Publications by authors named "Evan Nadler"

81 Publications

Granulocyte-colony stimulating factor GCSF mobilizes hematopoietic stem cells in Kasai patients with biliary atresia in a phase 1 study and improves short term outcome.

J Pediatr Surg 2021 Apr 9. Epub 2021 Apr 9.

Vietnam National Children Hospital, Hanoi, Vietnam.

Aims: In RCT of adults with decompensated cirrhosis, GCSF mobilizes hematopoietic stem cells HSC and improves short-term outcome. An FDA-IND for sequential Kasai-GCSF treatment in biliary atresia BA was approved. This phase 1 study examines GCSF safety in Kasai subjects. Preliminary short-term outcome was evaluated.

Methods: GCSF (Neupogen) at 5 or 10 μg/kg (n = 3/group) was given in 3 daily doses starting on day 3 of Kasai surgery (NCT03395028). Serum CD34+ HSC cell counts, and 1-month of GCSF-related adverse events were monitored. The 6-months Phase 1 clinical outcome was compared against 10 subsequent post Phase 1 Kasai patients who did not receive GCSF.

Results: With GCSF, WBC and platelet count transiently increased, LFT and serum creatinine remained stable. Reversible splenic enlargement (by 8.5-20%) occurred in 5/6 subjects. HSC count increased 12-fold and 17.5-fold for the 5 μg/kg and10 ug/kg dose respectively; with respective median total bilirubin levels for GCSF vs no-GCSF groups of 55 vs 91 μM at 1 month, p = 0.05; 15 vs 37 μM at 3 months, p = 0.24); and the 6-months cholangitis frequency of 40% vs 90%, p = 0.077.

Conclusions: GCSF safely mobilizes HSC in Kasai infants and may improve short-term biliary drainage and cholangitis. Phase 2 efficacy outcome of GCSF adjunct therapy for sequential Kasai and GCSF is pending.
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http://dx.doi.org/10.1016/j.jpedsurg.2021.03.038DOI Listing
April 2021

A framework for studying race-based disparities in the use of metabolic and bariatric surgery for the management of pediatric obesity.

Am J Surg 2020 Dec 2. Epub 2020 Dec 2.

University of Texas Medical Branch, Department of Surgery, 301 University Boulevard, Galveston, TX, 77555, USA.

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http://dx.doi.org/10.1016/j.amjsurg.2020.11.043DOI Listing
December 2020

Resolution of confluent and reticulated papillomatosis after bariatric surgery.

Clin Obes 2021 Feb 8;11(1):e12427. Epub 2020 Nov 8.

IDEAL Clinic, Children's National Health System, Washington, District of Columbia, USA.

Confluent and reticulated papillomatosis (CARP), a rare dermatologic disorder characterized by hyperpigmented papules that subsequently develop into plaques with reticulated margins, is frequently confused with acanthosis nigricans. The aetiology and pathogenesis of CARP is not yet fully understood, but it is often present in individuals with obesity and PCOS. This case report describes an African American adolescent female with obesity with a rash diagnosed as CARP after unsuccessful treatment with antifungals and corticosteroids. Her dermatosis proved recalcitrant to antibiotics and metformin but started to resolve immediately after bariatric surgery. This case report supports insulin resistance as a contributor to CARP's pathogenesis and as well as its association with obesity. Clinically significant weight reduction should be considered in the management of this challenging skin condition.
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http://dx.doi.org/10.1111/cob.12427DOI Listing
February 2021

Surgical Treatment of Type 2 Diabetes Mellitus in Youth.

Adv Exp Med Biol 2021 ;1307:321-330

Division of Pediatric Surgery, Children's National Health System, Washington, DC, USA.

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.
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http://dx.doi.org/10.1007/5584_2020_511DOI Listing
January 2021

Implications of Perioperative Polypharmacy in Adolescents Undergoing Bariatric Surgery: a Single-Center Experience.

Obes Surg 2020 07;30(7):2832-2835

Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA.

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.
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http://dx.doi.org/10.1007/s11695-020-04456-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473135PMC
July 2020

Altered neural correlates of episodic memory in adolescents with severe obesity.

Dev Cogn Neurosci 2019 12 6;40:100727. Epub 2019 Nov 6.

Psychology, Georgetown University, Washington, DC, 20007, United States; Children's Research Institute, Washington, DC, 20010, United States.

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.
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http://dx.doi.org/10.1016/j.dcn.2019.100727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974906PMC
December 2019

Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity.

Diabetol Metab Syndr 2019 27;11:98. Epub 2019 Nov 27.

1Center for Genetic Medicine Research, Children's Research Institute, Children's National Medical Center, Washington, DC USA.

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) or Obese (Ob; n = 15, age = 16 ± 2 years, BMI = 45.8 ± 9.8 kg/m) 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; 11/121 molecules in dataset/pathway) was significantly overrepresented in Ob VAT according to pathway analysis. Upregulations in the PI3K/AKT signaling pathway mRNAs (p = 0.03; fold change = 1.8) and (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.
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http://dx.doi.org/10.1186/s13098-019-0494-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881970PMC
November 2019

Pattern of Biliary Disease Following Laparoscopic Sleeve Gastrectomy in Adolescents.

Obesity (Silver Spring) 2019 11;27(11):1750-1753

Division of Pediatric Surgery, Children's National Health System, Washington, DC, USA.

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 . 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.
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http://dx.doi.org/10.1002/oby.22634DOI Listing
November 2019

Prophylactic Use of Enoxaparin in Adolescents During Bariatric Surgery-a Prospective Clinical Study.

Obes Surg 2020 01;30(1):63-68

Division of Pediatric Clinical Pharmacology, Children's National Health System/The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

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) and 60 mg SC (for a BMI ≥ 50 kg/m) 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 (38.4-58 kg/m). Four patients had a BMI of less than 50 kg/m 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) ranged from 0.14 to 0.30 IU/mL, median C was 0.205 IU/mL. Median T was 5.67 h (range 3.78-7.52 h). Median AUC 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.
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http://dx.doi.org/10.1007/s11695-019-04135-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375856PMC
January 2020

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

J Transl Med 2019 07 22;17(1):232. Epub 2019 Jul 22.

Center for Genetic Medicine Research, Children's Research Institute, Children's National Health System, Washington, DC, 20010, USA.

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) 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.
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http://dx.doi.org/10.1186/s12967-019-1980-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647309PMC
July 2019

Preoperative exercise as a predictor of weight loss in adolescents and young adults following sleeve gastrectomy: a cohort study.

Surg Obes Relat Dis 2019 Jul 5;15(7):1051-1057. Epub 2019 Apr 5.

Department of Pediatrics, George Washington University, Washington, DC; Department of Surgery, Children's National Health System, Washington, DC.

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). 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.
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http://dx.doi.org/10.1016/j.soard.2019.03.039DOI Listing
July 2019

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

Curr Gastroenterol Rep 2019 Apr 25;21(6):24. Epub 2019 Apr 25.

Division of Pediatric General and Thoracic Surgery, The George Washington University School of Medicine & Health Sciences, 111 Michigan Avenue NW, Washington, DC, 20010, USA.

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/m (8%) to 15.1 kg/m (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.
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http://dx.doi.org/10.1007/s11894-019-0691-8DOI Listing
April 2019

Sleeve Gastrectomy for Youth With Cognitive Impairment or Developmental Disability.

Pediatrics 2019 05 15;143(5). Epub 2019 Apr 15.

Center for Translational Research, Children's National Health System, Washington, District of Columbia.

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 ( = 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.
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http://dx.doi.org/10.1542/peds.2018-2908DOI Listing
May 2019

Analgesic Requirements in Adolescents Undergoing Bariatric Surgery-an Observational Study.

Obes Surg 2019 05;29(5):1557-1562

Department of Perioperative Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.

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.
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http://dx.doi.org/10.1007/s11695-019-03727-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338831PMC
May 2019

Psychiatric Diagnoses and Weight Loss Among Adolescents Receiving Sleeve Gastrectomy.

Pediatrics 2018 07 1;142(1). Epub 2018 Jun 1.

Center for Translational Science, Children's National Health System, Washington, District of Columbia; and.

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 ( = 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 ( = 53) and those who did ( = 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.
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http://dx.doi.org/10.1542/peds.2017-3432DOI Listing
July 2018

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

J Pediatr Psychol 2018 09;43(8):916-927

Department of Psychology, Georgetown University.

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).
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http://dx.doi.org/10.1093/jpepsy/jsy028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093427PMC
September 2018

Sleep Health and Psychopathology Mediate Executive Deficits in Pediatric Obesity.

Child Obes 2018 04 2;14(3):189-196. Epub 2018 Feb 2.

1 Department of Psychology, Georgetown University , Washington, DC.

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.
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http://dx.doi.org/10.1089/chi.2017.0281DOI Listing
April 2018

An academic career in global surgery: a position paper from the Society of University Surgeons Committee on Academic Global Surgery.

Surgery 2018 04 15;163(4):954-960. Epub 2017 Dec 15.

Department of Surgery, Division of Abdominal Organ Transplantation/Hepatobiliary Surgery, Oregon Health & Science University, Portland, OR, USA.

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.
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http://dx.doi.org/10.1016/j.surg.2017.10.019DOI Listing
April 2018

Effect of Adolescent Bariatric Surgery on the Brain and Cognition: A Pilot Study.

Obesity (Silver Spring) 2017 11;25(11):1852-1860

Psychology Department, Georgetown University, Washington, DC, USA.

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.
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http://dx.doi.org/10.1002/oby.22013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679722PMC
November 2017

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

J Pediatr Psychol 2018 05;43(4):443-451

Center for Translational Sciences, Children's National Health System.

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.
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http://dx.doi.org/10.1093/jpepsy/jsx127DOI Listing
May 2018

Expression of macrophage genes within skeletal muscle correlates inversely with adiposity and insulin resistance in humans.

Appl Physiol Nutr Metab 2018 Feb 16;43(2):187-193. Epub 2017 Oct 16.

a Department of Physical Medicine & Rehabilitation, University of Michigan, Ann Arbor, MI 48108, USA.

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.
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http://dx.doi.org/10.1139/apnm-2017-0228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284171PMC
February 2018

Perceived Social Support for Exercise and Weight Loss in Adolescents Undergoing Sleeve Gastrectomy.

Obes Surg 2018 02;28(2):421-426

Children's Research Institute, Children's National Health System, Washington, DC, USA.

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.
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http://dx.doi.org/10.1007/s11695-017-2853-9DOI Listing
February 2018

Dexmedetomidine as an adjuvant for perioperative pain management in adolescents undergoing bariatric surgery: An observational cohort study.

J Pediatr Surg 2017 Nov 19;52(11):1787-1790. Epub 2017 Apr 19.

Department of Anesthesiology, Pain and Preoperative Medicine, Children's Research Institute, Children's National Health System; Pain Neurobiology Laboratory, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's Research Institute, Children's National Health System.

Background: The anesthetic management of adolescents undergoing bariatric surgery presents a number of challenges, including increased risk of postoperative opioid-related respiratory depression. These patients could benefit from adjunctive analgesics with opioid-sparring effects to optimize perioperative pain control. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has sedative and analgesic properties with no respiratory depressant effects.

Objective: To determine the effect of intraoperative dexmedetomidine on opioid requirement and perioperative pain management in obese adolescents undergoing bariatric surgery.

Methods: An observational study of 26 consecutive patients treated with and without dexmedetomidine during the intraoperative period was conducted. The dexmedetomidine treated patients received a loading dose over 30min and a continuous infusion thereafter. The standard group represented patients who received an institutional standard anesthetic without dexmedetomidine. The primary outcome was total perioperative intravenous morphine equivalent (MEq). We also examined reported pain scores during the perioperative period.

Results: While there were no significant differences in age, height and weight category, there were imbalances on race distribution between the two groups. Both groups received similar doses of ketorolac and acetaminophen perioperatively. Overall, during 48h postoperatively, the dexmedetomidine group received significantly less total MEq administration compared with the standard group. Three patients in the dexmedetomidine group required ephedrine to treat an episode of hypotension.

Discussion: These results suggest that the use of dexmedetomidine during bariatric surgery in the morbidly obese adolescent population is associated with decreased opioid utilization during the perioperative period. Future randomized studies will determine the role of dexmedetomidine in the pain management of obese adolescents undergoing bariatric surgery.

Study Type: Therapeutic, Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2017.04.007DOI Listing
November 2017

The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection.

Surg Infect (Larchmt) 2017 Jan;18(1):1-76

12 Departments of Surgery and Pediatrics, Hofstra-Northwell School of Medicine , Hempstead, New York.

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.
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http://dx.doi.org/10.1089/sur.2016.261DOI Listing
January 2017

Circulating adipocyte-derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass.

Obesity (Silver Spring) 2017 01 24;25(1):102-110. Epub 2016 Nov 24.

Department of Integrative Systems Biology, George Washington University, Washington, DC, USA.

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 ) 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 ; 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.
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http://dx.doi.org/10.1002/oby.21709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5182153PMC
January 2017

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

Surg Endosc 2016 06 19;30(6):2281-7. Epub 2015 Oct 19.

Department of Surgery, George Washington University School of Medicine, Washington, DC, USA.

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.
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http://dx.doi.org/10.1007/s00464-015-4227-5DOI Listing
June 2016

Targeting Extracellular Cyclophilins Ameliorates Disease Progression in Experimental Biliary Atresia.

Mol Med 2015 Oct 24;21(1):657-664. Epub 2015 Jul 24.

Division of Pediatric Surgery, Children's National Medical Center, Washington, District of Columbia, United States of America.

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.
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http://dx.doi.org/10.2119/molmed.2015.00076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749494PMC
October 2015

Prevalence of Chronic Gastritis or Helicobacter pylori Infection in Adolescent Sleeve Gastrectomy Patients Does Not Correlate with Symptoms or Surgical Outcomes.

Surg Infect (Larchmt) 2015 Aug 15;16(4):401-4. Epub 2015 Jun 15.

Division of Pediatric Surgery, Children's National Medical Center , Washington, DC.

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.
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http://dx.doi.org/10.1089/sur.2014.153DOI Listing
August 2015

Use of Enoxaparin in Obese Adolescents During Bariatric Surgery--a Pilot Study.

Obes Surg 2015 Oct;25(10):1869-74

Clinical Pharmacology, Clinical and Translational Science Institute, Children's National Medical Center, Washington, DC, USA,

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.
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http://dx.doi.org/10.1007/s11695-015-1630-xDOI Listing
October 2015

Surgical cardiac denervation therapy for treatment of congenital ion channelopathies in pediatric patients: a contemporary, single institutional experience.

World J Pediatr Congenit Heart Surg 2015 Jan;6(1):33-8

Division of Cardiovascular Surgery, Children's National Health System, Washington, DC, USA

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.
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http://dx.doi.org/10.1177/2150135114555203DOI Listing
January 2015