Dorina Kallogjeri

Tinnitus is a common experience, and a minority of people experience severe distress related to their tinnitus. Studies of the contribution of psychological factors are often small and replications are rare. Here we examined adults ( N = 125) with tinnitus distress who responded to an average of 96 surveys regarding tinnitus distress, anxiety and worry, and cognitive symptoms. We replicated previous findings using dynamic structural equation modeling (DSEM). In addition, we examined an alternative method, the group iterative multiple model estimation (GIMME) procedure. Findings across methods suggested that most relationships between tinnitus distress and the psychological factors assessed in this study occurred contemporaneously or across a shorter time lag than that used here. Whereas DSEM found significant prospective cross-construct effects overall, GIMME suggested such paths were limited to individuals rather than groups or subgroups. Future work should examine how such modeling can inform prediction of outcomes (e.g., treatment effects).

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti–programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking. In a phase 2 trial (NCT02296684), we observed that 45% of patients treated with two doses of neoadjuvant pembrolizumab experienced marked pTRs (≥50%). Single-cell analysis of 17,158 CD8 ⁺ T cells from 14 tumor biopsies, including 6 matched pre-post neoadjuvant treatment, revealed that responding tumors had clonally expanded putative tumor-specific exhausted CD8 ⁺ tumor-infiltrating lymphocytes (TILs) with a tissue-resident memory program, characterized by high cytotoxic potential (CTX ⁺ ) and ZNF683 expression, within the baseline TME. Pathologic responses after 5 weeks of PD-1 blockade were consistent with activation of preexisting CTX ⁺ ZNF683 ⁺ CD8 ⁺ TILs, paralleling loss of viable tumor and associated tumor antigens. Response was associated with high numbers of CD103 ⁺ PD-1 ⁺ CD8 ⁺ T cells infiltrating pretreatment lesions, whereas revival of nonexhausted persisting clones and clonal replacement were modest. By contrast, nonresponder baseline TME exhibited a relative absence of ZNF683 ⁺ CTX ⁺ TILs and subsequent accumulation of highly exhausted clones. In HNSCC, revival of preexisting ZNF683 ⁺ CTX ⁺ TILs is a major mechanism of response in the immediate postneoadjuvant setting.

Objective: Identify clinically important factors associated with conservative treatment response in Meniere's disease and incorporate these factors into a composite clinical severity staging system.Study Design: Retrospective cohort.Setting: Tertiary academic medical center.Methods: Adult patients newly diagnosed with Meniere's disease between January 1, 2016 and December 31, 2019 were eligible. Patients with previous treatment for Meniere's disease, prior otologic surgery, or a lack of follow‐up data were excluded. Treatment‐responsive patients were managed with only conservative therapies (eg, dietary modifications, diuretics) and unresponsive patients underwent more intensive therapies (eg, intratympanic procedures, surgical interventions).Results: Of 78 patients included in the study, 49 (63%) were responsive to conservative therapies and 29 (37%) were not. Responsive patients had higher proportions of no or mild vertigo (24%, 95% confidence interval [CI]: 3.1%–45.8%) and none or mild comorbidity (27%, 95% CI: 9.2%–44.7%) and a lower proportion of hearing loss (19%, 95% CI: 5.6%–32.4%) compared to unresponsive patients. Conjunctive consolidation of these 3 factors was performed to develop a three‐stage system with a treatment response gradient ranging from 100% to 64% to 18% for stage 1 (n = 11), stage 2 (n = 56), and stage 3 (n = 11), respectively.Conclusions: This study identified decreased vertigo severity, reduced comorbidity burden, and absence of hearing loss as factors associated with conservative treatment response in Meniere's disease. A composite clinical severity staging system including these 3 factors can be used to optimize treatment selection and promote patient‐centered management of Meniere's disease.

Objective: Develop and validate a quality‐of‐life (QoL) outcome measure for patients with dysosmia.Study Design: Cross‐sectional survey study.Setting: Otolaryngology clinics, research registries, and Facebook support groups.Methods: A 59‐item pilot survey with questions addressing parosmia concerns was developed using input from subjects with parosmia and clinical expertise from Otolaryngologists. After item reduction, the Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR) was reduced to its final 29 items. DisODOR maximum score is 116 (each item score 0‐4) with higher scores indicating a higher degree of dysfunction from smell distortion. DisODOR was validated using participants with parosmia persisting >3 months after severe acute respiratory syndrome coronavirus 2 (cases) and healthy controls. Reliability, face and content validity, internal consistency, convergent validity, discriminative validity, sensitivity to change, and the minimal clinically important difference (MCID) were assessed.Results: A total of 134 cases and 20 controls completed DisODOR. The mean (SD) age was 45.9 (12.2) for cases and 29.6 (8.9) for controls. The mean score difference between cases and controls was 45.0 (95% confidence interval, 40.5‐49.5) displaying good discriminative validity. DisODOR showed strong test–retest reliability (r = .942) with high internal consistency (Cronbach's α = .971). DisODOR had a moderate correlation with SNOT‐22 scores (r = .619) indicating good convergent validity. There is an excellent association with the global impression of severity categories (η² = 0.447). Based on the distribution method, the MCID is 15.Conclusion: DisODOR is a valid, reliable QoL instrument for parosmia that can be used to measure the functional impact and QoL impairment for parosmia patients. DisODOR is sensitive to change and thus can be used in studies investigating treatments for parosmia.

Background:Hearing loss can lead to isolation and social withdrawal. The telephone oftentimes connects persons with hearing loss to society; however, telephone use is impeded by narrow bandwidth, loss of visual cues, electromagnetic interference, and inherent phone-line noise. In the past, research assessing telephone communication has consistently reported that switching from the microphone to a telecoil will typically result in the acoustic signal being discernibly softer. Properly used telecoils improve the signal-to-noise ratio (SNR), decrease the chance for acoustic feedback, and overcome the impact of distance and reverberation creating an opportunity for clearer telephone communication. Little research, however, has examined matching the telecoil frequency response to the prescribed target of the microphone frequency response (National Acoustics Laboratories, Non-Linear, version 1 [NAL-NL1]).Purpose:The primary goal of this study was to determine if differences exist in speech recognition for sentences (AZ-BIO) and consonant‐vowel nucleus-consonant monosyllabic words (CNC) between two telecoil conditions (default and programmed). A secondary goal was to determine if differences exist in speech recognition for sentences between male and female talkers.Research Design:A single-blinded randomized controlled trial.Study Sample:Twenty experienced adult hearing aid users with bilateral symmetric slight to severe sensorineural hearing loss were recruited from Washington University in St. Louis School of Medicine. In addition, ten normal-hearing participants were recruited to determine the presentation level of the speech stimuli for the hearing aid participants.Data Collection and Analysis:Participants underwent real-ear measures to program the microphone frequency response of a receiver-in-the-canal hearing aid to NAL-NL1. Using the manufacturer software, one telecoil program remained as the manufacturer default and a second telecoil program was programmed so the sound pressure level for an inductive telephone simulator frequency response matching the microphone’s frequency response to obtain as close to a 0 dB relative simulated equivalent telephone sensitivity value as possible. Participants then completed speech recognition measures including AZ-BIO sentences (male and female talkers) and CNC monosyllabic words and phonemes, using both telecoil programs. A mixed model analysis was performed to examine if significant differences in speech recognition exist between the two conditions and speech stimuli.Results:Results revealed significant improvement in overall speech recognition for the programmed telecoil performance compared with default telecoil performance (p < 0.001). Also, improved performance in the programmed telecoil was reported with a male talker (p < 0.001) and performance for sentences compared with monosyllabic words (p < 0.001) or phonemes (p < 0.001).Conclusions:The programmed telecoil condition revealed significant improvement in speech recognition for all speech stimuli conditions compared with the default telecoil (sentences, monosyllables, and phonemes). Additional improvement was observed in both telecoil conditions when the talker was male.