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Background and Objectives A large-scale community-based study of the general population has not been conducted. There have been no studies on the relationship between decreased renal function and the degree of hearing loss. Thus, the purpose was to evaluate the relationship between hearing loss and impaired renal function with a large number of populations.Subjects and Method We performed a cross-sectional population-based cohort study by enrolling 470718 adults, 18 to 80 years old with pure tone audiometry tests who had regular health screening between 2013 and 2018. Hearing loss was defined as a pure-tone average of thresholds at 500, 1000, and 2000 Hz in both right and left ears. Kidney function was evaluated based on eGFR. Chronic kidney disease (CKD) was diagnosed as an eGFR25 dB) and 5.0% had above moderate hearing loss (>40 dB). But those with normal kidney function, 2.0% either had any hearing loss and 0.4% had above moderate hearing loss. The odds ratio (OR) of above moderate hearing loss for participants with CKD was 1.51 (95% confidence interval [CI]: 1.15-2.00, p=0.003) but the OR of mild hearing loss for participants with CKD was 0.82 (95% CI: 0.67- 1.02, p=0.073). The result suggested that CKD and above moderate hearing loss were related even after correcting for potential confounders, but had no statistical significance with mild hearing loss.Conclusion Decreased kidney function is associated with above moderate hearing loss.

Background A considerable number of patients with sudden sensorineural hearing loss (SSNHL) have been reported to have dizziness. Objective To analyze vestibular functions and identify the clinical characteristics of SSNHL with dizzinessMETHODS:71 patients with SSNHL who complained of dizziness were investigated retrospectively. The patients underwent vestibular function tests consisting of video-nystagmography, video head impulse test and vestibular evoked myogenic potentials. Results Among 35 patients with spontaneous nystagmus (SN), 21 showed ipsilesional posterior canal gain deficit, 11 showed a gain deficit in the posterior canal only and 9 showed both horizontal and posterior canal gain deficit in video head impulse test. In only one subject with bilateral horizontal canal gain deficit with contralesional SN, AICA infarction was observed.Among 36 patients without SN, 10 were diagnosed as benign paroxysmal positional vertigo and 5 had ipsilesional canal paresis in caloric test. Other 21 patients showed no abnormal signs in vestibular function tests. Conclusions In VFT analysis of SSNHL with dizziness, diverse patterns were identified. In the absence of SN, no definite vestibular organ involvement was the most frequent. But in the case with SN, posterior canal deficit was most common and cerebellar ischemic stroke was rare.

Objective This study aimed to determine the radiation dose of temporal bone computed tomography (TBCT) to detect pediatric congenital cholesteatoma (CC), and suggests strategy for lowering perioperative radiation dose. Methods Fifty-three CC patients followed up for more than 12 months after surgery. Perioperative clinical findings and the effective radiation dose (ERD) of TBCT were investigated. Patients’ mean age at initial TBCT was 60 months; the mean follow-up period was 43 months. Results In 33 (62.3%) of 53 patients, only one TBCT was performed postoperatively. Postoperative CT imaging was performed to evaluate before second-stage ossiculoplasty, due to suspicion of CC recurrence on examinations, or as part of follow-up. When TBCT was performed on more than two occasions after surgery as a part of follow-up, there was no difference in the distribution of stage or type of CC compared to patients subjected to TBCT on less than three occasions ( p = 0.093 and p = 0.744, respectively). During the most-recent follow-up of these 53 cases, there was no CC recurrence. The mean ERD of a single TBCT was 1.2 mSv, and the mean cumulative ERD of TBCT was 2 mSv per patient. Conclusion Mean and cumulative ERD of TBCT performed in CC cases was not too high to consider radiation hazard. However, efforts to minimize the number of CT scans should be taken basically.

OBJECTIVE To compare the results of suppression head impulse paradigm (SHIMP) and head impulse paradigm (HIMP) in acute vestibular neuritis (AVN). STUDY DESIGN Retrospective study. SETTING Tertiary otology clinic. PATIENTS AND INTERVENTIONS We tested 21 patients with AVN with the HIMP, SHIMP, and caloric tests, and we analyzed the relationships between the tests' results. MAIN OUTCOME MEASURES For this study, we adopted vestibulo-ocular reflex (VOR) gains in the SHIMP and HIMP, peak saccade velocity (PSV) of SHIMP which is another indicator of residual vestibular function, and canal paresis of caloric test. RESULTS VOR gains showed significant correlation (R = 0.926, p

Objectives/Hypothesis To review surgical findings and hearing outcomes of incus footplate assembly (IFA) for the patients with conductive hearing loss due to missing stapes superstructure with a mobile stapes footplate. Study Design Retrospective case review and survey. Methods Pre- and postoperative audiometric data and intraoperative findings were reviewed. Postoperative air-bone gap (ABG) and ABG closure (postoperative air-conduction threshold–preoperative bone-conduction threshold) were analyzed. Results The causes of missing stapes superstructure and conductive hearing loss were congenital ossicular anomaly (n = 5), chronic otitis media (n = 2), and congenital cholesteatoma (n = 1). The prosthesis was designed to fit between the medial side of the incus and stapes footplate and had a mean length of 3.6 ± 0.5 mm. The mean pre- and postoperative ABG were 38.3 ± 4.8 and 13.3 ± 10.0 dB, respectively. The postoperative ABG at frequencies of 0.25, 0.5, 1.0, 2.0, 3.0, and 4.0 kHz were 20.0 ± 15.4, 16.9 ± 11.9, 16.3 ± 10.3, 10.6 ± 7.3, 12.9 ± 14.0, and 23.1 ± 16.2 dB, respectively. The mean ABG closure was 9.5 dB (range, −1.3∼35.8 dB). Seven cases obtained the best results (mean ABG closure ≤10 dB). In the remaining patient, the mean ABG closure was 9.5 dB until 6 months after surgery, but was 35.8 dB 1 year after surgery. Conclusions IFA seems to be a reasonable surgical option in patients with missing the stapes superstructure, but with a mobile footplate in which the long process of incus is preserved. Level of Evidence 4 Laryngoscope, 2016

Objectives/Hypothesis To analyze the clinical manifestations and genetic features of patients with hearing loss (HL) and incomplete partition (IP) type III malformation, and to evaluate speech performance after cochlear implantation (CI) in these patients. Study Design Individual retrospective cohort study. Methods Of 206 probands with inner ear malformations (IEMs), we constructed a homogeneous cohort of 11 genetically documented IP type III (DFNX2). Mutations affecting POU3F4 were classified as extension (n = 2), truncation (n = 3), large genomic deletion (n = 2), or missense substitution (n = 4). Postoperative outcomes were rigorously assessed with focus on POU3F4 genotypes and compared with 80 age-matched implantees without IEMs. Results HL in our cohort was prelingual in onset irrespective of degree. Serviceable hearing was obtained by wearing conventional hearing aids in three, and eight subjects required CI. No correlation was found between mutation types and initial auditory phenotype. As for the eight cochlear implantees, average Categories of Auditory Perception score was

OBJECTIVE The purpose was to evaluate brain plasticity that contributes to speech performance after cochlear implantation (CI) in postlingual elderly (>60 years) patients. MATERIALS AND METHODS Fifteen elderly postlingual deaf patients who underwent preoperative brain fluorodeoxyglucose positron emission tomography (FDG-PET) and were followed-up for more than 1 year after CI were included. The mean age of these patients was 64.6 years (range, 60-80 years). Based on their sentence score at 1 year after CI surgery, the patients were classified into two groups: poor performers (CID score of

Objectives/Hypothesis To evaluate the correlation between a narrow bony cochlear nerve canal (BCNC) and facial nerve stimulation (FNS) after cochlear implantation (CI) and their underlying mechanisms and to predict the risk of FNS preoperatively. Study Design Retrospective cohort study. Methods A total of 64 pediatric cases that underwent CI were included. Among them, 32 cases experienced FNS after CI, and another 32 cases were selected from 817 pediatric implantees by stratified random sampling. The width of the BCNC, the status of the cochlear nerve (CN) and the internal auditory canal (IAC), T level, and C level were compared and analyzed. Strategies for eliminating FNS were also analyzed. Results The FNS group showed a narrower BCNC (1.09 ± 0.52 mm) than the control group (1.99 ± 0.61 mm; P < .01), a lower CN/facial nerve ratio (0.32 ± 0.36) than the control group (1.34 ± 0.76; P < .01), and narrower IAC diameter (4.06 ± 1.71 mm) than the control group (5.66 ± 1.36 mm; P < .01). The FNS group also showed higher T level (165.7 ± 28.3 μA) than the control group (142.2 ± 21.2 μA; P < .01). Adjustment of the C levels and/or pulse width and switching off offending electrodes were attempted to eliminate FNS, with a 75.0% success rate. The FNS group still showed low Categories of Auditory Performance scores (3.00 ± 1.90) compared with the control group (5.94 ± 1.41, P < .01) after adjustment. Conclusions A narrow BCNC could be a cause of FNS after CI. Therefore, careful selection of the side for CI and programming strategies are required to reduce FNS. Level of Evidence 4. Laryngoscope, 2015

OBJECTIVE To demonstrate the efficacy and advantages of targeted exome sequencing (TES) of known deafness genes in cases with failed or misleading auditory phenotype-driven candidate gene screening. STUDY DESIGN Prospective cohort survey. SETTING Otolaryngology department of a tertiary referral hospital. PATIENTS Six hearing-impaired probands with seemingly non-syndromic features from six deaf families were enrolled in this study after failure of genetic diagnosis using auditory phenotype-driven candidate gene screening. INTERVENTION TES of known deafness genes was performed in the six probands, and a final causative variant was pursued using subsequent filtering steps. MAIN OUTCOME MEASURE Potential causative variants determined using TES were confirmed by previously introduced filtering steps. RESULTS We detected causative variants in three (50%) of six families, and these variants were in the COCH, PAX3, and GJB2 genes. Additionally, we also recapitulated the recent finding from other report arguing for the non-pathogenic potential of MYO1A variant. CONCLUSIONS TES of a deafness panel provides a comprehensive genetic screening tool that can be implemented without being misled by the audiogram configuration information and can complement incomplete clinical physical examinations. In addition, the secondary incidental finding obtained by TES contributes useful information regarding the deafness field.

Evaluation of the characteristic differences between click-and CE-Chirp-evoked auditory brainstem responses (ABRs) in normal hearing and sensorineural hearing loss.A prospective study. Ears with normal hearing and with sensorineural hearing loss were evaluated. Pure-tone audiometry and click-and CE-Chirp evoked ABRs exams were conducted for all ears. Visual detection levels, wave-V amplitudes, and latencies of the ABRs were assessed.Twenty-two ears with normal hearing and 22 ears with sloping type sensorineural hearing loss were examined.In normal-hearing ears, mean amplitudes were larger for CE-chirps than for clicks at all intensities until 80 dB nHL, at which the amplitudes dropped off, presumably due to upward spread of excitation. In ears with sensorineural hearing loss, however the drop-off was less significant at 80 dB nHL. Comparisons with pure-tone audiometry findings revealed ABRs to CE-Chirps to correlate at 0.5, 1, 2, and 3 kHz, and to clicks at 1, 2, 3, and 4 kHz.The CE-Chirp has advantages over clicks for examining normal ears. However, under high-level stimulation, these advantages are no longer present. In ears with sensorineural hearing loss, the upward spread of excitation is less prominent. The CE-Chirps results correlate significantly to low frequency audiometric findings at 0.5 kHz, while clicks do not.

To evaluate the efficacy of tinnitus retraining therapy (TRT), especially in patients who did not revisit the clinic after starting the program, and to determine the current status of patients who were lost to follow-up.Telephone survey.Tertiary referral center.Forty-seven patients enrolled in a TRT program at Seoul National University Hospital. Twenty-four patients who regularly visited the clinic were deemed the good follow-up (GF) group, and 23 patients who did not return after the initial counseling were deemed the follow-up loss (FL) group.Post-TRT questionnaires with the Tinnitus Handicap Inventory (THI) and a tinnitus visual analog scale (VAS), performed with a telephone survey.TRT efficacy, evaluated via the THI, and tinnitus VAS scores. A questionnaire on reasons for non-attendance after TRT was used.Pre-TRT VAS and THI scores showed no significant difference between groups. After TRT, both groups showed significant decreases in tinnitus VAS and THI scores. Post-TRT VAS scores for awareness, effects on daily life, and post-TRT THI scores were significantly lower in the FL group.Treatment outcomes were better in the FL group than in the GF group in several parameters. The FL group was greatly influenced by the first TRT counseling and obtained sufficient relief that they no longer felt the need for additional treatment. Treatment outcomes in patients lost to follow-up may not be as bad as presumed.

A narrow bony cochlear nerve canal (BCNC) is associated with sensorineural hearing loss necessitating cochlear implantation (CI). This study evaluated the implications of BCNC width for post-CI outcomes. A total of 56 children who had received CIs were included. The patients were divided into three groups according to the width of the BCNC (Group 1: diameter < 1.4 mm, n=17; Group 2: diameter 1.4–2.0 mm, n=14; Group 3: diameter > 2.0 mm, n=25). The post-CI speech performances were compared among the three groups according to BCNC width. The correlation between BCNC width and post-CI speech performance was evaluated. Logistic regression analysis was also performed to investigate factors that can impact post-CI speech performance. Cochlear nerve deficiency (CND) occurred more frequently in Group 1. Groups 1 and 2 had significantly worse post-CI outcomes. Patients with intact cochlear nerves had significantly better post-CI outcomes than those with CND. When the cochlear nerve was intact, patients with a narrower BCNC showed less favorable results. Therefore, patients with either a narrow BCNC or CND seemed to have poorer outcomes. A narrow BCNC is associated with higher CND rates and poor outcomes. Measurement of BCNC diameter may help predict CI outcomes.

Objective To extend our preliminary study by comparing the hearing outcomes of handle-malleostapedotomy (handle-MS; connecting the prosthesis to the malleus handle) and neck-MS (connecting the prosthesis to the malleus neck) in a larger case series. Patients Thirty-five patients who underwent MS at Seoul National University Hospital from January 1983 to December 2013. Intervention Review of pre- and postoperative audiometric data, intraoperative findings. Main outcome measures Postoperative air-bone gap (ABG) and closure of ABG. Results In 11 of 20 patients (55.0%) in the handle-MS group and 12 of 15 (80%) in the neck-MS group, the postoperative ABG closed to within 20 dB HL. For frequencies of 0.25, 0.5, 1, 2, 3, and 4 kHz, the ABGs did not differ significantly between the two groups. The postoperative ABG closure was lower in the neck-MS group (22.3 ± 12.6 dB HL) than in the handle-MS group (23.5 ± 11.6 dB HL), but without statistical significance (p = 0.78). Four patients in each group underwent MS as a revision procedure. One of them underwent neck-MS as revision surgery because of prosthesis extrusion after handle-MS. The mean ABG closure at 1 year postoperatively in patients who underwent revision neck-MS (19.9 ± 11.9 dB HL) was not different from that of the patients who underwent revision handle-MS (20.9 ± 8.7 dB HL). Conclusion As neck-MS provided results comparable to those of handle-MS in our extended case series, it might be a useful procedure in selected cases of otosclerosis or stapes fixation with an incus anomaly, especially in revision cases after handle-MS.

Appropriate customized auditory rehabilitation for hearing impaired subjects requires prediction of residual hearing and progression of hearing loss. Mutations in TMPRSS3 encoding a transmembrane serine protease were reported to be associated with two different autosomal recessive nonsyndromic hearing loss (arNSHL) phenotypes, DFNB8 and DFNB10, in terms of residual hearing that may mandate different rehabilitation. We aimed to reveal the genetic contribution of TMPRSS3 mutations among Korean populations and to correlate the clinical phenotype with TMPRSS3 genotypes. Fifty families that segregated arNSHL and have visited our clinic recently for 2 years were recruited for TMPRSS3 screening. Novel TMPRSS3 variants detected in our cohort were modeled using a predicted three-dimensional (3D) structure of the serine protease domain. The prevalence reached up to 11.2 % (3/27) among subjects with either prelingual hearing loss but retaining some degree of language development or with postlingual ski-slope hearing loss. We also found that a p.A306T allele is a founder allele in this population. Based upon the 3D modeling, we were able to correlate significant retention of residual low-frequency hearing and slower progression of its loss to this novel variant p.T248M that was predicted to have milder pathogenicity. A yeast-based protease assay confirmed a mild pathogenic potential of the p.T248M variant and a tight correlation between the protease activity and the residual hearing. Preservation of this low-frequency hearing should be of utmost importance when considering auditory rehabilitation. Our results significantly narrow down the candidate population for TMPRSS3 sequencing for more efficient genetic diagnosis. More importantly, genotype-phenotype correlation of this gene observed in our cohort suggests that TMPRSS3 can be an appropriate candidate for personalized and customized auditory rehabilitation.The prevalence of TMPRSS3 mutations among Korean postlingual hearing loss is 8.3 %. The p.A306T variant of TMPRSS3 is the common founder allele in Koreans. A novel variant, p.T248M of TMPRSS3, was predicted to have milder pathogenicity. There was a genotype-phenotype correlation of this gene in Koreans. Our data support implication of this gene for personalized rehabilitation.

Objective The purpose of the present study was to investigate the effect of dopamine as a possible regulator of epithelial Na + channel (ENaC) in the Reissner's membrane (RM). Methods RM was freshly dissected from the gerbil cochlea, and short-circuit current ( I sc ) was measured using the voltage-sensitive vibrating probe technique. The dopamine receptor expression was examined using immunohistochemistry. Results The results showed that dopamine induced activation of the amiloride-sensitive I sc , but not after pre-treatment with amiloride. The D 1 -like receptor antagonist SCH-23390, but not the D 2 -like receptor antagonist sulpiride, decreased the stimulatory effect of dopamine on RM. The effect of dopamine on Na + transport via ENaC was still observed after blockade of the Na + –K + -ATPase by ouabain. D 1 receptor immunoreactivity was observed in RM, stria vascularis and spiral ganglion. Conclusion Na + transport in RM is activated by dopamine possibly via D 1 -like receptors, and intracellular mechanisms other than cAMP-mediated pathway may be involved.

WD40 repeat protein 1 (WDR1) has been suggested as a protective mechanism or a sign of regeneration in avian cochlea. However, its role in mammalian cochlea has yet to be determined. Hence, we investigated WDR1 expression in sound-overstimulated Sprague-Dawley rats. Rats were divided into three groups (the permanent and temporary threshold shift [PTS and TTS] groups and the control group) according to the extent of noise exposure and euthanized immediately, 3, or 7 days after noise exposure for cochlear harvest. Immunocytochemistry localized WDR1 to outer hair cells, Deiter's cells, outer sulcus cells, and Reissner's membrane in the control group, and the PTS and TTS groups exhibited stronger WDR1 expression in the same cochlear regions than the controls. Moreover, WDR1 expression in these noise-exposed groups was extended to inner hair cells and basal cells of the stria vascularis. The expression of WDR1 in the PTS and TTS groups showed differences in intensity and shifts of localization, based on exposure length and recovery duration. Contrary to the avian cochlea, hair cell regeneration does not naturally occur in the acoustically damaged mammalian cochlea. Therefore, elevated WDR1 expression after acoustic overstimulation in the current experiments may provide a mechanism for protection against noise exposure.

Objective: To determine the optimal surgical approach for cochlear implantation (CI) preoperatively based on the spatial relation of a displaced facial nerve (FN) and middle ear structures and to analyze clinical outcomes of CHARGE syndrome. Methods: Facial nerve displacement and associated deviation of inner ear structures were analyzed in 13 patients (17 ears) with CHARGE syndrome who underwent CI. Surgical accessibility through the facial recess was assessed based on anatomical landmarks. Postoperative speech performance and associated clinical characteristics were analyzed. Results: The most consistently identified ear anomalies were semicircular canal aplasia (100%), ossicular anomaly (100%), and vestibular hypoplasia (88%). Facial nerve displacement was found in 77% of cases (anteroinferior: 47%, anterior: 24%, inferior: 6%). The width of available surgical space around facial recess was significantly greater in cases of facial recess approach (2.85 ± 0.9 mm) than those of alternative approach (0.12 ± 0.29 mm, P = .02). Postoperatively, 53% achieved better than category 4 on the categories of auditory perception (CAP) scale. The CAP category was significantly correlated with internal auditory canal diameter ( P = .025) and did not differ according to the applied surgical approach. Conclusion: Preoperative determination of surgical accessibility through facial recess would be useful for safe surgical approach, and successful hearing rehabilitation was achievable by applying appropriate surgical approaches.

We reported that the degree of conductive hearing loss resulting from a tympanic membrane (TM) perforation would be expected with the size of perforation and pneumatization of middle ear and mastoid, not location of perforation. This result was conflicted with previous study that revealed the influence of location of TM perforation on the severity of hearing loss in 1970 [1].

Objectives/Hypothesis To identify the clinical and laboratory characteristics of bilateral vestibulopathy (BVP) on the video head impulse test (vHIT). Study Design Retrospective chart analysis. Methods During 23 months, 1,789 patients with dizziness underwent vHIT in our tertiary referral hospital. Of these patients, 65 (3.6%) patients had bilaterally positive catch-up saccades. Based on the caloric test, 15 (group 1) had bilateral caloric weakness, 13 (group 2) had unilateral caloric weakness, and 37 (group 3) had normal caloric responses on both ears. We collected data on these patients regarding demographics, symptoms, gain, and type of saccade on horizontal canal plane vHIT, as well as gain and time constant on velocity step of the rotatory chair test. Results The average age of group 2 (70.38 ± 11.96 years) and group 3 (69.03 ± 11.01 years) were significantly older than that of group 1 (54.80 ± 11.96 years) (P = 0.029, P = 0.003, respectively). Although all patients had bilaterally positive vHIT, 10 of 15 in group 1 were finally diagnosed as classical BVP by clinical features. On comparison of average gain on bilateral horizontal vHIT, groups 2 (0.71 ± 0.17) and 3 (0.80 ± 0.14) had higher gain compared to group 1 (0.45 ± 0.22) (P = 0.001, P = 0.000, respectively). On velocity step test, time constant and gain of group 3 (11.60 ± 3.07, 0.49 ± 0.13) was significantly higher than those of group 1 (4.92 ± 1.36, 0.22 ± 0.17) (P = 0.000, P = 0.004, respectively). On the receiver operating characteristic curve analysis, vHIT alone seemed to be a discordant method for diagnosis of BVP compared to the caloric and step velocity tests. Conclusion About 3.6% patients with dizziness showed bilateral vestibular ocular reflex deficit during high-frequency acceleration, which was prevalent especially in elderly patients. Also, positive bilateral vHIT does not always correlate with caloric or rotatory chair test results. This may imply that a diverse spectrum of vestibulopathies exist according to the stimulation frequency of deficit. Level of Evidence 4. Laryngoscope, 2016

Most X-linked nonsyndromic hearing loss is caused by various types of mutations of the POU domain class 3 transcription factor 4 gene (POU3F4). We found five unique missense and frameshift truncation and extension mutations in Korean patients. Two missense mutations (p.Thr211Met and p.Gln229Arg) disturbed transcriptional activity. Two frameshift extension mutations (p.Thr354GlnfsX115 and p.X362ArgextX113) were located outside of POU domain and nuclear localization signal (NLS) at the C-terminus. POU3F4 protein levels were low and could be restored by MG132, a proteasome inhibitor, in vitro. These mutant POU3F4 proteins were exclusively localized to the cytoplasm and did not have transcriptional activity. Frameshift mutation (p.Leu317PhefsX12) in POU3F4 leads to the truncation of the C-terminal 44 amino acids spanning the POU domain and NLS. This frameshift truncation mutant protein was located in both the nucleus and cytoplasm and was present at low protein levels. This mutant was also transcriptionally inactive, even in the presence of MG132. From these results, we conclude that frameshift truncation and extension mutations in the C-terminus of POU3F4 lead to cytoplasmic localization and subsequent proteosomal degradation due to structural aberrations, which cause transcriptional inactivity and thus nonsyndromic hearing loss.

Systemic application of human mesenchymal stem cells (hMSCs) may be another effective tool for stem cell supply to the inner ear.Most researchers have used local application to provide the inner ear with stem cells. In spite of their efficacy, these methods can potentially cause irreversible damage to the inner ear. A homing phenomenon of systemically administered MSCs to the ischemic myocardium and brain was recently reported. Moreover, hMSCs have several advantages over conventional neural or embryonic stem cells. Thus we hypothesized that intense noise or ototoxic injury to the cochlea could induce the homing of hMSCs.We harvested hMSCs from bone marrow of the iliac crest of five normal individuals. Then hMSCs at a dose of 4 × 10(6) cells were given via intravenous injection of cell suspension into rats with cochleae damaged by noise or ototoxic drugs. Histological analysis was undertaken 30 days later.Systemically delivered hMSCs were usually largely entrapped in the lungs. However, we documented the homing of some hMSCs to the cochlea with degenerated inner hair cells. The recruitment of hMSCs was limited to the spiral ganglion area only. The migration of donor cells into the cochlea was accompanied by the expression of brain-derived neurotrophic factor (BDNF).

Non-technical summary Cerebellar vermis consists of 10 lobules, and each lobule receives different sensory information. Afferent inputs are integrated in cerebellar Purkinje cells (PCs) which are the sole output of the cerebellar cortex. We show that intrinsic membrane properties are widely different between PCs in the spinocerebellum (lobules III–V) and vestibulocerebellum (lobule X).

This study aimed to investigate the most prevalent stage in each age-group of children with congenital cholesteatoma (CC) and verify the correlation between the stage and the age of the patients for the type of CC ("closed" keratotic cyst and "open" infiltrative types). Patients diagnosed with CC between 2004 and 2009 (n = 156; 116 boys and 40 girls; mean age, 5 years and 5 months; range, 12 months-16 years and 7 months) were enrolled retrospectively. Assessment of stage and type of CC was performed with preoperative high-resolution temporal bone computed tomography and intraoperative findings. The stage of CC was determined using Potsic's staging system classified into four stages according to ossicular involvement and mastoid extension. The patients consisted of groups divided on the basis of a 2-year interval. The prevalence of stage I began to decline from the age-group of 1-2 years. In contrast, the prevalence of stages III increased from the age-group of 3-4 years and that of stage IV from the age-group 5-6 years. The prevalence of "open" infiltrative type CC increased from approximately the age of 7 years, thus showing some correlation with age but not with stage. The prevalence of CC with the advanced stage increased since the age of 2 years. Therefore, the importance of early diagnosis and treatment of CC should be more emphasized.

Mean incudostapedial joint (ISJ) angulation of atretic ears was statistically wider than ISJ angulation of non-atretic ears. Postoperative hearing results in the narrow tympanoplasty type II (T2) subgroup were better than those in the wide T2 subgroup. In cases of abnormally wide ISJ angulation, we recommend that partial ossicular reconstruction (POR) be used as a surgical means of achieving hearing improvement.To report the results of ISJ angulation in patients with congenital aural atresia and its effects on postoperative hearing improvement.Patients undergoing canaloplasty with T2 (149 ears) and canaloplasty with POR (32 ears) were enrolled. The T2 group was dichotomized according to an ISJ cut-off of an angle of 120° into the 'narrow' T2 and 'wide' T2 subgroups. The pre- and postoperative air-bone gap (ABG) and ABG change were analyzed.Mean ISJ angulation of non-atretic ears was 93.06 ± 13.21° and that of atretic ears in the T2 group was 118.39 ± 19.60° (p0.001). Mean short- and long-term postoperative ABGs were better in the narrow T2 subgroup than in the wide T2 subgroup (p = 0.01 and 0.03, respectively). The short-term postoperative ABG and ABG change in the POR showed superior results to those of the wide T2 subgroup (p0.001 and 0.041, respectively).

3-Nitropropionic acid (3-NP) induces hearing loss by impairing mitochondrial energy generation. Geranylgeranylacetone (GGA) is known to protect the cochlea from various injuries. The present study was designed to investigate the protective effect of GGA against acute 3-NP-induced damage to the cochlear mitochondria. Female Hartley guinea pigs were divided into 4 groups. The 3-NP vehicle was injected to control animals and in animals receiving GGA alone, only GGA was administered for 7 days. 3-NP (500 mM, 4 microl) was administered with (animals receiving both GGA and 3-NP) or without (animals receiving 3-NP alone) GGA pretreatment (800 mg/kg, 7 days). The auditory brainstem response (ABR) was recorded at click and at 8, 16 and 32 kHz before and after injection, respectively. After cochlear harvest, hematoxylin/eosin staining and immunohistochemistry for anti-HSP70 antibody were done. 3-NP exposure resulted in elevated ABR thresholds that exceeded the maximum recording limit, while GGA pretreatment before 3-NP exposure led to a significant decrease in hearing threshold shift. Histological analysis of above former group revealed loss of type II fibrocytes in the spiral ligament, hair cells in the organ of Corti, stellate fibrocytes in the spiral limbus and spiral ganglion cells, while in above latter group, these cells were preserved. Control animals revealed weak HSP70 expression in the nuclei of some supporting cells (pillar cells, Deiters' cells and Hensen's cells) and interdental cells. Animals receiving GGA alone showed strong HSP70 expression in the same area as in control animals, while animals receiving both GGA and 3-NP demonstrated slightly decreased HSP70 expression in that area. These results suggest that GGA may protect the cochlea against acute injury resulting from mitochondrial dysfunction.

Context: Enlargement of the vestibular aqueduct (EVA) is a commonly detected inner ear anomaly related to hearing loss and often associated with mutations of SLC26A4 encoding pendrin, a transmembrane exchanger of Cl−, I−, and HCO3−. Here we describe the phenotypes of 27 Korean EVA subjects and their SLC26A4 genotypes determined by bidirectional nucleotide sequencing. Results: The detected variants include two novel missense substitutions (p.V138L and p.P542R). We characterized the ability of p.V138L and p.P542R pendrin products to traffic to the plasma membrane in COS-7 cells and to transport Cl−, I−, and HCO3− in Xenopus oocytes. The results indicate that p.P542R is a benign polymorphic variant, whereas p.V138L is a pathogenic mutation. Since this and other studies of East Asian EVA cohorts show that the majority of SLC26A4 mutations affect either or both of two amplicons (exons 7–8 and 19), we developed a hierarchical protocol that integrates direct sequencing with denaturing high-performance liquid chromatography analyses for detection of SLC26A4 mutations in these populations. We validated the cost efficiency of the integrated protocol by a simulated screen of published East Asian EVA cohorts with known SLC26A4 genotypes. Conclusions: Our study further defines the spectrum of SLC26A4 mutations among East Asians and demonstrates a rapid and efficient protocol for their detection.

The purpose of this study was to investigate the developmental change of epithelial Na + channel function in epithelial cells of rat Reissner's membrane. The Reissner's membrane was isolated from the upper turn of the cochlea at different stages of development. The vibrating probe technique was chosen to measure transepithelial currents under short circuit conditions. Amiloride-sensitive Na + current in the Reissner's membrane developed postnatally between days 3 and 5, which was completely blocked by amiloride. This tendency remained from days 5 through 14. Development of Na + transport in epithelial cells of the Reissner's membrane may contribute considerably to the accomplishment of low Na + concentration in the endolymph during early neonatal period.

Objectives. The objective of this study was to compare the long-term auditory performance and language skill depending on the age of cochlear implantation in the Korean population. We especially tried to separate the effect of maturation/ development from that of the age at implantation. Methods. Eighty-six pre-lingual children with profound hearing loss who underwent a cochlear implantation before the age of six and had been followed for more than 3 yr were included in this study prospectively. Categories of Auditory Performance (CAP) and Korean Picture Vocabulary Test (K-PVT) were serially followed up. In order to separate the age at implantation effect, K-PVT results were readjusted to the child’s chronological age in the normal hearing population. Results. When the CAP and K-PVT scores were directly compared without chronological readjustment, we failed to show a significant difference for improvements according to the age at implantation. Early cochlear implantation was associated with better language development, only when the K-PVT scores were readjusted to percentile scores of their chronological age. Conclusion. Early cochlear implantation was associated with better language development even within the critical period. This advantage may be recognized only when the effect of the age at implantation is separated from the effect of maturation/development.

The first objective of this study was to identify rates, types, and laterality of clinically relevant inner ear malformations in children with unilateral sensorineural hearing loss (USNHL). The second objective was to assess the change of the ipsilesional and contralesional hearing thresholds of the patients with USNHL and the association between hearing change with time and the findings on high-resolution temporal bone computed tomography (TBCT).Retrospective case review.Tertiary referral center.A total of 322 children diagnosed with USNHL on initial audiometry were included.Otologic examination, pure-tone audiometry or auditory brainstem response, and high-resolution TBCT.Radiologic findings demonstrating clinically relevant bony or soft tissue malformations of the inner ear. Audiologic findings of change in thresholds.In a series of 322 consecutively investigated children with USNHL, 93 TBCT scans (28.9%) were identified as abnormal. The abnormal CT findings included cochleovestibular malformations (49 cases; 52.7%), vestibular malformations (27 cases; 29.0%), and malformations of vestibular or cochlear aqueducts (17 cases; 18.3%). Of these abnormal CT findings, 18 cases (19.4%) showed bilateral malformations. Incomplete partition type II was the most common type of malformation (28 cases), followed by narrow internal auditory canal (23 cases) and subsequently followed by enlarged vestibular aqueduct syndrome (17 cases). Of 244 patients, 77 (31.6%) in the profound USNHL group accompanied malformations, which was significantly higher than 23.8% (15 of 78) in the nonprofound (mild to severe) USNHL group (p = 0.036). Of 115 patients who were regularly followed up for more than 6 months, 7 (6.1%) had hearing decrement (including 3 cases of bilateral decrement). Of 85 patients in the normal TBCT group, 4 (4.7%) revealed hearing decrement, and considering there were only 27 patients with nonprofound USNHL in this group, the rate of decrement was as much as 14.8% (4 of 27). Of 24 patients in the unilateral malformation group, 1 patient (4.2%) showed worsening of hearing, and 2 of 6 (33.3%) patients showed worsening of hearing in the bilateral malformation group.Based on the results, we propose all children with USNHL should have a TBCT scan because management, including genetic counseling and prognostic predictions of these cases, may be significantly influenced by the CT outcome. Moreover, the non-negligible rate of progressive nature of ipsilateral and contralateral SNHL in normal-looking TBCT group and in groups with inner ear malformations mandates longitudinal audiologic assessments for both ears

Extracellular adenosine triphosphate (ATP) released from cellular sources plays an important role in variety of the cochlear physiologic processes. The primary purinergic receptor subtype in the cochlea is the P2X2 receptor, which is a subtype of P2X receptor. This receptor appears to mediate a protective decrease in the electrical driving force in response to acoustic overstimulation. Outer sulcus cells (OSCs) in the cochlear lateral wall appear to maintain an adequate K+ concentration in the cochlear endolymph in response to varying intensities of auditory stimulation. However, little is known about developing OSCs. The purpose of this study was to investigate subtypes of purinergic receptors in developing rat OSCs using a voltage-sensitive vibrating probe. Results showed that only two P2 receptors (P2Y4 and P2X2) contributed to the regulation of short circuit currents in neonatal OSCs. ATP increased cation absorption via apical nonselective cation channels after activating P2Y4 receptors in early neonatal OSCs. P2Y4 expression rapidly declined postnatally and reached near adult levels on postnatal day 14. P2X2 was co-expressed with P2Y4 in early neonatal OSCs. Temporal changes in P2Y4 during OSC development might be involved in the establishment of the endolymphatic ion composition needed for normal auditory transduction and/or specific cellular differentiation.

Benefits of the use of anteriorly and inferiorly based periosteal flaps (AIPFs) in congenital aural atresia (CAA) patients was found to be effective at reducing canal stenosis (CS) occurrence by long term F/U. However, in terms of minimizing CS, in addition to recruitment of AIPFs, considerations of patient factors, such as degree of microtia and age are mandatory.AIPF during canaloplasty were evaluated with a specific focus on whether this technique can offset the negative effects of several risk factors for postoperative CS after CAA surgery.The authors undertook a retrospective review of the medical records of 164 congenital aural atresia patients (190 ears) who had undergone surgery at Seoul National University Hospital. Median follow up period was 54 months. The anterior approach surgical method with and without the use of AIPFs were utilized in 111 and 79 ears respectively. Comparison of the influences of several factors on CS occurrence was undertaken by statistical analyses to evaluate whether this AIPFs technique can counterbalance the negative effect of patient factors in postoperative CS.Those with a younger age (12 yrs), moderate to severe microtia (grade II, III), or those in whom AIPF was not used in surgery (non AIPF group) were found to show statistically significant higher frequency of CS(+). Nevertheless, the positive effect of AIPF was not able to completely counterbalance the effects of negative patient factors on CS development. A protocol compatible with the results of this study that minimizes CS is presented in the discussion.

To review surgical findings and hearing outcomes of incus footplate assembly (IFA) for the patients with conductive hearing loss due to missing stapes superstructure with a mobile stapes footplate.Retrospective case review and survey.Pre- and postoperative audiometric data and intraoperative findings were reviewed. Postoperative air-bone gap (ABG) and ABG closure (postoperative air-conduction threshold-preoperative bone-conduction threshold) were analyzed.The causes of missing stapes superstructure and conductive hearing loss were congenital ossicular anomaly (n = 5), chronic otitis media (n = 2), and congenital cholesteatoma (n = 1). The prosthesis was designed to fit between the medial side of the incus and stapes footplate and had a mean length of 3.6 ± 0.5 mm. The mean pre- and postoperative ABG were 38.3 ± 4.8 and 13.3 ± 10.0 dB, respectively. The postoperative ABG at frequencies of 0.25, 0.5, 1.0, 2.0, 3.0, and 4.0 kHz were 20.0 ± 15.4, 16.9 ± 11.9, 16.3 ± 10.3, 10.6 ± 7.3, 12.9 ± 14.0, and 23.1 ± 16.2 dB, respectively. The mean ABG closure was 9.5 dB (range, -1.3∼35.8 dB). Seven cases obtained the best results (mean ABG closure ≤10 dB). In the remaining patient, the mean ABG closure was 9.5 dB until 6 months after surgery, but was 35.8 dB 1 year after surgery.IFA seems to be a reasonable surgical option in patients with missing the stapes superstructure, but with a mobile footplate in which the long process of incus is preserved.4 Laryngoscope, 126:2569-2573, 2016.

To evaluate the correlation between a narrow bony cochlear nerve canal (BCNC) and facial nerve stimulation (FNS) after cochlear implantation (CI) and their underlying mechanisms and to predict the risk of FNS preoperatively.Retrospective cohort study.A total of 64 pediatric cases that underwent CI were included. Among them, 32 cases experienced FNS after CI, and another 32 cases were selected from 817 pediatric implantees by stratified random sampling. The width of the BCNC, the status of the cochlear nerve (CN) and the internal auditory canal (IAC), T level, and C level were compared and analyzed. Strategies for eliminating FNS were also analyzed.The FNS group showed a narrower BCNC (1.09 ± 0.52 mm) than the control group (1.99 ± 0.61 mm; P.01), a lower CN/facial nerve ratio (0.32 ± 0.36) than the control group (1.34 ± 0.76; P.01), and narrower IAC diameter (4.06 ± 1.71 mm) than the control group (5.66 ± 1.36 mm; P.01). The FNS group also showed higher T level (165.7 ± 28.3 μA) than the control group (142.2 ± 21.2 μA; P.01). Adjustment of the C levels and/or pulse width and switching off offending electrodes were attempted to eliminate FNS, with a 75.0% success rate. The FNS group still showed low Categories of Auditory Performance scores (3.00 ± 1.90) compared with the control group (5.94 ± 1.41, P.01) after adjustment.A narrow BCNC could be a cause of FNS after CI. Therefore, careful selection of the side for CI and programming strategies are required to reduce FNS.4. Laryngoscope, 126:1433-1439, 2016.

Objectives (1) To assess the long-term effects of cochlear implantation (CI) on speech perception and school life, and (2) to evaluate behavioral and emotional development, including social skills, post-implantation. Methods We telephoned caregivers and asked them a standardized questionnaire. We used the data to explore the daily lives (including school life) of children who had undergone CI before the age of 4 years and who had used the device for >10 years. We also evaluated behavioral/emotional development. Results Most children used CI devices for virtually all their waking moments and attended mainstream schools. Moreover, more than 75% of them could comprehend common phrases or conversations without lip-reading and carry out a telephone conversation with a person known to them. The mean T-scores for all scales of behavioral/emotional assessment, including those concerning social skills, were within the normal ranges, although scores on the competence scale were lower than those on other scales. Conclusions This long-term study of early-CI children shows that CI improves not only speech perception, but also behavioral/emotional development, including social skills.

A cerebrospinal fluid (CSF) gusher during cochlear implantation can produce surgical difficulties and postoperative life-threatening morbidities such as meningitis. We reviewed our experiences of managing CSF gush during cochlear implantation, and assessed the radiologic characteristics of a CSF gusher. Seventy-two congenital deaf children with inner ear malformation underwent cochlear implantation in Seoul National University Children's Hospital from November 1988 to March 2004. Among these, 15 patients showed CSF gush intraoperatively. Total or partial defect of the modiolus increased the risk of CSF gush significantly. Dilated vestibular aqueduct and bulbous IAC showed no statistical significance. During surgery, the mucosa around the cochleostomy opening was removed and soft tissue plugs were packed alongside the active electrodes. Some additional procedures such as mastoid or posterior tympanic obliteration were performed in three patients with intractable CSF gush. No lumbar drain was used. Postoperative meningitis developed in one case after 7 months of implant usage; however, there was no evidence of CSF leak in all cases during the postoperative follow-up (1–47 months, mean 22 months). Surgeons should be prepared to cope with CSF gusher during cochlear implantation in cases with congenital inner ear malformation, particularly if the patient has radiological evidence of modiolar defect.

To propose management options for cochlear implantation in chronic otitis media based on our experiences.A retrospective review of 418 cochlear implantations performed by the 2 senior authors between November 1988 and February 2004 was conducted. Nine patients who had chronic otitis media in the ear to be implanted were included. Of these, three showed active inflammation at presentation; the other six cases had undergone previous tympanomastoidectomy surgery and did not show active inflammation at presentation.Five patients with active inflammation or without an adequate soft tissue layer in the mastoid bowl underwent a two-stage procedure. Four cases who showed inactive inflammation and had an adequate tissue layer to protect the electrode array underwent a single-stage technique, although two of them showed dry tympanic membrane perforation. No local or intracranial inflammation recurred. The electrode was exposed in the mastoid bowl in one case, who was managed with revisional mastoid obliteration with soft tissue.Complete eradication of inflammation and the securing of a strong protective soft tissue layer over the electrode are prerequisites for cochlear implantation in ears with chronic otitis media.

Cochlear implantation is an established method of auditory rehabilitation for the severe and profoundly hearing impaired; however, it may cause complications. This study focused upon the intraoperative problems and postoperative complications of cochlear implantation. The medical records of 430 patients who underwent cochlear implantation at our center from November 1988 through March 2004 were analyzed retrospectively. Major complications were reported in nine cases (2.1%), which included one device explantation. Minor complications (25 cases, 5.8%) such as dizziness, skin rash and hematoma were self-limited. The mechanical device failures were identified in nine cases (2.1%). The causes of the postoperative complications were examined, and the management methods and the results obtained are described. Surgeons must be prepared to cope with the intra- and postoperative problems associated with cochlear implantation. A careful preoperative evaluation would reduce the frequency of serious complications.