Morbid obesity is a relative contraindication for organ transplant because it is associated with higher postoperative morbidity and mortality. The safety and efficacy of laparoscopic sleeve ...gastrectomy (LSG) as a weight loss method for patients awaiting transplant has not been examined.
A retrospective review was performed on morbidly obese patients awaiting liver or kidney transplant who underwent LSG from 2006 to 2012. Data included patient demographic characteristics, operative details, 30-day complications, percentage of excess weight loss, postoperative laboratory data, and status of transplant candidacy.
Twenty-six pretransplant patients underwent LSG. The mean age was 57 years, and 17 (65%) were women. Six patients had end-stage renal disease, and 20 patients had end-stage liver disease. The preoperative mean body mass index was 48.3 kg/m(2) (range 38-60.4 kg/m(2)). There were no deaths, and there were 6 postoperative complications: 2 superficial wound infections, 1 staple line leak, 1 postoperative bleed requiring blood transfusion, 1 transient encephalopathy, and 1 temporary renal insufficiency. The mean percentage of excess weight loss at 1, 3, and 12 months was 17% (n = 24/26), 26% (n = 23/26), and 50% (n = 18/20), respectively. All patients met our institution's body mass index cutoffs for transplantation by 12 months after the procedure. One patient's renal function stabilized, and he was taken off the transplant list. Eight patients eventually underwent solid organ transplant. Six received liver transplants, 1 patient received a combined liver and kidney transplant, and 1 received a kidney transplant. The mean time between LSG and transplant was 16.6 months.
This is the largest case series involving LSG in patients awaiting solid organ transplantation. LSG is well tolerated, is technically feasible, and improves candidacy for transplantation.
Morbid obesity (body mass index BMI ≥40 kg/m2) is a relative contraindication to liver transplantation (LT) at many transplant centers. The safety and efficacy of pre‐LT bariatric surgery in morbidly ...obese LT candidates is unknown. Herein, we describe a cohort study of morbidly obese LT candidates who failed to achieve adequate weight loss through a medically supervised weight loss program and subsequently underwent sleeve gastrectomy (SG) at our institution. In total, 32 LT candidates with a median Model for End‐Stage Liver Disease (MELD) score of 12 (interquartile range IQR, 10‐13) underwent SG. All LT candidates had a history of hepatic decompensation, but complications of liver disease were required to be well controlled at the time of SG. Median pre‐SG BMI was 45.0 kg/m2 (IQR, 42.1‐49.0 kg/m2). There were no perioperative deaths or liver‐related morbidity. One patient experienced major perioperative morbidity secondary to a gastric leak, which was managed nonoperatively. Median weight loss at 6 and 12 months after SG was 22.0 kg (IQR, 18.9‐26.8 kg) and 31.0 kg (IQR, 23.6‐50.3 kg), respectively, corresponding to a percentage of excess body weight lost of 33.4% and 52.4%. Within 6 months after SG, 28 (88%) candidates were deemed eligible for LT. Our center’s experience highlights the potential option of SG in morbidly obese LT candidates with advanced liver disease who might otherwise be excluded from pursuing LT.
Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in ...preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment.
This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA1c <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant.
The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA1c level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients.
Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.
Strategies to optimize the management of obesity‐related metabolic complications after liver transplantation (LT) are needed. We examined the effect of pre‐LT sleeve gastrectomy (SG), as compared to ...medical weight loss (MWL), on post‐LT outcomes. This is a cohort study of adults (≥18 years) with medically complicated obesity who were eligible for pre‐LT SG and underwent LT from January 1, 2006 to June 1, 2016. Logistic regression models evaluated the association of SG on post‐LT diabetes and hypertension, defined as new‐onset or progressive disease post‐LT. Cox regression models evaluated the association of SG on recurrent and de novo nonalcoholic fatty liver disease (NAFLD). Among 70 LT recipients who were eligible for pre‐LT SG, 14 (20%) underwent SG and 56 (80%) underwent MWL only. Mean follow‐up was 5.2 years post‐LT. The SG cohort sustained higher % total body weight loss at 3 years post‐LT (28.9% vs. 5.4%, p < .001). In multivariable analyses, SG was associated with significantly lower risk of post‐LT diabetes (OR 0.04, 95% CI 0.00–0.41, p = .01), hypertension (OR 0.15, 95% CI 0.04–0.67, p = .01), and recurrent and de novo NAFLD (HR 0.19, 95% CI 0.04–0.91, p = .04). When compared to MWL, SG resulted in sustained weight loss and significantly lower risk of diabetes, hypertension, and recurrent and de novo NAFLD post‐LT.
In adult recipients with medically complicated obesity, sleeve gastrectomy prior to liver transplantation compared to medical weight loss alone is associated with sustained weight loss after transplantation as well as significantly lower risks of diabetes, hypertension, and recurrent or de novo nonalcoholic fatty liver disease.
Bariatric surgery results in reduced muscle mass as weight is lost, but postoperative changes in muscle strength and performance are incompletely understood.
To examine changes in body composition, ...strength, physical activity, and physical performance following Roux-en-Y gastric bypass (RYGB).
In a prospective cohort of 47 adults (37 women, 10 men) aged 45 ± 12 years (mean ± SD) with body mass index (BMI) 44 ± 8 kg/m2, we measured body composition by dual-energy X-ray absorptiometry, handgrip strength, physical activity, and physical performance (chair stand time, gait speed, 400-m walk time) before and 6 and 12 months after RYGB. Relative strength was calculated as absolute handgrip strength/BMI and as absolute strength/appendicular lean mass (ALM).
Participants experienced substantial 12-month decreases in weight (-37 ± 10 kg or 30% ± 7%), fat mass (-48% ± 12%), and total lean mass (-13% ± 6%). Mean absolute strength declined by 9% ± 17% (P < 0.01). In contrast, relative strength increased by 32% ± 25% (strength/BMI) and 9% ± 20% (strength/ALM) (P < 0.01 for both). There were clinically significant postoperative improvements in all physical performance measures, including mean improvement in gait speed of >0.1 m/s (P < 0.01) and decrease in 400-m walk time of nearly a full minute.
In the setting of dramatic weight loss, lean mass and absolute grip strength declined after RYGB. However, relative muscle strength and physical function improved meaningfully and are thus noteworthy positive outcomes of gastric bypass.
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 cm
) 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 cm
), 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.
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.
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