National Institutes of Health–Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities

Eight manufacturing facilities participating in the National Institutes of Health–sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed

Expanded indications for bariatric surgery: should patients on chronic steroids be offered bariatric procedures?

BackgroundPatients who take chronic corticosteroids are increasingly referred for bariatric surgery. Little is known about their clinical outcomes.ObjectiveDetermine whether chronic steroid use is associated with increased morbidity and mortality after stapled bariatric procedures.SettingAmerican College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database.MethodsAll patients who underwent laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass and were reported to the ACS-NSQIP from 2011 to 2013 were reviewed. Patients were grouped based on type of surgery and history of chronic steroid use. Primary outcome measures were mortality and serious morbidity in the first 30 days. Regression analyses were used to determine predictors of outcome.ResultsOf 23,798 patients who underwent laparoscopic sleeve gastrectomy and 38,184 who underwent Roux-en-Y gastric bypass, 385 (1.6%) and 430 (1.1%), respectively, were on chronic steroids. Patients on chronic steroids had a 3.4 times increased likelihood of dying within 30 days (95% confidence interval 1.4-8.1, P = .007), and 2-fold increased odds of serious complications (95% confidence interval 1.2-2.3, P = .008), regardless of surgery type. In multivariate regression, steroid usage remained an independent predictor of mortality and serious complications.ConclusionIn a large, nationally representative patient database, steroid use independently predicted mortality and serious postoperative complications after stapled bariatric procedures. Surgeons should be cautious about offering stapled bariatric procedures to patients on chronic steroids

Islet product characteristics and factors related to successful human islet transplantation from the collaborative islet transplant registry (CITR) 1999-2010

© 2014 The Authors. American Journal of Transplantation Published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants

Long-Term Renal Function and Cardiovascular Disease Risk in Obese Kidney Donors

Background and objectives: Increasing demand for live-donor kidneys has encouraged the use of obese donors despite the absence of long-term outcome data and evidence that obesity can adversely affect renal function. We wished to determine whether obesity increased the risk for renal dysfunction and other medical comorbidities in donors several years after donation

An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport.

Diffusion-based bioartificial pancreas (BAP) devices are limited by poor islet viability and functionality due to inadequate mass transfer resulting in islet hypoxia and delayed glucose-insulin kinetics. While intravascular ultrafiltration-based BAP devices possess enhanced glucose-insulin kinetics, the polymer membranes used in these devices provide inadequate ultrafiltrate flow rates and result in excessive thrombosis. Here, we report the silicon nanopore membrane (SNM), which exhibits a greater hydraulic permeability and a superior pore size selectivity compared to polymer membranes for use in BAP applications. Specifically, we demonstrate that the SNM-based intravascular BAP with ∼10 and ∼40 nm pore sized membranes support high islet viability (>60%) and functionality (<15 minute insulin response to glucose stimulation) at clinically relevant islet densities (5700 and 11 400 IE per cm2) under convection in vitro. In vivo studies with ∼10 nm pore sized SNM in a porcine model showed high islet viability (>85%) at clinically relevant islet density (5700 IE per cm2), c-peptide concentration of 144 pM in the outflow ultrafiltrate, and hemocompatibility under convection. These promising findings offer insights on the development of next generation of full-scale intravascular devices to treat T1D patients in the future

Correction: An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport

Correction for 'An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport' by Shang Song et al., Lab Chip, 2017, 17, 1778-1792

Increases in PYY and uncoupling of bone turnover are associated with loss of bone mass after gastric bypass surgery.

ContextThe gut hormones peptide YY (PYY) and ghrelin mediate in part the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. However, preclinical data suggest these hormones also affect the skeleton and could contribute to postoperative bone loss.ObjectiveWe investigated whether changes in fasting serum total PYY and ghrelin were associated with bone turnover marker levels and loss of bone mineral density (BMD) after RYGB.Design, setting, participantsProspective cohort of adults undergoing RYGB (n=44) at San Francisco academic hospitals.Main outcome measuresWe analyzed 6-month changes in PYY, ghrelin, bone turnover markers, and BMD by dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). We calculated the uncoupling index (UI), reflecting the relative balance of bone resorption and formation.ResultsPostoperatively, there was a trend for an increase in PYY (+25pg/mL, p=0.07) and a significant increase in ghrelin (+192pg/mL, p<0.01). PYY changes negatively correlated with changes in spine BMD by QCT (r=-0.36, p=0.02) and bone formation marker P1NP (r=-0.30, p=0.05). Relationships were significant after adjustments for age, sex, and weight loss. No consistent relationships were found between ghrelin and skeletal outcomes. Mean 6-month UI was -3.3; UI correlated with spine BMD loss by QCT (r=0.40, p=0.01).ConclusionsPostoperative PYY increases were associated with attenuated increases in P1NP and greater declines in spine BMD by QCT. Uncoupling of bone turnover correlated with BMD loss. These findings suggest a role for PYY in loss of bone mass after RYGB and highlight the relationship between intestinal and skeletal metabolism