The Impact of Social Determinants of Health on Vestibular Schwannoma Management: A Single Institution Review.

OBJECTIVE: To evaluate social determinants of health and their effect on the management of vestibular schwannoma (VS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Patients >18 years old with sporadic VS newly diagnosed between January 1, 2010, and December 31, 2020. INTERVENTIONS: Magnetic resonance imaging; audiogram; treatment recommendations. MAIN OUTCOME MEASURES: Differences in treatment recommendations for patients based on their social determinants of health, including race, ethnicity, and socioeconomic status. RESULTS: A total of 811 patients were included in analysis. Patients with a higher area deprivation index (ADI) presented with larger tumors. A higher ADI was associated with a higher likelihood of recommending radiation (or the option of surgery or radiation) compared with a recommendation of surgery alone. Tumor grade and patient age were significantly associated with treatment recommendation. Older age was associated with a recommendation of observation alone or a recommendation of radiation. Higher tumor grade was associated with a recommendation of surgery. There was a trend for higher hearing class to be associated with a recommendation of surgery, but this did not reach statistical significance. Race, ethnicity, and gender were not significantly associated with treatment recommendation. CONCLUSIONS: Patients with higher levels of disadvantage presented with higher tumor grade, suggesting that access to care influences diagnosis. Factors including age, ADI, and tumor grade were associated with treatment recommendation.

Propofol versus dexmedetomidine during drug-induced sleep endoscopy (DISE) for pediatric obstructive sleep apnea.

PURPOSE: To test for differences in DISE findings in children sedated with propofol versus dexmedetomidine. We hypothesized that the frequency of ≥ 50% obstruction would be higher for the propofol than dexmedetomidine group at the dynamic levels of the airway (velum, lateral walls, tongue base, and supraglottis) but not at the more static adenoid level. METHODS: A single-center retrospective review was performed on children age 1-18 years with a diagnosis of sleep disordered breathing or obstructive sleep apnea (OSA) who underwent DISE from July 2014 to Feb 2019 scored by the Chan-Parikh scale sedated with either propofol or dexmedetomidine (with or without ketamine). Logistic regression was used to test for a difference in the odds of ≥ 50% obstruction (Chan-Parikh score ≥ 2) at each airway level with the use of dexmedetomidine vs. propofol, adjusted for age, sex, previous tonsillectomy, surgeon, positional OSA, and ketamine co-administration. RESULTS: Of 117 subjects, 57% were sedated with propofol and 43% with dexmedetomidine. Subjects were 60% male, 66% Caucasian, 31% obese, 38% syndromic, and on average 6.5 years old. Thirty-three percent had severe OSA and 41% had previous tonsillectomy. There was no statistically significant difference in the odds of ≥ 50% obstruction between the two anesthetic groups at any level of the airway with or without adjustment for potential confounders. CONCLUSION: We did not find a significant difference in the degree of upper airway obstruction on DISE in children sedated with propofol versus dexmedetomidine. Prospective, randomized studies would be an important next step to confirm these findings.

Drug-Induced Sleep Endoscopy in Children With Positional Obstructive Sleep Apnea.

OBJECTIVE: Positional obstructive sleep apnea (POSA)-defined as obstructive sleep apnea twice as severe supine than nonsupine-may offer clues to the underlying pattern of upper airway collapse in children. We compared drug-induced sleep endoscopy (DISE) findings in children with and without POSA. We hypothesized that children with POSA would have significantly higher obstruction at the gravity-dependent palate and tongue base but not at the adenoid, lateral wall, or supraglottis. STUDY DESIGN: Retrospective case series. SETTING: Tertiary pediatric hospital. SUBJECTS AND METHODS: We included children aged 1 to 12 years with obstructive sleep apnea diagnosed by polysomnography who underwent DISE from July 2014 to February 2019. Scores were dichotomized as ≥50% obstruction (Chan-Parikh 2 or 3) vs <50% obstruction (Chan-Parikh 0 or 1). RESULTS: Of 99 children included, 32 (32%) had POSA and 67 (68%) did not. Children with POSA did not differ from children without POSA in age, overall apnea-hypopnea index, sex, race, syndromic diagnoses, obesity, or history of adenotonsillectomy. In logistic regression models, odds of ≥50% obstruction were significantly higher at the tongue base (odds ratio, 2.77; 95% CI, 1.04-7.39) after adjustment for age, sex, obesity, previous adenotonsillectomy, and syndrome. No difference was noted at the adenoid, velum, lateral wall, or supraglottis. CONCLUSION: POSA was associated with higher odds of obstruction on DISE at the tongue base but not at other levels.

Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis.

Although much progress has been made in identifying the mechanisms that trigger endothelial activation and inflammatory cell recruitment during atherosclerosis, less is known about the intrinsic pathways that counteract these events. Here we identified NOTCH1 as an antagonist of endothelial cell (EC) activation. NOTCH1 was constitutively expressed by adult arterial endothelium, but levels were significantly reduced by high-fat diet. Furthermore, treatment of human aortic ECs (HAECs) with inflammatory lipids (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine [Ox-PAPC]) and proinflammatory cytokines (TNF and IL1ß) decreased Notch1 expression and signaling in vitro through a mechanism that requires STAT3 activation. Reduction of NOTCH1 in HAECs by siRNA, in the absence of inflammatory lipids or cytokines, increased inflammatory molecules and binding of monocytes. Conversely, some of the effects mediated by Ox-PAPC were reversed by increased NOTCH1 signaling, suggesting a link between lipid-mediated inflammation and Notch1. Interestingly, reduction of NOTCH1 by Ox-PAPC in HAECs was associated with a genetic variant previously correlated to high-density lipoprotein in a human genome-wide association study. Finally, endothelial Notch1 heterozygous mice showed higher diet-induced atherosclerosis. Based on these findings, we propose that reduction of endothelial NOTCH1 is a predisposing factor in the onset of vascular inflammation and initiation of atherosclerosis.