TREM2 macrophages mediate the beneficial effects of bariatric surgery against MASH.

BACKGROUND AND AIMS: For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. APPROACH AND RESULT: Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner. Single-cell RNA sequencing revealed that hepatic lipid-associated macrophages (LAMs) expressing the triggering receptor expressed on myeloid cells 2 (TREM2) repress inflammation and increase their lysosomal activity in response to VSG. Remarkably, TREM2 deficiency in mice ablates the reparative effects of VSG, suggesting that TREM2 is required for MASH resolution. Mechanistically, TREM2 prevents the inflammatory activation of macrophages and is required for their efferocytic function. CONCLUSIONS: Overall, our findings indicate that bariatric surgery improves MASH through a reparative process driven by TREM2+ macrophages, providing insights into the mechanisms of disease reversal that may result in new therapies and improved surgical interventions.

Best Practice Alert to Promote Screening for Primary Aldosteronism Among People With Apparent Treatment-Resistant Hypertension.

OBJECTIVE: Guidelines recommend screening all individuals with resistant hypertension for primary aldosteronism (PA) but less than 2% are screened. We aimed to develop a noninterruptive Best Practice Alert (BPA) to assess if its implementation in the electronic health record improved PA screening rates among individuals with apparent treatment-resistant hypertension (aTRH). METHODS: We implemented a noninterruptive BPA on 9/17/2022 at our ambulatory primary care, endocrinology, nephrology, and cardiology clinics. We assessed clinical parameters of people with aTRH before (9/17/2021-9/16/2022) and after (9/17/2022-9/16/2023) the BPA was implemented. The noninterruptive BPA embedded with an order set identified people with aTRH and recommended screening for PA if it was not previously performed. RESULTS: There were 10 944 and 11 463 people with aTRH who attended office visits during the 12 months before and after the BPA implementation, respectively. There were no statistically significant differences in median age (P = .096), sex (P = .577), race (P = .753), and ethnicity (P = .472) between the pre- and post-BPA implementation groups. There was a significant increase in PA screening orders placed (227 [2.1%] vs 476 [4.2%], P < .001) and PA screening labs performed (169 [1.5%] vs 382 [3.3, P < .001) after BPA implementation. PA screening tests were positive in 26% (44/169) and 23% (88/382) of people in the pre- and post-BPA groups, respectively (P = .447). CONCLUSION: Implementation of a real-time electronic health record BPA doubled the screening rate for PA among people with aTRH; however, the overall screening rate was low.

Prediction of thirty-day morbidity and mortality after duodenal switch using an artificial neural network.

BACKGROUND: Understanding factors that increase risk of both mortality and specific measures of morbidity after duodenal switch (DS) is important in deciding to offer this weight loss operation. Artificial neural networks (ANN) are computational deep learning approaches that model complex interactions among input factors to optimally predict an outcome. Here, a comprehensive national database is examined for patient factors associated with poor outcomes, while comparing the performance of multivariate logistic regression and ANN models in predicting these outcomes. METHODS: 2907 DS patients from the 2019 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database were assessed for patient factors associated with the previously validated composite endpoint of 30-day postoperative reintervention, reoperation, readmission, or mortality using bivariate analysis. Variables associated (P ≤ 0.05) with the endpoint were imputed in a multivariate logistic regression model and a three-node ANN with 20% holdback for validation. Goodness-of-fit was assessed using area under receiver operating curves (AUROC). RESULTS: There were 229 DS patients with the composite endpoint (7.9%), and 12 mortalities (0.4%). Associated patient factors on bivariate analysis included advanced age, non-white race, cardiac history, hypertension requiring 3 + medications (HTN), previous foregut/obesity surgery, obstructive sleep apnea (OSA), and higher creatinine (P ≤ 0.05). Upon multivariate analysis, independently associated factors were non-white race (odds ratio 1.40; P = 0.075), HTN (1.55; P = 0.038), previous foregut/bariatric surgery (1.43; P = 0.041), and OSA (1.46; P = 0.018). The nominal logistic regression multivariate analysis (n = 2330; R2 = 0.02, P < 0.001) and ANN (R2 = 0.06; n = 1863 [training set], n = 467 [validation]) models generated AUROCs of 0.619, 0.656 (training set) and 0.685 (validation set), respectively. CONCLUSION: Readily obtainable patient factors were identified that confer increased risk of the 30-day composite endpoint after DS. Moreover, use of an ANN to model these factors may optimize prediction of this outcome. This information provides useful guidance to bariatricians and surgical candidates alike.

Gastroesophageal Reflux Disease Outcomes After Vertical Sleeve Gastrectomy and Gastric Bypass.

OBJECTIVE: The objective of this study is to assess whether vertical sleeve gastrectomy (VSG) increases the incidence of gastroesophageal reflux disease (GERD), esophagitis and Barrett esophagus (BE) relative to patients undergoing Roux-en-Y gastric bypass (RYGB) in patients with and without preoperative GERD. SUMMARY OF BACKGROUND DATA: Concerns for potentiation of GERD, supported by multiple high-quality retrospective studies, have hindered greater adoption of the VSG. METHODS: From the OptumLabs Data Warehouse, VSG and RYGB patients with ≥2 years enrollment were identified and matched by follow-up time. GERD [reflux esophagitis, prescription for acid reducing medication (Rx) and/or diagnosis of BE], upper endoscopy (UE), and re-admissions were evaluated beyond 90 days. RESULTS: A total of 8362 patients undergoing VSG were matched 1:1 to patients undergoing RYGB, on the basis of post-operative follow-up interval. Age, sex, and follow-up time were similar between the 2 groups (P > 0.05). Among all patients, postoperative GERD was more frequently observed in VSG patients relative to RYGB patients (60.2% vs 55.6%, respectively; P < 0.001), whereas BE was more prevalent in RYGB patients (0.7% vs 1.1%; P = 0.007). Postoperatively, de novo esophageal reflux symptomatology was more common in VSG patients (39.3% vs 35.3%; P < 0.001), although there was no difference in development of the histologic diagnoses reflux esophagitis and BE. Furthermore, postoperative re-admission was higher in the RYGB cohort (38.9% vs 28.9%; P < 0.001). CONCLUSIONS: Compared to RYGB, VSG may not have inferior long-term GERD outcomes, while also leading to fewer re-hospitalizations. These data challenge the prevailing opinion that patients with GERD should undergo RYGB instead of VSG.

Bariatric Surgery is Associated With Decreased Progression of Nonalcoholic Fatty Liver Disease to Cirrhosis: A Retrospective Cohort Analysis.

OBJECTIVE: This study sought to compare trends in the development of cirrhosis between patients with NAFLD who underwent bariatric surgery and a well-matched group of nonsurgical controls. SUMMARY OF BACKGROUND DATA: Patients with NAFLD who undergo bariatric surgery generally have improvements in liver histology. However, the long-term effect of bariatric surgery on clinically relevant liver outcomes has not been investigated. METHODS: From a large insurance database, patients with a new NAFLD diagnosis and at least 2 years of continuous enrollment before and after diagnosis were identified. Patients with traditional contraindications to bariatric surgery were excluded. Patients who underwent bariatric surgery were identified and matched 1:2 with patients who did not undergo bariatric surgery based on age, sex, and comorbid conditions. Kaplan-Meier analysis and Cox proportional hazards modeling were used to evaluate differences in progression from NAFLD to cirrhosis. RESULTS: A total of 2942 NAFLD patients who underwent bariatric surgery were identified and matched with 5884 NAFLD patients who did not undergo surgery. Cox proportional hazards modeling found that bariatric surgery was independently associated with a decreased risk of developing cirrhosis (hazard ratio 0.31, 95% confidence interval 0.19-0.52). Male gender was associated with an increased risk of cirrhosis (hazard ratio 2.07, 95% confidence interval 1.31-3.27). CONCLUSIONS: Patients with NAFLD who undergo bariatric surgery are at a decreased risk for progression to cirrhosis compared to well-matched controls. Bariatric surgery should be considered as a treatment strategy for otherwise eligible patients with NAFLD. Future bariatric surgery guidelines should include NAFLD as a comorbid indication when determining eligibility.

Prediction of thirty-day morbidity and mortality after laparoscopic sleeve gastrectomy: data from an artificial neural network.

BACKGROUND: Multiple patient factors may convey increased risk of 30-day morbidity and mortality after laparoscopic vertical sleeve gastrectomy (LVSG). Assessing the likelihood of short-term morbidity is useful for both the bariatric surgeon and patient. Artificial neural networks (ANN) are computational algorithms that use pattern recognition to predict outcomes, providing a potentially more accurate and dynamic model relative to traditional multiple regression. Using a comprehensive national database, this study aims to use an ANN to optimize the prediction of the composite endpoint of 30-day readmission, reoperation, reintervention, or mortality, after LVSG. METHODS: A cohort of 101,721 LVSG patients was considered for analysis from the 2016 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program national dataset. Select patient factors were chosen a priori as simple, pertinent and easily obtainable, and their association with the 30-day endpoint was assessed. Those factors with a significant association on both bivariate and multivariate nominal logistic regression analysis were incorporated into a back-propagation ANN with three nodes each assigned a training value of 0.333, with k-fold internal validation. Logistic regression and ANN models were compared using area under receiver-operating characteristic curves (AUROC). RESULTS: Upon bivariate analysis, factors associated with 30-day complications were older age (P = 0.03), non-white race, higher initial body mass index, severe hypertension, diabetes mellitus, non-independent functional status, and previous foregut/bariatric surgery (all P < 0.001). These factors remained significant upon nominal logistic regression analysis (n = 100,791, P < 0.001, r2= 0.008, AUROC = 0.572). Upon ANN analysis, the training set (80% of patients) was more accurate than logistic regression (n = 80,633, r2= 0.011, AUROC = 0.581), and it was confirmed by the validation set (n = 20,158, r2= 0.012, AUROC = 0.585). CONCLUSIONS: This study identifies a panel of simple and easily obtainable preoperative patient factors that may portend increased morbidity after LSG. Using an ANN model, prediction of these events can be optimized relative to standard logistic regression modeling.

Nonalcoholic Steatohepatitis: A Review.

Importance: Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) and is associated with disease progression, development of cirrhosis, and need for liver transplant. Despite its importance, NASH is underrecognized in clinical practice. Observations: NASH affects an estimated 3% to 6% of the US population and the prevalence is increasing. NASH is strongly associated with obesity, dyslipidemia, type 2 diabetes, and metabolic syndrome. Although a number of noninvasive tests and scoring systems exist to characterize NAFLD and NASH, liver biopsy is the only accepted method for diagnosis of NASH. Currently, no NASH-specific therapies are approved by the US Food and Drug Administration. Lifestyle modification is the mainstay of treatment, including dietary changes and exercise, with the primary goal being weight loss. Substantial improvement in histologic outcomes, including fibrosis, is directly correlated with increasing weight loss. In some cases, bariatric surgery may be indicated to achieve and maintain the necessary degree of weight loss required for therapeutic effect. An estimated 20% of patients with NASH will develop cirrhosis, and NASH is predicted to become the leading indication for liver transplants in the US. The mortality rate among patients with NASH is substantially higher than the general population or patients without this inflammatory subtype of NAFLD, with annual all-cause mortality rate of 25.56 per 1000 person-years and a liver-specific mortality rate of 11.77 per 1000 person-years. Conclusions and Relevance: Nonalcoholic steatohepatitis affects 3% to 6% of the US population, is more prevalent in patients with metabolic disease and obesity, progresses to cirrhosis in approximately 20% of cases, and is associated with increased rates of liver-specific and overall mortality. Early identification and targeted treatment of patients with nonalcoholic steatohepatitis are needed to improve patient outcomes, including directing patients toward intensive lifestyle modification to promote weight loss and referral for bariatric surgery as indicated for management of obesity and metabolic disease.

Antibiotic-induced Disruption of Intestinal Microbiota Contributes to Failure of Vertical Sleeve Gastrectomy.

OBJECTIVE: The aim of this study was to test whether the perioperative composition of intestinal microbiota can contribute to variable outcomes following vertical sleeve gastrectomy (VSG). SUMMARY OF BACKGROUND DATA: Although bariatric surgery is the most effective treatment for obesity, metabolic outcomes are variable. METHODS: Diet-induced obese mice were randomized to VSG or sham surgery, with or without exposure to antibiotics that selectively suppress mainly gram-positive (fidaxomicin, streptomycin) or gram-negative (ceftriaxone) bacteria on postoperative days (POD) 1-4. Fecal microbiota was characterized before surgery and on POD 7 and 28. Mice were metabolically characterized on POD 30-32 and euthanized on POD 35. RESULTS: VSG resulted in weight loss and shifts in the intestinal microbiota composition relative to sham-operated mice. Antibiotic exposure resulted in sustained reductions in alpha (within-sample) diversity of microbiota and shifts in its composition. All antibiotic treatments proved to be detrimental to metabolic VSG outcomes, regardless of antimicrobial specificity of antibiotics. These effects involved functionally distinct pathways. Specifically, fidaxomicin and streptomycin markedly altered hepatic bile acid signaling and lipid metabolism, while ceftriaxone resulted in greater reduction of key antimicrobial peptides. However, VSG mice exposed to antibiotics, regardless of their specificity, had significantly increased subcutaneous adiposity and impaired glucose homeostasis without changes in food intake relative to control VSG mice. CONCLUSION: Dysbiosis induced by brief perioperative antibiotic exposure attenuates weight loss and metabolic improvement following VSG. Potential mechanisms include disruption of bile acid homeostasis and reduction in the production of gut antimicrobial peptides. Results of this study implicate the intestinal microbiota as an important contributor to metabolic homeostasis and a potentially modifiable target influencing clinical outcomes following VSG.

Surgical repair of perforated peptic ulcers: laparoscopic versus open approach.

INTRODUCTION: Perforated peptic ulcers are a surgical emergency that can be repaired using either laparoscopic surgery (LS) or open surgery (OS). No consensus has been reached on the comparative outcomes and safety of each approach. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, we conducted a 12-year retrospective review (2005-2016) and identified 6260 adult patients who underwent either LS (n = 616) or OS (n = 5644) to repair perforated peptic ulcers. To mitigate selection bias and adjust for the inherent heterogeneity between groups, we used propensity-score matching with a case (LS):control (OS) ratio of 1:3. We then compared intraoperative outcomes such as operative time, and 30-day postoperative outcomes including infectious and non-infectious complications, and mortality. RESULTS: Propensity-score matching created a total of 2462 matched pairs (616 in the LS group, 1846 in the OS group). Univariate analysis demonstrated successful matching of patient characteristics and baseline clinical variables. We found that OS was associated with a shorter operative time (67.0 ± 28.6 min, OS versus 86.9 ± 57.5 min, LS; P < 0.001) but a longer hospital stay (8.6 ± 6.2 days, OS versus 7.8 ± 5.9 days, LS; P = 0.001). LS was associated with a lower rate of superficial surgical site infections (1.5%, LS versus 4.2%, OS; P = 0.032), wound dehiscence (0.3%, LS versus 1.6%, OS; P = 0.030), and mortality (3.2%, LS versus 5.4%, OS; P = 0.009). CONCLUSION: Fewer than 10% of patients with perforated peptic ulcers underwent LS, which was associated with reduced length of stay, lower rate of superficial surgical site infections, wound dehiscence, and mortality. Given our results, a greater emphasis should be provided to a minimally invasive approach for the surgical repair of perforated peptic ulcers.

Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study.

Importance: The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. Objective: To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Design, Setting, and Participants: Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Interventions: Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. Main Outcomes and Measures: The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg at 5 years. Results: Of 120 participants who were initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%) completed 5 years of follow-up. Baseline characteristics were similar between groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle-medical management group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (difference, 19%; 95% CI, 4%-34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle-medical management group achieved an HbA1c level of less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had more serious adverse events than did the lifestyle-medical management intervention, 66 events vs 38 events, most frequently gastrointestinal events and surgical complications such as strictures, small bowel obstructions, and leaks. Gastric bypass had more parathyroid hormone elevation but no difference in B12 deficiency. Conclusions and Relevance: In extended follow-up of obese adults with type 2 diabetes randomized to adding gastric bypass compared with lifestyle and intensive medical management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement. Trial Registration: clinicaltrials.gov Identifier: NCT00641251.

Bariatric Surgery: A Perspective for Primary Care.

IN BRIEF Bariatric surgery is the most efficacious treatment for obesity, type 2 diabetes, and other obesity-related comorbidities. In this article, the authors review the current indications for bariatric surgery and discuss the most commonly performed procedures. They analyze medical outcomes of bariatric procedures by reviewing key prospective trials and discuss changes in physiology after these procedures. They conclude by discussing long-term management of bariatric patients by reviewing current guidelines for nutritional support and listing common complications related to these procedures.

Bile Acids Increase Independently From Hypocaloric Restriction After Bariatric Surgery.

OBJECTIVES: To measure changes in the composition of serum bile acids (BA) and the expression of Takeda G-protein-coupled receptor 5 (TGR5) acutely after bariatric surgery or caloric restriction. SUMMARY BACKGROUND DATA: Metabolic improvement after bariatric surgery occurs before substantial weight loss. BA are important metabolic regulators acting through the farnesoid X receptor and TGR5 receptor. The acute effects of surgery on BA and the TGR5 receptor in subcutaneous white adipose tissue (WAT) are unknown. METHODS: A total of 27 obese patients with type 2 diabetes mellitus were randomized to Roux-en-Y gastric bypass (RYGB) or to hypocaloric diet (HC diet) restriction (NCT 1882036). A cohort of obese patients with and without type 2 diabetes mellitus undergoing vertical sleeve gastrectomy was also recruited (n = 12) as a comparison. RESULTS: After vertical sleeve gastrectomy, the level of BA increased [total: 1.17 ±â€Š1.56 µmol/L to 4.42 ±â€Š3.92 µmol/L (P = 0.005); conjugated BA levels increased from 0.99 ±â€Š1.42 µmol/L to 3.59 ±â€Š3.70 µmol/L (P = 0.01) and unconjugated BA levels increased from 0.18 ±â€Š0.24 µmol/L to 0.83 ±â€Š0.70 µmol/L (P = 0.009)]. With RYGB, there was a trend toward increased BA [total: 1.37 ±â€Š0.97 µmol/L to 3.26 ±â€Š3.01 µmol/L (P = 0.07); conjugated: 1.06 ±â€Š0.81 µmol/L to 2.99 ±â€Š3.02 µmol/L (P = 0.06)]. After HC diet, the level of unconjugated BA decreased [0.92 ±â€Š0.55 µmol/L to 0.32 ± 0.43 µmol/L (P = 0.05)]. The level of WAT TGR5 gene expression decreased after surgery, but not in HC diet. Protein levels did not change. CONCLUSIONS: The levels of serum BA increase after bariatric surgery independently from caloric restriction, whereas the level of WAT TGR5 protein is unaffected.

EUS-guided sutured gastropexy for transgastric ERCP (ESTER) in patients with Roux-en-Y gastric bypass: a novel, single-session, minimally invasive approach.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastric bypass (RYGB) is a challenging procedure. Available techniques are hampered by limited success, need for a separate delayed session for ERCP, potential complications,and/or invasiveness. This paper reports on a novel technique that involves endoscopic ultrasound(EUS)-guided access into the remnant stomach and sutured gastropexy for transgastric ERCP in a single combined session. PATIENTS AND METHODS: A total of 10 patients with RYGB underwent transgastric ERCP using the novel technique. EUS was used to puncture the excluded stomach through the gastric pouch or jejunum,the stomach was insufflated, and a direct percutaneous gastrostomy puncture followed by sutured gastropexy was performed. ERCP was performed by passing a duodenoscope through the gastrostomy. RESULTS: Technical success of EUS-assisted sutured gastropexy was achieved in nine patients (90 %),with immediate, same-session ERCP in all nine.There were no adverse events. CONCLUSIONS: EUS-assisted, fluoroscopically guided sutured gastropexy is a safe and effective method to obtain access into the excluded gastric remnant for same-session transgastric ERCP inpatients with Roux-en-Y gastric bypass anatomy.

Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial.

IMPORTANCE: Although conventional bariatric surgery results in weight loss, it does so with potential short-term and long-term morbidity. OBJECTIVE: To evaluate the effectiveness and safety of intermittent, reversible vagal nerve blockade therapy for obesity treatment. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, sham-controlled clinical trial involving 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition was conducted at 10 sites in the United States and Australia between May and December 2011. The 12-month blinded portion of the 5-year study was completed in January 2013. INTERVENTIONS: One hundred sixty-two patients received an active vagal nerve block device and 77 received a sham device. All participants received weight management education. MAIN OUTCOMES AND MEASURES: The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure, or therapy in the vagal block group was less than 15%. RESULTS: In the intent-to-treat analysis, the vagal nerve block group had a mean 24.4% excess weight loss (9.2% of their initial body weight loss) vs 15.9% excess weight loss (6.0% initial body weight loss) in the sham group. The mean difference in the percentage of the excess weight loss between groups was 8.5 percentage points (95% CI, 3.1-13.9), which did not meet the 10-point target (P = .71), although weight loss was statistically greater in the vagal nerve block group (P = .002 for treatment difference in a post hoc analysis). At 12 months, 52% of patients in the vagal nerve block group achieved 20% or more excess weight loss and 38% achieved 25% or more excess weight loss vs 32% in the sham group who achieved 20% or more loss and 23% who achieved 25% or more loss. The device, procedure, or therapy-related serious adverse event rate in the vagal nerve block group was 3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal. The adverse events more frequent in the vagal nerve block group were heartburn or dyspepsia and abdominal pain attributed to therapy; all were reported as mild or moderate in severity. CONCLUSION AND RELEVANCE: Among patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01327976.

Rates and Risk Factors for 30-Day Morbidity After One-Stage Vertical Banded Gastroplasty Conversions: A Retrospective Analysis.

Background: The vertical banded gastroplasty (VBG) is a historic restrictive bariatric operation often requiring further surgery. In this investigation utilizing the 2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) national dataset, we aim to better define the outcomes of VBG conversions.Methods: We queried the 2021 MBSAQIP dataset for patients who underwent a conversion from a VBG to Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Demographics, comorbidities, laboratory values, and additional patient factors were examined. Rates of key consequential outcome measures 30-day readmission, reoperation, reintervention, mortality, and a composite endpoint (at least 1 of the 4) were further calculated.Results: We identified 231 patients who underwent conversion from VBG to SG (n = 23), RYGB (n = 208), or other anatomy (n = 6), of which 93% of patients were female, and 22% of non-white race. The median age was 56 years and body-mass index (BMI) was 43 kg/m2. The most common surgical indications included weight considerations (48%), reflux (25%), anatomic causes (eg, stricture, fistula, and ulcer; 10%), and dysphagia (6.5%). Thirty-day morbidity rates included reoperation (7.8%), readmission (9.1%), reintervention (4.3%), mortality (.4%), and the composite endpoint (15%). Upon bivariate analysis, we did not identify any specific risk factor for the 30-day composite endpoint.Discussion: One-stage VBG conversions to traditional bariatric anatomy are beset with higher 30-day morbidity relative to primary procedures. Additional MBSAQIP data will be required for aggregation, to better characterize the risk factors inherent in these operations.

Prediction of 30-Day Morbidity and Mortality After Conversion of Sleeve Gastrectomy to Roux-en-Y Gastric Bypass: Use of an Artificial Neural Network.

BACKGROUND: Conversion of sleeve gastrectomy to Roux-en-Y gastric bypass is indicated primarily for unsatisfactory weight loss or gastroesophageal reflux disease (GERD). This study aimed to use a comprehensive database to define predictors of 30-day reoperation, readmission, reintervention, or mortality. An artificial neural network (ANN) was employed to optimize prediction of the composite endpoint (occurrence of 1+ morbid event). METHODS: Areview of 8895 patients who underwent conversion for weight-related or GERD-related indications was performed using the 2021 MBSAQIP national dataset. Demographics, comorbidities, laboratory values, and other factors were assessed for bivariate and subsequent multivariable associations with the composite endpoint (P ≤ .05). Factors considered in the multivariable model were imputed into a three-node ANN with 20% randomly withheld for internal validation, to optimize predictive accuracy. Models were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: 39% underwent conversion for weight considerations and 61% for GERD. Rates of 30-day reoperation, readmission, reintervention, mortality, and the composite endpoint were 3.0%, 7.1%, 2.1%, .1%, and 9.1%, respectively. Of the nine factors associated with the composite endpoint on bivariate analysis, only non-white race (P < .001; odds ratio 1.4), lower body-mass index (P < .001; odds ratio .22), and therapeutic anticoagulation (P = .001; odds ratio 2.0) remained significant upon multivariable analysis. Areas under ROC curves for the multivariable regression, ANN training, and validation sets were .587, .601, and .604, respectively. DISCUSSION: Identification of risk factors for morbidity after conversion offers critical information to improve patient selection and manage postoperative expectations. ANN models, with appropriate clinical integration, may optimize prediction of morbidity.

Ketogenesis protects against MASLD-MASH progression through fat oxidation-independent mechanisms.

The progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) to metabolic-dysfunction-associated steatohepatitis (MASH) involves complex alterations in both liver-autonomous and systemic metabolism that influence the liver's balance of fat accretion and disposal. Here, we quantify the relative contribution of hepatic oxidative pathways to liver injury in MASLD-MASH. Using NMR spectroscopy, UHPLC-MS, and GC-MS, we performed stable-isotope tracing and formal flux modeling to quantify hepatic oxidative fluxes in humans across the spectrum of MASLD-MASH, and in mouse models of impaired ketogenesis. We found in humans with MASH, that liver injury correlated positively with ketogenesis and total fat oxidation, but not with turnover of the tricarboxylic acid cycle. The use of loss-of-function mouse models demonstrated that disruption of mitochondrial HMG-CoA synthase (HMGCS2), the rate-limiting step of ketogenesis, impairs overall hepatic fat oxidation and induces a MASLD-MASH-like phenotype. Furthermore, disruption of mitochondrial ß-hydroxybutyrate dehydrogenase (BDH1), the terminal step of ketogenesis, also impaired fat oxidation, but surprisingly did not exacerbate steatotic liver injury. Taken together, these findings suggest that quantifiable variations in overall hepatic fat oxidation may not be a primary determinant of MASLD-to-MASH progression, but rather, that maintenance of hepatic ketogenesis could serve a protective role through alternative fat oxidation-independent mechanisms.

Gastric bypass after liver transplantation.

Few data are available for assessing the outcomes of bariatric surgery for patients who have undergone orthotopic liver transplantation (OLT). The University of Minnesota bariatric surgery database and transplant registry were retrospectively reviewed to identify patients who had undergone OLT and then open Roux-en-Y gastric bypass (RYGB) surgery between 2001 and 2009. Comorbidity-appropriate laboratory values, body mass indices (BMIs), histopathology reports, and immunosuppressive regimens were collected. Seven patients were identified with a mean age of 55.4 ± 8.64 years and a mean follow-up of 59.14 ± 41.49 months from the time of RYGB. The mean time between OLT and RYGB was 26.57 ± 8.12 months. The liver disease etiologies were hepatitis C (n = 4), jejunoileal bypass surgery (n = 1), hemangioendothelioma (n = 1), and alcoholic cirrhosis (n = 1). There were 2 deaths for patients with hepatitis C 6 and 9 months after bariatric surgery due to multiple-organ dysfunction syndrome and metastatic esophageal squamous carcinoma, respectively. One patient with hepatitis C required a reversal of the RYGB because of malnutrition and an inability to tolerate oral intake. Four of the 7 patients had type 2 diabetes mellitus (T2DM), 4 had hypertension, and 6 patients had dyslipidemia. All patients were on immunosuppressive medications, but only 4 were on corticosteroids. Glycemic control was improved in all surviving patients with T2DM. The mean BMI was 34.27 ± 5.51 kg/m(2) before OLT and 44.34 ± 6.08 kg/m(2) before RYGB; it declined to 26.47 ± 5.53 kg/m(2) after RYGB. In conclusion, in this case series of patients undergoing RYGB after OLT, we observed therapeutic weight loss, improved glycemic control, and improved high-density lipoprotein levels in the presence of continued dyslipidemia. RYGB may have contributed to the death of 1 patient due to multiple-organ dysfunction syndrome.