Search

Gastroparesis following duodenal switch (DS) is a known but rare complication. Typically, patients are managed with prokinetic agents, with pyloromyotomy being the first-line surgical therapy. The literature is sparse regarding how to manage patients whose symptoms remain refractory to these first-line therapies. We present a patient who experienced gastroparesis following DS, who fell into this category. Her symptoms of prandial pain and regurgitation remained resistant to medical management and pyloromyotomy. She was successfully treated with subtotal gastrectomy with Roux-en-Y reconstruction with resolution of these symptoms. The literature suggests that bypassing or resecting the pylorus and removing overstretched aperistaltic gastric muscle could be the mechanism behind this treatment's effectiveness., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Despite recognized improvements in obesity-related comorbidities, mounting evidence implicates surgical weight loss in the onset of skeletal fragility. Sleeve gastrectomy (SG) is the most commonly performed bariatric procedure and is associated with 3-7% axial bone loss in the year following surgery. Bisphosphonates are FDA-approved medications for the prevention and treatment of age-related bone loss and may represent a strategy to reduce bone loss following SG surgery., Methods: The Strategies to Reduce the Onset of Sleeve Gastrectomy Associated Bone Loss (STRONG BONES) trial (NCT04922333) is designed to definitively test whether monthly administration of the bisphosphonate, risedronate, for six months can effectively counter SG-associated bone loss. Approximately 120 middle-aged and older (≥40 years) SG patients will be randomized to six months of risedronate or placebo treatment, with skeletal outcomes assessed at baseline, six, and 12-months post-surgery. The primary outcome of the trial is 12-month change in total hip areal bone mineral density (aBMD), measured by dual energy x-ray absorptiometry (DXA). This will be complemented by DXA-acquired aBMD assessment at other skeletal sites and quantitative computed tomography (QCT) derived changes in bone quality. Change in muscle mass and function will also be assessed, as well as biomarkers of bone health, turnover, and crosstalk, providing mechanistic insight into intervention-related changes to the bone-muscle unit., Discussion: Results from the STRONG BONES trial have the potential to influence current clinical practice by determining the ability of bisphosphonate use to mitigate bone loss and concomitant fracture risk in middle-aged and older SG patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Background: Biliary dyskinesia (BD) is a poorly understood functional gallbladder disorder. Diagnosis is made with abdominal pain and an intact gallbladder without signs of anatomical obstruction on imaging or pathology. Our aim was to assess whether laparoscopic cholecystectomy (LC) resolves hyperkinetic BD symptoms., Methods: Records of patients ≥18 years of age, who underwent LC by four surgeons at a tertiary care center between 2012 and 2020, were retrospectively reviewed. Patients were excluded if they had a documented gallbladder ejection fraction (GBEF) <80% or had biliary stones or sludge on pathology or imaging. Demographic information, HIDA results, preoperative testing, operative details, gallbladder pathology, and symptom status at follow-up were collected from electronic medical records. Improvement in BD symptoms was assessed using McNemar's test. Risk differences with standard errors were employed to estimate percent reduction in symptoms., Results: Ninety-eight patients met inclusion criteria. Of those who presented for follow-up (n = 91), 92.3% (n = 84) reported partial or complete resolution of symptoms. Preoperative symptoms, including back pain (16.7%, 95% CI: [7.9%, 25.5%]; P < .0001), epigastric pain (31.1% [21.3%, 41.3%]; P < .0001), nausea (56.7% [45.0%, 65.8%]; P < .0001), RUQ pain (57.8% [46.1%, 66.9%]; P < .0001), and vomiting (27.8% [18.4%, 37.7%]; P < .0001) showed significant improvement after LC. Chronic cholecystitis and/or cholesterolosis were present on pathology in 79.8% of gallbladders., Discussion: Our study currently represents the largest cohort of patients with hyperkinetic BD. Laparoscopic cholecystectomy appears to result in resolution of symptoms for this clinical entity.

The purpose of this study was to explore the efficacy of 150 mg once monthly oral risedronate use in the prevention of sleeve gastrectomy (SG) associated bone loss. Twenty-four SG patients (56 ± 7 years, 83% female, 21% black) were randomized to risedronate or placebo for 6 months, with an optional 12-month assessment. Outcome measures included 6 (n = 21) and 12 (n = 14) month change in dual energy x-ray absorptiometry-acquired regional areal bone mineral density (aBMD). Six-month treatment effect estimates [mean (95% CI)] revealed significant between group aBMD differences at the femoral neck [risedronate: +0.013 g/cm 2 (-0.021, 0.046) vs. placebo: -0.041 g/cm 2 (-0.067, -0.015)] and lumbar spine [risedronate: +0.028 g/cm 2 (-0.006, 0.063) vs. placebo: -0.029 g/cm 2 (-0.054, -0.004)]; both p ≤ 0.02. When followed postoperatively to 12 months, differential aBMD treatment effects were observed at the total hip [risedronate: -0.035 g/cm 2 (-0.061, -0.009) vs. placebo: -0.072 g/cm 2 (-0.091, -0.052)] and lumbar spine [risedronate: +0.012 g/cm 2 (-0.038, 0.063) vs. placebo: -0.052 g/cm 2 (-0.087, -0.017)]; both p < 0.05. Preliminary treatment effect estimates signal 6 months of risedronate use may be efficacious in reducing aBMD loss at the axial skeleton post-SG, with benefit largely maintained throughout the 1-year postoperative period. Confirmatory data from an adequately powered trial are needed., (© 2021 World Obesity Federation.)

Background and study aims  Efficacy and safety of NAAP for gastrointestinal endoscopy have been widely documented, although there is no information about the outcomes of colonoscopy when the endoscopist supervises the sedation. In this context, the aim of this trial was to determine the equivalence of adenoma detection rate (ADR) in colorectal cancer (CRC) screening colonoscopies performed with non-anesthesiologist-administered propofol (NAAP) and performed with monitored anesthesia care (MAC). Patients and methods  This was a single-blind, non-randomized controlled equivalence trial that enrolled adults from a national CRC screening program (CRCSP). Patients were blindly assigned to undergo either colonoscopy with NAAP or MAC. The main outcome measure was the ADR in CRCSP colonoscopies performed with NAAP. Results  We included 315 patients per group. The median age was 59.76 ± 5.81 years; 40.5 % of patients were women. The cecal intubation rate was 97 %, 81.8 % of patients had adequate bowel preparation, withdrawal time was > 6 minutes in 98.7 %, and the median global exploration time was 24.25 ± 8.86 minutes (range, 8-70 minutes). The ADR was 62.9 % and the complication rate (CR) was 0.6 %. Analysis by intention-to-treat showed an ADR in the NAAP group of 64.13 % compared with 61.59 % in the MAC group, a difference (δADR) of 2.54 %, 95 %CI: -0.10 to 0.05. Analysis by per-protocol showed an ADR in the NAAP group of 62.98 %, compared with 61.94 % in the MAC group, δADR: 1.04 %, 95 %CI: -0.09 to 0.07. There was no difference in CR (NAAP: 0,63 vs. MAC: 0.63); P  = 1.0. Conclusions  ADR in colorectal cancer screening colonoscopies performed with NAAP was equivalent to that in those performed with MAC. Similarly, there was no difference in complication rates., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Gastrostomy placement is the preferred means of long-term enteral feeding for patients who cannot eat by mouth. During laparoscopic gastrostomy, it is standard to perform gastropexy, apposing visceral and parietal peritoneum. In some settings, due to altered anatomy from prior surgery, direct apposition of the stomach to the abdominal wall is not possible. This study reports a series of cases where laparoscopic gastrostomy was performed via a Witzel approach without gastropexy., Methods: A retrospective chart review was performed of all patients at a tertiary academic medical center who underwent Witzel gastrostomy without gastropexy over a 3-year period. In each case, an 18-French tube was placed into the fundus of the stomach and secured with a purse-string suture. A 5-cm serosalized Witzel tunnel was created around the tube using running silk suture. No gastropexy was performed., Results: Six patients underwent 7 Witzel gastrostomy procedures. In three cases, patients had undergone prior major upper abdominal surgery where adhesive disease prevented gastropexy. In the other four cases, the patients had undergone prior gastric bypass with antecolic antegastric position of the roux limb. No patient suffered leak of gastric contents into the peritoneum, and there were no postoperative complications or mortality related to the gastrostomy., Conclusion: In cases where enteral access is necessary, and where the stomach cannot reach the anterior abdominal wall for gastropexy due to prior surgeries, a Witzel gastrostomy without gastropexy is a safe option which resulted in no morbidity or mortality in our series.

Mounting evidence implicates bariatric surgery as a cause of increased skeletal fragility and fracture risk. Bisphosphonate therapy reduces osteoporotic fracture risk and may be effective in minimizing bone loss associated with bariatric surgery. The main objective of this pilot randomized controlled trial (RCT; Clinical Trial No. NCT03411902) was to determine the feasibility of recruiting, treating, and following 24 older patients who had undergone sleeve gastrectomy in a 6 month RCT examining the efficacy of 150-mg once-monthly risedronate (versus placebo) in the prevention of surgical weight-loss-associated bone loss. Feasibility was defined as: (i) >30% recruitment yield, (ii) >80% retention, (iii) >80% pills taken, (iv) <20% adverse events (AEs), and (v) >80% participant satisfaction. Study recruitment occurred over 17 months. Seventy participants were referred, with 24 randomized (34% yield) to risedronate ( n = 11) or placebo ( n = 13). Average age was 56 ± 7 years, 83% were female (63% postmenopausal), and 21% were black. The risedronate group had a higher baseline BMI than the placebo group (48.1 ± 7.2 versus 41.9 ± 3.8 kg/m 2 ). The 10-year fracture risk was low (6.0% major osteoporotic fracture, 0.4% hip fracture); however, three individuals (12.5%, all risedronate group) were osteopenic at baseline. Twenty-one participants returned for 6-month follow-up testing (88% retention) with all ( n = 3) loss to follow-up occurring in the risedronate group. Average number of pills taken among completers was 5.9 ± 0.4 and 6.0 ± 0.0 in the risedronate and placebo groups, respectively ( p = 0.21), with active participants taking >80% of allotted pills. Five AEs (3.7% AE rate) were reported; one definitely related, four not related, and none serious. All participants reported high satisfaction with participation in the study. Use of bisphosphonates as a novel therapeutic to preserve bone density in patients who had undergone a sleeve gastrectomy appears feasible and well-tolerated. Knowledge gained from this pilot RCT will be used to inform the design of an appropriately powered trial., Clinical Trial Registration: http://clinicaltrials.gov/show/NCT03411902. Weight Loss With Risedronate for Bone Health. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Background: The technique for attaining photographic evidence of the critical view of safety (CVS) in laparoscopic cholecystectomy (LC) has previously been defined; however, the consistency, accuracy, and feasibility of CVS in practice is unknown. The aim of this study was to use an already established image sharing and grading system to determine the feasibility of timely feedback after sharing intraoperative images of the CVS and to evaluate if and how cholecystitis affects the ability to attain a CVS., Study Design: We studied 193 laparoscopic cholecystectomies performed by 14 surgeons between August 2017 and January 2019. Anterior and posterior intraoperative CVS images were shared using a standard multimedia messaging system (MMS). Images were graded remotely by members of the group using an established scoring system, and their times to response and scores were recorded. Response data were analyzed for the ability to attain timely and consistent CVS scores., Results: There were 74 urgent laparoscopic cholecystectomies for acute cholecystitis and 119 nonurgent cholecystectomies performed during the study period. Scoring of shared images occurred in less than 5 minutes, and peer review (mean 3 responses) showed agreement that was not significantly different. In patients with acute cholecystitis, a small but significant difference was observed between anterior and posterior image scoring agreement., Conclusions: An established image sharing and grading system for CVS can be used for real-time intraoperative feedback without increasing operative time or compromising private health information. The CVS is almost always attainable; however, decreases in CVS quality and grading agreement are observed in patients with acute cholecystitis., (Published by Elsevier Inc.)

Background: Laparoscopic-assisted transgastric endoscopic retrograde cholangiopancreatography (LAERCP) is used for treatment in patients after Roux-en-Y gastric bypass (RYGB), where transoral access to the biliary tree is not possible. We describe our technique and experience with this procedure., Methods: Electronic medical record search was performed from September 2012 to January 2016, identifying patients who underwent LAERCP per operative records. Charts were reviewed for demographic, clinical, and outcomes data., Results: Sixteen patients were identified. Average time since bypass was 6.9 years, and length of stay was 3.7 days. Five patients underwent simultaneous cholecystectomy. Eleven patients, or 43%, had cholecystectomy more than 2 years previously. ERCP with sphincterotomy was completed in 15 of 16 patients (94%). Our technique involves access to the bypassed stomach via a laparoscopically placed 15 mm port. We observed one major complication of post-ERCP necrotizing pancreatitis. No minor complications nor mortalities were seen in our series., Conclusion: Biliary obstruction can occur many years after RYGB and cholecystectomy. Our findings suggest that RYGB patients may be at a higher risk of primary CBD stone formation. LAERCP is a reliable option for common bile duct (CBD) clearance; our technique of LAERCP is technically simple and associated with low complication rate, making it appealing to surgeons not trained in advanced laparoscopy.

Background: Transection of gastric tissue during laparoscopic sleeve gastrectomy (LSG) can be challenging. Reinforcing the staple line may decrease the incidence of issues requiring intervention., Methods: The objective of this study was to compare the number of intraoperative surgical interventions for a surgical stapler and reload system with Gripping Surface Technology (GST) to standard reloads in patients who underwent LSG. Patients who underwent elective LSG were enrolled. The study was conducted in two stages. For Stage 1, procedures were performed using a powered stapler and standard reloads. For Stage 2, a reload system with GST was used. The primary endpoint was surgical interventions for bleeding and/or staple line issues during transection of the greater curvature of the stomach. Propensity score matching was applied to create two groups similar in baseline characteristics and risk factors., Results: A total of 111 subjects were enrolled across four centers. Propensity-matched procedures were completed with the standard (n = 38) or GST reloads (n = 38). The mean number of interventions in the standard group was 1.9 (1.29) versus 1.1 (1.45) in the GST group. Nonparametric comparisons were statistically significant, indicating a reduction in the distribution of interventions for GST subjects (P = .0036 for matched pair data). Tissue slippage during transection was low for both groups. Intraoperative leak testing was negative in all procedures, and no procedures were converted to open., Conclusions: Use of the GST stapling system reduces the need for staple line interventions in LSG. Both stapling systems had an acceptable safety profile.

Background: Complications after gastric bypass (RYGB) are well documented. Reversal of RYGB is indicated in select cases but can lead to weight gain. Conversion from RYGB to sleeve gastrectomy (SG) has been proposed for correction of complications of RYGB without associated weight gain. However, little is known about outcomes after this procedure., Objectives: To examine outcomes after conversion from RYGB to SG., Setting: University hospital., Methods: A retrospective study of patients who underwent RYGB to SG conversion was undertaken., Results: Twelve patients underwent RYGB to SG conversion for refractory marginal ulceration, stricture, dumping, gastrogastric fistula, hypoglycemia, and failed weight loss. No deaths occurred. Four patients experienced 7 major complications, including portal vein thrombosis, bleeding, pancreatic leak, pulmonary embolus, seroma, anastomotic leak, and stricture. Two required reoperation, and 6 were readmitted within 30 days. Four required nasoenteric feeding postoperatively because of prolonged nausea. The complication of RYGB resolved in 11 of 12 patients. At 14.7 months, change in body mass index for all patients was a decrease of 2.2 kg/m(2). In 5 patients with morbid obesity at conversion, the change in body mass index was a decrease of 6.4 kg/m(2) at 19 months., Conclusions: Laparoscopic conversion from RYGB to SG is successful in resolving certain complications of RYGB and does not result in short-term weight gain. However, conversion has a high rate of major complications as well as a high rate of readmission and need for supplemental nutrition. Although conversion to SG may be appropriate in carefully-selected patients, other options for patients with severe chronic complications after RYGB should be considered., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Conservative management for gastric leak and fistulae after laparoscopic sleeve gastrectomy (LSG) often results in prolonged hospitalization as well as requirement of TPN or recurrent surgery (Casella et al., 2009) [1]. Endoscopically-placed stents are an additional non-invasive method, but are associated with the complication of stent migration in up to 50% of cases (Casella and co-workers, 2009) [1,4]. As other non-invasive means of treatment are absent, we believe this case demonstrates a new technique for multiple gastric leaks following LSG in patients without sepsis or peritonitis., Presentation of Case: A patient developed a staple line gastric leak that persisted for 10 weeks following LSG despite multiple modalities of treatment. She refused to undergo stent placement, so via esophagogastroduodenoscopy (EGD), fistula margins were cauterized with argon plasma coagulation and a fibrin sealant was injected to include the surrounding area. Endoclips were placed along the fistula tracts. A repeat procedure was required. Follow up imaging confirmed resolution of gastric leak and patient did not experience additional complications., Discussion: The patient was able to discontinue TPN and return to an oral diet. Both procedures were well tolerated and did not require hospitalization., Conclusion: Endoscopic management of multiple gastric leaks and fistulae using fibrin seal, endoclips, and cauterization appears to be a promising noninvasive form of treatment with a lower associated morbidity and shortened hospitalization., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The enzymatic activities of protein methyltransferases serve to write covalent modifications on histone and non-histone proteins in the control of gene transcription. Here, we describe gene expression changes in human endothelial cells caused by treatment with methyltransferase inhibitors 7,7'-carbonylbis (azanediyl) bis(4-hydroxynaphthalene-2 -sulfonic acid (AMI-1) and disodium-2-(2,4,5,7- tetrabromo-3-oxido-6-oxoxanthen-9-yl) benzoate trihydrate (AMI-5). Deep sequencing of mRNA indicated robust change on transcription following AMI-5 treatment compared with AMI-1. Functional annotation analysis revealed that both compounds suppress the expression of genes associated with translational regulation, suggesting arginine methylation by protein arginine methyltransferases (PRMTs) could be associated with regulation of this pathway. Interestingly, AMI-5 but not AMI-1 was found to decrease methylation of H3 histones at lysine 4 and down-regulate gene expression associated with interleukin-6 (IL-6) and activator protein-1 (AP-1) signaling pathways. These results imply that inhibition of protein methylation by AMI-1 and AMI-5 can differentially regulate specific pathways with potential to interrupt pathological signaling in the vascular endothelium., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Over the past 20 years bariatric surgery proved to be a valid treatment for reduction and elimination of obesity-related diseases and long-term sustainable weight loss. Minimally invasive or laparoscopic techniques such as laparoscopic Roux-en-Y (LRNY) have replaced open procedures. Many factors play important roles in the small intricacies and variations of the procedure, chief of which is the creation and size of the gastrojejunostomy. Regardless of the variations in technique, the LRNY remains the gold standard for the surgical treatment of clinically severe or morbid obesity, with relatively low morbidity and mortality., (Copyright © 2011. Published by Elsevier Inc.)

It is evident that metabolic memory, whereby diabetic complications continue to develop and progress in individuals who returned to normal glycemic control after a period of transient hyperglycemia, can have long lasting effects. We have primary findings that transient hyperglycemia causes profound transcriptional changes in vascular endothelial cells. We hypothesized that ambient hyperglycemia triggers gene-activating events of the NFκB p65 promoter that are mediated by changes in epigenetic modifications. In a follow-up study we identified two histone-specific writing and erasing enzymes involved in the underlying regulation of gene expression during transient hyperglycemia and subsequent return to normoglycemia. Experimental evidence indicates that previous hyperglycemia is associated with persistent expression of the NFκB p65 gene, which activates NFκB-dependent proteins, such as MCP-1, which are implicated in diabetes-associated vascular injury. Increased gene transcription is correspondent with H3K4m1, but not H3K4m2 and H3K4m3, on the NFκB p65 gene. In vascular endothelial cells the histone methyltransferase Set7 can write the mono-methylation mark H3K4m1 and this methyl-writing enzyme is recruited as a gene co-activator in response to glucose. Furthermore, Set7 knockdown prevents glucose-induced p65 expression. We hypothesize that these molecular events represent an integrated response of the epigenome that lead to changes in the expression of genes and proteins that regulate the development and progression of diabetic vascular complications. Further characterisation of these glucose-induced epigenetic events and the identification of key enzymes involved will improve our understanding of the pathways implicated in diabetic vascular injury., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: The concept that advanced surgical training can reduce or eliminate the learning curve for complex procedures makes logical sense but is difficult to verify and has not been tested for laparoscopic Roux-en-Y gastric bypass (LRYGB). We sought to determine if minimally invasive/bariatric surgery fellowship graduates (FGs) would demonstrate complication-related outcomes (CRO) equivalent to the outcomes achieved during their training experience under the supervision of experienced bariatric surgeons., Methods: We compared CRO for the first 100 consecutive LRYGBs performed in practice by five consecutive minimally invasive/bariatric fellows at new institutions (total 500 cases) to CRO for the 611 consecutive LRYGBs performed during their fellowship training experience under the supervision of three experienced bariatric surgeons at the host training institution., Results: The two patient groups did not differ demographically. The 18 types of major and minor complications identified after LRYGB did not differ among the five fellowship graduates. The mentors' CRO were compatible with published benchmark data. As compared with the training institution data, the overall incidence of complications for the combined experience of fellowship graduates did not differ statistically from that of the mentors. The fellowship graduates' early experience included zero non-gastrojejunostomy leaks (0% versus 1.5%) and a low rate of anastomotic stricture (0.8% versus 3.0%), incisional hernia (1% versus 4.4%), bowel obstruction (0% versus 3%), wound infection (0.3% versus 3.1%), and gastrointestinal hemorrhage (0.2% versus 1.6%). The rate of gastrojejunostomy leak (1.8% versus 2.6%) and, most importantly, mortality (0.8% versus 0.7%) did not differ between the two groups., Conclusions: Fellowship graduates achieved high-quality surgical outcomes from the very beginning of their post-fellowship practices, which are comparable to those of their experienced mentors. These data validate the concept that advanced surgical training can eliminate the learning curve often associated with complex minimally invasive procedures, specifically LRYGB.

Hypercholesterolemia, homocysteine, oxidative stress, and hyperglycemia have been recognized as the major risk factors for atherogenesis. Their impact on the physiology and biochemistry of vascular cells has been widely demonstrated for the last century. However, the recent discovery of the role of epigenetics in human disease has opened up a new field in the study of atherogenic factors. Thus, epigenetic tags in endothelial, smooth muscle, and immune cells seem to be differentially affected by similar atherogenic stimuli. This paper summarizes some recent works on expression of histone-modifying enzymes and DNA methylation directly linked to the presence of risk factors that could lead to the development or prevention of the atherosclerotic process.

Inflammation has been recognized as an important hallmark of atherosclerosis. The pharmacological activation of PPAR-gamma by the thiazolidinediones in diabetes, and of PPAR-alpha by the fibrates in hyperlipidemia has been shown to help to reduce inflammatory markers in preclinical and clinical studies. PPARs are known to modulate immune pathways through at least three different mechanisms: by direct binding to PPRE of anti-inflammatory cytokines genes; by transrepression of transcription factors like NF-kappaB and AP-1; or by corepression. The regulation of the inflammatory pathways by PPARs can be achieved on each one of the cells involved in the atherosclerotic process, that is, monocytes, macrophages, T cells, endothelial cells, and smooth muscle cells. Moreover, as each of these cellular components is interconnected with each other, PPAR activation in one cell type could affect the other ones. As activation of PPARs has clear ant-inflammatory benefits, PPARs ligands should be considered as a new therapeutical approach to ameliorate the exacerbated immune response in atherosclerotic diseases.

Background: It has been suggested that super-super obesity (body mass index [BMI] > or =60 kg/m2) increases the risk of complications after laparoscopic Roux-en-Y gastric bypass (LapRYGB). We hypothesized that a higher BMI does not increase risk the morbidity or mortality rate., Methods: Complication rates for patients with a BMI > or =60 kg/m2 were compared to those for patients with a BMI <60 kg/m2 who underwent LapRYGB during the same time period. Differences between the groups were analyzed by Fisher's exact test, t-tests, and analysis of variance., Results: Forty-five patients with a BMI > or =60 kg/m2 and 640 patients with a BMI <60 kg/m2 underwent LapRYGB. There were no statistically significant differences between the two groups in the complication or mortality rates. Excess weight loss was less, but actual weight lost was greater in the BMI > or =60 kg/m2 group., Conclusions: The complication and mortality rates are not increased in super-super obese patients who undergo LapRYGB. Acceptable weight loss can be achieved safely in these patients.

Peroxisome proliferator-activated receptor (PPAR) agonists have long been used for the treatment of diabetes and hypercholesterolemia--disorders that give individuals a high predisposition for cardiovascular disease. Prevention of the onset of the latter can begin when a diagnosis of metabolic syndrome, a pathology that groups glucose and lipid disturbances, is made. Although the characteristic components of metabolic syndrome (ie, high blood pressure, obesity, dyslipidemia, insulin resistance and proinflammatory state) are likely to improve through a radical change in lifestyle, a therapeutic approach is also advisable, and the PPAR agonists are the first in a growing list of drugs that may be effective in the prevention of the development of cardiovascular disease.

Objective: To identify the factors that increase mortality for either open or laparoscopic Roux-en-Y gastric bypass., Summary Background Data: Perioperative mortality is the most feared outcome of bariatric surgery, reported to occur in between 0.5% and 1.5% of patients., Methods: The bariatric database at Virginia Commonwealth University was queried for patients who had undergone either an open gastric bypass (O-GBP) or a laparoscopic gastric bypass (L-GBP). A multivariate logistic regression analysis to identify factors related to perioperative mortality was performed. Factors examined included age, gender, body mass index, preoperative weight, hypertension, diabetes mellitus, sleep apnea, obesity hypoventilation syndrome, venous stasis ulcers, intestinal leak, small bowel obstruction, and pulmonary embolus., Results: Since 1992, more than 2000 patients had either an O-GBP (n = 1431) or a L-GBP (n = 580). Of the O-GBP, 547 patients had a proximal GBP (P-GBP) and 884 superobese (body mass index > 50 kg/m) patients had a long-limb GBP (LL-GBP). The differences in patient demographics, complications, and perioperative mortality rates between L-GBP and O-GBP and P-GBP and LL-GBP patients were examined. Overall, the independent risk factors associated with perioperative death included leak, pulmonary embolus, preoperative weight, and hypertension., Conclusions: The risk factors for perioperative death can be separated into patient characteristics and complications. The access method, open versus laparoscopic, was not independently predictive of death, but the operation type, proximal versus long limb, was predictive. The data do not suggest that superobese patients should not undergo surgery, as they are high risk for early death due to their body weight and comorbidities without surgery. Surgery should not be reserved as a desperate last measure for weight loss.

Background: Intestinal leak is a potentially lethal complication of Roux en-Y gastric bypass (GBP). Identification of patients at high risk for leak may reduce complication rates of surgeons early in the procedure learning curve., Methods: A total of 3073 patients who underwent GBP were analyzed using univariate and multivariate logistic regression analyses of the following preoperative factors: hypertension (HTN), diabetes mellitus (DM), sleep apnea (SA), age, gender, weight, body mass index (BMI), and surgery type. Multivariate logistic regression analysis was performed for each procedure type., Results: There were 48 (1.5%) deaths. Independent risk factors for death included leak, weight, procedure type, and HTN. A total of 102 (3.2%) leaks were found. Independent factors for leak included age, male gender, SA, and procedure type., Conclusion: The data suggests that older, heavier male patients with multiple comorbid conditions are at increased risk for leak and mortality. Surgeons early in their learning curve should avoid these high-risk patients to reduce complications.

The infusion of pig progenitor cells into baboons is associated with a thrombotic microangiopathy probably related to the interaction of these cells with the baboon endothelial cells and platelets. We have shown previously that pig peripheral blood mononuclear cells (p-PBMC), are able to activate the human coagulation cascade as they are able to generate thrombin when added to defibrinated plasma. In this work, we have tested the interaction of p-PBMC with human platelets to assess the capacity of p-PBMC to cause platelet aggregation and the possible role of complement activation in this aggregation. Human platelet aggregation assays, using collagen (1 or 2 microg/ml), were performed with platelets in platelet-rich plasma (PRP) or platelets washed by filtration. PRP or washed platelets were also incubated with p-PBMC or human PBMC (h-PBMC) at several concentrations and aggregation was measured. The effect of Dansylarginine N-(3-ethyl-1,5-pentanediyl)amide (DAPA), an inhibitor of thrombin, was studied on platelet aggregation caused by the pig cells. Complement activation was measured by deposition of fragment c derived from C3 splitting (C3c) on pig cells incubated with citrated platelet poor plasma (PPP). When human PRP was incubated with p-PBMC, aggregation was a consistent event quantitatively similar to that induced by collagen. No aggregation of washed platelets was observed when these were incubated with p-PBMC or h-PBMC. Aggregation of human platelets in PRP, induced by p-PBMC, was inhibited when DAPA (100 microm) was added to the incubation mixture (23%), indicating that the thrombin inhibitor blocked the capacity of p-PBMC to aggregate human platelets. No deposition of C3c fragments on p-PBMC was detected when the porcine cells were incubated for up to 20 min with citrated PPP. The fact is that p-PBMC induces human platelet aggregation in plasma being thrombin generation a likely explanation for this observation. Our data suggest that, in the system assayed, complement activation is not a cause of platelet aggregation. These findings are relevant for the clarification of the reported thrombotic microangiopathy complicating the intravenous infusion of pig cells in primates in attempts to induce pig tolerance in baboons.

The infusion of large numbers of porcine cells into primates in order to induce specific immunologic tolerance by mixed hematopoietic chimerism, results in thrombotic microangiopathy that can be fatal. For this reason, it is important to study in vitro the interaction of primate endothelial cells with pig cells. We show that pig peripheral blood mononuclear cells (p-PBMC) activate human endothelial cells (hECs) through direct contact. Thus, when endothelial cells are cultured in the presence of p-PBMC, overexpression of VCAM-1 and E-selectin adhesion molecules occurs within 3 h of culture and continues for at least 9 h. The co-culture of p-PBMC and hECs also results in an important adhesion of human platelets to both types of cell. Thus, viewed with the microscope, platelets aggregate above the endothelial cells and also around the pig cells. We present data that suggest that the presence of p-PBMC may be more important with regard to the increase of platelet adhesion to the endothelial cells than the activation alone of the cells. Our results also show that p-PBMC, and not the activated endothelia or the culture supernatant of activated hECs, are able to activate the coagulation cascade because they are able to generate thrombin when added to defibrinated human plasma. Overall, these findings suggest that p-PBMC are of primary importance for the development of the thrombotic disorders that occur in primates transplanted with pig progenitor cells.

Free radical mediated oxidation of apoB lipoproteins in the arterial intima appears to contribute to atherogenicity of the entrapped particles. A plausible pathogenic mechanism for oxidation is the one induced by heme leaking from erythrocytes that is then carried into the arterial wall by its high affinity for lipoproteins. In the intima, in the presence of H(2)O(2) secreted by macrophages, heme can be a potent oxidant. To study the role of heme as a promoter of oxidative stress damage in vivo we used a model of intravascular hemolysis (IVH) caused by phenylhydrazine in rabbits with and without diet-induced moderate hypercholesterolemia (MHC). Evaluation of the antioxidant status of plasma indicated that at the end of the treatment period this was compromised by the MHC-IVH. After 10 weeks the animals with combined MHC-IVH showed more of the aorta surface covered by lesions (27%+/-8, mean (SD) than the animals with only MHC (11%+/-7), in spite of having similar plasma levels of VLDL+LDL lipoproteins. The animals with only IVH, as well as the controls, showed minimal lesions (<1%). Heme oxygenase (HO-1) expression in aorta and other tissues was markedly increased in the group with MHC-IVH and it was correlated with the extent of IVH. The data suggest that the oxidative stress associated with IVH potentiates the atherogenicity of moderate hypercholesterolemia and that in spite of a strong induction of HO-1 this is not sufficient to counteract the atherogenicity of the combined condition.

The kinetic mechanism of action of Draculin on activated Factor X (FXa) is established. Draculin inhibits activated Factor X within seconds of incubation at near equimolar concentration (2-6 times on molar basis). Fitting the data to the equation for a tight-binding inhibitor gives a value for K(i)(K(d)) = 14.8+/-1.5 nM. The formation of the Draculin-FXa complex can be explained by a two-step mechanism, where for the first, reversible step, k(on) = 1.117 (+/- 0.169, S.E.M.) x 10(6) M(-1)s(-1) and k(off) = 15.388 (+/- 1.672) x 10(-3) s(-1), while for the second, irreversible step, which is concentration-independent, k(2) = 0.072 s(-1). K(d) obtained from k(off)/k(on) = 13.76 nM. Lineweaver-Burk plot shows a noncompetitive behavior. This noncompetitive mode of inhibition of Draculin is supported by the observation that Draculin, at concentrations giving complete inhibition, does not impair binding of p-aminobenzamidine to FXa. Moreover, under the same conditions, Draculin induces <14% decrease of the fluorescence intensity of the p-aminobenzamidine-FXa complex. We conclude that Draculin is a noncompetitive, tight-binding inhibitor of FXa, a characteristic so far unique amongst natural FXa inhibitors.

Draculin, a glycoprotein isolated from vampire bat (Desmodus rotundus) saliva, is a natural anticoagulant which inhibits activated coagulation factors IX (IXa) and X (Xa). The observation that under captivity conditions, the anticoagulant activity present in vampire bat saliva is dependent upon the salivation protocol, led us to investigate the possible relationship between the expression of biological activity of native draculin and the post-translational glycosylation of the protein backbone. Daily salivation of vampire bats yields a saliva that progressively decreases in anticoagulant activity, without any significant change in overall protein content, or in the amount of protein specifically recognized by a polyclonal anti-draculin antibody. Anticoagulant activity of the saliva is restored after a 4-day period of rest. Besides the marked difference in anticoagulant activity, purified native draculin, obtained from high- and low-activity saliva, shows significant differences in: (a) composition of the carbohydrate moiety, and (b) Glycosylation pattern. Furthermore, controlled chemical deglycosylation of native draculin, under conditions that do not affect the polypeptide backbone, progressively leads to complete loss of the biological activity. Our present results implicate that correct glycosylation of draculin is a seminal event for the expression of the biological activity of this glycoprotein.

Adenosine (ADO) attenuates polymorphonuclear neutrophil (PMN)-mediated damage, partly by inhibiting superoxide anion (O2-.) generation and PMN adherence to the coronary artery endothelium. This study tests the hypothesis that the antineutrophil effects of ADO are mediated by A2-receptor activation. Isolated canine PMN were activated by 100 nM platelet-activating factor (PAF). Compared with untreated activated PMN (100%), ADO attenuated O2-. production (46 +/- 9% of activated PMN), which was mimicked by the A2 agonist CGS-21680 (50 +/- 6% of activated PMN), unaltered by A1-selective antagonism with KW-3902 in the presence of ADO (40 +/- 7%), but blocked by combined A1-A2 blockade with 8-p-sulfophenyl theophylline (8-SPT, 94 +/- 14%). ADO reduced adherence of fluorescent PMN to endothelial surfaces of isolated canine coronary artery segments from 174 +/- 12 to 29 +/- 9/mm2 (P < 0.01), which was unaltered by A1 antagonism (35 +/- 7/mm2) but was reversed by 8-SPT (150 +/- 11/mm2). CGS-21680 inhibited adherence (48 +/- 8/mm2), comparable to that of ADO. Canine coronary artery rings were incubated with activated PMN to induce injury to the endothelium. The concentration of drug required to elicit 50% of maximal relaxation (-log M) derived from dose-relaxation responses to acetylcholine in PMN-damaged rings was significantly (P < 0.05) less in ADO-treated (6.88 +/- 0.08) and CGS-21680-treated (7.12 +/- 0.09) rings than untreated rings (6.54 +/- 0.10). This protection with ADO was reversed by inclusion of 8-SPT (6.49 +/- 0.12) but not KW-3902 (6.96 +/- 0.07). We conclude that ADO reduces PMN-induced coronary endothelial injury by A2-receptor-mediated inhibition of O2-. generation and adherence.