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.

Gender Microaggressions During Virtual Residency Interviews and Impact on Ranking of Programs During the Residency Match.

Background: Microaggressions are one form of gender bias contributing to gender disparities and mistreatment, but their prevalence during virtual residency interviews has not been explored. Objective: To explore applicants' recall of experiencing gender microaggressions during virtual residency interviews and whether these experiences affected programs' rank position on applicants' rank lists. Methods: Fourth-year medical students at a single institution who participated in the 2021 Match were surveyed after submitting their rank lists. Students were surveyed categorically on (1) their recall of the frequency they experienced 17 gender microaggressions during interviews, and (2) how these affected reported ranking of programs on their rank lists. Results: Sixty-one percent (103 of 170) of eligible students responded to the survey. Seventy-two percent (36 of 50) of women experienced at least one microaggression compared to 30% (9 of 30) of men. The largest difference was in the experience of environmental microaggressions, which are demeaning cues communicated individually or institutionally, delivered visually, or that refer to climate (P<.001). Women experienced more microaggressions than men in nonsurgical (P=.003) and surgical specialties excluding obstetrics and gynecology (P=.009). When microaggressions were experienced at 1 to 2 programs, 36% of applicants (26 of 73) reported significantly lowering program ranking, compared to 5% (1 of 19) when microaggressions occurred at more than 5 programs (P=.038). Conclusions: Women applicants experience more microaggressions than men do during nonsurgical and male-dominated surgical specialty residency interviews. Respondents who recalled experiencing microaggressions at fewer programs were more likely to report significantly lowering the rank of those programs compared to those who experienced them at more programs.

A Longitudinal Comparison of Telemedicine Versus In-Person Otolaryngology Clinic Efficiency and Patient Satisfaction During COVID-19.

OBJECTIVES: Telemedicine was increasingly adopted in otolaryngology as a result of the COVID-19 pandemic, but how it compares to in-person visits over the longitudinal course of the pandemic has not been characterized. This study compares telemedicine visits to in-person visits on measures of clinical efficiency and patient satisfaction. METHODS: We examined all in-person and telemedicine encounters that occurred during the 13-month period from April 1, 2020 to April 30, 2021 at a pediatric otolaryngology clinic associated with a large tertiary care children's hospital. We compared patient demographics, primary encounter diagnoses, completions, cancellations, no-shows, cycle time, and patient satisfaction. RESULTS: A total of 19 541 (90.5%) in-person visits and 2051 (9.5%) telemedicine visits were scheduled over the study period. There was no difference in patient age or gender between the visit types. There was a difference in race (75% White or Caucasian for in-person and 73% for telemedicine, P = .007) and average travel distance (53.3 miles for in-person vs 71.0 for telemedicine, P = .000). The most common primary diagnosis was Eustachian tube dysfunction for in-person visits (11.8%) and sleep disordered breathing for telemedicine visits (13.7%). Completion rate was greater for telemedicine visits (52.4% in-person vs 62.5% telemedicine). Cancellations were greater for in-person visits (42.6% in-person vs 24.2% telemedicine), but no-shows were greater for telemedicine (5.0% in-person vs 13.3% telemedicine, all P = .000). Average cycle time was shorter for telemedicine visits (56.5 minutes in-person vs 47.6 minutes telemedicine, P = .000). Patient satisfaction with provider interactions and overall care experience was high for both visit types. CONCLUSIONS: Telemedicine was utilized more during months of heightened COVID-19 cases, with higher completion rates, fewer cancellations, shorter cycle times, saved travel distance, and comparable patient satisfaction to in-person visits. Telemedicine has the potential to remain an efficient mode of care delivery in the post-pandemic era.

Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis.

Transcription and metabolism both influence cell function, but dedicated transcriptional control of metabolic pathways that regulate cell fate has rarely been defined. We discovered, using a chemical suppressor screen, that inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) rescues erythroid differentiation in bloodless zebrafish moonshine (mon) mutant embryos defective for transcriptional intermediary factor 1 gamma (tif1γ). This rescue depends on the functional link of DHODH to mitochondrial respiration. The transcription elongation factor TIF1γ directly controls coenzyme Q (CoQ) synthesis gene expression. Upon tif1γ loss, CoQ levels are reduced, and a high succinate/α-ketoglutarate ratio leads to increased histone methylation. A CoQ analog rescues mon's bloodless phenotype. These results demonstrate that mitochondrial metabolism is a key output of a lineage transcription factor that drives cell fate decisions in the early blood lineage.

Adoption of Telemedicine for Multidisciplinary Care in Pediatric Otolaryngology.

OBJECTIVE: The COVID-19 pandemic has introduced a period of social isolation that has challenged the ability of providers to uphold in-person patient care. Although commonplace in pediatric otolaryngology, multidisciplinary clinics pose a unique challenge during this time due to increased infection risk from multiple patient-provider interactions. Guidance on the application of telemedicine for multidisciplinary clinics in pediatric otolaryngology is limited. METHODS: We provide comprehensive guidance on best practices for conducting telemedicine visits for a number of multidisciplinary otolaryngology clinics using our experiences at a single tertiary care children's hospital. A review of literature to support the adoption of telemedicine in multidisciplinary pediatric otolaryngology is also incorporated. RESULTS: Telemedicine was successfully adopted for 7 multidisciplinary pediatric clinics with a variety of specialists: aerodigestive disorders, congenital hearing loss, microtia/aural atresia, orofacial clefting, sleep disorders, tracheostomy care, and velopharyngeal dysfunction. CONCLUSIONS: Telemedicine is feasible for a variety of multidisciplinary clinics and its optimization is critical for providing care to complex pediatric otolaryngology patients during the COVID-19 pandemic and beyond.

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.

Common variants in signaling transcription-factor-binding sites drive phenotypic variability in red blood cell traits.

Genome-wide association studies identify genomic variants associated with human traits and diseases. Most trait-associated variants are located within cell-type-specific enhancers, but the molecular mechanisms governing phenotypic variation are less well understood. Here, we show that many enhancer variants associated with red blood cell (RBC) traits map to enhancers that are co-bound by lineage-specific master transcription factors (MTFs) and signaling transcription factors (STFs) responsive to extracellular signals. The majority of enhancer variants reside on STF and not MTF motifs, perturbing DNA binding by various STFs (BMP/TGF-ß-directed SMADs or WNT-induced TCFs) and affecting target gene expression. Analyses of engineered human blood cells and expression quantitative trait loci verify that disrupted STF binding leads to altered gene expression. Our results propose that the majority of the RBC-trait-associated variants that reside on transcription-factor-binding sequences fall in STF target sequences, suggesting that the phenotypic variation of RBC traits could stem from altered responsiveness to extracellular stimuli.

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.