

    Kwon, Jeanny; Eom, Keun-Yong; Koo, Tae Ryool; Kim, Byoung Hyuck; Kang, Eunyoung; Kim, Sung-Won; Kim, Yu Jung; Park, So Yeon

    2017-01-01

    Purpose Considering the distinctive biology of triple-negative breast cancer (TNBC), this study aimed to identify TNBC-specific prognostic factors and determine the prognostic value of the Nottingham Prognostic Index (NPI) and its variant indices. Methods A total of 233 patients with newly diagnosed stage I to III TNBC from 2003 to 2012 were reviewed. We retrospectively analyzed the patients' demographics, clinicopathologic parameters, treatment, and survival outcomes. The NPI was calculated as follows: tumor size (cm)×0.2+node status+Scarff-Bloom-Richardson (SBR) grade. The modified NPI (MNPI) was obtained by adding the modified SBR grade rather than the SBR grade. Results The median follow-up was 67.8 months. Five-year disease-free survival (DFS) and overall survival (OS) were 81.4% and 89.9%, respectively. Multivariate analyses showed that the MNPI was the most significant and common prognostic factor of DFS (p=0.001) and OS (p=0.019). Young age (≤35 years) was also correlated with poor DFS (p=0.006). A recursive partitioning for establishing the prognostic model for DFS was performed based on the results of multivariate analysis. Patients with a low MNPI (≤6.5) were stratified into the low-risk group (p<0.001), and patients with a high MNPI (>6.5) were subdivided into the intermediate (>35 years) and high-risk (≤35 years) groups. Age was not a prognostic factor in patients with a low MNPI, whereas in patients with a high MNPI, it was the second key factor in subdividing patients according to prognosis (p=0.023). Conclusion The MNPI could be used to stratify patients with stage I to III TNBC according to prognosis. It was the most important prognosticator for both DFS and OS. The prognostic significance of young age for DFS differed by MNPI. PMID:28382096

  19. Adverse drug reactions.

    PubMed

    O'Reilly-Foley, Georgina

    2017-04-05

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article defined the different types of adverse drug reactions (ADRs) and explored when they can occur. It emphasised the importance of being knowledgeable about medications, considering patient safety when patients are taking medications, being alert to the possibility of ADRs, and recognising and responding to suspected ADRs.

  20. 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.

  1. Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates1

    PubMed Central

    Kwok, Man Leung; Yuen, Hon; Lai, Sik To

    2003-01-01

    Severe acute respiratory syndrome (SARS) poses a major threat to the health of people worldwide. We performed a retrospective case series analysis to assess clinical outcome and identify pretreatment prognostic correlates of SARS, managed under a standardized treatment protocol. We studied 127 male and 196 female patients with a mean age of 41±14 (range 18–83). All patients, except two, received ribavirin and steroid combination therapy. In 115 (36%) patients, the course of disease was limited. Pneumonitis progressed rapidly in the remaining patients. Sixty-seven (21%) patients required intensive care, and 42 (13%) required ventilator support. Advanced age, high admission neutrophil count, and high initial lactate dehydrogenase level were independent correlates of an adverse clinical outcome. SARS-associated coronavirus caused severe illnesses in most patients, despite early treatment with ribavirin and steroid. This study has identified three independent pretreatment prognostic correlates. PMID:14519241

  2. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  3. Adverse reactions to vaccines.

    PubMed

    Martin, Bryan L; Nelson, Michael R; Hershey, Joyce N; Engler, Renata J M

    2003-06-01

    (The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.) Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prolonged disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rare reaction risk. There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced risk communication intervention. When they occur, vaccine related adverse events must be treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

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

    PubMed Central

    2013-01-01

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

  5. 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.

  6. 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.

  7. Prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation

    PubMed Central

    Tannuri, Ana Cristina Aoun; Lima, Fabiana; de Mello, Evandro Sobroza; Tanigawa, Ryan Yukimatsu; Tannuri, Uenis

    2016-01-01

    OBJECTIVE: Chronic rejection remains a major cause of graft failure with indication for re-transplantation. The incidence of chronic rejection remains high in the pediatric population. Although several risk factors have been implicated in adults, the prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation are not known. Hence, the current study aimed to determine the factors involved in the progression or reversibility of pediatric chronic rejection by evaluating a series of chronic rejection cases following liver transplantation. METHODS: Chronic rejection cases were identified by performing liver biopsies on patients based on clinical suspicion. Treatment included maintaining high levels of tacrolimus and the introduction of mofetil mycophenolate. The children were divided into 2 groups: those with favorable outcomes and those with adverse outcomes. Multivariate analysis was performed to identify potential risk factors in these groups. RESULTS: Among 537 children subjected to liver transplantation, chronic rejection occurred in 29 patients (5.4%). In 10 patients (10/29, 34.5%), remission of chronic rejection was achieved with immunosuppression (favorable outcomes group). In the remaining 19 patients (19/29, 65.5%), rejection could not be controlled (adverse outcomes group) and resulted in re-transplantation (7 patients, 24.1%) or death (12 patients, 41.4%). Statistical analysis showed that the presence of ductopenia was associated with worse outcomes (risk ratio=2.08, p=0.01). CONCLUSION: The presence of ductopenia is associated with poor prognosis in pediatric patients with chronic graft rejection. PMID:27166772

  8. Prognostic Indicators as Provided by the EPIC ClearView

    ClinicalTrials.gov

    2011-11-18

    Coronary Artery Disease; Congestive Heart Failure; Valvular Heart Disease; Atrial Fibrillation; Hypertension; Pyelonephritis; Acute Renal Failure; Renal Failure; Viral Hepatitis; Alcoholic Hepatitis; Steatohepatitis; Cirrhosis; Asthma; COPD; Bronchitis; Emphysema; Pneumonia; Inflammatory Bowel Disease; Crohn's Disease; Ulcerative Colitis; Diverticulitis; Peptic Ulcer Disease; Irritable Bowel Syndrome; Cholecystitis; Pancreatitis; Malabsorption Disorders; Celiac Sprue; Diabetes

  9. Diagnostic and prognostic histopathology system using morphometric indices

    DOEpatents

    Parvin, Bahram; Chang, Hang; Han, Ju; Fontenay, Gerald V

    2015-05-12

    Determining at least one of a prognosis or a therapy for a patient based on a stained tissue section of the patient. An image of a stained tissue section of a patient is processed by a processing device. A set of features values for a set of cell-based features is extracted from the processed image, and the processed image is associated with a particular cluster of a plurality of clusters based on the set of feature values, where the plurality of clusters is defined with respect to a feature space corresponding to the set of features.

  10. Prognostic Modelling of Crack Growth in a Tensioned Steel Band

    NASA Astrophysics Data System (ADS)

    Swanson, David C.; Michael Spencer, J.; Arzoumanian, Sevag H.

    2000-09-01

    The general problem of identifying the condition of a structure or machine, and in particular its vibration signature, as a means to optimise maintenance costs and reliability is currently of great interest. This work presents a method for predicting the state of damage in the future for prognostic maintenance, rather than just identifying the current state of damage for diagnostic maintenance. Prognostics carries great economic importance because it allows the assessment of the likelihood of failure as a function of future time in terms of past and current conditions. We present an experimental example using the modal response of a notched, tensioned, steel band undergoing broadband vibration excitation to propagate cracks across the notched area until failure. The natural modes of the band are monitored during fatigue and the modal frequency shifts are used as a prognostic observable. A Kalman filter is then used track these modal frequency shifts and predict the likelihood and time when the amount of frequency shift is indicative of imminent failure. As a practical approach for prognostics of the band failure, we examine whether the modal frequencies are converging towards a stable state (such as during the break-in period), or diverging away from a stable state. A new probability density function for the remaining useful life is derived from the kinematic model. This method of using the kinematic state of a damage observable for failure prognostics can be extended to any dynamical system with observable features which correlate with damage or fatigue state.

  11. [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.

  12. Adverse reactions to drug additives.

    PubMed

    Simon, R A

    1984-10-01

    There is a long list of additives used by the pharmaceutical industry. Most of the agents used have not been implicated in hypersensitivity reactions. Among those that have, only reactions to parabens and sulfites have been well established. Parabens have been shown to be responsible for rare immunoglobulin E-mediated reactions that occur after the use of local anesthetics. Sulfites, which are present in many drugs, including agents commonly used to treat asthma, have been shown to provoke severe asthmatic attacks in sensitive individuals. Recent studies indicate that additives do not play a significant role in "hyperactivity." The role of additives in urticaria is not well established and therefore the incidence of adverse reactions in this patient population is simply not known. In double-blind, placebo-controlled studies, reactions to tartrazine or additives other than sulfites, if they occur at all, are indeed quite rare for the asthmatic population, even for the aspirin-sensitive subpopulation.

  13. VNN1 overexpression is associated with poor response to preoperative chemoradiotherapy and adverse prognosis in patients with rectal cancers

    PubMed Central

    Chai, Chi-Yung; Zhang, Yimin; Song, Junlong; Lin, Shih-Chun; Sun, Shengrong; Chang, I-Wei

    2016-01-01

    Background: Colorectal cancer is prevalent worldwide and it is also the fourth most common cause of cancer mortality. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a public dataset of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that VNN1 was the most significantly upregulated gene among those related to nitrogen compound metabolic process (GO:0006807). Therefore, we analyzed the clinicopathological correlation and prognostic impact of VNN1 protein (pantetheinase), which encoded by VNN1 gene. Methods: VNN1 immunostaining was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by surgery, which were bisected into high- and low-expression subgroups. Furthermore, statistical analyses were performed to correlate the relationship between VNN1 immunoreactivity and clinicopathological features, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: High VNN1 immunoexpression was significantly associated with advanced pre-treatment and post-treatment disease and poor response to CCRT (all P ≤ .026). In addition, VNN1 overexpression was linked to adverse DSS, LRFS and MeFS in univariate analysis and served as an independent prognosticator indicating worse DSS and LRFS in multivariate analysis (all P ≤ .019). Conclusion: VNN1 may play a crucial role in rectal cancer progression and responsiveness to CCRT, and serve as a novel prognostic biomarker. Additional studies to clarify the molecular pathway are essential for developing potential VNN1-targeted therapies for rectal cancer. PMID:27830030

  14. 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

  15. 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

  16. Adverse cutaneous drug reaction.

    PubMed

    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.

  17. Damage Mechanics Approach for Bearing Lifetime Prognostics

    NASA Astrophysics Data System (ADS)

    Qiu, Jing; Seth, Brij B.; Liang, Steven Y.; Zhang, Cheng

    2002-09-01

    The ability to achieve accurate bearing prognostics is critical to the optimal maintenance of rotating machinery in the interest of cost and productivity. However, techniques to real time predict the lifetime of a bearing under practical operating conditions have not been well developed. In this paper, a stiffness-based prognostic model for bearing systems based on vibration response analysis and damage mechanics is discussed. As the bearing system is considered as a single-degree-of-freedom vibratory system, its natural frequency and its acceleration amplitude at the natural frequency can be related to the system stiffness. On the other hand, the relationship between failure lifetime, running time and stiffness variation can be established from the damage mechanics. Combining the above two, the natural frequency and the acceleration amplitude of a bearing system can be related to its running time and failure lifetime. Thus, the failure lifetime of a bearing system can be predicted on-line based on vibration measurement. Experiments have been performed on a tapered roller bearing life testing stand under various operation conditions to calibrate and to validate the proposed model. The comparison between model-calculated data and experimental results indicates that this model can be used to effectively predict the failure lifetime and the remaining life of a bearing system.

  18. 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

  19. Cumulative early life adversity predicts longevity in wild baboons

    PubMed Central

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

    2016-01-01

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

  20. Cumulative early life adversity predicts longevity in wild baboons.

    PubMed

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

    2016-04-19

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations.

  1. 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

  2. p16 expression as a prognostic and predictive marker in high-grade localized osteosarcoma of the extremities: an analysis of 357 cases.

    PubMed

    Righi, Alberto; Gambarotti, Marco; Sbaraglia, Marta; Sisto, Andrea; Ferrari, Stefano; Dei Tos, Angelo P; Picci, Piero

    2016-12-01

    The potential prognostic and predictive value of p16 in high-grade localized osteosarcoma of the extremities has been recently investigated in small series of cases, and the results from different studies were somewhat controversial. A retrospective immunohistochemical analysis of p16 expression was performed in a series of 357 patients, included in different neoadjuvant chemotherapy protocols from 1986 to 2010, to explore its potential prognostic and predictive value. Immunohistochemistry was performed with a commercially available p16 monoclonal mouse antibody. Follow-up data were available in all cases with a median of 120 months. Positivity for p16 was detected in 70.6% (252/357) of cases. The p16 expression did not differ by age, sex, tumor site, histologic subtype, tumor volume, surgical margin, serum alkaline phosphatase levels, and lactate dehydrogenase levels. In the different chemotherapy protocols included, the incidence of p16 expression was similar. The absence of p16 expression was significantly associated with an adverse disease-free survival (P=.04) and overall survival (P=.05) when compared with the presence of p16 expression. At the multivariate Cox regression analysis, p16 expression lost its prognostic significance. Multivariate logistic regression analysis showed that as p16 expression was the only statistically significant parameter to predict the pathological response to neoadjuvant chemotherapy treatment with an odds ratio of 3.025 (P<.001) for "good" chemotherapy response. Our data indicate that the negative expression of p16 is associated with a reduced rate of good response to primary chemotherapy and to a worse probability of survival, although it was not confirmed as an independent prognostic biomarker after multivariate analysis.

  3. Telithromycin: review of adverse effects.

    PubMed

    2014-11-01

    Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.

  4. Forkhead box protein A1 is a prognostic predictor and promotes tumor growth of gastric cancer

    PubMed Central

    Ren, Hongyu; Zhang, Pei; Tang, Yong; Wu, Mengping; Zhang, Weikang

    2015-01-01

    Previous studies have demonstrated the cancer-type specific role of forkhead box protein A1 (FOXA1) in human malignancies. However, the clinical significance of FOXA1 and its biological function in gastric cancer remain unknown. In this study, the expression of FOXA1 in 80 pairs of gastric cancer tissues and corresponding non-tumor tissues was analyzed using immunohistochemistry and quantitative real-time polymerase chain reaction. We found that the levels of FOXA1 protein and mRNA in gastric cancer tissues were significantly higher than those in matched tumor-adjacent tissues. Furthermore, clinical association analysis indicated that the positive expression of FOXA1 was associated with adverse clinicopathological characteristics of gastric cancer patients including poor tumor differentiation, large tumor size, and advanced tumor-node-metastasis tumor stage. Notably, gastric cancer patients with positive expression of FOXA1 had a poorer 5-year overall survival and recurrence-free survival. In addition, FOXA1 knockdown remarkably inhibited cell proliferation and induced apoptosis in both SGC-7901 and MGC-803 cells. In vivo studies indicated that FOXA1 knockdown prominently suppressed tumor growth of gastric cancer in a nude mouse xenograft model. Mechanistically, we disclosed that the expression of Yes-associated protein was decreased accordingly after FOXA1 knockdown in both SGC-7901 and MGC-803 cells. Taken together, our data suggest that FOXA1 may serve as a promising prognostic indicator and an attractive therapeutic target of gastric cancer. PMID:26527889

  5. The Significance of the Prognostic Nutritional Index in Patients with Completely Resected Non-Small Cell Lung Cancer

    PubMed Central

    Mori, Shunsuke; Usami, Noriyasu; Fukumoto, Koichi; Mizuno, Tetsuya; Kuroda, Hiroaki; Sakakura, Noriaki; Yokoi, Kohei; Sakao, Yukinori

    2015-01-01

    Objectives Immunological parameters and nutritional status influence the outcome of patients with malignant tumors. A prognostic nutritional index, calculated using serum albumin levels and peripheral lymphocyte count, has been used to assess prognosis for various cancers. This study aimed to investigate whether this prognostic nutritional index affects overall survival and the incidence of postoperative complications in patients with completely resected non-small cell lung cancer. Methods We retrospectively reviewed the medical records of 409 patients with non-small cell lung cancer who underwent complete resection between 2005 and 2007 at the Aichi Cancer Center. Results The 5-year survival rates of patients with high (≥50) and low (<50) prognostic nutritional indices were 84.4% and 70.7%, respectively (p = 0.0011). Univariate analysis showed that gender, histology, pathological stage, smoking history, serum carcinoembryonic antigen levels, and prognostic nutritional index were significant prognostic factors. Multivariate analysis identified pathological stage and the prognostic nutritional index as independent prognostic factors. The frequency of postoperative complications tended to be higher in patients with a low prognostic nutritional index. Conclusions The prognostic nutritional index is an independent prognostic factor for survival of patients with completely resected non-small cell lung cancer. PMID:26356222

  6. 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.

  7. 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.

  8. Analyzing risks of adverse pregnancy outcomes.

    PubMed

    Kramer, Michael S; Zhang, Xun; Platt, Robert W

    2014-02-01

    Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

  9. 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

  10. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia.

    PubMed

    Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell

    2013-10-01

    Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.

  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. Generic Software Architecture for Prognostics (GSAP) User Guide

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

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

  13. Histopathologic Features of Prognostic Significance in High-Grade Osteosarcoma.

    PubMed

    Chui, Michael Herman; Kandel, Rita A; Wong, Marcus; Griffin, Anthony M; Bell, Robert S; Blackstein, Martin E; Wunder, Jay S; Dickson, Brendan C

    2016-08-23

    Context .- In osteosarcoma treated with neoadjuvant chemotherapy the extent of tumor necrosis on resection is considered an indicator of treatment response, and this has been shown to correlate with survival in most but not all studies. Objective .- To identify additional histologic variables of prognostic significance in high-grade osteosarcoma. Design .- Slides of pretreatment biopsy and primary postneoadjuvant chemotherapy resections from 165 patients with high-grade osteosarcoma were reviewed. Univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were performed to identify clinical and histomorphologic attributes associated with overall survival. Results .- Univariate analyses confirmed the prognostic significance of metastatic status on presentation, primary tumor size, anatomic site, and histologic subtype. Additionally, the identification of lymphovascular invasion, 10% or more residual viable tumor, and 10 or more mitoses per 10 high-powered fields assessed in posttreatment resections were associated with poor survival, retaining significance in multivariate analyses. Based on results from multivariate analysis, we developed a prognostic index incorporating primary tumor size and site, and significant histologic features assessed on resection (ie, lymphovascular invasion status, mitotic rate, and extent of viable tumor). This scoring system segregates patients into 3 risk categories with significant differences in overall survival and retained significance in an independent validation set of 42 cases. Conclusions .- The integration of clinical and microscopic features improves prognostication of patients with osteosarcoma.

  14. Clinical characteristics and prognostic factors of brain central neurocytoma

    PubMed Central

    Zhou, Xilei; Tong, Yusuo; Wang, Wanwei

    2016-01-01

    Background & Aims This study is designed for the clinical characteristics and prognostic factors of central neurocytoma (CN). Methods CN patients from 2004 to 2012 were enrolled from the Surveillance Epidemiology and End Results (SEER) data. Clinical characteristics including age, sex, race, tumor size, tumor number, surgery, and radiation therapy were summarized. Univariate and multivariate analysis were performed to explore the prognostic factors of CN. Results CN tended to be borderline malignant and single lesion. Compared with other brain tumor (NCN), Patients with CN (CNs) were more likely to be female, young, and non-white race. Surgery was the primary treatment of CN. Univariate and Multivariate analysis indicated tumor number and surgery were both independent prognostic factors of CN (P < 0.05). Unifocal CNs had a lower mortality risk than multifocal ones (HR 0.167, 95% CI 0.052-0.537), surgery significantly reduced the death risk of CNs (HR 0.284, 95% CI 0.088-0.921). Conclusions CN tend to be borderline malignant, single lesion, operated on. Most CNs are female and younger. single lesion and surgery are the independent positive prognostic factors of CN. PMID:27542237

  15. Specimen banks for cancer prognostic factor research.

    PubMed

    Burke, H B; Henson, D E

    1998-10-01

    Prognostic factors are necessary for determining whether a patient will require therapy, for selecting the optimal therapy, and for evaluating the effectiveness of the therapy chosen. Research in prognostic factors has been hampered by long waiting times and a paucity of outcomes. Specimen banks can solve these problems, but their implementation and use give rise to many important and complex issues. This paper presents an overview of some of the issues related to the use of specimen banks in prognostic factor research.

  16. Rethinking the Measurement of Adversity.

    PubMed

    Mersky, Joshua P; Janczewski, Colleen E; Topitzes, James

    2017-02-01

    Research on adverse childhood experiences (ACEs) has unified the study of interrelated risks and generated insights into the origins of disorder and disease. Ten indicators of child maltreatment and household dysfunction are widely accepted as ACEs, but further progress requires a more systematic approach to conceptualizing and measuring ACEs. Using data from a diverse, low-income sample of women who received home visiting services in Wisconsin ( N = 1,241), this study assessed the prevalence of and interrelations among 10 conventional ACEs and 7 potential ACEs: family financial problems, food insecurity, homelessness, parental absence, parent/sibling death, bullying, and violent crime. Associations between ACEs and two outcomes, perceived stress and smoking, were examined. The factor structure and test-retest reliability of ACEs was also explored. As expected, prevalence rates were high compared to studies of more representative samples. Except for parent/sibling death, all ACEs were intercorrelated and associated at the bivariate level with perceived stress and smoking. Exploratory factor analysis confirmed that conventional ACEs loaded on two factors, child maltreatment and household dysfunction, though a more complex four-factor solution emerged once new ACEs were introduced. All ACEs demonstrated acceptable test-retest reliability. Implications and future directions toward a second generation of ACE research are discussed.

  17. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

    PubMed

    Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

    2011-06-01

    A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

  18. 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.

  19. Clinicians' recognition of the metabolic adverse effects of antipsychotic medications.

    PubMed

    Buckley, Peter F; Miller, Del D; Singer, Beth; Arena, John; Stirewalt, Edna M

    2005-11-15

    There is a growing concern regarding the propensity of second generation antipsychotics (SGAs) to induce weight gain and metabolic adverse effects. Recent consensus guidelines have recommended assessment and monitoring procedures to appropriately detect and manage these adverse effects. This study addresses the appreciation and readiness of clinicians to implement management guidelines for these adverse effects. Respondents indicated awareness of the risks of treatment with SGAs. The extent of monitoring for metabolic adverse effects was low and inconsistent across measures and in frequency of evaluation. Ongoing efforts are needed to support and encourage change in clinician practice.

  20. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment.

  1. Reporting hospital adverse events using the Alfred Hospital's morbidity data.

    PubMed

    Carroll, Rhonda; McLean, Jenny; Walsh, Michael

    2003-01-01

    Hospital morbidity data were analysed to determine their usefulness for reporting adverse events. The entire ICD-10-AM classification system was reviewed in conjunction with the Australian Coding Standards to identify external cause codes and code prefixes associated with adverse events. For the 50,712 separations registered at The Alfred from July 2000-June 2001, 4,740 external cause codes were associated with adverse events. Place of occurrence code CY92.22 was considered the best indicator of the number of separations associated with adverse events. Approximately 4% of all separations were associated with adverse events occurring during an episode of care. Results suggest that hospital morbidity data are useful for monitoring adverse events at hospital level. Reliable reporting across the health care industry requires consistent reporting requirements at state and national levels and the adoption of standard code prefixes nationally.

  2. 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.

  3. 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

  4. Prognostic significance of tumour stroma ratio in inflammatory breast cancer.

    PubMed

    Downey, Candice L; Thygesen, Helene H; Sharma, Nisha; Shaaban, Abeer M

    2015-01-01

    Tumour stroma ratio (TSR) is emerging as an important prognostic indicator in cancer. We have previously shown TSR to be prognostic in oestrogen receptor positive breast cancer. Its role in inflammatory breast cancer, a rare but aggressive form of breast cancer, has not been identified. Here we aimed to determine the prognostic significance of TSR in a cohort of patients with inflammatory breast carcinoma. TSR was measured by point counting virtual H&E stained tissue sections in 45 inflammatory breast cancer cases. The whole tumour area was sampled. Optimum cut-offs to distinguish high and low TSR was determined by log-rank test. The relationship of TSR to overall survival and disease-free survival (DFS) was analysed alongside multivariate analysis. The optimal cut-offs between high and low TSR were determined to be 31% for OS and 46% for DFS. There was no significant difference in OS (p = 0.53) nor DFS (p = 0.66) between high and low TSR groups. Multivariate analysis did not demonstrate any new trends, within the limits of a small data sample. A significant correlation was found between pathological response to neoadjuvant chemotherapy and survival (p = 0.008). There is no evidence that TSR has prognostic significance in inflammatory breast cancer. When compared with published data in non-inflammatory breast carcinoma, this supports the view that differences in stromal biology exist between tumour types and highlights the importance of considering this when interpreting the prognostic value of TSR. However, these findings must be interpreted in the light of the small sample size.

  5. Cutaneous adverse reactions to lenalidomide.

    PubMed

    Imbesi, S; Allegra, A; Calapai, G; Musolino, C; Gangemi, S

    2015-01-01

    Lenalidomide is an immunomodulatory drug (IMiD) used principally in the treatment of multiple myeloma (MM), myelodysplastic syndromes (MS) and amyloidosis. Adverse reactions related to lenalidomide include myelosuppression (mainly neutropenia but also thrombocytopenia), gastrointestinal problems, skin eruption, atrial fibrillation and asthenia, decreased peripheral blood stem cell yield during stem cell collection, venous thromboembolism, and secondary malignances. In this review we focused our attention on the cutaneous adverse reactions to lenalidomide.

  6. 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.

  7. 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

  8. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  9. [Prognostic study of liver abscess].

    PubMed

    Nouira, Ramzi; Bedoui, Riadh; Miaadi, Naoufel; Guesmi, Fethi; Ben Achour, Jamel; Hani, Mohamed; Daghfous, Mounir; Ben Osman, Samia; Zoghlami, Ayoub; Najah, Nabil

    2003-04-01

    The objective of this work is to study factors of prognostic of mortality of abscesses of the liver. We have treated between 1990 and 2000 in our service, 38 patient for abscess of the liver. The symptoms are dominated by the pain of the right hypochondria (37 cases) and the fever (34 cases). An unique abscess has been recovered in 25 cases. Some multiple localizations have been observed in 12 cases. 21 patients have been operated. The bacteriological study at all patients revealed the presence of germ in 27 cases. In 6 cases, there were two germs. It was a bacillus negative gram in 26 cases and a cocci positive gram in 7 cases. Six complications have been observed at the operated patients. In 5 cases, it was a septic shock having leads to the death. After survey univariate and multivariate the only factor of bad prognostic recovered is the septic shock. The aetiology was identified in only 9 cases; it was abscess cholangiotis.

  10. 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.

  11. 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

  12. Dynamic assessment of RBC-transfusion dependency improves the prognostic value of the revised-IPSS in MDS patients.

    PubMed

    Hiwase, Devendra K; Singhal, Deepak; Strupp, Corinna; Chhetri, Rakchha; Kutyna, Monika M; Wee, L Amilia; Harrison, Peter B; Nath, Shriram V; Wickham, Nicholas; Hui, Chi-Hung; Gray, James X; Bardy, Peter; Ross, David M; Lewis, Ian D; Reynolds, John; To, L Bik; Germing, Ulrich

    2017-03-01

    RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R. We analyzed MDS patients not treated with disease-modifying therapy, and enrolled in SA-MDS Registry (derivation cohort; n = 295) and Dusseldorf registry (Germany; validation cohort; n = 113) using time-dependent Cox proportional regression and serial landmark analyses. In the derivation cohort, RBC-TD patients had inferior OS compared to RBC transfusion-independent (RBC-TI) patients (P < 0.0001) at 6- (18 vs. 64 months), 12- (24 vs. 71 months), and 24-months (40 vs. 87 months). In a Cox proportional regression analysis, RBC-TD was an independent adverse prognostic marker in addition to age, sex, and IPSS-R variables (P < 0.0001). A prognostic index (PI) was derived using these Cox-proportional regression model variables. In the validation cohort, this PI classified patients into four prognostic groups with significantly different OS (P < 0.001) as in the derivation cohort. In conclusion, multivariate analysis by Cox proportional hazards regression and serial landmark analyses clearly demonstrates that development of RBC-TD at any time during the course of MDS is associated with poor OS, independent of IPSS-R. This study demonstrates that dynamic assessment of RBC-TD provides additional prognostic value to IPSS-R and should be included in treatment decision algorithms for MDS patients.

  13. 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.

  14. 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.

  15. Prognostic value of normal adenosine-stress cardiac magnetic resonance imaging.

    PubMed

    Pilz, Guenter; Jeske, Andrea; Klos, Markus; Ali, Eman; Hoefling, Berthold; Scheck, Roland; Bernhardt, Peter

    2008-05-15

    We investigated the prognostic value of normal adenosine stress cardiac magnetic resonance (CMR) in suspected coronary artery disease (CAD). Prospectively enrolled in the study were 218 patients with suspected CAD, no stress hypoperfusion, and no delayed enhancement in CMR, and consecutively deferred coronary angiography. The primary end point was a 12-month rate of major adverse cardiac events (MACE; cardiovascular mortality, myocardial infarction, revascularization, hospitalization due to cardiovascular event). CMR indication was symptomatic angina (Canadian Cardiovascular Society II in 42% and III in 7%) or evaluation of myocardial ischemia in patients with arrhythmia, syncope, and/or equivocal stress tests and cardiovascular risk factors (51%). As the main result, the 12-month MACE rate was 2/218 (1 stent implantation, 1 bypass surgery) and CMR negative predictive value 99.1%. There was no cardiac death or myocardial infarction. In conclusion, normal adenosine stress CMR predicts a very low MACE rate and an excellent 1-year prognosis in patients with suspected CAD. Our results provide clinical reassurance that patients at risk for CAD-associated MACE were not missed by CMR. Hence, CMR may serve as a reliable noninvasive gatekeeper to reduce the number of redundant coronary angiographies.

  16. 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.

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

    PubMed

    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

    2015-06-01

    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

  18. 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.

  19. Summary Report on the Graded Prognostic Assessment: An Accurate and Facile Diagnosis-Specific Tool to Estimate Survival for Patients With Brain Metastases

    PubMed Central

    Sperduto, Paul W.; Kased, Norbert; Roberge, David; Xu, Zhiyuan; Shanley, Ryan; Luo, Xianghua; Sneed, Penny K.; Chao, Samuel T.; Weil, Robert J.; Suh, John; Bhatt, Amit; Jensen, Ashley W.; Brown, Paul D.; Shih, Helen A.; Kirkpatrick, John; Gaspar, Laurie E.; Fiveash, John B.; Chiang, Veronica; Knisely, Jonathan P.S.; Sperduto, Christina Maria; Lin, Nancy; Mehta, Minesh

    2012-01-01

    Purpose Our group has previously published the Graded Prognostic Assessment (GPA), a prognostic index for patients with brain metastases. Updates have been published with refinements to create diagnosis-specific Graded Prognostic Assessment indices. The purpose of this report is to present the updated diagnosis-specific GPA indices in a single, unified, user-friendly report to allow ease of access and use by treating physicians. Methods A multi-institutional retrospective (1985 to 2007) database of 3,940 patients with newly diagnosed brain metastases underwent univariate and multivariate analyses of prognostic factors associated with outcomes by primary site and treatment. Significant prognostic factors were used to define the diagnosis-specific GPA prognostic indices. A GPA of 4.0 correlates with the best prognosis, whereas a GPA of 0.0 corresponds with the worst prognosis. Results Significant prognostic factors varied by diagnosis. For lung cancer, prognostic factors were Karnofsky performance score, age, presence of extracranial metastases, and number of brain metastases, confirming the original Lung-GPA. For melanoma and renal cell cancer, prognostic factors were Karnofsky performance score and the number of brain metastases. For breast cancer, prognostic factors were tumor subtype, Karnofsky performance score, and age. For GI cancer, the only prognostic factor was the Karnofsky performance score. The median survival times by GPA score and diagnosis were determined. Conclusion Prognostic factors for patients with brain metastases vary by diagnosis, and for each diagnosis, a robust separation into different GPA scores was discerned, implying considerable heterogeneity in outcome, even within a single tumor type. In summary, these indices and related worksheet provide an accurate and facile diagnosis-specific tool to estimate survival, potentially select appropriate treatment, and stratify clinical trials for patients with brain metastases. PMID:22203767

  20. 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…

  1. 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

  2. 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

  3. Reverse engineering adverse outcome pathways.

    PubMed

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

    2011-01-01

    The toxicological effects of many stressors are mediated through unknown, or incompletely characterized, mechanisms of action. The application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) can be used to overcome these limitations. This approach was used to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows (FHM, Pimephales promelas). Gene expression changes in FHM ovaries in response to seven different chemicals, over different times, doses, and in vivo versus in vitro conditions, were captured in a large data set of 868 arrays. Potential AOPs of the antiandrogen flutamide were examined using two mutual information-based methods to infer gene regulatory networks and potential AOPs. Representative networks from these studies were used to predict network paths from stressor to adverse outcome as candidate AOPs. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment, thus leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biological processes, biomarkers, or alternative endpoints that can be used to monitor an AOP. Finally, the unique challenges facing the application of this approach in ecotoxicology were identified and a road map for the utilization of these tools presented.

  4. Prognostic nutritional index as a prognostic biomarker for survival in digestive system carcinomas

    PubMed Central

    Zhao, Yang; Xu, Peng; Kang, Huafeng; Lin, Shuai; Wang, Meng; Yang, Pengtao; Dai, Cong; Liu, Xinghan; Liu, Kang; Zheng, Yi; Dai, Zhijun

    2016-01-01

    The prognostic nutritional index (PNI) has been reported to correlate with the prognosis in patients with various malignancies. We performed a meta-analysis to determine the predictive potential of PNI in digestive system cancers. Twenty-three studies with a total of 7,384 patients suffering from digestive system carcinomas were involved in this meta-analysis. A lower PNI was significantly associated with the shorter overall survival (OS) [Hazard Ratio (HR) 1.83, 95% Confidence Interval (CI) 1.62–2.07], the poorer disease-free survival (DFS) (HR 1.85, 95% CI 1.19–2.89), and the higher rate of post-operative complications (HR 2.31, 95% CI 1.63–3.28). In conclusion, PNI was allowed to function as an efficient indicator for the prognosis of patients with digestive system carcinomas. PMID:27888808

  5. Statin-Associated Muscle Adverse Events

    PubMed Central

    Al-Mohaissen, Maha A.; Ignaszewski, Martha J.; Frohlich, Jiri; Ignaszewski, Andrew P.

    2016-01-01

    Statins are potent medications which reduce low-density lipoprotein cholesterol (LDL-C) levels. Their efficacy in cardiovascular risk reduction is well established and indications for their use are expanding. While statins are generally well tolerated and safe, adverse events are relatively common, particularly statin-associated muscle adverse events (SaMAEs), which are the most frequently encountered type of adverse event. Recent guidelines and guideline updates on SaMAEs and statin intolerance have included revised definitions of SaMAEs, incorporating new evidence on their pathogenesis and management. As SaMAEs emerge as a therapeutic challenge, it is important for physicians to be aware of updates on management strategies to ensure better patient outcomes. The majority of patients who are considered statin-intolerant can nevertheless tolerate some forms of statin therapy and successfully achieve optimal LDL-C levels. This review article discusses the recent classification of SaMAEs with emphasis on pathogenesis and management strategies. PMID:28003885

  6. Combating adverse selection in secondary PC markets.

    PubMed

    Hickey, Stewart W; Fitzpatrick, Colin

    2008-04-15

    Adverse selection is a significant contributor to market failure in secondary personal computer (PC) markets. Signaling can act as a potential solution to adverse selection and facilitate superior remarketing of second-hand PCs. Signaling is a means whereby usage information can be utilized to enhance consumer perception of both value and utility of used PCs and, therefore, promote lifetime extension for these systems. This can help mitigate a large portion of the environmental impact associated with PC system manufacture. In this paper, the computer buying and selling behavior of consumers is characterized via a survey of 270 Irish residential users. Results confirm the existence of adverse selection in the Irish market with 76% of potential buyers being unwilling to purchase and 45% of potential vendors being unwilling to sell a used PC. The so-called "closet affect" is also apparent with 78% of users storing their PC after use has ceased. Results also indicate that consumers place a higher emphasis on specifications when considering a second-hand purchase. This contradicts their application needs which are predominantly Internet and word-processing/spreadsheet/presentation applications, 88% and 60% respectively. Finally, a market solution utilizing self monitoring and reporting technology (SMART) sensors for the purpose of real time usage monitoring is proposed, that can change consumer attitudes with regard to second-hand computer equipment.

  7. Adverse childhood experiences and health anxiety in adulthood.

    PubMed

    Reiser, Sarah J; McMillan, Katherine A; Wright, Kristi D; Asmundson, Gordon J G

    2014-03-01

    Childhood experiences are thought to predispose a person to the development of health anxiety later in life. However, there is a lack of research investigating the influence of specific adverse experiences (e.g., childhood abuse, household dysfunction) on this condition. The current study examined the cumulative influence of multiple types of childhood adversities on health anxiety in adulthood. Adults 18-59 years of age (N=264) completed a battery of measures to assess adverse childhood experiences, health anxiety, and associated constructs (i.e., negative affect and trait anxiety). Significant associations were observed between adverse childhood experiences, health anxiety, and associated constructs. Hierarchical multiple regression analysis indicted that adverse childhood experiences were predictive of health anxiety in adulthood; however, the unique contribution of these experience were no longer significant following the inclusion of the other variables of interest. Subsequently, mediation analyses indicated that both negative affect and trait anxiety independently mediated the relationship between adverse childhood experiences and health anxiety in adulthood. Increased exposure to adverse childhood experiences is associated with higher levels of health anxiety in adulthood; this relationship is mediated through negative affect and trait anxiety. Findings support the long-term negative impact of cumulative adverse childhood experiences and emphasize the importance of addressing negative affect and trait anxiety in efforts to prevent and treat health anxiety.

  8. 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

    Li, Ling; Xu-Monette, Zijun Y; Ok, Chi Young; Tzankov, Alexandar; Manyam, Ganiraju C; Sun, Ruifang; 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, Jinfen; Parsons, Ben M; Winter, Jane N; Piris, Miguel A; Pham, Lan V; Medeiros, L Jeffrey; Young, Ken H

    2015-09-15

    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.

  9. Prognostic markers of acute decompensated heart failure: the emerging roles of cardiac biomarkers and prognostic scores.

    PubMed

    Cohen-Solal, Alain; Laribi, Said; Ishihara, Shiro; Vergaro, Giuseppe; Baudet, Mathilde; Logeart, Damien; Mebazaa, Alexandre; Gayat, Etienne; Vodovar, Nicolas; Pascual-Figal, Domingo A; Seronde, Marie-France

    2015-01-01

    Rapidly assessing outcome in patients with acute decompensated heart failure is important but prognostic factors may differ from those used routinely for stable chronic heart failure. Multiple plasma biomarkers, besides the classic natriuretic peptides, have recently emerged as potential prognosticators. Furthermore, prognostic scores that combine clinical and biochemical data may also be useful. However, compared with the scores used in chronic heart failure, scores for acute decompensated heart failure have not been validated. This article reviews potential biomarkers, with a special focus on biochemical biomarkers, and possible prognostic scores that could be used by the clinician when assessing outcome in patients with acute heart failure.

  10. Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma

    PubMed Central

    Bossi, Paolo; Resteghini, Carlo; Paielli, Nicholas; Licitra, Lisa; Pilotti, Silvana; Perrone, Federica

    2016-01-01

    EGFR is an extensively studied biomarker in head and neck squamous cell carcinoma (HNSCC). In this review, we discuss the prognostic and predictive role of EGFR in HNSCC, focusing on the different molecular alterations in specific treatment modalities such as radiotherapy alone (RT), combination of surgery, RT and chemotherapy (CT), EGFR inhibitors. We considered EGFR at different molecular levels: protein expression, protein activation, gene copy number, polymorphisms, mutation, EGFRvIII expression and EGFR ligand expression. Considering RT alone, evidence supports the predictive and prognostic role of high EGFR expression only when evaluated by quantitative assays: this may help select the patients who can mostly benefit from accelerated treatment. Conversely, no predictive biomarkers are available when treatment is a combination of surgery, CT and RT. For this combined treatment, several studies indicate that EGFR expression represents a good prognostic parameter only when measured by a “quantitative” or at least semi-quantitative method. With respect to EGFR inhibitors, neither EGFR expression nor increased gene copy number represent prognostic/predictive factors. If validated, nuclear EGFR, TGFα levels, EGFR phopshorylation and polymorphisms could represent additional prognostic factors in relation to combination of surgery, CT and RT, while EGFR polymorphisms and high amphiregulin levels could have prognostic value in patients treated with EGFR inhibitors. PMID:27556186

  11. 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

  12. Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Park, Jae-Hyeong; Park, Margaret M.; Farha, Samar; Sharp, Jacqueline; Lundgrin, Erika; Comhair, Suzy; Tang, Wai Hong; Erzurum, Serpil C.

    2015-01-01

    Background New 2-dimensional strain echocardiography enables quantification of right ventricular (RV) mechanics by assessing global longitudinal strain of RV (GLSRV) in patients with pulmonary arterial hypertension (PAH). However, the prognostic significance of impaired GLSRV is unclear in these patients. Methods Comprehensive echocardiography was performed in 51 consecutive PAH patients without atrial fibrillation (40 females, 48 ± 14 years old) with long-term follow-up. GLSRV was measured with off-line with velocity vector imaging (VVI, Siemens Medical System, Mountain View, CA, USA). Results GLSRV showed significant correlation with RV fractional area change (r = -0.606, p < 0.001), tricuspid annular plane systolic excursion (r = -0.579, p < 0.001), and RV Tei index (r = 0.590, p < 0.001). It showed significant correlations with pulmonary vascular resistance (r = 0.469, p = 0.001) and B-natriuretic peptide concentration (r = 0.351, p = 0.012). During a clinical followup time (45 ± 15 months), 20 patients experienced one or more adverse events (12 death, 2 lung transplantation, and 15 heart failure hospitalization). After multivariate analysis, age [hazard ratio (HR) = 2.343, p = 0.040] and GLSRV (HR = 2.122, p = 0.040) were associated with adverse clinical events. Age (HR = 3.200, p = 0.016) and GLSRV (HR = 2.090, p = 0.042) were also significant predictors of death. Impaired GLSRV (≥ -15.5%) was associated with lower event-free survival (HR = 4.906, p = 0.001) and increased mortality (HR = 8.842, p = 0.005). Conclusion GLSRV by VVI showed significant correlations with conventional echocardiographic parameters indicating RV systolic function. Lower GLSRV (≥ -15.5%) was significantly associated with presence of adverse clinical events and deaths in PAH patients. PMID:26140151

  13. Diagnostic and Prognostic Biomarkers in Melanoma

    PubMed Central

    Leininger, Jennifer; Hamby, Carl; Safai, Bijan

    2014-01-01

    Melanoma is a lethal melanocytic neoplasm. Unfortunately, the histological diagnosis can be difficult at times. Distinguishing ambiguous melanocytic neoplasms that are benign nevi from those that represent true melanoma is important both for treatment and prognosis. Diagnostic biomarkers currently used to assist in the diagnosis of melanoma are usually specific only for melanocytic neoplasms and not necessarily for their ability to metastasize. Traditional prognostic biomarkers include depth of invasion and mitotic count. Newer diagnostic and prognostic biomarkers utilize immunohistochemical staining as well as ribonucleic acid, micro-ribonucleic acid, and deoxyribonucleic acid assays and fluorescence in situ hybridization. Improved diagnostic and prognostic biomarkers are of increasing importance in the treatment of melanoma with the development of newer and more targeted therapies. Herein, the authors review many of the common as well as newer diagnostic and prognostic biomarkers used in melanoma. PMID:25013535

  14. Clinicopathological Features and Prognostic Factors of Colorectal Neuroendocrine Neoplasms

    PubMed Central

    Jiang, Mengjie; Tan, Yinuo; Li, Xiaofen; Fu, Jianfei; Hu, Hanguang; Ye, Xianyun; Cao, Ying; Xu, Jinghong

    2017-01-01

    Background. Limited research is available regarding colorectal NENs and the prognostic factors remain controversial. Materials and Methods. A total of 68 patients with colorectal NENs were studied retrospectively. Clinical characteristics and prognosis between colonic and rectal NENs were compared. The Cox regression models were used to evaluate the predictive capacity. Results. Of the 68 colorectal NENs patients, 43 (63.2%) had rectal NENs, and 25 (36.8%) had colonic NENs. Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size (P < 0.0001) and distant metastasis (P < 0.0001). Colonic NENs had a worse prognosis (P = 0.027), with 5-year overall survival rates of 66.7% versus 88.1%. NET, NEC, and MANEC were noted in 61.8%, 23.5%, and 14.7% of patients, respectively. Multivariate analyses revealed that tumor location was not an independent prognostic factor (P = 0.081), but tumor size (P = 0.037) and pathological classification (P = 0.012) were independent prognostic factors. Conclusion. Significant differences exist between colonic and rectal NENs. Multivariate analysis indicated that tumor size and pathological classification were associated with prognosis. Tumor location was not an independent factor. The worse outcome of colonic NENs observed in clinical practice might be due not only to the biological differences, but also to larger tumor size in colonic NENs caused by the delayed diagnosis. PMID:28194176

  15. A prognostic gene expression signature in infratentorial ependymoma.

    PubMed

    Wani, Khalida; Armstrong, Terri S; Vera-Bolanos, Elizabeth; Raghunathan, Aditya; Ellison, David; Gilbertson, Richard; Vaillant, Brian; Goldman, Stewart; Packer, Roger J; Fouladi, Maryam; Pollack, Ian; Mikkelsen, Tom; Prados, Michael; Omuro, Antonio; Soffietti, Riccardo; Ledoux, Alicia; Wilson, Charmaine; Long, Lihong; Gilbert, Mark R; Aldape, Ken

    2012-05-01

    Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.

  16. Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer

    PubMed Central

    2012-01-01

    Background Results from large epidemiologic studies on the association between vitamin D and gastric cancer are controversial. Vitamin D significantly promotes apoptosis in the undifferentiated gastric cancer cell, but the prognostic effects of its levels are unknown. Methods 197 gastric carcinoma patients who received treatment in the cancer centre of Sun Yat-sen University from January 2002 to January 2006 were involved in the study. The stored blood drawn before any treatment was assayed for 25-hydroxyvitamin D levels. The clinicopathologic data were collected to examine the prognostic effects of vitamin D. Results The mean vitamin D levels of the 197 gastric patients was 49.85 ± 23.68 nmol/L, among whom 114(57.9%) were deficient in Vitamin D(< 50 nmol/L), 67(34%) were insufficient (50-75 nmol/L) and 16(8.1%) were sufficient (> 75 nmol/L). Clinical stage (P = 0.004) and lymph node metastasis classification (P = 0.009) were inversely associated with vitamin D levels. The patients with high vitamin D levels group (≥ 50 nmol/L) had a higher overall survival compared with the low vitamin D levels group (< 50 nmol/L)(P = 0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (P = 0.019). Conclusions Vitamin D deficiency may be associated with poor prognosis in gastric cancer. PMID:22284859

  17. Diagnosis of potential stressors adversely affecting benthic ...

    EPA Pesticide Factsheets

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was impaired. Second, the presence of source, stressor, and effect were established. Then linkages between source, stressor, and effect were developed. This allows identification of probable stressors adversely affecting the waterbody. Three pollutant categories were assessed: chemicals, nutrients, and suspended sediments. This weight of evidence approach indicated that Greenwich Bay was primarily impacted by eutrophication-related stressors. The sediments of Greenwich Bay were carbon enriched and low dissolved oxygen concentrations were commonly seen, especially in the western portions of Greenwich Bay. The benthic community was depauperate, as would be expected under oxygen stress. Although our analysis indicated that contaminant loads in Greenwich Bay were at concentrations where adverse effects might be expected, no toxicity was observed, as a result of high levels of organic carbon in these sediments reducing contaminant bioavailability. Our analysis also indicated that suspended sediment impacts were likely nonexistent for much of the Bay. This analysis demonstrates that the diagnostic procedure was useful to organize and assess the potential stressors impacting the ecological well-being

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Adverse drug reactions: part II.

    PubMed

    Wooten, James M

    2010-11-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.

  4. Adverse drug reactions: Part I.

    PubMed

    Wooten, James M

    2010-10-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must effectively be practiced by all health providers in order to avoid ADRs.

  5. Prognostic Implication of the QRS Axis and its Association with Myocardial Scarring in Patients with Left Bundle Branch Block

    PubMed Central

    Park, Chan Soon; Cha, Myung-jin; Choi, Eue-Keun

    2017-01-01

    Background and Objectives Left bundle branch block (LBBB) with left axis deviation (LAD) has a worse prognosis than LBBB with a normal axis, and myocardial dysfunction has been suggested as a cause of left axis deviation. This study investigated the prognostic significance of the QRS axis in patients with LBBB and analyzed its relationship with the amount of myocardial scarring. Subjects and Methods A total of 829 patients were diagnosed with LBBB at Seoul National University Hospital from October 2004 to June 2014. Of these, 314 who were asymptomatic and had no previous history of cardiac disease were included in the present study. Myocardial scarring was calculated using the Selvester QRS scoring system, and LAD was defined as a QRS axis between -180° and -30°. Results Of the total patients, 91 (29%) had LAD, and patients were followed for a median of 30 months. During follow-up, two patients were hospitalized for de novo heart failure, four had pacemaker implants, and 10 died. There was a significant inverse correlation between myocardial scar score and the QRS axis (r=-0.356, p<0.001). Patients with concomitant LAD had a higher rate of major cardiac adverse events compared with patients with a normal axis (5.5% vs. 1.3%, log-rank p=0.010); the prognostic value was attenuated in multivariable analysis (hazard ratio 4.117; 95% confidence interval 0.955-17.743; p=0.058). Conclusion Concomitant LAD is an indicator of poor prognosis for patients with LBBB and may be associated with greater myocardial scarring. PMID:28382083

  6. Prognostic Value of Splenic Artery Invasion in Patients Undergoing Adjuvant Chemoradiotherapy after Distal Pancreatectomy for Pancreatic Adenocarcinoma

    PubMed Central

    Kim, Byoung Hyuck; Kim, Kyubo; Chie, Eui Kyu; Jang, Jin-Young; Kim, Sun Whe; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Joo, Ijin; Ha, Sung W.

    2015-01-01

    Purpose The purpose of this study was to evaluate the outcome of adjuvant chemoradiotherapy (CRT) after distal pancreatectomy (DP) in patients with pancreatic adenocarcinoma, and to identify the prognostic factors for these patients. Materials and Methods We performed a retrospective review of 62 consecutive patients who underwent curative DP followed by adjuvant CRT between 2000 and 2011. There were 31 men and 31 women, and the median age was 64 years (range, 38 to 80 years). Adjuvant radiotherapy was delivered to the tumor bed and regional lymph nodes with a median dose of 50.4 Gy (range, 40 to 55.8 Gy). All patients received concomitant chemotherapy, and 53 patients (85.5%) also received maintenance chemotherapy. The median follow-up period was 24 months. Results Forty patients (64.5%) experienced relapse. Isolated locoregional recurrence developed in 5 patients (8.1%) and distant metastasis in 35 patients (56.5%), of whom 13 had both locoregional recurrence and distant metastasis. The median overall survival (OS) and disease-free survival (DFS) were 37.5 months and 15.4 months, respectively. On multivariate analysis, splenic artery (SA) invasion (p=0.0186) and resection margin (RM) involvement (p=0.0004) were identified as significant adverse prognosticators for DFS. Also, male gender (p=0.0325) and RM involvement (p=0.0007) were associated with a significantly poor OS. Grade 3 or higher hematologic and gastrointestinal toxicities occurred in 22.6% and 4.8% of patients, respectively. Conclusion Adjuvant CRT may improve survival after DP for pancreatic body or tail adenocarcinoma. Our results indicated that SA invasion was a significant factor predicting inferior DFS, as was RM involvement. When SA invasion is identified preoperatively, neoadjuvant treatment may be considered. PMID:25544574

  7. Diagnostic and Prognostic Value of Lead aVR During Exercise Testing in Patients Suspected of Having Myocardial Ischemia.

    PubMed

    Wagener, Max; Abächerli, Roger; Honegger, Ursina; Schaerli, Nicolas; Prêtre, Gil; Twerenbold, Raphael; Puelacher, Christian; Sunier, Germaine; Reddiess, Philipp; Rubini Gimenez, Maria; Wildi, Karin; Boeddinghaus, Jasper; Nestelberger, Thomas; Badertscher, Patrick; Sabti, Zaid; Schmid, Ramun; Leber, Remo; Widmer, Dayana Flores; Shrestha, Samyut; Strebel, Ivo; Wild, Damian; Osswald, Stefan; Zellweger, Michael; Mueller, Christian; Reichlin, Tobias

    2017-01-05

    We aimed to assess the diagnostic and prognostic value of ST-segment deviation in aVR, a lead often ignored in clinical practice, during exercise testing and to compare it to the most widely used criterion of ST-segment depression in V5. We enrolled 1,596 patients with suspected myocardial ischemia referred for nuclear perfusion imaging undergoing bicycle stress testing. ST-segment amplitudes in leads aVR and V5 were automatically measured. The presence of inducible myocardial ischemia was the diagnostic end point and adjudicated based on nuclear perfusion imaging and coronary angiography. Major adverse cardiac events (MACE) during 2 years of follow-up including death, acute myocardial infarction, and coronary revascularization were the prognostic end point. Exercise-induced myocardial ischemia was detected in 470 patients (29%). Median ST amplitudes for leads aVR and V5 differed significantly among patients with and without ischemia (p <0.01). The diagnostic accuracy of ST changes for myocardial ischemia as quantified by the area under the receiver operating characteristic curve was highest 2 minutes into recovery and similar in aVR and V5 (0.62, 95% confidence interval CI 0.60 to 0.65 vs 0.60, 95% confidence interval 0.58 to 0.63, p = 0.08 for comparison). In multivariate analysis, ST changes in lead aVR, but not lead V5, contributed independent diagnostic information on top of clinical parameters and manual electrocardiographic interpretation. Within 2 years of follow-up, MACE occurred in 33% of patients with ST elevations in aVR and in 16% without (p <0.001). In conclusion, ST elevation in lead aVR during exercise testing indicates inducible myocardial ischemia independently of ST depressions in lead V5 and clinical factors and also predicts MACE during follow-up.

  8. [Finasteride adverse effects: An update].

    PubMed

    Carreño-Orellana, Néstor; Moll-Manzur, Catherina; Carrasco-Zuber, Juan Eduardo; Álvarez-Véliz, Sergio; Berroeta-Mauriziano, Daniela; Porras-Kusmanic, Ninoska

    2016-12-01

    Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

  9. 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.

  10. 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

  11. Cryocooler Prognostic Health Management System

    NASA Astrophysics Data System (ADS)

    Shah, A.; Penswick, L.; Dodson, C.; Roberts, T.

    2008-03-01

    High performance sensors are playing an increasingly important role in all aspects of all critical DoD missions. There is a family of sensors that operate with improved sensitivities if cooled to very low (cryogenic) temperatures. For these sensors, a healthy and reliable mechanical refrigeration system (cryocooler) is required. The ability to accurately predict the "health" or remaining useful life of the cryocooler has significant benefits from the viewpoint of ensuring that mission critical functions can be carried out with a high probability of success. The paper provides an overview and approaches used for the development of a Cryocooler Prognostic Health Management System (CPHMS) capable of assessing the cryocooler "health" from the viewpoint of the level of performance degradation and/or the potential for near term failure. Additionally, it quantifies the reliable remaining useful life of the cryocooler. While the proposed system is focused on the specific application to linear drive cryocoolers, especially for DoD, many of the attributes of the system can be applied to other specialized system hardware in both commercial and U.S. Government agency for situations where it is critical that all aspects of the hardware "health" and "remaining useful life" be fully understood. Several benefits of the health monitoring system are also described in the paper.

  12. Circulating plasma cells in newly diagnosed symptomatic multiple myeloma as a possible prognostic marker for patients with standard-risk cytogenetics.

    PubMed

    Vagnoni, Davide; Travaglini, Fosco; Pezzoni, Valerio; Ruggieri, Miriana; Bigazzi, Catia; Dalsass, Alessia; Mestichelli, Francesca; Troiani, Emanuela; Falcioni, Sadia; Mazzotta, Serena; Natale, Annalisa; Angelini, Mario; Ferretti, Silvia; Angelini, Stefano; Galieni, Piero

    2015-08-01

    Detection of circulating plasma cells (PCs) in multiple myeloma (MM) patients is a well-known prognostic factor. We evaluated circulating PCs by flow cytometry (FC) in 104 patients with active MM at diagnosis by gating on CD38(+)  CD45(-) cells and examined their relationship with cytogenetic risk. Patients had an average follow-up of 36 months. By using a receiver operating characteristics analysis, we estimated the optimal cut-off of circulating PCs for defining poor prognosis to be 41. Patients with high-risk cytogenetics (n = 24) had poor prognosis, independently of circulating PC levels [PC < 41 vs. PC ≥ 41: overall survival (OS) = 0% vs. OS = 17%, P = not significant (n.s.); progression-free survival (PFS) = 0% vs. 17%, P = n.s.]. Patients with standard-risk cytogenetics (n = 65) showed a better prognosis when associated with a lower number of circulating PCs (PC < 41 vs. PC ≥ 41: OS = 62% vs. 24%, P = 0·008; PFS = 48% vs. 21%, P = 0·001). Multivariate analysis on the subgroup with standard-risk cytogenetics confirmed that the co-presence of circulating PCs ≥ 41, older age, Durie-Salmon stage >I and lack of maintenance adversely affected PFS, while OS was adversely affected only by lactate dehydrogenase, older age and lack of maintenance. Our results indicate that the quantification of circulating PCs by a simple two-colour FC analysis can provide useful prognostic information in newly diagnosed MM patients with standard-risk cytogenetics.

  13. Phosphorylation of GSK3α/β correlates with activation of AKT and is prognostic for poor overall survival in acute myeloid leukemia patients

    PubMed Central

    Ruvolo, Peter P.; Qiu, YiHua; Coombes, Kevin R.; Zhang, Nianxiang; Neeley, E. Shannon; Ruvolo, Vivian R.; Hail, Numsen; Borthakur, Gautam; Konopleva, Marina; Andreeff, Michael; Kornblau, Steven M.

    2015-01-01

    Background Acute myeloid leukemia (AML) patients with highly active AKT tend to do poorly. Cell cycle arrest and apoptosis are tightly regulated by AKT via phosphorylation of GSK3α and β isoforms which inactivates these kinases. In the current study we examine the prognostic role of AKT mediated GSK3 phosphorylation in AML. Methods We analyzed GSK3α/β phosphorylation by reverse phase protein analysis (RPPA) in a cohort of 511 acute myeloid leukemia (AML) patients. Levels of phosphorylated GSK3 were correlated with patient characteristics including survival and with expression of other proteins important in AML cell survival. Results High levels of p-GSK3α/β correlated with adverse overall survival and a lower incidence of complete remission duration in patients with intermediate cytogenetics, but not in those with unfavorable cytogenetics. Intermediate cytogenetic patients with FLT3 mutation also fared better respectively when p-GSK3α/β levels were lower. Phosphorylated GSK3α/β expression was compared and contrasted with that of 229 related cell cycle arrest and/or apoptosis proteins. Consistent with p-GSK3α/β as an indicator of AKT activation, RPPA revealed that p-GSK3α/β positively correlated with phosphorylation of AKT, BAD, and P70S6K, and negatively correlated with β-catenin and FOXO3A. PKCδ also positively correlated with p-GSK3α/β expression, suggesting crosstalk between the AKT and PKC signaling pathways in AML cells. Conclusions These findings suggest that AKT-mediated phosphorylation of GSK3α/β may be beneficial to AML cell survival, and hence detrimental to the overall survival of AML patients. Intrinsically, p-GSK3α/β may serve as an important adverse prognostic factor for a subset of AML patients. PMID:26674329

  14. Thiocolchicoside: review of adverse effects.

    PubMed

    2016-02-01

    Thiocolchicoside has long been used as a muscle relaxant, despite a lack of proven efficacy beyond the placebo effect. Its chemical structure consists of colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its adverse effects are therefore likely to be similar to those of colchicine. Using the standard Prescrire methodology, we reviewed the available data on the adverse effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.

  15. Adverse food-drug interactions.

    PubMed

    de Boer, Alie; van Hunsel, Florence; Bast, Aalt

    2015-12-01

    Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented.

  16. 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

  17. Prognostic value of FOXQ1 in patients with malignant solid tumors: a meta-analysis

    PubMed Central

    Cui, Xiaohai; Zhang, Jing; Lv, Jiajun; Yan, Yan; Liu, Xu; Wang, Jizhao; Lv, Yi; Zhang, Jia

    2017-01-01

    Background Forkhead box Q1 (FOXQ1, also known as HFH1), a member of the forkhead transcription factor family, has been demonstrated to be overexpressed in multiple tumors and is thought to be an indicator of poor clinical outcomes. Methods A meta-analysis using qualified relevant literature was performed to evaluate the prognostic significance of FOXQ1 in various malignant solid tumors. A search of electronic databases was conducted in MEDLINE, Embase, and the Cochrane Library to identify relevant studies published from 1966 to July 30, 2016, and the studies were identified by further evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for analyses were assessed to investigate the association between FOXQ1 expression and overall survival (OS) of patients with malignant solid tumors. Results A total of 1,520 patients from six studies (seven cohorts) with multiple malignant solid tumors were included. For OS, high FOXQ1 expression could significantly predict worse outcome with the pooled HR of 1.38 (95% CI: 1.17–1.59; P<0.001). The subgroup analysis suggested that the elevated levels of FOXQ1 appear to be associated with worse OS in hepatocellular carcinoma (HR =1.34; 95% CI: 1.11–1.57; P<0.001) and other cancers (HR =1.62; 95% CI: 1.09–2.14; P<0.001). Conclusion This meta-analysis indicated that the high expression of FOXQ1 is associated with an adverse OS in malignant solid tumors, suggesting that FOXQ1 may be a predictor of poor prognosis for the development of malignant solid tumors. PMID:28367060

  18. The prognostic factors for patients with hematological malignancies admitted to the intensive care unit.

    PubMed

    Cheng, Qian; Tang, Yishu; Yang, Qing; Wang, Erhua; Liu, Jing; Li, Xin

    2016-01-01

    Owing to the nature of acute illness and adverse effects derived from intensive chemotherapy, patients with hematological malignancies (HM) who are admitted to the Intensive Care Unit (ICU) often present with poor prognosis. However, with advances in life-sustaining therapies and close collaborations between hematologists and intensive care specialists, the prognosis for these patients has improved substantially. Many studies from different countries have examined the prognostic factors of these critically ill HM patients. However, there has not been an up-to-date review on this subject, and very few studies have focused on the prognosis of patients with HM admitted to the ICU in Asian countries. Herein, we aim to explore the current situation and prognostic factors in patients with HM admitted to ICU, mainly focusing on studies published in the last 10 years.

  19. Evaluation of Prognostic Nutritional Index in Patients Undergoing Radical Surgery with Nonsmall Cell Lung Cancer.

    PubMed

    Qiu, Chen; Qu, Xiao; Shen, Hongchang; Zheng, Chunlong; Zhu, Linhai; Meng, Long; Du, Jiajun

    2015-01-01

    The prognostic nutritional index (PNI) has been reported to be a prognostic indicator in some malignant tumors. However, its prognostic value in nonsmall cell lung cancer (NSCLC) has not been fully investigated. A retrospective review of 1416 patients with NSCLC who underwent radical surgery between January 2006 and December 2011 was conducted. To obtain optimal cutoff levels of PNI, running log-rank statistics was applied. Survival was calculated by the Kaplan-Meier method. The prognostic significance of PNI, together with various clinicopathological factors, was evaluated by multivariate analysis. The optimal cutoff point for PNI was 52. The 1-, 3-, and 5-yr survival rates in patients with PNI of less than 52 were 80.0%, 61.3%, and 50.4%, respectively, and were significantly more unfavorable than those in patients with PNI 52 or higher (84.7%, 71.5%, and 60.3%, respectively, P < 0.001). Multivariate analysis suggested that gender (P = 0.026), age (P < 0.001), PNI (P = 0.005), differentiation (P = 0.024), pathology T category (P = 0.003), and pathology N category (P < 0.001) were revealed to be independent prognostic factors. Our results indicate that PNI is an independent predictor of survival for patients undergoing radical surgery with NSCLC.

  20. Adverse responses to local anaesthetics.

    PubMed

    Fisher, M M; Graham, R

    1984-11-01

    Progressive challenge was used to investigate twenty-seven patients with a history of an adverse response to local anaesthesia. True allergy was detected in only one patient. The method does not exclude reactions to additives and preservatives in local anaesthetics. If preservative-free local anaesthetics are used for subsequent exposure in patients with no response to progressive challenge, subsequent exposure is safe. The possibility that some of these patients may be reacting to preservatives in the solutions cannot be excluded by such testing. Where possible preservative-free local anaesthetic preparations should be used for subsequent anaesthesia.

  1. Adverse Outcomes in Group Psychotherapy

    PubMed Central

    Roback, Howard B.

    2000-01-01

    Group forms of therapy have been growing at a rapid rate, in part because of their documented effectiveness and economic considerations such as managed care. It is therefore becoming increasingly important to assess the psychological risks of these interventions. The author provides an overview of the published literature and conference presentations on negative effects in adult outpatient groups. Although much of the literature on adverse outcomes in group therapy focuses on single risk factors (e.g., negative leader, group process, or patient characteristics), the author argues that an interactional model should be encouraged. Means of reducing casualties are also discussed, as well as methodological issues and research directions. PMID:10896735

  2. [Prognostic significance of helical CT in patients with destructive pancreatitis].

    PubMed

    Bulanova, T V

    2000-01-01

    Spiral scanning computed tomography (CT) is able not only to image the pancreas and to evaluate its structure, but to interpret the status of the adjacent organs and tissues. CT symptoms of pancreatic necrotic changes and multiorgan failure were studied in the prospective follow-up of 47 patients with prior destructive pancreatitis (158 studies). CT differentially substantiated indications for choosing treatment policy for different forms of pancreatic lesions. The paper gives a quantitative assessment of necrotic pancreatic parencymatous areas and shows its prognostic value.

  3. Adverse effects of isolation in hospitalised patients: a systematic review.

    PubMed

    Abad, C; Fearday, A; Safdar, N

    2010-10-01

    The use of transmission precautions such as contact isolation in patients known to be colonised or infected with multidrug-resistant organisms is recommended in healthcare institutions. Although essential for infection control, contact isolation has recently been associated with adverse effects in patients. We undertook a systematic review to determine whether contact isolation leads to psychological or physical problems for patients. Studies were included if (1) hospitalised patients were placed under isolation precautions for an underlying medical indication, and (2) any adverse events related to the isolation were evaluated. We found 16 studies that reported data regarding the impact of isolation on patient mental well-being, patient satisfaction, patient safety or time spent by healthcare workers in direct patient care. The majority showed a negative impact on patient mental well-being and behaviour, including higher scores for depression, anxiety and anger among isolated patients. A few studies also found that healthcare workers spent less time with patients in isolation. Patient satisfaction was adversely affected by isolation if patients were kept uninformed of their healthcare. Patient safety was also negatively affected, leading to an eight-fold increase in adverse events related to supportive care failures. We found that contact isolation may negatively impact several dimensions of patient care. Well-validated tools are necessary to investigate these results further. Large studies examining a number of safety indicators to assess the adverse effects of isolation are needed. Patient education may be an important step to mitigate the adverse psychological effects of isolation and is recommended.

  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. 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

  6. Adverse effects of statins - myths and reality.

    PubMed

    Šimić, Iveta; Reiner, Željko

    2015-01-01

    Statins reduce cardiovascular mortality and morbidity as well as cardiovascular events in patients with a very high risk of cardiovascular disease (CVD) and also in subjects with high or moderate risk by reducing the levels of low-density lipoprotein cholesterol (LDL-C). Although they are considered to be drugs with a very good safety profile, because of their wide use there are many concerns that their adverse effects might compromise their proven beneficial effects. Therefore this article reviews all the data and provides an evidence- based insight what are the proven adverse effects of statins and what are the "myths" about them. The most important side effects include myopathy and rhabdomyolysis. Another side effect is increased activity of liver tests which occurs occasionally and is reversible. However, recent studies even suggest that statin therapy can improve hepatic steatosis. It is beyond any doubt that statins do slightly increase the incidence of type 2 diabetes mellitus in people with two or more components of metabolic syndrome but the cardiovascular benefits of such a treatment by far exceed this risk. Statin therapy has also been associated with some adverse renal effects, eg. acute renal failure, but recent data suggest even a possible protective effect of these drugs on renal dysfunction. Concerns that statins might increase cancer have not been proven. On the contrary, several studies have indicated a possible benefit of these drugs in patients with different types of cancer. Early concerns about cognitive dysfunction and memory loss associated with statins use could not be proven and most recent data even suggest a possible beneficial effect of statins in the prevention of dementia. Systematic reviews and clinical guidelines suggest that the cardiovascular benefits of statins by far out-weight non-cardiovascular harms in patients with cardiovascular risk.

  7. 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

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

    PubMed Central

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

    2017-01-01

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

  9. Clinical and prognostic significance of coagulation assays in lung cancer.

    PubMed

    Tas, Faruk; Kilic, Leyla; Serilmez, Murat; Keskin, Serkan; Sen, Fatma; Duranyildiz, Derya

    2013-03-01

    Activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are supposed to be associated with higher risk of invasion, metastases and eventually worse outcome. The aim of this study is to explore the prognostic value of blood coagulation tests for lung cancer patients. The study comprised 110 lung cancer patients. Pretreatment blood coagulation tests including PT, aPTT, PTA, INR, D-dimer, fibrinogen levels and platelet counts were evaluated. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group (p < 0.001). There was a significant association between D-Dimer levels and histological subtypes of NSCLC, pointing an elevated plasma D-dimer level in squamous cell cancer (p = 0.035). Patients with extensive stage SCLC exhibited evidently higher levels of D-Dimer, INR and PLT (p = 0.037, p = 0.042, p = 0.04, respectively). Prolongation of PT and INR had statistically significant adverse effect on survival (p = 0.05 and p = 0.014, respectively). Although prolonged aPTT and high levels of D-dimer was associated with worse survival, the difference was not statistically significant (p = 0.117, p = 0.104). Multivariate analysis revealed INR as the sole independent prognostic variable among coagulation parameters (p = 0.05). In conclusion, elevation of PT and INR are associated with decreased survival in lung cancer patients.

  10. Diagnosis, progression patterns and prognostication in mastocytosis.

    PubMed

    Sperr, Wolfgang R; Valent, Peter

    2012-06-01

    Mastocytosis is a heterogeneous group of disorders defined by abnormal growth and accumulation of clonal mast cells. CM is the predominant variant in childhood, whereas the majority of adult patients present with systemic mastocytosis. In over 80% of the latter patients, the KIT mutation D816V is detectable. Whereas childhood mastocytosis often resolves spontaneously before adolescence and has a good prognosis, in most adult patients mastocytosis is a persistent systemic disorder. The course and prognosis in these patients are variable; in indolent variants, the clinical course remains stable over years or even decades. In advanced mastocytosis, the prognosis is less favorable despite novel drugs counteracting growth of neoplastic mast cells. Although WHO criteria are clearly separating prognostic subsets of mastocytosis, little is known about specific prognostic factors predicting the outcome in individual patients. In this article, we review current concepts in mastocytosis, including prognostic parameters for indolent and advanced systemic mastocytosis.

  11. Prognostic Awareness and Communication of Prognostic Information in Malignant Glioma: A Systematic Review

    PubMed Central

    Diamond, Eli L.; Corner, Geoffrey W.; DeRosa, Antonio; Breitbart, William; Applebaum, Allison J.

    2016-01-01

    Malignant glioma (MG) is a devastating neurological disease with a uniformly poor prognosis and a clinical course characterized by progressive functional and cognitive impairment. A small body of literature addresses patients’ and caregivers’ prognostic awareness (PA), or understanding of prognosis in patients with cancer. Studies that examine PA and desire for prognostic information among patients with MG are limited. We sought to review the existing literature on PA and communication of prognostic information to patients with MG. Fourteen studies examining PA or experience and preferences regarding communication of prognostic information were included. The definition and measurement of PA across studies varied, and the prevalence of accurate PA ranged from 25% to 100% of participants. There is likely a subset of patients who do not desire accurate prognostic information, although the patient and disease characteristics that predict this preference are currently unknown. This review suggests that patients with MG desire prognostic information communicated in a manner that preserves hope. Systematic investigation to define communication needs for prognostic information in the unique clinical setting of MG is needed. PMID:24874468

  12. Prognostic awareness and communication of prognostic information in malignant glioma: a systematic review.

    PubMed

    Diamond, Eli L; Corner, Geoffrey W; De Rosa, Antonio; Breitbart, William; Applebaum, Allison J

    2014-09-01

    Malignant glioma (MG) is a devastating neurological disease with a uniformly poor prognosis and a clinical course characterized by progressive functional and cognitive impairment. A small body of literature addresses patients' and caregivers' prognostic awareness (PA), or understanding of prognosis in patients with cancer. Studies that examine PA and desire for prognostic information among patients with MG are limited. We sought to review the existing literature on PA and communication of prognostic information to patients with MG. Fourteen studies examining PA or experience and preferences regarding communication of prognostic information were included. The definition and measurement of PA across studies varied, and the prevalence of accurate PA ranged from 25 to 100 % of participants. There is likely a subset of patients who do not desire accurate prognostic information, although the patient and disease characteristics that predict this preference are currently unknown. This review suggests that patients with MG desire prognostic information communicated in a manner that preserves hope. Systematic investigation to define communication needs for prognostic information in the unique clinical setting of MG is needed.

  13. "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)

  14. The international serious adverse events consortium.

    PubMed

    Holden, Arthur L; Contreras, Jorge L; John, Sally; Nelson, Matthew R

    2014-11-01

    The International Serious Adverse Events Consortium is generating novel insights into the genetics and biology of drug-induced serious adverse events, and thereby improving pharmaceutical product development and decision-making.

  15. Adverse outcome pathway development II: best practices.

    PubMed

    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

    2014-12-01

    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.

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

    MedlinePlus

    ... Diagnosis, and Types 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 ...

  17. Local-Level Prognostics Health Management Systems Framework for Passive AdvSMR Components. Interim Report

    SciTech Connect

    Ramuhalli, Pradeep; Roy, Surajit; Hirt, Evelyn H.; Pardini, Allan F.; Jones, Anthony M.; Deibler, John E.

    2014-09-12

    This report describes research results to date in support of the integration and demonstration of diagnostics technologies for prototypical AdvSMR passive components (to establish condition indices for monitoring) with model-based prognostics methods. The focus of the PHM methodology and algorithm development in this study is at the localized scale. Multiple localized measurements of material condition (using advanced nondestructive measurement methods), along with available measurements of the stressor environment, enhance the performance of localized diagnostics and prognostics of passive AdvSMR components and systems.

  18. Community indicators

    PubMed Central

    Flynn, Andrea; Wells, Samantha

    2014-01-01

    Community indicators are used to assess the impact of alcohol on communities. This article reviews the main data sources for community indicators, discusses their strengths and limitations, and discusses indicators used in reference to four main topics relating to alcohol use and problems at the community level: alcohol use, patterns, and problems; alcohol availability; alcohol-related health outcomes/trauma; and alcohol-related crime and enforcement. It also reviews the challenges associated with collecting community indicator data, along with important innovations in the field that have contributed to better knowledge of how to collect and analyze community-level data on the impact of alcohol. PMID:24881322

  19. The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

    PubMed Central

    Wong, Li-Fan; Lee, Jang-Ming

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P<0.001), increased risk of death (Hazard ratio HR [95 % CI=2.09[1.09-4.04], P=0.028], and distant metastasis (odds ratio OR [95 %CI]=3.96 (1.16-13.60), P=0.029). The adverse clinical impact of AXL was more evident when cumulatively expressed with HER2. In cell model, ESCC cells were more sensitive to AXL inhibitor foretinib than to the HER2 inhibitor lapatinib. Meanwhile, the AXL inhibitor foretinib showed a synergistic effect with HER2 inhibitors and the potential to overcome drug resistance to lapatinib. We thus concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. PMID:27172793

  20. [Prognostic value of beta-2-microglobulin in Hodgkin disease in young adults].

    PubMed

    Fleury, J; Tortochaux, J; Legros, M; Cure, H; Kwiatkowski, F; Ferrière, J P; Travade, P; Dionet, C; Gaillard, G; Chassagne, J

    1994-07-01

    From 1977 to 1989, we measured serum beta-2-microglobulin (beta 2-MG) levels from 64 unselected and untreated patients, between 18 to 50-year-old, affected by Hodgkin's disease. Serum beta 2-MG level was measured by radioimmunoassay (Phadebas beta 2 microtest). Then, all patients received a chemotherapy such as MOPP or alternating MOPP/ABVD followed or not by radiotherapy. Elevated serum beta 2-MG level (> 2.4 mg/l) is associated with advanced stage disease (stage III-IV), presence of systemic symptoms and bulky tumor. Nevertheless, a multivariate analysis shows that the serum beta 2-MG level is the most significant prognostic indicator for disease free survival. The prognostic value of serum beta 2-MG is demonstrated for myeloma and non Hodgkin's lymphoma. A few authors have evaluated the prognostic impact of serum beta 2-MG in Hodgkin's disease. This study requires confirmation by multicentric and prospective trial.

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

    PubMed

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

    2013-01-01

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

  2. Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma.

    PubMed

    Nakamoto, Mitsuhiro; Matsuyama, Atsuji; Shiba, Eisuke; Shibuya, Ryo; Kasai, Takahiko; Yamaguchi, Koji; Hisaoka, Masanori

    2014-10-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P = 0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P = 0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P = 0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P = 0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.

  3. 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.

  4. Prognostic significance of nucleolar organizer regions (NORS) in malignant melanoma.

    PubMed

    Ronan, S G; Farolan, M J; McDonald, A; Manaligod, J R; Das Gupta, T K

    1994-12-01

    Nucleolar organizer regions (NORs) are loops of ribosomal DNA (rDNA) in the nucleolus and are associated with acidic proteins. They are seen in routinely processed paraffin sections by using a one-step colloidal silver (Ag) staining method; they appear as black dots termed "AgNORs". The quantitative assay of AgNORs has been used to differentiate benign from malignant neoplasms. Melanocytic lesions differ significantly in AgNOR counts between malignant melanoma and nevi. However, conflicting results have been reported as to AgNORs' prognostic value in melanoma. A recent study showed AgNOR counts to be a more accurate prognostic indicator than Breslow's thickness. In this study, we counted the AgNORs in 26 patients with primary cutaneous melanomas (CMM) between 2.0 mm and 2.5 mm thick. Of these, 14 are alive without disease (AN) at 5 years after diagnosis (group 1) and 12 are dead of disease (DD) in less than 5 years (group 2). The AgNORs were scored in 30 nuclei per tumor, and the means were calculated. For group 1, the mean number of AgNORs per nucleus was 6.88, ranging from 3.73 to 12.70. For group 2, the mean number was 6.97, ranging from 3.63 to 11.67. Statistical analysis using analysis of variance (ANOVA) showed no significant difference between the groups (p = 0.33). In our study, AgNOR counts did not prove to be of prognostic value in malignant melanoma.

  5. Prognostic factors in early-stage ovarian cancer

    PubMed Central

    Tognon, Germana; Carnazza, Mario; Ragnoli, Monica; Calza, Stefano; Ferrari, Federico; Gambino, Angela; Zizioli, Valentina; Notaro, Sara; Sostegni, Benedetta; Sartori, Enrico

    2013-01-01

    The purpose of this study was to identify the main prognostic factors in patients with early-stage epithelial ovarian cancer. Data were extracted from 222 patients with initial stage (I–IIA) invasive epithelial ovarian cancer treated with primary surgery followed or not followed by adjuvant therapy, from 1 January 1980 to 31 December 2008, at the Division of Obstetrics and Gynecology, Spedali Civili, Brescia, Italy; the median follow-up was 79 months (SD ± 35,945, range 20–250 months). The negative prognostic factors that were statistically significant (p<0.050) in univariate analysis were grade 2, 3, and X (clear cell in our study); stage IB, IC, IIA; positive peritoneal cytology, age equal to/greater than 54; dense adhesions; capsule rupture (pre-operative or intra-operative) and endometrioid histotype (only for disease-free survival (DFS)). Positive cytology was strongly associated with peritoneal relapses, while adhesions were associated with pelvic relapses. A positive prognosis was associated with the mucinous histotype. Conservative treatment had been carried out in 52% of patients under 40 years of age, and we detected only two relapses and three completions of surgery after a few weeks among 31 women in total. Our study indicated a possible execution in patients with patients with cancer stage IA G1–G2 (p=0.030) or IC G1 (p=0.050), provided well staged. Adjuvant chemotherapy improved the survival of cancers that were not IA G1. The positive prognostic role of taxanes must be emphasised, when used in combination with platino. PMID:23781280

  6. 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.

  7. 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.

  8. Maternal Psychosocial Adversity and the Longitudinal Development of Infant Sleep

    ERIC Educational Resources Information Center

    Cronin, Alison; Halligan, Sarah L.; Murray, Lynne

    2008-01-01

    Research has identified associations between indicators of social disadvantage and the presence of child sleep problems. We examined the longitudinal development of infant sleep in families experiencing high (n = 58) or low (n = 64) levels of psychosocial adversity, and the contributions of neonatal self-regulatory capacities and maternal settling…

  9. Adolescent Friendships Mediating Childhood Adversity and Adult Outcome.

    ERIC Educational Resources Information Center

    Pawlby, Susan J.; Mills, Alice; Taylor, Alan; Quinton, David

    1997-01-01

    Compares the friendships of girls (N=50) at risk for difficulties in early adult partnerships with those of 50 girls of the same age. Results indicate key differences in both romantic and non-romantic adolescent friendships between the two groups. Findings offer a clearer understanding of processes linking childhood adversity and poor adult…

  10. 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

  11. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  12. 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

  13. Conceptualizing prognostic awareness in advanced cancer: a systematic review.

    PubMed

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2014-09-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness.

  14. Histological characterisation and prognostic evaluation of 62 gastric neuroendocrine carcinomas

    PubMed Central

    Chen, Xiaohui; Ye, Yuhong; Shi, Xi; Zhu, Kunshou; Huang, Liming; Zhang, Sheng; Ying, Mingang; Lin, Xuede

    2016-01-01

    Aim of the study To determine the significance of expression of synaptophysin, chromogranin A, and Ki-67 and their association with clinicopathological parameters, and to find out the possible prognostic factors in gastric neuroendocrine carcinoma (G-NEC). Material and methods We investigated the immunohistochemical features and prognosis of 62 G-NECs, and evaluated the association among expressions of synaptophysin, chromogranin A, and Ki-67, clinicopathological variables, and outcome. Results Chromogranin A expression was found more commonly in small-cell NECs (9/9, 100%) than in large-cell NECs (27/53, 51%) (p = 0.008). No statistical significance was found in Ki-67 (p = 0.494) or synaptophysin (p > 0.1) expression between NEC cell types. Correlation analyses revealed that Ki-67 expression was significantly associated with mid-third disease of stomach (p = 0.005) and vascular involvement (p = 0.006), and had a trend of significant correlation with tumour relapse (p = 0.078). High expression of chromogranin A was significantly associated with histology of small-cell NECs (p = 0.008) and lesser tumour greatest dimension (p = 0.038). The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests, and as a result, early TNM staging and postoperative chemotherapy were found to be correlated with longer overall survival (p < 0.05). Univariate analysis revealed associations between poor prognosis in NECs and several factors, including high TNM staging (p = 0.048), vascular involvement (p = 0.023), relapse (p = 0.004), and microscopic/macroscopic residual tumour (R1/2, p < 0.001). In a multivariate analysis, relapse was identified as the sole independent prognostic factor. Conclusions No significant correlation between survival and expression of synaptophysin, chromogranin A, or Ki-67 has been determined in G-NECs. Our study indicated that early diagnosis, no-residual-tumour resection, and postoperative chemotherapy were

  15. 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

  16. Prognostic Value of Epicardial Fat Volume Measurements by Computed Tomography: A Systematic Review of the Literature

    PubMed Central

    Spearman, James V.; Renker, Matthias; Schoepf, U. Joseph; Krazinski, Aleksander W.; Herbert, Teri L.; De Cecco, Carlo N.; Nietert, Paul J.; Meinel, Felix G.

    2015-01-01

    Objectives To perform a systematic review of the growing body of literature evaluating the prognostic value of epicardial fat volume (EFV) quantified by cross-sectional imaging for adverse clinical outcomes. Methods Two independent reviewers performed systematic searches on both PubMed and Scopus using search terms developed with a medical librarian. Peer-reviewed articles were selected based on the inclusion of outcome data, utilization of epicardial fat volume and sufficient reporting for analysis. Results A total of 411 studies were evaluated with 9 studies meeting the inclusion criteria. In all, the studies evaluated 10,252 patients. All 9 studies were based on CT measurements. Seven studies evaluated the prognostic value of EFV unadjusted for calcium score, and 6 of these studies found a significant association between EFV and clinical outcomes. Seven studies evaluated the incremental value of EFV beyond calcium scoring, and 6 of these studies found a significant association. Conclusions The majority of studies suggest that EFV quantification is significantly associated with clinical outcomes and provides incremental prognostic value over coronary artery calcium scoring. Future research should use a binary cut-off of 125mL for evaluation of EFV to provide consistency with other research. PMID:25925354

  17. 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.

  18. Independent prognostic value of peritoneal immunocytodiagnosis in endometrial carcinoma.

    PubMed

    Benevolo, M; Mariani, L; Vocaturo, G; Vasselli, S; Natali, P G; Mottolese, M

    2000-02-01

    Among the clinical parameters that play a pivotal role in predicting the outcome of patients with endometrial carcinoma, intraperitoneal microscopic dissemination represents an important cause of recurrences. To date, peritoneal cytology has been incorporated into the current surgical staging system (International Federation of Gynecology and Obstetrics 88), although its predictive value remains a controversial issue. In this study the authors investigated the possibility of applying immunocytochemistry (ICC) to the diagnosis of peritoneal washing (PW) aimed at improving conventional cytology and verifying the prognostic value of peritoneal malignant cells. The authors analyzed 182 PWs sampled from endometrial cancer patients. The ICC analysis was performed using two monoclonal antibodies (MAbs)--AR-3 and B72.3--that in combination recognize more than 95% of endometrial carcinomas. The presence of peritoneal-free cancer cells was identified morphologically in 27 of 182 lavages (14.8%) and ICC in 50 of 182 (27.5%), with a significant improvement (p <0.0001). Five-year survival analysis, comparing results of ICC and cytodiagnosis, demonstrated a significant decrease of disease-free survival in patients with peritoneal microscopic disease. Furthermore, multivariate analysis showed that ICC diagnosis of PWs is an independent prognostic factor. Data indicate that the use of selected MAbs allows one to identify cytologically false-negative cases, providing results that are highly predictive of a worse clinical outcome.

  19. Value of coronary computed tomography as a prognostic tool.

    PubMed

    Contractor, Tahmeed; Parekh, Maansi; Ahmed, Shameer; Martinez, Matthew W

    2012-08-01

    Coronary computed tomography angiography (CCTA) has become an important part of our armamentarium for noninvasive diagnosis of coronary artery disease (CAD). Emerging technologies have produced lower radiation dose, improved spatial and temporal resolution, as well as information about coronary physiology. Although the prognostic role of coronary artery calcium scoring is known, similar evidence for CCTA has only recently emerged. Initial, small studies in various patient populations have indicated that CCTA-identified CAD may have a prognostic value. These findings were confirmed in a recent analysis of the international, prospective Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) registry. An incremental increase in mortality was found with a worse severity of CAD on a per-patient, per-vessel, and per-segment basis. In addition, age-, sex-, and ethnicity-based differences in mortality were also found. Whether changing our management algorithms based on these findings will affect outcomes is unclear. Large prospective studies utilizing targeted management strategies for obstructive and nonobstructive CAD are required to incorporate these recent findings into our daily practice.

  20. Prognostic value of circulating tumor cells in esophageal cancer

    PubMed Central

    Xu, Hai-Tao; Miao, Jing; Liu, Jian-Wei; Zhang, Lian-Guo; Zhang, Qing-Guang

    2017-01-01

    AIM To perform a meta-analysis of the related studies to assess whether circulating tumor cells (CTCs) can be used as a prognostic marker of esophageal cancer. METHODS PubMed, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival (OS). The meta-analysis was performed using the random effects model, with hazard ratio (HR), risk ratio (RR) and 95% confidence intervals (95%CIs) as effect measures. RESULTS Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression (HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS (HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage (RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage (RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer. CONCLUSION Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted. PMID:28275311

  1. Multimodal Degradation Prognostics Based on Switching Kalman Filter Ensemble.

    PubMed

    Lim, Pin; Goh, Chi Keong; Tan, Kay Chen; Dutta, Partha

    2017-01-01

    For accurate prognostics, users have to determine the current health of the system and predict future degradation pattern of the system. An increasingly popular approach toward tackling prognostic problems involves the use of switching models to represent various degradation phases, which the system undergoes. Such approaches have the advantage of determining the exact degradation phase of the system and being able to handle nonlinear degradation models through piecewise linear approximation. However, limitations of such existing methods include, limited applicability due to the discretization of predicted remaining useful life, insufficient robustness due to the use of single models and others. This paper circumvents these limitations by proposing a hybrid of ensemble methods with switching methods. The proposed method first implements a switching Kalman filter (SKF) to classify between various linear degradation phases, then predict the future propagation of fault dimension using appropriate Kalman filters for each phase. This proposed method achieves both continuous and discrete prediction values representing the remaining life and degradation phase of the system, respectively. The proposed framework is shown via a case study on benchmark simulated aeroengine data sets. The evaluation of the proposed framework shows that the proposed method achieves better accuracy and robustness against noise compared with other methods reported in the literature. The results also indicate the effectiveness of the SKF in detecting the switching point between various degradation modes.

  2. Evaluation of etiologic and prognostic factors in neonatal convulsions.

    PubMed

    Yıldız, Edibe Pembegul; Tatlı, Burak; Ekici, Barış; Eraslan, Emine; Aydınlı, Nur; Calışkan, Mine; Ozmen, Meral

    2012-09-01

    This study evaluated etiologic and risk factors affecting long-term prognoses of neurologic outcomes in newborns with neonatal seizures. We enrolled patients at chronologic ages of 23-44 months, referred to the Department of Pediatric Neurology, Istanbul Medical Faculty, from January 1, 2007-December 31, 2009, after manifesting seizures in their first postnatal 28 days. Of 112 newborns, 41 were female, 71 were male, 33 were preterm, and 79 were full-term. Perinatal asphyxia (28.6%) and intracranial hemorrhage (17%) were the most common causes of neonatal seizures. Cerebral palsy developed in 27.6% of patients during follow-up. The incidence of epilepsy was 35.7%. Almost 50% of patients manifested developmental delay in one or more areas. Global developmental delay was the most common (50.8%) neurologic disorder. The correlation between gestational age or birth weight and adverse outcomes was nonsignificant. Etiology, Apgar score, need for resuscitation at birth, background electroencephalogram, neonatal status epilepticus, cranial imaging findings, type/duration of antiepileptic treatment, and response to acute treatment were all strong prognostic factors in neurologic outcomes. Neonatal seizures pose a threat of neurologic sequelae for preterm and full-term infants. Although the number of recognized etiologic factors in neonatal seizures has increased because of improvements in neonatology and diagnostic methods, perinatal asphyxia remains the most common factor.

  3. Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors

    PubMed Central

    Falloon, Judith; Bennett, John E.; Shaw, Pamela A.; Chaitt, Doreen; Baseler, Michael W.; Adelsberger, Joseph W.; Metcalf, Julia A.; Polis, Michael A.; Kovacs, Stephen J.; Kovacs, Joseph A.; Davey, Richard T.; Lane, H. Clifford; Masur, Henry

    2008-01-01

    Idiopathic CD4+ lymphocytopenia (ICL) is a rare non–HIV-related syndrome with unclear natural history and prognosis. This prospective natural history cohort study describes the clinical course, CD4 T lymphocyte kinetics, outcome, and prognostic factors of ICL. Thirty-nine patients (17 men, 22 women) 25 to 85 years old with ICL were evaluated between 1992 and 2006, and 36 were followed for a median of 49.5 months. Cryptococcal and nontuberculous mycobacterial infections were the major presenting opportunistic infections. Seven patients presented with no infection. In 32, CD4 T-cell counts remained less than 300/mm3 throughout the study period and in 7 normalized after an average of 31 months. Overall, 15 (41.6%) developed an opportunistic infection in follow-up, 5 (13.8%) of which were “AIDS-defining clinical conditions,” and 4 (11.1%) developed autoimmune diseases. Seven patients died, 4 from ICL-related opportunistic infections, within 42 months after diagnosis. Immunologic analyses revealed increased activation and turnover in CD4 but not CD8 T lymphocytes. CD8 T lymphocytopenia (< 180/mm3) and the degree of CD4 T cell activation (measured by HLA-DR expression) at presentation were associated with adverse outcome (opportunistic infection-related death; P = .003 and .02, respectively). This trial is registered at http://clinicaltrials.gov as #NCT00001319. PMID:18456875

  4. Hospital deaths and adverse events in Brazil

    PubMed Central

    2011-01-01

    Background Adverse events are considered a major international problem related to the performance of health systems. Evaluating the occurrence of adverse events involves, as any other outcome measure, determining the extent to which the observed differences can be attributed to the patient's risk factors or to variations in the treatment process, and this in turn highlights the importance of measuring differences in the severity of the cases. The current study aims to evaluate the association between deaths and adverse events, adjusted according to patient risk factors. Methods The study is based on a random sample of 1103 patient charts from hospitalizations in the year 2003 in 3 teaching hospitals in the state of Rio de Janeiro, Brazil. The methodology involved a retrospective review of patient charts in two stages - screening phase and evaluation phase. Logistic regression was used to evaluate the relationship between hospital deaths and adverse events. Results The overall mortality rate was 8.5%, while the rate related to the occurrence of an adverse event was 2.9% (32/1103) and that related to preventable adverse events was 2.3% (25/1103). Among the 94 deaths analyzed, 34% were related to cases involving adverse events, and 26.6% of deaths occurred in cases whose adverse events were considered preventable. The models tested showed good discriminatory capacity. The unadjusted odds ratio (OR 11.43) and the odds ratio adjusted for patient risk factors (OR 8.23) between death and preventable adverse event were high. Conclusions Despite discussions in the literature regarding the limitations of evaluating preventable adverse events based on peer review, the results presented here emphasize that adverse events are not only prevalent, but are associated with serious harm and even death. These results also highlight the importance of risk adjustment and multivariate models in the study of adverse events. PMID:21929810

  5. The preoperative sensitive-modified Glasgow prognostic score is superior to the modified Glasgow prognostic score in predicting long-term survival for esophageal squamous cell carcinoma

    PubMed Central

    Tian, Rui; Zhang, Fei; Sun, Peng; Wu, Jing; Yan, Hong; Wu, Ai-Ran; Zhang, Min; Jiang, Yu-Lu; Lu, Yan-Hong; Xu, Qiu-Yan; Zhan, Xiao-Hong; Zhang, Rong-Xin; Qian, Li-Ting; He, Jie

    2016-01-01

    The present study was designed to investigate the prognostic significance of the preoperative sensitive-modified Glasgow prognostic score (S-mGPS) and its superiority in esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative albumin and C-reactive protein (CRP) levels were retrospectively collected in 442 patients who underwent transthoracic esophagectomy. The S-mGPS was calculated before surgery based on optimal cutoff values of 45.6 g/L for albumin and 10.0 mg/L for CRP. 360, 74 and 8 cases were assigned an mGPS of 0, 1 and 2, respectively. In contrast, the S-mGPS was 0 in 114, 1 in 258 and 2 in 70 patients. Of the 360 patients with an mGPS of 0, 246 migrated to the S-mGPS-1 group. Both mGPS and S-mGPS were significantly correlated with tumor length, depth of invasion, pathological tumor-node-metastasis (pTNM) stage and adjuvant treatment. In addition, they were significantly associated with disease free survival (DFS) and overall survival (OS) in univariate analysis. Furthermore, multivariate Cox regression analysis identified S-mGPS as an independent prognostic indicator for both DFS [hazard ratio (HR), 1.577; 95% confidence interval (CI), 1.149-2.163; P = 0.005] and OS (HR, 1.762; 95% CI, 1.250-2.484; P = 0.001), but not mGPS (HR, 0.957; 95% CI, 0.692-1.323; P = 0.790 for DFS and HR, 1.089; 95% CI, 0.781-1.517; P = 0.615 for OS, respectively). Moreover, subgroup analysis revealed that the prognostic impact of the S-mGPS was especially striking in pTNM stage II patients. The preoperative S-mGPS is superior to the mGPS as a prognostic predictor in patients with resectable ESCC. PMID:27528228

  6. Characterizing "Adversity" of Pathology Findings in ...

    EPA Pesticide Factsheets

    The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop in June 2015 to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports. The international group of expert pathologists and toxicologists emphasized that a holistic, weight-of-evidence, case-specific approach should be followed for each adversity assessment. It was recommended that nonclinical adversity should typically be determined at a morphological level (most often the organ) in the pathology report and should refer specifically to the test species. Final adversity calls, integration of target pharmacology/pathway information, and consideration of human translation should generally be made in toxicology overview reports. Differences in interpretation and implications of adversity calls between (agro)chemical and pharmaceutical industries and among world regions were highlighted. The results of this workshop should serve a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP. This

  7. Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia.

    PubMed

    Gottardo, Nicholas G; Hoffmann, Katrin; Beesley, Alex H; Freitas, Joseph R; Firth, Martin J; Perera, Kanchana U; de Klerk, Nicolas H; Baker, David L; Kees, Ursula R

    2007-05-01

    In the last four decades the survival of patients with newly diagnosed childhood T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to determine if gene expression profiling could uncover a signature of outcome for children with T-ALL. Using 12 patient specimens obtained before therapy started, we examined the gene expression profile by oligonucleotide microarrays. We identified three genes, CFLAR, NOTCH2 and BTG3, whose expression at the time of diagnosis accurately distinguished the patients according to disease outcome. These genes are involved in the regulation of apoptosis and cellular proliferation. The prognostic value of the three predictive genes was assessed in an independent cohort of 25 paediatric T-ALL patients using quantitative real-time reverse transcription polymerase chain reaction. Patients assigned to the adverse outcome group had a significantly higher cumulative incidence of relapse compared with patients assigned to the favourable outcome group (46% vs. 8%, P = 0.029). Five-year overall survival was also significantly worse in the patients assigned to the adverse outcome group (P = 0.0039). The independent influence of the 3-gene predictor was confirmed by multivariate analysis. Our study provides proof of principle that genome-wide expression profiling can detect novel molecular prognostic markers in paediatric T-ALL.

  8. [The use of human immunoglobulins--adverse reactions].

    PubMed

    Pituch-Noworolska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna

    2010-09-01

    The primary immunodeficiency, mainly humoral immunity, secondary immunodeficiency and autoimmune diseases are the indications for immunoglobulins substitution. The prolonged substitution in primary immunodeficiency includes regular intravenous infusion of immunoglobulins in 0.4-0.6 g/kg of body weight every 21-28 days. The purpose of such substitution is decrease of frequency and diminishes the clinical course of infections. The high-dose use of immunoglobulins (1-2 g/kg body weight) is preferred in autoimmune diseases based on suppressive and anti-inflammatory activity of immunoglobulins. The subcutaneous administration of immunoglobulins is an alternative to intravenous way, but the singular dose (0.1 g/kg body weight) is too low for suppressive and anti-inflammatory activity of immunoglobulins, so this substitution is indicated in primary immunodeficiency only. The adverse events of immunoglobulins differentiate because of time of occurrence and clinical character. The rapid symptoms occurred just after beginning of infusion and often present the clinical features of anaphylactoid reaction. During the infusion the occurring adverse symptoms are mild and the life-threatening situations are very rare. The next periods of typical adverse reaction are 24-48 hrs after infusion, 72 hrs and later. The mechanisms leading to adverse reaction to immunoglobulins are based on presence of IgG dimmers, stimulating high production of pro-inflammatory cytokines by immunocompetent cells. High level of cytokines is associated with high fever, chills, flu-like symptoms, feeling malaise and sick. The reaction of anti-IgA antibodies present in patient serum with IgA in immunoglobulins preparation is responsible for moderate and severe adverse clinical symptoms. The late adverse events present the symptoms of aseptic meningo-encephalitis. In case of adverse events the stopping of infusion, additions saline/ glucose infusion, anti-histaminic drugs of I and II generation and steroids

  9. 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

  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. Life adversity is associated with smoking relapse after a quit attempt.

    PubMed

    Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

    2016-09-01

    Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted.

  12. A comparison of the prognostic value of preoperative inflammation-based scores and TNM stage in patients with gastric cancer

    PubMed Central

    Pan, Qun-Xiong; Su, Zi-Jian; Zhang, Jian-Hua; Wang, Chong-Ren; Ke, Shao-Ying

    2015-01-01

    characteristic curve as compared to other inflammation-based prognostic scores. Conclusion The present study indicates that preoperative GPS and TNM stage are robust predictors of gastric cancer survival as compared to NLR, PLR, PI, and PNI in patients undergoing tumor resection. PMID:26124667

  13. 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.

  14. Diagnostic and prognostic epigenetic biomarkers in cancer.

    PubMed

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

    2015-01-01

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

  15. [Maternal and foetal prognostic during severe toxemia].

    PubMed

    Rachdi, Radhouane; Kaabi, Mehdi; Zayene, Houssine; Basly, Mohamed; Messaoudi, Fathi; Messaoudi, Lotfi; Chibani, Mounir

    2005-02-01

    Severe gravidic toxemia gives heavy maternal and foetal morbidity and mortality. The purpose of our study is to loosen the factors of bad maternal and foetal prognostic. It's a retrospective study about 100 cases of severe and complicated gravidic toxemia repertorieted in the maternity of Military Hospital of Tunis. Maternal morbidity is dominated by the complications of hypertension and a blood disorders. We raised 4 cases of eclampsia, 9 cases of retro placental hematome and 5 cases of HELLP syndrome. We don't deplore any maternal death. Perinatal mortality is 28.8%. The rate of delay intra-uterine growth was 43.8% and the prematurity 65.9%. More toxemia appears early during pregnancy more maternal and foetal prognostic is compromised.

  16. [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.

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

    PubMed Central

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

    2015-01-01

    AIM: To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer. METHODS: We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias. RESULTS: Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively. CONCLUSION: PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer. PMID:26019461

  18. Prognostic factors in bunion surgery.

    PubMed

    Scranton, P E; McDermott, J E

    1995-11-01

    Between 1977 and 1992, 42 patients were seen who had 51 feet operated upon for bunions in which the surgery failed. A total of 105 procedures were done on these 51 feet until the patients either achieved satisfactory correction (N = 28) or they declined (N = 14) further surgery. An analysis of these failures and review of literature revealed 12 anatomic variations and 7 secondary factors that were seen in association with surgical failure. These findings were correlated with published criteria and our experience with various bunion procedures to advance general indications and contraindications for specific bunion procedures.

  19. Towards Performance Prognostics of a Launch Valve

    DTIC Science & Technology

    2014-10-02

    works are related to this paper’s efforts. Gomes et. al. developed a health monitoring system for a pneumatic valve using a Probability Integral...Transform based technique (Gomes 2010) and Daigle et. al. developed a model-based prognostics approach for pneumatic valves (Daigle 2011). While the...Launch Valve in this work is hydraulically controlled, the methods used for pneumatic valve PHM are quite relevant. Diagle et. al. used a Probability

  20. Identification of Prostate Cancer Prognostic Markers

    DTIC Science & Technology

    2014-10-01

    Assessment post- Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict early...operative PSA levels, GS, T-Stage and CAPRA -S risk scores respectively, improved the overall prognostication in these patients (log rank, Pɘ.001...Risk Assessment post-Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict

  1. Identification of Prostate Cancer Prognostic Markers

    DTIC Science & Technology

    2013-10-01

    aims. Ethics approval has been obtained for the samples collection of AIM1. The chromosome 16p13.3 gain was found to be associated with high Gleason...Prostate cancer, Genomic alteration, Fluorescence in situ hybridization (FISH), Prognostic markers, ectopic expression, gene silencing, cDNA cloning ...In regard to AIM1 and AIM2, we have recently obtained the final approval from the Ethics committee of our hospital after a lengthy process. We have

  2. No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival

    PubMed Central

    Orlow, Irene; Kanetsky, Peter A.; Thomas, Nancy E.; Fang, Shenying; Lee, Jeffrey E.; Berwick, Marianne; Lee, Ji-Hyun

    2017-01-01

    The prognostic improvement attributed to genetic markers over current prognostic system has not been well studied for melanoma. The goal of this study is to evaluate the added prognostic value of Vitamin D Pathway (VitD) SNPs to currently known clinical and demographic factors such as age, sex, Breslow thickness, mitosis and ulceration (CDF). We utilized two large independent well-characterized melanoma studies: the Genes, Environment, and Melanoma (GEM) and MD Anderson studies, and performed variable selection of VitD pathway SNPs and CDF using Random Survival Forest (RSF) method in addition to Cox proportional hazards models. The Harrell’s C-index was used to compare the performance of model predictability. The population-based GEM study enrolled 3,578 incident cases of cutaneous melanoma (CM), and the hospital-based MD Anderson study consisted of 1,804 CM patients. Including both VitD SNPs and CDF yielded C-index of 0.85, which provided slight but not significant improvement by CDF alone (C-index = 0.83) in the GEM study. Similar results were observed in the independent MD Anderson study (C-index = 0.84 and 0.83, respectively). The Cox model identified no significant associations after adjusting for multiplicity. Our results do not support clinically significant prognostic improvements attributable to VitD pathway SNPs over current prognostic system for melanoma survival. PMID:28323902

  3. 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.

  4. New prognostic markers in liver cirrhosis

    PubMed Central

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-01-01

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of “inflammatory stress” and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value. PMID:26019739

  5. [Prognostic factors in acute nonlymphoid leukemias].

    PubMed

    Capelli, D; Tedeschi, A; Montillo, M; Corvatta, L; Bartocci, C; Montroni, M; Leoni, P

    1996-10-01

    Our retrospective study was aimed at assessing parameters affecting the prognosis of acute non lymphoid leukemia (ANLL). Since 1988 to 1994 we observed 84 patients: 52 males, 32 females. For each patient we considered at diagnosis: age, fever, performance status, platelets, hemoglobin and white blood cell count, extramidollary disease, bone marrow blastosis, phenotype and cytogenetic abnormalities of blasts cells. All the parameters listed above were correlated with the time to achieve the complete remission (CR), CR duration and the overall survival. Statistical tests as t-student and chi square test were used. Statistical analysis of the parameters considered revealed that the only value affecting the achievement of a CR was the age. The prognostic significance of immunophenotyping in ANLL has been a controversial issue, with a number of conflicting reports. In our study only the terminal deoxynucleotidyl transferase was significantly associated with prognosis. Our study, as data reported in literature, confirms that the prognostic impact of the various parameters in ANLL is controversial. The study of prognostic factors and of the immunophenotype is important to identify the clinical and the biologic profile of the disease and to evaluate the optimal post-remission treatment.

  6. Angiogenesis: a prognostic determinant in pancreatic cancer?

    PubMed

    van der Zee, Jill A; van Eijck, Casper H J; Hop, Wim C J; van Dekken, Herman; Dicheva, Bilyana M; Seynhaeve, Ann L B; Koning, Gerben A; Eggermont, Alexander M M; ten Hagen, Timo L M

    2011-11-01

    Angiogenesis has been associated with disease progression in many solid tumours, however the statement that tumours need angiogenesis to grow, invade and metastasise seems no longer applicable to all tumours or to all tumour subtypes. Prognostic studies in pancreatic cancer are conflicting. In fact, pancreatic cancer has been suggested an example of a tumour in which angiogenesis is less essential for tumour progression. The aim of the present study was therefore to measure angiogenesis in two anatomically closely related however prognostically different types of pancreatic cancer, pancreatic head and periampullary cancer, and investigate its relation with outcome. Vessels were stained by CD31 on original paraffin embedded tissue from 206 patients with microscopic radical resection (R0) of pancreatic head (n=98) or periampullary cancer (n=108). Angiogenesis was quantified by microvessel density (MVD) and measured by computerised image analysis of three randomly selected fields and investigated for associations with recurrence free survival (RFS), cancer specific survival (CSS), overall survival (OS) and conventional prognostic factors. MVD was heterogeneous both between and within tumours. A higher MVD was observed in periampullary cancers compared with pancreatic head cancers (p<.01). Furthermore, MVD was associated with lymph node involvement in pancreatic head (p=.014), but not in periampullary cancer (p=.55). Interestingly, MVD was not associated with RFS, CSS or with OS. In conclusion, angiogenesis is higher in periampullary cancer and although associated with nodal involvement in pancreatic head cancer, pancreatic cancer prognosis seems indeed angiogenesis independent.

  7. New prognostic markers in liver cirrhosis.

    PubMed

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-05-28

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of "inflammatory stress" and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value.

  8. Social indicators.

    PubMed

    Sheldon, E B; Parke, R

    1975-05-16

    The notions of social indicators and social accounting, expressed by analogy with the national economic accounts, generated excitement in the 1960's, and the interest continues to grow if we may judge from governmental activity and the publication of programmatic and research papers. But the concepts which focused much of the early enthusiasm gave exaggerated promise of policy applications and provided an unproductive basis for research. The essential theoretical prerequisites for developing a system of social accounts-defining the variables and the interrelationships among them-are missing. It is now realized that evaluation research, particularly experimentation, must be relied on for evaluation of government programs. Through the development and analysis of descriptive time series and the modeling of social processes, we will be able to describe the state of the society and its dynamics and thus improve immensely our ability to state problems in a productive fashion, obtain clues as to promising lines of endeavor, and ask good questions. But these activities cannot measure program effectiveness. Finally, we must be skeptical about definitions of the social indicators enterprise which confine it to social engineering efforts. The issue is not whether social indicators are useful for policy but, rather, how this usefulness comes about. The interest in social indicators has stimulated a revival of interest in quantitative, comparative, social analysis (60), in the analysis of social change, in conceptual and measurement work on such topics as prejudice, crime, and learning, and in the development of models of social processes. The fruit of these efforts will be more directly a contribution to the policy-maker's cognition than to his decisions. Decision emerges from a mosaic of inputs, including valuational and political, as well as technical components. The work we have described deals with only one type of input; it is a contribution to the intellectual mapping

  9. 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

  10. 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...

  11. UV "Indices"-What Do They Indicate?

    PubMed

    Moshammer, Hanns; Simic, Stana; Haluza, Daniela

    2016-10-24

    Ultra-Violet (UV) radiation covers the spectrum of wavelengths from 100 to 400 nm. The potency and biological activity for a variety of endpoints differ by wavelength. For monitoring and communication purposes, different UV action spectra have been developed. These spectra use different weighting functions. The action spectrum for erythemal dose is the most widely used one. This erythemal dose per time or dose-rate has been further simplified into a "UV index". Following this example, in our review we use the term "index" or (plural) "indices" in a more general description for all simplified single-value measures for any biologically effective UV dose, e.g., for human non-melanoma skin cancer and for previtamin D production rate. Ongoing discussion about the existence of an increased melanoma risk due to UV-A exposure underscores the uncertainties inherent in current weighting functions. Thus, we performed an online literature search to review the data basis for these indices, to understand their relevance for an individual, and to assess the applicability of the indices for a range of exposure scenarios. Even for natural (solar) UV, the spectral composition varies spatially and temporally. Artificial UV sources and personal protection introduce further variation to the spectral composition. Many biological effects are proposed for UV radiation. Only few endpoints have been studied sufficiently to estimate a reliable index. Weighting functions for chronic effects and most importantly for cancer endpoints have been developed in animal models, and often for proxy endpoints only. Epidemiological studies on biological effects of UV radiation should not only depend on single-value weighted UV dose estimates (indexes) but should strive for a more detailed description of the individual exposure. A better understanding of the adverse and beneficial effects of UV radiation by wavelength would also improve medical counseling and health communication regarding individual

  12. Expression and prognostic significance of unique ULBPs in pancreatic cancer

    PubMed Central

    Chen, Jiong; Zhu, Xing-Xing; Xu, Hong; Fang, Heng-Zhong; Zhao, Jin-Qian

    2016-01-01

    Background Pancreatic cancer is one of the most lethal cancers worldwide, due to the lack of efficient therapy and difficulty in early diagnosis. ULBPs have been shown to behave as important protectors with prognostic significance in various cancers. Materials and methods Immunohistochemistry and enzyme-linked immunosorbent assays were used to explore the expression of ULBPs in cancer tissue and in serum, while survival analysis was used to evaluate the subsequent clinical value of ULBPs. Results Statistics showed that high expression of membrane ULBP1 was a good biomarker of overall survival (18 months vs 13 months), and a high level of soluble ULBP2 was deemed an independent poor indicator for both overall survival (P<0.001) and disease-free survival (P<0.001). Conclusion ULBP1 provides additional information for early diagnosis, and soluble ULBP2 can be used as a novel tumor marker to evaluate the risk of pancreatic cancer patients. PMID:27621649

  13. Prognostic value of early features in rheumatoid disease.

    PubMed Central

    Fleming, A; Crown, J M; Corbett, M

    1976-01-01

    Extensive data on 102 patients who presented with rheumatoid disease within a year of onset were gathered by a prospective study to assess the prognostic value of early features. Outcome was evaluated at a mean 4-5 years from onset on the basis of functional grade, extent of joint disease, early morning stiffness, and grip strength. Twenty-six patients improved, 14 pursued a mild steady course, and 62 had a persistently severe or deteriorating condition. The features recorded at the first visit were correlated with outcome. Those indicating a poor prognosis were: older age at onset, being underweight, poor grip strength, many affected joints, involvement of wrist or metatarsophalangeal joints, poor functional status, fulfilment of many of the American Rheumatism Association criteria for rheumatoid disease, raised erythrocyte sedimentation rate, seropositivity on sheep cell agglutination or latex tests, low haemoglobin level, raised blood urea level, and early erosions on x-ray films. PMID:1083760

  14. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  15. Prognostic Value of Discs Large Homolog 7 Transcript Levels in Prostate Cancer

    PubMed Central

    Gomez, Christian R.; Kosari, Farhad; Munz, Jan-Marie; Schreiber, Claire A.; Knutson, Gaylord J.; Ida, Cristiane M.; El Khattouti, Abdelouahid; Karnes, R. Jeffrey; Cheville, John C.; Vasmatzis, George; Vuk-Pavlović, Stanimir

    2013-01-01

    Hypoxia has been associated with malignant progression, metastasis and resistance to therapy. Hence, we studied expression of hypoxia–regulated genes in 100 prostate cancer (CaP) bulk tissues and 71 adjacent benign tissues. We found 24 transcripts significantly overexpressed (p≤0.02). Importantly, higher transcript levels of disc large (drosophila) homolog-associated protein 5 (DLGAP5)/discs large homolog 7 (DLG7)/hepatoma up-regulated protein (HURP), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with higher Gleason score and more advanced systemic progression. Since the products of HMMR and CCNB1 have been identified recently as molecular markers of CaP progression, we postulated that DLG7 has prognostic value too. To test this hypothesis, we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within six years of surgery) and controls (no progression within eight years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CI, 0.68 to 0.8). Overall, our data indicate that expression of DLG7, a hypoxia-controlled gene, holds prognostic potential in high-risk CaP; this also demonstrates that variation of oxygen tension may constitute a tool for identification of novel biomarkers for CaP. PMID:24349376

  16. Accelerated Aging System for Prognostics of Power Semiconductor Devices

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Vashchenko, Vladislav; Wysocki, Philip; Saha, Sankalita

    2010-01-01

    Prognostics is an engineering discipline that focuses on estimation of the health state of a component and the prediction of its remaining useful life (RUL) before failure. Health state estimation is based on actual conditions and it is fundamental for the prediction of RUL under anticipated future usage. Failure of electronic devices is of great concern as future aircraft will see an increase of electronics to drive and control safety-critical equipment throughout the aircraft. Therefore, development of prognostics solutions for electronics is of key importance. This paper presents an accelerated aging system for gate-controlled power transistors. This system allows for the understanding of the effects of failure mechanisms, and the identification of leading indicators of failure which are essential in the development of physics-based degradation models and RUL prediction. In particular, this system isolates electrical overstress from thermal overstress. Also, this system allows for a precise control of internal temperatures, enabling the exploration of intrinsic failure mechanisms not related to the device packaging. By controlling the temperature within safe operation levels of the device, accelerated aging is induced by electrical overstress only, avoiding the generation of thermal cycles. The temperature is controlled by active thermal-electric units. Several electrical and thermal signals are measured in-situ and recorded for further analysis in the identification of leading indicators of failures. This system, therefore, provides a unique capability in the exploration of different failure mechanisms and the identification of precursors of failure that can be used to provide a health management solution for electronic devices.

  17. Synergistic childhood adversities and complex adult psychopathology.

    PubMed

    Putnam, Karen T; Harris, William W; Putnam, Frank W

    2013-08-01

    Numerous studies find a cumulative effect of different types of childhood adversities on increasing risk for serious adult mental and medical outcomes. This study uses the National Comorbidity Survey-Replication sample to investigate the cumulative impact of 8 childhood adversities on complex adult psychopathology as indexed by (a) number of lifetime diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994); (b) number of 4 DSM-IV disorder categories (mood, anxiety, impulse control, and substance abuse disorders); and (c) coexistence of internalizing and externalizing disorders. Seven of the 8 childhood adversities were significantly associated with complex adult psychopathology. Individuals with 4 or more childhood adversities had an odds ratio of 7.3, 95% confidence interval [4.7, 11.7] for 4 disorder categories. Additive and multiplicative synergistic effects increasing adult psychopathology were found for specific pairwise combinations of childhood adversities. Synergistic patterns differed by gender suggesting that women are more impacted by sexual abuse and men by economic hardship. The absence of childhood adversities was protective, in that it significantly decreased an individual's risk for subsequent adult mental illness. The results support the clinical impression that increased childhood adversity is associated with more complex adult psychopathology.

  18. Prognostic relevance of β-catenin expression in T2-3N0M0 esophageal squamous cell carcinoma

    PubMed Central

    Situ, Dong-Rong; Hu, Yi; Zhu, Zhi-Hua; Wang, Jian; Long, Hao; Rong, Tie-Hua

    2010-01-01

    AIM: To study the expression of β-catenin in esophageal squamous cell carcinoma (ESCC) at stage T2-3N0M0 and its relation with the prognosis of ESCC patients. METHODS: Expression of β-catenin in 227 ESCC specimens was detected by immunohistochemistry (IHC). A reproducible semi-quantitative method which takes both staining percentage and intensity into account was applied in IHC scoring, and receiver operating characteristic curve analysis was used to select the cut-off score for high or low IHC reactivity. Then, correlation of β-catenin expression with clinicopathological features and prognosis of ESCC patients was determined. RESULTS: No significant correlation was observed between β-catenin expression and clinicopathological parameters in terms of gender, age, tumor size, tumor grade, tumor location, depth of invasion and pathological stage. The Kaplan-Meier survival curve showed that the up-regulated expression of β-catenin indicated a poorer post-operative survival rate of ESCC patients at stage T2-3N0M0 (P = 0.004), especially of those with T3 lesions (P = 0.014) or with stage IIB diseases (P = 0.007). Multivariate analysis also confirmed that β-catenin was an independent prognostic factor for the overall survival rate of ESCC patients at stage T2-3N0M0 (relative risk = 1.642, 95% CI: 1.159-2.327, P = 0.005). CONCLUSION: Elevated β-catenin expression level may be an adverse indicator for the prognosis of ESCC patients at stage T2-3N0M0, especially for those with T3 lesions or stage IIB diseases. PMID:21049553

  19. Prognostic significance of exercise-induced premature ventricular complexes: a systematic review and meta-analysis of observational studies

    PubMed Central

    Lee, Victor; Perera, Dhanuka; Lambiase, Pier

    2017-01-01

    Background Exercise-induced premature ventricular complexes (EI-PVCs) are common during exercise stress tests. Their optimal management and prognostic significance remain uncertain. Aim To perform meta-analysis of observational studies on the prognostic significance of EI-PVCs. Methods A search was conducted on Medline and Embase. Inclusion criteria were observational studies comparing the prognosis of patients with and without EI-PVCs whilst exclusion criteria were studies without confounder adjustment and studies with zero endpoints. Composite endpoints included all-cause mortality, cardiac mortality and cardiovascular events. Relative risk of endpoints were analysed with random effects model. Meta-regression and sensitivity analysis were performed. Results Ten studies were included. In asymptomatic patients who had no clinical evidence of heart disease, EI-PVCs were associated with a pooled risk ratio of 1.82 (95% CI 1.44 to 2.30) of developing adverse cardiovascular events over 16 years. The corresponding pooled RR for patients with symptomatic heart disease was 1.36 (95% CI 1.18 to 1.57) over 5.4 years. Sensitivity analysis: only EI-PVCs on the recovery phase of an exercise test, not during exercise, had adverse prognostic significance. Conclusions EI-PVCs are correlated with a higher risk of all cause death or cardiovascular events in the long term. This risk is elevated in asymptomatic patients without clinical heart disease and in patients with symptomatic heart disease. The fact that only EI-PVCs during recovery, and not during exercise, have poor prognostic value suggests that autonomic dysfunction may play a role in this association. Further studies are needed to see if autonomic manipulation by drugs or catheter-based methods can improve the poor prognosis associated with EI-PVCs. PMID:28123456

  20. 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.

  1. 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

  2. Weight-of-evidence evaluation of an adverse outcome ...

    EPA Pesticide Factsheets

    Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating staple food crops. Chemical and non-chemical stressors both have been implicated as possible contributors to colony failure, however, the potential role of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptor (nAChR) to eliminate target pest insects, however, mounting evidence indicates that these chemicals may adversely affect beneficial pollinators, such as the honey bee, via impacts on learning and memory thereby affecting foraging success. However, the mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. Therefore, the objective of this work was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between the nAChR and colony level impacts. Development of these AOPs has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect honey bee health, causing colony instability and further failure. From this effort, an AOP network also was developed, laying the f

  3. iADRs: towards online adverse drug reaction analysis.

    PubMed

    Lin, Wen-Yang; Li, He-Yi; Du, Jhih-Wei; Feng, Wen-Yu; Lo, Chiao-Feng; Soo, Von-Wun

    2012-12-01

    Adverse Drug Reaction (ADR) is one of the most important issues in the assessment of drug safety. In fact, many adverse drug reactions are not discovered during limited pre-marketing clinical trials; instead, they are only observed after long term post-marketing surveillance of drug usage. In light of this, the detection of adverse drug reactions, as early as possible, is an important topic of research for the pharmaceutical industry. Recently, large numbers of adverse events and the development of data mining technology have motivated the development of statistical and data mining methods for the detection of ADRs. These stand-alone methods, with no integration into knowledge discovery systems, are tedious and inconvenient for users and the processes for exploration are time-consuming. This paper proposes an interactive system platform for the detection of ADRs. By integrating an ADR data warehouse and innovative data mining techniques, the proposed system not only supports OLAP style multidimensional analysis of ADRs, but also allows the interactive discovery of associations between drugs and symptoms, called a drug-ADR association rule, which can be further developed using other factors of interest to the user, such as demographic information. The experiments indicate that interesting and valuable drug-ADR association rules can be efficiently mined.

  4. [Cardiovascular pharmacotherapy. Risks and adverse effects].

    PubMed

    Voigt, N; Heijman, J; Dobrev, D

    2014-03-01

    Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.

  5. 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

  6. Childhood adversity: a review of measurement instruments.

    PubMed

    Burgermeister, Diane

    2007-01-01

    Measurement instruments are needed to stimulate research on the long-term outcomes of childhood adversity. Therefore, the purpose of this review was to locate, describe, and assess instruments to measure retrospective perceptions of childhood adversity. An electronic search of instruments was conducted using a combination of keywords that included child maltreatment, child trauma, and childhood stressful events. Nine instruments were located and described according to format, definition of childhood adversity as measured by the instrument, characteristics of the sample used in development and testing, reliability and validity evidence, and feasibility for use. Six out of the nine instruments were suitable for investigators who require a comprehensive measure of childhood adversity. Corroboration with independent sources and use of randomized samples are needed to improve upon reports of validity.

  7. 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...

  8. 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...

  9. Brain Metastases From Breast Carcinoma: Validation of the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification and Proposition of a New Prognostic Score

    SciTech Connect

    Le Scodan, Romuald Massard, Christophe; Mouret-Fourme, Emmanuelle; Guinebretierre, Jean Marc; Cohen-Solal, Christine; De Lalande, Brigitte; Moisson, Patricia; Breton-Callu, Christelle; Gardner, Miriam; Goupil, Alain; Renody, Nicole; Floiras, Jean Louis; Labib, Alain

    2007-11-01

    Purpose: To validate the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification and determine independent prognostic factors, to create a simple and specific prognostic score for patients with brain metastases (BM) from breast carcinoma treated with whole-brain radiotherapy (WBRT). Methods and Materials: From January 1998 through December 2003, 132 patients with BM from breast carcinoma were treated with WBRT. We analyzed several potential predictors of survival after WBRT: age, Karnofsky performance status, RTOG-RPA class, number of BM, presence and site of other systemic metastases, interval between primary tumor and BM, tumor hormone receptor (HR) status, lymphocyte count, and HER-2 overexpression. Results: A total of 117 patients received exclusive WBRT and were analyzed. Median survival with BM was 5 months. One-year and 2-year survival rates were 27.6% (95% confidence interval [CI] 19.9-36.8%) and 12% (95% CI 6.5-21.2%), respectively. In multivariate analysis, RTOG RPA Class III, lymphopenia ({<=}0.7 x 10{sup 9}/L) and HR negative status were independent prognostic factors for poor survival. We constructed a three-factor prognostic scoring system that predicts 6-month and 1-year rates of overall survival in the range of 76.1-29.5% (p = 0.00033) and 60.9-15.9% (p = 0.0011), respectively, with median survival of 15 months, 5 months, or 3 months for patients with none, one, or more than one adverse prognostic factor(s), respectively. Conclusions: This study confirms the prognostic value of the RTOG RPA classification, lymphopenia, and tumor HR status, which can be used to form a prognostic score for patients with BM from breast carcinoma.

  10. Design of Adverse Drug Events-Scorecards.

    PubMed

    Marcilly, Romaric; Chazard, Emmanuel; Beuscart-Zéphir, Marie-Catherine; Hackl, Werner; Băceanu, Adrian; Kushniruk, Andre; Borycki, Elizabeth M

    2011-01-01

    This paper presents the design of Adverse Drug Event-Scorecards. The scorecards described are innovative and novel, not having previously been reported in the literature. The Scorecards provide organizations (e.g. hospitals) with summary information about Adverse Drug Events (ADEs) using a Web-based platform. The data used in the Scorecards are routinely updated and report on ADEs detected through data mining processes. The development of the ADE Scorecards is ongoing and they are currently undergoing clinical testing.

  11. [Allergies and adverse events associated with fluoroquinolones].

    PubMed

    Muller, Y; Andrey, D; Emonet, S; Harr, T; Spoerl, D

    2015-04-08

    The prescription ot fluoroquinolones has been constantly increasing over the past decade. consequently, an increasing number of hyper-sensitivity reactions and adverse events have been reported. The aim of the review is to discuss the incidence of hypersensitivity reactions either IgE (immediate) or T cells mediated (delayed). We will make an overview ofthe diagnostic tools available to detect such hypersensitivity reactions. Finally, the specific adverse events associated with fluoroquinolones, including tendinopathy, chondrotoxicity, peripheral neuropathy or retinal detachment will be discussed.

  12. Childhood adversity and frequent medical consultations.

    PubMed

    Fiddler, Maggie; Jackson, Judy; Kapur, Navneet; Wells, Adrian; Creed, Francis

    2004-01-01

    We assessed possible psychological mediators of the relationship between childhood adversity and frequent medical consultations among new outpatients at neurology, cardiology, and gastroenterology clinics. We assessed whether these differed in patients with and without organic disease that explained their symptoms. At first clinic visit we recorded Hospital Anxiety and Depression scale (HADS--anxiety and depression subscale scores), Illness Perception Questionnaire (IPQ--four subscales: consequences, cure, identity, timeline), Health Anxiety Questionnaire (total score), and Symptom Amplification Scale (total score). Subjects were divided into two groups according to whether they had experienced any type of childhood adversity using the Childhood Experience of Care and Abuse Schedule. Outcome was the (log) number of medical consultations for 12 months before and 6 months after the index clinic visits. Multiple regression analysis was used to determine mediators; this was performed separately for patients with symptoms explained and not explained by organic disease. One-hundred and twenty-nine patients (61% response) were interviewed. Fifty-two (40.3%) had experienced childhood adversity; they made a median of 16 doctor visits compared with 10 for those without adversity (adjusted P=.026). IPQ identity score (number of symptoms attributed to the illness) and HAD depression scores were significantly associated with both childhood adversity and number of medical consultations and these variables acted as mediators between childhood adversity and frequency of consultation in the multiple regression analyses. This association was limited to patients with medically unexplained symptoms and was mediated by IPQ Identity Score (number of symptoms attributed to the patient's illness) and HAD depression score. Sexual abuse and overt neglect were the adversities most closely associated with frequent consultations. In patients with medically unexplained symptoms the association

  13. Adverse drug reactions in hospitalized Colombian children

    PubMed Central

    Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa

    2016-01-01

    Introduction: The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. Objective: To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. Methods: A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Results: Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p= 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p= 0.005). Conclusions: Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics. PMID:27821893

  14. BRAF V600E mutation in prognostication of papillary thyroid cancer (PTC) recurrence

    PubMed Central

    Oczko-Wojciechowska, Małgorzata; Barczyński, Marcin

    2016-01-01

    Papillary thyroid cancer (PTC) offers excellent prognosis, however relapse risk or persistent disease is related to ~30%. Currently, attention is paid to the possibility of patient group selection of different risk of unfavorable outcome to match a particular therapeutic approach. Therefore, interest in new prognostic and predictive markers known preoperatively is observed. BRAF V600E mutation is such a marker. Many studies analyzing the prevalence of the mutation and its relationship with other clinico-pathological risk factors were reported but with controversial conclusions. The prognostic significance of BRAF mutation was confirmed by some single centre studies, a few meta-analyses and a large multicenter retrospective international study. They confirmed a correlation between the mutation and the risk of recurrence. The strongest argument against using BRAF mutation as an independent prognostic and predictive factor in PTC is its high prevalence (30–80%). At present it seems that BRAF mutation is one of the factors influencing the prognosis and it should be analyzed in correlation with other prognostic factors. The most recent ATA recommendations do not indicate a routine application of BRAF status for initial risk stratification in differentiated thyroid cancer due to a lack of evident confirmation of a direct influence of mutation on the increase in relapse risk. However, ATA demonstrates the continuous risk scale for the relapse risk assessment, considering BRAF and/or TERT status. At present, researchers are working on determining the role of BRAF mutation in patients from a low-risk group and its correlations with others molecular events. Currently, BRAF mutation cannot be used as a single, independent predictive factor. However, its usefulness in the context of other molecular and clinico-pathological risk factors cannot be excluded. They may be used to make modern prognostic scales of relapse risk and be applied to individualized diagnostic and

  15. Prognostic Impact of Immunonutritional Status Changes During Preoperative Chemoradiation in Patients With Rectal Cancer

    PubMed Central

    Lee, Yong Joon; Kim, Woo Ram; Han, Jeonghee; Han, Yoon Dae; Cho, Min Soo; Hur, Hyuk; Lee, Kang Young; Kim, Nam Kyu

    2016-01-01

    Purpose Previous studies have demonstrated the prognostic impact of the prognostic nutritional index (PNI), a proposed indicator of immunonutritional statuses of surgical patients, on patients with various gastrointestinal cancers. Although the prognostic impact of the PNI on patients with colorectal cancer has been well established, its value has not been studied in patients treated with preoperative chemoradiation (pCRT). This study aimed to evaluate the prognostic impact of PNI on patients receiving pCRT for locally advanced rectal cancer (LARC). Methods Patients with LARC who underwent curative pCRT followed by surgical resection were enrolled. The PNI was measured in all patients before and after pCRT, and the difference in values was calculated as the PNI difference (dPNI). Patients were classified according to dPNI (<5, 5–10, and >10). Clinicopathologic parameters and long-term oncologic outcomes were assessed according to dPNI classification. Results No significant intergroup differences were observed in clinicopathologic parameters such as age, histologic grade, tumor location, tumor-node-metastasis stage, and postoperative complications. Approximately 53% of the patients had a mild dPNI (<5); only 15% had a high dPNI (>10). Univariate and multivariate analyses identified the dPNI as an independent prognostic factor for disease-free status (P < 0.01; hazard ratio [HR], 2.792; 95% confidence interval [CI], 1.577–4.942) and for cancer-specific survival (P = 0.012; HR, 2.469; 95%CI, 1.225–4.978). Conclusion The dPNI is predictive of long-term outcomes in pCRT-treated patients with LARC. Further prospective studies should investigate whether immune-nutritional status correction during pCRT would improve oncologic outcomes. PMID:28119863

  16. 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.

  17. Topoisomerase II alpha--a fundamental prognostic factor in breast carcinoma.

    PubMed

    Hajduk, Magdalena

    2009-01-01

    Because of the introduction of modern diagnostic methods, numerous prognostic and predictive factors have been recognized and are today considered classic, yet they seem to be insufficient in assessment of prognosis, hence the need for further investigations. Among factors newly discovered by molecular techniques, there are class I and II topoisomerases, the role of which as prognosticators has not been fully determined. The objective of the present investigation was the assessment of topoisomerase II alpha (TOP2A) expression in patients with infiltrating breast carcinoma, as a prognostic factor in correlation with other recognized prognosticators and patient survival. The study was carried out in 151 patients treated by mastectomy and lymph node excision followed by adjuvant chemotherapy. The material was evaluated histopathologically according to the pTNM system, taking into consideration such parameters as grade of malignancy (G); the ER, PR as well as HER2 and TOP2A receptors status--all of them were assessed immunohistochemically. TOP2A was expressed with varying intensity in the majority of infiltrating ductal carcinomas studied, more frequently in large T3 and T4, grade G2 and G3 tumours, in patients with extensive metastases to regional N2 and N3 lymph nodes, a positive HER2 and negative ER and PR status. Five-year mortality rates were higher and 5-year symptom-free survival rates were lower in patients with TOP2A-positive tumours as compared to individuals with a negative TOP2A status. The study indicates that TOP2A expression is a negative predictive factor and may be recognized as a prognostic factor.

  18. Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone

    PubMed Central

    Webster, Joshua D; Yuzbasiyan-Gurkan, Vilma; Thamm, Douglas H; Hamilton, Elizabeth; Kiupel, Matti

    2008-01-01

    Background Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease associated with a variable biologic behavior. Surgery remains the primary treatment for canine MCT; however, radiation therapy (RT) and chemotherapy are commonly used to treat aggressive MCT. The goals of this study were to evaluate the prognostic utility of histologic grade, c-KIT mutations, KIT staining patterns, and the proliferation markers Ki67 and AgNORs in dogs postoperatively treated with vinblastine and prednisone +/- RT, and to compare the outcome of dogs treated with post-operative chemotherapy +/- RT to that of a prognostically matched group treated with surgery alone. Associations between prognostic markers and survival were evaluated. Disease-free intervals (DFI) and overall survival times (OS) of dogs with similar pretreatment prognostic indices postoperatively treated with chemotherapy were compared to dogs treated with surgery alone. Results Histologic grade 3 MCTs, MCTs with c-KIT mutations, MCTs with increased cytoplasmic KIT, and MCTs with increased Ki67 and AgNOR values were associated with decreased DFI and OS. Dogs with histologic grade 3 MCT had significantly increased DFI and OS when treated with chemotherapy vs. surgery alone. Although not statistically significant due to small sample sizes, MCTs with c-KIT mutations had increased DFI and OS when treated with chemotherapy vs. surgery alone. Conclusion and clinical importance This study confirms the prognostic value of histologic grade, c-KIT mutations, KIT staining patterns, and proliferation analyses for canine MCT. Additionally, the results of this study further define the benefit of postoperative vinblastine and prednisone for histologic grade 3 MCTs. PMID:18700956

  19. Prognostic nutritional index is an independent prognostic factor for gastric cancer patients with peritoneal dissemination

    PubMed Central

    Nie, Runcong; Yuan, Shuqiang; Chen, Shi; Chen, Xiaojiang; Chen, Yongming; Zhu, Baoyan; Qiu, Haibo; Zhou, Zhiwei; Peng, Junsheng; Chen, Yingbo

    2016-01-01

    Objective The predictive and prognostic role of prognostic nutritional index (PNI) in gastric cancer patients with peritoneal dissemination remains unclear. This study aims to explore the role of the PNI in predicting outcomes of gastric cancer patients with peritoneal dissemination. Methods A total of 660 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis between January 2000 and April 2014 at Sun Yat-sen University Cancer Center and the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed. Results Compared with PNI-high group, PNI-low group was correlated with advanced age (P=0.036), worse performance status (P<0.001), higher frequency of ascites (P<0.001) and higher frequency of multisite distant metastasis (P<0.001). Kaplan-Meier survival curves showed that PNI-high group had a significantly longer median overall survival than PNI-low group (13.13 vs. 9.03 months, P<0.001). Multivariate survival analysis revealed that Borrmann type IV (P=0.014), presence of ascites (P=0.017) and lower PNI (P=0.041) were independent poor prognostic factors, and palliative surgery (P<0.001) and first-line chemotherapy (P<0.001) were good prognostic factors. For patients receiving palliative surgery, the postoperative morbidity rates in the PNI-low group and PNI-high group were 9.1% and 9.9%, respectively (P=0.797). The postoperative mortality rate was not significantly different between PNI-low and PNI-high groups (2.3% vs. 0.9%, P=0.362). Conclusions PNI is a useful and practical tool for evaluating the nutritional status of gastric cancer patients with peritoneal dissemination, and is an independent prognostic factor for these patients. PMID:28174485

  20. Recognizing and reporting adverse drug reactions.

    PubMed Central

    Lucas, L. M.; Colley, C. A.

    1992-01-01

    Although physicians in practice are most likely to see patients with adverse drug reactions, they may fail to recognize an adverse effect or to attribute it to a drug effect and, when recognized, they may fail to report serious reactions to the US Food and Drug Administration (FDA). To recognize and attribute an adverse event to a drug effect, physicians should review the patient's clinical course, looking at patient risk factors, the known adverse reactions to the suspected drug, and the likelihood of a causal relationship between the drug and the adverse event-based on the temporal relationship, response to stopping or restarting the drug, and whether other factors could explain the reaction. Once an adverse drug reaction has been identified, the patient should be informed and appropriate documentation made in the patient's medical record. Serious known reactions and all reactions to newly released drugs or those not previously known to occur (even if the certainty is low) should be reported to the FDA. PMID:1536067

  1. Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma

    PubMed Central

    Bhandaru, Madhuri; Martinka, Magdalena; McElwee, Kevin J.; Rotte, Anand

    2015-01-01

    UV radiation induced genomic instability is one of the leading causes for melanoma. Phosphorylation of Ataxia Telangiectasia Mutated (ATM) is one of the initial events that follow DNA damage. Phospho-ATM (p-ATM) plays a key role in the activation of DNA repair and several oncogenic pathways as well as in the maintenance of genomic integrity. The present study was therefore performed to understand the significance of p-ATM in melanoma progression and to correlate it with patient prognosis. Tissue microarray and immunohistochemical analysis were employed to study the expression of p-ATM in melanoma patients. A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma) were used for the study. Chi-square test, Kaplan-Meier, univariate and multivariate Cox regression analysis were used to elucidate the prognostic significance of p-ATM expression. Results revealed that both loss of, and gain in, p-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma. Patients whose samples showed negative or strong p-ATM staining had significantly worse 5-year survival compared to patients who had weak to moderate expression. Loss of p-ATM expression was associated with relatively better 5-year survival, but the corresponding 10-year survival curve almost overlapped with that of strong p-ATM expression. p-ATM expression was found to be an independent prognostic factor for 5-year but not for 10-year patient survival. In conclusion our findings show that loss of p-ATM expression and gain-in p-ATM expression are indicators of worse melanoma patient survival. PMID:26275218

  2. A Gaussian process based prognostics framework for composite structures

    NASA Astrophysics Data System (ADS)

    Liu, Yingtao; Mohanty, Subhasish; Chattopadhyay, Aditi

    2009-03-01

    Prognostic algorithms indicate the remaining useful life based on fault detection and diagnosis through condition monitoring framework. Due to the wide-spread applications of advanced composite materials in industry, the importance of prognosis on composite materials is being acknowledged by the research community. Prognosis has the potential to significantly enhance structural monitoring and maintenance planning. In this paper, a Gaussian process based prognostics framework is presented. Both off-line and on-line methods combined state estimation and life prediction of composite beam subject to fatigue loading. The framework consists of three main steps: 1) data acquisition, 2) feature extraction, 3) damage state prediction and remaining useful life estimation. Active piezoelectric and acoustic emission (AE) sensing techniques are applied to monitor the damage states. Wavelet transform is used to extract the piezoelectric sensing features. The number of counts from AE system was used as a feature. Piezoelectric or AE sensing features are used to build the input and output space of the Gaussian process. The future damage states and remaining useful life are predicted by Gaussian process based off-line and on-line algorithms. Accuracy of the Gaussian process based prognosis method is improved by including more training sets. Piezoelectric and AE features are also used for the state prediction. In the test cases presented, the piezoelectric features lead to better prognosis results. On-line prognosis is completed sequentially by combining experimental and predicted features. On-line damage state prediction and remaining useful life estimation shows good correlation with experimental data at later stages of fatigue life.

  3. Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma.

    PubMed

    Bhandaru, Madhuri; Martinka, Magdalena; McElwee, Kevin J; Rotte, Anand

    2015-01-01

    UV radiation induced genomic instability is one of the leading causes for melanoma. Phosphorylation of Ataxia Telangiectasia Mutated (ATM) is one of the initial events that follow DNA damage. Phospho-ATM (p-ATM) plays a key role in the activation of DNA repair and several oncogenic pathways as well as in the maintenance of genomic integrity. The present study was therefore performed to understand the significance of p-ATM in melanoma progression and to correlate it with patient prognosis. Tissue microarray and immunohistochemical analysis were employed to study the expression of p-ATM in melanoma patients. A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma) were used for the study. Chi-square test, Kaplan-Meier, univariate and multivariate Cox regression analysis were used to elucidate the prognostic significance of p-ATM expression. Results revealed that both loss of, and gain in, p-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma. Patients whose samples showed negative or strong p-ATM staining had significantly worse 5-year survival compared to patients who had weak to moderate expression. Loss of p-ATM expression was associated with relatively better 5-year survival, but the corresponding 10-year survival curve almost overlapped with that of strong p-ATM expression. p-ATM expression was found to be an independent prognostic factor for 5-year but not for 10-year patient survival. In conclusion our findings show that loss of p-ATM expression and gain-in p-ATM expression are indicators of worse melanoma patient survival.

  4. Lung Cancer Indicators Recurrence

    Cancer.gov

    This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

  5. Regular treatment with formoterol for chronic asthma: serious adverse events

    PubMed Central

    Cates, Christopher J; Cates, Matthew J

    2014-01-01

    regular formoterol was compared with placebo (Peto odds ratio (OR) 1.57; 95% CI 1.06 to 2.31). One extra serious adverse event occurred over 16 weeks for every 149 people treated with regular formoterol (95% CI 66 to 1407 people). The increase was larger in children than in adults, but the impact of age was not statistically significant. Data submitted to the FDA indicate that the increase in asthma-related serious adverse events remained significant in patients taking regular formoterol who were also on inhaled corticosteroids. No significant increase in fatal or non-fatal serious adverse events was found when regular formoterol was compared with regular salbutamol or terbutaline. Authors’ conclusions In comparison with placebo, we have found an increased risk of serious adverse events with regular formoterol, and this does not appear to be abolished in patients taking inhaled corticosteroids. The effect on serious adverse events of regular formoterol in children was greater than the effect in adults, but the difference between age groups was not significant. Data on all-cause serious adverse events should be more fully reported in journal articles, and not combined with all severities of adverse events or limited to those events that are thought by the investigator to be drug-related. PMID:22513944

  6. 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.

  7. [Significance of prognostic parameters in acute pancreatitis].

    PubMed

    Guastella, T; Scuderi, M; Di Stefano, A; Scala, R; Rapisarda, D; Succi, L; Russello, D

    1993-07-01

    The diagnostic and therapeutic approach to Acute Pancreatitis (A.P.) is directly related to the clinical presentation. The Authors reviewed the data of 66 patients, hospitalized between October 1989 and December 1991, to verify the effectiveness of the prognostic criteria suggested by Ranson (1974), Mercadier (1977) and Imrie (1978). A.P. was of biliary origin in the majority of the patients (63.5%); five patients (7.5%) had an acute alcoholic pancreatitis, while the aetiology was traumatic or unknown in the remaining cases. A complicated clinical course was defined by the development of pseudocyst, pancreatic abscess, digestive haemorrhage, death or prolonged hospitalization (more than 20 days). The 28.8% of the patients developed complications during hospitalization. There were seven pancreatic pseudocysts, six pulmonary complications, three renal insufficiencies, two vascular complications, two sepsies and a gastrointestinal haemorrhage. The mean hospitalization period was 15.1 days (range 1-112). The Authors conclude that the three different prognostic criteria are equally useful to test the severity of A.P. attacks allowing to identify patients with the higher risk to develop complications during hospitalization.

  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. Frailty as a predictor of short-term adverse outcomes

    PubMed Central

    Coelho, Tiago; Paúl, Constança; Gobbens, Robbert J.J.

    2015-01-01

    The objectives of this study were to compare how different frailty measures (Frailty Phenotype/FP, Groningen Frailty Indicator/GFI and Tilburg Frailty Indicator/TFI) predict short-term adverse outcomes. Secondarily, adopting a multidimensional approach to frailty (integral conceptual model–TFI), this study aims to compare how physical, psychological and social frailty predict the outcomes. A longitudinal study was carried out with 95 community-dwelling elderly. Participants were assessed at baseline for frailty, determinants of frailty, and adverse outcomes (healthcare utilization, quality of life, disability in basic and instrumental activities of daily living/ADL and IADL). Ten months later the outcomes were assessed again. Frailty was associated with specific healthcare utilization indicators: the FP with a greater utilization of informal care; GFI with an increased contact with healthcare professionals; and TFI with a higher amount of contacts with a general practitioner. After controlling for the effect of life-course determinants, comorbidity and adverse outcome at baseline, GFI predicted IADL disability and TFI predicted quality of life. The effect of the FP on the outcomes was not significant, when compared with the other measures. However, when comparing TFI’s domains, the physical domain was the most significant predictor of the outcomes, even explaining part of the variance of ADL disability. Frailty at baseline was associated with adverse outcomes at follow-up. However, the relationship of each frailty measure (FP, GFI and TFI) with the outcomes was different. In spite of the role of psychological frailty, TFI’s physical domain was the determinant factor for predicting disability and most of the quality of life. PMID:26246968

  10. Frequency and prognostic value of cardiac troponin I elevation after coronary stenting.

    PubMed

    Garbarz, E; Iung, B; Lefevre, G; Makita, Y; Farah, B; Michaud, P; Graine, H; Vahanian, A

    1999-09-01

    Mild myocardial injuries after coronary angioplasty are associated with adverse late outcomes. The incidence and prognostic value of this phenomenon when using cardiac troponin I (cTnI) after stent implantation is unknown. We studied cTnI and creatine kinase (CK) release in 109 patients after stenting. Clinical success was achieved in 103 patients (94%). In-hospital major adverse coronary events were: death in 1 patient, Q-wave myocardial infarction in 1 patient, and non-Q-wave myocardial infarction in 2 patients. Twenty-nine patients (27%) had postprocedural cTnI increase, 16 (15%) had CK elevation. No preprocedural variables predicted marker elevation. Marker release was related to the occurrence of in-lab complications (59% vs 29% [p = 0.004 for cTnI] and 69% vs 32% [p = 0.011 for CK]). In 34% no explanation was found for cTnI increase. Success was more frequent in patients without cTnI elevation (100% vs 86%, p <0.001). The negative predictive value of cTnI increase was 100% for in-hospital major adverse coronary events (MACE), whereas its positive predictive value was 14%. cTnI and CK concordant elevation was associated with more intra- and postprocedural adverse events. During a mean follow-up of 8+/-3 months, major adverse coronary events were: death in 2 patients, myocardial infarction in 2 patients, and repeat PTCA in 8 patients. cTnI elevation was not predictive of these late MACE. cTnI elevation is common after stenting, and is related to the occurrence of in-lab complications. Its isolated elevation is not a good predictor of MACE. Patients with concordant cTnI and CK elevation seem to be at higher risk of in-hospital MACE.

  11. Adverse-event profile of Crataegus spp.: a systematic review.

    PubMed

    Daniele, Claudia; Mazzanti, Gabriela; Pittler, Max H; Ernst, Edzard

    2006-01-01

    ), gastrointestinal complaints (n = 24), headache (n = 9), migraine (n = 8) and palpitation (n = 11). The WHO spontaneous reporting scheme received 18 case reports. In the identified trials, the most frequent adverse events were dizziness (n = 6), nausea (n = 5), fall (n = 2), gastrointestinal haemorrhage (n = 2), circulation failure (n = 2) and erythematous rash (n = 2). There were no reports of drug interactions. In conclusion, all data reviewed in this article seem to indicate that hawthorn is well tolerated even if some severe adverse events were reported; this suggests that further studies are needed to better assess the safety of hawthorn-containing preparations. Moreover, the unsupervised use of this drug can be associated with problems, especially if given with concomitant medications.

  12. Drug-Related Adverse Events of Osteoporosis Therapy.

    PubMed

    Khan, Moin; Cheung, Angela M; Khan, Aliya A

    2017-03-01

    Postmenopausal osteoporosis is associated with microarchitectural deterioration and increased risk of fracture. Osteoporosis therapy effectively reduces the risk of vertebral, nonvertebral, and hip fracture and has been associated with increased survival. Currently approved treatments for osteoporosis include bisphosphonates, denosumab, selective estrogen receptor modulators, and teriparatide. This article reviews the adverse events of therapy associated with these medical interventions. Hormone replacement therapy is not included, because it is no longer indicated for the treatment of osteoporosis in all countries. Calcitonin and strontium ranelate are also not included, because their indication for osteoporosis has recently been limited or withdrawn.

  13. Component-Level Prognostics Health Management Framework for Passive Components - Advanced Reactor Technology Milestone: M2AT-15PN2301043

    SciTech Connect

    Ramuhalli, Pradeep; Roy, Surajit; Hirt, Evelyn H.; Prowant, Matthew S.; Pitman, Stan G.; Tucker, Joseph C.; Dib, Gerges; Pardini, Allan F.

    2015-06-19

    This report describes research results to date in support of the integration and demonstration of diagnostics technologies for prototypical advanced reactor passive components (to establish condition indices for monitoring) with model-based prognostics methods. Achieving this objective will necessitate addressing several of the research gaps and technical needs described in previous technical reports in this series.

  14. Concomitant renal insufficiency and diabetes mellitus as prognostic factors for acute myocardial infarction

    PubMed Central

    2011-01-01

    Background Diabetes mellitus and renal dysfunction are prognostic factors after acute myocardial infarction (AMI). However, few studies have assessed the effects of renal insufficiency in association with diabetes in the context of AMI. Here, we investigated the clinical outcomes according to the concomitance of renal dysfunction and diabetes mellitus in patients with AMI. Methods From November 2005 to August 2008, 9905 patients (63 ± 13 years; 70% men) with AMI were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR) and were categorized into 4 groups: Group I (n = 5700) had neither diabetes nor renal insufficiency (glomerular filtration rate [GFR] ≥ 60 ml/min/1.73 m2), Group II (n = 1730) had diabetes but no renal insufficiency, Group III (n = 1431) had no diabetes but renal insufficiency, and Group IV (n = 1044) had both diabetes and renal insufficiency. The primary endpoints were major adverse cardiac events (MACE), including a composite of all cause-of-death, myocardial infarction, target lesion revascularization, and coronary artery bypass graft after 1-year clinical follow-up. Results Primary endpoints occurred in 1804 (18.2%) patients. There were significant differences in composite MACE among the 4 groups (Group I, 12.5%; Group II, 15.7%; Group III, 30.5%; Group IV, 36.5%; p < 0.001). In a Cox proportional hazards model, after adjusting for multiple covariates, the 1-year mortality increased stepwise from Group III to IV as compared with Group I (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.34-2.86; p = 0.001; and HR, 2.42; 95% CI, 1.62-3.62; p < 0.001, respectively). However, Kaplan-Meier analysis showed no significant difference in probability of death at 1 year between Group III and IV (p = 0.288). Conclusions Renal insufficiency, especially in association with diabetes, is associated with the occurrence of composite MACE and indicates poor prognosis in patients with AMI. Categorization of patients with

  15. Predictive and Prognostic Value of High-density Lipoprotein Cholesterol in Young Male Patients with Acute Myocardial Infarction

    PubMed Central

    Li, Zhao; Huang, Ji; Li, Nan

    2017-01-01

    Background: The level of high-density lipoprotein cholesterol (HDL-C) is an important risk indicator and used in risk factor counting and quantitative risk assessment; however, the effect of HDL-C in young male patients with acute myocardial infarction (AMI) is unclear. The aim of this study was to investigate the effect of HDL-C in young male patients. Methods: We recruited 267 consecutive young male patients (≤44 years) diagnosed with AMI. Other 247 participants free from coronary heart disease were enrolled as controls. HDL-C levels of AMI patients and controls were evaluated to analyze the predictive value on AMI. According to the cutoff point of 1.04 mmol/L HDL-C, patients of AMI were divided into two subgroups (normal HDL-C group and low HDL-C group) and were followed up for 2 years. Clinical end points included all major adverse coronary events (MACEs): the main cause of death, nonfatal myocardial infarction, readmissions for acute coronary syndrome, arrhythmias, or revascularization. The prognostic value of HDL-C was evaluated using Cox regression according to MACE. Results: Patients of AMI had decreased proportion in normal HDL-C group compared to controls (47.2% vs. 57.9%; P = 0.017). Logistic regression analysis showed that there was an inverse relationship between HDL-C and AMI in young males. In the low HDL-C subgroup of AMI patients (n = 141), 34 (24.1%) patients experienced a MACE during the 2-year follow-up, compared with 15 (11.9%) patients in normal HDL-C subgroup (n = 126). The Cox regression analysis showed that HDL-C was an independent predictor of a MACE during the follow-up period (hazard ratio = 0.354, P = 0.006). Conclusion: HDL-C was an important parameter for predicting the risk and the clinical outcomes of AMI in young male patients. PMID:28051027

  16. 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

  17. Putative adverse outcome pathways relevant to neurotoxicity

    PubMed Central

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  18. The Complement System and Adverse Pregnancy Outcomes

    PubMed Central

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

    2015-01-01

    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 feta 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

  19. Is It Adverse, Nonadverse, Adaptive, or Artifact?

    PubMed

    Pandiri, Arun R; Kerlin, Roy L; Mann, Peter C; Everds, Nancy E; Sharma, Alok K; Myers, L Peyton; Steinbach, Thomas J

    2017-01-01

    One of the principal challenges facing a toxicologic pathologist is to determine and differentiate a true adverse effect from a nonadverse or an adaptive response. Recent publications from the Society of Toxicologic Pathology (STP) and the European STP provide guidance for determining and communicating adversity in nonclinical toxicology studies. In order to provide a forum to inform and engage in a discussion on this important topic, a continuing education (CE) course was held during the 2016 STP Annual meeting in San Diego, CA. The lectures at this course provided guidance on determining and communicating adversity using case studies involving both clinical pathology and anatomic pathology. In addition, one talk also focused on data quality, study design, and interpretation of artifacts that could hinder the determination of adversity. The CE course ended with a talk on understanding adversity in preclinical studies and engaging the regulatory agencies in the decision-making process. This manuscript is designed to provide brief summaries of all the talks in this well-received CE course.

  20. Environmental adversity and uncertainty favour cooperation

    PubMed Central

    Andras, Peter; Lazarus, John; Roberts, Gilbert

    2007-01-01

    Background A major cornerstone of evolutionary biology theory is the explanation of the emergence of cooperation in communities of selfish individuals. There is an unexplained tendency in the plant and animal world – with examples from alpine plants, worms, fish, mole-rats, monkeys and humans – for cooperation to flourish where the environment is more adverse (harsher) or more unpredictable. Results Using mathematical arguments and computer simulations we show that in more adverse environments individuals perceive their resources to be more unpredictable, and that this unpredictability favours cooperation. First we show analytically that in a more adverse environment the individual experiences greater perceived uncertainty. Second we show through a simulation study that more perceived uncertainty implies higher level of cooperation in communities of selfish individuals. Conclusion This study captures the essential features of the natural examples: the positive impact of resource adversity or uncertainty on cooperation. These newly discovered connections between environmental adversity, uncertainty and cooperation help to explain the emergence and evolution of cooperation in animal and human societies. PMID:18053138

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

    PubMed

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

    2015-01-01

    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 attention to Aurora A

  2. [Reported adverse reactions of veterinary drugs and vaccines in 2005].

    PubMed

    Müntener, C R; Bruckner, L; Gassner, B; Demuth, D C; Althaus, F R; Zwahlen, R

    2007-02-01

    We received 105 reports of suspected adverse events (SARs) following the use of veterinary drugs for the year 2005. This corresponds to a 35% increase compared to 2004. Practicing veterinarians sent most of these declarations. 73% of these concerned drugs used on companion animals. Antiparasitic drugs approved for topical use were the most frequently represented group with 48%, followed by drugs used to treat gastrointestinal disorders (11%) and drugs used off-label (14%; other target species or other indication). For the first time 2 declarations concerning the application of permethrin containing spot-on preparations used by mistake on cats were received. An overview of 20 declarations about adverse reactions following application of different vaccines is also presented with emphasis on the problem of fibrosarcoma in cats. We are pleased by the growing interest shown by practicing veterinarians for the vigilance system and hope to further develop this collaboration in the future.

  3. BIOBEHAVIORAL PROGNOSTIC FACTORS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: Results from the INSPIRE-II Trial

    PubMed Central

    Blumenthal, James A.; Smith, Patrick J.; Durheim, Michael; Mabe, Stephanie; Emery, Charles F.; Martinu, Tereza; Diaz, Philip T.; Babyak, Michael; Welty-Wolf, Karen; Palmer, Scott

    2015-01-01

    Objective To examine the prognostic value of select biobehavioral factors in patients with chronic obstructive pulmonary disease (COPD) in a secondary analysis of participants from the INSPIRE-II trial. Methods Three hundred twenty six outpatients with COPD underwent assessments of pulmonary function, physical activity, body mass index, inflammation, pulmonary symptoms, depression, and pulmonary quality of life, and were followed for up to 5.4 years for subsequent clinical events. The prognostic value of each biobehavioral factor, considered individually and combined, also was examined in the context of existing Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 risk stratification. Results Sixty-nine individuals experienced a hospitalization or died over a mean follow-up time period of 2.4 (interquartile range = 1.6) years. GOLD classification was associated with an increased risk of clinical events (HR = 2.72 [95% CI 1.63, 4.54], per stage); Six Minute Walk (HR = 0.50 [0.34, 0.73] per 500 feet), total steps (HR = 0.82 [0.71, 0.94] per 1,000 steps), hsC-reactive protein (HR = 1.44 [1.01, 2.06] per 4.5 mg/L), depression (HR = 1.12 [1.01, 1.25] per 4 points), and pulmonary quality of life (HR = 1.73 [1.14, 2.63] per 25 points) were each predictive over and above the GOLD assessment. However, only GOLD group and Six Minute Walk were predictive of all-cause mortality and COPD hospitalization when all biobehavioral variables were included together in a multivariable model. Conclusion Biobehavioral factors provide added prognostic information over and above measures of COPD severity in predicting adverse events in patients with COPD. PMID:26780299

  4. Rectal Adenocarcinoma: Proposal for a Model Based on Pretreatment Prognostic Factors

    PubMed Central

    Cabanillas, Fernando; Freire, Viviana; Nieves-Plaza, Mariely; Quevedo, Gerardo; Echenique, Ignacio A.

    2012-01-01

    Objective Currently the choice of chemotherapy regimen in rectal cancer is made prior to surgery in contrast to colon cancer where it is made postoperatively after the pathological stage has been determined. If we could identify which are the important pretreatment prognostic factors in rectal cancer, we could then target those patients with unfavorable features to investigate potentially more effective preoperative chemotherapy regimens aimed at those with unfavorable features. The present study aims to determine pre-treatment prognostic factors that are associated with an unfavorable outcome. Methods A retrospective review of 99 rectal cancer patients operated at the Hospital Auxilio Mutuo and Hospital San Pablo was done. Sociodemographic characteristics, clinical and treatment data was collected. Results 54% were males. The mean ± sd age was 62.2 ± 10.4. In age-adjusted Cox model, male gender [HR (95%CI): 3.32 (1.09–10.13)], mucinous carcinoma [HR (95%CI): 3.67 (1.25–10.77)], and clinical stages II & III [HR (95%CI): 8.19 (1.08–62.08)] were predictors of poor prognosis. In multivariate age-adjusted analysis, a tendency towards a poorer prognosis was observed for male patients [HR: 2.60] CEA level ≥ 5ng/ml [HR: 2.55], mucinous carcinoma [HR:2.96], and clinical stages II & III [HR:4.96], although results were not statistically significant (p>0.05), Conclusion Although current therapeutic results are relatively favorable with preoperative 5-Fluorouracil (5FU) and radiotherapy, future clinical trials should address the management of those cases with adverse pretreatment prognostic factors so that they can be treated with potentially more effective albeit more toxic chemotherapy regimens. PMID:22783696

  5. Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients

    PubMed Central

    Wang, Lin-Fang; Fokas, Emmanouil; Juricko, Janko; You, An; Rose, Frank; Pagenstecher, Axel; Engenhart-Cabillic, Rita; An, Han-Xiang

    2008-01-01

    Background Malignant gliomas are lethal cancers, highly dependent on angiogenesis and treatment options and prognosis still remain poor for patients with recurrent glioblastoma multiforme (GBM). Ephs and ephrins have many well-defined functions during embryonic development of central nervous system such as axon mapping, neural crest cell migration, hindbrain segmentation and synapse formation as well as physiological and abnormal angiogenesis. Accumulating evidence indicates that Eph and ephrins are frequently overexpressed in different tumor types including GBM. However, their role in tumorigenesis remains controversial, as both tumor growth promoter and suppressor potential have been ascribed to Eph and ephrins while the function of EphA7 in GBM pathogenesis remains largely unknown. Methods In this study, we investigated the immunohistochemical expression of EphA7 in a series of 32 primary and recurrent GBM and correlated it with clinical pathological parameters and patient outcome. In addition, intratumor microvascular density (MVD) was quantified by immunostaining for endothelial cell marker von Willebrand factor (vWF). Results Overexpression of EphA7 protein was predictive of the adverse outcome in GBM patients, independent of MVD expression (p = 0.02). Moreover, high density of MVD as well as higher EphA7 expression predicted the disease outcome more accurately than EphA7 variable alone (p = 0.01). There was no correlation between MVD and overall survival or recurrence-free survival (p > 0.05). However, a statistically significant correlation between lower MVD and tumor recurrence was observed (p = 0.003). Conclusion The immunohistochemical assessment of tissue EphA7 provides important prognostic information in GBM and would justify its use as surrogate marker to screen patients for tyrosine kinase inhibitor therapy. PMID:18366728

  6. Childhood adversity and adult health: Evaluating intervening mechanisms.

    PubMed

    Turner, R Jay; Thomas, Courtney S; Brown, Tyson H

    2016-05-01

    Substantial evidence has accumulated supporting a causal link between childhood adversity and risk for poor health years and even decades later. One interpretation of this evidence is that this linkage arises largely or exclusively from a process of biological embedding that is not modifiable by subsequent social context or experience - implying childhood as perhaps the only point at which intervention efforts are likely to be effective. This paper considers the extent to which this long-term association arises from intervening differences in social context and/or environmental experiences - a finding that would suggest that post-childhood prevention efforts may also be effective. Based on the argument that the selected research definition of adult health status may have implications for the early adversity-adult health linkage, we use a representative community sample of black and white adults (N = 1252) to evaluate this relationship across three health indices: doctor diagnosed illnesses, self-rated health, and allostatic load. Results generally indicate that observed relationships between childhood adversity and dimensions of adult health status were totally or almost totally accounted for by variations in adult socioeconomic position (SEP) and adult stress exposure. One exception is the childhood SEP-allostatic load association, for which a statistically significant relationship remained in the context of adult stress and SEP. This lone finding supports a conclusion that the impact of childhood adversity is not always redeemable by subsequent experience. However, in general, analyses suggest the likely utility of interventions beyond childhood aimed at reducing exposure to social stress and improving social and economic standing. Whatever the effects on adult health that derive from biological embedding, they appear to be primarily indirect effects through adult social context and exposure.

  7. The protein arginine methyltransferase 5 promotes malignant phenotype of hepatocellular carcinoma cells and is associated with adverse patient outcomes after curative hepatectomy

    PubMed Central

    Shimizu, Dai; Kanda, Mitsuro; Sugimoto, Hiroyuki; Shibata, Masahiro; Tanaka, Haruyoshi; Takami, Hideki; Iwata, Naoki; Hayashi, Masamichi; Tanaka, Chie; Kobayashi, Daisuke; Yamada, Suguru; Nakayama, Goro; Koike, Masahiko; Fujiwara, Michitaka; Fujii, Tsutomu; Kodera, Yasuhiro

    2017-01-01

    The prognosis of advanced hepatocellular carcinoma (HCC) is dismal. Novel molecular targets for diagnosis and therapy is urgently required. This study evaluated expression and functions of the protein arginine methyltransferase 5 (PRMT5) in HCC. Using HCC cell lines, the expression levels of PRMT5 mRNA were determined using the quantitative real-time reverse-transcription polymerase chain reaction, and the effect of a small interfering PRMT5-siRNA on cell phenotype was evaluated. Further, PRMT5 expression was determined in 144 pairs of resected liver tissues to evaluate its clinical significance. Regardless of their differentiated phenotypes, nine HCC cell lines expressed different levels of PRMT5 mRNA. Inhibition of PRMT5 expression significantly decreased the proliferation, invasion, and migration of HCC cell lines. Although the level of PRMT5 mRNA was not influenced by patient's background liver status, it was significantly higher in HCC tissues than in the corresponding noncancerous tissues. High levels of PRMT5 mRNA in HCC tissues were significantly associated with advanced disease stage and adverse prognosis. In conclusion, our results indicate that PRMT5 may act as a putative oncogene in HCC and that the levels of PRMT5 mRNA represent a promising prognostic marker and a potential target of molecular therapy for HCC. PMID:28101581

  8. 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.

  9. 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.

  10. [Adverse reaction to not iodinated contrast].

    PubMed

    Palma-Gómez, Samuel; González-Díaz, Sandra Nora; Arias-Cruz, Alfredo; Macías-Weinmann, Alejandra; Amaro-Vivian, Laura Elizabeth; Pérez-Vanzzini, Rafael; Gutiérrez-Mujica, José Julio; Yong-Rodríguez, Adrián

    2014-01-01

    Adverse reactions to drugs are relatively frequent in clinical practice, and some of them can be life threatening. Reactions to contrast material (CM) represent an important percentage of these adverse reactions. It has been found that 70% of reactions to contrast material happen within the first five minutes of their administration. Despite the fact that hypersensitivity reactions are traditionally classified as non-allergic, in recent years investigators have reported positive skin prick tests in patients with immediate and late reactions to contrast material. This paper reports the case of a female patient with non-Hodgkin lymphoma that has presented on two distinct occasions adverse reactions to contrast material. We discuss on the type of reaction, severity, suggested prophylaxis, prognosis and recommendations, keeping in mind the underlying disease and the need to have further image studies performed.

  11. Adverse events related to blood transfusion.

    PubMed

    Sahu, Sandeep; Hemlata; Verma, Anupam

    2014-09-01

    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.

  12. Adverse perinatal events associated with ART.

    PubMed

    Skora, Daniel; Frankfurter, David

    2012-04-01

    Since the advent of ART, much research has focused on the potential adverse for resultant harm. Prematurity, low birth-weight, PIH, congenital malformations, and CP are closely tied to multiple gestation. With the increase in elective single embryo transfer, there will be a reduction in adversity related to multiple birth. It is understood that underlying causes of infertility, including advanced maternal age, PCOS, thyroid disease, and uterine fibroids, predispose to adverse outcomes. However, imprinting abnormalities do not appear to stem from multiple births, and thus the need to consider the association between fertility treatment and methylation disorders remains essential. These, as well as risks of multi-fetal gestation, must be discussed with patients when considering using assisted reproduction.

  13. Early Adverse Experiences and the Developing Brain

    PubMed Central

    Bick, Johanna; Nelson, Charles A

    2016-01-01

    Children exposed to various forms of adversity early in life are at increased risk for a broad range of developmental difficulties, affecting both cognitive and emotional adjustment. We review a growing body of evidence suggesting that exposure to adverse circumstances affects the developing brain in ways that increase risk for a myriad of problems. We focus on two forms of adversity, one in which children are exposed to childhood maltreatment in family environments, and another in which children are exposed to extreme psychosocial deprivation in contexts of institutional rearing. We discuss ways in which each of these experiences represent violations of species-expected caregiving conditions, thereby imposing challenges to the developing brain. We also review emerging data pointing to the effectiveness of early intervention in remediating neurodevelopmental consequences associated with maltreatment or institutional rearing. We conclude by discussing implications of this work for public health efforts and highlight important directions for the field. PMID:26334107

  14. Alexithymia as a prognostic risk factor for health problems: a brief review of epidemiological studies.

    PubMed

    Kojima, Masayo

    2012-12-17

    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.

  15. Prognostic value of inflammation-based scores in patients with osteosarcoma

    PubMed Central

    Liu, Bangjian; Huang, Yujing; Sun, Yuanjue; Zhang, Jianjun; Yao, Yang; Shen, Zan; Xiang, Dongxi; He, Aina

    2016-01-01

    Systemic inflammation responses have been associated with cancer development and progression. C-reactive protein (CRP), Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS) have been shown to be independent risk factors in various types of malignant tumors. This retrospective analysis of 162 osteosarcoma cases was performed to estimate their predictive value of survival in osteosarcoma. All statistical analyses were performed by SPSS statistical software. Receiver operating characteristic (ROC) analysis was generated to set optimal thresholds; area under the curve (AUC) was used to show the discriminatory abilities of inflammation-based scores; Kaplan-Meier analysis was performed to plot the survival curve; cox regression models were employed to determine the independent prognostic factors. The optimal cut-off points of NLR, PLR, and LMR were 2.57, 123.5 and 4.73, respectively. GPS and NLR had a markedly larger AUC than CRP, PLR and LMR. High levels of CRP, GPS, NLR, PLR, and low level of LMR were significantly associated with adverse prognosis (P < 0.05). Multivariate Cox regression analyses revealed that GPS, NLR, and occurrence of metastasis were top risk factors associated with death of osteosarcoma patients. PMID:28008988

  16. 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.

  17. Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications

    PubMed Central

    Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

    2015-01-01

    The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671

  18. Prognostic value of serum tumor abnormal protein in gastric cancer patients

    PubMed Central

    LAN, FENG; ZHU, MING; QI, QIUFENG; ZHANG, YAPING; LIU, YONGPING

    2016-01-01

    Aberrant glycosylation of protein occurs in nearly all types of cancers and has been confirmed to be associated with tumor progression, metastasis and the survival rate of patients. The present study aimed to explore the prognostic value of tumor abnormal protein (TAP) in gastric cancer patients. TAP was detected in the blood of 42 gastric cancer patients and 56 healthy volunteers by using the TAP testing kit. Univariate and multivariate Cox regression analysis were performed to evaluate the prognostic value of TAP. In total, 64.3% of gastric cancer patients were positive for TAP, and TAP was significantly correlated with poor prognosis [progression-free survival (PFS), 4.2 vs. 12.6 months; P=0.043]. TAP [hazard ratio (HR), 64.487; P<0.01), differentiation (HR, 17.279; P<0.01) and TNM stage (HR, 45.480; P<0.01) were found to be independent predictive factors for PFS. Furthermore, Kaplan-Meier curves indicated that TAP is associated with a reduced PFS in gastric cancer patients. The results of the present study therefore indicated that the TAP test has significant prognostic value for gastric cancer patients. PMID:27330802

  19. Spectral kurtosis for fault detection, diagnosis and prognostics of rotating machines: A review with applications

    NASA Astrophysics Data System (ADS)

    Wang, Yanxue; Xiang, Jiawei; Markert, Richard; Liang, Ming

    2016-01-01

    Condition-based maintenance via vibration signal processing plays an important role to reduce unscheduled machine downtime and avoid catastrophic accidents in industrial enterprises. Many machine faults, such as local defects in rotating machines, manifest themselves in the acquired vibration signals as a series of impulsive events. The spectral kurtosis (SK) technique extends the concept of kurtosis to that of a function of frequency that indicates how the impulsiveness of a signal. This work intends to review and summarize the recent research developments on the SK theories, for instance, short-time Fourier transform-based SK, kurtogram, adaptive SK and protrugram, as well as the corresponding applications in fault detection and diagnosis of the rotating machines. The potential prospects of prognostics using SK technique are also designated. Some examples have been presented to illustrate their performances. The expectation is that further research and applications of the SK technique will flourish in the future, especially in the fields of the prognostics.

  20. Glucocorticoid dependency as a prognostic factor in radiotherapy for cerebral gliomas.

    PubMed

    Hohwieler Schloss, M; Freidberg, S R; Heatley, G J; Lo, T C

    1989-01-01

    Records of 76 consecutive patients treated with radiotherapy for cerebral gliomas were reviewed. Eleven patients had no tissue diagnosis, and their outcome was comparable to that of patients with glioblastoma. Patients with other histologic diagnoses had much better results. Among the entire study population, the most important prognostic factors included age and histologic grade. Even with stratification by histologic grade and age, glucocorticoid (steroid) dependency was a reliable prognostic indicator in terms of survival. Fifteen of the 47 patients (32%) who were less steroid dependant are still alive with a median survival time of 29 months. Among the 29 patients who were heavily dependant on steroids during the course of radiotherapy, the median survival time was 5 months with only 2 patients (7%) still alive.

  1. mTOR pathway activation is a favorable prognostic factor in human prostate adenocarcinoma

    PubMed Central

    Stelloo, Suzan; Sanders, Joyce; Nevedomskaya, Ekaterina; de Jong, Jeroen; Peters, Dennis; van Leenders, Geert J.L.H.; Jenster, Guido; Bergman, Andries M.; Zwart, Wilbert

    2016-01-01

    Prostate cancer patients with localized disease are treated with curative intent. However, the disease will recur in approximately 30% of patients with a high incidence of morbidity and mortality. Prognostic biomarkers are needed to identify patients with high risk of relapse. mTOR pathway activation is reported in prostate cancer, but clinical trials testing efficacy of mTOR inhibitors were unsuccessful. To explain this clinical observation, we studied the expression and prognostic impact of mTOR-S2448 phosphorylation in localized prostate carcinomas. mTOR-S2448 phosphorylation is indicative for an activated mTOR pathway in prostate cancer. Surprisingly, the mTOR signaling pathway is activated specifically in prostate cancer patients with a favorable outcome. Since tumors from poor-outcome patients have low levels of mTOR-S2448 phosphorylation, this may explain why mTOR inhibitors proved unsuccessful in prostate cancer trials. PMID:27096957

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

    PubMed

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

    2016-11-01

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

  3. Sensor systems for prognostics and health management.

    PubMed

    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.

  4. Physiologic and prognostic significance of "alpha coma".

    PubMed Central

    Iragui, V J; McCutchen, C B

    1983-01-01

    A patient with posthypoxic "alpha coma" is described whose EEGs were recorded before coma, within two hours following the onset of coma and after recovery. The differences observed between the alpha activity during coma and that seen before and after suggest that the alpha activity during coma and the physiologic alpha rhythm are different phenomena. This case, as well as others reported, also suggests that "alpha coma" resolving in the first 24 hours following hypoxia may have a better prognosis than "alpha coma" detected after the first day, and stresses the need for EEG monitoring begun in the immediate period following hypoxia in order to assess accurately the prognostic significance of this EEG pattern in the early stages of postanoxic encephalopathy. The aetiology of "alpha coma" also affects outcome. The survival rate appears higher in patients with respiratory arrest than in those with combined cardiopulmonary arrest. PMID:6886700

  5. 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

  6. Adaptive Prognostics for Rolling Element Bearing Condition

    NASA Astrophysics Data System (ADS)

    Li, Y.; Billington, S.; Zhang, C.; Kurfess, T.; Danyluk, S.; Liang, S.

    1999-01-01

    Rolling element bearing failure is one of the foremost causes of breakdown in rotating machinery. This paper proposes a remaining life adaptation methodology based on mechanistic modeling and parameter tuning. Vibration measurement is used to estimate defect severity by monitoring the signals generated from rotating bearings. Through a defect propagation model and defect diagnostic model, an adaptive algorithm is developed to fine tune the parameters involved in the propagation model by comparing predicted and measured defect sizes. In this manner, the instantaneous rate of defect propagation can be captured despite defect growth behavior variation. Therefore, a precise estimation of the remaining life can be determined. Simulations and experimental results are presented to illustrate the implementation principles and to verify the applicability of the adaptive prognostic methodology.

  7. 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.

  8. Prognostic role of the cumulative toxicity in patients affected by metastatic renal cells carcinoma and treated with first-line tyrosine kinase inhibitors.

    PubMed

    Iacovelli, Roberto; Verri, Elena; Cossu Rocca, Maria; Aurilio, Gaetano; Cullurà, Daniela; de Cobelli, Ottavio; Nolè, Franco

    2017-02-01

    Tyrosine kinase inhibitor-related toxicities have been reported to be predictive and/or prognostic factors in patients affected by metastatic renal cell carcinoma (mRCC). We aim to investigate the incidence of cumulative toxicity and its prognostic role in mRCC patients treated with sunitinib or pazopanib. mRCC patients treated with sunitinib or pazopanib at the European Institute of Oncology in Milan were reviewed for the incidence of adverse events. Cumulative toxicity was defined as the presence of more than one selected adverse event of any grade. Prognoses were evaluated by the International mRCC Database Consortium criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and Cox analysis. A total of 104 patients were included in the final analysis. Only 18.3% did not experience any of the selected toxicities: 26.9% had one, 35.6% had two and 19.2% all three toxicities. Accordingly, 54.8% of patients experienced cumulative toxicity. In those with or without cumulative toxicity, the median PFS was 27.6 versus 7.2 months and the median OS was 61.2 versus 18.7 months, respectively. When cumulative toxicity was adjusted for International mRCC Database Consortium prognostic groups, it maintained its prognostic role for both PFS (hazard ratio: 0.31, 95% confidence interval, 0.20-0.49; P<0.001) and OS (hazard ratio: 0.27, 95% confidence interval, 0.15-0.48; P<0.001). A major limitation was the retrospective and monocentric nature of the analysis. We reported the prognostic role of cumulative toxicity because of hypertension, hypothyroidism and hand-foot syndrome in patients affected by mRCC and treated with sunitinib or pazopanib.

  9. 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.

  10. Prognostic and therapeutic value of mitochondrial serine hydroxyl-methyltransferase 2 as a breast cancer biomarker.

    PubMed

    Zhang, Lahong; Chen, Zhaojun; Xue, Dan; Zhang, Qi; Liu, Xiyong; Luh, Frank; Hong, Liquan; Zhang, Hang; Pan, Feng; Liu, Yuhua; Chu, Peiguo; Zheng, Shu; Lou, Guoqiang; Yen, Yun

    2016-11-01

    Mitochondrial serine hydroxylmethyltransferase 2 (SHMT2) is a key enzyme in the serine/glycine synthesis pathway. SHMT2 has been implicated as a critical component for tumor cell survival. The aim of the present study was to evaluate the prognostic value and efficiency of SHMT2 as a biomarker in patients with breast cancer. Individual and pooled survival analyses were performed on five independent breast cancer microarray datasets. Gene signatures enriched by SHMT2 were also analyzed in these datasets. SHMT2 protein expression was detected using immunohistochemistry (IHC) assay in 128 breast cancer cases. Gene set enrichment analysis revealed that SHMT2 was significantly associated with gene signatures of mitochondrial module, cancer invasion, metastasis and poor survival among breast cancer patients (p<0.05). The clinical relevance of SHMT2 was validated on IHC data. The mitochondrial localization of SHMT2 protein was visualized on IHC staining. Independent and pooled analysis confirmed that SHMT2 expression was associated with breast cancer tumor aggressiveness (TNM staging and Elson grade) in a dose-dependent manner (p<0.05). The prognostic performance of SHMT2 mRNA was comparable to other gene signatures and proved superior to TNM staging. Further analysis results indicated that SHMT2 had better prognostic value for estrogen receptor (ER)-negative breast cancer patients, compared to ER-positive patients. In cases involving stage IIb breast cancer, chemotherapy significantly extended survival time among patients with high SHMT2 expression. These results indicate that SHMT2 may be a valuable prognostic biomarker in ER-negative breast cancer cases. Furthermore, SHMT2 may be a potential target for breast cancer treatment and drug discovery.

  11. Negative affect predicts adults' ratings of the current, but not childhood, impact of adverse childhood events.

    PubMed

    LaNoue, Marianna; Graeber, David A; Helitzer, Deborah L; Fawcett, Jan

    2013-10-01

    Adverse childhood events (ACE's) have been empirically related to a wide range of negative health and mental health outcomes. However, not all individuals who experience ACE's follow a trajectory of poor outcomes, and not all individuals perceive the impact of ACE's as necessarily negative. The purpose of this study was to investigate positive and negative affect as predictors of adults' ratings of both the childhood and adult impact of their childhood adversity. Self-report data on ACE experiences, including number, severity, and 'impact' were collected from 158 community members recruited on the basis of having adverse childhood experiences. Results indicated that, regardless of event severity and number of different types of adverse events experienced, high levels of negative affect were the strongest predictor of whether the adult impact of the adverse childhood events was rated as negative. All individuals rated the childhood impact of events the same. Implications are discussed.

  12. Prognostic factors of renal dysfunction induced by environmental cadmium pollution

    SciTech Connect

    Nishijo, Muneko; Nakagawa, Hideaki; Morikawa, Yuko; Tabata, Masaji; Senma, Masami; Kitagawa, Yumiko; Kawano, Shunichi; Ishizaki, Masao ); Sugita, Naomichi; Nishi, Masami )

    1994-02-01

    To assess the influence of environmental cadmium (Cd) exposure on long-term outcome, a follow-up study was conducted from 1981-1982 to March 1991 on 3178 inhabitants living in the Cd-polluted Kakehashi River basin. The standardized mortality ratios of the urinary [beta][sub 2]-microglobulin ([beta]2-MG)-, protein-, and amino acid-positive subjects of both sexes and the urinary glucose-positive female subjects were higher than those of the subjects with urinary-negative findings or the general Japanese population during the observation period. After adjusting for age using Cox's proportional hazards model, significant associations were found between mortality and urinary indices. In multiple comparisons using all of the indices, urinary protein and [beta]2-MG in the women and urinary protein in the men were the factors most contributing to the mortality rates. In the urinary protein-negative female group as well, as significant association was found between urinary [beta]2-MG and mortality. These results suggest that the prognosis of subjects with Cd-induced renal dysfunction is unfavorable, with the mortality rate increasing even in the early stage of proximal tubular dysfunction. Urinary protein and urinary [beta]2-MG are important prognostic factors, with the latter, in particular, considered to be useful as an early index predictive of premature mortality. 30 refs., 6 tabs.

  13. 6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis.

    PubMed

    Ocio, E M; Schop, R F J; Gonzalez, B; Van Wier, S A; Hernandez-Rivas, J M; Gutierrez, N C; Garcia-Sanz, R; Moro, M J; Aguilera, C; Hernandez, J; Xu, R; Greipp, P R; Dispenzieri, A; Jalal, S M; Lacy, M Q; Gonzalez-Paz, N; Gertz, M A; San Miguel, J F; Fonseca, R

    2007-01-01

    Fluorescence in situ hybridisation (FISH) is an effective technique for the cytogenetic analysis of Waldenström macroglobulinemia (WM), but the potential impact of molecular cytogenetics on disease evolution and as a prognostic marker is still unknown. Deletion of the long arm of chromosome 6 (6q-) is the most frequent cytogenetic abnormality in WM. This study analysed the prevalence of this aberration in 102 WM patients, and correlated it with disease characteristics. The incidence of 6q21 deletion was 7% by conventional cytogenetics and 34% when analysed by FISH (54% when cytoplasmic immunoglobulin M-FISH was used). Patients with deletion of 6q displayed features of adverse prognosis, such as higher levels of beta2-microglobulin and monoclonal paraprotein and a greater tendency to display anaemia and hypoalbuminemia. Interestingly, there was a correlation between the presence of 6q deletion and the International Staging System prognostic index (incidence of 6q- among patients stratified in stages 1, 2 and 3 was 24%, 42% and 67% respectively). Those patients diagnosed with smouldering WM who displayed the abnormality showed a trend to an earlier requirement of treatment. Finally, the survival analysis did not show differences between the two groups of patients, probably due to the short follow up of our series.

  14. Comparison of Prognostic and Diagnostic Approaches to Modeling Evapotranspiration in the Nile River Basin

    NASA Astrophysics Data System (ADS)

    Yilmaz, M.; Anderson, M. C.; Zaitchik, B. F.; Crow, W. T.; Hain, C.; Ozdogan, M.; Chun, J. A.

    2012-12-01

    may be a valuable model evaluation tool. Motivated by the complementary information that exists in prognostic and diagnostic energy balance modeling, as well as the need for evaluation of water consumption estimates over the Nile basin, the purpose of this study is to 1) better describe the conceptual differences between prognostic and diagnostic modeling, 2) present the potential for diagnostic models to capture important hydrologic features that are not explicitly represented in prognostic model, 3) explore the differences in these two approaches over the Nile Basin, where ground data are sparse and transnational data sharing is unreliable. More specifically, we will compare output from the Noah prognostic model and the Atmosphere-Land Exchange Inverse (ALEXI) diagnostic model generated over ground truth data-poor Nile basin. Preliminary results indicate spatially, temporally, and magnitude wise consistent flux estimates for ALEXI and NOAH over irrigated Delta region, while there are differences over river-fed wetlands.

  15. Prognostic Impact of IPSS-R and Chromosomal Translocations in 751 Korean Patients with Primary Myelodysplastic Syndrome

    PubMed Central

    Kim, Inho; Kim, Hyeoung-Joon; Shin, Dong-Yeop; Koh, Youngil; Yoon, Sung-Soo; Min, Yoo Hong; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Lee, Yun-Gyoo; Lee, Jeong-Ok; Bang, Soo-Mee; Mun, Yeung-Chul; Seong, Chu-Myoung; Park, Yong; Kim, Byung-Soo; Hong, Junshik; Park, Jinny; Lee, Jae Hoon; Kim, Sung-Yong; Lee, Hong Ghi

    2016-01-01

    Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations, 30 (75%) of whom also fulfilled complex karyotype criteria. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P < 0.01). Multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06–2.63]; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06–2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment. PMID:27824923

  16. 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.

  17. 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:…

  18. Educational Leadership: The Uses of Adversity

    ERIC Educational Resources Information Center

    Culbertson, Jack

    1976-01-01

    Skepticism about the power of education challenges the educational administrator to (1) attain a better understanding of the sources of dissatisfaction and their implications for change, (2) learn to cope with adversity and make constructive use of it, and (3) define the leadership requirements needed to address education's problems. (MB)

  19. 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...

  20. Clinical spectrum of adverse reactions to tartrazine.

    PubMed

    Collins-Williams, C

    1985-01-01

    Tartrazine, a common additive in foods and drugs, often causes adverse reactions such as recurrent urticaria, angioedema, and asthma and is frequently implicated in hyperkinesis. This paper summarizes the recent literature on the subject and outlines a practical approach for the practicing physician to diagnose and treat these patients in an optimal manner.

  1. The Public Health Burden of Early Adversity

    ERIC Educational Resources Information Center

    Schlueter, Lisa J.; Watamura, Sarah Enos

    2017-01-01

    Severe and chronic stress in early childhood has enormous physical and mental health costs across an individual's lifespan. Unfortunately, exposure to early life adversity is common, and costs accrue to individuals and society. This article highlights several promising approaches to buffer children from the negative health consequences associated…

  2. [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.

  3. Adverse skin reactions following intravitreal bevacizumab injection

    PubMed Central

    Ameen, S; Entabi, M; Lee, N; Stavrakoglou, A

    2011-01-01

    The authors describe two separate cases of skin eruption following intravitreal bevacizumab injection with evidence to suggest that these were adverse drug reactions to bevacizumab. The authors also discuss how each case was treated and report on the final outcome. PMID:22715260

  4. Due Process in Adverse Personnel Action.

    ERIC Educational Resources Information Center

    Scriven, Michael

    1997-01-01

    A detailed checklist and timeline for ensuring due process are provided for adverse personnel actions, and the need to supplement this with expert, same-jurisdiction legal advice is stressed. This approach emphasizes the importance of treating due process as an ethical as well as a legal requirement. (SLD)

  5. 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...

  6. [Laser trabeculoplasty: therapeutic options and adverse effects].

    PubMed

    Wacker, T; Eckert, S

    2010-01-01

    Laser trabeculoplasty is a simple method for treating glaucoma and ocular hypertension and has few adverse effects. There are different laser systems for reducing the intraocular pressure of patients with glaucoma and ocular hypertension. Complications include transient intraocular pressure elevation, iritis, and anterior synechiae.

  7. 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…

  8. Evaluation of prognostic markers for patients with curatively resected thoracic esophageal squamous cell carcinomas

    PubMed Central

    Ikeguchi, Masahide; Kouno, Yusuke; Kihara, Kyoichi; Suzuki, Kazunori; Endo, Kanenori; Nakamura, Seiichi; Sawada, Takashi; Shimizu, Tetsu; Matsunaga, Tomoyuki; Fukumoto, Yoji; Saito, Hiroaki

    2016-01-01

    The Glasgow Prognostic Score (GPS), neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are prognostic parameters for malignancies. Additionally, serum squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA 21-1) are tumor markers for squamous cell carcinoma. In the present study, the prognostic importance of these markers in patients with resectable thoracic esophageal cancer was investigated. In this retrospective study, 84 enrolled patients diagnosed with resectable clinical stage I–III thoracic esophageal squamous cell carcinomas (ESCCs) underwent thoracic esophageal resection and three-field lymph node dissection at Tottori University Hospital between January 2007 and December 2013. The correlations among preoperative patient markers (GPS, NLR, PNI, SCC-Ag and CYFRA 21-1) and the occurrence of postoperative complications and patient survival were analyzed. The operative mortality was 2.4%, and morbidity was 42.9%. Strong correlations between occurrence of postoperative complications and open thoracotomy (P=0.083) and high-serum CYFRA 21-1 (P=0.007) were observed. In 15 patients with high-serum CYFRA 21-1, postoperative complications were detected in 11 of them (73.3%); on the other hand, complications occurred in 25 of 69 (36.2%) with low-serum CYFRA 21-1. The 5-year disease-free survival rate and 5-year overall survival rate of all the patients were 52.2 and 50.8%, respectively. Among the prognostic parameters, preoperative high NLR was determined to be a poor prognostic factor, independent of the tumor stage in the multivariate analysis. These results may indicate that, in patients with preoperative high-serum CYFRA 21-1, more attention should be paid to the occurrence of postoperative complications. Therefore, in such cases, anastomosis between blood vessels of the substitute esophagus and cervical vessels would be recommended. Furthermore, in patients with high preoperative NLR, effective adjuvant

  9. Pharmacogenomics of statins: understanding susceptibility to adverse effects

    PubMed Central

    Kitzmiller, Joseph P; Mikulik, Eduard B; Dauki, Anees M; Murkherjee, Chandrama; Luzum, Jasmine A

    2016-01-01

    Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. PMID:27757045

  10. Adverse childhood experiences and behavioral problems in middle childhood.

    PubMed

    Hunt, Tenah K A; Slack, Kristen S; Berger, Lawrence M

    2016-11-21

    Children who have been exposed to maltreatment and other adverse childhood experiences (ACEs) are at increased risk for various negative adult health outcomes, including cancer, liver disease, substance abuse, and depression. However, the proximal associations between ACEs and behavioral outcomes during the middle childhood years have been understudied. In addition, many of the ACE studies contain methodological limitations such as reliance on retrospective reports and limited generalizability to populations of lower socioeconomic advantage. The current study uses data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort, to prospectively assess the adverse experiences and subsequent behavior problems of over 3000 children. Eight ACE categories to which a child was exposed by age 5 were investigated: childhood abuse (emotional and physical), neglect (emotional and physical), and parental domestic violence, anxiety or depression, substance abuse, or incarceration. Results from bivariate analyses indicated that Black children and children with mothers of low education were particularly likely to have been exposed to multiple ACE categories. Regression analyses showed that exposure to ACEs is strongly associated with externalizing and internalizing behaviors and likelihood of ADHD diagnosis in middle childhood. Variation in these associations by racial/ethnic, gender, and maternal education subgroups are examined. This study provides evidence that children as young as 9 begin to show behavioral problems after exposure to early childhood adversities.

  11. Using Drug Similarities for Discovery of Possible Adverse Reactions

    PubMed Central

    Muñoz, Emir; Nováček, Vít; Vandenbussche, Pierre-Yves

    2016-01-01

    We propose a new computational method for discovery of possible adverse drug reactions. The method consists of two key steps. First we use openly available resources to semi-automatically compile a consolidated data set describing drugs and their features (e.g., chemical structure, related targets, indications or known adverse reaction). The data set is represented as a graph, which allows for definition of graph-based similarity metrics. The metrics can then be used for propagating known adverse reactions between similar drugs, which leads to weighted (i.e., ranked) predictions of previously unknown links between drugs and their possible side effects. We implemented the proposed method in the form of a software prototype and evaluated our approach by discarding known drug-side effect links from our data and checking whether our prototype is able to re-discover them. As this is an evaluation methodology used by several recent state of the art approaches, we could compare our results with them. Our approach scored best in all widely used metrics like precision, recall or the ratio of relevant predictions present among the top ranked results. The improvement was as much as 125.79% over the next best approach. For instance, the F1 score was 0.5606 (66.35% better than the next best method). Most importantly, in 95.32% of cases, the top five results contain at least one, but typically three correctly predicted side effect (36.05% better than the second best approach). PMID:28269889

  12. Childhood adversity profiles and adult psychopathology in a representative Northern Ireland study.

    PubMed

    McLafferty, Margaret; Armour, Cherie; McKenna, Aine; O'Neill, Siobhan; Murphy, Sam; Bunting, Brendan

    2015-10-01

    Childhood adversities are key aetiological factors in the onset and persistence of psychopathology. The aims of this study were to identify childhood adversity profiles, and investigate the relationship between the adversity classes and psychopathology in Northern Ireland. The study utilized data from the Northern Ireland Study of Health and Stress, an epidemiological survey (N=1986), which used the CIDI to examine mental health disorders and associated risk factors. Latent Class Analysis revealed 3 distinct typologies; a low risk class (n=1709; 86%), a poly-adversity class (n=122; 6.1%), and an economic adversity class (n=155; 7.8%). Logistic Regression models revealed that individuals in the economic adversity class had a heightened risk of anxiety and substance disorders, with individuals in the poly-adversity class more likely to have a range of mental health problems and suicidality. The findings indicate the importance of considering the impact of co-occurring childhood adversities when planning treatment, prevention, and intervention programmes.

  13. Adverse childhood experiences and substance use among Hispanic emerging adults in Southern California

    PubMed Central

    Allem, Jon-Patrick; Soto, Daniel W.; Baezconde-Garbanati, Lourdes; Unger, Jennifer B.

    2015-01-01

    Introduction Emerging adults who experienced stressful childhoods may engage in substance use as a maladaptive coping strategy. Given the collectivistic values Hispanics encounter growing up, adverse childhood experiences may play a prominent role in substance use decisions as these events violate the assumptions of group oriented cultural paradigms. Alternatively, adverse childhood events might not increase the risk of substance use because strong family ties could mitigate the potential maladaptive behaviors associated with these adverse experiences. This study examined whether adverse childhood experiences were associated with substance use among Hispanic emerging adults. Method Participants (n=1420, mean age=22, 41% male) completed surveys indicating whether they experienced any of 8 specific adverse experiences within their first 18 years of life, and past-month cigarette use, marijuana use, hard drug use, and binge drinking. Logistic regression models examined the associations between adverse childhood experiences and each category of substance use, controlling for age, gender, and depressive symptoms. Results The number of adverse childhood experiences was significantly associated with each category of substance use. A difference in the number of adverse childhood experiences, from 0 to 8, was associated with a 22% higher probability of cigarette smoking, a 24% higher probability of binge drinking, a 31% higher probability of marijuana use, and a 12% higher probability of hard drug use respectively. Conclusions These findings should be integrated into prevention/intervention programs in hopes of quelling the duration and severity of substance use behaviors among Hispanic emerging adults. PMID:26160522

  14. Amplifications of chromosomal region 20q13 as a prognostic indicator breast cancer

    DOEpatents

    Gray, Joe W.; Collins, Colin; Pinkel, Daniel; Kallioniemi, Olli-Pekka; Tanner, Minna M.

    2001-01-01

    The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

  15. Amplifications of chromosomal region 20q13 as a prognostic indicator in breast cancer

    DOEpatents

    Gray, Joe W.; Collins, Colin; Pinkel, Daniel; Kallioniemi, Olli-Pekka; Tanner, Minna M.

    1998-01-01

    The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

  16. [Typical pulmonary carcinoid tumor: evolution, related prognostic factors and lymphadenectomy indications].

    PubMed

    Bagan, P; Das-Neves-Pereira, J C; Rivera, C; Gibault, L; Badia, A; Mordant, P; Riquet, M; Le Pimpec Barthes, F

    2014-01-01

    The bronchopulmonary typical carcinoid tumors are often considered as non-metastatic neoplasia. The appearance of metastases is observed in 10% of the cases. We detail here studies based on the identification of the risk factors of metastases occurrence to adapt the lung surgery and lymph node dissection to the individual patient risk.

  17. Infant Attentional Behaviours as Prognostic Indicators in Cornelia-de-Lange Syndrome

    ERIC Educational Resources Information Center

    Sarimski, Klaus

    2007-01-01

    Background: Cornelia-de-Lange syndrome is a rare congenital syndrome with poor social relatedness as one of several characteristics of its behavioural phenotype. Methods: Video observations were collected from seven children in their first year of life and again with age 2-4 years. Data were analysed for distribution of object-related and social…

  18. Gene Expression Profile Analysis as a Prognostic Indicator of Normal Tissue Response to Simulated Space Radiations

    NASA Technical Reports Server (NTRS)

    Story, Michael; Stivers, David N.

    2004-01-01

    This project was funded as a pilot project to determine the feasibility of using gene expression profiles to characterize the response of human cells to exposure to particulate radiations such as those encountered in the spaceflight environment. We proposed to use microarray technology to examine the gene expression patterns of a bank of well-characterized human fibroblast cell cultures. These fibroblast cultures were derived from breast or head and neck cancer patients who exhibited normal, minimal, or severe normal tissue reactions following low LET radiation exposure via radiotherapy. Furthermore, determination of SF2 values from fibroblasts cultured from these individuals were predictive of risk for severe late reactions. We hypothesized that by determining the expression of thousands of genes we could identify gene expression patterns that reflect how normal tissues respond to high Z and energy (HZE) particles, that is, that there are molecular signatures for HZE exposures. We also hypothesized that individuals who are intrinsically radiosensitive may elicit a unique response. Because this was funded as a pilot project we focused our initial studies on logistics and appropriate experimental design, and then to test our hypothesis that there is a unique molecular response to specific particles, in this case C and Fe, for primary human skin fibroblasts.

  19. Stromal fibers in oral squamous cell carcinoma: A possible new prognostic indicator?

    PubMed Central

    Kardam, Priyanka; Mehendiratta, Monica; Rehani, Shweta; Kumra, Madhumani; Sahay, Khushboo; Jain, Kanu

    2016-01-01

    Background: Many studies have been carried out to study the role of extracellular matrix proteins, growth factors and matrix metalloproteinases on tumor invasion. However, literature related to the analysis of connective tissue fibers in varying grades of oral squamous cell carcinoma (OSCC) is very limited. Aim: To analyze the changes in collagen and elastic fibers in varying grades of (OSCC). Settings and Design: This retrospective study was carried out using a light and polarizing microscope. Materials and Methods: Three sections each were cut from fifty samples of varying grades of OSCC and ten samples of control followed by staining with H and E, Picrosirius-Red and Verhoeff–Van Gieson. Qualitative and quantitative analysis of collagen and elastic fibers were accomplished using set criteria. Statistical Analysis: Data were entered into the Statistical Package for Social Sciences (SPSS) version 13.5 for analysis. Results: A change in colors of collagen fibers was seen on progressing from well to poorly differentiated OSCC. Thin collagen fibers predominantly exhibited greenish yellow, but the thick fibers exhibited a variety of colors. As the grade of OSCC progressed, collagen fibers were loosely packed haphazardly arranged. Statistically insignificant results were obtained for quantitative analysis of collagen and qualitative analysis of elastic fibers. Conclusion: The collagen fibers undergo a change in color, orientation and packing in the stroma of varying grades of OSCC. The uniqueness of this study lies in the exploration of elastic fibers in OSCC which has not been done so far. PMID:27721605

  20. [Indices of the responsiveness of system blood circulation as prognostic index of gastric ulcer development].

    PubMed

    Liutov, V V; Dergunov, A A; Liutov, R V

    2010-12-01

    118 patients with gastric ulcer and 112 healthy people (control set) were examined. It is established that determination of connections between phenotype, responsiveness of general circulation, variability of cardiac rhythm, types of personality and levels of reactive anxiety allows to diagnose not only the prenosological and initial forms of gastric ulcer, but also to determine the tactics of conservative and surgical treatment of this disease.

  1. Prognostic indicators of poor outcome in horses with laminitis at a tertiary care hospital.

    PubMed

    Orsini, James A; Parsons, Corrina Snook; Capewell, Linda; Smith, Gary

    2010-06-01

    This retrospective study investigated the factors associated with a poor outcome (death by euthanasia or from other causes) in horses treated for laminitis at a tertiary care hospital. Cases (n = 247) were defined as patients with laminitis that were euthanized or that died of other causes during hospitalization. Controls (n = 344) were patients with laminitis that survived to be discharged from the hospital. In the final multivariate analysis, the factors significantly associated with an increased risk for death and their respective odds ratios (OR) were as follows: Thoroughbred (OR = 1.57); racehorse (OR = 1.76); treatment with flunixin meglumine (OR = 1.76); vascular pathology (OR = 2.12); distal displacement of the third phalanx (OR = 2.68); pneumonia (OR = 2.87); and lameness of Obel grade II (OR = 2.99), grade III (OR = 9.63), or grade IV (OR = 20.48). The use of glue-on shoes significantly reduced the risk for death (OR = 0.36).

  2. Adverse drug events: database construction and in silico prediction.

    PubMed

    Cheng, Feixiong; Li, Weihua; Wang, Xichuan; Zhou, Yadi; Wu, Zengrui; Shen, Jie; Tang, Yun

    2013-04-22

    Adverse drug events (ADEs) are the harms associated with uses of given medications at normal dosages, which are crucial for a drug to be approved in clinical use or continue to stay on the market. Many ADEs are not identified in trials until the drug is approved for clinical use, which results in adverse morbidity and mortality. To date, millions of ADEs have been reported around the world. Methods to avoid or reduce ADEs are an important issue for drug discovery and development. Here, we reported a comprehensive database of adverse drug events (namely MetaADEDB), which included more than 520,000 drug-ADE associations among 3059 unique compounds (including 1330 drugs) and 13,200 ADE items by data integration and text mining. All compounds and ADEs were annotated with the most commonly used concepts defined in Medical Subject Headings (MeSH). Meanwhile, a computational method, namely the phenotypic network inference model (PNIM), was developed for prediction of potential ADEs based on the database. The area under the receive operating characteristic curve (AUC) is more than 0.9 by 10-fold cross validation, while the AUC value was 0.912 for an external validation set extracted from the US-FDA Adverse Events Reporting System, which indicated that the prediction capability of the method was reliable. MetaADEDB is accessible free of charge at http://www.lmmd.org/online_services/metaadedb/. The database and the method provide us a useful tool to search for known side effects or predict potential side effects for a given drug or compound.

  3. 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

  4. High expression of CXCR3 is an independent prognostic factor in glioblastoma patients that promotes an invasive phenotype.

    PubMed

    Pu, Yi; Li, Shouwei; Zhang, Chuanbao; Bao, Zhaoshi; Yang, Zhengxiang; Sun, Lihua

    2015-03-01

    Chemokines are a superfamily of small heparin-binding cytokines that induce leukocytes to migrate to sites of inflammation or injury through interacting with specific transmembrane G protein-coupled receptors. Currently, attention is focused on chemokine/chemokine receptor pairs and their ability to promote tumor cell migration and angiogenesis. The chemokine receptor CXCR3 is involved in tumor metastasis and is used as a prognostic biomarker. However, its relationship with the clinicopathological features of primary glioblastoma multiforme (pGBM) and its potential prognostic value have yet to be investigated. Here, we report that high CXCR3 expression conferred poor survival in pGBM patients. Further analysis showed that CXCR3 served as an independent prognostic biomarker for pGBM patients. In addition, functional assays indicated that CXCR3 induced glioma cell invasion. Therefore, this evidence indicates CXCR3 is an independent prognostic factor for pGBM patients and promotes an invasive phenotype, which suggests a new potential biotarget for glioblastoma multiforme therapy.

  5. The lifelong effects of early childhood adversity and toxic stress.

    PubMed

    Boyce, W Thomas

    2014-01-01

    A rapidly expanding body of research indicates that early social environments characterized by adversity, subordination and stress, along with individual differences in susceptibility to such environments, create risks for lifelong chronic diseases, including declines in oral health. Emerging findings suggest that gene-environment interplay, resulting in epigenetically regulated differences in gene expression, underlie many such declines in health. The origins of these processes in early life reveal how many of the chronic morbidities of adulthood should be viewed as developmental disorders, with etiologic roots in childhood.

  6. Analysis of Adverse Events in Identifying GPS Human Factors Issues

    NASA Technical Reports Server (NTRS)

    Adams, Catherine A.; Hwoschinsky, Peter V.; Adams, Richard J.

    2004-01-01

    The purpose of this study was to analyze GPS related adverse events such as accidents and incidents (A/I), Aviation Safety Reporting System (ASRS) reports and Pilots Deviations (PDs) to create a framework for developing a human factors risk awareness program. Although the occurrence of directly related GPS accidents is small the frequency of PDs and ASRS reports indicated there is a growing problem with situational awareness in terminal airspace related to different types of GPs operational issues. This paper addresses the findings of the preliminary research and a brief discussion of some of the literature on related GPS and automation issues.

  7. Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors.

    PubMed

    Day, Daphne; Hansen, Aaron R

    2016-12-01

    Immune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1), have shown durable treatment responses in multiple tumor types by enhancing antitumor immunity. However, removal of self-tolerance can induce autoimmunity and produce a unique immune-driven toxicity profile, termed immune-related adverse events (irAEs). As ICIs gain approval for a growing number of indications, it is imperative clinicians increase their knowledge of and ability to manage irAEs. This review examines the etiology, presentation, kinetics, and treatment of irAEs and aims to provide practical guidance for clinicians.

  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. Special considerations in prognostic research in cancer involving genetic polymorphisms

    PubMed Central

    2013-01-01

    Analysis of genetic polymorphisms may help identify putative prognostic markers and determine the biological basis of variable prognosis in patients. However, in contrast to other variables commonly used in the prognostic studies, there are special considerations when studying genetic polymorphisms. For example, variable inheritance patterns (recessive, dominant, codominant, and additive genetic models) need to be explored to identify the specific genotypes associated with the outcome. In addition, several characteristics of genetic polymorphisms, such as their minor allele frequency and linkage disequilibrium among multiple polymorphisms, and the population substructure of the cohort investigated need to be accounted for in the analyses. In addition, in cancer research due to the genomic differences between the tumor and non-tumor DNA, differences in the genetic information obtained using these tissues need to be carefully assessed in prognostic studies. In this article, we review these and other considerations specific to genetic polymorphism by focusing on genetic prognostic studies in cancer. PMID:23773794

  10. Serologic and immunohistochemical prognostic biomarkers of cutaneous malignancies

    PubMed Central

    Utikal, Jochen; Schadendorf, Dirk

    2007-01-01

    Biomarkers are important tools in clinical diagnosis and prognostic classification of various cutaneous malignancies. Besides clinical and histopathological aspects (e.g. anatomic site and type of the primary tumour, tumour size and invasion depth, ulceration, vascular invasion), an increasing variety of molecular markers have been identified, providing the possibility of a more detailed diagnostic and prognostic subgrouping of tumour entities, up to even changing existing classification systems. Recently published gene expression or proteomic profiling data relate to new marker molecules involved in skin cancer pathogenesis, which may, after validation by suitable studies, represent future prognostic or predictive biomarkers in cutaneous malignancies. We, here, give an overview on currently known serologic and newer immunohistochemical biomarker molecules in the most common cutaneous malignancies, malignant melanoma, squamous cell carcinoma and cutaneous lymphoma, particularly emphasizing their prognostic and predictive significance. PMID:17221215

  11. Identifying Suitable Degradation Parameters for Individual-Based Prognostics

    SciTech Connect

    Coble, Jamie B.; Hines, Wes

    2012-09-30

    The ultimate goal of most prognostic systems is accurate prediction of the remaining useful life of individual systems or components based on their use and performance. Traditionally, individual-based prognostic methods use a measure of degradation to make lifetime estimates. Degradation measures may include sensed measurements, such as temperature or vibration level, or inferred measurements, such as model residuals or physics-based model predictions. Often, it is beneficial to combine several measures of degradation into a single parameter. Parameter features such as trendability, monotonicity, and prognosability can be used to compare candidate prognostic parameters to determine which is most useful for individual-based prognosis. By quantifying these features for a given parameter, the metrics can be used with any traditional optimization technique to identify an appropriate parameter. This parameter may be used with a parametric extrapolation model to make prognostic estimates for an individual unit. The proposed methods are illustrated with an application to simulated turbofan engine data.

  12. Transient paralysis during acupuncture therapy: a case report of an adverse event.

    PubMed

    Beable, Anne

    2013-09-01

    A patient with apparently well-controlled epilepsy with a painful musculoskeletal condition was treated successfully with two sessions of acupuncture. However, 4 h after the first treatment and during the second, an adverse event involving impairment of consciousness occurred. The patient subsequently experienced an increased frequency of complex partial seizures resulting in the loss of his driving licence. A detailed retrospective review of the past medical history indicated that the patient probably had comorbidities in the form of rapid eye movement sleep behaviour disorder and dysfunctional somatosensory/vestibular processing. Acupuncture may have triggered the adverse event via shared neurosubstrates. This adverse event raises possible implications regarding safe clinical acupuncture practice.

  13. Interventions designed to prevent adverse programming outcomes resulting from exposure to maternal obesity during development

    PubMed Central

    Nathanielsz, PW; Ford, SP; Long, NM; Vega, CC; Reyes-Castro, LA; Zambrano, E

    2013-01-01

    Maternal obesity is a global epidemic affecting the developed and developing world. Human and animal studies indicate that maternal obesity programs development predisposing offspring to later-life chronic diseases. Several mechanisms act together to produce these adverse health problems. There is a need for effective interventions that prevent these outcomes and guide management in human pregnancy. We report here dietary and exercise intervention studies in both altricial and precocial species, rats and sheep, designed to prevent adverse offspring outcomes. Both interventions present exciting opportunities to at least in part prevent adverse metabolic and other outcomes in mother and offspring. PMID:24147928

  14. The Prognostic Role of SIRT1-Autophagy Axis in Gastric Cancer

    PubMed Central

    Qiu, Guanglin

    2016-01-01

    Aim. Sirtuin 1 (SIRT1) can induce autophagy through deacetylation of Beclin-1 and other autophagy mediators. However, the relationship between SIRT1 and autophagy in GC has not been defined. Therefore, the aim of this study was to confirm the prognostic value of SIRT1 and Beclin-1 and their relationship in GC patients. Methods. Transmission electron microscopy (TEM) was performed to examine the autophagy in GC patients. Immunohistochemistry was used to examine the expression of SIRT1, Beclin-1 in GC, and adjacent nonneoplastic mucosa. Results. In 7 out of 8 GC patients' samples examined by TEM, more autophagic vesicles were observed in GC tissues compared to adjacent nonneoplastic mucosa tissue. A positive correlation between SIRT1 and Beclin-1 expression was observed. Furthermore, Beclin-1 or SIRT1 expression alone or their combined expression were significantly correlated with advanced clinicopathological parameters. High Beclin-1 and SIRT1 expression alone and their combined high expression predicted shorter overall survival and relapse-free survival. Both high Beclin-1 and SIRT1 expressions were independent prognostic factors for poor survival of GC. Conclusions. Based on our results we can conclude that SIRT1 and Beclin-1 expression alone or in combination can be used as prognostic indicator and may represent new therapeutic targets in GC. PMID:28070138

  15. Development of Asset Fault Signatures for Prognostic and Health Management in the Nuclear Industry

    SciTech Connect

    Vivek Agarwal; Nancy J. Lybeck; Randall Bickford; Richard Rusaw

    2014-06-01

    Proactive online monitoring in the nuclear industry is being explored using the Electric Power Research Institute’s Fleet-Wide Prognostic and Health Management (FW-PHM) Suite software. The FW-PHM Suite is a set of web-based diagnostic and prognostic tools and databases that serves as an integrated health monitoring architecture. The FW-PHM Suite has four main modules: Diagnostic Advisor, Asset Fault Signature (AFS) Database, Remaining Useful Life Advisor, and Remaining Useful Life Database. This paper focuses on development of asset fault signatures to assess the health status of generator step-up generators and emergency diesel generators in nuclear power plants. Asset fault signatures describe the distinctive features based on technical examinations that can be used to detect a specific fault type. At the most basic level, fault signatures are comprised of an asset type, a fault type, and a set of one or more fault features (symptoms) that are indicative of the specified fault. The AFS Database is populated with asset fault signatures via a content development exercise that is based on the results of intensive technical research and on the knowledge and experience of technical experts. The developed fault signatures capture this knowledge and implement it in a standardized approach, thereby streamlining the diagnostic and prognostic process. This will support the automation of proactive online monitoring techniques in nuclear power plants to diagnose incipient faults, perform proactive maintenance, and estimate the remaining useful life of assets.

  16. Distinct prognostic values of S100 mRNA expression in breast cancer

    PubMed Central

    Zhang, Shizhen; Wang, Zhen; Liu, Weiwei; Lei, Rui; Shan, Jinlan; Li, Ling; Wang, Xiaochen

    2017-01-01

    S100 family genes encode low molecular weight, acidic-Ca2+ binding proteins implicating in a wide spectrum of biological processes. S100 family contains at least 20 members, most of which are frequently dysregulated in human malignancies including breast cancer. However, the prognostic roles of each individual S100, especially the mRNA level, in breast cancer patients remain elusive. In the current study, we used “The Kaplan-Meier plotter” (KM plotter) database to investigate the prognostic values of S100 mRNA expression in breast cancer. Our results indicated that high mRNA expression of S100A8, S100A9, S100A11 and S100P were found to be significantly correlated to worse outcome, while S100A1 and S100A6 were associated with better prognosis in all breast cancer patients. We further assessed the prognostic value of S100 in different intrinsic subtypes and clinicopathological features of breast cancer. The associated results will elucidate the role of S100 in breast cancer and may further lead the research to explore the S100-targeting reagents for treating breast cancer patients. PMID:28051137

  17. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

    PubMed

    Wilczynski, Milosz; Danielska, Justyna; Dzieniecka, Monika; Szymanska, Bozena; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

  18. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer

    PubMed Central

    Wilczynski, Milosz; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients’ clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker. PMID:27737015

  19. Predictive and Prognostic Value of sPRR in Patients with Primary Epithelial Ovarian Cancer

    PubMed Central

    Franz, Annika; Richter, Rolf; Dragun, Duska; Heidecke, Harald; Dechend, Ralf; Muller, Dominik N.; Sehouli, Jalid; Braicu, Elena I.

    2016-01-01

    Aim. The purpose of the present study was to analyze the predictive and prognostic role of soluble (pro)renin receptor (sPRR) as a biomarker for clinicopathological outcome in patients with primary epithelial ovarian cancer (EOC). As part of the renin-angiotensin system (RAS) whose activity is known to increase in ovarian cancer patients, the relation of sPRR and ovarian cancer should be further investigated. Patients and Methods. In this study 197 patients with primary EOC in our institution from 2000 to 2011 were included. sPRR was determined by enzyme-linked immunosorbent assay (ELISA) in preoperative taken blood sera. Associations with clinicopathological outcome were analyzed and serum levels of sPRR in patients have been compared to those in healthy specimen. Kaplan-Meier and logistic/Cox regression assessed the impact of the markers on progression-free survival (PFS) and overall survival (OS). Results. There have been no correlations proved of sPRR levels with neither clinicopathological factors nor prognostic data. Also the distribution of sPRR in patients and controls was normal. Conclusion. sPRR seems to have no predictive, prognostic, or diagnostic value in EOC. As several factors of the RAS which might indicate cancer events have been shown, sPRR seems not to be affected. PMID:27660742

  20. Clinical significance and prognostic value of Vav1 expression in Non-small cell lung cancer

    PubMed Central

    Qi, Yao; Kong, Fan-Ming; Deng, Qi; Li, Jing-Yi; Cui, Rui; Pu, Ye-Di; Zhai, Qiong-Li; Jia, Ying-Jie; Li, Yu-Ming

    2015-01-01

    Vav1 has been reported to be involved in human cancers, however, the expression and clinical significance of Vav1 in NSCLC are not fully understood. In the present study, we examined the expression of Vav1 in 170 NSCLC patients who underwent radical resection by the immunohistochemical analyses. The association between the Vav1 expression and clinicopathological variables was analyzed. The multivariate Cox proportional hazards model was conducted to determine the prognostic value of Vav1 on the long-term survival. The results showed that the elevated Vav1 expression was correlated positively with lymph node metastasis (P<0.001), T stage (P<0.001) and poor histological differentiation (P<0.001). Patients with negative or low Vav1 expression had better prognoses than those with high Vav1 expression (P<0.001). Multivariate analysis indicated that Vav1 was independent prognostic factor for overall survival (OS) (HR 2.079, 95% CI 1.564 to 2.762, P<0.001) and disease-free survival (DFS) (HR 1.810, 95% CI 1.391 to 2.356, P<0.001). Our findings showed that overexpressed Vav1 was correlated with aggressive tumor behavior. Val1 was an independent factor for NSCLC prognosis, which may serve as a novel prognostic factor and potential target to improve the long-term outcome of NSCLC. PMID:26396925

  1. Prognostic value of amphiregulin and epiregulin mRNA expression in metastatic colorectal cancer patients

    PubMed Central

    You, Zhai; Qiong, Qian; Jun, Zhou

    2016-01-01

    Epidermal growth factor receptor (EGFR) and its ligands amphiregulin (AREG) and epiregulin (EREG) play a central role in the development of colorectal cancer, but the prognostic values of AREG and EREG are controversial. We conducted a meta-analysis of studies that investigated AREG and/or EREG mRNA levels in primary tumors to determine their prognostic value in metastatic colorectal cancer (mCRC). In addition, RAS status was assessed. Relevant articles were identified by searching the EMBASE, PubMed, and Cochrane Library databases. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated using a random-effects model. Nine studies involving 2167 patients were included in this meta-analysis. High AREG expression was associated with longer overall survival (OS) and progression-free survival (PFS). High EREG expression was also associated with prolonged OS and PFS. In RAS wild-type (WT) patients who received anti-EGFR therapy, high AREG and EREG expression was associated with longer OS. Our results indicate that high AREG and EREG mRNA expression are independent favorable prognostic biomarkers in mCRC. The expression of these ligands should be considered when evaluating prognoses in RAS-WT patients receiving anti-EGFR therapy. PMID:27344184

  2. The Prognostic Value of TRAIL and its Death Receptors in Cervical Cancer

    SciTech Connect

    Maduro, John H. Noordhuis, Maartje G.; Hoor, Klaske A. ten; Pras, Elisabeth; Arts, Henriette J.G.; Eijsink, Jasper J.H.; Hollema, Harry; Mom, Constantijne H.; Jong, Steven de; Vries, Elisabeth G.E. de; Bock, Geertruida H. de; Zee, Ate G.J. van der

    2009-09-01

    Purpose: Preclinical data indicate a synergistic effect on apoptosis between irradiation and recombinant human (rh) tumor necrosis factor-related apoptosis inducing ligand (TRAIL), making the TRAIL death receptors (DR) interesting drug targets. The aim of our study was to analyze the expression of DR4, DR5, and TRAIL in cervical cancer and to determine their predictive and prognostic value. Methods and Materials: Tissue microarrays were constructed from tumors of 645 cervical cancer patients treated with surgery and/or (chemo-)radiation between 1980 and 2004. DR4, DR5, and TRAIL expression in the tumor was studied by immunohistochemistry and correlated to clinicopathological variables, response to radiotherapy, and disease-specific survival. Results: Cytoplasmatic DR4, DR5, and TRAIL immunostaining were observed in cervical tumors from 99%, 88%, and 81% of the patients, respectively. In patients treated primarily with radiotherapy, TRAIL-positive tumors less frequently obtained a pathological complete response than TRAIL-negative tumors (66.3% vs. 79.0 %; in multivariate analysis: odds ratio: 2.09, p {<=}0.05). DR4, DR5, and TRAIL expression were not prognostic for disease-specific survival. Conclusions: Immunostaining for DR4, DR5, and TRAIL is frequently observed in the cytoplasm of tumor cells in cervical cancer patients. Absence of TRAIL expression was associated with a higher pathological complete response rate to radiotherapy. DR4, DR5, or TRAIL were not prognostic for disease-specific survival.

  3. GERD—Barrett—Adenocarcinoma: Do We Have Suitable Prognostic and Predictive Molecular Markers?

    PubMed Central

    Illig, Romana; Klieser, Eckhard; Kiesslich, Tobias; Neureiter, Daniel

    2013-01-01

    Due to unfavorable lifestyle habits (unhealthy diet and tobacco abuse) the incidence of gastroesophageal reflux disease (GERD) in western countries is increasing. The GERD-Barrett-Adenocarcinoma sequence currently lacks well-defined diagnostic, progressive, predictive, and prognostic biomarkers (i) providing an appropriate screening method identifying the presence of the disease, (ii) estimating the risk of evolving cancer, that is, the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC), (iii) predicting the response to therapy, and (iv) indicating an overall survival—prognosis for EAC patients. Based on histomorphological findings, detailed screening and therapeutic guidelines have been elaborated, although epidemiological studies could not support the postulated increasing progression rates of GERD to BE and EAC. Additionally, proposed predictive and prognostic markers are rather heterogeneous by nature, lack substantial proofs, and currently do not allow stratification of GERD patients for progression, outcome, and therapeutic effectiveness in clinical practice. The aim of this paper is to discuss the current knowledge regarding the GERD-BE-EAC sequence mainly focusing on the disputable and ambiguous status of proposed biomarkers to identify promising and reliable markers in order to provide more detailed insights into pathophysiological mechanisms and thus to improve prognostic and predictive therapeutic approaches. PMID:23573078

  4. Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma.

    PubMed

    Lennerz, Jochen K; Hoffmann, Karl; Bubolz, Anna-Maria; Lessel, Davor; Welke, Claudia; Rüther, Nele; Viardot, Andreas; Möller, Peter

    2015-10-06

    Suppressor of cytokine signaling 1 (SOCS1) mutations are among the most frequent somatic mutations in classical Hodgkin lymphoma (cHL), yet their prognostic relevance in cHL is unexplored. Here, we performed laser-capture microdissection of Hodgkin/Reed-Sternberg (HRS) cells from tumor samples in a cohort of 105 cHL patients. Full-length SOCS1 gene sequencing showed mutations in 61% of all cases (n = 64/105). Affected DNA-motifs and mutation pattern suggest that many of these SOCS1 mutations are the result of aberrant somatic hypermutation and we confirmed expression of mutant alleles at the RNA level. Contingency analysis showed no significant differences of patient-characteristics with HRS-cells containing mutant vs. wild-type SOCS1. By predicted mutational consequence, mutations can be separated into those with non-truncating point mutations ('minor' n = 49/64 = 77%) and those with length alteration ('major'; n = 15/64 = 23%). Subgroups did not differ in clinicopathological characteristics; however, patients with HRS-cells that contained SOCS1 major mutations suffered from early relapse and significantly shorter overall survival (P = 0.03). The SOCS1 major status retained prognostic significance in uni-(P = 0.016) and multivariate analyses (P = 0.005). Together, our data indicate that the SOCS1 mutation type qualifies as a single-gene prognostic biomarker in cHL.

  5. Long noncoding RNAs are novel potential prognostic biomarkers for esophageal squamous cell carcinoma: an overview.

    PubMed

    Deng, Han-Yu; Wang, Yun-Cang; Ni, Peng-Zhi; Lin, Yi-Dan; Chen, Long-Qi

    2016-08-01

    Esophageal squamous cell carcinoma (ESCC) still has a poor prognosis. The prognostic biomarkers of ESCC are not yet well established. Long noncoding RNAs (lncRNAs) have recently been intensively investigated in various cancers including ESCC, and are found to be closely correlated to ESCC. Dysregulated expression of lncRNAs was widely observed in ESCC tumor tissue and was closely related to the tumorigenesis and progression of ESCC. More and more studies have found that lncRNAs were significantly correlated with the prognosis and diagnosis of patients with ESCC. Therefore, all those accumulating evidence indicated that lncRNAs could serve as a prognostic biomarker of ESCC. In this, we summarized the relation between lncRNAs and ESCC as well as the potential biomarker role of lncRNAs in ESCC, especially the prognostic value of lncRNAs. Our current review highlighted the need of further studies to explore the biomarker functions as well as therapeutic values of lncRNAs in ESCC.

  6. Neuroticism mediates the relationship between childhood adversity and adult sleep quality.

    PubMed

    Ramsawh, Holly J; Ancoli-Israel, Sonia; Sullivan, Sarah G; Hitchcock, Carla A; Stein, Murray B

    2011-01-01

    This study investigated the relationship of childhood adversity and adult sleep quality in 327 college students (91 males), with a mean age of 18.9 years (SD = 2.1) and also examined whether neuroticism significantly mediated the observed association. Regression findings indicate that the relationship between childhood adversity and adult sleep quality is significant, and that there is a stronger association in men. Furthermore, a bootstrapping approach to testing the significance of the indirect effect (i.e., mediation) indicated that neuroticism mediated this relationship in both men and women. These data suggest that otherwise healthy young adults with a history of childhood adversity are at increased risk for sleep disturbance. Neuroticism may represent a potential target for change in future insomnia interventions, particularly in adults with a history of childhood adversity.

  7. The preoperative alkaline phosphatase-to-platelet ratio index is an independent prognostic factor for hepatocellular carcinoma after hepatic resection

    PubMed Central

    Yu, Ya-Qun; Li, Jun; Liao, Yan; Chen, Qian; Liao, Wei-Jia; Huang, Jian

    2016-01-01

    Abstract A simple, inexpensive, and readily available prognostic index is highly needed to accurately predict the prognosis of hepatocellular carcinoma (HCC). This study aimed to develop a simple prognostic index using routine laboratory tests, alkaline phosphatase-to-platelet count ratio index (APPRI), to predict the likelihood of postoperative survival in HCC patients. A total of 246 patients with HCC undergoing curative resection were retrospectively analyzed. Cutoff point for APPRI was calculated using receiver operating characteristic curve analysis, and then the patients were divided into the low-APPRI group (APPRI ≤ 4.0) and the high-APPRI group (APPRI > 4.0). The influences of APPRI on disease-free survival (DFS) and overall survival (OS) were tested by the Kaplan–Meier method, and multivariate analysis using Cox regression. Elevated APPRI was associated with age, cirrhosis, and aspartate aminotransferase (AST) in HCC. Univariate analysis showed that APPRI > 4.0, tumor size >6 cm, multiple tumors, Barcelona-clinic liver cancer stages B to C, and AST > 40 U/L were significant predictors of worse DFS and OS. A multivariate analysis suggested that APPRI > 4.0 was an independent factor for DFS (hazard ratio [HR] = 1.689; 95% confidence interval [CI], 1.139–2.505; P = 0.009) and OS (HR = 1.664; 95% CI, 1.123–2.466; P = 0.011). Preoperative APPRI > 4.0 was a powerful prognostic predictor of adverse DFS and OS in HCC after surgery. The APPRI may be a promising prognostic marker for HCC after surgical resection. PMID:28002346

  8. Economic Inequalities in Latin America at the Base of Adverse Health Indicators.

    PubMed

    Ferre, Juan Cruz

    2016-07-01

    There is increasing evidence supporting the existence of a link between income inequalities and health outcomes. The main purpose of this article is to test whether economic inequalities are associated with poor population health in Latin American countries. Multi-country data from 1970 to 2012 were used to assess this question. The results show that the Gini coefficient has a strong correlation with health outcomes. Moreover, multiple linear regression analysis using fixed effects shows that after controlling for gross national income per capita, literacy rate, and health expenditure, the Gini coefficient is independently negatively associated with health outcomes. In Latin American countries, for every percentage point increase in the Gini coefficient, the infant mortality rate grows by 0.467 deaths per 1,000 live births, holding all other variables constant. Additionally, an ordinary least squares estimation model suggests that countries that do not use International Monetary Fund loans perform better on health outcomes. These findings should alert policymakers, elected officials, and the public of the need to fight income inequalities and rethink the role of international financial institutions that dictate state policies.

  9. Cytogenetics of Anodonta cygnea (Mollusca: Bivalvia) as possible indicator of environmental adversity

    NASA Astrophysics Data System (ADS)

    Carrilho, J.; Leitão, A.; Vicente, C.; Malheiro, I.

    2008-11-01

    Anodonta cygnea is a freshwater clam, belonging to the Unionidae family, which can be found in rivers and lagoons all over Europe and Northern America. As they appear as important case studies for ecological damage assessments, the various species of the Unionidae family have been submitted to a sort of recent studies on their chromosomal or cytogenetic status. In this study we confirmed the diploid chromosome number of 2 n = 38 for this species, and established for the first time the karyotype, which comprised six metacentric, 12 submetacentric and one subtelocentric chromosome pairs. We also found a high percentage of cells with an abnormal number of chromosomes. Considering that karyotype disturbances in Unionids have been previously related with exposure to chemicals, either natural or produced by human activity, we determined the aneuploidy index for our population. The aneuploidy index is an excellent marker for pollutant presence/effect. The animals acclimatized in tap water and in natural water from the lake where the individuals were collected showed different levels of aneuploidy. The higher values were found in tap water. Chromosome analysis techniques seem a suitable tool to study the impact of contaminants referred above, and making A. cygnea a suitable organism for assessment of an eugenic damage in aquatic systems. On the other hand, our results also point out to the importance of doing the acclimatizing process of the collected animals in their own natural water.

  10. Play as a Resource for Children Facing Adversity: An Exploration of Indicative Case Studies

    ERIC Educational Resources Information Center

    Fearn, Maggie; Howard, Justine

    2012-01-01

    In this paper, we suggest that the ability and opportunity to play affords children a natural resource to meet intellectual and emotional challenge. Analysis of case studies focusing on interventions with children caught in the bombing of Beirut, children abandoned to the state system in Romania, and the street children in Rio de Janeiro and Cali…

  11. Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis.

    PubMed

    Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

    2017-01-01

    The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83-2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59-2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76-2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction.

  12. Heterogeneity of Prognostic