Meta-analysis of CHADS2 Score in Predicting Atrial Fibrillation.

The CHADS2 score is a validated clinical tool used for the risk stratification of stroke in the presence of atrial fibrillation (AF). Recently, some studies have shown that CHADS2 score may predict the risk of AF, which yielded conflicting results. The purpose of this study is to perform a meta-analysis of observational studies to examine the association between the CHADS2 score and risk of AF. Using PubMed and EMBASE database, we searched published articles by November 2014 to identify studies that evaluated the association between CHADS2 score and the risk of AF. We used both fixed-effects and random-effects models to calculate the overall effect estimate. A sensitivity analysis and subgroup analysis were performed to find the origin of heterogeneity. Of the 1,806 studies identified initially, 19 studies were included into our analysis, with a total of 714,672 patients. The CHADS2 score was found to be an independent predictor of AF as both a continuous variable (odds ratio 1.43, 95% confidence interval 1.10 to 1.86, p = 0.007) and categorical variable (odds ratio 3.37, 95% confidence interval 2.65 to 4.28, p <0.00001). Subgroup analysis revealed that different patients' age in study population may be a possible reason for the significant heterogeneity in our meta-analysis. In conclusion, CHADS2 score predicts the risk of AF. Addressing risk factors and early recognition of AF are important and also awareness of CHADS2 score to reduce stroke risk with pharmacologic prophylaxis.

Diabetes mellitus and atrial remodeling: mechanisms and potential upstream therapies.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, and its prevalence has increasing substantially over the last decades. Recent data suggest that there is an increased risk of AF among the patients with diabetes mellitus (DM). However, the potential molecular mechanisms regarding DM-related AF and diabetic atrial remodeling are not fully understood. In this comprehensive review, we would like to summarize the potential relationship between diabetes and atrial remodeling, including structural, electrical, and autonomic remodeling. Also, some upstream therapies, such as thiazolidinediones, probucol, ACEI/ARBs, may play an important role in the prevention and treatment of AF. Therefore, large prospective randomized, controlled trials and further experimental studies should be challengingly continued.

Involvement of osteopontin in the matrix-degrading and proangiogenic changes mediated by nicotine in pancreatic cancer cells.

BACKGROUND: Substantial evidence indicates that exposure to cigarette smoke is associated with an elevated risk of pancreatic ductal adenocarcinoma (PDA). However, the mechanisms underlying the effects of nicotine on the development or progression of PDA remain to be investigated. Previously, we showed that nicotine promotes the expression of osteopontin c (OPNc), an isoform of OPN protein that confers on cancer cells a migratory phenotype. In this study, we explored the potential prometastatic role of nicotine in PDA through studying its effect on the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) and evaluated the role of OPN in mediating these effects. MATERIALS AND METHODS: MMP-9 and VEGF mRNA and protein were analyzed in PDA cells treated with or without nicotine (3-300 nM). Transient transfection and luciferase-labeled promoter studies evaluated the effects of OPNc and OPN protein on the transcription and translation of MMP-9 and VEGF. Real-time PCR and immunohistochemistry were used to analyze the mRNA expression levels and localization of OPN, MMP-9, and VEGF proteins in matched invasive human PDA and surrounding nonmalignant tissues. RESULTS AND DISCUSSION: Nicotine significantly enhanced the expression of MMP-9 and VEGF mRNA and protein in PDA cells. Blocking OPN with siRNA or OPN antibody prevented the nicotine-mediated increase of both MMP-9 and VEGF. Transient transfection of OPNc gene in PDA cells or their treatment with recombinant OPN protein significantly (p < 0.05) increased MMP-9 and VEGF mRNA expression levels and induced their promoter activities. In invasive PDA lesions, MMP-9 mRNA levels were significantly (p < 0.005) higher in smokers vs. nonsmokers. VEGF protein co-localized with MMP-9 and OPN in the malignant ducts and correlated well with their higher levels in invasive PDA lesions. CONCLUSIONS: Our data show for the first time that cigarette smoking and nicotine may contribute to PDA metastasis through inducing MMP-9 and VEGF and suggest that OPN plays a central role in mediating these effects. The presence of OPN as a downstream effector of nicotine that is capable of mediating its prometastatic effects in PDA cells is novel and could provide a unique therapeutic target to control pancreatic cancer aggressiveness, especially in the cigarette-smoking population.