Faculty Bibliography

INTRODUCTION/BACKGROUND:This study investigates factors that relate to long-term educational and occupational outcomes of adults who received cochlear implants (CIs) during childhood. METHODS:A retrospective chart review was conducted on 109 adults who received a CI before the age of 15 between 2000 and 2012 at a US tertiary medical center. Demographic variables, speech perception scores, and educational and vocational achievements were analyzed. Current US Census and Bureau of Labor Statistics data were used for comparison. RESULTS:The median age at implantation was 2.81 years, and the median age at data collection was 27.30 years. Most subjects were unilaterally implanted (63.3%) and used an oral communication approach (89.0%). Educational outcomes showed that 17% completed a high school diploma or less, and 9% completed an associates or technical degree. Seventy-two percent of the subjects achieved a bachelor's degree or higher, significantly higher than the general US population (37.9%). Occupational outcomes indicated that subjects were employed across various job categories, with a higher proportion in jobs requiring considerable preparation (job zone 4) compared to the general population. There was a significant negative correlation between age at implantation and speech perception scores. Better word recognition scores were also associated with better educational and occupational outcomes. CONCLUSIONS:Adults who received CIs as children demonstrate excellent educational and occupational outcomes, surpassing those of the general US population. Early implantation and the absence of additional disabilities positively influence these outcomes. Continued investigation of nonspeech outcomes and the factors that influence them is essential to provide better support services for future cohorts.

INTRODUCTION/BACKGROUND:Prior studies have demonstrated that comorbid conditions can negatively impact cochlear implantation (CI) outcomes in elderly patients, but few have examined how comorbidities affect younger adult CI recipients. This study examines the relationship between comorbidities and CI outcomes in adults under 60 years old. METHODS:We reviewed all CI recipients between 20 and 60 years old from 2015 to 2019 at a tertiary academic medical center. Patient data were collected including comorbidities, demographics, etiology, and length of deafness (LOD). Patients' Charlson Comorbidity Index (CCI) was calculated. The primary outcome was speech perception scores at 1 year on the consonant-nucleus-consonant (CNC) word test. RESULTS:There were 118 patients who underwent CI (20-29 years [15%], 30-39 years [22%], 40-49 years [21%], 50-60 years [42%]), averaging 1.8 comorbidities. Mean LOD was 19.7 years, and most etiologies were unknown (53.4%). 34% had no comorbidities, and the most frequent comorbidities were hypertension (14%), asthma (10%), anxiety (8%), acoustic neuroma (8%), and arthritis (7%). Comorbidity frequency was similar across ages, but cardiovascular comorbidities varied by patient decade (50-60 years: 41% vs. 20-49 years: 12-22%, p = 0.004). Compared to studies on elderly CI outcomes, our cohort had fewer comorbidities with reduced cardiac events and neurological conditions. We did not find differences in 1-year CNC scores or complications based on the number of comorbidities or any single comorbidity. However, there was a difference in individual improvement in CNC word scores by age group (p = 0.024). Patients' CCI did not correlate to post-op scores. CONCLUSION/CONCLUSIONS:Subjects showed improved speech understanding post-CI. The number and type of comorbidities were not meaningful predictors of 1-year speech perception scores, suggesting adult CI users under 60 years with comorbidities can expect comparable outcomes to those without comorbidities.

Congenital cholesteatomas are defined as a collection of epithelium in the absence of prior surgery or pathologic retraction. They are most commonly found in the middle ear and are thought to arise from a residual epithelial rest present since birth; however, a small number of cases present with disease isolated to the mastoid bone. One such case and a review of prior reports are presented. A 29-year-old male with a 2-year history of headaches and no otologic surgery was found to have a destructive mass centered in the right mastoid bone, invading the jugular foramen and posterior fossa without middle ear disease. He underwent a mastoidectomy with complete resection of the cholesteatoma. A literature review identified 21 prior cases of isolated mastoid congenital cholesteatoma. Congenital cholesteatoma should be considered in the differential diagnosis when patients present with postauricular pain or headaches. Mastoidectomy is considered the treatment of choice.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To identify vocal tract configuration patterns in vocally healthy contemporary commercial music (CCM) singers during the production of five industry-typical vocal qualities, including various belting qualities and traditional/legit musical theater singing. STUDY DESIGN/METHODS:Prospective, observational study. METHODS:Seven professional musical theater singers (four females, three males) performed arpeggiated patterns using five different vocal qualities: traditional/legit, neutral belt, brassy belt, warm belt, and rock belt. Real-time magnetic resonance imaging captured midsagittal vocal tract configurations. Eight morphological measures were analyzed: lip opening, jaw opening, jaw protrusion, tongue dorsum height, uvula elevation, oropharyngeal opening, laryngeal height, and laryngeal tilt. Linear mixed-effects modeling explored relationships between vocal qualities and anatomical measurements. RESULTS:Lip opening, jaw opening, oropharyngeal opening, and laryngeal height showed significant differences across vocal qualities. The traditional/legit voice quality demonstrated the smallest lip, jaw, and oropharyngeal openings with the lowest laryngeal position. Rock belt showed the largest lip and jaw openings. Brassy belt and rock belt featured larger oropharyngeal space and higher tongue positions than other qualities, creating a "tube-like" shape rather than the previously suggested megaphone shape. Laryngeal positioning was elevated in all belting styles, but not in traditional/legit. No significant differences were found between male and female participants. Lower pitch tasks were characterized by smaller lip, jaw, and oropharyngeal openings compared with higher pitch tasks. CONCLUSION/CONCLUSIONS:This pilot study revealed distinct vocal tract configurations for different vocal qualities, particularly between traditional/legit and belting styles. The findings challenge previous assumptions about megaphone-shaped vocal tracts in belting, demonstrating more complex configurations. These results provide a foundation for identifying typical versus atypical vocal tract adjustments in CCM singing, with implications for voice pedagogy and clinical practice.

OBJECTIVE:Limited evidence guides the optimal timing of treatment after the detection of tumor growth during the observation of sporadic vestibular schwannoma (VS). The current work aimed to inform the timing of radiosurgical intervention based on an analysis of patient outcomes among those who ultimately failed stereotactic radiosurgery (SRS) and underwent salvage microsurgery. STUDY DESIGN/METHODS:A historical cohort study. SETTING/METHODS:Seven centers across the United States and Norway. METHODS:Adults with sporadic VS who underwent salvage microsurgery following failed primary SRS were included. The primary outcome of interest was the association between tumor size at the time of primary SRS and the ability to achieve gross total resection (GTR) and maintain postoperative House-Brackmann (HB) facial nerve grade I at the last follow-up after salvage microsurgery. RESULTS:Among 96 patients, the median (interquartile range [IQR]) cerebellopontine angle (CPA) tumor size at primary SRS was 14.5 mm (10.0-19.0). Each 1-mm increase in CPA tumor size at the time of primary SRS was associated with a 13% increased likelihood of near-total/subtotal resection or most recent postoperative HB grade >I (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.05-1.21, P = .001), with an optimal tumor size threshold to distinguish this outcome of 12 mm of CPA extension (c-index 0.73). Similarly, for each 1-mm increase in CPA tumor size at the time of primary SRS, a 9% increase in any postoperative complication with salvage microsurgery was observed (OR 1.09, 95% CI 1.02-1.15, P = .009). CONCLUSION/CONCLUSIONS:Corroborated by size threshold surveillance data informing the timing of primary microsurgical resection, the current study suggests that VS outcomes are optimized when primary radiosurgical intervention is undertaken on growing tumors when they harbor 10-15 mm of cerebellopontine angle extension or less.

OBJECTIVES/OBJECTIVE:Real-time monitoring of cochlear function to predict the loss of residual hearing after cochlear implantation is now possible. Current approaches monitor the cochlear microphonic (CM) during implantation from the electrode at the tip of the implant. A drop in CM response of >30% is associated with poorer hearing outcomes. However, there is prior evidence that CM amplitude can fluctuate in a manner unrelated to hearing trauma, leading to false positives. By monitoring another cochlear response, the auditory nerve neurophonic (ANN), a differentiation between CM drops that result in reduced cochlear output from false positives may be possible. The hypothesis tested in the present work was that ANN/CM ratios measured during a CM drop will increase during drops not associated with postoperative hearing loss. DESIGN/METHODS:Twenty-eight adult participants with known CM drops during implantation were taken from a larger data set. This contains adult cochlear implant candidates scheduled to receive a Cochlear Nucleus cochlear implant with either the slim-straight or slim-modiolar electrode array with preoperative audiometric low-frequency average thresholds of ≤80 dB HL at 500, 750, and 1000 Hz in the ear to be implanted. Patients were recruited from eight international implant sites. Pure-tone audiometry was measured postoperatively and 4 to 6 weeks after implantation. Electrocochleography was measured during and immediately after the implantation of the array in response to a 500-Hz, 6-msec pure-tone pip at 110 dB HL. RESULTS:The ANN/CM ratio rose during CM drops in 19 of these patients and decreased in 9. At the follow-up timepoint, patients with a decreasing ANN/CM ratio had a median hearing loss of 29.0 dB, significantly worse than the group with increasing ratio at 13.3 dB ( p = 0.004). Considering only the change in ANN amplitude during a CM drop led to smaller groups (ANN drop during CM drop N = 17, ANN increasing during CM drop N = 6) due to 5 patients having undetectable ANN during the CM drop. Using the ANN alone also led to as poorer prediction of hearing preservation, with median hearing preservation in the ANN increasing group of 12.9 dB, significantly better than the ANN decreasing group of 25 dB ( p = 0.02). The group with a decreasing ANN/CM ratio had maximum CM amplitude immediately after insertion lower than the maximum amplitude reached during insertion (mean maximum postinsertion amplitude of 98% of during-insertion amplitude). In comparison, the ANN/CM ratio increasing group tended to have a larger CM amplitude immediately after insertion (mean maximum CM amplitude postinsertion of 164% of the maximum during-insertion amplitude). CONCLUSIONS:These data show that the ANN/CM ratio is a measure that can differentiate between patients with CM drops that lead to a loss of residual hearing and those that do not. The ANN/CM ratio is easily measured and responds rapidly during a CM drop, showing clinical promise for improving current and developing approaches to intraoperative monitoring.

Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells - the output neurons of the cerebellar cortex - as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.

We leverage a clinical trial (NCT04080804) that compared neoadjuvant anti-PD-1, anti-PD-1+CTLA-4, and anti-PD-1+LAG-3 therapies in head and neck squamous cell carcinoma patients. Combination therapies promote higher pathologic response rates versus monotherapy, and major pathologic response is associated with better survival. To address whether successful immune checkpoint inhibitor (ICI) regimens act through similar or distinct pathways, we robustly and longitudinally characterize transcriptional and proteomic dynamics of CD8⁺ tumor-infiltrating lymphocytes (TILs) in a clonal manner. Anti-PD-1+LAG-3 reprograms CD8⁺ TIL with type-I interferon response and exhaustion gene programs into effector memory and resident memory (T_EM/T_RM). In contrast, anti-PD-1+CTLA-4 activates and expands pre-existing T_EM/T_RM CD8⁺ TIL, but does not rejuvenate exhausted phenotypes into T effector cells. Anti-PD-1+LAG-3, but not anti-PD-1+CTLA-4, induces widespread TCR sharing among the different transcriptional states, as well as increased TCR diversity in responding patients. Our data suggest doublet regimen-specific transcriptional and clonal dynamics of tumor-reactive CD8⁺ T cells.

OBJECTIVE:The purpose of this study is to characterize patients who work professionally as musical performers and undergo potassium titanyl phosphate (KTP) laser ablation of vocal fold lesions in the outpatient setting. METHODS:A retrospective chart review of patients who are vocal performers and underwent in-office KTP laser ablation of benign vocal fold lesions at a single academic institution between 2012 and 2023 was conducted. Demographics including occupation, were descriptively reviewed. Acoustic measures, including cepstral peak prominence (CPP) and mean fundamental frequency variance (F0CoV), were analyzed. Vocal fold vibratory amplitude and mucosal wave were evaluated on videostroboscopy utilizing the voice vibratory assessment with laryngeal imaging. Preablation and postablation outcome measures were compared via Wilcoxon signed rank and McNemar's test. RESULTS:26 patients who identified as singers successfully underwent single-treatment in-office KTP laser ablation of vocal fold polyps. Ten patients (38.5%) identified as professional performers, and all patients continued their occupation after ablation. 84.2% of patients had either complete recovery or mildly reduced mucosal wave and amplitude of the treated vocal fold following KTP laser ablation. Additionally, CPP vowel improved following in-office KTP laser ablation, and F0CoV decreased following the ablation. All patients were able to continue their occupation in the same capacity. CONCLUSION/CONCLUSIONS:In-office KTP ablation is a valuable, safe, and feasible intervention for professional performers with benign vocal fold polyps. This study provides insight into vocal outcomes in the largest cohort of professional performers with apt follow-up.