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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 in cystosarcoma phylloides.

    PubMed

    Hines, J R; Murad, T M; Beal, J M

    1987-03-01

    Cystosarcoma phylloides is a breast neoplasm that has a frequently unpredictable clinical course. We made a retrospective study of 25 patients with this disease in an attempt to evaluate the indicators of aggressive behavior. In our series, older patient age, nulliparity, rapid tumor growth, pain, and large size of tumors increased the suspicion of malignancy but were not always reliable indicators of malignancy. Skin ulceration, tumor necrosis, and infiltrating tumor margins were the most ominous characteristics. High-grade tumors, that is, those with increased cellularity, vascularity, mitotic figure, and pleomorphism, often indicated aggressive behavior. Mixed mesenchymal components were sometimes related to a malignant course. We found a 24 percent incidence of associated breast cancer. Carcinoma of the ipsilateral breast was found in four patients and later in the contralateral breast in two patients. Of our 25 patients, 10 (40 percent) had recurrence and 4 (16 percent) died from disease. Recurrences after treatment usually occurred within 3 years. Patients must be followed carefully for local recurrence or metastases, since the clinical course is not predictable. Forty percent of the lesions were diagnosed as being malignant. Local excision was associated with recurrence in six of eight patients and was clearly inadequate treatment. Quadrantectomy was effective for benign peripheral lesions when a generous margin could be obtained. From these data, we believe that mastectomy is indicated in all patients with malignant lesions and in those with large benign lesions. PMID:3030151

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

    PubMed Central

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

    2015-01-01

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

  4. Prognostic Indicators for Ebola Patient Survival

    PubMed Central

    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.

    2016-01-01

    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. PMID:26812579

  5. 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. PMID:26812579

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2011-08-01

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

  8. 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

  9. Feline mammary adenocarcinoma: tumor size as a prognostic indicator

    PubMed Central

    Viste, Jodi R.; Myers, Sherry L.; Singh, Baljit; Simko, Elemir

    2002-01-01

    Mammary carcinomas and adenocarcinomas (MACs) are relatively common tumors in cats. The postexcisional survival period of affected cats is inversely proportional to tumor size, but the reported median survival periods for different tumor size categories is quite variable. This variability diminishes the prognostic value of reported data. In our study, cats with MACs greater than 3 cm in diameter had a 12-month median survival period, whereas those with MACs less than 3 cm in diameter had a 21-month survival period. Survival periods for cats with MACs smaller than 3 cm ranged from 3 to 54 months; therefore, tumor size alone is of limited prognostic value in cats with MACs smaller than 3 cm in diameter. In cats with MACs larger than 3 cm in diameter, tumor size appears to have much higher prognostic relevance, because this study, as well as others, have indicated that cats with MACs greater than 3 cm in diameter have a poor prognosis, with median survival periods ranging from 4 to 12 months. PMID:11802667

  10. 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

  11. Notch Signaling Components: Diverging Prognostic Indicators in Lung Adenocarcinoma.

    PubMed

    Liu, Zhi-Yan; Wu, Tao; Li, Qing; Wang, Min-Cong; Jing, Li; Ruan, Zhi-Ping; Yao, Yu; Nan, Ke-Jun; Guo, Hui

    2016-05-01

    Non-small-cell lung cancer (NSCLC) is a lethal and aggressive malignancy. Currently, the identities of prognostic and predictive makers of NSCLC have not been fully established. Dysregulated Notch signaling has been implicated in many human malignancies, including NSCLC. However, the prognostic value of measuring Notch signaling and the utility of developing Notch-targeted therapies in NSCLC remain inconclusive. The present study investigated the association of individual Notch receptor and ligand levels with lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) prognosis using the Kaplan-Meier plotte database. This online database encompasses 2437 lung cancer samples. Hazard ratios with 95% confidence intervals were calculated. The results showed that higher Notch1, Notch2, JAG1, and DLL1 mRNA expression predicted better overall survival (OS) in lung ADC, but showed no significance in SCC patients. Elevated Notch3, JAG2, and DLL3 mRNA expression was associated with poor OS of ADC patients, but not in SCC patients. There was no association between Notch4 and OS in either lung ADC or SCC patients. In conclusion, the set of Notch1, Notch2, JAG1, DLL1 and that of Notch3, JAG2, DLL3 played opposing prognostic roles in lung ADC patients. Neither set of Notch receptors and ligands was indicative of lung SCC prognosis. Notch signaling could serve as promising marker to predict outcomes in lung ADC patients. The distinct features of lung cancer subtypes and Notch components should be considered when developing future Notch-targeted therapies. PMID:27196489

  12. Prognostic indicators for failed nonsurgical reduction of intussusception

    PubMed Central

    Khorana, Jiraporn; Singhavejsakul, Jesda; Ukarapol, Nuthapong; Laohapensang, Mongkol; Siriwongmongkol, Jakraphan; Patumanond, Jayanton

    2016-01-01

    Purpose To identify the risk factors for failure of nonsurgical reduction of intussusception. Methods Data from intussusception patients who were treated with nonsurgical reduction in Chiang Mai University Hospital and Siriraj Hospital between January 2006 and December 2012 were collected. Patients aged 0–15 years and without contraindications (peritonitis, abdominal X-ray signs of perforation, and/or hemodynamic instability) were included for nonsurgical reduction. The success and failure groups were divided according to the results of the reduction. Prognostic indicators for failed reduction were identified by using generalized linear model for exponential risk regression. The risk ratio (RR) was used to report each factor. Results One hundred and ninety cases of intussusception were enrolled. Twenty cases were excluded due to contraindications. A total of 170 cases of intussusception were included for the final analysis. The significant risk factors for reduction failure clustered by an age of 3 years were weight <12 kg (RR =1.48, P=0.004), symptom duration >3 days (RR =1.26, P<0.001), vomiting (RR =1.63, P<0.001), rectal bleeding (RR =1.50, P<0.001), abdominal distension (RR =1.60, P=0.003), temperature >37.8°C (RR =1.51, P<0.001), palpable abdominal mass (RR =1.26, P<0.001), location of mass (left over right side) (RR =1.48, P<0.001), poor prognostic signs on ultrasound scans (RR =1.35, P<0.001), and method of reduction (hydrostatic over pneumatic) (RR =1.34, P=0.023). The prediction ability of this model was 82.21% as assessed from the area under the receiver operating characteristic curve. Conclusion The identified prognostic factors for the nonsurgical reduction failure may help to predict the reduction outcome and provide information to the parents. PMID:27563245

  13. 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.

  14. Brainstem gangliogliomas: prognostic factors, surgical indications and functional outcomes.

    PubMed

    Pan, Chang-Cun; Chen, Xin; Xu, Cheng; Wu, Wen-Hao; Zhang, Peng; Wang, Yu; Wu, Tao; Tang, Jie; Xiao, Xin-Ru; Wu, Zhen; Zhang, Jun-Ting; Zhang, Li-Wei

    2016-07-01

    To explore the prognostic factors and discuss the surgical indications of brainstem gangliogliomas. Twenty-one patients with brainstem ganglioglioma were surgically treated at our hospital between 2006 and 2014. The clinical, radiological, operative, and pathological findings of these patients were retrospectively reviewed. The 3-years overall survival and event-free survival (EFS) rates were 90.5 % and 68.4 %, respectively. Four patients (4/18, 22 %) experienced a recurrence with a mean recurrence-free survival of 5.5 months and a mean follow-up of 37 months. Three patients died of surgery-related complications. Three growth patterns were identified: exophytic (6/21), intrinsic (2/21), and endo-exophytic (13/21). Eight patients (8/15, 53 %) harbored a BRAF V600E mutation. All recurrent tumors were endo-exophytic, and except the one without molecular information, were BRAF V600E mutants. A Cox hazard proportion ratio model was used to identify factors influencing EFS, including sex, age, location, growth patterns, extent of resection (EOR), and BRAF V600E mutation status. On univariate analysis, none of these factors reached statistical significance. Among them, EOR and growth patterns were strongly associated with each other (Fisher's exact test, P < 0.01). A multivariate analysis demonstrated that growth patterns were the only factor associated with EFS (P = 0.02; HR 49.05; 95 % CI 1.76-1365.13). Growth patterns may be useful to select surgery candidates and predict prognosis for patients with brainstem gangliogliomas. BRAF V600E was frequently present and appeared to be associated with shorter recurrence-free survival. Studies on BRAF V600E-targeted therapy for patients with high surgical risks are needed. PMID:27112924

  15. Fibronectin as a Prognostic Indicator in Portal Hypertension

    PubMed Central

    Maharaj, D. P.; Garden, O. J.; Carter, D. C.

    1992-01-01

    Plasma fibronectin levels were measured in 33 patients with portal hypertension and c6mpared with modified Child’s grading and a previously described prognostic index. Outcome at one year from blood sampling was recorded. Mean plasma fibronectin level was 304.1 mg/ml (sem 24.3) and significantly lower levels were found in patients who had had a variceal bleed within the previous seven days. Plasma fibronectin levels tended to be lower in patients with poor liver function as assessed by modified Child’s grading but this did not achieve statistical significance. Plasma fibronectin alone was not an accurate predictor of one year survival in these patients but only one of seven patients who had a plasma fibronectin level below 300mg/l in association with a poor prognostic index survived for one year. PMID:1390363

  16. Breast thermography. A prognostic indicator for breast cancer survival.

    PubMed

    Isard, H J; Sweitzer, C J; Edelstein, G R

    1988-08-01

    A prognostic classification for thermographic staging of breast cancer has been applied to a cohort of 70 patients from 5040 screenees enrolled in the Albert Einstein Medical Center (AEMC) Breast Cancer Detection Demonstration Project (BCDDP). A diagnosis of breast cancer was established in each case before December 31, 1980. None of the patients have been lost to follow-up which extended from a minimum of 6 to a maximum of 13 years. Survival rates for those with favorable, equivocal, and poor thermographic factors are compared with each other and with results in accordance with tumor-node-metastasis (TNM) classification. As of December 31, 1986, there have been 22 (31.4%) deaths, all attributed to breast cancer. The thermographic scoring system clearly shows shorter survival for patients with poor thermographic prognostic factors, 30% surviving at 5 years and only 20% at 10 years compared with overall survival of 80% at 5 years and 70% at 10 years. PMID:3390789

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

    PubMed Central

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

    2015-01-01

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

  18. Platelet activation risk index as a prognostic thrombosis indicator.

    PubMed

    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

  19. 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

  20. 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.

  1. 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.

  2. Prognostic Indicators of Cardiovascular Risk in Renal Disease

    PubMed Central

    Hildreth, Cara M.

    2011-01-01

    Although the annual mortality rate for end-stage renal disease (ESRD) is decreasing, likely due to an increase in kidney transplantation rate, the survival probability for ESRD patients from day one of dialysis has not changed, and is still poor with a 5-year survival rate of approximately 34%. This is contributed to by a high prevalence of cardiovascular disease, which is the leading cause of death in ESRD patients. In order to improve survival outcomes, patients at high risk of cardiovascular related mortality need to be identified. Heart rate variability (HRV), baroreceptor sensitivity, and baroreceptor reflex effectiveness index can be used to assess heart rate control and may predict cardiovascular mortality. This paper will discuss how HRV, baroreceptor sensitivity, and baroreceptor reflex effectiveness index are altered in renal disease and the utility of these indices as markers of cardiac risk in this patient population. PMID:22294981

  3. 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

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

    PubMed

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

    1990-11-01

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

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

    PubMed Central

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

    1998-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. Prognostic indices in chronic lymphocytic leukaemia: where do we stand how do we proceed?

    PubMed

    Baliakas, P; Mattsson, M; Stamatopoulos, K; Rosenquist, R

    2016-04-01

    The remarkable clinical heterogeneity in chronic lymphocytic leukaemia (CLL) has highlighted the need for prognostic and predictive algorithms that can be employed in clinical practice to assist patient management and therapy decisions. Over the last 20 years, this research field has been rewarding and many novel prognostic factors have been identified, especially at the molecular genetic level. Whilst detection of recurrent cytogenetic aberrations and determination of the immunoglobulin heavy variable gene somatic hypermutation status have an established role in outcome prediction, next-generation sequencing has recently revealed novel mutated genes with clinical relevance (e.g. NOTCH1, SF3B1 and BIRC3). Efforts have been made to combine variables into prognostic indices; however, none has been universally adopted. Although a unifying model for all groups of patients and in all situations is appealing, this may prove difficult to attain. Alternatively, focused efforts on patient subgroups in the same clinical context and at certain clinically relevant 'decision points', that is at diagnosis and at initiation of first-line or subsequent treatments, may provide a more accurate approach. In this review, we discuss the advantages and disadvantages as well as the clinical applicability of three recently proposed prognostic models, the MD Anderson nomogram, the integrated cytogenetic and mutational model and the CLL-international prognostic index. We also consider future directions taking into account novel aspects of the disease, such as the tumour microenvironment and the dynamics of (sub)clonal evolution. These aspects are particularly relevant in view of the increasing number of new targeted therapies that have recently emerged. PMID:26709197

  8. 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

  9. Chromatin CKAP2, a New Proliferation Marker, as Independent Prognostic Indicator in Breast Cancer

    PubMed Central

    Choi, Yong-Bock; Ro, Jungsil; Kim, Hyun-Kyoung; Kim, Mi-Kyung; Nam, Byung-Ho; Kim, Kyung-Tae; Chandra, Vishal; Seol, Hye-Sil; Noh, Woo-Chul; Kim, Eun-Kyu; Park, Joobae; Bae, Chang-Dae; Hong, Kyeong-Man

    2014-01-01

    Background The level of proliferation activity is a strong prognostic or predictive indicator in breast cancer, but its optimal measurement is still in debate, necessitating new proliferation markers. In the present study, the prognostic significance of the CKAP2-positive cell count (CPCC), a new proliferation marker, was evaluated, and the results were compared with those for the mitotic activity index (MAI). Methods This study included 375 early-stage breast cancer samples collected from two institutions between 2000 and 2006. Immunohistochemical staining was performed using a CKAP2 monoclonal antibody. Cox proportional hazard regression models were fitted to determine the association between the CPCC and relapse-free survival (RFS) amongst three groups formed on the basis of the CPCC or MAI value: groups 2 and 3 showing the middle and highest values, respectively, and group 1 the lowest. Results After adjustment for age, T stage, N stage, HER2 status, estrogen receptor status, progesterone receptor status, institution, and year of surgical resection, the CPCC was associated with a significantly worse RFS {hazard ratio [HR]  = 4.10 (95% CI: 1.64–10.29) for group 2; HR  = 4.35 (95% CI: 2.04–10.35) for group 3}. Moreover, its prognostic significance was similar to or higher than that based on the MAI {HR  = 2.05 (95% CI: 0.94–4.65) for group 2; HR  = 2.35 (95% CI: 1.09–5.10) for group 3}. In subgroup analyses, the CPCC showed a prognostic significance in the luminal A and triple-negative subgroups, but not in the HER2-positive subgroup. Conclusions Chromatin CKAP2 is an independent prognostic marker for RFS in early-stage breast cancer, and could potentially replace the MAI in clinical evaluation of proliferation activity. Additionally, our study results suggest that the prognostic significance of proliferation activity differs among the various subgroups of breast cancer. PMID:24887265

  10. Use of surface-enhanced Raman scattering as a prognostic indicator of acute kidney transplant rejection

    PubMed Central

    Chi, Jingmao; Zaw, Thet; Cardona, Iliana; Hosnain, Mujtaba; Garg, Neha; Lefkowitz, Heather R.; Tolias, Peter; Du, Henry

    2015-01-01

    We report an early, noninvasive and rapid prognostic method of predicting potential acute kidney dysfunction using surface-enhanced Raman scattering (SERS). Our analysis was performed on urine samples collected prospectively from 58 kidney transplant patients using a He-Ne laser (632.8 nm) as the excitation source. All abnormal kidney function episodes (three acute rejections and two acute kidney failures that were eventually diagnosed independently by clinical biopsy) consistently exhibited unique SERS spectral features in just one day following the transplant surgery. These results suggested that SERS analysis provides an early and more specific indication to kidney function than the clinically used biomarker, serum creatinine (sCr). PMID:25798301

  11. 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

  12. 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

  13. Prognostic Scoring Indicator in Evaluation of Clinical Outcome In Intestinal Perforations

    PubMed Central

    Ahuja, Ashish; Pal, Ravinder

    2013-01-01

    Introduction: Acute generalised peritonitis coming forth due to underlying intestinal perforation is a critical & life-threatening medical condition. It is a common surgical emergency most of the times across the world. Misleading data on crude morbidity and mortality due to the condition usually contaminates substantially the very purpose of medical audit. Thus, early prognostic evaluation is not only desirable but mandate to much extent. High-risk patients require timely & aggressive treatment especially in severe peritonitis & to select them reasonably well, evaluation through prognostic scoring is an approach of choice. Well sought after & reasonably reliable APACHE II scoring system is used for the purpose & scores are correlated well to accentuate & measure the various factors needed for better management of condition. Material and Methods: The study was conducted over the period of 18 months (Jan 2010 to June 2011) on 50 patients with confirmed diagnosis of intestinal perforation. APACHE II score was calculated and correlated with their symptoms & clinical outcomes regarding morbidity and mortality. Results: APACHE II score correlated well with the outcome of the study, showing score affects of two major aspects in the treatment outcome & management.1.) APACHE II score of less than 10 included 30 low risk group patients discharged in a satisfactory gratifying manner. Three out of four in high risk group with APACHE II score >20, shown adverse outcomes. 2.)Mean ICU stay of 9.75 days was found in patients with APACHE II score 20 or more compared to those with mean ICU stay of 0.13 days in patients with APACHE II score 10 or less. Conclusion: Acute generalized peritonitis being life–threatening medical emergency requires careful consideration in its management that needs to be economically viable, acceptably feasible and outcome oriented with better allocation & utilization of ICU resources that needs meticulous case analysis & prioritization. This present

  14. Wilms' tumor gene 1 expression: an independent acute leukemia prognostic indicator following allogeneic hematopoietic SCT.

    PubMed

    Zhao, X-S; Jin, S; Zhu, H-H; Xu, L-P; Liu, D-H; Chen, H; Liu, K-Y; Huang, X-J

    2012-04-01

    To evaluate the prognostic significance of Wilms' tumor gene 1 (WT1) expression for monitoring minimal residual disease and predicting relapse in patients with acute leukemia (AL) following allogeneic hematopoietic SCT (allo-HSCT), the WT1 expression levels of 138 AL patients were measured using real-time quantitative reverse transcription PCR at designed time points after allo-HSCT. All patients were divided into four groups based on the HSCT outcomes and intervention application. A low level of WT1 expression following HSCT indicated a low risk of relapse, whereas WT1 expression >1.05% was indicative of a higher probability of relapse. Only the advanced stage of disease (hazard ratio (HR)=2.73; 95% confidence interval (CI)=1.337-5.573, P=0.006) and a WT1 expression ≥ 0.60% (HR=4.774; 95% CI=2.410-9.459, P=0.000) were associated with lower disease-free survival. Relapse (HR=0.119; 95% CI=0.056-0.250, P=0.000) and a WT1 expression 0.60% (HR=2.771; 95% CI=1.316-5.834, P=0.007) were associated with lower OS. In conclusion, the WT1 expression level is an independent prognostic factor that can predict clinical outcomes for AL patients after HSCT and provide a guide for suitable interventions. PMID:21643023

  15. [Viscum album L. (Iscador) in the cat: tolerance, adverse reactions and indications].

    PubMed

    Glardon; Pache; Magnenat; Pin; Parvis

    2014-08-01

    In this retrospective study, the tolerance to subcutaneus mistletoe injections (Viscum album L.), adverse reactions and possible indications have been evaluated in feline patients of a small animal clinic. Among the 22 cats treated between 2008 and 2013, 4 did not accept the injections done by the owner, 7 showed slight short time adverse reactions, that disappeared spontaneously. No long term (more than 70 days) adverse reaction directly related to the Viscum album treatment could be identified. This study shows that Iscador(®) can be injected subcutaneously without a risk of worsening of the clinical signs or exacerbation of tumors. The antitumoral, but also immune-modulating and anti-inflammatory properties offer interesting treatment opportunities for dermatologic, odonto-stomatologic or allergic patients. PMID:25082635

  16. Lactate Dehydrogenase Is an Important Prognostic Indicator for Hepatocellular Carcinoma after Partial Hepatectomy12

    PubMed Central

    Zhang, Jing-Ping; Wang, Hong-Bo; Lin, Yue-Hao; Xu, Jing; Wang, Jun; Wang, Kai; Liu, Wan-Li

    2015-01-01

    Preoperative serum lactate dehydrogenase (LDH) has been used as a prognostic indicator for patients with hepatocellular carcinoma (HCC) treated with sorafenib or undergoing transcatheter arterial chemoembolization, but its significance in predicting survival of HCC patients who received curative resection remains undefined. A total of 683 patients with histopathologically confirmed HCC were enrolled in this study. The prognostic significance of preoperative serum LDH was determined by Kaplan-Meier analysis and a Cox proportional hazards regression model. The association between the preoperative serum LDH and clinicopathological parameters was evaluated by the χ2 test or linear regression analysis when appropriate. Higher preoperative serum LDH level was associated with worse prognosis. In a multivariate Cox proportional hazards analysis, the preoperative serum LDH level could predict overall survival and recurrence independently. Higher preoperative serum LDH level is associated with the elevated serum alpha-fetoprotein, the presence of hepatitis B surface antigen, larger tumor size, the presence of macrovascular invasion, the advanced tumor–lymph node–metastasis stage, worse tumor differentiation, and Child-Pugh B. Preoperative serum LDH level was an inexpensive, simple, convenient, and routinely measured biomarker exhibiting a potential to select patients at high risk with poor clinical outcome for appropriate treatment strategies. PMID:26692531

  17. Are prognostic indicators for poor outcome different for acute and chronic low back pain consulters in primary care?

    PubMed

    Grotle, Margreth; Foster, Nadine E; Dunn, Kate M; Croft, Peter

    2010-12-01

    Few studies have investigated whether prognostic indicators, which contribute to the transition from acute to chronic low back pain (LBP), are also those which contribute to continuing persistence of chronic LBP. We compared the contribution of physical, psychological and social indicators to predicting disability after one year between consulters with LBP of less than 3 months duration and more than 3 months duration. Data from two large prospective cohort studies of consecutive patients consulting with LBP in general practices were merged, providing complete data for 258 cases with acute/subacute LBP and 668 cases with chronic LBP at 12 months follow-up. There were significant differences between the two LBP groups in baseline characteristics and clinical course of disability, assessed by Roland Morris Disability Questionnaire, during the year of follow-up. Adjusted associations between potential prognostic indicators and disability at 12months were carried out in the two LBP subgroups. The final multivariable regression models showed that being non-employed, having widespread pain, a high level of Chronic Pain Grade, and catastrophising were the strongest prognostic indicators for disability at 12 months in both LBP groups. Fear of pain was significantly associated with disability in chronic LBP. Importantly, beyond baseline disability, the effect size of the other prognostic indicators for poor outcome was rather low. These findings must continue to challenge researchers to identify useful early predictors of outcome in persons with disabling back pain, as screening and targeted treatment approaches are dependent upon prognostic indicators with clinical significance. PMID:20932646

  18. Clinical Profile and Prognostic Indicators in Adults Hospitalized with Severe Malaria Caused by Different Plasmodium Species

    PubMed Central

    Gupta, Bal Kishan; Gupta, Anjli; Nehra, Hardev Ram; Balotia, Heera Ram; Meena, Shyam Lal; Kumar, Surendra

    2015-01-01

    INTRODUCTION Severe malaria remains a major cause of death and morbidity among adults in the Asiatic tropics. This study was planned to evaluate clinical profile and prognostic indicators of severe malaria in adults so as to improve insight into this highly prevalent disease. MATERIALS AND METHODS This prospective observational study was conducted on 60 confirmed cases of malaria. Cases were divided into two groups: (a) study group: suffering from severe malaria and (b) control group: no severe manifestations. All cases were thoroughly studied for clinical features, laboratory evaluation, and outcome. Prognostic evaluation was also done by different score systems. RESULTS In all, 40 cases suffer from severe malaria (study group), while 20 cases belong to the control group. The majority of our cases were males of age 21–40 years. The most common species of malaria in the study group was vivax (52.5%), followed by falciparum (25%) and mixed malaria species (22.5%). The clinical predictors for severe malaria were rural habitat, longer duration of fever, marked chills, tiredness, giddiness, nausea, vomiting, decreased urine output, jaundice, and altered sensorium. Extreme weakness (80%), jaundice (55%), renal failure (50%), and severe anemia (27.5%) were the most common presenting features in severe malaria. Two patients died of severe mixed malaria. The mortality rate was significantly associated with lower hemoglobin level (P = 0.002); higher total leukocyte count (P = 0.006), blood urea (P < 0.001), serum creatinine (P < 0.001), SGOT (P = 0.001), SGPT (P < 0.007), serum bilirubin (P = 0.003), and parasite density (P = 0.033); lower platelet count (P = 0.043); and those who had more APACHE II score (P = 0.003), SOFA score (P = 0.04), and Multiple Organ Dysfunction Score (P < 0.001) and lower Glasgow Coma Scale (P < 0.001). CONCLUSIONS Manifestations of severe malaria is becoming increasingly more prevalent specifically in vivax and mixed malaria cases. Our study

  19. Chromosomal markers as prognostic indicators in transitional-cell carcinomas of the bladder.

    PubMed

    Dobrowolski, Z; Papla, B

    1993-08-01

    Clinical-cytogenetic correlations were assessed in 79 patients with transitional cell carcinomas of the bladder to whom cytogenetic analysis of the primary tumor had been successful. High-grade (G2+G3) and high-stage (T2-T4) tumors had in general a higher ploidy level and contained more marker chromosomes, including multiple markers, compared to low-grade (G0+G1) and low stage (Ta+T1) tumors. The early recurrence rate (within 7 months) was significantly higher (p<0.05) in patients whose tumors contained marker chromosomes compared to cases without markers. Also, a significantly higher proportion of patients with marker chromosomes died due to their disease during the study period (follow-up time 30 months) compared to those without markers (84% versus 16%, p<0.005). The results confirm and extend previous studies showing that cytogenetic findings may be an important prognostic indicator in bladder cancer patients. PMID:21573351

  20. 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. PMID:24366846

  1. 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

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

    PubMed

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

    2016-10-15

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

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

    PubMed

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

    2016-03-01

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

  4. 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

  5. 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

  6. White blood cell and platelet indices as prognostic markers in patients with invasive ductal breast carcinoma

    PubMed Central

    Mantas, Dimitrios; Kostakis, Ioannis D.; Machairas, Nikolaos; Markopoulos, Christos

    2016-01-01

    A growing body of evidence suggests that oncogenesis is associated with systemic inflammation. The present study investigated white blood cell and platelet indices, whose values change during the inflammatory response, in women with invasive ductal breast carcinoma. Preoperatively obtained white blood cell and platelet counts from 53 patients with early breast cancer, who developed systemic metastases over a mean follow-up period of 65 months, were analyzed and compared with those of a matching control group formed of 37 patients with the same characteristics, who remained recurrence-free during the same time period. Patients who developed distant metastasis had a significantly higher mean platelet volume and lower neutrophil count than patients who did not present with distant metastasis. Furthermore, time to distant metastasis development was longer in patients with a lower mean platelet volume, whilst patients with a lower neutrophil count had a shorter systemic disease-free time interval. However, receiver operating characteristic curve analysis demonstrated that these parameters provided moderate accuracy in predicting which patients may develop distant metastasis. No differences were detected between patient groups regarding additional parameters. Patients who developed systemic disease during a mean follow-up period of 65 months were observed to have an increased mean platelet volume and decreased neutrophil count preoperatively. These results indicate that such parameters may be of prognostic value in patients with breast cancer. Studies with a larger number of patients are required to further investigate this hypothesis. PMID:27446480

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

    PubMed Central

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

    2010-01-01

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

  8. Outcome and prognostic indicators in 20 cats with surgically treated primary lung tumors.

    PubMed

    Maritato, Karl C; Schertel, Eric R; Kennedy, Shawn C; Dudley, Robert; Lamm, Catherine; Barnhart, Matthew; Kass, Phillip

    2014-12-01

    The purpose of this retrospective study of 20 client-owned cats was to describe the clinical signs, surgical interventions, histological features, stage and treatments of primary lung tumors removed by surgical excision, and to determine which factors significantly influence survival. Any cat that underwent surgical resection of a primary lung tumor between 2000 and 2007 was included in the study. Patient records were reviewed and signalment, clinical signs, preoperative diagnostics, surgical findings and histopathological results recorded. Histological reports were reviewed and scored using World Health Organization criteria. The Kaplan-Meier test was used to evaluate each potential prognostic factor with survival. Twenty cats met the inclusion criteria. The presence of clinical signs (such as dyspnea) at the time of diagnosis (P = 0.032), pleural effusion (P = 0.046), stage M1 (P = 0.015), and moderately and poorly differentiated tumors on histopathology (P = 0.011) were factors that were significantly correlated with reduced survival times. The median survival time of the 20 cats was 11 days. Cats presenting with no clinical signs had a median survival time of 578 days post-surgery vs 4 days post-surgery when presented with clinical signs. Cats staged T1N0M0 lived longer than cats at other stages (P = 0.044). Of the cats that survived to the time of suture removal, median survival time was 64 days. The results indicate that the presence of clinical signs, pleural effusion, moderately and poorly differentiated tumors on histopathology, evidence of metastasis and any stage beyond T1N0M0 are negative prognostic indicators for cats with primary lung tumors. The findings demonstrate that cats that presented with clinical signs, pleural effusion, any stage other than T1N0M0, or moderately and poorly differentiated tumors on histopathology had a poor prognosis. Therefore, extensive preoperative diagnostics, including computed tomography scans, should be performed

  9. 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

  10. Machine health prognostics using the Bayesian-inference-based probabilistic indication and high-order particle filtering framework

    NASA Astrophysics Data System (ADS)

    Yu, Jianbo

    2015-12-01

    Prognostics is much efficient to achieve zero-downtime performance, maximum productivity and proactive maintenance of machines. Prognostics intends to assess and predict the time evolution of machine health degradation so that machine failures can be predicted and prevented. A novel prognostics system is developed based on the data-model-fusion scheme using the Bayesian inference-based self-organizing map (SOM) and an integration of logistic regression (LR) and high-order particle filtering (HOPF). In this prognostics system, a baseline SOM is constructed to model the data distribution space of healthy machine under an assumption that predictable fault patterns are not available. Bayesian inference-based probability (BIP) derived from the baseline SOM is developed as a quantification indication of machine health degradation. BIP is capable of offering failure probability for the monitored machine, which has intuitionist explanation related to health degradation state. Based on those historic BIPs, the constructed LR and its modeling noise constitute a high-order Markov process (HOMP) to describe machine health propagation. HOPF is used to solve the HOMP estimation to predict the evolution of the machine health in the form of a probability density function (PDF). An on-line model update scheme is developed to adapt the Markov process changes to machine health dynamics quickly. The experimental results on a bearing test-bed illustrate the potential applications of the proposed system as an effective and simple tool for machine health prognostics.

  11. 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

  12. Prognostic assessment in COPD without lung function: the B-AE-D indices.

    PubMed

    Boeck, Lucas; Soriano, Joan B; Brusse-Keizer, Marjolein; Blasi, Francesco; Kostikas, Konstantinos; Boersma, Wim; Milenkovic, Branislava; Louis, Renaud; Lacoma, Alicia; Djamin, Remco; Aerts, Joachim; Torres, Antoni; Rohde, Gernot; Welte, Tobias; Martinez-Camblor, Pablo; Rakic, Janko; Scherr, Andreas; Koller, Michael; van der Palen, Job; Marin, Jose M; Alfageme, Inmaculada; Almagro, Pere; Casanova, Ciro; Esteban, Cristobal; Soler-Cataluña, Juan J; de-Torres, Juan P; Miravitlles, Marc; Celli, Bartolome R; Tamm, Michael; Stolz, Daiana

    2016-06-01

    Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD). However, choice of parameters and score complexity restrict clinical applicability. Our aim was to provide and validate a simplified COPD risk index independent of lung function.The PROMISE study (n=530) was used to develop a novel prognostic index. Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality. External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C. It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05). Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively). External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05).The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk. PMID:27103389

  13. Evaluation of serum amyloid A and haptoglobin concentrations as prognostic indicators for horses with colic.

    PubMed

    Westerman, Trina L; Foster, Crystal M; Tornquist, Susan J; Poulsen, Keith P

    2016-04-15

    OBJECTIVE To evaluate the use of the acute-phase proteins serum amyloid A (SAA) and haptoglobin as prognostic indicators in horses with colic with regard to the need for surgical intervention, development of complications, and hospitalization cost and duration. DESIGN Prospective observational study. ANIMALS 20 clinically normal horses and 42 horses with colic. PROCEDURES Total WBC and neutrophil counts and plasma fibrinogen, SAA, and haptoglobin concentrations were compared between healthy (control) horses and horses admitted to a veterinary teaching hospital for colic. Clinicopathologic values were compared between medical and surgical colic cases to test the ability of acute-phase proteins to predict indication for surgical intervention, development of complications, and duration and cost of hospitalization. RESULTS Mean SAA concentration was significantly higher in the surgical group, compared with that for both the control and medical groups. Haptoglobin concentration did not differ significantly among groups. Horses with colic and an abnormally increased SAA concentration (> 5 μg/mL) were more likely to be managed surgically than medically (OR, 5.7; 95% confidence interval, 1.4 to 22.8). Horses with small intestinal lesions had significantly higher SAA concentrations than did control horses. Euthanasia due to a poor prognosis or the development of thrombophlebitis was more likely for horses with an SAA concentration > 5 μg/mL (OR, 7.6; 95% confidence interval, 1.1 to 52.4). A weak positive correlation (r = 0.30) was observed between cost of treatment and SAA concentration. CONCLUSIONS AND CLINICAL RELEVANCE Horses with colic that had an abnormally increased SAA concentration were more likely to require surgical intervention, develop thrombophlebitis, or be euthanized because of a poor prognosis despite treatment. PMID:27031421

  14. Prognostic assessment in COPD without lung function: the B-AE-D indices

    PubMed Central

    Boeck, Lucas; Blasi, Francesco; Kostikas, Konstantinos; Boersma, Wim; Milenkovic, Branislava; Louis, Renaud; Lacoma, Alicia; Djamin, Remco; Aerts, Joachim; Torres, Antoni; Rohde, Gernot; Welte, Tobias; Martinez-Camblor, Pablo; Rakic, Janko; Scherr, Andreas; Koller, Michael; van der Palen, Job; Marin, Jose M.; Alfageme, Inmaculada; Almagro, Pere; Casanova, Ciro; Esteban, Cristobal; Soler-Cataluña, Juan J.; de-Torres, Juan P.; Miravitlles, Marc; Celli, Bartolome R.; Tamm, Michael

    2016-01-01

    Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD). However, choice of parameters and score complexity restrict clinical applicability. Our aim was to provide and validate a simplified COPD risk index independent of lung function. The PROMISE study (n=530) was used to develop a novel prognostic index. Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality. External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988). Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C. It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer–Lemeshow test all p>0.05). Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively). External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer–Lemeshow test all p>0.05). The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk. PMID:27103389

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

    PubMed

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

    2011-11-01

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

  16. 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

  17. 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)

  18. 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

  19. Amplification of D22S283 as a favorable prognostic indicator in liver fluke related cholangiocarcinoma

    PubMed Central

    Thanasai, Jongkonnee; Limpaiboon, Temduang; Jearanaikoon, Patcharee; Bhudhisawasdi, Vajarabhongsa; Khuntikeo, Narong; Sripa, Banchob; Miwa, Masanao

    2006-01-01

    AIM: To analyze the DNA copy number of target genes NF2, TIMP3, ST13, TOB2, BIK, and TP and the reference microsatellite markers D22S283, D22S423, and D22S274 mapped on 22q12-qter in liver fluke related cholangiocarcinoma (CCA) and define its correlation with clinical parameters. METHODS: Quantitative real time PCR (qPCR) was used for determining allelic imbalances in 65 liver fluke related CCA tissues. Statistical correlations between allelic imbalances and clinicopathological parameters, i.e. age, sex, tumor stage, histological type, blood vessel invasion, nerve invasion and lymphatic invasion were evaluated by means of the χ2 test. Cox regression analysis was used for determining patient’s survival. RESULTS: Amplifications of the TP (22q13.33), TOB2 (22q13.2-13.31), D22S283 (22q12.3), TIMP3 (22q12.3) and NF2 (22q12.2) were found in 35 (53.8%), 28 (43.1%), 27 (41.5%), 24 (36.9%), and 24 (36.9%), respectively. Losses at the D22S423 (22q13.1-13.2) and BIK (22q13.31) were detected in 26 (40%) and 23 (35.4%), respectively. Significant correlations were observed between lymphatic invasion and allelic losses of BIK (P = 0.025) and D22S283 (P = 0.041). Univariate and multivariate Cox regression analysis revealed D22S283 amplification as an independent predictor of good prognosis (P = 0.006, death hazard ratio = 0.411, 95% CI = 0.217-0.779) and blood vessel invasion as an independent poor prognostic factor (P = 0.042, death hazard ratio = 1.911, 95% CI = 1.022-3.571) in CCA patients. CONCLUSION: This study provides evidence for the involvement of gene amplification and deletion on chromosome 22q in liver fluke related CCA. This is the first report of D22S283 amplification as an independent indicator of favorable prognosis in liver fluke related CCA. PMID:16865775

  20. Medical Manuscript: Serum Total Testosterone as a Prognostic Indicator in Male Patients With Terminal Cancer.

    PubMed

    Kim, Se Won; Hwang, In Cheol; Ahn, Hee Kyung; Kyung, Sun Young; Ahn, Hong Yup

    2016-06-01

    The role of total serum testosterone in the prognosis of terminal cancer is unclear. We retrospectively investigated the total serum testosterone level in 69 male patients with terminal cancer in a palliative care unit. The association between the serum testosterone level and survival was assessed using Cox proportional hazard model. The median value of serum total testosterone was 44.5 ng/dL, far lower than previously reported in patients with advanced cancer. Multivariate analysis revealed thrombocytopenia (adjusted hazard ratio [aHR], 2.68), hypoalbuminemia (aHR, 2.02), azotemia (aHR, 2.67), and lower serum testosterone level (aHR, 2.03) were significantly negatively prognostic of survival. Lower serum testosterone level was an independent unfavorable prognostic factor for life expectancy in male patients with terminal cancer. PMID:25712105

  1. Using AHRQ patient safety indicators to detect postdischarge adverse events in the Veterans Health Administration.

    PubMed

    Mull, Hillary J; Borzecki, Ann M; Chen, Qi; Shin, Marlena H; Rosen, Amy K

    2014-01-01

    Patient safety indicators (PSIs) use inpatient administrative data to flag cases with potentially preventable adverse events (AEs) attributable to hospital care. This study explored how many AEs the PSIs identified in the 30 days post discharge. PSI software was run on Veterans Health Administration 2003-2007 administrative data for 10 recently validated PSIs. Among PSI-eligible index hospitalizations not flagged with an AE, this study evaluated how many AEs occurred within 1 to 14 and 15 to 30 days post discharge using inpatient and outpatient administrative data. Considering all PSI-eligible index hospitalizations, 11 141 postdischarge AEs were identified, compared with 40 578 inpatient-flagged AEs. More than 60% of postdischarge AEs were detected within 14 days of discharge. The majority of postdischarge AEs were decubitus ulcers and postoperative pulmonary embolisms or deep vein thromboses. Extending PSI algorithms to the postdischarge period may provide a more complete picture of hospital quality. Future work should use chart review to validate postdischarge PSI events. PMID:23939485

  2. Biomarkers in Natural Fish Populations Indicate Adverse Biological Effects of Offshore Oil Production

    PubMed Central

    Balk, Lennart; Hylland, Ketil; Hansson, Tomas; Berntssen, Marc H. G.; Beyer, Jonny; Jonsson, Grete; Melbye, Alf; Grung, Merete; Torstensen, Bente E.; Børseth, Jan Fredrik; Skarphedinsdottir, Halldora; Klungsøyr, Jarle

    2011-01-01

    Background Despite the growing awareness of the necessity of a sustainable development, the global economy continues to depend largely on the consumption of non-renewable energy resources. One such energy resource is fossil oil extracted from the seabed at offshore oil platforms. This type of oil production causes continuous environmental pollution from drilling waste, discharge of large amounts of produced water, and accidental spills. Methods and principal findings Samples from natural populations of haddock (Melanogrammus aeglefinus) and Atlantic cod (Gadus morhua) in two North Sea areas with extensive oil production were investigated. Exposure to and uptake of polycyclic aromatic hydrocarbons (PAHs) were demonstrated, and biomarker analyses revealed adverse biological effects, including induction of biotransformation enzymes, oxidative stress, altered fatty acid composition, and genotoxicity. Genotoxicity was reflected by a hepatic DNA adduct pattern typical for exposure to a mixture of PAHs. Control material was collected from a North Sea area without oil production and from remote Icelandic waters. The difference between the two control areas indicates significant background pollution in the North Sea. Conclusion It is most remarkable to obtain biomarker responses in natural fish populations in the open sea that are similar to the biomarker responses in fish from highly polluted areas close to a point source. Risk assessment of various threats to the marine fish populations in the North Sea, such as overfishing, global warming, and eutrophication, should also take into account the ecologically relevant impact of offshore oil production. PMID:21625421

  3. Ruptured abdominal aortic aneurysms: review of 33 cases treated surgically and discussion of prognostic indicators.

    PubMed

    Sink, J D; Myers, R T; James, P M

    1976-05-01

    Over an eight-year peroid at NCBH, 33 patients were operated for ruptured abdominal aortic aneurysm. Factors associated with an increased mortality included preoperative blood urea nitrogen levels of more than 20 mg per cent, severe preoperative hypotension, duration of symptoms of less than 24 hours, free peritoneal rupture and blood transfusions of greater than 19 units. Preoperative hypotension was the most selective preoperative prognostic parameter. From a review of this and other reported series, it was concluded that reduced mortality from ruptured abdominal aortic aneurysm can best be achieved by prompt diagnosis followed by surgical treatment before cardiovascular collapse can occur. PMID:1267283

  4. Baseline renal function as a prognostic indicator in patients with newly diagnosed diffuse large B-cell lymphoma

    PubMed Central

    Hong, Junshik; Lee, Sojung; Chun, Gayoung; Jung, Ji Yong; Park, Jinny; Ahn, Jeong Yeal; Cho, Eun Kyung; Shin, Dong Bok

    2016-01-01

    Background The association between baseline renal impairment (RI) and the prognosis of diffuse large B-cell lymphoma (DLBCL) was previously not defined. The aim of this study was to evaluate the prognostic value of RI in patients with DLBCL treated with three-weekly rituximab plus cyclophosphamide, Adriamycin, vincristine, and prednisolone immunochemotherapy (R-CHOP21). Methods Patients with newly diagnosed de novo DLBCLs treated with ≥1 cycle of R-CHOP21 were analyzed retrospectively. Pretreatment blood samples were collected and the glomerular filtration rate (GFR) was calculated. RI was defined by a GFR of <60 mL/min/1.73 m2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Results Of the 185 patients enrolled in the present study, 19 patients (10.3%) had RI. The reasons for baseline RI were pre-existing CKD (N=5), acute kidney injury due to either obstruction (N=2) or electrolyte imbalance (N=2) related to DLBCL, and undefined causes (N=10). Patients with baseline RI showed inferior overall survival (OS) compared to those without RI (P<0.001). In multivariate analysis, RI was identified as an International Prognostic Index (IPI)-independent prognostic indicator. A baseline hemoglobin level of <10 g/dL and the presence of RI effectively discriminated a portion of the patients with far inferior event-free survival and OS among the patients having high or high-intermediate risk cancers according to either the standard- or the National Comprehensive Cancer Network-IPI. Conclusion Pretreatment RI was an independent prognostic marker for inferior OS in patients with DLBCL treated with R-CHOP21 immunochemotherapy. PMID:27382556

  5. A six-microRNA set as prognostic indicators for bile duct cancer

    PubMed Central

    Wang, Ming; Wen, Tian-Fu; He, Lin-Hai; Li, Chuan; Zhu, Wen-Jiang; Trishul, Narasimha Murthy

    2015-01-01

    MicroRNAs (miRNAs) play important roles in cancer progression by altering transcriptional control. The purpose of this study is to identify and explore specific miRNAs as prognostic and predictive biomarkers for bile duct cancer (BDC) by analyzing Next-generation data. miRNA expression profiles and corresponding clinical information of BDC samples were extracted from The Cancer Genome Atlas (TCGA). The differentially expressed miRNAs were determined by SAMR package in R software. Target genes of those miRNAs were predicted by Targetscan. Functional enrichment analysis and hypergeometric test analysis of target genes were performed. Then, diagnosis accuracy of miRNAs was judged by ROC Curves analysis. Total 120 differentially expressed miRNAs were obtained, of which six important miRNAs were selected and predicted as prognosis and predicting biomarkers in BDC. Besides, functional analysis showed that both enriched pathways were significantly related with ion binding, which might involve in the carcinogenesis of BDC. Moreover, top 3 important pathways sharing the most influence were noted. Our results demonstrated that hsa-miR-483-5p, hsa-miR-675, hsa-miR-139-3p, hsa-miR-598, hsa-miR-625 and hsa-miR-187 could serve as prognostic and predictive markers for survival of BDC patients and could potentially be provided as targets for future therapy. PMID:26770318

  6. A six-microRNA set as prognostic indicators for bile duct cancer.

    PubMed

    Wang, Ming; Wen, Tian-Fu; He, Lin-Hai; Li, Chuan; Zhu, Wen-Jiang; Trishul, Narasimha Murthy

    2015-01-01

    MicroRNAs (miRNAs) play important roles in cancer progression by altering transcriptional control. The purpose of this study is to identify and explore specific miRNAs as prognostic and predictive biomarkers for bile duct cancer (BDC) by analyzing Next-generation data. miRNA expression profiles and corresponding clinical information of BDC samples were extracted from The Cancer Genome Atlas (TCGA). The differentially expressed miRNAs were determined by SAMR package in R software. Target genes of those miRNAs were predicted by Targetscan. Functional enrichment analysis and hypergeometric test analysis of target genes were performed. Then, diagnosis accuracy of miRNAs was judged by ROC Curves analysis. Total 120 differentially expressed miRNAs were obtained, of which six important miRNAs were selected and predicted as prognosis and predicting biomarkers in BDC. Besides, functional analysis showed that both enriched pathways were significantly related with ion binding, which might involve in the carcinogenesis of BDC. Moreover, top 3 important pathways sharing the most influence were noted. Our results demonstrated that hsa-miR-483-5p, hsa-miR-675, hsa-miR-139-3p, hsa-miR-598, hsa-miR-625 and hsa-miR-187 could serve as prognostic and predictive markers for survival of BDC patients and could potentially be provided as targets for future therapy. PMID:26770318

  7. 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.

  8. Can we use methylation markers as diagnostic and prognostic indicators for bladder cancer?

    PubMed Central

    Kim, Yong-June

    2016-01-01

    Urothelial carcinomas of the urinary bladder have diverse biological and functional characteristics, and numerous factors are likely to be involved in recurrence, progression, and patient survival. While several molecular markers used to evaluate the development and prognosis of bladder cancer have been studied, they are of limited value; therefore, new molecular parameters useful for predicting the prognosis of bladder cancer patients (particularly patients at high risk of progression and recurrence) are required. Recent progress in the understanding of epigenetic modification and gene silencing has provided new opportunities for the detection, treatment, and prevention of cancer. Methylation is an important molecular mechanism in bladder cancer and may have utility as a prognostic and/or diagnostic marker. This review discusses the epigenetic issues involved in the detection and prediction of bladder cancer. PMID:27326410

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

    PubMed

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

    2013-01-01

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

  10. 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…

  11. A widened pulse pressure: a potential valuable prognostic indicator of mortality in patients with sepsis

    PubMed Central

    Al-khalisy, Hassan; Nikiforov, Ivan; Jhajj, Manjit; Kodali, Namratha; Cheriyath, Pramil

    2015-01-01

    Background Sepsis is one of the leading causes of death in the United States and the most common cause of death among critically ill patients in non-coronary intensive care units. Previous studies have showed pulse pressure (PP) to be a predictor of fluid responsiveness in patients with sepsis. Additionally, previous studies have correlated PP to cardiovascular risk factors and increase in mortality in end-stage renal disease patients. Objectives To determine the correlation between PP and mortality in patients with sepsis. Methods A retrospective review was conducted on 5,003 patients admitted with the diagnosis of sepsis using ICD-9 codes during the time period from January 2010 to December 2014 at two community-based hospitals in central Pennsylvania. Results Our study findings showed significant decrease in the mortality when the PP was greater than 70 mmHg of patients with sepsis (p-value: 0.0003, odds ratio: 0.67, 95% confidence limit: 0.54–0.83). Conclusion Based on our findings, we suggest that PP could be a valuable clinical tool in the early assessment of patients admitted with sepsis and could be used as a prognostic factor to assess and implement management therapy for the patients with sepsis. PMID:26653692

  12. 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

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

    PubMed Central

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

    2015-01-01

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

  14. 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

  15. HOXD13 methylation status is a prognostic indicator in breast cancer

    PubMed Central

    Zhong, Zhenbin; Shan, Ming; Wang, Ji; Liu, Tong; Xia, Bingshu; Niu, Ming; Ren, Yanlv; Pang, Da

    2015-01-01

    Homeobox protein Hox-D13 is encoded by HOXD13 gene which is frequently methylated in cancer and has been recognized as a tumor suppressor in pancreatic cancer. In this study, we examined HOXD13 mRNA expression in 40 pairs of breast cancers and corresponding normal breast tissues. Bisulfite sequencing of HOXD13 promoter was performed in 6 pairs of breast tumors and corresponding normal breast tissues to examine the potential HOXD13 CpG methylated sites. HOXD13 DNA methylation frequency analysis was performed using MethyLight in 196 pairs of breast cancers and corresponding normal breast samples. DNA methylation status and clinico-pathological features were investigated. Kaplan-Meier survival analysis and Cox proportional hazards models were utilized to assess the effect of methylation status on overall survival. We found that 60% (24/40) of breast cancers showed low HOXD13 mRNA expression when compared with corresponding normal breast tissue. The predicted CpG island was located in the -1325 bp to +675 bp region. Next, the -332 bp site in HOXD13 gene promoter was further examined and in 57.7% (113/196) samples methylation was detected at this site. HOXD13 methylation was correlated with larger tumor size (P = 0.004), but not with other clinico-pathological parameters. In addition, patients with methylated -HOXD13 promoter had worse overall survival (OS) (P = 0.005). Based on our results we conclude that HOXD13 methylation is a common event in primary breast cancer and is associated with poor survival of breast cancer patients. HOXD13 methylation could therefore potentially be used as a prognostic factor for breast cancer. PMID:26617782

  16. Prognostic indicators in primary biliary cirrhosis: significance of revised IAHG (International Autoimmune Hepatitis Group) score

    PubMed Central

    Jung, Ho Eun; Jeong, Soung Won; Kim, Jin Nyoung; Jang, Hee Yoon; Cho, Yun Ju; Woo, Sung Ae; Lee, Sae Hwan; Kim, Sang Gyune; Cha, Sang-Woo; Kim, Young Seok; Cho, Young Deok; Kim, Hong Soo; Kim, Boo Sung

    2012-01-01

    Background/Aims Primary biliary cirrhosis (PBC) is a slowly progressing autoimmune disease of the liver that is characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Serum total bilirubin is one of the various prognostic factors that have been proposed. A recent study found that PBC with accompanying autoimmune hepatitis (AIH) carries a negative prognosis. This study examined the clinical characteristics of PBC and analyzed the factors that affect its prognosis. Methods Patients diagnosed with PBC between January 1998 and December 2010 based on clinical and histopathological findings were compiled and analyzed retrospectively. Results Among 27 patients, 24 (1 male and 23 females, ages 50.0±9.3 years) were followed up. The follow-up period was 8.6±0.9 years. Of the 24 patients, 9 patients progressed to liver cirrhosis (LC). Comparison between patients who did and did not progress to LC revealed statistically significant differences in the patients' serum total bilirubin (2.7±1.8 vs. 0.8±0.4, P=0.012), the Mayo risk score (5.1±0.7 vs. 3.9±0.6, P=0.001), the revised IAHG (International Autoimmune Hepatitis Group) score (9.2±2.3 vs. 5.4±3.0, P=0.004) and frequency of AIH overlap (5/9 [55.6%] vs. 0/15 [0%], P=0.001) at the time of diagnosis. Conclusions We propose that serum total bilirubin, the Mayo risk score, and the revised IAHG score at the time of diagnosis are helpful for predicting PBC prognosis. In particular, since all of the patients with accompanying AIH progressed to LC, the presence of overlap syndrome at the time of diagnosis is helpful for predicting PBC prognosis and providing an adequate treatment. PMID:23323253

  17. Lymphatic vessel endothelial hyaluronan receptor-1 is a novel prognostic indicator for human hepatocellular carcinoma.

    PubMed

    Kitagawa, Koichi; Nakajima, Go; Kuramochi, Hidekazu; Ariizumi, Shun-Ichi; Yamamoto, Masakazu

    2013-11-01

    Angiogenesis is an important mechanism of tumor development, growth and metastasis in hepatocellular carcinoma (HCC). The poor prognosis of HCC patients has been associated with a failure to detect recurrences following surgery. In the present study, we investigated the association between the patient characteristics and the expression of angiogenic genes to identify early biomarkers of HCC. A comprehensive angiogenic gene expression profile was obtained by paired TaqMan gene array analysis of primary HCC nodules and adjacent non-HCC liver tissue from 12 patients. A total of 14 genes were found to be differentially expressed in HCC liver nodules (>2-fold change); the genes encoding collagen type XVα1, IVα1 and IVα2 were upregulated and the genes associated with vessel growth, neuropilin 2 (NRP2) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) were downregulated. The histopathological analysis revealed that the evolution of HCC nodules from well to poorly differentiated was associated with a 5-fold decrease in LYVE-1 expression, reaching its lowest level early during the transition. The significance of this gene as a biomarker of postoperative survival was demonstrated by a 2-fold decrease in overall survival (OS) rates in the low expression group compared to the high expression group. The multivariate and univariate Cox regression analyses identified LYVE-1 expression as a significant independent prognostic parameter of OS [hazard ratio (HR)=3.067; 95% confidence interval (CI): 1.507-6.273; P=0.0021]. Thus, the results of this study suggested that LYVE-1 expression may constitute a novel early biomarker of postoperative survival in HCC patients. PMID:24649290

  18. The Modification Effect of Influenza Vaccine on Prognostic Indicators for Cardiovascular Events after Acute Coronary Syndrome: Observations from an Influenza Vaccination Trial.

    PubMed

    Sribhutorn, Apirak; Phrommintikul, Arintaya; Wongcharoen, Wanwarang; Chaikledkaew, Usa; Eakanunkul, Suntara; Sukonthasarn, Apichard

    2016-01-01

    Introduction. The prognosis of acute coronary syndrome (ACS) patients has been improved with several treatments such as antithrombotics, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI) as well as coronary revascularization. Influenza vaccination has been shown to reduce adverse outcomes in ACS, but no information exists regarding the interaction of other treatments. Methods. This study included 439 ACS patients from Phrommintikul et al. A single dose of inactivated influenza vaccine was given by intramuscular injection in the vaccination group. The cardiovascular outcomes were described as major cardiovascular events (MACEs) which included mortality, hospitalization due to ACS, and hospitalization due to heart failure (HF). The stratified and multivariable Cox's regression analysis was performed. Results. The stratified Cox's analysis by influenza vaccination for each cardiovascular outcome and discrimination of hazard ratios showed that beta-blockers had an interaction with influenza vaccination. Moreover, the multivariable hazard ratios disclosed that influenza vaccine is associated with a significant reduction of hospitalization due to HF in patients who received beta-blockers (HR = 0.05, 95% CI = 0.004-0.71, P = 0.027), after being adjusted for prognostic indicators (sex, dyslipidemia, serum creatinine, and left ventricular ejection fraction). Conclusions. The influenza vaccine was shown to significantly modify the effect of beta-blockers in ACS patients and to reduce the hospitalization due to HF. However, further study of a larger population and benefits to HF patients should be investigated. PMID:27200206

  19. The Modification Effect of Influenza Vaccine on Prognostic Indicators for Cardiovascular Events after Acute Coronary Syndrome: Observations from an Influenza Vaccination Trial

    PubMed Central

    Sribhutorn, Apirak; Phrommintikul, Arintaya; Wongcharoen, Wanwarang; Chaikledkaew, Usa; Eakanunkul, Suntara; Sukonthasarn, Apichard

    2016-01-01

    Introduction. The prognosis of acute coronary syndrome (ACS) patients has been improved with several treatments such as antithrombotics, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI) as well as coronary revascularization. Influenza vaccination has been shown to reduce adverse outcomes in ACS, but no information exists regarding the interaction of other treatments. Methods. This study included 439 ACS patients from Phrommintikul et al. A single dose of inactivated influenza vaccine was given by intramuscular injection in the vaccination group. The cardiovascular outcomes were described as major cardiovascular events (MACEs) which included mortality, hospitalization due to ACS, and hospitalization due to heart failure (HF). The stratified and multivariable Cox's regression analysis was performed. Results. The stratified Cox's analysis by influenza vaccination for each cardiovascular outcome and discrimination of hazard ratios showed that beta-blockers had an interaction with influenza vaccination. Moreover, the multivariable hazard ratios disclosed that influenza vaccine is associated with a significant reduction of hospitalization due to HF in patients who received beta-blockers (HR = 0.05, 95% CI = 0.004–0.71, P = 0.027), after being adjusted for prognostic indicators (sex, dyslipidemia, serum creatinine, and left ventricular ejection fraction). Conclusions. The influenza vaccine was shown to significantly modify the effect of beta-blockers in ACS patients and to reduce the hospitalization due to HF. However, further study of a larger population and benefits to HF patients should be investigated. PMID:27200206

  20. 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.

  1. CEBPD amplification and overexpression in urothelial carcinoma: a driver of tumor metastasis indicating adverse prognosis

    PubMed Central

    Wang, Yu-Hui; Wu, Wen-Jeng; Wang, Wei-Jan; Huang, Hsuan-Ying; Li, Wei-Ming; Yeh, Bi-Wen; Wu, Ting-Feng; Shiue, Yow-Ling; Sheu, Jim Jinn-Chyuan; Wang, Ju-Ming; Li, Chien-Feng

    2015-01-01

    The molecular aberrations responsible for the progression of urothelial carcinoma (UC) remain largely obscure. To search candidate driver oncogenes in UC, we performed array-based genomic hybridization (aCGH) on 40 UBUC samples. Amplification of 8q11.21 was preferentially identified in patients who developed disease-specific death (53.8%) and distal metastasis (50.0%) but was barely detected in non-eventful cases (3.7% and 0%, respectively). In order to quantify the expression of candidate genes harbored in 8q11.21, laser-capture microdissection coupled with RT-PCR was performed on 32 of the 40 cases submitted to aCGH. With this, we identified CEBPD mRNA expression as most significantly associated with gains of 8q11.21, suggesting amplification-driven expression. By performing CEBPD-specific FISH and immunohistochemistry on 295 UBUCs, we confirmed CEBPD amplification (21.3%) and overexpression (29.8%) were strongly related to each other (p<0.001). Moreover, both were associated with adverse clinicopathologic features and worse outcomes. Furthermore, the clinical significance of CEBPD expression was also confirmed in an independent cohort comprised of 340 UCs from the upper urinary tract. Interestingly, CEBPD knockdown suppressed cell proliferation, migration and, most significantly, cell invasion ability in UC cells. The latter phenotype is attributed to downregulation of MMP2 as identified by RT2 Profiler PCR array. Moreover, expression of CEBPD significantly enhanced MMP2 expression and transcriptional activation by directly binding to its promoter region, as confirmed by promoter reporter assay and chromatin immunoprecipitation assay. Conclusively, CEBPD amplification is a mechanism driving increased mRNA and protein expression that confers aggressiveness in UC through MMP2-mediated cell invasiveness. PMID:26307680

  2. 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. PMID:18184870

  3. ERAP140/Nbla10993 is a novel favorable prognostic indicator for neuroblastoma induced in response to retinoic acid.

    PubMed

    Arai, Hiroshi; Ozaki, Toshinori; Niizuma, Hidetaka; Nakamura, Yohko; Ohira, Miki; Takano, Kunio; Matsumoto, Masahiko; Nakagawara, Akira

    2008-06-01

    In the present study, we identified a gene termed Nbla10993 whose expression levels are higher in favorable neuroblastomas versus unfavorable ones. Structural analysis showed that Nbla10993 is a novel splicing variant of the ER-associated protein of 140 kDa (ERAP140), which lacks the central acidic as well as the COOH-terminal Cys/His-rich domain. Similarly, ERAP140 was preferentially expressed in favorable neuroblastomas relative to unfavorable ones. During the all-trans-retinoic acid (ATRA)-mediated neuronal differentiation in neuroblastoma-derived RTBM1 cells, the expression levels of ERAP140/Nbla10993 increased at the mRNA level. Consistent with these observations, the luciferase reporter analysis demonstrated that the ERAP140/Nbla10993 promoter responds to ATRA. In addition, the immunoprecipitation/immunoblotting experiments showed that ERAP140 forms a stable complex with RARalpha but not with RXRalpha in cells, suggesting that ERAP140 is involved in RAR-mediated transcriptional regulation. Furthermore, the quantitative real-time PCR analysis using 109 primary neuroblastoma samples demonstrated that the expression levels of ERAP140/Nbla10993 significantly correlate with a better clinical outcome of neuroblastomas. Taken together, our present findings indicate that ERAP140/Nbla10993 plays an important role in the regulation of ATRA-mediated neuronal differentiation, and is a novel member of prognostic indicators for neuroblastoma. PMID:18497940

  4. 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. PMID:26310868

  5. Evaluation of ethyl acetate on three dimensions: investigation of behavioral, physiological and psychological indicators of adverse chemosensory effects.

    PubMed

    Kleinbeck, Stefan; Juran, Stephanie A; Kiesswetter, Ernst; Schäper, Michael; Blaszkewicz, Meinolf; Brüning, Thomas; van Thriel, Christoph

    2008-11-10

    A variety of national occupational exposure limits for ethyl acetate exist based on different studies, mostly relying on subjective evaluations of ethyl acetate as an irritant. Only one study also used physiological methods with inconsistent results in subjective and objective data. The present study was designed to investigate ethyl acetate on three different dimensions: behavioral, physiological and psychological indicators of adverse chemosensory effects were investigated during acute exposures to different concentrations of ethyl acetate. Twenty-four subjects were challenged with ethyl acetate in three exposure patterns (2 ppm, 400 ppm, 400 ppm including peaks of 800 ppm). While the odor intensity is rated "strong", trigeminal perceptions were rated less than "moderate". The absence of substantial trigeminal ratings was supported by physiological data. There was neither an effect of concentration on blinking frequency nor on nasal resistance which both are indicators of irritation. Furthermore, there are no effects of ethyl acetate concentration on behavioral measures indicating no olfactory or trigeminally mediated disturbance of cognitive processing. In conclusion, the results of this multilevel approach revealed no adverse chemosensory effects at ethyl acetate concentrations as recommended by the German MAK-value. PMID:18812215

  6. Overexpression of Transient Receptor Protein Cation Channel Subfamily A Member 1, Confers an Independent Prognostic Indicator in Nasopharyngeal Carcinoma

    PubMed Central

    Wu, You-Ting; Yen, Shao-Lun; Li, Chien-Feng; Chan, Ti-Chun; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Shiue, Yow-Ling

    2016-01-01

    Background: Detection of oncogenes provides chances to understand tumor development and progression. Transient receptor protein cation channel subfamily A, member 1 (TRPA1) transcript was significantly upregulated in nasopharyngeal carcinoma (NPC) with a stepwise upregulation from low- to high-stage NPCs from a preliminary data analysis in the Gene Expression Omnibus database. The TRPA1 gene is a member of the TRP channel family, encoding integral membrane proteins that functions as cation channels. Loss of calcium homeostasis takes place in cancer cells. Methods: Immunostaining of TRPA1 was analyzed on 124 biopsies from NPC patients retrospectively. The H-score method was used to evaluate the immunoexpression of TRPA1. The correlations between H-score of TRPA1 protein level and clinicopathological factors, as well as the significances of TRPA1 protein level for disease-specific, distal-metastasis-free and local recurrence-free survivals were assessed. Results: These patients were characterized to be no initial metastasis and medicated with the traditional procedure. The TRPA1 score was found to be associated with clinicopathological parameters and patient survivals. Along with the guideline of 7th edition of the American Joint Committee on Cancer, we found that TRPA1 upregulation (50%) was associated with advanced primary tumor (P = 0.009) and overall clinical stage (P = 0.019). In univariate log-rank testing, primary tumor, nodal status, stage and TRPA1 protein level significantly contributed to worse disease-specific survival, distal metastasis-free survival and local recurrence-free survival. In multivariate analysis, high TRPA1 protein level and tumor stage emerged as independent prognostic indicators for inferior disease-specific survival (P = 0.014; P = 0.003), distal metastasis-free survival (P = 0.004; P = 0.034) and recurrence-free survival (P = 0.017; P = 0.015). Conclusions: The upregulation of TRPA1 protein level is frequently correlated to unfavorable

  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. PMID:27542493

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

    PubMed

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

    2014-09-01

    Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) <60 g/L, fasting blood glucose (FBG) >100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p < 0.001). Our new prognostic model had a better prognostic value than did the KPI model alone (p < 0.001). Our proposed prognostic model for ENKTL, including the newly identified prognostic indicators, TP and FBG, demonstrated a balanced distribution of patients into different risk groups with better prognostic discrimination compared with the KPI model alone. PMID:24782120

  9. CK19 and Glypican 3 Expression Profiling in the Prognostic Indication for Patients with HCC after Surgical Resection

    PubMed Central

    Chang, Chun; Yu, Lu; Cao, Fang; Zhu, Guohua; Chen, Feng; Xia, Hui; Lv, Fudong; Zhang, Shijie; Sun, Lin

    2016-01-01

    This retrospective study was designed to investigate the correlation between a novel immunosubtyping method for hepatocellular carcinoma (HCC) and biological behavior of tumor cells. A series of 346 patients, who received hepatectomy at two surgical centers from January 2007 to October 2010, were enrolled in this study. The expressions of cytokeratin 19 (CK19), glypican 3 (GPC3), and CD34 were detected by immunohistochemical staining. The clinical stage was assessed using the sixth edition tumor–node–metastasis (TNM) system (UICC/AJCC, 2010).Vascular invasion comprised both microscopic and macroscopic invasion. The tumor size, lymph node involvement, and metastasis were determined by pathological as well as imaging studies. Recurrence was defined as the appearance of new lesions with radiological features typical of HCC, seen by at least two imaging methods. Survival curves for the patients were plotted using the Kaplan–Meier method, and differences between the curves were assessed using the log-rank test. Significant differences in morphology, histological grading, and TNM staging were observed between groups. Based on the immunohistochemical staining, the enrolled cases were divided into CK19+/GPC3+, CK19−/GPC3+ and CK19−/GPC3− three subtypes. CK19+/GPC3+ HCC has the highest risk of multifocality, microvascular invasion, regional lymph node involvement, and distant metastasis, followed by CK19−/GPC3+ HCC, then CK19−/GPC3−HCC. CK19+/GPC3+ HCC has the shortest recurrence time compared to other immunophenotype HCCs. CK19 and GPC3 expression profiling is an independent prognostic indicator in patients with HCC, and a larger sample size is needed to further investigate the effect of this immunosubtyping model in stratifying the outcome of HCC patients. PMID:26977595

  10. Transforming growth factor beta1 (TGF-beta1) is a preoperative prognostic indicator in advanced gastric carcinoma.

    PubMed Central

    Nakamura, M.; Katano, M.; Kuwahara, A.; Fujimoto, K.; Miyazaki, K.; Morisaki, T.; Mori, M.

    1998-01-01

    It has been generally accepted that transforming growth factor beta1 (TGF-beta1) has both negative and positive effects on tumour growth and progression. This study analysed the prognostic value of TGF-beta1 mRNA in advanced gastric carcinoma. A reverse transcriptase-polymerase chain reaction analysis (RT-PCR) was used for TGF-beta1 in endoscopic biopsy specimens from 42 advanced gastric carcinomas. Thirty specimens expressed TGF-beta1 mRNA while 12 specimens did not. The follow-up duration ranged from 4 to 37 months (mean 22.8 months). TGF-beta1-positive group demonstrated a shorter overall survival compared with the TGF-beta1 -negative group (P=0.0014). A significant correlation was also found in the 32 patients who underwent curative resection (P=0.0048). Significant correlations were found between TGF-beta1 mRNA expression and both stage (P=0.0015) and nodal involvement (P=0.0060). Multivariate analysis demonstrated that only TGF-beta1 mRNA expression (P=0.0306) was an independent prognostic factor. All of ten patients who underwent non-curative resection expressed TGF-beta1 mRNA. Expression of TGF-beta1 mRNA in gastric biopsy specimens may be an important preoperative prognostic variable for advanced gastric carcinoma. Images Figure 1 PMID:9823982

  11. 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

  12. WPSS is a strong prognostic indicator for clinical outcome of allogeneic transplant for myelodysplastic syndrome in Southeast Asian patients.

    PubMed

    Ma, Liyuan; Hao, Siguo; Diong, Colin; Goh, Yeow-Tee; Gopalakrishnan, Sathish; Ho, Aloysius; Hwang, William; Koh, Liang-Piu; Koh, Mickey; Lim, Zi-Yi; Loh, Yvonne; Poon, Michelle; Tan, Lip-Kun; Tan, Patrick; Linn, Yeh-Ching

    2015-05-01

    To better understand the predictive factors and improve clinical outcome of allogeneic transplant for patients with myelodysplastic syndrome (MDS), we retrospectively analyzed the post-transplant outcome of 60 Southeast Asian patients with MDS. Multivariate analysis showed that WHO classification-based Prognostic Scoring System (WPSS) significantly affect overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), and cumulative incidence of non-relapse mortality (CINRM). Stratified by WPSS into very low/low, intermediate, high, and very high-risk categories, 3-year OS was 100, 61, 37, and 18% (p = 0.02); PFS was 100, 55, 32, and 18% (p = 0.014); CIR was 12, 24, 38, and 59% (p = 0.024); CINRM was 0, 6, 12, and 26% (p = 0.037), respectively. WHO classification, Revised International Prognostic Scoring System (IPSS-R), IPSS-R-defined cytogenetic risk groups, donor gender, and acute and chronic graft vs host disease (GVHD) also influenced different aspects of transplant outcome. We found that WPSS is a powerful predictor of post-transplant outcome. WPSS provides an important model not only for prognostication but also for exploration of further post-transplant measures such as immunological maneuvers or novel therapy to improve the poor outcome of high-risk patients. PMID:25519475

  13. Prognostic performance of clinical indices and model scorings for acute-on-chronic liver failure: A study of 164 patients

    PubMed Central

    ZHANG, QIANQIAN; GUO, XIAOLIN; ZHAO, SHIXING; PANG, XIAOLI; WANG, YANG; ZHANG, YUJIAO; CHI, BAORONG

    2016-01-01

    The present study aimed to analyze the prognostic factors of acute-on-chronic liver failure (ACLF), with the perspective of an improved selection of optimal therapeutic schemes. A retrospective analysis was used to study 164 patients with ACLF hospitalized between 2010 and 2014 in a single center. Patients were divided into favorable and unfavorable groups, according to the treatment outcomes. General characteristics and clinical manifestations were analyzed to determine whether they would affect the prognosis of the patients with ACLF, with a particular focus on the scoring systems Child-Pugh, model for end-stage liver disease (MELD), MELD with incorporation of sodium (MELD-Na), MELD and serum sodium ratio (MESO) and integrated MELD (iMELD). Hepatitis B virus infection was the predominant cause of ACLF, accounting for 88 cases (53.7%). Age, prothrombin time, thrombin time, international normalized ratio (INR), prothrombin activity, serum sodium, albumin, total bilirubin, serum creatinine, platelets, fasting blood sugar, infections, hepatic encephalopathy, hepatorenal syndrome (HRS), and electrolyte disorder were revealed to be associated with prognosis. Age, serum sodium, INR, HRS, and infection were independent prognostic risk factors, as determined by multivariate analysis. Child-Pugh, MELD, MELD-Na, MESO and iMELD scoring systems all demonstrated adequate predictive values, with MELD-Na as the most effective scoring system. In conclusion, age, hyponatremia, INR, HRS and bacterial or fungal infections were reported to be independent prognostic risk factors for ACLF. Among the various liver function scoring systems, MELD-Na was the most accurate in predicting the prognosis of ACLF. PMID:27073448

  14. Preoperative CYFRA 21-1 level as a prognostic indicator in resected primary squamous cell lung cancer.

    PubMed Central

    Niklinski, J.; Furman, M.; Burzykowski, T.; Chyczewski, L.; Laudanski, J.; Chyczewska, E.; Rapellino, M.

    1996-01-01

    The CYFRA 21-1 assay is a test that has been developed recently for detection of a cytokeratin 19 fragment in serum. A diagnostic role for CYFRA 21-1 has already been proposed. The question of whether this marker is prognostically significant is important in clarifying the role of CYFRA 21-1 in clinical practice. The aim of this study was to evaluate the prognostic significance of elevated preoperative CYFRA 21-1 levels in patients with resected primary squamous-cell lung cancer (SqCC). Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 91 patients with operable SqCC. Survival and disease-free survival curves related to initial levels of this marker were estimated using the Kaplan-Meier method. In the univariate analysis the log-rank test and the log-rank test for trend were used. In the multivariate analysis the stratified log-rank test and the proportional hazard model were used. Elevated preoperative CYFRA 21-1 levels were identified in 55% of patients with SqCC. The number of patients with elevated levels of this marker increased with TNM stage (P = 0.0001). In univariate analysis elevated levels of CYFRA 21-1 were significantly associated with poor overall survival (P < 0.00005) and with disease-free survival (P < 0.00005). In multivariate analysis elevated levels of this marker were also found to be associated with poor overall and disease-free survival (P = 0.01 and P = 0.003 respectively). In conclusion, CYFRA 21-1 may be an independent prognostic parameter of survival and tumour relapse in SqCC and may be useful in identifying resected SqCC patients at high risk of treatment failure. PMID:8826865

  15. Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008

    PubMed Central

    2009-01-01

    Background Health-related quality of life and survival are two important outcome measures in cancer research and practice. The aim of this paper is to examine the relationship between quality of life data and survival time in cancer patients. Methods A review was undertaken of all the full publications in the English language biomedical journals between 1982 and 2008. The search was limited to cancer, and included the combination of keywords 'quality of life', 'patient reported-outcomes' 'prognostic', 'predictor', 'predictive' and 'survival' that appeared in the titles of the publications. In addition, each study was examined to ensure that it used multivariate analysis. Purely psychological studies were excluded. A manual search was also performed to include additional papers of potential interest. Results A total of 451 citations were identified in this rapid and systematic review of the literature. Of these, 104 citations on the relationship between quality of life and survival were found to be relevant and were further examined. The findings are summarized under different headings: heterogeneous samples of cancer patients, lung cancer, breast cancer, gastro-oesophageal cancers, colorectal cancer, head and neck cancer, melanoma and other cancers. With few exceptions, the findings showed that quality of life data or some aspects of quality of life measures were significant independent predictors of survival duration. Global quality of life, functioning domains and symptom scores - such as appetite loss, fatigue and pain - were the most important indicators, individually or in combination, for predicting survival times in cancer patients after adjusting for one or more demographic and known clinical prognostic factors. Conclusion This review provides evidence for a positive relationship between quality of life data or some quality of life measures and the survival duration of cancer patients. Pre-treatment (baseline) quality of life data appeared to provide the

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

    PubMed Central

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

    2016-01-01

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

  17. Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer cell proliferation in vitro and in vivo.

    PubMed

    Wang, Lan; Wu, Jueheng; Yuan, Jie; Zhu, Xun; Wu, Hongmei; Li, Mengfeng

    2016-03-01

    Midline2 (MID2) is an ubiquitin-conjugating E2 enzyme linked to tumor progression and a novel interacting partner of breast cancer 1, early-onset (BRCA1). However, the role of MID2 in breast cancer remains unknown. This study investigated the expression, prognostic value, and role of MID2 in breast cancer. The expression of MID2 mRNA and protein was significantly upregulated in breast cancer tissue and established cell lines compared with that in normal breast epithelial cells and paired adjacent non-tumor tissue (P < 0.001). Immunohistochemical analysis demonstrated that MID2 was overexpressed in 272 of 284 (95.8%) paraffinembedded, archived breast cancer tissue. Moreover, MID2 expression increased with advanced clinical stage (P < 0.001). High MID2 expression was significantly associated with advanced clinical stages and T, N, and M staging (all P < 0.05). Univariate and multivariate analyses indicated that high MID2 expression was an independent prognostic factor for poor overall survival in the entire cohort (93.73 vs. 172.1 months; P < 0.001, logrank test) and in subgroups with stages Tis + I + II and III + IV. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide colony formation, and anchorage-independent growth ability assays were conducted. Results showed that siRNA silencing of MID2 expression significantly reduced MCF-7 and MDA-MB-231 cell proliferation in vitro and blocked the growth of MDA-MB-231 cell xenograft tumors in vivo (P < 0.05). This study indicated that MID2 may be a novel prognostic marker and interventional target in breast cancer. PMID:26791755

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

    PubMed

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

    2008-03-25

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

  19. 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. PMID:25428156

  20. Canine Distemper Virus Antigen Detection in External Epithelia of Recently Vaccinated, Sick Dogs by Fluorescence Microscopy Is a Valuable Prognostic Indicator

    PubMed Central

    Neel, Tina

    2014-01-01

    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. PMID:25428156

  1. Primary tumor SUVmax on preoperative FDG-PET/CT is a prognostic indicator in stage IA2-IIB cervical cancer patients treated with radical hysterectomy

    PubMed Central

    Yagi, Shigetaka; Yahata, Tamaki; Mabuchi, Yasushi; Tanizaki, Yuko; Kobayashi, Aya; Shiro, Michihisa; Ota, Nami; Minami, Sawako; Terada, Masaki; Ino, Kazuhiko

    2016-01-01

    The objective of the present study was to investigate the prognostic value of 18F-fluoro-2-deoxy-D-glucose (FDG) uptake by primary tumors on positron emission tomography/computed tomography (PET/CT) in surgically resectable cervical cancer. A total of 59 patients with stage IA2-IIB cervical cancer who underwent preoperative FDG-PET/CT, followed by radical hysterectomy and lymphadenectomy, were included in the study. The maximum standardized uptake value (SUVmax) of the primary tumor was measured, and the association between the SUVmax and clinicopathological factors or patient outcomes was analyzed. The SUVmax was significantly higher in patients with an advanced stage, lymph node metastasis, lymph-vascular space involvement and large tumors. The overall survival (OS) and progression-free survival (PFS) of patients with a high SUVmax were significantly lower compared with patients with a low SUVmax, using an optimal cut-off value of 7.36 for OS and 5.59 for PFS obtained from receiver operating characteristic curve analysis. Similarly, OS and PFS in patients with a high SUVmax were significantly lower in 39 patients with stage IB using a cut-off value of 7.90 and 6.69 for OS and PFS, respectively. Finally, multivariate analyses showed that the SUVmax of the primary tumor was an independent prognostic factor for impaired PFS in all patients and those with stage IB alone. These findings demonstrated that a high SUVmax on preoperative PET/CT was correlated with unfavorable clinical outcomes in patients receiving radical hysterectomy, suggesting that the SUVmax of the primary tumor may be a prognostic indicator for surgically-treated, early-stage invasive cervical cancer.

  2. 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.

  3. Transfontanellar Duplex Brain Ultrasonography Resistive Indices as a Prognostic Tool in Neonatal Hypoxic-Ischemic Encephalopathy Before and After Treatment with Therapeutic Hypothermia

    PubMed Central

    Gerner, Gwendolyn J; Burton, V Joanna; Poretti, Andrea; Bosemani, Thangamadhan; Cristofalo, Elizabeth; Tekes, Aylin; Seyfert, Donna; Parkinson, Charlamaine; Leppert, Mary; Allen, Marilee; Huisman, Thierry A G M; Northington, Frances J; Johnston, Michael V

    2015-01-01

    OBJECTIVE Prior to therapeutic hypothermia (i.e., cooling), transfontanellar duplex brain sonography resistive indices (RI) were studied as bedside non-invasive measures of cerebral hemodynamics in neonates who suffered from hypoxic-ischemic encephalopathy (HIE). We compared pre- and post-cooling RI values and examined the relationships between RI values and specific long-term neurodevelopmental outcomes. STUDY DESIGN Transfontanellar duplex brain sonography, including RI, were obtained for 28 neonates prior to brain cooling and for 20 neonates following brain cooling. All RI values were sampled in the anterior cerebral artery at the beginning of each ultrasound study. Neurodevelopmental assessment was conducted between ages 20-32 months with the Mullen Scale of Early Learning. The relationships between pre- and post-cooling RI and cognitive and motor outcomes were studied. RESULT Neonates with RI values <0.60 prior to and following cooling were more likely to die or have severe neurodevelopmental disability by ages 20-32 months than those with RI >0.60. Lower RI values were associated with specific neurodevelopmental deficits in motor skill attainment. CONCLUSION Pre- and post-cooling transfontanellar duplex brain sonography RI values may be a useful prognostic tool, in conjunction with other clinical information, for neonates diagnosed with HIE. The results of this study suggest that further study of the prognostic value of RI values for short- and long-term outcomes is warranted. PMID:26609871

  4. Evaluation of tumor angiogenesis measured with microvessel density (MVD) as a prognostic indicator in nasopharyngeal carcinoma: Results of RTOG 9505

    SciTech Connect

    Foote, Robert L. . E-mail: foote.robert@mayo.edu; Weidner, Noel; Harris, Jonathan; Hammond, Elizabeth; Lewis, Jean E.; Vuong, Te; Ang, K. Kian; Fu, Karen K.

    2005-03-01

    Purpose: The objective of this study was to evaluate tumor angiogenesis as measured by microvessel density (MVD) as an independent prognostic factor in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy alone. Methods and materials: Eligible patients included those with NPC treated with radiotherapy. Paraffin blocks of the primary tumor had a hematoxylin and eosin-stained section prepared at the block face. One representative section for tumor was stained for factor VIII-related antigen using a standard immunoperoxidase staining technique. MVD was determined by light microscopy in areas of invasive tumor containing the highest numbers of capillaries and microvessels per area. Individual microvessel counts were made on a 200x field within the area of most intense tumor neovascularization. Results were expressed as the highest number of microvessels identified within any single 200x field. Using a breakpoint of MVD < 60 vs. {>=}60, the distributions between the two MVD groups were compared by the method of Gray. Overall survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. A multivariate Cox proportional hazard model was employed to examine the relationship between MVD and disease outcomes while adjusting for other concomitant variables. Results: One hundred sixty-six were eligible, of whom 123 had values determined for MVD. The MVD values ranged from 9 to 243 with a median of 70. In the multivariate analysis of overall survival, distant metastases, and local-regional failure, MVD did not significantly improve the model containing T stage, N stage, age, radiation dose, and World Health Organization class. Conclusions: We found no significant differences in overall survival, time to distant metastasis, or time to local-regional failure using a breakpoint of MVD < 60 vs. MVD {>=}60. The study was perhaps limited by the small size of the NPC samples.

  5. Screening of Target Genes and Regulatory Function of miRNAs as Prognostic Indicators for Prostate Cancer.

    PubMed

    Xiaoli, Zhang; Yawei, Wei; Lianna, Liu; Haifeng, Li; Hui, Zhang

    2015-01-01

    important molecular targets that could serve as prognostic and predictive markers in the treatment of prostate cancer. Further research on the function of the target genes in the MAPK signal pathway could provide references for treatment of prostate cancer. PMID:26628405

  6. Screening of Target Genes and Regulatory Function of miRNAs as Prognostic Indicators for Prostate Cancer

    PubMed Central

    Xiaoli, Zhang; Yawei, Wei; Lianna, Liu; Haifeng, Li; Hui, Zhang

    2015-01-01

    important molecular targets that could serve as prognostic and predictive markers in the treatment of prostate cancer. Further research on the function of the target genes in the MAPK signal pathway could provide references for treatment of prostate cancer. PMID:26628405

  7. Genetic mutational profiling analysis of T cell acute lymphoblastic leukemia reveal mutant FBXW7 as a prognostic indicator for inferior survival.

    PubMed

    Yuan, Lan; Lu, Ling; Yang, Yongchen; Sun, Hengjuan; Chen, Xi; Huang, Yi; Wang, Xingjuan; Zou, Lin; Bao, Liming

    2015-11-01

    T cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplasm for which there are currently no adequate biomarkers for developing risk-adapted therapeutic regimens to improve the treatment outcome. In this prospective study of 83 Chinese patients (54 children and 29 adults) with de novo T-ALL, we analyzed mutations in 11 T-ALL genes: NOTCH1, FBXW7, PHF6, PTEN, N-RAS, K-RAS, WT1, IL7R, PIK3CA, PIK3RA, and AKT1. NOTCH1 mutations were identified in 51.9 and 37.9 % of pediatric and adult patients, respectively, and these patients showed improved overall survival (OS) and event-free survival (EFS). The FBXW7 mutant was present in 25.9 and 6.9 % of pediatric and adult patients, respectively, and was associated with inferior OS and EFS in pediatric T-ALL. Multivariate analysis revealed that mutant FBXW7 was an independent prognostic indicator for inferior EFS (hazard ratio [HR] 4.38; 95 % confidence interval [CI] 1.15-16.71; p = 0.03) and tended to be associated with reduced OS (HR 2.81; 95 % CI 0.91-8.69; p = 0.074) in pediatric T-ALL. Mutant PHF6 was present in 13 and 20.7 % of our childhood and adult cohorts, respectively, while PTEN mutations were noted in 11.1 % of the pediatric patients. PTEN and NOTCH1 mutations were almost mutually exclusive, while IL7R and WT1 mutations were rare in pediatric T-ALL and PTPN11 and AKT1 mutations were infrequent in adult T-ALL. This study revealed differences in the mutational profiles of pediatric and adult T-ALL and suggests mutant FBXW7 as an independent prognostic indicator for inferior survival in pediatric T-ALL. PMID:26341754

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

    PubMed Central

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

    2015-01-01

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

  9. Overexpression of CIP2A is an independent prognostic indicator in nasopharyngeal carcinoma and its depletion suppresses cell proliferation and tumor growth

    PubMed Central

    2014-01-01

    Background Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a prognostic marker for several human malignancies. In this study, we investigated the clinical significance of CIP2A and its function in nasopharyngeal carcinoma (NPC). Methods Quantitative RT-PCR, western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in NPC cell lines and clinical samples. Kaplan-Meier curves were used to estimate the association between CIP2A expression and patient survival. The functional role of CIP2A in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and xenograft growth. Results CIP2A levels were upregulated in NPC cell lines and clinical samples at both the mRNA and protein levels (P < 0.01). Patients with high CIP2A expression had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and poorer disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) rates than patients with low CIP2A expression. In addition, CIP2A expression status was an independent prognostic indicator for NPC patients. The depletion of CIP2A expression inhibited c-Myc protein expression in NPC cell lines, suppressed cell viability, colony formation, and anchorage-independent growth in vitro, and inhibited xenograft tumor growth in vivo. Conclusions Our data demonstrate that high CIP2A expression in patients was associated with poor survival in NPC, and depletion of CIP2A expression inhibited NPC cell proliferation and tumor growth. Thus, these results warrant further investigation of CIP2A as a novel therapeutic target for the treatment of NPC. PMID:24884612

  10. Overexpression of SULT2B1b is an independent prognostic indicator and promotes cell growth and invasion in colorectal carcinoma

    PubMed Central

    Hu, Liang; Yang, Guang-Zhen; Zhang, Yu; Feng, Dan; Zhai, Yan-Xia; Gong, Hui; Qi, Chen-Ye; Fu, Hao; Ye, Ming-Ming; Cai, Qing-Ping; Gao, Chun-Fang

    2015-01-01

    Aberrant expression of cytosolic sulfotransferase 2B1b (SULT2B1b) has been reported in several human malignancies. However, the expression pattern and clinical significance of SULT2B1b in colorectal carcinoma (CRC) remains unknown. Real-time quantitative PCR, western blot, and immunohistochemistry analyses were used to determine SULT2B1b expression in CRC clinical samples and CRC-derived cell lines. Kaplan–Meier and Cox proportional regression analyses were used to evaluate the association between SULT2B1b expression and patient survival in two independent cohorts of 485 patients with CRC. Gain- and loss-of-function approaches were employed to investigate the role of SULT2B1b in regulation of CRC cell growth and invasion. We found that SULT2B1b expression was frequently upregulated in CRC clinical samples and CRC-derived cell lines and was significantly correlated with lymph node metastasis and TNM stage in both the training and validation cohorts. Patients with higher intratumoral SULT2B1b expression had a significantly shorter disease-specific survival (DSS) and disease-free survival (DFS) than those with lower expression. Importantly, increased expression of SULT2B1b significantly predicted poor DSS and DFS and was an independent unfavorable prognostic indicator for stage II patients in both cohorts. Functional studies revealed that overexpression of SULT2B1b promoted CRC cell growth and invasion in vitro. Conversely, knockdown of SULT2B1b inhibited these processes. In conclusion, our findings suggest that SULT2B1b expression correlates with disease progression and metastasis and may serve as a novel prognostic biomarker and potential therapeutic target for patients with CRC. PMID:26121319

  11. 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

  12. IGF-1 and VEGF can be used as prognostic indicators for patients with uterine fibroids treated with uterine artery embolization

    PubMed Central

    MU, YONGXU; HE, JUNFENG; YAN, RUIQIANG; HU, XIAOYAN; LIU, HAIYAN; HAO, ZHIMING

    2016-01-01

    The aim of the present study was to investigate the association between serum vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) levels and the prognosis of patients with uterine fibroids following uterine artery embolization (UAE) treatment. A total of 70 patients with uterine fibroids and 20 healthy controls were enrolled in this study between 2012 and 2014. The serum levels of IGF-1 and VEGF were measured using ELISA. Multiple-factor analysis was performed to assess the association between serum levels of IGF-1/VEGF and certain clinical characteristics, including size, location, number of uterine fibroids and adenomyosis. Progression-free survival curves were analyzed using the Kaplan-Meier method. The serum levels of IGF-1 and VEGF in patients with uterine fibroids prior to UAE treatment were significantly higher than those in controls (P<0.05). At 1 week after UAE treatment, the serum levels of IGF-1 and VEGF were significantly lower compared with those prior to UAE treatment. The serum levels of IGF-1 and VEGF at 1 or 3 months after UAE treatment were significantly higher than those at 1 week after UAE treatment. The serum levels of IGF-1 and VEGF were significantly correlated with the clinical characteristics of uterine fibroids (P<0.05). Lower levels of IGF-1 and VEGF in the serum following UAE treatment were associated with an enhanced progression-free survival of patients. In conclusion, the levels of IGF-1 and VEGF in the serum following UAE treatment can be used as indicators of prognosis in patients with uterine fibroids. PMID:26893660

  13. 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 FIO2 , 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. PMID:27016353

  14. 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. PMID:27459845

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

    PubMed Central

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

    2016-01-01

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

  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. 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

  18. Impact of familial risk and mammography screening on prognostic indicators of breast disease among women from the Ontario site of the Breast Cancer Family Registry.

    PubMed

    Walker, Meghan J; Mirea, Lucia; Cooper, Kristine; Nabavi, Mitra; Glendon, Gord; Andrulis, Irene L; Knight, Julia A; O'Malley, Frances P; Chiarelli, Anna M

    2014-06-01

    Although several studies have found screen-detected cancers in women with familial breast cancer risk have favorable prognostic features compared with symptomatic cancers, the impact of level of familial risk is unknown. A cohort of 899 first-degree female relatives of cases of breast cancer from the Ontario site of the Breast Cancer Family Registry was followed for 2 years. Logistic regression analyses compared diagnoses of breast cancer or benign breast disease (BBD) between women at high (n = 258, 28.7 %) versus low/moderate (n = 641, 71.3 %) familial risk. Similar analyses compared prognostic features of invasive cancers and BBD by level of familial risk and mammography screening status. Among 899 women, 44 (4.9 %) were diagnosed with invasive breast cancer and/or ductal carcinoma in situ, and 56 (6.2 %) with BBD. Women with high familial risk were significantly more likely to be diagnosed with breast cancer [odds ratio (OR) = 2.84, 95 % confidence interval (CI) 1.50-5.38] than low/moderate risk women, particularly if diagnosed at age ≥50 (OR = 2.99, 95 % CI 1.37-6.56) or screened with mammography (OR = 3.33, 95 % CI 1.54-7.18). High risk women were more likely to be diagnosed with BBD (OR = 1.94, 95 % CI 1.03-3.66). Level of familial risk was not associated with prognostic features. Cancers among unscreened women were larger (OR = 9.72, 95 % CI 1.01-93.61) and diagnosed at stage II or above (OR = 7.80, 95 % CI 1.18-51.50) compared with screen-detected cancers. Screening mammography may be effective for women with a first-degree family history of breast cancer, irrespective of level of familial risk. PMID:24097051

  19. Multi-Indication Carbamazepine and the Risk of Severe Cutaneous Adverse Drug Reactions in Korean Elderly Patients: A Korean Health Insurance Data-Based Study

    PubMed Central

    Kim, Ji Young; Lee, Joongyub; Ko, Young-Jin; Shin, Ju-Young; Jung, Sun-Young; Choi, Nam-Kyong; Park, Byung-Joo

    2013-01-01

    Objective To evaluate the risk of severe cutaneous adverse drug reactions (SCAR) after exposure to multi-indication antiepileptic drugs for in Korean elderly patients. Methods We used a nationwide database from the Korean Health Insurance Review and Assessment Service claims constructed for the monitoring of drug utilization among the entire Korean elderly population from January 2005 to June 2006. We identified cases of SCARs among inpatients aged ≥65 years and those newly diagnosed with erythema multiforme according to the International Classification of Diseases, 10th revision code (L51). Each case was matched to four controls for gender, age, and the first hospitalization date as the index date. The use of carbamazepine, gabapentin, lamotrigine, topiramate, phenobarbital, phenytoin, and valproate during a 60-day period before the index date was compared. A conditional logistic regression analysis was performed to calculate the odds ratios (OR) and 95% confidence intervals (CI) of SCARs for antiepileptic drug. Results We identified 286 cases of SCAR and 1,144 matched controls. Among the 25 patients who were prescribed antiepileptic drugs within 60 days of the index date. There were 11 cases (3.8%) of severe ocular manifestations, and most elderly patients were first-time or short-term users of antiepileptic drugs. Among the 10 cases of carbamazepine use, only 2 cases were prescribed carbamazepine for seizure. All antiepileptic drugs were associated with an increased SCAR risk (adjusted OR = 3.42, 95% CI: 1.75–6.63). The SCAR risk was highest in patients treated with carbamazepine (adjusted OR = 10.39, 95% CI: 2.64–40.86, for multi-indication; adjusted OR = 6.84, 95% CI: 1.55–30.10, for neuropathic pain). Conclusion Carbamazepine use was associated with a nearly 10-fold increase in severe cutaneous drug reactions in Korean elderly patients. This association was consistently high with SCAR patients who received carbamazepine for neuropathic

  20. CEBPA single mutation can be a possible favorable prognostic indicator in NPM1 and FLT3-ITD wild-type acute myeloid leukemia patients with intermediate cytogenetic risk.

    PubMed

    Park, Sang Hyuk; Chi, Hyun-Sook; Cho, Young-Uk; Jang, Seongsoo; Park, Chan-Jeoung

    2013-11-01

    The aim of this study was to evaluate the prognostic impact of CEBPA single mutation in acute myeloid leukemia (AML) patients with intermediate cytogenetic risk. CEBPA single and double mutations were detected in 11 (9.7%) and 17 (15.1%) of 113 NPM1 wild-type patients, but no CEBPA mutations were detected in a group of 44 NPM1 mutated patients. Among patients with NPM1/FLT3-ITD wild-type, those with CEBPA double mutations (P=0.013 and 0.007 for overall survival and relapse-free survival, respectively) or a single mutation (P=0.039 and 0.020 for overall survival and relapse-free survival, respectively) demonstrated a favorable prognosis compared with CEBPA wild-type patients. Subsequent multivariate analysis confirmed the favorable prognostic impact of CEBPA single and double mutations. Despite the low statistical power of this study due to the small number of patients, our preliminary data suggest that CEBPA single mutation may be associated with favorable clinical outcomes in NPM1/FLT3-ITD wild-type AML patients with intermediate cytogenetic risk. PMID:24054719

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

    PubMed

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

    2016-04-12

    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

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

    PubMed

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

    2006-06-01

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

  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. Exercise hypertension: an adverse prognosis?

    PubMed

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

    2009-01-01

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

  6. Caveolin 1 (Cav-1) and actin-related protein 2/3 complex, subunit 1B (ARPC1B) expressions as prognostic indicators for oral squamous cell carcinoma (OSCC).

    PubMed

    Auzair, Lukman Bin Md; Vincent-Chong, Vui King; Ghani, Wan Maria Nabillah; Kallarakkal, Thomas George; Ramanathan, Anand; Lee, Chia Ee; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Abraham, Mannil Thomas; Zain, Rosnah Binti

    2016-07-01

    Caveolin-1 (Cav-1) and Actin-Related Protein 2/3 Complex, Subunit 1B (ARPC1B) have been implicated in various human cancers, yet its role in tumorigenesis remains controversial. Therefore, this study aims to determine the protein expression of these two genes in oral squamous cell carcinomas (OSCCs) and to evaluate the clinical and prognostic impact of these genes in OSCC. Protein expressions of these two genes were determined by immunohistochemistry technique. The association between Cav-1 and ARPC1B with clinico-pathological parameters was evaluated by Chi-square test (or Fisher exact test where appropriate). Correlation between the protein expressions of these 2 genes with survival was analyzed using Kaplan-Meier and Cox regression models. Cav-1 and ARPC1B were found to be significantly over-expressed in OSCC compared to normal oral mucosa (p = 0.002 and p = 0.033, respectively). Low level of ARPC1B protein expression showed a significant correlation with lymph node metastasis (LNM) (p = 0.010) and advanced tumor staging (p = 0.003). Kaplan-Meier survival analyses demonstrated that patients with over-expression of Cav-1 protein were associated with poor prognosis (p = 0.030). Adjusted multivariate Cox regression model revealed that over-expression of Cav-1 remained as an independent significant prognostic factor for OSCC (HRR = 2.700, 95 % CI 1.013-7.198, p = 0.047). This study demonstrated that low-expression of ARPC1B is significantly associated with LNM and advanced tumor staging whereas high expression of Cav-1 can be a prognostic indicator for poor prognosis in OSCC patients. PMID:26138391

  7. 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. PMID:26111072

  8. MicroRNA-203 Is a Prognostic Indicator in Bladder Cancer and Enhances Chemosensitivity to Cisplatin via Apoptosis by Targeting Bcl-w and Survivin

    PubMed Central

    Zhang, Xin; Zhang, Yanli; Liu, Xinfeng; Fang, Aiju; Li, Peilong; Li, Zewu; Liu, Tong; Yang, Yongmei; Du, Lutao; Wang, Chuanxin

    2015-01-01

    Resistance to cisplatin-based chemotherapy is a major cause of treatment failure in advanced bladder cancer (BC) patients. There is increasing evidence that microRNAs are involved in the development and progression of BC. However, little is known about the function of microRNAs in predicting the effect of adjuvant chemotherapy on BC survival and regulating response to cisplatin. To address this issue, we employed RT-qPCR to evaluate the clinical significance of miR-203 expression in 108 tissues of BC patients receiving cisplatin-based adjuvant chemotherapy, and performed in vitro studies to explore chemotherapeutic sensitivity to cisplatin in miR-203 overexpressing BC cells. We found miR-203 levels were significantly lower in BC progression group than non-progression group (P<0.001). ROC curve analysis illustrated miR-203 could significantly distinguish progressed patients from those without progression (P<0.001), yielding an area under the ROC curve of 0.839 (95% CI, 0.756–0.903). Moreover, low miR-203 expression correlated with shortened progression free survival (PFS) and overall survival (OS) of BC patients, and was an independent prognostic factor. Overexpression of miR-203 in 5637 and T24 BC cells could decrease cell viability, enhance cisplatin cytotoxicity, and promote apoptosis. Western blotting and luciferase reporter assay showed Bcl-w and Survivin were direct downstream targets of miR-203. There was also a significant inverse association between miR-203 and Bcl-w or Survivin expression in BC tissues (r = -0.781, -0.740, both P<0.001). In conclusion, decreased miR-203 predicts progression and poor prognosis for BC patients treated with cisplatin-based chemotherapy while miR-203 overexpression can enhance cisplatin sensitization by promoting apoptosis via directly targeting Bcl-w and Survivin. PMID:26599571

  9. PinX1 serves as a potential prognostic indicator for clear cell renal cell carcinoma and inhibits its invasion and metastasis by suppressing MMP-2 via NF-κB-dependent transcription

    PubMed Central

    Meng, Fei; Liu, Qing-Hua; Pan, Zhen-Qiang; Bai, Jin; Zheng, Jun-Nian

    2015-01-01

    PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a novel cloned gene which has been identified as a major haploinsufficient tumor suppressor essential for maintaining telomerase activity, the length of telomerase and chromosome stability. This study explored the clinical significance and biological function of PinX1 in human clear cell renal cell carcinoma (ccRCC). The clinical relevance of PinX1 in ccRCC was evaluated using tissue microarray and immunohistochemical staining in two independent human ccRCC cohorts. Our data demonstrated that PinX1 expression was dramatically decreased in ccRCC tissues compared with normal renal tissues and paired adjacent non-tumor tissues. Low PinX1 expression was significantly correlated with depth of invasion, lymph node metastasis and advanced TNM stage in patients, as well as with worse overall and disease-specific survival. Cox regression analysis revealed that PinX1 expression was an independent prognostic factor for ccRCC patients. Moreover, PinX1 inhibited the migration and invasion of ccRCC by suppressing MMP-2 expression and activity via NF-κB-dependent transcription in vitro. In vivo studies confirmed that PinX1 negatively regulated ccRCC metastasis and the expression of MMP-2 and NF-κB-p65. These findings indicate that PinX1 suppresses ccRCC metastasis and may serve as a ccRCC candidate clinical prognostic marker and a potential therapeutic target. PMID:26033551

  10. 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.

  11. A vulnerability driven approach to identify adverse climate and land use change combinations for critical hydrologic indicator thresholds: Application to a watershed in Pennsylvania, USA

    NASA Astrophysics Data System (ADS)

    Singh, R.; Wagener, T.; Crane, R.; Mann, M. E.; Ning, L.

    2014-04-01

    Large uncertainties in streamflow projections derived from downscaled climate projections of precipitation and temperature can render such simulations of limited value for decision making in the context of water resources management. New approaches are being sought to provide decision makers with robust information in the face of such large uncertainties. We present an alternative approach that starts with the stakeholder's definition of vulnerable ranges for relevant hydrologic indicators. Then the modeled system is analyzed to assess under what conditions these thresholds are exceeded. The space of possible climates and land use combinations for a watershed is explored to isolate subspaces that lead to vulnerability, while considering model parameter uncertainty in the analysis. We implement this concept using classification and regression trees (CART) that separate the input space of climate and land use change into those combinations that lead to vulnerability and those that do not. We test our method in a Pennsylvania watershed for nine ecological and water resources related streamflow indicators for which an increase in temperature between 3°C and 6°C and change in precipitation between -17% and 19% is projected. Our approach provides several new insights, for example, we show that even small decreases in precipitation (˜5%) combined with temperature increases greater than 2.5°C can push the mean annual runoff into a slightly vulnerable regime. Using this impact and stakeholder driven strategy, we explore the decision-relevant space more fully and provide information to the decision maker even if climate change projections are ambiguous.

  12. Black Carbon as an Additional Indicator of the Adverse Health Effects of Airborne Particles Compared with PM10 and PM2.5

    PubMed Central

    Hoek, Gerard; Simic-Lawson, Milena; Fischer, Paul; van Bree, Leendert; ten Brink, Harry; Keuken, Menno; Atkinson, Richard W.; Anderson, H. Ross; Brunekreef, Bert; Cassee, Flemming R.

    2011-01-01

    Background: Current air quality standards for particulate matter (PM) use the PM mass concentration [PM with aerodynamic diameters ≤ 10 μm (PM10) or ≤ 2.5 μm (PM2.5)] as a metric. It has been suggested that particles from combustion sources are more relevant to human health than are particles from other sources, but the impact of policies directed at reducing PM from combustion processes is usually relatively small when effects are estimated for a reduction in the total mass concentration. Objectives: We evaluated the value of black carbon particles (BCP) as an additional indicator in air quality management. Methods: We performed a systematic review and meta-analysis of health effects of BCP compared with PM mass based on data from time-series studies and cohort studies that measured both exposures. We compared the potential health benefits of a hypothetical traffic abatement measure, using near-roadway concentration increments of BCP and PM2.5 based on data from prior studies. Results: Estimated health effects of a 1-μg/m3 increase in exposure were greater for BCP than for PM10 or PM2.5, but estimated effects of an interquartile range increase were similar. Two-pollutant models in time-series studies suggested that the effect of BCP was more robust than the effect of PM mass. The estimated increase in life expectancy associated with a hypothetical traffic abatement measure was four to nine times higher when expressed in BCP compared with an equivalent change in PM2.5 mass. Conclusion: BCP is a valuable additional air quality indicator to evaluate the health risks of air quality dominated by primary combustion particles. PMID:21810552

  13. Acute pancreatitis: prognostic value of CT

    SciTech Connect

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

    1985-09-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-07-01

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

  1. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. 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 ...

  5. Post-operative urothelial recurrence in patients with upper urinary tract urothelial carcinoma managed by radical nephroureterectomy with an ipsilateral bladder cuff: Minimal prognostic impact in comparison with non-urothelial recurrence and other clinical indicators

    PubMed Central

    TAKAHARA, KIYOSHI; INAMOTO, TERUO; KOMURA, KAZUMASA; WATSUJI, TOSHIKAZU; AZUMA, HARUHITO

    2013-01-01

    Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, and novel prognostic factors for patients who have undergone a radical nephroureterectomy (RNU) for UTUC have been studied intensely. To the best of our knowledge, the prognostic value of urothelial recurrence in patients with UTUC has not been previously described in studies. The present study compared the prognostic value of urothelial and non-urothelial recurrence in patients with UTUC of the kidney and ureter managed by surgery. The inclusion criteria consisted of a diagnosis of non-metastatic UTUC (any T stage, N0–1 and M0) and receipt of an RNU with an ipsilateral bladder cuff as the primary treatment. Of the 153 patients that were screened for the study, comprehensive clinical and pathological data was available for 103 patients, who were consequently included in the analysis. Overall survival (OS) and cancer-specific survival (CSS) times were estimated. A multivariate analysis was performed using the Cox regression model. The median follow-up period was 29 months (interquartile range, 14–63 months). The patient population was comprised of 71 males (68.9%) and 32 females (31.1%). A total of 32 patients (31.1%) showed non-urothelial recurrence, while 38 patients (36.9%) exhibited urothelial recurrence and 33 patients (32.0%) exhibited no recurrence. When comparing the risk parameters between the non-urothelial recurrence categories, the factors of pathological grade, microvascular invasion, lymphatic invasion and pT classification showed significant differences. However, there were no significant differences between the urothelial recurrence categories. No significant difference was observed between the OS and CSS times within the urothelial recurrence categories (P=0.3955 and P=0.05891, respectively), but significant differences were identified in the non-urothelial recurrence categories (P<0.0001 and P<0.0001, respectively). Among the other relevant descriptive pre

  6. 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.

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

    PubMed Central

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

    2016-01-01

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

  8. Prognostic Impact of Cytogenetic Abnormalities in Multiple Myeloma

    PubMed Central

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

    2016-01-01

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

  9. 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.

  10. 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

  11. Population-specific prognostic models are needed to stratify outcomes for African-Americans with diffuse large B-cell lymphoma.

    PubMed

    Chen, Qiushi; Ayer, Turgay; Nastoupil, Loretta J; Koff, Jean L; Staton, Ashley D; Chhatwal, Jagpreet; Flowers, Christopher R

    2016-04-01

    Diffuse large B-cell lymphoma (DLBCL) demonstrates significant racial differences in age of onset, stage, and survival. To examine whether population-specific models improve prediction of outcomes for African-American (AA) patients with DLBCL, we utilized Surveillance, Epidemiology, and End Results data and compared stratification by the international prognostic index (IPI) in general and AA populations. We also constructed and compared prognostic models for general and AA populations using multivariable logistic regression (LR) and artificial neural network approaches. While the IPI adequately stratified outcomes for the general population, it failed to separate AA DLBCL patients into distinct risk groups. Our AA LR model identified age ≥ 55 (odds ratio 0.45, [95% CI: 0.36, 0.56], male sex (0.75, [0.60, 0.93]), and stage III/IV disease (0.43, [0.34, 0.54]) as adverse predictors of 5-year survival for AA patients. In addition, general-population prognostic models were poorly calibrated for AAs with DLBCL, indicating a need for validated AA-specific prognostic models. PMID:26415108

  12. Adverse reactions to sulfites

    PubMed Central

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

    1985-01-01

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

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

    PubMed

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

    2015-02-01

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

  14. 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…

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

    SciTech Connect

    Kim, Jun-Sang; Kim, Jin-Man; Liang, Zhe Long; Jang, Ji Young; Kim, Sup; Huh, Gil Ja; Kim, Ki-Hwan; Cho, Moon-June

    2012-01-01

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

  16. DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers.

    PubMed

    Abdel-Fatah, Tarek M A; Arora, Arvind; Moseley, Paul M; Perry, Christina; Rakha, Emad A; Green, Andrew R; Chan, Stephen Y T; Ellis, Ian O; Madhusudan, Srinivasan

    2015-09-01

    Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol β, FEN1, APE1, XRCC1, SMUG1, PARP1, BRCA1, ATR, ATM, DNA-PKcs, Chk1, Chk2, p53, and TOPO2. Multivariate Cox proportional hazards models (with backward stepwise exclusion of these factors, using a criterion of p < 0.05 for retention of factors in the model) were used to identify factors that were independently associated with clinical outcomes. XRCC1 (p = 0.002), pol β (p = 0.032) FEN1 (p = 0.001) and BRCA1 (p = 0.040) levels were independently associated with poor BCSS. Subsequently, DNA repair index prognostic (DRPI) scores for breast cancer specific survival (BCSS) were calculated and two prognostic groups (DRPI-PGs) were identified. Patients in prognostic group 2 (DRPI-PG2) have higher risk of death (p < 0.001). Furthermore, in DRPI-PG2 patients, exposure to anthracycline reduced the risk of death [(HR (95% CI) = 0.79 (0.64-0.98), p = 0.032) by 21-26%. In addition, DRPI-PG2 patients have adverse clinicopathological features including higher grade, lympho-vascular invasion, Her-2 positive phenotype, compared to those in DRPI-PG1 (p < 0.01). Receiver operating characteristic (ROC) curves indicated that the DRPI outperformed the currently used prognostic factors and adding DRPI to lymph node stage significantly improved their performance as a predictor for BCSS [p < 0.00001, area under curve (AUC) = 0.70]. BER strongly influences pathogenesis of ER- and TNBCs. The DRPI accurately predicts BCSS and can also serve as a valuable prognostic and predictive tool for TNBCs. PMID:26267318

  17. Prognostic significance of QRS duration and morphology.

    PubMed

    Brenyo, Andrew; Zaręba, Wojciech

    2011-01-01

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

  18. Stage-specific prognostic biomarkers in melanoma.

    PubMed

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

    2015-02-28

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

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

    PubMed Central

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

    2015-01-01

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

  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. [Adverse reaction of pseudoephedrine].

    PubMed

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

    2005-04-01

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

  2. Screening for adverse events.

    PubMed

    Karson, A S; Bates, D W

    1999-02-01

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

  3. Molecular predictive and prognostic factors in ependymoma.

    PubMed

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

    2016-01-01

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

  4. Prognostic factors and classification in multiple myeloma.

    PubMed Central

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

    1989-01-01

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

  5. A consensus prognostic gene expression classifier for ER positive breast cancer

    PubMed Central

    Teschendorff, Andrew E; Naderi, Ali; Barbosa-Morais, Nuno L; Pinder, Sarah E; Ellis, Ian O; Aparicio, Sam; Brenton, James D; Caldas, Carlos

    2006-01-01

    Background A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. Results Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation. Conclusion The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors. PMID:17076897

  6. 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

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

    PubMed Central

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

    2015-01-01

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

  8. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

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

  9. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

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

  10. Heart failure prognostic model.

    PubMed

    Axente, L; Sinescu, C; Bazacliu, G

    2011-05-15

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

  11. Heart failure prognostic model

    PubMed Central

    Axente, L; Sinescu, C; Bazacliu, G

    2011-01-01

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

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

    PubMed

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

    2013-05-01

    The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score including C-reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T-cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T-cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more adverse clinical characteristics, lower rates of complete remission (P < 0.001), inferior progression-free survival (PFS, P < 0.001), and inferior overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low-risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL. PMID:23423859

  13. 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.

  14. Urethral hypermobility after anti-incontinence surgery - a prognostic indicator?

    PubMed

    Viereck, Volker; Pauer, Hans-Ulrich; Hesse, Oda; Bader, Werner; Tunn, Ralf; Lange, Rainer; Hilgers, Reinhard; Emons, Günter

    2006-11-01

    The aim of this study was to define the concept of hypermobility of the bladder neck and determine its effects on the cure rate and postoperative complications in patients undergoing colposuspension. In a retrospective study, 310 patients who underwent primary colposuspension for urodynamically proven genuine stress urinary incontinence were assessed by introital ultrasound before surgery and during follow-up for up to 48 months postoperatively. A total of 152 women completed 48 months of follow-up. Mobility of the bladder neck during straining was described as linear dorsocaudal movement (LDM) with LDM >15 mm being defined as hypermobility. The overall objective cure rate was 90.0% at 6-month follow-up vs 76.8% at 48-month follow-up (Kaplan-Meier estimators). Urge symptoms occurred in 12.6% (39/310) of the women and de novo urge incontinence in 2.3% (7/310). Bladder neck hypermobility was significantly reduced after anti-incontinence surgery, from 67.1% (208/310) before surgery to 5.5% (17/310) immediately after surgery (P<0.0001). Postoperative hypermobility was associated with a higher recurrence rate. In the hypermobility group, 52.9 and 34.0% of the patients were continent for up to 6 and 48 months, respectively, as opposed to 92.2 and 79.2% in the group without hypermobility (P<0.0001). Women with postoperative hypermobility had a 3.2-fold higher risk of recurrence within 48 months. Bladder neck hypermobility after surgery was also associated with postoperative voiding difficulty (P=0.0278). Patients in whom hypermobility of the bladder neck diagnosed before surgery persists after colposuspension have a higher risk of recurrence and are more likely to develop postoperative complications than those without this hypermobility. PMID:16538422

  15. 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

  16. 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.

  17. Early prognostic indicators in acute meningococcemia: implications for management.

    PubMed

    Bausher, J C; Baker, R C

    1986-09-01

    Three pediatric patients presenting with fever and petechiae with unexpected rapid development of shock are reported. Clinical and laboratory parameters which may identify patients at risk for rapid deterioration are presented. The pathophysiology of meningococcal disease is discussed with emphasis on the possible implications in management. Patients identified at increased risk should be monitored closely; cardiovascular decompensation should be treated aggressively with fluids, pressors, and steroids in an attempt to reverse this process. PMID:3097626

  18. Prognostic significance of modified Glasgow Prognostic Score in patients with non-metastatic clear cell renal cell carcinoma.

    PubMed

    Cho, Dae Sung; Kim, Sun Il; Choo, Seol Ho; Jang, Seok Heun; Ahn, Hyun Soo; Kim, Se Joong

    2016-06-01

    Objective The aim of this study was to evaluate the usefulness of the modified Glasgow Prognostic Score (mGPS) as a prognostic factor in patients with non-metastatic clear cell renal cell carcinoma (RCC). Materials and methods Between June 1994 and July 2012, 469 patients with RCC underwent radical or partial nephrectomy at two hospitals. Among these patients, 65 with non-clear cell type histology and 16 with lymph-node or distant metastasis were excluded. The medical records of the remaining 388 patients were retrospectively reviewed. The mGPS was calculated using a selective combination of C-reactive protein (CRP) and albumin as previously described. The prognostic significance of various clinicopathological variables including mGPS was analyzed using univariate and multivariate analyses. Results Of the total 388 patients, 40 patients (10.3%) developed local recurrence or distant metastasis and 18 patients (4.6%) died of disease during the follow-up period. The univariate analysis identified CRP, mGPS, thrombocytosis, T stage, Fuhrman's nuclear grade and lymphovascular invasion as significant prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS). The multivariate analysis indicated that mGPS (p < 0.001), T stage (p = 0.024) and lymphovascular invasion (p = 0.046) were independent prognostic factors for RFS, whereas mGPS (p = 0.001) was the only independent prognostic factor for CSS. Conclusions The mGPS is an independent prognostic factor for RFS and CSS in patients with non-metastatic clear cell RCC treated with radical or partial nephrectomy. These findings suggest that mGPS should be used for predicting recurrence or survival in patients undergoing nephrectomy for non-metastatic clear cell RCC. PMID:26878156

  19. Prognostic significance of NQO1 expression in intrahepatic cholangiocarcinoma

    PubMed Central

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

    2011-01-01

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

  20. High level amplification of N-MYC is not associated with adverse histology or outcome in primary retinoblastoma tumours

    PubMed Central

    Lillington, D M; Goff, L K; Kingston, J E; Onadim, Z; Price, E; Domizio, P; Young, B D

    2002-01-01

    Twenty-five primary retinoblastoma tumours were analysed by real-time quantitative polymerase chain reaction to determine the genomic copy number of the N-MYC gene (2p24) relative to the copy number for REL, B2M, ALB, AF10 and MLL. Twenty-one of these tumours were shown by Comparative Genomic Hybridization to contain variable copy number increases of chromosomal material mapping to 2p. High level amplification (>30-fold) of N-MYC was found in three tumours, none of which showed adverse histological features and all patients are surviving at between 54 and 108 months post enucleation. Furthermore, the three tumours associated with metastasis and adverse patient outcome showed normal N-MYC copy number. Although high level amplification of N-MYC is an unfavourable prognostic indicator in neuroblastoma, these data show no evidence of a correlation between amplification of N-MYC and adverse outcome in retinoblastoma. British Journal of Cancer (2002) 87, 779–782. doi:10.1038/sj.bjc.6600532 www.bjcancer.com © 2002 Cancer Research UK PMID:12232763

  1. 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

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

    PubMed

    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

  3. Adverse antibiotic drug interactions.

    PubMed

    Bint, A J; Burtt, I

    1980-07-01

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

  4. ADVERSE CUTANEOUS DRUG REACTION

    PubMed Central

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

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

  5. Multivariate analysis of prognostic factors in early stage Hodgkin's disease

    SciTech Connect

    Tubiana, M.; Henry-Amar, M.; van der Werf-Messing, B.; Henry, J.; Abbatucci, J.; Burgers, M.; Hayat, M.; Somers, R.; Laugier, A.; Carde, P.

    1985-01-01

    A multivariate analysis of the prognostic factors was carried out with a Cox model on 1,139 patients with clinical Stage I + II Hodgkin's disease included in three controlled clinical trials. The following indicators had been prospectively registered: aged, sex, systemic symptoms, erythrocyte sedimentation, results of staging laparotomy when performed, as well as the date and type of treatment. A linear logistic analysis showed that most of the indicators are interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The two main prognostic indicators for relapse-free survival are systemic symptoms and/or ESR and number of involved areas. The only significant factor for survival after relapse is age. Sex has a small but significant influence on relapse-free survival. The relative influence of each indicator varies with the type of treatment and these variations may help in understanding the biologic significance of the indicators.

  6. Adverse reactions to food additives.

    PubMed

    Simon, R A

    1986-01-01

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

  7. 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

  8. 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

  9. 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

  10. Prognostic biomarkers in acute coronary syndrome.

    PubMed

    Salvagno, Gian Luca; Pavan, Chiara

    2016-07-01

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

  11. 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

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

    PubMed

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

    2003-07-01

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

  13. 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.

  14. 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…

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

    PubMed Central

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

    2016-01-01

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

  16. FOXM1 expression in rhabdomyosarcoma: a novel prognostic factor and therapeutic target.

    PubMed

    Kuda, Masaaki; Kohashi, Kenichi; Yamada, Yuichi; Maekawa, Akira; Kinoshita, Yoshiaki; Nakatsura, Tetsuya; Iwamoto, Yukihide; Taguchi, Tomoaki; Oda, Yoshinao

    2016-04-01

    The transcription factor Forkhead box M1 (FOXM1) is known to play critical roles in the development and progression of various types of cancer, but the clinical significance of FOXM1 expression in rhabdomyosarcoma (RMS) is unknown. This study aimed to determine the role of FOXM1 in RMS. We investigated the expression levels of FOXM1 and vascular endothelial growth factor (VEGF) and angiogenesis in a large series of RMS clinical cases using immunohistochemistry (n = 92), and we performed clinicopathologic and prognostic analyses. In vitro studies were conducted to examine the effect of FOXM1 knock-down on VEGF expression, cell proliferation, migration, and invasion in embryonal RMS (ERMS) and alveolar RMS (ARMS) cell lines, using small interference RNA (siRNA). High FOXM1 expression was significantly increased in the cases of ARMS, which has an adverse prognosis compared to ERMS (p = 0.0310). The ERMS patients with high FOXM1 expression (n = 25) had a significantly shorter survival than those with low FOXM1 expression (n = 24; p = 0.0310). FOXM1 expression was statistically correlated with VEGF expression in ERMS at the protein level as shown by immunohistochemistry and at the mRNA level by RT-PCR. The in vitro study demonstrated that VEGF mRNA levels were decreased in the FOXM1 siRNA-transfected ERMS and ARMS cells. FOXM1 knock-down resulted in a significant decrease of cell proliferation and migration in all four RMS cell lines and invasion in three of the four cell lines. Our results indicate that FOXM1 overexpression may be a prognostic factor of RMS and that FOXM1 may be a promising therapeutic target for the inhibition of RMS progression. PMID:26553361

  17. 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

  18. 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.

  19. Neurological prognostication after cardiac arrest

    PubMed Central

    Sandroni, Claudio; Geocadin, Romergryko G.

    2016-01-01

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

  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. PMID:23836598

  1. Sudden Sensorineural Hearing Loss; Prognostic Factors

    PubMed Central

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

    2015-01-01

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

  2. Prognostic Significance of Imaging Myocardial Sympathetic Innervation.

    PubMed

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

    2015-08-01

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

  3. Adverse possession of subsurface minerals

    SciTech Connect

    Bowles, P.N.

    1983-01-01

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

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

    PubMed

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

    2016-08-01

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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Prognostic factors in lupus nephritis.

    PubMed

    Mok, C C

    2005-01-01

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

  10. Critical Assessment of Clinical Prognostic Tools in Melanoma.

    PubMed

    Mahar, Alyson L; Compton, Carolyn; Halabi, Susan; Hess, Kenneth R; Gershenwald, Jeffrey E; Scolyer, Richard A; Groome, Patti A

    2016-09-01

    The 7th edition American Joint Committee on Cancer (AJCC) melanoma staging system classifies patients according to prognosis. Significant within-stage heterogeneity remains and the inclusion of additional clinicopathologic and other host- and tumor-based prognostic factors have been proposed. Clinical prognostic tools have been developed for use in clinical practice to refine survival estimates. Little is known about the comparative features of tools in melanoma. We performed a systematic search of the scientific published literature for clinical prognostic tools in melanoma and web-based resources. A priori criteria were used to evaluate their quality and clinical relevance, and included intended clinical use, model development approaches, validation strategies, and performance metrics. We identified 17 clinical prognostic tools for primary cutaneous melanoma. Patients with stages I-III and T1 or thin melanoma were the most frequently considered populations. Seventy-five percent of tools were developed using data collected from patients diagnosed in 2006 or earlier, and the well-established factors of tumor thickness, ulceration, and age were included in 70 % of tools. Internal validity using cross-validation or bootstrapping techniques was performed for two tools only. Fewer than half were evaluated for external validity; however, when done, the appropriate statistical methodology was applied and results indicated good generalizability. Several clinical prognostic tools have the potential to refine survival estimates for individual melanoma patients; however, there is a great opportunity to improve these tools and to foster the development of new, validated tools by the inclusion of contemporary clinicopathological covariates and by using improved statistical and methodological approaches. PMID:27052645

  11. Prognostic factors in patients with intracerebral haematoma.

    PubMed Central

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

    1992-01-01

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

  12. 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.

  13. Adverse environments and children's creativity development: transforming the notion of "success in adversity" in China.

    PubMed

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications for China's future as it brings together one of China's core cultural values-"success in adversity"-the importance of creativity, and very real social and economic needs. "Success in adversity" reflects the strongly held belief that individuals who suffer adverse environments can rise to excellence and success through persistence, effort, and creativity. In this article, we briefly explore the historical sources of this belief and how it is closely related to the Chinese conception of creativity. We then present some studies on the creativity of some of China's migrant children. Findings show that while migrant children as a group may not generally exhibit higher creativity than their urban peers as hypothesized, indications of resilience and creative potential suggest that the notion of success in adversity may contribute to the positive development of China's migrant children more substantially when it is informed by research and augmented by research-supported policy. PMID:25732020

  14. 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.

  15. 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

  16. The Prognostic Impact of High On-Treatment Platelet Reactivity with Aspirin or ADP Receptor Antagonists: Systematic Review and Meta-Analysis

    PubMed Central

    D'Ascenzo, Fabrizio; Barbero, Umberto; Bisi, Marta; Moretti, Claudio; Omedè, Pierluigi; Cerrato, Enrico; Quadri, Giorgio; Zoccai, Giuseppe Biondi; DiNicolantonio, James J.; Gasparini, Mauro; Bangalore, Sripal; Gaita, Fiorenzo

    2014-01-01

    Objective. Negative results of recent randomized clinical trials testing the hypothesis of target therapy for patients with high on-treatment platelet reactivity (HOPR) have questioned its independent impact on clinical outcomes. 26 studies with 28.178 patients were included, with a median age of 66.8 (64–68) and 22.7% (22.4–27.8), of female gender. After a median follow-up of 1 year (0.1–1), cardiac adverse events occurred in 8.3% (3–11; all results are reported as median and interquartile range) of patients. Pooling all studies together, on-treatment platelet reactivity significantly increased the risk of adverse events (OR 1.33 [1.09, 1.64], I2 = 0%). However, a sensitivity analysis showed that HOPR did not increase the risk of adverse events for patients with ACS, AMI, or stable angina as well as patients resistant to aspirin, ADP antagonists, or both. For all studies, publication bias was formally evident; after adjusting for this, HOPR did not significantly increase adverse cardiac events (OR 1.1 : 0.89–1.22, I2 0%). Conclusions. After adjusting for clinical confounders (like risk factors and clinical presentation) and for relevant publication bias, HOPR was not an independent prognostic indicator in unselected patients with both stable and unstable coronary disease for an adverse cardiac event. The clinical importance of HOPR for high-risk populations remains to be assessed. PMID:25374889

  17. Pan-cancer analysis of intratumor heterogeneity as a prognostic determinant of survival

    PubMed Central

    Desrichard, Alexis; Şenbabaoğlu, Yasin; Hakimi, A. Ari; Makarov, Vladimir; Reis-Filho, Jorge S.; Chan, Timothy A.

    2016-01-01

    As tumors accumulate genetic alterations, an evolutionary process occurs in which genetically distinct subclonal populations of cells co-exist, resulting in intratumor genetic heterogeneity (ITH). The clinical implications of ITH remain poorly defined. Data are limited with respect to whether ITH is an independent determinant of patient survival outcomes, across different cancer types. Here, we report the results of a pan-cancer analysis of over 3300 tumors, showing a varied landscape of ITH across 9 cancer types. While some gene mutations are subclonal, the majority of driver gene mutations are clonal events, present in nearly all cancer cells. Strikingly, high levels of ITH are associated with poorer survival across diverse types of cancer. The adverse impact of high ITH is independent of other clinical, pathologic and molecular factors. High ITH tends to be associated with lower levels of tumor-infiltrating immune cells, but this association is not able to explain the observed survival differences. Together, these data show that ITH is a prognostic marker in multiple cancers. These results illuminate the natural history of cancer evolution, indicating that tumor heterogeneity represents a significant obstacle to cancer control. PMID:26840267

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2015-10-01

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

  20. Biologics in dermatology: adverse effects.

    PubMed

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

    2015-12-01

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

  1. 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.

  2. Peri-operative adverse respiratory events in children.

    PubMed

    von Ungern-Sternberg, B S; Ramgolam, A; Hall, G L; Sly, P D; Habre, W

    2015-04-01

    Three quarters of all critical incidents and a third of all peri-operative cardiac arrests in paediatric anaesthesia are caused by adverse respiratory events. We screened for risk factors from children's and their families' histories, and assessed the usefulness of common markers of allergic sensitisation of the airway as surrogates for airway inflammation and increased risk for adverse respiratory events. One hundred children aged up to 16 years with two or more risk factors undergoing elective surgery were included in the study. Eosinophil counts, IgE level, specific IgE for D. pteronyssinus, cat epithelia and Gx2 (grass pollen) were measured for each child and adverse respiratory events (bronchospasm, laryngospasm, oxygen desaturation < 95%, severe persistent coughing, airway obstruction and postoperative stridor) were recorded. Twenty-one patients had an adverse respiratory event but allergic markers were poor predictors. Binary logistic regression showed a lack of predictive value of the eosinophil range and adverse respiratory events (p = 0.249). Receiver operating characteristic (ROC) curves for the presence of adverse respiratory events vs level of specific IgE antibody (to Gx2 (AUC 0.614), cat epithelia (0.564) and D. pteronyssinus (0.520)) demonstrated poor predictive values. However, the presence of risk factors was strongly associated with adverse respiratory events (p < 0.001) and a ROC-curve analysis indicated a fair capacity to predict adverse respiratory events (AUC 0.788). There was a significant difference (p = 0.001) between the presence of adverse respiratory events in patients with more than four (p = 0.006), compared with less than four (p = 0.001), risk factors. We conclude that while risk factors taken from the child's (or family) history proved good predictors of adverse respiratory events, immunological markers of allergic sensitisation demonstrated low predictive values. Pre-operative identification of children at high risk for an adverse

  3. 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. PMID:24011493

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

    PubMed

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

    2014-10-01

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

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

    SciTech Connect

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

    1983-10-01

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

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

    SciTech Connect

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

    1983-10-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Adversity and advancing nursing knowledge.

    PubMed

    Reed, Pamela G

    2008-04-01

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

  9. 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…

  10. 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

  11. 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

  12. Prognostic factors in histiocytosis X.

    PubMed

    Lahey, M E

    1981-01-01

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

  13. 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

  14. The demographic features, clinicopathologic characteristics, treatment outcome and disease-specific prognostic factors of solitary fibrous tumor: a population-based analysis

    PubMed Central

    Wushou, Alimujiang; Jiang, Yi-Zhou; Liu, Yi-Rong; Shao, Zhi-Ming

    2015-01-01

    Background Solitary fibrous tumor's (SFT) demographic features, clinicopathologic characteristics, treatment outcome and disease-specific prognostic factors were unexplored comprehensively. Methods SEER program was used to identify patients diagnosed with SFT from 1973 to 2012. Overall collected data were analyzed by using the SPSS 18.0. Results In total, 804 cases were found including 613 cases with SFT-specific mortality and 801 patients were analyzed for overall survival (OS). The 3-year disease specific survival (DSS), 5-year DSS and 10-year DSS were 73.3%, 65.7% and 53.3%. The 3-year OS, 5-year OS and 10-year OS were 71.9%, 63.3% and 47.3%. In the multivariate survival analysis, the age > 51 years (hazard ratio [HR] = 1.851 for DSS, P = 0.024 and HR = 1.652 for OS, P = 0.033; Reference [Ref] ≤ 51 years for DSS and ≤ 53 years for OS), SEER stage metastasized tumor (HR = 4.269 for DSS, P = 0.000 and HR = 2.905 for OS, P = 0.028, Ref - localized + regional tumor), pathologic grade III + IV (HR = 2.734 for DSS, P = 0.001 and HR = 2.585 for OS, P = 0.000, Ref - grade I + II) were adversely associated with DSS and OS. In addition, surgery was favorably associated with DSS (HR = 0.217, P = 0.045, Ref - surgery + radiotherapy). Conclusions The surgery was an independent prognostic factor for DSS. The patient's age, SEER stage and pathologic grade were SFT-specific independent prognostic indicators for DSS and OS. PMID:26496033

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

    PubMed Central

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

    2015-01-01

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

  16. 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.

  17. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

    PubMed

    Soukavong, Mick; Kim, Jungmee; Park, Kyounghoon; Yang, Bo Ram; Lee, Joongyub; Jin, Xue Mei; Park, Byung Joo

    2016-09-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  18. 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

  19. CMR Quantification of Myocardial Scar Provides Additive Prognostic Information in Nonischemic Cardiomyopathy

    PubMed Central

    Neilan, Tomas G.; Coelho-Filho, Otavio R.; Danik, Stephan B.; Shah, Ravi V.; Dodson, John A.; Verdini, Daniel J.; Tokuda, Michifumi; Daly, Caroline A.; Tedrow, Usha B.; Stevenson, William G.; Jerosch-Herold, Michael; Ghoshhajra, Brian B.; Kwong, Raymond Y.

    2014-01-01

    OBJECTIVES This study sought to determine whether the extent of late gadolinium enhancement (LGE) can provide additive prognostic information in patients with a nonischemic dilated cardiomyopathy (NIDC) with an indication for implantable cardioverter-defibrillator (ICD) therapy for the primary prevention of sudden cardiac death (SCD). BACKGROUND Data suggest that the presence of LGE is a strong discriminator of events in patients with NIDC. Limited data exist on the role of LGE quantification. METHODS The extent of LGE and clinical follow-up were assessed in 162 patients with NIDC prior to ICD insertion for primary prevention of SCD. LGE extent was quantified using both the standard deviation–based (2-SD) method and the full-width half-maximum (FWHM) method. RESULTS We studied 162 patients with NIDC (65% male; mean age: 55 years; left ventricular ejection fraction [LVEF]: 26 ± 8%) and followed up for major adverse cardiac events (MACE), including cardiovascular death and appropriate ICD therapy, for a mean of 29 ± 18 months. Annual MACE rates were substantially higher in patients with LGE (24%) than in those without LGE (2%). By univariate association, the presence and the extent of LGE demonstrated the strongest associations with MACE (LGE presence, hazard ratio [HR]: 14.5 [95% confidence interval (CI): 6.1 to 32.6; p < 0.001]; LGE extent, HR: 1.15 per 1% increase in volume of LGE [95% CI: 1.12 to 1.18; p < 0.0001]). Multivariate analyses showed that LGE extent was the strongest predictor in the best overall model for MACE, and a 7-fold hazard was observed per 10% LGE extent after adjustments for patient age, sex, and LVEF (adjusted HR: 7.61; p < 0.0001). LGE quantitation by 2-SD and FWHM both demonstrated robust prognostic association, with the highest MACE rate observed in patients with LGE involving >6.1% of LV myocardium. CONCLUSIONS LGE extent may provide further risk stratification in patients with NIDC with a current indication for ICD implantation for

  20. Cardiovascular adverse effects of phenytoin.

    PubMed

    Guldiken, B; Rémi, J; Noachtar, Soheyl

    2016-05-01

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

  1. [Adverse events of psychotropic drugs].

    PubMed

    Watanabe, Koichiro; Kikuchi, Toshiaki

    2014-01-01

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

  2. A prognostic gene expression signature in infratentorial ependymoma

    PubMed Central

    Wani, Khalida; Armstrong, Terri; 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; Aldape, Ken

    2013-01-01

    Patients with ependymoma exhibit a wide range of clinical outcomes that is currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggests 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. PMID:22322993

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

    PubMed Central

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

    2013-01-01

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

  4. Determinants and prognostic implications of Cardiac Troponin T measured by a sensitive assay in Type 2 Diabetes Mellitus

    PubMed Central

    2010-01-01

    Background The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. Methods cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if availabe (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). Results One-hundred thirteen (90 %) had detectable cTnT at baseline and of those, 22 (18 % of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r = 0.92, p > 0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p = 0.058). Conclusions Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found. PMID:20843304

  5. Prognostic Value of Basic Fibroblast Growth Factor (bFGF) in Lung Cancer: A Systematic Review with Meta-Analysis

    PubMed Central

    Hu, Mingming; Hu, Ying; He, Jiabei; Li, Baolan

    2016-01-01

    Background Basic fibroblast growth factor (bFGF) is known to stimulate angiogenesis and thus to influence the proliferation, migration and survival of tumor cells. Many studies examined the relationship between human bFGF overexpression and survival in lung cancer patients, but the results have been mixed. To systematically summarize the clinical prognostic function of bFGF in lung cancer, we performed this systematic review with meta-analysis. Method Studies were identified by an electronic search of PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang databases, including publications prior toAugust 2014. Pooled hazard ratios (HR) for overall survival (OS) were aggregated and quantitatively analyzed by meta-analysis. Results Twenty-two studies (n = 2154) were evaluated in the meta-analysis. Combined HR suggested that bFGF overexpression had an adverse impact on survival of patients with lung cancer(HR = 1.202,95%CI, 1.022–1.382). Our subgroup analysis revealed that the combined HR evaluating bFGF expression on OS in operable non-small cell lung cancer (NSCLC) was 1.553 (95%CI, 1.120–1.986); the combined HR in small cell lung cancer (SCLC) was 1.667 (95%CI, 1.035–2.299). There was no significant impact of bFGF expression on survival in advanced NSCLC. Conclusion This meta-analysis showed that bFGF overexpression is a potential indicator of worse prognosis for patients with operable NSCLC and SCLC, but is not associated with outcome in advanced NSCLC. The data suggests that high bFGF expression is highly related to poor prognosis. Nevertheless,more high-quality studies should be performed in order to provide additional evidence for the prognostic value of bFGF in lung cancer. PMID:26824699

  6. 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

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

    PubMed Central

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

    2016-01-01

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

  8. Adverse effects of spinal manipulation: a systematic review

    PubMed Central

    Ernst, E

    2007-01-01

    Objective To identify adverse effects of spinal manipulation. Design Systematic review of papers published since 2001. Setting Six electronic databases. Main outcome measures Reports of adverse effects published between January 2001 and June 2006. There were no restrictions according to language of publication or research design of the reports. Results The searches identified 32 case reports, four case series, two prospective series, three case-control studies and three surveys. In case reports or case series, more than 200 patients were suspected to have been seriously harmed. The most common serious adverse effects were due to vertebral artery dissections. The two prospective reports suggested that relatively mild adverse effects occur in 30% to 61% of all patients. The case-control studies suggested a causal relationship between spinal manipulation and the adverse effect. The survey data indicated that even serious adverse effects are rarely reported in the medical literature. Conclusions Spinal manipulation, particularly when performed on the upper spine, is frequently associated with mild to moderate adverse effects. It can also result in serious complications such as vertebral artery dissection followed by stroke. Currently, the incidence of such events is not known. In the interest of patient safety we should reconsider our policy towards the routine use of spinal manipulation. PMID:17606755

  9. Prognostic value of sarcopenia in liver surgery.

    PubMed

    Cornet, M; Lim, C; Salloum, C; Lazzati, A; Compagnon, P; Pascal, G; Azoulay, D

    2015-11-01

    Current knowledge indicates that malnutrition increases the rate of post-operative complications, particularly respiratory and infectious, after major surgery. Almost all liver surgery is performed in patients with cancer, a factor that increases the risk of malnutrition. The primary risk factors for post-operative complications are pre-operative hypo-albuminemia and a body mass index less than 20 kg/m(2). To improve the prediction of complications in these patients, some teams have suggested measurement of muscle thickness by computed tomography. Muscular mass can thus be quantified by measuring the total surface of the psoas muscle or the total surface of all muscles (i.e. external and internal oblique, transverse, psoas and paravertebral muscles) seen on an axial CT slice at L3. As well, data exist suggesting that sarcopenia is an independent predictive factor of post-operative morbidity and poor long-term survival after resection for cancer. Nonetheless, the literature on the subject is limited, there are no standardized definitions for sarcopenia, and the need of special software to calculate the surfaces limits its usefulness. Lastly, there are little if any data concerning the nutritional or pharmacologic means to treat sarcopenia. This update, based on a literature review, deals with the value and the prognostic impact of sarcopenia in surgery for liver tumors. The current definition of sarcopenia, validated internationally, the methods of measurement, and the consequences of sarcopenia on the outcome of liver resections are detailed in this review. PMID:26476674

  10. 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.

  11. 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.

  12. 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.

  13. Therapeutic apheresis in Sweden: update of epidemiology and adverse events.

    PubMed

    Norda, Rut; Stegmayr, Bernd G

    2003-10-01

    The indications of apheresis have changed over time due to results from various studies as well as the innovation of new techniques and ideas. To get an overview of the indications used for apheresis by colleagues elsewhere, data from registries are valuable. In addition, registries can be used for detection of severe adverse events as well as extent of adverse events in various types of treatment. To have a basis for statistical calculations, apheresis units need to be very large or centralisation of data needs to be performed. Data from more than 20000 procedures show that in about 4.3% of occasions adverse events and other problems will develop. Interruption of the procedure was done in 1%, most frequently a plasma exchange. Technical problems can be expected more frequent when performing LDL apheresis and immunoadsorption. Severe adverse events needing medication or interruption of the treatment, such as hypotension and arrhythmia, will develop in about 1% of the procedures. Such an episode occurs more often in patients with TTP/HUS and Guillain-Barré syndrome than in hypercholesterolemia, hyperviscosity syndrome or septic shock/MODS. The non-severe adverse events have increased over time. The results will provide focus in analyses for the reduction of such adverse events. PMID:12941356

  14. Detecting Adverse Events Using Information Technology

    PubMed Central

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

    2003-01-01

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

  15. Incidence and prognostic significance of atrial fibrillation in acute myocardial infarction: the GISSI-3 data

    PubMed Central

    Pizzetti, F; Turazza, F; Franzosi, M; Barlera, S; Ledda, A; Maggioni, A; Santoro, L; Tognoni, G

    2001-01-01

    BACKGROUND—Atrial fibrillation is the most common supraventricular arrhythmia in patients with acute myocardial infarction. Recent advances in pharmacological treatment of myocardial infarction may have changed the impact of this arrhythmia.
OBJECTIVE—To assess the incidence and prognosis of atrial fibrillation complicating myocardial infarction in a large population of patients receiving optimal treatment, including angiotensin converting enzyme (ACE) inhibitors.
METHODS—Data were derived from the GISSI-3 trial, which included 17 944 patients within the first 24 hours after acute myocardial infarction. Atrial fibrillation was recorded during the hospital stay, and follow up visits were planned at six weeks and six months. Survival of the patients at four years was assessed through census offices.
RESULTS—The incidence of in-hospital atrial fibrillation or flutter was 7.8%. Atrial fibrillation was associated with indicators of a worse prognosis (age > 70 years, female sex, higher Killip class, previous myocardial infarction, treated hypertension, high systolic blood pressure at entry, insulin dependent diabetes, signs or symptoms of heart failure) and with some adverse clinical events (reinfarction, sustained ventricular tachycardia, ventricular fibrillation). After adjustment for other prognostic factors, atrial fibrillation remained an independent predictor of increased in-hospital mortality: 12.6% v 5%, adjusted relative risk (RR) 1.98, 95% confidence interval (CI) 1.67 to 2.34. Data on long term mortality (four years after acute myocardial infarction) confirmed the persistent negative influence of atrial fibrillation (RR 1.78, 95% CI 1.60 to 1.99).
CONCLUSIONS—Atrial fibrillation is an indicator of worse prognosis after acute myocardial infarction, both in the short term and in the long term, even in an unselected population.


Keywords: atrial fibrillation; acute myocardial infarction; prognosis PMID:11602545

  16. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

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

  17. Adverse Effects of Electroconvulsive Therapy.

    PubMed

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

    2016-09-01

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

  18. Pharmacogenetics of idiosyncratic adverse drug reactions.

    PubMed

    Pirmohamed, Munir

    2010-01-01

    Idiosyncratic adverse drug reactions are unpredictable and thought to have an underlying genetic etiology. With the completion of the human genome and HapMap projects, together with the rapid advances in genotyping technologies, we have unprecedented capabilities in identifying genetic predisposing factors for these relatively rare, but serious, reactions. The main roadblock to this is the lack of sufficient numbers of well-characterized samples from patients with such reactions. This is now beginning to be solved through the formation of international consortia, including developing novel ways of identifying and recruiting patients affected by these reactions, both prospectively and retrospectively. This has been led by the research on abacavir hypersensitivity - its association with HLA-B*5701 forms the gold standard of how we need to identify associations and implement them in clinical practice. Strong genetic predisposing factors have also been identified for hypersensitivity reactions such as are associated with carbamazepine, allopurinol, flucloxacillin, and statin-induced myopathy. However, for most other idiosyncratic adverse drug reactions, the genetic effect sizes have been low to moderate, although this may partly be due to the fact that only small numbers have been investigated and limited genotyping strategies have been utilized. It may also indicate that genetic predisposition will be dependent on multiple genes, with complex interactions with environmental factors. Irrespective of the strength of the genetic associations identified with individual idiosyncratic adverse drug reactions, it is important to undertake functional investigations to provide insights into the mechanism(s) of how the drug interacts with the gene variant to lead to a phenotype, which can take a multitude of clinical forms with variable severity. Such investigations will be essential in preventing the burden caused by idiosyncratic reactions, both in healthcare and in industry

  19. Psychological Well-Being and the Human Conserved Transcriptional Response to Adversity

    PubMed Central

    Fredrickson, Barbara L.; Grewen, Karen M.; Algoe, Sara B.; Firestine, Ann M.; Arevalo, Jesusa M. G.; Ma, Jeffrey; Cole, Steve W.

    2015-01-01

    Research in human social genomics has identified a conserved transcriptional response to adversity (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of Type I interferon- and antibody-related genes. This report seeks to identify the specific aspects of positive psychological well-being that oppose such effects and predict reduced CTRA gene expression. In a new confirmation study of 122 healthy adults that replicated the approach of a previously reported discovery study, mixed effect linear model analyses identified a significant inverse association between expression of CTRA indicator genes and a summary measure of eudaimonic well-being from the Mental Health Continuum – Short Form. Analyses of a 2- representation of eudaimonia converged in finding correlated psychological and social subdomains of eudaimonic well-being to be the primary carriers of CTRA associations. Hedonic well-being showed no consistent CTRA association independent of eudaimonic well-being, and summary measures integrating hedonic and eudaimonic well-being showed less stable CTRA associations than did focal measures of eudaimonia (psychological and social well-being). Similar results emerged from analyses of pooled discovery and confirmation samples (n = 198). Similar results also emerged from analyses of a second new generalization study of 107 healthy adults that included the more detailed Ryff Scales of Psychological Well-being and found this more robust measure of eudaimonic well-being to also associate with reduced CTRA gene expression. Five of the 6 major sub-domains of psychological well-being predicted reduced CTRA gene expression when analyzed separately, and 3 remained distinctively prognostic in mutually adjusted analyses. All associations were independent of demographic characteristics, health-related confounders, and RNA indicators of leukocyte subset distribution. These results identify specific sub-dimensions of eudaimonic

  20. Psychological well-being and the human conserved transcriptional response to adversity.

    PubMed

    Fredrickson, Barbara L; Grewen, Karen M; Algoe, Sara B; Firestine, Ann M; Arevalo, Jesusa M G; Ma, Jeffrey; Cole, Steve W

    2015-01-01

    Research in human social genomics has identified a conserved transcriptional response to adversity (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of Type I interferon- and antibody-related genes. This report seeks to identify the specific aspects of positive psychological well-being that oppose such effects and predict reduced CTRA gene expression. In a new confirmation study of 122 healthy adults that replicated the approach of a previously reported discovery study, mixed effect linear model analyses identified a significant inverse association between expression of CTRA indicator genes and a summary measure of eudaimonic well-being from the Mental Health Continuum - Short Form. Analyses of a 2- representation of eudaimonia converged in finding correlated psychological and social subdomains of eudaimonic well-being to be the primary carriers of CTRA associations. Hedonic well-being showed no consistent CTRA association independent of eudaimonic well-being, and summary measures integrating hedonic and eudaimonic well-being showed less stable CTRA associations than did focal measures of eudaimonia (psychological and social well-being). Similar results emerged from analyses of pooled discovery and confirmation samples (n = 198). Similar results also emerged from analyses of a second new generalization study of 107 healthy adults that included the more detailed Ryff Scales of Psychological Well-being and found this more robust measure of eudaimonic well-being to also associate with reduced CTRA gene expression. Five of the 6 major sub-domains of psychological well-being predicted reduced CTRA gene expression when analyzed separately, and 3 remained distinctively prognostic in mutually adjusted analyses. All associations were independent of demographic characteristics, health-related confounders, and RNA indicators of leukocyte subset distribution. These results identify specific sub-dimensions of eudaimonic well

  1. 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

  2. Prognostic Disclosures to Children: A Historical Perspective.

    PubMed

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

    2016-09-01

    Prognostic disclosure to children has perpetually challenged clinicians and parents. In this article, we review the historical literature on prognostic disclosure to children in the United States using cancer as an illness model. Before 1948, there was virtually no literature focused on prognostic disclosure to children. As articles began to be published in the 1950s and 1960s, many clinicians and researchers initially recommended a "protective" approach to disclosure, where children were shielded from the harms of bad news. We identified 4 main arguments in the literature at this time supporting this "protective" approach. By the late 1960s, however, a growing number of clinicians and researchers were recommending a more "open" approach, where children were included in discussions of diagnosis, which at the time was often synonymous with a terminal prognosis. Four different arguments in the literature were used at this time supporting this "open" approach. Then, by the late 1980s, the recommended approach to prognostic disclosure in pediatrics shifted largely from "never tell" to "always tell." In recent years, however, there has been a growing appreciation for the complexity of prognostic disclosure in pediatrics. Current understanding of pediatric disclosure does not lead to simple "black-and-white" recommendations for disclosure practices. As with most difficult questions, we are left to balance competing factors on a case-by-case basis. We highlight 4 categories of current considerations related to prognostic disclosure in pediatrics, and we offer several approaches to prognostic disclosure for clinicians who care for these young patients and their families. PMID:27561728

  3. Adverse drug reactions in dermatology.

    PubMed

    Ferner, R E

    2015-03-01

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

  4. [Recipients adverse reactions: guidance supports].

    PubMed

    Bazin, A

    2010-12-01

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

  5. Adverse effects of plasma transfusion.

    PubMed

    Pandey, Suchitra; Vyas, Girish N

    2012-05-01

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

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

    PubMed

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

    2016-05-01

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

  7. Adverse Outcome Pathway Development II: Best Practices

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of “functional equivalence” can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  8. "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)

  9. RBC indices

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003648.htm RBC indices To use the sharing features on this page, please enable JavaScript. Red blood cell (RBC) indices are part of the complete blood count ( ...

  10. Prognostic DNA Methylation Markers for Prostate Cancer

    PubMed Central

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

    2014-01-01

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

  11. Prognostic DNA methylation markers for prostate cancer.

    PubMed

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

    2014-01-01

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

  12. 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

  13. 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.

  14. 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

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

    PubMed

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

    2004-05-15

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

  16. Adverse Childhood Experiences and Adult Smoking, Nebraska, 2011

    PubMed Central

    Safranek, Thomas; Buss, Bryan; Cadwell, Betsy L.; Mannino, David

    2013-01-01

    Introduction Smoking is a public health risk; the prevalence of smoking among adults in Nebraska is 18.4%. Studies indicate that maltreatment of children alters their brain development, possibly increasing risk for tobacco use. Previous studies have documented associations between childhood maltreatment and adult health behaviors, demonstrating the influence of adverse experiences on tobacco use. We examined prevalence and associations between adverse childhood experiences and smoking among Nebraskans. Methods We analyzed 2011 Nebraska Behavioral Risk Factor Surveillance System (Adverse Childhood Experience module) data, defining adverse childhood experience exposures as physical, sexual, and verbal abuse (ie, direct exposures), and household dysfunction associated with mental illness, substance abuse, divorce, domestic violence, and living with persons with incarceration histories (ie, environmental exposures). We estimated prevalence of exposures, taking into account the complex survey design. We used logistic regression with predicted margins to estimate adjusted relative risk for smoking by direct or environmental exposure. Results Approximately 51% of Nebraskans experienced 1 or more adverse childhood events; 7% experienced 5 or more. Prevalence of environmental exposures (42%) was significantly higher than that of direct exposures (31%). Prevalence of individual exposures ranged from 6% (incarceration of a household member) to 25% (verbal abuse). Adjusted relative risks of smoking for direct and environmental exposures were 1.5 and 1.8, respectively. Conclusion We present a new method of evaluating adverse childhood experience data. Prevalence of adverse childhood experiences is high among Nebraskans, and these exposures are associated with smoking. State-specific strategies to monitor adverse events among children and provide interventions might help to decrease the smoking rate in this population. PMID:24050529

  17. Fiber optics in adverse environments

    SciTech Connect

    Lyous, P.B.

    1982-01-01

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

  18. Current evidence for therapeutic interventions and prognostic factors in polymyalgia rheumatica: a systematic literature review informing the 2015 European League Against Rheumatism/American College of Rheumatology recommendations for the management of polymyalgia rheumatica.

    PubMed

    Dejaco, Christian; Singh, Yogesh P; Perel, Pablo; Hutchings, Andrew; Camellino, Dario; Mackie, Sarah; Matteson, Eric L; Dasgupta, Bhaskar

    2015-10-01

    To summarise evidence on therapeutic interventions and prognostic factors in polymyalgia rheumatica (PMR). A systematic literature review was conducted using Ovid Medline, Embase, PubMed, CINAHL, Web of Science and the Cochrane Library (1970 through April 2014). Quality of evidence (QoE) of identified studies was appraised by Grading of Recommendations Assessment, Development and Evaluation (GRADE) (interventions) and the Quality In Prognosis Studies (QUIPS) methodologies (prognostic factors). Out of 10 931 titles identified, 52 articles were finally selected. A single study indicated that an initial prednisone dose of 20 mg/day is associated with a lower short-term relapse rate than 10 mg/day but at the cost of a higher rate of adverse events. Another study suggested a comparable efficacy of intramuscular methylprednisolone and oral glucocorticoids (GCs) with lower cumulative GC doses and less weight gain in the former group. Moderate to high QoE (1-2 studies) indicated a benefit of methotrexate in remission rates and cumulative GC doses in early PMR. Anti-tumour necrosis factor α agents are ineffective for PMR treatment. Among prognostic factors, female sex, high erythrocyte sedimentation rate (ESR) and peripheral arthritis were associated in some studies with a higher relapse risk. Women and patients with high ESR also appeared to have a longer duration of treatment. Several studies of varying quality, however, failed to prove these associations. In PMR, evidence for initial GC doses and subsequent tapering regimens is limited. Intramuscular methylprednisolone and methotrexate may be effective GC sparing agents. Female sex, high ESR and peripheral arthritis at disease outset are potential risk factors for a worse prognosis. PMID:26359489

  19. Adverse events in healthcare: learning from mistakes.

    PubMed

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

    2015-04-01

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

  20. Correlations Between Apoptotic and Proliferative Indices in Malignant Non-Hodgkin's Lymphomas

    PubMed Central

    Leoncini, Lorenzo; Del Vecchio, Maria Teresa; Megha, Tiziana; Barbini, Paolo; Galieni, Piero; Pileri, Stefano; Sabattini, Elena; Gherlinzoni, Filippo; Tosi, Piero; Kraft, Rainer; Cottier, Hans

    1993-01-01

    Cell Production versus cell loss rates were estimated, across the boundaries of histological classification, in 50 cases of malignant non-Hodgkin's lymphomas by use of mitotic indices, percentage of Ki-67+ cells and percentage of PC10+ cells as proliferative indices, and the relative number of apoptotic bodies (apoptotic indices, AIs) as parameters. Regression analysis revealed significant (P < 0.01) positive correlations between the AIs and the proliferative indices; among the immunohistochemically assessed proliferative indices; and between these, the mitotic indices and the AIs on the one band and histological malignancy grades on the other band. The Cellular protein BCL-2, which counteracts apoptosis, was significantly (p < 0.01) more often expressed in lymphomas with low than in those with high AIs. Multivariate analysis of data showed that of all parameters tested in this series, only the AIs correlated significantly (P < 0.05) with overall lethality. The correlation between BCL-2 positivity of lymphoma cells and overall survival did not quite attain significance (P = 0.08). Results of the present study suggest that high AIs and lack of BCL-2 expression may be adverse prognostic factors, independent of histological grade. ImagesFigure 1 PMID:7681257

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

    MedlinePlus

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

  2. A new prognostic score based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer

    PubMed Central

    Zhu, Lizhen; Li, Xiaofen; Shen, Yanwei; Cao, Ying; Fang, Xuefeng; Chen, Jiaqi; Yuan, Ying

    2016-01-01

    Purpose Pretreatment systemic inflammatory response has been confirmed to have prognostic value in patients with inoperable non-small-cell lung cancer (NSCLC). Increasing studies show that the modified Glasgow prognostic score (mGPS), a prognostic score based on C-reactive protein (CRP) and albumin, is a prognostic factor in these patients. This study was aimed at recognizing possible prognostic factors and new prognostic scores of inoperable NSCLC based on pretreatment systemic inflammatory response. Patients and methods We retrospectively reviewed the clinicopathological data of 105 patients with inoperable NSCLC who received first-line chemotherapy as initial treatment. Univariate and multivariate analyses of progression-free survival (PFS) and overall survival (OS) for prognostic factors and scores were performed. Results The serum CRP, lactate dehydrogenase (LDH), cancer antigen 125 (CA125), and pathological type were independent pretreatment prognostic factors for PFS and OS. A new score was assembled by CRP, LDH, and CA125. In multivariate analysis, when the mGPS and the new score were covariates, only the new score retained independent prognostic value for both PFS (P<0.001; hazard ratio =2.12; 95% confidence interval: 1.60–2.82) and OS (P<0.001; hazard ratio =1.82; 95% confidence interval: 1.33–2.48). Conclusion The new score based on pretreatment serum level of CRP, LDH, and CA125, indicates the prognosis of both PFS and OS in patients with inoperable NSCLC who were treated with first-line systemic chemotherapy, and it was found to be more effective than mGPS. PMID:27540301

  3. 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…

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

    PubMed

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

    2014-10-01

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

  5. 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.; Pitman, Stan G.; Tucker, Joseph C.; Prowant, Matthew S.; Suter, Jonathan D.

    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.

  6. Anhedonia Predicts Major Adverse Cardiac Events and Mortality in Patients 1 Year After Acute Coronary Syndrome

    PubMed Central

    Davidson, Karina W.; Burg, Matthew M.; Kronish, Ian M.; Shimbo, Daichi; Dettenborn, Lucia; Mehran, Roxana; Vorchheimer, David; Clemow, Lynn; Schwartz, Joseph E.; Lespérance, Francois; Rieckmann, Nina

    2010-01-01

    Context Depression is a consistent predictor of recurrent events and mortality in ACS patients, but it has 2 core diagnostic criteria with distinct biological correlates—depressed mood and anhedonia. Objective To determine if depressed mood and/or anhedonia (loss of pleasure or interest) predict 1-year medical outcomes for patients with Acute Coronary Syndrome (ACS). Design Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within one week of admission, patients underwent a structured psychiatric interview to assess clinically impairing depressed mood, anhedonia, and major depressive episode (MDE); also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity. Setting Coronary care and cardiac care step-down units of 3 university hospitals in New York and Connecticut. Participants Consecutive sample of 453 ACS patients (aged 25–93 years; 42% women). Main Outcomes Measures All-cause mortality (ACM) and documented major adverse cardiac events (MACE; myocardial infarction, hospitalization for unstable angina, or urgent revascularization) were actively surveyed for 1 year after admission. Results There were 67 events (16 deaths and 51 MACE; 14.8%). 108 (24%) and 77 (17%) patients with anhedonia and depressed mood, respectively. After controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16–2.14; P<.01) and MDE (adjusted hazard ratio, 1.48; 95% confidence interval, 1.07–2.04; P=.02) were significant predictors of combined MACE/ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes controlling for MDE diagnosis and depressive symptom severity, each of which were no longer significant. Conclusions Anhedonia identifies risk for MACE/ACM beyond that of established medical prognostic indicators

  7. Development and validation of a prognostic scale for use in patients with advanced cancer.

    PubMed

    Stone, P; Kelly, L; Head, R; White, S

    2008-09-01

    The aim of this study was to develop a new prognostic indicator to help predict survival in advanced cancer patients more accurately. Data on 329 patients obtained from a multi-centre study in London were analysed. A multifactorial Cox regression model was applied and validated using bootstrapping techniques. Predictive scores were calculated and used to produce a new prognostic index. The value of the index in predicting 14-day survival was then assessed. Four variables were found to be associated with worse survival: primary lung cancer, secondary liver cancer, raised C-Reactive protein and poor performance status (ECOG 4). Survival curves showed that patients designated as 'high' risk by the resulting index had significantly shorter survival than those designated as 'low' risk. A high score on the newly derived prognostic index is associated with poorer survival, but its clinical utility is limited by the relatively low predictive probability of the score. PMID:18715969

  8. 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

  9. Prognostic factors in early-stage ovarian cancer.

    PubMed

    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

  10. Prognostic value of left ventricular diastolic function and association with heart rate variability after a first acute myocardial infarction

    PubMed Central

    Poulsen, S; Jensen, S; Moller, J; Egstrup, K

    2001-01-01

    OBJECTIVE—To study the prognostic value of left ventricular (LV) diastolic function and its relation with autonomic balance expressed by heart rate variability (HRV) in patients after a first acute myocardial infarction.
DESIGN—The study population consisted of 64 consecutive patients with first acute myocardial infarction and 31 control subjects. Long and short term HRV indices were evaluated by 24 hour Holter monitoring, and LV systolic and diastolic function were assessed by two dimensional and Doppler echocardiography before discharge. Patients were divided into two groups: those with restrictive LV filling characteristics (deceleration time ⩽ 140 ms) and those with non-restrictive LV filling characteristics (deceleration time > 140 ms).
RESULTS—Both long and short term HRV indices were significantly reduced in patients with restrictive LV filling compared with the non-restrictive group and control subjects. Mitral deceleration time and isovolumetric relaxation time correlated weakly but significantly with all indices of HRV whereas ejection fraction correlated weakly with the long term HRV indices. The mean follow up time was 14.9 (8.7) months. Multivariate analysis showed that mitral deceleration time (χ2 = 6.4, p < 0.001) and ejection fraction ⩽ 40% (χ2 = 4.4, p < 0.05) were independent predictors of cardiac death and readmission to hospital with congestive heart failure.
CONCLUSIONS—A restrictive LV filling pattern was found to be the strongest predictor of adverse outcome independent of HRV and ejection fraction during follow up after a first acute myocardial infarction. Patients with restrictive LV filling characteristics had more reduced HRV than those with non-restrictive diastolic filling.


Keywords: diastole; infarction; autonomic balance PMID:11559672

  11. RBC indices

    MedlinePlus

    ... corpuscular hemoglobin concentration (MCHC); Mean corpuscular volume (MCV); Red blood cell indices ... and hemoglobin. The MCV reflects the size of red blood cells. The MCH and MCHC reflect the ...

  12. 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.

  13. 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.

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

    PubMed Central

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

    2015-01-01

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

  15. 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

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

    PubMed Central

    2012-01-01

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

  17. The Biochemical Prognostic Factors of Subclinical Hypothyroidism

    PubMed Central

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

    2014-01-01

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

  18. 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. PMID:27100471

  19. Severe cutaneous adverse drug reactions.

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. 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

  2. Position indicator

    DOEpatents

    Tanner, David E.

    1981-01-01

    A nuclear reactor system is described in which a position indicator is provided for detecting and indicating the position of a movable element inside a pressure vessel. The movable element may be a valve element or similar device which moves about an axis. Light from a light source is transmitted from a source outside the pressure vessel to a first region inside the pressure vessel in alignment with the axis of the movable element. The light is redirected by a reflector prism to a second region displaced radially from the first region. The reflector prism moves in response to movement of the movable element about its axis such that the second region moves arcuately with respect to the first region. Sensors are arrayed in an arc corresponding to the arc of movement of the second region and signals are transmitted from the sensors to the exterior of the reactor vessel to provide indication of the position of the movable element.

  3. Prognostic values of aldehyde dehydrogenase 1 isoenzymes in ovarian cancer

    PubMed Central

    Ma, Yu-mei; Zhao, Shan

    2016-01-01

    Aldehyde dehydrogenase 1 (ALDH1) activity has been used as a functional stem cell marker to isolate cancer stem cells in different cancer types, including ovarian cancer. However, which ALDH1’s isoenzymes are contributing to ALDH1 activity in ovarian cancer remains elusive. In addition, the prognostic value of an individual ALDH1 isoenzyme in ovarian cancer is not clear. Thus, we accessed the prognostic value of ALDH1 isoenzymes in ovarian cancer patients through the “Kaplan–Meier plotter” online database, which can be used to determine the effect of the genes on ovarian cancer prognosis. We found that high mRNA expression of five ALDH1 isoenzymes, such as ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, and ALDH1L1, was not correlated with overall survival (OS) for all 1,306 ovarian cancer patients. In addition, all five of the ALDH1 isoenzymes’ high mRNA expression was found to be uncorrelated with OS in serous cancer or endometrioid cancer patients. However, ALDH1A3’s high mRNA expression is associated with worse OS in grade II ovarian cancer patients, hazard ratio (HR) 1.53 (1.14–2.07), P=0.005. ALDH1A2’s high mRNA expression is significantly associated with worse OS in TP53 wild-type ovarian cancer patients, HR 2.86 (1.56–5.08), P=0.00036. In addition, ALDH1A3’s high mRNA expression is significantly associated with better OS in TP53 wild-type ovarian cancer patients, HR 0.56 (0.32–1.00), P=0.04. Our results indicate that although ALDH1 isoenzyme mRNA might not be a prognostic marker for overall ovarian cancer patients, some isoenzymes, such as ALDH1A2 and ALDH1A3, might be a good prognostic marker for some types of ovarian cancer patients. PMID:27110126

  4. 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.

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

    PubMed

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

    2016-02-01

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

  6. SEMA6A is a prognostic biomarker in glioblastoma.

    PubMed

    Zhao, Jiaxin; Tang, Haitao; Zhao, Hong; Che, Wanli; Zhang, Lei; Liang, Peng

    2015-11-01

    Glioblastoma multiforme (GBM) is one of the most aggressive tumors in the central nervous system. SEMA6A, the first identified class 6 semaphorin, is contributed to regulate vascular development and adult angiogenesis. However, the function of SEMA6A in GBM is still undefined. In the present study, we investigated the expression of SEMA6A protein in 200 GBM tissues using immunohistochemistry (IHC). SEMA6A expression was associated with time to progression (P = 0.001) and mean tumor diameter (P = 0.038). Kaplan-Meier analysis revealed that patients expressing high SEMA6A protein levels had a significantly longer overall survival (OS, P = 0.013) and progression-free survival (PFS, P = 0.005) compared to those with low SEMA6A expression level. Cox multivariate regression analysis confirmed that low SEMA6A expression was an independent unfavorable prognostic factors for PFS (HR, 1.896; 95% CI, 1.147-2.768; P = 0.009) and OS (HR, 1.712; 95% CI, 1.011-2.657; P = 0.012). Furthermore, in vitro experiments showed that SEMA6A could inhibit proliferation, migration, and invasion in different glioma cell lines. In conclusion, our findings indicated that SEMA6A may be a potential prognostic biomarker in the treatment of GBM. PMID:26014517

  7. Cutaneous malignant melanoma: update on diagnostic and prognostic biomarkers.

    PubMed

    Abbas, Ossama; Miller, Daniel D; Bhawan, Jag

    2014-05-01

    The incidence of cutaneous malignant melanoma has rapidly increased in recent years in all parts of the world, and melanoma is a leading cause of cancer death. As even relatively small melanomas may have metastatic potential, accurate assessment of progression is critical. Although diagnosis of cutaneous malignant melanoma is usually based on histopathologic criteria, these criteria may at times be inadequate in differentiating melanoma from certain types of benign nevi. As for prognosis, tumor (Breslow) thickness, mitotic rate, and ulceration have been considered the most important prognostic indicators among histopathologic criteria. However, there are cases of thin primary melanomas that have ultimately developed metastases despite complete excision. Given this, an accurate assessment of melanoma progression is critical, and development of molecular biomarkers that identify high-risk melanoma in its early phase is urgently needed. Large-scale genomic profiling has identified considerable heterogeneity in melanoma and suggests subgrouping of tumors by patterns of gene expression and mutation will ultimately be essential to accurate staging. This subgrouping in turn may allow for more targeted therapy. In this review, we aim to provide an update on the most promising new biomarkers that may help in the identification and prognostication of melanoma. PMID:24803061

  8. [Acute adverse effects of dialysis].

    PubMed

    Opatrný, K

    2003-02-01

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

  9. Prognostic factors in primary cutaneous lymphomas other than mycosis fungoides and the Sézary syndrome. The French Study Group on Cutaneous Lymphomas.

    PubMed

    Grange, F; Hedelin, G; Joly, P; Beylot-Barry, M; D'Incan, M; Delaunay, M; Vaillant, L; Avril, M F; Bosq, J; Wechsler, J; Dalac, S; Grosieux, C; Franck, N; Esteve, E; Michel, C; Bodemer, C; Vergier, B; Laroche, L; Bagot, M

    1999-06-01

    Prognostic studies of primary cutaneous lymphomas (PCL) other than mycosis fungoides (MF) and the Sézary syndrome (SS; non-MF/SS PCL) have been mainly performed on subgroups or on small numbers of patients by using univariate analyses. Our aim was to identify independent prognostic factors in a large series of patients with non-MF/SS PCL. We evaluated 158 patients who were registered in the French Study Group on Cutaneous Lymphomas database from January 1, 1986 to March 1, 1997. Variables analyzed for prognostic value were: age; sex; type of clinical lesions; maximum diameter, location, and number of skin lesions; cutaneous distribution (ie, local, regional, or generalized); prognostic group according to the European Organization for Research and Treatment of Cancer (EORTC) classification for PCL; B- or T-cell phenotype; serum lactate dehydrogenase (LDH) level; and B symptoms. Univariate and multivariate analyses were performed using a model of relative survival. Forty-nine patients (31%) died. The median relative survival time was 81 months. In univariate analysis, EORTC prognostic group, serum LDH level, B symptoms, and variables related to tumor extension (ie, distribution, maximum diameter, and number of skin lesions) were significantly associated with survival. When these variables were considered together in a multivariate analysis, EORTC prognostic group and distribution of skin lesions remained statistically significant, independent prognostic factors. This study confirms the good predictive value of the EORTC classification for PCL and shows that the distribution of skin lesions at initial evaluation is an important prognostic indicator. PMID:10339469

  10. Bone Scan Index as a prognostic imaging biomarker during androgen deprivation therapy

    PubMed Central

    2014-01-01

    Background Bone Scan Index (BSI) is a quantitative measurement of tumour burden in the skeleton calculated from bone scan images. When analysed at the time of diagnosis, it has been shown to provide prognostic information on survival in men with metastatic prostate cancer (PCa). In this study, we evaluated the prognostic value of BSI during androgen deprivation therapy (ADT). Methods Prostate cancer patients who were at high risk of a poor outcome and who had undergone bone scan at the time of diagnosis and during ADT were recruited from two university hospitals for a retrospective study. BSI at baseline and follow-up were calculated using an automated software package (EXINIbonebsi). Associations between BSI, other prognostic biomarkers and overall survival (OS) were evaluated using a Cox proportional hazards regression model. Results One hundred forty-six PCa patients were included in the study. A total of 102 patient deaths were registered, with a median survival time after the follow-up bone scan of 2.4 years (interquartile range (IQR) =0.8 to 4.4). Both at baseline and during ADT, BSI was significantly associated with OS in univariate and multivariate analyses. When BSI was added to a prognostic base model including age, prostate-specific antigen, clinical tumour stage and Gleason score, the concordance index increased from 0.73 to 0.77 (p =0.0005) at baseline and from 0.77 to 0.82 (p <0.0001) during ADT. Conclusions Automated BSI during ADT is an independent prognostic indicator of OS in PCa patients with bone metastasis. It represents an emerging imaging biomarker that can be used in a prognostic model for risk stratification of PCa patients at the time of diagnosis and at later stages of the disease. BSI could then help physicians identify patients who could benefit from more aggressive therapies. PMID:25386390

  11. Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score

    PubMed Central

    Clive, Amelia O; Kahan, Brennan C; Hooper, Clare E; Bhatnagar, Rahul; Morley, Anna J; Zahan-Evans, Natalie; Bintcliffe, Oliver J; Boshuizen, Rogier C; Fysh, Edward T H; Tobin, Claire L; Medford, Andrew R L; Harvey, John E; van den Heuvel, Michel M; Lee, Y C Gary; Maskell, Nick A

    2014-01-01

    Background Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system. Methods Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated. Results Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228–549; n=43), 130 days (47–467; n=129) and 44 days (22–77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, p<0.01), 3 months (0.84 vs 0.75, p<0.01) and 6 months (0.85 vs 0.76, p<0.01). Conclusions The LENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population. PMID:25100651

  12. 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...

  13. Adverse Drug Reactions in Dental Practice

    PubMed Central

    Becker, Daniel E.

    2014-01-01

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

  14. A fuzzy logic based-method for prognostic decision making in breast and prostate cancers.

    PubMed

    Seker, Huseyin; Odetayo, Michael O; Petrovic, Dobrila; Naguib, Raouf N G

    2003-06-01

    Accurate and reliable decision making in oncological prognosis can help in the planning of suitable surgery and therapy, and generally, improve patient management through the different stages of the disease. In recent years, several prognostic markers have been used as indicators of disease progression in oncology. However, the rapid increase in the discovery of novel prognostic markers resulting from the development in medical technology, has dictated the need for developing reliable methods for extracting clinically significant markers where complex and nonlinear interactions between these markers naturally exist. The aim of this paper is to investigate the fuzzy k-nearest neighbor (FK-NN) classifier as a fuzzy logic method that provides a certainty degree for prognostic decision and assessment of the markers, and to compare it with: 1) logistic regression as a statistical method and 2) multilayer feedforward backpropagation neural networks an artificial neural-network tool, the latter two techniques having been widely used for oncological prognosis. In order to achieve this aim, breast and prostate cancer data sets are considered as benchmarks for this analysis. The overall results obtained indicate that the FK-NN-based method yields the highest predictive accuracy, and that it has produced a more reliable prognostic marker model than the statistical and artificial neural-network-based methods. PMID:12834167

  15. 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

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

    PubMed Central

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

    2016-01-01

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

  17. 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

  18. Nurses must report adverse drug reactions.

    PubMed

    Griffith, Richard

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

  19. Adulthood personality correlates of childhood adversity

    PubMed Central

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

    2014-01-01

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

  20. 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

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

    PubMed

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

    2015-01-01

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

  2. Soft tissue sarcomas of the distal lower extremities: A single-institutional analysis of the prognostic significance of surgical margins in 120 patients.

    PubMed

    Harati, Kamran; Kirchhoff, Pascal; Behr, Björn; Daigeler, Adrien; Goertz, Ole; Hirsch, Tobias; Lehnhardt, Marcus; Ring, Andrej

    2016-08-01

    Soft tissue sarcomas (STS) arising in the distal lower extremities pose a therapeutic challenge due to concerns of functional morbidity. The impact of surgical margins on local recurrence‑free survival (LRFS) and overall survival (OS) still remains controversial. The aim of this study was to identify prognostic indicators of survival and functional outcome in patients with STS of the distal lower extremities through a long‑term follow‑up. Between 1999 and 2014, 120 patients with STS of the foot, ankle and lower leg were treated surgically at our institution. The median follow‑up was 6.3 years. The results reveal that the 5‑year estimate of the OS rate was 80.0% [95% confidence interval (CI): 69.6‑87.1] for the entire series. Surgical margins attained at the resection of the primary tumor did not influence OS significantly [5‑year OS: R0 80.5% (69.7‑87.9) vs. R1 74.1% (28.9‑93.0); P=0.318]. Within the R0 subgroup, negative surgical margin widths ≤1 and >1 mm led to similar outcomes, as well as ≤5 and >5 mm, respectively. In the multivariate analysis, significant adverse prognostic features included male gender and age >60 years at the time point of primary diagnosis. In conclusion, the data from this study could not underscore the long‑term benefit of negative margins achieved at the resection of the primary tumor. Surgical efforts should aim at function‑sparing resections when feasible with negative margins. Here, close negative margins seem to be adequate. PMID:27278861

  3. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

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

  4. 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

  5. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the... exceeds criteria. I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse... section. (b) The following table indicates the study types and the criteria to be applied to each....

  6. Assessing calibration of prognostic risk scores.

    PubMed

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

    2016-08-01

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

  7. 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.

  8. [Prognostic factors of early breast cancer].

    PubMed

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

    2016-02-19

    Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies. PMID:25726309

  9. Prognostic Value of Colorectal Cancer Biomarkers

    PubMed Central

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

    2011-01-01

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

  10. [Analyze causes of adverse reactions induced by traditional Chinese medicine injections from its quality standards].

    PubMed

    Cui, Hong-Yu; Liang, Ai-Hu

    2014-03-01

    Reviewing the literatures about adverse reactions induced by traditional Chinese medicine injections (TCMI) reported on CNKI from 1983 to 2013. Analyzing the causes of adverse reactions induced by TCMI from its quality standards. Provide ideas for improving security of TCMI and completing its quality standards. This review indicates that TCMI-induced adverse reactions have little relationship with the number of compositions, but have tight connection with chemical ingredients and solvents. Adverse reactions can be decreased by perfecting the quality standards of TCMI. PMID:25204194

  11. 1991 Gulf War Exposures and Adverse Birth Outcomes

    PubMed Central

    Arnetz, Bengt; Drutchas, Alexis; Sokol, Robert; Kruger, Michael; Jamil, Hikmet

    2014-01-01

    We studied 1991 Gulf War (GW)-related environmental exposures and adverse birth outcomes in Iraqis. A random cross-sectional sample of 307 Iraqi families that immigrated to the United States responded to a structured interview covering socioeconomics, lifestyle, environmental exposures, and birth outcome. Data per each family was collected either from the man or the woman in the respective family. The respondents were divided into those that resided in Iraq during and following the GW (post-GW, n=185) and those that had left before (pre-GW, n=122). The primary outcome was lifetime prevalence of adverse birth outcomes, ie, congenital anomalies, stillbirth, low birth weight, and preterm delivery and its relationship to GW exposures. Mean number of adverse birth outcomes increased from 3.43 (SD=2.11) in the pre-GW to 4.63 (SD=2.63) in the post-GW group (P<.001). Mean chemical (Ch) and nonchemical (NCh) environmental exposure scores increased from pre-GW scores of 0.38 units (SD=1.76) and 0.43 (SD=1.86), respectively, to post-GW scores of 5.65 units (SD=6.23) and 7.26 (SD =5.67), P <.001 between groups for both exposures. There was a significant dose-response relationship between Ch environmental exposure (P=.001), but not NCh exposure, and number of adverse birth outcomes. Exposure to burning oil pits and mustard gas increased the risks for specific adverse birth outcomes by 2 to 4 times. Results indicate that Gulf War Ch, but not NCh exposures are related to adverse birth outcomes. Pregnancies in women with a history of war exposures might benefit from more intensive observation. PMID:23584910

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

    PubMed Central

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

    2012-01-01

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

  13. 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.

  14. Adverse reproductive events and electromagnetic radiation

    SciTech Connect

    Stewart, W.; Ouellet-Hellstrom, R.

    1991-07-31

    In 1989 approximately 42,000 questionnaires were mailed to female physical therapists to assess the risk of adverse reproductive effects among those exposed to electromagnetic radiation at radiofrequencies. From the resulting data, the risk of early recognized fetal loss was assessed using a nested case-control design. The cases (1753 miscarriages) were matched to controls (1753 other pregnancies except ectopics) on mothers age at conception and the number of years elapsed between conception and interview. The results of the study indicate that female physical therapists who work with microwave diathermy 6 months prior to the pregnancy and/or during the first trimester were at increased risk of experiencing a recognized early fetal loss, but female physical therapists who work with shortwave diathermy were not at an increased risk. This association was shown to hold even when the mother's age at conception, the number of years elapsed between conception and interview, the number of prior early fetal losses, mother's conditions ever diagnosed, and use of other modalities were controlled. The data also suggest a possible association between exposure to transcutaneous electrical nerve stimulation with an elevated risk of early recognized fetal loss.

  15. 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

  16. New prognostic biomarkers in multiple myeloma.

    PubMed

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

    2016-01-01

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

  17. Prognostic factors in neuroendocrine cervical carcinoma

    PubMed Central

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

    2016-01-01

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

  18. Collateral Adverse Outcomes After Lumbar Spine Surgery.

    PubMed

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

    2016-01-01

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

  19. Adverse event recording post hip fracture surgery.

    PubMed

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

    2013-01-01

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

  20. Sun exposure and melanoma prognostic factors

    PubMed Central

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

    2016-01-01

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

  1. A prognostic risk model for patients with triple negative breast cancer based on stromal natural killer cells, tumor-associated macrophages and growth-arrest specific protein 6.

    PubMed

    Tian, Wenjing; Wang, Le; Yuan, Lili; Duan, Wenming; Zhao, Wenhui; Wang, Shuhuai; Zhang, Qingyuan

    2016-07-01

    The aim of this study was to establish a prognostic risk model for patients with triple negative breast cancer (TNBC). A total of 278 specimens of human TNBC tissues were investigated by immunohistochemistry for growth-arrest specific protein 6 expression, infiltrations of stromal natural killer cells and tumor-associated macrophages. According to their prognostic risk scores based on the model, patients were divided into three groups (score 0, 1-2, 3). Correlations of prognostic risk scores, clinicopathologic features and overall survival (OS) were analyzed. To study the clinical value of this stratification model in early disease recurrence or metastasis, 177 patients were screened out for further analysis. Based on disease free survival (DFS), 90 patients fell within the DFS ≤3 years group and 87 patients within the DFS ≥5 years group. We analyzed the differences in prognostic risk scores between the two groups. The prognostic risk scores were negatively related to tumor size, lymph node metastasis and P53 status (P < 0.001 for all). Patients with low prognostic risk scores had longer OS (P = 0.001). Using multivariate analysis, it was determined that TNM stage (HR = 0.432, 95% confidence interval [CI] = 0.281-0.665, P = 0.003), FOXP3 positive lymphocytes (HR = 1.712, 95% CI = 1.085-2.702, P = 0.021) and prognostic risk scores (HR = 1.340, 95% CI = 1.192-1.644, P = 0.005) were independent prognostic factors for OS. Compared with the DFS ≥5 years group, the DFS ≤3 years group patients had significantly higher prognostic risk scores (P < 0.001). In conclusion, the prognostic risk score of the model was a significant indicator of prognosis for patients with TNBC. PMID:27145494

  2. Learning from adverse incidents involving medical devices.

    PubMed

    Amoore, John; Ingram, Paula

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

  3. 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

  4. Prognostic Significance of MiR-34a Expression in Patients with Gastric Cancer after Radical Gastrectomy

    PubMed Central

    Hui, Wen-Tao; Ma, Xiao-Bin; Zan, Ying; Wang, Xi-Jing; Dong, Lei

    2015-01-01

    Background: MiR-34a dysregulation has been implicated in tumorigenesis and progression of gastric cancer, but its role in prognosis of patients with gastric cancer remains unknown. The aim of this study was to investigate the expression and prognostic significance of miR-34a in gastric cancer patients after radical gastrectomy. Methods: Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-34a in human gastric cancer cell lines and tissues in 76 patients with gastric adenocarcinoma from China. Results are assessed for association with clinical features and overall survival (OS) using Kaplan–Meier analysis. Prognostic values of miR-34a expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating miR-34a expression was determined using receiver operating characteristic analysis. Results: The results show that the expression level of miR-34a was decreased in human gastric cancer cell lines and tissues, and down-regulated expression of miR-34a was associated with Lauren classification (P = 0.034). Decreased miR-34a expression in gastric cancer tissues was positively correlated with poor OS of gastric cancer patients (P = 0.013). Further multivariate Cox regression analysis suggested that miR-34a expression was an independent prognostic indicator for gastric cancer (P = 0.027). Applying the prognostic value of miR-34a expression to tumor node metastasis (TNM) stage system showed a better prognostic value in patients with gastric cancer than miR-34a expression (P = 0.0435) or TNM stage (P = 0.0249) alone. Conclusion: The results reinforce the critical role for the down-regulated miR-34a expression in gastric cancer and suggest that miR-34a could be a prognostic indicator for this disease. PMID:26415802

  5. Identifying Prognostic Features by Bottom-Up Approach and Correlating to Drug Repositioning

    PubMed Central

    Li, Wei; Yu, Jian; Lian, Baofeng; Sun, Han; Li, Jing; Zhang, Menghuan; Li, Ling; Li, Yixue; Liu, Qian; Xie, Lu

    2015-01-01

    Background Traditionally top-down method was used to identify prognostic features in cancer research. That is to say, differentially expressed genes usually in cancer versus normal were identified to see if they possess survival prediction power. The problem is that prognostic features identified from one set of patient samples can rarely be transferred to other datasets. We apply bottom-up approach in this study: survival correlated or clinical stage correlated genes were selected first and prioritized by their network topology additionally, then a small set of features can be used as a prognostic signature. Methods Gene expression profiles of a cohort of 221 hepatocellular carcinoma (HCC) patients were used as a training set, ‘bottom-up’ approach was applied to discover gene-expression signatures associated with survival in both tumor and adjacent non-tumor tissues, and compared with ‘top-down’ approach. The results were validated in a second cohort of 82 patients which was used as a testing set. Results Two sets of gene signatures separately identified in tumor and adjacent non-tumor tissues by bottom-up approach were developed in the training cohort. These two signatures were associated with overall survival times of HCC patients and the robustness of each was validated in the testing set, and each predictive performance was better than gene expression signatures reported previously. Moreover, genes in these two prognosis signature gave some indications for drug-repositioning on HCC. Some approved drugs targeting these markers have the alternative indications on hepatocellular carcinoma. Conclusion Using the bottom-up approach, we have developed two prognostic gene signatures with a limited number of genes that associated with overall survival times of patients with HCC. Furthermore, prognostic markers in these two signatures have the potential to be therapeutic targets. PMID:25738841

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  7. 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.

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

    PubMed Central

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

    2015-01-01

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

  9. Prognostic values of four Notch receptor mRNA expression in gastric cancer

    PubMed Central

    Wu, Xiaoyu; Liu, Wentao; Tang, Ding; Xiao, Haijuan; Wu, Zhenfeng; Chen, Che; Yao, Xuequan; Liu, Fukun; Li, Gang

    2016-01-01

    Notch ligands and receptors are frequently deregulated in several human malignancies including gastric cancer. The activation of Notch signaling has been reported to contribute to gastric carcinogenesis and progression. However, the prognostic roles of individual Notch receptors in gastric cancer patients remain elusive. In the current study, we accessed the prognostic roles of four Notch receptors, Notch 1–4, in gastric cancer patients through “The Kaplan-Meier plotter” (KM plotter) database, in which updated gene expression data and survival information include a total of 876 gastric cancer patients. All four Notch receptors’ high mRNA expression was found to be correlated to worsen overall survival (OS) for all gastric cancer patients followed for 20 years. We further accessed the prognostic roles of individual Notch receptors in different clinicopathological features using Lauren classification, pathological grades, clinical grades, HER2 status and different choices of treatments of gastric cancer patients. These results indicate that there are critical prognostic values of the four Notch receptors in gastric cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of gastric cancer and to develop tools to more accurately predict their prognosis. PMID:27363496

  10. Non-invasive prognostic protein biomarker signatures associated with colorectal cancer

    PubMed Central

    Surinova, Silvia; Radová, Lenka; Choi, Meena; Srovnal, Josef; Brenner, Hermann; Vitek, Olga; Hajdúch, Marián; Aebersold, Ruedi

    2015-01-01

    The current management of colorectal cancer (CRC) would greatly benefit from non-invasive prognostic biomarkers indicative of clinicopathological tumor characteristics. Here, we employed targeted proteomic profiling of 80 glycoprotein biomarker candidates across plasma samples of a well-annotated patient cohort with comprehensive CRC characteristics. Clinical data included 8-year overall survival, tumor staging, histological grading, regional localization, and molecular tumor characteristics. The acquired quantitative proteomic dataset was subjected to the development of biomarker signatures predicting prognostic clinical endpoints. Protein candidates were selected into the signatures based on significance testing and a stepwise protein selection, each within 10-fold cross-validation. A six-protein biomarker signature of patient outcome could predict survival beyond clinical stage and was able to stratify patients into groups of better and worse prognosis. We further evaluated the performance of the signature on the mRNA level and assessed its prognostic value in the context of previously published transcriptional signatures. Additional signatures predicting regional tumor localization and disease dissemination were also identified. The integration of rich clinical data, quantitative proteomic technologies, and tailored computational modeling facilitated the characterization of these signatures in patient circulation. These findings highlight the value of a simultaneous assessment of important prognostic disease characteristics within a single measurement. PMID:26253080

  11. 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...

  12. Adverse cutaneous drug eruptions: current understanding.

    PubMed

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

    2016-01-01

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

  13. 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

  14. 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...

  15. Monoclonal antibody BrE-3 participation in a multivariate prognostic model for infiltrating ductal carcinoma of the breast.

    PubMed

    Chan, C M; Baratta, F S; Ozzello, L; Ceriani, R L

    1994-01-01

    Monoclonal antibody (MoAb) BrE-3, an anti-human milk fat globule (HMFG) MoAb, is used here as a novel prognostic indicator for survival and relapse time in patients with infiltrating ductal carcinoma of the breast. A scoring system (4-Score method) was developed to this effect that measured, in a statistically reliable fashion, the level of expression of the epitope for MoAb BrE-3 in the cytoplasm and membranes of breast carcinoma cells in paraffin-embedded sections. In univariate analysis, data obtained by the 4-Score Method as well as data from traditional prognostic indicators (tumor size, axillary node status, and grade of differentiation) were found to be associated with patient survival and relapse. In multivariate analysis, using a Cox proportional hazards regression model, levels of expression of BrE-3 epitope plus tumor size and axillary node status were weighted and combined in an Individual Linear Composite Prognostic Score (ILCPS) that had a high level of association with survival and relapse time in this sample model of patients with infiltrating ductal carcinoma of the breast. This level of association was found to be higher than the level of association for any other combination of traditional or 4-Score method variables. The level of expression of BrE-3 significantly adds to the prognostic capacity of traditional prognostic markers for infiltrating ductal carcinoma of the breast. PMID:7981443

  16. 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

  17. Plasma peptidases as prognostic biomarkers in patients with first-episode psychosis.

    PubMed

    Fernández-Atucha, Ainhoa; Echevarría, Enrique; Larrinaga, Gorka; Gil, Javier; Martínez-Cengotitabengoa, Mónica; González-Pinto, Ana M; Irazusta, Jon; Seco, Jesús

    2015-08-15

    The plasma activity of nine aminopeptidases was monitored over a year in first-episode psychotic patients. We observed significant differences in aminopeptidase B (APB), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPPIV), but not in puromycin-sensitive aminopeptidase (PSA), prolyl endopeptidase (PEP), cysteine aminopeptidase (Cys-AP), aspartate aminopeptidase (Asp-AP), glutamate aminopeptidase (Glu) or piroglutamate aminopeptidase (PGI) in these patients compared to controls, and also a progressive increase in plasma activity, correlated to changes in scores on clinical scales, Global Assessment of Functioning scale (GAF) and Hamilton Depression Rating Scale (HDRS), at 1 month of follow-up. At 1 month after diagnosis, the median score obtained by patients on the GAF was negatively associated with the plasma activity of APB and PEP measured at the beginning of the psychotic episode, indicating a role as a negative prognostic factor that can predict psychiatric symptomatology. In the case of HDRS, scores at 1 month after diagnosis were found to be positively associated with the initial plasma activity of DPPIV, APN and PSA, indicating that their initial elevation is a negative prognostic factor that can predict subsequent depressive symptomatology. Taken together, these results suggest a pathophysiological involvement of plasma peptidases and indicate that aminopeptidase activity can predict the course of first-episode psychosis patients, acting as a prognostic indicator. PMID:25997998

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

    PubMed Central

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

    1991-01-01

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

  19. 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

  20. Thymidine labeling index: prognostic role in breast cancer.

    PubMed

    Bilir, Ayhan; Ozmen, V; Kecer, M; Eralp, Yesim; Cabioglu, Neslihan; Ahishali, Bulent; Agizhali, Bulent; Camlica, Hakan; Aydiner, Adnan

    2004-08-01

    The aim of this study is to evaluate the prognostic role of thymidine labeling index in patients with breast cancer. Cellular proliferation rates in 155 breast cancer specimens were investigated by 3H-thymidine labeling index (3H-TLI). Median age was 47 years (range: 23-76). At presentation, 11 patients (7.1%) had stage I disease, 76 (49%) had stage II, 64 (41.3%) had stage III disease, and 4 (2.6%) had metastatic involvement. Patients were placed in 2 groups based on their proliferative indices. The cut-off level was assigned as the median TLI value of the whole group. Correlations between proliferative activity of the tumors based on 3H-TLI levels and various previously established prognostic factors, as well as the influence of proliferative activity on survival as a clinical outcome, were analyzed. The mean and median TLI values for the whole group of patients were 4.36 +/- 4.96% and 2.76% (range: 0-23.6), respectively. There was a significant association of nuclear grade with TLI (P = 0.04). Patients who were alive with no sign of disease at the final follow-up examination had a significantly lower median TLI rate than those who were either alive with disease or those who had eventually died with disease progression (3.7% versus 1.9%, respectively; P = 0.04). Patients with locally advanced disease (N2 + N3 involvement) had a significantly higher median TLI rate than those with local nodal involvement (N1) (3.4% versus 1.7%, respectively, P = 0.026). Furthermore, TLI levels showed a significant association with overall survival in patients with node-negative disease (P = 0.02). Based on the results of this study, it can be concluded that TLI plays a significant prognostic role in a subset of patients with node-negative breast cancer. Furthermore, TLI appears to have a predictive value for the clinical outcome of patients with breast cancer. These findings may justify a more aggressive therapeutic approach in patients with high TLI levels. Further large

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

    PubMed Central

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

    2014-01-01

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

  2. 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.

  3. Prognostic Factors in Cholinesterase Inhibitor Poisoning

    PubMed Central

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

    2015-01-01

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

  4. Protein electrophoresis as a diagnostic and prognostic tool in raptor medicine.

    PubMed

    Tatum, L M; Zaias, J; Mealey, B K; Cray, C; Bossart, G D

    2000-12-01

    Plasma proteins of 139 healthy adult birds of prey from 10 species were separated by electrophoresis to characterize and document normal reference ranges and species-specific electrophoretic patternsand to evaluate the value of this technique for health screening, disease diagnosis, and prognostic indication. Species studied included bald eagle (Haliaeetus leucocephalus), red-tailed hawk (Buteo jamaicensis), barn owl (Tyto alba), great horned owl (Bubo virginianus), turkey vulture (Cathartes aura), Harris' hawk (Parabuteo unicinctus), Stellar's sea eagle (Haliaeetus pelagicus), barred owl (Strix varia), screech owl (Otus asio), and black vulture (Coragyps atratus). Several clinical cases show the diagnostic/therapeutic value of protein electrophoresis in raptors. This study establishes species-specific reference ranges for several birds of prey and discusses the benefit of electrophoresis as a diagnostic technique in health screens, as a diagnostic aid in conjunction with other tests, and as a prognostic indicator in clinical evaluation of raptors. PMID:11428396

  5. 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

  6. Cellular prognostic markers in hepatocellular carcinoma.

    PubMed

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

    2015-01-01

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

  7. The opposite prognostic effect of NDUFS1 and NDUFS8 in lung cancer reflects the oncojanus role of mitochondrial complex I

    PubMed Central

    Su, Chia-Yi; Chang, Yu-Chan; Yang, Chih-Jen; Huang, Ming-Shyan; Hsiao, Michael

    2016-01-01

    A recent surge of research on complex I mitochondrial DNA indicates that complex I disassembly regulated by mutation threshold plays a critical role in tumor progression. However, nuclear DNA (nDNA)-encoded core subunits are still a neglected area for cancer investigation. In this study, respective prognostic contributions of 7 nDNA-encoded core subunits were analyzed by immunohistochemical staining and RNA expression data extracted from public resources. The results showed that NDUFS1 and NDUFS8 had the most significant prognostic power in NSCLC patients among all 7 nDNA-encoded core subunits. Patients with low NDUFS1 or high NDUFS8 IHC and RNA expression levels had poor overall survival. Because of the significant correlation between expressions of 7 nDNA-encoded core subunits, multivariate analysis was performed and identified NDUFS1 and NDUFS8 IHC and RNA expression levels retained their leading prognostic roles. By combining NDFUS1 and NDUFS8 as a panel, the most unfavorable prognostic group had a 14-fold increased risk of poor prognosis than the most favorable prognostic group. In conclusion, the opposite prognostic effect of nDNA-encoded core subunits suggests the oncojanus role of nuclear genes regulating complex I dysfunction. The panel with NDUFS1 and NDUFS8 reflecting tumor metabolism status is a novel prognostic predictor for lung cancer. PMID:27516145

  8. The opposite prognostic effect of NDUFS1 and NDUFS8 in lung cancer reflects the oncojanus role of mitochondrial complex I.

    PubMed

    Su, Chia-Yi; Chang, Yu-Chan; Yang, Chih-Jen; Huang, Ming-Shyan; Hsiao, Michael

    2016-01-01

    A recent surge of research on complex I mitochondrial DNA indicates that complex I disassembly regulated by mutation threshold plays a critical role in tumor progression. However, nuclear DNA (nDNA)-encoded core subunits are still a neglected area for cancer investigation. In this study, respective prognostic contributions of 7 nDNA-encoded core subunits were analyzed by immunohistochemical staining and RNA expression data extracted from public resources. The results showed that NDUFS1 and NDUFS8 had the most significant prognostic power in NSCLC patients among all 7 nDNA-encoded core subunits. Patients with low NDUFS1 or high NDUFS8 IHC and RNA expression levels had poor overall survival. Because of the significant correlation between expressions of 7 nDNA-encoded core subunits, multivariate analysis was performed and identified NDUFS1 and NDUFS8 IHC and RNA expression levels retained their leading prognostic roles. By combining NDFUS1 and NDUFS8 as a panel, the most unfavorable prognostic group had a 14-fold increased risk of poor prognosis than the most favorable prognostic group. In conclusion, the opposite prognostic effect of nDNA-encoded core subunits suggests the oncojanus role of nuclear genes regulating complex I dysfunction. The panel with NDUFS1 and NDUFS8 reflecting tumor metabolism status is a novel prognostic predictor for lung cancer. PMID:27516145

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

    PubMed

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

    2016-05-01

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

  10. Prognostic implications of expression of the cell cycle inhibitor protein p27Kip1.

    PubMed

    Cariou, S; Catzavelos, C; Slingerland, J M

    1998-01-01

    Mitogenic and growth inhibitory signals influence the activity of a family of cyclin dependent kinases (cdks). p27 is an important cdk inhibitor, acting in G1 to inhibit cyclin-cdks. As negative growth regulators, the cdk inhibitors may function as tumor suppressors. While the p16 gene plays a tumor suppressor role in cancers, p27 gene mutations have been identified only rarely. While high levels of p27 protein are expressed in normal human mammary epithelium, loss of p27 is frequent and is of independent prognostic significance in breast cancers. Low p27 is also a poor prognostic factor in colon, gastric, esophageal, lung, and prostate carcinomas, and enhanced proteasomal degradation may underlie loss of p27 in tumor cells. Loss of p27 has not been significantly correlated with tumor proliferation in a number of studies and may reflect alterations in differentiation and adhesion-dependent growth regulation germane to oncogenesis and tumor progression. Efforts to confirm the prognostic value of p27 are under way in a number of large breast cancer studies. These studies may also indicate whether loss of p27 in association with other traditional or novel markers has greater prognostic potential than each factor alone. p27 immunostaining is inexpensive and reliable and may become part of the routine histopathologic processing of tumors in the near future. Widespread application of p27 in prognostic testing will require greater uniformity in scoring techniques and determination of the cut off levels which distinguish individuals at high and low risk of cancer recurrence and death. Finally, the greatest utility of p27 may lie in the information it sheds on the biology of aberrant growth regulation in breast cancer and the potential to use this in the generation of novel therapeutic strategies. PMID:10066070

  11. 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

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

    PubMed Central

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

    2013-01-01

    Background: Limited research exists regarding the influence of a treating physical therapist on patient recovery (deemed therapist effects). Recent randomized clinical trials data provide an indication of small therapist effects for manual therapy; however, the extent to which therapist effects exist in the average outpatient facility is not clear. Moreover, patient-related prognostic factors, like fear-avoidance or pain duration, are important to consider since these may also influence the extent of therapist effects. Objective: To assess therapist effects and the influence of patient prognostic factors on recovery from axial pain in an outpatient orthopedic physical therapy facility. Methods: Clinical data were collected from consecutive patients with musculoskeletal neck and low back pain. Patient outcomes included pain intensity (visual analog scale) and functional measure (CareConnections functional outcomes index) scores. Therapist effects estimates and the influence of intake fear-avoidance (fear-avoidance beliefs questionnaire) and pain duration (days) were examined using multilevel linear or regression modeling. Results: A total of 258 patients (160 females; mean age 46.4±14.9 years) completed physical therapy and the required outcome measures. Five physical therapists (1–13 years of experience, mean 5.8 years) provided treatment. Therapists effects did not exist for discharge pain intensity or function after accounting for intake scores (P > 0.05). Further, therapist experience did not influence patient outcomes. Patient prognostic factors of fear-avoidance and pain duration did not influence therapists effects on the same patient outcome measures (P > 0.05). Discussion: Preliminary findings suggest that there are no major differences in patient outcome based on either the individual therapist (therapist effect) or therapist experience in this type of PT setting. Established prognostic factors had no influence on therapist effects for this cohort

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

    PubMed

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

    2010-08-01

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

  14. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Dharmarajan, Lavanya; Salazar, Lucrecia; Hasbun, Rodrigo

    2016-01-01

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

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

    PubMed

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

    2013-09-01

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

  18. 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

  19. The complement system and adverse pregnancy outcomes.

    PubMed

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

    2015-09-01

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

  20. 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. PMID:27030896

  1. Vitex agnus castus: a systematic review of adverse events.

    PubMed

    Daniele, Claudia; Thompson Coon, Joanna; Pittler, Max H; Ernst, Edzard

    2005-01-01

    Vitex agnus castus L. (VAC) [Verbenaceae] is a deciduous shrub that is native to Mediterranean Europe and Central Asia. Traditionally, VAC fruit extract has been used in the treatment of many female conditions, including menstrual disorders (amenorrhoea, dysmenorrhoea), premenstrual syndrome (PMS), corpus luteum insufficiency, hyperprolactinaemia, infertility, acne, menopause and disrupted lactation. The German Commission E has approved the use of VAC for irregularities of the menstrual cycle, premenstrual disturbances and mastodynia. Clinical reviews are available for the efficacy of VAC in PMS, cycle disorders, hyperprolactinaemia and mastalgia, but so far no systematic review has been published on adverse events or drug interactions associated with VAC. Therefore, this review was conducted to evaluate all the available human safety data of VAC monopreparations. Literature searches were conducted in six electronic databases, in references lists of all identified papers and in departmental files. Data from spontaneous reporting schemes of the WHO and national drug safety bodies were also included. Twelve manufacturers of VAC-containing preparations and five herbalist organisations were contacted for additional information. No language restrictions were imposed. Combination preparations including VAC or homeopathic preparations of VAC were excluded. Data extraction of key data from all articles reporting adverse events or interactions was performed independently by at least two reviewers, regardless of study design. Data from clinical trials, postmarketing surveillance studies, surveys, spontaneous reporting schemes, manufacturers and herbalist organisations indicate that the adverse events following VAC treatment are mild and reversible. The most frequent adverse events are nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, pruritus and erythematous rash. No drug interactions were reported. Use of VAC should be avoided during pregnancy or

  2. Prognostic factors in canine mammary cancer.

    PubMed

    Misdorp, W; Hart, A A

    1976-04-01

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

  3. 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.

  4. 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.

  5. Epidemiologic and Molecular Prognostic Review of Glioblastoma

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. The prognostic value of histological grading of posterior fossa ependymomas in children: a Children's Oncology Group study and a review of prognostic factors.

    PubMed

    Tihan, Tarik; Zhou, Tianni; Holmes, Emi; Burger, Peter C; Ozuysal, Sema; Rushing, Elisabeth J

    2008-02-01

    We performed a retrospective analysis of 96 pediatric posterior fossa ependymomas in order to determine the prognostic value of histological grade based on the current WHO grading scheme. The patients were selected among Children's Oncology Group (previously Pediatric Oncology Group-POG) patients enrolled in clinical trials, and on the basis of central pathology review, location, and age. We excluded entities such as sub-ependymoma, myxopapillary, or clear-cell ependymoma, after a consensus diagnosis by three neuropathologists. A total of 66 males and 30 females with a median age of 48 months were identified. The group was analyzed to determine the effects of histological grade, age, gender, and extent of resection on event-free and overall survival. Our results showed that extent of resection, age, and histological grade were independent prognostic variables for event-free survival. The relative risk for extent of resection and histological grade was calculated as 3.59 (P<0.001) and 3.58 (P<0.001), respectively. Overall survival significantly correlated with extent of resection and age, but not with histological grade. We compared our results with peer-reviewed publications on pediatric intracranial ependymomas in the English language between 1990 and 2005. Selection criteria identified 32 manuscripts involving 1444 patients. Extent of resection was a significant factor in 21, age in 12, and histological grading in nine of these studies. Other factors reported to be significant by more than one study included tumor location and radiation treatment. Our findings suggest that histological grade (WHO Grade II vs III) is an independent prognostic indicator for event-free survival, but may not be so for overall survival in pediatric posterior fossa ependymomas. We believe that an accurate assessment of the prognostic value of histological grade depends on the selection of a well-characterized clinical cohort of sufficient size, and the inclusion of relevant

  8. Lysosomal and autophagic reactions as predictive indicators of environmental impact in aquatic animals.

    PubMed

    Moore, Michael N; Allen, J Icarus; McVeigh, Allan; Shaw, Jenny

    2006-01-01

    The lysosomal-autophagic system appears to be a common target for many environmental pollutants as lysosomes accumulate many toxic metals and organic xenobiotics, which perturb normal function and damage the lysosomal membrane. In fact, lysosomal membrane integrity or stability appears to be an effective generic indicator of cellular well-being in eukaryotes: in bivalve molluscs and fish, stability is correlated with many toxicological responses and pathological reactions. Prognostic use of adverse lysosomal and autophagic reactions to environmental pollutants has been explored in relation to predicting cellular dysfunction and health in marine mussels, which are extensively used as sensitive bioindicators in monitoring ecosystem health. Derivation of explanatory frameworks for prediction of pollutant impact on health is a major goal; and we have developed a conceptual mechanistic model linking lysosomal damage and autophagic dysfunction with injury to cells and tissues. This model has also complemented the creation of a cell-based computational model for molluscan hepatopancreatic cells that simulates lysosomal, autophagic and other cellular reactions to pollutants. Experimental and simulated results have also indicated that nutritional deprivation-induced autophagy has a protective function against toxic effects mediated by reactive oxygen species (ROS). Finally, coupled measurement of lysosomal-autophagic reactions and modelling is proposed as a practical toolbox for predicting toxic environmental risk. PMID:16874099

  9. Prognostic factors of early outcome in pediatric hemophagocytic lymphohistiocytosis: an analysis of 116 cases.

    PubMed

    Bin, Qiong; Gao, Jin-Hong; Luo, Jian-Ming

    2016-09-01

    Early mortality remains a major challenge for the treatment of hemophagocytic lymphohistiocytosis (HLH), which warrants the need for prompt risk stratification in the early phase of the disease. We retrospectively analyzed clinical features of a cohort of pediatric patients managed at a tertiary hospital in southern China from 2005 to 2015. A total of 116 patients (median age 27.5 months) with predominantly secondary HLH were included. In a multivariate Cox regression model, neutrophils <0.5 × 10(9)/L (risk ratio (RR) = 5.01; 95 % confidence interval (CI) 1.55-16.20; P = 0.007), total bilirubin over twofold upper limit of normal value (RR = 2.86; 95 % CI 0.83-9.88; P = 0.097), and albumin ≤20 g/L (RR = 5.79; 95 % CI 1.70-19.73; P = 0.005) at diagnosis were independent risk factors for 30-day mortality. The 30-day overall survival rate (OS) of patients with three risk factors was significantly lower than that of patients with zero to two risk factors (0 vs 90.7 %; P<0.001). Patients with three risk factors were 64-fold more likely to have early adverse outcome as compared to patients with zero to two risk factors (RR = 64.45; 95 % CI 18.35-226.33; P<0.001). Platelet count normalization in 2 weeks was an independent predictor for resolution after initial therapy with an odds ratio (OR) of 18.4 (95 % CI 2.7-122.9; P = 0.003). Our results indicate that severe neutropenia and liver function damage are prognostic factors for early death in HLH and platelet count normalization in 2 weeks is a critical predictor for resolution after initial therapy. PMID:27307280

  10. 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

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

    PubMed Central

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

    2000-01-01

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

  12. Prognostic Significance of Tag SNP rs1045411 in HMGB1 of the Aggressive Gastric Cancer in a Chinese Population

    PubMed Central

    He, Li; Zhao, Huadong; Wang, Nan; Ji, Gang; He, Xianli

    2016-01-01

    Compelling evidences have suggested that high mobility group box-1 (HMGB1) gene plays a crucial role in cancer development and progression. This study aimed to evaluate the effects of single nucleotide polymorphisms (SNPs) in HMGB1 gene on the survival of gastric cancer (GC) patients. Three tag SNPs from HMGB1 gene were selected and genotyped using Sequenom iPEX genotyping system in a cohort of 1030 GC patients (704 in training set, 326 in validation set). Multivariate Cox proportional hazard model and Kaplan-Meier Curve were used for prognosis analysis. AG/AA genotypes of SNP rs1045411 in HMGB1 gene were significantly associated with better overall survival (OS) in a set of 704 GC patients when compared with GG genotypes (HR = 0.77, 95% CI: 0.60–0.97, P = 0.032). This prognostic effect was verified in an independent validation set and pooled analysis (HR = 0.80, 95% CI: 0.62–0.99, P = 0.046; HR = 0.78, 95% CI: 0.55–0.98, P = 0.043, respectively). In stratified analysis, the protective effect of rs1045411 AG/AA genotypes was more prominent in patients with adverse strata, compared with patients with favorable strata. Furthermore, strong joint predictive effects on OS of GC patients were noted between rs1045411 genotypes and Lauren classification, differentiation, stage or adjuvant chemotherapy. Additionally, functional assay indicated a significant effect of rs1045411 on HMGB1 expression. Our results suggest that rs1045411 in HMGB1 is significantly associated with clinical outcomes of Chinese GC patients after surgery, especially in those with aggressive status, which warrants further validation in other ethnic populations. PMID:27116470

  13. Endothelial NOS, estrogen receptor β, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer

    PubMed Central

    Nanni, Simona; Benvenuti, Valentina; Grasselli, Annalisa; Priolo, Carmen; Aiello, Aurora; Mattiussi, Stefania; Colussi, Claudia; Lirangi, Vittoria; Illi, Barbara; D’Eletto, Manuela; Cianciulli, Anna Maria; Gallucci, Michele; De Carli, Piero; Sentinelli, Steno; Mottolese, Marcella; Carlini, Paolo; Strigari, Lidia; Finn, Stephen; Mueller, Elke; Arcangeli, Giorgio; Gaetano, Carlo; Capogrossi, Maurizio C.; Donnorso, Raffaele Perrone; Bacchetti, Silvia; Sacchi, Ada; Pontecorvi, Alfredo; Loda, Massimo; Farsetti, Antonella

    2009-01-01

    The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor β (ERβ). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production. Upon estrogen treatment, formation of ERβ/eNOS, ERβ/HIF-1α, or ERβ/HIF-2α combinatorial complexes led to chromatin remodeling and transcriptional induction of prognostic genes. Tissue microarray analysis, using an independent cohort of patients, established a hierarchical predictive power for these proteins, with expression of eNOS plus ERβ and nuclear eNOS plus HIF-2α being the most relevant indicators of adverse clinical outcome. Genetic or pharmacologic modulation of eNOS expression and activity resulted in reciprocal conversion of the transcriptional signature in cells from patients with bad or good outcome, respectively, highlighting the relevance of eNOS in PCa progression. Our work has considerable clinical relevance, since it may enable the earlier diagnosis of aggressive PCa through routine biopsy assessment of eNOS, ERβ, and HIF-2α expression. Furthermore, proposing eNOS as a therapeutic target fosters innovative therapies for PCa with NO inhibitors, which are employed in preclinical trials in non-oncological diseases. PMID:19363294

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. MACROPHAGE AGGREGATES AS INDICATORS OF ENVIRONMENTAL STRESS

    EPA Science Inventory

    The growing awareness of adverse effects of environmental contamination has lead to scrutiny of various biomarkers as early indicators of these effects. he use of splenic macrophage aggregates (MA) as indicators of fish health and environmental degradation was evaluated using thr...

  17. Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer.

    PubMed

    Krishnan, Preethi; Ghosh, Sunita; Wang, Bo; Heyns, Mieke; Li, Dongping; Mackey, John R; Kovalchuk, Olga; Damaraju, Sambasivarao

    2016-01-01

    Transfer RNAs (tRNAs, key molecules in protein synthesis) have not been investigated as potential prognostic markers in breast cancer (BC), despite early findings of their dysregulation and diagnostic potential. We aim to comprehensively profile tRNAs from breast tissues and to evaluate their role as prognostic markers (Overall Survival, OS and Recurrence Free Survival, RFS). tRNAs were profiled from 11 normal breast and 104 breast tumor tissues using next generation sequencing. We adopted a Case-control (CC) and Case-Only (CO) association study designs. Risk scores constructed from tRNAs were subjected to univariate and multivariate Cox-proportional hazards regression to investigate their prognostic value. Of the 571 tRNAs profiled, 76 were differentially expressed (DE) and three were significant for OS in the CC approach. We identified an additional 11 tRNAs associated with OS and 14 tRNAs as significant for RFS in the CO approach, indicating that CC alone may not capture all discriminatory tRNAs in prognoses. In both the approaches, the risk scores were significant in the multivariate analysis as independent prognostic factors, and patients belonging to high-risk group were associated with poor prognosis. Our results confirmed global up-regulation of tRNAs in BC and identified tRNAs as potential novel prognostic markers for BC. PMID:27604545

  18. Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer

    PubMed Central

    Krishnan, Preethi; Ghosh, Sunita; Wang, Bo; Heyns, Mieke; Li, Dongping; Mackey, John R.; Kovalchuk, Olga; Damaraju, Sambasivarao

    2016-01-01

    Transfer RNAs (tRNAs, key molecules in protein synthesis) have not been investigated as potential prognostic markers in breast cancer (BC), despite early findings of their dysregulation and diagnostic potential. We aim to comprehensively profile tRNAs from breast tissues and to evaluate their role as prognostic markers (Overall Survival, OS and Recurrence Free Survival, RFS). tRNAs were profiled from 11 normal breast and 104 breast tumor tissues using next generation sequencing. We adopted a Case-control (CC) and Case-Only (CO) association study designs. Risk scores constructed from tRNAs were subjected to univariate and multivariate Cox-proportional hazards regression to investigate their prognostic value. Of the 571 tRNAs profiled, 76 were differentially expressed (DE) and three were significant for OS in the CC approach. We identified an additional 11 tRNAs associated with OS and 14 tRNAs as significant for RFS in the CO approach, indicating that CC alone may not capture all discriminatory tRNAs in prognoses. In both the approaches, the risk scores were significant in the multivariate analysis as independent prognostic factors, and patients belonging to high-risk group were associated with poor prognosis. Our results confirmed global up-regulation of tRNAs in BC and identified tRNAs as potential novel prognostic markers for BC. PMID:27604545

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

    PubMed

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

    1990-06-01

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

  20. Aquaporin 1 protein expression is associated with BRAF V600 mutation and adverse prognosis in cutaneous melanoma.

    PubMed

    Imrédi, Eleonóra; Tóth, Béla; Doma, Viktória; Barbai, Tamás; Rásó, Erzsébet; Kenessey, István; Tímár, József

    2016-06-01

    Despite experimental findings suggesting the prognostic significance of Aquaporin 1 (AQP1) in human melanoma, no published clinical data are available. We studied the expression of AQP1 protein in cutaneous melanoma, correlated our findings with standard histological and genetic markers, and long-term clinical follow-up. Our study evaluated the AQP1 protein expression in 78 melanoma patients, representing two predefined risk cohorts using the immune labeling technique with commercially available anti-AQP1 antibodies on routinely formalin-fixed and paraffin-embedded tumor tissue samples. BRAF V600E mutation analyses were carried out successfully in 70 patients using PCR and restriction fragment length polymorphism analyses, followed by confirmatory analysis with the Sanger sequencing technique. AQP1-expressing melanoma cells were found in 52 cases (66.7%, median H-score=124.24). Significantly higher AQP1 H-scores (P=0.047) were found in the 'high-risk' patients. No correlations were found with the established histological markers, such as mitotic index (P=0.42), Clark level (P=0.95), and Breslow thickness (P=0.51). BRAF V600 mutation analyses were successful in 89%, and showed a two times higher mutation frequency in the 'high-risk' group. The BRAF V600 mutations were significantly associated with AQP1 expression (P=0.014). Long-term follow-up indicated a reduced progression-free survival (P=0.036) and overall survival (P=0.017) for the AQP1-positive cutaneous melanoma patients. AQP1 expression is likely to be associated with an adverse prognosis in cutaneous melanoma. PMID:26848795

  1. Identifying Adverse Drug Events by Relational Learning

    PubMed Central

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

    2013-01-01

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

  2. Standardizing drug adverse event reporting data.

    PubMed

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

    2013-01-01

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

  3. A revised inventory of Adverse Childhood Experiences.

    PubMed

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

    2015-10-01

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

  4. Adverse health consequences of the Iraq War.

    PubMed

    Levy, Barry S; Sidel, Victor W

    2013-03-16

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

  5. Adverse events related to blood transfusion

    PubMed Central

    Sahu, Sandeep; Hemlata; Verma, Anupam

    2014-01-01

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

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

    PubMed

    Glina, Sidney; Vieira, Marcelo

    2013-01-01

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

  7. Combined Molecular and Clinical Prognostic Index for Relapse and Survival in Cytogenetically Normal Acute Myeloid Leukemia

    PubMed Central

    Pastore, Friederike; Dufour, Annika; Benthaus, Tobias; Metzeler, Klaus H.; Maharry, Kati S.; Schneider, Stephanie; Ksienzyk, Bianka; Mellert, Gudrun; Zellmeier, Evelyn; Kakadia, Purvi M.; Unterhalt, Michael; Feuring-Buske, Michaela; Buske, Christian; Braess, Jan; Sauerland, Maria Cristina; Heinecke, Achim; Krug, Utz; Berdel, Wolfgang E.; Buechner, Thomas; Woermann, Bernhard; Hiddemann, Wolfgang; Bohlander, Stefan K.; Marcucci, Guido; Spiekermann, Karsten; Bloomfield, Clara D.; Hoster, Eva

    2014-01-01

    Purpose Cytogenetically normal (CN) acute myeloid leukemia (AML) is the largest and most heterogeneous cytogenetic AML subgroup. For the practicing clinician, it is difficult to summarize the prognostic information of the growing number of clinical and molecular markers. Our purpose was to develop a widely applicable prognostic model by combining well-established pretreatment patient and disease characteristics. Patients and Methods Two prognostic indices for CN-AML (PINA), one regarding overall survival (OS; PINAOS) and the other regarding relapse-free survival (RFS; PINARFS), were derived from data of 572 patients with CN-AML treated within the AML Cooperative Group 99 study (www.aml-score.org). Results On the basis of age (median, 60 years; range, 17 to 85 years), performance status, WBC count, and mutation status of NPM1, CEBPA, and FLT3-internal tandem duplication, patients were classified into the following three risk groups according to PINAOS and PINARFS: 29% of all patients and 32% of 381 responding patients had low-risk disease (5-year OS, 74%; 5-year RFS, 55%); 56% of all patients and 39% of responding patients had intermediate-risk disease (5-year OS, 28%; 5-year RFS, 27%), and 15% of all patients and 29% of responding patients had high-risk disease (5-year OS, 3%; 5-year RFS, 5%), respectively. PINAOS and PINARFS stratified outcome within European LeukemiaNet genetic groups. Both indices were confirmed on independent data from Cancer and Leukemia Group B/Alliance trials. Conclusion We have developed and validated, to our knowledge, the first prognostic indices specifically designed for adult patients of all ages with CN-AML that combine well-established molecular and clinical variables and that are easily applicable in routine clinical care. The integration of both clinical and molecular markers could provide a basis for individualized patient care through risk-adapted therapy of CN-AML. PMID:24711548

  8. Adverse Drug Reactions of the Lower Extremities.

    PubMed

    Adigun, Chris G

    2016-07-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. Possible adverse drug events leading to hospital admission in a Brazilian teaching hospital

    PubMed Central

    Varallo, Fabiana Rossi; Capucho, Helaine Carneiro; da Silva Planeta, Cleópatra; de Carvalho Mastroianni, Patrícia

    2014-01-01

    OBJECTIVES: Drug safety problems can lead to hospital admission. In Brazil, the prevalence of hospitalization due to adverse drug events is unknown. This study aims to estimate the prevalence of hospitalization due to adverse drug events and to identify the drugs, the adverse drug events, and the risk factors associated with hospital admissions. METHOD: A cross-sectional study was performed in the internal medicine ward of a teaching hospital in São Paulo State, Brazil, from August to December 2008. All patients aged ≥18 years with a length of stay ≥24 hours were interviewed about the drugs used prior to hospital admission and their symptoms/complaints/causes of hospitalization. RESULTS: In total, 248 patients were considered eligible. The prevalence of hospitalization due to potential adverse drug events in the ward was 46.4%. Overprescribed drugs and those indicated for prophylactic treatments were frequently associated with possible adverse drug events. Frequently reported symptoms were breathlessness (15.2%), fatigue (12.3%), and chest pain (9.0%). Polypharmacy was a risk factor for the occurrence of possible adverse drug events. CONCLUSION: Possible adverse drug events led to hospitalization in a high-complexity hospital, mainly in polymedicated patients. The clinical outcomes of adverse drug events are nonspecific, which delays treatment, hinders causality analysis, and contributes to the underreporting of cases. PMID:24626940

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective

    PubMed Central

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  20. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective.

    PubMed

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  1. 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

  2. Prognostic Value of Osteopontin Splice Variant-c Expression in Breast Cancers: A Meta-Analysis

    PubMed Central

    Hao, Chengcheng; Wang, Zhiyan; Gu, Yanan; Jiang, Wen G.

    2016-01-01

    Objectives. Osteopontin (OPN) is overexpressed in breast cancers, while its clinical and prognostic significance remained unclear. This study aimed to assess the prognostic value of OPN, especially its splice variants, in breast cancers. Methods. Data were extracted from eligible studies concerning the OPN and OPN-c expression in breast cancer patients and were used to calculate the association between OPN/OPN-c and survival. Two reviewer teams independently screened the literatures according to the inclusion and exclusion criteria based on quality evaluation. Following the processes of data extraction, assessment, and transformation, meta-analysis was carried out via RevMan 5.3 software. Results. A total of ten studies involving 1,567 patients were included. The results demonstrated that high level OPN indicated a poor outcome in the OS (HR = 2.22, 95% CI: 1.23–4.00, and P = 0.008; random-effects model) with heterogeneity (I2 = 62%) of breast cancer patients. High level OPN-c appeared to be more significantly associated with poor survival (HR = 2.14, 95% CI: 1.51–3.04, and P < 0.0001; fixed-effects model) with undetected heterogeneity (I2 = 0%). Conclusions. Our analyses indicated that both OPN and OPN-c could be considered as prognostic markers for breast cancers. The high level of OPN-c was suggested to be more reliably associated with poor survival in breast cancer patients. PMID:27462610

  3. Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas

    PubMed Central

    Driml, Jack; Pulford, Emily; Moffat, David; Karapetis, Christos; Kao, Steven; Griggs, Kim; Henderson, Douglas Warrington; Klebe, Sonja

    2016-01-01

    (1) Background: Malignant mesothelioma (MM) is an aggressive tumour of the serosal membranes, associated with exposure to asbestos. Survival is generally poor, but prognostication for individual patients is difficult. We recently described Aquaporin 1 (AQP1) as independent prognostic factor in two separate retrospective cohorts of MM patients. Here we assess the usefulness of AQP1 prospectively, and determine the inter-observer agreement in assessing AQP1 scores; (2) Methods: A total of 104 consecutive cases of MM were included. Sufficient tissue for immunohistochemistry was available for 100 cases, and these cases were labelled for AQP1. Labelling was assessed by two pathologists. Complete clinical information and follow up was available for 91 cases; (3) Results: Labelling of ≥50% of tumour cells for AQP indicated improved prognosis in a univariate model (median survival 13 versus 8 months, p = 0.008), but the significance was decreased in a multivariate analysis. Scoring for AQP1 was robust, with an inter-observer kappa value of 0.722, indicating substantial agreement between observers; (4) Conclusion: AQP1 is a useful prognostic marker that can be easily incorporated in existing diagnostic immunohistochemical panels and which can be reliably interpreted by different pathologists. PMID:27376267

  4. Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas.

    PubMed

    Driml, Jack; Pulford, Emily; Moffat, David; Karapetis, Christos; Kao, Steven; Griggs, Kim; Henderson, Douglas Warrington; Klebe, Sonja

    2016-01-01

    (1) BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumour of the serosal membranes, associated with exposure to asbestos. Survival is generally poor, but prognostication for individual patients is difficult. We recently described Aquaporin 1 (AQP1) as independent prognostic factor in two separate retrospective cohorts of MM patients. Here we assess the usefulness of AQP1 prospectively, and determine the inter-observer agreement in assessing AQP1 scores; (2) METHODS: A total of 104 consecutive cases of MM were included. Sufficient tissue for immunohistochemistry was available for 100 cases, and these cases were labelled for AQP1. Labelling was assessed by two pathologists. Complete clinical information and follow up was available for 91 cases; (3) RESULTS: Labelling of ≥50% of tumour cells for AQP indicated improved prognosis in a univariate model (median survival 13 versus 8 months, p = 0.008), but the significance was decreased in a multivariate analysis. Scoring for AQP1 was robust, with an inter-observer kappa value of 0.722, indicating substantial agreement between observers; (4) CONCLUSION: AQP1 is a useful prognostic marker that can be easily incorporated in existing diagnostic immunohistochemical panels and which can be reliably interpreted by different pathologists. PMID:27376267

  5. 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. PMID:27454099

  6. 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.

  7. Pathologic Assessment of Rectal Carcinoma after Neoadjuvant Radio(chemo)therapy: Prognostic Implications

    PubMed Central

    Hav, Monirath; Libbrecht, Louis; Ferdinande, Liesbeth; Geboes, Karen; Pattyn, Piet; Cuvelier, Claude A.

    2015-01-01

    Neoadjuvant radio(chemo)therapy is increasingly used in rectal cancer and induces a number of morphologic changes that affect prognostication after curative surgery, thereby creating new challenges for surgical pathologists, particularly in evaluating morphologic changes and tumour response to preoperative treatment. Surgical pathologists play an important role in determining the many facets of rectal carcinoma patient care after neoadjuvant treatment. These range from proper handling of macroscopic specimens to accurate microscopic evaluation of pathological features associated with patients' prognosis. This review presents the well-established pathological prognostic indicators and discusses challenging features in order to provide both surgical pathologists and treating physicians with a checklist that is useful in a neoadjuvant setting. PMID:26509160

  8. Stress testing on silicon carbide electronic devices for prognostics and health management.

    SciTech Connect

    Kaplar, Robert James; Brock, Reinhard C.; Marinella, Matthew; King, Michael Patrick; Smith, Mark A.; Atcitty, Stanley

    2011-01-01

    Power conversion systems for energy storage and other distributed energy resource applications are among the drivers of the important role that power electronics plays in providing reliable electricity. Wide band gap semiconductors such as silicon carbide (SiC) and gallium nitride (GaN) will help increase the performance and efficiency of power electronic equipment while condition monitoring (CM) and prognostics and health management (PHM) will increase the operational availability of the equipment and thereby make it more cost effective. Voltage and/or temperature stress testing were performed on a number of SiC devices in order to accelerate failure modes and to identify measureable shifts in electrical characteristics which may provide early indication of those failures. Those shifts can be interpreted and modeled to provide prognostic signatures for use in CM and/or PHM. Such experiments will also lead to a deeper understanding of basic device physics and the degradation mechanisms behind failure.

  9. 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...

  10. Adverse Effects of Psychotropic Medications on Sleep.

    PubMed

    Doghramji, Karl; Jangro, William C

    2016-09-01

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

  11. Resilience in the Face of Adversity.

    ERIC Educational Resources Information Center

    Patterson, Jerry

    2001-01-01

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

  12. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

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

  13. Helping Student Teachers Avoid Adverse Legal Actions.

    ERIC Educational Resources Information Center

    Peach, Larry; Reddick, Thomas L.

    1984-01-01

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

  14. Pharmacogenomics and adverse drug reactions in children

    PubMed Central

    Rieder, Michael J.; Carleton, Bruce

    2014-01-01

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

  15. [Analysis of Spontaneously Reported Adverse Events].

    PubMed

    Nakamura, Mitsuhiro

    2016-01-01

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

  16. 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...

  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: intense…

  18. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

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

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

    PubMed

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

    2011-08-01

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

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

    PubMed

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

    2014-10-01

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

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

    SciTech Connect

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

    2012-10-01

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

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

    PubMed

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

    2016-07-01

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

  3. Early Local Recurrence Presents Adverse Effect on Outcomes of Primary Breast Sarcoma

    PubMed Central

    Hu, Qun-Chao; Mei, Xin; Feng, Yan; Ma, Jin-Li; Yang, Zhao-Zhi; Shao, Zhi-Min; Yu, Xiao-Li; Guo, Xiao-Mao

    2016-01-01

    Abstract Primary breast sarcomas (PBSs) are spectrum heterogeneous sarcomas in breast and the optimal treatment for them is still under discussion. Our study was to investigate clinical characteristics and identify potential prognostic factors for this rare malignancy. The authors retrospectively reviewed 38 patients with PBSs between October 2000 and February 2014 in FuDan University Shanghai Cancer Center. Local control rate and overall survival (OS) were determined by Kaplan–Meier actuarial method. Univariate analysis and Cox proportional hazards model were applied to identify potential prognostic factors. With median follow-up of 40.19 months, 14 patients (14/38) were found with local recurrence. Extensive operation like mastectomy was not superior to local resection (P = 0.167). Three-year recurrence-free survival and OS rate were 61.9% and 89%, respectively. Larger tumor size and local recurrence were indicated as unfavorable prognostic factors in univariate analysis. Cox model identified narrow interval of recurrence free survival as an unfavorable factor (P = 0.048). Surgery remains crucial treatment for PBSs. Mastectomy, however, is not routinely necessary if clear margin could be achieved by local excision. Early recurrence indicates a poor OS. PMID:26735546

  4. Prognostic and predictive markers in pancreatic adenocarcinoma.

    PubMed

    Le, Nha; Sund, Malin; Vinci, Alessio

    2016-03-01

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

  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. 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

  7. Probability of severe adverse events as a function of hospital occupancy.

    PubMed

    Boyle, Justin; Zeitz, Kathryn; Hoffman, Richard; Khanna, Sankalp; Beltrame, John

    2014-01-01

    A unique application of regression modeling is described to compare hospital bed occupancy with reported severe adverse events amongst inpatients. The probabilities of the occurrence of adverse events as a function of hospital occupancy are calculated using logistic and multinomial regression models. All models indicate that higher occupancy rates lead to an increase in adverse events. The analysis identified that at an occupancy level of 100%, there is a 22% chance of one severe event occurring and a 28% chance of at least one severe event occurring. This modeling contributes evidence toward the management of hospital occupancy to benefit patient outcomes. PMID:24403399

  8. Nonrhabdomyosarcomatous abdominopelvic sarcomas: Analysis of prognostic factors

    PubMed Central

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

    2016-01-01

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

  9. Minimally invasive follicular thyroid carcinomas: prognostic factors.

    PubMed

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

    2016-08-01

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

  10. Renal tumors: diagnostic and prognostic biomarkers.

    PubMed

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

    2013-10-01

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

  11. The Prognostic Role of SOCS3 and A20 in Human Cholangiocarcinoma

    PubMed Central

    Wang, Yimin; Wan, Ming; Zhou, Qingxin; Wang, Hao; Wang, Zhidong; Zhong, Xiangyu; Zhang, Lei; Tai, Sheng; Cui, Yunfu

    2015-01-01

    As an antagonist of the JAK/STAT pathway, suppressor of cytokine signaling 3 (SOCS3) plays an integral role in shaping the inflammatory environment, tumorigenesis and disease progression in cholangiocarcinoma (CCA); however, its prognostic significance remains unclear. Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown. In this study, we investigated the expression of SOCS3 and A20 in human CCA tissues to assess the prognostic significance of these proteins. The expression of SOCS3 and A20 was initially detected by western blot in 22 cases of freshly frozen CCA tumors with corresponding peritumoral tissues and 22 control normal bile duct tissues. Then, these proteins were investigated in 86 CCA patients by immunohistochemistry (IHC) and were evaluated for their association with clinicopathological parameters in human CCA. The results indicated that SOCS3 expression was significantly lower in CCA tumor tissues than in corresponding peritumoral biliary tissues and normal bile duct tissues. Conversely, A20 was overexpressed in CCA tissues. Thus, an inverse correlation between the expression of SOCS3 and A20 was discovered. Furthermore, patients with low SOCS3 expression or high A20 expression showed a dramatically lower overall survival rate. These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate. However, only A20 showed a significant association with the tumor node metastasis (TNM) stage, while SOCS3 showed a significant association with tumor differentiation. Multivariate Cox analysis revealed that SOCS3 and A20 were independent prognostic indicators for overall survival in CCA. Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA. PMID:26485275

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

    PubMed Central

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

    2012-01-01

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

  13. 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.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  16. 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.

  17. Vaginal douching and adverse health effects: a meta-analysis.

    PubMed Central

    Zhang, J; Thomas, A G; Leybovich, E

    1997-01-01

    OBJECTIVES: The meta-analysis described here reviewed the current literature on adverse health effects of vaginal douching. METHODS: Papers published in English from 1965 through 1995 were potentially eligible. RESULTS: One third of White women and two thirds of Black women of reproductive age reported douching regularly. Analyses indicated that vaginal douching increases the overall risk of pelvic inflammatory disease by 73% and the risk of ectopic pregnancy by 76%. Frequent douching was shown to be highly associated with pelvic inflammatory disease and modestly associated with cervical cancer. CONCLUSIONS: Current literature suggests that frequent douching increases the risk of pelvic inflammatory disease, ectopic pregnancy, and, possibly, cervical cancer. PMID:9240115

  18. Adverse Events Associated with Hormonal Therapy for Prostate Cancer

    PubMed Central

    Kumar, Ravi J; Barqawi, Al; Crawford, E. David

    2005-01-01

    With expanding indications for androgen deprivation therapy for the treatment of prostate cancer, it is imperative that health care providers be cognizant of the possible adverse effects of therapy, as well as their prevention and treatment. Neurologic and psychiatric effects include depression and declines in cognitive function. Musculoskeletal effects of hormonal therapy include osteoporosis, decrease in muscle mass, and fatigue. Gynecomastia, weight gain, and erectile dysfunction are also seen, as are hematologic effects. Further research is needed to evaluate alternative forms of therapy, such as intermittent hormonal deprivation and antiandrogen monotherapy. PMID:16985883

  19. Possible significance of adverse reactions to glutamate in humans.

    PubMed

    Reif-Lehrer, L

    1976-09-01

    Of those exposed to Chinese restaurant food, our studies indicate that 25% report adverse reactions (Chinese restaurant syndrome (CRS)), presumably to the mono-sodium glutamate (MSG) content. The possible significance of the symptoms is discussed in the light of the known neuroexcitatory activity of MSG. It is suggested that CRS may result from a "benign" inborn "error" of metabolism that is deserving of further study, particularly in individuals with certain other metabolic abnormalities or who are on certain types of drug therapy. PMID:782921

  20. Magnitude of income-related disparities in adverse perinatal outcomes

    PubMed Central

    2014-01-01

    Background To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. Methods A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. Results The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. Conclusions This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases. PMID:24589212

  1. Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

    PubMed Central

    Fabregat-Andrés, Óscar; Estornell-Erill, Jordi; Ridocci-Soriano, Francisco; Pérez-Boscá, José Leandro; García-González, Pilar; Payá-Serrano, Rafael; Morell, Salvador; Cortijo, Julio

    2016-01-01

    Background Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. Results 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). Conclusions In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF. PMID:26840055

  2. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  3. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  4. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  5. Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: a large case series study with a long-term follow-up.

    PubMed

    Bustreo, Sara; Osella-Abate, Simona; Cassoni, Paola; Donadio, Michela; Airoldi, Mario; Pedani, Fulvia; Papotti, Mauro; Sapino, Anna; Castellano, Isabella

    2016-06-01

    Although Ki67 index suffers from poor reproducibility, it is one of the most important prognostic markers used by oncologists to select the treatment of estrogen receptor (ER) positive breast cancer patients. In this study, we aim to establish the optimal Ki67 cut-offs for stratifying patient prognosis and to create a comprehensive prognostic index for clinical applications. A mono-institutional cohort of 1.577 human epidermal growth factor receptor 2 negative/ER+ breast cancer patients having complete clinical, histological, and follow-up data was collected. The 14 and 20 % Ki67 cut-offs were correlated to disease-free interval (DFI) and disease-specific survival (DSS). To create a comprehensive prognostic index, we used independent variables selected by uni/multivariate analyses. In terms of DFI and DSS, patients bearing tumors with Ki67 < 14 % proliferation index did not differ from those with Ki67 values between 14 and 20 %. Patients with tumor with Ki67 > 20 % showed the poorest prognosis. Moreover, to tumor size, the number of metastatic lymph nodes and Ki67 > 20 % was given a score value, varying depending on definite cut-offs and used to create a prognostic index, which was applied to the population. Patients with a prognostic index ≥3 were characterized by significant risk of relapse [DFI: Hazard Ratio (HR) = 4.74, p < 0.001] and death (DSS: HR = 5.03, p < 0.001). We confirm that the 20 % Ki67 cut-off is the best to stratify high-risk patients in luminal breast cancers, and we suggest to integrate it with other prognostic factors, to better stratify patients at risk of adverse outcome. PMID:27155668

  6. Emotion Dysregulation Mediates the Relationship between Lifetime Cumulative Adversity and Depressive Symptomatology

    PubMed Central

    Abravanel, Benjamin T.; Sinha, Rajita

    2014-01-01

    Repeated exposure to stressful events across the lifespan, referred to as cumulative adversity, is a potent risk factor for depression. Research indicates that cumulative adversity detrimentally affects emotion regulation processes, which may represent a pathway linking cumulative adversity to vulnerability to depression. However, empirical evidence that emotion dysregulation mediates the relationship between cumulative adversity and depression is limited, particularly in adult populations. We examined the direct and indirect effects of cumulative adversity on depressive symptomatology in a large community sample of adults (n = 745) who were further characterized by risk status: never-depressed (n = 638) and “at-risk” remitted mood-disordered (n = 107). All participants completed the Cumulative Adversity Inventory (CAI), the Difficulties in Emotion Regulation Scale (DERS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Bootstrapped confidence intervals were computed to estimate the indirect effect of emotion dysregulation on the relationship between cumulative adversity and depressive symptomatology and to test whether this indirect effect was moderated by risk status. Emotion dysregulation partially and significantly mediated the relationship between cumulative adversity and depressive symptomatology independent of risk status. Overall, cumulative adversity and emotion dysregulation accounted for 50% of the variance in depressive symptomatology. These findings support the hypothesis that disruption of adaptive emotion regulation processes associated with repeated exposure to stressful life events represents an intrapersonal mechanism linking the experience of adverse events to depression. Our results support the utility of interventions that simultaneously emphasize stress reduction and emotion regulation to treat and prevent depressive vulnerability and pathology. PMID:25528603

  7. 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

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

    PubMed Central

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

    2014-01-01

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

  9. Outcome and Prognostic Indicators in Cats Undergoing Splenectomy for Splenic Mast Cell Tumors.

    PubMed

    Kraus, Kelly A; Clifford, Craig A; Davis, Garrett J; Kiefer, Kristina M; Drobatz, Kenneth J

    2015-01-01

    This was a multi-institutional retrospective study evaluating the outcome and clinical parameters associated with the postoperative prognosis of 36 cats with splenic mast cell tumors treated with splenectomy. Clinical parameters reviewed included signalment, clinical history, results of staging tests, surgical variables, administration of blood products, presence of metastasis, postoperative complications, administration of chemotherapy postoperatively, chemotherapy protocol, and response to chemotherapy. Overall median survival time was 390 days (range, 2-1737 days). Administration of a blood product (P < .0001), metastasis to a regional lymph node (P = .022), and evidence of either concurrent or historical neoplasia (P = .037) were negatively associated with survival. Response to chemotherapy (P = .0008) was associated with an improved median survival time. Larger-scale prospective studies evaluating different chemotherapy protocols are required to elucidate the discrepancy between lack of survival benefit with administration of chemotherapy and improvement in survival time with positive response to chemotherapy. PMID:26083443

  10. Serum Lactate Dehydrogenase in Non-Hodgkin's Lymphoma: A Prognostic Indicator.

    PubMed

    Yadav, Charu; Ahmad, Afzal; D'Souza, Benedicta; Agarwal, Ashish; Nandini, M; Ashok Prabhu, K; D'Souza, Vivian

    2016-04-01

    Non-Hodgkin's lymphoma constitutes a group of disorders originating from the malignant transformation of lymphocytes and involving either the lymph nodes or extranodal sites. NHL commonly presents in the sixth to seventh decade of life with a male preponderance (50-75 %). Recent studies have shown importance of serum LDH in prognosis of NHL. Authors report a case of a 63 year old male presenting with complaints of fever and backache for past 4 months. General and systemic examination revealed bilateral axillary lymphadenopathy and splenomegaly respectively. Serum LDH level was highly elevated (3441 U/l). Excisional axillary and bone marrow biopsy were done before oncology referral. Complete workup revealed diffuse Non-Hodgkin's lymphoma with bone marrow infiltration. Patient died because of acute renal failure due to NHL and DM 2 (Type 2 diabetes mellitus). PMID:27069334

  11. DNA flow cytometry of colorectal carcinoma: correlation of DNA stemlines with other prognostic indices.

    PubMed

    Bawani, M; Tibrewala, S; Copur, S; Harris, D; Gilman-Sachs, A

    1991-02-01

    DNA flow cytometry (FCM) was performed on paraffin-embedded tissue blocks of 38 surgically resected colorectal carcinoma