A single-cell atlas of human and mouse white adipose tissue.

White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence1. High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes2. Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions.

Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes.

Importance: Randomized clinical trials of bariatric surgery have been limited in size, type of surgical procedure, and follow-up duration. Objective: To determine long-term glycemic control and safety of bariatric surgery compared with medical/lifestyle management of type 2 diabetes. Design, Setting, and Participants: ARMMS-T2D (Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes) is a pooled analysis from 4 US single-center randomized trials conducted between May 2007 and August 2013, with observational follow-up through July 2022. Intervention: Participants were originally randomized to undergo either medical/lifestyle management or 1 of the following 3 bariatric surgical procedures: Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding. Main Outcome and Measures: The primary outcome was change in hemoglobin A1c (HbA1c) from baseline to 7 years for all participants. Data are reported for up to 12 years. Results: A total of 262 of 305 eligible participants (86%) enrolled in long-term follow-up for this pooled analysis. The mean (SD) age of participants was 49.9 (8.3) years, mean (SD) body mass index was 36.4 (3.5), 68.3% were women, 31% were Black, and 67.2% were White. During follow-up, 25% of participants randomized to undergo medical/lifestyle management underwent bariatric surgery. The median follow-up was 11 years. At 7 years, HbA1c decreased by 0.2% (95% CI, -0.5% to 0.2%), from a baseline of 8.2%, in the medical/lifestyle group and by 1.6% (95% CI, -1.8% to -1.3%), from a baseline of 8.7%, in the bariatric surgery group. The between-group difference was -1.4% (95% CI, -1.8% to -1.0%; P < .001) at 7 years and -1.1% (95% CI, -1.7% to -0.5%; P = .002) at 12 years. Fewer antidiabetes medications were used in the bariatric surgery group. Diabetes remission was greater after bariatric surgery (6.2% in the medical/lifestyle group vs 18.2% in the bariatric surgery group; P = .02) at 7 years and at 12 years (0.0% in the medical/lifestyle group vs 12.7% in the bariatric surgery group; P < .001). There were 4 deaths (2.2%), 2 in each group, and no differences in major cardiovascular adverse events. Anemia, fractures, and gastrointestinal adverse events were more common after bariatric surgery. Conclusion and Relevance: After 7 to 12 years of follow-up, individuals originally randomized to undergo bariatric surgery compared with medical/lifestyle intervention had superior glycemic control with less diabetes medication use and higher rates of diabetes remission. Trial Registration: ClinicalTrials.gov Identifier: NCT02328599.

Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D): Study rationale, design, and methods.

AIMS: Long-term data from randomized clinical trials comparing metabolic (bariatric) surgery versus a medical/lifestyle intervention for treatment of patients with obesity/overweight and type 2 diabetes (T2D) are lacking. The Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) is a consortium of four randomized trials designed to compare long-term efficacy and safety of surgery versus medical/lifestyle therapy on diabetes control and clinical outcomes. MATERIALS AND METHODS: Patients with T2D and body mass index (BMI) of 27-45 kg/m2 who were previously randomized to metabolic surgery (Roux-en-Y gastric bypass, adjustable gastric band, or sleeve gastrectomy) versus medical/lifestyle intervention in the STAMPEDE, SLIMM-T2D, TRIABETES, or CROSSROADS trials have been enrolled in ARMMS-T2D for observational follow-up. The primary outcome is change in glycated haemoglobin after a minimum 7 years of follow-up, with additional analyses to determine rates of diabetes remission and relapse, as well as cardiovascular and renal endpoints. RESULTS: In total, 302 patients (192 surgical, 110 medical/lifestyle) previously randomized in the four parent studies were eligible for participation in the ARMMS-T2D observational study. Participant demographics were 71% white, 27% African-American and 68% female. At baseline: age, 50 ± 8 years; BMI, 36.5 ± 3.5 kg/m2 ; duration of diabetes, 8.8 ± 5.6 years; glycated haemoglobin, 8.6% ± 1.6%; and fasting glucose, 168 ± 64 mg/dl. More than 35% of patients had a BMI <35 kg/m2 . CONCLUSIONS: ARMMS-T2D will provide the largest body of long-term, level 1 evidence to inform clinical decision-making regarding the comparative durability, efficacy and safety of metabolic surgery relative to a medical/lifestyle intervention among patients with T2D, including those with milder class I obesity or mere overweight.

Lifestyle management for enhancing outcomes after bariatric surgery.

Bariatric surgery has been safe and effective for treatment of severe obesity and comorbidities like type 2 diabetes mellitus (T2D). Nonetheless, weight loss and health outcomes vary considerably across individuals. Although the factors associated with outcomes are not fully understood, postoperative weight loss following any type of bariatric surgery is largely dependent on the extent to which patients can make and sustain changes in eating and activity. Therefore, lifestyle management including diet, exercise, and behavior modification is critical to helping patients achieve long-term weight loss. Pharmacotherapy and reoperation may also play a role after bariatric surgery. In this article, we highlight recent research findings in all of these areas to provide suggestions for how to enhance outcomes following bariatric surgery. Research on the mechanisms for weight loss and improvements in T2D following the different surgical procedures is needed to support the development of more personalized approaches to the multidisciplinary management of severe obesity.

Gut adaptation after gastric bypass in humans reveals metabolically significant shift in fuel metabolism.

OBJECTIVE: Roux-en-Y gastric bypass surgery (RYGB) is among the most effective therapies for obesity and type 2 diabetes, and intestinal adaptation is a proposed mechanism for these effects. It was hypothesized that intestinal adaptation precedes and relates to metabolic improvement in humans after RYGB. METHODS: This was a prospective, longitudinal, first-in-human study of gene expression (GE) in the "Roux limb" (RL) collected surgically/endoscopically from 19 patients with and without diabetes. GE was determined by microarray across six postoperative months, including at an early postoperative (1 month ± 15 days) time point. RESULTS: RL GE demonstrated tissue remodeling and metabolic reprogramming, including increased glucose and amino acid use. RL GE signatures were established early, before maximal clinical response, and persisted. Distinct GE fingerprints predicted concurrent and future improvements in HbA1c and in weight. Human RL exhibited GE changes characterized by anabolic growth and shift in metabolic substrate use. Paradoxically, anabolic growth in RL appeared to contribute to the catabolic state elicited by RYGB. CONCLUSIONS: These data support a role for a direct effect of intestinal energy metabolism to contribute to the beneficial clinical effects of RYGB, suggesting that related pathways might be potential targets of therapeutic interest for patients with obesity with or without type 2 diabetes.

Laparoscopic sleeve gastrectomy for super obese patients: forty-eight percent excess weight loss after 6 to 8 years with 93% follow-up.

OBJECTIVES: In this study, we report long-term outcomes of high-risk, high-BMI (body mass index) patients who underwent laparoscopic sleeve gastrectomy (LSG). BACKGROUND: Short- and medium-term data appear to support the effectiveness of LSG, but long-term data to support its durability are sparse. METHODS: A prospective database was reviewed on all high-risk patients who underwent LSG as part of a staged approach for surgical treatment of severe obesity between January 2002 and February 2004. We included only patients who did not proceed to second-stage surgery (gastric bypass). Analyzed data included demographics, BMI, comorbidities, and surgical outcomes. All partial gastrectomies were performed using a 50F bougie. RESULTS: Seventy-four patients underwent LSG, and follow-up data were available on 69 of 74 patients (93%). The mean age was 50 years (25-78) and the mean number of co-morbidities was 9.6. Perioperative mortality (<30 days) was zero, and the incidence of short- and long-term postoperative complications was 15%. The mean overall follow-up time period was 73 months (38-95). Mean excess weight loss (EWL) at 72, 84, and 96 months after LSG was 52%, 43%, and 46%, respectively, with an overall EWL of 48%. The mean BMI decreased from 66 kg/m(2) (43-90) to 46 kg/m(2) (22-73). Seventy-seven percent of the diabetic patients showed improvement or remission of the disease. CONCLUSIONS: This study reports the longest follow-up of LSG patients thus far and supports the effectiveness, safety, and durability of laparoscopic sleeve gastrectomy as a definitive therapeutic option for severe obesity, even in high-risk, high-BMI patients.

MRI as First Line Imaging for Suspected Acute Appendicitis during Pregnancy: Diagnostic Accuracy and level of Inter-Radiologist Agreement.

OBJECTIVE: Evaluation of acute appendicitis (AA) in pregnancy is supported with diagnostic imaging. Typically, ultrasound (US) is performed first, and then often followed by magnetic resonance imaging (MRI) due to continued diagnostic uncertainty. The purpose of our study was to evaluate the sensitivity, specificity, and accuracy of US as compared to MRI and to evaluate the inter-radiologist agreement amongst body Radiologists with varying levels of expertise. MATERIALS AND METHODS: We performed a retrospective study of 364 consecutive pregnant patients with clinical suspicion of AA at a single center over a 6-year period. Sensitivity, Specificity, accuracy, positive and negative predictive values were calculated for US and MRI. Inter Radiologist agreement was determined using Cohen's Kappa analysis between original interpreting Radiologist and retrospective review by expert Radiologist. RESULTS: Thirty-one of 364 patients (8.5%) underwent appendectomy based on preoperative diagnosis, with confirmation of acute appendicitis (AA) by pathology in 19. US was able to visualize the appendix in only 6 (1.65%), 5 of whom had appendicitis. 141 patients underwent MRI, and correctly diagnosed appendicitis in 9. No patient with a negative MRI diagnosis had AA. The sensitivity, and negative predictive value for diagnosing AA with MRI was 100%. The MRI inter-reader agreement for appendix visualization and overall accuracy were 87.9 and 98% with Cohen Kappa of 0.7 and 0.56 respectively. CONCLUSIONS: Our data suggests that MRI should be considered the first line imaging modality in pregnant patients suspected of having AA. Body Radiologists with varied levels of experience in MRI readouts had substantial agreement.

Five-year attrition, active enrollment, and predictors of level of participation in the Longitudinal Assessment of Bariatric Surgery (LABS-2) study.

BACKGROUND: Reporting high-quality bariatric surgery outcomes depends on participant attrition and level of study participation among enrolled participants. OBJECTIVES: Our aims are to report participant attrition, active enrollment, and level of participation, and to evaluate pre-surgery sociodemographic, physical health, and psychosocial factors as predictors of attrition and level of participation through 5 years. SETTING: The Longitudinal Assessment of Bariatric Surgery-2 study which enrolled 2458 adults undergoing a first bariatric surgical procedure at 1 of 6 US cites from 2006 through 2009. METHODS: In-person research assessments were conducted pre-surgery and annually for five years. Extensive retention strategies including offering remote assessments (telephone, email, mail, or a combination) were fully implemented in 2009. Among living participants, including those inactivated, annual follow-up assessments were categorized as in-person, remote or missed through 5 years. RESULTS: By year 5, 1.7% of participants had died and 3.2% had withdrawn or were inactivated by the study staff; thus, attrition was 4.9% (n = 121). Controlling for site and calendar year, missed assessments increased from 14.7%-21.8% between years 1 and 2 and then stayed relatively stable (20.8%-19.6%) for years 3-5. Younger age, male sex, White race, lower body mass index, smoking, illicit drug use, and higher weight loss expectations preoperatively were independently associated with a higher likelihood of a missed versus in-person assessment across follow-up. CONCLUSION: The LABS-2 participant attrition was low. The percentage of missed assessments did not increase after year 2, perhaps due to implementation of a comprehensive retention plan. Predictors of missed assessments highlight subgroups to target for focused retention efforts.

American Society of Metabolic and Bariatric Surgery consensus statement on laparoscopic adjustable gastric band management.

BACKGROUND: Laparoscopic adjustable gastric band (LAGB) management continues to be an important part of many metabolic and bariatric surgery practices. OBJECTIVES: To replace the existing American Society for Metabolic and Bariatric Surgery (ASMBS) LAGB adjustment credentialing guidelines for physician extenders with consensus statements that reflect the current state of LAGB management. SETTING: ASMBS Integrated Health Clinical Issues Committee. METHODS: A modified Delphi process using a 2-stage consensus approach was conducted on LAGB management. Thirty-four consensus statements were developed following a literature search on a wide range of LAGB topics. A 5-point Likert scale was implemented to measure consensus agreement with a Delphi panel of 39 expert participants who were invited and agreed to participate in 2 rounds of Delphi questionnaires. Consensus was set a priori at 75% agreement, defined as the proportion of participants responding with agreement (i.e., 4 or 5) or disagreement (i.e., 1 or 2) on the Likert scale. RESULTS: Consensus was reached on 74% (25 of 34) of the LAGB management statements. In Delphi round 1, 95% (37 of 39) of the participants responded to 34 consensus statements; 21 of the statements (62%) met the 75% criteria for consensus. Thirty-one participants (80%) responded in round 2, shifting the agreement on 4 more statements to the 75% threshold. CONCLUSION: The ASMBS consensus statement on LAGB management is intended to guide practice with current evidence-based knowledge and professional experience. The ASMBS is not a credentialing body and does not seek to guide credentialing with this document.

Diabetes Remission in the Alliance of Randomized Trials of Medicine Versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D).

OBJECTIVE: The overall aim of the Alliance of Randomized Trials of Medicine versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) consortium is to assess the durability and longer-term effectiveness of metabolic surgery compared with medical/lifestyle management in patients with type 2 diabetes (NCT02328599). RESEARCH DESIGN AND METHODS: A total of 316 patients with type 2 diabetes previously randomly assigned to surgery (N = 195) or medical/lifestyle therapy (N = 121) in the STAMPEDE, TRIABETES, SLIMM-T2D, and CROSSROADS trials were enrolled into this prospective observational cohort. The primary outcome was the rate of diabetes remission (hemoglobin A1c [HbA1c] ≤6.5% for 3 months without usual glucose-lowering therapy) at 3 years. Secondary outcomes included glycemic control, body weight, biomarkers, and comorbidity reduction. RESULTS: Three-year data were available for 256 patients with mean 50 ± 8.3 years of age, BMI 36.5 ± 3.6 kg/m2, and duration of diabetes 8.8 ± 5.7 years. Diabetes remission was achieved in more participants following surgery than medical/lifestyle intervention (60 of 160 [37.5%] vs. 2 of 76 [2.6%], respectively; P < 0.001). Reductions in HbA1c (Δ = -1.9 ± 2.0 vs. -0.1 ± 2.0%; P < 0.001), fasting plasma glucose (Δ = -52 [-105, -5] vs. -12 [-48, 26] mg/dL; P < 0.001), and BMI (Δ = -8.0 ± 3.6 vs. -1.8 ± 2.9 kg/m2; P < 0.001) were also greater after surgery. The percentages of patients using medications to control diabetes, hypertension, and dyslipidemia were all lower after surgery (P < 0.001). CONCLUSIONS: Three-year follow-up of the largest cohort of randomized patients followed to date demonstrates that metabolic/bariatric surgery is more effective and durable than medical/lifestyle intervention in remission of type 2 diabetes, including among individuals with class I obesity, for whom surgery is not widely used.

Auricular nerve stimulation using the NSS-2 BRIDGE device to reduce opioid requirement following laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Evidence supports the use of complementary techniques to reduce pain and opioid use after surgery. The NSS-2 BRIDGE device (NBD; Innovative Health Solutions, Inc., Versailles, Indiana) modulates pain via stimulation of the nucleus of the auricular branch of the cranial nerves at the level of the brainstem and the limbic system. OBJECTIVE: To investigate the role of auricular nerve field stimulation for pain control following gastric bypass surgery. SETTINGS: U.S. academic medical center. METHODS: A total of 18 subjects were included. Subjects were divided in 2 groups: NBD group (n = 8) and a control group (n = 10). The NBD was placed following laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery in the recovery room. The effectiveness of NBD was assessed comparing the relative use of opioid consumption (oral morphine equivalents) and pain (0 = no pain to 10= worst possible pain) at 24 and 48 hours after surgery. In addition, the device tolerability (1-10) was assessed, with 8-10 considered excellent. Data were analyzed using unpaired t tests and presented as mean ± standard deviation. Alpha was set up at .1. RESULTS: Compared with the control group, the use of NBD was associated with a 60.2% reduction in oral morphine equivalents (38.15 vs 15.2 mg; P < .1) and a 28% reduction in pain (5.0 vs 3.6; P = .1) at 24 hours after surgery. The tolerability of NBD was reported to be excellent. CONCLUSIONS: This report suggests that NBD may represent an interesting alternative to control perioperative pain and limit opioid use following bariatric surgery. This needs to be confirmed by a placebo-controlled, randomized study.

Surgical placement of customized abdominal vagus nerve stimulating and gastrointestinal serosal surface recording electrodes.

Bioelectronic medical approaches to control vagus nerve-to-organ signaling have the potential to treat cardiac, respiratory, gastrointestinal (GI) and metabolic diseases, such as obesity. Unlike cervical vagus nerve stimulation (VNS), abdominal VNS could provide specific therapeutic control of the GI tract without off-target effects on thoracic organs; however, surgical approaches for abdominal VNS electrode placement are not well established. Moreover, optimal device configurations and additional placement of GI recording electrodes for closed-loop control are largely unknown. We designed VNS cuff and GI planar serosal electrodes and tested placement of these devices in laparoscopic surgery in two cadavers. We determined that electrode positioning on the ventral abdominal vagus nerve and gastric antrum was feasible but other sites, such as the duodenum and proximal stomach, were more difficult. The current investigation can guide potential placement and design of VNS cuff and GI electrodes for development of closed-loop GI therapeutic devices.

Bariatric Surgery vs Lifestyle Intervention for Diabetes Treatment: 5-Year Outcomes From a Randomized Trial.

CONTEXT: Questions remain about bariatric surgery for type 2 diabetes mellitus (T2DM) treatment. OBJECTIVE: Compare the remission of T2DM following surgical or nonsurgical treatments. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial at the University of Pittsburgh, in the United States. Five-year follow-up from February 2015 until June 2016. INTERVENTIONS: 61 participants with obesity and T2DM who were initially randomized to either bariatric surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) or an intensive lifestyle weight loss intervention (LWLI) program for 1 year. Lower level lifestyle weight loss interventions (LLLIs) were then delivered for 4 years. MAIN OUTCOMES AND MEASURES: Diabetes remission assessed at 5 years. RESULTS: The mean age of the patients was 47 ±â€…6.6 years, 82% were women, and 21% African American. Mean hemoglobin A1c level 7.8% ±â€…1.9%, body mass index (BMI) 35.7 ±â€…3.1 kg/m2, and 26 participants (43%) had BMI < 35 kg/m2. Partial or complete T2DM remission was achieved by 30% (n = 6) of RYGB, 19% (n = 4) of LAGB, and no LWLI participants (P = .0208). At 5 years those in the RYGB group had the largest percentage of individuals (56%) not requiring any medications for T2DM compared with those in the LAGB (45%) and LWLI (0%) groups (P = .0065). Mean reductions in percent body weight at 5 years was the greatest after RYGB 25.2% ±â€…2.1%, followed by LAGB 12.7% ±â€…2.0% and lifestyle treatment 5.1% ±â€…2.5% (all pairwise P < .01). CONCLUSIONS: Surgical treatments are more effective than lifestyle intervention alone for T2DM treatment.

The Feasibility of Examining the Effects of Gastric Bypass Surgery on Intestinal Metabolism: Prospective, Longitudinal Mechanistic Clinical Trial.

BACKGROUND: Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the best treatment for severe obesity and its complications including type 2 diabetes mellitus (T2DM). Understanding the mechanisms responsible for the beneficial metabolic effects will help to engineer ways to improve the procedure or produce these effects without surgery. OBJECTIVE: The aim is to present data on recruitment and feasibility of a translational study designed to collect intestinal samples before and after bariatric surgery. The goal of biobanking is to allow future studies to test the hypothesis that the mechanism of action of RYGB involves specific changes in the postsurgical short- and long-term metabolism and morphology of the jejunum (Roux limb). Specifically, to test whether the intestine enhances its metabolism and activity after RYGB and increases its fuel utilization, we designed a prospective, longitudinal study, which involved the recruitment of candidates for RYGB with and without T2DM. We describe the tissue bank that we have generated, and our experience, hoping to further facilitate the performance of longitudinal mechanistic studies in human patients undergoing bariatric surgery and especially those involving post-RYGB intestinal biology. METHODS: We conducted a trial to characterize the effects of RYGB on intestinal metabolism. Intestinal tissue samples were collected from the jejunum at surgery, 1, 6, and 12 months postoperatively for the analysis of intestinal gene expression and metabolomic and morphologic changes. The target number of patients who completed at least the 6-month follow-up was 26, and we included a 20% attrition rate, increasing the total number to 32. RESULTS: To enroll 26 patients, we had to approach 79 potential participants. A total of 37 agreed to participate and started the study; 33, 30, and 26 active participants completed their 1-month, 6-month, and 12-month studies, respectively. Three participants withdrew, and 30 participants are still active. Altruism and interest in research were the most common reasons for participation. Important factors for feasibility and successful retention included (1) large volume case flow, (2) inclusion and exclusion criteria broad enough to capture a large segment of the patient population but narrow enough to ensure the completion of study aims and protection of safety concerns, (3) accurate assessment of willingness and motivation to participate in a study, (4) seamless integration of the recruitment process into normal clinical flow, (5) financial reimbursement and nonfinancial rewards and gestures of appreciation, and (6) nonburdensome follow-up visits and measures and reasonable time allotted. CONCLUSIONS: Human translational studies of the intestinal mechanisms of metabolic and weight changes after bariatric surgery are important and feasible. A tissue bank with unique samples has been established that could be used by investigators in many research fields, further enabling mechanistic studies on the effects of bariatric surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02710370; https://clinicaltrials.gov/ct2/show/NCT02710370 (Archived by WebCite at http://www.webcitation.org/75HrQT8Dl).

Proximal Roux-en-Y gastric bypass: Addressing the myth of limb length.

BACKGROUND: Some studies suggest that changes in weight or metabolic outcomes are affected by the lengths of the gastrointestinal limbs in the Roux-en-Y gastric bypass. METHODS: Participants (N = 1,770) underwent primary Roux-en-Y gastric bypass and were followed ≤7 years in the Longitudinal Assessment of Bariatric Surgery-2, a multicenter US cohort study. Alimentary limb and biliopancreatic limb lengths were measured according to research protocol; common channel was measured in a subsample (N = 547). Aimentary limb, biliopancreatic limb, and common channel ratio to total small bowel length were calculated. RESULTS: Median presurgery body mass index was 46 (25th-75th percentile: 43-51) kg/m2. Medians (25th-75th percentiles) for alimentary limb length were 125 cm (100-150), for biliopancreatic limb length were 50 cm (50-60), and common channel length were 410 cm (322-520). Statistics for ratios to the small bowel length were 0.23 (0.18-0.27) for alimentary limb, 0.09 (0.07-0.10) for biliopancreatic limb, and 0.69 (0.63-0.73) for common length. There were no significant associations between alimentary limb, biliopancreatic limb, common channel, alimentary limb ratio, biliopancreatic limb ratio or common channel ratio, and either weight loss or improvement in cardiometabolic outcomes. CONCLUSION: The common channel length in Roux-en-Y gastric bypass is highly variable between individuals. None of the limb lengths in this study, nor alimentary limb, biliopancreatic limb, or common channel ratios, seem to be related to weight loss or metabolic improvements >7 years.

Selective nonoperative management of leaks after gastric bypass: lessons learned from 2675 consecutive patients.

OBJECTIVE: To compare outcomes of patients with leaks after primary Roux-en-Y gastric bypass (GBP) managed operatively with those managed nonoperatively and subsequently derive indications for selective nonoperative management. SUMMARY OF BACKGROUND DATA: There is no consensus on the management of leaks complicating GBP, which remains the commonest cause of death. METHODS: We evaluated 2675 consecutive GBP procedures, determining incidence and outcomes of leaks in a program emphasizing early detection, routine drainage, and selective nonoperative management. RESULTS: Leaks occurred in 46 patients (41 women) with mean (+/-SD) age of 46.9 +/- 8.7 years, weight and body mass index (BMI) of 307.8 +/- 56.9 lb and 51.2 +/- 9.5 kg/m, respectively. Leaks were initially identified by upper gastrointestinal contrast swallow (UGI) on the first postoperative day (22), abnormal drain output (11), delayed UGI (3), or on clinical suspicion (10) with a respective interval to diagnosis of 1.1*, 6.5, 7, and 7.9 days (*P < 0.007 vs. other groups). Leaks were located in the gastrojejunal (GJ) anastomosis (37), gastric pouch (4), gastric remnant (2), jejuno-jejunostomy (1), Roux limb (1), and cervical esophagus (1), and were radiologically contained (40) or diffuse (3) or not demonstrable (3). Contained leaks were treated nonoperatively (31), by operation (7), or required no treatment (2). Patients with diffuse leaks or bilious drain output were operatively managed. They were similar in duration for nil per oral order, drain and antibiotic use and readmission rates, whereas hospital stays were longer in the operative group, P < 0.01. There were no deaths. CONCLUSIONS: Many leaks after gastric bypass are radiologically contained GJ and pouch leaks and can be safely managed nonoperatively. Radiologic features and bilious drainage were key determinants of treatment, with operative treatment used for diffuse GJ leaks, bilious drainage, or clinical suspicion with a negative UGI. Outcomes were similar in both groups.

Long-term weight change and health outcomes for sleeve gastrectomy (SG) and matched Roux-en-Y gastric bypass (RYGB) participants in the Longitudinal Assessment of Bariatric Surgery (LABS) study.

BACKGROUND: Data from a US multicenter longitudinal study of bariatric surgery were used to compare weight change (primary outcome) and comorbidities (secondary outcome) in patients who underwent sleeve gastrectomy versus Roux-en-Y gastric bypass. METHODS: This study includes participants who underwent sleeve gastrectomy and matched participants who underwent Roux-en-Y gastric bypass from the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study. Adults undergoing initial bariatric surgical procedures between 2006 and 2009 were enrolled. Participants who underwent sleeve gastrectomy were high-risk or superobese and intended to have a second-stage procedure. Mixed models were used to evaluate percent weight change from baseline through 7 years, and diabetes, dyslipidemia, and hypertension prevalence through 5 years. RESULTS: Fifty-seven of 59 participants who underwent sleeve gastrectomy were matched one to one. Most were female (68%) and white (81%), and had a median age of 49 (37-56) years and median body mass index of 56.4 (35.5-76.8) kg/m2 presurgery. Weight loss was significantly less 1 to 7 years after sleeve gastrectomy versus matched Roux-en-Y gastric bypass (eg, year 7 mean weight loss was 23.6% vs 30.4%, respectively; P = .001). For both surgical groups, prevalence of diabetes, low high-density lipoprotein, and hypertension were significantly (P < .05) lower 5 years postsurgery versus baseline. CONCLUSION: Higher-risk or super-obese participants after sleeve gastrectomy lost less weight than did matched Roux-en-Y gastric bypass counterparts throughout 7 years. Both groups exhibited improvements in comorbidities from presurgery through 5 years.

4-Year Changes in Sex Hormones, Sexual Functioning, and Psychosocial Status in Women Who Underwent Bariatric Surgery.

BACKGROUND: Initial weight loss after bariatric surgery has been associated with improvements in reproductive hormones and sexual functioning in women. Few studies have investigated the durability of these changes. OBJECTIVES: The objective of this paper is to investigate changes in sex hormones, sexual functioning, and relevant psychosocial constructs over 4 years in women who underwent bariatric surgery. SETTING: The setting is a prospective cohort of 106 women from the Longitudinal Assessment of Bariatric Surgery consortium. METHODS: Changes in sex hormones were assessed by blood assay. Sexual functioning, quality of life (QOL), body image, depressive symptoms, and marital adjustment were assessed by psychometric measures. RESULTS: Women lost on average (95% confidence interval) 32.3% (30.4%, 34.3%) at postoperative year 3 and 30.6% (28.5%, 32.8%) at postoperative year 4. Compared to baseline, women experienced significant changes at 4 years in all hormones assessed, except estradiol. Women reported significant improvements in sexual functioning (i.e., arousal, desire, and satisfaction) through year 3, but these changes were not maintained through year 4. Changes in relationship quality followed a similar pattern. Improvements in physical aspects of QOL, body image, and depressive symptoms were maintained through 4 years. CONCLUSIONS: Improvements in reproductive hormones and physical aspects of QOL, body image, and depressive symptoms were maintained 4 years after bariatric surgery. Improvements in sexual functioning, relationship satisfaction, and mental components of QOL eroded over time.

Time-Dependent Molecular Responses Differ between Gastric Bypass and Dieting but Are Conserved Across Species.

The effectiveness of Roux-en-Y gastric bypass (RYGB) against obesity and its comorbidities has generated excitement about developing new, less invasive treatments that use the same molecular mechanisms. Although controversial, RYGB-induced improvement of metabolic function may not depend entirely upon weight loss. To elucidate the differences between RYGB and dieting, we studied several individual organ molecular responses and generated an integrative, interorgan view of organismal physiology. We also compared murine and human molecular signatures. We show that, although dieting and RYGB can bring about the same degree of weight loss, post-RYGB physiology is very different. RYGB induces distinct, organ-specific adaptations in a temporal pattern that is characterized by energetically demanding processes, which may be coordinated by HIF1a activation and the systemic repression of growth hormone receptor signaling. Many of these responses are conserved in rodents and humans and may contribute to the remarkable ability of surgery to induce and sustain metabolic improvement.