Long-Term Weight Outcome After Bariatric Surgery in Patients with Melanocortin-4 Receptor Gene Variants: a Case-Control Study of 105 Patients.

INTRODUCTION: Pathogenic heterozygous MC4R variants are associated with hyperphagia and variable degrees of obesity. Several research groups have reported short-term weight loss outcomes after bariatric surgery in a few patients with MC4R variants, but lack of longer-term data prevents evidence-based clinical decision-making. MATERIALS AND METHODS: Bariatric surgery patients with heterozygous (likely) pathogenic MC4R variants, from three collaborating centers in the Netherlands, France, and the UK, were compared to matched controls (matched 2:1 for age, sex, preoperative BMI, surgical procedure, and diabetes mellitus, but without MC4R mutations). Weight loss and regain outcomes up to 6 years of follow-up were compared. RESULTS: At 60 months of follow-up after RYGB, cases with MC4R variants showed weight regain with a mean of 12.8% (± 10.4 SD) total weight loss (TWL) from nadir, compared to 7.9% (± 10.5 SD) in the controls (p = 0.062). Among patients receiving SG, the cases with MC4R variants experienced inferior weight loss (22.6% TWL) during the first year of follow-up compared to the controls (29.9% TWL) (p = 0.010). CONCLUSIONS: This multicenter study reveals inferior mid-term weight outcomes of cases with MC4R variants after SG, compared to RYGB. Since adequate weight loss outcomes were observed after RYGB, this procedure would appear to be an appropriate surgical approach for this group. However, the pattern of weight regain seen in cases with MC4R variants after both RYGB and SG highlights the need for pro-active lifelong management to prevent relapse, as well as careful expectation management.

Bone mineral density at extremely low weight in patients with anorexia nervosa.

OBJECTIVE: Low bone mineral density (BMD) is a frequent and invalidating consequence of chronic undernourishment in patients with anorexia nervosa (AN). The aim of this study was to assess prevalence and clinic-biological correlates of low BMD and fractures in extremely undernourished inpatients with AN. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: This study included 97 extremely malnourished female inpatients with AN consecutively admitted over 2 years. Clinical-biological variables, history of fractures and BMD by dual-energy X-ray absorptiometry (DXA) were examined to find predictors of low BMD and fractures. RESULTS: The prevalence of low BMD was of 51% for lumbar spine and 38% for femoral neck. Z-scores were lower at lumbar spine (-2.2 ± 1.2 SD) than at femoral neck (-1.9 ± 0.9 SD) (P<.01). Fragility fractures were reported by 10% of patients. BMD was mainly predicted by FFM, illness duration, age at onset and restricting AN (P<.05). Fractures were predicted by sodium concentrations, femoral neck Z-score and illness duration (P<.03). CONCLUSION: Extremely severe patients with AN have high prevalence of low BMD, predicted by severity and chronicity of malnutrition.

Evaluation of muscle-skeletal strength and peak expiratory flow in severely malnourished inpatients with anorexia nervosa: A pilot study.

OBJECTIVES: Anorexia nervosa is a complex psychiatric disorder that can lead to specific somatic complications. Malnutrition is frequent and can involve a decrease of mobility, up to functional impotence, in individuals with extremely severe cases. The aim of this pilot study was to examine muscle strength and peak expiratory flow (PEF) in severely undernourished patients with anorexia nervosa at admission and after 5 wk of renutrition by tube feeding, and to find the clinical and biological correlates of muscle-strength impairment. METHODS: A prospective observational study was conducted over 6 mo. Manual muscle testing, measures of PEF, and clinical and biologic assessments were performed at baseline and after 5 wk of renutrition. RESULTS: Twenty-three extremely malnourished female participants (mean body mass index: 11.4 ± 1.3 kg/m2) were included. All participants had global impairment in muscle strength (manual muscle testing: 37.7 ± 7.7) and PEF (253.3 ± 60 mL/min) at admission. Muscle weakness was higher in axial than peripheral muscle groups (P < 0.01), with no significant difference between proximal and distal muscles (P > 0.05). Muscle strength at admission was significantly associated with severity of undernourishment (body mass index and albumin) and transaminitis (P < 0.05). At follow-up, musculoskeletal strength and PEF were significantly improved after partial weight recovery (P < 0.01). CONCLUSIONS: Extremely undernourished people with anorexia nervosa present a decrease of PEF and musculoskeletal strength predominant on axial muscles. Both are associated with severity of malnutrition and liver damage. Partial recovery was observed after 5 wk of enteral nutrition.

What distinguish patients with compulsory treatment for severely undernourished anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a mental disorder potentially leading to severe malnutrition and life-threatening complications, with high mortality rates and dropouts from treatment. In the most severe cases, treatment refusal associated with acute nutritional disorders may require compulsory admission in specialised units. The aim of this study was to investigate clinical and nutritional parameters associated with the use of compulsory treatment for severely ill AN patients requiring intensive nutritional care. METHODS: This retrospective, single-centre study performed in a unit of specialised nutritional care compared severely undernourished inpatients, compulsorily admitted for AN, with a population of sex- and age-matched voluntarily admitted patients. Socio-demographic and clinical variables were collected for univariate comparison and logistic regression. RESULTS: Compulsory treatment in AN was mainly associated with lower socio-economic status (p < 0.01), history of lower weight (p < 0.05), more frequently prescribed psychotropic medication (p = 0.02), more previous admissions for AN, longer hospitalisations (p < 0.01) and binge eating/purging subtype (p = 0.02). Binge eating/purging subtype and the number of past admissions showed the strongest odds of compulsory treatment in multivariate analysis. CONCLUSION: The knowledge of factors associated with compulsory treatment may help practitioners of all fields to better evaluate its pertinence and indications in AN.

Echocardiographic abnormalities in 124 severely malnourished adult anorexia nervosa patients: frequency and relationship with body composition and biological features.

BACKGROUND: Anorexia Nervosa (AN) is a complex psychiatric disorder that can lead to specific somatic complications. Heart abnormalities are frequently reported, while their frequency and associated factors in severely malnourished AN patients remain poorly defined. OBJECTIVES: This study aimed to characterize echocardiographic abnormalities in severely malnourished AN patients and to assess associated clinical, biological and related body composition features. METHODS: Between January 2013 and January 2015, all severely malnourished adult patients with AN (Mental Disorders, 4th Edn.-DSM IVr) were included in a monocentric study performed in in a highly specialized AN inpatient unit. Electrocardiogram (ECG) and echocardiography were used to assess both heart rhythm and function. All inpatients underwent a Doppler echocardiography procedure after undergoing combined blood volume adjustment, micronutrients deficiencies supplementation and electrolyte disorders correction. Right Ventricular (RV) and Left Ventricular (LV) systolic and diastolic functions were collected and compared to 29 healthy normal subjects in a control group. RESULTS: One hundred and 24 patients (119 (96%) women, 5 (4%) men) with a mean age of 30.1 ± 11 years old and an average Body Mass Index (BMI) of 12 kg/m2 were included. Ninety patients (73%) had been diagnosed with AN Restrictive type (AN-R), 34 (27%) an AN Binge eating/Purging type (AN-BP). Eighteen patients (15%) disclosed an abnormal Left Ventricular Ejection Fraction (LVEF) (< 52% for male and < 54% for female). LVEF impairment was associated with AN-BP patients (p < 0.017) and hypertransaminasemia (AST and/or ALT ≥2 N) (p < 0.05). Left Ventricular mass (LV mass) and Left Ventricular End Diastolic Diameter (LVEDD) were significantly reduced in patients (p < 0.001, p < 0.001). Left and right ventricular tissue Doppler Imaging Velocities (TDI) peak were reduced in patients: Septal and Lateral LV Sm velocities peaks respectively 10 ± 2 cm/s (vs 14 ± 2 cm/s in controls, p < 0.001), 12 ± 3 cm/s (vs 16 ± 3 cm/s in controls, p < 0.001), basal RV Sm velocity peaks at 14 ± 3 cm/s (vs 19 ± 3 cm/s in controls, p < 0.001). Additionally, LV and RV diastolic velocity peaks were reduced: LV septal and lateral velocity peaks were respectively 13 ± 3 cm/s (vs 18 ± 2 cm/s p < 0.001), 12 ± 3 cm/s (vs 22 ± 4 cm/s, p < 0.001) and RV diastolic velocity peaks at 14 ± 3 cm/s (vs 21 ± 4 cm/s p < 0.001). LV diastolic velocity TDI peaks were significantly associated with hypertransaminasemia (p < 0.05) and tended to be associated with a low all body Fat-Free Mass Index (FFMI) (using Dual-energy X- ray Absorptiometry (DXA) (HOLOGICQDR 4500) (p = 0.056). Thirty-four patients (27%) had a pericardial effusion and were significantly associated with a decreased all body FFMI (p < 0.036). CONCLUSION: Heart abnormalities are frequent in malnourished patients with AN, particularly in AN-BP type. Both liver enzymes and body composition abnormalities tended to be associated with heart dysfunction (non-significant association). Prospective studies are needed to better characterize and describe the evolution of cardiac abnormalities during the refeeding period and subsequent weight restoration.