A comparative study of audiological outcomes and compliance between the Osia system and other bone conduction hearing implants.

PURPOSE: To examine the subjective and objective audiological benefits of the Osia system compared to devices commonly implanted prior to the introduction of this system. METHODS: Osia recipients with either conductive hearing loss (CHL/MHL) (n = 9) or single-sided deafness (SSD) (n = 8) who underwent surgery from February 2021 to March 2022 were prospectively recruited. The audiological outcomes and usage rate of Osia implantees were compared with those of retrospectively recruited patients implanted with other devices (n = 50). The subjective satisfaction of the Osia implantees was also evaluated through questionnaires. RESULTS: All users of the Osia system were classified as regular users. In the CHL/MHL group, the effective gain of the Osia system (11.1 ± 14.9 dB) surpassed that of the Baha and Bonebridge (- 2.7 ± 12.6 dB) at 2 kHz (p = 0.01, Mann-Whitney U test). Among the devices, the Osia system tended to tolerate the worst bone conduction thresholds, up to the level of 61 dB. In the SSD group, the functional gain of Osia at 4 kHz (37.5 ± 3.1 dB) was higher than that of the Baha and Bonebridge group (26.9 ± 3.0 dB) (p = 0.05, Mann-Whitney U test). CONCLUSION: The Osia system yielded larger audiological gain than the Baha Attract and Bonebridge devices, especially at high frequencies, leading to substantially higher compliance. The Osia system tended to have the strongest tolerance to aggravated bone conduction thresholds among the available transcutaneous bone conduction hearing implants. Therefore, the Osia system could potentially be a good option for CHL/MHL patients with bone conduction thresholds of 50 dB HL or more, as well as patients with SSD.

Update on CD164 and LMX1A genes to strengthen their causative role in autosomal dominant hearing loss.

Novel hearing loss (HL) genes are constantly being discovered, and evidence from independent studies is essential to strengthen their position as causes of hereditary HL. To address this issue, we searched our genetic data of families with autosomal dominant HL (ADHL) who had been tested with high-throughput DNA sequencing methods. For CD164, only one pathogenic variant in one family has so far been reported. For LMX1A, just two previous studies have revealed its involvement in ADHL. In this study we found two families with the same pathogenic variant in CD164 and one family with a novel variant in LMX1A (c.686C>A; p.(Ala229Asp)) that impairs its transcriptional activity. Our data show recurrence of the same CD164 variant in two HL families of different geographic origin, which strongly suggests it is a mutational hotspot. We also provide further evidence for haploinsufficiency as the pathogenic mechanism underlying LMX1A-related ADHL.

Molecular aetiology of ski-slope hearing loss and audiological course of cochlear implantees.

PURPOSE: A challenge for patients with ski-slope hearing loss is that hearing aids do not adequately amplify the mid-to-high frequencies necessary for speech perception and conversely, cochlear implant (CI) may damage low-frequency hearing. We aimed to describe the clinical profile of patients with ski-slope hearing loss, with a special focus on aetiology of such hearing loss and audiological course of low-frequency hearing after CI. METHODS: We recruited hearing-impaired patients who visited a tertiary referral centre and met the criteria for ski-slope hearing loss patients from 2015 to 2021. Genetic testing was performed in all ski-slope hearing loss patients unless refused. Baseline audiograms of patients who continued to use hearing aids or who finally underwent CIs were reviewed. As for CI patients, outcome and hearing preservation rate were rigorously analysed. RESULTS: Of 46 recruited patients with ski-slope hearing loss, 45 agreed to undergo genetic testing and causative variants were identified in 17 (37.8%) patients. The TMC1, MYO7A, and TMPRSS3 variants were the most common, while LRTOMT was newly identified as a causative gene. Twenty-five patients eventually received CI, while 13 continued to wear the hearing aid and 8 patients did not ever try hearing aids. CI in ski-slope hearing loss led to immediate and sufficient improvement of sentence recognition by as early as 3 months, however, the duration of hearing loss was inversely correlated with the sentence recognition score. The average hearing preservation rate (using the HEARRING classification) after CI was 53.0% (SD 30.0) and 45.6% (SD 31.1) at 1 year. Seventy-nine percent of implantees maintained functional low-frequency hearing (better than 85 dB at 250 and 500 Hz) eligible for electric-acoustic stimulation (EAS). A trend was found that patients with hair cell stereocilia-associated genetic variants may have a slightly better preservation, albeit with no statistical significance. CONCLUSION: Detection rate of a molecular genetic aetiology of ski-slope hearing loss appears to be lower than other type of hearing loss reported in the literature. Especially with short hearing loss duration, CI in ski-slope hearing loss leads to immediate and sufficient speech improvement, while preserving functional low-frequency hearing eligible for EAS as many as in 79%. A certain genetic aetiology might be associated with a trend towards better low-frequency hearing preservation.

Tight modiolar proximity and feasibility of slim modiolar cochlear implant electrode array insertion in diverse etiologies of hearing loss.

PURPOSE: To report on our experience with the slim modiolar electrode (SME) especially focusing on the wide range of etiologies including inner ear anomalies, tumors, ossifications, and even revision surgeries. METHODS: All the cochlear implantation cases performed from June 2018 to September 2019 by a single surgeon was prospectively recruited. The molecular/radiological etiology of hearing loss, intraoperative outcomes, and radiographic studies of cases where the SME was implanted was reviewed to evaluate compatibility of SME for the wide range of etiologies. For cases where SME replaced the other electrode as a revision, audiologic assessment was also made. RESULTS: Among the 99 ears implanted during the study period, the SME was successfully implanted in 86 ears. These SME cases comprised inner ear anomaly/cochear nerve deficiency (n = 21) including cochlear hypoplasia type IV with the modiolus, intracochlear schwannoma (n = 1), far advanced otosclerosis (n = 1) and 7 revision cases. The SME was successfully used in 7 revision surgeries to replace the existing electrode. Shorter spiral diameter and decreased intracochlear position index for SME was found compared with their previous electrodes. Four out of the 6 patients who received revision implantation showed better speech perception after their surgeries. CONCLUSION: The SME can be implanted in any cases unless the integrity of the modiolus is totally compromised. Due to its slim design and tight modiolar-hugging feature, good functional outcome can also be anticipated. Additionally, it is suitable for revision surgeries possibly allowing better hearing outcomes which may be attributed to its closer proximity to the modiolus.

Cortical reorganization following auditory deprivation predicts cochlear implant performance in postlingually deaf adults.

Long-term hearing loss in postlingually deaf (PD) adults may lead to brain structural changes that affect the outcomes of cochlear implantation. We studied 94 PD patients who underwent cochlear implantation and 37 patients who were MRI-scanned within 2 weeks after the onset of sudden hearing loss and expected with minimal brain structural changes in relation to deafness. Compared with those with sudden hearing loss, we found lower gray matter (GM) probabilities in bilateral thalami, superior, middle, inferior temporal cortices as well as the central cortical regions corresponding to the movement and sensation of the lips, tongue, and larynx in the PD group. Among these brain areas, the GM in the middle temporal cortex showed negative correlation with disease duration, whereas the other areas displayed positive correlations. Left superior, middle temporal cortical, and bilateral thalamic GMs were the most accurate predictors of post-cochlear implantation word recognition scores (mean absolute error [MAE] = 10.1, r = .82), which was superior to clinical variables used (MAE: 12.1, p < .05). Using the combined brain morphological and clinical features, we achieved the best prediction of the outcome (MAE: 8.51, r = .90). Our findings suggest that the cross-modal plasticity allowing the superior temporal cortex and thalamus to process other modal sensory inputs reverses the initially lower volume when deafness becomes persistent. The middle temporal cortex processing higher-level language comprehension shows persistent negative correlations with disease duration, suggesting this area's association with degraded speech comprehensions due to long-term deafness. Morphological features combined with clinical variables might play a key role in predicting outcomes of cochlear implantation.

Risk Factors for Lateral Neck Recurrence of N0/N1a Papillary Thyroid Cancer.

BACKGROUND: Current guidelines advocate no prophylactic dissection of the lateral neck compartment for papillary thyroid carcinoma (PTC) without clinical evidence of lateral neck metastasis (cN1b). However, lateral neck recurrence can affect patient treatment outcomes and quality of life. Therefore, this study examined the risk factors for lateral neck recurrence after the definitive treatment of PTC without cN1b. METHODS: The study enrolled 1928 consecutive patients who underwent total thyroidectomy between 2006 and 2012 for PTC without cN1b. Logistic regression analysis was used to identify the relationship of clinicopathologic factors with lateral neck recurrence. Uni- and multivariate Cox-proportional hazards regression analyses were used to identify factors predictive of lateral neck recurrence-free survival (LRFS). RESULTS: During a median follow-up period of 94 months (range, 24-133 months), lateral neck recurrence occurred in 47 patients (2.4%). Binary logistic regression showed that tumor size (>2 cm), multifocality, clinical central neck metastasis (cN1a), number of positive lymph nodes (LNs, >5), and LN ratio (>0.5) were significantly associated with lateral neck recurrence (P < 0.05). Multivariate analyses showed that multifocality (hazards ratio [HR], 2.338; 95% confidence interval [CI], 1.126-4.858; P = 0.023), cN1a (HR, 5.301; 95% CI, 2.416-11.630; P < 0.001), LN ratio (HR, 2.628; 95% CI, 1.228-5.626; P = 0.013), extranodal extension (HR, 2.570; 95% CI, 1.063-6.213; P = 0.036), and MACIS (distant metastasis, patient age, completeness of resection, local invasion and tumour size) score (HR, 2.513; 95% CI, 1.211-5.216; P = 0.013) were independent factors for LRFS. CONCLUSIONS: Lateral neck recurrence after thyroidectomy is predicted by the clinicopathologic factors of multifocality, cN1a, LN ratio, extranodal extension, and MACIS score in N0/N1a PTC patients.

Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation.

Mutations in microRNA-96 (MIR96) cause autosomal dominant deafness-50 (DFNA50), a form of delayed-onset hearing loss. Genome editing has shown efficacy in hearing recovery through intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications, which has not been done. Here, we developed a genome editing therapy for the MIR96 mutation 14C>A by screening different CRISPR systems and optimizing Cas9 expression and the sgRNA scaffold for efficient and specific mutation editing. AAV delivery of the KKH variant of Staphylococcus aureus Cas9 (SaCas9-KKH) and sgRNA to the cochleae of presymptomatic (3-week-old) and symptomatic (6-week-old) adult Mir9614C>A/+ mutant mice improved hearing long term, with efficacy increased by injection at a younger age. Adult inner ear delivery resulted in transient Cas9 expression without evidence of AAV genomic integration, indicating the good safety profile of our in vivo genome editing strategy. We developed a dual-AAV system, including an AAV-sgmiR96-master carrying sgRNAs against all known human MIR96 mutations. Because mouse and human MIR96 sequences share 100% homology, our approach and sgRNA selection for efficient and specific hair cell editing for long-term hearing recovery lay the foundation for the development of treatment for patients with DFNA50 caused by MIR96 mutations.

An endoscopic approach to stapes surgery needs less external auditory canal wall removal than a microscopic approach.

BACKGROUND: Although many advantages of endoscopic stapes surgery have been reported, there is little objective data on whether it provides better visualization than the microscopic approach. OBJECTIVES: To evaluate and compare audiological results, external auditory canal wall removal area, and adverse event rates between endoscopic and microscopic stapes surgery. MATERIAL AND METHODS: Data from patients who received stapedotomy were collected. Pre and postoperative audiometry, procedure-related parameters, and adverse events were analyzed in conventional microscopic and endoscopic groups. RESULTS: There were no differences in procedure time or postoperative hearing between the endoscopic and microscopic surgery groups. The mean procedure times were 87.3 ± 18.9 min in the endoscopic group and 79.9 ± 23.5 min in the microscopic group. The mean postoperative air-bone gaps were 10.9 ± 8.3 dB in the endoscopic group and 10.5 ± 7.8 dB in the microscopic group. There were no differences in the rate of sensorineural hearing loss, postoperative pain, facial palsy, vertigo, or dysgeusia between the two groups. The bony removal area of the posterosuperior external auditory canal wall measured by two observers was significantly less in the endoscopic group than in the microscopic group. CONCLUSIONS: Endoscopic stapedotomy needed less external auditory canal wall removal and showed similar audiological outcomes to microscopic stapedotomy.

Two Discrete Types of Tip Fold-Over in Cochlear Implantation Using Slim Modiolar Electrodes: Influence of Cochlear Duct Length on Tip Fold-Over.

OBJECTIVE: Precise electrode positioning is crucial for achieving optimal audiological outcomes in cochlear implantation. The slim modiolar electrode (SME), a thin, flexible, and precurved electrode, exhibits favorable modiolar proximity. However, tip fold-over can affect optimal electrode placement. Herein, we share our experiences with tip fold-over in SMEs and present an analysis of conditions that may predispose to tip fold-over. STUDY DESIGN: Retrospective medical record review. PATIENTS: In total, 475 patients (671 ears) underwent cochlear implantation using SMEs (Nucleus CI532 or CI632 from Cochlear) performed by a single surgeon at a tertiary center between June 14, 2018, and December 1, 2022. INTERVENTIONS: Intraoperative x-ray scans (cochlear view), operative records, and cochlear duct length (CDL) were reviewed. MAIN OUTCOME MEASURES: Tip fold-over patterns on plain x-ray images (proximal versus distal). RESULTS: Electrode tip fold-over was observed in 18 (2.7%) of the 671 ears with SMEs. This fold-over occurred more frequently in cases with long CDL (>36 mm). Among the 14 cases with available initial x-rays before correction of the tip fold-over, half were classified as proximal and the other half as distal. A predilection for proximal tip fold-over was found in those with a CDL of 36 mm or longer, and longer CDLs were observed for proximal cases than for distal cases. Our pilot data suggest that identifying the type of tip fold-over can aid in correcting it more efficiently. CONCLUSIONS: Tip fold-over of SME does not occur uniformly and is more common in ears with long CDL. This tendency is particularly pronounced for the proximal type of tip fold-over. Therefore, preoperative measurement of the CDL and meticulous examination of intraoperative imaging are essential for customized correction.

Audiogram Configuration, Molecular Etiology, and Outcome of Cochlear Implantation in Postlingual Auditory Neuropathy Spectrum Disorder.

OBJECTIVE: To explore the diverse molecular etiologies of postlingual auditory neuropathy spectrum disorder (ANSD) and report on the electrically evoked compound action potential (ECAP) thresholds and the outcome of cochlear implantation (CI). METHODS: Patients with late-onset, progressive hearing loss who went through molecular genetic testing were enrolled. Type of sensorineural hearing loss (SNHL) was classified as flat, reverse-slope, midfrequency, downsloping, or ski slope. We identified postlingual ANSD subjects through diagnostic tracts applied differently depending on the degree of SNHL. For CI recipients, individual ECAP thresholds, postoperative speech perception abilities, and the genetic cause were analyzed. RESULTS: The detection rate of ANSD among patients with postlingual SNHL was 5.1% (15/293 probands). Diverse genetic etiologies were identified in 7 (46.6%) of the 15 postlingual ANSD subjects, the genetic cause being found exclusively in subjects with reverse-slope SNHL. The pattern of intraoperative ECAP responses was also diverse and showed some correlation with the genetic etiology. Despite the diverse molecular etiology and ECAP responses, CI in postlingual ANSD patients, including those with features involving the postsynaptic component, yielded significant improvements in speech understanding. CONCLUSIONS: This study proposes a differentiated diagnostic approach that focuses on both poor speech discrimination and reverse-slope hearing loss for the diagnosis of ANSD. Based on the improvement of speech understanding from all cochlear implantees with ANSD as well as the correlation between the genetic etiology and ECAP thresholds, we suggest that CI can significantly benefit ANSD subjects even those with unknown etiologies unless there is overt peripheral neuropathy.

Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation.

Mutations in microRNA-96 ( MIR96 ) cause dominant delayed onset hearing loss DFNA50 without treatment. Genome editing has shown efficacy in hearing recovery by intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications. Here, we developed an editing therapy for a C>A point mutation in the seed region of the Mir96 gene, Mir96 14C>A associated with hearing loss by screening gRNAs for genome editors and optimizing Cas9 and sgRNA scaffold for efficient and specific mutation editing in vitro. By AAV delivery in pre-symptomatic (3-week-old) and symptomatic (6-week-old) adult Mir96 14C>A mutant mice, hair cell on-target editing significantly improved hearing long-term, with an efficacy inversely correlated with injection age. We achieved transient Cas9 expression without the evidence of AAV genomic integration to significantly reduce the safety concerns associated with editing. We developed an AAV-sgmiR96-master system capable of targeting all known human MIR96 mutations. As mouse and human MIR96 sequences share 100% homology, our approach and sgRNA selection for efficient and specific hair cell editing for long-term hearing recovery lays the foundation for future treatment of DFNA50 caused by MIR96 mutations.

Precision Medicine Approach to Cochlear Implantation.

In the early days of cochlear implantation (CI) surgery, when the types of electrodes were limited and the etiology of sensorineural hearing loss (SNHL) was not well understood, the one-size-fits-all approach to CI held true, as in all other fields. However, in the era of personalized medicine, there have been attempts to associate CI performance with the etiology of SNHL and to establish customized surgical techniques that can maximize performance according to individual cochlear dimensions. Personalized genomic-driven assessments of CI candidates and a better understanding of genotype-phenotype correlations could provide clinically applicable diagnostic and prognostic information about questions such as who, how, and when to implant. Rigorous and strategic imaging assessments also provide better insights into the anatomic etiology of SNHL and cochlear dimensions, leading to individualized surgical techniques to augment CI outcomes. Furthermore, the precision medicine approach to CI is not necessarily limited to preoperative planning, but can be extended to either intraoperative electrode positioning or even the timing of the initial switch-on. In this review, we discuss the implications of personalized diagnoses (both genetic and nongenetic) on the planning and performance of CI in patients with prelingual and postlingual SNHL.

Bechterew's Phenomenon in Bilateral Sequential Vestibular Neuritis: A Report of Two Cases.

The brain can compensate for the vestibular imbalance. When the unilateral labyrinthine function is lost, the asymmetry between the peripheral vestibular inputs is compensated centrally by readjusting the signal difference from both ears and regaining vestibular balance. If the other healthy labyrinth is destroyed, the vestibular nuclei become imbalanced again, creating spontaneous nystagmus even though there is no input to the vestibular nuclei from either labyrinth. This is called Bechterew's phenomenon; a rare and not widely recognized phenomenon that occurs in cases of bilateral sequential vestibular neuritis. This is of clinical importance because spontaneous nystagmus with bilaterally absent or diminished caloric responses may give a misleading impression of a central lesion rather than a second peripheral lesion superimposed upon the effects of central compensation for the first. Although well-documented in experimental animals, this phenomenon rarely occurs in human beings. The objective of this study is to highlight the characteristics and the progression of test results from two patients from our own experience. Along with careful history taking and physical examination, a complex interpretation of various vestibular function tests, including induced nystagmus, head impulse test, caloric test, and fundus photography, is needed to make an accurate diagnosis of bilateral sequential vestibular neuritis (BSVN).

Differential Involvement of Lateral Semicircular Canal and Otolith Organs in Common Vestibular Disorders.

Semicircular canal and otolith functions came to be evaluated recently, but comprehensive and comparative analysis of canal and otolith dysfunction in common vestibular disorders is lacking. We aimed to analyze the abnormal rates of canal and otolith function in common vestibular disorders. We enrolled 302 patients who were managed for 2 months in a dizziness clinic. Results of caloric, video head impulse test (vHIT), and cervical and ocular vestibular evoked myogenic potential (cVEMP and oVEMP) tests were analyzed and compared among various diagnoses. Vestibular disorders diagnosed included recurrent vestibulopathy (RV, 27%), vestibular migraine (VM, 21%), benign paroxysmal positional vertigo (BPPV, 17%), Meniere's disease (MD, 11%), vestibular neuritis (VN, 10%), orthostatic dizziness (7%), and central lesions (3%). Lateral canal dysfunction was found most in VN (100%) and less commonly in definite MD (75%), RV (46%) and definite VM (29%). Abnormal caloric results were more common than abnormal vHIT in all disorders. Otolith dysfunction was found more frequently than lateral canal dysfunction in most vestibular disorders except VN. An abnormal cVEMP was more frequent in definite MD than the other disorders. Isolated otolith dysfunction without lateral canal dysfunction was the most found in BPPV, followed by definite VM, RV, and definite MD in decreasing order. Various patterns of involvement in canal and otoliths were revealed in vestibular disorders, suggesting different pathogenesis.

Serial histological changes in the cartilaginous eustachian tube in the rat following balloon dilation.

Although balloon dilation has shown promising results in the treatment of dilatory Eustachian tube (ET) dysfunction, the histological effects of ET balloon dilation (ETBD) is unknown because histological examination of the whole human cartilaginous ET is impossible. Animal studies are needed to elucidate the effect of ETBD so we evaluated the histological changes after ETBD in a rat model. The left ET of 20 Wistar rats was dilated with a balloon catheter and the right ET was used as a control. Five rats were sacrificed immediately after ETBD, at 1, 4 and 12 weeks after the procedure for histological examination. The epithelial cells, presence of epithelial hyperplasia, and the proportion of the goblet cells in the epithelium; the vascular structures and dimensions of the submucosa; and presence of cartilage fracture and the area of the ET lumen were evaluated and compared between the groups. Desquamation of nearly all epithelial cells and the fracture of tubal cartilages were observed immediately after ETBD. At 1-week post-ETBD, the ciliated epithelial cells started to recover with epithelial hyperplasia. The goblet cells recovered by 4 weeks post-ETBD and epithelial hyperplasia decreased but was still present at 12 weeks post-ETBD. The depth of the submucosa increased and neovascularization in this region was observed at 1-week post-ETBD and persisted up to 12 weeks post-ETBD. The lumen of the cartilaginous ET increased immediately after ETBD but decreased at 1-week post-ETBD. The cartilaginous ET lumen recovered to the normal value at 4 weeks post-ETBD. This study is the first to describe the serial histological changes to the cartilaginous ET after ETBD and helps our understanding of the histological changes that occur after an ETBD intervention for intractable ET dysfunction.

Auditory Phenotype and Histopathologic Findings of a Mutant Nlrp3 Expression Mouse Model.

Objective: The pathogenesis of hearing loss in autoinflammatory disorders due to activation of the inflammasome remains incompletely understood. Previously no animals expressing mutant Nlrp3 (NOD-, LRR- and pyrin domain-containing protein 3) survived to an age when hearing evaluation was possible due to embryonic lethality. We aimed to establish a novel mouse model that manifests quantifiable hearing loss with other syndromic features due to alteration of Nlrp3 and investigate the audiologic and histopathologic phenotype in the cochlea to clarify how the genetic alterations of NLRP3 could induce autoinflammatory hearing loss. Methods: To induce inner ear expression of the mutant Nlrp3, Nlrp3 D301NneoR mice were bred with Gfi1 Cre knock-in mice for conditional mutant Nlrp3 activation in the cochlea and hematopoietic cells. Hearing thresholds were measured. Hematoxylin-eosin sections of the cochlea, brain, kidney, and liver were examined under light microscopy. Immunohistochemical analyses using polyclonal anti-NLRP3 antibodies on cochlear whole-mount preparations and frozen sections were performed. Results: We, for the first time in the literature, established a mouse model that manifests quantifiable hearing loss due to Nlrp3 alteration. ABR recordings of Nlrp3 D301NneoR/+; Gfi1 Cre/+ mice, albeit with limited life expectancy, exhibited severe to profound hearing loss at postnatal day 20 (P20). There was overall overexpression of mutant Nlrp3, and mutant Nlrp3 expression was noted in the spiral prominence, the outer sulcus region (Claudius cells and outer sulcus cells), the organ of Corti, the inner sulcus, and the spiral ganglion neurons in the cochlea. The hematoxylin-eosin sections of Nlrp3 D301NneoR/+; Gfi1 Cre/+ mice cochleae at P12 exhibited a disorganized organ of Corti between the outer hair cells/supporting Deiters' cells and basilar membrane compared with the normal phenotype mice, leading to a collapsed Nuel's space. This morphologic feature gradually returned to normal by P15. Varying degrees of inflammation with lymphocytic infiltrations were observed in the brain, kidney, and liver. Conclusion: We report the first mutant Nlrp3 overexpression mouse model (Nlrp3 D301NneoR/+; Gfi1 Cre/+) that shows obvious overexpression of Nlrp3 in the cochlea, a transient developmental lag of the cochlea, and severe to profound hearing loss. We expect that this mouse line, which models human autoinflammatory hearing loss, could provide a valuable tool to elucidate the underlying pathogenic mechanism of inflammasome activation-mediated hearing loss.

Efficacy of cochlear implants in children with borderline hearing who have already achieved significant language development with hearing aids.

There are still debates about timing and effectiveness of cochlear implants (CI) in pediatric subjects with significant residual hearing who do not belong to traditional indication of CI. In this study, we aimed to investigate the outcomes of CI, specifically on improvement of pronunciation, among hearing-impaired children already with a substantial degree of language skills as evaluated by Categories of Auditory Perception (CAP) scores or sentence score. Our cohort comprised pediatric CI recipients from July 2018 through October 2020. Among them, cases with CAP scores of 5 or 6 preoperatively were defined as "borderline cases". We investigated prevalence and etiologies, and compared speech evaluation data preoperatively and postoperatively at three time points (3, 6 and 9-12 months after implantation). Among 86 pediatric CI recipients, 13 subjects (15.12%) had language development that reached CAP scores of 5 or 6 before implantation. Postoperative speech evaluation data 6 months after implantation revealed significant improvement of pronunciation (Urimal Test of Articulation and Phonation scores: UTAP), Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and word perception scores, but not of CAP and sentence perception scores. Notably, the significant improvement of pronunciation based on UTAP scores outstripped that of other speech parameters and this continued steadily up to one-year postoperatively. The result of the study serves as evidence for what to expect from cochlear implantation in hearing-impaired children who have already achieved a substantial degree of language development in terms of CAP scores or sentence perception scores, preoperatively.

Correlation of clinical parameters with endolymphatic hydrops on MRI in Meniere's disease.

A clinical diagnosis of Ménière's disease (MD) is made based on medical history and audiometry findings. The 1995 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines requires histopathological confirmation of endolymphatic hydrops (EH) for a diagnosis of "certain" MD. Symptoms such as dizziness and ear fullness are important diagnostic features; however, the descriptions provided by patients are frequently vague and non-specific. A recently developed magnetic resonance imaging (MRI) protocol to document EH is, therefore, useful for the evaluation of inner ear status in patients with MD. In this study, patients with MD were assessed using MRI and the HYDROPS (HYbriD of Reversed image Of Positive endolymph signal and native image of positive perilymph Signal) protocol to investigate the effectiveness of MRI for visualization of the endolymphatic space in the diagnosis of MD by correlating clinical laboratory parameters with the grade of EH. Of the 123 patients with MD recruited in this study, 80 had definite MD, 11 had probable MD, and 32 had possible MD based on the 1995 AAO-HNS guidelines. The EH grade based on HYDROPS MRI was determined independently by two otorhinolaryngologists and compared with several clinical parameters, including the diagnostic scale of MD (1995 AAO-HNS guidelines), pure tone average (PTA), low tone average (LTA), canal paresis (CP) on the caloric test, and disease duration. Cochlear hydrops and vestibular hydrops were detected in 58 and 80% of 80 definite MD ears, in 33 and 58% of 12 probable MD ears, and in 5 and 27% of 37 possible MD ears, respectively. The proportion of higher hydrops grades increased significantly with grade according to the MD diagnostic scale (p < 0.0001). Both PTA and LTA were significantly higher in patients with hydrops grade 2 than hydrops grade 0 in both the cochlea and the vestibule. CP was significantly higher in patients with grade 2 than grade 0 vestibular hydrops. Disease duration was not associated with hydrops grade. Radiological evaluation of MD using the HYDROPS protocol is useful for evaluation of the extent and severity of EH in the diagnosis of MD based on its pathophysiological mechanism.