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Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent complication of extreme obesity. Loading of the liver with fat can progress to inflammation and fibrosis including cirrhosis. The molecular factors involved in the progression from simple steatosis to fibrosis remain poorly understood.Methods: Gene expression profiling using microarray, PCR array, and RNA sequencing was performed on RNA from liver biopsy tissue from patients with extreme obesity. Patients were grouped based on histological findings including normal liver histology with no steatosis, lobular inflammation, or fibrosis, and grades 1, 2, 3, and 4 fibrosis with coexistent steatosis and lobular inflammation. Validation of expression was conducted using quantitative PCR. Serum analysis was performed using ELISA. Expression analysis of hepatocytes and hepatic stellate cells in response to lipid loading were conducted in vitro using quantitative PCR and ELISA.Results: Three orthogonal methods to profile human liver biopsy RNA each identified the chemokine CCL20 (CC chemokine ligand 20 or MIP-3 alpha) gene as one of the most up-regulated transcripts in NAFLD fibrosis relative to normal histology, validated in a replication group. CCL20 protein levels in serum measured in 224 NAFLD patients were increased in severe fibrosis (p < 0.001), with moderate correlation of hepatic transcript levels and serum levels. Expression of CCL20, but not its cognate receptor CC chemokine receptor 6, was significantly (p < 0.001) increased in response to fatty acid loading in LX-2 hepatic stellate cells, with relative increases greater than those in HepG2 hepatocyte cells.Conclusions: These results suggest that expression of CCL20, an important inflammatory mediator, is increased in NAFLD fibrosis. CCL20 serves as a chemoattractant molecule for immature dendritic cells, which have been shown to produce many of the inflammatory molecules that mediate liver fibrosis. These data also point to hepatic stellate cells as a key cell type that may respond to lipid loading of the liver. [ABSTRACT FROM AUTHOR]

Background Health care in the United States is expensive and quality is variable. The aim of this study was to investigate whether our integrated health system, composed of academic hospitals, a practice plan, and a managed care payer, could reliably implement an evidence-based program for gastric bypass surgery. A secondary aim was to evaluate the impact of the program on clinical outcomes. Study Design A standardized program for delivery of clinical best-practice elements for patients undergoing initial open or laparoscopic Roux-en-Y gastric bypass was implemented in 2008. Best-practice elements were embedded into the workflow. The best-practice elements were refined after reviewing failures observed during the early implementation period. The study period was divided into 3 groups: group α = year preceding program implementation (control), group β = first year of implementation (unreliable), and group Ω = 2nd to 4th years of implementation (reliable). Outcomes data were collected for all patients who had undergone Roux-en-Y gastric bypass between May 2008 and April 2012 and were compared with a control group from the preceding year using multiple logistic regression analysis. Results Two thousand and sixty-one patients were studied, with no significant demographic differences between study groups. Best-practice elements delivery was 40% in group β, but was >90% for group Ω (p < 0.001). Length of stay for group α was 3.5 days and improved to 2.2 days (p < 0.001) for group Ω. Complications and readmission rates improved considerably with reliable delivery of best-practice elements. Conclusions Standardization of evidence-based care delivery for Roux-en-Y gastric bypass was feasible and reliable delivery of this pathway improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Challenges of specimen extraction during laparoscopic sleeve gastrectomy and other resectional laparoscopic procedures can often be proven to be time consuming and frustrating, and the risk of wound infection and port site tumor implantation increases. In this paper, we discuss our experience with an efficient approach to specimen extraction utilizing a novel technique for deployment of a very small self-expanding wound protector through a 12- or 15-mm port. We also report our observations with regard to the learning curve of this technique and the influence of BMI to retractor insertion times and specimen extraction times during laparoscopic sleeve gastrectomy. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of weight loss therapies is commonly measured using body mass index and other obesity-related variables. Although these data are often stored in electronic health records (EHRs) and potentially very accessible, few studies on obesity and weight loss have used data derived from EHRs. We developed processes for obtaining data from the EHR in order to construct a database on patients undergoing Roux-en-Y gastric bypass (RYGB) surgery. Methods: Clinical data obtained as part of standard of care in a bariatric surgery program at an integrated health delivery system were extracted from the EHR and deposited into a data warehouse. Data files were extracted, cleaned, and stored in research datasets. To illustrate the utility of the data, Kaplan-Meier analysis was used to estimate length of post-operative follow-up. Results: Demographic, laboratory, medication, co-morbidity, and survey data were obtained from 2028 patients who had undergone RYGB at the same institution since 2004. Pre-and post-operative diagnostic and prescribing information were available on all patients, while survey laboratory data were available on a majority of patients. The number of patients with post-operative laboratory test results varied by test. Based on Kaplan-Meier estimates, over 74% of patients had post-operative weight data available at 4 years. Conclusion: A variety of EHR-derived data related to obesity can be efficiently obtained and used to study important outcomes following RYGB. [ABSTRACT FROM AUTHOR]

Iron is an essential nutrient in living organisms with multiple vital functions. Iron deficiency (ID) can cause long term health consequences beyond iron deficiency anemia (IDA). The high prevalence of ID and its long-term effects in patients with obesity and after metabolic and bariatric surgery (MBS) is recognized. Nevertheless, there is limited knowledge of the optimal route or dose for treatment of patients with obesity and post-MBS, and an evidence-based universal guideline for prevention and treatment of ID in short- and long-term post-MBS (PMBS) is not yet available. ID in the general population is currently treated with oral or parenteral iron, where oral iron treatment is considered the preferred option with parenteral iron as a second-line treatment in case there is intolerance or lack of response to oral iron. In patients with obesity with chronic low-grade inflammation and PMBS patients with altered gut anatomy and function, there are also alterations in the bioavailability and higher risks of side effects of available oral irons. The conclusions of current studies exploring effective treatment of iron deficiency in this population have been inconsistent and further well-planned randomized and prospective studies are needed. This is a narrative review of the literature on the available treatment options and strategies for treatment of ID in PMBS patients to recognize the knowledge gaps and provides topics of future research.

Iron deficiency has been recognized as a potentially modifiable nutritional complication of metabolic and bariatric surgery (MBS) since prior to the turn of the century. Despite this, it remains the most common and clinically significant nutritional complication of this surgery with the potential to negate quality of life and the health benefits of surgical weight loss. This narrative review summarizes the current literature regarding iron deficiency as it relates to patients with severe obesity and those who undergo MBS. Advances in the clinical knowledge of iron homeostasis in severe obesity as a chronic disease, current diagnostic criteria for the diagnosis of iron deficiency in this patient population, the significance of preoperative iron deficiency, postoperative iron deficiency, and the status of supplementation and treatment will be reviewed with emphasis on gaps in knowledge and needed areas of further study., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Iron deficiency (ID), a known complication after metabolic surgery, is common among preoperative patients in the presence of inflammation. Evidence is now accumulating that preoperative ID may adversely affect perioperative outcomes., Objectives: To investigate the relationship between preoperative iron status and the risk of postoperative severe anemia. In addition, this study investigates the relationship between preoperative iron status and length of surgical stay SETTING: A large regional tertiary health system., Methods: Among patients who underwent metabolic surgery between 2004 and 2020, 5171 patients had a full iron nutritional assessment prior to surgery. Study patients were divided into multiple smaller groups (10 female groups and 7 male groups) on the basis of levels of serum ferritin and Transferrin Saturation (T Sat) < or ≥20%. Study patients were followed after surgery and the time to the development of severe anemia (hemoglobin < 8 gm/dL) was recorded. Hospital length of stay (LOS) was analyzed in relation to preoperative iron status., Results: Lower ferritin levels were associated with older age in males (P = .0001) and younger age in females (P < .0001). For males, after adjustment for age, body mass index (BMI), and year of surgery, surgical LOS was prolonged in those with T Sat <20% (P = .0041). For females the time until the development of severe anemia was associated with baseline iron status (P < .0001)., Conclusions: Male preoperative patients for metabolic surgery with T Sat <20% are at risk for increased surgical LOS. Females with low ferritin levels consistent with ID are at increased risk for the development of postoperative severe anemia., (Copyright © 2023 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is a risk factor for COVID-19 severity. Recent studies suggest that prior metabolic surgery (MS) modifies the risk of COVID-19 severity., Methods: COVID-19 outcomes were compared between patients with MS (n = 287) and a matched cohort of unoperated patients (n = 861). Multiple logistic regression was used to identify predictors of hospitalization. A systematic literature review and pooled analysis was conducted to provide overall evidence of the influence of prior metabolic surgery on COVID-19 outcomes., Results: COVID-19 patients with MS had less hospitalization (9.8% versus 14.3%, p = 0.049). Age 70+, higher BMI, and low weight regain after MS were associated with more hospitalization after COVID-19. A systematic review of 7 studies confirmed that MS reduced the risk of post-COVID-19 hospitalization (OR = 0.71, 95%CI = [0.61-0.83], p < 0.0001) and death (OR = 0.44, 95%CI = [0.30-0.65], p < 0.0001)., Conclusion: MS favorably modifies the risks of severe COVID-19 infection. Older age and higher BMI are major risk factors for severity of COVID-19 infection., Competing Interests: There are no conflicts of interest for any authors., (© 2023 The Authors.)

Taste-signaling proteins, which are expressed throughout the digestive tract, are involved in regulating metabolism and immunity. This study aimed to determine if these genes are expressed and altered in jejunal tissues from patients with extreme obesity who received bariatric surgery. Reverse transcription polymerase chain reaction revealed that phospholipase C beta 2 and transient receptor potential channel M5 expression was downregulated in the jejunum of patients with a body mass index above 50, whereas gustducin expression remained unchanged. Our data suggest that taste-signaling dysregulation might contribute to obesity., Competing Interests: Conflicts of interest None of the authors declares a conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Obesity increases the risk of developing type 2 diabetes, hypertension, and hyperlipidemia. We sought to determine the impact of obesity maintenance, weight regain, weight loss maintenance, and magnitudes of weight loss on future risk and time to developing these cardiometabolic conditions. This was a retrospective cohort study of adults receiving primary care at Geisinger Health System between 2001 and 2017. Using electronic health records, patients with ≥3-weight measurements over a 2-year index period were identified and categorized. Obesity maintainers (OM) had obesity (body mass index ≥30 kg/m²) and maintained their weight within ±3% from baseline (reference group). Both weight loss rebounders (WLR) and weight loss maintainers (WLM) had obesity at baseline and lost >5% body weight in year 1; WLR regained ≥20% of weight loss by end of year 2 and WLM maintained ≥80% of weight loss. Incident type 2 diabetes, hypertension, and hyperlipidemia, and time-to-outcome were determined for each study group and by weight loss category for WLM. Of the 63,567 patients included, 67% were OM, 19% were WLR, and 14% were WLM. The mean duration of follow-up was 6.6 years (SD, 3.9). Time until the development of electronic health record-documented type 2 diabetes, hypertension, and hyperlipidemia was longest for WLM and shortest for OM (log-rank test p <0.0001). WLM had the lowest incident type 2 diabetes (adjusted hazard ratio [HR] 0.676 [95% confidence interval [CI] 0.617 to 0.740]; p <0.0001), hypertension (adjusted HR 0.723 [95% CI 0.655 to 0.799]; p <0.0001), and hyperlipidemia (adjusted HR 0.864 [95% CI 0.803 to 0.929]; p <0.0001). WLM with the greatest weight loss (>15%) had a longer time to develop any of the outcomes compared with those with the least amount of weight loss (<7%) (p <0.0001). In an integrated delivery network population, sustained weight loss was associated with a delayed onset of cardiometabolic diseases, particularly with a greater magnitude of weight loss., Competing Interests: Disclosures Abhilasha Ramasamy, Neeraj N. Iyer, and B. Gabriel Smolarz are employed by Novo Nordisk, Inc., which sponsored this research. At the time this study was conducted, Neela Kumar was an employee of Novo Nordisk, Inc. Lisa Bailey-Davis, G. Craig Wood, Peter Benotti, Adam Cook, James Dove, Jacob Mowery, and Christopher Still are employed by Geisinger Health, which received funding from Novo Nordisk, Inc. for work performed on this study., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The presence of chronic low-grade inflammation, commonly identified in patients with severe obesity, alters iron homeostasis and indicators of iron status, fostering the development of updated guidelines for the diagnosis of iron deficiency (ID). Current recommended diagnostic thresholds for ID in obesity derived from expert opinion include a ferritin level of <30 ng/mL and/or transferrin saturation (TSAT) < 20%. Earlier studies of ID among candidates for metabolic surgery using low levels of ferritin or iron as diagnostic thresholds demonstrated a prevalence of 5%-20%., Objectives: Using the current recommended diagnostic thresholds for ID, this study measures the prevalence of ID in a large cohort of surgical candidates and its relationship to surgical outcomes., Setting: Geisinger Medical Center, Danville, Pennsylvania., Methods: The study cohort included 3,723 patients who underwent pre- operative nutritional assessment which included markers of iron nutrition over the period 2004-2018., Results: The cohort included 2,988 women (80.3%) and 735 men (19.7%); body mass index: 49.4 ± 9 kg/m 2 . The diagnosis of ID was based on ferritin level <30 ng/mL (true ID) and/or TSAT < 20% representing a combination of true ID and inflammation (serum ferritin ≥ 30 ng/mL and TSAT < 20%). A total of 399 patients (10.8%) were anemic. A serum ferritin level of < 30 ng/mL was found in 488 patients (13%; 481 women and 7 men). Of these, 122 patients (25.2%) were also anemic. An additional 1,204 had serum ferritin ≥ 30 ng/mL and TSAT < 20%. Overall, 1,692 patients (45.4%) in this cohort had laboratory evidence of ID by current criteria that adjusts for the very high prevalence of inflammation. Men with serum ferritin levels ≥30 ng/mL with TSAT < 20% had an increased surgical length of stay., Conclusion: The prevalence of ID among surgical candidates (45.4%) is more than twice that identified as ID in earlier studies. ID was commonly identified in the absence of anemia. The most severe ID was found in those with a serum ferritin level <30 ng/mL and TSAT < 20%. ID in the presence of inflammation is often unrecognized and has implications regarding surgical outcomes after metabolic surgery., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Sarcopenic obesity and its association with nonalcoholic fatty liver disease (NAFLD) is under-recognized by many healthcare providers in Western medicine due to the lack of awareness and diagnostic guidelines. The result is delayed recognition and treatment, which leads to further health deterioration and increased healthcare costs. Sarcopenic obesity is characterized by the presence of increased fat mass in combination with muscle catabolism related to chronic inflammation and/or inactivity. Previous research has recommended evaluating body composition and physical function performance to adequately diagnose sarcopenic obesity. Body composition analysis can be performed by imaging applications through magnetic resonance imaging, computed tomography, and dual-energy x-ray absorptiometry. Due to the cost of each device and radiation exposure for patients as evidenced in all three modalities, bioelectrical impedance analysis offers a noninvasive approach capable of providing quick and reliable estimates of lean body and fat mass., Methods and Results: This review analyzes the current evidence-based literature, indicating a lower skeletal muscle mass and increased visceral adipose tissue correlation to the advancement of fibrosis in fatty liver disease., Conclusion: Given the substantial promising research conducted in predominantly Asian populations regarding body tissue distribution and NAFLD, additional prospective research is needed to extend these findings in Western populations., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

The near universal presence of chronic low-grade systemic inflammation among patients with severe obesity disrupts iron homeostasis and underlies the association between obesity and iron deficiency. Immune activation and inflammation result in a reduction in circulating iron and diminished iron bioavailability for erythropoiesis. Inflammation also alters blood levels of commonly measured markers of iron nutrition status, which makes the diagnosis of iron deficiency difficult and has led to new recommendations regarding laboratory markers for the diagnosis. Recent evidence using these newly recommended laboratory markers, which include levels of ferritin, C-reactive protein, and transferrin saturation, suggests that the actual prevalence of iron deficiency among candidates for metabolic surgery may be double or triple the prevalence identified by low levels of ferritin alone. Thus large numbers of surgical candidates have iron deficiency that has been heretofore largely unrecognized and inadequately treated. The assessment of iron status using the currently recommended markers in the presence of chronic inflammatory diseases and repletion of depleted stores for surgical candidates with deficiency during the preoperative period present an important opportunity for mitigating this condition in postoperative patients., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to validate an algorithm designed to identify patients with post-gastric bypass hypoglycemia (PGBH) using clinician chart review., Methods: We conducted a chart review study of non-diabetic patients who underwent Roux-en-Y gastric bypass (RYGB) at our institution from 2004 to 2013. The electronic medical record (EMR) algorithm was based on any post-operative glucose <60 mg/dl, diagnosis of hypoglycemia, or medication use for treatment of PGBH and identified 158 charts as PGBH and 1048 charts without PGBH. Two clinicians independently reviewed a random selection of 80 cases and 80 control charts and determined the presence or absence of PGBH by searching the chart using keywords and reviewing laboratory results, medications, and clinic notes., Results: Of the 160 charts reviewed, the EMR algorithm agreed with the chart review for 130 (accuracy = 80%, 95% CI = 75-87%) with sensitivity of 89% (95% CI = 83-96%) and specificity of 86% (95% CI = 78-93%). We improved the algorithm's accuracy to 90% by limiting the search to data obtained 3 months or more following RYGB., Conclusion: The EMR algorithm has high sensitivity, specificity, and accuracy to identify post-gastric bypass hypoglycemia within our patient cohort. The use EMR-based algorithms may be a useful tool for future research to improve our understanding of epidemiology and risk factors for post-bariatric surgery hypoglycemia.

Background: DiaRem is a validated tool for predicting the likelihood of type 2 diabetes (T2D) remission after Roux-en-Y gastric bypass (RYGB) surgery., Objectives: The objective of this study was to determine if the addition of duration of T2D to DiaRem improves its ability to discriminate between patients with or without T2D remission and/or to reclassify presurgery patients into accurate risk groups., Setting: Academic Medical Center., Methods: This study included patients consented into a prospective registry of Roux-en-Y gastric bypass between July 2009 and November 2015 with known duration of T2D (n = 307). Electronic health record-derived duration of T2D was compared with patient reported duration of T2D in a subset of patients (n = 48). DiaRem2 was created using clinical variables from DiaRem and duration of T2D. Area under the curve and the net reclassification index were used to assess increased performance of DiaRem2., Results: Self-reported duration of T2D was highly concordant with electronic health record-derived T2D duration (96% agreement). Early T2D remission occurred in 44% of patients. DiaRem2 included age, hemoglobin A1C, insulin medication use, and duration of T2D. DiaRem2 had a higher area under the curve than DiaRem (.876 versus .850, P = .026), reduced the number of remission risk groups from 5 down to 3, and reclassified patients from intermediate to either high or low remission groups (net reclassification index, P < .0001)., Conclusions: DiaRem2 simplifies and improves the accuracy of assessing probability of T2M remission after Roux-en-Y gastric bypass. Self-reported duration of T2D is an acceptable surrogate for T2D duration derived from clinical data., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: The objective of this descriptive study was to identify clinical characteristics of Roux-en-Y gastric bypass (RYGB) patients who died from intentional self-harm or accidental overdose postoperatively., Materials and Methods: This retrospective, descriptive study included RYGB patients from a large rural medical center that completed surgery between January 2004 and December 2014 and died from intentional self-harm or accidental overdose through December 2015. Specific causes of death were obtained from the National Death Index and clinical data from electronic health records. Clinical characteristics explored were age, sex, time to surgery, weight loss expectations, postoperative weight loss, medication, diagnoses, psychiatric histories (diagnoses, self-harm, suicidal ideation and behaviors, medications, substance use, preoperative Beck Depression Inventory-II scores), pain, social support, and reported life stressors., Results: Overall, 22 patients of 146 total deceased patients died from intention self-harm (n = 6) or accidental overdose (n = 16) over the study period (77.3% female, mean age at time of surgery = 38.4 ± 9.1 years). Younger age (< 40 years), history of self-harm or depression, preoperative pain, and use of opioids at the time of surgery emerged as common characteristics in weight loss surgery patients who died from intentional self-harm or accidental overdose. No trends regarding social support, life stressors, or actual or expected weight loss were identified., Conclusion: Certain weight loss surgery patients may be at risk for death from self-harm or overdose and may benefit from greater surveillance postoperatively.

Background: Weight change trajectories after weight-loss surgery may vary significantly., Objectives: This study evaluated the weight trajectories of Roux-en-Y gastric bypass (RYGB) patients and identified the distinct clinical, behavioral, and demographic features of patients by trajectory., Setting: Data from 2918 RYGB patients from a comprehensive medical center between January 2004 and November 2016 were included., Methods: This retrospective, observational study used data for RYGB patients up to year 7 postsurgery. Group-based trajectory models were fitted for percentage weight change. Variables evaluated by trajectory included age, sex, diagnoses, medications, smoking, presurgical body mass index, preoperative weight loss, and early postoperative weight loss., Results: Of 3215 possible patients, 2918 (90.8%) were included (mean age = 46.2 ± 11.2 yr, body mass index = 46.9 ± 7.9 kg/m 2 at the time of surgery). Three weight change trajectories were identified (above average, average, and below average). Mean percentage weight change at the nadir for the above average group was -42.85% ± 5.7% compared with -31.57% ± 5.0% in the average group and -22.74% ± 5.7% in the below average group. Compared with the above average group, the below average group was more likely to be male (odds ratio [OR] = 2.40, P < .0001) and have diabetes (noninsulin users, OR = 2.08, P < .0001), but less likely to have a smoking history (OR = .62, P = .0007) or take sleep medications (OR = .50, P = .005). Below average group patients had a lower BMI at the time of surgery (OR = .91, P < .0001). Lower initial weight loss postsurgery was associated with a greater chance of a poorer weight outcomes (OR = 1.64, P < .0001)., Conclusion: Select clinical, demographic, and behavioral factors may increase or decrease the chance for better weight loss after RYGB., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The current popularity of metabolic surgery has led to increasing attention to long-term nutritional complications., Objective: The purpose of this retrospective study is to accurately define the long-term incidence of clinically significant anemia after Roux-en-Y gastric bypass (RYGB) and to identify factors that contribute to increased risk., Methods: The study cohort consisted of 2116 patients who underwent RYGB with necessary laboratory information available, and with longitudinal follow-up available (mean 5.3 ± 3.3 yr). A concurrent cohort of nonoperated patients matched for age, sex, body mass index, and baseline hemoglobin was identified (N = 1126). The RYGB and control cohorts were followed longitudinally to estimate the percent that develop mild, moderate, or severe anemia using Kaplan-Meier analysis. Predictors of severe anemia within the RYGB cohort were identified using Cox regression., Results: The percent developing postRYGB mild, moderate, and severe anemia was 27%, 9%, and 2% at 1 year postRYGB and increased to 68%, 33%, and 11% at 5 years postRYGB. As compared with the nonoperated control cohort, the RYGB cohort was more likely to develop mild anemia (hazard ratio [HR] = 1.36, P<.001), moderate anemia (HR = 1.75, P<.001), and severe anemia (HR = 1.87, P<.001). Severity of anemia was associated with an increasing percentage of microcytosis (P<.0001). Clinical factors independently associated with an increased risk of severe anemia within the RYGB cohort included females and males>40 years of age (HR = 2.97, 95% confidence interval [CI] = 1.14, 7.75, P = .026), preoperative anemia (HR = 1.65, 95% CI = 1.19, 2.29, P = .0029), preoperative low ferritin level (HR = 2.28, 95% CI = 1.39, 3.74, P = .0029), and a rapid 6-month weight loss trajectory (HR = 1.71, 95% CI = 1.22, 2.38, P = .0018)., Conclusions: The long-term incidence of clinically significant anemia after RYGB is alarmingly high and warrants more detailed study., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10 -10 ), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.

Total Knee Arthroplasty (TKA, also known as total knee replacement) is a highly effective surgical intervention for the restoration of physical function and improving quality of life in patients with disabling knee osteoarthritis. Recent data suggest that obesity is a major risk factor in the pathogenesis and progression of knee osteoarthritis, with increases in body mass index (BMI, kg/m 2 ) directly correlating with the prevalence of knee osteoarthritis. However, recent data also suggest that there are increased risks associated with TKAs when performed in patients with morbid obesity (BMI > 40 kg/m 2 ). Patients with morbid obesity are routinely referred for weight management prior to surgery. Many of these patients fail to meet the recommended weight loss goals prior to TKA, potentially making them ineligible for surgery or placing them at increased risk for sub-optimal outcomes. Thus, the purpose of this study is to examine the potential therapeutic impact and long-term outcomes of surgically induced weight loss on TKA outcomes. Specifically, these outcomes will include measures of physical function, mobility, and indices of joint function at 1 and 2 years post-TKA compared between extremely obese patients who undergo TKA (Control group, n = 150) and those with TKA performed ~1 year after bariatric surgery (Test group, n = 150). An additional primary endpoint will be the percent of bariatric patients that negate or delay the need for TKA. Secondary endpoints include perioperative outcomes after TKA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: This study evaluated the social environment of bariatric surgery patients in the preoperative period., Methods: Forty bariatric surgery patients (mean = 46.2 ± 11.2 years), 35 adult cohabitating family members (mean = 45.2 ± 12.7 years), and 15 cohabitating children (mean = 11.5 ± 3.6 years) were recruited from a large rural medical center. Adult participants (patients and family members) completed height, weight, body composition, blood draws, and physical activity assessments (accelerometry), as well as eating behavior and social support inventories before the patient underwent bariatric surgery. Child participants completed demographic, height, and weight assessment only., Results: Over 90 % of adult family members were overweight or obese (body mass index (BMI) ≥ 25 kg/m 2 , as were 50 % of children (BMI percentile ≥ 85 %). More than one third (37.1 %) of family members met the criteria for moderate to severe insulin resistance. Physical activity measured by accelerometry was moderately correlated between the patient and adult family members (r = 0.46, p = 0.023). Bariatric surgery patients reported high levels of social support from their family members on multiple social support measures., Conclusions: Many family members of bariatric surgery patients also lived with obesity and related comorbidities, and demonstrate high sedentary behavior. However, patients reported high levels of support from family members, including support in following a healthy diet and engaging in physical activity. Engaging families in behavior change may help bariatric surgery patients and their families to become healthier., Competing Interests: The authors declare that they have no conflicts of interest.

Background: Recent studies have suggested that metabolic surgery reduces cancer risk. This study aims to determine if incident cancer is associated with the extent of weight loss after Roux-en-Y gastric bypass (RYGB)., Methods: Patients at a large tertiary bariatric surgery center were retrospectively reviewed to identify patients with no history of cancer at the time of RYGB. Diagnoses in the electronic health record, a tumor registry, and chart review were used to identify postoperative incident solid organ cancer. The overall incidence of organ cancer was estimated using Kaplan-Meier analysis. The percent total body weight loss (%TWL) in the 48 months after surgery but prior to cancer was compared between those that developed organ cancer versus those that did not using repeated measures linear regression., Results: The 2943 patients had a mean age of 45.6 years (SD = 11.1), 81 % were female, and a mean baseline body mass index (BMI) of 47.2 kg/m 2 (SD = 7.9). Median follow-up after surgery was 3.8 years (range = [<1, 12]). Incident organ cancer developed and was verified in 54 of the 2943 patients (1.8 %). Kaplan-Meier estimates for cancer at 3, 5, and 10 years postsurgery were 1.3, 2.5, and 4.2 %. After adjusting for age, BMI, sex, diabetes, hypertension, and dyslipidemia, patients that developed organ cancer achieved less weight loss (-1.5 % TWL, 95 % CI = [-2.9 %, -0.1 %], p = 0.034)., Conclusions: Greater weight loss after metabolic surgery may be associated with lower organ cancer risk., Competing Interests: Disclosure Statement: Marie A. Hunsinger RN BSHS: no conflict of interest G. Craig Wood MS: no conflict of interest Christopher D. Still DO: no conflict of interest Anthony T. Petrick MD: no conflict of interest Joseph A. Blansfield MD: no conflict of interest Mohsen M. Shabahang MD, PhD: no conflict of interest Peter N. Benotti MD: no conflict of interest

Background: Nonalcoholic fatty liver disease (NAFLD) is common in adults with extreme obesity and can impact long-term health and survival. Liver biopsy is the only accurate test for diagnosis and staging, but is invasive and costly. Non-invasive testing offers an attractive alternate, but the overall accuracy remains a significant issue. This study was conducted to determine the accuracy and clinical utility of pre-operative ultrasound and liver transaminase levels, as well as intra-operative hepatic visual inspection, for assessing presence of NAFLD as confirmed by hepatic histology., Methods: Data was collected prospectively from 580 morbidly obese adult patients who underwent Roux-en-Y gastric bypass surgery with intraoperative wedge biopsy between January 2004 and February 2009. Complete data for ultrasound, ALT and AST levels, and documented visual inspection was available for 513 patients., Results: The prevalence of NAFLD was 69 % and that of NASH was 32 %. The individual non-invasive clinical assessments demonstrated low sensitivity, specificity, and accuracy for detecting the presence of steatosis, steatohepatitis, or fibrosis. The combination of normal or abnormal results for all tests improved predictive utility. Abnormal tests with all three assessments had a sensitivity of 95-98 % and a specificity of 28-48 % for major histologic findings in NAFLD/NASH. Normal tests with all three assessments had a sensitivity of 12-22 % and a specificity of 89-97 % for major histologic findings in NAFLD/NASH., Conclusions: Although individual clinical tests for NAFLD have limited accuracy, the use of combined clinical tests may prove useful.

Background: About 60% of patients with type 2 diabetes achieve remission after Roux-en-Y gastric bypass (RYGB) surgery. No accurate method is available to preoperatively predict the probability of remission. Our goal was to develop a way to predict probability of diabetes remission after RYGB surgery on the basis of preoperative clinical criteria., Methods: In a retrospective cohort study, we identified individuals with type 2 diabetes for whom electronic medical records were available from a primary cohort of 2300 patients who underwent RYGB surgery at the Geisinger Health System (Danville, PA, USA) between Jan 1, 2004, and Feb 15, 2011. Partial and complete remission were defined according to the American Diabetes Association criteria. We examined 259 clinical variables for our algorithm and used multiple logistic regression models to identify independent predictors of early remission (beginning within first 2 months after surgery and lasting at least 12 months) or late remission (beginning more than 2 months after surgery and lasting at least 12 months). We assessed a final Cox regression model with a consistent subset of variables that predicted remission, and used the resulting hazard ratios (HRs) to guide creation of a weighting system to produce a score (DiaRem) to predict probability of diabetes remission within 5 years. We assessed the validity of the DiaRem score with data from two additional cohorts., Findings: Electronic medical records were available for 690 patients in the primary cohort, of whom 463 (63%) had achieved partial or complete remission. Four preoperative clinical variables were included in the final Cox regression model: insulin use, age, HbA1c concentration, and type of antidiabetic drugs. We developed a DiaRem score that ranges from 0 to 22, with the greatest weight given to insulin use before surgery (adding ten to the score; HR 5·90, 95% CI 4·41–7·90; p<0·0001). Kaplan-Meier analysis showed that 88% (95% CI 83–92%) of patients who scored 0–2, 64% (58–71%) of those who scored 3–7, 23% (13–33%) of those who scored 8–12, 11% (6–16%) of those who scored 13–17, and 2% (0–5%) of those who scored 18–22 achieved early remission (partial or complete). As in the primary cohort, the proportion of patients achieving remission in the replication cohorts was highest for the lowest scores, and lowest for the highest scores., Interpretation: The DiaRem score is a novel preoperative method to predict the probability of remission of type 2 diabetes after RYGB surgery., Funding: Geisinger Health System and the US National Institutes of Health.

Objectives: Genome-wide association studies (GWAS) have led to the identification of single nucleotide polymorphisms in or near several loci that are associated with the risk of obesity and nonalcoholic fatty liver disease (NAFLD). We hypothesized that missense variants in GWAS and related candidate genes may underlie cases of extreme obesity and NAFLD-related cirrhosis, an extreme manifestation of NAFLD., Methods: We performed whole-exome sequencing on 6 Caucasian patients with extreme obesity [mean body mass index (BMI) 84.4] and 4 obese Caucasian patients (mean BMI 57.0) with NAFLD-related cirrhosis., Results: Sequence analysis was performed on 24 replicated GWAS and selected candidate obesity genes and 5 loci associated with NAFLD. No missense variants were identified in 19 of the 29 genes analyzed, although all patients carried at least 2 missense variants in the remaining genes without excess homozygosity. One patient with extreme obesity carried 2 novel damaging mutations in BBS1 and was homozygous for benign and damaging MC3R variants. In addition, 1 patient with NAFLD-related cirrhosis was compound heterozygous for rare damaging mutations in PNPLA3., Conclusions: These results indicate that analyzing candidate loci previously identified by GWAS analyses using whole-exome sequencing is an effective strategy to identify potentially causative missense variants underlying extreme obesity and NAFLD-related cirrhosis., (© 2013 S. Karger AG, Basel.)

Critically ill obese patients require timely nutrition in the intensive care unit. Hypocaloric, high protein nutritional feeding might have a role in critically ill obese patients. Although critically ill obese patients need special medical and nutritional care as do nonobese patients in the ICU, there are some differences in the literature about the initiation, routes, and nature of nutritional support. This article reviews the norms of nutritional care among critically ill obese patients and the differences between these patients and those with a normal BMI., (Copyright © 2010. Published by Elsevier Inc.)

Laparoscopic sleeve gastrectomy has recently become a feasible option in the management of morbid obesity. One of the most feared complications of this procedure is staple line disruption and leakage. There are, to our knowledge, few literature reports that try to explain the reasons and management of this rare but serious complication. We report a case of staple line disruption that was managed using a T-tube gastrostomy. A 50-year-old female, 2 weeks status post-sleeve gastrectomy in an outside facility, was admitted to the emergency room at Cleveland Clinic Florida with new onset of fever, abdominal pain, jaundice, hematemesis, and melena. A computed tomography scan of the abdomen revealed a large extravasation of contrast material parallel to the gastric sleeve. A diagnostic laparoscopy was performed that showed a distal and proximal disruption of the staple line. A T-tube gastrostomy with a large proximal and distal limb was placed into the most distal area of disruption. After thorough over sewing and drainage of the proximal site and T-tube, a feeding jejunostomy was placed. The T-tube permitted to control the leak and to have a controlled fistula. Four weeks postoperatively, the T-tube was removed after the patient had a negative Gastrografin study and tolerated oral fluids with a clamped T-tube. The long-term recovery and follow-up were uneventful. T-tube gastrostomy appears to be a safe and feasible treatment option for staple line disruption after vertical sleeve gastrectomy. Early detection and drainage remain the most important principles to manage this type of complication.

Hypothesis: Preoperative weight loss reduces the frequency of surgical complications in patients undergoing bariatric surgery., Design: Review of records of patients undergoing open or laparoscopic gastric bypass., Setting: A comprehensive, multidisciplinary obesity treatment center at a tertiary referral center that serves central Pennsylvania., Patients: A total of 881 patients undergoing open or laparoscopic gastric bypass from May 31, 2002, through February 24, 2006., Intervention: All preoperative patients completed a 6-month multidisciplinary program that encouraged a 10% preoperative weight loss., Main Outcome Measures: Loss of excess body weight (EBW) and total and major complication rates., Results: Of the 881 patients, 592 (67.2%) lost 5% or more EBW and 423 (48.0%) lost more than 10% EBW. Patients referred for open gastric bypass (n = 466) were generally older (P < .001), had a higher body mass index (P < .001), and were more often men (P < .001) than those undergoing laparoscopic gastric bypass (n = 415). Total and major complication rates were higher in patients undergoing open gastric bypass (P < .001 and P = .03, respectively). Univariate analysis revealed that increasing preoperative weight loss is associated with reduced complication frequencies for the entire group for total complications (P =.004) and most likely for major complications (P = .06). Controlling for age, sex, baseline body mass index, and type of surgery in a multiple logistic regression model, increased preoperative weight loss was a predictor of reduced complications for any (P =.004) and major (P = .03) complications., Conclusion: Preoperative weight loss is associated with fewer complications after gastric bypass surgery.

Objective: To determine whether 2 single nucleotide polymorphisms (SNPs) in the obesity genes the fat mass and obesity associated gene (FTO) and the insulin induced gene 2 (INSIG2) are associated with class III, or morbid, obesity in patients undergoing bariatric weight loss operations., Design: Retrospective analysis of genotype and clinical data., Setting: Large rural tertiary care health system., Patients: A total of 707 adult patients with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of at least 40 undergoing open or laparoscopic Roux-en-Y gastric bypass operations for morbid obesity or its comorbid medical problems at Geisinger Medical Center, Danville, Pennsylvania., Results: The mean BMI in the predominantly white female cohort was 51.2. Approximately 21% of patients were homozygous for the FTO obesity SNP variant, 13% were homozygous for the INSIG2 obesity SNP variant, and 3.4% were homozygous for both. Mean BMIs in the groups homozygous for each of these genes were not significantly different from nonhomozygotes. However, FTO/INSIG2 double homozygotes and homozygote/heterozygote pairs had significantly higher BMIs than the other groups., Conclusion: Increased BMI in morbid obesity is associated with a combination of FTO and INSIG2 SNPs.

Genomic medicine research requires substantial time and resources to obtain phenotype data. The electronic health record offers potential efficiencies in addressing these temporal and economic challenges, but few studies have explored the feasibility of using such data for genetics research. The main objective of this study was to determine the association of two genetic variants located on chromosome 9p21 conferring susceptibility to coronary heart disease and type 2 diabetes with a variety of clinical phenotypes derived from the electronic health record in a population of morbidly obese patients. Data on more than 100 clinical measures including diagnoses, laboratory values, and medications were extracted from the electronic health records of a total of 709 morbidly obese (body mass index (BMI) >/= 40 kg/m(2)) patients. Two common single nucleotide polymorphisms located at chromosome 9p21 recently linked to coronary heart disease and type 2 diabetes (McPherson et al. Science 316:1488-1491, 2007; Saxena et al. Science 316:1331-1336, 2007; Scott et al. Science 316:1341-1345, 2007) were genotyped to assess statistical association with clinical phenotypes. Neither the type 2 diabetes variant nor the coronary heart disease variant was related to any expected clinical phenotype, although high-risk type 2 diabetes/coronary heart disease compound genotypes were associated with several coronary heart disease phenotypes. Electronic health records may be efficient sources of data for validation studies of genetic associations.

Hypothesis: Modest, preoperative weight loss will improve perioperative outcomes among high-risk, morbidly obese patients undergoing Roux-en-Y gastric bypass., Design: A prospective, longitudinal assessment of characteristics and outcomes of gastric bypass patients., Setting: All patients undergoing open or laparoscopic Roux-en-Y gastric bypass surgery for morbid obesity or its comorbid medical problems at Geisinger Medical Center in Danville, Pennsylvania, during a 3-year period from May 31, 2002, to February 24, 2006, were included in this analysis. Patients were required to participate in a standardized multidisciplinary preoperative program that encompasses medical, psychological, nutritional, and surgical interventions and education. In addition, patients were encouraged to achieve a 10% loss of excess body weight prior to surgical intervention., Results: Of the 884 subjects, 425 (48%) lost more than 10% of their excess body weight prior to the operation. After surgery (mean follow-up, 12 months), this group was more likely to achieve 70% loss of excess body weight (P < .001). Those who lost more than 5% of excess body weight prior to surgery were statistically less likely to have a length of stay of greater than 4 days (P = .03)., Conclusions: This study shows that high-risk morbidly obese candidates for bariatric surgery who are able to achieve a loss of 5% to 10% excess body weight prior to surgery have a higher probability of a shorter length of hospital stay and more rapid postoperative weight loss.

Background: The rapid national expansion in bariatric surgical procedures has been accompanied by recent reports of significant complication rates. This has resulted in increased public scrutiny of bariatric surgery outcomes, restrictions on patient eligibility criteria by payors, and credentialing requirements for providers. This focus on outcomes has resulted in interest in bariatric risk analysis., Methods: During an 8-year period, 1210 patients were evaluated for bariatric surgery. Clinical information was recorded prospectively. Co-morbid medical conditions were analyzed according to proven surgical risk factors: age, body mass index (BMI), and male gender., Results: The prevalence of many co-morbid conditions and the total number of co-morbid conditions correlate highly with increasing age, increasing BMI, and male gender., Conclusion: The established surgical risk factors, age, BMI, and male gender, are markers for a sicker patient population, as evidenced by a greater obesity disease burden.

Liposuction, the most common aesthetic procedure performed in the United States, is not without risk, but the overall complication rate in the literature varies from less than 1% to 9.3%. A 55-year-old woman who had undergone abdominal liposuction with bilateral breast augmentation was hospitalized in a state of profound septic shock. A diagnosis of necrotizing fasciitis was made on the basis of findings that included abdominal skin discoloration, subcutaneous emphysema, and air in the subcutaneous plane seen on abdominal computed tomography (CT) scan. During the operative procedure for abdominal wall debridement, extensive necrosis of abdominal wall fascia with leakage of bilious fluid from defects in the rectus sheath was found. Subsequent peritoneal cavity exploration showed two perforations in the mid ileum with gross peritoneal cavity contamination.

Background: Laparoscopic bariatric surgery has experienced a rapid expansion of interest over the past 5 years, with a 470% increase. This rapid expansion has markedly increased overall cost, reducing surgical access. Many surgeons believe that the traditional open approach is a cheaper, safer, equally effective alternative., Methods: 16 highly experienced "open" bariatric surgeons with a combined total of 25,759 cases representing >200 surgeon years of experience, pooled their open Roux-en-Y gastric bypass (ORYGBP) data, and compared their results to the leading laparoscopic (LRYGBP) papers in the literature., Results: In the overall series, the incisional hernia rate was 6.4% using the standard midline incision. Utilizing the left subcostal incision (LSI), it was only 0.3%. Return to surgery in <30 days was 0.7%, deaths 0.25%, and leaks 0.4%. Average length of stay was 3.4 days, and return to usual activity 21 days. Small bowel obstruction was significantly higher with the LRYGBP. Surgical equipment costs averaged approximately $3,000 less for "open" cases. LRYGBP had an added expense for longer operative time. This more than made up for the shorter length of stay with the laparoscopic approach., Conclusions: The higher cost, higher leak rate, higher rate of small bowel obstruction, and similar long-term weight loss results make the "open" RYGBP our preferred operation. If the incision is taken out of the equation (i.e. use of the LSI), the significant advantages of the open technique become even more obvious.

Objective: Surgical treatment of severe obesity is the most rapidly growing specialty area of surgery. The rapid expansion of bariatric surgery has raised questions and concerns regarding possible increased surgical mortality and morbidity rates in both academic and community settings. The purpose of this study was to evaluate postoperative outcomes and risk factors for bariatric gastric surgery for severe obesity., Methods: A community experience of 1009 consecutive patients who underwent open surgical treatment of morbid obesity during a 9-year period was reviewed from a prospective database. The series included 858 primary gastric bypass operations and 151 revision operations. Perioperative outcomes, late complications, and weight loss results were recorded. Morbidity and mortality rates were analyzed according to patient age, body mass index (BMI), and gender., Results: The mortality rate in the series was 0.6%, and the morbidity rate was 20%. The major complication rate was 6.6%. There were no deaths in the 151 revision patients. The gastrointestinal leak rate was 0.8%, and the thromboembolism rate was 1%. Statistical analysis indicates that BMI is a risk factor for surgical complications., Conclusion: Open gastric surgery for morbid obesity can be carried out in the community setting with low mortality and morbidity rates. BMI is a proven surgical risk factor.