Individual Patient Comorbidities and Effect on Cochlear Implant Performance.

OBJECTIVE: To examine the association between preoperative comorbidities and cochlear implant speech outcomes. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS: A total of 976 patients who underwent cochlear implantation (CI) between January 2015 and May 2022. Adult patients with follow-up, preoperative audiologic data, and a standardized anesthesia preoperative note were included. EXPOSURE: Adult Comorbidity Evaluation 27 (ACE-27) based on standardized anesthesia preoperative notes. MAIN OUTCOME MEASURES: Postoperative change in consonant-nucleus-consonant (CNC) score, AzBio Sentence score in quiet, and AzBio + 10 dB signal-to-noise ratio (SNR). Sentence score of the implanted ear at 3, 6, and 12 months. RESULTS: A total of 560 patients met inclusion criteria; 112 patients (20%) had no comorbidity, 204 patients (36.4%) had mild comorbidities, 161 patients (28.8%) had moderate comorbidities, and 83 patients (14.8%) had severe comorbidities. Mixed model analysis revealed all comorbidity groups achieved a clinically meaningful improvement in all speech outcome measures over time. This improvement was significantly different between comorbidity groups over time for AzBio Quiet ( p = 0.045) and AzBio + 10 dB SNR ( p = 0.0096). Patients with severe comorbidities had worse outcomes. From preop to 12 months, the estimated marginal mean difference values (95% confidence interval) between the no comorbidity group and the severe comorbidity group were 52.3 (45.7-58.9) and 32.5 (24.6-40.5), respectively, for AzBio Quiet; 39.5 (33.8-45.2) and 21.2 (13.6-28.7), respectively, for AzBio + 10 dB SNR; and 43.9 (38.7-49.0) and 31.1 (24.8-37.4), respectively, for CNC. CONCLUSIONS: Comorbidities as assessed by ACE-27 are associated with CI performance. Patients with more severe comorbidities have clinically meaningful improvement but have worse outcome compared to patients with no comorbidities.

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.

Identifying Predictors of Treatment Response in Meniere's Disease: A Clinical Severity Staging System.

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.

Identifying Slim Modiolar Electrode Tip Fold-Over With Intracochlear Electrocochleography.

OBJECTIVE: To evaluate the predictive value of intracochlear electrocochleography (ECochG) for identifying tip fold-over during cochlear implantation (CI) using the slim modiolar electrode (SME) array. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHODS: From July 2022 to June 2023, 142 patients, including adults and children, underwent intracochlear ECochG monitoring during and after SME placement. Tone-bursts were presented from 250 Hz to 2 kHz at 108 to 114 dB HL. A fast Fourier transform (FFT) allowed for frequency-specific evaluation of ECochG response. ECochG patterns during insertion and postinsertion were evaluated using sensitivity and specificity analysis to predict tip fold-over. Intraoperative plain radiographs served as a reference standard. RESULTS: Fifteen tip fold-over cases occurred (10.6%) with significant ECochG response (>2 µV). Sixty-one cases without tip fold-over occurred (43.0%) with significant ECochG response. All tip fold-overs had both a nontonotopic postinsertion sweep and nonrobust active insertion pattern. No patients with robust insertion or tonotopic sweep patterns had tip fold-over. Sensitivity of detecting tip fold-over when having both nonrobust insertion and nontonotopic sweep patterns was 100% (95% confidence inteval [CI] 78.2%-100%), specificity was 68.9% (95% CI 55.7%-80.1%), and the overall accuracy was 72.0% (95% CI 60.5%-81.7%). CONCLUSION: Intracochlear ECochG monitoring during cochlear implantation with the SME can be a valuable tool for identifying properly positioned electrode arrays. In cases where ECochG patterns are nonrobust on insertion and nontonotopic for electrode sweeps, there may be a concern for tip fold-over, and intraoperative imaging is necessary to confirm proper insertion.

Improved Cochlear Implant Performance Estimation Using Tonotopic-Based Electrocochleography.

Importance: Cochlear implantation produces remarkable results in postlingual deafness, although auditory outcomes vary. Electrocochleography (ECochG) has emerged as a valuable tool for assessing the cochlear-neural substrate and evaluating patient prognosis. Objective: To assess whether ECochG-total response (ECochG-TR) recorded at the best-frequency electrode (BF-ECochG-TR) correlates more strongly with speech perception performance than ECochG-TR measured at the round window (RW-ECochG-TR). Design, Setting, and Participants: This single-center cross-sectional study recruited 142 patients from July 1, 2021, to April 30, 2022, with 1-year follow-up. Exclusions included perilymph suctioning, crimped sound delivery tubes, non-native English speakers, inner ear malformations, nonpatent external auditory canals, or cochlear implantation revision surgery. Exposures: Cochlear implantation. Main Outcomes and Measures: Speech perception testing, including the consonant-nucleus-consonant (CNC) words test, AzBio sentences in quiet, and AzBio sentences in noise plus 10-dB signal to noise ratio (with low scores indicating poor performance and high scores indicating excellent performance on all tests), at 6 months postoperatively; and RW-ECochG-TR and BF-ECochG-TR (measured for 250, 500, 1000, and 2000 Hz). Results: A total of 109 of the 142 eligible postlingual adults (mean [SD] age, 68.7 [15.8] years; 67 [61.5%] male) were included in the study. Both BF-ECochG-TR and RW-ECochG-TR were correlated with 6-month CNC scores (BF-ECochG-TR: r = 0.74; 95% CI, 0.62-0.82; RW-ECochG-TR: r = 0.67; 95% CI, 0.54-0.76). A multivariate model incorporating age, duration of hearing loss, and angular insertion depth did not outperform BF-ECochG-TR or RW-ECochG-TR alone. The BF-ECochG-TR correlation with CNC scores was significantly stronger than the RW-ECochG-TR correlation (r difference = -0.18; 95% CI, -0.31 to -0.01; z = -2.02). More moderate correlations existed between 6-month AzBio scores in noise, Montreal Cognitive Assessment (MoCA) scores (r = 0.46; 95% CI, 0.29-0.60), and BF-ECochG-TR (r = 0.42; 95% CI, 0.22-0.58). MoCA and the interaction between BF-ECochG-TR and MoCA accounted for a substantial proportion of variability in AzBio scores in noise at 6 months (R2 = 0.50; 95% CI, 0.36-0.61). Conclusions and Relevance: In this case series, BF-ECochG-TR was identified as having a stronger correlation with cochlear implantation performance than RW-ECochG-TR, although both measures highlight the critical role of the cochlear-neural substrate on outcomes. Demographic, audiologic, and surgical factors demonstrated weak correlations with cochlear implantation performance, and performance in noise was found to require a robust cochlear-neural substrate (BF-ECochG-TR) as well as sufficient cognitive capacity (MoCA). Future cochlear implantation studies should consider these variables when assessing performance and related interventions.

Factors Affecting Performance in Adults With Cochlear Implants: A Role for Cognition and Residual Cochlear Function.

OBJECTIVE: To evaluate the impact of preoperative and perioperative factors on postlinguistic adult cochlear implant (CI) performance and design a multivariate prediction model. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Two hundred thirty-nine postlinguistic adult CI recipients. MAIN OUTCOME MEASURES: Speech-perception testing (consonant-nucleus-consonant [CNC], AzBio in noise +10-dB signal-to-noise ratio) at 3, 6, and 12 months postoperatively; electrocochleography-total response (ECochG-TR) at the round window before electrode insertion. RESULTS: ECochG-TR strongly correlated with CNC word score at 6 months ( r = 0.71, p < 0.0001). A multivariable linear regression model including age, duration of hearing loss, angular insertion depth, and ECochG-TR did not perform significantly better than ECochG-TR alone in explaining the variability in CNC. AzBio in noise at 6 months had moderate linear correlations with Montreal Cognitive Assessment (MoCA; r = 0.38, p < 0.0001) and ECochG-TR ( r = 0.42, p < 0.0001). ECochG-TR and MoCA and their interaction explained 45.1% of the variability in AzBio in noise scores. CONCLUSIONS: This study uses the most comprehensive data set to date to validate ECochG-TR as a measure of cochlear health as it relates to suitability for CI stimulation, and it further underlies the importance of the cochlear neural substrate as the main driver in speech perception performance. Performance in noise is more complex and requires both good residual cochlear function (ECochG-TR) and cognition (MoCA). Other demographic, audiologic, and surgical variables are poorly correlated with CI performance suggesting that these are poor surrogates for the integrity of the auditory substrate.

Responsible Imputation of Missing Speech Perception Testing Data & Analysis of 4,739 Observations and Predictors of Performance.

OBJECTIVE: To address outcome heterogeneity in cochlear implant (CI) research, we built imputation models using multiple imputation by chained equations (MICEs) and K-nearest neighbors (KNNs) to convert between four common open-set testing scenarios: Consonant-Nucleus-Consonant word (CNCw), Arizona Biomedical (AzBio) in quiet, AzBio +5, and AzBio +10. We then analyzed raw and imputed data sets to evaluate factors affecting CI outcome variability. STUDY DESIGN: Retrospective cohort study of a national CI database (HERMES) and a nonoverlapping single-institution CI database. SETTING: Multi-institutional (32 CI centers). PATIENTS: Adult CI recipients (n = 4,046 patients). MAIN OUTCOME MEASURES: Mean absolute error (MAE) between imputed and observed speech perception scores. RESULTS: Imputation models of preoperative speech perception measures demonstrate a MAE of less than 10% for feature triplets of CNCw/AzBio in quiet/AzBio +10 (MICE: MAE, 9.52%; 95% confidence interval [CI], 9.40-9.64; KNN: MAE, 8.93%; 95% CI, 8.83-9.03) and AzBio in quiet/AzBio +5/AzBio +10 (MICE: MAE, 8.85%; 95% CI, 8.68-9.02; KNN: MAE, 8.95%; 95% CI, 8.74-9.16) with one feature missing. Postoperative imputation can be safely performed with up to four of six features missing in a set of CNCw and AzBio in quiet at 3, 6, and 12 months postcochlear implantation using MICE (MAE, 9.69%; 95% CI, 9.63-9.76). For multivariable analysis of CI performance prediction, imputation increased sample size by 72%, from 2,756 to 4,739, with marginal change in adjusted R2 (0.13 raw, 0.14 imputed). CONCLUSIONS: Missing data across certain sets of common speech perception tests may be safely imputed, enabling multivariate analysis of one of the largest CI outcomes data sets to date.

Imputation of missing values for cochlear implant candidate audiometric data and potential applications.

OBJECTIVE: Assess the real-world performance of popular imputation algorithms on cochlear implant (CI) candidate audiometric data. METHODS: 7,451 audiograms from patients undergoing CI candidacy evaluation were pooled from 32 institutions with complete case analysis yielding 1,304 audiograms. Imputation model performance was assessed with nested cross-validation on randomly generated sparse datasets with various amounts of missing data, distributions of sparsity, and dataset sizes. A threshold for safe imputation was defined as root mean square error (RMSE) <10dB. Models included univariate imputation, interpolation, multiple imputation by chained equations (MICE), k-nearest neighbors, gradient boosted trees, and neural networks. RESULTS: Greater quantities of missing data were associated with worse performance. Sparsity in audiometric data is not uniformly distributed, as inter-octave frequencies are less commonly tested. With 3-8 missing features per instance, a real-world sparsity distribution was associated with significantly better performance compared to other sparsity distributions (Δ RMSE 0.3 dB- 5.8 dB, non-overlapping 99% confidence intervals). With a real-world sparsity distribution, models were able to safely impute up to 6 missing datapoints in an 11-frequency audiogram. MICE consistently outperformed other models across all metrics and sparsity distributions (p < 0.01, Wilcoxon rank sum test). With sparsity capped at 6 missing features per audiogram but otherwise equivalent to the raw dataset, MICE imputed with RMSE of 7.83 dB [95% CI 7.81-7.86]. Imputing up to 6 missing features captures 99.3% of the audiograms in our dataset, allowing for a 5.7-fold increase in dataset size (1,304 to 7,399 audiograms) as compared with complete case analysis. CONCLUSION: Precision medicine will inevitably play an integral role in the future of hearing healthcare. These methods are data dependent, and rigorously validated imputation models are a key tool for maximizing datasets. Using the largest CI audiogram dataset to-date, we demonstrate that in a real-world scenario MICE can safely impute missing data for the vast majority (>99%) of audiograms with RMSE well below a clinically significant threshold of 10dB. Evaluation across a range of dataset sizes and sparsity distributions suggests a high degree of generalizability to future applications.

One-Year Hearing Preservation and Speech Outcomes Comparing Slim Modiolar and Lateral Wall Arrays.

OBJECTIVE: Compare postoperative speech outcomes in hearing preservation (HP) cochlear implantation (CI) patients with a low-frequency pure-tone average (LFPTA) ≤ 60 dB using 2 electrode array designs. STUDY DESIGN: Retrospective cohort study. SETTING: Large academic cochlear implant referral center. METHODS: We reviewed adult HP CI cases using either the slim modiolar electrode (SME) (CI 532/CI 632) or th slim lateral wall electrode (SLWE) (CI 624). One-year speech outcomes and HP status were the primary outcomes. RESULTS: A total of 132 implanted ears were analyzed (mean age 73.1 years, standard deviation [SD] 12.6), with 72% (N = 95) with CI 532/632 and 28% (N = 37) with CI 624. The mean preoperative LFPTA was 44.8 dB, SD 11.8. One-year functional HP was 27.2% (mean LFPTA shift 46.1 dB, SD 22.1) and was as follows: SME 23.9% and SLWE 36.4%, p = .168. The mean age at implantation was significantly younger only in SLWE patients with preserved hearing (66.9 vs 80.3 years, p = .008). At 6 months, speech measures were significantly better in all outcomes in HP patients with an SLWE than nonpreserved SLWE patients; this effect abated at 1 year as performance among nonpreserved SLWE patients became equivalent to the remaining cohort. Speech outcomes in SME patients were similar regardless of HP status. Age at implantation and datalogging was correlated with speech outcomes. CONCLUSION: In this cohort of HP patients, a 1-year functional HP rate of 23.9% (SME) and 36.4% (SLWE) was observed (p = 0.168). This was initially 57.1% (SME) and 70.3% (SLWE) at activation, p = .172. Datalogging and age at implantation were correlated with postoperative speech outcomes.

Predictors of Short-Term Changes in Quality of Life after Cochlear Implantation.

OBJECTIVE: This study aimed 1) to measure the effect of cochlear implantation on health-related quality of life (HR-QOL) using the Cochlear Implant Quality of Life (CIQOL) questionnaire and 2) to determine audiologic, demographic, and non-CI/hearing-related QOL factors influencing the CIQOL. STUDY DESIGN: Prospective observational study. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Thirty-seven adult patients with sensorineural hearing loss undergoing cochlear implantation. MAIN OUTCOME MEASURES: CIQOL-global score preimplantation and 6 months postimplantation. Physical function score as measured by the short-form survey, audiologic, and demographic variables. RESULTS: CIQOL showed significant improvement from preimplantation to 6 months postactivation with a mean difference of 14.9 points (95% confidence interval, 11.3 to 18.5, p < 0.0001). Improvement in CIQOL (ΔCIQOL) correlated linearly with age ( r = -0.49, p = 0.001) and improvement in speech perception testing ( r = 0.63, p < 0.0001). Multivariate modeling using age and change in consonant-vowel nucleus-consonant (CNC) score explained 46% of the variability measured by the ΔCIQOL-global score. CONCLUSIONS: Nearly all CI recipients achieve significant gains for all domains as measured by the CIQOL. However, younger patients and those with a greater improvement in speech perception performance (CNC) are more likely to achieve a greater CIQOL benefit. Results here suggest the importance of considering preoperative CIQOL and speech perception measures when evaluating predictors of HR-QOL.

Cognitive Assessment in Elderly Cochlear Implant Recipients: Long-Term Analysis.

OBJECTIVES: To examine long-term speech and cognition outcomes in older adult cochlear implant (CI) recipients. First, by evaluating if CI performance was maintained over an extended follow-up period regardless of preoperative cognitive status. Secondly, by evaluating if there was a difference in the rate of cognitive decline between preoperative mild and normal cognition following CI over an extended period of time. STUDY DESIGN AND SETTING: Retrospective cohort study. METHODS: CI recipients ≥65 years of age implanted between 2009 and 2014 with 4+ years follow up. Pre- and postoperative audiometric and speech outcome assessments were collected. Cognitive status was measured using the mini mental status examination (MMSE) at numerous time points. RESULTS: Fifty-three patients met inclusion. Patients were divided into two groups based on preoperative MMSE with scores considered normal (28-30) and those with mildly impaired cognition (MIC, scores 25-27). Audiometric and speech performance improved significantly at one-year post implantation and this was maintained without significant change at 4+ years, regardless of cognitive status. Mixed modeling analysis controlling for age demonstrated no significant difference in the rate of cognitive decline at 4+ years post implantation between the normal cognition cohort (1.74; 95%CI 0.89-2.6) and MIC (2.9; 95%1.91-3.88). CONCLUSION: Speech performance was significantly improved and sustained after CI in both normal cognition and MIC patients. The rate of cognitive decline in older adult CI patients appears to be similar regardless of preoperative cognitive status. Although results demonstrate rates of cognitive decline following CI did not differ between cognition groups over 4+ years, future studies will need to further investigate this over extended time periods with a more comprehensive cognitive testing battery. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2379-2387, 2023.

External Validation of Cochlear Implant Screening Tools Demonstrates Modest Generalizability.

OBJECTIVE: To assess the clinical application of five recently published cochlear implant (CI) candidacy evaluation (CICE) referral screening tools through external validation. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary otology/neurotology practice. PATIENTS: Adults who underwent CICE between December 2020 and September 2021. INTERVENTIONS: CICE referral screening tools versus CI candidacy criteria. MAIN OUTCOME MEASURES: CICE screening tool performance, based on the ability to identify patients who met the CI candidacy criteria, was evaluated. CI candidacy criteria were defined as best-aided AzBio sentences at +10 signal-to-noise ratio and either 60% or less accuracy to reflect traditional criteria used in clinical settings or 40% or less accuracy (only patients 65 years or older) to reflect Medicare-eligible criteria. RESULTS: Screening criteria of proposed CICE referral tools vary widely across pure-tone average and word recognition scores. When screened by traditional criteria, the sensitivities and specificities of these referral tools varied from 40 to 77% and from 22 to 86%, respectively. When screened by Medicare-eligible criteria, sensitivities and specificities varied from 41 to 81% and from 24 to 91%, respectively. The screening tool proposed by Zwolan et al. ( Otol Neurotol 2020;41(7):895-900) demonstrated the best overall performance for traditional (Youden's J , 0.37; sensitivity, 62%; specificity, 75%) and Medicare-eligible patients (Youden's J , 0.44; sensitivity, 66%; specificity, 78%). All screening tools performed worse on the validation cohort compared with their respective development cohorts. CONCLUSIONS: Current tools for determining CICE referral have diverse screening criteria. These combinations of pure-tone average and word recognition score are modestly successful at identifying CI candidates.

Is Characteristic Frequency Limiting Real-Time Electrocochleography During Cochlear Implantation?

Objectives: Electrocochleography (ECochG) recordings during cochlear implantation have shown promise in estimating the impact on residual hearing. The purpose of the study was (1) to determine whether a 250-Hz stimulus is superior to 500-Hz in detecting residual hearing decrement and if so; (2) to evaluate whether crossing the 500-Hz tonotopic, characteristic frequency (CF) place partly explains the problems experienced using 500-Hz. Design: Multifrequency ECochG comprising an alternating, interleaved acoustic complex of 250- and 500-Hz stimuli was used to elicit cochlear microphonics (CMs) during insertion. The largest ECochG drops (≥30% reduction in CM) were identified. After insertion, ECochG responses were measured using the individual electrodes along the array for both 250- and 500-Hz stimuli. Univariate regression was used to predict whether 250- or 500-Hz CM drops explained low-frequency pure tone average (LFPTA; 125-, 250-, and 500-Hz) shift at 1-month post-activation. Postoperative CT scans were performed to evaluate cochlear size and angular insertion depth. Results: For perimodiolar insertions (N = 34), there was a stronger linear correlation between the largest ECochG drop using 250-Hz stimulus and LFPTA shift (r = 0.58), compared to 500-Hz (r = 0.31). The 250- and 500-Hz CM insertion tracings showed an amplitude peak at two different locations, with the 500-Hz peak occurring earlier in most cases than the 250-Hz peak, consistent with tonotopicity. When using the entire array for recordings after insertion, a maximum 500-Hz response was observed 2-6 electrodes basal to the most-apical electrode in 20 cases (58.9%). For insertions where the apical insertion angle is >350 degrees and the cochlear diameter is <9.5 mm, the maximum 500-Hz ECochG response may occur at the non-apical most electrode. For lateral wall insertions (N = 14), the maximum 250- and 500-Hz CM response occurred at the most-apical electrode in all but one case. Conclusion: Using 250-Hz stimulus for ECochG feedback during implantation is more predictive of hearing preservation than 500-Hz. This is due to the electrode passing the 500-Hz CF during insertion which may be misidentified as intracochlear trauma; this is particularly important in subjects with smaller cochlear diameters and deeper insertions. Multifrequency ECochG can be used to differentiate between trauma and advancement of the apical electrode beyond the CF.

Promontory Electrocochleography Recordings to Predict Speech-Perception Performance in Cochlear Implant Recipients.

OBJECTIVE: 1) To determine the relationship of electrocochleography (ECochG) responses measured on the promontory with responses measured at the round window (RW) and various intracochlear sites. 2) To evaluate if promontory ECochG responses correlate with postoperative speech-perception performance using the cochlear implant (CI). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Ninety-six adult CI recipients with no cochlear malformations or previous otologic surgery. MAIN OUTCOME MEASURES: Acoustically evoked ECochG responses were measured intraoperatively at both extracochlear and intracochlear locations. ECochG total response (ECochG-TR), a measure of residual cochlear function, was calculated by summing the fast Fourier transformation amplitudes in response to 250-Hz to 2-kHz acoustic stimuli. Speech-perception performance was measured at 3 months. RESULTS: There were strong linear correlations for promontory ECochG-TR with the ECochG-TRs measured at the RW ( r = 0.95), just inside scala tympani ( r = 0.91), and after full insertion ( r = 0.83). For an individual subject, the morphology of the ECochG response was similar in character across all positions; however, the response amplitude increased from promontory to RW (~1.6-fold) to just inside scala tympani (~2.6-fold), with the largest response at full insertion (~13.1-fold). Promontory ECochG-TR independently explained 51.8% of the variability ( r2 ) in consonant-nucleus-consonant at 3 months. CONCLUSIONS: Promontory ECochG recordings are strongly correlated with responses previously recorded at extracochlear and intracochlear sites and explain a substantial portion of the variability in CI performance. These findings are a critical step in supporting translation of transtympanic ECochG into the clinic preoperatively to help predict postoperative CI performance.

Electrocochleography and cognition are important predictors of speech perception outcomes in noise for cochlear implant recipients.

Although significant progress has been made in understanding outcomes following cochlear implantation, predicting performance remains a challenge. Duration of hearing loss, age at implantation, and electrode positioning within the cochlea together explain ~ 25% of the variability in speech-perception scores in quiet using the cochlear implant (CI). Electrocochleography (ECochG) responses, prior to implantation, account for 47% of the variance in the same speech-perception measures. No study to date has explored CI performance in noise, a more realistic measure of natural listening. This study aimed to (1) validate ECochG total response (ECochG-TR) as a predictor of performance in quiet and (2) evaluate whether ECochG-TR explained variability in noise performance. Thirty-five adult CI recipients were enrolled with outcomes assessed at 3-months post-implantation. The results confirm previous studies showing a strong correlation of ECochG-TR with speech-perception in quiet (r = 0.77). ECochG-TR independently explained 34% of the variability in noise performance. Multivariate modeling using ECochG-TR and Montreal Cognitive Assessment (MoCA) scores explained 60% of the variability in speech-perception in noise. Thus, ECochG-TR, a measure of the cochlear substrate prior to implantation, is necessary but not sufficient for explaining performance in noise. Rather, a cognitive measure is also needed to improve prediction of noise performance.

Early Hearing Preservation Outcomes Following Cochlear Implantation With New Slim Lateral Wall Electrode Using Electrocochleography.

OBJECTIVE: Describe early hearing preservation (HP) cochlear implantation (CI) outcomes using a new slim lateral wall electrode (SLWE). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: Adult CI candidates with preoperative low-frequency pure-tone average (LFPTA; 125, 250, 500 Hz) ≤60 dB HL. INTERVENTION: CI with and without intracochlear real-time electrocochleography (RT-ECochG). MAIN OUTCOME MEASURE: HP (LFPTA ≤80 dB HL), LFPTA shift, speech-perception performance measures, postoperative CT reconstruction. RESULTS: Forty-two subjects were implanted with the SLWE. Thirty patients underwent full insertion without RT-ECochG feedback, and HP was maintained at 3-months postactivation for 7 (23.3%) patients with mean LFPTA shift of 57.5 ±â€Š25.6 dB HL. RT-ECochG feedback was utilized on 12 patients, of whom 6 patients had full insertions and 6 patients had anywhere from 1 to 3 electrodes left outside of the cochlea based on RT-ECochG feedback. At 3 months postoperatively, HP was achieved on 10 (83.3%) patients and mean LFPTA shift was 18.9 c 11.7 dB HL. Mean difference between LFPTA threshold shift at 3-months postactivation with and without RT-ECochG was 38.6 dB HL (95% CI, 25.6-51.67). There was an improvement in delta CNC from preoperative to 3-months postactivation when using RT-ECochG, with mean difference 20.7% (95% CI, 3.3-38.1). CONCLUSIONS: Use of RT-ECochG monitoring during SLWE placement results in fewer full electrode insertions and significantly better HP rates and speech-perception outcomes when compared with unmonitored insertions. Further investigation is needed to evaluate long-term audiologic outcomes to better understand the relationships among ECochG, cochlear trauma, functional outcomes, and HP.

Machine Learning to Predict Treatment in Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVES: This study seeks to (1) demonstrate how machine learning (ML) can be used for prediction modeling by predicting the treatment patients with T1-2, N0-N1 oropharyngeal squamous cell carcinoma (OPSCC) receive and (2) assess the impact patient, socioeconomic, regional, and institutional factors have in the treatment of this population. METHODS: A retrospective cohort of adults diagnosed with T1-2, N0-N1 OPSCC from 2004 to 2013 was obtained using the National Cancer Database. The data was split into 80/20 distribution for training and testing, respectively. Various ML algorithms were explored for development. Area under the curve (AUC), accuracy, precision, and recall were calculated for the final model. RESULTS: Among the 19,111 patients in the study, the mean (standard deviation) age was 61.3 (10.8) years, 14,034 (73%) were male, and 17,292 (91%) were white. Surgery was the primary treatment in 9,533 (50%) cases and radiation in 9,578 (50%) cases. The model heavily utilized T-stage, primary site, N-stage, grade, and type of treatment facility to predict the primary treatment modality. The final model yielded an AUC of 78% (95% CI, 77-79%), accuracy of 71%, precision of 72%, and recall of 71%. CONCLUSION: This study created a ML model utilizing clinical variables to predict primary treatment modality for T1-2, N0-N1 OPSCC. This study demonstrates how ML can be used for prediction modeling while also highlighting that tumor and facility realted variables impact the decision making process on a national level.

The Impact of Age on Noise Sensitivity in Cochlear Implant Recipients.

OBJECTIVE: To evaluate the impact of different open set sentence recognition tests in quiet, +10 dB signal to noise ratio (SNR), and +5 dB SNR in adult cochlear implant (CI) recipients above and below 65 years of age. STUDY DESIGN AND SETTING: Multi-institution, prospective, non-randomized, single-subject repeated measures design. PATIENTS: Ninety six adults more than or equal to 18 years old with postlingual bilateral sensorineural hearing loss. INTERVENTIONS: Participants received a CI532 in one ear. Speech perception measures were evaluated before and 6-months after activation. MAIN OUTCOME MEASURES: Subjects completed consonant-nucleus-constant (CNC) words in quiet and AzBio sentences in noise using +10 and +5 dB SNR, and Montreal Cognitive Assessment (MOCA). RESULTS: Ninety six adult patients were enrolled (n = 70 older [≥65 yr], n = 26 younger [<65 yr]). There was no difference in CNC scores (CI alone 58.4% versus 67.5%, p = 0.0857; best aided 66.7% versus 76.1%, p = 0.3357). Older adults performed worse on AzBio +10 dB SNR compared with younger patients (CI alone 37.4% versus 56.9%, p = 0.0006; best aided 51.4% versus 68.2%; p = 0.01), and in AzBio +5 dB SNR (CI alone 7.7% versus 11.2%, p = 0.0002; best aided 15.3% versus 22.3%, p = 0.0005). The magnitude of change in AzBio +10 dB SNR was significantly less in older adults in CI alone (15.3% versus 22.3%; p = 0.0493) but not best aided (21.5% versus 31.3%; p = 0.105). The magnitude of change was drastically worse in AzBio +5 dB SNR for older adults (CI alone 6.7% versus 22.1%, p = 0.0014; best aided 9.5% versus 21.5%; p = 0.0142). There was no significant difference in MOCA between the two age groups. CONCLUSIONS: While both older and younger patients have similar outcomes with respect to CNC word scores in quiet, the addition of noise disproportionally impacts older patients. Caution should be exercised testing the elderly in noise; testing in noise may disproportionally impact performance expectations and should be more carefully considered when used for candidacy criteria and counseling. Future studies need to further investigate the disproportionate effect of noise on candidacy testing and its impact on how elderly patients are qualified.

Successful Treatment of Noise-Induced Hearing Loss by Mesenchymal Stromal Cells: An RNAseq Analysis of Protective/Repair Pathways.

Mesenchymal stromal cells (MSCs) are an adult derived stem cell-like population that has been shown to mediate repair in a wide range of degenerative disorders. The protective effects of MSCs are mainly mediated by the release of growth factors and cytokines thereby modulating the diseased environment and the immune system. Within the inner ear, MSCs have been shown protective against tissue damage induced by sound and a variety of ototoxins. To better understand the mechanism of action of MSCs in the inner ear, mice were exposed to narrow band noise. After exposure, MSCs derived from human umbilical cord Wharton's jelly were injected into the perilymph. Controls consisted of mice exposed to sound trauma only. Forty-eight hours post-cell delivery, total RNA was extracted from the cochlea and RNAseq performed to evaluate the gene expression induced by the cell therapy. Changes in gene expression were grouped together based on gene ontology classification. A separate cohort of animals was treated in a similar fashion and allowed to survive for 2 weeks post-cell therapy and hearing outcomes determined. Treatment with MSCs after severe sound trauma induced a moderate hearing protective effect. MSC treatment resulted in an up-regulation of genes related to immune modulation, hypoxia response, mitochondrial function and regulation of apoptosis. There was a down-regulation of genes related to synaptic remodeling, calcium homeostasis and the extracellular matrix. Application of MSCs may provide a novel approach to treating sound trauma induced hearing loss and may aid in the identification of novel strategies to protect hearing.

Long-term Hearing Preservation and Speech Perception Performance Outcomes With the Slim Modiolar Electrode.

OBJECTIVE: Describe audiologic outcomes in hearing preservation (HP) cochlear implant candidates using a slim modiolar electrode (SME). STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: Two hundred three adult cochlear implant patients with preoperative low-frequency pure-tone average (LFPTA) ≤ 80 dB HL that received the SME. INTERVENTION: Implantation with a SME electrode. MAIN OUTCOME MEASURES: Primary outcome was postoperative HP, defined as LFPTA ≤80 dB HL. HP status was analyzed at "early" (activation or 3 mo) and "long-term" (6 or 12 mo) time frames using the patient's worst audiogram. Speech perception tests were compared between HP and non-HP cohorts. RESULTS: Of the 203 HP candidates, the tip fold-over rate was 7.4%. The mean shifts in LFPTA at the "early" and "long-term" time points were 25.9 ±â€Š16.2 dB HL and 29.6 ±â€Š16.9 dB HL, respectively. Of 117 patients with preoperative LFPTA ≤60 dB HL, the early and long-term mean LFPTA shifts were 19.5 ±â€Š12.3 dB HL and 32.6 ±â€Š17.2 dB HL, respectively; early and long-term HP rates were 61.1% and 50.8%, respectively. For patients with preoperative LFPTA ≤80 dB HL, early and long-term HP rates were 45.5% and 43.7%, respectively. No significant difference was observed in postoperative speech perception performance (CNC, AzBio, HINT) at 3, 6, or 12 months between HP versus non-HP groups. CONCLUSIONS: HP is feasible using the SME. While electroacoustic stimulation was not studied in this cohort, HP provided no clear advantage in speech perception abilities in this group of patients. The current reporting standard of what constitutes HP candidacy (preoperative LFPTA ≤80 dB HL) should be reconsidered.