Baseline mitral regurgitation predicts outcome in patients referred for dobutamine stress echocardiography

Purpose: A number of parameters recorded during dobutamine stress echocardiography (DSE) are associated with worse outcome. However, the relative importance of baseline mitral regurgitation (MR) is unknown. The aim of this study was to assess the prevalence and associated implications of functional MR with long-term mortality in a large cohort of patients referred for DSE. Methods: 6745 patients (mean age 64.9±12.2 years) were studied. Demographic, baseline and peak DSE data were collected. All-cause mortality was retrospectively analyzed. DSE was successfully completed in all patients with no adverse outcomes. Results: MR was present in 1019 (15.1%) patients. During a mean follow up of 5.1±1.8 years, 1642 (24.3%) patients died and MR was significantly associated with increased all-cause mortality (p<0.001). With Kaplan-Meier analysis, survival was significantly worse for patients with moderate and severe MR (p<0.001). With multivariate Cox regression analysis, moderate and severe MR (HR 2.78; 95% CI 2.17 - 3.57; and HR 3.62; 95% CI 2.89 - 4.53, respectively) were independently associated with all-cause mortality. The addition of MR to C statistic models significantly improved discrimination. Conclusions: MR is associated with all-cause mortality and adds incremental prognostic information among patients referred for DSE. The presence of MR should be taken into account when evaluating the prognostic significance of DSE results

Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems

BACKGROUND: Brain metastases (BM) are the most common form of intracranial cancer. The incidence of BM seems to have increased over the past decade. Recursive partitioning analysis (RPA) of data from three Radiation Therapy Oncology Group (RTOG) trials (1200 patients) has allowed three prognostic groups to be identified. More recently a simplified stratification system that uses the evaluation of three main prognostics factors for radiosurgery in BM was developed. METHODS: To analyze the overall survival rate (OS), prognostic factors affecting outcomes and to estimate the potential improvement in OS for patients with BM from breast cancer, stratified by RPA class and brain metastases score (BS-BM). From January 1996 to December 2004, 174 medical records of patients with diagnosis of BM from breast cancer, who received WBRT were analyzed. The surgery followed by WBRT was used in 15.5% of patients and 84.5% of others patients were submitted at WBRT alone; 108 patients (62.1%) received the fractionation schedule of 30 Gy in 10 fractions. Solitary BM was present in 37.9 % of patients. The prognostic factors evaluated for OS were: age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, neurosurgery, chemotherapy, absence extracranial disease, RPA class, BS-BM and radiation doses and fractionation. RESULTS: The OS in 1, 2 and 3 years was 33.4 %, 16.7%, and 8.8 %, respectively. The RPA class analysis showed strong relation with OS (p < 0.0001). The median survival time by RPA class in months was: class I 11.7, class II 6.2 and class III 3.0. The significant prognostic factors associated with better OS were: higher KPS (p < 0.0001), neurosurgery (P < 0.0001), single metastases (p = 0.003), BS-BM (p < 0.0001), control primary tumor (p = 0.002) and absence of extracranial metastases (p = 0.001). In multivariate analysis, the factors associated positively with OS were: neurosurgery (p < 0.0001), absence of extracranial metastases (p <0.0001) and RPA class I (p < 0.0001). CONCLUSION: Our data suggests that patients with BM from breast cancer classified as RPA class I may be effectively treated with local resection followed by WBRT, mainly in those patients with single BM, higher KPS and cranial extra disease controlled. RPA class was shown to be the most reliable indicators of survival

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Abarema cochliacarpos: Gastroprotective and ulcer-healing activities

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Ethnopharmacological relevance: Abarema cochliacarpos (Gomes) Barneby & Grimes (Mimosaceae) is a species - in folk medicine of Lagarto city, Sergipe state, northeastern Brazil - reputed to heal gastric ulcer and gastritis. Aim of the study: Chloroform (CE) and methanolic (ME) extracts as well as ethyl acetate fraction (AF), butanolic fraction (AC) and aqueous fraction (AQF) of the methanolic extract of Abarema cochliacarpos bark were evaluated against acute gastric ulcer. The AC fraction was selected to assess its activity in ulcer healing and its gastroprotective effects via mucus and gastric secretion. Material and methods: The gastroprotective action of CE and ME extracts and the fractions of the latter were evaluated in a rodent experimental model. The action mechanisms, involvements of the antisecretory action and mucus production, toxicological and healing activity of the AC (150 mg/kg, p.o.) were evaluated. We also used histological analysis (HE and PAS) and immunohistochemical (PCNA, COX-2, VEGF and HSP-70) assays to evaluate the effects of Abarema cochliacarpos. Results: CE (200 and 400 mg/kg, p.o.) and ME (100, 200 and 400 mg/kg, p.o.) extracts were able to protect gastric mucosa against absolute ethanol. Respective inhibitions produced were: 65.31% and 83.80% by the first; 91.69%, 96.75% and 99.80% by the second; and 74.24% by the AC fraction. Antisecretory and mucus production effects were exhibited by the AC fraction, which also accelerated the healing of ulcerated gastric mucosa by stimulating proliferation factors (PCNA) and induced healing factors including COX-2, VEGF and HSP-70. Conclusion: All these results suggest that Abarema cochliacarpos (Comes) Barneby & Grimes presents gastroprotective effects and wound-healing properties. (C) 2010 Elsevier Ireland Ltd. All rights reserved.1321134142Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Instituto Federal de EducacaoCiencia e Tecnologia de Sergipe (IFS, Brazil)Universidade Estadual de Alagoas (UNEAL, Brazil)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling.

The small intestinal tuft cell-ILC2 circuit mediates epithelial responses to intestinal helminths and protists by tuft cell chemosensory-like sensing and IL-25-mediated activation of lamina propria ILC2s. Small intestine ILC2s constitutively express the IL-25 receptor, which is negatively regulated by A20 (Tnfaip3). A20 deficiency in ILC2s spontaneously triggers the circuit and, unexpectedly, promotes adaptive small-intestinal lengthening and remodeling. Circuit activation occurs upon weaning and is enabled by dietary polysaccharides that render mice permissive for Tritrichomonas colonization, resulting in luminal accumulation of acetate and succinate, metabolites of the protist hydrogenosome. Tuft cells express GPR91, the succinate receptor, and dietary succinate, but not acetate, activates ILC2s via a tuft-, TRPM5-, and IL-25-dependent pathway. Also induced by parasitic helminths, circuit activation and small intestinal remodeling impairs infestation by new helminths, consistent with the phenomenon of concomitant immunity. We describe a metabolic sensing circuit that may have evolved to facilitate mutualistic responses to luminal pathosymbionts