Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass at 5 years (YOMEGA): a prospective, open-label, non-inferiority, randomised extension study.

BACKGROUND: The multicentre randomised trial YOMEGA (NCT02139813) comparing the one anastomosis gastric bypass (OAGB) with the Roux-en-Y gastric bypass (RYGB) confirmed the non-inferiority of OAGB on weight loss outcomes at 24 months. We aimed to report weight loss, metabolic, and safety outcomes at 5 years. METHODS: YOMEGA is a prospective, open-label, non-inferiority, randomised trial conducted at nine centres in France. Inclusion criteria were BMI of 40 kg/m2 or more, or 35 kg/m2 or more with comorbidities. Key exclusion criteria were severe gastro-oesophageal reflux disease or Barrett's oesophagus and previous bariatric surgery. Patients were randomly assigned (1 :1) to OAGB (one gastrojejunal anastomosis with a 200 cm biliopancreatic limb) or RYGB (with a 150 cm alimentary limb and a 50 cm biliary limb), stratified by centre, with blocks of variable size. The primary endpoint of this extension study was percentage excess BMI loss and was analysed in the per-protocol population, including patients with data who were operated on with the technique randomly assigned to them and excluding patients with major deviations from the protocol during the follow-up (change of surgical technique, death, or withdrawal of consent). Non-inferiority was concluded for the primary endpoint if the upper bound of the CI was less than the non-inferiority limit (7 percentage points). YOMEGA is registered with ClinicalTrials.gov, NCT02139813, and the 5-year follow-up of YOMEGA is registered with ClinicalTrials.gov, NCT05549271. FINDINGS: Between May 13, 2014, and March 2, 2016, 253 patients were randomly assigned to OAGB (n=129) or RYGB (n=124), and from these patients 114 in the OAGB group and 118 in the RYGB group were included in the per-protocol analysis. In the per-protocol population, at baseline, mean age was 43·0 years (SD 10·8), mean BMI was 44·0 kg/m2 (5·6), 54 (23%) patients were male and 178 (77%) were female; 55 (27%) of 207 patients had type 2 diabetes. After 5 years, mean percentage excess BMI loss was -75·6% (SD 28·1) in the OAGB group versus -71·4% (SD 29·8) in the RYGB group, confirming non-inferiority (mean difference -4·1% [90% CI -12·0 to 3·7], p=0·0099). Remission of type 2 diabetes was similar in both groups. Nutritional status did not differ; the most common adverse event was clinical gastro-oesophageal reflux disease, occurring in 27 (41%) of 66 patients in the OAGB group versus 14 (18%) of 76 patients in the RYGB group (p=0·0030). Among serious adverse events, ten (8%) of 127 patients converted from OAGB to RYGB. 171 (68%) of 253 patients were followed up. INTERPRETATION: OAGB was not inferior to RYGB regarding percentage excess BMI loss at 5 years with similar metabolic outcomes. The high rate of clinical gastro-oesophageal reflux disease after OAGB raises questions about its long-term consequences, which need to be further investigated. FUNDING: Medtronic.

Management of Severe Malnutrition Post-bariatric Surgery Using Artificial Nutrition.

BACKGROUND: Bariatric surgery (BS) results in major and sustained weight loss and improves comorbidities in patients with obesity but can also lead to malnutrition, especially through severe malabsorption and/or surgical complications. Little is known about the efficacy of artificial nutrition (AN) in this setting. METHODS: In this case series, we describe data from consecutive severely malnourished patients after BS (resectional and non-resectional), managed by AN at our hospital unit over a 4-year period. RESULTS: Between January 2018 and June 2022, 18 patients (mean ± SD age 42.2 ± 10.4 years, 94% women) required AN following BS complications. At the time of AN initiation, more than half of the patients (53%) had multiple revisional surgeries (up to four). Mean BMI was 49.7 ± 11.3 kg/m2 before BS and 29.6 ± 9.6 kg/m2 when AN was initiated. Most patients (n=16, 90%) received enteral nutrition. AN management resulted in weight regain (+4.7kg ± 8.0, p=0.034), increased serum albumin (+28%, p=0.02), pre-albumin (+88%, p=0.002), and handgrip strength (+38%, p=0.078). No major AN complication nor death was observed. Median total AN duration was 4.5 months [1-12]. During follow-up, the cumulative duration of hospitalization was 33 days [4-88] with a median of 2.5 hospitalizations [1-8] per patient. CONCLUSION: Malnutrition can occur after any BS procedure, and AN when required in this setting appears safe and effective on nutritional parameters. It is important to recognize the potential risk factors for malnutrition, which include excessive weight loss resulting from surgical complications, eating disorders, multiple revisional BS, and pregnancy.

Revisional Roux-en-Y Gastric Bypass After Sleeve Gastrectomy for Gastro-esophageal Reflux Disease and or Insufficient Weight-Loss: a Comparative Study.

INTRODUCTION: Sleeve gastrectomy (SG) is a popular surgical weight-loss procedure, but there are increasing reports of revisional Roux-Y-gastric-bypass (R-RYGB) to manage weight-loss failure (WLF) or proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) after SG, with little data available in these settings. METHODS: This retrospective study included all consecutive patients undergoing R-RYGB for WLF or RGERD after SG in two bariatric care centers from 2012 to 2018. RESULTS: Of 720 patients, 46 (3.6%) underwent R-RYGB (RGERD, n = 25; 54.4%; WLF, n = 21; 45.6%) within 44.8 ± 27.5 months post-SG. SG had enabled 27% ± 11.6 total weight loss (TWL) in the RGERD group vs. 7.2% ± 12.5% TWL in the WLF group (p < 0.001). At R-RYGB, WLF-group patients had a higher BMI (47.8 ± 8.4 vs. 34.7 ± 6.1 kg/m2; p < 0.001) and a higher number of comorbidities (2.4 ± 1.5 vs 1.5 ± 1.2; p < 0.02) compared to RGERD-group patients, while severe morbidity (Clavien-Dindo ≥ IIIb) was not significantly different between groups (6.5% vs 2.1%, p = 0.6). %TWL was still higher in the RGERD group at 12 months post-R-RYGB (35.6% ± 10.4 vs. 23.8% ± 9.2; p < 0.01) but not after 24 months post-R-RYGB. R-RYGB corrected reflux symptoms in 32 (94%) patients and reduced PPI use in 29 (97%) patients (p < 0.001), with no significant between-group difference. A history of adjustable gastric banding (AGB) (N = 8;17.4%) prior to SG was associated with a similar prevalence of GERD at R-RYGB and a lower %TWL (AGB:13.1 ± 10.2 vs. No AGB:31.6 ± 8.5; p < 0.05) at 3 years post-R-RYGB. CONCLUSION: R-RYGB following SG provides remission of reflux symptoms in 94% of patients and extra weight loss in patients with WLF, except in patients with a history of AGB prior to SG.

Follow-Up, Safety, and Satisfaction with Tele-bariatric Follow-Up Implemented During the COVID-19 French Lockdown: a 2-Year Follow-Up Study.

BACKGROUND: The COVID-19 pandemic was initially responsible for a global restricted access to healthcare resources including the follow-up of at-risk populations such as bariatric patients. We substituted face-to-face bariatric follow-up outpatient clinics (FTFC) with teleclinics (TC) during the lockdown. MATERIAL AND METHODS: We retrospectively reviewed data collected on all patients scheduled for TC during the French lockdown period (March 15 to May 15, 2020) (N = 87). Our aims were to present the patients' outcomes at one and 2 years post-TC implementation and describe patient/practitioner satisfaction. RESULTS: Seven (8%) patients required FTFC, and 80 (92%) underwent TC (study population) for preoperative bariatric assessment (N = 3) and postoperative follow-up (N = 77) after 23.6 ± 29 months following surgery. TC was performed with video and audio (N = 46; 57.5%) or audio alone when video was impossible (N = 34; 42.5%). Sixteen (20%) patients presented at least one complication identified at the first TC and were managed accordingly. There were no readmissions at 30/90 days post-TC. At 1-year after the first TC, overall follow-up rate was 94.9% (TC: 73% vs FTFC: 27%). Patients surveyed on the main advantages of TC over FTFC (N = 46) cited: saving time (97.8%) at a mean 3.9 ± 6.4 h saved per TC, work-advantages (94.3%), and comparable relevance of TC (84.8%). At 2 years post-TC implementation, follow-up rate was 93.5% and satisfaction rate was 80%, with 33% of patients preferring to return to FTFC. CONCLUSIONS: TC is a satisfactory substitute for FTFC, enabling continued bariatric follow-up during and beyond the pandemic setting without compromising patient safety. However, the modest satisfaction outcomes at 2 years highlight a need to discuss follow-up preferences in order to achieve optimal outcomes.

Endoscopy management of sleeve gastrectomy stenosis: what we learned from 202 consecutive patients.

BACKGROUND: Gastric sleeve stenosis (GSS) is described in 1%-4% of patients. OBJECTIVE: To evaluate the role of endoscopy in the management of stenosis after laparoscopic sleeve gastrectomy using a standardized approach according to the characteristic of stenosis. SETTING: Retrospective, observational, single-center study on patients referred from several bariatric surgery departments to an endoscopic referral center. METHODS: We enrolled 202 patients. All patients underwent endoscopy in a fluoroscopy setting, and a systematic classification of the type, site, and length of the GSS was performed. According to the characteristics of the stenosis, patients underwent pneumatic dilatation or placement of a self-expandable metal stent or a lumen-apposed metal stent. Failure of endoscopic treatment was considered an indication for redo surgery, whereas patients with partial or complete response were followed up for 2 years. In the event of a recurrence, a different endoscopic approach was used. RESULTS: We found inflammatory strictures in 4.5% of patients, pure narrowing in 11%, and functional stenosis in 84.5%. Stenosis was in the upper tract of the stomach in 53 patients, whereas medium and distal stenosis was detected in 138 and 11 patients, respectively, and short stenosis in 194 patients. A total of 126 patients underwent pneumatic dilatation, 8 self-expandable metal stent placement, 64 lumen-apposed metal stent positioning, and 36 combined therapy. The overall rate of endoscopy success was 69%. CONCLUSION: GSS should be considered to be a chronic disease, and the endoscopic approach seems to be the most successful treatment, with a prolonged positive outcome of 69%. Characteristics of the stenosis should guide the most suitable endoscopic approach.

Effect of exercise training after bariatric surgery: A 5-year follow-up study of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: We previously showed in a 6-month randomized controlled trial that resistance training and protein supplementation after bariatric surgery (Roux-en-Y gastric bypass, RYGB) improved muscle strength without significant effect on weight loss and body composition changes. We performed a 5-year follow-up study in these subjects with the aim 1) to assess the long-term effect of this exercise training intervention and 2) to analyze associations between habitual physical activity (PA) and weight regain at 5 years. METHODS: Fifty-four out of 76 initial participants (follow-up rate of 71%) completed the 5-year follow-up examination (controls, n = 17; protein supplementation, n = 22; protein supplementation and resistance training, n = 15). We measured body weight and composition (DXA), lower-limb strength (leg-press one-repetition maximum) and habitual PA (Actigraph accelerometers and self-report). Weight regain at 5 years was considered low when <10% of 12-month weight loss. RESULTS: Mean (SD) time elapse since RYGB was 5.7 (0.9) y. At 5 years, weight loss was 32.8 (10.1) kg, with a mean weight regain of 5.4 (SD 5.9) kg compared with the 12-month assessment. Moderate-to-vigorous PA (MVPA) assessed by accelerometry did not change significantly compared with pre-surgery values (+5.2 [SD 21.7] min/d, P = 0.059), and only 4 (8.2%) patients reported participation in resistance training. Muscle strength decreased over time (overall mean [SD]: -49.9 [53.5] kg, respectively, P<0.001), with no statistically significant difference between exercise training intervention groups. An interquartile increase in MVPA levels was positively associated with lower weight regain (OR [95% CI]: 3.27 [1.41;9.86]). CONCLUSIONS: Early postoperative participation in a resistance training protocol after bariatric surgery was not associated with improved muscle strength after 5 years of follow-up; however, increasing physical activity of at least moderate intensity may promote weight maintenance after surgery. PA may therefore play an important role in the long-term management of patients with obesity after undergoing bariatric procedure.

Endoscopic Management of Bariatric Surgery Complications According to a Standardized Algorithm.

BACKGROUND AND AIMS: Endoscopy is effective in management of bariatric surgery (BS) adverse events (AEs) but a comprehensive evaluation of long-term results is lacking. Our aim is to assess the effectiveness of a standardized algorithm for the treatment of BS-AE. PATIENTS AND METHODS: We retrospectively analyzed 1020 consecutive patients treated in our center from 2012 to 2020, collecting data on demographics, type of BS, complications, and endoscopic treatment. Clinical success (CS) was evaluated considering referral delay, healing time, surgery, and complications type. Logistic regression was performed to identify variables of CS. RESULTS: In the study period, we treated 339 fistulae (33.2%), 324 leaks (31.8%), 198 post-sleeve gastrectomy twist/stenosis (19.4%), 95 post-RYGB stenosis (9.3 %), 37 collections (3.6%), 15 LAGB migrations (1.5%), 7 weight regains (0.7%), and 2 hemorrhages (0.2%). Main endoscopic treatments were as follows: pigtail-stent positioning under endoscopic view for both leaks (CS 86.1%) and fistulas (CS 77.2%), or under EUS-guidance for collections (CS 88.2%); dilations and/or stent positioning for sleeve twist/stenosis (CS 80.6%) and bypass stenosis (CS 81.5%). After a median (IQR) follow-up of 18.5 months (4.29-38.68), complications rate was 1.9%. We found a 1% increased risk of redo-surgery every 10 days of delay to the first endoscopic treatment. Endoscopically treated patients had a more frequent regular diet compared to re-operated patients. CONCLUSIONS: Endoscopic treatment of BS-AEs following a standardized algorithm is safe and effective. Early endoscopic treatment is associated with an increased CS rate.

Endoscopic internal drainage for the management of leak, fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients.

BACKGROUND: Endoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases. OBJECTIVES: To evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG. SETTING: Retrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center. METHODS: EID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)-guided deployment of DPS or lumen apposing metal stents. RESULTS: A total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818). CONCLUSION: Early EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results.

Cholangiocarcinoma Following Bariatric Surgery: a Prospective Follow-Up Single-Center Audit.

BACKGROUND: Cholangiocarcinoma (CC) incidence is rising worldwide. Obesity and its related metabolic impairments are associated with primitive liver malignancies including CC. While bariatric surgery (BS) is associated with decreased risk of incident cancer, few data are available regarding CC incidence, presentation, and management issues after BS. METHODS: We retrospectively reviewed collected data on 1911 consecutive patients undergoing BS from 2010 to 2019. RESULTS: We recorded three cases (0.16%) of CC during the postoperative follow-up. All cases underwent a Roux-en-Y gastric bypass (RYGB) for class III obesity with metabolic diseases (i.e., type 2 diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea) without any personal or familial history of biliary disease. The patients presented with an inaugural jaundice or pruritus at 8, 12, and 13 months after RYBG, which enabled the diagnosis of metastatic CCs in all cases. In such palliative setting without access to the pancreato-biliary system, biliary drainage was ensured by a percutaneous trans-hepatic biliary drain. Chemotherapy was initiated in two patients. All the patients died within a delay of 2, 11, and 17 months after the diagnosis, respectively. CONCLUSION: The incidence of post-BS CC appears low, but the prognosis is poor because of advanced stages at diagnosis. These cases illustrate the difficulty to make both on-time diagnosis and optimal management of CC especially in patients operated of RYGB with limited access to the excluded anatomy.

Changes in Body Composition, Comorbidities, and Nutritional Status Associated with Lower Weight Loss After Bariatric Surgery in Older Subjects.

BACKGROUND: To provide greater insight into bariatric surgery outcomes in aging patients, we compared changes in body weight, body composition, obesity-related comorbidities, and nutritional status between older and younger subjects. METHODS: We analyzed data collected between January 2004 and December 2014 from our prospective bariatric cohort. Older patients (OP, ≥ 60 years at the time of surgery, n = 93; 66% Roux-en-Y gastric bypass, 34% sleeve gastrectomy) were compared with younger patients (YP, < 60 years, n = 186), matched 1:2 on sex, body mass index, diabetes, and surgical procedure. Body composition was assessed by dual-energy X-ray absorptiometry. RESULTS: Weight loss and excess weight loss at 12 months were lower in OP vs. YP (mean ± SD, 30.1 ± 10.1 vs. 34.1 ± 11.9 kg, 60.6 ± 21.2 vs. 66.8 ± 23.4%, respectively, p < 0.05 for both). Both lean body mass and fat mass loss were lower in OP vs. YP (8.4 ± 3.4 vs. 9.2 ± 9.0 kg, 19.4 ± 8.7 vs. 21.9 ± 9.1 kg, respectively, p < 0.05). The remission rate for type 2 diabetes was significantly lower in OP vs. YP (24 vs. 45%), as well as improvement in hypertension (14 vs. 46%), dyslipidemia (27 vs. 47%), and knee pain. There was no difference in micronutrient deficiencies between groups. CONCLUSIONS: These data indicate that although bariatric surgery is not as effective for weight loss in older as in younger subjects, it is a safe option regarding a comprehensive set of nutritional variables which enables significant improvement in obesity-related outcomes.

Changes in Cardiorespiratory Fitness After Gastric Bypass: Relations with Accelerometry-Assessed Physical Activity.

BACKGROUND: Exercise training optimizes cardiorespiratory fitness (CRF) after bariatric surgery, but the effect of spontaneous physical activity is not well known. This study aimed to objectively quantify changes in CRF and habitual physical activity 6 months after bariatric surgery and to examine whether change in CRF was related to change in physical activity. METHODS: Secondary analyses were performed on data from women who underwent Roux-en-Y gastric bypass (RYGB) between 2010 and 2014. Measurements were performed before and 6 months after RYGB and included V̇O2peak (graded maximal exercise test on a cycle ergometer), habitual physical activity (Actigraph GT3x accelerometer worn during 7 days), and body composition (DXA absorptiometry). Changes after RYGB were analyzed using Wilcoxon signed-rank test. Relations between change in CRF and change in physical activity were analyzed with Spearman correlations adjusted on age and preoperative BMI. RESULTS: Forty-five women (median [P25-P75] age, 43.0 [38.0-51.0] year; BMI, 42.6 [40.0-45.5] kg/m2) were included. Mean (SD) weight loss 6 months after RYGB was - 27.5 (7.9) kg (P < 0.001). Absolute V̇O2peak decreased by 0.35 (0.50) L/min (P < 0.001) and relative V̇O2peak tended to increase by 1.7 (5.3) mL/kg/min (P = 0.06), both with large inter-individual variability. Based on objective accelerometry data, daily steps and moderate-to-vigorous physical activity increased by 1275 (3164) steps/day and 7.6 (19.3) min/day, respectively (both P < 0.05). Change in absolute V̇O2peak was positively related to change in moderate-to-vigorous physical activity (r = 0.35; P = 0.03). CONCLUSIONS: The decrease in absolute CRF observed 6 months after RYGB might be prevented by increasing habitual physical activity. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01113996.

Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass for obesity (YOMEGA): a multicentre, randomised, open-label, non-inferiority trial.

BACKGROUND: One anastomosis gastric bypass (OAGB) is increasingly used in the treatment of morbid obesity. However, the efficacy and safety outcomes of this procedure remain debated. We report the results of a randomised trial (YOMEGA) comparing the outcomes of OAGB versus standard Roux-en-Y gastric bypass (RYGB). METHODS: This prospective, multicentre, randomised non-inferiority trial, was held in nine obesity centres in France. Patients were eligible for inclusion if their body-mass index (BMI) was 40 kg/m2 or higher, or 35 kg/m2 or higher with the presence of at least one comorbidity (type 2 diabetes, high blood pressure, obstructive sleep apnoea, dyslipidaemia, or arthritis), and were aged 18-65 years. Key exclusion criteria were a history of oesophagitis, Barrett's oesophagus, severe gastro-oesophageal reflux disease resistant to proton-pump inhibitors, and previous bariatric surgery. Participants were randomly assigned (1:1) to OAGB or RYGB, stratified by centre with blocks of variable size; the study was open-label, with no masking required. RYGB consisted of a 150 cm alimentary limb and a 50 cm biliary limb and OAGB of a single gastrojejunal anastomosis with a 200 cm biliopancreatic limb. The primary endpoint was percentage excess BMI loss at 2 years. The primary endpoint was assessed in the per-protocol population and safety was assessed in all randomised participants. This study is registered with ClinicalTrials.gov, number NCT02139813, and is now completed. FINDINGS: From May 13, 2014, to March 2, 2016, of 261 patients screened for eligibility, 253 (97%) were randomly assigned to OAGB (n=129) or RYGB (n=124). Five patients did not undergo their assigned surgery, and after undergoing their surgery 14 were excluded from the per-protocol analysis (seven due to pregnancy, two deaths, one withdrawal, and four revisions from OAGB to RYGB) In the per-protocol population (n=117 OAGB, n=117 RYGB), mean age was 43·5 years (SD 10·8), mean BMI was 43·9 kg/m2 (SD 5·6), 176 (75%) of 234 participants were female, and 58 (27%) of 211 with available data had type 2 diabetes. After 2 years, mean percentage excess BMI loss was -87·9% (SD 23·6) in the OAGB group and -85·8% (SD 23·1) in the RYGB group, confirming non-inferiority of OAGB (mean difference -3·3%, 95% CI -9·1 to 2·6). 66 serious adverse events associated with surgery were reported (24 in the RYGB group vs 42 in the OAGB group; p=0·042), of which nine (21·4%) in the OAGB group were nutritional complications versus none in the RYGB group (p=0·0034). INTERPRETATION: OAGB is not inferior to RYGB regarding weight loss and metabolic improvement at 2 years. Higher incidences of diarrhoea, steatorrhoea, and nutritional adverse events were observed with a 200 cm biliopancreatic limb OAGB, suggesting a malabsorptive effect. FUNDING: French Ministry of Health.

Resistance Training and Protein Supplementation Increase Strength After Bariatric Surgery: A Randomized Controlled Trial.

OBJECTIVE: Physical activity and dietary regimens to optimize health outcomes after bariatric surgery are not well known. This study aimed to determine whether resistance training with dietary protein supplementation is effective in maintaining body composition and physical fitness after obesity surgery. METHODS: Seventy-six women with obesity undergoing Roux-en-Y gastric bypass were randomly assigned at the time of surgery to receive either usual care (controls [CON], n = 22), usual care and additional (whey) protein intake (PRO, n = 31), or usual care, additional protein intake, and supervised strength training for 18 weeks (PRO+EX, n = 23). The primary outcome was pre- to 6-month postsurgery change in lean body mass (by dual-energy x-ray absorptiometry). Secondary outcomes included changes in muscle strength (by one-repetition maximum testing). RESULTS: Loss over time in lean body mass did not differ between groups (CON: mean,-8.8 kg; 95% CI: -10.1 to -7.5 kg; PRO: mean, -8.2 kg; 95% CI: -9.3 to -7.1 kg; PRO+EX: mean, -7.7 kg; 95% CI: -9.0 to -6.5 kg; P = 0.899). The increase in relative lower-limb muscle strength was higher in the PRO+EX group (+0.6 [0.3 to 0.8]) versus +0.1 (-0.1 to 0.4) and +0.2 (0.0 to 0.4) kg/kg body mass in CON and PRO groups, respectively (P = 0.021). CONCLUSIONS: Loss in muscle strength observed after bariatric surgery can be overcome by resistance training with additional protein intake.

Sleeve Gastrectomy in Morbidly Obese HIV Patients: Focus on Anti-retroviral Treatment Absorption After Surgery.

CONTEXT: Anti-retroviral therapy (ART) dramatically reduced AIDS development, thus enabling patients to live as long as the general population. New challenges have emerged particularly cardiometabolic diseases and weight gain, with some HIV patients seeking bariatric surgery (BS). However, BS outcomes during HIV remain poorly described, with scarce data on ART pharmacokinetic post-BS. OBJECTIVE: Describing sleeve gastrectomy (SG) results in HIV patients in terms of ART pharmacokinetic, HIV control, weight loss, and metabolic outcomes. DESIGN, SETTING, AND PATIENTS: Prospective study of HIV patients undergoing SG in a referral academic center, with at least 6 months follow-up. MAIN OUTCOME MEASURE: Clinical and biological parameters, HIV medical history, and ART pharmacokinetics were gathered before and post-SG. RESULTS: Seventeen patients (mean BMI = 44.2 ± 5.7 kg m-2) and major obesity-related diseases (47% type-2 diabetes, 64% obstructive sleep apnea, 70% hypertension) underwent SG during a mean 2 years of follow-up. They displayed an average of 20% reduction of initial BMI and improved body composition, similarly to obese non-HIV patients. SG improved metabolic status. All patients had undetectable viral load before BS. Upon HIV follow-up, 12 patients had undetectable viral load with correct ART kinetic parameters (3 and 6 months); 4 displayed detectable viral load along with significant decrease in raltegravir and atazanavir treatment exposure, leading to ART change with subsequent undetectable viral load; and 1 had persistent detectable viral load despite ART change. CONCLUSIONS: SG seems effective and safe in obese HIV patients. However, ART treatment should be monitored post-SG to control HIV infection. We suggest that some ART should be adapted before SG conjoints with infectious disease specialists.

Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue.

Adipose tissue contains a variety of immune cells, which vary in abundance and phenotype with obesity. The contribution of immune cell-derived factors to inflammatory, fibrotic and metabolic alterations in adipose tissue is not well established in human obesity. Human primary adipose tissue cells, including pre-adipocytes, endothelial cells and mature adipocytes, were used to investigate deregulation of cell- and pathway-specific gene profiles. Among factors known to alter adipose tissue biology, we focus on inflammatory (IL-1ß and IL-17) and pro-fibrotic (TGF-ß1) factors. rIL-1ß and rIL-17 induced concordant pro-inflammatory transcriptional programs in pre-adipocytes and endothelial cells, with a markedly more potent effect of IL-1ß than IL-17. None of these cytokines had significant effect on fibrogenesis-related gene expression, contrasting with rTGF-ß1-induced up-regulation of extracellular matrix components and pro-fibrotic factors. In mature adipocytes, all three factors promoted down-regulation of genes functionally involved in lipid storage and release. IL-1ß and IL-17 impacted adipocyte metabolic genes in relation with their respective pro-inflammatory capacity, while the effect of TGF-ß1 occurred in face of an anti-inflammatory signature. These data revealed that IL-1ß and IL-17 had virtually no effect on pro-fibrotic alterations but promote inflammation and metabolic dysfunction in human adipose tissue, with a prominent role for IL-1ß.

A PDGFRα-Mediated Switch toward CD9high Adipocyte Progenitors Controls Obesity-Induced Adipose Tissue Fibrosis.

Obesity-induced white adipose tissue (WAT) fibrosis is believed to accelerate WAT dysfunction. However, the cellular origin of WAT fibrosis remains unclear. Here, we show that adipocyte platelet-derived growth factor receptor-α-positive (PDGFRα+) progenitors adopt a fibrogenic phenotype in obese mice prone to visceral WAT fibrosis. More specifically, a subset of PDGFRα+ cells with high CD9 expression (CD9high) originates pro-fibrotic cells whereas their CD9low counterparts, committed to adipogenesis, are almost completely lost in the fibrotic WAT. PDGFRα pathway activation promotes a phenotypic shift toward PDGFRα+CD9high fibrogenic cells, driving pathological remodeling and altering WAT function in obesity. These findings translated to human obesity as the frequency of CD9high progenitors in omental WAT (oWAT) correlates with oWAT fibrosis level, insulin-resistance severity, and type 2 diabetes. Collectively, our data demonstrate that in addition to representing a WAT adipogenic niche, different PDGFRα+ cell subsets modulate obesity-induced WAT fibrogenesis and are associated with loss of metabolic fitness.

Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of morbid obesity, but its severity varies greatly and thus there is a strong need to better define its natural history in these patients. DESIGN: Liver biopsies were systematically performed in 798 consecutive patients with severe obesity undergoing bariatric surgery. Histology was compared with clinical, biological, anthropometrical and body composition characteristics. RESULTS: Patients with presumably normal liver (n=179, 22%) were significantly younger at bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, p<0.0001). However, both groups showed quite similar obesity duration, since patients with presumably normal liver reported the onset of obesity at a significantly younger age than those with NAFLD (14.8 vs 20.0 year, p<0.0001). The trunk/limb fat mass ratio increased according to liver disease severity (presumably normal liver: 1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, p<0.0001), although the total body fat mass decreased (presumably normal liver: 50%, steatosis: 49.1%, NASH: 47.4%, p<0.0001). The volume of subcutaneous adipocytes increased according to severity of liver disease but only in female patients (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996 picolitres). CONCLUSIONS: These results suggest that young adults are more prone to store fat in subcutaneous tissue and reach the threshold of bariatric surgery indication before their liver is damaged. A shift of fat storage from subcutaneous to visceral adipose tissue compartment is associated with liver damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in females since hypertrophic adipocytes are more exposed to lipolysis and to the production of inflammatory mediators.