Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer.

The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present a unique case of a patient with recurrent/metastatic (R/M) HNSCC who, despite initial response to nivolumab-based treatment, developed rapidly progressive metastatic disease after the acquisition of MYC amplification. We conducted comparative transcriptomic analysis of this patient's tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. This study highlights MYC amplification as a potential mechanism of immune checkpoint inhibitor resistance and suggest its use as a predictive biomarker and potential therapeutic target in R/M HNSCC.

The Time Burden of Office Visits in Contemporary Pituitary Care, 2016 to 2019.

BACKGROUND: The concept of "time toxicity" has emerged to address the impact of time spent in the healthcare system; however, little work has examined the phenomenon in the field of otolaryngology. OBJECTIVE: To validate the use of Evaluation and Management (E/M) current procedural terminology codes as a method to assess time burden and to pilot this tool to characterize the time toxicity of office visits associated with a diagnosis of pituitary adenoma between 2016 and 2019. METHODS: A retrospective cohort study of outpatient office visits quantified differences between timestamps documenting visit length and their associated E/M code visit length. The IBM MarketScan database was queried to identify patients with a diagnosis of pituitary adenoma in 2016 and to analyze their new and return claims between 2016 and 2019. One-way ANOVA and two-sample t-tests were used to examine claim quantity, time in office, and yearly visit time. RESULTS: In the validation study, estimated visit time via E/M codes and actual visit time were statistically different (P < 0.01), with E/M codes underestimating actual time spent in 79.0% of visits. In the MarketScan analysis, in 2016, 2099 patients received a primary diagnosis of pituitary adenoma. There were 8490 additional-related claims for this cohort from 2016 to 2019. The plurality of new office visits were with endocrinologists (n = 857; 29.3%). Total time spent in office decreased yearly, from a mean of 113 min (2016) to 69 min (2019) (P < 0.001). CONCLUSIONS: E/M codes underestimate the length of outpatient visits; therefore, time toxicity experienced by pituitary patients may be greater than reported. Further studies are needed to develop additional assessment tools for time toxicity and promote increased efficiency of care for patients with pituitary adenomas.

Racial Disparities in Surgical Management For Early-Stage Laryngeal Squamous Cell Carcinoma and Recurrent Dysplasia.

Objective: The aim of this study is to evaluate the association between race and the treatment of laryngeal dysplasia and early-stage laryngeal squamous cell carcinoma (LSCC). Study design: Retrospective Cohort Study. Setting: Large multispecialty academic medical center. Methods: Patients were treated for laryngeal dysplasia or LSCC between September 2019 and September 2022. A retrospective chart review was conducted to collect demographic and clinical information. Two-sample t tests, chi-square tests, and linear regression models were used to compare characteristics (α = 0.05). Analyses were performed in STATA 17. Results: Sixty-five patients were identified that underwent potassium titanyl phosphate (KTP) transoral laser microsurgery for management of early-stage LSCC (n = 29) or dysplasia (n = 36). The cohort consisted of 23 Black and 42 White patients. No significant difference was found in age, alcohol or tobacco use, rate of adjuvant radiotherapy, stage of disease, nor insurance status between the 2 groups. White patients underwent more procedures to address initial disease and subsequent recurrent dysplasia on average than Black patients (2.52 vs 1.52, P = .02). This remained true after adjusting for demographic and clinical characteristics and insurance status in a linear regression model. While Black patients were more likely to be lost to follow-up than White patients (30.4% vs 9.5%, P = .03), the average number of procedures between the groups still differed significantly (2.63 vs 1.56, P = .04) when controlling for those lost to follow-up. Conclusion: The findings presented here highlight potential inequities that exist for racial minorities at early stages of treatment and in addressing premalignant conditions, which may contribute to the known downstream disparities in laryngeal cancer outcomes.

Otolaryngology Away Subinternships: An Analysis of the Application Process and Survey of Current Applicants' Perspectives.

Objective: To assess the availability and uniformity of application information for away subinternships and survey 4th-year medical students on their experiences obtaining away subinternships in otolaryngology-head and neck surgery (OHNS) during the 2022 to 2023 application cycle. Study Design: Cross-sectional study. Setting: Online survey. Methods: The Association of American Medical College's Visiting Student Learning Opportunities (VSLO) program was queried for information on OHNS away subinternship applications. A survey assessing 4th-year medical students' perceptions of the away subinternship application process was distributed via OHNS residency program directors and Otomatch. Results: Of 129 OHNS residency programs, 103 (80%) offered away subinternship opportunities on VSLO. Variability in application release dates (January 18 to June 3, 2022), offer release dates (January 27 to August 7, 2022), and estimated cost ($22-$5500) were found. The most common application requirements were a transcript (98.1%) and a CV/resume (90.3%). There were 64 survey respondents, for a 13% response rate. The most common concerns include applying to too few programs (80%) and not knowing offer release dates (77%). The most common stressors include choosing a number of programs to which to apply (48%) and cost (35%). The majority (76%) reported difficulty finding updated information on program websites. Among the proposed changes, the greatest support was found for having all applications on VSLO (88%), uniform application release date (84%), and uniform application requirements (82%). Conclusion: The OHNS away subinternship application process is a significant source of anxiety for medical students due to the tremendous variability in application and acceptance procedures. Having all applications on VSLO, uniform application requirements, and uniform application opening and offer release dates would better facilitate this process.

Embolization in Juvenile Nasopharyngeal Angiofibroma Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare outcomes of juvenile nasopharyngeal angiofibroma (JNA) resection between embolized and non-embolized cohorts, and between transarterial embolization (TAE) and direct puncture embolization (DPE). DATA SOURCES: Per PRISMA guidelines, PubMed, Embase, Web of Science, Scopus, and Cochrane databases were searched for publications prior to or in 2021. MATERIALS AND METHODS: Original English manuscripts investigating the resection of JNA with and without preoperative embolization were included. Embolization type, recurrence rate, complication rates, blood loss, and transfusions were extracted. Risk of bias was assessed by the Risk of Bias in Non-randomized Studies-of Interventions method. RESULTS: There were 61 studies with 917 patients included. Preoperative embolization was performed in 79.3% of patients. Of those embolized, 75.8% (N = 551) underwent TAE and 15.8% (N = 115) underwent DPE. JNA recurrence in embolized patients was lower than in non-embolized patients (9.3% vs. 14.4%; odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.35, 1.06). DPE resulted in lower rates of disease recurrence (0% vs. 9.5%; OR: 0.066, 95% CI: 0.016, 0.272) and complications (1.8% vs. 21.9%; OR: 0.07, 95% CI: 0.02, 0.3) than TAE. A random effects Bayesian model was performed to analyze the difference in mean blood loss in 6 studies that included both embolized and non-embolized patients. This analysis showed a mean reduction in blood loss of 798 mL in the embolized group. CONCLUSIONS: We found embolization decreases blood loss in JNA resection. DPE led to improved recurrence and complication rates when compared to TAE, but future prospective studies are needed to further evaluate which embolization technique can optimize outcomes in JNA. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1529-1539, 2023.

Laryngeal and pharyngeal actinomycosis: a systematic review and report of 3 cases.

INTRODUCTION: Actinomycosis is a granulomatous infection that rarely involves the larynx or pharynx. Three cases of actinomycosis of the larynx or pharynx from our institution were reviewed and a systematic literature review was performed to better define surgical management, antibiotic therapy, risk factors, and incidence of recurrence or complications. MATERIALS AND METHODS: PubMed/Medline, Cochrane, Embase, and Google Scholar were searched on November 30, 2021 using the terms "laryngeal actinomycosis", "pharyngeal actinomycosis", "actinomycosis AND larynx", and "actinomycosis AND pharynx." Articles which did not describe appropriate sites or were non-English were excluded. Results were collected for demographic information, site(s) of infection, comorbidities, lesion characteristics and treatments. RESULTS: Along with three cases reported from our institution, 40 unique cases were reviewed from 37 studies for a total of 43 patients (Table 1). 34 (81.0 %) of the patients were male with the highest incidence of infection in the seventh decade (54.8 %). The most common site for the infection was the larynx (69.0 %) followed by the pharynx (16.7 %). Risk factors included a history of radiation therapy, immunosuppression, inhalational irritant, and diabetes (Table 3). The duration of antibiotic therapy varied greatly, from one month to one year and total follow up ranged from 1 month to 2.5 years (Table 1). CONCLUSIONS: A comprehensive review of the literature on pharyngolaryngeal actinomycosis shows that this infection has increased prevalence within the head and neck cancer patient population. Similar to cervicofacial actinomycosis, these atypical sites have shown favorable responses to extended antibiotic therapy and generally do not require aggressive surgical management.

Measuring SARS-CoV-2 aerosolization in rooms of hospitalized patients.

Objective: Airborne spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a significant risk for healthcare workers. Understanding transmission of SARS-CoV-2 in the hospital could help minimize nosocomial infection. The objective of this pilot study was to measure aerosolization of SARS-CoV-2 in the hospital rooms of COVID-19 patients. Methods: Two air samplers (Inspirotec) were placed 1 and 4 m away from adults with SARS-CoV-2 infection hospitalized at an urban, academic tertiary care center from June to October 2020. Airborne SARS-CoV-2 concentration was measured by quantitative reverse transcription polymerase chain reaction and analyzed by clinical parameters and patient demographics. Results: Thirteen patients with COVID-19 (eight females [61.5%], median age: 57 years old, range 25-82) presented with shortness of breath (100%), cough (38.5%) and fever (15.4%). Respiratory therapy during air sampling varied: mechanical ventilation via endotracheal tube (n = 3), high flow nasal cannula (n = 4), nasal cannula (n = 4), respiratory helmet (n = 1), and room air (n = 1). SARS-CoV-2 RNA was identified in rooms of three out of three intubated patients compared with one out of 10 of the non-intubated patients (p = .014). Airborne SARS-CoV-2 tended to decrease with distance (1 vs. 4 m) in rooms of intubated patients. Conclusions: Hospital rooms of intubated patients had higher levels of aerosolized SARS-CoV-2, consistent with increased aerosolization of virus in patients with severe disease or treatment with positive pressure ventilation through an endotracheal tube. While preliminary, these data have safety implications for health care workers and design of protective measures in the hospital. Level of Evidence: 2.