European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint European Society for Clinical Nutrition and Metabolism / United European Gastroenterology guideline

Background Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. Objective The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. Methods The present guideline was developed according to the standard operating procedure for European Society for Clinical Nutrition and Metabolism guidelines, following the Scottish Intercollegiate Guidelines Network grading system (A, B, 0, and good practice point [GPP]). The procedure included an online voting (Delphi) and a final consensus conference. Results In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. Conclusion The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Muscle, nutrition et tumeurs primitives hépatiques : de la prise en charge médico chirurgicale à l'optimisation pronostique

Malnutrition is currently a public health problem around the world, and is characterized by a loss of muscle mass. This negatively impacts the prognosis of many cancers, especially liver cancers. Sarcopenic obesity, the prevalence of which is increasing, also plays a negative prognostic role. The assessment of body composition by CT scan targeted on the 3rd lumbar vertebra level is currently advised to diagnose malnutrition. Computed tomography has the advantage of being routinely used during the follow-up of patients with cancer. In the first part of our work, we assessed the prevalence of decreased muscle mass and the impact of body composition on overall survival and recurrence-free survival in patients operated for curative treatment of intrahepatic cholangiocarcinoma, the 2nd most frequent primary liver tumor. We show that the preoperative prevalence of malnutrition is high and that the increase of visceral fat area is associated with worse survival. In the absence of a standardized large mammal model of protein-energy malnutrition, our second objective was to develop a Yucatan minipig model of marasmic-type malnutrition as observed in human restrictive anorexia. Pigs are physiologically close to humans, allowing the study of body composition and metabolism. An 8-week protein-energy restriction induced a weight loss greater than 10%, a decrease in muscle mass and fat mass, as well as a decrease in the cross-sectional area of muscle fibers. We observed activations of AMPK (energetic sensor of the cell) and Akt both in biceps femoris and trapezius without activation of 4EBP1 and P70S6K. Myostatin mRNA levels tended to decrease in the trapezius muscle, whereas no significant change was reported in the biceps femoris A decreased alpha diversity of the gut microbiota was reported. This model therefore mimics human marasmic malnutrition and could be used in particular in preclinical studies investigating the impact of malnutrition on liver regeneration.La dénutrition est un problème de santé publique dans le monde. Elle se manifeste par une perte de masse musculaire. Celle-ci impacte négativement le pronostic de nombreux cancers, notamment les cancers du foie. L’obésité sarcopénique, dont la prévalence augmente, joue également un rôle pronostique péjoratif. La composition corporelle par scanner sur une coupe axiale passant par la 3ème vertèbre lombaire est une des méthodes de diagnostic de la dénutrition et de la sarcopénie. La tomodensitométrie a l’avantage d’être utilisée au cours du suivi des patients atteints de cancer. Dans la première partie de cette thèse, nous avons évalué la prévalence de la diminution de masse musculaire, puis l’impact de la composition corporelle sur la survie globale et la survie sans récidive chez les patients opérés à visée curative de cholangiocarcinome intrahépatique, 2ème tumeur hépatique primitive la plus fréquente. Nous avons mis en évidence que la prévalence de la dénutrition pré-opératoire était élevée et que c’est l’augmentation de la graisse viscérale qui était un facteur de mauvais pronostic. En l’absence de modèle standardisé de dénutrition protéino-énergétique chez le gros mammifère, nous avons eu pour second objectif de développer chez le miniporc Yucatan un modèle de dénutrition de type marasmique, proche de ce qui est observé dans l’anorexie restrictive humaine. Les porcs sont des animaux proches de l’Homme sur le plan physiologique, constituant un bon modèle d’étude de la composition corporelle et du métabolisme musculaire. Une restriction protéino-énergétique de 8 semaines a induit une perte de poids supérieure à 10%, une baisse de la masse musculaire et de la masse grasse, ainsi qu’une diminution de la surface des fibres musculaires. La restriction s’accompagne d’une stimulation de la phosphorylation de l’AMPK, (senseur métabolique de la cellule) et de Akt sans activation de 4EBP1 and P70S6K dans les muscles trapezius et biceps femoris, ainsi que d’une tendance à la diminution de l’expression de la myostatine dans le trapezius. Il a également été observé une diminution de l’alpha-diversité du microbiote intestinal. Ce modèle mime donc bien la dénutrition marasmique humaine et pourrait notamment servir dans des études précliniques explorant l’impact de la dénutrition sur la régénération du foie

Muscle, nutrition, primary liver tumors : from medico-surgical management to prognostic optimization

La dénutrition est un problème de santé publique dans le monde. Elle se manifeste par une perte de masse musculaire. Celle-ci impacte négativement le pronostic de nombreux cancers, notamment les cancers du foie. L’obésité sarcopénique, dont la prévalence augmente, joue également un rôle pronostique péjoratif. La composition corporelle par scanner sur une coupe axiale passant par la 3ème vertèbre lombaire est une des méthodes de diagnostic de la dénutrition et de la sarcopénie. La tomodensitométrie a l’avantage d’être utilisée au cours du suivi des patients atteints de cancer. Dans la première partie de cette thèse, nous avons évalué la prévalence de la diminution de masse musculaire, puis l’impact de la composition corporelle sur la survie globale et la survie sans récidive chez les patients opérés à visée curative de cholangiocarcinome intrahépatique, 2ème tumeur hépatique primitive la plus fréquente. Nous avons mis en évidence que la prévalence de la dénutrition pré-opératoire était élevée et que c’est l’augmentation de la graisse viscérale qui était un facteur de mauvais pronostic. En l’absence de modèle standardisé de dénutrition protéino-énergétique chez le gros mammifère, nous avons eu pour second objectif de développer chez le miniporc Yucatan un modèle de dénutrition de type marasmique, proche de ce qui est observé dans l’anorexie restrictive humaine. Les porcs sont des animaux proches de l’Homme sur le plan physiologique, constituant un bon modèle d’étude de la composition corporelle et du métabolisme musculaire. Une restriction protéino-énergétique de 8 semaines a induit une perte de poids supérieure à 10%, une baisse de la masse musculaire et de la masse grasse, ainsi qu’une diminution de la surface des fibres musculaires. La restriction s’accompagne d’une stimulation de la phosphorylation de l’AMPK, (senseur métabolique de la cellule) et de Akt sans activation de 4EBP1 and P70S6K dans les muscles trapezius et biceps femoris, ainsi que d’une tendance à la diminution de l’expression de la myostatine dans le trapezius. Il a également été observé une diminution de l’alpha-diversité du microbiote intestinal. Ce modèle mime donc bien la dénutrition marasmique humaine et pourrait notamment servir dans des études précliniques explorant l’impact de la dénutrition sur la régénération du foie.Abstract: Malnutrition is currently a public health problem around the world, and is characterized by a loss of muscle mass. This negatively impacts the prognosis of many cancers, especially liver cancers. Sarcopenic obesity, the prevalence of which is increasing, also plays a negative prognostic role. The assessment of body composition by CT scan targeted on the 3rd lumbar vertebra level is currently advised to diagnose malnutrition. Computed tomography has the advantage of being routinely used during the follow-up of patients with cancer. In the first part of our work, we assessed the prevalence of decreased muscle mass and the impact of body composition on overall survival and recurrence-free survival in patients operated for curative treatment of intrahepatic cholangiocarcinoma, the 2nd most frequent primary liver tumor. We show that the preoperative prevalence of malnutrition is high and that the increase of visceral fat area is associated with worse survival. In the absence of a standardized large mammal model of protein-energy malnutrition, our second objective was to develop a Yucatan minipig model of marasmic-type malnutrition as observed in human restrictive anorexia. Pigs are physiologically close to humans, allowing the study of body composition and metabolism. An 8-week protein-energy restriction induced a weight loss greater than 10%, a decrease in muscle mass and fat mass, as well as a decrease in the cross-sectional area of muscle fibers. We observed activations of AMPK (energetic sensor of the cell) and Akt both in biceps femoris and trapezius without activation of 4EBP1 and P70S6K. Myostatin mRNA levels tended to decrease in the trapezius muscle, whereas no significant change was reported in the biceps femoris A decreased alpha diversity of the gut microbiota was reported. This model therefore mimics human marasmic malnutrition and could be used in particular in preclinical studies investigating the impact of malnutrition on liver regeneration

In Response to "The Outcome of Bariatric Surgery in Patients Aged 75 Years and Older"

International audienc

Complications nutritionnelles de la chirurgie de l’obésité : prévalence, prévention, traitement. Revue systématique de littérature

International audienceBackgroundIn France, the use of obesity surgery is increasing sharply. Yet effective on severe obesity and its comorbidities, it exposes to the risk of serious postoperative complications, including nutritional issues. We aimed to synthesize the research-based evidence concerning these nutritional complications: prevalence, risk factors, recommendations on their treatment and prevention.MethodsWe carried out a PRISMA systematic review, the articles included were analyzed into a synoptic table, allowing the development of summary tables.ResultsPostoperative nutritional deficiencies are frequent (vitamin D 25-100%, B12 7-70%, iron 7-63%). A lifelong micronutrient supplementation is essential (multivitamin and minerals, vitamin D-calcium, iron, vitamin B12) to prevent the hematological, neurological, or musculoskeletal consequences of deficiencies. Their prevention-screening-treatment are part of a global postoperative management which must be multimodal and interdisciplinary. Severe malnutrition exists (<5%) and could lead to serious complications ("nutritional disasters") that may require artificial nutrition. Studies with high level of evidence on postoperative follow-up and supplementation are rare, not allowing the development of consensus guidelines. To prevent nutritional deficiencies and their consequences, the collaboration between general practitioners and medico-surgical teams should be strengthened.ConclusionNutritional complications are common after obesity surgery. Potentially serious, they are accessible to screening and prevention, through lifelong biochemical and clinical monitoring, and micronutrient supplementation. A coordinated follow-up, as part of a tailored "community care-hospital" patient healthcare pathway, could improve postoperative outcomes.Contexte Bien qu’indiquée pour améliorer les comorbidités de l’obésité, la chirurgie de l’obésité, en forte augmentation, expose au risque de complications postopératoires, notamment nutritionnelles. Notre objectif a été de synthétiser les données de la littérature concernant ces complications nutritionnelles :prévalence, facteurs de risque, recommandations sur leurs traitement et prévention.MéthodeNous avons conduit cette revue systématique de la littérature selon la méthode PRISMA, les articles inclus ont été analysés en tableau synoptique, permettant l’élaboration de tableaux de synthèse.RésultatsLes déficits nutritionnels sont fréquents après chirurgie de l’obésité (vitamine D25–100 %, B12 7–70 %, fer 7–63 %), imposant une supplémentation en micronutriments (complexes multivitamines-minéraux, vitamine D-calcium, fer, B12), pour en prévenir les conséquences hématologiques, neurologiques ou musculosquelettiques. Leurs prévention-dépistage-correction s’intègrent dans une prise en charge multimodale et interdisciplinaire. Les dénutritions sévères ou « catastrophes nutritionnelles » existent (<5 %) et peuvent nécessiter une nutrition artificielle. Les études de haut niveau de preuve sur les modalités de suivi et de supplémentations sont rares, ne permettant pas l’élaboration de recommandations consensuelles. Pour prévenir les déficits nutritionnels et leurs conséquences, la collaboration entre le médecin traitant et l’équipe médicochirurgicale doit se renforcer.ConclusionLes complications nutritionnelles de la chirurgie de l’obésité sont fréquentes, potentiellement graves, accessibles au dépistage et à la prévention, au moyen d’un suivi bioclinique et d’une supplémentation en micronutriments à vie. Un suivi coordonné, intégré dans un parcours de soins« ville-hôpital », pourrait optimiser les résultats postopératoires

High visceral fat is associated with a worse survival after liver resection for intrahepatic cholangiocarcinoma

International audienceThe impact of body composition (BC) on the prognosis of resected intrahepatic cholangiocarcinoma (ICC) has been poorly studied. Aims: i) to evaluate the prevalence of low muscle mass (MM) in patients; ii) to assess the impact of BC on patient overall survival (OS) and disease-free survival (DFS), and iii) on the incidence of postoperative complications. All consecutive patients who underwent liver resection for ICC between 2004 and 2016 and who had preoperative CT scans were included. Ninety-three patients were included. Sixty percent (55/91) had low total MM. On multivariable analysis, high visceral fat (HR 2.48, CI95% [1.63; 3.77], p 1 (HR 3.15 [1.67; 5.93], p = 0.0004), involvement adjacent organ (HR 6.67 [1.88; 23.69], p = 0.003), and postoperative sepsis (HR 3.04 [1.54; 5.99], p = 0.0013) were independently associated with OS. High visceral fat (HR 2.10 [1.31; 3.38], p = 0.002], nodules >1 (HR 3.01, [1.49; 6.10], p = 0.002), postoperative sepsis (HR 5.16 [2.24; 11.89], p = 0.0001), ASA score (p = 0.02) and perineural invasion (HR 3.30 [1.62; 6.76], p = 0.001) were independently associated with lower DFS. Conclusion: 60% of ICC patients had low MM before surgery. High visceral fat, but not muscle mass, was an independent prognostic factor for poor OS and DFS in European patients with resected ICC

Excess Body Mass Index Loss at 3 Months: A Predictive Factor of Long-Term Result after Sleeve Gastrectomy

Introduction. Laparoscopic Sleeve Gastrectomy (SG) is considered as successful if the percentage of Excess Body Mass Index Loss (% EBMIL) remains constant over 50% with long-term follow-up. The aim of this study was to evaluate whether early % EBMIL was predictive of success after SG. Methods. This retrospective study included patients who had SG with two years of follow-up. Patients had follow-up appointments at 3 (M3), 6, 12, and 24 months (M24). Data as weight and Body Mass Index (BMI) were collected systematically. We estimated the % EBMIL necessary to establish a correlation between M3 and M24 compared to % EBMIL speeds and calculated a limit value of % EBMIL predictive of success. Results. Data at operative time, M3, and M24 were available for 128 patients. Pearson test showed a correlation between % EBMIL at M3 and that at M24 (r=0.74;  p<0.0001). % EBMIL speed between surgery and M3 (p=0.0011) was significant but not between M3 and M24. A linear regression analysis proved that % EBMIL over 20.1% at M3 (p<0.0001) predicted a final % EBMIL over 50%. Conclusions. % EBMIL at M3 after SG is correlated with % EBMIL in the long term. % EBMIL speed was significant in the first 3 months. % EBMIL over 20.1% at M3 leads to the success of SG