Faculty Bibliography

Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity Score (modified) post-INO-3107 and assessment of immune responses. 81% (26/32) of patients experienced surgery reduction following INO-3107 compared with the year prior to treatment. Blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction. RNA sequencing identified an inflammatory response in papillomas, inclusive of cytolytic CD8 + T-cell signatures. T-cell receptor sequencing revealed emergent T-cell clones in blood and confirmed trafficking to papillomas. Treatment-related adverse events (AEs) were reported in 13/32 (41%) patients, all low-grade. INO-3107 provides clinical benefit to HPV-6 and/or HPV-11-associated RRP adults and is well-tolerated. Importantly, treatment-induced peripheral T-cell responses traffic to airway tissue and are associated with clinical response.

OBJECTIVE:This study aims to evaluate the clinical outcomes of patients receiving in-office vocal fold steroid injections (VFSI), highlighting relatively new measures around vocal pitch. METHODS:Patients with a diagnosis of vocal fold scar who received in-office VFSI from 2013 to 2024 were evaluated. Pre- and post-steroid Voice Handicap Index (VHI-10) scores, stroboscopic vibratory parameters, acoustic measures of cepstral peak prominence (CPP), and fundamental frequency coefficient of variation (F0CoV) during sustained phonation were analyzed using Wilcoxon signed-rank tests and McNemar's tests. RESULTS:Twenty-two patients had follow-up data 1-3 months after steroid injection. The median decrease in VHI-10 after one injection was 4 points (p = 0.02). We found no difference in CPP and F0CoV measures at follow-up. Forty-five percent of patients improved in mucosal wave and amplitude of at least one vocal fold. Earlier presentation from vocal injury was associated with improvement in mucosal wave and amplitude of the left vocal fold (p = 0.03). We found no difference in sex, tobacco smoking history, singing status, secondary diagnosis, and baseline VHI-10 score between patients who improved in vibratory parameters and those who did not. CONCLUSION/CONCLUSIONS:This single-center study is one of the largest exploring patient outcomes following in-office VFSI. Though patients reported modest improvement in voice use after VFSI, this may not be as impactful as previously believed. Improvement in videostroboscopy is expected in about half of the patients, with recency from vocal injury a likely predictor of success. These partially negative results provide insight into counseling patients regarding benefits from in-office VFSI. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2024.

BACKGROUND/UNASSIGNED:) and intensity modulation), patient perception of their voice remains unexamined despite its clinical importance. This study aimed to characterize the relationship between patient-reported vocal tremor severity and acoustic voice outcomes at baseline and after botulinum toxin injections. METHOD/UNASSIGNED: RESULTS/UNASSIGNED: DISCUSSION/UNASSIGNED:Participants reporting more severe vocal tremor demonstrated more aberrant acoustic voice outcomes. After botulinum toxin injection, substantial heterogeneity was observed in acoustic voice measures which varied based on patient perception of change. These preliminary, exploratory findings provide a foundation for future investigations to define meaningful change in this population.

OBJECTIVES/UNASSIGNED:Acute post-thyroidectomy bilateral vocal cord paresis or paralysis (BVCP) is often managed with observation, botulinum toxin injection or tracheostomy. However, only a few cases discuss obstructive sleep apnea (OSA) in the context of BVCP with limited exploration of home sleep test (HST) and continuous positive airway pressure (CPAP) as post-operative assessment and management tools. This study suggests CPAP as a less invasive approach while awaiting vocal cord recovery. METHODS/UNASSIGNED:A retrospective chart review was conducted on 2 female patients who presented with dyspnea and sleep-disordered breathing (SDB) symptoms post-thyroidectomy. Both patients underwent laryngoscopy and HSTs, followed by CPAP prescription. RESULTS/UNASSIGNED:), aged 66 and 77 respectively, presented with post-surgery dyspnea and SDB symptoms. Laryngoscopy revealed left vocal cord paresis and right vocal cord paralysis in both cases. Although tracheostomy could provide definitive treatment, both cases were deferred for non-invasive options, which led to HST, confirming moderate OSA (PAT-derived apnea-hypopnea index (pAHI): 18/hour and 27.1/hour) leading to CPAP recommendation. In Case 2, 5 weeks of CPAP use resulted in dramatic improvements in her sleep quality, with continued benefits at 3-month follow-up. CONCLUSION/UNASSIGNED:These cases underscore the value of considering sleep studies and CPAP as adjunctive tools in acute post-thyroidectomy BVCP management while awaiting vocal motion recovery. This report also further supports that BVCP sufficiently narrows the glottic airway, predisposing patients to OSA.

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.

OBJECTIVE/UNASSIGNED:The objective of this study is to assess disparities in adherence to swallowing therapy for clinically diagnosed oropharyngeal dysphagia (OD) patients. METHODS/UNASSIGNED:Analysis was conducted on data from 600 patients with OD and confirmed impairments in swallowing safety and/or efficiency on a videofluoroscopic swallow study. Patients were classified based on their adherence to treatment sessions, defined as the number of swallow treatment sessions attended. The outcome of treatment adherence was categorized into two groups: those who attended fewer than 50% of the prescribed treatment sessions and those who attended 50% or more of the sessions. Continuous variables were presented as mean ± standard deviation or median ± interquartile range. Categorical variables were compared using Pearson chi-square tests and Fisher's exact test when appropriate. Univariable and multivariable binary logistic regression models were employed to identify factors associated with successful adherence. RESULTS/UNASSIGNED: > 0.05). CONCLUSION/UNASSIGNED:The variables analyzed in this study were not significantly associated with nonadherence to swallow therapy. Nevertheless, our study still addressed an important knowledge gap and future studies would benefit from exploring other relevant socioeconomic and disease-related factors. LEVEL OF EVIDENCE/UNASSIGNED:Level 4.

This aim of this study is to characterize the nature and pathophysiology of dysphagia after ACDF surgery by precisely and comprehensively capturing within-subject changes on videofluoroscopy between preoperative and postoperative time points. 21 adults undergoing planned primary ACDF procedures were prospectively recruited and enrolled. Participants underwent standardized preoperative and six-week postoperative videofluoroscopic swallow studies. Videos were blindly rated using the Penetration-Aspiration Scale (PAS) and analysis of total pharyngeal residue (%C2-4²), swallowing timing, kinematics, and anatomic change was completed. Linear mixed-effects modeling was used to explore the relationships between possible predictor variables and functional outcomes of interest that changed across timepoints. There was no change in PAS scores across timepoints. Total pharyngeal residue (%C2-C4²) was increased postoperatively (p < 0.001). Our statistical model revealed significant main effects for timepoint (p = 0.002), maximum pharyngeal constriction area (MPCA_N) (p < 0.001), and maximum thickness of posterior pharyngeal (PPWT_MAX) (p = 0.004) on the expression of total pharyngeal residue. There were significant two-way interactions for timepoint and MPCA_N (p = 0.028), timepoint and PPWT_MAX (p = 0.005), and MPCA_N and PPWT_MAX (p = 0.010). Unsurprisingly, we found a significant three-way interaction between these three predictors (p = 0.027). Our findings suggest that in planned ACDF procedures without known complications, swallowing efficiency is more likely to be impaired than airway protection six weeks after surgery. The manifestation of impaired swallowing efficiency at this timepoint appears to be driven by a complex relationship between reduced pharyngeal constriction and increased prevertebral edema.

OBJECTIVE:The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. METHODS:Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. RESULTS:After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. CONCLUSION/CONCLUSIONS:A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. LEVEL OF EVIDENCE/METHODS:5 Laryngoscope, 134:1614-1624, 2024.

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.

OBJECTIVE:To compare improvement in patient-reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD). METHODOLOGY/METHODS:Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10-item Eating Assessment Tool (EAT-10) pre- and post-procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t-test, Wilcoxon rank sum test or chi-square test, as appropriate. RESULTS:One hundred and forty-seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT-10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT-10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow-up was 86 and 97.5 days, respectively. CONCLUSION/CONCLUSIONS:Both endoscopic and open surgical management of ZD provide significant improvement in patient-reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group. LEVEL OF EVIDENCE/METHODS:Level 3 Laryngoscope, 2023.