Faculty Bibliography

Acoustic vocoders play a key role in simulating the speech information available to cochlear implant (CI) users. Traditionally, the intelligibility of vocoder CI simulations is assessed through speech recognition experiments with normally-hearing subjects, a process that can be time-consuming, costly, and subject to individual variability. As an alternative approach, we utilized an advanced deep learning speech recognition model to investigate the intelligibility of CI simulations. We evaluated model's performance on vocoder-processed words and sentences with varying vocoder parameters. The number of vocoder bands, frequency range, and envelope dynamic range were adjusted to simulate sound processing settings in CI devices. Additionally, we manipulated the low-cutoff frequency and intensity quantization of vocoder envelopes to simulate psychophysical temporal and intensity resolutions in CI patients. The results were evaluated within the context of the audio analysis performed in the model. Interestingly, the deep learning model, despite not being originally designed to mimic human speech processing, exhibited a human-like response to alterations in vocoder parameters, resembling existing human subject results. This approach offers significant time and cost savings compared to testing human subjects, and eliminates learning and fatigue effects during testing. Our findings demonstrate the potential of speech recognition models in facilitating auditory research.

OBJECTIVE/UNASSIGNED:To describe the phenotypic characteristics of the epiglottis at rest and their impact on vallecular residue. METHODS/UNASSIGNED:Videofluoroscopic studies (VFSS) were pooled from 2 Laryngology practices, and Image J was used to measure epiglottic anatomic features at rest. Studies were rated by the MBSImp and presence of vallecular residue following swallow of thin and puree boluses. A conditional inference tree analysis was performed to isolate which epiglottic parameters were risk factors for presence of vallecular reside followed by logistic regression. RESULTS/UNASSIGNED: < .001), and this relationship was further modulated by increased distance of the epiglottic tip from the posterior pharyngeal wall. No other anatomic features of the resting epiglottis were associated with residue. Comorbidities potentially affecting swallow were infrequent in the cohort and were not associated with residue. CONCLUSION/UNASSIGNED:Abnormal epiglottic movement is associated with aspiration, and in this study we find that abnormal epiglottic movement increases the risk of vallecular residue and that older age is a risk factor for residue. The resting properties of the epiglottis do not appear to be associated with abnormal epiglottic movement or residue.

Legumain is a cysteine protease broadly associated with inflammation. It has been reported to cleave and activate protease-activated receptor 2 to provoke pain associated with oral cancer. Outside of gastric and colon cancer, little has been reported on the roles of legumain within the gastrointestinal tract. Using a legumain-selective activity-based probe, LE28, we report that legumain is activated within colonocytes and macrophages of the murine colon, and that it is upregulated in models of acute experimental colitis. We demonstrated that loss of legumain activity in colonocytes, either through pharmacological inhibition or gene deletion, had no impact on epithelial permeability in vitro. Moreover, legumain inhibition or deletion had no obvious impacts on symptoms or histological features associated with dextran sulfate sodium-induced colitis, suggesting its proteolytic activity is dispensable for colitis initiation. To gain insight into potential functions of legumain within the colon, we performed field asymmetric waveform ion mobility spectrometry-facilitated quantitative proteomics and N-terminomics analyses on naïve and inflamed colon tissue from wild-type and legumain-deficient mice. We identified 16 altered cleavage sites with an asparaginyl endopeptidase signature that may be direct substrates of legumain and a further 16 cleavage sites that may be indirectly mediated by legumain. We also analyzed changes in protein abundance and proteolytic events broadly associated with colitis in the gut, which permitted comparison to recent analyses on mucosal biopsies from patients with inflammatory bowel disease. Collectively, these results shed light on potential functions of legumain and highlight its potential roles in the transition from inflammation to colorectal cancer.

OBJECTIVE:Vocal tremor (VT) poses treatment challenges due to uncertain pathophysiology. VT is typically classified into two phenotypes: isolated vocal tremor (iVT) and essential tremor-related voice tremor (ETvt). The impact of phenotypes on upper aerodigestive tract physiology during swallowing remains unclear. Qualitative and quantitative measures were employed to characterize tremor phenotypes and investigate the effects on swallowing physiology. METHODS:Eleven ETvt participants (1 Male, 10 Female; x̄ age = 74) and 8 iVT participants (1 Male, 7 Female; x̄ age = 71) swallowed 20 mL boluses in cued and uncued conditions under standardized fluoroscopic visualization. Sustained/a/productions were captured to assess the rate and extent of fundamental frequency (F0) modulation. Penetration and Aspiration Scale (PAS) scores were obtained and swallowing biomechanics were captured using Swallowtail™ software. Participants also completed the Swallowing Quality of Life (SWAL-QOL) questionnaire. RESULTS:Hypopharyngeal transit was faster in both VT phenotypes compared with Swallowtail™ normative reference data. Total pharyngeal transit times, however, were only faster in patients with iVT, relative to reference data. No significant differences were observed on the SWAL-QOL or PAS between tremor phenotypes. SWAL-QOL scores revealed that these patients rarely reported dysphagia symptoms. CONCLUSIONS:Subtle differences in swallowing patterns were observed across VT phenotypes, possibly related to adaptive mechanisms resulting in quicker pharyngeal bolus transit. Most patients did not report swallowing issues or dysphagia symptoms. This study is foundational for larger studies on this challenging population. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 134:4599-4603, 2024.

Adolescents and young adults (ie, individuals aged 15-39 years, known as AYAs) with cancer face unique vulnerabilities yet remain underrepresented in clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8%-12%). We used the Pediatric Oncology COVID-19 Case Report to examine the clinical course of COVID-19 among AYAs with cancer. The Pediatric Oncology COVID-19 Case Report collects deidentified clinical and sociodemographic data regarding individuals aged from birth to 39 years with cancer (37%) and COVID-19 from more than 100 institutions. Between April 1, 2020, and November 28, 2023, 191 older AYAs (individuals 22-39 years of age) and 640 younger AYAs (individuals 15-21 years of age) were captured. Older AYAs were less often hospitalized (P < .001), admitted to the intensive care unit (P = .02), and required respiratory support (P = .057). In multivariable analyses, older AYAs faced 80% lower odds of intensive care unit admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of intensive care unit admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform oncology teams directing COVID-19 management and prevention in AYA patients with cancer.

Oral-ocular synkinesis is a common, uncomfortable, and disfiguring sequela of facial nerve palsy. Despite widespread use of chemodenervation as a non-surgical intervention, limited literature exists on optimal dosage and administration techniques in these patients. This study aims to describe a reliable chemodenervation injection technique and report objective measurements and subjective satisfaction outcomes. Prospective pre-post interventional study where new, consecutive patients with previously untreated oral-ocular synkinesis secondary to facial nerve palsy were included. Patients completed a Synkinesis Assessment Questionnaire and standardized photographs were taken before and after botulinum toxin injections. Palpebral fissure symmetry was measured from photographs, with the unaffected side functioning as the control. Sixteen patients were included in the prospective study. Mean age was 48 years old and 56% male. Botulinum toxin was injected into the upper and lower medial preseptal, upper and lower lateral pretarsal, and lateral orbital orbicularis oculi (10-13 units). Standardized photographic comparison demonstrated significant improvement in palpebral fissure height with smile (p < 0.01) and lip pucker (p < 0.01). Relevant items on the Synkinesis Assessment Questionnaire also significantly improved (p < 0.01). This reliable botulinum toxin injection technique for oral-ocular synkinesis demonstrated significant improvement in subjective quality of life metrics and objective palpebral fissure height during both smile and pucker.

Evidence on facial rehabilitation therapy (FRT) for acute facial paralysis (FP) remains limited. We present a retrospective review of patients with acute FP who have received FRT with physical therapists within 1 year of FP onset as determined by Sunnybrook Facial Grading Scale (SFGS) composite scores. A total of 702 patients with a clinical diagnosis of FP were referred to a university rehabilitation program between January 1, 2015 and January 1, 2022. Seventy-six patients met the criteria, defined as FP diagnosis <12 months before FRT initiation, ≥3 therapy sessions, and sufficient follow-up data. Average number of treatment sessions between SFGS scores was 7.7. History of cancer, sex, number of treatment sessions, and initial SFGS score were correlated with change in SFGS. Time to treatment was not correlated with change in SFGS score. SFGS improved with each additional treatment session (p < 0.01). Each additional point in the initial SFGS was correlated with less change in the final SFGS score (p < 0.01). FRT can provide meaningful improvement in functionality for patients with acute FP, regardless of time to treatment. Furthermore, patients who present with poorer functionality at baseline and those who undergo more treatment are most likely to see SFGS improvement. Research comparing the effect of facial rehabilitation with other treatment modalities and to a control cohort is warranted.

Hearing loss is common among Veterans, and extensive hearing care resources are prioritized within the Veterans Administration (VA). Severe hearing loss poses unique communication challenges with speech understanding that may not be overcome with amplification. We analyzed data from the VA Audiometric Repository between 2005 and 2017 and the relationship between hearing loss severity with speech recognition scores. We hypothesized that a significant subset of Veterans with severe or worse hearing loss would have poor unaided speech perception outcomes even with adequate audibility. Sociodemographic characteristics and comorbidities were compiled using electronic medical records as was self-report measures of hearing disability. We identified a cohort of 137,500 unique Veterans with 232,789 audiograms demonstrating bilateral severe or worse hearing loss (four-frequency PTA > 70 dB HL). The median (IQR; range) age of Veterans at their first audiogram with severe or worse hearing loss was 81 years (74 to 87; 21-90+), and a majority were male (136,087 [99%]) and non-Hispanic white (107,798 [78.4%]). Among those with bilateral severe or worse hearing loss, 41,901 (30.5%) also had poor speech recognition scores (<50% words), with greater hearing loss severity correlating with worse speech perception. We observed variability in speech perception abilities in those with moderate-severe and greater levels of hearing loss who may derive limited benefit from amplification. Veterans with communication challenges may warrant alternative approaches and treatment strategies such as cochlear implants to support communication needs.

BACKGROUND & AIMS/OBJECTIVE:Abdominal pain is a major symptom of diseases that are associated with microbial dysbiosis, including irritable bowel syndrome and inflammatory bowel disease. Germ-free mice are more prone to abdominal pain than conventionally housed mice, and reconstitution of the microbiota in germ-free mice reduces abdominal pain sensitivity. However, the mechanisms underlying microbial modulation of pain remain elusive. We hypothesized that disruption of the intestinal microbiota modulates the excitability of peripheral nociceptive neurons. METHODS:In vivo and in vitro assays of visceral sensation were performed on mice treated with the nonabsorbable antibiotic vancomycin (50 μg/mL in drinking water) for 7 days and water-treated control mice. Bacterial dysbiosis was verified by 16s rRNA analysis of stool microbial composition. RESULTS:Treatment of mice with vancomycin led to an increased sensitivity to colonic distension in vivo and in vitro and hyperexcitability of dorsal root ganglion (DRG) neurons in vitro, compared with controls. Interestingly, hyperexcitability of DRG neurons was not restricted to those that innervated the gut, suggesting a widespread effect of gut dysbiosis on peripheral pain circuits. Consistent with this, mice treated with vancomycin were more sensitive than control mice to thermal stimuli applied to hind paws. Incubation of DRG neurons from naive mice in serum from vancomycin-treated mice increased DRG neuron excitability, suggesting that microbial dysbiosis alters circulating mediators that influence nociception. The cysteine protease inhibitor E64 (30 nmol/L) and the protease-activated receptor 2 (PAR-2) antagonist GB-83 (10 μmol/L) each blocked the increase in DRG neuron excitability in response to serum from vancomycin-treated mice, as did the knockout of PAR-2 in NaV1.8-expressing neurons. Stool supernatant, but not colonic supernatant, from mice treated with vancomycin increased DRG neuron excitability via cysteine protease activation of PAR-2. CONCLUSIONS:Together, these data suggest that gut microbial dysbiosis alters pain sensitivity and identify cysteine proteases as a potential mediator of this effect.

BACKGROUND:Guidelines recommend treatment package time < 85 days and time from surgery to radiation initiation < 6 weeks in head and neck cancer patients. However, HPV positive primaries treated with TORS and adjuvant radiotherapy traditionally demonstrate favorable outcomes. METHODS:Single center retrospective chart review of patients diagnosed with HPV positive treatment naïve primary squamous cell carcinoma treated with TORS and postoperative radiation therapy with or without Chemotherapy from 2012 to 2022 with data collection from December 2022-April 2023. Kaplan-Meier survival analysis with log-rank testing assessed the impact of time intervalsbetween diagnosis, TORS, radiation initiation and radiation completion on recurrence free and disease specific survival. Univariate Cox proportional hazards regression analysis was performed to identify factors associated with recurrence free and disease specific survival. Subgroup analysis was done with high risk (positive lymph nodes > 5, >1mm extracapsular extension, positive margins) patients who underwent concurrent Chemotherapy. RESULTS:Of 255 patients (225 males [89 %], average age 58 years, 163 [64 %] high-risk, median follow-up 4.3 years), 22 (8.6 %) had recurrence and 14 died due after disease recurrence.Only radiation length of 5-7 weeks prolonged survival in the entire population. In the high-risk cohort, time from TORS to radiation initiation < 6 weeks improvedrecurrence free survival, while total package time < 14 weeks wasassociated with greater recurrence free and disease specific survival.