Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation.

Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cysteinyl t-RNA synthetases. However, regulation of these species under cell stress conditions, such as hypoxia, that are known to modulate RSS remain poorly understood. Here we define an important mechanism of increased persulfide and polysulfide production involving cystathionine gamma lyase (CSE) phosphorylation at serine 346 and threonine 355 in a substrate specific manner, under acute hypoxic conditions. Hypoxic phosphorylation of CSE occurs in an AMP kinase dependent manner increasing enzyme activity involving unique inter- and intramolecular interactions within the tetramer. Importantly, both cellular hypoxia and tissue ischemia result in AMP Kinase dependent CSE phosphorylation that regulates blood flow in ischemic tissues. Our findings reveal hypoxia molecular signaling pathways regulating CSE dependent persulfide and polysulfide production impacting tissue and cellular response to stress.

End-stage renal disease patients undergoing angioplasty and bypass for critical limb ischemia have worse outcomes compared to non-ESRD patients: Systematic review and meta-analysis.

BACKGROUND: End-stage renal disease (ESRD) is associated with increased morbidity and mortality following lower extremity amputation for critical limb ischemia (CLI). Angioplasty and bypass are used in ESRD patients with CLI; however, the treatment of choice remains controversial. We compared the long-term outcomes in patients with CLI undergoing angioplasty or bypass to evaluate the differences between patients with ESRD and those without ESRD. METHODS: Established databases were searched for observational studies comparing outcomes following bypass or angioplasty for CLI in patients with ESRD to those in non-ESRD patients. End points included survival, limb salvage, amputation-free survival (AFS), and primary and secondary patency at 1-year post-procedure. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effect model. RESULTS: We included 20 studies with a total of 24,851 patients. ESRD patients compared to non-ESRD patients with CLI had significantly lower survival post-angioplasty (OR 0.51, 95% CI 0.36-0.72, p < .001) and post-bypass (OR 0.26, 95% CI 0.15-0.45, p < .001). ESRD patients had lower rates of limb salvage post-bypass (OR 0.33, 95% CI 0.21-0.53, p < .001) and post-angioplasty (OR 0.54, 95% CI 0.41-0.70, p < .001). AFS was significantly lower in ESRD patients compared to non-ESRD patients following angioplasty (OR 0.48, 95% CI 0.32-0.71, p < .001) and bypass (OR 0.28, 95% CI 0.16-0.47, p < .001) despite no significant differences in primary patency. ESRD patients had overall worse secondary patency post-angioplasty and/or bypass (OR 0.54, 95% CI 0.32-0.94, p = .03) compared to non-ESRD patients. A meta-analysis of four studies directly comparing survival in ESRD patients with CLI based on whether they underwent angioplasty or bypass showed no difference (OR 0.93, 95% CI 0.64-1.35, p = .69). CONCLUSION: ESRD patients have worse survival, limb salvage, and AFS outcomes following angioplasty and bypass for CLI compared to non-ESRD patients. Large randomized controlled trials comparing these two modalities of treatment in this patient population are needed for further clarity.

Early results of trans-oral endoscopic plication and revision of the gastric pouch and stoma following Roux-en-Y gastric bypass surgery.

OBJECTIVE: A new technique for endoscopic plication and revision of the gastric pouch (EPRGP) for patients who underwent gastric bypass (RGB) surgery was evaluated in patients with severe GERD, dumping syndrome, failure of weight loss, or all of these. PATIENTS AND METHODS: Patients underwent EPRGP over a 12-month period. The StomaphyX device (Endogastric Solutions, Redmond, WA) was utilized over a standard flexible gastroscope. Patients were kept on a liquid diet for 1 week. RESULTS: The study included 64 patients with a mean age of 48 years who underwent 67 procedures. EPRGP was performed an average of 5 years after RGB. The mean preoperative BMI was 39.5 kg/m². The primary indications for the procedure were inadequate weight loss, dumping syndrome (42), and GERD (15). The mean follow-up period was 5.8 months (range, 3 to 12). The average operative time was 50 minutes, with a significant reduction with increased operator experience. There were only 2 (3%) intraoperative complications during the early period (equipment failure), which did not result in any morbidity. All symptoms from dumping syndrome or reflux improved, with no further operative-related complications. The mean weight loss was 7.3 kg. CONCLUSIONS: This study demonstrates the technical feasibility, safety, and efficacy of EPRGP.

Endoscopic gastric pouch plication - a novel endoluminal incision free approach to revisional bariatric surgery.

10-40% of Roux-en-Y gastric bypass (RYGB) patients regain significant weight after Roux-en-Y gastric bypass surgery due to dilation of the pouch and/or the gastrojejunal (GJ) anastomosis. Traditional revision surgery is associated with significant morbidity (e.g. post-anastomotic GJ leak) where less invasive endoluminal procedures may represent safer alternatives. The present article reports a case of the safe and successful use of endoluminal gastric pouch plication (EGPP) using the StomaphyX™ device to correct both a dilated gastric pouch and a dilated gastrojejunostomy in a post-RYGB patient who regained significant weight.