The transplantation of pancreatic islet cells could restore glycaemic control in patients with type-I diabetes. Microspheres for islet encapsulation have enabled long-term glycaemic control in diabetic rodent models; yet human patients transplanted with equivalent microsphere formulations have experienced only transient islet-graft function, owing to a vigorous foreign-body reaction (FBR), to pericapsular fibrotic overgrowth (PFO) and, in upright bipedal species, to the sedimentation of the microspheres within the peritoneal cavity. Here, we report the results of the testing, in non-human primate (NHP) models, of seven alginate formulations that were efficacious in rodents, including three that led to transient islet-graft function in clinical trials. Although one month post-implantation all formulations elicited significant FBR and PFO, three chemically modified, immune-modulating alginate formulations elicited reduced FBR. In conjunction with a minimally invasive transplantation technique into the bursa omentalis of NHPs, the most promising chemically modified alginate derivative (Z1-Y15) protected viable and glucose-responsive allogeneic islets for 4 months without the need for immunosuppression. Chemically modified alginate formulations may enable the long-term transplantation of islets for the correction of insulin deficiency

Background & Aims Early reports suggested androgen/androgen receptor (AR) signals promote hepatocarcinogenesis. However, all antiandrogen clinical trials failed in advanced hepatocellular carcinoma (HCC) without reasonable explanations. We have examined AR functions in HCC cancer metastasis in this study. Methods We examined hepatic AR roles in HCC metastasis by comparing liver hepatocyte AR knockout and wildtype in carcinogen-induced HCC mouse model. We examined tumor histology, cancer metastatic risks, and cancer survival in vivo, as well as cell anoikis and migration using primary hepatic tumor culture in vitro. We also examined therapeutic potentials of AR expression combined with molecular targeting agent, Sorafenib, in HCC metastasis mouse model. Results We found a novel cancer phenotype in which mice lacking hepatic AR developed more undifferentiated tumors and larger tumor size at later metastatic stage. These mice also died earlier with increased lung metastasis, suggesting hepatic-AR may play dual yet opposite roles to promote HCC initiation but suppress HCC metastasis. Mechanistic dissection found that hepatic AR could enhance anoikis and suppress migration of HCC cells via suppression of p38 phosphorylation/activation and the NFκB-MMP9 pathway, respectively. In addition, the in vivo pre-clinical trials concluded that a combination therapy of increased AR expression and reduced multiple-kinase inhibitor (Sorafenib) exhibited better therapeutic efficacy. Conclusions Our study demonstrated that AR could orchestrate intrahepatic signalling hierarchies and cellular behavior, consequently affect HCC progression. Results from combination therapy shed a light on developing new therapeutic paradigm for battling HCC at later metastatic stage.

Early initiation of CAPD with surgically implanted Tenckhoff catheters is feasible and safe. Shorter break-in periods are not associated with more catheter-related complications. The data from our peritoneal dialysis population suggest that early initiation is not associated with an increased number of complications. This needs to be confirmed in a randomized trial.

OBJECTIVETo investigate whether diabetes affects perioperative complications or mortality and to gauge its impact on medical expenditures for noncardiac surgeries.RESEARCH DESIGN AND METHODSWith the use of reimbursement claims from the Taiwan National Health Insurance system, we performed a population-based cohort study of patients with and without diabetes undergoing noncardiac surgeries. Outcomes of postoperative complications, mortality, hospital stay, and medical expenditures were compared between patients with and without diabetes.RESULTSDiabetes increased 30-day postoperative mortality (odds ratio 1.84 [95% CI 1.46–2.32]), particularly among patients with type 1 diabetes or uncontrolled diabetes and patients with preoperative diabetes-related comorbidities, such as eye involvement, peripheral circulatory disorders, ketoacidosis, renal manifestations, and coma. Compared with nondiabetic control patients, coexisting medical conditions, such as renal dialysis (5.17 [3.68–7.28]), liver cirrhosis (3.59 [2.19–5.88]), stroke (2.87 [1.95–4.22]), mental disorders (2.35 [1.71–3.24]), ischemic heart disease (2.08 [1.45–2.99]), chronic obstructive pulmonary disease (1.96 [1.29–2.97]), and hyperlipidemia (1.94 [1.01–3.76]) were associated with mortality for patients with diabetes undergoing noncardiac surgery. Patients with diabetes faced a higher risk of postoperative acute renal failure (3.59 [2.88–4.48]) and acute myocardial infarction (3.65 [2.43–5.49]). Furthermore, diabetes was associated with prolonged hospital stay (2.30 [2.16–2.44]) and increased medical expenditures (1.32 [1.25–1.40]).CONCLUSIONSDiabetes increases postoperative 30-day mortality, complications, and medical expenditures in patients undergoing in-hospital noncardiac surgeries.

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Patients with mental disorders have an increased risk of TBI. Intensity of psychiatric medication is associated with increased post-injury mortality. Special attention to prevent TBI among this disabled population is mandatory.

The risk of epilepsy after TBI varied by patient gender, age, latent interval and complexity of TBI. Integrated care for early identification and treatment of post-trauma epilepsy were crucial for TBI patients.

OBJECTIVEThe relationship between diabetes and fracture is not completely understood. This study evaluated fracture risk and postfracture mortality in patients with diabetes. RESEARCH DESIGN AND METHODSWe identified 32,471 adults newly diagnosed with diabetes in 2000-2003 using Taiwan's National Health Insurance Research Database. A comparison cohort of 64,942 adults without diabetes was randomly selected from the same dataset, with frequency matched by age and sex. Fracture events in 2000-2008 were ascertained from medical claims. Adjusted hazard ratios (HRs) and 95% CIs of fracture associated with diabetes were calculated. A nested cohort study of 17,002 patients with fracture receiving repair surgeries between 2004 and 2010 calculated adjusted odds ratios (ORs) and 95% CIs of adverse events after fracture in patients with and without diabetes. RESULTSDuring 652,530 person-years of follow-up, there were 12,772 newly diagnosed fracture cases. The incidences of fracture for people with diabetes and without were 24.2 and 17.1 per 1,000 person-years, respectively (P < 0.0001). Compared with people without diabetes, the adjusted HR of fracture was 1.66 (95% CI 1.60-1.72) for people with diabetes. The ORs of postfracture deep wound infection, septicemia, and mortality associated with diabetes were 1.34 (95% CI 1.06-1.71), 1.42 (95% CI 1.23-1.64), and 1.27 (95% CI 1.02-1.60), respectively. CONCLUSIONSDiabetes was associated with fracture. Patients with diabetes had more adverse events and subsequent mortality after fracture. Prevention of fracture and postfracture adverse events is needed in this susceptible population.Although the epidemiology, pathogenesis, prevention, and treatment of diabetes have been well established over the past two centuries (1), diabetes remains a pandemic chronic disease that is projected to reach an estimated global prevalence of 4.4% by 2030 (2). Diabetes also presents a high economic burden, with an estimated cost of 245 billion USD in 2012 in the U.S. (3). Recognized complications