Gut microbiota of obese subjects with Prader-Willi syndrome is linked to metabolic health.

OBJECTIVE: The gut microbiota has been implicated in the aetiology of obesity and associated comorbidities. Patients with Prader-Willi syndrome (PWS) are obese but partly protected against insulin resistance. We hypothesised that the gut microbiota of PWS patients differs from that of non-genetically obese controls and correlate to metabolic health. Therefore, here we used PWS as a model to study the role of gut microbiota in the prevention of metabolic complications linked to obesity. DESIGN: We conducted a case-control study with 17 adult PWS patients and 17 obese subjects matched for body fat mass index, gender and age. The subjects were metabolically characterised and faecal microbiota was profiled by 16S ribosomal RNA gene sequencing. The patients' parents were used as a non-obese control group. Stool samples from two PWS patients and two obese controls were used for faecal microbiota transplantations in germ-free mice to examine the impact of the microbiota on glucose metabolism. RESULTS: The composition of the faecal microbiota in patients with PWS differed from that of obese controls, and was characterised by higher phylogenetic diversity and increased abundance of several taxa such as Akkermansia, Desulfovibrio and Archaea, and decreased abundance of Dorea. Microbial taxa prevalent in the PWS microbiota were associated with markers of insulin sensitivity. Improved insulin resistance of PWS was partly transmitted by faecal microbiota transplantations into germ-free mice. CONCLUSION: The gut microbiota of PWS patients is similar to that of their non-obese parents and might play a role for the protection of PWS patients from metabolic complications.

Increasing physical activity in adult women with Prader-Willi syndrome: A transferability study.

BACKGROUND: The present authors aimed (a) to objectively quantify spontaneous physical activity (PA) in adult patients with Prader-Willi syndrome (PWS) and (b) to evaluate the transferability of a home-based exercise training programme in these patients. METHOD: Physical activity was compared between 10 adult women with PWS (PWS group) and 20 adult women with non-syndromic obesity (CON group, for cross-sectional comparison). In the PWS group, PA, body composition, walking capacity, quality of life and eating behaviour were then compared before and after a 16-week supervised exercise programme. RESULTS: The PWS group displayed lower PA and higher sedentary time compared to the CON group. Median attendance to exercise sessions reached 100% (Q1-Q3: 97%-100%) sessions. Moderate-to-vigorous PA and walking capacity increased after the programme without significant effect on body composition. CONCLUSION: Supervised home-based exercise sessions are an effective strategy to improve PA in women with PWS who are less active than women matched for adiposity.

Senescence Alters PPARγ (Peroxisome Proliferator-Activated Receptor Gamma)-Dependent Fatty Acid Handling in Human Adipose Tissue Microvascular Endothelial Cells and Favors Inflammation.

OBJECTIVE: Adipose tissue (AT) dysfunction associated with obesity or aging is a major cause for lipid redistribution and the progression of cardiometabolic disorders. Our goal is to decipher the contribution of human AT microvascular endothelial cells (ECs) in the maintenance of fatty acid (FA) fluxes and the impact of senescence on their function. APPROACH AND RESULTS: We used freshly isolated primary microvascular ECs from human AT. Our data identified the endothelial FA handling machinery including FATPs (FA transport proteins) FATP1, FATP3, FATP4, and CD36 as well as FABP4 (FA binding protein 4). We showed that PPARγ (peroxisome proliferator-activated receptor gamma) regulates the expression of FATP1, CD36, and FABP4 and is a major regulator of FA uptake in human AT EC (hATEC). We provided evidence that endothelial PPARγ activity is modulated by senescence. Indeed, the positive regulation of FA transport by PPARγ agonist was abolished, whereas the emergence of an inflammatory response was favored in senescent hATEC. This was associated with the retention of nuclear FOXO1 (forkhead box protein O1), whereas nuclear PPARγ translocation was impaired. CONCLUSIONS: These data support the notion that PPARγ is a key regulator of primary hATEC function including FA handling and inflammatory response. However, the outcome of PPARγ activation is modulated by senescence, a phenomenon that may impact the ability of hATEC to properly respond to and handle lipid fluxes. Finally, our work highlights the role of hATEC in the regulation of FA fluxes and reveals that dysfunction of these cells with accelerated aging is likely to participate to AT dysfunction and the redistribution of lipids.

Human white and brite adipogenesis is supported by MSCA1 and is impaired by immune cells.

Obesity-associated inflammation contributes to the development of metabolic diseases. Although brite adipocytes have been shown to ameliorate metabolic parameters in rodents, their origin and differentiation remain to be characterized in humans. Native CD45-/CD34+/CD31- cells have been previously described as human adipocyte progenitors. Using two additional cell surface markers, MSCA1 (tissue nonspecific alkaline phosphatase) and CD271 (nerve growth factor receptor), we are able to partition the CD45-/CD34+/CD31- cell population into three subsets. We establish serum-free culture conditions without cell expansion to promote either white/brite adipogenesis using rosiglitazone, or bone morphogenetic protein 7 (BMP7), or specifically brite adipogenesis using 3-isobuthyl-1-methylxanthine. We demonstrate that adipogenesis leads to an increase of MSCA1 activity, expression of white/brite adipocyte-related genes, and mitochondriogenesis. Using pharmacological inhibition and gene silencing approaches, we show that MSCA1 activity is required for triglyceride accumulation and for the expression of white/brite-related genes in human cells. Moreover, native immunoselected MSCA1+ cells exhibit brite precursor characteristics and the highest adipogenic potential of the three progenitor subsets. Finally, we provided evidence that MSCA1+ white/brite precursors accumulate with obesity in subcutaneous adipose tissue (sAT), and that local BMP7 and inflammation regulate brite adipogenesis by modulating MSCA1 in human sAT. The accumulation of MSCA1+ white/brite precursors in sAT with obesity may reveal a blockade of their differentiation by immune cells, suggesting that local inflammation contributes to metabolic disorders through impairment of white/brite adipogenesis. Stem Cells 2015;33:1277-1291.

Impact of bariatric surgery on fetal growth restriction: experience of a perinatal and bariatric surgery center.

BACKGROUND: Bariatric surgery is known to improve some pregnancy outcomes, but there is concern that it may increase the risk of small for gestational age. OBJECTIVE: To assess the impact of bariatric surgery on pregnancy outcomes and specifically of the type of bariatric surgery on the risk of fetal growth restriction. STUDY DESIGN: A single-center retrospective case-control study. The study group comprised all deliveries in women who had undergone bariatric surgery. To investigate the effects of weight loss on pregnancy outcomes, we compared the study group with a control group matched for presurgery body mass index. Secondly, to assess the specific impact of the type of surgery on the incidence of fetal growth restriction in utero, we distinguished subgroups with restrictive and malabsorptive bariatric surgery, and compared outcomes for each of these subgroups with a second control group, matched for prepregnancy body mass index. RESULTS: Among 139 patients operated, 58 had a malabsorptive procedure (gastric bypass) and 81 a purely restrictive procedure (72 a gastric banding and 9 a sleeve gastrectomy). Compared with controls matched for presurgery body mass index, the study group had a decreased rate of gestational diabetes (12% vs 23%, P = .02) and large for gestational age >90th percentile (11% vs 22%, P = .01) but an increased rate of small for gestational age <10th percentile. The incidence of small for gestational age was higher after gastric bypass (29%) than it was after restrictive surgery (9%) or in controls matched for prepregnancy body mass index (6%) (P < .01 between bypass and controls). In multivariable analysis, after adjustment for other risk factors, gastric bypass remained strongly associated with small for gestational age (adjusted odds ratio, 7.16; 95% confidence interval, 2.74-18.72). CONCLUSION: Malabsorptive bariatric surgery was associated with an increased risk of fetal growth restriction.

Long-term evolution of nutritional deficiencies after gastric bypass: an assessment according to compliance to medical care.

OBJECTIVE: To study long-term nutritional deficits based on adherence to a standardized nutritional care after gastric bypass (GBP). BACKGROUND: Long-term prospective data on nutritional complications after GBP are missing. It is not known whether severe deficiencies are prevented by standard multivitamin supplementation and what parameters are influenced by patient adherence to nutritional care. DESIGN: One hundred forty-four consecutive subjects from our prospective database (90% women, initial body mass index: 48 ± 15 kg/m2, age: 43 ± 10 years) who underwent GBP more than 3 years before the study were assessed. Multivitamins were systematically prescribed after GBP, and additional supplements were introduced if deficiencies were recorded during follow-up. We identified a group of 66 compliant subjects who attended yearly medical visits and a group of 32 noncompliant subjects who were recalled because they had not attended any visit for more than 2 years. RESULTS: Weight loss was 42 ± 14 kg at 3 years or later. The number of nutritional deficits per subject was 3.2 ± 2.3 before surgery and did not significantly increase between 1 and 3 years or later after GBP (3.4 ± 2.0 and 3.5 ± 2.3, respectively). However, specific nutritional deficits occurred despite long-term multivitamin supplementation, including vitamins B1, B12, and D and iron. Noncompliant subjects had more deficits than compliant subjects (4.2 ± 1.9 vs 2.9 ± 2.0 deficits per patient, P < 0.01) and the number of deficits correlated with the time from last visit (r = 0.285, P < 0.01). CONCLUSIONS: Lifelong medical care is required to maintain a good nutritional status after GBP. Monitoring of nutritional parameters is necessary to add supplementation for deficits that are not prevented by multivitamin preparations.

Comparison of pregnancy outcomes after bariatric surgery by sleeve gastrectomy versus gastric bypass.

Objective: Bariatric surgery has an impact on subsequent pregnancies, in particular an association between gastric bypass and small for gestational age. Knowledge is lacking on whether sleeve gastrectomy is associated with more favorable pregnancy outcomes. This study aimed to compare the impact of sleeve gastrectomy and Roux-en-Y gastric bypass on the incidence of small for gestational age (SGA), and of adverse pregnancy outcomes. Study design: We conducted a retrospective study in a single reference center, including all patients with a history of sleeve or bypass who delivered between 2004 and 2021 after their first pregnancy following bariatric surgery. We compared the incidence of SGA, intrauterine growth retardation, preterm delivery and adverse maternal outcomes between patients who had sleeve versus bypass. Results: Of 244 patients, 145 had a sleeve and 99 had a bypass. The proportion of SGA < 10th percentile did not differ between the two groups (38/145 (26.2 %) vs 22/99 (22.22 %), respectively, p = 0.48). Preterm birth < 37 WG was lower in the sleeve group (5/145 (3.45%) vs 12/99 (12.12 %) in the bypass group (p = 0.01), as well as NICU hospitalizations (3 (2.07%) vs 12/99 (12.12%), p < 0.01). There was no difference regarding adverse maternal outcomes such as gestational diabetes and hypertensive complications. The proportion of SGA was not lower in patients with bypass when adjusting for other risk factors (BMI, smoking, geographic origin, diabetes and hypertension) (aOR 0.70; 95%CI 0.01 - 2.85). Conclusion: sleeve was associated with an incidence of SGA which was as high as after bypass, however the incidence of preterm birth was lower.

ACTION-FRANCE: Insights into Perceptions, Attitudes, and Barriers to Obesity Management in France.

Background/Objectives: ACTION-FRANCE (Awareness, Care, and Treatment In Obesity maNagement in France) aims to identify the perceptions, attitudes, behaviors, and potential barriers to effective obesity management in France and guide collaborative actions. Methods: ACTION-FRANCE is a cross-sectional survey of people with obesity (PwO) and healthcare professionals (HCPs) in France. The PwO and HCP survey questionnaire periods ran from 27 September 2022 to 1 February 2023 and from 19 December 2022 to 31 March 2023, respectively. Results: The study, encompassing 1226 PwO and 166 HCPs, reveals a shared recognition of obesity as a chronic condition. However, despite being requested by most PwO, weight-related discussions are surprisingly infrequent, leading to delayed diagnosis and care. PwO and HCPs held different views as to why: HCPs often attributed it to PwO's lack of motivation or disinterest, whereas PwO avoided them because they felt weight management was their own responsibility and were uncomfortable discussing it. When weight was discussed, primarily with general practitioners (GPs), discussions mostly focused on physical activity and diet. However, results identified the strong psychosocial impact of obesity: 42% of respondents reported anxiety/depressive symptoms, and many more hesitated to engage in certain social activities because of their weight. Psychotherapy was only discussed by 55% of HCPs. Pharmaceutical options were also rarely discussed (19.5% of HCPs), though 56.1% of PwO reported they would want to. Conclusions: HCPs' and PwO's perceptions differed significantly and need to converge through enhanced communication. A holistic approach, integrating comprehensive training for GPs and recognizing psychological comorbidities, would help to bridge perceptual gaps effectively and foster more empathetic and effective patient care.

Prader-Willi syndrome: Symptoms and topiramate response in light of genetics.

Introduction: Prader-Willi Syndrome (PWS) is a rare genetic condition, which affects one in 25,000 births and results in various phenotypes. It leads to a wide range of metabolic and endocrine disorders including growth delay, hypogonadism, narcolepsy, lack of satiety and compulsive eating, associated with mild to moderate cognitive impairment. Prognosis is especially determined by the complications of obesity (diabetes, cardiorespiratory diseases) and by severe behavioral disorders marked by impulsivity and compulsion. This heterogeneous clinical picture may lead to mis- or delayed diagnosis of comorbidities. Moreover, when diagnosis is made, treatment remains limited, with high interindividual differences in drug response. This may be due to the underlying genetic variability of the syndrome, which can involve several different genetic mutations, notably deletion or uniparental disomy (UPD) in a region of chromosome 15. Here, we propose to determine whether subjects with PWS differ for clinical phenotype and treatment response depending on the underlying genetic anomaly. Methods: We retrospectively included all 24 PWS patients who were referred to the Reference Center for Rare Psychiatric Disorders (GHU Paris Psychiatrie and Neurosciences) between November 2018 and July 2022, with either deletion (N = 8) or disomy (N = 16). The following socio-demographic and clinical characteristics were recorded: age, sex, psychiatric and non-psychiatric symptoms, the type of genetic defect, medication and treatment response to topiramate, which was evaluated in terms of eating compulsions and impulsive behaviors. We compared topiramate treatment doses and responses between PWS with deletion and those with disomy. Non-parametric tests were used with random permutations for p-value and bootstrap 95% confidence interval computations. Results: First, we found that disomy was associated with a more severe clinical phenotype than deletion. Second, we observed that topiramate was less effective and less tolerated in disomy, compared to deletion. Discussion: These results suggest that a pharmacogenomic-based approach may be relevant for the treatment of compulsions in PWS, thus highlighting the importance of personalized medicine for such complex heterogeneous disorders.

Corrigendum: Prader-Willi syndrome: Symptoms and topiramate response in light of genetics.

[This corrects the article DOI: 10.3389/fnins.2023.1126970.].

Endoscopic Follow-Up Between 3 and 7 Years After Sleeve Gastrectomy Reveals Antral Reactive Gastropathy but no Barrett's Esophagus.

BACKGROUND: The main concerns following sleeve gastrectomy (SG) include the risk of gastroesophageal reflux disease (GERD) and its complications, such as Barrett's esophagus (BE). However, there is conflicting data on esophageal conditions, and studies on alterations of gastric mucosa after SG are lacking, despite reported cases of gastric cancer. Our aim was to assess esophageal and gastric lesions after SG. METHODS: From November 2017, an upper gastrointestinal endoscopy (UGE) was proposed at least 3 years after SG to all patients operated on in our institution. Endoscopic results and gastric histological findings were analyzed. BE was defined as endoscopically suspected esophageal metaplasia with histological intestinal metaplasia. RESULTS: Between September 2008 and August 2018, 375 patients underwent SG at our institution, of which 162 (43%) underwent at least one UGE 3 years or more after SG (91% women, mean preoperative age: 43.3±10.3 years). Despite a significant increase in the prevalence of symptomatic GERD, hiatal hernia, and esophagitis after SG (p<0.001 vs. preoperatively), no cases of BE were detected. Gastric dysplasia was not found and the prevalence of gastric atrophy tended to decrease after SG. However, 27% of patients with gastric biopsies developed antral reactive gastropathy. CONCLUSIONS: At a mean follow-up of 54 months after SG, no BE or gastric dysplasia was identified. However, reactive gastric lesions appeared, and their long-term consequences need to be further clarified. Thus, the timing of endoscopic follow-up, starting as early as 3 years after SG should be reevaluated to improve patient adherence with long-term endoscopies.

No Long-Term Mucosal Lesions in the Esophagus but More Gastric Mucosal Lesions after Sleeve Gastrectomy in Obese Rats.

Sleeve gastrectomy (SG) often induces gastroesophageal reflux, with few and discordant long-term data on the risk of Barrett's esophagus (BE) in operated patients. The aim of this study was to analyze the impact of SG on esogastric mucosa in a rat model at 24 weeks postoperatively, which corresponds to approximately 18 years in humans. After 3 months of a high-fat diet, obese male Wistar rats were subjected to SG (n = 7) or sham surgery (n = 9). Esophageal and gastric bile acid (BA) concentrations were measured at sacrifice, at 24 weeks postoperatively. Esophageal and gastric tissues were analyzed by routine histology. The esophageal mucosa of the SG rats (n = 6) was not significantly different in comparison to that of the sham rats (n = 8), with no esophagitis or BE. However, there was more antral and fundic foveolar hyperplasia in the mucosa of the residual stomach 24 weeks after SG than in the sham group (p < 0.001). Luminal esogastric BA concentrations did not differ between the two groups. In our study, SG induced gastric foveolar hyperplasia but no esophageal lesions at 24 weeks postoperatively in obese rats. Therefore, long-term endoscopic esophageal follow-up that is recommended in humans after SG to detect BE may also be useful for detecting gastric lesions.

Early humoral response to COVID-19 vaccination in patients living with obesity and diabetes in France. The COVPOP OBEDIAB study with results from the ANRS0001S COV-POPART cohort.

BACKGROUND: Patients with diabetes and obesity are populations at high-risk for severe COVID-19 outcomes and have shown blunted immune responses when administered different vaccines. Here we used the 'ANRS0001S COV-POPART' French nationwide multicenter prospective cohort to investigate early humoral response to COVID-19 vaccination in the sub-cohort ('COVPOP OBEDIAB') of patients with obesity and diabetes. METHODS: Patients with diabetes (n = 390, type 1 or 2) or obesity (n = 357) who had received two vaccine doses and had no history of previous COVID-19 infection and negative anti-nucleocapsid (NCP) antibodies were included and compared against healthy subjects (n = 573). Humoral response was assessed at baseline, at one month post-first dose (M0) and one-month post-second dose (M1), through percentage of responders (positive anti-spike SARS-CoV-2 IgG antibodies (Sabs), geometric means of Sabs; BAU/mL), proportion of individuals with anti-RBD antibodies, and proportion of individuals with anti-SARS-CoV-2-specific neutralizing antibodies (Nabs). Potential clinical and biological factors associated with weak response (defined as Sabs < 264 BAU/mL) and presence of non-reactive anti-RBD antibodies at M1 were evaluated. Univariate and multivariate regressions were performed to estimate crude and adjusted coefficients with 95 % confidence intervals. Poor glycemic control was defined as HbA1c ≥ 7.5 % at inclusion. RESULTS: Patients with diabetes, particularly type 2 diabetes, and patients with obesity were less likely to have positive Sabs and anti-RBD antibodies after the first and second dose compared to controls (p < 0.001). At M1, we found Sabs seroconversion in 94.1 % of patients with diabetes versus 99.7 % in controls, anti-RBD seroconversion in 93.8 % of patients with diabetes versus 99.1 % in controls, and Nabs seroconversion in 95.7 % of patients with diabetes versus 99.6 % in controls (all p < 0.0001). Sabs and anti-RBD seroconversion at M0 and M1 were also significantly lower in obese patients than controls, at respectively 82.1 % versus 89.9 % (p = 0.001; M0 Sabs), 94.4 % versus 99.7 % (p 0.001; M1 Sabs), 79.0 % vs 86.2 % (p = 0.004 M0 anti-RBD), and 96.99 % vs 99.1 % (p = 0.012 M1 anti-RBD). The factors associated with low vaccine response (BAU < 264/mL) in patients with diabetes were chronic kidney disease (adjusted OR = 6.88 [1.77;26.77], p = 0.005) and poor glycemic control (adjusted OR = 3.92 [1.26;12.14], p = 0.018). In addition, BMI ≥ 40 kg/m2 was found to be associated with a higher vaccine response (adjusted OR = 0.10 [0.01;0.91], p = 0.040) than patients with BMI < 40 kg/m2. CONCLUSION: COVID-19 vaccine humoral response was lower in patients with obesity and diabetes one month after second dose compared to controls, especially in diabetic patients with CKD or inadequate glycemic control. These findings point to the need for post-vaccination serological checks in these high-risk populations.

Risk-Benefit Balance Associated With Obstetric, Neonatal, and Child Outcomes After Metabolic and Bariatric Surgery.

Importance: Metabolic and bariatric surgery (MBS) is the most efficient therapeutic option for severe obesity. Most patients who undergo MBS are women of childbearing age. Data in the scientific literature are generally of a low quality due to a lack of well-controlled prospective trials regarding obstetric, neonatal, and child outcomes. Objective: To assess the risk-benefit balance associated with MBS around obstetric, neonatal, and child outcomes. Design, Setting, and Participants: The study included 53 813 women on the French nationwide database who underwent an MBS procedure and delivered a child between January 2012 and December 2018. Each women was their own control by comparing pregnancies before and after MBS. Exposures: The women included were exposed to either gastric bypass or sleeve gastrectomy. Main Outcomes and Measures: The study team first compared prematurity and birth weights in neonates born before and after maternal MBS with each other. Then they compared the frequencies of all pregnancy and child diagnoses in the first 2 years of life before and after maternal MBS with each other. Results: A total of 53 813 women (median [IQR] age at surgery, 30 [26-35] years) were included, among 3686 women who had 1 pregnancy both before and after MBS. The study team found a significant increase in the small-for-gestational-age neonate rate after MBS (+4.4%) and a significant decrease in the large-for-gestational-age neonate rate (-12.6%). The study team highlighted that compared with pre-MBS births, after MBS births had fewer occurrences of gestational hypertension (odds ratio [OR], 0.16; 95% CI, 0.10-0.23) and gestational diabetes for the mother (OR, 0.39; 95% CI, 0.34-0.45), as well as fewer birth injuries to the skeleton (OR, 0.27; 95% CI, 0.11-0.60), febrile convulsions (OR, 0.39; 95% CI, 0.21-0.67), viral intestinal infections (OR, 0.56; 95% CI, 0.43-0.71), or carbohydrate metabolism disorders in newborns (OR, 0.54; 95% CI 0.46-0.63), but an elevated respiratory failure rate (OR, 2.42; 95% CI, 1.76-3.36) associated with bronchiolitis. Conclusions and Relevance: The risk-benefit balance associated with MBS is highly favorable for pregnancies and newborns but may cause an increased risk of respiratory failure associated with bronchiolitis. Further studies are needed to better assess the middle- and long-term benefits and risks associated with MBS.

Malignancies in Prader-Willi Syndrome: Results From a Large International Cohort and Literature Review.

CONTEXT: Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of the PWS critical region, a cluster of paternally expressed genes on chromosome 15q11.2-q13. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health. OBJECTIVE: To investigate the prevalence and risk factors of malignancies in patients with PWS and to provide clinical recommendations for cancer screening. METHODS: We included 706 patients with PWS (160 children, 546 adults). We retrospectively collected data from medical records on past or current malignancies, the type of malignancy, and risk factors for malignancy. Additionally, we searched the literature for information about the relationship between genes on chromosome 15q11.2-q13 and malignancies. RESULTS: Seven adults (age range, 18-55 years) had been diagnosed with a malignancy (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, stomach adenocarcinoma, biliary cancer, parotid adenocarcinoma, and colon cancer). All patients with a malignancy had a paternal 15q11-13 deletion. The literature review showed that several genes on chromosome 15q11.2-q13 are related to malignancies. CONCLUSION: Malignancies are rare in patients with PWS. Therefore, screening for malignancies is only indicated when clinically relevant symptoms are present, such as unexplained weight loss, loss of appetite, symptoms suggestive of paraneoplastic syndrome, or localizing symptoms. Given the increased cancer risk associated with obesity, which is common in PWS, participation in national screening programs should be encouraged.

[Pregnancy after bariatric surgery]. / Grossesse après une chirurgie bariatrique.

PREGNANCY AFTER BARIATRIC SURGERY Pregnancy after bariatric surgery is a high-risk pregnan¬cy that requires multidisciplinary management. Although maternal pathologies (gestational diabetes and gravid hypertension) and the risk of macrosomia are greatly reduced, the risk of prematurity and small for gestatio¬nal age is increased. Nutritional needs are specific, and require adapting supplements and reinforcing biological monitoring during pregnancy and lactation, taking into account the specificities of interpretation of biological results in this context. Surgical complications are rare (displacement of the gastric band, occlusion due to internal hernia after Roux-en-Y gastric bypass) but must be systematically evoked in the presence of vomiting or abdominal pain because the maternal-fetal prognosis depends on the rapidity of surgical management. A postoperative conception delay of at least 12 months should be respected and effective contraception pres¬cribed in this perspective. Long-term cohort studies are necessary to better understand the long-term outcomes for children.

GROSSESSE APRÈS UNE CHIRURGIE BARIATRIQUE La grossesse après chirurgie bariatrique est une grossesse à risque qui nécessite une prise en charge multidisciplinaire. Si les pathologies maternelles (diabète gestationnel et hypertension artérielle gravidique) et le risque de macrosomie sont considérablement réduits, celui de prématurité et de foetus petit pour l'âge gestationnel augmente. Les besoins nutritionnels sont spécifiques, ce qui nécessite d'adapter les supplémentations et de renforcer la surveillance biologique pendant la grossesse et l'allaitement, en tenant compte des spécificités d'interprétation des résultats biologiques dans ce contexte. Les complications chirurgicales sont rares (déplacement de l'anneau gastrique, occlusion sur hernie interne après bypass gastrique en Y) mais doivent être systématiquement évoquées devant des vomissements ou des douleurs abdominales car le pronostic materno-foetal dépend de la rapidité de la prise en charge chirurgicale. Un délai de conception postopératoire d'au moins douze mois devrait être respecté, et une contraception efficace prescrite pour cette raison. Des études de cohorte à long terme sont nécessaires pour mieux connaître les enjeux de ces grossesses, notamment sur le devenir des enfants.

Conversion of One Anastomosis Gastric Bypass to Roux-en-Y Gastric Bypass: Results of a Retrospective Multicenter Study.

BACKGROUND: One anastomosis gastric bypass (OAGB) may expose the patient to certain specific complications. Here, we report the results of conversion of OAGB to Roux-en-Y gastric bypass (RYGB) in terms of outcomes and weight loss. METHODS: Between January 2009 and January 2019, all patients undergoing conversion of OAGB to RYGB because of complications due to OAGB (n = 23) were included. The primary efficacy endpoint was the effectiveness of converting OAGB to RYGB. The secondary endpoints were overall mortality and morbidity during the first 3 postoperative months, specific morbidity, reoperation, length of hospitalization, weight loss, and progression of comorbidities related to obesity at 2-year follow-up. RESULTS: Indications for conversion were bile reflux (n = 14; 60.9%), severe malnutrition (n = 3; 13%), gastro-gastric fistula (n = 4; 17.4%), and anastomotic leak (n = 2; 8.7%). The median time interval between OAGB and conversion to RYGB was 34 months (0-158). At the time of RYGB, median body mass index (BMI) was 28.0 kg/m2 (18.2-50.7), representing a median BMI change of 14.0 (- 1.7-43.5). Fifteen surgeries (65.1%) were completed laparoscopically. Five complications (21.7%) were recorded, including 2 major ones (8.7%). Reoperation rate was 4.3% (n = 1). At 24 months of follow-up (n = 18; 78.3%), median BMI was 28.7 kg/m2 (19.4-35.4), representing a median BMI change of 19.5 (12.2-43.1). No patient complained of bile reflux or persistent malnutrition. CONCLUSION: RYGB performed as revisional surgery for complications after OAGB is an effective procedure with no major weight regain at 2 years of follow-up.

Sleep Disorders in Adults with Prader-Willi Syndrome: Review of the Literature and Clinical Recommendations Based on the Experience of the French Reference Centre.

Prader-Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered breathing and central disorders of hypersomnolence. Excessive daytime sleepiness represents the main manifestation that should be addressed by eliciting the detrimental effects on quality of life and neurocognitive function from the patients' caregivers. Patients with PWS have impaired ventilatory control and altered pulmonary mechanics caused by hypotonia, respiratory muscle weakness, scoliosis and obesity. Consequently, respiratory abnormalities are frequent and, in most cases, severe, particularly during sleep. Adults with PWS frequently suffer from sleep apnoea syndrome, sleep hypoxemia and sleep hypoventilation. When excessive daytime sleepiness persists after adequate control of sleep-disordered breathing, a sleep study on ventilatory treatment, followed by an objective measurement of excessive daytime sleepiness, is recommended. These tests frequently identify central disorders of hypersomnolence, including narcolepsy, central hypersomnia or a borderline hypersomnolent phenotype. The use of wake-enhancing drugs (modafinil, pitolisant) is discussed in multidisciplinary expert centres for these kinds of cases to ensure the right balance between the benefits on quality of life and the risk of psychological and cardiovascular side effects.

Bone Health in Adults With Prader-Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study.

CONTEXT: Prader-Willi syndrome (PWS) is a rare complex genetic syndrome, characterized by delayed psychomotor development, hypotonia, and hyperphagia. Hormone deficiencies such as hypogonadism, hypothyroidism, and growth hormone deficiency are common. The combination of hypotonia, low physical activity, and hypogonadism might lead to a decrease in bone mass and increase in fracture risk. Moreover, one would expect an increased risk of scoliosis due to hypotonia and low physical activity. OBJECTIVE: To study the prevalence and risk factors for skeletal problems (reduced bone mineral density, fractures, and scoliosis) in adults with PWS. METHODS: We retrospectively collected patient characteristics, medical history, medication, biochemical measurements, dual-energy X-ray absorptiometry scans, and spinal X-rays and reviewed the current literature. RESULTS: We included 354 adults with PWS (median age 31 years; 43% males), of whom 51 (14%) had osteoporosis (T-score below -2.5) and 143 (54%) had osteopenia (T-score -1 to -2.5). The most prevalent modifiable risk factors for osteoporosis were hypogonadism, insufficient dairy intake, sedentary lifestyle, and corticosteroid use. Male sex was associated with osteoporosis (P = .005). Growth hormone treatment was not associated with osteoporosis. A history of vertebral fractures was present in 10 (3%) and nonvertebral fractures in 59 (17%). Scoliosis was present in 263 (80%), but no modifiable risk factors were identified. CONCLUSION: Besides scoliosis, osteoporosis is common in adults with PWS. Based on the literature and the risk factors for osteoporosis found in our cohort, we provide practical clinical recommendations to avoid skeletal complications in these vulnerable patients.