A Randomized Crossover Study in Single-Sided Deafness Comparing a Cartilage Conduction CROS System and an Air-Conduction CROS System.

OBJECTIVE: To investigate if cartilage conduction (CC) rerouting devices are noninferior to air-conduction (AC) rerouting devices for single-sided deafness (SSD) patients by measuring objective and subjective performance using speech-in-noise tests that resemble a realistic hearing environment, sound localization tests, and standardized questionnaires. STUDY DESIGN: Prospective, single-subject randomized, crossover study. SETTING: Anechoic room inside a university. PATIENTS: Nine adults between 21 and 58 years of age with severe or profound unilateral sensorineural hearing loss. INTERVENTIONS: Patients' baseline hearing was assessed; they then used both the cartilage conduction contralateral routing of signals device (CC-CROS) and an air-conduction CROS hearing aid (AC-CROS). Patients wore each device for 2 weeks in a randomly assigned order. MAIN OUTCOME MEASURES: Three main outcome measures were 1) speech-in-noise tests, measuring speech reception thresholds; 2) proportion of correct sound localization responses; and 3) scores on the questionnaires, "Abbreviated Profile of Hearing Aid Benefit" (APHAB) and "Speech, Spatial, and Qualities of Hearing Scale" with 12 questions (SSQ-12). RESULTS: Speech reception threshold improved significantly when noise was ambient, and speech was presented from the front or the poor-ear side with both CC-CROS and AC-CROS. When speech was delivered from the better-ear side, AC-CROS significantly improved performance, whereas CC-CROS had no significant effect. Both devices mainly worsened sound localization, whereas the APHAB and SSQ-12 scores showed benefits. CONCLUSION: CC-CROS has noninferior hearing-in-noise performance except when the speech was presented to the better ear under ambient noise. Subjective measures showed that the patients realized the effectiveness of both devices.

Application of Machine Learning to Predict Hearing Outcomes of Tympanoplasty.

OBJECTIVE: This retrospective study aimed to evaluate the performance of machine learning techniques in predicting air-bone gap after tympanoplasty compared with conventional scoring models and to identify the influential factors. METHODS: We reviewed the charts of 105 patients (114 ears) with chronic otitis media who underwent tympanoplasty. Two numerical scoring systems (middle ear risk index [MERI] and ossiculoplasty outcome parameter staging [OOPS]) and three algorithms (random forest [RF], support vector machine [SVM], and k nearest neighbor [kNN]) were created. Experimental variables included age, preoperative air-bone gap, soft-tissue density lesion in the tympanic cavity in CT, otorrhea, surgical history, ossicular bone problems in CT, tympanic perforation location, perforation type (central or marginal), grafting material, smoking history, endoscopy use, and the operator whose experience was 20 years or longer, or shorter. Binary classification, postoperative air-bone gap ≤15 or >15 dB, and multiclass classification, classification into seven categories by 10 dB, were performed, and the percentages of correct prediction were calculated. The importance of features in the RF model was calculated to identify influential factors. RESULTS: The percentages of correct prediction in binary classification were 62.3%, 72.8%, 81.5%, 81.5%, and 81.5% in MERI, OOPS, RF, SVM, and kNN, respectively, and those in multiclass classification were 29.8%, 21.9%, 63.1%, 44.7%, and 50% in the same order. The RF model suggested larger preoperative air-bone gap, and older age could make the postoperative air-bone gap larger. CONCLUSION: The machine learning techniques, especially the RF model, are promising methods for precise postoperative air-bone gap prediction. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2371-2378, 2023.

Evidence for the spread of SARS-CoV-2 and olfactory cell lineage impairment in close-contact infection Syrian hamster models.

Objectives: Close contact with patients with COVID-19 is speculated to be the most common cause of viral transmission, but the pathogenesis of COVID-19 by close contact remains to be elucidated. In addition, despite olfactory impairment being a unique complication of COVID-19, the impact of SARS-CoV-2 on the olfactory cell lineage has not been fully validated. This study aimed to elucidate close-contact viral transmission to the nose and lungs and to investigate the temporal damage in the olfactory receptor neuron (ORN) lineage caused by SARS-CoV-2. Methods: Syrian hamsters were orally administered SARS-CoV-2 nonvariant nCoV-19/JPN/TY/WK521/2020 as direct-infection models. On day 3 after inoculation, infected and uninfected hamsters were housed in the same cage for 30 minutes. These uninfected hamsters were subsequently assigned to a close-contact group. First, viral presence in the nose and lungs was verified in the infection and close-contact groups at several time points. Next, the impacts on the olfactory epithelium, including olfactory progenitors, immature ORNs, and mature ORNs were examined histologically. Then, the viral transmission status and chronological changes in tissue damage were compared between the direct-infection and close-contact groups. Results: In the close-contact group, viral presence could not be detected in both the nose and lungs on day 3, and the virus was identified in both tissues on day 7. In the direct-infection group, the viral load was highest in the nose and lungs on day 3, decreased on day 7, and was no longer detectable on day 14. Histologically, in the direct-infection group, mature ORNs were most depleted on day 3 (p <0.001) and showed a recovery trend on day 14, with similar trends for olfactory progenitors and immature ORNs. In the close-contact group, there was no obvious tissue damage on day 3, but on day 7, the number of all ORN lineage cells significantly decreased (p <0.001). Conclusion: SARS-CoV-2 was transmitted even after brief contact and subsequent olfactory epithelium and lung damage occurred more than 3 days after the trigger of infection. The present study also indicated that SARS-CoV-2 damages all ORN lineage cells, but this damage can begin to recover approximately 14 days post infection.

Vestibular Imaging and Function in Patients With Inner Ear Malformation Presenting With Profound Hearing Loss.

Objective: Vestibular impairment has been observed in patients with congenital hearing loss, but little is known about the vestibular anatomy and function of those in this group with inner ear malformations. This study aims to investigate the association between vestibulocochlear anatomy and vestibular function test results in children with inner ear malformations. Study Design: Case series with chart review. Setting: Pediatric patients with inner ear malformations presenting with bilateral profound hearing loss at a tertiary hospital from 1999 to 2017. Methods: Ears were classified into subgroups based on anatomic abnormalities seen on computed tomography imaging. Cervical vestibular evoked myogenic potential (cVEMP), rotatory chair, and caloric test results were obtained and collated. Descriptive and inferential statistics were calculated. Results: Of 82 ears, 29.3% had incomplete partition type II malformation, the most common type. The second-most common type was isolated vestibular organ anomaly (20.7%), which is not included in currently accepted categories. Most ears exhibited abnormal vestibular function. Abnormal vestibule volume was associated with a nonreactive cVEMP (P < .001). Radiologically abnormal lateral semicircular canals were associated with abnormal caloric and rotatory chair results (P < .001). Conclusion: With a relatively large number of cases of isolated vestibular organ anomaly not only in our study but also in previous publications, we suggest that this category be added to the subsets of inner ear malformations. Abnormal vestibule volume was significantly associated with a nonreactive cVEMP finding. The majority of patients with hearing loss secondary to inner ear malformations have abnormal vestibular function test results.

Oral SARS-CoV-2 Inoculation Causes Nasal Viral Infection Leading to Olfactory Bulb Infection: An Experimental Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause long-lasting anosmia, but the impact of SARS-CoV-2 infection, which can spread to the nasal cavity via the oral route, on the olfactory receptor neuron (ORN) lineage and olfactory bulb (OB) remains undetermined. Using Syrian hamsters, we explored whether oral SARS-CoV-2 inoculation can lead to nasal viral infection, examined how SARS-CoV-2 affects the ORN lineage by site, and investigated whether SARS-CoV-2 infection can spread to the OB and induce inflammation. On post-inoculation day 7, SARS-CoV-2 presence was confirmed in the lateral area (OCAM-positive) but not the nasal septum of NQO1-positive and OCAM-positive areas. The virus was observed partially infiltrating the olfactory epithelium, and ORN progenitor cells, immature ORNs, and mature ORNs were fewer than in controls. The virus was found in the olfactory nerve bundles to the OB, suggesting the nasal cavity as a route for SARS-CoV-2 brain infection. We demonstrated that transoral SARS-CoV-2 infection can spread from the nasal cavity to the central nervous system and the possibility of central olfactory dysfunction due to SARS-CoV-2 infection. The virus was localized at the infection site and could damage all ORN-lineage cells.

Cochlear Implantation in Patients with Mitochondrial Gene Mutation: Decline in Speech Perception in Retrospective Long-Term Follow-Up Study.

Clinical evidence of the effectiveness of cochlear implantation for hearing loss with mitochondrial DNA mutation is limited. Most reports have only described short-term postoperative speech perception, which may not reflect the limitations of cochlear implantation caused by progressive retrocochlear dysfunction. The present study aimed to investigate long-term speech perception after cochlear implantation in patients with severe to profound hearing loss associated with mitochondrial DNA mutation. A retrospective chart review was performed on patients with mitochondrial DNA mutation who had undergone cochlear implantation at the Department of Otolaryngology and Head and Neck Surgery at the University of Tokyo Hospital. We extracted data on causative mutations, clinical types, clinical course, perioperative complications, and short-term and long-term postoperative speech perception. Nine patients with mitochondrial DNA mutation underwent cochlear implantation. The mean observation period was 5.5 ± 4.2 years (range, 1-13 years), and seven patients were followed for more than 3 years. Two of the seven patients who initially showed good speech perception exhibited deterioration during long-term follow-up. The absence of an acute progression of cognitive decline in patients, showing a gradual decrease in speech perception, suggests that the deterioration of speech perception was caused by progressive retrocochlear degeneration. Although most patients with mitochondrial DNA mutation maintained good speech perception for more than 3 years after cochlear implantation, retrocochlear degeneration could cause the deterioration of speech perception during long-term follow-up.

Long-Term Progression and Rapid Decline in Hearing Loss in Patients with a Point Mutation at Nucleotide 3243 of the Mitochondrial DNA.

Patients with m.3243A>G mutation of mitochondrial DNA develop bilaterally symmetric sensorineural hearing loss. However, it is unclear how fast their hearing loss progresses over time, and whether they experience rapid progression of hearing loss. In the present study, we conducted a long-term hearing evaluation in patients with MELAS or MIDD who harbored the m.3243A>G mutation of mitochondrial DNA. A retrospective chart review was performed on 15 patients with this mutation who underwent pure-tone audiometry at least once a year for more than two years. The mean follow-up period was 12.8 years. The mean progression rate of hearing loss was 5.5 dB per year. Hearing loss progressed rapidly to be profoundly deaf in seven patients during the observation period. Heteroplasmy and age-corrected heteroplasmy levels correlated with the age of onset of hearing loss. These results indicate that patients with m.3243A>G mutation have a gradual progression of hearing loss in the early stages and rapid decline in hearing to be profoundly deaf in approximately half of the patients. Although it is possible to predict the age of onset of hearing loss from heteroplasmy and age-corrected heteroplasmy levels, it is difficult to predict whether and when the rapid hearing loss will occur.

Alteration of Vestibular Function in Pediatric Cochlear Implant Recipients.

Background: Vestibular dysfunction is a complication of cochlear implantation (CI). Reports on the evaluation of vestibular function before and after CI are limited, especially in children. We investigated the effect of CI on vestibular function in pediatric patients. Patients and Methods: We routinely evaluated vestibular function before but not immediately after CI. Therefore, patients who underwent sequential bilateral CI were enrolled in this study. Seventy-three children who underwent sequential CI from 2003 to 2020 at our hospital were included. Since the vestibular function of the first implanted ear was evaluated before the second surgery for the contralateral ear, post-CI evaluation timing differed among the cases. The evaluation included a caloric test, a cervical vestibular-evoked myogenic potential (cVEMP) test, and a damped rotation test. The objective variables included the results of these tests, and the explanatory variables included the age at surgery, cause of hearing loss, electrode type, and surgical approach used. The associations of these tests were analyzed. Results: cVEMP was the most affected after CI (36.1%), followed by the caloric test (23.6%), and damped rotation test (7.8%). Cochleostomy was significantly more harmful than a round window (RW) approach or an extended RW approach based on the results of the caloric test (p = 0.035) and damped rotation test (p = 0.029). Perimodiolar electrodes affected the caloric test results greater than straight electrodes (p = 0.041). There were no significant associations among these tests' results. Conclusions: Minimally invasive surgery in children using a round window approach or an extended round window approach with straight electrodes is desirable to preserve vestibular function after CI.

Expression of ACE2, TMPRSS2, and Furin in Mouse Ear Tissue, and the Implications for SARS-CoV-2 Infection.

OBJECTIVES/HYPOTHESIS: Intracellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on the interaction between its spike protein with the cellular receptor angiotensin-converting enzyme 2 (ACE2) and depends on Furin-mediated spike protein cleavage and spike protein priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). As the expression of ACE2, TMPRSS2, and Furin in the middle and inner ear remain unclear, we analyzed the expression of these proteins in mouse ear tissues. STUDY DESIGN: Animal Research. METHODS: We performed immunohistochemical analysis to examine the distribution of ACE2, TMPRSS2, and Furin in the Eustachian tube, middle ear spaces, and cochlea of mice. RESULTS: ACE2 was present in the nucleus of the epithelium of the middle ear and Eustachian tube, as well as in some nuclei of the hair cells in the organ of Corti, in the stria vascularis, and the spiral ganglion cells. ACE2 was also expressed in the cytoplasm of the stria vascularis. TMPRSS2 was expressed in both the nucleus and cytoplasm in the middle spaces, with the expression being stronger in the nucleus in the mucosal epithelium of the middle ear spaces and Eustachian tube. TMPRSS2 was present in the cytoplasm in the organ of Corti and stria vascularis and in the nucleus and cytoplasm in the spiral ganglion. Furin was expressed in the cytoplasm in the middle ear spaces, Eustachian tube, and cochlea. CONCLUSIONS: ACE2, TMPRSS2, and Furin are diffusely present in the Eustachian tube, middle ear spaces, and cochlea, suggesting that these tissues are susceptible to SARS-CoV-2 infection. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2013-E2017, 2021.

Classification of the Chorda Tympani: An Endoscopic Study.

OBJECTIVES: To determine the ability of preoperative computed tomography (CT) to predict the variable surgical anatomy of the chorda tympani nerve (CTN) based on endoscopic tympanotomy. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: We identified 192 ears of 162 patients who underwent transcanal endoscopic ear surgery from August 2013 to June 2018. Patients with middle ear malformations, revision surgeries, myringoplasty, and cholesteatoma involving the CTN were excluded. INTERVENTIONS: An intraoperative endoscopic image depicting the chorda tympani was selected for each patient and classified into one of five types. Preoperative CT images were analyzed to match the pictorial classification. MAIN OUTCOME MEASURES: The visible tympanic segment of the chorda tympani was classified into the following five types: external auditory canal (EAC), detached, attached long, attached short, and ultrashort. RESULTS: A total of 128 ears from 101 patients ranging in age from 2 to 81 years were enrolled. The EAC, detached, attached long, attached short, and ultrashort types of CTN were found in 7 (5.5%), 6 (4.7%), 84 (65.6%), 18 (14.0%), and 13 (10.2%) patients, respectively. The presence of the EAC type could be predicted by preoperative CT while the other four types could be predicted by binning into two groups, with a sensitivity of 0.61 and specificity of 0.72. CONCLUSION: The variable anatomy of the chorda tympani nerve can be classified into five major groups based on endoscopic tympanotomy.

Acute bilateral vestibulopathy with simultaneous involvement of both superior and inferior vestibular nerves.

We report a case of acute vestibulopathy with the simultaneous involvement of both superior and inferior vestibular nerves on both sides. A 36-year-old female presented with dizziness, oscillopsia and a walking impairment subsequent to a high fever. Vestibular function tests including caloric testing, video head impulse testing (vHIT) and cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) were performed. In the first examination, vHIT and caloric testing showed severe impairments in all three semicircular canals in each ear, and both cVEMPs and oVEMPs were absent on both sides. During a 1-year follow-up, the gain of vHIT gradually recovered by more than 0.5 to normal. cVEMPs also recovered to normal on both sides while oVEMPs remained absent on both sides. This is the first reported case of acute bilateral vestibulopathy with simultaneous involvement of both superior and inferior vestibular nerves on both sides. Repeated evaluation of vestibular function using vHIT, cVEMPs and oVEMPs is helpful to assess the time course of recovery in patients with vestibulopathy.