Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury

AIM To investigate the hypothesis that treatment with dimethyl fumarate(D MF) mayame liorate liver ischemia/reperfusion injury(I/RI).METHODS Rats were divided into 3 groups: sham, control(CTL), and DMF. DMF(25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase(ALT) and malondialdehyde(MDA) levels, adenosine triphosphate(ATP), NO × metabolites, anti-oxidant enzyme expression level, antiinflammatory effect, and anti-apoptotic effect were determined.RESULTS Histological tissue damage was significantly reduced in the DMF group(Suzuki scores: sham: 0 ± 0; CTL: 9.3± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT(DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA(DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content(DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity(DMF 7.8 ± 0.4 m U/m L vs CTL 6.0 ± 0.5 m U/m L, P = 0.01) and level of endothelial nitric oxide synthase expression(DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes(catalase and glutamatecysteine ligase modifier subunit and lower levels of key inflammatory mediators(nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group.CONCLUSION DMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.

Total pancreatectomy and islet autotransplantation: A decade nationwide analysis

AIM: To investigate outcomes and predictors of inhospital morbidity and mortality after total pancreatectomy(TP) and islet autotransplantation. METHODS: The nationwide inpatient sample(NIS) database was used to identify patients who underwent TP and islet autotransplantation(IAT) between 2002-2012 in the United States. Variables of interest were inherent variables of NIS database which included demographic data(age, sex, and race), comorbidities(such as diabetes mellitus, hypertension, and deficiency anemia), and admission type(elective vs nonelective). The primary endpoints were mortality and postoperative complications according to the ICD-9 diagnosis codes which were reported as the second to 25 th diagnosis of patients in the database. Risk adjusted analysis was performed to investigate morbidity predictors. Multivariate regression analysis was used to identify predictors of in-hospital morbidity.RESULTS: We evaluated a total of 923 patients who underwent IAT after pancreatectomy during 2002-2012. Among them, there were 754 patients who had TP + IAT. The most common indication ofsurgery was chronic pancreatitis(86%) followed by acute pancreatitis(12%). The number of patients undergoing TP + IAT annually significantly increased during the 11 years of study from 53 cases in 2002 to 155 cases in 2012. Overall mortality and morbidity of patients were 0% and 57.8 %, respectively. Postsurgical hypoinsulinemia was reported in 42.3% of patients, indicating that 57.7% of patients were insulin independent during hospitalization. Predictors of inhospital morbidity were obesity [adjusted odds ratio(AOR): 3.02, P = 0.01], fluid and electrolyte disorders(AOR: 2.71, P < 0.01), alcohol abuse(AOR: 2.63, P < 0.01), and weight loss(AOR: 2.43, P < 0.01). CONCLUSION: TP + IAT is a safe procedure with no mortality, acceptable morbidity, and achieved high rate of early insulin independence. Obesity is the most significant predictor of in-hospital morbidity.

Kidney transplantation in obese patients

The World Health Organization estimated that in 2014, over 600 million people met criteria for obesity. In 2011, over 30% of individuals undergoing kidney transplant had a body mass index(BMI) 35 kg/m^2 or greater. A number of recent studies have confirmed the relationship between overweight/obesity and important comorbidities in kidney transplant patients. As with non-transplant surgeries, the rate of wound and soft tissue complications are increased following transplant as is the incidence of delayed graft function. These two issues appear to contribute to longer length of stay compared to normal BMI. New onset diabetes after transplant and cardiac outcomes also appear to be increased in the obese population. The impact of obesity on patient survival after kidney transplantation remains controversial, but appears to mirror the impact of extremes of BMI in non-transplant populations. Early experience with(open and laparoscopic) Rouxen-Y gastric bypass and laparoscopic sleeve gastrectomy support excellent weight loss(in the range of 50%-60% excess weight lost at 1 year), but experts have recommended the need for further studies. Long term nutrient deficiencies remain a concern but in general, these procedures do not appear to adversely impact absorption of immunosuppressive medications. In this study, we review the literature to arrive at a better understanding of the risks related to renal transplantation among individuals with obesity.