Middle-ear osteolytic transthyretin amyloidosis: A CARE case report.

INTRODUCTION: Wild-type transthyretin amyloidosis (ATTRwt) is a rare but serious disease that is underestimated due to asymptomatic progression. Cardiac deposits worsen prognosis, highlighting the importance of early detection for preventive treatment. CASE REPORT: An elderly patient presented with an osteolytic lesion of the middle ear. Pathology diagnosed amyloid transthyretin deposits associated with cholesteatoma. DISCUSSION: Identifying reliable markers to screen for risk of cardiac amyloidosis is important, due to poor prognosis. Recent studies found higher prevalence of hearing loss in ATTRwt than in the general population. The present case identified the middle ear as a target of ATTR, which could improve our understanding of the pathophysiology.

Effect of hearing intervention on communicative function: A secondary analysis of the ACHIEVE randomized controlled trial.

BACKGROUND: The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) Study was designed to determine the effects of a best-practice hearing intervention on cognitive decline among community-dwelling older adults. Here, we conducted a secondary analysis of the ACHIEVE Study to investigate the effect of hearing intervention on self-reported communicative function. METHODS: The ACHIEVE Study is a parallel-group, unmasked, randomized controlled trial of adults aged 70-84 years with untreated mild-to-moderate hearing loss and without substantial cognitive impairment. Participants were randomly assigned (1:1) to a hearing intervention (audiological counseling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed semiannually for 3 years. Self-reported communicative function was measured with the Hearing Handicap Inventory-Elderly Screening version (HHIE-S, range 0-40, higher scores indicate greater impairment). Effect of hearing intervention versus control on HHIE-S was analyzed through an intention-to-treat model controlling for known covariates. RESULTS: HHIE-S improved after 6-months with hearing intervention compared to control, and continued to be better through 3-year follow-up. We estimated a difference of -8.9 (95% CI: -10.4, -7.5) points between intervention and control groups in change in HHIE-S score from baseline to 6 months, -9.3 (95% CI: -10.8, -7.9) to Year 1, -8.4 (95% CI: -9.8, -6.9) to Year 2, and - 9.5 (95% CI: -11.0, -8.0) to Year 3. Other prespecified sensitivity analyses that varied analytical parameters did not change the observed results. CONCLUSIONS: Hearing intervention improved self-reported communicative function compared to a control intervention within 6 months and with effects sustained through 3 years. These findings suggest that clinical recommendations for older adults with hearing loss should encourage hearing intervention that could benefit communicative function and potentially have positive downstream effects on other aspects of health.

Genomic and phenotypic landscapes of X-linked hereditary hearing loss in the Chinese population.

BACKGROUND: Hearing loss (HL) is the most common sensory birth deficit worldwide, with causative variants in more than 150 genes. However, the etiological contribution and clinical manifestations of X-linked inheritance in HL remain unclear within the Chinese HL population. In this study, we focused on X-linked hereditary HL and aimed to assess its contribution to hereditary HL and identify the genotype-phenotype relationship. METHODS: We performed a molecular epidemiological investigation of X-linked hereditary HL based on next-generation sequencing and third-generation sequencing in 3646 unrelated patients with HL. We also discussed the clinical features associated with X-linked non-syndromic HL-related genes based on a review of the literature. RESULTS: We obtained a diagnostic rate of 52.72% (1922/3646) among our patients; the aggregate contribution of HL caused by genes on the X chromosome in this cohort was ~ 1.14% (22/1922), and POU3F4 variants caused ~ 59% (13/22) of these cases. We found that X-linked HL was congenital or began during childhood in all cases, with representative audiological profiles or typical cochlear malformations in certain genes. Genotypic and phenotypic analyses showed that causative variants in PRPS1 and AIFM1 were mainly of the missense type, suggesting that phenotypic variability was correlated with the different effects that the replaced residues exert on structure and function. Variations in SMPX causing truncation of the protein product were associated with DFNX4, which resulted in typical audiological profiles before and after the age of 10 years, whereas nontruncated proteins typically led to distal myopathy. No phenotypic differences were identified in patients carrying POU3F4 or COL4A6 variants. CONCLUSIONS: Our work constitutes a preliminary evaluation of the molecular contribution of X-linked genes in heritable HL (~ 1.14%). The 15 novel variants reported here expand the mutational spectrum of these genes. Analysis of the genotype-phenotype relationship is valuable for X-linked HL precise diagnostics and genetic counseling. Elucidation of the pathogenic mechanisms and audiological profiles of HL can also guide choices regarding treatment modalities.

Does cochlear implantation affect personality of hearing-impaired patients? A five-year follow-up study.

BACKGROUND: Previous studies found that in patients with profound hearing loss the NEO- personality factor Openness-to-experience is lowered. OBJECTIVE: Assuming that lowered Openness-to-experience may be due to limited access to sounds, we hypothesized that levels of Openness-to-experience would increase in these patients after cochlear implantation. MATERIAL AND METHODS: Twenty adults (mean age: 61 years; active CI users) with bilateral profound hearing loss were assessed with the NEO-Five-Factor-Inventory before cochlear implantation (pre) and five years later (post). RESULTS: No significant pre-post changes in personality were seen. Both before and five years after cochlear implantation, the sample had normal age- and gender-specific mean values on the factors Extraversion, Neuroticism, Agreeableness, and Conscientiousness (T ≈ 50), but significantly lowered mean values on Openness-to-experience (T ≈ 42, p < 0.001). CONCLUSIONS AND SIGNIFICANCE: Cochlear implantation apparently has no (or at best very little) effect on Openness-to-experience in profoundly hearing impaired patients. While this study demonstrates once again, that high-grade hearing loss may be associated with less openness to new experiences, the reason for this association remains unclear.

[The LittlEARS® Auditory Questionnaire : An analysis of multicentre data of children after early bilateral cochlear implant placement]. / Der LittlEARS® Hörfragebogen : Auswertung multizentrischer Daten von Kindern nach früher bilateraler Cochleaimplantatversorgung.

BACKGROUND: In order to optimise the support of children with cochlear implants (CI), it is very important to detect slow developmental processes as early as possible. Data from the LittlEARS® Auditory Questionnaire (LEAQ) from children with early bilateral CI are evaluated and presented in relation to age and hearing age and compared with language development data recorded later. MATERIALS AND METHODS: This retrospective multicentre study included data from a total of 554 children for whom at least one LEAQ was completed during the course of CI rehabilitation. Children without additional disabilities who received bilateral simultaneous or sequential CI treatment were included. RESULTS: As expected, there are high correlations between hearing age (HA) and the overall LEAQ total score. When analysed according to chronological age (CA), development runs roughly parallel to the development of children with normal hearing, albeit at a lower level. Children implanted early up to an age of ≤ 12 months consistently achieve approximately 7-8 raw points more. Only the LEAQ results of the later test times (from the age of 18 months) correlate with some areas of the speech development test for children (SETK; areas 3-5). CONCLUSION: The earliest possible detection of critical developmental processes in children with CI is extremely important. In the case of very early CI fitting, the CA should be used as a reference measure in diagnostics. The LEAQ values determined for the group of children with CI are suitable to a limited extent as generally valid reference values for children with early bilateral CI. Further studies should continue to work out the correlations between early preverbal development and later speech development.

The relationship between changes in functional connectivity gradients and cognitive-emotional disorders in sudden sensorineural hearing loss.

Sudden sensorineural hearing loss, a prevalent emergency in otolaryngology, is known to potentially precipitate cognitive and emotional disorders in affected individuals. Extensive research has documented the phenomenon of cortical functional reorganization in patients with sudden sensorineural hearing loss. However, the potential link between this neural functional remodelling and cognitive-emotional disorders remains unclear. To investigate this issue, 30 bilateral sudden sensorineural hearing loss patients and 30 healthy adults were recruited for this study. We collected clinical data and resting-state functional magnetic resonance imaging data from the participants. Gradient mapping analysis was employed to calculate the first three gradients for each subject. Subsequently, gradient changes in sudden sensorineural hearing loss patients were compared with healthy controls at global, regional and network levels. Finally, we explored the relationship between gradient values and clinical variables. The results revealed that at the global level, sudden sensorineural hearing loss did not exhibit significant differences in the primary gradient but showed a state of compression in the second and third gradients. At the regional level, sudden sensorineural hearing loss patients exhibited a significant reduction in the primary gradient values in the temporal pole and ventral prefrontal cortex, which were closely related to neuro-scale scores. Regarding the network level, sudden sensorineural hearing loss did not show significant differences in the primary gradient but instead displayed significant changes in the control network and default mode network in the second and third gradients. This study revealed disruptions in the functional hierarchy of sudden sensorineural hearing loss, and the alterations in functional connectivity gradients were closely associated with cognitive and emotional disturbances in patients. These findings provide new evidence for understanding the functional remodelling that occurs in sudden sensorineural hearing loss.

Development of a family-centred intervention for families and children with hearing loss transitioning into early intervention: application of the Behaviour Change Wheel.

OBJECTIVE: To describe the application of the Behaviour Change Wheel (BCW) to the development of a family-centred intervention for families of children with hearing loss transitioning into early intervention. DESIGN: The BCW was used in a mixed methods design to understand the gaps in family-centred service provision and to identify appropriate intervention functions and implementation options to address these gaps. STUDY SAMPLE: Families and health professionals participated in different steps of the BCW. RESULTS: The qualitative interviews revealed that families required individualised information and support. The quantitative and interview data suggested inconsistencies in the provision of information and support to some families. It was determined that administration of a needs assessment by the support professionals was the most appropriate target behaviour to address this issue. In the analysis of the professionals' capabilities, opportunities, and motivations for administration of a needs assessment, a resource limitation was identified, and therefore, a Minimum Data Set for a Needs Assessment Tool was developed to facilitate the assessment of families' needs during the transition period. CONCLUSIONS: This study provided an example of how the BCW could be successfully applied to the design of a family-centred intervention for families of children with hearing loss.

Central Hearing Loss in a Pediatric Patient.

Sensorineural hearing loss is typically caused by dysfunction of the inner ear or auditory nerve. In pediatric patients diagnosed with sensorineural hearing loss, work-up often includes genetic testing and imaging studies of the auditory pathway. Here, we report a case of a pediatric patient with a history of sensorineural hearing loss following cisplatin and radiation therapy for brainstem medulloblastoma, developing symptoms and signs of central hearing loss based on audiometric and MRI/diffusion tensor imaging studies. Though rare, central hearing loss should be considered among the causes of sensorineural hearing loss in children. Laryngoscope, 2024.

Sensorineural Hearing Loss in Patients With the m.1555A>G Mutation in the MTRNR1 Gene.

OBJECTIVE: Mutations in the MTRNR1 gene of mitochondrial DNA are associated with non-syndromic hearing loss and increased susceptibility to aminoglycoside ototoxicity. The aim of our study was to determine the clinical characteristics of sensorineural hearing loss caused by the m.1555A>G mutation in MTRNR1. METHODS: An observational retrospective study of the m.1555A>G mutation was conducted in patients with suspected hereditary bilateral sensorineural hearing loss in the Department of Otolaryngology of the Marqués de Valdecilla University Hospital (Cantabria, Spain) and in 100 controls with normal hearing. RESULTS: The m.1555A>G mutation was found in 82 individuals from 20 different families and in none of the controls. Variable degrees of hearing loss were observed, ranging from normal hearing to profound deafness. Patients with a history of streptomycin administration exhibited significantly more pronounced hearing loss. The onset of hearing loss occurred from childhood to adulthood, with progression or stability over the years. No associated vestibular alterations or other clinical manifestations outside the ear were found. Two cochlear implant recipients showed significant improvement in speech comprehension. CONCLUSIONS: Patients with the m.1555A>G mutation in the MTRNR1 gene often develop bilateral, symmetric sensorineural hearing loss, predominantly affecting high frequencies, worsened by streptomycin administration. This mutation does not affect the vestibular function. The variability in the severity of hearing loss, the heterogeneity of phenotypic expression, and the presence of carrier individuals with normal hearing may indicate the existence of modifying factors, both environmental and genetic. Cochlear implantees showed a good response in terms of speech intelligibility. Genetic testing for this mutation is recommended in patients with a family history of hearing loss to prevent the use of aminoglycosides if the mutation is found. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort.

INTRODUCTION: Hearing loss is identified as one of the largest modifiable risk factors for cognitive impairment and dementia. Studies evaluating this relationship have yielded mixed results. METHODS: We investigated the longitudinal relationship between self-reported hearing loss and cognitive/functional performance in 695 cognitively normal (CN) and 941 participants with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative. RESULTS: Within CN participants with hearing loss, there was a significantly greater rate of cognitive decline per modified preclinical Alzheimer's cognitive composite. Within both CN and MCI participants with hearing loss, there was a significantly greater rate of functional decline per the functional activities questionnaire (FAQ). In CN and MCI participants, hearing loss did not significantly contribute to the risk of progression to a more impaired diagnosis. DISCUSSION: These results confirm previous studies demonstrating a significant longitudinal association between self-reported hearing loss and cognition/function but do not demonstrate an increased risk of conversion to a more impaired diagnosis. CLINICAL TRIAL REGISTRATION INFORMATION: NCT00106899 (ADNI: Alzheimer's Disease Neuroimaging Initiative, clinicaltrials.gov), NCT01078636 (ADNI-GO: Alzheimer's Disease Neuroimaging Initiative Grand Opportunity, clinicaltrials.gov), NCT01231971 (ADNI2: Alzheimer's Disease Neuroimaging Initiative 2, clinicaltrials.gov), NCT02854033 (ADNI3: Alzheimer's Disease Neuroimaging Initiative 3, clinicaltrials.gov). HIGHLIGHTS: Hearing loss is a potential modifiable risk factor for dementia. We assessed the effect of self-reported hearing loss on cognition and function in the ADNI cohort. Hearing loss contributes to significantly faster cognitive and functional decline. Hearing loss was not associated with conversion to a more impaired diagnosis.

Exploring delivery systems for targeted nanotechnology-based gene therapy in the inner ear.

Hearing loss places a significant burden on our aging population. However, there has only been limited progress in developing therapeutic techniques to effectively mediate this condition. This review will outline several of the most commonly utilized practices for the treatment of sensorineural hearing loss before exploring more novel techniques currently being investigated via both in vitro and in vivo research. This review will place particular emphasis on novel gene-delivery technologies. Primarily, it will focus on techniques used to deliver genes that have been shown to encourage the proliferation and differentiation of sensory cells within the inner ear and how these technologies may be translated into providing clinically useful results for patients.

[Box: see text].

Urolithin A prevents age-related hearing loss in C57BL/6J mice likely by inducing mitophagy.

Mitochondrial dysfunction with aging is associated with the development of age-related hearing loss. Mitophagy is a cardinal mechanism to maintain a healthy mitochondrial population through the turnover of damaged mitochondria. Declining mitophagy with age causes a buildup of damaged mitochondria, leading to sensory organ dysfunction. The effect of Urolithin A (UA), a mitophagy inducer, was investigated on age-related hearing loss in a mouse model. C57BL/6J mice were treated with UA from 6 to 10 months of age. UA attenuated an auditory brainstem responses (ABR) threshold shift at 8, 16, and 32 kHz frequencies, and improved mitochondrial DNA integrity and ATP production in the cochlea and auditory cortex. The mRNA levels of mitophagy-related genes and protein levels of PINK1, Parkin, BNIP3, and LC3B increased in the cochlea and auditory cortex. The expression of mitophagosomes and mitophagolysosomes in the cochlea, spiral ganglion, auditory cortex, and inferior colliculus increased, together with the expression of Parkin and BNIP3 in the cochlea, spiral ganglion, auditory cortex, and inferior colliculus. These results indicate that UA counteracted mitophagy decline in the auditory system and prevented age-related hearing loss. UA can be used as a potential agent to prevent age-related hearing loss.

Sudden Hearing Loss Waves: The Effect of COVID-19 Infection and Vaccination on the Inner Ear.

Sudden sensorineural hearing loss (SSNHL) has emerged as a potential complication of COVID-19 infection and vaccination. Various mechanisms by which the SARS-CoV-2 virus can cause hearing loss have been reported, including direct viral invasion, neuroinflammation, blood flow disturbances, and immune-mediated response. However, the temporal relationship between COVID-19 infection and SSNHL remains unclear, with mixed findings and conflicting results reported in different studies. Similarly, while anecdotal reports have linked COVID-19 vaccination to SSNHL, evidence remains scarce. Establishing a correlation between COVID-19 vaccines and SSNHL implies a complex and multifactorial pathogenesis involving interactions between the immune system and the body's stress response. Nevertheless, it is important to consider the overwhelming evidence of the vaccines' safety and efficacy in limiting the spread of the disease and remains the primordial tool in reducing death.

Apple AirPods Pro as a Hearing Assistive Device in Patients with Mild to Moderate Hearing Loss.

PURPOSE: This study aimed to assess the feasibility of the Apple AirPods Pro with the headphone accommodation feature as a hearing assistive device for patients with mild to moderate hearing loss (HL). MATERIALS AND METHODS: The study included a total of 35 participants with mild to moderate HL. To determine the degree of HL in the participants, a screening test using pure-tone audiometry was conducted prior to the main tests of functional gain, word recognition score (WRS), and sentence recognition in noisy environments. The study employed two hearing devices: the Bean (a personal sound amplification product, PSAP) and the AirPods Pro. RESULTS: Regarding functional gain, there were no significant differences between the Bean and the AirPods Pro at all frequencies, except 8 kHz. In terms of WRS, both the Bean and the AirPods Pro had higher scores than the unaided condition. In sentence recognition, both the Bean and the AirPods Pro had higher scores than the unaided condition. During real-ear measurement, the Bean demonstrated consistent frequency responses, while the AirPods had a deviation exceeding 10 dB SPL at 6 kHz in the left ear. This deviation was absent for all other frequencies. CONCLUSION: This study shows that the Apple AirPods Pro, with its headphone accommodation feature, performed similarly to a validated PSAP and improved hearing compared to unaided conditions.

Comparison of Outcomes After Cochlear Implantation in a Veteran Versus Nonveteran Population.

Objective: To evaluate for equivalence in postoperative changes of speech recognition scores in a veteran patient population undergoing cochlear implantation (CI) compared to matched nonveteran patients. Study Design: Retrospective chart review. Setting: Tertiary referral center. Patients: A total of 83 veteran patients who underwent CI at a single Veterans Affairs Medical Center (VA cohort) were matched to 83 nonveteran patients from the Health Insurance Portability and Accountability Act-secure, Encrypted, Research, Management and Evaluation Solution database (HERMES cohort) based on age, sex, and baseline Consonant-Nucleus-Consonant (CNC) scores. Intervention: Patients underwent CI. Main Outcome Measures: Comparison of postoperative CNC and Arizona Biomedical Institute recognition scores. Results: The mean difference and lower confidence interval of CNC scores between matched Veterans Affairs and HERMES cohorts were within a -ΔNI boundary of -15% at the 3-month (mean = 6.15, lower confidence interval = -2.38), 6-month (mean = 7.36, lower confidence interval = -2.21), and 12-month (mean = 4.03, lower confidence interval = -4.88) postoperative time points. The mean difference and lower confidence interval of Arizona Biomedical Institute scores between cohorts were within the -ΔNI boundary of -30% at 3 months (mean = 1, lower confidence interval = -8.71), 6 months (mean = 0.31, lower confidence interval = -12.30), and 12 months (mean = 0.72, lower confidence interval = -10.48). Conclusion: Our veteran population demonstrated improvements in speech recognition scores after CI comparable to a matched nonveteran population. Although veterans face unique factors that affect their hearing, access to medical care, and baseline general health, these findings affirm appropriate veteran candidates should be offered CI.

Automatic Segmentation of Heschl Gyrus and Planum Temporale by MRICloud.

Objectives: This study used a cloud-based program, MRICloud, which parcellates T1 MRI brain scans using a probabilistic classification based on manually labeled multi-atlas, to create a tool to segment Heschl gyrus (HG) and the planum temporale (PT). Methods: MRICloud is an online platform that can automatically segment structural MRIs into 287 labeled brain regions. A 31-brain multi-atlas was manually resegmented to include tags for the HG and PT. This modified atlas set with additional manually labeled regions of interest acted as a new multi-atlas set and was uploaded to MRICloud. This new method of automated segmentation of HG and PT was then compared to manual segmentation of HG and PT in MRIs of 10 healthy adults using Dice similarity coefficient (DSC), Hausdorff distance (HD), and intraclass correlation coefficient (ICC). Results: This multi-atlas set was uploaded to MRICloud for public use. When compared to reference manual segmentations of the HG and PT, there was an average DSC for HG and PT of 0.62 ± 0.07, HD of 8.10 ± 3.47 mm, and an ICC for these regions of 0.83 (0.68-0.91), consistent with an appropriate automatic segmentation accuracy. Conclusion: This multi-atlas can alleviate the manual segmentation effort and the difficulty in choosing an HG and PT anatomical definition. This protocol is limited by the morphology of the MRI scans needed to make the MRICloud atlas set. Future work will apply this multi-atlas to observe MRI changes in hearing-associated disorders.

Hearing impairment amongst people with Osteogenesis Imperfecta in Germany.

INTRODUCTION: Hearing impairment concerns a relevant percentage of individuals with Osteogenesis Imperfecta (OI). When looking at the current literature, the percentage of affected individuals with OI varies greatly from 32 to 58% of patients having mild OI and 21% to 27% of patients having moderate to severe OI. Little is known about the German population with OI. METHOD: The goal of this study was to detect how many patients with OI, who visited the annual meeting of the German Association for Osteogenesis Imperfecta in 2023, proved to have a hearing impairment. In this prospective, cross-sectional study, each included individual obtained ear microscopy, audiometry, stapedius reflexes, tympanometry, and OAEs. Furthermore, each patient was asked a set of questions concerning the medical history. RESULTS: Of the included patients, 33% had hearing impairment. A significant difference was found for the mean air-bone gap (ABG) as well as the hearing threshold of the right ears. The difference was found between OI type III and IV (p = 0.0127) for the mean ABG and OI type I and IV (p = 0.0138) as well as III and IV (p = 0.0281) for the hearing threshold. Spearman's rank correlation showed a high correlation between age and hearing threshold. Of the patients between 40 and 50 years old, 56% had hearing loss. CONCLUSION: Hearing loss in individuals with OI is still a relevant problem, especially age-related in OI type I. Audiometry should be performed at least when individuals experience subjective hearing loss. The implementation of a screening starting at 40 years should be discussed and studied.

Cochlear Implantation for Isoleucyl-tRNA Synthetase Mutation-Associated Mitochondrial Disease: A Case Report.

Biallelic missense mutations in the nuclear-encoded, cytosolic isoleucyl-tRNA synthetase (IARS) gene are associated with a rare and complex multisystemic phenotype, including growth retardation, intellectual disability, muscular hypotonia, diabetes mellitus, and deafness. These mutations impact the cytosolic isoform of IARS, which plays a crucial role in protein synthesis. The pathogenesis involves mitochondrial dysfunction, despite IARS being primarily a cytosolic enzyme, potentially linking it to the observed clinical manifestations. The efficacy of cochlear implantation for deafness due to IARS mutations and the safety of general anesthesia in such patients remain unclear. This report describes a rare case of progressive sensorineural hearing loss caused by IARS mutation-associated mitochondrial disease, which was successfully treated with cochlear implantation. Additionally, we discuss the safety of general anesthesia in this patient. A Japanese woman with IARS mutation-associated mitochondrial disease was diagnosed with severe bilateral sensorineural hearing loss at five years of age and immediately received hearing aids. Her hearing progressively deteriorated to profound impairment, necessitating cochlear implantation at 26 years of age, which resulted in satisfactory hearing. Furthermore, no perioperative general anesthesia-related adverse events were reported. Our case demonstrates that cochlear implantation can effectively restore hearing. This suggests that sensorineural hearing loss caused by IARS deficiency is primarily due to cochlear dysfunction. This case demonstrated that hearing loss is a crucial feature of IARS mutation-associated mitochondrial disease, which can be mitigated by cochlear implantation. While general anesthesia can be safely administered, careful consideration of anesthetic choices, such as avoiding depolarizing muscle relaxants and prolonged use of propofol, is essential to prevent complications. In this case, general anesthesia was well tolerated without perioperative events, providing valuable insight into the potential safety of such procedures in similar patients. Nevertheless, further studies are needed to confirm these findings across a broader population.

Changes in participatory and societal outcomes during the waiting period for cochlear implantation - an observational study.

INTRODUCTION: Various factors, including an aging population and expanding eligibility criteria, may increase the demand for cochlear implants (CIs), potentially resulting in longer waiting times. In most Dutch CI centers, the time between referral and surgery exceeds 6 months. Clinical experience suggests that during the waiting period for cochlear implantation, hearing and communication difficulties increase. Simultaneously, there is an interest in outcomes more closely aligned with patient values and needs, which resulted in the SMILE (Societal Merit of Interventions on hearing Loss Evaluation) study. This paper presents results on observed changes in societal and participatory outcomes during waiting time in participants with a time to CI surgery exceeding 6 months. METHODS: SMILE is a prospective multi-center study including 232 individuals who were referred for unilateral CI. Continuous and nominal data from multiple questionnaires, sent immediately after referral and shortly before surgery, were analyzed by computing differences, Cohen's D, and odds ratios. RESULTS: Of the total 232 participants, 102 had a time between inclusion and surgery exceeding 6 months. Of these, 89 had (partially) filled out surveys at both time points. Of all the domain scores 55% did not show differences between timepoints. All Cohen's D estimates were relatively small, ranging from - 0.298 to 0.388 for those outcomes that showed noteworthy changes. CONCLUSION: Waiting time from referral to surgery, even though exceeding 6 months, was observed to not seriously affect non-clinically-prioritized patients in an adverse way. Future investigations should identify subgroups on tolerable waiting times regarding short- and long-term outcomes. TRIAL REGISTRATION: Trial registration number at ClinicalTrials.gov: NCT05525221, 25-8-2022.

Developmental cochlear defects are involved in early-onset hearing loss in A/J mice.

BACKGROUND: A/J mice exhibited a severe hearing loss (HL) at juvenile stage. Up-to-date, studies on HL in A/J mice have mostly focused on the damage or dysfunction of hair cells (HCs), spiral ganglion neurons (SGNs), and stereocilia. We examined A/J mice at the early postnatal stage and found that the damage and the loss of outer hair cells (OHCs) are not severe enough to explain the profound HL observed at this age, which suggests that other cochlear defects may be responsible for HL. To better understand the mechanisms of early-onset HLin A/J mice, we characterized the pathology of the cochlea from postnatal day 3 to day 21. RESULTS: Our results showed defects in cochlear HC stereocilia and MET channel function as early as 3 days old. We also found abnormal localization and a significant reduction in the number of ribbon synapses in 2-week-old A/J mice. There are also abnormalities in the cochlear nerve innervation and terminal swellings in 3-week-old A/J mice. CONCLUSION: All of the abnormalities of cochlear existed in the A/J mice were identified in the juvenile stage and occurred before HCs or auditory nerve loss and was the initial pathological change. Our results suggest that developmental defects and subsequent cochlear degeneration are responsible for early-onset hearing loss in A/J mice.