Obstructive sleep apnea and early weight loss among adolescents undergoing bariatric surgery.

BACKGROUND: Little is known regarding obstructive sleep apnea's (OSA's) prevalence or the factors related to OSA remission post-metabolic bariatric surgery (MBS) in adolescents. OBJECTIVES: To identify the baseline OSA prevalence in adolescents with severe obesity and examine factors associated with post-MBS OSA remission. SETTING: Tertiary-care children's hospital. METHODS: We conducted a retrospective chart review of 81 patients pre-MBS with OSA assessments done between June 2017 to September 2020 to collect demographic characteristics; co-morbidities; polysomnography (PSG) results, if indicated; and weight data. Chi-square or Mann-Whitney tests compared baseline characteristics and surgical outcomes by pre-MBS OSA status. McNemar's test or t tests assessed differences in baseline characteristics, stratified by remission versus no remission of OSA. RESULTS: The patients were 71% female, had an average age of 16.9 ± 2.0 years, and had a mean body mass index (BMI) of 47.9 ± 7.3 kg/m2. Half (50%) of the patients were Hispanic and 20% had type 2 diabetes. The OSA prevalence, defined as an Obstructive Apnea Hypopnea Index (OAHI) score ≥5, was 54% pre-MBS (n = 44), with 43% having severe OSA (OAHI > 30). Those with OSA were older (17.3 versus 16.4 yr, respectively; P = .05), more likely to be male (79% versus 42%, respectively; P = .022), and had higher baseline weights (142.0 versus 126.4 kg, respectively; P = .001) than those without OSA. Of the 23 patients with a post-MBS PSG result (average 5 mo post MBS), 15 (66%) had remission of OSA. Patients with OSA remission had a lower average pre-MBS BMI (46.0 versus 57.7 kg/m2, respectively; P < .001) and weight (132.9 versus 172.6 kg, respectively; P = .002) but no significant differences in percentage weight loss through 12 months post MBS versus those with continued OSA. CONCLUSION: The OSA prevalence in an adolescent MBS population was higher than that in the general adolescent population with severe obesity. Remission of OSA was correlated with lower pre-MBS BMI and weight, but not weight loss within the first year post-MBS.

Ablation of nectin4 binding compromises CD46 usage by a hybrid vesicular stomatitis virus/measles virus.

Measles virus (MV) immunosuppression is due to infection of SLAM-positive immune cells, whereas respiratory shedding and virus transmission are due to infection of nectin4-positive airway epithelial cells. The vaccine lineage MV strain Edmonston (MV-Edm) acquired an additional tropism for CD46 which is the basis of its oncolytic specificity. VSVFH is a vesicular stomatitis virus (VSV) encoding the MV-Edm F and H entry proteins in place of G. The virus spreads faster than MV-Edm and is highly fusogenic and a potent oncolytic. To determine whether ablating nectin4 tropism from VSVFH might prevent shedding, increasing its safety profile as an oncolytic, or might have any effect on CD46 binding, we generated VSVFH viruses with H mutations that disrupt attachment to SLAM and/or nectin4. Disruption of nectin4 binding reduced release of VSVFH from the basolateral side of differentiated airway epithelia composed of Calu-3 cells. However, because nectin4 and CD46 have substantially overlapping receptor binding surfaces on H, disruption of nectin4 binding compromised CD46 binding and greatly diminished the oncolytic potency of these viruses on human cancer cells. Thus, our results support continued preclinical development of VSVFH without ablation of nectin4 binding.