Outcomes of adolescent bariatric surgery: liver disease.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing among children in the United States as pediatric obesity rates continue to rise. As such, metabolic and bariatric surgery (MBS) has become a more recognized option for treatment of obesity and has been recommended by the American Academy of Pediatrics. Although MBS is known to improve many obesity-associated comorbidities, such as hypertension and type 2 diabetes, less is known about its effect as a treatment for MASLD. This article reviewed the impact MBS has on the course of liver disease as measured by histopathology, serum markers, and radiographic imaging, among adolescents with severe obesity. Improvements were seen in alanine transaminase (ALT) liver enzymes, rates of hepatocyte steatosis, and degree of fibrosis on histopathology, and fat content in the liver on computed tomography and magnetic resonance imaging. Greater improvements in ALT were seen in patients with higher baseline values and/or a higher stage of biopsy-confirmed steatohepatitis. Biopsy-proven MASLD and metabolic dysfunction-associated steatohepatitis (MASH) have even been shown to disappear completely, but fibrosis does not completely resolve by 12 months post-MBS. To better understand the outcome of pediatric MASLD following MBS treatment, more longitudinal radiographic data and liver histology in patients with fibrosis would be informative beyond 12 months post-MBS.

Exposure to per- and polyfluoroalkyl substances and alterations in plasma microRNA profiles in children.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans. OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children. METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs. RESULTS: Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis. CONCLUSION: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways.

Exposure to 4,4'-DDE in visceral adipose tissue and weight loss in adolescents from the Teen-LABS cohort.

OBJECTIVE: Dichlorodiphenyldichloroethylene (DDE), an obesogen accumulating in adipose tissue, is released into circulation with weight loss, although its impact is underexplored among adolescents. We tested the association using an integrative translational approach of epidemiological analysis among adolescents with obesity and in vitro measures exploring the impact of DDE on adipogenesis via preadipocytes. METHODS: We included 63 participants from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. We assessed 4,4'-DDE in visceral adipose tissue at surgery and BMI and waist circumference at surgery and 0.5, 1, 3, and 5 years after. We conducted longitudinal analysis to estimate the interaction on weight loss between DDE and time since surgery. In vitro analysis quantified adipogenic differentiation in commercial human preadipocytes exposed to 4,4'-DDE via fluorescent staining and imaging. RESULTS: A dose-response relationship was observed, with the low-exposure group having a greater reduction in BMI during the first year compared to higher-exposure groups and showing smaller regains compared to higher-exposure groups after the first year. In vitro analysis of preadipocytes treated with 4,4'-DDE during adipogenic differentiation for 12 days showed a concentration-dependent increase in lipid accumulation. CONCLUSIONS: DDE could contribute to weight trajectory among adolescents undergoing bariatric surgery, potentially mediated via promoted adipogenesis in preadipocytes.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents. AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD. METHODS: This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD. RESULTS: We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B. CONCLUSION: Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Changes in adipose tissue distribution and relation to cardiometabolic risk factors after Roux-en-Y gastric bypass in adolescents.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) among adolescents with obesity results in significant weight loss; however, depot-specific changes have been understudied. OBJECTIVE: We hypothesized that visceral adipose tissue (VAT) reduction in adolescents undergoing RYGB would be greater than other depots and associated with improvement in cardiometabolic risk factors. SETTING: Three specialized treatment centers in Sweden. METHODS: Fifty-nine adolescents underwent dual x-ray absorptiometry before surgery and at 1, 2, and 5 years after RYGB. Changes in body composition in multiple depots (total fat, lean body, gynoid fat, android fat, subcutaneous adipose tissue, and VAT) and cardiometabolic risk factors were assessed using multiple linear regression analysis and generalized estimating equations adjusting for age, sex, and baseline risk factor levels. Data are presented as percent change (95% CI) with regression models showing slopes and estimated P values. RESULTS: At 1 year post-RYGB, a significant reduction was observed across all body composition measures (P < .001) with the greatest reduction observed in VAT (-65.1% [-68.7, -61.8]). From year 1 to 5 years post-RYGB, a regain was observed in all depots except lean body mass (1.2% [.3, 2.7], P = .105). A sex-specific difference in overall trajectories was only observed in lean body mass with males consistently having higher mean levels. Change in VAT at 1 year correlated with change in triglycerides (slope: .21 mg/dL/kg, P = .034) and fasting plasma insulin (slope: 44 pmol/L/kg, P = .027). CONCLUSIONS: Adiposity measures all decreased after RYGB but poorly predicted change in cardiometabolic risk. Despite significant reductions at 1 year, a steady regain was observed out to 5 years, with values still well below baseline. Further research should consider control group comparison and extended follow-up.

Maternal obesity and acute lymphoblastic leukemia risk in offspring: A summary of trends, epidemiological evidence, and possible biological mechanisms.

Acute lymphoblastic leukemia, a heterogenous malignancy characterized by uncontrolled proliferation of lymphoid progenitors and generally initiated in utero, is the most common pediatric cancer. Although incidence of ALL has been steadily increasing in recent decades, no clear reason for this trend has been identified. Rising concurrently with ALL incidence, increasing maternal obesity rates may be partially contributing to increasing ALL prevelance. Epidemiological studies, including a recent meta-analysis, have found an association between maternal obesity and leukemogenesis in offspring, although mechanisms underlying this association remain unknown. Therefore, the purpose of this review is to propose possible mechanisms connecting maternal obesity to ALL risk in offspring, including changes to fetal/neonatal epigenetics, altered insulin-like growth factor profiles and insulin resistance, modified adipokine production and secretion, changes to immune cell populations, and impacts on birthweight and childhood obesity/adiposity. We describe how each proposed mechanism is biologically plausible due to their connection with maternal obesity, presence in neonatal and/or fetal tissue, observation in pediatric ALL patients at diagnosis, and association with leukemogenesis, A description of ALL and maternal obesity trends, a summary of epidemiological evidence, a discussion of the pathway from intrauterine environment to subsequent malignancy, and propositions for future directions are also presented.

Effect of surgical versus medical therapy on estimated cardiovascular event risk among adolescents with type 2 diabetes and severe obesity.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of mortality in type 2 diabetes (T2D). Better interventions are needed to mitigate the high lifetime risk for CVD in youth T2D. OBJECTIVE: To compare 30-year risk for CVD events in 2 cohorts of adolescents with T2D and severe obesity undergoing medical or surgical treatment of T2D. SETTING: Longitudinal multicenter studies at University hospitals. METHODS: A secondary analysis of data collected from the participants with T2D enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS, n = 30) and participants of similar age and racial distribution from the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY, n = 63) studies was performed. Teen-LABS participants underwent metabolic bariatric surgery (MBS). TODAY participants were randomized to metformin alone or in combination with rosiglitazone or intensive lifestyle intervention, with insulin therapy given for glycemic progression. A 30-year CVD event score developed by the Framingham Heart Study was the primary outcome, assessed at baseline (preoperatively for Teen-LABS), 1 year, and 5 years of follow-up. RESULTS: Participants with T2D from Teen-LABS (n = 30; mean ± SD age = 16.9 ± 1.3 yr; 70% female; 60% white; body mass index (BMI) = 54.4 ± 9.5 kg/m2) and TODAY (n = 63; 15.3 ± 1.3 yr; 56% female; 71% white; BMI 40.5 ± 4.9 kg/m2) were compared. The likelihood of CVD events was higher in Teen-LABS versus TODAY at baseline (17.66 [1.59] versus 12.11 [.79]%, adjusted P = .002). One year after MBS, event risk was significantly lower in Teen-LABS versus TODAY (6.79 [1.33] versus 13.64 [0.96]%, adjusted P < .0001), and sustained at 5 years follow-up (adjusted P < .0001). CONCLUSION: Despite higher pretreatment risk for CVD events, treatment with MBS resulted in a reduction in estimated CVD event risks, whereas medical therapy associated with an increase in risk among adolescents with T2D and severe obesity.

Body mass index associated with childhood and adolescent high-risk B-cell acute lymphoblastic leukemia risk: A Children's Oncology Group report.

BACKGROUND: Obesity is a risk factor for many adulthood cancers, but its role in childhood, adolescent, and young adult (AYA) cancer is unknown. Childhood and AYA acute lymphoblastic leukemia (ALL) incidence and obesity prevalence have shown concurrent increases. We sought to identify whether obesity may be a risk factor for childhood and AYA ALL. METHODS: Characteristics from individuals with ALL, aged 2-30 years, diagnosed 2004-2017 and treated on Children's Oncology Group (COG) protocols with available pre-treatment anthropometric data (N = 4726) were compared to National Health and Nutrition Examination Survey controls (COG AALL17D2). Body mass index (BMI) was defined using standard CDC definitions. Multivariate conditional logistic regression assessed associations between BMI and ALL with additional analyses stratified by sex and race/ethnicity. RESULTS: Among cases (72% high-risk (HR) B-ALL, 28% T-ALL), 5% had underweight, 58% normal weight, 17% overweight, and 20% obesity. Underweight (OR 2.11, 95% CI 1.56-2.85) and obesity (OR 1.32, 95% CI 1.15-1.53) were associated with B-ALL diagnosis. Specifically, obesity was associated with B-ALL among males (OR 1.57, 95% CI 1.30-1.91) and Hispanic children (OR 1.78, 95% CI 1.39-2.29). Obesity was also associated with central nervous system (CNS) involvement. CONCLUSION: Pre-treatment obesity is associated with HR B-ALL among males and Hispanics, as well as with CNS involvement, suggesting common physiology between obesity and leukemogenesis. An association between underweight and ALL was confirmed, likely due to cancer-associated wasting. These results have important public health implications for obesity prevention and treatment in children and adolescents to reduce cancer risk.

Thirty-Year Risk of Cardiovascular Disease Events in Adolescents with Severe Obesity.

OBJECTIVE: Quantifying risk for cardiovascular disease (CVD) events among adolescents is difficult owing to the long latent period between risk factor development and disease outcomes. This study examined the 30-year CVD event risk among adolescents with severe obesity treated with and without metabolic and bariatric surgery (MBS), compared with youths with moderate obesity, overweight, or normal weight. METHODS: Cross-sectional and longitudinal comparisons of five frequency-matched (age and diabetes status) groups were performed: normal weight (n = 247), overweight (n = 54), obesity (n = 131), severe obesity without MBS (n = 302), and severe obesity undergoing MBS (n = 215). A 30-year CVD event score developed by the Framingham Heart Study was the primary outcome. Data are mean (SD) with differences between time points for MBS examined using linear mixed models. RESULTS: Preoperatively, the likelihood of CVD events was higher among adolescents undergoing MBS (7.9% [6.7%]) compared with adolescents with severe obesity not referred for MBS (5.5% [4.0%]), obesity (3.9% [3.0%]), overweight (3.1% [2.4%]), and normal weight (1.8% [0.8%]; all P < 0.001). At 1 year after MBS, event risk was significantly reduced (7.9% [6.7%] to 4.0% [3.4%], P < 0.0001) and was sustained for up to 5 years after MBS (P < 0.0001, all years vs. baseline). CONCLUSIONS: Adolescents with severe obesity are at elevated risk for future CVD events. Following MBS, the predicted risk of CVD events was substantially and sustainably reduced.

Relation of secondhand smoke exposure to vascular phenotypes in children and adolescents.

BACKGROUND: Subclinical cardiovascular risks of secondhand smoke (SHS) exposure among children and adolescents remains insufficiently described. METHODS: This was a cross-sectional study of 298 children and adolescents (48.0% male, body mass index: 27.0 ± 8.9 kg/m2), including 49 self-reported cases with SHS. Arterial elasticity and stiffness (distensibility, compliance, incremental elastic modulus [IEM]) were obtained via ultrasound imaging in the abdominal aorta, brachial, and carotid arteries. A one-way analysis of variance compared differences between groups, and multiple linear regression adjusted for covariates. RESULTS: SHS was associated with lower abdominal aorta diameter distensibility (aDD) (13.4 ± 3.6% vs. 16.0 ± 5.2%, p = 0.009) and abdominal aorta cross-sectional distensibility (aCSD) (28.8 ± 8.3% vs. 35.1 ± 12.2%, p = 0.009), as well as higher abdominal aorta IEM (aIEM) (1241 ± 794 vs. 935 ± 388 mmHg, p = 0.001). After adjustment for covariates, aDD (p = 0.047), aCSD (p = 0.040), and aIEM (p = 0.017) remained significant; this significance persisted with the additional adjustment of percent body fat. Measures of brachial and carotid compliance and distensibility were not associated with SHS. CONCLUSIONS: SHS was associated with abdominal aorta stiffness; the majority of vascular measures within the brachial and carotid artery remained unaffected following adjustment for covariates, including hypertension and adiposity. SHS may predispose individuals to increased abdominal aorta stiffness, an artery previously reported to exhibit increased susceptibility to atherosclerosis.

Musculoskeletal Pain, Physical Function, and Quality of Life After Bariatric Surgery.

OBJECTIVES: To evaluate the longitudinal effects of metabolic and bariatric surgery (MBS) on the prevalence of musculoskeletal and lower extremity (LE) pain, physical function, and health-related quality of life. METHODS: The Teen Longitudinal Assessment of Bariatric Surgery study (NCT00474318) prospectively collected data on 242 adolescents undergoing MBS at 5 centers over a 3-year follow-up. Joint pain and physical function outcomes were assessed by using the Health Assessment Questionnaire Disability Index, Impact of Weight on Quality of Life - Kids, and the Short Form 36 Health Survey. Adolescents with Blount disease (n = 9) were excluded. RESULTS: Prevalent musculoskeletal and LE pain were reduced by 40% within 12 months and persisted over 3 years. Adjusted models revealed a 6% lower odds of having musculoskeletal pain (odds ratio = 0.94, 95% confidence interval: 0.92-0.99) and a 10% lower odds of having LE pain (odds ratio = 0.90, 95% confidence interval: 0.86-0.95) per 10% reduction of BMI. The prevalence of poor physical function (Health Assessment Questionnaire Disability Index score >0) declined from 49% to <20% at 6 months (P < .05), Physical comfort and the physical component scores, measured by the Impact of Weight on Quality of Life - Kids and the Short Form 36 Health Survey, improved at 6 months postsurgery and beyond (P < .01). Poor physical function predicted persistent joint pain after MBS. CONCLUSIONS: Joint pain, impaired physical function, and impaired health-related quality of life significantly improve after MBS. These benefits in patient-reported outcomes support the use of MBS in adolescents with severe obesity and musculoskeletal pain and suggest that MBS in adolescence may reverse and reduce multiple risk factors for future joint disease.

Precision medicine in adult and pediatric obesity: a clinical perspective.

It remains largely unknown as to why some individuals experience substantial weight loss with obesity interventions, while others receiving these same interventions do not. Person-specific characteristics likely play a significant role in this heterogeneity in treatment response. The practice of precision medicine accounts for an individual's genes, environment, and lifestyle when deciding upon treatment type and intensity in order to optimize benefit and minimize risk. In this review, we first discuss biopsychosocial determinants of obesity, as understanding the complexity of this disease is necessary for appreciating how difficult it is to develop individualized treatment plans. Next, we present literature on person-specific characteristics associated with, and predictive of, weight loss response to various obesity treatments including lifestyle modification, pharmacotherapy, metabolic and bariatric surgery, and medical devices. Finally, we discuss important gaps in our understanding of the causes of obesity in relation to the suboptimal treatment outcomes in certain patients, and offer solutions that may lead to the development of more effective and targeted obesity therapies.

Severe Obesity in the Pediatric Population: Current Concepts in Clinical Care.

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. Treatment of severe pediatric obesity requires a chronic care management approach utilizing multidisciplinary teams of health care providers and multi-pronged therapies.

Heterogeneity in Response to Treatment of Adolescents with Severe Obesity: The Need for Precision Obesity Medicine.

OBJECTIVE: Treating pediatric severe obesity is challenging because of the complex biological, behavioral, and environmental factors that underpin the disease. The multifactorial etiology of obesity combined with the physiologic complexity of the energy regulatory system contributes to treatment variability. The goal of this secondary analysis of pooled data was to describe the degree of individual variation in response to various interventions among adolescents with severe obesity. METHODS: Data from three centers across the United States conducting either lifestyle (n = 53), pharmacotherapy (n = 40), or metabolic and bariatric surgery (n = 78) interventions were pooled. Inclusion criteria were severe obesity at baseline and at least one follow-up visit > 30 days after treatment start. RESULTS: Change in BMI following intervention ranged from -50.2% to +12.9%, with each intervention (lifestyle [range: -25.4% to 5.0%], pharmacotherapy [range: -10.8% to 12.9%], and metabolic and bariatric surgery [range: -50.2% to -13.3%]) exhibiting wide individual variation in response. Changes in cardiometabolic risk factors demonstrated similarly high variability. CONCLUSIONS: Adolescents with severe obesity demonstrated a high degree of heterogeneity in terms of BMI reduction and cardiometabolic risk factor response across treatment modalities. Reporting individual response data in trials and identifying factors driving variability in response will be vital for advancing precision medicine approaches to address obesity.

Treatment Options for Severe Obesity in the Pediatric Population: Current Limitations and Future Opportunities.

OBJECTIVE: Severe obesity is the only obesity classification increasing in prevalence among children and adolescents. Treatment options that produce meaningful and sustained weight loss and comorbidity resolution are urgently needed. METHODS: The purpose of this review is to provide a brief overview of the current treatment options for pediatric severe obesity and offer suggestions regarding future opportunities for accelerating the development and evaluation of innovative treatment strategies. RESULTS: At present, there are three treatment options for youth with severe obesity: lifestyle modification therapy, pharmacotherapy, and bariatric surgery. Lifestyle modification therapy can be useful for improving many chronic disease risk factors and comorbid conditions but often fails to achieve clinically meaningful and sustainable weight loss. Pharmacotherapy holds promise as an effective adjunctive treatment but remains in the primordial stages of development in the pediatric population. Bariatric surgery provides robust weight loss and risk factor/comorbidity improvements but is accompanied by higher risks and lower uptake compared to lifestyle modification therapy and pharmacotherapy. New areas worth pursuing include combination pharmacotherapy, device therapy, identification of predictors of response aimed at precision treatment, and interventions in the postbariatric surgical setting to improve long-term outcomes. CONCLUSIONS: Treating pediatric severe obesity effectively and safely is extremely challenging. Some progress has been made, but substantially more effort and innovation are needed in the future to combat this serious and ongoing medical and public health issue.

Heritability of Vascular Structure and Function: A Parent-Child Study.

BACKGROUND: Understanding the heritable contribution of vascular measures, from parent to offspring, may aid in risk stratification and atherosclerosis prevention efforts. We hypothesized that measures of vascular structure and function would be heritable in this cohort of parents and their adolescent offspring. METHODS AND RESULTS: High-resolution ultrasound scans of the brachial and carotid arteries were obtained in parents (n=558) and their offspring (n=369). Lumen diameter and flow-mediated dilation were measured in the brachial artery. Intima-media thickness, lumen diameter, incremental elastic modulus, diameter distensibility, and cross-sectional distensibility were measured, and carotid cross-sectional compliance was measured in the carotid artery. Carotid-radial pulse wave velocity was obtained using SphygmoCor®. Heritability analysis (h2, expressed as %) using Sequential Oligogenic Linkage Analysis Routines was performed on the entire cohort and adjusted for age, sex, race, body-mass index, smoking, and mean arterial pressure. Data are presented as mean±SE. Measures of brachial artery diameter (h2=25±9%, P=0.001), lumen diameter (h2=55±9%, P<0.001), intima-media thickness (h2=29±13%, P=0.014), diameter distensibility (h2=28±7%, P<0.001), cross-sectional distensibility (h2=27±7%, P<0.001), and pulse wave velocity (h2=26±9%, P<0.001) were significantly heritable. Flow-mediated dilation and incremental elastic modulus were not significantly heritable. Similar associations were observed in analysis restricted to siblings and complete Trios (mother, father, and child). CONCLUSIONS: These data show that the majority of noninvasive measures of vascular structure and function are heritable, suggesting that measurement of these subclinical risk factors in parents may be helpful in assessing childhood risk for future cardiovascular disease.

Changes in Functional Mobility and Musculoskeletal Pain After Bariatric Surgery in Teens With Severe Obesity: Teen-Longitudinal Assessment of Bariatric Surgery (LABS) Study.

IMPORTANCE: Severe obesity is associated with mobility limitations and higher incidence of multijoint musculoskeletal pain. It is unknown whether substantial weight loss improves these important outcomes in adolescents with severe obesity. OBJECTIVE: To examine the association of bariatric surgery with functional mobility and musculoskeletal pain in adolescents with severe obesity up to 2 years after surgery. DESIGN, SETTING, AND PARTICIPANTS: The Teen-Longitudinal Assessment of Bariatric Surgery Study is a prospective, multicenter, observational study, which enrolled 242 adolescents (≤19 years of age) who were undergoing bariatric surgery from March 2007 through February 2012 at 5 US adolescent bariatric surgery centers. This analysis was conducted in November 2015. INTERVENTIONS: Roux-en-Y gastric bypass (n = 161), sleeve gastrectomy (n = 67), or laparoscopic adjustable gastric band (n = 14). MAIN OUTCOMES AND MEASURES: Participants completed a 400-m walk test prior to bariatric surgery (n = 206) and at 6 months (n = 195), 12 months (n = 176), and 24 months (n = 149) after surgery. Time to completion, resting heart rate (HR), immediate posttest HR, and HR difference (resting HR minus posttest HR) were measured and musculoskeletal pain concerns, during and after the test, were documented. Data were adjusted for age, sex, race/ethnicity, baseline body mass index (calculated as weight in kilograms divided by height in meters squared), and surgical center (posttest HR and HR difference were further adjusted for changes in time to completion). RESULTS: Of the 206 adolescents with severe obesity included in the study, 156 were female (75.7%), the mean (SD) age was 17.1 (1.6) years, and the mean (SD) body mass index was 51.7 (8.5). Compared with baseline, significant improvements were observed at 6 months for the walk test time to completion (mean, 376 seconds; 95% CI, 365-388 to 347 seconds; 95% CI, 340-358; P < .01), resting HR (mean, 84 beats per minute [bpm]; 95% CI, 82-86 to 74 bpm; 95% CI, 72-76), posttest HR (mean, 128 bpm; 95% CI, 125-131 to 113 bpm; 95% CI, 110-116), and HR difference (mean, 40 bpm; 95% CI, 36-42 to 34 bpm; 95% CI, 31-37). These changes in time to completion, resting HR, and HR difference persisted at 12 months and 24 months. Posttest HR further improved from 6 months to 12 months (mean, 113 bpm; 95% CI, 110-116 to 108 bpm; 95% CI, 105-111). There were statistically significant reductions in musculoskeletal pain concerns at all points. CONCLUSIONS AND RELEVANCE: These data provide evidence that bariatric surgery in adolescents with severe obesity is associated with significant improvement in functional mobility and in the reduction of walking-related musculoskeletal pain up to 2 years after surgery.

Reproducibility of circulating endothelial cell enumeration and activation in children and adolescents.

INTRODUCTION: We examined the reproducibility of circulating endothelial cells (CEC) enumeration and activation among youth. MATERIALS AND METHODS: CECs from 151 youth were measured at baseline and 1 week follow-up. Enumeration of CEC in fresh whole blood was determined by direct assessment of buffy coat smears (CD146+ nucleated cells) and activated CEC (%VCAM-1 expression) was determined after immunomagnetic enrichment and co-staining of nuclei, plus positivity for P1H12 and VCAM-1. RESULTS: No statistically significant difference in CEC enumeration (1.2 ± 2.5 vs 1.3 ± 2.2 CEC/milliliter of whole blood, p = 0.745) or activated CEC (57.1 ± 24.4 vs 58.0 ± 21.3 %VCAM-1, p = 0.592) between baseline and 1 week follow-up. CONCLUSION: On a cohort basis, CEC enumeration and activation are reproducible in youth. Relatively high individual biological variability may limit its clinical utility.