Saba, Leslie

Pediatric obesity is an increasingly prevalent, chronic, and multifactorial disease. Achieving successful and sustained weight reduction with current interventions remains challenging due to significant heterogeneity in treatment response. This review summarizes current evidence describing variability in outcomes across lifestyle, pharmacologic, and metabolic/bariatric surgery interventions in children and adolescents, and examines key biological, metabolic, behavioral, environmental, and psychosocial factors that influence response. In adults, recent findings on energy balance obesity phenotypes (characterized by abnormal satiation, abnormal postprandial satiety, abnormal hedonic eating, and reduced energy expenditure) have demonstrated promise in predicting weight loss outcomes and guiding tailored interventions. However, data on obesity phenotyping within children and adolescents remain limited. Addressing this gap is essential for advancing precision medicine approaches in pediatric obesity, with the potential to improve treatment selection, enhance effectiveness, and optimize long-term clinical outcomes.

ABSTRACT Melanocortin‐4 receptor (MC4R) deficiency is the most common cause of monogenic obesity; yet treatment options for children with MC4R mutations are limited. We describe significant improvement in weight in three patients with pathogenic or likely pathogenic MC4R mutations; two adolescents treated with semaglutide, and a younger child treated with metformin and topiramate. These findings indicate GLP‐1 receptor agonists, topiramate and metformin can be helpful in managing obesity associated with MC4R deficiency.

Objective This study aimed to determine the prevalence and heteroplasmy level(s) of MT-RNR1 variants m.1555A > G and m.1494C > T, which are associated with aminoglycoside-induced hearing loss, in a general perinatal population. This study also aimed to characterize the association of these variants and their heteroplasmy levels with hearing loss outcomes with and without aminoglycoside exposure. Study Design Droplet digital polymerase chain reaction was performed on 479 maternal DNA samples from a general perinatal biobank at our institution to detect the presence and heteroplasmy levels of MT-RNR1 variants m.1555A > G and m.1494C > T. Testing of paired neonatal specimen(s) was planned for positive maternal tests. A retrospective chart review was performed to characterize the population, identify aminoglycoside exposures, and determine hearing outcomes. Results All maternal samples tested negative for MT-RNR1 variants m.1555A > G and m.1494C > T. Maternal and neonatal subjects had high rates of aminoglycoside exposure (15.9 and 13.9%, respectively). No subjects with sensorineural or mixed hearing loss had documented aminoglycoside exposure. Conclusion This study demonstrated that a larger sample size is needed to establish the prevalence of these variants as no subjects tested positive. Determination of variant prevalence in the neonatal population, association of variant heteroplasmy levels with hearing outcomes, and reliability of maternal testing as a surrogate for neonatal testing are important next steps toward universal prenatal or newborn screening. Key Points

Purpose of review Hyponatremia and hypernatremia are commonly encountered electrolyte abnormalities that require timely and careful intervention, as they can be associated with significant morbidity and mortality. Recent findings This review article addresses the etiology, presentation, diagnosis, and management of both hyponatremia and hypernatremia, emphasizing the latest advancements and emerging trends in pediatric care. Summary A methodical approach is needed to accurately assess and treat hyponatremia and hypernatremia. Both conditions continue to rely on serum and urine testing, however newer tests such as copeptin and stimulated testing may hold promise to further refine testing in the future.