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Craniopharyngiomas are tumors located in the hypothalamic region which leads to obesity in about 50% of cases. Long-term efficacy and safety of bariatric surgery are lacking in this peculiar population. The aim of this study is to determine the 5-year weight loss and resolution of type 2 diabetes (T2D) after bariatric surgery in patients operated on craniopharyngioma who had developed hypothalamic obesity.This is a multicenter french retrospective case-control study. Subjects with craniopharyngioma (n = 23) who underwent sleeve gastrectomy (SG) (n = 9) or Roux-en-Y gastric bypass (RYGB) (n = 14) (median age 35 years [25;43] and BMI 44.2 kg/mTWL% after 1 and 5 years was lower in the craniopharyngioma group than in the control group: 23.1 [15.4; 31.1] (23/23) vs 31.4 [23.9; 35.3] at 1 year (p = 0.008) (46/46) and 17.8 [7.1; 21.9] (23/23) vs 26.2 [18.9; 33.9] at 5 years (p = 0.003) (46/46). After RYGB, TWL% was lower in the craniopharyngioma group compared to the control group (p 0.001) and comparable after SG both at 1 and 5 years. No difference between the two groups was observed in T2D remission rate and in early and late adverse events. No hormonal deficiency-related acute disease was reported.Bariatric surgery induced a significant weight loss in the craniopharyngioma group at 1 and 5 years, but less than in common obesity. SG may be more effective than RYGB but this remains to be demonstrated in a larger cohort. more...

Background: Obesity is a well-known risk factor for cancer. We have previously reported the role of adipose-tissue-derived mesenchymal stem cells from obese individuals (ob-ASC) in the promotion of pathogenic Th17 cells and immune check point (ICP) upregulation. Thus, we postulated herein that this mechanism could contribute to breast cancer (BC) aggressiveness. Methods: Conditioning medium (CM) from mitogen-activated ob-ASC and immune cell co-cultures were added to two human breast cancer cell line (BCCL) cultures. Expressions of pro-inflammatory cytokines, angiogenesis markers, metalloproteinases, and PD-L1 (a major ICP) were measured at the mRNA and/or protein levels. BCCL migration was explored in wound healing assays. Anti-cytokine neutralizing antibodies (Ab) were added to co-cultures. Results: CM from ob-ASC/MNC co-cultures increased IL-1β, IL-8, IL-6, VEGF-A, MMP-9, and PD-L1 expressions in both BCCLs and accelerated their migration. The use of Abs demonstrated differential effects for IL-17A and IFNγ on BCCL pro-inflammatory cytokine over-expression or PD-L1 upregulation, respectively, but potentiating effects on BCCL migration. Finally, co-cultures with ob-ASC, but not lean ASC, enhanced PD-L1 expression. Conclusions: Our results demonstrate increased inflammation and ICP markers and accelerated BCCL migration following the activation of pathogenic Th17 cells by ob-ASC, which could represent a new mechanism linking obesity with BC progression. more...

Herbivorous insects encounter diverse plant specialized metabolites (PSMs) in their diet, that have deterrent, anti-nutritional, or toxic properties. Understanding how they cope with PSMs is crucial to understand their biology, population dynamics, and evolution. This review summarizes current and emerging cutting-edge methods that can be used to characterize the metabolic fate of PSMs, from ingestion to excretion or sequestration. It further emphasizes a workflow that enables not only to study PSM metabolism at different scales, but also to tackle and validate the genetic and biochemical mechanisms involved in PSM resistance by herbivores. This review thus aims at facilitating research on PSM-mediated plant-herbivore interactions. more...

International audience; BACKGROUND: Revisional procedures in bariatric surgery are increasing with several debated failure risk factors, such as super obesity and old age. No study has yet evaluated the outcomes and risks of a third bariatric procedure indicated for weight loss failure or weight regain. OBJECTIVES: To assess failure risks of a third bariatric procedure according to Reinhold's criteria (percentage excess weight loss [%EWL] ≤50% and/or body mass index [BMI] ≥35 kg/m(2)). SETTING: A university-affiliated tertiary care center, France. METHODS: From 2009 to 2019, clinical data and weight loss results of patients who benefited from 3 bariatric procedures for weight loss failure or weight regain were collected prospectively and analyzed using a binary logistic regression. Weight loss failure was defined according to Reinhold's criteria. RESULTS: Among 1401 bariatric procedures performed, 336 patients benefited from 2 or more procedures, and 45 had a third surgery. Eleven patients that were reoperated on because of malnutrition or gastroesophageal reflux disease were excluded from the final analysis. Among 34 patients with 3 procedures because of weight loss failure or regain, mean BMI was 48.3 ± 8.3 kg/m(2), and mean age was 30 ± 10.7 years. Three out of 34 patients (9%) presented a severe complication (Dindo-Clavien IIIb) and 2 (6%) had a minor one. Achieving Reinhold's weight loss criteria after the second bariatric procedure was a significant predictor of success of the third procedure (β = 2.9 ± 1.3 S.E.). CONCLUSION: Not reaching Reinhold's criteria after a second bariatric procedure was identified as a significant risk factor of failure of a third procedure. A third surgery should be carefully discussed especially in case of primary failure of previous procedures. more...

Gastropleural and gastrobronchial fistulas (GPF/GBFs) are serious but rare complications after bariatric surgery whose management is not consensual. The aim was to establish a cohort and evaluate different clinical presentations and therapeutic options. A multicenter and retrospective study analyzing GPF/GBFs after bariatric surgery in France between 2007 and 2018, via a questionnaire sent to digestive and thoracic surgery departments. The study included 24 patients from 9 surgical departments after initial bariatric surgery (21 sleeve gastrectomies; 3 gastric bypass) for morbid obesity (mean BMI = 42 ± 8 kg/m2). The GPF/GBFs occurred, on average, 124 days after bariatric surgery, complicating an initial post-operative gastric fistula (POGF) in 66% of cases. Endoscopic digestive treatment was performed in 79% of cases (n = 19) associated in 25% of cases (n = 6) with thoracic endoscopy. Surgical treatment was performed in 83% of cases (n = 20): thoracic surgery (n = 5), digestive surgery (n = 8), and combined surgery (n = 7). No patient died. Overall morbidity was 42%. The overall success rate of the initial and secondary strategies was 58.5% and 90%, respectively. The average healing time was approximately 7 months. Patients who had undergone thoracic surgery (n = 12) had more initial management failures (n = 9/12) than patients who had not (n = 3/12), p = 0.001. Complex and life-threatening fistulas that are revealed late require a multidisciplinary strategy. Thoracic surgery should be reserved once the abdominal leak heals; otherwise, it is associated with a higher risk of failure. more...

Changes in food preferences after bariatric surgery may alter its effectiveness as a treatment for obesity. We aimed to compare food reward for a comprehensive variety of food categories between patients who received a sleeve gastrectomy (SG) or a Roux-en-Y gastric bypass (RYGB) and to explore whether food reward differs according to weight loss. In this cross-sectional exploratory study, food reward was assessed using the Leeds Food Preference Questionnaire (LFPQ). We assessed liking and wanting of eleven food categories. Comparisons were done regarding type of surgery and Total Weight Loss (TWL; based on tercile distribution). Fifty-six patients (30 SG and 26 RYGB) were included (women: 70%; age: 44.0 (11.1) y). Regarding the type of surgery, scores were not significantly different between SG and RYGB, except for ‘non-dairy products – without color’ explicit liking (p = 0.04). Regarding TWL outcomes, explicit liking, explicit wanting and implicit wanting, scores were significantly higher for Good responders than Low responders for ‘No meat – High fat’ (post-hoc corrected p-value: 0.04, 0.03 and 0.04, respectively). Together, our results failed to identify major differences in liking and wanting regarding the type of surgery and tended to indicate that higher weight loss might be related to a higher reward for high protein-content food. Rather to focus only on palatable foods, future studies should also consider a broader range of food items, including protein reward. more...

IntroductionPrevious studies have demonstrated that one anastomosis gastric bypass (OAGB) is not inferior to Roux-en-Y gastric bypass (RYGB) in treating obesity. However, high level evidence comparing the efficacy and safety of both procedures in type 2 diabetes (T2D) treatment is still lacking, which is another main aim of bariatric surgery. The presented trial has been designed to aim at investigating the superiority of OAGB over the reference procedure RYGB in treating T2D as primary endpoint. And diabetes-related microvascular and macrovascular complications, cardiovascular comorbidities, weight loss, postoperative nutritional status, quality of life and overall complications will be followed up for 5 years as secondary endpoints.Methods and analysisThis prospective, multicentre, randomised superiority open-label trial will be conducted in patients of Asian descent. A total of 248 patients (BMI≥27.5 kg/m2) who are diagnosed with T2D will be randomly assigned (1:1) to OAGB or RYGB with blocks of four. The primary endpoint is the complete diabetes remission rate defined as HbA1c≤6.0% and fasting plasma glucose≤5.6 mmol/L without any antidiabetic medications at 1 year after surgery. All secondary endpoints will be measured at different follow-up visit points, which will start at least 3 months after enrolment, with a continuous annual follow-up for five postoperative years in order to provide solid evidence on the efficacy and safety of OAGB in patients with T2D.Ethics and disseminationThe study has been approved by the ethics committee of leading centre (Beijing Friendship Hospital, Capital Medical University, no. 2021-P2-037-03). The results generated from this work will be disseminated to academic audiences and the public via publications in international peer-reviewed journals and conferences. The data presented will be imported into a national data registry. Findings are expected to be available in 2025, which will facilitate clinical decision-making in the field.Trial registration numberNCT05015283. more...

International audience; No abstract available

PSYCHIATRIC DISORDERS AND BARIATRIC SURGERY Psychiatric disorders are common in people with obesity and their lifetime prevalence is estimated to range from 30 % to 70 %. The most frequently reported disorders are mood and anxiety disorders, attention deficit disorder, and binge eating disorder. These disorders will usually improve after bariatric surgery and do not appear to have a significant negative impact on weight loss. However, increased attention is needed regarding some aspects of these disorders (e. G., emotional dysregulation, impulsivity) as well as regarding the increased risk of developing a substance abuse disorder or increased suicide risk after bariatric surgery. As well as a high quality pre-operative psychiatric assessment is required, post-operative psychiatric follow-up is required.TROUBLES PSYCHIATRIQUES ET CHIRURGIE BARIATRIQUE Les troubles psychiatriques sont fréquents en cas d’obésité, et leur prévalence est estimée entre 30 et 70 %. Les plus fréquents sont les troubles de l’humeur, les troubles anxieux, le trouble du déficit de l’attention, et l’hyperphagie boulimique. La plupart d’entre eux s’améliorent après une chirurgie bariatrique et ne semblent pas affecter de façon importante le pronostic pondéral. Cependant, un regain de vigilance s’impose quant à certaines composantes de ces troubles (par exemple la dysrégulation émotionnelle, l’impulsivité) et devant une augmentation des risques de développer une addiction et de suicide après une chirurgie bariatrique. Au-delà de la nécessité d’une évaluation psychiatrique préopératoire de qualité, un suivi psychiatrique postopératoire apparaît de plus en plus nécessaire, ne serait-ce que pour identifier les risques émergents. more...

International audience; BACKGROUND: Liver steatosis in morbidly obese individuals undergoing bariatric surgery increases liver volume and may complicate the surgical procedure. This study aimed to assess whether a 4-week supplementation with omega-3 polyunsaturated fatty acids (PUFA) is effective in reducing liver left lateral section (LLLS) volume. PATIENTS AND METHODS: This randomized controlled trial included morbidly obese individuals with metabolic syndrome undergoing bariatric surgery at 3 French bariatric centers between 2017 and 2020. The experimental group had a 4-week preoperative supplementation with omega-3 PUFA, whereas the control group had only placebo. The primary outcome was the reduction of the LLLS volume measured with Magnetic Resonance Imaging (MRI). RESULTS: 42 patients were randomized and 37 completed the study (19 in the experimental group and 18 in the placebo group). The mean LLLS volume decreased of 3.3% (±9.6) in the experimental group vs 1.0% (±18.3) in the placebo group, indicating that omega-3 PUFA were not effective in reducing the LLLS volume compared to the placebo (p = 0.3741). Omega-3 PUFA supplementation was not effective in reducing total liver volume, liver steatosis, rate of liver injuries during surgery and operative time. CONCLUSION: A 4-week preoperative supplementation with omega-3 PUFA was not effective in reducing LLLS volume in morbidly obese individuals undergoing bariatric surgery. more...

International audience; BACKGROUND: Marginal ulcers (MU) after gastric bypass are a challenging problem. The first-line treatment is a medical therapy with eviction of risk factors but is sometimes insufficient. The management strategies of intractable ulcers are still not clearly defined. The aim of our study was to analyse the risk factors for recurrence, the management strategies used and their efficiencies. METHODS: Based on a retrospective analysis of all MU managed in our tertiary care centre of bariatric surgery during the last 14 years, a descriptive analysis of the cohort, the management strategies and their efficiency were analysed. A logistic regression was done to identify the independent associated risk factors of intractable ulcer. RESULTS: Fifty-six patients matched inclusion criteria: 30 were referred to us (13 Roux-en-Y Gastric Bypass-RYGB and 17 One Anastomosis Gastric Bypass-OAGB), 26 were operated on in our institution (24 RYGB and 2 OAGB). 11 patients had a complicated inaugural MU requiring an interventional procedure in emergency: 7 perforations, 4 haemorrhages. The majority of MU were treated medically as a first-line therapy (n = 45; 80.4%). 32 MU recurred: 20 patients required surgery as a 2nd line therapy, 6 were operated on as a 3rd line therapy and 1 had a surgery as a 5th line therapy. The OAGB was the only risk factor of recurrence (p = 0.018). We found that the Surgical management was significantly more frequent for patients with a OAGB (84% versus 35% for RYGB, p = 0.001); the most performed surgical procedure was a conversion of OAGB to RYGB (n = 11, 37.9%). CONCLUSION: Surgery was required for a large number of MU especially in case of recurrence, but recurrence can still occur after the surgery. The OAGB was the only risk factor of recurrence identified and conversion to RYGB seemed to be effective for the healing. more...

International audience; The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly differentiated adipocytes, depending on IFNγ. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFNγ secretion, leading to T cell dysfunction and notably reduced cytolytic activity. Such a mechanism could shed light on why adipose-tissue-infiltrating viruses, such as SARS-CoV-2, can worsen disease in obese individuals. more...

BACKGROUND: Incisional hernia (IH) may occur in 20% of patients after laparotomy. The hernia sac volume may be of significance, with reintegration of visceral contents potentially leading to repair failure or abdominal compartment syndrome. The present study aimed to evaluate a two-step surgical strategy comprising right colectomy for hernia reduction with synchronous absorbable mesh repair followed by definitive non-absorbable mesh repair in recurrence. METHODS: Patients operated between 2012 and 2017 at two university centers were retrospectively included. Volumetric evaluation of the IH was performed by CT imaging. RESULTS: Eleven patients were included. The mean BMI was 43 kg/m(2) (23-52 kg/m(2)). Progressive preoperative pneumoperitoneum was performed in 82% of patients, with complications in 22%. The mean volumetric ratio of the volume of the hernia to the volume of the abdominal cavity was 70% (48-100%). The first parietal repair was performed using an synthetic absorbable mesh (36%), a biologic mesh (27%), or a slowly absorbable mesh (36%). No patients died as a result of the procedure. Seven (64%) patients developed grade III-IV complications, including one case of an anastomotic fistula. Recurrence occurred in eight (73%) patients after the first repair. Of these, four (50%) patients were reoperated using a non-absorbable mesh, leading to solid repair in 75% of cases. After 27 ± 18 months of follow-up, the residual IH rate was 46%. CONCLUSIONS: Right colectomy for volume reduction in IH with loss of domain potentially represents an appropriate salvage option, supporting bowel reintegration and temporary hernia repair with absorbable material. more...

Resume Introduction La chirurgie metabolique est maintenant consideree comme une option therapeutique dans le diabete de type 2 (DT2). Cependant, peu de donnees sont disponibles concernant la gestion perioperatoire du DT2. Objectifs Evaluer les pratiques actuelles au sein des equipes bariatriques en matiere de gestion perioperatoire du DT2 afin de proposer des recommandations pratiques de prise en charge. Methodes Une methode Delphi a deux tours utilisant des enquetes en ligne a ete utilisee par les experts des equipes bariatriques (chirurgiens, diabetologues, anesthesistes, nutritionnistes) : premier tour, 63 questions portant sur 6 sujets (caracteristiques des experts/equipes, caracteristiques des patients, technique operatoire, gestion pre/postoperatoire, remission du diabete) ; deuxieme tour, 44 points a clarifier. Les resultats ont ete discutes au congres national des societes savantes correspondantes. Le consensus etait defini comme un accord superieur ou egal a 66 %. Resultats Au total, 170 experts ont participe. Les experts ont privilegie le bypass gastrique pour obtenir une remission (76,7 %). Un depistage de la retinopathie, une echographie cardiaque et une HbA1c Conclusion Les modifications postoperatoires rapides de la glycemie necessitent une surveillance etroite et un ajustement immediat des traitements antidiabetiques. more...

Resumen La derivacion o bypass gastrico, descrita en la decada de 1970, es una tecnica mixta, consistente en una pequena bolsa gastrica restrictiva y una derivacion digestiva malabsortiva. En paises como Francia supone el 30% de los procedimientos bariatricos y sigue siendo una tecnica de referencia para los pacientes obesos graves y morbidos, gracias a su eficacia sobre el peso, pero tambien metabolica y, en particular, sobre la remision de la diabetes tipo 2. La tecnica de la derivacion gastrica con asa en Y de Roux sigue siendo el procedimiento de referencia. La tecnica de Lonroth es la mas utilizada, con posibles variantes y modificaciones como la derivacion en «omega» aun en fase de evaluacion. La tecnica de derivacion gastrica tambien presenta el interes de utilizarse como procedimiento de rescate tras el fracaso de un primer procedimiento restrictivo puro. La derivacion gastrica sigue siendo un procedimiento tecnicamente dificil, con una curva de aprendizaje de mas de 100 casos, que exige un buen dominio de la laparoscopia en pacientes obesos. La persistencia de la morbilidad a largo plazo y la necesidad de una suplementacion vitaminica y de sales minerales de por vida debido al riesgo nutricional obligan a una seleccion y preparacion adecuadas de los pacientes y a un seguimiento adecuado tambien de por vida. more...

International audience; No abstract available

International audience; AIM: The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype. METHODS: To better understand the complex metabolic pattern of lean and obese T2D and non-T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry-based lipid analysis. RESULTS: Lipid homeostasis was strongly altered in a disease- and tissue-specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso-, diacyl- and ether-phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1-deoxyceramide accumulation in a disease-specific manner in serum and visceral adipose tissue. The high amounts of non-canonical 1-deoxyceramide present in human adipose tissue most likely come from cell-autonomous synthesis because 1-deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments. CONCLUSION: Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes. more...

International audience; PURPOSE: In people with obesity, food addiction (FA) tends to be associated with poorer outcomes. Its diagnosis can be challenging in primary care. Based on the SCOFF example, we aim to determine whether a quicker and simpler screening tool for FA in people with obesity could be developed, using artificial intelligence (machine learning). METHODS: The first step was to look for the most discriminating items, among 152 different ones, to differentiate between FA-positive and FA-negative populations of patients with obesity. Items were ranked using the Fast Correlation-Based Filter (FCBF). Retained items were used to test the performance of nine different predictive algorithms. Then, the construction of a graphic tool was proposed. RESULTS: Data were available for 176 patients. Only three items had a FCBF score \textgreater 0.1: "I eat to forget my problems"; "I eat more when I'm alone"; and "I eat sweets or comfort foods". Naive Bayes classification obtained best predictive performance. Then, we created a 3-item nomogram to predict a positive scoring on the YFAS. CONCLUSION: A simple and fast screening tool for detecting high-disordered eating risk is proposed. The next step will be a validation study of the FAST nomogram to ensure its relevance for emotional eating diagnosis. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study. CLINICAL TRIAL REGISTRY NUMBER: NCT02857179 at clinicaltrials.gov. more...

International audience; PURPOSE: Changes in food preferences, taste, and smell following bariatric surgery have been previously described but with inconsistent results. We aimed to describe current food preferences and their perceived changes before and after the surgery. We further compared food preferences between patients with and without taste or smell alterations, before and above 2 years follow-up, and concerning the success or failure of their surgery. MATERIALS AND METHODS: This cross-sectional study was conducted with a self-administered online questionnaire. Two years was the cut-off between short- and long-term follow-up. Success was defined as an excess weight loss (EWL) greater or equal to 50%. RESULTS: In total, 220 postoperative patients answered the questionnaire. Patients with taste alterations (64%) had significantly lower preferences for red meat, milk, cheese, desserts, fried foods, and water (all p \textless 0.05) relative to the non-taste alteration group, while those with smell alterations (38%) had significantly lower preference for cheese only (p \textless 0.05) relative to the non-smell alteration group. Patients with a ≥ 2-year follow-up had a higher liking for desserts, fried foods, fat, bread, hot drinks, and alcohol compared to patients with a \textless 2-year follow-up (all p \textless 0.05). Patients having success in surgery had higher liking scores for green vegetables and lower liking scores for starchy foods, milk, and sweet dairy products (all p \textless 0.05). CONCLUSIONS: Our study suggests that patients who underwent bariatric surgery have different food preference patterns according to their sensory perceptions, the duration of their follow-up, and the success of bariatric surgery. more...

International audience; BACKGROUND: Vertical banded gastroplasty (VBG) presents a significant rate of long-term complications, and revisions are often necessary. Conversion to Roux-en-Y gastric bypass (RYGB) seems to be preferred, but literature data remain limited. OBJECTIVES: To analyze the indications, safety, results of conversions from VBG to RYGB, and to identify predictive factors of success or failure. SETTING: Two specialized centers of bariatric surgery. METHODS: This bicentric retrospective study included all the patients who benefited from a conversion from VBG to RYGB between 2008 and January 2020. Demographic characteristics, indications, preoperative workups, intraoperative data, complications, and weight loss results were analyzed. RESULTS: During the study period, 85 patients underwent a conversion to RYGB. The mean body mass index (BMI_ before conversion was 40.6 kg/m(2). 82.3% of the patients were converted because of weight loss failure and 17.6% because of a complication of their VBG. The global rate of complications was 25%. After an average follow-up of 35 months and a rate of loss to follow-up of 33%, the mean BMI was 33.5 kg/m. The weight loss success rate according to Reinhold's criteria was 64.7%, and resolution of complications was obtained in 89.1%. The association of a fundectomy was a predictive factor of weight loss (odds ratio, .27; P = .04), whereas primary failure of the VBG was a predictive factor of failure. CONCLUSION: Conversion from VBG to RYGB remains the procedure of choice to achieve satisfying weight loss and resolution of functional complications. The addition of a fundectomy appeared to have a significant positive impact on weight loss outcomes. more...

IntroductionDespite the non-negligible weight loss failure rate at midterm, Roux-en-Y gastric bypass (RYGB) remains the reference procedure in the treatment of morbid obesity with metabolic comorbidities. A recently emerged procedure, the single anastomosis duodeno–ileal bypass with sleeve gastrectomy (SADI-S), could be more effective on weight loss with similar morbidity and lower weight loss failure rate than RYGB. We propose the first randomised, open, multicentre superiority trial comparing the SADI-S to RYGB (SADISLEEVE).Methods and analysisThe main objective is to demonstrate the superiority at 2 years after surgery of the SADI-S compared with RYGB in term of excess weight loss percentage. The secondary objectives are the evaluation of nutritional status, metabolic outcomes, overall complication rates and quality of life, within 2 years after surgery. Key inclusion criteria are obese patients with body mass index (BMI) ≥40 kg/m2 or ≥35 kg/m2 with at least one comorbid condition and candidate to a first bariatric procedure or after failure of sleeve gastrectomy. Patients randomised by minimisation in two arms, based on centre, surgery as a revisional procedure, presence of type 2 diabetes and BMI >50 kg/m2 will be included over 2 years.A sample size of 166 patients in each group will have a power of 90% to detect a probability of 0.603 that excess weight loss in the RYGB arm is less than excess weight loss in the SADI-S arm with a 5% two-sided significance level. With a drop-out rate of 10%, it will be necessary to include 183 patients per group.Ethics and disseminationThe study was approved by Institutional Review Board of Centre Hospitalier Universitaire Morvan (CPP1089-HPS1). Study was also approved by the French national agency for drug safety (2018061500148). Results will be reported in peer-reviewed scientific journals.Trial registration numberNCT03610256. more...

Resume Face a l’emergence de la pandemie a COVID 19, l’activite de chirurgie bariatrique/metabolique a ete arretee. Le confinement et l’arret de cette chirurgie ont eu un impact sous-estime sur la population obese avec prise de poids, et aggravation des comorbidites. Un certain nombre de candidats a cette chirurgie sont exposes a un risque important de mortalite liee a la pandemie. En effet, l’obesite et le diabete sont deux facteurs de risque majeurs de forme grave d’infection a COVID-19. Le seul traitement efficace actuel de l’obesite est la chirurgie metabolique avec un benefice rapide et durable. Il parait donc necessaire de reprendre une activite de chirurgie metabolique. Le but de ce travail est de hierarchiser la reprise chirurgicale afin qu’elle soit progressive et coherente. Les organigrammes proposes aideront les centres a determiner les patients prioritaires selon la balance benefice-risque. Le diabete a une place centrale dans l’arbre decisionnel. Les modalites de reprise seront variables d’un centre a l’autre selon les ressources humaines, materielles et medicamenteuses, et seront a adapter a l’evolution epidemique. Un consentement eclaire specifique sera necessaire. Un depistage chez les patients obeses est a envisager dont les modalites de depistage sont elaborees sur la base des connaissances disponibles. En cas de suspicion de COVID, la chirurgie doit etre differee. Il faut insister sur les mesures et gestes barrieres afin de proteger le patient et le personnel soignant. Un confinement est fortement suggere pour le patient durant le premier mois postoperatoire. Le suivi des patients sera effectue de preference par teleconsultation. more...

PURPOSE: Gastric leak occurs after sleeve gastrectomy (SG) in 2% of cases. Most staple-line disruptions (SLD) can be successfully treated with first-line endoscopic procedures. Less favorable situations may lead to more complex therapeutic strategies, like conversion to Roux-en-Y gastric bypass (RYGBP). The aim of our study is to predict the factors of endoscopic treatment failure and to assess the safety of conversion to RYGBP. METHODS: We included all patients treated in two centers of academic excellence (n = 100) between 2013 and 2017 who had a malignant SLD after SG. A "malignant" leakage met one of the following poor prognosis criteria suggested in the literature: unsuccessfully treated by the first-line endoscopic treatment; generalized peritonitis; anatomical anomalies; gastro-cutaneous or gastro-pleural fistula (GCF/GPF); or chronic leaks (\textgreater 4 weeks). RESULTS: No deaths occurred during the follow-up (20 ± 12 months). The endoscopy reported an anatomically abnormal gastric tube in 35 (35%) patients (stenosis [n = 21 (21%)], twist [n = 9 (9%)], or both [n = 5 (5%)]). We could maintain the SG in place in 92% of cases without stenosis, twist, or GCF/GPF. Conversion to RYGBP due to leakage was necessary in 37 (37%) patients. Stenosis, twist, or GCF/GPF significantly prevented healing in multivariate analysis (respectively: p = 0.020, OR = 0.17, and p \textless 0.001, OR = 0.07-logistic regression). CONCLUSION: Endoscopy is the treatment of choice for the management of chronic leaks after SG. The association of anatomical anomalies and GCF/GPF should lead to consideration of conversion to RYGBP. more...

Different factors, such as age, gender, preoperative weight but also the patient’s motivation, are known to impact outcomes after Roux-en-Y gastric bypass (RYGBP). Weight loss prediction is helpful to define realistic expectations and maintain motivation during follow-up, but also to select good candidates for surgery and limit failures. Therefore, developing a realistic predictive tool appears interesting. A Swiss cohort (n = 444), who underwent RYGBP, was used, with multiple linear regression models, to predict weight loss up to 60 months after surgery considering age, height, gender and weight at baseline. We then applied our model on two French cohorts and compared predicted weight to the one finally reached. Accuracy of our model was controlled using root mean square error (RMSE). Mean weight loss was 43.6 ± 13.0 and 40.8 ± 15.4 kg at 12 and 60 months respectively. The model was reliable to predict weight loss (0.37 more...

Introduction En 2020, les personnes diabetiques disposent de nouvelles solutions pour prendre en charge leur diabete en complement de l’equilibre alimentaire et d’une activite physique reguliere : medicaments, dispositifs medicaux ou chirurgie. Une enquete transversale ayant comme objectif de documenter la connaissance et le recours aux differents traitements du diabete avec un focus particulier sur la chirurgie bariatrique a ete conduite. Methode Le questionnaire etait disponible sur la plateforme securisee du DiabetLab du 14 mai au 06 juin 2020 et a ete communique via differents canaux comme la base de contacts de la plateforme Diabet’Acteurs (n = 2936), un echantillon aleatoire de la base de la Fed. Francaise des Diabetiques (emailing a n = 10 000) et les reseaux sociaux (Facebook, etc.). Resultats Sur les 4504 repondants, 60 % etaient atteints de diabete de type 2 (DT2), 50,5 % etaient des femmes et 66 % avaient moins de 65 ans avec une moyenne d’âge a 57 ans (ecart type : 15,1). Concernant les differents traitements du diabete, les plus connus etaient l’injection journaliere d’insuline a 89,5 % et les antidiabetiques oraux a 79,9 %. Les traitements les moins connus etaient la transplantation d’ilots a 16,9 %, les injections sans insuline a 26,6 %, le pancreas artificiel a 33,7 % et la chirurgie bariatrique a 38,7 %. L’âge des repondants (≤ 65 ans ou > 65 ans) influe sur leur connaissance des traitements. Par exemple, le pancreas artificiel (39,3 % vs 22,7 %), la chirurgie bariatrique (44,1 % vs 28,1 %) ainsi que la transplantation (52,9 % vs 37,6 %) sont mieux connus des patients plus jeunes a l’inverse des antidiabetiques oraux (76,0 % vs 87,5 %). Parmi les 1744 repondants ayant deja entendu parler de la chirurgie bariatrique comme traitement du diabete, les 3 principales reponses ont ete : 3,4 % y avaient eu recours, 7,4 % savaient qu’ils pouvaient y avoir acces mais ne le souhaitaient pas et 20,4 % ne savaient pas si ce traitement etait adapte a leur situation medicale. Parmi les 489 DT2 sous insuline (population cible de la chirurgie bariatrique) 11,7 % se l’etaient vu proposer par leur medecin, 9,4 % en avaient parle a leur medecin et le sujet n’avait jamais ete aborde pour 78,9 % d’entre eux. Parmi les 129 repondants ne souhaitant pas avoir recours a cette methode, 54,3 % affirmaient ne pas vouloir perdre de poids de cette maniere, 42,6 % craignaient les effets secondaires et 41,9 % etaient inquiets des risques operatoires. Parmi les 60 repondants ayant eu recours a la chirurgie, la raison principale etait la perte de poids pour 51,7 % et equilibrer son diabete pour 25,0 %. La qualite de vie apres l’operation etait jugee tres positive avec 61,7 % entre 8 et 10 sur 10. Les contraintes et changements d’habitudes de vie etaient juges relativement simples a mettre en œuvre avec 86,7 % au-dessus de 5 sur 10 dont 48,3 % entre 8 et 10 sur 10. Conclusion La chirurgie bariatrique etait connue d’un peu plus d’un tiers des repondants, sans distinction entre les types de diabete mais davantage chez les patients de moins de 65 ans. La crainte des risques operatoires et l’irreversibilite de l’acte sont les raisons majeures freinant les personnes eligibles. Le sujet n’est que peu aborde en consultation que ce soit a l’initiative du medecin ou du patient. Cette enquete pourrait etre completee par une interrogation du niveau d’information et des representations des medecins concernant la chirurgie bariatrique afin d’identifier les freins a une information plus large des patients. more...

International audience; BACKGROUND: Advanced glycation end products (AGE) are a marker of various diseases including diabetes, in which they participate to vascular damages such as retinopathy, nephropathy and coronaropathy. Besides those vascular complications, AGE are involved in altered metabolism in many tissues, including adipose tissue (AT) where they contribute to reduced glucose uptake and attenuation of insulin sensitivity. AGE are known to contribute to type 1 diabetes (T1D) through promotion of interleukin (IL)-17 secreting T helper (Th17) cells. AIM: To investigate whether lean adipose-derived stem cells (ASC) could be able to induce IL-17A secretion, with the help of AGE. METHODS: As we have recently demonstrated that ASC are involved in Th17 cell promotion when they are harvested from obese AT, we used the same co-culture model to measure the impact of glycated human serum albumin (G-HSA) on human lean ASC interacting with blood mononuclear cells. IL-17A and pro-inflammatory cytokine secretion were measured by ELISA. Receptor of AGE (RAGE) together with intercellular adhesion molecule 1 (ICAM-1), human leukocyte Antigen (HLA)-DR, cluster of differentiation (CD) 41, and CD62P surface expressions were measured by cytofluorometry. Anti-RAGE specific monoclonal antibody was added to co-cultures in order to evaluate the role of RAGE in IL-17A production. RESULTS: Results showed that whereas 1% G-HSA only weakly potentiated the production of IL-17A by T cells interacting with ASC harvested from obese subjects, it markedly increased IL-17A, but also interferon gamma and tumor necrosis factor alpha production in the presence of ASC harvested from lean individuals. This was associated with increased expression of RAGE and HLA-DR molecule by co-cultured cells. Moreover, RAGE blockade experiments demonstrated RAGE specific involvement in lean ASC-mediated Th-17 cell activation. Finally, platelet aggregation and ICAM-1, which are known to be induced by AGE, were not involved in these processes. CONCLUSION: Thus, our results demonstrated that G-HSA potentiated lean ASC-mediated IL-17A production in AT, suggesting a new mechanism by which AGE could contribute to T1D pathophysiology. more...

Background Adipose tissue is infiltrated with various immune cells, including Th17 lymphocytes and monocytes/macrophages, in obese individuals. We have previously demonstrated the role of obese adipose-derived stem cells (ob-ASC) and adipocytes (AD) in the mediation of inflammation through promotion of Th17 cells and activation of monocytes. Such an inflammation resulted in impaired ob-ASC adipogenesis and AD insulin response. In the present study, we investigated the role of IL-17A in the impairment of these functions. Methods With this aim, we used Secukinumab, a potent human anti-IL17A monoclonal antibody which has been approved for the treatment of some IL-17A related inflammatory diseases, notably Psoriasis. This antibody was added or not to phytohemagglutinin A-activated co-cultures of ob-ASC and mononuclear cells. The conditioning media of those co-cultures were harvested and added to AD ongoing differentiation from ob-ASC. Adipogenesis, insulin sensitivity and secretion of inflammatory cytokines were then measured using qRT-PCR, Western blots and ELISAs, respectively. Results Surprisingly, we did not observe any direct effect of IL-17A on ob-ASC adipogenesis, despite sensitivity of ob-ASC to IL-17A. Moreover, IL-17A blockade, with the help of Secukinumab, did not lead to the recovery of adipogenesis and insulin response, when these functions were impaired by the presence of an inflammatory conditioning medium. However, the up-regulation of IL6 and IL1B mRNA expression by AD submitted to inflammatory conditioning medium was inhibited in the presence of Secukinumab, which indicates that IL-17A may play a role in the propagation of inflammation towards AD. In conclusion we show herein that IL-17A does not play a major role in the impairment of adipogenesis and/or insulin resistance mediated by an inflammatory environment, but contributes to the propagation of inflammation in human obese adipose tissues. This suggests a beneficial effect of anti-IL17A mAb in inflammatory pathologies, where obesity contributes to poorer response to biologic treatments. more...

There have been conflicting results from trials of gastric electrical stimulation (GES) for treatment of refractory vomiting, associated or not with gastroparesis. We performed a large, multicenter, randomized, double-blind trial with crossover to study the efficacy of GES in patients with refractory vomiting, with or without gastroparesis.For 4 months, we assessed symptoms in 172 patients (66% women; mean age ± standard deviation, 45 ± 12 years; 133 with gastroparesis) with chronic (12 months) of refractory vomiting (idiopathic, associated with a type 1 or 2 diabetes, or postsurgical). A GES device was implanted and left unactivated until patients were randomly assigned, in a double-blind manner, to groups that received 4 months of stimulation parameters (14 Hz, 5 mA, pulses of 330 μs) or no stimulation (control); 149 patients then crossed over to the other group for 4 months. Patients were examined at the end of each 4-month period (at 5 and 9 months after implantation). Primary endpoints were vomiting score, ranging from 0 (daily vomiting) to 4 (no vomiting), and the quality of life, assessed by the Gastrointestinal Quality of Life Index scoring system. Secondary endpoints were changes in other digestive symptoms, nutritional status, gastric emptying, and control of diabetes.During both phases of the crossover study, vomiting scores were higher in the group with the device on (median score, 2) than the control group (median score, 1; P.001), in diabetic and nondiabetic patients. Vomiting scores increased significantly when the device was ON in patients with delayed (P.01) or normal gastric emptying (P = .05). Gastric emptying was not accelerated during the ON period compared with the OFF period. Having the GES turned on was not associated with increased quality of life.In a randomized crossover study, we found that GES reduced the frequency of refractory vomiting in patients with and without diabetes, although it did not accelerate gastric emptying or increase of quality of life. Clinicaltrials.gov, Number: NCT00903799. more...

Background: The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype. Methods: To better understand the complex metabolic pattern of lean and obese T2D and non-T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry-based lipid analysis. Findings: Lipid homeostasis was strongly altered in a disease and tissue-specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity-independent. Lipid changes encompassed lyso-, diacyl- and ether-phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1-deoxyceramide accumulation in a disease-specific manner in serum and visceral adipose tissue. Increased production of non-canonical 1-deoxyceramides in human adipose tissue was confirmed in adipocytes cell culture experiments. Interpretation: Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes. Funding Statement: This study was supported by the SNSF grants 31003A_166700/1 and 310030-184708, the Vontobel Foundation, the Olga Mayenfisch Foundation, the Novartis Foundation for Medical-Biological Research, the Fondation Ernst et Lucie Schmidheiny, the Jubilaumsstiftung Swiss Life Foundation, and the Fondation pour la Recherche sur le Cancer (C.D.); by SNSF grant CRSII3_154405 (H.R., C.D., E.L.); SNSF grant CRSII3_160741 (S.A.B., J.P, E.T.D); SNSF grant 310030B_166686 (H.R.), the NCCR Chemical Biology funded by the SNSF (H.R.), by the Bo & Kerstin Hjelt diabetes Foundation (U.L.-M.), and by the Young Independent Investigator Grant SGED/SSED (F. S.). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study had ethics committee approval (CER11-015). The study conformed to the Declaration of Helsinki and the experimental protocol (‘DIOMEDE’) was approved by the Ethical Committee SUD EST IV (Agreement 12/111) and performed according to the French legislation (Huriet’s law). more...

International audience; OBJECTIVE: The aim of this study was to compare the efficacy and safety of 12-month implantation of a duodeno-jejunal bypass liner (DJBL) with conventional medical care in patients with metabolic syndrome (MS). SUMMARY BACKGROUND DATA: DJBL is an endoscopic device for treating obesity and related disorders. The persistence of favorable results after 6 months has not been tested in a controlled study. METHODS: We conducted a multicenter randomized controlled trial, stratified by center and diabetes status. The primary endpoint was the remission of MS at 12 months. The secondary endpoints included body mass index (BMI), glucose control, blood pressure, and lipids, assessed at 12 months after implantation, and again, at 12 months after the removal of the DJBL. Up to 174 subjects were planned to be randomized into either the DJBL or the control arm at a 2:1 ratio, respectively. Study enrollment was discontinued by the Scientific Monitoring Committee due to the early termination of the ENDO trial (NCT01728116) by the US Food and Drug Administration. The study was terminated after withdrawal of the device's European Conformity marking by the European Medicines Agency, and an interim analysis was performed. RESULTS: A total of 82 patients were enrolled (67.5% female, 48.8% with diabetes). At 12 months after randomization, the primary endpoint was met in 6 (12%) DJBL patients and 3 (10%) controls (P = 0.72). Patients in the DJBL group experienced greater BMI loss [mean adjusted difference (95% confidence interval, CI) -3.1 kg/m (-4.4 to -1.9) kg/m, P \textless 0.001] and HbA1c change [mean adjusted difference -0.5% (95% CI -0.9 to -0.2); P \textless 0.001] than those in the control group. No difference remained statistically significant at 12 months after the removal of the DJBL. In the DJBL group, 39% of patients experienced at least one device-related serious adverse event, which was classified as Grade III Dindo-Clavien in 22%, and required premature device explantation in 16%. CONCLUSIONS: The present study showed a transient clinical benefit of DJBL, which was only apparent at 1 year, when the device was still in situ, and was obtained at the risk of serious device-related adverse events in 39% of patients. These results do not support the routine use of DJBL for weight loss and glucose control in patients with MS. more...

The specific management of the surgical risks linked to obesity, as well as technological advances combined with the standardisation of techniques, have significantly reduced the morbidity and mortality associated with bariatric surgery over recent decades. However, as with all surgery, patients are exposed to medical and surgical failures and complications. more...

Surgical treatment of obesity, also called "bariatric surgery", is the reference treatment for severe and morbid forms of obesity after proper multidisciplinary medical treatment has failed. However, it is only one step in the pathway of the obese patient and should only be envisaged in the framework of lifelong nutritional care. more...

International audience; OBJECTIVES: The success of longitudinal sleeve gastrectomy (LSG) is perceived as being potentially limited by dilatation of the remaining gastric tube during the follow-up. The aim of this prospective study was to determine the incidence and the characteristics of sleeve dilatation during the first post-operative year. MATERIALS AND METHODS: Gastric volumetry using 3D gastric computed tomography with gas expansion was performed in 54 successive subjects who underwent an LSG for morbid obesity at 3 and 12 months following surgery. Total gastric volume, volume of the gastric tube and the antrum, and diameter of the gastric tube were assessed after multiplanar reconstructions. An increase of at least 25 % of the total gastric volume was considered as sleeve dilatation. Percentage of excess BMI loss (%EBMIL) and daily caloric intakes were recorded during the first 18 months. RESULTS: Sixty-one percent of the subjects experienced sleeve dilatation 1 year after surgery. The gastric tube was mainly involved in the sleeve dilatation process (+91 %). Sleeve dilatation occurred especially in subjects with smaller total gastric volume at baseline (189 vs 236 ml, p = 0.02). Daily caloric intake was similar between the groups at each point of the follow-up. No difference concerning %EBMIL was observed between the groups during the 18 months of follow-up. CONCLUSIONS: Sleeve dilatation occurred in more than 50 % of the patients. Dilatation was not necessarily linked to an increase of daily caloric intake and insufficient weight loss during the first 18 months following surgery. Small LSG at baseline is at higher risk of dilatation. more...

Background Biliopancreatic diversion with duodenal switch (BPD-DS) with a 100-cm common channel has been our treatment of choice for morbid obesity since the early 1990s. This procedure offers excellent long-term weight loss but can be associated with significant side effects. Objectives To assess the effect on clinical and nutritional parameters of increasing the common channel to 200 cm. Settings University-affiliated tertiary care center. Methods Patients who underwent a BPD-DS with a 200-cm common channel (study group, n=36) were matched 1:1 for age, sex, body mass index (BMI), and main co-morbidities with patients who underwent a BPD-DS with a 100-cm common channel (control group). The strict alimentary limb was 150 cm in both groups. Results The mean age was 55±9 versus 53±7 years ( P = .3), with 50% women and a BMI of 49±8 kg/m 2 versus 50±6 kg/m 2 ( P = .9). Follow-up rate was 97%, with a minimum follow-up of 3 years. There were no significant differences in the remission rate of major co-morbidities between the 2 groups. At 3 years, the excess weight loss was 61±22% versus 68±18% ( P = .18) and the total weight loss was 33±11% versus 38±9% ( P = .055) in the study group versus control group, respectively. The study group had a lower incidence of severe protein deficiency (11% versus 19%, P = .3) and hyperparathyroidism (17.1% versus 35.3%, P = .17); required a lower amount of vitamins A and D ( P P = .03). Conclusion In this population, BPD-DS with a 200-cm common channel offered similar remission rate of co-morbidities compared with standard BPD-DS. It was associated with similar weight loss at nadir, followed by a more significant weight regain. It might yield a lower rate of nutritional complications. Long-term randomized data are needed to detect other potential advantages. more...

Background Laparoscopic adjustable gastric banding (LAGB) was one of the first performed bariatric procedure performed in Europe in the 2000s with low postoperative morbidity and mortality. Our goal was to determine long term outcomes of LAGB. Methods 138 consecutive patients underwent a LAGB between 2007 and 2019. Demographic data were recorded. Weight loss evolution over time, gastric band removal and revisional procedures were analyzed. Weigth loss success was defined at the end of the follow-up according to Reinhold’s criteria: BMI ≤ 35 and / or EBL% ≥50 %. Results 125 patients were analyzed. Initial body weight was 121,9 kg (SD +/- 22,2) and initial body mass index (BMI) was 44 kg/m2 (SD+/- 6,5). Age at the first surgery (gastric banding) was 32,7 years (SD +/- 11,9). 45.6 % of all the patients had a successful outcome according to Reinhold's criteria with a median follow-up of 75,6 months (SD+/- 50,3). Mean excess weight loss was 40,4 (SD+/- 36,6) at last follow-up. 54 patients (43,2 %) underwent band removal in a mean time of 54,2 months (SD+/- 35,8): 37 patients (29,6 %) had a second bariatric procedure. Success rate was 50 % after conversion. In univariate analysis, factors implicated with weight loss success at the last visit were success at 6 months, 1 and 2 years, the number of band tightening, lower initial BMI and better follow up. Conclusion The factors significantly associated with LAGB success were early weight loss, better follow-up, a band not too tightened whereas high initial BMI was associated to failure. more...

International audience; SCOPE: Obese adipose tissue (AT) is infiltrated by inflammatory immune cells including IL-17A-producing-T (Th17) cells. It has been previously demonstrated that adipose-derived stem cells from obese (ob-ASCs), but not lean AT promote Th17 cells. Because n-3 PUFAs are known to inhibit obese AT inflammation, it is tested here whether they could inhibit ob-ASC-mediated IL-17A secretion. METHODS AND RESULTS: The n-3 PUFA precursor, alpha-linolenic acid (ALA), or its derivatives, eicosapentaenoic, or docosahexaenoic acid, is added to co-cultures of human ob-ASCs and mononuclear cells (MNCs). All three inhibited IL-17A, but not IL-1beta, IL-6, nor TNFalpha secretion. As a control, palmitic acid (PA), a saturated fatty acid, did not inhibit IL-17A secretion. ALA also inhibited IL-17A secretion mediated by adipocytes differentiated from ob-ASCs. Toll-like-receptor 4 is shown to be involved in ob-ASC-mediated-IL-17A secretion, and to be inhibited by ALA, together with Cyclo-Oxygenase-2 and Signal-Transducer-and-Activator-of-transcription-3. In addition, ALA down-regulated Intercellular-Adhesion-Molecule-1 (ICAM-1) expression in both monocytes and ASCs, which resulted in decreased interactions between ob-ASCs and MNCs, and inhibition of IL-17A secretion. CONCLUSION: It is demonstrated herein that ALA inhibits Th17 cell promotion, through decreased ICAM-1expression in both ob-ASCs and monocytes. This novel mechanism may contribute to explain the beneficial effects of n-3 PUFA in IL-17A-related inflammatory pathologies. more...

BACKGROUND: Recent evidence has indicated an increased risk of Barrett's esophagus (BE) in the long term after sleeve gastrectomy (SG). AIM: The aim of the study is to investigate the spectrum of gastroesophageal reflux disease (GERD) symptoms as well as the prevalence of BE, at minimum 5 years after SG in patients who underwent SG in different bariatric centers of two countries: France and Italy. PATIENTS AND METHODS: Five high volume outpatient centers dedicated to bariatric surgery that routinely perform upper GI endoscopy before any bariatric procedures were invited to participate in the study. From January 2017 to June 2018, each center during scheduled postoperative evaluation after surgery asked a minimum 10 consecutive patients, which had performed SG at least 5 years before and with no evidence of BE preoperatively, to undergo another upper GI endoscopy. RESULTS: Ninety (66 F) consecutive patients were enrolled. The mean follow-up was 78 +/- 15 months, and the mean total body weight loss was 25 +/- 12%. The prevalence of BE was 18.8% with no significant difference among centers. Weight loss failure was significantly associated with BE (p \textless 0.01). The prevalence of GERD symptoms, erosive esophagitis, and the usage of PPIs increased from 22%, 10%, and 22% before the SG to 76%, 41%, and 52% at the time of follow-up, respectively (p \textless 0.05). CONCLUSIONS: This multicenter study show a high rate of BE at least 5 years after SG. Weight loss failure was significantly associated with BE. We suggest to provide systematic endoscopy in these patients to rule out this condition. more...

International audience; BACKGROUND & AIMS: Liver macrosteatosis (MS) is a major predictor of graft dysfunction after transplantation. However, frozen section techniques to quantify steatosis are often unavailable in the context of procurements, and the findings of preoperative imaging techniques correlate poorly with those of permanent sections, so that the surgeon is ultimately responsible for the decision. Our aim was to assess the accuracy of a non-invasive pocket-sized micro-spectrometer (PSM) for the real-time estimation of MS. METHODS: We prospectively evaluated a commercial PSM by scanning the liver capsule. A double pathological quantification of MS was performed on permanent sections. Initial calibration (training cohort) was performed on 35 livers (MS\textless/=60%) and an algorithm was created to correlate the estimated (PSM) and known (pathological) MS values. A second assessment (validation cohort) was then performed on 154 grafts. RESULTS: Our algorithm achieved a coefficient of determination R2=0.81. Its validation on the second cohort demonstrated a Lin's concordance coefficient of 0.78. Accuracy reached 0.91%, with reproducibility of 86.3%. The sensitivity, specificity, positive and negative predictive values for MS \textgreater/=30% were 66.7%, 100%, 100% and 98%, respectively. The PSM could predict the absence (\textless30%)/presence (\textgreater/=30%) of MS with a kappa coefficient of 0.79. Neither graft weight nor height, donor body mass index nor the CT-scan liver-to-spleen attenuation ratio could accurately predict MS. CONCLUSION: We demonstrated that a PSM can reliably and reproducibly assess mild-to-moderate MS. Its low cost and the immediacy of results may offer considerable added-value decision support for surgeons. This tool could avoid the detrimental and prolonged ischaemia caused by the pathological examination of (potentially) marginal grafts. This device now needs to be assessed in the context of a large-scale multicentre study. LAY SUMMARY: Macro-vacuolar liver steatosis is a major prognostic factor for outcomes after liver transplantation. However, it is often difficult for logistical reasons to get this estimation during procurement. Therefore, we developed an algorithm for a commercial, portable and affordable spectrometer to accurately estimate this content in a real-time fashion. This device could be of great interest for clinical decision-making to accept or discard a potential human liver graft. more...

International audience; 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/m(2) or higher, or 35 kg/m(2) 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/m(2) (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. more...

This chapter summarizes the early postoperative and long-term complications of biliopancreatic diversion with duodenal switch (BPD-DS) procedures. Perioperative mortality for BPD-DS is currently around 0.1%, with an early complication rate of 7%. The standard follow-up required for the prevention of nutritional deficiencies as well as the management of short- and long-term complications specific to metabolic surgeries are also discussed. The data and clinical views expressed in this chapter are based to a large extent on the authors’ experience with 5,000 BPD-DS surgeries in our institution over the last 25 years, and which have been reported extensively in the literature. In our experience, severe protein malnutrition occurred in 10% patients, of whom 5% required readmission and 1.5% a surgical revision to correct the problem. more...

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International audience; Modifications of the interactions between endoplasmic reticulum (ER) and mitochondria, defined as mitochondria-associated membranes (MAMs), were recently shown to be involved in the control of hepatic insulin action and glucose homeostasis, but with conflicting results. Whereas skeletal muscle is the primary site of insulin-mediated glucose uptake and the main target for alterations in insulin-resistant states, the relevance of MAM integrity in muscle insulin resistance is unknown. Deciphering the importance of MAMs on muscle insulin signaling could help to clarify this controversy. Here, we show in skeletal muscle of different mice models of obesity and type 2 diabetes (T2D) a marked disruption of ER-mitochondria interactions as an early event preceding mitochondrial dysfunction and insulin resistance. Furthermore, in human myotubes, palmitate-induced insulin resistance is associated with a reduction of structural and functional ER-mitochondria interactions. Importantly, experimental increase of ER-mitochondria contacts in human myotubes prevents palmitate-induced alterations of insulin signaling and action, whereas disruption of MAM integrity alters the action of the hormone. Lastly, we found an association between altered insulin signaling and ER-mitochondria interactions in human myotubes from obese subjects with or without T2D compared with healthy lean subjects. Collectively, our data reveal a new role of MAM integrity in insulin action of skeletal muscle and highlight MAM disruption as an essential subcellular alteration associated with muscle insulin resistance in mice and humans. Therefore, reduced ER-mitochondria coupling could be a common alteration of several insulin-sensitive tissues playing a key role in altered glucose homeostasis in the context of obesity and T2D. more...

Circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. More extensive rhythmic transcription was observed in human skeletal muscle compared to in vitro cell culture as a large part of the in vivo mRNA rhythmicity was lost in vitro. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin-stimulated glucose uptake were significantly reduced upon CLOCK depletion. Our findings suggest an essential role for the circadian coordination of skeletal muscle glucose homeostasis and lipid metabolism in humans. more...