OBJECTIVEob/ob and db/db mice manifest myocardial hypertrophy, insulin resistance, altered substrate utilization, mitochondrial dysfunction, and lipid accumulation. This study was designed to determine the contribution of central and peripheral leptin signaling to myocardial metabolism and function in ob/ob and db/db mice in the absence of diabetes and morbid obesity.RESEARCH DESIGN AND METHODSMale ob/ob mice (aged 4 weeks) were caloric restricted by pairfeeding to a leptin-treated ob/ob group. In addition to determining glucose tolerance and circulating lipid concentrations, myocardial substrate metabolism and mitochondrial function were determined in saponin-permeabilized cardiac fibers. Second, experiments were performed to determine whether leptin treatment by intraperitoneal injection or intracerebroventricular infusion could normalize myocardial palmitate oxidation in caloric-restricted ob/ob mouse hearts.RESULTSDespite normalizing body weight and glucose tolerance, fat mass and circulating lipid levels remained increased in caloric-restricted ob/ob animals. Palmitate oxidation remained elevated in caloric-restricted ob/ob hearts and was normalized by intraperitoneal or intracerebroventricular leptin. Intraperitoneal and intracerebroventricular treatment also normalized circulating free fatty acid levels, myocardial fatty acid oxidation gene expression, and myocardial insulin sensitivity.CONCLUSIONSThese data suggest that impaired hypothalamic leptin signaling is sufficient to increase myocardial fatty acid oxidation by increasing delivery of free fatty acid substrates and peroxisome proliferator–activated receptor-α ligands to the heart.

The current meta-analyses have demonstrated that old age, female sex, low BMI, and poor bowel preparation were the predictors for prolonged CIT.

Background:Balancing the risk of bleeding and thromboembolic events for patients who use aspirin and need to undergo endoscopic submucosal dissection (ESD) for gastric neoplasms is a delicate process. The current guidelines from different associations provide inconsistent recommendations.Methods:MEDLINE and EMBASE databases were searched through August 2017 for studies that compared the risk of post-ESD bleeding in patients who continued aspirin vs. those who discontinued aspirin preoperatively. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random-effect model, generic inverse variance method. The between-study heterogeneity was quantified using the Q statistic and I2.Results:A total of five studies that included 700 patients were identified. Our meta-analysis could not demonstrate a significantly increased risk of post-ESD bleeding among the aspirin-continued group compared to the aspirin-interrupted group, the pooled OR being 1.81 (95%CI 0.85-3.83). The statistical heterogeneity was insignificant, with an I2 of 25%. Nine thrombotic events occurred in the aspirin-interrupted group whereas none occurred in the aspirin-continued group.Conclusions:This meta-analysis could not demonstrate that continuation of aspirin significantly increases the risk of post-ESD bleeding. However, the analysis was restricted by the small sample size and the observational nature of the primary studies. Randomized controlled trials are still needed to clarify this risk.

Aim: Long-term survival after hepatocellular cancer (HCC) is difficult to achieve likely related to recurrence. This study aimed to identify factors that were predictive of 10-year survival after the diagnosis of HCC. Methods:In a prospectively collected database of 1374 HCC cases , we identified 70 patients who survived over 10 years regardless of treatment. We then identified 164 patients in the entire cohort who either had liver resection or transplant, and died before 10 years. Demographics, tumor characteristics, treatment, recurrence and treatment of recurrence were compared.Results: Of the 10-year survivors, 36 underwent transplant, 27 had liver resection and 7 patients had only locoregional therapy. Compared to the non-survivors, the 10-year survivors were younger and had fewer comorbidities or recurrence, smaller tumor size, lower AST, ALT, AFP, platelets, neutrophil-to-lymphocyte ratio. Multivariate analysis showed only age and diabetes to be negative predictors. Recurrence occurred in 24 survivors (34.3%) with mean time to recurrence with standard deviation 57.1 ± 42.6 months compared to 80 non-survivors (48.7%) with mean time to recurrence of 15.3 ± 14.8 months. For hepatic resection, 10-year survivors had longer time to recurrence compared to non-survivors (median: 31.3 months). Conclusion:Long-term survivors mostly occur after resection or transplant, but 10% of our cohort survived 10 years with only locoregional therapy. Underlying health status maybe an important predictor of 10-year survival for patients receiving liver resections. Recurrence of HCC occurs in both 10-year survivors and non-survivors, but later recurrence with aggressive treatment of the recurrence may allow for 10-year survival.