Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results.

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 .

AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial.

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 × 1011 vector genomes [vg] and five received 1·5 × 1012 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 0·5-4·0 kHz. In the participant who received the 9 × 1011 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 1·5 × 1012 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. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.

Unexpected Branch Malformation of the Facial Nerve during Stapes Surgery: Comparison between Intraoperative and Radiographic Findings.

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.

Atypical manifestations of acute coronary syndrome - throat discomfort: a multi-center observational study.

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.

Genome-wide miRNA analysis and integrated network for flavonoid biosynthesis in Osmanthus fragrans.

BACKGROUND: Osmanthus fragrans is an important economical plant containing multiple secondary metabolites including flavonoids and anthocyanins. During the past years, the roles of miRNAs in regulating the biosynthesis of secondary metabolites in plants have been widely investigated. However, few studies on miRNA expression profiles and the potential roles in regulating flavonoid biosynthesis have been reported in O. fragrans. RESULTS: In this study, we used high-throughput sequencing technology to analyze the expression profiles of miRNAs in leaf and flower tissues of O. fragrans. As a result, 106 conserved miRNAs distributed in 47 families and 88 novel miRNAs were identified. Further analysis showed there were 133 miRNAs differentially expressed in leaves and flowers. Additionally, the potential target genes of miRNAs as well as the related metabolic pathways were predicted. In the end, flavonoid content was measured in flower and leaf tissues and potential role of miR858 in regulating flavonoid synthesis was illustrated in O. fragrans. CONCLUSIONS: This study not only provided the genome-wide miRNA profiles in the flower and leaf tissue of O. fragrans, but also investigated the potential regulatory role of miR858a in flavonoid synthesis in O. fragrans. The results specifically indicated the connection of miRNAs to the regulation of secondary metabolite biosynthesis in non-model economical plant.

Direct Functional Protein Delivery with a Peptide into Neonatal and Adult Mammalian Inner Ear In Vivo.

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.

Otolaryngology Providers Must Be Alert for Patients with Mild and Asymptomatic COVID-19.

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.

Frequency-specific hearing results after stapes surgery for Chinese population otosclerosis with different degrees of hearing loss.

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.

Factors Affecting Bimodal Benefit in Pediatric Mandarin-Speaking Chinese Cochlear Implant Users.

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.

Cerebrospinal fluid otorrhea secondary to congenital inner ear dysplasia: diagnosis and management of 18 cases.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effect of Tinnitus and Duration of Deafness on Sound Localization and Speech Recognition in Noise in Patients With Single-Sided Deafness.

Patients with single-sided deafness (SSD) often experience poor sound localization, reduced speech understanding in noise, reduced quality of life, and tinnitus. The present study aims to evaluate effects of tinnitus and duration of deafness on sound localization and speech recognition in noise by SSD subjects. Sound localization and speech recognition in noise were measured in 26 SSD and 10 normal-hearing (NH) subjects. Speech was always presented directly in front of the listener. Noise was presented to the deaf ear, in front of the listener, or to the better hearing ear. Tinnitus severity was measured using visual analog scale and Tinnitus Handicap Inventory. Relative to NH subjects, SSD subjects had significant deficits in sound localization and speech recognition in all listening conditions ( p < .001). For SSD subjects, speech recognition in noise was correlated with mean hearing thresholds in the better hearing ear ( p < .001) but not in the deaf ear. SSD subjects with tinnitus performed poorer in sound localization and speech recognition in noise than those without tinnitus. Shorter duration of deafness was associated with greater tinnitus and sound localization difficulty. Tinnitus visual analog scale and Tinnitus Handicap Inventory were highly correlated; the degree of tinnitus was negatively correlated with sound localization and speech recognition in noise. Those experiencing noticeable tinnitus may benefit more from cochlear implantation than those without; subjective tinnitus reduction may be correlated with improved sound localization and speech recognition in noise. Subjects with longer duration of deafness demonstrated better sound localization, suggesting long-term compensation for loss of binaural cues.

Comparable Electrode Impedance and Speech Perception at 12 Months after Cochlear Implantation Using Round Window versus Cochleostomy: An Analysis of 40 Patients.

OBJECTIVE: The objective of this study was to examine whether cochlear implantation using the round window (RW) route versus cochleostomy achieves comparable electrode impedance and hearing results. METHODS: This retrospective analysis included 40 patients receiving a cochlear implant (REZ-1): 20 using the RW approach and the remaining 20 using cochleostomy. Electrode impedance and tone, vowel, consonant, disyllable and sentence perception were measured during and after the implantation. RESULTS: Electrode impedance did not differ significantly between the 2 groups at any time points [F(1, 38) = 1.84; p = 0.184]: 1.87, 5.16, 6.47 and 6.70 kΩ in the RW group versus 2.86, 5.33, 6.92 and 8.16 kΩ in the cochleostomy group at 0, 1, 3 and 12 months, respectively. There was no significant difference between the RW and cochleostomy groups for tone (77.50 vs. 80.50%; p = 0.472), vowel (77.70 vs. 78.65%; p = 0.760), consonant (75.50 vs. 78.25%; p = 0.443), disyllable (78.60 vs. 81.50%; p = 0.317) and sentence (50.90 vs. 52.50%; p = 0.684) perception at 12 months. CONCLUSION: The RW approach is comparable to cochleostomy in electrode placement as reflected by impedance and function as reflected by tone, vowel, consonant, disyllable and sentence perception.

The Benefits of Residual Hair Cell Function for Speech and Music Perception in Pediatric Bimodal Cochlear Implant Listeners.

Objective: The aim of this study was to investigate the benefits of residual hair cell function for speech and music perception in bimodal pediatric Mandarin-speaking cochlear implant (CI) listeners. Design: Speech and music performance was measured in 35 Mandarin-speaking pediatric CI users for unilateral (CI-only) and bimodal listening. Mandarin speech perception was measured for vowels, consonants, lexical tones, and sentences in quiet. Music perception was measured for melodic contour identification (MCI). Results: Combined electric and acoustic hearing significantly improved MCI and Mandarin tone recognition performance, relative to CI-only performance. For MCI, performance was significantly better with bimodal listening for all semitone spacing conditions (p < 0.05 in all cases). For tone recognition, bimodal performance was significantly better only for tone 2 (rising; p < 0.05). There were no significant differences between CI-only and CI + HA for vowel, consonant, or sentence recognition. Conclusions: The results suggest that combined electric and acoustic hearing can significantly improve perception of music and Mandarin tones in pediatric Mandarin-speaking CI patients. Music and lexical tone perception depends strongly on pitch perception, and the contralateral acoustic hearing coming from residual hair cell function provided pitch cues that are generally not well preserved in electric hearing.

Modulation of Glucose Takeup by Glucose Transport on the Isolated OHCs.

Glucose is a fundamental source of energy for mammalian cells; however, whether glucose is taken up through the lateral walls of cochlear outer hair cells (OHCs) is unknown. The OHC lateral wall is complex, composed of a plasma membrane, cortical lattice, and subsurface cisternae. This study assessed the uptake of glucose by OHCs using live-cell microscopy and examined the distribution of glucose transporter isoforms by immunohistochemistry. We found that glucose transporter-4 was mostly expressed on the lateral wall of OHCs. Glucose crossed the lateral walls of OHCs via glucose transporters-4 mainly, and this process could be modulated. These results suggest that the lateral walls are involved in modulating energy transport into OHCs.

Music Training Can Improve Music and Speech Perception in Pediatric Mandarin-Speaking Cochlear Implant Users.

Due to limited spectral resolution, cochlear implants (CIs) do not convey pitch information very well. Pitch cues are important for perception of music and tonal language; it is possible that music training may improve performance in both listening tasks. In this study, we investigated music training outcomes in terms of perception of music, lexical tones, and sentences in 22 young (4.8 to 9.3 years old), prelingually deaf Mandarin-speaking CI users. Music perception was measured using a melodic contour identification (MCI) task. Speech perception was measured for lexical tones and sentences presented in quiet. Subjects received 8 weeks of MCI training using pitch ranges not used for testing. Music and speech perception were measured at 2, 4, and 8 weeks after training was begun; follow-up measures were made 4 weeks after training was stopped. Mean baseline performance was 33.2%, 76.9%, and 45.8% correct for MCI, lexical tone recognition, and sentence recognition, respectively. After 8 weeks of MCI training, mean performance significantly improved by 22.9, 14.4, and 14.5 percentage points for MCI, lexical tone recognition, and sentence recognition, respectively ( p < .05 in all cases). Four weeks after training was stopped, there was no significant change in posttraining music and speech performance. The results suggest that music training can significantly improve pediatric Mandarin-speaking CI users' music and speech perception.

Effect of esterified hyaluronic acid as middle ear packing in tympanoplasty for adhesive otitis media.

OBJECTIVES: The goal of this study was to evaluate the effects of middle ear packing agents (MEPA) on post-operative hearing improvement and complications after tympanoplasty in patients with adhesive otitis media (OM). MATERIALS AND METHODS: Patients with adhesive OM who underwent tympanoplasty surgery were enrolled in the study between January 2012 and January 2015. A total of 205 patients who received canal wall-down tympanoplasty with ossicular chain reconstruction were randomized into one of the three groups with different MEPA. Group 1 (n = 72) received MeroGel as the MEPA, Group 2 (n = 64) cartilage, and Group 3 (n = 69) both. Air conduction (AC) and bone conduction (BC) thresholds at 0.5, 1, 2, and 4 kHz were measured, and air-bone gaps (ABG) were analyzed before and after the surgery for each patient. RESULTS: Mean pre- and post-operative ABG was 30.9 dB and 17.6 dB in Group 1, 31.4 dB and 21.9 dB in Group 2, and 32.2 dB and 19.1 dB in Group 3. The ABG closure was 13.3 ± 7.5 in Group 1, 9.5 ± 5.9 in Group 2, and 13.1 ± 9.3 in Group 3. The improvement of ABG after surgery was statistically significant in all three groups (p < .05). The ABG closure was statistically significantly smaller in Group 2 than in other two groups (p < .05). CONCLUSIONS: Tympanoplasty using esterified hyaluronic acid (i.e. MeroGel) or cartilage as the MEPA resulted in improved hearing for patients with conductive hearing loss due to adhesive OM. Using MeroGel as the MEPA appeared to achieve a better post-operative outcome than using cartilage.

Clinical observation on hearing conditions of centenarians in northern district of China.

CONCLUSION: The hearing conditions of the centenarians were quite poor as regards hearing thresholds and speech detection ability. OBJECTIVE: To investigate hearing conditions of centenarians. METHODS: A total of 54 centenarians in Rizhao and Linyi Districts in Shandong Province were investigated to assess hearing conditions of centenerians comprehensively by questionnaire investigation, pure-tone audiometry, acoustic immitance, intelligence evaluation, and speech detection scores. Also, 135 individuals were recruited as controls and divided into four groups according to their age: 45-59 years, 60-69 years, 70-79 years, and 80-89 years. RESULTS: The hearing thresholds of the centenarians were dramatically higher than those of the control group (p < 0.05) and all centenarians suffered moderate to profound hearing loss according to the World Health Organization (WHO) criteria. Few centenarians had normal level of speech detection scores. All centenarians showed descending hearing curve, and the hearing threshold of the male centenarians at 8000 Hz was higher than that of the females (p = 0.047). There was a significant air-bone conduction gap in the centenarians (p < 0.05).