PFHpA alters lipid metabolism and increases the risk of metabolic dysfunction-associated steatotic liver disease in youth-a translational research framework.

To address the growing epidemic of liver disease, particularly in pediatric populations, it is crucial to identify modifiable risk factors for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Per- and polyfluoroalkyl substances (PFAS) are persistent ubiquitous chemicals and have emerged as potential risk factors for liver damage. However, their impact on the etiology and severity of MASLD remains largely unexplored in humans. This study aims to bridge the gap between human and in vitro studies to understand how exposure to perfluoroheptanoic acid (PFHpA), one of the emerging PFAS replacements which accumulates in high concentrations in the liver, contributes to MASLD risk and progression. First, we showed that PFHpA plasma concentrations were significantly associated with increased risk of MASLD in obese adolescents. Further, we examined the impact of PFHpA on hepatic metabolism using 3D human liver spheroids and single-cell transcriptomics to identify major hepatic pathways affected by PFHpA. Next, we integrated the in vivo and in vitro multi-omics datasets with a novel statistical approach which identified signatures of proteins and metabolites associated with MASLD development triggered by PFHpA exposure. In addition to characterizing the contribution of PFHpA to MASLD progression, our study provides a novel strategy to identify individuals at high risk of PFHpA-induced MASLD and develop early intervention strategies. Notably, our analysis revealed that the proteomic signature exhibited a stronger correlation between both PFHpA exposure and MASLD risk compared to the metabolomic signature. While establishing a clear connection between PFHpA exposure and MASLD progression in humans, our study delved into the molecular mechanisms through which PFHpA disrupts liver metabolism. Our in vitro findings revealed that PFHpA primarily impacts lipid metabolism, leading to a notable increase of lipid accumulation in human hepatocytes after PFHpA exposure. Among the pathways involved in lipid metabolism in hepatocytes, regulation of lipid metabolism by PPAR-a showed a remarkable activation. Moreover, the translational research framework we developed by integrating human and in vitro data provided us biomarkers to identify individuals at a high risk of MASLD due to PFHpA exposure. Our framework can inform policies on PFAS-induced liver disease and identify potential targets for prevention and treatment strategies.

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.

Changes in plasma concentrations of per- and Polyfluoroalkyl substances after bariatric surgery in adolescents from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study.

Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery. Adolescents (Mean age = 17.1 years, SD = 1.5 years) undergoing bariatric surgery were enrolled in the Teen-LABS study. Plasma-PFAS were measured at the time of surgery and then 6-, 12-, and 36 months post-surgery. Linear mixed effect models were used to evaluate longitudinal changes in plasma-PFAS after the time of bariatric surgery. This study included 214 adolescents with severe obesity who had available longitudinal measures of plasma-PFAS and underwent bariatric surgery between 2007 and 2012. Underlying effects related to undergoing bariatric surgery were found to be associated with an initial increase or plateau in concentrations of circulating PFAS up to 6 months after surgery followed by a persistent decline in concentrations of 36 months (p < 0.001 for all plasma-PFAS). Bariatric surgery in adolescents was associated with a decline in circulating PFAS concentrations. Initially following bariatric surgery (0-6 months) concentrations were static followed by decline from 6 to 36 months following surgery. This may have large public health implications as PFAS are known to be associated with numerous metabolic related diseases and the significant reduction in circulating PFAS in individuals who have undergone bariatric surgery may be related to the improvement of such metabolic related diseases following bariatric surgery.

Lack of Association of Pediatric Surgical Patient Outcomes With Increased Disposable Operating Room Supply Costs.

INTRODUCTION: There is wide variation in the cost of disposable operating room supplies between surgeons performing the same operation at the same institution. The general relationship between variation in disposable supply cost and patient outcomes is unknown. We aimed to evaluate the relationship between disposable supply cost and patient outcomes for sixteen common operations. METHODS: Cost data were reviewed for the most common procedures performed by five surgical divisions at a single children's hospital over a six-month period in 2021. For procedure, the median disposable OR costs were calculated. Each operation performed was categorized as low cost (below the group median) or high cost (above the group median. We compared the rates of adverse events (clinic visit within 5 days, 30-day emergency department visit, unplanned reoperation, unplanned readmission, anesthesia complications, prolonged hospital length of stay, need for blood product transfusion, or death) between procedures with low and high disposable supply costs. RESULTS: 1139 operations performed by 48 unique surgeons from five specialties were included; 596 (52%) were low-cost and 543 (48%) high-cost. The low and high-cost groups did not differ regarding most demographic characteristics. Overall, 21.9% of children suffered any adverse outcome; this rate did not differ between the low and high-cost groups when evaluated individually or in aggregate (20.5% vs 23.6%, p = 0.23). CONCLUSION: Our data demonstrate that across a wide range of pediatric surgical procedures, the cost of disposable operating room supplies was not associated with the risk of adverse outcomes. LEVEL OF EVIDENCE: Level 3.

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.

Cognitive function 10 years after adolescent bariatric surgery.

BACKGROUND: Adolescent bariatric surgery produces substantial weight loss and reduction of medical co-morbidities. Research in adult samples shows improved cognitive function postoperatively, although much less is known about the potential cognitive benefits of bariatric surgery in adolescents-especially at extended follow-up. OBJECTIVE: Examine cognitive function 10 years after adolescent bariatric surgery. SETTING: University hospital. METHODS: A total of 99 young adults who underwent bariatric surgery as adolescents completed a computerized cognitive test battery as part of a larger 10-year postoperative assessment. All had been long-term participants in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. RESULTS: Cognitive dysfunction was prevalent on tests of attention and executive function (e.g., Continuous Performance Test - Reaction Time 30%; Maze Errors - Overrun 30%), and 53.5% met research criteria for mild cognitive impairment (MCI). Modified Poisson regression with robust error variance revealed participants with preoperative hypertension and those completing Roux-en-Y gastric bypass were more likely to meet criteria for MCI at 10-year follow-up. CONCLUSIONS: The current findings indicate that cognitive deficits are common 10 years after bariatric surgery. Additional studies are needed to clarify possible cohort effects, determine whether these cognitive deficits persist to even later follow-up (e.g., 20 yr after surgery), and identify underlying mechanisms and mitigation strategies.

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.

Associations between marital status and weight loss trajectories entering into early adulthood: a Teen-LABS study.

BACKGROUND: Among adolescents who underwent metabolic and bariatric surgery (MBS), it is unclear how relationships and specifically marital status (MS) may be associated with long-term weight loss. OBJECTIVE: In this analysis, we tested for associations between the MS of adolescents who underwent MBS and the MS of their primary caregiver and weight loss trajectory over 8 years. SETTING: Teen-LABS participating sites. METHODS: This sample included 231 participants (75.3% female, 71.4% White, 68.0% Roux-en-Y gastric bypass, 27.7% vertical sleeve gastrectomy, 4.3% laparoscopic adjustable gastric band). A linear mixed model was conducted with the dependent variable percent body mass index (BMI) change from preoperatively through 8 years with between-participant factors (1) participant MS, (2) caregiver MS, and (3) interaction between caregiver and participant MS. RESULTS: One third of participants and 87% of caregivers were ever married (EM). Compared with never-married (NM) participants and caregivers (-14.6%), EM participants and caregivers (-20.6%), EM participants and NM caregivers (-25.9%), and NM participants and EM caregivers (-19.8%), each had significantly greater BMI loss at 8 years (each P < .05). No other group comparisons achieved statistical significance. CONCLUSIONS: NM participants with NM caregivers had less favorable long-term BMI. Additional research is needed to better understand how relationships affect behavior change and weight loss after MBS.

Bone mineral density in young adults 5 to 11 years after adolescent metabolic and bariatric surgery for severe obesity compared to peers.

OBJECTIVE: Metabolic and bariatric surgery (MBS) is associated with decreased bone mineral density (BMD) in adults. The long-term impact of MBS during adolescence on BMD is unknown. We report bone health status 5 to 11 years after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) from the Teen-LABS study cohort. METHODS: Between 2016 and 2022, BMD was measured by dual energy x-ray absorptiometry (DXA) in 106 young adults who had undergone MBS as adolescents. Volumetric BMD by peripheral quantitative computed tomography was measured on a subset. Ninety-one controls who had not undergone MBS were recruited for comparison. RESULTS: In cases (RYGB: mean age 26.8 ± 1.9 years, mean BMI 42.1 ± 9.9 kg/m2, VSG: mean age 25.1 ± 2.1 years, mean BMI 37.1 ± 8.4 kg/m2), compared to controls (mean age 26.5 ± 2.7 years, mean BMI 40.2 ± 8.7 kg/m2) (age p < 0.001, BMI p = 0.02), adjusted mean DXA-BMD (g/cm2) of the RYGB (n = 58) and VSG (n = 48) groups were lower at the hip (-10.0% and -6.3%), femoral neck (-9.6% and -5.7%) and ultra-distal radius (-7.9% and -7.0%; all p < 0.001), respectively. DXA-BMD did not differ between RYGB and VSG groups. Trabecular volumetric BMD at the radius and tibia were lower in the RYGB (-30% and -26%) and VSG (-15% and -14%) groups compared to the control group (p < 0.001). Greater time since MBS was associated with lower BMD Z-scores at the hip (p = 0.05) and femoral neck (p = 0.045). Percent change in body mass index (BMI) from baseline or in the first year after MBS were not associated with bone measures at a median of 9.3 years post MBS. CONCLUSION: BMD, especially of the hip and femoral neck, was lower in young adults who underwent MBS during adolescence compared to matched peers who had not undergone MBS. BMD Z-scores of the femoral neck were inversely associated with time since MBS but were not associated with BMI change.

Prognostic factors in resolution of nonalcoholic fatty liver disease post bariatric surgery in adolescents.

BACKGROUND: The long-term effect of bariatric surgery on adolescent non-alcoholic fatty liver disease is not clear. OBJECTIVES: To evaluate longitudinal change in serum alanine aminotransferase (ALT) levels and to determine the factors independently associated with this change over 2 years after bariatric surgery in adolescents with severe obesity. SETTING: An observational prospective cohort from the Teen-LABS Consortium. METHODS: We examined the relationship of longitudinal change in serum ALT (% change and normalization) to change in body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), high- (HDL) and low-density lipoprotein cholesterol, A1C and fasting glucose, accounting for age, sex, race-ethnicity, blood pressure, and baseline BMI in 219 adolescents during the first 2 years post-surgery. RESULTS: Mean BMI declined from a baseline of 52.6 to 37.2 kg/m2 at 2 years (P < .01). Alanine aminotransferase decreased significantly from baseline (36.5 [95% CI: 31.4, 41.7]) to 6 months (30.5 [95% CI: 25.4, 35.6]), and remained stable at 12 and 24 months, all P < .01 versus baseline. After adjustment, improvement in BMI, fasting glucose, HOMA-IR, triglycerides, TG/HDL ratio, and HDL were independently associated with reduced ALT at 6 months. These remained significantly associated with a decline in ALT after adjusting for BMI change. The %participants with elevated ALT decreased from 71% at baseline to 42% and 36% at 1 and 2 years post-surgery. CONCLUSIONS: Bariatric surgery resulted in significant and sustained improvement in ALT levels over 2 years. Although associated with weight loss, this decline was also associated with improved metabolic indices, independent of weight loss.

Bone mineral density 5 to 11 years after metabolic and bariatric surgery in adolescents with severe obesity compared to peers.

Objective: Metabolic and bariatric surgery (MBS) is associated with decreased bone mineral density (BMD) in adults. The long-term impact of MBS during adolescence on BMD is unknown. We report bone health status 5 to 11 years after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) from the Teen-LABS study cohort. Methods: Between 2016 and 2022, BMD was measured by dual energy x-ray absorptiometry (DXA) in 106 young adults who had undergone MBS as adolescents. Volumetric BMD by peripheral quantitative computed tomography was measured on a subset. Ninety-one controls who had not undergone MBS were recruited for comparison. Results: Compared to controls, adjusted mean DXA-BMD of the RYGB (n = 58) and VSG (n = 48) groups were lower at the hip (-10.0% and - 6.3%), femoral neck (-9.6% and - 5.7%) and ultra-distal radius (-7.9% and - 7.0%; all p < 0.001), respectively. DXA-BMD did not differ between RYGB and VSG groups. Trabecular volumetric BMD at the radius and tibia were lower in the RYGB (-30% and - 26%) and VSG (-15% and - 14%) groups compared to the control group (p < 0.001). Greater time since MBS was associated with lower BMD Z-scores at the hip (p = 0.05) and femoral neck (p = 0.045). Percent change in body mass index (BMI) from baseline or in the first year after MSB were not associated with bone measures at a median of 9.3 years post MSB. Conclusion: BMD, especially of the hip and femoral neck, was lower in young adults who underwent MBS during adolescence compared to matched peers who had not undergone MBS. BMD Z-scores of the femoral neck decreased with time since MBS but were not associated with BMI change.

Paired Liver:Plasma PFAS Concentration Ratios from Adolescents in the Teen-LABS Study and Derivation of Empirical and Mass Balance Models to Predict and Explain Liver PFAS Accumulation.

Animal studies have pointed at the liver as a hotspot for per- and polyfluoroalkyl substances (PFAS) accumulation and toxicity; however, these findings have not been replicated in human populations. We measured concentrations of seven PFAS in matched liver and plasma samples collected at the time of bariatric surgery from 64 adolescents in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Liver:plasma concentration ratios were perfectly explained (r2 > 0.99) in a multilinear regression (MLR) model based on toxicokinetic (TK) descriptors consisting of binding to tissue constituents and membrane permeabilities. Of the seven matched plasma and liver PFAS concentrations compared in this study, the liver:plasma concentration ratio of perfluoroheptanoic acid (PFHpA) was considerably higher than the liver:plasma concentration ratio of other PFAS congeners. Comparing the MLR model with an equilibrium mass balance model (MBM) suggested that complex kinetic transport processes are driving the unexpectedly high liver:plasma concentration ratio of PFHpA. Intratissue MBM modeling pointed to membrane lipids as the tissue constituents that drive the liver accumulation of long-chain, hydrophobic PFAS, whereas albumin binding of hydrophobic PFAS dominated PFAS distribution in plasma. The liver:plasma concentration data set, empirical MLR model, and mechanistic MBM modeling allow the prediction of liver from plasma concentrations measured in human cohort studies. Our study demonstrates that combining biomonitoring data with mechanistic modeling can identify underlying mechanisms of internal distribution and specific target organ toxicity of PFAS in humans.

Comparative Analysis of Global Hepatic Gene Expression in Adolescents and Adults with Non-alcoholic Fatty Liver Disease.

Introduction: To gain insights into the mechanisms underlying distinct nonalcoholic fatty liver disease (NAFLD) histological phenotypes between children and adults, we compared hepatic gene expression profiles associated with NAFLD phenotypes between the two age groups. Methods: Histological characteristics of intra-operative liver biopsies from adolescents and adults undergoing bariatric surgery were assessed by the same pathologist using the non-alcoholic steatohepatitis (NASH) Clinical Research Network scoring system. Hepatic gene expression was measured by microarray analysis. Transcriptomic signatures of histological phenotypes between the two groups were compared, with significance defined as p-value <0.05 and a fold change >1.5. Results: In 67 adolescents and 76 adults, distribution of histological phenotypes was: not-NAFLD (controls) 51% vs 39%, NAFL 39% vs 37%, and NASH 10% vs 24%, respectively. There were 279 differentially expressed genes in adolescents and 213 in adults with NAFLD vs controls. In adolescents, transcriptomes for NAFL vs controls, and borderline vs definite NASH were undifferentiable, whereas in adults, NAFL and borderline NASH demonstrated a transcriptomic gradient between controls and definite NASH. When applied to adolescents, significant adult genes discriminated borderline and definite NASH from control and NAFL, but the majority of significant pediatric genes were not portable to adults. Genes associated with NASH in adolescents and adults showed some ontological consistency but notable differences. Conclusions: There is some similarity but major differences in the transcriptomic profiles associated with NAFLD between adolescents and adults with severe obesity. These data suggest different mechanisms contribute to the pathogenesis of NAFLD severity at different stages in life.

Glycerol as a precursor for hepatic de novo glutathione synthesis in human liver.

BACKGROUND: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components of glutathione, the major antioxidant in the liver. In principle, glycerol could be incorporated into glutathione via the TCA cycle or 3-phosphoglycerate, but it is unknown whether glycerol contributes to hepatic de novo glutathione biosynthesis. METHODS: Glycerol metabolism to hepatic metabolic products including glutathione was examined in the liver from adolescents undergoing bariatric surgery. Participants received oral [U-13C3]glycerol (50 mg/kg) prior to surgery and liver tissue (0.2-0.7g) was obtained during surgery. Glutathione, amino acids, and other water-soluble metabolites were extracted from the liver tissue and isotopomers were quantified with nuclear magnetic resonance spectroscopy. RESULTS: Data were collected from 8 participants (2 male, 6 female; age 17.1 years [range 14-19]; BMI 47.4 kg/m2 [range 41.3-63.3]). The concentrations of free glutamate, cysteine, and glycine were similar among participants, and so were the fractions of 13C-labeled glutamate and glycine derived from [U-13C3]glycerol. The signals from all component amino acids of glutathione - glutamate, cysteine and glycine - were strong and analyzed to obtain the relative concentrations of the antioxidant in the liver. The signals from glutathione containing [13C2]glycine or [13C2]glutamate derived from the [U-13C3]glycerol drink were readily detected, and 13C-labelling patterns in the moieties were consistent with the patterns in corresponding free amino acids from the de novo glutathione synthesis pathway. The newly synthesized glutathione with [U-13C3]glycerol trended to be lower in obese adolescents with liver pathology. CONCLUSIONS: This is the first report of glycerol incorporation into glutathione through glycine or glutamate metabolism in human liver. This could represent a compensatory mechanism to increase glutathione in the setting of excess glycerol delivery to the liver.

A Prospective Cohort of Alcohol Use and Alcohol-related Problems Before and After Metabolic and Bariatric Surgery in Adolescents.

OBJECTIVE: To describe alcohol use, alcohol-related harm, and alcohol-related problems preoperatively and up to 8 years following metabolic and bariatric surgery (MBS) in adolescents. BACKGROUND: Risk for alcohol use and alcohol use disorders (AUD) increases post-Roux-en-Y gastric bypass and vertical sleeve gastrectomy in adults. However, data are lacking in adolescents who undergo MBS. METHODS: This study includes 217 adolescents (aged 13-19 y) enrolled in a 5-center prospective cohort study who underwent Roux-en-Y gastric bypass or vertical sleeve gastrectomy (2007-2011) and reported alcohol use preoperatively and annually postoperatively for up to 8 years. Time to elevated Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) score, alcohol-related harm, and alcohol-related problems were analyzed with Kaplan-Meier estimates of cumulative incidence. RESULTS: Preoperatively, the median age was 17 years; the median body mass index was 51 kg/m 2 . Alcohol use frequency and average quantity of drinks per drinking day increased postoperatively (2% consumed alcohol 2-4 times/month 6 months versus 24% 8 years postoperatively, P <0.001; 2% consumed≥3 drinks per drinking day 6 months versus 35% 8 years postoperatively, P <0.001). Cumulative incidence of postoperative onset elevated AUDIT-C score, alcohol-related harm, and alcohol-related problems at year 8 were 45% (95% CI:37-53), 43% (95% CI:36-51), and 47% (95% CI:40-55), respectively. CONCLUSIONS: Nearly half of those who underwent MBS as adolescents screened positively for AUD, symptoms of alcohol-related harm, or alcohol-related problems 8 years post-MBS, highlighting the risk for alcohol use and AUD after MBS in adolescents. AUD evaluation and treatment should be integrated into routine long-term care for adolescents undergoing MBS.

The association of sagittal abdominal diameter with metabolic syndrome risk before and after weight-loss surgery in adolescents.

BACKGROUND: Metabolic syndrome (MetS) affects ∼10% of U.S. adolescents. Abdominal obesity is the most prevalent component and may indicate MetS risk in adolescents undergoing weight loss surgery. OBJECTIVES: Assess MetS risk/severity and its association with abdominal obesity (measured by sagittal abdominal diameter, SAD) before and after weight loss surgery in adolescents to determine whether SAD predicts MetS risk in this population. SETTING: Data were collected in the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study at 5 sites (U.S. children's hospitals) performing weight-loss surgery in adolescents. The current study is a secondary analysis of these data. METHODS: We examined data collected presurgery through 5 years postsurgery. MetS risk/severity was defined using the MetS severity z score (MetS-z), and MetS prevalence was determined using age-appropriate criteria. Association between SAD and MetS-z was evaluated with an adjusted linear mixed model. RESULTS: Among 228 individuals (75% female, 72% White), mean age 16.5 years and body mass index (BMI) 53 kg/m2, 79% met MetS criteria pre-urgery. MetS-z (1.5) and SAD (32cm) were correlated (r = 0.6, P < .0001) presurgery, and both improved significantly at 6 months, 1, and 5 years postsurgery, remaining highly correlated at each timepoint. SAD predicted MetS-z (ß = 0.118; 95% CI, 0.109, 0.127) after adjustment for age, visit, surgery type, and caregiver education. CONCLUSIONS: Abdominal obesity is a key MetS risk marker in youth undergoing weight loss surgery. Both SAD and Met-z measures may be useful for MetS risk assessment and tracking postsurgery changes in this population, but more research is needed to identify effective lifestyle interventions targeting abdominal obesity.

Skeletal Effects of Sleeve Gastrectomy in Adolescents and Young Adults: A 2-Year Longitudinal Study.

CONTEXT: Vertical sleeve gastrectomy (VSG) is an increasingly common tool to achieve weight loss and improve metabolic health in adolescents and young adults with obesity, although it may adversely affect bone health. OBJECTIVE: This work aimed to evaluate the effect of VSG on bone health in youth. METHODS: An observational 2-year study was conducted at a tertiary care center of 66 patients aged 13 to 24 years with moderate-to-severe obesity meeting criteria for VSG. The patients underwent VSG (n = 30) or nonsurgical (n = 36) management per the decision of patient and clinical team. Main outcome measures included dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of bone mineral density (BMD), geometry, and microarchitecture. RESULTS: VSG patients achieved 25.3 ± 2.0% weight loss at 2 years (P < .001) while control subjects gained 4.0 ± 2.0% (P = .026). Total hip BMD declined 8.5 ± 1.0% following VSG compared with 0.1 ± 1.0% gain in controls (P < .001), with similar results at the femoral neck (P < .001). Total volumetric BMD (vBMD) decreased both at the distal radius and tibia following VSG (P < .001) driven primarily by trabecular vBMD loss (P < .001). Two-year changes in cortical vBMD did not differ between groups, though cortical porosity decreased following VSG both at the radius and tibia (P = .048 and P < .001). Cortical thickness increased in controls but not in VSG (P = .022 and P = .002 for between-group comparisons at the radius and tibia, respectively). Following VSG, estimated failure load decreased at the radius and did not demonstrate the physiologic increases at the tibia observed in controls. CONCLUSION: VSG leads to progressive changes in bone health over 2 years, and may lead to increased skeletal fragility in adolescents and young adults.

Variation in cost of disposable operating room supplies at a children's hospital.

BACKGROUND: Operating room (OR) costs account for 40% of hospital costs. Disposable supplies make up a portion of OR costs and are the only cost that is under control of the surgeon. There are little data to explain how surgeons select surgical supplies and what factors predict supply selection. Our goal with the current work was to assess variation in cost of disposable OR supplies at the surgeon level, hypothesizing high variability would be observed. STUDY DESIGN: Cost data were reviewed for the most common procedures performed by five surgical divisions at a single children's hospital over a six-month period in 2021. For each procedure, the average disposable OR costs for each surgeon were tabulated and compared to the median supply cost for a given procedure at the group level. RESULTS: For each procedure, the variation ranged from 149% (gastrostomy tube placement) to 758% (tonsillectomy and adenoidectomy). The median supply cost for an individual surgeon was not always above or below the median supply cost for that procedure for the group. No relationship was observed between whether the supply cost was above or below the median for a given case and a surgeon's case volume, years in practice, or operative length. There was also no relationship between surgeon volume and median cost, surgery length, and years of experience. CONCLUSION: These data demonstrate variation in the cost of disposable OR supplies at the individual surgeon level at a single institution. This variation is not explained by case volume, years in practice, or operative length.

Psychosocial predictors of problematic eating in young adults who underwent adolescent bariatric surgery.

Introduction: This study examined problematic eating and eating-related psychopathology among young adults who underwent adolescent bariatric surgery including concurrent and prospective associations with psychosocial factors and weight change. Methods: VIEW point is a 6-year follow-up study within a prospective observational study series observing adolescents with severe obesity who had bariatric surgery (n = 139) or who presented to nonsurgical lifestyle modification programs (n = 83). Participants completed height/weight measurements, questionnaires, and diagnostic interviews. Regression analyses compared problematic eating across groups and examined Year 6 correlates (i.e., psychosocial factors and weight change) and baseline predictors (i.e., psychosocial factors) of eating-related psychopathology. Results: Compared to the nonsurgical group, the surgical group reported lower eating-related psychopathology, objective binge eating, and grazing at Year 6. While chewing/spitting out and vomiting for weight/shape-related reasons were very infrequent for the surgical group, self-induced vomiting for other reasons (e.g., avoid plugging) was more common. For the surgical group, lower self-worth, greater internalizing symptoms, and higher weight-related teasing in adolescence predicted increased eating-related psychopathology in young adulthood. Year 6 eating-related psychopathology was concurrently associated with lower percent weight loss for the surgical group and greater percent weight gain for the nonsurgical group. Conclusion: Undergoing adolescent bariatric surgery appears to afford benefit for problematic eating and eating-related psychopathology. Current findings suggest that the clinical intervention related to problematic eating and associated psychosocial concerns may be needed for young adults with obesity, regardless of surgical status.