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Objective: Postprandial hypoglycemia is an infrequent but disabling complication of Roux-en-Y gastric bypass (RYGB) surgery. Controversy still exists as to whether the postprandial hyperinsulinemia observed is due to inherent changes in pancreatic β-cell mass or function or to reversible alterations caused by RYGB anatomy. We aimed to determine if gastric feeding or reversal of RYGB would normalize postprandial glucose and hormone excursions in patients with symptomatic hypoglycemia. Methods: We completed a prospective study of six patients with severe symptomatic RYGB hypoglycemia who underwent RYGB reversal. An additional subject without hypoglycemia who underwent RYGB reversal was also studied prospectively. Mixed meal tolerance testing (MTT) was done orally (RYGB anatomy), via gastrostomy tube in the excluded stomach in the setting of RYGB, and several months after RYGB reversal. Results: All subjects reported symptomatic improvement of hypoglycemia after reversal of RYGB. Weight gain after reversal was moderate and variable. Postprandial glucose, insulin, and GLP-1 excursions were significantly diminished with gastric feeding and after reversal. Insulin secretion changed proportional to glucose levels and insulin clearance increased after reversal. Glucagon/insulin ratios were similar throughout study. We further compared the impact of modified sleeve gastrectomy reversal surgery to those with restoration of complete stomach and found no significant differences in weight regain or in postprandial glucose or hormone levels. Conclusions: Reversal of RYGB is an effective treatment option for severe postprandial hypoglycemia. The pathophysiology of this disorder is primarily due to RYGB anatomy resulting in altered glucose, gut, and pancreatic hormone levels and decreased insulin clearance, rather than inherent β-cell hyperplasia or hyperfunction. Keywords: Hypoglycemia, Insulin, Glucagon-like peptide 1, Roux en Y gastric bypass, Gastric bypass reversal, Bariatric surgery

Background The anatomic and physiologic changes with Roux-en-Y gastric bypass (RYGB) may lead to uncommon but occasionally difficult to treat complications such as hyperinsulinemic hypoglycemia with neuroglycopenia and recalcitrant hypocalcemia associated to hypoparathyroidism. Medical management of these complications is challenging. Laparoscopic reversal of RYGB anatomy with restoration of pyloric function and duodenal continuity is a potential treatment. The objective of this study was to present the indications, surgical technique, and clinical outcomes of laparoscopic reversal of RYGB. Methods Prospective study of consecutive patients offered laparoscopic reversal of RYGB. Results Five patients with remote laparoscopic RYGB underwent laparoscopic reversal of RYGB to normal anatomy (n = 2) or modified sleeve gastrectomy (n = 3). Indications were medically refractory hyperinsulinemic hypoglycemia with neuroglycopenia (n = 3), recalcitrant hypocalcemia with hypoparathyroidism (n = 1), and both conditions simultaneously (n = 1). Before reversal, all patients had a gastrostomy tube placed in the excluded stomach to document improvement of symptoms. Laparoscopic reversal was accomplished successfully in all patients. Three postoperative complications occurred: bleeding that required transfusion, gallstone pancreatitis, and a superficial trocar site infection. Average length of stay was 3 days. At a mean follow-up of 12 months (range 3 to 22), no additional episodes of neuroglycopenia occurred, average number of hypoglycemic episodes per week decreased from 18.5±12.4 to 1.5±1.9 ( P = .05), and hypocalcemia became responsive to oral replacement therapy in both patients. Conclusions Laparoscopic reversal of RYGB to normal anatomy or modified sleeve gastrectomy is feasible and may be a therapeutic option for selected patients with medically refractory hyperinsulinemic hypoglycemia and/or recalcitrant hypocalcemia associated with hypoparathyroidism.

The complement system is an essential component of innate immunity and plays a major role in the pathogenesis of ischemia-reperfusion injury (IRI). In this study, we investigated the impact of human C1-inhibitor (C1INH) on the early inflammatory response to IRI and the subsequent progression to fibrosis in mice. We evaluated structural damage, renal function, acute inflammatory response, progression to fibrosis and overall survival at 90-days post-injury. Animals receiving C1INH prior to reperfusion had a significant improvement in survival rate along with superior renal function when compared to vehicle (PBS) treated counterparts. Pre-treatment with C1INH also prevented acute IL-6, CXCL1 and MCP-1 up-regulation, C5a release, C3b deposition and infiltration by neutrophils and macrophages into renal tissue. This anti-inflammatory effect correlated with a significant reduction in the expression of markers of fibrosis alpha smooth muscle actin, desmin and picrosirius red at 30 and 90 days post-IRI and reduced renal levels of TGF-β1 when compared to untreated controls. Our findings indicate that intravenous delivery of C1INH prior to ischemic injury protects kidneys from inflammatory injury and subsequent progression to fibrosis. We conclude that early complement blockade in the context of IRI constitutes an effective strategy in the prevention of fibrosis after ischemic acute kidney injury.

Selection of an optimal donor pancreas is the first key task for successful islet isolation. We conducted a retrospective multicenter study in 11 centers in North America to develop an islet donor scoring system using donor variables. The data set consisting of 1,056 deceased donors was used for development of a scoring system to predict islet isolation success (defined as postpurification islet yield >400,000 islet equivalents). With the aid of univariate logistic regression analyses, we developed the North American Islet Donor Score (NAIDS) ranging from 0 to 100 points. The c index in the development cohort was 0.73 (95% confidence interval 0.70–0.76). The success rate increased proportionally as the NAIDS increased, from 6.8% success in the NAIDS < 50 points to 53.7% success in the NAIDS ≥ 80 points. We further validated the NAIDS using a separate set of data consisting of 179 islet isolations. A comparable outcome of the NAIDS was observed in the validation cohort. The NAIDS may be a useful tool for donor pancreas selection in clinical practice. Apart from its utility in clinical decision making, the NAIDS may also be used in a research setting as a standardized measurement of pancreas quality.