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Summary: 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/m2), 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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/m2 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/m2 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. [ABSTRACT FROM AUTHOR]

Summary: 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/m2, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/m2) and without (CON; n = 7, 43 ± 6 years, 51.0 ± 9.2 kg/m2) 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]