Adipocyte-Derived Small Extracellular Vesicles from Patients with Alzheimer Disease Carry miRNAs Predicted to Target the CREB Signaling Pathway in Neurons.

Alzheimer disease (AD) is characterized by amyloid-ß (Aß) plaques, neurofibrillary tangles, synaptic dysfunction, and progressive dementia. Midlife obesity increases the risk of developing AD. Adipocyte-derived small extracellular vesicles (ad-sEVs) have been implicated as a mechanism in several obesity-related diseases. We hypothesized that ad-sEVs from patients with AD would contain miRNAs predicted to downregulate pathways involved in synaptic plasticity and memory formation. We isolated ad-sEVs from the serum and cerebrospinal fluid (CSF) of patients with AD and controls and compared miRNA expression profiles. We performed weighted gene co-expression network analysis (WGCNA) on differentially expressed miRNAs to identify highly interconnected clusters correlating with clinical traits. The WGCNA identified a module of differentially expressed miRNAs, in both the serum and CSF, that was inversely correlated with the Mini-Mental State Examination scores. Within this module, miRNAs that downregulate CREB signaling in neurons were highly represented. These results demonstrate that miRNAs carried by ad-sEVs in patients with AD may downregulate CREB signaling and provide a potential mechanistic link between midlife obesity and increased risk of AD.

The impact of parental bariatric surgery and patient age on laparoscopic sleeve gastrectomy outcomes in adolescents.

BACKGROUND: Adolescent obesity is multifactorial, but parental history is the most significant risk factor. Laparoscopic sleeve gastrectomy (LSG) is part of the multidisciplinary approach to adolescent weight loss. OBJECTIVE: We aimed to evaluate the effects of parental history of bariatric surgery, as well as age at time of operation, on adolescents who underwent LSG at our institution. METHODS: We performed a retrospective review of patients, aged 10 to 19 years, who underwent LSG from January 2010 to December 2019. The adolescent bariatric surgical dataset maintained by our group was used to obtain patient demographics, weight, body mass index (BMI), and parental history of bariatric surgery. RESULTS: Among 328 patients, 76 (23.2%) had parents who had previously undergone bariatric surgery. These patients were significantly heavier by weight (p = 0.012) at the time of operation but had no difference in postoperative weight loss. When all patients were compared by age at operation (< 16 years, n = 102, ≥ 16 years, n = 226), there were few differences in outcomes. CONCLUSIONS: LSG is an effective approach to surgical weight loss in adolescents. Patient age should not be a barrier to weight loss surgery, especially among patients with a parental history of obesity. By intervening at a younger age, the metabolic sequelae of obesity may be reduced.

The Role of the Gut Microbiome in Pediatric Obesity and Bariatric Surgery.

Obesity affects 42.4% of adults and 19.3% of children in the United States. Childhood obesity drives many comorbidities including hypertension, fatty liver disease, and type 2 diabetes mellitus. Prior research suggests that aberrant compositional development of the gut microbiome, with low-grade inflammation, precedes being overweight. Therefore, childhood may provide opportunities for interventions that shape the microbiome to mitigate obesity-related diseases. Children with obesity have gut microbiota compositional and functional differences, including increased proinflammatory bacterial taxa, compared to lean controls. Restoration of the gut microbiota to a healthy state may ameliorate conditions associated with obesity and help maintain a healthy weight. Pediatric bariatric (weight-loss) surgery is an effective treatment for childhood obesity; however, there is limited research into the role of the gut microbiome after weight-loss surgery in children. This review will discuss the magnitude of childhood obesity, the importance of the developing microbiome in establishing metabolic pathways, interventions such as bariatric surgery that may modulate the gut microbiome, and future directions for the potential development of microbiome-based therapeutics to treat obesity.

Surgical Treatment of Type 2 Diabetes Mellitus in Youth.

Bariatric surgery is currently the most effective weight loss treatment of severe obesity and its associated comorbidities and is being increasingly used to treat children and adolescents with severe obesity, including those with Type 2 Diabetes (T2D). This review focuses on the conventional management of T2D in children and adolescents, comparison of various types of bariatric surgeries, effect of bariatric surgery on gastrointestinal physiology and metabolism, current literature on the use of bariatric surgery to treat youth with severe obesity and T2D, and the potential complications of bariatric surgery in this population.

Cholesterol efflux alterations in adolescent obesity: role of adipose-derived extracellular vesical microRNAs.

BACKGROUND: Macrophage cholesterol efflux capacity has been identified as a predictor for cardiovascular disease. We assessed the relationship between adipocyte-derived extracellular vesicle microRNAs and macrophage cholesterol efflux capacity. METHODS: We assessed an adolescent cohort (n = 93, Age, median (IQR) = 17 (3) year, Female = 71, Male = 22) throughout the BMI continuum (BMI = 45.2 (13.2) kg/m2) for: (1) cholesterol efflux capacity and lipoprotein profiles; (2) adipocyte-derived extracellular vesicle microRNAs in serum; (3) the role of visceral adipose tissue extracellular vesicle in regulation of cholesterol efflux and cholesterol efflux gene expression in THP-1 macrophages in vitro. RESULTS: Efflux capacity was significantly associated with HDL (r = 0.30, p = 0.01) and LDL (r = 0.33, p = 0.005) particle size. Multivariate-analysis identified six microRNAs associated (p < 0.05) with cholesterol efflux capacity: miR-3129-5p (Beta = 0.695), miR-20b (0.430), miR9-5p (0.111), miR-320d (- 0.190), miR301a-5p (0.042), miR-155-5p (0.004). In response to increasing concentrations (1 µg/mL vs. 3 µg/mL) of VAT extracellular vesicle, cholesterol efflux (66% ± 10% vs. 49% ± 2%; p < 0.01) and expression of ABCA1 (FC = 1.9 ± 0.8 vs 0.5 ± 0.2; p < 0.001), CD36 (0.7 ± 0.4 vs. 2.1 ± 0.8, p = 0.02), CYP27A1 (1.4 ± 0.4 vs. 0.9 ± 0.5; p < 0.05), and LXRA (1.8 ± 1.1 vs. 0.5 ± 0.2; p < 0.05) was altered in THP-1 cells in vitro. CONCLUSION: Adipocyte-derived extracellular vesicle microRNAs may, in part, be involved macrophage cholesterol efflux regulation.

Bariatric Surgery in Children: Indications, Types, and Outcomes.

PURPOSE OF REVIEW: The purpose of this review is to discuss the current state of surgical intervention for obesity in children and adolescents. Specifically, this review will discuss the different types of metabolic and bariatric surgery (MBS) procedures, guidelines for patient selection, and recent findings regarding surgical outcomes and complications. RECENT FINDINGS: MBS is safe in adolescents and has also demonstrated sustainable long term weight loss and improvement in obesity-associated comorbidities. A recent prospective multi-institutional trial demonstrated BMI reductions of 3.8 kg/m2 (8%) to 15.1 kg/m2 (28%) after 3 years among adolescents undergoing the three most common MBS procedures. Moreover, MBS is associated with remission of type 2 diabetes, prediabetes, hypertension, dyslipidemia, and abnormal kidney function in 65-95% of patients in the study. Childhood and adolescent obesity is a continuing problem that has not been adequately addressed by the medical community. MBS is currently the most successful strategy for significant and sustained weight loss and improvement of associated comorbidities. This review focuses on the different types of MBS, the selection and preparation of patients for surgery, and the expected outcomes and common complications.

Impulse Control in Negative Mood States, Emotional Eating, and Food Addiction are Associated with Lower Quality of Life in Adolescents with Severe Obesity.

Objectives: Quality of life (QoL) is an important outcome to evaluate in adolescents with severe obesity, yet intrapersonal predictors of QoL are understudied. The current study assessed whether difficulty with impulse control when experiencing a negative mood (negative urgency) is associated with poorer QoL, mediated by more emotional eating and food addiction. Method: Participants consisted of 69 primarily female (71%), minority (76%) adolescents aged 13-21 (M age = 16.5, SD = 1.5) with severe obesity presenting for prebariatric surgery psychological evaluations. Structural Equation Modeling was used to appraise a model of the association of adolescent report of negative urgency with more emotional eating (Emotional Eating Scale for Children) and food addiction (Yale Food Addiction Scale) and poorer weight-related QoL (Impact of Weight on Quality of Life-Kids). Results: Greater difficulty controlling behavior when experiencing a negative mood was significantly associated with poorer weight-related QoL, and this relationship was mediated by an association with emotional eating and food addiction such that adolescents with severe obesity who reported more difficulties with impulse control in negative mood states were more likely to report more emotional eating and food addiction, which was in turn associated with lower QoL. Conclusions: Intrapersonal factors, including impulse control in negative mood states, are associated with lower QoL in adolescents with severe obesity. Interventions aimed at reducing frequency of negative affect, reducing impulsivity in negative mood states, and improving coping skills that are not eating based may contribute to improved QoL and merit further study.

Cognitive Performance as Predictor and Outcome of Adolescent Bariatric Surgery: A Nonrandomized Pilot Study.

Objectives: Evidence in adults suggests that improvements in cognitive performance may follow weight loss resulting from bariatric surgery, and baseline cognitive performance may be associated with weight loss following surgery. This has not been evaluated in adolescents. Method: Participants were 38 adolescents of age 14-21 years composed of three groups: (1) 12 adolescents with severe obesity who received vertical sleeve gastrectomy during the study (VSG); (2) 14 adolescents with severe obesity who were wait-listed for VSG (WL); and (3) 12 healthy weight controls (HC). Participants completed testing of visual memory, verbal memory, and executive functioning at baseline (T1), which occurred presurgery for the VSG group, and approximately 4 months after baseline (T2). Body mass index (BMI) was assessed at T1, T2, and additionally at 6 months following VSG for the adolescents who received surgery. Results: Although there was evidence of greater improvement for the VSG as compared with WL and HC groups in visual and verbal memory, group differences did not reach significance and effect sizes were small (η2 < 0.01). There was a significant positive association between indices of baseline executive functioning and excess BMI loss at 6 months postsurgery. Conclusions: This small pilot study showed no significant differences by group in cognitive performance post-VSG. There was a significant association of baseline cognitive performance with weight loss outcomes. Given the very preliminary nature of these results in a small sample, future research should examine these relationships in a larger sample and evaluate mechanisms of these associations (e.g., insulin resistance, sleep, physical activity).

Evaluating the impact of a minimally invasive pediatric surgeon on hospital practice: comparison of two children's hospitals.

PURPOSE: Widespread adoption of minimally invasive surgery (MIS) techniques in pediatric surgery has progressed slowly, and the shift in practice patterns has been variable among surgeons. We hypothesized that a pediatric surgeon committed to MIS could effectively change surgical practice by creating an emphasis on MIS. METHODS: Annual case volumes from 2000 to 2009 at two tertiary care pediatric hospitals, one with a dedicated minimally invasive pediatric surgeon, were evaluated for trends in MIS for ten different operations. Univariate analyses of the differences between hospitals in the use of the open versus laparoscopic approach were performed. The Breslow-Day test was used to examine differences in use of laparoscopic procedures across hospitals in early versus middle and middle versus late time periods. RESULTS: Between the two hospitals, for 9 of the 10 types of surgery, the number of laparoscopic and open procedures differed significantly (p values ranged from <0.0001 to 0.003). Over the 10-year period, the hospital with a dedicated MIS surgeon had a larger proportion of procedures done laparoscopically for all years. This difference reached statistical significance for appendectomy (p < 0.0001), congenital diaphragmatic hernia (p < 0.0002), chest wall reconstruction (p < 0.0001), cholecystectomy (p = <0.0001), gastrostomy (p < 0.0001), nissen fundoplication (p < 0.0001) oophorectomy (p < 0.0001), pyloromyotomy (p < 0.0001) and splenectomy (p = 0.0006). After grouping the years into early (2000-2003), middle (2004-2006) and late (2007-2009) categories, the hospital with a dedicated MIS surgeon had a significantly higher rate of increase in use of laparoscopic surgery between the early and middle years for four procedures: diaphragmatic hernia repair (p = 0.003), chest wall reconstruction (p = 0.0086), cholecystectomy (0.0083) and endorectal pull-through (p = 0.025). CONCLUSION: The presence of a dedicated minimally invasive pediatric surgeon led to a significant change in surgical practice with an overall trend of increasing MIS several years in advance of a hospital that did not have a dedicated MIS surgeon. This has implications for resident training in academic medical centers and potential patient care outcomes.

Targeting Extracellular Cyclophilins Ameliorates Disease Progression in Experimental Biliary Atresia.

Biliary atresia (BA) is a devastating liver disease of unknown etiology affecting children generally within the first 3 months of life. The disease is manifested by inflammation and subsequent obstruction of the extrahepatic bile ducts, fibrosis and liver failure. The mechanisms responsible for disease pathogenesis are not fully understood, but a number of factors controlled by the SMAD signaling pathway have been implicated. In this study, we investigated the role of a known proinflammatory factor, extracellular cyclophilin A (CypA), in the pathogenesis of biliary atresia using the rhesus rotavirus (RRV) murine model. We used a unique cyclosporine A derivative, MM284, which does not enter cells and therefore inactivates exclusively extracellular cyclophilins, as a potential treatment. We demonstrated that levels of CypA in plasma of RRV-infected mice were increased significantly, and that treatment of mice with MM284 prior to or one day after disease initiation by RRV infection significantly improved the status of mice with experimental BA: weight gain was restored, bilirubinuria was abrogated, liver infiltration by inflammatory cells was reduced and activation of the SMAD pathway and SMAD-controlled fibrosis mediators and tissue inhibitor of metalloproteinases (TIMP)-4 and matrix metalloproteinase (MMP)-7 was alleviated. Furthermore, treatment of human hepatic stellate cells with recombinant cyclophilin recapitulated SMAD2/3 activation, which was also suppressed by MM284 treatment. Our data provide the first evidence that extracellular cyclophilins activate the SMAD pathway and promote inflammation in experimental BA, and suggest that MM284 may be a promising therapeutic agent for treating BA and possibly other intrahepatic chronic disorders.

Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease.

BACKGROUND: Obesity is frequently complicated by comorbid conditions, yet how excess adipose contributes is poorly understood. Although adipocytes in obese individuals induce systemic inflammation via secreted cytokines, another potential mediator has recently been identified (i.e., adipocyte-derived exosomes). We hypothesized that adipocyte-derived exosomes contain mediators capable of activating end-organ inflammatory and fibrotic signaling pathways. METHODS: We developed techniques to quantify and characterize exosomes shed by adipocytes from seven obese (age: 12-17.5 y, BMI: 33-50 kg/m(2)) and five lean (age: 11-19 y, BMI: 22-25 kg/m(2)) subjects. RESULTS: Abundant exosomal miRNAs, but no mRNAs, were detected. Comparison of obese vs. lean visceral adipose donors detected 55 differentially expressed miRNAs (P < 0.05; fold change ≥|1.2|). qRT-PCR confirmed downregulation of miR-148b (ratio = 0.2 (95% confidence interval = 0.1, 0.6)) and miR-4269 (0.3 (0.1, 0.8)), and upregulation of miR-23b (6.2 (2.2, 17.8)) and miR-4429 (3.8 (1.1-13.4)). Pathways analysis identified TGF-ß signaling and Wnt/ß-catenin signaling among the top canonical pathways expected to be altered with visceral adiposity based on projected mRNA targets for the 55 differentially expressed miRNAs. A select mRNA target was validated in vitro. CONCLUSION: These data show that visceral adipocytes shed exosomal-mediators predicted to regulate key end-organ inflammatory and fibrotic signaling pathways.

The impact of leukoreduced red blood cell transfusion on mortality of neonates undergoing extracorporeal membrane oxygenation.

BACKGROUND: Blood products containing leukocytes have been associated with negative immunomodulatory and infectious effects. Transfusion-related acute lung injury is partially explained by leucocyte agglutination. The Food and Drug Administration has therefore recommended leukoreduction strategies for blood product transfusion. Our institution has been using leukocyte-reduced blood via filtration for neonates on Extracorporeal Membrane Oxygenation (ECMO). We hypothesized that the use of leukocyte-reduced blood would decrease mortality and morbidity of neonatal ECMO patients. METHODS: Retrospective review of noncardiac ECMO in neonates from 1984-2011, stratified into year groups I and II (≤1996 and ≥1997). Demographics, duration and type of ECMO, complications, and outcome data were collected. Blood product use data was collected. Univariate, bivariate, and multivariate analyses determined predictors of risk-adjusted mortality by year group. RESULTS: Patients (827) underwent ECMO with 65.3% (540) in group I. Overall median blood product use in mL/kg/d was 36.2 packed red blood cells (pRBC), 8.1 platelets, and 0 cyroprecipitate and/or fresh-frozen plasma. Overall mortality was 16.4%. Median pRBC used or transfused was 42.1 mL/kg/d in group I versus 19.1 mL/kg/d group II (P <0.001). On bivariate analysis, there was no difference in crude mortality between the 2 year groups (17.2% versus 16.0%, P = 0.66). However, on multivariate analysis adjusting for demographics, diagnosis, complications, and blood product use other than pRBCs, each additional transfusion of 10 mL/kg/d of pRBC was associated with a 33% increase in mortality in group I (P <0.05). Group II also showed an increase in mortality with each additional transfusion (21%) but this was not statistically significant (P = 0.07). Days on ECMO were not associated with pRBC transfusion in group I but increased in group II (additional 3 d for each 10 mL/kg/d transfused). There was no difference in infectious complications between groups I and II. CONCLUSIONS: Blood transfusion requirement has diminished in newborns undergoing ECMO at our institution. Transfusion of non leukocyte-reduced blood is associated with an increase in mortality whereas transfusion of leukocyte-reduced blood provided no benefit with a trend toward increased mortality. Further research is recommended to understand these trends.

Adipocyte exosomes induce transforming growth factor beta pathway dysregulation in hepatocytes: a novel paradigm for obesity-related liver disease.

BACKGROUND: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) has been attributed to increased systemic inflammation and insulin resistance mediated by visceral adipose tissue (VAT), although the exact mechanisms are undefined. Exosomes are membrane-derived vesicles containing messenger RNA, microRNA, and proteins, which have been implicated in cancer, neurodegenerative, and autoimmune diseases, which we postulated may be involved in obesity-related diseases. We isolated exosomes from VAT, characterized their content, and identified their potential targets. Targets included the transforming growth factor beta (TGF-ß) pathway, which has been linked to NAFLD. We hypothesized that adipocyte exosomes would integrate into HepG2 and hepatic stellate cell lines and cause dysregulation of the TGF-ß pathway. METHODS: Exosomes from VAT from obese and lean patients were isolated and fluorescently labeled, then applied to cultured hepatic cell lines. After incubation, culture slides were imaged to detect exosome uptake. In separate experiments, exosomes were applied to cultured cells and incubated 48-h. Gene expression of TGF-ß pathway mediators was analyzed by polymerase chain reaction, and compared with cells, which were not exposed to exosomes. RESULTS: Fluorescent-labeled exosomes integrated into both cell types and deposited in a perinuclear distribution. Exosome exposure caused increased tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and integrin ανß-5 expression and decreased matrix metalloproteinase-7 and plasminogen activator inhibitor-1 expression in to HepG2 cells and increased expression of TIMP-1, TIMP-4, Smad-3, integrins ανß-5 and ανß-8, and matrix metalloproteinase-9 in hepatic stellate cells. CONCLUSIONS: Exosomes from VAT integrate into liver cells and induce dysregulation of TGF-ß pathway members in vitro and offers an intriguing possibility for the pathogenesis of NAFLD.

Integrin ß-8, but not ß-5 or -6, protein expression is increased in livers of children with biliary atresia.

OBJECTIVES: Our previous work demonstrated altered messenger RNA expression of integrin ß-5 and -8, using an in silico analysis of publically available data from patients with biliary atresia (BA); however, we were unable to demonstrate statistically significant differences in protein expression because of sample size. In the present study, we repeated the analysis of liver fibrosis and protein expression of the integrins in a larger cohort of patients with BA and compared them with patients undergoing liver biopsy for other diagnoses, with the hypothesis that ≥ 1 of the integrins would be differentially expressed. METHODS: Liver specimens were obtained at 2 collaborating institutions. Samples from infants with BA (n = 23) were compared with samples from those who underwent liver biopsy for neonatal hepatitis (n = 9). All of the specimens were analyzed by 2 pathologists (C.R. and R.A.), who were blinded to the diagnoses. Standard Ishak scoring was performed to evaluate fibrosis and inflammation, and immunohistochemical (IHC) positivity was graded from 0 to 4. Comparisons between the IHC positivity and Ishak scoring for the BA and control groups were performed using the Student t test with P < 0.01 considered significant because of the multiple comparisons. Interobserver variability was assessed by intraclass correlation (ICC). RESULTS: Pooled analysis from specimens from patients with BA showed significantly more fibrosis than controls based on Ishak scores (3.21 ± 1.82 vs 1.17 ± 1.00, P < 0.005). IHC evaluation showed increased integrin ανß8 protein expression when compared with controls (2.67 ± 0.81 vs 1.72 ± 0.62, P < 0.005); however, there were no significant differences in integrin ανß5 (1.93 ± 0.84 vs 1.50 ± 0.90, P = 0.23) or integrin ανß6 (0.85 ± 1.20 vs 0.94 ± 0.85, P = 0.82) expression. These data were confirmed on individual analysis. Interobserver agreement was fair for integrin ανß5 (ICC 0.52), good for integrin ανß6 (ICC 0.72), and excellent for integrin ανß8 (ICC 0.79) and fibrosis (ICC 0.89). CONCLUSIONS: Our data show that integrin ανß8, but not integrin ανß5 or integrin ανß6, protein expression is increased in liver specimens of patients with BA. These data support the mounting evidence that transforming growth factor-ß (TGF-ß) activation is responsible for the fibrosis found in BA. Anti-integrin ανß8 or more global integrin blocking strategies may be therapeutic options in BA, but further work is clearly needed.

Predicting sleep apnea in morbidly obese adolescents undergoing bariatric surgery.

INTRODUCTION: In adults, the association between obesity and obstructive sleep apnea (OSA) is established, and many are concerned OSA increases surgical risk. Pre-operative screening for OSA is standard, and this is also the case in adolescent bariatric surgery. We noted many of our patients were without significant OSA, despite being obese. We reviewed our experience with screening polysomnography (PSG) to determine any predictive variables or complications. METHODS: All bariatric surgery patients from our hospital who had undergone PSG were included, and were stratified into 'OSA' or 'no OSA' by obstructive apnea-hypopnea index (OAHI), as well as by sex. RESULTS: A total of 49 adolescents enrolled during the study period: 10 males and 39 females. OSA prevalence was 42.9 %; males 80 %, females 33.3 %. Height, weight, body mass index (BMI), and prevalence of hypertension were significantly higher in patients with OSA. By sex, females also had more metabolic syndrome and witnessed apneas, while only weight and BMI remained significant in males. There were no peri-operative complications. CONCLUSIONS: Despite uniform obesity, less than half our adolescents had significant OSA on PSG. As no modeling exists to predict OSA in morbidly obese adolescents, we continue to recommend routine PSG, especially in higher weight and BMI patients, and those with hypertension.

Outcomes after metabolic and bariatric surgery in preteens versus teens using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database and center-specific data.

OBJECTIVE: The American Academy of Pediatrics (AAP) recently released clinical guidelines for the treatment of childhood obesity, including surgery being appropriate for children 13 years of age and older. The use of this age cut-off was due to a lack of data for children younger than 13. To address this knowledge gap, the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried to compare outcomes in preteens to teens after bariatric surgery hypothesizing that there would be no difference in outcomes between the two groups. METHODS: Patients from the MSAQIP database (2016-2021) were identified and divided into groups <13 years and 13-18 years and were matched using propensity scores based on race, sex, and preoperative BMI. Outcomes were compared including change in BMI, complication rates, 30-day readmission or reoperation, and mortality. Additionally, the centers responsible for the bulk of the preteen patient entries queried their center-specific databases to evaluate weight loss over time. RESULTS: A total of 4755 patients were identified, 47 of whom were <13 years of age. Preteens had similar sex distribution (66% vs. 75% female), were more likely to be Black (27.7% vs. 18.3%) or Hispanic (21.3% vs. 7.6%) race, and weighed less (274 ± 58 vs. 293 ± 85 lb, p = 0.01), but they had similar BMI (46.9 ± 7 vs. 47 ± 13 kg/m2 ) as their teen counterparts. Preteens were more likely to suffer from sleep apnea (34% vs. 19%, p < 0.01) and insulin-dependent type 2 diabetes (10.6% vs. 1.8%, p < 0.01). There were no complications in the preteens compared to teens (0% vs. 0.5%), and they did not undergo any unplanned readmissions (0% vs. 2.9%) or reoperations (0% vs. 0.8%) within 30 days of surgery. There were also no mortalities reported in preteens (0% vs. 0.1%). The risk-adjusted decrease in BMI between preteens and teens was also comparable at 30 days (4.2 [95% CI: 3.0-5.4] vs. 4.6 [95% CI: 4.4-4.7], p = 0.6). Decrease in BMI in preteens was 7 ± 3 kg/m2 at 3 months and 9 ± 4 kg/m2 at 12 months after surgery, which represented a percentage BMI change of 16 ± 7 and 20 ± 8, respectively. CONCLUSIONS: This study demonstrates that bariatric surgery in preteens is safe and efficacious when performed at specialized centers, and that age criteria may not be required. The AAP and others are encouraged to include age cut-offs in their guidelines for children with obesity and bariatric surgery only when data are available to support their inclusion.

Immune profile of adipose tissue from youth with obesity and asthma.

BACKGROUND: Obesity is a risk factor for paediatric asthma. Obesity-mediated systemic inflammation correlates with metabolic dysregulation; both are associated with asthma burden. However, adipose tissue inflammation is not defined in obesity-related asthma. OBJECTIVE: Define adipose tissue inflammation and its association with metabolic measures in paediatric obesity-related asthma. METHODS: Cellular profile of stromal vascular fraction from visceral adipose tissue (VAT) from youth with obesity-related asthma (n = 14) and obesity without asthma (n = 23) was analyzed using flow cytometry and correlated with metabolic measures. RESULTS: Compared to youth without asthma, VAT from youth with obesity-related asthma was enriched for leukocytes and macrophages, including M1 and dual M1M2 cells, but did not differ for CD4+ lymphocytes, and endothelial cells, their progenitors, and preadipocytes. M1 macrophage counts positively correlated with glucose, while M1M2 cells, CD4+ lymphocytes, and their subsets negatively correlated with high-density lipoprotein, in youth with obesity without asthma, but not among those with obesity-related asthma. CONCLUSIONS: Enrichment of macrophage-mediated inflammation in VAT from youth with obesity-related asthma supports its role in systemic inflammation linked with asthma morbidity. Lack of correlation of VAT cells with metabolic dysregulation in youth with obesity-related asthma identifies a need to define distinguishing factors associated with VAT inflammation in obesity-related asthma.

The changing population of the United States and use of extracorporeal membrane oxygenation.

BACKGROUND: Neonatal extracorporeal membrane oxygenation (ECMO) has been widely used for the last 25 y. The impact of ethno-demographic changes on ECMO outcomes has not been fully examined. We evaluated the Extracorporeal Life Support Organization registry over a 21-y period to understand these trends. METHODS: A retrospective review of all neonates undergoing noncardiac ECMO in the United States between the years 1990 and 2010 was conducted based on the years of available live birth census data. Demographic, clinical, and outcome data were collated. Patient specifics, ECMO type, ECMO length, arterial blood gases, and mortality were analyzed. Univariate, bivariate, and multivariate analyses were then performed. Changes in ethnic composition of neonates on ECMO were compared with similar ethnic trend in available U.S. live birth data. RESULTS: Data were available for 18,130 neonates. Comparing ethnicity by year, the proportion of Caucasian neonates requiring ECMO dropped from 64.3% in 1990 to 49.5% in 2010, while African-American and Hispanic neonates on ECMO increased from 21.1% and 11.1% to 26.1% and 17.4%, respectively (P < 0.001). By diagnosis, congenital diaphragmatic hernia surpassed meconium aspiration syndrome as the leading indication for ECMO compared with 1990 (congenital diaphragmatic hernia, 21.5%-28.4%; meconium aspiration syndrome, 47.0%-15.7%; P < 0.05). ECMO mortality nearly doubled, from 18.5% to 34.0% over the study period. On adjusted analysis, African-Americans were 17% less likely to die on ECMO compared with Caucasian neonates. CONCLUSIONS: Neonates of ethnic minorities continue to disproportionally require ECMO support in comparison to their birth rates. Although ethnicity alone does not impact the outcome of these newborns, the increased requirement of ECMO may highlight the need for targeted education, improved prenatal care, and decision making in these groups.

Left thoracoscopic sympathectomy used as primary therapy for a young child with intractable long QT syndrome.

A 3-year-old boy with familial long QT syndrome type 2 presented with recurrent syncope despite adequate beta-blocker therapy. Two family members had experienced sudden cardiac arrest, and one other relative had experienced sudden cardiac death. Given the high risk for ventricular arrhythmia/syncope, the decision was made to perform primary cardiac denervation therapy through a minimally invasive approach without concomitant automatic cardioverter-defibrillator implantation. Using video-assisted thoracoscopic surgery, the left-sided sympathetic ganglia from T2-T5 were identified, and dissection along the sympathetic chain with transection of the corresponding rami along T2-T5 in addition to the lower half of the stellate ganglion was performed. The chest tube was removed on day 1 after surgery, and the patient was discharged on postoperative day 4. During 14 months of follow-up evaluation, no intervening episodes of ventricular arrhythmia or syncope and no symptoms of Horner's syndrome were noted.

Child and Adolescent Bariatric Surgery in an Urban Tertiary Center: Special Anesthetic Considerations for Obesity.

Children and adolescents with obesity who present for weight loss surgery are a unique subset of patients. A thorough understanding of the perioperative needs of these individuals is essential to avoid deleterious complications. This review illustrates the necessity for specialized care, including the continued need of specified drug dosing and a systematic approach in the management of the pediatric bariatric patient.