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Fatty acid binding protein 4 (FABP4) is a secreted adipokine linked to obesity and progression of a variety of cancers. Obesity increases extracellular FABP4 (eFABP4) levels in animal models and in obese breast cancer patients compared with lean healthy controls. Using MCF-7 and T47D breast cancer epithelial cells, we show herein that eFABP4 stimulates cellular proliferation in a time and concentration dependent manner while the non-fatty acid-binding mutant, R126Q, failed to potentiate growth. When E0771 murine breast cancer cells were injected into mice, FABP4 null animals exhibited delayed tumor growth and enhanced survival compared with injections into control C57Bl/6J animals. eFABP4 treatment of MCF-7 cells resulted in a significant increase in phosphorylation of extracellular signal-regulated kinase 1/2 (pERK), transcriptional activation of nuclear factor E2-related factor 2 (NRF2) and corresponding gene targets ALDH1A1, CYP1A1, HMOX1, SOD1 and decreased oxidative stress, while R126Q treatment did not show any effects. Proximity-labeling employing an APEX2–FABP4 fusion protein revealed several proteins functioning in desmosomes as eFABP4 receptor candidates including desmoglein (DSG), desmocollin, junction plankoglobin, desomoplankin, and cytokeratins. AlphaFold modeling predicted an interaction between eFABP4, and the extracellular cadherin repeats of DSG2 and pull-down and immunoprecipitation assays confirmed complex formation that was potentiated by oleic acid. Silencing of DSG2 in MCF-7 cells attenuated eFABP4 effects on cellular proliferation, pERK levels, and ALDH1A1 expression compared with controls. Implications: These results suggest desmosomal proteins, and in particular desmoglein 2, may function as receptors of eFABP4 and provide new insight into the development and progression of obesity-associated cancers.

Current guidelines consider endoscopic resection appropriate treatment for malignant colon polyps with negative margins, low-grade histology, and no lymphovascular invasion. While increasing literature demonstrates a worse prognosis for advanced stage right- versus left-sided colon cancers after curative treatment, there is paucity of data regarding prognostic effect of location in patients undergoing endoscopic resection of T1 polyps. We hypothesized the more aggressive biologic behavior observed in advanced right-sided cancers would be similarly represented in malignant polyps, and this location would be associated with lower overall survival.The National Cancer Database was queried for adults with T1NxMx tumors who underwent endoscopic polypectomy (2004-2017). Patients with positive margins or without follow-up information were excluded.A total of 2,337 patients met inclusion criteria; 22% had right-sided polyps. Endoscopically excised proximal tumors were more common in elderly, and those with public insurance and more comorbidities (all P.01). Among patients with complete pathologic data, there were no statistical differences between right- and left-sided polyps with 1 cm median size,92% without lymphovascular invasion, and 100% without tumor deposits. Univariate analysis showed 73% vs 86% 5-year overall survival for right versus left polyps (P.01). After adjustment for available confounders, right-sided location remained significantly associated with worse overall survival (hazard ratio 1.49, 95% confidence interval 1.21-1.83).In this national cohort of patients with endoscopically excised malignant polyps, we identified right colon location as an independent prognostic factor associated with increased risk of mortality. Our data suggest polyp location should be taken into consideration when making clinical decisions regarding treatment and/or surveillance.

S1. DSC and DSG isoforms expressed in MCF-7 cells.

Fatty acid binding protein 4 (FABP4) is a secreted adipokine linked to obesity and progression of a variety of cancers. Obesity increases extracellular FABP4 (eFABP4) levels in animal models and in obese breast cancer patients compared with lean healthy controls. Using MCF-7 and T47D breast cancer epithelial cells, we show herein that eFABP4 stimulates cellular proliferation in a time and concentration dependent manner while the non-fatty acid-binding mutant, R126Q, failed to potentiate growth. When E0771 murine breast cancer cells were injected into mice, FABP4 null animals exhibited delayed tumor growth and enhanced survival compared with injections into control C57Bl/6J animals. eFABP4 treatment of MCF-7 cells resulted in a significant increase in phosphorylation of extracellular signal-regulated kinase 1/2 (pERK), transcriptional activation of nuclear factor E2-related factor 2 (NRF2) and corresponding gene targets ALDH1A1, CYP1A1, HMOX1, SOD1 and decreased oxidative stress, while R126Q treatment did not show any effects. Proximity-labeling employing an APEX2–FABP4 fusion protein revealed several proteins functioning in desmosomes as eFABP4 receptor candidates including desmoglein (DSG), desmocollin, junction plankoglobin, desomoplankin, and cytokeratins. AlphaFold modeling predicted an interaction between eFABP4, and the extracellular cadherin repeats of DSG2 and pull-down and immunoprecipitation assays confirmed complex formation that was potentiated by oleic acid. Silencing of DSG2 in MCF-7 cells attenuated eFABP4 effects on cellular proliferation, pERK levels, and ALDH1A1 expression compared with controls.Implications:These results suggest desmosomal proteins, and in particular desmoglein 2, may function as receptors of eFABP4 and provide new insight into the development and progression of obesity-associated cancers.

S2. Predicted orientation of the F57 side chain in the apoFABP4 form.

Background Preoperative anemia has been suggested as a contraindication to gastric bypass. Using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement database, this study sought to determine the role of preoperative hematocrit on 30-day morbidity and mortality after laparoscopic Roux-en-Y gastric bypass for weight loss. Methods A cohort of 31 981 patients was reviewed for factors associated with a composite primary end point including 30-day reoperation, readmission, reintervention, or mortality, including degree of anemia. Analyzed separately by gender, factors significant on bivariate analysis were included in nominal logistic multivariate analysis to assess for independent significance of the hematocrit level as a risk factor for the primary end point. Results Upon multivariate analysis, the hematocrit level was significantly associated with the 30-day end point in the male cohort ( P = .05), specifically, severe anemia (hematocrit Conclusion Bariatricians should carefully consider the appropriateness of a gastric bypass over a less anemogenic procedure such as sleeve gastrectomy in patients, particularly men with preoperative anemia.

Background The Medicare population is increasing while the prevalence of obesity remains high. Bariatric surgery is the most efficacious treatment of obesity and its comorbidities. The objective of this investigation was to assess trends in utilization, readmission, mortality, and cost of bariatric surgery in the Medicare population. Methods Utilizing the Medicare Provider Analysis and Review database, patients with clinically severe obesity undergoing laparoscopic Roux‐en‐Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (SG), and laparoscopic adjustable gastric banding (LAGB) from 2011–2015 were identified. Trends in procedure selection, readmissions, mortality, and cost were examined. A multivariable logistic regression analysis to evaluate factors associated with readmission and mortality was performed. Results Of the 73,718 patients identified, 53,949 (73%) of patients were enrolled in Medicare due to disability, 19,191 (26%) due to age, and 578 (

Bariatric surgery is the most effective treatment for weight loss. Vertical sleeve gastrectomy (VSG) involves the resection of ~ 80% of the stomach and was conceived to purely restrict oral intake. However, evidence suggests more complex mechanisms, particularly postoperative changes in gut microbiota, in facilitating weight loss and resolving associated comorbidities. VSG in humans is a complex procedure and includes peri-operative antibiotics and caloric restriction in addition to the altered anatomy. The impact of each of these factors on the intestinal microbiota have not been evaluated. The aim of this study was to determine the relative contributions of each of these factors on intestinal microbiota composition following VSG prior to substantial weight loss. Thirty-two obese patients underwent one of three treatments: (1) VSG plus routine intravenous peri-operative antibiotics (n = 12), (2) VSG with intravenous vancomycin chosen for its low intestinal penetrance (n = 12), and (3) caloric restriction (n = 8). Fecal samples were evaluated for bacterial composition prior to and 7 days following each intervention. Only patients undergoing VSG with routine peri-operative antibiotics showed a significant shift in community composition. Our data support the single dose of routine peri-operative antibiotics as the most influential factor of intestinal microbial composition acutely following VSG.

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.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).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; RReadily 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.

Introduction: Bariatric surgery leads to significant weight loss and improvements in cardiometabolic risk factors. To date, limited data exist investigating the relationship between bariatric surgery and markers of impaired glucose regulation. We hypothesize that participants who underwent bariatric surgery will have lower levels of HOMA-IR, fasting glucose and A1c after multivariable adjustment. Methods: A total of 9134 participants (52% female, mean age 48 +/- 17.7) in the National Health and Nutrition Examination Survey (NHANES) who were older then 20 years of age, not pregnant and not taking any diabetic medication were assessed. Participants were classified as having bariatric surgery and not having bariatric surgery. Survey design adjusted linear models regressed cardiometabolic outcomes on bariatric surgery status. LSMEANS +/- standard error and p-values are presented summarizing the association between bariatric surgery status and cardiometabolic outcomes including HOMA-IR, glycohemoglobin, mean systolic and diastolic blood pressure, fasting glucose, triglycerides LDL and HDL. Results: Among the 9134 participants , 89 underwent bariatric surgery. Those with vs. without a history of bariatric surgery were 3 years older (51 +/- 12 vs 48 +/- 18 yrs, p < 0.05), more likely to be female (80% vs. 52%, p < 0.05) and more likely to report a history of depression (20.3% vs. 7.8%, p < 0.05). After adjusting for demographic variables, behavioral risk factors and measures of adiposity, bariatric surgery was associated with lower HOMA-IR and triglycerides but higher HDL levels (Table). Conclusion: Bariatric Surgery was associated with HOMA-IR, triglycerides, and HDL in a nationally representative sample of U.S. adults.

Background Bariatric surgery patients are at risk for vitamin deficiencies. Objectives Investigate the prevalence of deficiencies of vitamins A, B1, B12, D, and folate in sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) patients in a single institution. Setting An academic medical center. Methods Retrospective chart reviews of 468 bariatric surgery patients (358 SG and 110 RYGB) were analyzed for vitamin levels, calcium, and parathyroid hormone. Both preoperative and postoperative measurements were obtained. Results Deficiency of vitamin D was the most common, seen in 27% preoperatively. Postoperatively, RYGB patients had a higher prevalence of vitamin D deficiency than SG patients (11.5% RYGB versus 5.2% SG within the first postoperative year, and 20.3% RYGB versus 13.4% SG after 1 year). Elevated parathyroid hormone was observed in 45% of RYGB patients after 1 year postoperatively. Vitamin A deficiency was uncommon preoperatively (2.7% SG versus 1.7% RYGB), but increased after surgery (9.4% SG versus 15.9% RYGB within 1 year postoperatively, and 5.2% SG versus 7.7% RYGB after 1 year). Vitamin B1 deficiency was observed in 8.1% SG versus 1.7% RYGB patients preoperatively and increased during the first year postoperatively (SG 10.5% and RYGB 13.7%), but improved after 1 year (7.2% SG versus 5.9% RYGB). Less than 2% of Vitamin B12 deficiencies and no folate deficiencies occurred in both SG and RYGB patients. Conclusions The highest prevalence of vitamin B1 and A deficiencies were seen in the first year postoperatively. Vitamin B12 and folate deficiency were uncommon in our patients. Vitamin D deficiency improved after surgery, but elevated parathyroid hormone was common after RYGB.

Background NonHispanic black patients bear a disproportionate burden of the obesity epidemic and its related medical co-morbidities. While bariatric surgery is the most effective treatment for morbid obesity, black patients access bariatric surgery at lower rates than nonHispanic white patients. Objectives To examine racial differences before bariatric surgery and in short-term perioperative outcomes and complications, and the extent to which race is independently associated with perioperative morbidity and mortality. Setting Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program national database. Methods Data were extracted from the 2015 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Participant Use File. Multivariate analysis was used to identify differences in mortality, length of stay, readmission, and reintervention by race in patients undergoing laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy (SG). Results A total of 108,198 patients were included in the analysis. There were significant differences in perioperative disease burden. Black patients had a higher body mass index at the time they underwent surgery (laparoscopic Roux-en-Y gastric bypass: 48.0 versus 45.7 kg/m2; SG: 46.8 versus 44.9 kg/m2; P Conclusions We found significant racial disparities in bariatric surgery outcomes, including higher mortality in black patients undergoing SG. The specific causes of these disparities remain unclear and must be the subject of future research.

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.

Obesity and diabetes are associated with an increased incidence of pancreatic cancer. Fatty acid binding protein 4 (FABP4), noted to be higher in patients with severe obesity, is linked to the development and progression of several cancers, and its level in the circulation decreases after bariatric surgery.In this paper, we evaluate the role of FABP4 in pancreatic cancer progression.University Hospital and Laboratories, United States.When Panc-1 (human) and Pan02 (mouse) pancreatic cancer cells were treated with FABP4 or the-single-point mutant FABP4 (R126Q, fatty acid binding site mutant), only FABP4 stimulated cellular proliferation. The transcriptional activity of nuclear factor E2-related factor 2 (NRF2) was increased in response to FABP4 but not the R126Q. FABP4 treatment also led to downregulation of reactive oxygen species (ROS) activity. Consistent with induced cell propagation by FABP4, the growth of Pan02 tumor was decreased in FABP4-null animals compared with C57BL/6J controls.These results suggest that FABP4 increases pancreatic cancer proliferation via activation of NRF2 and downregulation of ROS activity.

Nonalcoholic fatty liver disease and its inflammatory subtype, nonalcoholic steatohepatitis, are closely correlated with obesity. There are currently no approved pharmacologic treatments for nonalcoholic steatohepatitis. However, total body weight loss of >7% is associated with histologic improvement or even complete resolution of nonalcoholic steatohepatitis. Observational cohort studies have found that nonalcoholic steatohepatitis improves after both sleeve gastrectomy and Roux-en-Y gastric bypass. However, the lack of randomized trials has made medical societies reluctant to recommend bariatric surgery as a treatment for nonalcoholic steatohepatitis.

Background SARS-CoV-2 (COVID-19) disease causes significant morbidity and mortality through increased inflammation and thrombosis. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are states of chronic inflammation and indicate advanced metabolic disease. The purpose of this observational study was to characterize the risk of hospitalization for COVID-19 in patients with NAFLD/NASH and evaluate the mitigating effect of various metabolic treatments. Objective ▪▪▪ Setting ▪▪▪ Methods Retrospective analysis of electronic medical record data of 26,896 adults from a 12-hospital Midwest healthcare system with a positive COVID-19 polymerase chain reaction (PCR) test from March 1, 2020, to January 26, 2021. Variable selection was guided by the least absolute shrinkage and selection operator (LASSO) method, and multiple imputation was used to account for missing data. Multivariable logistic regression and competing risk models were used to assess the odds of being hospitalized within 45 days of a COVID-19 diagnosis. Analysis assessed the risk of hospitalization among patients with a prescription for metformin and statin use within the 3 months prior to the COVID-19 PCR result, history of home glucagon-like peptide 1 receptor agonist (GLP-1 RA) use, and history of metabolic and bariatric surgery (MBS). Interactions were assessed by sex and race. Results A history of NAFLD/NASH was associated with increased odds of admission for COVID-19 (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.57–2.26; P < .001) and mortality (OR, 1.96; 95% CI, 1.45–2.67; P < .001). Each additional year of having NAFLD/NASH was associated with a significant increased risk of being hospitalized for COVID-19 (OR, 1.24; 95% CI, 1.14–1.35; P < .001). NAFLD/NASH increased the risk of hospitalization in men, but not women, and increased the risk of hospitalization in all multiracial/multiethnic subgroups. Medication treatments for metabolic syndrome were associated with significantly reduced risk of admission (OR, .81; 95% CI, .67–.99; P < .001 for home metformin use; OR, .71; 95% CI, .65–.83; P < .001 for home statin use). MBS was associated with a significant decreased risk of admission (OR, .48; 95% CI, .33–.69; P < .001). Conclusions NAFLD/NASH is a significant risk factor for hospitalization for COVID-19 and appears to account for risk attributed to obesity. Other significant risks include factors associated with socioeconomic status and other co-morbidities, such as history of venous thromboembolism. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm the risk associated with visceral adiposity, and patients should be screened for and informed of treatments for metabolic syndrome.

BackgroundCovid-19 disease causes significant morbidity and mortality through increase inflammation and thrombosis. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are states of chronic inflammation and indicate advanced metabolic disease. We sought to understand the risk of hospitalization for Covid-19 associated with NAFLD/NASH.MethodsRetrospective analysis of electronic medical record data of 6,700 adults with a positive SARS-CoV-2 PCR from March 1, 2020 to Aug 25, 2020. Logistic regression and competing risk were used to assess odds of being hospitalized. Additional adjustment was added to assess risk of hospitalization among patients with a prescription for metformin use within the 3 months prior to the SARS-CoV-2 PCR result, history of home glucagon-like-peptide 1 receptor agonist (GLP-1 RA) use, and history of metabolic and bariatric surgery (MBS). Interactions were assessed by gender and race.ResultsA history of NAFLD/NASH was associated with increased odds of admission for Covid-19: logistic regression OR 2.04 (1.55, 2.96, pConclusionsNAFLD/NASH is a significant risk factor for hospitalization for Covid-19, and appears to account for risk attributed to obesity. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm risk associated with visceral adiposity, and patients should be screened for and informed of treatments for metabolic syndrome.Key QuestionsQuestionDoes NAFLD/NASH independently increase risk for poor outcomes from Covid-19?FindingsIn this observational study, a history of NAFLD/NASH was associated with a significantly increased odds of hospitalization. Metabolic surgery was protective against admission in persons with NAFLD/NASH and Covid-19. Metformin and glucagon like peptide 1 receptor agonists were associated with non-significant protecting against admission.MeaningTreatment for metabolic syndrome greatly reduce the elevated risk of hospitalization for Covid-19 among persons with NAFLD/NASH.

Obesity (OB) is associated with cognitive impairments, though the mechanisms are not well understood. OB-related chronic systemic inflammation has been postulated to contribute to cognitive dysfunction. Inflammation improves after vertical sleeve gastrectomy (VSG) and could be a potential mechanism for cognitive improvement. We examined cognitive functions in morbidly obese adults without diabetes (n 10, mean age 35 ± 4 yrs, BMI 46±11, A1C 5.3±0.4) before and 6 months after VSG. Blood inflammatory markers including IL 6 and CRP were quantified at both assessments. Paired t-tests were used to index pre versus post VSG changes. Spearman correlations quantified associations between cognition and inflammatory markers. There were post VSG improvements in bilateral fine motor skills (Grooved Pegboard, dominant 73 ±21.2 vs. 61 ±8.0, p 0.003, non-dominant 81 ± 24 vs. 67±9 p 0.01), working memory (backward digit span 5.2 ±1.8 vs. 6.1±1.2, p 0.18; NIH Toolbox List Sort Working Memory 102 ± 14 vs. 108 ± 11, p 0.069), and Fluid Reasoning (NIH Toolbox 94 ± 18 vs. 102 ±17, p 0.048). Depression levels (Beck Inventory) significantly decreased; levels were sub-clinical prior to VSG. Functions that remained stable pre to post VSG included estimated nonverbal and verbal IQ (Matrix Reasoning and Picture Vocabulary Tasks), verbal learning (Rey Auditory Verbal Learning Test), basic attention (Digit span forward), and self-reported impulsivity. When pre-to-post VSG changes in cognitive performance was correlated with pre-to-post VSG changes in systemic inflammation (IL6 and CRP levels), decreased inflammation was associated with improvements in working memory and other fluid abilities (r’s from .4 to .8). These findings are novel and show that cognitive function improves after VSG in obese subjects without diabetes and inflammation may contribute to cognitive alterations in OB. Disclosure A. Moheet: None. N. Rubin: None. L.E. Eberly: None. S. Ikramuddin: Other Relationship; Self; Reshape Life Sciences (formerly EnteroMedics). M. Luciana: None. Funding National Institutes of Health (R21NS101140)

Corona Virus Disease 2019 (COVID-19) has affected over 8 million people worldwide. We underscore the potential benefits of conducting a randomized open-label unblinded clinical trial to evaluate the role of ursodeoxycholic acid (UDCA) in the treatment of COVID-19. Some COVID-19 patients are characterized with cytokine storm syndrome that can cause severe and irreversible damage to organs leading to multi-organ failure and death. Therefore, it is critical to control both programmed cell death (apoptosis) and the hyper-immune inflammatory response in COVID-19 patients to reduce the rising morbidity and mortality. UDCA is an existing drug with proven safety profiles that can reduce inflammation and prevent cell death. National Geographic reported that, “China Promotes Bear Bile as Coronavirus Treatment”. Bear bile is rich in UDCA, comprising up to 40–50% of the total bile acid. UDCA is a logical and attainable replacement for bear bile that is available in pill form and merits clinical trial consideration.

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.

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. 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. 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

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.

Cholelithiasis is more prevalent in obese populations, and assessment of the gallbladder is important in patients who undergo bariatric surgery. After rapid weight loss through diet or surgery, a significant proportion of patients develop new gallstones. However, a significantly lower percentage of patients (6–10%) develop symptomatic disease. This has led to controversy in management of the gallbladder at the time of bariatric operations, with some surgeons arguing in favor of prophylactic cholecystectomy for all patients, regardless of biliary pathology. The dominant approach is currently selective cholecystectomy in patients with known cholelithiasis with a trend toward a conventional approach, with cholecystectomy only performed for symptomatic disease. Ursodeoxycholic acid administration in the postoperative period appears to reduce the incidence of gallstone formation but has not been conclusively demonstrated to reduce the rate of symptomatic disease or subsequent cholecystectomy. Management of biliary tract disease may be difficult in patients with surgically altered anatomy, such as Roux-en-Y gastric bypass, as conventional endoscopic approaches may not be sufficient to treat choledocholithiasis. A range of options for biliary access including endoscopic and percutaneous approaches, laparoscopic-assisted transgastric ERCP, and novel transcystic approaches have been described after bariatric surgery. Biliary tract disease is a common problem for bariatric patients before and after surgery, and knowledge of management strategies for these processes is crucial for the bariatric surgeon.

Excess body weight has been associated with worsening breast cancer survival. While bariatric surgery has been associated with less incident of breast cancer, the role that bariatric surgery plays after breast cancer diagnosis in terms of both feasibility and in preventing breast cancer recurrence is unclear. We report the outcomes of 13 individuals who underwent bariatric surgery after definitive breast cancer treatment at a single institution. Thirteen females diagnosed with breast cancer (69.2% stage I, 23.1% stage II) at a median age of 42 years received bariatric surgery between 2001 and 2017. The median age of bariatric surgery was 52 years. Of the 13 patients, 46.2% underwent laparoscopic Roux-en-Y gastric bypass and 38.5% laparoscopic sleeve gastrectomy. The median time from breast cancer treatment to bariatric surgery was 3 years. The procedures were well tolerated. One female developed an abdominal wall hematoma. The average weight loss after 1 year and 2 years was 28.1% and 28.2%, respectively. There was a single breast cancer recurrence with a median follow-up of 11.7 years after breast cancer diagnosis and 5.3 years after bariatric surgery. Bariatric surgery after breast cancer treatment is feasible and well tolerated. Prospective trials evaluating bariatric surgery in obese breast cancer survivors should be considered.

Obesity is associated with alterations in brain structure and cognitive impairment. The mechanisms underlying obesity related decline in cognitive function are not well understood. Obesity related chronic systemic inflammation is postulated to be one of the potential mechanisms leading to cognitive dysfunction. It is unknown whether inflammation impacts brain areas important for higher level cognition such as the anterior cingulate cortex (ACC). Elevated myo-inositol (Ins), as measured by magnetic resonance spectroscopy (MRS), may be a marker of neuroinflammation and reflects activated astrocytes and microglia. We hypothesized that obese subjects (OB) will have higher ACC Ins compared to normal weight controls (CON) and that higher Ins will be associated with elevated blood inflammatory markers and reduced cognitive performance. We examined neurochemical profile from a 24x24x12mm3 voxel over the ACC using 1H MRS at 3 and 7 Tesla (T), in 5 nondiabetic OB (age 33 ± 5 years, BMI 43 ± 6 kg/m2) and 4 CON (age 36 ± 3 years, BMI 23 ± 3 kg/m2). Subjects also underwent cognitive testing and measurement of blood inflammatory markers. MR spectra were quantified using LCModel and the concentrations are expressed as a ratio to total creatine (tCr). There was a strong trend of higher Ins/tCr in ACC in OB compared to CON both at 3T (0.96 ± 0.06 vs. 0.88 ± 0.05, p =0.07) and 7T (0.91 ± 0.07 vs. 0.83 ± 0.08, p =0.17). Pearson correlations were used to test the relationship between Ins/tCr and markers of inflammation among all subjects. Higher blood inflammatory markers were associated with higher Ins/tCr (3T) in ACC (CRP, r=.74, p= 0.04; TNF α, r=.89, p=0.003) and with low levels of crystallized ability as measured by the NIH Toolbox Cognition Battery (CRP, r=-.73, p=0.03). Higher ACC Ins/tCr was also associated with poorer performance on a measure of fine motor coordination (r=.93, p=0.001). These data support the hypothesis that inflammation may contribute to the pathogenesis of brain and cognitive alterations in obesity. Disclosure A. Khan: None. J.M. Joers: None. M. Luciana: None. N. Rubin: None. Y. Siddiqui: None. S. Mangia: None. L.E. Eberly: None. S. Ikramuddin: Research Support; Self; Medtronic. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company, Zucara Therapeutics Inc. Consultant; Self; 360 Consulting, MannKind Corporation. Research Support; Self; Eli Lilly and Company, JDRF, National Institutes of Health. Other Relationship; Self; American Diabetes Association, Sanofi, WebMD. G. Oz: None. A. Moheet: None. Funding National Institutes of Health

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. 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). 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

The ReCharge Trial demonstrated that a vagal blocking device (vBloc) is a safe and effective treatment for moderate to severe obesity. This report summarizes 24-month outcomes.Participants with body mass index (BMI) 40 to 45 kg/mAt 24 months, 123 (76 %) vBloc participants remained in the trial. Participants who presented at 24 months (n = 103) had a mean excess weight loss (EWL) of 21 % (8 % total weight loss [TWL]); 58 % of participants had ≥5 % TWL and 34 % had ≥10 % TWL. Among the subset of participants with abnormal preoperative values, significant improvements were observed in mean LDL (-16 mg/dL) and HDL cholesterol (+4 mg/dL), triglycerides (-46 mg/dL), HbA1c (-0.3 %), and systolic (-11 mmHg) and diastolic blood pressures (-10 mmHg). QOL measures were significantly improved. Heartburn/dyspepsia and implant site pain were the most frequently reported adverse events. The primary related serious adverse event rate was 4.3 %.vBloc therapy continues to result in medically meaningful weight loss with a favorable safety profile through 2 years.https://clinicaltrials.gov/ct2/show/NCT01327976.

Archaic surgical procedures such as the jejunoileal bypass, vertical banded gastroplasty and duodenal switch have contributed to the current best practice of Roux-en-Y gastric bypass (RYGB) procedure for the treatment of obesity and its consequences. Despite this, RYGB has been blighted with late occurring adverse events such as severe malnutrition, marginal ulcer and reactive hypoglycemia. Despite this, RYGB has given us an opportunity to examine the effect of surgery on gut hormones and the impact on metabolic syndrome which in turn has allowed us to carry out a lower impact but equally, if not more effective, procedure - the vertical sleeve gastrectomy (VSG). We examine the benefits of sleeve gastrectomy from the less challenging technical aspect to the effect on obesity and its metabolic syndrome long-term and have concluded that sleeve gastrectomy is possibly the next current best practice.