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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.
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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.
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Exposición a Riesgos Ambientales , Contaminantes Ambientales , Fluorocarburos , MicroARNs , Humanos , MicroARNs/sangre , Femenino , Niño , Fluorocarburos/sangre , Masculino , Adolescente , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/sangre , Biomarcadores/sangre , Estudios de Cohortes , Estados Unidos , Grecia , Estudios LongitudinalesRESUMEN
OBJECTIVE: Weight loss following vertical sleeve gastrectomy (VSG) in youth can range from 10% to 50%. We examined whether there are differences in demographic or metabolic parameters before VSG in youth who achieve above-average weight loss (AAWL) versus below-average weight loss (BAWL) at 1 year post VSG and if youth with BAWL still achieve metabolic health improvements at 1 year post VSG. METHODS: Demographic, anthropometric, and clinical lab data were collected before VSG and at 1, 3, 6, and 12 months after VSG. RESULTS: Forty-three youth with a mean age of 16.9 (SD 1.7) years before VSG were studied; 70% were female, 19% non-Hispanic Black, 58% non-Hispanic White, and 23% mixed/other race. Mean baseline BMI was 51.1 (SD 10.5) kg/m2. Average weight loss was 25.8%. The AAWL group lost 18.6 kg/m2 (35.3%) versus the BAWL group, who lost 8.8 kg/m2 (17.5%). BMI, age, race, sex, and socioeconomic status at baseline were similar between AAWL and BAWL groups; however, the BAWL group had a higher frequency of pre-VSG dysglycemia, steatotic liver disease, and dyslipidemia. At 1 year post VSG, fewer youth in the BAWL group achieved ideal health parameters, and they had less resolution of comorbidities. CONCLUSIONS: The presence of comorbidities before VSG is associated with less weight loss and reduced resolution of metabolic conditions at 1 year post VSG.
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Índice de Masa Corporal , Gastrectomía , Pérdida de Peso , Humanos , Femenino , Masculino , Adolescente , Gastrectomía/métodos , Gastrectomía/efectos adversos , Resultado del Tratamiento , Obesidad Mórbida/cirugía , Obesidad Infantil/cirugía , Dislipidemias/epidemiología , Cirugía Bariátrica/métodos , Periodo PreoperatorioRESUMEN
PURPOSE: The utility of pulmonary function testing (PFT) in pectus excavatum (PE) has been subject to debate. Although some evidence shows improvement from preoperative to postoperative values, the clinical significance is uncertain. A high failure-to-completion rate for operative PFT (48%) was identified in our large institutional cohort. With such a high non-completion rate, we questioned the overall utility of PFT in the preoperative assessment of PE and sought to evaluate if other measures of PE severity or cardiopulmonary function could explain this finding. METHODS: Demographics, clinical findings, and results from cardiac MRI, PFT (spirometry and plethysmography), and cardiopulmonary exercise tests (CPET) were reviewed in 270 patients with PE evaluated preoperatively between 2015 and 2018. Regression modeling was used to measure associations between PFT completion and cardiopulmonary function. RESULTS: There were no differences in demographics, symptoms, connective tissue disorders, or multiple indices of pectus severity and cardiac deformation in PFT completers versus non-completers. While regression analysis revealed higher RVEF, LVEF, and LVEF-Z scores, lower RV-ESV/BSA, LV-ESV/BSA, and LV-ESV/BSA-Z scores, and abnormal breathing reserve in PFT completers vs. non-completers, these findings were not consistent across continuous and binary analyses. CONCLUSIONS: We found that PFT completers were not significantly different from non-completers in most structural and functional measures of pectus deformity and cardiopulmonary function. Inability to complete PFT is not an indicator of pectus severity.
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Tórax en Embudo , Humanos , Tórax en Embudo/cirugía , EspirometríaRESUMEN
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.
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Cirugía Bariátrica , Contaminantes Ambientales , Humanos , Adolescente , Masculino , Femenino , Estudios Longitudinales , Contaminantes Ambientales/sangre , Exposición a Riesgos Ambientales/estadística & datos numéricos , Fluorocarburos/sangre , Obesidad Mórbida/cirugía , Obesidad Mórbida/sangreRESUMEN
BACKGROUND: The benefit of targeting high ratio fresh frozen plasma (FFP)/red blood cell (RBC) transfusion in pediatric trauma resuscitation is unclear as existing studies are limited to patients who retrospectively met criteria for massive transfusion. The purpose of this study is to evaluate the use of high ratio FFP/RBC transfusion and the association with outcomes in children presenting in shock. METHODS: A post hoc analysis of a 24-institution prospective observational study (April 2018 to September 2019) of injured children younger than 18 years with elevated age-adjusted shock index was performed. Patients transfused within 24 hours were stratified into cohorts of low (<1:2) or high (≥1:2) ratio FFP/RBC. Nonparametric Kruskal-Wallis and χ 2 were used to compare characteristics and mortality. Competing risks analysis was used to compare extended (≥75th percentile) ventilator, intensive care, and hospital days while accounting for early deaths. RESULTS: Of 135 children with median (interquartile range) age 10 (5-14) years and weight 40 (20-64) kg, 85 (63%) received low ratio transfusion and 50 (37%) high ratio despite similar activation of institutional massive transfusion protocols (low-38%, high-46%, p = 0.34). Most patients sustained blunt injuries (70%). Median injury severity score was greater in high ratio patients (low-25, high-33, p = 0.01); however, hospital mortality was similar (low-24%, high-20%, p = 0.65) as was the risk of extended ventilator, intensive care unit, and hospital days (all p > 0.05). CONCLUSION: Despite increased injury severity, patients who received a high ratio of FFP/RBC had comparable rates of mortality. These data suggest high ratio FFP/RBC resuscitation is not associated with worst outcomes in children who present in shock. Massive transfusion protocol activation was not associated with receipt of high ratio transfusion, suggesting variability in MTP between centers. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.
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Transfusión de Eritrocitos , Plasma , Resucitación , Humanos , Niño , Adolescente , Femenino , Masculino , Preescolar , Transfusión de Eritrocitos/estadística & datos numéricos , Transfusión de Eritrocitos/métodos , Resucitación/métodos , Estudios Prospectivos , Heridas y Lesiones/terapia , Heridas y Lesiones/mortalidad , Heridas y Lesiones/complicaciones , Puntaje de Gravedad del Traumatismo , Transfusión de Componentes Sanguíneos/estadística & datos numéricos , Transfusión de Componentes Sanguíneos/métodos , Resultado del Tratamiento , PrevalenciaRESUMEN
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.
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Adipogénesis , Cirugía Bariátrica , Índice de Masa Corporal , Diclorodifenil Dicloroetileno , Grasa Intraabdominal , Pérdida de Peso , Humanos , Adolescente , Masculino , Femenino , Grasa Intraabdominal/metabolismo , Estudios Longitudinales , Obesidad Infantil/metabolismo , Adipocitos/metabolismo , Estudios de Cohortes , Circunferencia de la CinturaRESUMEN
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.
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Cirugía Bariátrica , Disfunción Cognitiva , Obesidad Mórbida , Humanos , Adolescente , Masculino , Femenino , Cirugía Bariátrica/efectos adversos , Disfunción Cognitiva/etiología , Obesidad Mórbida/cirugía , Obesidad Mórbida/psicología , Adulto Joven , Cognición/fisiología , Estudios de Seguimiento , Obesidad Infantil/cirugía , Obesidad Infantil/psicología , Pruebas Neuropsicológicas , Función Ejecutiva/fisiologíaRESUMEN
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.
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MicroARN Circulante , MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Obesidad Mórbida , Niño , Adolescente , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Hígado/patología , MicroARN Circulante/genética , MicroARN Circulante/metabolismo , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Obesidad Mórbida/metabolismo , MicroARNs/metabolismo , Obesidad/complicaciones , Fibrosis , Inflamación/patologíaRESUMEN
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.
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Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Humanos , Adolescente , Adulto Joven , Adulto , Densidad Ósea , Obesidad Mórbida/cirugía , Derivación Gástrica/métodos , Absorciometría de FotónRESUMEN
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.
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Trayectoria del Peso Corporal , Derivación Gástrica , Laparoscopía , Obesidad Mórbida , Humanos , Femenino , Adolescente , Adulto , Masculino , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Estado Civil , Pérdida de Peso , Gastrectomía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: Plant diversification, especially sowing crops with the addition of companion plants has been demonstrated as a suitable practice to increase insect pest control in multiple cropping systems. Since the ban on use of neonicotinoid seed treatments in oilseed rape (OSR), the harvested area has reduced significantly in Europe, mainly because of the damage caused by cabbage stem flea beetle (Psylliodes chrysocephala). Several companion plants such as legumes and other species of Brassicaceae have been reported as potential companions for OSR but robust evaluation of their efficiency to reduce cabbage stem flea beetle damage in replicated trials is lacking. RESULTS: Four field trials were conducted in the UK and Germany to test the effect of different companion plants, or the addition of straw mulch, on cabbage stem flea beetle adult feeding and larval infestation in OSR. We found significant differences in the level of feeding damage between treatments in all experiments. Combinations of OSR with cereal companion plants or with straw mulch showed the strongest reduction in adult feeding damage. A protective effect of legumes was also observed in one trial. Differences in larval infestation were also observed between treatments but were not consistent and might be more related to the OSR plant biomass than to treatments. CONCLUSION: This study shows that companion planting can protect OSR crops from cabbage stem flea beetle adult feeding damage. We show for the first time that not only legumes, but also cereals and the application of straw mulch can have a strong protective effect on the crop. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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Brassica napus , Brassica , Escarabajos , Insecticidas , Siphonaptera , Animales , Insecticidas/farmacología , Verduras , Productos AgrícolasRESUMEN
BACKGROUND: Dynamic compression system (DCS) is often effective at treating pectus carinatum (PC). However, some patients will fail therapy. This study reports outcomes from a nurse-practitioner led bracing program, and evaluates what factors are predictive of successful therapy. METHODS: We performed a retrospective cohort study involving all patients treated with DCS bracing at our institution between February 2018 and February 2022. Patients with at least three visits were included. The primary outcome was achieving neutral chest. Factors considered potentially predictive included patient age, sex, initial pressure of correction (PIC), and the change in pressure of correction between the first two visits (deltaPC1). A Cox proportional hazards model was used for analysis, and Kaplan-Meier analyses estimated the median time to correction. RESULTS: 283 patients were evaluated. The median age was 14 (IQR 12-15), the majority were male (90.1 %) and white (92.6 %). The median PIC and deltaPC1was 4.13 PSI (IQR 3.17-5.3), and 1.34 PSI (IQR 0.54-2.25), respectively. 117 patients achieved correction. The median estimated time to correction was 7.5 months (95 % CI 5.9-10.1). In the final Cox model, greater deltaPC1 was associated with increased risk of correction (HR: 2.46; 95 % CI 2.03-2.98), and increased PIC was associated with decreased risk of correction up to one year of therapy (0-3 months HR 0.62, 95 % CI 0.50-0.78; 3-12 months HR 0.62; 95 % CI 0.45-0.85). CONCLUSIONS: DCS bracing administered by advanced care providers in collaboration with surgeons can effectively treat PC. The deltaPC1 and PIC are the factors most predictive of successful therapy. LEVEL OF EVIDENCE: Level III.
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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.
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Cirugía Bariátrica , Enfermedad del Hígado Graso no Alcohólico , Obesidad Mórbida , Adolescente , Humanos , Alanina Transaminasa , Cirugía Bariátrica/métodos , Glucosa , Enfermedad del Hígado Graso no Alcohólico/cirugía , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Pronóstico , Estudios Prospectivos , Triglicéridos , Pérdida de Peso , Masculino , FemeninoRESUMEN
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.
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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.
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Ácidos Alcanesulfónicos , Cirugía Bariátrica , Contaminantes Ambientales , Fluorocarburos , Animales , Humanos , Adolescente , Estudios de Cohortes , Hígado , Fluorocarburos/análisisRESUMEN
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.
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Hepatoblastoma is the most common malignant liver tumor of childhood, with liver transplant and extended resection used as surgical treatments for locally advanced tumors. Although each approach has well-described post-operative complications, quality-of-life outcomes have not been described following the two interventions. Long-term pediatric survivors of hepatoblastoma who underwent conventional liver resection or liver transplantation at a single institution from January 2000-December 2013 were recruited to complete quality-of-life surveys. Survey responses for the Pediatric Quality of Life Generic Core 4.0 (PedsQL, n = 30 patient and n = 31 parent surveys) and Pediatric Quality of Life Cancer Module 3.0 (PedsQL-Cancer, n = 29 patient and n = 31 parent surveys) were collected from patients and parents. The mean total patient-reported PedsQL score was 73.7, and the parent-reported score was 73.9. There were no significant differences in scores on the PedsQL between patients who underwent resection compared to those who underwent transplantation (p > 0.05 for all comparisons). On the PedsQL-Cancer module, procedural anxiety scores were significantly lower for patients who underwent resection as compared to transplant (M = 33.47 points less, CI [-60.41, -6.53], p-value 0.017). This cross-sectional study demonstrates that quality of life outcomes are overall similar among patients receiving transplants and resections. Patients who received a resection reported worse procedural anxiety.
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BACKGROUND: Few studies have evaluated racial/ethnic inequities in acute pain control among hospitalized injured children. We hypothesized that there would be inequities in time to pain control based on race/ethnicity and socioeconomic status. METHODS: We performed a retrospective cohort study of all injured children (7-18 years) admitted to our level 1 trauma center between 2010 and 2019 with initial recorded numerical rating scale (NRS) scores of >3 who were managed nonoperatively. A Cox regression survival analysis was used to evaluate the time to pain control, defined as achieving an NRS score of ≤3. RESULTS: Our cohort included 1,787 admissions. The median age was 14 years (interquartile range, 10-18), 59.5% were male, 76.6% identified as White, 19.9% as Black, and 2.4% as Hispanic. The median initial NRS score was 7 (interquartile range, 5-9), and the median time to pain control was 4.9 hours (95% confidence interval, 4.6-5.3). Insurance status, as a marker of socioeconomic status, was not associated with time to pain control ( p = 0.29). However, the interaction of race/ethnicity and deprivation index was significant ( p = 0.002). Specifically, the socioeconomic deprivation of a child's home neighborhood was an important predictor for non-White children ( p <0.003) but not for White children ( p = 0.41) and non-White children from higher deprivation neighborhoods experienced greater times to pain control (hazard ratio, 1.55; 95% confidence interval, 1.16-2.07). Being female, older, presenting with higher initial NRS scores, and having history of attention-deficit/hyperactivity disorder were all associated with longer times to pain control. Other injury characteristics and psychiatric history were evaluated but ultimately excluded, as they were not significant. CONCLUSION: Greater neighborhood socioeconomic deprivation was associated with prolonged time to pain control for non-White children admitted after injury and managed nonoperatively. Further work is needed to understand inequities in pain control for injured patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.
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Etnicidad , Manejo del Dolor , Grupos Raciales , Clase Social , Tiempo de Tratamiento , Adolescente , Niño , Femenino , Humanos , Masculino , Dolor , Estudios Retrospectivos , Heridas y LesionesRESUMEN
PURPOSE: Injury is the leading cause of childhood morbidity and mortality. Injury prevention (IP) initiatives are often created in isolation from the communities most affected. We hypothesized that the use of a comprehensive approach to injury prevention through community partnerships will result in a measurable reduction in pediatric injuries. METHODS: The IP program at our free-standing level 1 pediatric trauma center developed partnerships within eight targeted high-risk communities. IP coordinators and community partners implemented programs driven by community-specific injury data and community input. Programs focused on home, bike, playground, pedestrian, and child passenger safety. Program components included in-home education with free safety equipment and installation; free bike helmet fittings and distribution; community playground builds; and car seat classes with education, free car seat distribution and installation. Using trauma registry data, we compared injuries rates in targeted communities with non-intervention communities county-wide over an eight-year period. RESULTS: Between 2012 and 2019, nearly 4000 families received home safety equipment and education through community partnerships. Approximately 2000 bike helmets, 900 car/booster seats, in addition to safety messages and education were provided across the intervention communities. Over this 8-year time period, the injury rates significantly decreased by 28.4%, across the eight targeted high-risk communities, compared to a 10.9% reduction in non-intervention communities across the county. CONCLUSIONS: Effective injury prevention can be achieved through partnerships, working in solidarity with community members to address actual areas of concern to them. Sharing data, seeking ongoing community input, continuously reviewing learnings, and implementing identified changes are crucial to the success of such partnerships. LEVEL OF EVIDENCE: Level III.