Faculty Bibliography

BACKGROUND:After head and neck cancer (HNC) treatment, dysgeusia may be a barrier to oral intake. In this exploratory study, we prospectively examined taste perception, clinician-rated (CRO) and patient-reported (PRO) taste changes and their effect on oral intake postradiotherapy. METHODS:Twenty-eight patients were assessed at baseline, treatment weeks 2 and 4, and 1, 3, and 6 months post-treatment using a whole-mouth taste test and associated CRO and subjective PRO measures. RESULTS:Greater taste impairment was reflected by subjective than by a whole-mouth taste test. The most significant and consistent decline occurred mid-treatment. The Chemotherapy-Induced Taste Alteration Scale (PRO) discomfort subscale correlated significantly with maintaining an oral diet, percent of oral intake, and appetite level from mid-treatment to 6 months post-treatment. CONCLUSIONS:PRO results indicated ongoing oral intake issues. Whole-mouth taste tests may fail to fully reflect functional taste-loss. Dysgeusia prevention and treatment methods are needed to improve patient outcomes.

OBJECTIVE:The American Joint Committee on Cancer (AJCC) 8th edition introduced distinct clinical and pathological staging paradigms for human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Treatment planning for OPSCC often utilizes positron emission tomography/computed tomography (PET/CT) to assess clinical stage. We hypothesize that PET/CT will accurately predict final pathologic AJCC 8th edition staging in patients with HPV+ OPSCC. METHODS:All patients with primary HPV+ OPSCC with preoperative PET/CT who underwent transoral robotic surgery and neck dissection between 2011 and 2017 were identified. Data were collected via chart review. Two neuroradiologists performed blinded re-evaluation of all scans. Primary tumor size and cervical nodal disease characteristics were recorded and TNM staging was extrapolated. Cohen's kappa statistic was used to assess interrater reliability. Test for symmetry was performed to analyze discordance between radiologic and pathologic staging. RESULTS:Forty-nine patients met inclusion criteria. Interrater reliability was substantial between radiologists for nodal (N) and overall staging (OS) (κ = 0.715 and 0.715). Radiologist A review resulted in identical OS for 67% of patients, overstaging for 31%, and understaging for 2%. Radiologist B review resulted in 61% identical OS, 39% overstaging, and 0% understaging. In misclassified cases, the test of symmetry shows strong bias toward overstaging N stage and OS (P < .001). Radiologic interpretation of extracapsular extension showed poor interrater reliability (κ = 0.403) and poor accuracy. CONCLUSION:PET/CT predicts a higher nodal and overall stage than pathologic staging. PET/CT should not be relied upon for initial tumor staging, as increased FDG uptake is not specific for nodal metastases. PET/CT is shown to be a poor predictor of ECE. LEVEL OF EVIDENCE:4 Laryngoscope, 131:1535-1541, 2021.

Vocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.

Explicit rewards are commonly used to reinforce a behavior, a form of learning that engages the dopaminergic neuromodulatory system. In contrast, skill acquisition can display dramatic improvements from a social learning experience, even though the observer receives no explicit reward. Here, we test whether a dopaminergic signal contributes to social learning in naïve gerbils that are exposed to, and learn from, a skilled demonstrator performing an auditory discrimination task. Following five exposure sessions, naïve observer gerbils were allowed to practice the auditory task and their performance was assessed across days. We first tested the effect of an explicit food reward in the observer's compartment that was yoked to the demonstrator's performance during exposure sessions. Naïve observer gerbils with the yoked reward learned the discrimination task significantly faster, as compared to unrewarded observers. The effect of this explicit reward was abolished by administration of a D1/D5 dopamine receptor antagonist during the exposure sessions. Similarly, the D1/D5 antagonist reduced the rate of learning in unrewarded observers. To test whether a dopaminergic signal was sufficient to enhance social learning, we administered a D1/D5 receptor agonist during the exposure sessions in which no reward was present and found that the rate of learning occurred significantly faster. Finally, a quantitative analysis of vocalizations during the exposure sessions suggests one behavioral strategy that contributes to social learning. Together, these results are consistent with a dopamine-dependent reward signal during social learning.

INTRODUCTION/UNASSIGNED:Deep brain stimulation (DBS) is a common surgical option for the treatment of medically refractory Parkinson's disease (PD). Manufacturer and User Facility Device Experience (MAUDE), a United States Food and Drug Administration (FDA)-compiled database of adverse event reports related to medical devices, is a public resource that can provide insight into the relative frequency of complications and patient complaints. MATERIALS AND METHODS/UNASSIGNED:We accessed the MAUDE database and queried for adverse reports for deep brain stimulators implanted for PD from January 1, 2009 to December 31, 2018. Complaints were classified into device malfunction, patient non-compliance, patient complaint, surgically managed complications (i.e. complications that are corrected via surgery), and death. Patient complaints were further stratified into ineffective stimulation, shock, overstimulation, battery-related problems, or pain at the pulse generator site. Surgically managed complications were classified as intraoperative complications, impedance, migration, erosion, infection, lead fracture, and lead disconnection. Each event could receive multiple classifications and subclassifications. RESULTS/UNASSIGNED:A total of 4,189 adverse event reports was obtained. These encompassed 2,805 patient complaints. Within this group, 797 (28%) events were classified as ineffective stimulation. There were 1,382 surgically managed complications, 104 (8%) of which were intraoperative complications, 757 (55%) documented impedance issues, 381 (28%) infections, and 413 (30%) lead-related issues. There were 53 documented deaths. CONCLUSIONS/UNASSIGNED:The MAUDE database has potential use as a real time monitor for elucidating the relative occurrence of complications associated with deep brain stimulation. It also allows for the analysis of device-related complications in specific patient populations. Although the database is useful in this endeavor, it requires improvements particularly in the standardization of reporting adverse events.

PURPOSE/OBJECTIVE:Since the COVID-19 pandemic began, emergency departments (ED) across the country have seen a significant decrease in patient visits. We aim to evaluate the impact of COVID-19 on ED visits for acute otolaryngologic complaints in New York City, one of the first epicenters of the pandemic in the US. MATERIALS AND METHODS/METHODS:We conducted a retrospective study of patients who presented to the ED with a primary diagnosis of an acute otolaryngologic complaint between March 1 and May 31 in 2019 and 2020. This was a multicenter study, including two tertiary care hospital systems encompassing Manhattan, Bronx, Queens, and Long Island. RESULTS:A total of 10,162 patients were identified. Significantly fewer patients presented to the ED for acute otolaryngologic complaints in 2020 (7332 vs 2830, p < 0.001). The rate of total otolaryngology-related ED visits was decreased by a factor of 0.635 (95% CI 0.6079 to 0.6634). In a subgroup analysis of each individual diagnosis, there was a significant decrease in rate of ED visits for 13 out of 18 diagnoses, including for life-threatening conditions, such as anaphylaxis. There was no significant difference based on which borough in New York City. Pediatric patients (age 0-17) were more significantly impacted by the pandemic compared to other age groups. CONCLUSION/CONCLUSIONS:The COVID-19 pandemic has led to a reduction in the utilization of ED for acute otolaryngologic complaints, including those requiring emergent management, and an even more significant reduction in the pediatric population. Healthcare providers should encourage patients to seek appropriate care, particularly for those illnesses with significant associated morbidity and mortality.

INTRODUCTION/UNASSIGNED:Understanding the clinical manifestations of the coronavirus disease (COVID-19) has become an urgent objective in the research community. Amongst the emerging neurologic complications is sensorineural hearing loss. While several cases of hearing loss amongst COVID-19 patients have been reported, the management of these patients has yet to be discussed and determined. Herein we present cochlear implant outcomes for a patient who suffered from unilateral sensorineural hearing loss after a prolonged hospital course for COVID-19. METHODS/UNASSIGNED:A patient who was hospitalized for COVID-19 for one month and subsequently developed unilateral profound sensorineural hearing loss underwent cochlear implantation for single-sided deafness. His COVID-19 hospital course was reviewed in detail. Speech perception and audiometric assessments were used to evaluate cochlear implant outcomes. RESULTS/UNASSIGNED:After cochlear implantation, the patient demonstrated improved speech perception on the implanted side and decreased tinnitus within 1 month of activation. CONCLUSIONS/UNASSIGNED:Cochlear implantation may be an appropriate intervention for patients who suffer from severe sensorineural hearing loss following infection with COVID-19.

PURPOSE/OBJECTIVE:The aim of this systematic review is to compare the perioperative characteristics and outcomes of submental artery island flap (SAIF) to free tissue transfer (FTT) in head and neck reconstruction. MATERIALS AND METHODS/METHODS:Screening and data extraction were done with Pubmed, Embase, and Web of Science databases by two independent authors to identify randomized and observational studies that compared patient outcomes for SAIF vs. FTT for reconstruction head and neck cancer ablative surgery. Data were pooled with random-effects meta-analysis to determine pooled difference in means (DM), absolute risk differences, and 95% confidence intervals (CI). Heterogeneity was assessed with the I-squared statistic. RESULTS:(95% CI 6.5 to 38.4). SAIF had a 5% higher incidence of partial flap necrosis than FTT (95% CI, 1 to 10), but all other perioperative complications, including recurrence rate in malignant cases, were statistically comparable. CONCLUSIONS:The SAIF requires less operative time, hospital stay, and has comparable perioperative outcomes to FTT, but the area of flap harvest is significantly smaller. The findings of this study add to the growing body of evidence demonstrating the safety and reliability of SAIF in head and neck reconstruction.

Although macrophages (MΦ) are known to play a central role in neuropathic pain, their contribution to cancer pain has not been established. Here we report that depletion of sciatic nerve resident MΦs (rMΦ) in mice attenuates mechanical/cold hypersensitivity and spontaneous pain evoked by intraplantar injection of melanoma or lung carcinoma cells. MΦ-colony stimulating factor (M-CSF) was upregulated in the sciatic nerve trunk and mediated cancer-evoked pain via rMΦ expansion, transient receptor potential ankyrin 1 (TRPA1) activation, and oxidative stress. Targeted deletion of Trpa1 revealed a key role for Schwann cell TRPA1 in sciatic nerve rMΦ expansion and pain-like behaviors. Depletion of rMΦs in a medial portion of the sciatic nerve prevented pain-like behaviors. Collectively, we identified a feed-forward pathway involving M-CSF, rMΦ, oxidative stress and Schwann cell TRPA1 that operates throughout the nerve trunk to signal cancer-evoked pain.