Novel multiparametric bulk and single EV pipeline for adipose cell-specific biomarker discovery in paired human biospecimens.

Obesity is a global health crisis that contributes to morbidity and mortality worldwide. Obesity's comorbid association with a variety of diseases, from metabolic syndrome to neurodegenerative disease, underscores the critical need to better understand the pathobiology of obesity. Adipose tissue, once seen as an inert storage depot, is now recognized as an active endocrine organ, regulating metabolic and systemic homeostasis. Recent studies spotlight the theranostic utility of extracellular vesicles (EVs) as novel biomarkers and drivers of disease, including obesity-related complications. Adipose-derived EVs (ADEVs) have garnered increased interest for their roles in diverse diseases, however robust isolation and characterization protocols for human, cell-specific EV subsets are limited. Herein, we directly address this technical challenge by establishing a multiparametric analysis framework that leverages bulk and single EV characterization, mRNA phenotyping and proteomics of human ADEVs directly from paired visceral adipose tissue, cultured mature adipocyte conditioned media, and plasma from obese subjects undergoing bariatric surgery. Importantly, rigorous EV phenotyping at the tissue and cell-specific level identified top 'adipose liquid biopsy' candidates that were validated in circulating plasma EVs from the same patient. In summary, our study paves the way toward a tissue and cell-specific, multiparametric framework for studying tissue and circulating adipose EVs in obesity-driven disease.

The impact of bariatric surgery on admissions for gastrointestinal complications and conditions associated with obesity: A nationwide study.

BACKGROUND: Obesity worsens various gastrointestinal pathologies. While bariatric surgery ameliorates obesity, it substantially modifies the gastrointestinal system depending on surgery type, with limited data on subsequent impact on obesity-related gastrointestinal admissions. METHODS: Using the 2012-2014 Nationwide Readmission Database, we included individuals with obesity who received vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), or hernia repair (HR-control surgery). Our main focus was the adjusted odds ratio (aOR) for gastrointestinal inpatient admissions within 6 months following surgery compared to the 6 months preceding it, while controlling for several confounding factors. Gastrointestinal admissions were grouped into postoperative complications or obesity-associated gastrointestinal conditions. RESULTS: Our cohort included 140,103 adults with RYGB, 132,253 with VSG, and 12,436 HR controls. Postoperative gastrointestinal complications were most common after RYGB, prominently obstruction (aOR = 33.17, 95%CI: 18.01, 61.10), and Clostridium difficile infection (aOR: 12.52, 95%CI: 6.22, 25.19). VSG also saw significantly increased but less frequent similar conditions. Notably, for gastrointestinal conditions associated with obesity, acute pancreatitis risk was higher post-VSG (aOR = 6.26, 95%CI: 4.02, 9.73). Post-RYGB patients were most likely to be admitted for cholelithiasis with cholecystitis (aOR: 4.15, 95% CI: 3.24, 5.31), followed by chronic liver disease (aOR: 3.00, 95% CI: 2.33, 3.87). The risk of noninfectious colitis admissions was threefold higher after RYGB and VSG. No gastrointestinal conditions showed an increase after HR. CONCLUSION: Despite weight loss, bariatric surgery was associated with an increased risk of hepato-pancreatobiliary and colitis admissions related to obesity in the first six postoperative months, with considerable variations in rates of gastrointestinal conditions by surgery type.

Transportation Factors and Postoperative Attendance and Weight Loss Through 24 Months.

PURPOSE: Transportation, access to follow-up care, and association with weight loss are understudied in the bariatric population. The objective of this study was to determine how transportation variables associate with postoperative attendance and weight loss through 24 months. MATERIALS AND METHODS: Seven hundred eighty-seven patients (81.3% female; 59.1% White) who had primary surgery (48.6% gastric bypass) from 2015 to 2019 were included. Sidewalk coverage and number of bus stops from patients' homes, driving distance in miles and minutes from patients' homes to the nearest bus stop and the clinic were measured. Bivariate analyses were conducted with the transportation variables and attendance and %TWL at 2 or 3, 6, 12, and 24 months. One mixed multilevel model was conducted with dependent variable %TWL over 24 months with visits as the between-subjects factor and covariates: race, insurance, surgical procedure, and driving distance to the clinic in minutes, attendance, and %TWL over 24 months; an interaction between distance, attendance, and visits. RESULTS: There were no significant differences between the majority of the transportation variables and postoperative attendance or %TWL. Patients who had perfect attendance had improved %TWL at 12 months [t(534)=-1.92, p=0.056] and 24 months [t(393)=-2.69, p=0.008] compared to those who missed at least one appointment. Patients with perfect attendance and who had shorter driving times (under 20 min) to the clinic had greater weight loss through 24 months [F(10, 1607.50)=2.19, p=0.016)]. CONCLUSIONS: Overall, transportation factors were not associated with attendance and weight loss, with the exception of the interaction between shorter driving minutes to follow-up and perfect attendance.

How Does the Sequence of the American Board of Surgery Examinations Impact Pass/Fail Outcomes?

OBJECTIVE: Historically, the American Board of Surgery required surgeons to pass the qualifying examination (QE) before taking the certifying examination (CE). However, in the 2020-2021 academic year, with mitigating circumstances related to COVID-19, the ABS removed this sequencing requirement to facilitate the certification process for those candidates who were negatively impacted by a QE delivery failure. This decoupling of the traditional order of exam delivery has provided a natural comparator to the traditional route and an analysis of the impact of examination sequencing on candidate performance. METHODS: All candidates who applied for the canceled July 2020 QE were allowed to take the CE before passing the QE. The sample was then reduced to include only first-time candidates to ensure comparable groups for performance outcomes. Logistic regression was used to analyze the relationship between the order of taking the QE and the CE, controlling for other examination performance, international medical graduate status, and gender. RESULTS: Only first-time candidates who took both examinations were compared (n=947). Examination sequence was not a significant predictor of QE pass/fail outcomes, OR=0.54; 95% CI, 0.19-1.61, P =0.26. However, examination sequence was a significant predictor of CE pass/fail outcomes, OR=2.54; 95% CI, 1.46-4.68, P =0.002. CONCLUSIONS: This important study suggests that preparation for the QE increases the probability of passing the CE and provides evidence that knowledge may be foundational for clinical judgment. The ABS will consider these findings for examination sequencing moving forward.

Social History of Bariatric Surgery: Relationship to Patient and Associations with Postoperative Outcomes.

PURPOSE: There is limited research about the prevalence of patients initiating metabolic and bariatric surgery (MBS) who also know someone who had MBS, referred to as having a social history of MBS. Evidence about the specific relationship of these individuals to the patient, how having a social history of MBS is associated with patients' choice of surgical procedure, and how having a social history of MBS is associated with patients' postoperative outcomes can be used to inform future preoperative assessments. The objective was to (a) define the number of people patients knew who had MBS and relationship to patient, (b) assess congruence between those who had MBS with patients' procedure selection, and (c) explore associations between social history of MBS and postoperative outcomes. MATERIALS AND METHODS: The sample included 123 patients who had MBS in 2021 (83.7% female; 44.7% Sleeve Gastrectomy, 55.3% Gastric Bypass). For up to 5 people, patients provided their relationship and surgical procedure, and completed the Family Assessment Device (FAD). Bivariate analyses assessed congruence in type of procedure, and social history of MBS with complications, readmissions, and %TWL. Three mixed multilevel models were conducted with (1) close friend, (2) coworker, and (3) close family history of MBS including the FAD on change in %TWL over 12 months with surgical procedure as a covariate. RESULTS: Ninety-one percent of patients knew someone who had MBS, average 2.66±1.45. Patients reported a close friend (56.1%), close family member (43.9%), and coworker (19.5%) who had MBS. Patients with a close family member who had MBS and reported healthy vs impaired family functioning had greater %TWL over 12 months (p=0.016). Patients with a close friend who had MBS had less %TWL (p=0.015), and patients with a coworker who had MBS had greater %TWL (p=0.012), which did not change over time. CONCLUSION: Patients with coworkers or close family members with healthy family functioning with a history of MBS had more weight loss, whereas those with close friends with a history of MBS had less weight loss.

Proximity to High/Moderate vs Low Diversity Selection Food Stores and Patient Weight loss through 24 Months.

PURPOSE: Explorations into the neighborhood food environment have not adequately extended to adults with obesity who undergo bariatric surgery. The objective of this study is to determine how diversity of food selection at food retail stores within proximities of 5- and 10-min walks associate with patient postoperative weight loss over 24 months. MATERIALS AND METHODS: Eight hundred eleven patients (82.1% female; 60.0% White) who had primary bariatric surgery (48.6% gastric bypass) from 2015 to 2019 at The Ohio State University were included. EHR variables included race, insurance, procedure, and percent total weight loss (%TWL) at 2, 3, 6, 12, and 24 months. Proximity from patients' home addresses to food stores within a 5- (0.25 mile)- and 10-min (0.50 mile) walk were totaled for low (LD) and moderate/high (M/HD) diversity food selections. Bivariate analyses were conducted with %TWL at all visits and LD and M/HD selections within 5- (0, ≥ 1) and 10-min (0, 1, ≥ 2) walk proximities. Four mixed multilevel models were conducted with dependent variable %TWL over 24 months with visits as the between subjects factor and covariates: race, insurance, procedure, and interaction between proximity to type of food store selections with visits to determine association with %TWL over 24 months. RESULTS: There were no significant differences for patients living within a 5- (p = 0.523) and 10-min (p = 0.580) walk in proximity to M/HD food selection stores and weight loss through 24 months. However, patients living in proximity to at least 1 LD selection store within a 5- (p = 0.027) and 1 or 2 LD stores within a 10-min (p = 0.015) walk had less weight loss through 24 months. CONCLUSION: Overall, living in proximity to LD selection stores was a better predictor of postoperative weight loss over 24 months than living within proximity of M/HD selection stores.

Truth of Colorectal Enhanced Recovery Programs: Process Measure Compliance in 151 Hospitals.

BACKGROUND: Commonly cited studies have reported substantial improvements (defined as >20%) in process measure compliance after implementation of colorectal enhanced recovery programs (ERPs). However, hospitals have anecdotally reported difficulties in achieving similar improvement gains. This study evaluates improvement uniformity among 151 hospitals exposed to an 18-month implementation protocol for 6 colorectal ERP process measures (oral antibiotics, mechanical bowel preparation, multimodal pain control, early mobilization, early liquid intake, and early solid intake). STUDY DESIGN: One hundred fifty-one hospitals implemented a colorectal ERP with pathway, educational and supporting materials, and data capture protocols; 906 opportunities existed for process compliance improvement across the cohort (151 hospitals × 6 process measures). However, 240 opportunities were excluded due to high starting compliance rates (ie compliance >80%) and 3 opportunities were excluded because compliance rates were recorded for fewer than 2 cases. Thus, 663 opportunities for improvement across 151 hospitals were studied. RESULTS: Of 663 opportunities, minimal improvement (0% to 20% increase in compliance) occurred in 52% of opportunities, substantial improvement (>20% increase in compliance) in 20%, and worsening compliance occurred in 28%. Of the 6 processes, multimodal pain control and use of oral antibiotics improved the most. CONCLUSIONS: Contrary to published ERP literature, the majority of study hospitals had difficulty improving process compliance with 80% of the opportunities not achieving substantial improvement. This discordance between ERP implementation success rates reported in the literature and what is observed in a large sample could reflect differences in hospitals' culture or characteristics, or a publication bias. Attention needs to be directed toward improving ERP adoption across the spectrum of hospital types.

The BARI-hoods Project: neighborhood social determinants of health and postoperative weight loss using integrated electronic health record, census, and county data.

BACKGROUND: While social determinants of health (SDoH) have gained attention for their role in weight loss following bariatric surgery, electronic health record (EHR) data provide limited information beyond demographics associated with disparities in weight loss. OBJECTIVE: To integrate EHR, census, and county data to explore disparities in SDoH and weight loss among patients in the largest populous county of Ohio. SETTING: Seven hundred seventy-two patients (82.1% female; 37.0% Black) who had primary bariatric surgery (48.7% gastric bypass) from 2015 to 2019 at Ohio State University. METHODS: EHR variables included race, insurance, procedure, and percent total weight lost (%TWL) at 2/3, 6, 12, and 24 months. Census variables included poverty and unemployment rates. County variables included food stores, fitness/recreational facilities, and open area within a 5- and 10-minute walk from home. Two mixed multilevel models were conducted with %TWL over 24 months, with visits as the between-subjects factor; race, census, county, insurance, and procedure variables were covariates. Two additional sets of models determined within-group differences for Black and White patients. RESULTS: Access to more food stores within a 10-minute walk was associated with greater %TWL over 24 months (P = .029). Black patients with access to more food stores within a 10-minute (P = .017) and White patients with more access within a 5-minute walk (P = .015) had greater %TWL over 24 months. Black patients who lived in areas with higher poverty rates (P = .036) experienced greater %TWL over 24 months. No significant differences were found for unemployment rate or proximity to fitness/recreational facilities and open areas. CONCLUSIONS: Close proximity to food stores is associated with better weight loss 2 years after bariatric surgery. Lower poverty levels did not negatively affect weight loss in Black patients.

Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity.

Decreased adipose tissue regulatory T cells contribute to insulin resistance in obese mice, however, little is known about the mechanisms regulating adipose tissue regulatory T cells numbers in humans. Here we obtain adipose tissue from obese and lean volunteers. Regulatory T cell abundance is lower in obese vs. lean visceral and subcutaneous adipose tissue and associates with reduced insulin sensitivity and altered adipocyte metabolic gene expression. Regulatory T cells numbers decline following high-fat diet induction in lean volunteers. We see alteration in major histocompatibility complex II pathway in adipocytes from obese patients and after high fat ingestion, which increases T helper 1 cell numbers and decreases regulatory T cell differentiation. We also observe increased expression of inhibitory co-receptors including programmed cell death protein 1 and OX40 in visceral adipose tissue regulatory T cells from patients with obesity. In human obesity, these global effects of interferon gamma to reduce regulatory T cells and diminish their function appear to instigate adipose inflammation and suppress adipocyte metabolism, leading to insulin resistance.

Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity.

Importance: Obesity increases the incidence and mortality from some types of cancer, but it remains uncertain whether intentional weight loss can decrease this risk. Objective: To investigate whether bariatric surgery is associated with lower cancer risk and mortality in patients with obesity. Design, Setting, and Participants: In the SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) matched cohort study, adult patients with a body mass index of 35 or greater who underwent bariatric surgery at a US health system between 2004 and 2017 were included. Patients who underwent bariatric surgery were matched 1:5 to patients who did not undergo surgery for their obesity, resulting in a total of 30 318 patients. Follow-up ended in February 2021. Exposures: Bariatric surgery (n = 5053), including Roux-en-Y gastric bypass and sleeve gastrectomy, vs nonsurgical care (n = 25 265). Main Outcomes and Measures: Multivariable Cox regression analysis estimated time to incident obesity-associated cancer (a composite of 13 cancer types as the primary end point) and cancer-related mortality. Results: The study included 30 318 patients (median age, 46 years; median body mass index, 45; 77% female; and 73% White) with a median follow-up of 6.1 years (IQR, 3.8-8.9 years). The mean between-group difference in body weight at 10 years was 24.8 kg (95% CI, 24.6-25.1 kg) or a 19.2% (95% CI, 19.1%-19.4%) greater weight loss in the bariatric surgery group. During follow-up, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group had an incident obesity-associated cancer (incidence rate of 3.0 events vs 4.6 events, respectively, per 1000 person-years). The cumulative incidence of the primary end point at 10 years was 2.9% (95% CI, 2.2%-3.6%) in the bariatric surgery group and 4.9% (95% CI, 4.5%-5.3%) in the nonsurgical control group (absolute risk difference, 2.0% [95% CI, 1.2%-2.7%]; adjusted hazard ratio, 0.68 [95% CI, 0.53-0.87], P = .002). Cancer-related mortality occurred in 21 patients in the bariatric surgery group and 205 patients in the nonsurgical control group (incidence rate of 0.6 events vs 1.2 events, respectively, per 1000 person-years). The cumulative incidence of cancer-related mortality at 10 years was 0.8% (95% CI, 0.4%-1.2%) in the bariatric surgery group and 1.4% (95% CI, 1.1%-1.6%) in the nonsurgical control group (absolute risk difference, 0.6% [95% CI, 0.1%-1.0%]; adjusted hazard ratio, 0.52 [95% CI, 0.31-0.88], P = .01). Conclusions and Relevance: Among adults with obesity, bariatric surgery compared with no surgery was associated with a significantly lower incidence of obesity-associated cancer and cancer-related mortality.

First report from the American Society of Metabolic and Bariatric Surgery closed-claims registry: prevalence, causes, and lessons learned from bariatric surgery medical malpractice claims.

BACKGROUND: Bariatric surgery has demonstrated sustained improvements in quality. Malpractice closed claims have been offered as a means of assessing quality. Few studies have investigated malpractice closed claims and opportunities for improvement in bariatric surgery. OBJECTIVES: To examine the prevalence and causes of malpractice claims with examination of prospects for quality improvement. SETTING: University hospital, United States; private practice. METHODS: Four national malpractice insurers participated in the closed-claims registry. Data regarding patients, staff, procedures, and hospital status were gathered from closed-claims files. Following data collection, a clinical summary of each closed claim was collected and later assessed by an expert panel on the basis of the following: contributing diagnosis and treatment events; whether complications were potentially preventable by the surgeon; the role of language, fatigue, distraction, workload, or teaching hospital/trainee supervision; communication concerns; and final care determination. RESULTS: A total of 175 closed claims were collected from index bariatric surgeries within the period from 2006-2014. Of these, 75.9% of surgeons were board certified and 43.3% of the hospitals were accredited for bariatric surgery. Most clinical complications after bariatric surgery that led to malpractice lawsuits were mortality (35.1%) and leaks (17.5%). While they were not the common cause for malpractice suits, bleeding (5.3%), retained foreign body (5.3%), and vascular injury (4.4%) occurred at higher rates than national averages. CONCLUSION: Prevalence of malpractice claims regarding bariatric surgery is low. Failure to diagnose, delay in treatment, postoperative care, and communication domain responses indicate future opportunities for improvement.

An analysis of readmission trends by urgency and race/ethnicity in the MBSAQIP registry, 2015-2018.

BACKGROUND: Large-scale analyses stratifying bariatric surgery readmissions by urgency are lacking. OBJECTIVES: Identify predictors of urgent/nonurgent readmission among "ideal" bariatric candidates, using a national registry. SETTING: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) national database. METHODS: We extracted an "ideal" patient cohort from the 2015-2018 Metabolic and Bariatric Surgery Accreditation Quality Improvement Program (MBSAQIP) registry, characterized by only typical weight-related comorbidities (hypertension [HTN], obstructive sleep apnea [OSA], gastroesophageal reflux disease [GERD], and diabetes (insulin-dependent diabetes mellitus [IDDM] and non-insulin-dependent diabetes mellitus [NIDDM]) undergoing primary bariatric surgery with an uneventful postoperative course. Readmissions were classified as "urgent" (UR; e.g., leak, obstruction, bleeding) or "nonurgent" (NUR; e.g., dehydration, nonspecific abdominal pain). χ2 or t test analyses were used for bivariate significance testing. Multivariate logistic regression models were constructed to assess independent predictors of readmission. RESULTS: The cohort (N = 292,547) comprised 38.5% of all MBSAQIP patients (mean age [standard deviation] = 43.2 [11.7]; body mass index [BMI] = 44.9 [6.6]; 81% female; 62% White, 17% Black, 14% Hispanic). Total readmission rates were 2.75% (n = 8046) and decreased from 2015-2018 (3.00%-2.63%; P < .001). Independent predictors of readmissions included Roux-en-Y gastric bypass (RYGB) (odds ratio [OR] = 1.97, p < .001), Black (OR = 1.46, P < .001) and Hispanic race (OR = 1.14, P < .001), GERD (OR = 1.27, P < .001), HTN (OR = 1.08, P = .003), and IDDM (OR = 1.39, P < .001). NUR and UR readmission rates were 1.27% (n = 3702) and 1.06% (n = 3090), respectively. NURs decreased over time (1.42%-1.16%, P < .001), with no change in Urs (1.01%-1.06%, P = .51); this trend persisted in multivariate analysis (2017: NUR OR = .85, P < .001; 2018: NUR OR = .82, p < .001). Independent predictors of both URs and NURs included Black (NUR OR = 1.71, p < .001; UR OR = 1.27, p < .001) and Hispanic (NUR OR = 1.15, P < .001; UR OR = 1.19, P < .001) race, RYGB (NUR OR = 1.84, P < .001; UR OR = 2.34, P < .001), and GERD (NUR OR = 1.39, p < .001; UR OR = 1.17, P < .001). Female sex (NUR OR = 1.64, P < .001), age (NUR OR = .98, P < .001), HTN (NUR OR = 1.22, P < .001), and IDDM (NUR OR = 1.41, P < .001) predicted NURs, while higher BMI (UR OR = 1.01, P < .001), and OSA (UR OR = 1.10, P = .02) predicted URs. CONCLUSION: Readmission rates for "ideal" bariatric patients improved over time, driven by reductions in non-urgent etiologies. Racial disparities persist for both urgent and non-urgent causes of readmission.

The Impact of Bariatric Surgery on Diverticulitis Outcomes and Risk of Recurrent Hospitalizations in Adults with Clinically Severe Obesity.

PURPOSE: Clinically severe obesity (SO) is a known risk factor for worsened outcomes and recurrence of acute diverticulitis. Paucity of data exist on outcomes of diverticulitis after bariatric surgery. METHODS: The Nationwide Readmissions Database was queried for diverticulitis hospitalizations between the years 2010 and 2014. We restricted analysis to patients with SO and those who had bariatric surgery (BRS). Outcomes of mortality, surgical events, and recurrent diverticulitis admissions were compared using multivariable analysis and one-to-one propensity score matching. RESULTS: Among 52,274 diverticulitis admissions, 91.2% (47,694) patients had SO and 8.8% (4580) had prior BRS. Patients with SO had higher odds of suffering mortality on index diverticulitis admission when compared to those with prior BRS [adjusted odds ratio (aOR): 10.55; 95%CI 1.45,76.75]. Patients with SO were also more likely to undergo emergency surgery (aOR: 1.71; 95%CI 1.25,2.34) and colectomy (aOR: 1.45; 95%CI 1.26,1.68). Rates of recurrent diverticulitis readmissions within 30 days and 6 months were also higher in patients with SO compared to BRS patients (aOR: 7.94; 95%CI 1.09,57.83 and aOR: 1.98; 95%CI 1.14,3.43, respectively). Propensity score matching confirmed our findings of increased rates of mortality (OR: 17.28; 95%CI 2.02,147.6), recurrent diverticulitis, and worsened surgical outcomes within 30 days in patients with SO compared to BRS. CONCLUSION: This study is first to show improved outcomes and less recurrent hospitalizations for diverticulitis after bariatric surgery compared to patients with clinically severe obesity. Further studies are needed to understand mechanisms leading to this improvement and the role of weight loss in prevention of severe diverticulitis.

Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis.

IMPORTANCE: No therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH). OBJECTIVE: To investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis. DESIGN, SETTING, AND PARTICIPANTS: In the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25 828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021. EXPOSURES: Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care. MAIN OUTCOMES AND MEASURES: The primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework. RESULTS: A total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE. Among the patients analyzed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P = .01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P = .007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n = 2) and respiratory failure (n = 2). CONCLUSIONS AND RELEVANCE: Among patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.

Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity: Comparison of Gastric Bypass, Sleeve Gastrectomy, and Usual Care.

OBJECTIVE: To determine which one of the two most common metabolic surgical procedures is associated with greater reduction in risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM) and obesity. RESEARCH DESIGN AND METHODS: A total of 13,490 patients including 1,362 Roux-en-Y gastric bypass (RYGB), 693 sleeve gastrectomy (SG), and 11,435 matched nonsurgical patients with T2DM and obesity who received their care at the Cleveland Clinic (1998-2017) were analyzed, with follow-up through December 2018. With multivariable Cox regression analysis we estimated time to incident extended MACE, defined as first occurrence of coronary artery events, cerebrovascular events, heart failure, nephropathy, atrial fibrillation, and all-cause mortality. RESULTS: The cumulative incidence of the primary end point at 5 years was 13.7% (95% CI 11.4-15.9) in the RYGB groups and 24.7% (95% CI 19.0-30.0) in the SG group, with an adjusted hazard ratio (HR) of 0.77 (95% CI 0.60-0.98, P = 0.04). Of the six individual end points, RYGB was associated with a significantly lower cumulative incidence of nephropathy at 5 years compared with SG (2.8% vs. 8.3%, respectively; HR 0.47 [95% CI 0.28-0.79], P = 0.005). Furthermore, RYGB was associated with a greater reduction in body weight, glycated hemoglobin, and use of medications to treat diabetes and cardiovascular diseases. Five years after RYGB, patients required more upper endoscopy (45.8% vs. 35.6%, P < 0.001) and abdominal surgical procedures (10.8% vs. 5.4%, P = 0.001) compared with SG. CONCLUSIONS: In patients with obesity and T2DM, RYGB may be associated with greater weight loss, better diabetes control, and lower risk of MACE and nephropathy compared with SG.

Patient-reported Outcomes After Metabolic Surgery Versus Medical Therapy for Diabetes: Insights From the STAMPEDE Randomized Trial.

OBJECTIVE: The aim of this study was to investigate the long-term effects of medical and surgical treatments of type 2 diabetes mellitus (T2DM) on patient-reported outcomes (PROs). BACKGROUND: Robust data on PROs from randomized trials comparing medical and surgical treatments for T2DM are lacking. METHODS: The Surgical Treatment And Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial showed that 5 years after randomization, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were superior to intensive medical therapy (IMT) alone in achieving glycemic control in patients with T2DM and obesity. A subset of 104 patients participating in the STAMPEDE trial were administered two generic health-related quality of life (QoL) questionnaires (RAND-36 and EQ-5D-3L) and a diabetes-specific instrument at baseline, and then on an annual basis up to 5 years after randomization. RESULTS: On longitudinal analysis, RYGB and SG significantly improved the domains of physical functioning, general health perception, energy/fatigue, and diabetes-related QoL compared with IMT group. In the IMT group, none of the QoL components in the generic questionnaires improved significantly from baseline. No significant long-term differences were observed among the study groups in measures of psychological and social aspects of QoL. On multivariable analysis, independent factors associated with improved general health perception at long-term included baseline general health (P < 0.001), insulin independence at 5 years (P = 0.005), RYGB versus IMT (P = 0.005), and SG versus IMT (P = 0.034). Favorable changes following RYGB and SG were comparable. CONCLUSIONS: In patients with T2DM, metabolic surgery is associated with long-term favorable changes in certain PROs compared with IMT, mainly on physical health and diabetes-related domains. Psychosocial well-being warrants greater attention after metabolic surgery.

Foregut Exclusion Enhances Incretin and Insulin Secretion After Roux-en-Y Gastric Bypass in Adults With Type 2 Diabetes.

INTRODUCTION: Patients with type 2 diabetes experience resolution of hyperglycemia within days after Roux-en-Y gastric bypass (RYGB) surgery. This is attributed, in part, to enhanced secretion of hindgut factors following exclusion of the gastric remnant and proximal intestine during surgery. However, evidence of the mechanisms of remission remain limited due to the challenges of metabolic evaluation during the early postoperative period. The purpose of this investigation was to determine the role of foregut exclusion in the resolution of type 2 diabetes after RYGB. METHODS: Patients with type 2 diabetes (n = 15) undergoing RYGB had a gastrostomy tube (G-tube) placed in their gastric remnant at time of surgery. Patients were randomized to receive a mixed meal tolerance test via oral or G-tube feeding immediately prior to and 2 weeks after surgery in a repeated measures crossover design. Plasma glucose, insulin, C-peptide, incretin responses, and indices of meal-stimulated insulin secretion and sensitivity were determined. RESULTS: Body weight, fat mass, fasting glucose and insulin, and circulating lipids were significantly decreased 2 weeks after surgery. The glycemic response to feeding was reduced as a function of total area under the curve but not after adjustment for the reduction in fasting glucose. Oral feeding significantly enhanced insulin and incretin secretion after RYGB, which was entirely ablated by G-tube feeding. CONCLUSION: Foregut exclusion accounts for the rise in incretin and insulin secretion but may not fully explain the early improvements in glucose metabolism after RYGB surgery.

Roux-en-Y gastric bypass restores islet function and morphology independent of body weight in ZDF rats.

Reductions in ß-cell number and function contribute to the onset type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) surgery can resolve T2D within days of operation, indicating a weight-independent mechanism of glycemic control. We hypothesized that RYGB normalizes glucose homeostasis by restoring ß-cell structure and function. Male Zucker Diabetic Fatty (fa/fa; ZDF) rats were randomized to sham surgery (n = 16), RYGB surgery (n = 16), or pair feeding (n = 16). Age-matched lean (fa/+) rats (n = 8) were included as a secondary control. Postprandial metabolism was assessed by oral glucose tolerance testing before and 27 days after surgery. Fasting and postprandial plasma GLP-1 was determined by mixed meal tolerance testing. Fasting plasma glucagon was also measured. ß-cell function was determined in isolated islets by a glucose-stimulated insulin secretion assay. Insulin and glucagon positive areas were evaluated in pancreatic sections by immunohistochemistry. RYGB reduced body weight (P < 0.05) and improved glucose tolerance (P < 0.05) compared with sham surgery. RYGB reduced fasting glucose compared with both sham (P < 0.01) and pair-fed controls (P < 0.01). Postprandial GLP-1 (P < 0.05) was elevated after RYGB compared with sham surgery. RYGB islets stimulated with 20 mM glucose had higher insulin secretion than both sham and pair-fed controls (P < 0.01) and did not differ from lean controls. Insulin content was greater after RYGB compared with the sham (P < 0.05) and pair-fed (P < 0.05) controls. RYGB improves insulin secretion and pancreatic islet function, which may contribute to the remission of type 2 diabetes following bariatric surgery.NEW & NOTEWORTHY The onset and progression of type 2 diabetes (T2D) results from failure to secrete sufficient amounts of insulin to overcome peripheral insulin resistance. Here, we demonstrate that Roux-en-Y gastric bypass (RYGB) restores islet function and morphology compared to sham and pair-fed controls in ZDF rats. The improvements in islet function were largely attributable to enhanced insulin content and secretory function in response to glucose stimulation.

The Effect of an Enhanced Recovery Protocol on Colorectal Surgery Patients With Diabetes.

BACKGROUND: The effect of an enhanced recovery protocol including preoperative carbohydrate loading on patients with diabetes is unclear. This study investigated the effect of both on perioperative glucose management and postoperative outcomes in patients with diabetes undergoing colorectal surgery. MATERIALS AND METHODS: A retrospective study was conducted on patients undergoing elective colorectal surgery before and after implementation of an enhanced recovery protocol. Ninety-nine patients with type 2 diabetes (DM, 41 control versus 58 enhanced recovery) and 366 patients without diabetes (NDM, 158 control versus 158 enhanced recovery) were included. Multivariate analyses were run to compare mean peak perioperative serum glucose and postoperative outcomes in enhanced recovery and control cohorts with (DM) and without diabetes (NDM). RESULTS: Mean peak preoperative glucose was elevated in DM enhanced recovery compared with DM control patients (192.2 [72.2] versus 139.8 [41.4]; P < 0.001). Mean peak intraoperative (162.3 [43.1] versus 163.8 [39.6]; P = 0.869) and postoperative glucose (207.7 [75.8] versus 217.8 [78.5]; P = 0.523) were similar in DM enhanced recovery compared with DM control group. Enhanced recovery led to decreased LOS in DM (P = 0.001) and NDM enhanced recovery patients (P < 0.000) compared with their control groups. CONCLUSIONS: An enhanced recovery protocol may lead to increased peak preoperative glucose levels and 30-d readmissions in patients with type 2 diabetes undergoing colorectal surgery. However, the ultimate clinical significance of transiently elevated preoperative glucose in DM patients is uncertain. Our results suggest that an enhanced recovery protocol and preoperative carbohydrate loading does not lead to poorer postoperative glycemic control overall in patients with diabetes undergoing colorectal surgery.

Assessment of empiric body mass index-based thromboprophylactic dosing of enoxaparin after bariatric surgery: evidence for dosage adjustment using anti-factor Xa in high-risk patients.

BACKGROUND: Despite thromboprophylaxis, postoperative deep vein thrombosis and pulmonary embolism occur after bariatric surgery, perhaps because of failure to achieve optimal prophylactic levels in the obese population. OBJECTIVES: The aim of this study was to evaluate the adequacy of prophylactic dosing of enoxaparin in patients with severe obesity by performing an antifactor Xa (AFXa) assay. SETTING: An academic medical center METHODS: In this observational study, all bariatric surgery cases at an academic center between December 2016 and April 2017 who empirically received prophylactic enoxaparin (adjusted by body mass index [BMI] threshold of 50 kg/m2) were studied. The AFXa was measured 3-5 hours after the second dose of enoxaparin. RESULTS: A total of 105 patients were included; 85% were female with a median age of 47 years. In total, 16 patients (15.2%) had AFXa levels outside the prophylactic range: 4 (3.8%) cases were in the subprophylactic and 12 (11.4%) cases were in the supraprophylactic range. Seventy patients had a BMI <50 kg/m2 and empirically received enoxaparin 40 mg every 12 hours; AFXa was subprophylactic in 4 (5.7%) and supraprophylactic in 6 (8.6%) of these patients. Of the 35 patients with a BMI ≥50 who empirically received enoxaparin 60 mg q12h, no AFXa was subprophylactic and 6 (17.1%) were supraprophylactic. Five patients (4.8%) had major bleeding complications. One patient developed pulmonary embolism on postoperative day 35. CONCLUSION: BMI-based thromboprophylactic dosing of enoxaparin after bariatric surgery could be suboptimal in 15% of patients with obesity. Overdosing of prophylactic enoxaparin can occur more commonly than underdosing. AFXa testing can be a practical way to measure adequacy of pharmacologic thromboprophylaxis, especially in patients who are at higher risk for venous thromboembolism or bleeding.