Re-administration of adeno-associated virus (AAV)-mediated gene therapy remains challenging due to neutralizing antibodies (NAbs) induced by the initial dose. We previously conducted a single-arm trial showing that single-dose administration of AAV-hOTOF gene therapy in individuals with OTOF-related deafness is safe and leads to hearing improvements. Here we initially demonstrate that AAV1-hOTOF re-administration to the contralateral ear in Otof-/- mice with peak serum NAb titers successfully rescued hearing with limited immune activation. After a protocol amendment of our trial, four patients (aged 2.2-3.4 years) with pre-existing NAbs (titers 1:135-1:3,645), who had previously received a single dose of the gene therapy, were enrolled to receive a second dose in the contralateral ear, as part of the ongoing trial, with a follow-up ranging from 26 weeks to 52 weeks. The primary endpoint was the occurrence of dose-limiting toxicities at 6 weeks and secondary endpoints included safety and auditory function. No dose-limiting toxicity occurred within 6 weeks. In the secondary outcomes, the 26-week average auditory brainstem response threshold in the second treated ear improved from >95 dB at baseline to 43 dB, 63 dB, 80 dB and 53 dB in patients 1-4, respectively. Safety assessment showed that all adverse events were grade 1-2, except one grade 3 decreased neutrophil count; no serious adverse events occurred. These data provide preliminary insights on the safety and efficacy of re-administration of AAV1-hOTOF gene therapy in patients with congenital deafness. Longer follow-up and larger cohorts are needed to establish the safety and efficacy of repeated administration of gene therapies. Trial registration no.: ChiCTR2200063181 .

Autosomal recessive deafness 9, caused by OTOF gene mutations, is characterized by severe-to-complete congenital deafness1. Although gene therapy has shown benefits in a small number of patients2-5, its safety and efficacy across broader age ranges and longer follow-up periods, as well as predictors of treatment outcomes, remain unclear. In this single-arm, multicentre trial conducted at eight centres, 42 participants (aged 0.8-32.3 years) received adeno-associated virus (AAV) serotype 1 carrying a human OTOF coding transgene (AAV1-hOTOF) at three vector dose groups, with up to 2.5-year follow-up. The primary end point was dose-limiting toxicity within 6 weeks. The secondary end point assessed efficacy and adverse events. No dose-limiting toxicities were observed. Grade 3 adverse events included decreased neutrophil count. Hearing was recovered in 90% of participants treated with AAV1-hOTOF, with gradual and stable improvement in auditory brainstem response threshold from greater than 97 ± 1 dB normalized hearing level at baseline to 54 ± 3, 51 ± 3, 50 ± 3 and 42 ± 5 dB normalized hearing level at 1, 1.5, 2 and 2.5 years, respectively, and behavioural audiometry improving from greater than 96 ± 3 dB hearing level at baseline to 37 ± 5 dB hearing level at 2.5 years. Participants aged 0.5-18 years showed greater hearing improvement than adults. A higher number of present distortion product otoacoustic emissions at baseline or biallelic non-truncated OTOF variants was associated with better hearing recovery. Participants with hearing recovery demonstrated gradual improvement in speech perception. AAV1-hOTOF is well-tolerated and efficacious across a broader patient population, with sustained therapeutic benefits for up to 2.5 years. Chinese Clinical Trial Registry registration: ChiCTR2200063181 .

Background Sudden sensorineural hearing loss (SSNHL) is a highly heterogeneous condition with unpredictable recovery. We aimed to develop and validate an interpretable, subtype-specific machine learning (ML) framework for prognostic assessment using the largest SSNHL clinical cohort reported to date to overcome the "black-box" nature of existing models. Method In this retrospective cohort study, 3,957 patients diagnosed with SSNHL between 2010 and 2017 were analyzed. Eight ML algorithms were trained and validated for five predefined audiogram subtypes: ascending, descending, atypical, profound, and flat. Model performance was evaluated using accuracy, area under the receiver operating characteristic curve (AUC), and Brier score. SHapley Additive exPlanations (SHAP) and partial dependence plots (PDPs) were used to interpret the models and quantify the nonlinear impact of predictors. Results In total, 3,957 patients were included in the analysis. The subtype-specific models demonstrated robust performance with test accuracies ranging from 0.706 to 0.774. Support Vector Machine and Logistic Regression emerged as the optimal classifiers. Five core prognostic factors were identified: disease duration, pure-tone average, age, WHO hearing classification, and systemic glucocorticoid therapy. Notably, the study quantified subtype-specific treatment windows, showing the disease duration threshold for a 50% recovery probability ranged from 7.5 to 13.1 days. Conclusion ML is a reliable tool for high-precision prognostic assessment in SSNHL. By quantifying actionable intervention thresholds, this interpretable framework moves beyond "black-box" predictions, providing a real-time decision support tool that reinforces the necessity of early systemic glucocorticoid therapy.

BACKGROUND:Hereditary hearing loss is one of the most common disabling disorders in children and lacks effective pharmacological treatments. Recent breakthroughs in OTOF gene therapy clinical trials necessitate standardized frameworks to guide emerging therapies. This study aims to establish the first international consensus on the clinical application of gene therapy for hereditary hearing loss. METHODS:A modified Delphi process was conducted from March 2024 to March 2025, involving 46 multidisciplinary experts from several countries across otology, genetics, audiology, gene therapy, and hearing rehabilitation. After a systematic literature review, as well as integration of research and clinical expertise and experience, three iterative voting rounds (two anonymous surveys and one online consensus meeting) were performed. Statements required ≥75% agreement for inclusion. FINDINGS:From 9,093 publications, 69 were used to draft and support the consensus statements. A total of 30 statements relevant to six domains achieved consensus on gene therapy for hereditary hearing loss, including ethical review (1 statement), patient selection criteria (12 statements), diagnosis and preoperative evaluation (9 statements), gene therapy drug delivery (4 statements), follow-up (3 statements), and post-treatment auditory and speech rehabilitation (1 statement). CONCLUSIONS:This consensus provides the first globally endorsed framework for gene therapy in hereditary hearing loss. It standardizes clinical trial design and patient management, accelerating translation from research to practice while ensuring safety. The guidelines are immediately applicable to OTOF-related hearing loss and adaptable to other genetic forms. FUNDING:This work was supported by the National Natural Science Foundation of China, the German Research Foundation (DFG) via the Cluster of Excellence, and others.

Individuals with congenital deafness that have received gene therapy represent a unique group who experience hearing recovery and speech development. However, it is unclear how hearing-related cortex changes because of gene therapy. Here we study neural processing in ten patients using functional near-infrared spectroscopy and electroencephalography during a six-month follow-up period. Patients showed an enhancement of activation in the auditory cortex, particularly in parts of the Sylvian parietotemporal area while listening to music. Activation in the right anterior temporal lobe and left Sylvian parietotemporal area was also enhanced when listening to speech. The electroencephalography data showed that the power of the resting-state electroencephalography beta band at time points T2 and T3 was statistically significantly increased after gene therapy, and mismatch negativity amplitudes at T2 and T3 were statistically significantly higher than those at T0. The mental developmental level of the patients also increased after gene therapy. These preliminary findings illuminate the neural and cognitive effects of gene therapy, supporting its potential effectiveness in auditory and mental development.

Importance:OTOF gene therapy (GT) has been shown to improve hearing and speech. The efficacy of GT remains to be compared against cochlear implantation (CI), the current gold standard for congenital deafness. Objective:To evaluate treatment outcomes in auditory and speech perception between patients with congenital deafness treated with GT, CI, or both. Design, Setting, and Participants:This nonblind cohort study was conducted between December 2022 and November 2024. GT patients received follow-up at 3, 6, and 12 months; CI patients received 1-time evaluation at the corresponding time intervals or longer (3, 6, or 12 months). The study was conducted at a single class A tertiary hospital in China. Participants with congenital severe to complete hearing loss, aged 1 to 18 years, who received GT or CI were enrolled. They were matched on duration of deafness, hearing thresholds, and speech ability at the presurgical baseline. Of 1568 participants screened, 72 participants enrolled. Participants were excluded if they had inner ear malformations or vestibular-cochlear nerve abnormalities. Exposures:GT only vs CI; bimodal (unilateral GT plus contralateral CI) vs bilateral CI; GT (CI turned off [CI-off]) vs unilateral CI. Main Outcomes and Measures:The primary outcomes were auditory and speech perception evaluated by questionnaires, including the Infant-Toddler Meaningful Auditory Integration Scale/Meaningful Auditory Integration Scale (IT-MAIS/MAIS), and tests, including audiometry, speech, and music tests. The main secondary outcome was auditory information processing ability assessed by mismatch negativity (MMN). Results:A total of 11 GT patients (6 male [55%]; mean [SD] age at baseline, 3.7 [2.8] years) and 61 CI patients (34 male [56%]; mean [SD] age at baseline, 1.9 [1.5] years) were enrolled. The mean (SD) auditory brainstem response thresholds were restored from greater than 95.0 (0.0) decibels normalized hearing level (dB nHL) to 54.8 (15.9) dB nHL in 9 GT patients at 12 months. For GT-only vs CI in auditory and speech perception, GT patients performed better in IT-MAIS/MAIS at 6 months (median [IQR] score, 31.0 [30.0-32.0] vs 23.5 [19.0-26.3]; P = .01) and 12 months (median [IQR] score, 32.0 [31.0-32.0] vs 28.0 [24.5-30.5]; P = .007). GT patients showed shorter latencies of MMN at 6 months (median [IQR], 0.20 [0.05-0.21] seconds vs 0.23 [0.22-0.25] seconds; P = .006). For bimodal patients at 12 months, GT (CI-off) patients performed better than unilateral CI patients in speech in a noisy environment (median [IQR] disyllable, -1.0 [-3.0 to 2.4] dB sound pressure level (SPL) vs 5.3 [3.1 to 12.1] dB SPL; P = .03); GT plus CI patients performed better than bilateral CI patients in singing in-tune rates (median [IQR], 66.6% [53.7%-83.9%] vs 37.1% [30.3%-56.3%]; P = .04); GT plus CI patients showed shorter latencies of MMN at 12 months (median [IQR], 0.08 [0.07-0.10] seconds vs 0.21 [0.15-0.23] seconds, P = .01). Conclusions and Relevance:GT patients showed stable hearing recovery and exhibited more rapid improvements in auditory and speech performance than CI patients, while outperforming CI patients in speech in noise performance and music perception. These findings suggest that GT may provide a novel effective treatment alternative for patients with genetically driven congenital deafness.

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181.

The aim of this study was to replicate previous English-language musician advantage studies in Mandarin-speaking musicians and nonmusicians. Segregation of competing speech, melodic pitch perception, and spectro-temporal pattern perception were measured in normal-hearing native Mandarin-speaking musicians and nonmusicians. Speech recognition thresholds were measured in the presence of two-talker masker speech. The masker sex was either the same as or different from the target; target and masker speech were either co-located or spatially separated. Melodic pitch perception was tested using a melodic contour identification task. Spectro-temporal resolution was measured using a modified spectral ripple detection task. We hypothesized that, given musician advantages in pitch perception, musician effects would be larger when the target and masker sex was the same than when different. For all tests, performance was significantly better for musicians than for nonmusicians. Contrary to our expectation, larger musician effects were observed for segregation of competing speech when the target and masker sex was different. The results show that musician effects observed for non-tonal language speakers extend to tonal language speakers. The data also suggest that musician effects may depend on the difficulty of the listening task and may be reduced when listening tasks are too easy or too difficult.

Background Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9. Methods This single -arm, single -centre trial enrolled children (aged 1-18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF , and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing. Findings Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 x 10 11 vector genomes [vg] and five received 15 x 10 12 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1-2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40-57 dB reduction in the average auditory brainstem response (ABR) thresholds at 05-40 kHz. In the participant who received the 9 x 10 11 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 15 x 10 12 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery. Interpretation AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9.

A teenage girl presentedwith persistent ear pain after an uneventful piercing of her right auricle to place an earring. Five days after the piercing, she noticed otalgia adjacent to the piercing, and pain in the right side of her neck. Shehadnoothermedical conditions. Before presentation she had received a course of intravenous antibiotics and had undergone incision and drainage of the affected area, but her symptoms persisted. On examination, she had a swollen, mildly fluctuant pinna (fig 1). Her temperature, heart rate, and respiratory rate were normal. A complete blood count showed a white cell count of 12.63×10/L (normal range 4.0-10.0×10/L).

Extended experience with meaningful pitch information has been shown to benefit music perception as well as speech perception where pitch cues are important, such as segregation of competing speech and tonal language perception. Interestingly, pitch perception has been shown to be similar between non-musicians who speak a tonal language and musicians who speak a non-tonal language, both of which outperform non-musicians who speak a non-tonal language. However, it is unknown whether extensive music training can further benefit pitch perception in tonal language speakers. In this study, melodic contour identification, spectro-temporal pattern perception, and masked speech recognition was measured in 16 adult normal-hearing musicians and 16 non-musicians; all were Chinese native speakers of Mandarin. Melodic contour identification, spectro-temporal pattern perception, and masked speech recognition all were significantly better for musicians than for non-musicians. Compared to non-musicians, musicians better utilized talker sex cues to segregate competing speech; utilization of talker sex cues by musicians was associated with the onset and extent of music training. Across all participants, spectro-temporal pattern perception was associated with better masked speech understanding. The data suggest that early and extensive music training may further benefit tonal language speakers’ perception and utilization of pitch cues.

The aim of this study was to determine the prevalence of facial nerve (FN) bifurcation in patients who undergo stapes surgery, and to ascertain the correlation between the intraoperative and radiographic findings in cases where an unexpected branch malformation for patients undergoing stapes surgery. Patients who underwent stapes surgery were retroactively examined for confirmed FN bifurcation. Among the 887 patients, 10 had a bifurcated FN confirmed during surgery and had a preoperative high-resolution computed tomography (HRCT) scan. The HRCT scans were examined by two radiologists who were blinded to the operational findings. The diagnostic accuracy of HRCT imaging was examined along with their preoperative audiometry. In total, 887 patients underwent stapes surgery and among them the prevalence of FN bifurcation was 1.13%. These 10 patients had a 1:1 male-female ratio with a mean age of 17.9 ± 7.0 years. From a surgical review, all cases had bifurcation at the horizontal segment of FN, including 1 case of FN trifurcation. The diagnostic difference between HRCT imaging and intraoperation observations for malformations in the middle ear varies widely depending on the location, ranging from 0% to 90%. The prevalence of incus and stapes malformations was high in both imaging and operation findings (≥60%). The detection rate of abnormal positioning and bifurcation of the FN during HRCT imaging was 30% and 0%, respectively. The mean air-bone gap hearing threshold for patients was significantly improved from 42.3 dB preoperatively to 15.6 dB postoperatively without any complications. These results showed that it is extremely difficult to predict the FN bifurcation prior to surgery with a detection rate of 0%. The diagnostic difference between HRCT imaging and intraoperation observations for malformations of different parts of the middle ear varies widely. These results highlight the importance of being vigilant in regard to FN anatomical variation during stapes surgery for any unexpected malformations that are not detected during HRCT evaluation. In addition, the surgical outcomes for these patients were optimal when treatment was performed by senior surgeons.

To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort, we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments. Records of patients with primary complaint of throat discomfort, absence of chest pain at onset, and an ultimate diagnosis of acute coronary syndrome, as well as patients with pharyngitis (as controls) were collected from May 2015 to April 2016. The patients’ main manifestations were compared. Logistic regression results showed that chest tightness, dyspnea, perspiring, and exertional throat symptoms were significantly associated with acute coronary syndrome, with odds ratios of 8.3 (95% CI 2.2–31.5), 10.9 (95% CI 1.8–66.9), 25.4 (95% CI 3.6–179.9), and 81.2 (95% CI 13.0–506.7). A total of 25 (56.82%) out of 44 acute coronary syndrome patients, who were first admitted to the otorhinolaryngology department, were misdiagnosed, with a 12% (3/25) mortality rate. Throat discomfort can be the principal manifestation of acute coronary syndrome. Such patients exhibit high misdiagnosis and mortality rates. Exertional throat symptoms, chest tightness, perspiring, and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort. The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.

Background: Frequency-specific hearing studies are important for predicting hearing results and the prognosis after stapes surgery, to prepare for the rehabilitation of frequency-specific hearing in patients with otosclerosis. Objectives: To evaluate outcomes of stapes surgery of Chinese otosclerosis patients with different degrees of hearing loss. Methods: We conducted a retrospective analysis of 213 otosclerosis patients who underwent stapes surgery in our hospital. Pre- and post-operative audiometric evaluation using conventional audiometry. Results: The post-op ABG was less than 20 dB in 94.52% of all cases after surgery. There was no statistical significance of the post-op ABG among different groups at all frequencies except extremely severe group (p < .05). There was a significant improvement of both AC and BC thresholds in post-op period and the most significant improvement was found in severe group. There were no serious post-op complications and no re-operations during the follow-up period. Conclusion: Stapes surgery is a suitable treatment option for otosclerosis with mild to extremely severe HL. The mild to moderate hearing loss groups had the most significant improvement of AC thresholds in the low frequency region, and the severe to extremely severe groups appeared in the high frequency region.

The aim of this study was to study an antimicrobial peptide (AMP), aurein 1.2, which substantially increased protein delivery directly into multiple mammalian inner-ear cell types in vivo. Different concentrations of aurein 1.2 with superpositively charged GFP (+36 GFP) protein fused with Cre recombinase were delivered to postnatal day 1-2 (P1-2) and adult cochleae of Cre reporter transgenic mice with various delivery methods. By cochleostomy at different concentrations of aurein 1.2-+36 GFP (1 μM, 5 μM, 22.5 μM, and 50 μM, respectively), the tdTomato (tdT) expression was observed in outer hair cells (OHCs; 20.77%, 23.02%, 76.36%, and 92.47%, respectively) and inner hair cells (IHCs; 14.90%, 44.50%, 89.59%, and 96.13%, respectively) in the cochlea. The optimal concentration was 22.5 μM with the highest transfection efficiency and the lowest cytotoxicity. Wide-spread tdT signals were detected in the cochlear-supporting cells, utricular-supporting cells, auditory nerve, and spiral ligament in neonatal and adult mice. Compared to cochleostomy, injection through the round window membrane (RWM) also produced highly efficient tdT+ labeled cells with less cell loss. In summary, the peptide aurein 1.2 fused with +36 GFP dramatically expanded the target cells with increased efficiency in direct protein delivery in the inner ear. Aurein 1.2-+36 GFP has the potential to be developed as protein-based therapy in regeneration and genome editing in the mammalian inner ear.

More than half of COVID-19 patients are afebrile early in the disease course, yet mildly ill or asymptomatic patients can still spread SARS-CoV-2 with high efficiency. Atypically presenting patients may be seen in noninfectious disease settings such as otolaryngology, which is a specialty prone to occupational exposure. Otolaryngologists have been infected with COVID-19 at higher rates than other specialties in China and other countries. Otolaryngology providers should maintain high clinical suspicion for mild and asymptomatic COVID-19 patients. Protective strategies should be implemented including preappointment screening, triaging, restriction of nonurgent visits and surgeries, telemedicine, and appropriate personal protective equipment use.

To describe the characteristics of the clinical presentation, diagnosis, surgical methods, and outcomes of patients with otogenic cerebrospinal fluid (CSF) leakage secondary to congenital inner ear dysplasia. A retrospective review was performed of 18 patients with otogenic CSF leakage secondary to inner ear dysplasia who underwent surgery in our group from 2007 to 2017 and had a follow-up of at least 4 months. The average length of follow-up was three years. The characteristics of the clinical presentations of all patients, such as self-reported symptoms, radiographic findings, surgical approaches and methods of repair, position of the leakage during surgery, and postoperative course, including the success rate of surgery, are presented. The patients presented mostly with typical symptoms of meningitis, severe hearing impairment, and CSF otorrhea or rhinorrhea. All 18 patients had at least one previous episode of meningitis accompanied by a severe hearing impairment. The preoperative audiograms of 17 patients showed profound sensorineural hearing loss, and one patient had conductive hearing loss. Twelve patients presented with an initial onset of otorrhea, and two had accompanying rhinorrhea. Six patients complained of rhinorrhea, two of whom were misdiagnosed with CSF rhinorrhea and underwent transnasal endoscopy at another hospital. High-resolution computed tomography (HRCT) images can reveal developments in the inner ear, such as expansion of a vestibular cyst, unclear structure of the semicircular canal or cochlea, or signs of effusion in the middle ear or mastoid, which strongly suggest the possibility of CSF otorrhea. The children in the study suffered more severe dysplasia than adults. All 18 patients had CSF leakage identified during surgery. The most common defect sites were in the stapes footplates (55.6%), and 38.9% of patients had a leak around the oval window. One patient had a return of CSF otorrhea during the postoperative period, which did not re-occur following a second repair. CSF otorrhea due to congenital inner ear dysplasia is more severe in children than in adults. The most common symptoms were meningitis, hearing impairment, and CSF otorrhea or rhinorrhea. HRCT has high diagnostic accuracy for this disease. The most common fistula site was around the oval window, including the stapes footplates and the annular ligament.

OBJECTIVES:While fundamental frequency (F0) cues are important to both lexical tone perception and multitalker segregation, F0 cues are poorly perceived by cochlear implant (CI) users. Adding low-frequency acoustic hearing via a hearing aid in the contralateral ear may improve CI users' F0 perception. For English-speaking CI users, contralateral acoustic hearing has been shown to improve perception of target speech in noise and in competing talkers. For tonal languages such as Mandarin Chinese, F0 information is lexically meaningful. Given competing F0 information from multiple talkers and lexical tones, contralateral acoustic hearing may be especially beneficial for Mandarin-speaking CI users' perception of competing speech. DESIGN:Bimodal benefit (CI+hearing aid - CI-only) was evaluated in 11 pediatric Mandarin-speaking Chinese CI users. In experiment 1, speech recognition thresholds (SRTs) were adaptively measured using a modified coordinated response measure test; subjects were required to correctly identify 2 keywords from among 10 choices in each category. SRTs were measured with CI-only or bimodal listening in the presence of steady state noise (SSN) or competing speech with the same (M+M) or different voice gender (M+F). Unaided thresholds in the non-CI ear and demographic factors were compared with speech performance. In experiment 2, SRTs were adaptively measured in SSN for recognition of 5 keywords, a more difficult listening task than the 2-keyword recognition task in experiment 1. RESULTS:In experiment 1, SRTs were significantly lower for SSN than for competing speech in both the CI-only and bimodal listening conditions. There was no significant difference between CI-only and bimodal listening for SSN and M+F (p > 0.05); SRTs were significantly lower for CI-only than for bimodal listening for M+M (p < 0.05), suggesting bimodal interference. Subjects were able to make use of voice gender differences for bimodal listening (p < 0.05) but not for CI-only listening (p > 0.05). Unaided thresholds in the non-CI ear were positively correlated with bimodal SRTs for M+M (p < 0.006) but not for SSN or M+F. No significant correlations were observed between any demographic variables and SRTs (p > 0.05 in all cases). In experiment 2, SRTs were significantly lower with two than with five keywords (p < 0.05). A significant bimodal benefit was observed only for the 5-keyword condition (p < 0.05). CONCLUSIONS:With the CI alone, subjects experienced greater interference with competing speech than with SSN and were unable to use voice gender difference to segregate talkers. For the coordinated response measure task, subjects experienced no bimodal benefit and even bimodal interference when competing talkers were the same voice gender. A bimodal benefit in SSN was observed for the five-keyword condition but not for the two-keyword condition, suggesting that bimodal listening may be more beneficial as the difficulty of the listening task increased. The present data suggest that bimodal benefit may depend on the type of masker and/or the difficulty of the listening task.

Conductive hearing loss is the impairment in the mechanical transduction of sound wave through the external ear and the middle ear.Although most cases are sporadic due to acquired causes such as infections （otitis media and otitis externa）,cerumen obstruction,and injuries,congenital structural defects are uncommon for significant etiologies to recognize.Stapes ankylosis is characterized by conductive hearing loss.It may be difficult to differentiate from otosclerosis,the most common cause of progressive conductive hearing loss,by audiologic evaluation,when the diagnosis is delayed.Skeletal anomalies may be subtle,such that