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.

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.

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.

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

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

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.

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.

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.

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.

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.

[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.

Hypogonadism in Women with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion.

Prader-Willi syndrome (PWS) is a rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent. Untreated hypogonadism can cause osteoporosis, which is already an important issue in PWS. Therefore, timely detection and treatment of hypogonadism is crucial. To increase understanding and prevent undertreatment, we (1) performed a cohort study in the Dutch PWS population, (2) thoroughly reviewed the literature on female hypogonadism in PWS and (3) provide clinical recommendations on behalf of an international expert panel. For the cohort study, we retrospectively collected results of a systematic health screening in 64 female adults with PWS, which included a medical questionnaire, medical file search, medical interview, physical examination and biochemical measurements. Our data show that hypogonadism is frequent in females with PWS (94%), but is often undiagnosed and untreated. This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or drug interactions. To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS.

Prospective comparison of transient elastography, MRI and serum scores for grading steatosis and detecting non-alcoholic steatohepatitis in bariatric surgery candidates.

BACKGROUND & AIMS: Tools for the non-invasive diagnosis of non-alcoholic steatohepatitis (NASH) in morbidly obese patients with suspected non-alcoholic fatty liver disease (NAFLD) are an unmet clinical need. We prospectively compared the performance of transient elastography, MRI, and 3 serum scores for the diagnosis of NAFLD, grading of steatosis and detection of NASH in bariatric surgery candidates. METHODS: Of 186 patients screened, 152 underwent liver biopsy, which was used as a reference for NAFLD (steatosis [S]>5%), steatosis grading and NASH diagnosis. Biopsies were read by a single expert pathologist. MRI-based proton density fat fraction (MRI-PDFF) was measured in an open-bore, vertical field 1.0T scanner and controlled attenuation parameter (CAP) was measured by transient elastography, using the XL probe. Serum scores (SteatoTest, hepatic steatosis index and fatty liver index) were also calculated. RESULTS: The applicability of MRI was better than that of FibroScan (98% vs. 79%; p <0.0001). CAP had AUROCs of 0.83, 0.79, 0.73 and 0.69 for S>5%, S>33%, S>66% and NASH, respectively. Transient elastography had an AUROC of 0.80 for significant fibrosis (F0-F1 vs. F2-F3). MRI-PDFF had AUROCs of 0.97, 0.95, 0.92 and 0.84 for S>5%, S>33%, S>66% and NASH, respectively. When compared head-to-head in the 97 patients with all valid tests available, MRI-PDFF outperformed CAP for grading steatosis (S>33%, AUROC 0.97 vs. 0.78; p <0.0003 and S>66%, AUROC 0.93 vs. 0.75; p = 0.0015) and diagnosing NASH (AUROC 0.82 vs. 0.68; p = 0.0056). When compared in "intention to diagnose" analysis, MRI-PDFF outperformed CAP, hepatic steatosis index and fatty liver index for grading steatosis (S>5%, S>33% and S>66%). CONCLUSION: MRI-PDFF outperforms CAP for diagnosing NAFLD, grading steatosis and excluding NASH in morbidly obese patients undergoing bariatric surgery. LAY SUMMARY: Non-invasive tests for detecting fatty liver and steatohepatitis, the active form of the disease, have not been well studied in obese patients who are candidates for bariatric surgery. The most popular tests for this purpose are Fibroscan, which can be used to measure the controlled attenuation parameter (CAP), and magnetic resonance imaging, which can be used to measure the proton density fat fraction (MRI-PDFF). We found that, when taking liver biopsy as a reference, MRI-PDFF performed better than CAP for detecting and grading fatty liver as well as excluding steatohepatitis in morbidly obese patients undergoing bariatric surgery.

Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients.

Type 2 diabetes mellitus (T2DM) affects 20% of patients with Prader-Willi syndrome (PWS), with many cases diagnosed during the transition period. Our aim was to describe the natural history of T2DM in patients with PWS before the age of 25 years and to develop screening and preventive strategies. Thirty-nine patients followed in the French PWS Reference Center were included (median age 25.6 years [23.7; 31.7]). Twenty-one had been treated with growth hormone (GH), fifteen had not, and three had an unknown status. The median age at T2DM diagnosis was 16.8 years (11-24) and the median BMI was 39 kg/m2 [34.6; 45], with 34/35 patients living with obesity. The patients displayed frequent psychiatric (48.3% hospitalization,) and metabolic (56.4% hypertriglyceridemia,) comorbidities and a parental history of T2DM (35.7%) or overweight (53.6%) compared to the PWS general population. There was no difference in BMI and metabolic complications between the GH-treated and non-GH-treated groups at T2DM diagnosis. Patients with PWS who develop early T2DM have severe obesity, a high frequency of psychiatric and metabolic disorders, and a family history of T2DM and overweight. These results underline the need for early identification of patients at risk, prevention of obesity, and repeated blood glucose monitoring during the transition period.

Hypogonadism in Adult Males with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion.

Prader-Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue. Therefore, timely diagnosis and treatment of male hypogonadism is important. In this article, we share our experience with hypogonadism and its treatment in adult males with PWS and present a review of the literature. In order to report the prevalence and type of hypogonadism, treatment regimen and behavioral issues, we retrospectively collected data on medical interviews, physical examinations, biochemical measurements and testosterone replacement therapy (TRT) in 57 Dutch men with PWS. Fifty-six (98%) of the patients had either primary, central or combined hypogonadism. Untreated hypogonadism was associated with higher body mass index and lower hemoglobin concentrations. TRT was complicated by behavioral challenges in one third of the patients. Undertreatment was common and normal serum testosterone levels were achieved in only 30% of the patients. Based on the Dutch cohort data, review of the literature and an international expert panel discussion, we provide a practical algorithm for TRT in adult males with PWS in order to prevent undertreatment and related adverse health outcomes.

Hepcidin and Iron Deficiency in Women One Year after Sleeve Gastrectomy: A Prospective Cohort Study.

Iron deficiency with or without anemia, needing continuous iron supplementation, is very common in obese patients, particularly those requiring bariatric surgery. The aim of this study was to address the impact of weight loss on the rescue of iron balance in patients who underwent sleeve gastrectomy (SG), a procedure that preserves the duodenum, the main site of iron absorption. The cohort included 88 obese women; sampling of blood and duodenal biopsies of 35 patients were performed before and one year after SG. An analysis of the 35 patients consisted in evaluating iron homeostasis including hepcidin, markers of erythroid iron deficiency (soluble transferrin receptor (sTfR) and erythrocyte protoporphyrin (PPIX)), expression of duodenal iron transporters (DMT1 and ferroportin) and inflammatory markers. After surgery, sTfR and PPIX were decreased. Serum hepcidin levels were increased despite the significant reduction in inflammation. DMT1 abundance was negatively correlated with higher level of serum hepcidin. Ferroportin abundance was not modified. This study shed a new light in effective iron recovery pathways after SG involving suppression of inflammation, improvement of iron absorption, iron supply and efficiency of erythropoiesis, and finally beneficial control of iron homeostasis by hepcidin. Thus, recommendations for iron supplementation of patients after SG should take into account these new parameters of iron status assessment.

Hyponatremia in Children and Adults with Prader-Willi Syndrome: A Survey Involving Seven Countries.

In Prader-Willi syndrome (PWS), conditions that are associated with hyponatremia are common, such as excessive fluid intake (EFI), desmopressin use and syndrome of inappropriate antidiuretic hormone (SIADH) caused by psychotropic medication. However, the prevalence of hyponatremia in PWS has rarely been reported. Our aim was to describe the prevalence and severity of hyponatremia in PWS. In October 2020, we performed a retrospective study based on the medical records of a large cohort of children and adults with PWS from seven countries. Among 1326 patients (68% adults), 34 (2.6%) had at least one episode of mild or moderate hyponatremia (125 ≤ Na < 135 mmol/L). The causes of non-severe hyponatremia were often multi-factorial, including psychotropic medication in 32%, EFI in 24% and hyperglycemia in 12%. No obvious cause was found in 29%. Seven (0.5%) adults experienced severe hyponatremia (Na < 125 mmol/L). Among these, five recovered completely, but two died. The causes of severe hyponatremia were desmopressin treatment for nocturnal enuresis (n = 2), EFI (n = 2), adrenal insufficiency (n = 1), diuretic treatment (n = 1) and unknown (n = 1). In conclusion, severe hyponatremia was very rare but potentially fatal in PWS. Desmopressin treatment for nocturnal enuresis should be avoided. Enquiring about EFI and monitoring serum sodium should be included in the routine follow-ups of patients with PWS.

Paradoxical low severity of COVID-19 in Prader-Willi syndrome: data from a French survey on 647 patients.

BACKGROUND: Patients with Prader-Willi syndrome (PWS) often have comorbidities, especially obesity, that may constitute a risk factor for severe forms of COVID-19. We aimed to assess prevalence and medical course of SARS-CoV-2 infection in children and adults with PWS. From November 2020 to January 2021, we performed a detailed medical survey on 342 adults and 305 children with PWS followed in the French reference center. RESULTS: We obtained responses from 288 adults (84%) and 239 children (78%). From March 2020 to January 2021, 38 adults (13.2%) and 13 children (5.4%) with PWS had SARS-CoV-2 infection. Mean age of adults was 34.1 ± 11.9 years and mean body mass index was 40.6 ± 12.7 kg/m2; 82% had obesity and 37% had diabetes. Only 3 children (23%) had obesity and none had diabetes. Similar to the general population, the most frequent symptoms of COVID-19 were asthenia, fever, cough, headache and shortness of breath. All patients had a favorable outcome. CONCLUSION: PWS itself is not a risk factor for severe COVID-19 in children and adults. On the contrary, evolution of SARS-CoV-2 infection in adults with PWS seems more favorable than expected, given their comorbidities.

Change in Birth Rate Before and After Bariatric Surgery in France.

IMPORTANCE: Bariatric surgery worldwide has grown significantly over the past years and is performed, in a vast majority, in women of childbearing age. The impact of these procedures on birth rates remains largely unknown. OBJECTIVE: The main objective was to study the evolution of the birth rates in these women, before and after bariatric surgery and in comparison with women from the general population. The secondary objectives were to compare the birth rates before and after surgery according to the Body Mass Index (BMI) (BMI 40-50 versus >50 kg/m2). METHOD: Our analyses are based on a national medico-administrative database. All women of childbearing age and who had bariatric surgery between 2012 and 2016 were included, and we included all deliveries between 2012 and 2018 in this population. We compared the birth rates before and after bariatric surgery. National statistics (INSEE, Institut National de la Statistique et des Etudes Economiques) were used for comparison with women from the general population. FINDINGS: A total of 69,932 women were included between 2012 and 2016, with a median age at surgery of 33 years [27; 39]. Among them, 9391 (13%) had a BMI over 50 kg/m2 before surgery, 46,818 (67%) benefited from a sleeve gastrectomy (SG), and 23,376 (33%) from a gastric bypass (GBP). Birth rates tend to be smaller after surgery compared to before surgery for women under 27 years (OR: 0.92, CI95% [0.88; 0.96]), while being not different after 27 in both groups (OR: 1.00, CI95% [0.97; 1.03]). Birth rates of obese women who have benefited or will benefit from the bariatric surgery were higher than the general population, with a peak at a younger age, and then decline earlier than the general population. Trends were different according to BMI class. Birth rates were higher for women with BMI between 40 and 50 kg/m2 compared to women with BMI greater than 50 kg/m2 (OR=1.28, CI95% [1.21; 1.36]) before surgery while slightly lower after surgery (OR=0.95, CI95% [0.91; 0.99]). CONCLUSIONS AND RELEVANCE: We showed that birth rates after bariatric surgery were not different before and after bariatric surgery except for women under 27 years old who had a smaller birth rate. Interestingly, we observed an improvement of birth rates after surgery for women with a BMI of 50 kg/m2 or more.