Bariatric procedures including Roux-en-Y gastric bypass in French adolescents.

INTRODUCTION: In France, approximately 100 obese adolescents undergo a bariatric procedure every year. To date, only data from laparoscopic adjustable gastric banding (LAGB) or sleeve gastrectomy (SG) have been published. Our objective was to report the outcomes of a series of French obese adolescents who underwent a Roux-en-Y gastric bypass (RYGB). METHODS: We included all obese adolescents aged 13-19 years who underwent RYGB in our department from 2008 with at least 2 years of follow-up after surgery. We analyzed the course of the anthropometric data, comorbidities, and subsequent adverse events. RESULTS: Starting in September 2008, out of 93 obese adolescents who requested bariatric surgery, 39 (35%) underwent a bariatric procedure. From these adolescents, 2-year follow-up data were available for 26 patients who had a RYGB. At the time of surgery, the mean patient age was 17.4 years (standard deviation [SD]=1.4) and the body mass index (BMI) was 52.0 kg/m² (SD=7.8). One patient was lost to follow-up. At 2 years after surgery,  the mean BMI was 35.7 kg/m² (SD=9.4) with a mean decrease in BMI of 31.9% (SD=11.6). Comorbidities improved for most of the patients: high blood pressure (2/2) and pseudotumor cerebri (1/1) were cured after surgery, and dyslipidemia improved globally. The complications observed were anemia, abdominal pain requiring celioscopy (n = 2), and oxalic nephrolithiasis. CONCLUSION: Only one third of the obese adolescents requesting bariatric surgery were operated on. Our series including exclusively obese adolescents who underwent an RYGB presents the results of this technique on weight loss and comorbidities; mechanical and nutritional complications remain uncommon. These results are similar to those obtained in studies of adult patients.

Implication of Heterozygous Variants in Genes of the Leptin-Melanocortin Pathway in Severe Obesity.

CONTEXT: Unlike homozygous variants, the implication of heterozygous variants on the leptin-melanocortin pathway in severe obesity has not been established. OBJECTIVE: To describe the frequency, the phenotype, and the genotype-phenotype relationship for heterozygous variants in LEP, LEPR, POMC, and PCSK1 in severe obesity. METHODS: In this retrospective study, genotyping was performed on at least 1 of the LEP, LEPR, POMC, and PCSK1 genes in 1486 probands with severe obesity (600 children, 886 adults). The phenotype was collected in 60 subjects with heterozygous variants and 16 with homozygous variants. We analyzed variant frequency, body mass index (BMI), age of obesity onset, food impulsivity, and endocrine abnormalities. RESULTS: The frequency of subjects with homozygous variants was 1.7% (n = 26), and 6.7% (n = 100) with heterozygous variants. Adults with homozygous variants had a higher BMI (66 vs 53 kg/m2, P = .015), an earlier onset of obesity (0.4 vs 5.4 years, P < .001), more often food impulsivity (83% vs 42%, P = .04), and endocrine abnormalities (75% vs 26%, P < .01). The BMI was higher for subjects with high-impact heterozygous variants (61 vs 50 kg/m², P = .045) and those with a second heterozygous variant on the pathway (65 vs 49 kg/m², P < .01). In children, no significant differences were found for the age of obesity onset and BMI. CONCLUSION: Heterozygous variants in LEP, LEPR, POMC, and PCSK1 are frequent in severe obesity and sometimes associated with a phenotype close to that of homozygotes. These data suggest a systematic search for variants in severe early-onset obesity, to discuss therapy that targets this key pathway.

Multichamber Dysfunction in Children and Adolescents With Severe Obesity: A Cardiac Magnetic Resonance Imaging Myocardial Strain Study.

BACKGROUND: In severe obesity, left ventricular (LV) and right ventricular (RV) remodeling and contractile dysfunction have been documented, but less is known regarding left atrial (LA) dysfunction and its association with LV/RV remodeling, especially in children. PURPOSE: To assess the effects of severe childhood obesity on cardiac function by using multichamber strain analysis with MRI. STUDY TYPE: Prospective. SUBJECTS: Forty-five children aged 7-18 years (including 20 with severe obesity, defined as a body mass index values above the 99th percentile). FIELD STRENGTH: 5 T. SEQUENCE: Steady-state-free-precession (SSFP) images in short-axis views and longitudinal two- and four-chamber views. ASSESSMENT: Cardiac strain measurements were derived from standard SSFP cine images by using a dedicated MR imaging feature tracking software. Inter- and intra-rater reliability were evaluated. STATISTICAL TESTS: Independent sample t test, Spearman's correlation coefficient, principal component analysis, Bland-Altman analysis, and intra-class correlation coefficients (ICC). A P value <0.05 was considered statistically significant. RESULTS: As compared to children without obesity, those with obesity showed significantly reduced LA reservoir function (22.2% ± 6.4% vs. 33.8% ± 9.0%) and contractile function (5.4% ± 3.2% vs. 13.3% ± 8.0%) as well as significantly decreased absolute values for LA longitudinal strain in reservoir and contraction phases and LA radial motion fraction in reservoir and contraction phases. Children with severe obesity showed significantly reduced absolute RV radial motion fraction (-10.6% ± 2.9% vs. -18.2% ± 2.9%) and circumferential strain (-10.6% ± 2.9% vs. -16% ± 2.5%) as well as higher LV mass index (28.7% ± 5.1% vs. 21.7 ± 4.6 g/m2 ) along with significantly reduced LV ejection fraction (56.4% ± 3.9% vs. 60% ± 4.1%), LV radial strain (56% ± 6% vs. 61.8% ± 11.3%), and longitudinal strain (-17.8% ± 1.8% vs. -20.3% ± 3.2%). Reliability was good to excellent, with ICC ranging from 79.1% to 97.7%. DATA CONCLUSION: MR feature-tracking strain analysis revealed multichamber dysfunction in severely obese children with impaired LA reservoir and atrial contraction phases, which suggest an early loss in the compensatory ability of atrial contraction with severe obesity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Intermediate-Term Efficacy and Tolerance of Statins in Children.

OBJECTIVES: To evaluate the intermediate-term efficacy and tolerance of statins in children and adolescents with familial hypercholesterolemia. STUDY DESIGN: A total of 131 children or adolescents treated with statins for familial hypercholesterolemia were prospectively included. The efficacy of treatment was established by the percentage of children who achieved low density lipoprotein-cholesterol (LDL-C) levels <160 mg/dL during treatment. Treatment tolerance was evaluated by the occurrence of clinical or laboratory side effects, regularity of increases in height and weight, and pubertal development. RESULTS: The median duration of treatment with statins was 4 years. A median decrease of 32% in LDL-C levels was observed (P < .0001). The therapeutic target (LDL-C <160 mg/dL) was achieved in 67% of cases. Increases in height and weight and sexual maturation were not affected by the treatment. Minor side effects were reported for 24 (18.4%) patients including 3 cases of a clinically asymptomatic increase in creatine phosphokinase (CPK) levels, 2 cases of an increase in CPK levels with muscular symptoms, 14 cases of myalgia without an increase in CPK levels, 3 cases of abdominal pain, 1 case of dysuria, and 1 case of diffuse pain. None of these side effects led to the discontinuation of statin therapy, although a change of statin was required in 7 cases. This new statin was tolerated in all cases. No patients had abnormal liver function during treatment. CONCLUSIONS: The results of this large cohort confirm the intermediate-term safety and efficacy of statin therapy in children with familial hypercholesterolemia.

Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France.

Autosomal dominant hypercholesterolemia (ADH) is a human disorder characterized phenotypically by isolated high-cholesterol levels. Mutations in the low density lipoprotein receptor (LDLR), APOB, and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes are well known to be associated with the disease. To characterize the genetic background associated with ADH in France, the three ADH-associated genes were sequenced in a cohort of 120 children and 109 adult patients. Fifty-one percent of the cohort had a possible deleterious variant in LDLR, 3.1% in APOB, and 1.7% in PCSK9. We identified 18 new variants in LDLR and 2 in PCSK9. Three LDLR variants, including two newly identified, were studied by minigene reporter assay confirming the predicted effects on splicing. Additionally, as recently an in-frame deletion in the APOE gene was found to be linked to ADH, the sequencing of this latter gene was performed in patients without a deleterious variant in the three former genes. An APOE variant was identified in three patients with isolated severe hypercholesterolemia giving a frequency of 1.3% in the cohort. Therefore, even though LDLR mutations are the major cause of ADH with a large mutation spectrum, APOE variants were found to be significantly associated with the disease. Furthermore, using structural analysis and modeling, the identified APOE sequence changes were predicted to impact protein function.