Predictive capacity of immune-related adverse events and cytokine profiling in neoadjuvant immune checkpoint inhibitor trials for head and neck squamous cell carcinoma.

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status. METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival were compared. Canonical linear discriminant analysis (LDA) was performed to identify combinations of circulating cytokines predictive of irAEs using plasma sample multiplex assay. RESULTS: Of 113 participants meeting inclusion criteria, 32 (28.3%) developed irAEs during treatment or follow-up. Positive p16 status was associated with irAEs (odds ratio [OR] 2.489; 95% CI 1.069-6.119; p = 0.043). irAEs were associated with pathologic treatment response (OR 3.73; 95% CI 1.34-10.35; p = 0.011) and with higher OS in the combined cohort (HR 0.319; 95% CI 0.113-0.906; p = 0.032). Patients with irAEs within the nivolumab cohort had significant elevations of select cytokines pre-treatment. Canonical LDA identified key drivers of irAEs among all trials, which were highly predictive of future irAE status. CONCLUSIONS: irAEs are associated with response to neoadjuvant ICI therapy in HNSCC and can serve as clinical indicators for improved clinical outcomes. irAEs can be predicted by concentrations of several circulating cytokines prior to treatment.

Evaluation of Subjective Tinnitus Severity and Distortion Product Otoacoustic Emissions and Extended High-Frequency Audiometry.

OBJECTIVE: Tinnitus is a multifactorial phenomenon with quality-of-life detriments for those affected by it. We aim to establish a relationship between subjective tinnitus severity with objective audiometric data in the extended high frequency (EHF) from 9 to 16 khz and with distortion product otoacoustic emissions (DPOAE). We hypothesize that severe subjective tinnitus as measured by the Tinnitus Handicap Inventory (THI) does not correlate with increased hearing thresholds in the EHF range. STUDY DESIGN: Prospective. SETTING: Single Tertiary Care Center. METHODS: Patients identified with tinnitus and normal hearing thresholds within standard frequency range (250-8000 Hz) were consented for participation. Those with underlying otologic disease, trauma, radiotherapy, or ototoxic drug use were excluded. The THI questionnaire was given to eligible patients and audiometric test results were collected. THI scores were categorized by severity groups. An n = 20 to 30 was determined to have an effect size of 0.7 with a significance level of P = .05. RESULTS: THI and audiometric data were collected for 38 patients and categorized into mild (n = 18, 47.4%), moderate (n = 8, 21.1%), slight (n = 7, 18.4%), and severe (n = 5, 13.2%) tinnitus severity groups. Mean THI score was 32.3 ± 19.6 with a statistically significant difference in scores by assigned THI severity group (P < .01). There were no significant differences or linear relationship among hearing thresholds in EHF range or DPOAE stratified by subjective tinnitus group (P = .49, r2 = 0.10) CONCLUSION: Subjective tinnitus severity is not predictive of audiometric outcomes. This finding can be used as a counseling tool to help tinnitus patients manage symptoms, expectations, and overall treatment outcomes.

Safety of Ambulatory Surgery For Obstructive Sleep Apnea: A Retrospective Review.

OBJECTIVE: Assess the safety of ambulatory surgery performed for obstructive sleep apnea. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care hospital. METHODS: Demographic data including age, gender, race, body mass index, insurance status, socioeconomic status, and distance traveled for surgery was collected, as well as comorbidities, and apnea-hypopnea index (AHI). Outcome variables included continuous positive airway pressure reinitiation, planned/unplanned postoperative admission, emergency department (ED) presentation, or readmission within 7 and 14 days of surgery. RESULTS: A total of 601 patients were included, who underwent sleep surgery between 2017 and 2022. The median age was 55 years [interquartile range: 19]. A total of 437 patients (73%) were male, 502 (84%) were Caucasian, and the median distance traveled was 20 miles [27]. The median AHI was 27.1 [26]. A total of 286 hypoglossal nerve stimulators, 12 tonsillectomies, 160 expansion sphincteroplasties (ESP), and 201 nasal procedures were performed. There were 9 (1%) planned and 23 (4%) total admissions postoperatively. Sixteen patients (2%) presented to ED within 7 days, and 22 (3%) within 14 days. Nine (1%) were readmitted within 7 days, and 12 (2%) within 14 days. There were significantly more planned admissions, unplanned admissions, ED presentations, and readmissions for ESP. There were no significant differences in demographic or clinical data between patients who underwent single versus multiple surgeries. CONCLUSION: Outpatient sleep surgery is generally safe. Close postoperative monitoring is necessary and overnight observation should be considered in those with very severe sleep apnea and/or significant comorbidities. The distance a patient travels should also be considered for overnight admission.

The relationship between positive airway pressure tolerance and adherence: defining a new metric.

STUDY OBJECTIVES: Positive airway pressure (PAP) therapy adherence rates range from 30-60%, yet adherent patients may still express dissatisfaction with treatment. Identification of factors affecting PAP tolerance could provide insight into its impact on adherence. METHODS: Obstructive sleep apnea (OSA) patients presenting for first follow up visit after newly initiating PAP therapy were given a 10-question PAP tolerance survey encompassing domains of psychosocial perception, practical issues, and side effects, utilizing 10-point visual analog scales. Relationships between adherence data, tolerance scores, and patient variables (demographics, sleep-related factors, comorbidities, usage data) were explored via two-tailed t-tests, multivariable regression analysis, and recursive partitioning regression trees with significance level p≤0.05. RESULTS: For 105 patients, tolerance scores were higher in patients considered adherent to therapy (p=0.033), as were scores for individual survey questions addressing ability to fall asleep (p=0.013) and sleep through the night (p=0.020). Depression positively (p=0.006) and insomnia medication use negatively (p=0.010) predicted tolerance score. Data-driven tolerance score cutoffs were identified to correlate with PAP adherence, with higher tolerance scores correlating with greater adherence rates. CONCLUSIONS: PAP tolerance may play an important role in therapy adherence. Tolerance can be statistically defined and categorized based on prior adherence data. Its utility as a predictive tool in assessing future adherence is warranted.

Factors Predicting Discharge Disposition Following Head and Neck Free Flap Reconstruction.

OBJECTIVES: Patients undergoing head and neck free flap reconstruction (HNFFR) may have significant change to their baseline functional status requiring inpatient rehabilitation (IPR) after discharge. We sought to identify patient/procedure characteristics predictive of discharge destination. METHODS: Patients undergoing elective HNFFR between July 2017 and July 2022 were reviewed for discharge destination. Those discharged to IPR versus home were compared across patient/procedure characteristics and physical/occupational therapy metrics. Significance was assessed via bivariate and multivariable analyses. RESULTS: Of the 531 patients, 102 (19.2%) required IPR postoperatively. Patients discharged to IPR versus home were significantly older (70.1 [11.6] vs. 64.1 [13.1] years; p < 0.001) and more likely to lack family assistance (26.5% vs. 8.6%; p < 0.001), require baseline assistance for activities of daily living (ADLs) (31.4% vs. 9.8%; p < 0.001), have baseline cognitive dysfunction (15.7% vs. 6.1%; p = 0.001), were more likely to have neoplasm as the surgical indication for HNFFR (89.2% vs. 80.0%; p = 0.033) and more likely to have a tracheostomy postop (62.7% vs. 51.7%), and had a significantly longer length of stay (11.2 [8.0] vs. 6.8 [8.3] days; p < 0.001). There was no significant difference in gender, donor site, use of tube feeds, and use of assistive devices between the two groups. Following logistic regression, the strongest predictors of discharge to IPR include lack of family assistance (OR = 3.8; p < 0.001) and baseline assistance for ADLs (OR = 4.0, p < 0.001). CONCLUSION: Certain patient factors predict the need for discharge to rehab after HNFFR. Perioperative identification of these factors may facilitate patient counseling and discharge planning with potential to reduce hospital length of stay and further optimize patient care. LEVEL OF EVIDENCE: III Laryngoscope, 134:2721-2725, 2024.

Differences in Functional and Survival Outcomes Between Patients Receiving Primary Surgery vs Chemoradiation Therapy for Treatment of T1-T2 Oropharyngeal Squamous Cell Carcinoma.

Importance: Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear. Objectives: To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT. Design, Setting, and Population: This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform. Exposure: Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy. Main Outcomes and Measures: Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT. Results: Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79). Conclusions and Relevance: This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.

Anterior Skull Base Reconstruction.

Anterior skull base reconstruction requires careful preoperative planning to use the most effective technique for the expected defect. Adherence to the principles of skull base reconstruction is imperative to minimize complications and improve patient outcomes.

Multimodal Analgesia and Patient Education Reduce Postoperative Opioid Consumption in Otology.

OBJECTIVE: This study sought to validate alternative pain management strategies that can reduce reliance on opioids for postoperative pain management in otology. STUDY DESIGN: Prospective cohort study. SETTING: Single tertiary-care facility. METHODS: Adult patients who underwent outpatient otologic surgery from September 2021 to July 2022 were randomized into treatment cohorts. The opioid monotherapy cohort received a standard opioid prescription. The multimodal analgesia cohort received the same opioid prescription, prescriptions for acetaminophen and naproxen, and additional pain management education with a flyer on discharge. All patients completed a questionnaire 1 week after surgery to evaluate opioid usage and pain scores. RESULTS: Eighty-six patients completed the study. The opioid monotherapy cohort (n = 42) and multimodal analgesia cohort (n = 44) were prescribed an average of 42.1 ± 20.4 morphine milligram equivalents (MME) and 38.4 ± 5.7 MME, respectively (p = 0.373). Four patients (9.52%) in the opioid monotherapy cohort required opioid refills compared to 1 patient (2.27%) in the multimodal analgesia cohort (p = 0.156). Multivariate analysis demonstrated that the multimodal analgesia cohort consumed significantly fewer opioids on average than the opioid monotherapy cohort (11.9 ± 15.9 MME vs 22.8 ± 28.0 MME, respectively). There were no significant differences in postoperative rehospitalizations (p = 0.317) or Emergency Department visits (p = 0.150). Pain scores on the day of surgery, postoperative day (POD) 1, POD3, and POD7 were not significantly different between cohorts (p = 0.395, 0.896, 0.844, 0.765, respectively). CONCLUSION: The addition of patient education, acetaminophen, and naproxen to postoperative opioid prescriptions significantly reduced opioid consumption without affecting pain scores, refill rates, or complication rates after otologic surgery.

DIAGNOSTIC YIELD OF IN VITRO VITREOUS BIOPSY FOR INTRAOCULAR LYMPHOMA AT VARIABLE VITREOUS CUTTER SPEEDS USING 25-GAUGE VITRECTOMY.

PURPOSE: Primary vitreoretinal lymphoma is the most common intraocular lymphoproliferative disorder. We evaluated the diagnostic yield of pars plana vitrectomy, specifically using modern high cut rate dual-cycle cutters, on in vitro cell viability and diagnostic yield. METHODS: Human Burkitt lymphoma cell line Namalwa at 2 x 10^5 cells/mL was aspirated by 25-gauge dual-blade guillotine-type vitrectomy at five speeds (500, 1,000, 4,000, 7,500, or 15,000 cuts per minute). Cell viability and diagnostic yield in each subtype group were determined using hemocytometry, viable cell count using Cell Counting Kit-8, and pathologist-guided manual count. RESULTS: No significant deviation in cell count was identified in any cut rate by ANOVA ( P = 0.61), and no trends in the number of viable cells were identified across cut rates (R 2 = 0.188, P = 0.47). Among histologic cell counts per cut-rate, neither linear regression (R = 0.531, P = 0.16) nor ANOVA ( P = 0.096) were statistically significant. CONCLUSION: There was no significant degradation in the number of viable cells with increasing cut speed. These results suggest that in contrast to previous findings using 20g or 23g vitrectomy for diagnostic vitrectomy, modern vitrectomy systems may be used at up to 15,000 cpm without compromising the viability of lymphoma cells.

Large Bilateral Compressible Neck Mass in 55-Year-Old Man.

A 55-year-old man with a medical history significant for hypertension, coronary artery disease, and obstructive sleep apnea presents with an enlarging neck mass of more than 2 years' duration. What is your diagnosis?