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Introduction: We have previously shown that rabbit breast milk, or breast milk-derived secretory IgA (sIgA), but not IgG nor lactoferrin, protects neonatal rabbits from bacterial translocation (BT). However, it is not known whether this protection is species-specific. Cross-species effectiveness of sIgA could make it an important adjunct in the treatment or prevention of necrotizing enterocolitis (NEC) or gut-origin sepsis. We hypothesized that human breast milk (HBM) may protect neonatal rabbits from BT by agglutinating the indigenous intestinal microbial flora, a process known as immune exclusion. Methods: Newborn rabbits were randomized to receive a nutritionally complete artificial formula, or an equal volume of HBM. Quantitative cultures of the blood, mesenteric lymph nodes, liver, spleen, and cecum were obtained on day 6 for BT. sIgA, IgG, and lactoferrin were isolated from HBM via ion-exchange chromatography and tested for their ability to agglutinate translocating bacteria in vitro. Results: Neonates fed HBM had a significantly lower incidence of BT than those fed formula (4/9 v. 8/8; p =0.029, Fischer's Exact test). There was no significant difference in the cecal flora, or in the species of transiocating organisms between the two groups. E coli, Enterobacter, Enterococcus, and Lactobacillus were the most common translocating organisms. HBM, sIgA, and IgG agglutinated each species of bacteria to varying degrees. Lactoferrin and formula had no effect. Conclusion: Our data show that HBM protects neonatal rabbits from BT without altering the composition or quantity of cecal flora. The mechanism likely involves IgA-mediated immune exclusion, since it is 5 times more abundant in human breast milk than IgG and is more resistant to proteolytic degradation in the stomach than IgG. This finding may have far-reaching implications for the prevention of NEC or of intestinal barrier failure, especially in formula-fed premature infants., EP Nadler MD, X Zhou PhD, K Wong, P Boyle, Y Chen MD, PhD, HR Ford MD, FAAP; Children's Hospital of Pittsburgh, Pittsburgh, PA [...]

Background: Up to 50% of adolescents who undergo metabolic and bariatric surgery (MBS) have obesity 3 years post-MBS, placing them at continued risk for the consequences of obesity., Objectives: We conducted an open-label, 16-week pilot study of liraglutide in adolescents with obesity after sleeve gastrectomy (SG) to investigate liraglutide effects on weight and body mass index (BMI) post-SG., Methods: Adolescents aged 12-20.99 years with obesity and a history of SG ≥1 year prior were enrolled. Liraglutide was initiated at 0.6 mg/day, escalated weekly to a maximum of 3 mg/day, with treatment duration 16 weeks. Fasting laboratory assessments and an oral glucose tolerance test were performed at baseline and end-treatment., Results: A total of 43 participants were screened, 34 initiated liraglutide (baseline BMI 41.2 ± 7.7 kg/m 2 ), and 31 (91%) attended the end-treatment visit. BMI decreased by 4.3% (p < 0.001) with liraglutide. Adolescents who had poor initial response to SG (<20% BMI reduction at BMI nadir) had less weight loss with liraglutide. Fasting glucose and haemoglobin A1C concentrations significantly decreased. There were no serious treatment-emergent adverse events reported., Conclusions: Liraglutide treatment was feasible and associated with a BMI reduction of 4.3% in adolescents who had previously undergone SG, quantitatively similar to results obtained in adolescents with obesity who have not undergone MBS., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown., Objectives: 1) To comprehensively examine gut microbiome and metabolome changes after laparoscopic vertical sleeve gastrectomy (VSG) in adolescents and 2) to assess whether the microbiome/metabolome changes observed with VSG influence phenotype using germ-free murine models., Design: 1) A longitudinal observational study in adolescents undergoing VSG with serial stool samples undergoing shotgun metagenomic microbiome sequencing and metabolomics (polar metabolites, bile acids and short chain fatty acids) and 2) a human-to-mouse fecal transplant study., Results: We show adolescents exhibit significant gut microbiome and metabolome shifts several months after VSG, with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited an inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG., Conclusion: We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG., Competing Interests: Declaration of interests: B.A.S. is a former SomaLogic, Inc. (Boulder, CO, USA) employee and a company shareholder. All other authors declare that they have no competing interests.

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., (© 2023 World Obesity Federation.)

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/m 2 ) 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/m 2 at 3 months and 9 ± 4 kg/m 2 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., (© 2023 The Obesity Society.)

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., (© 2023, The American College of Clinical Pharmacology.)

Competing Interests: I declare no competing interests.

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.

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 (&lt; 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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Approximately 20% of children and adolescents in the USA suffer from obesity with significant long-term effects well into adulthood. Metabolic and bariatric surgery, although well adopted in the adult population, has been underutilized in children., Recent Findings: There are four categories of weight loss devices regulated by the Food and Drug Administration for use in adults - gastric bands, gastric balloon systems, electrical stimulation systems, and gastric emptying systems. In this commentary we discuss the role these devices may play in increasing the adoption of procedural intervention for severe obesity in children and adolescents., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Melanocortin-4 receptor ( MC4R ) mutations are the most common of the rare monogenic forms of obesity. However, the efficacy of bariatric surgery (BS) and pharmacotherapy on weight and glycemic control in individuals with MC4R deficiency (MC4R-d) is not well-established. We investigated and compared the outcomes of BS and pharmacotherapy in patients with and without MC4R-d., Methods: Pertinent details were derived from the electronic database among identified patients who had BS with MC4R-d (study group, SG) and wild-type controls (age- and sex-matched control group, CG). Short- and long-term outcomes were reported for the SG. Short-term outcomes were compared between the two groups., Results: Seventy patients were screened for MC4R-d. The SG [six individuals (four females, two males); 18 (10-27) years old at BS; 50.3 (41.8-61.9) kg/m 2 at BS, three patients with homozygous T162I mutations, two patients with heterozygous T162I mutations, and one patient with heterozygous I170V mutation] had a follow-up duration of up to 10 years. Weight loss, which varied depending on mutation type [17.99 (6.10-22.54) %] was stable for 6 months; heterogeneity of results was observed thereafter. BS was found superior to liraglutide on weight and glycemic control outcomes. At a median follow-up of 6 months, no significant difference was observed on weight loss (20.8% vs. 23.0%, p = 0.65) between the SG and the CG [eight individuals (four females, four males); 19.0 (17.8-36.8) years old at BS, 46.2 (42.0-48.3) kg/m 2 at BS or phamacotherapeutic intervention]. Glycemic control in patients with MC4R-d and Type 2 diabetes improved post-BS., Conclusion: Our data indicate efficacious short-term but varied long-term weight loss and glycemic control outcomes of BS on patients with MC4R-d, suggesting the importance of ongoing monitoring and complementary therapeutic interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fojas, Radha, Ali, Nadler and Lessan.)

Background: Metabolic and bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity., Objectives: This study examined the safety of MBS in adolescents during the coronavirus disease 2019 (COVID-19) pandemic., Methods: This was a global, multicentre and observational cohort study of MBS performed between May 01, 2020, and October 10,2020, in 68 centres from 24 countries. Data collection included in-hospital and 30-day COVID-19 and surgery-specific morbidity/mortality., Results: One hundred and seventy adolescent patients (mean age: 17.75 ± 1.30 years), mostly females (n = 122, 71.8%), underwent MBS during the study period. The mean pre-operative weight and body mass index were 122.16 ± 15.92 kg and 43.7 ± 7.11 kg/m 2 , respectively. Although majority of patients had pre-operative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 146; 85.9%), only 42.4% (n = 72) of the patients were asked to self-isolate pre-operatively. Two patients developed symptomatic SARS-CoV-2 infection post-operatively (1.2%). The overall complication rate was 5.3% (n = 9). There was no mortality in this cohort., Conclusions: MBS in adolescents with obesity is safe during the COVID-19 pandemic when performed within the context of local precautionary procedures (such as pre-operative testing). The 30-day morbidity rates were similar to those reported pre-pandemic. These data will help facilitate the safe re-introduction of MBS services for this group of patients., (© 2021 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Bariatric surgery is the most effective current treatment option for patients with severe obesity. More children and adolescents are having surgery, many whose parents have also had surgery. The current study examines whether parental surgery status moderates the association between perceived social support, emotional eating, food addiction and weight loss following surgery, with those whose parents have had surgery evidencing a stronger relationship between the psychosocial factors and weight loss as compared to their peers., Methods: Participants were 228 children and adolescents undergoing sleeve gastrectomy between 2014 and 2019 at one institution. Children and adolescents completed self-report measures of perceived family social support, emotional eating, and food addiction at their pre-surgical psychological evaluation. Change in body mass index (BMI) from pre-surgery to 3, 6, and 12 months post-surgery was assessed at follow-up clinic visits. Parents reported their surgical status as having had surgery or not., Results: There were no differences in perceived family support, emotional eating, or food addiction symptoms between those whose parents had bariatric surgery and those whose parents did not. There were some moderating effects of parent surgery status on the relationship between social support, emotional eating/food addiction, and weight loss following surgery. Specifically, at 3 months post-surgery, higher change in BMI was associated with lower perceived family support only in those whose parents had not had surgery. More pre-surgical food addiction symptoms were associated with greater weight loss at 3 months for those whose parents had not had surgery, whereas this finding was true only for those whose parents had surgery at 12 months post-surgery., Conclusions: Children and adolescents whose parents have had bariatric surgery may have unique associations of psychosocial factors and weight loss. More research is needed to determine mechanisms of these relationships.

Introduction: Roux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes mellitus (T2DM) that can result in remission of clinical symptoms, yet mechanisms for improved skeletal muscle health are poorly understood. We sought to define the impact of existing T2DM on RYGB-induced muscle transcriptome changes., Methods: Vastus lateralis biopsy transcriptomes were generated pre- and 1-year post-RYGB in black adult females with (T2D; n = 5, age = 51 ± 6 years, BMI = 53.0 ± 5.8 kg/m 2 ) and without (CON; n = 7, 43 ± 6 years, 51.0 ± 9.2 kg/m 2 ) T2DM. Insulin, glucose, and HOMA-IR were measured in blood at the same time points. ANCOVA detected differentially expressed genes ( p < 0.01, fold change < |1.2|), which were used to identify enriched biological pathways., Results: Pre-RYGB, 95 probes were downregulated with T2D including subunits of mitochondrial complex I. Post-RYGB, the T2D group had normalized gene expression when compared to their non-diabetic counterparts with only three probes remaining significantly different. In the T2D, we identified 52 probes upregulated from pre- to post-RYGB, including NDFUB7 and NDFUA1., Conclusion: Black females with T2DM show extensive downregulation of genes across aerobic metabolism pathways prior to RYGB, which resolves 1 year post-RYGB and is related to improvements in clinical markers. These data support efficacy of RYGB for improving skeletal muscle health, especially in patients with T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barberio, Dohm, Pories, Gadaleta, Houmard, Nadler and Hubal.)

Objective: Neurocognitive differences in pediatric obesity may be underpinned by cortical structural alterations. Differences in cortical thickness associated with severe obesity were examined, and preliminary evidence was sought for changes following vertical sleeve gastrectomy (VSG)., Methods: A total of 18 adolescents with severe obesity (OB) and 17 without obesity (nOB), aged 14 to 21, underwent T1-weighted structural magnetic resonance imaging. A subset was scanned twice 5 months apart to compare cortical thickness following VSG (n = 6) with two control groups: wait-listed (n = 9) and nOB (n = 12)., Results: At baseline, OB had a thinner cortex than nOB in motor and superior parietal cortices. At follow-up, VSG adolescents lost weight, the wait-listed group gained weight, and nOB did not change. Group × Time interactions indicated that VSG had cortical thinning in orbitofrontal, primary sensorimotor, superior, and middle temporal cortices and thickening in lingual, fusiform, and lateral occipital cortices. Wait-listed and nOB groups largely did not change., Conclusions: Severe obesity is associated with a thinner cortex in motor and attentional function-associated regions. VSG resulted in cortical thinning in reward valuation, sensory, and perceptual regions and thickening in visual regions. Surgery-related changes in regions distinct from those associated with obesity suggest compensation, rather than normalization. These results provide preliminary evidence supporting structural neural alterations following sleeve gastrectomy., (© 2021 The Obesity Society.)

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.

Adolescents seeking bariatric surgery may present with pre-existing psychiatric diagnoses for which they use chronic medications. To heighten awareness concerning perioperative polypharmacy in adolescents with extreme obesity, we conducted a retrospective review of patients undergoing laparoscopic sleeve gastrectomy between February 2010 and May 2017 at Children's National Health System (CNHS). A total of 167 adolescent patients had pre-existing psychiatric diagnoses which included depression (50%), anxiety (23%), ADHD (23%), and binge eating disorder (11%). Medications prescribed to treat these diagnoses included selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Additionally, all patients were given fentanyl, ondansetron, morphine, and acetaminophen perioperatively. Although no life threatening symptoms of drug-drug interactions (DDIs) were appreciated, the combined use of many different potent drugs in these patients warrants attention.

Introduction: Severe obesity predisposes youth to a higher risk of venous thromboembolism (VTE). This study evaluates a BMI-stratified prophylactic dosing regimen of enoxaparin in adolescents with severe obesity undergoing surgery., Methods: Adolescents aged 12-20 years received prophylactic enoxaparin at 40 mg SC (for a BMI < 50 kg/m 2 ) and 60 mg SC (for a BMI ≥ 50 kg/m 2 ) every 12 h until discharge. Blood samples were drawn at pre-dose, 1, 2, 4, 6, and 12 h. Plasma Anti-Factor Xa (Anti-FXa) activity was used as a surrogate marker for enoxaparin pharmacokinetics., Results: Ten female and two male obese adolescents (age range 14-19 years) had a mean BMI of 49.9 kg/m 2 (38.4-58 kg/m 2 ). Four patients had a BMI of less than 50 kg/m 2 and received 40 mg enoxaparin, resulting in a mean dosage of 0.352 ± 0.070 mg/kg body weight. Eight patients were dosed with 60 mg enoxaparin every 12 h, resulting in a mean dosage of 0.395 ± 0.028 mg/kg. Peak plasma anti-FXa activity (C max ) ranged from 0.14 to 0.30 IU/mL, median C max was 0.205 IU/mL. Median T max was 5.67 h (range 3.78-7.52 h). Median AUC i was 1.00 h IU/mL (range 0.42-1.67 h IU/mL). Ten out of 12 patients (83%) reached the primary endpoint with anti-FXa activity in the range for VTE prevention (0.1-0.3 IU/mL)., Conclusions: Our dosing scheme of 40 mg vs. 60 mg enoxaparin stratified according to BMI proved to be effective in reaching prophylactic anti-FXa activity in 83% of adolescent patients.

Negative effects of obesity on memory and associated medial temporal circuitry have been noted in animal models, but the status in humans, particularly children, is not well established. Our study is the first to examine neural correlates of successful memory encoding of visual scenes and their associated context in adolescents with severe obesity (age 14-18 years, 43% male). Despite similar subsequent memory as adolescents without obesity (BMI for age and sex <95th percentile), those with severe obesity (BMI for age and sex 120% above the 95th percentile) showed reduced hippocampal, parahippocampal, frontal, and parietal engagement during encoding of remembered visual scenes and greater lateral temporal engagement during encoding of their associated context. Standardized testing revealed a trend level group difference in memory performance, with a larger magnitude of obesity-related difference in recollection-related memory that was mediated by individual differences in lateral temporal activation during contextual encoding. The observed widespread functional alterations are concerning in light of the importance of mnemonic processing for academic achievement and feeding behavior and underscore the need for prevention and intervention initiatives for pediatric obesity., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Epigenetic changes in visceral adipose tissue (VAT) with obesity and their effects on gene expression are poorly understood, especially during emergent obesity in youth. The current study tested the hypothesis that methylation and gene expression profiles of key growth factor and inflammatory pathways are altered in VAT from obese compared to non-obese youth., Methods: VAT samples from adolescent females grouped as Lean (L; n = 15; age = 15 ± 3 years, BMI = 21.9 ± 3.0 kg/m 2 ) or Obese (Ob; n = 15, age = 16 ± 2 years, BMI = 45.8 ± 9.8 kg/m 2 ) were collected. Global methylation (n = 20) and gene expression (N = 30) patterns were profiled via microarray and interrogated for differences between groups by ANCOVA (p < 0.05), followed by biological pathway analyses., Results: Overlapping differences in methylation and gene expression in 317 genes were found in VAT from obese compared to lean groups. PI3K/AKT Signaling (p = 1.83 × 10 -6 ; 11/121 molecules in dataset/pathway) was significantly overrepresented in Ob VAT according to pathway analysis. Upregulations in the PI3K/AKT signaling pathway mRNAs TFAM (p = 0.03; fold change = 1.8) and PPP2R5C (p = 0.03, FC = 2.6) were confirmed via qRT-PCR., Conclusion: Our analyses show obesity-related differences in DNA methylation and gene expression in visceral adipose tissue of adolescent females. Specifically, we identified methylation site/gene expression pairs differentially regulated and mapped these differences to pathways including PI3K/AKT signaling, suggesting that PI3K/AKT signaling pathway dysfunction in obesity may be driven in part by changes in DNA methylation., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Objective: The use of laparoscopic sleeve gastrectomy (LSG) has risen steadily as a treatment for adolescents with obesity. This study determined whether obstructive biliary complications after rapid, LSG-related weight loss occur similarly in adolescents compared with adults., Methods: Between 2010 and 2019, 309 patients underwent LSG. Demographics and clinical factors, including pre- and perioperative BMI and weight changes, were included., Results: Overall, 21 patients (7%) had post-LSG biliary disease (BD), of whom 13 presented with acute pancreatitis (AP) and 8 with biliary colic. No differences existed between those with BD (n = 21) and the remaining cohort (n = 288). Patients with BD were 16.3 (SD 2.4) years of age at LSG, with a preoperative BMI of 49.3 (SD 6.7) kg/m 2 . Preoperative excess BMI loss was 7.1% (SD 11.3%). An ultrasound revealed gallstones (71%) and sludge or crystals (12%). Eighteen patients underwent cholecystectomy between 4 weeks and 29 months after LSG., Conclusions: Pediatric patients present with BD at a similar rate after LSG compared with adults. The majority of adolescents, however, manifest with AP. Thus, pancreatitis should be high on the differential diagnosis list when evaluating post-LSG abdominal symptoms. Additional studies are warranted to elucidate the pathophysiology of post-LSG AP for prevention in the future because its etiology may or may not be solely related to BD., (© 2019 The Obesity Society.)

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/m 2 ) 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.

Background: Preoperative exercise is associated with weight loss following bariatric surgery in adults, but this relationship in adolescents and young adults (AYA) is not well studied., Objectives: The present study examined AYA-reported preoperative exercise and demographic factors and their prediction of percent excess body mass index (BMI) loss at 6 and 12 months following sleeve gastrectomy., Setting: The setting for recruitment and surgeries was in a children's hospital in the United States., Methods: Participants were 173 AYA aged 12-21 years (mean age, 16.5 [SD, 2.0] yr; mean preoperative BMI, 50 [SD, 8.5] kg/m 2 ). Demographic characteristics including age, sex, ethnicity, and preoperative BMI were extracted from the medical record. Preoperatively, adolescents self-reported on exercise using 5 items from the Center for Disease Control's Youth Risk Behavior Surveillance Survey. The study evaluated the association of self-reported preoperative exercise in total and obtained a threshold of higher exercise to weight loss at 6 and 12 months after surgery., Results: More preoperative exercise was associated with greater weight loss at 12 months. Grouping participants by those who reported exercising at high levels (≥5 hr/wk) compared with those who reported <5 hr/wk, high levels of exercise predicted greater weight loss at 6 and marginally at 12 months postoperatively. Lower preoperative BMI was a significant predictor of weight loss in all analyses., Conclusions: Preoperative exercise may predict and contribute to weight loss in AYA and could be a target for pre- and postoperative intervention to improve outcomes. The importance of lower preoperative BMI for maximizing postoperative weight loss was also supported., (Copyright © 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Youth with cognitive impairment or developmental disability (CI/DD) face higher rates of obesity and secondary medical issues. Bariatric surgery may be a helpful tool for health improvement because it has been shown efficacious for adolescents. We aim to contribute to literature regarding bariatric surgery for adolescents with CI/DD and explore the association between cognitive functioning and weight loss outcomes., Methods: Adolescents ( N = 64) received a preoperative psychological evaluation, including cognitive assessment, and bariatric surgery at 1 weight loss program between 2010 and 2017. For these adolescents with measured cognitive performance, CI/DD was defined by an IQ <80 or previous diagnosis. In analyses, we compared adolescents with and without CI/DD. Structural equation modeling was used to assess the impact of cognitive functioning on weight loss 3 to 24 months postsurgery., Results: There were no significant differences between adolescents with or without CI/DD in terms of preoperative BMI, age, and sex. Having CI/DD did not significantly impact weight loss or weight loss trajectory in the 2 years after surgery, although modeling revealed a trend toward individuals with CI/DD losing more weight over time. Similarly, intelligence scores did not predict weight loss after surgery., Conclusions: Bariatric surgery may be a helpful tool for adolescents with severe obesity and CI/DD. They could benefit from the surgery as much as those with typical development, and having CI/DD should not be used as a criterion to deny surgery. Continuing research with this population can be used to determine long-term outcomes in addition to defining best practices., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Aim: To examine the impact of preexisting psychiatric/psychological diagnoses on perioperative analgesic requirements in adolescents with morbid obesity undergoing bariatric surgery., Methods: A retrospective cohort study of adolescents with morbid obesity undergoing bariatric surgery. Primary and secondary outcomes included perioperative analgesic intake and pain scores (Numerical Rating Scale (0-10) NRS) throughout the hospital stay., Results: From our Bariatric Surgery Research Registry, we identified 17 adolescents with psychiatric/psychological diagnoses prior to undergoing bariatric surgery. Fifteen patients from the same registry and without such diagnosis undergoing bariatric surgery during the same time interval served as controls. In both groups, there was a predominance of female patients. During the perioperative period, in both groups, oral morphine equivalent and ketorolac and acetaminophen intake were similar. Notably, the perioperative median pain scores at the times examined were below 5 for all patients. The median pain scores in the PACU, day of surgery, and first postoperative day were similar. Conversely, on postoperative day 2, pain scores were higher in patients with diagnoses of psychiatric/psychological disorders (p = 0.004) compared to those without., Conclusion: In this cohort of morbidly obese adolescents undergoing bariatric surgery, patients with and without preexisting psychiatric/psychological diagnoses had similar analgesic requirements during the perioperative period. This finding appears contrary to those suggesting that preexisting depression and/or anxiety might be associated with increased analgesic requirements during the perioperative period.

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).

Background and Objectives: Severe obesity is associated with higher risk of psychiatric difficulties. Bariatric surgery is the most effective treatment of severe obesity. Few guidelines exist regarding the association of psychiatric diagnoses in adolescents and outcomes after surgery because of the lack of longitudinal research. Our objective is to evaluate the rates of psychiatric diagnoses in adolescents undergoing surgery compared with those not receiving surgery and the association of preoperative psychiatric diagnoses with postsurgical weight loss outcomes., Methods: Adolescents ( N = 222) referred for psychological evaluation at one institution for bariatric surgery (2009-2017) completed semistructured clinical interviews to assess the presence and number of psychiatric diagnoses. Comparison analyses were conducted between those who did not end up receiving surgery ( N = 53) and those who did ( N = 169). Using longitudinal modeling, we assessed the association of preoperative diagnoses with weight loss outcomes between 3 and 12 months after surgery., Results: Seventy-one percent of adolescents qualified for a psychiatric disorder. There were no differences in rates of specific disorders or numbers of diagnoses between those receiving surgery and those not receiving surgery. The presence or absence or number of diagnoses before surgery was not associated with weight loss outcomes after surgery., Conclusions: Psychiatric diagnoses are prevalent among adolescents with severe obesity. These diagnoses are not associated with weight loss outcomes. The presurgical psychological evaluation serves as an opportunity to identify adolescents experiencing psychiatric problems and provide them with care but should not necessarily be considered a contraindication to surgery., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

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.

In recent years, as the high burden of surgical disease and poor access to surgical care in low- and middle-income countries have gained recognition as major public health problems, interest in global health has surged among surgical trainees and faculty. Traditionally, clinical volunteerism was at the forefront of the high-income country response to the significant burden of surgical disease in low- and middle-income countries. However, sustainable strategies for providing surgical care in low- and middle-income countries increasingly depend on bilateral clinical, research, and education collaborations to ensure effective resource allocation and contextual relevance. Academic global surgery creates avenues for interested surgeons to combine scholarship and education with their clinical global surgery passions through incorporation of basic/translational, education, clinical outcomes, or health services research with global surgery. Training in global health, either within residency or through advanced degrees, can provide the necessary skills to develop and sustain such initiatives. We further propose that creating cross-continental, bidirectional collaborations can maximize funding opportunities. Academic institutions are uniquely positioned to lead longitudinal and, importantly, sustainable global surgery efforts. However, for the individual global surgeon, the career path forward may be unclear. This paper reviews the development of academic global surgery, delineates the framework and factors critical to training global surgeons, and proposes models for establishing an academic career in this field. Overall, with determination, the academic global surgeon will not only carve out a niche of expertise but will define this critical field for future generations., (Copyright © 2017. Published by Elsevier Inc.)

Objective: Executive and motivational dysfunction have been associated with pediatric obesity. Poor sleep quality and psychopathology, often comorbid with obesity, are also associated with executive and motivational dysfunction. We examined the contribution of these comorbid factors to the association between obesity and executive function and reward-related decision-making., Methods: Seven- to 18-year-old children with and without obesity performed a working memory task with low and high loads, a response inhibition task, and a probabilistic reward-related decision-making task. Parents filled out standardized measures of executive function in everyday behavior, sleep health, and psychiatric symptoms. Analyses controlled for age, gender, IQ, and parental education., Results: Children with obesity showed worse working memory performance under higher load (p = 0.007), and worse parent-reported behavioral regulation (p = 0.05) and metacognition (p = 0.04) in everyday behavior and their reward-related decision-making was less consistent with learned probabilistic conditions (p = 0.04). Response inhibition did not differ between groups. Children with obesity had worse parent-reported sleep health (p < 0.01) and 4.27 greater odds of clinically relevant internalizing symptomology (p = 0.03), both of which mediated the effect of obesity on behavioral regulation (p's < 0.01) and metacognition (p's < 0.01). Performance-based assessments were not associated with sleep health or psychopathology., Conclusions: Sleep quality and internalizing psychopathology were worse in children with obesity and contributed to parent-reported executive dysfunction in their everyday behavior. Performance-based measures of working memory and decision-making were not associated with those comorbidities of obesity.

Objectives: Bariatric surgery is an effective treatment for youth with severe obesity. However, outcomes are variable and there remains sparse understanding of predictors of weight loss following surgery. The current study examines the role of adolescent-reported pre-operative social support around exercise, binge eating, and exercise to predict excess body mass index (EBMI) loss from 3 to 12 months post-surgery., Method: Participants were 101 adolescents ages 12-21 (M age = 16.6, SD = 1.8). Pre-operative body mass index (BMI) ranged from 35 to 87 (M = 50.3, SD = 8.6). Structural equation modeling (SEM) was used to evaluate a model of the association of adolescent report of perceived social support for exercise with less binge eating (items from the Eating Disorder Diagnostic Scale) and more self-reported exercise (items from the Youth Risk Behavior Surveillance System). The model was used to predict EBMI loss at 3, 6, 9, and 12 months post-surgery., Results: Social support significantly predicted exercise and demonstrated a trend for predicting binge eating, such that more social support was associated with more exercise and a trend for less binge eating. Binge eating was associated with less EBMI loss. However, there was no association of exercise with EBMI loss., Conclusions: Pre-operative binge eating should be a target for identification and treatment prior to sleeve gastrectomy in adolescents. Although not directly or indirectly associated with EBMI loss, perceived social support around exercise was associated with increased exercise, which may make it a consideration for a target for intervention as well.

Local inflammation in obese adipose tissue has been shown to contribute to insulin resistance; however, the role of macrophage infiltration within skeletal muscle is still debatable. This study aimed to evaluate the association of skeletal muscle macrophage gene expression with adiposity levels and insulin sensitivity in obese patients. Twenty-two nondiabetic obese patients and 23 healthy lean controls were included. Obese patients underwent a 3-month weight loss intervention. Macrophage gene expression in skeletal muscle (quantitative real-time polymerase chain reaction), body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (homeostatic model assessment (HOMA) and oral glucose tolerance test) were compared between groups and their associations were analyzed. To validate skeletal muscle findings, we repeated the analyses with macrophage gene expression in adipose tissue. Expression levels of macrophage genes (CD68, CD11b, CD206, CD16, CD40, and CD163) were lower in skeletal muscle tissue of obese versus lean participants. Macrophage gene expression was also found to be inversely associated with adiposity, fasting insulin, and HOMA (r = -0.4 ∼ -0.6, p < 0.05), as well as positively associated with insulin sensitivity (r = 0.4 ∼ 0.8, p < 0.05). On the other hand, adipose tissue macrophage gene expression showed higher levels in obese versus lean participants, presenting a positive association with adiposity levels. Macrophage gene expression, in both skeletal and adipose tissue samples, was only minimally affected by the weight loss intervention. In contrast with the established positive relationship between adiposity and macrophage gene expression, an unexpected inverse correlation between these 2 variables was observed in skeletal muscle tissue. Additionally, muscle macrophage gene expression was inversely correlated with insulin resistance.

Objective: Neurocognitive deficits in pediatric obesity relate to poor developmental outcomes. We sought preliminary evidence for changes in brain and cognitive functioning relevant to obesogenic behavior following vertical sleeve gastrectomy (VSG) in adolescents relative to wait-listed (WL) and healthy controls (HC)., Methods: Thirty-six adolescents underwent fMRI twice 4 months apart, during executive, reward, and episodic memory encoding, in addition to behavioral testing for reward-related decision making., Results: VSG adolescents lost weight, while WL gained weight and HC did not change between time points. Gains in executive and reward-related performance were larger in VSG than control groups. Group × Time interaction (P < 0.05 corrected) in left prefrontal cortex during N-back showed greater presurgical activation and postsurgical reduction comparable to HC levels but increased in WL between time points. Similarly, left striatal parametric response to reward value reduced after surgery to HC levels; WL did not change. Memory-related medial temporal activation did not change in any group., Conclusions: Results provide pilot evidence for functional brain changes induced by VSG in adolescents with severe obesity. Weight loss and gain were paralleled by reduced and increased prefrontal activation, respectively, suggesting neural plasticity related to metabolic change., (© 2017 The Obesity Society.)

The obesity epidemic continues to affect millions of children and adolescents. Non-surgical options do not result in significant or sustained weight loss; thus bariatric surgery has become increasingly utilized. Limited data exist regarding safety for paediatric bariatric surgery, especially outside of National Institutes of Health (NIH)-funded centres. We hypothesized that the perioperative outcomes of paediatric patients undergoing laparoscopic sleeve gastrectomy (LSG) at our free-standing children's hospital would provide adequate safety profiles. We retrospectively reviewed demographics, comorbidities and 30-d outcomes for all patients who underwent LSG from 2010 to 2015 at a free-standing children's hospital. A total of 105 patients underwent 107 LSG procedures (two revisions). Mean age was 17.2 ± 2.4 years. Male to female ratio was 1:4. The majority were Black (57.1%), followed by White (21.0%) and Hispanic (18.1%). The mean body mass index was 51.0 ± 9.8 kg/m 2 . Comorbidities included obstructive sleep apnea (59.0%), hypertension (15.2%), polycystic ovarian disease (16.7% of females only), depression (12.4%) and diabetes (11.4%). Median length of stay was 2.0 d (1-7 d). There were no deaths. Major complications occurred in four patients (3.8%); three required reoperation. Four patients (3.8%) experienced minor complications. Laparoscopic sleeve gastrectomy can be safely performed for children and adolescents at a free-standing children's hospital without NIH-support., (© 2017 World Obesity Federation.)

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations., Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council., Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included., Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline.

Objective: Exosomes from obese adipose contain dysregulated microRNAs linked to insulin signaling, as compared with lean controls, providing a direct connection between adiposity and insulin resistance. This study tested the hypotheses that gastric bypass surgery and its subsequent weight loss would normalize adipocyte-derived exosomal microRNAs associated with insulin signaling and the associated metabolome related to glucose homeostasis., Methods: African American female subjects with obesity (N = 6; age: 38.5 ± 6.8 years; BMI: 51.2 ± 8.8 kg/m 2 ) were tested before and 1 year after surgery. Insulin resistance (HOMA), serum metabolomics, and global microRNA profiles of circulating adipocyte-derived exosomes were evaluated via ANCOVA and correlational analyses., Results: One year postsurgery, patients showed decreased BMI (-18.6 ± 5.1 kg/m 2 ; P < 0.001), ameliorated insulin resistance (HOMA: 1.94 ± 0.6 presurgery, 0.49 ± 0.1 postsurgery; P < 0.001), and altered metabolites including branched chain amino acids (BCAA). Biological pathway analysis of predicted mRNA targets of 168 surgery-responsive microRNAs (P < 0.05) identified the insulin signaling pathway (P = 1.27E-10; 52/138 elements), among others, in the data set. The insulin signaling pathway was also a target of 10 microRNAs correlated to changes in HOMA (P < 0.05; r > 0.4), and 48 microRNAs correlated to changes in BCAA levels., Conclusions: These data indicate that circulating adipocyte-derived exosomes are modified following gastric bypass surgery and correlate to improved postsurgery insulin resistance., Competing Interests: The authors declare no conflict of interest., (© 2016 The Obesity Society.)

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.

Homozygous or compound heterozygous melanocortin-4 receptor (MC4R) mutations are rare with fewer than 10 patients described in current literature. Here we report the short- and long-term outcomes for four children ages 4.5-14 who are homozygous for loss-of-function mutations in the MC4R and underwent laparoscopic sleeve gastrectomy. All four patients experienced significant weight loss and improvement in, or resolution of, their comorbidities in the short term. One patient, however, has had significant weight regain in the long term. We conclude that MC4R signaling is not required for short-term weight loss after laparoscopic sleeve gastrectomy in children. Behavior modification may be more important for long-term weight maintenance, but patients with homozygous MC4R deficiency should not be excluded from consideration for sleeve gastrectomy. However, as at least one copy of functional MC4R is necessary and sufficient to induce long-term postoperative weight loss benefits, patients with complete loss of MC4R functionality might be less likely to exhibit the same benefits resulting from bariatric surgery.

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.

Background: Obese patients have a higher risk of venous thromboembolism when immobilized due to surgery. The objective of this study was to assess anti-factor Xa activity in adolescent bariatric surgical patients receiving prophylactic enoxaparin., Methods: Four morbidly obese adolescents undergoing laparoscopic sleeve gastrectomy were enrolled. Enoxaparin was administered (40 mg subcutaneous (SC) if BMI ≤50 kg/m(2) or 60 mg SC if BMI >50 kg/m(2)) for prevention of venous thromboembolism every 12 h starting after induction of anesthesia until discharge. Plasma anti-factor Xa activity was assessed over 12 h after the first dose and used as a surrogate marker for enoxaparin levels. Non-compartmental analysis of anti-factor Xa activity levels was performed and compared with previously published studies., Results: Patients recruited were 16 to 18 years of age with a mean BMI of 52.6 ± 5.8 kg/m(2) (>99th BMI percentile). Peak anti-factor Xa activity ranged from 0.20 to 0.23 IU/mL in our study population, compared to 0.38 to 0.53 IU/mL in the cited lean comparator groups., Conclusions: Our current dosing practice of 40 mg SC for individuals with a BMI ≤50 kg/m(2) and 60 mg for individuals with a BMI ≥50 kg/m(2) resulted in anti-factor Xa activity that was sufficient for adequate thromboprophylaxis in adolescent bariatric surgical patients. Our data also demonstrates lower drug exposures in the obese when compared to lean patients. Therefore, randomized controlled efficacy and safety studies are urgently needed to guide the use of low-molecular-weight heparins in the pediatric and adolescent obese population.

Background: In adults undergoing gastric bypass surgery, it is routine practice to perform pre-operative testing for Helicobacter pylori infection. Evidence suggests that infection impairs anastomotic healing and contributes to complications. There currently are no data for adolescents undergoing bariatric procedures. Despite few patients with pre-operative symptoms, we noted occasional patients with H. pylori detected after sleeve gastrectomy. We reviewed our experience with our adolescent sleeve gastrectomy cohort to determine the prevalence of H. pylori infection, its predictive factors, and association with outcomes. We hypothesized that H. pylori infection would be associated with pre-operative symptoms, but not surgical outcomes., Methods: All patients undergoing sleeve gastrectomy at our hospital were included. We conducted a chart review to determine pre- or post-operative symptoms of gastroesophageal reflux disease GERD or gastritis, operative complications, and long-term anti-reflux therapy after surgery. Pathology reports were reviewed for evidence of gastritis and H. pylori infection., Results: 78 adolescents had laparoscopic sleeve gastrectomy from January 2010 through July 2014. The prevalence of chronic gastritis was 44.9% (35/78) and 11.4% of those patients had H. pylori (4/35). Only one patient with H. pylori had pre-operative symptoms, and only 25.7% (9/35) of patients with pathology-proven gastritis had symptoms. One staple line leak occurred but this patient did not have H. pylori or gastritis. Mean patient follow-up was 10 (3-26) mos., Conclusions: There is a moderate prevalence of gastritis among adolescents undergoing sleeve gastrectomy, but only a small number of these patients had H. pylori infection. Neither the presence of chronic gastritis nor H. pylori infection correlated with symptoms or outcomes. Thus, in the absence of predictive symptomology or adverse outcome in those who are infected, we advocate for continued routine pathologic evaluation without the required need for pre-operative determination unless or until H. pylori infection is associated with adverse surgical outcomes.

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-β signaling and Wnt/β-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.

Background: Congenital ion channel disorders, including congenital long QT syndrome (LQTS), cause significant morbidity in pediatric patients. When medication therapy does not control symptoms or arrhythmias, more invasive treatment strategies may be necessary. This study examines our institution's clinical experience with surgical cardiac denervation therapy for management of these arrhythmogenic disorders in children., Methods: An institutional review board-approved retrospective review identified ten pediatric patients with congenital ion channelopathies who underwent surgical cardiac denervation therapy at a single institution between May 2011 and April 2014. Eight patients had a diagnosis of congenital LQTS, two patients were diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT). All patients underwent sympathectomy and partial stellate ganglionectomy via video-assisted thoracoscopic surgery (VATS)., Results: Six of the ten patients had documented ventricular arrhythmias preoperatively, and 70% of the patients had preoperative syncope. The corrected QT interval decreased in 75% of patients with LQTS following sympathectomy. Postoperative arrhythmogenic symptoms were absent in 88% of congenital LQTS patients, but both patients with CPVT continued to have symptoms throughout the duration of follow-up. All patients were alive after a median follow-up period of 10 months., Conclusions: Surgical cardiac denervation therapy via VATS is a useful treatment strategy for congenital LQTS patients who fail medical management, and its potential benefit in the management of CPVT is unclear. A prospective comparison of the efficacy of surgical cardiac denervation therapy and implantable cardioverter-defibrillator use in congenital ion channelopathies is timely and crucial., (© The Author(s) 2014.)

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-β) 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-β 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-β 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 ανβ-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 ανβ-5 and ανβ-8, and matrix metalloproteinase-9 in hepatic stellate cells., Conclusions: Exosomes from VAT integrate into liver cells and induce dysregulation of TGF-β pathway members in vitro and offers an intriguing possibility for the pathogenesis of NAFLD., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Our previous work demonstrated altered messenger RNA expression of integrin β-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 ανβ8 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 ανβ5 (1.93 ± 0.84 vs 1.50 ± 0.90, P = 0.23) or integrin ανβ6 (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 ανβ5 (ICC 0.52), good for integrin ανβ6 (ICC 0.72), and excellent for integrin ανβ8 (ICC 0.79) and fibrosis (ICC 0.89)., Conclusions: Our data show that integrin ανβ8, but not integrin ανβ5 or integrin ανβ6, protein expression is increased in liver specimens of patients with BA. These data support the mounting evidence that transforming growth factor-β (TGF-β) activation is responsible for the fibrosis found in BA. Anti-integrin ανβ8 or more global integrin blocking strategies may be therapeutic options in BA, but further work is clearly needed.

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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.