Purpose of Review This review describes (1) the clinical assessment of pediatric patients with severe obesity, including a summary of salient biological, psychological, and social factors that may be contributing to the patient's obesity and (2) the current state of treatment strategies for pediatric severe obesity, including lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Recent Findings Lifestyle modification therapy alone is insufficient for achieving clinically significant BMI reduction for most youth with severe obesity and metabolic and bariatric surgery, though effective and durable, is not a scalable treatment strategy. Pharmacological agents in the pipeline may 1 day fill this gap in treatment. Summary Treatment of severe pediatric obesity requires a chronic care management approach utilizing multidisciplinary teams of health care providers and multi-pronged therapies.

Osteosarcoma exhibits marked patient-to-patient heterogeneity, but little is known about heterogeneity within individual tumors. This study focuses on the roles that phenotypic plasticity and clonal selection play as tumors adapt to primary and metastatic microenvironments. We show that osteosarcomas have a high degree of transcriptional heterogeneity, like osteoblasts, that is retained even after prolonged cell culture or adaptation to changing microenvironments. We find that both cell lines and PDXs grown in cell culture or as flank tumors adopt markedly different transcriptional profiles when grown as primary bone tumors or metastatic lung lesions. By combining lineage tracing with single-cell transcriptomics, we find that very little clonal selection occurs when tumors grow in the tibia, but significant expansion of select clones occurs when grown as experimental metastases in the lung. Interestingly, the selective pressures that drive clonal expansion do not cause narrowing of transcriptional phenotypes. By comparing the phenotypes from transcriptional clusters in orthotopic/metastatic tumor pairs, we identify a transcriptional signature that is shared among clusters that become enriched during lung colonization. This includes responses to IFNG, TNF, PDGF, previously unidentified IL1B, and a shift away from genes associated with glycolysis and toward those associated with oxidative metabolism. The metastatic microenvironment enriches for phenotypically diverse clones that each display metabolic properties that engender fitness within the metastatic microenvironment. Together, these data suggest that an underlying program, possibly a developmental program retained from the tissue of origin, maintains phenotypic heterogeneity, even during adaptation to changing microenvironmental conditions.

SummaryBackgroundAlthough obesity affects approximately one in five youths, only a fraction is treated in pediatric weight management clinics. Characteristics distinguishing youth with obesity who seek weight management treatment from those who do not are largely unknown. Yet identification of specific health characteristics which differentiate treatment‐seeking from non‐treatment seeking youth with obesity may shed light on underlying motivations for pursuing treatment.ObjectivesCompare the cardiometabolic profiles of an obesity treatment‐seeking sample of youth to a population‐based sample of youth with obesity, while controlling for body mass index (BMI).MethodsThis cross‐sectional study included participants, ages 12–17 years, with obesity from the Pediatric Obesity and Weight Evaluation Registry (POWER) and National Health and Nutrition Examination Survey, representing the treatment‐seeking and population samples, respectively. Mean differences were calculated for systolic and diastolic blood pressure percentiles, total cholesterol, low‐density and high‐density lipoprotein‐cholesterol, triglycerides, fasting glucose, glycated hemoglobin and alanine aminotransferase, while adjusting for age, sex, race/ethnicity, insurance status, and multiple of the 95th BMI percentile.ResultsThe POWER and National Health and Nutrition Examination Survey cohorts included 1,823 and 617 participants, respectively. The POWER cohort had higher systolic blood pressure percentile (mean difference 17.4, 95% confidence interval [14.6, 20.1], p < 0.001), diastolic blood pressure percentile (21.8 [19, 24.5], p < 0.001), triglycerides (42.3 [28, 56.5], p < 0.001) and alanine aminotransferase (7.5 [5.1, 9.8], p < 0.001) and lower fasting glucose (−6.9 [−8.2, −5.6], p < 0.001) and high‐density lipoprotein‐cholesterol (−2.3 [−3.8, −0.9], p < 0.002). There were no differences in total cholesterol or low‐density lipoprotein‐cholesterol or clinical differences in glycated hemoglobin.ConclusionFor a given BMI, obesity treatment‐seeking youth are more adversely affected by cardiometabolic risk factors than the general population of youth with obesity. This suggests that treatment‐seeking youth may represent a distinct group that is at particularly high risk for the development of future cardiometabolic disease.

Background/Objectives-Bariatric surgery produces robust weight-loss, however, factors associated with long-term weight-loss maintenance among adolescents undergoing Roux-en-Y gastric bypass surgery (RYGB) are unknown. Subjects/Methods-Fifty adolescents (mean±SD age and BMI = 17.1±1.7yrs and 59±11kg/m 2) underwent RYGB, had follow-up visits at 1-yr and at a visit between 5-12yrs following surgery (FABS-5+ visit; mean±SD 8.1±1.6yrs). A non-surgical comparison group (n=30; mean±SD age and BMI = 15.3±1.7yrs and BMI=52±8kg/m 2) was recruited to compare weight trajectories overtime. Questionnaires (health-related and eating behaviors, health responsibility, impact of weight on quality of life, international physical activity questionnaire (IPAQ), and dietary habits via surgery guidelines) were administered at the FABS-5+ visit. Post-hoc, participants were split into 2 groups: long-term weight loss maintainers (n=23; baseline BMI=58.2kg/m 2 ; 1-yr BMI=35.8kg/m 2 ; FABS-5+ BMI=34.9kg/m 2) and re-gainers (n=27; baseline BMI=59.8kg/m 2 ; 1yr BMI=36.8 kg/m 2 ; FABS-5+ BMI=48.0kg/m 2) to compare factors which might contribute to differences. Data were analyzed using generalized estimating equations adjusted for age, sex, baseline BMI, baseline diabetes status, and length of follow-up. Results-The BMI of the surgical group declined from baseline to 1-yr (−38.5±6.9%), which, despite some regain, was largely maintained until FABS-5+ (−29.6±13.9 % change). The BMI of the comparison group increased from baseline to the FABS-5+ visit (+10.3±20.6%). When the surgical group was split into maintainers and re-gainers, no differences in weight-related and