Search

Objectives. The impacts of ventilation tube (VT) type and effusion composition on the VT extrusion rate and complications in children with otitis media remain unclear. This part II study evaluated the factors affecting the extrusion rate, recurrence rate, and complications of VT insertion.Methods. A prospective study was conducted between June 2014 and December 2016 (the EVENT study [analysis of the effectiveness of ventilation tube insertion in pediatric patients with chronic otitis media]), with follow-up data collected until the end of 2017. Patients aged PP=0.005), age (HR, 3.949; 95% CI, 1.239–12.590; P=0.02), and effusion composition (P=0.005) were significantly associated with the time to recurrence of middle ear effusion. Ears with purulent (mean, 567 days) and glue-like (mean, 588 days) effusions exhibited a shorter time to recurrence than ears with serous (mean, 846 days) or mucoid (mean, 925 days) effusions. The revision VT rates during follow-up were 3.5%, 15.5%, 10.4%, and 38.9% in ears with serous, mucoid, glue-like, and purulent effusions, respectively (P

Syphilis is a sexually transmitted disease caused by Treponema pallidum, which can invade various organs. Syphilis can also cause otologic symptoms such as hearing impairment, tinnitus or dizziness and these otologic symptoms can occur at any stage of syphilis and can be associated with neurosyphilis. We report here a case of rapid progressive neurosyphilis showing hearing impairment in a patient with ankylosing spondylitis. He was treated with anti-interleukin 17A monoclonal antibody. Since syphilis is one of the causes of reversible sensorineural hearing loss and syphilis infection with immunosuppression can cause progressive hearing loss if patients in immunomodulatory therapy have sensorineural hearing loss, the possibility of syphilis should be considered.

Background Cisplatin (CP) is an effective anticancer drug broadly used for various types of cancers, but it has shown ototoxicity that results from oxidative stress. Berberine has been reported for its anti-oxidative stress suggesting its therapeutic potential for many diseases such as colitis, diabetes, and vascular dementia. Objective Organ of Corti of postnatal day 3 mouse cochlear explants were used to compare hair cells after the treatment with cisplatin alone or with berberine chloride (BC) followed by CP. Methods We investigated the potential of the anti-oxidative effect of BC against the cisplatin-induced ototoxicity. We observed a reduced aberrant bundle of stereocilia in hair cells in CP with BC pre-treated group. Caspase-3 immunofluorescence and TUNEL assay supported the hypothesis that BC attenuates the apoptotic signals induced by CP. Reactive oxygen species level in the mitochondria were investigated by MitoSOX Red staining and the mitochondrial membrane potentials were compared by JC-1 assay. Results BC decreased ROS generation with preserved mitochondrial membrane potentials in mitochondria as well as reduced DNA fragmentation in hair cells. In summary, our data indicate that BC might act as antioxidant against CP by reducing the stress in mitochondria resulting in cell survival. Conclusion Our result suggests the therapeutic potential of BC for prevention of the detrimental effect of CP-induced ototoxicity.

Background and Objectives The purpose of this study is to investigate the replacement of external sound processors and to help understand the economic burden experienced from cochlear implant users.Subjects and Method Among the 500 cases of cochlear implant surgery from 1992 to 2019, 336 cases from 311 patients who had used a cochlear implant for more than 1 year were enrolled. The period of cochlear implant use, replacement of the sound processor, the number, method, and reason of replacements were examined.Results One hundred sixty cases (47.62%) replaced the sound processor at least once. There were a total of 213 replacements made in 160 cases. The most common reason for replacing the sound processors was because it could not be repaired (71 replacements, 33.33%), with their period of use being an average of 12 years. The most common replacement method of the sound processors was by purchasing with medical insurance benefits (100 replacements, 46.95%), with the usage period being an average of 11 years and 4 months.Conclusion Cochlear implant users replaced the sound processor for various reasons and the period of using one sound processor was relatively short. About half of all replacement cases were made by applying for medical insurance benefits. Others purchased directly through a sales company and paid a relatively high cost. Therefore, it is necessary to expand the medical insurance for external sound processor of cochlear implants to include exchange times considering the economic burden of cochlear implant users.

Background and Objectives The optimal dose or type of systemic steroid for treating idiopathic sudden sensorineural hearing loss (ISSNHL) is unclear. Herein, we compare the efficacy of three steroid treatment protocols.Subjects and Method We reviewed the medical records of 140 adult ISSNHL patients from a tertiary medical center. The patients were divided into three groups based on their treatment regimen: Group 1 received intravenous 10 mg/day dexamethasone combined with intratympanic (IT) steroid injection, followed by prednisolone for 5 days after discharge; Group 2 received 10 mg/day dexamethasone for 5 days, followed by 5 mg/day for 5 days over a 10-day hospitalization period; and Group 3 received 10 mg/day dexamethasone combined with IT steroid injection during a 5-day hospital stay, followed by 5 mg/day dexamethasone for 5 days after discharge. The hearing thresholds were measured using an automatic audiometer at 0.5, 1, 2, 3, 4, and 8 kHz. Hearing recovery on Day 90 was categorized according to Siegel’s criteria.Results Univariate and multivariate analyses showed that patients in Group 3 had the lowest hearing thresholds, and the best results for speech reception threshold and speech discrimination scores. The impact of favorable thresholds in Group 3 was better among patients with a baseline average hearing threshold of ＜70 dB. Complete recovery was more likely in Group 3 than in the other groups, based on the odds ratios.Conclusion Administration of dexamethasone-based systemic steroid combined with IT steroid injection and a relatively long hospitalization period produced the most favorable result.

Objective This study aimed to evaluate success rates after ossicular chain reconstruction using different materials. Study design Retrospective cohort study. Setting Tertiary referral center. Patients Four hundred forty-three participants who underwent ossiculoplasty at a tertiary medical center were included. Intervention Ossicular chain reconstruction using five materials: autologous malleus, incus, and cortical bone, as well as Hydroxyapatite (HA) and titanium. Main outcome measures Hearing data were measured 1 day preoperatively and 6 months postoperatively. Successful hearing outcomes were defined by the fulfillment of more than one of the following criteria: postoperative air-bone gap of 20 dB or less, hearing air conduction (AC) gain of 15 dB or more, or postoperative AC hearing less than 30 dB. Results Preoperative median AC values (95% confidence interval) among participants with malleus, incus, cortical bone, HA, and titanium transplants or prostheses were 50 (39.6-54.6) dB, 51.3 (48.1-51.8) dB, 50 (45.2-52.2) dB, 56.3 (50.9-57.6) dB, and 54.3 (48.5-56.0) dB, respectively (p = 0.092). The success rates in malleus, incus, cortical bone, HA, and titanium were 53.3%, 60.3%, 51.7%, 61.6%, and 69.7%, respectively. Titanium had the highest success rate among the five materials, but the differences between the materials were not statistically significant (p = 0.283). Titanium had highest success rate among the participants with erosive stapes suprastructure or obstructed Eustachian tubes (p = 0.042 for erosive stapes suprastructure and p = 0.010 for obstructed Eustachian tubes). Conclusion Our study demonstrated that titanium prostheses would be a good alternative for ossiculoplasty in cases wherein autologous material is unavailable, especially in association with unfavorable conditions, such as with the presence of cholesteatoma, erosive stapes suprastructure, edematous middle ear mucosa, and obstructed Eustachian tube.

Skull base osteomyelitis (SBO) is an uncommon and a potentially life-threatening condition if not promptly recognized and properly treated. The aim of our study was to present a 32-case series of patients diagnosed with SBO at a single center. In this retrospective study, we reviewed the data of patients diagnosed with otogenic SBO between January 2011 and January 2020. 32 patients were enrolled in the study. SBO diagnosis was based on a combination of symptoms and physical examination, bone scan, brain magnetic resonance imaging, and pathologic examination findings. The following clinical data were collected during the follow-up period: types of antibiotics used, duration of antibiotic treatment, C-reactive protein level, presence of disease control, duration from the onset of symptoms to diagnosis, and patient survival. The mean follow-up period was 11 (1–110) months. The mean duration of antibiotic treatment was 115 (19–223) days. The mean C-reactive protein levels at the time of diagnosis and at the endpoint of follow-up were 3.05 (0.56–18.31) and 0.21 (0.03–33.61) mg/dL, respectively (P

Idiopathic intracranial hypertension (IIH) is a disorder that commonly occurs in obese young women of childbearing age and is characterized by symptoms such as pulsatile tinnitus, dizziness, headache, nausea, vomiting, and visual loss without any structural or vascular abnormalities in the intracranial cavity. We recently experienced a case of a 33-year-old obese woman who presented with right-sided pulsatile tinnitus, which is an early symptom for IIH. The patient was successfully treated with weight reduction and carbonic anhydrase inhibitor (acetazolamide). Pulsatile tinnitus requires thorough diagnosis and examination because it can be cured if the anatomical or functional cause is identified and treated. When obese women of childbearing age present with pulsatile tinnitus at the otorhinolaryngology outpatient department, treatment for IIH should be initiated after appropriate examination and diagnosis as pulsatile tinnitus may be the only symptom for IIH.

Previous studies have shown that inflammatory markers are associated with hearing impairment in participants with inflammatory diseases. Therefore, screening for inflammatory status may have value in predicting the risk of hearing loss (HL) in participants with underlying inflammation. Therefore, red cell distribution width (RDW), an indirect indicator of inflammatory status, was used. The aim of the present study was to evaluate the clinical association between RDW and hearing impairment in a Korean population with chronic kidney disease (CKD).In this cross sectional study, a total of 461 participants with estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 mThe numbers of participants in the Low, Middle, and High tertiles were 172, 154, and 135, respectively. The AUROCs of RDW and hs-CRP for HL were 0.644 and 0.522, respectively. In the multivariate analysis, the Low/Mid-Freq, High-Freq, and AHT values were lowest in the participants in the Low tertile compared with those in the Middle or High tertiles Multivariate logistic regression analyses showed that participants in the High tertile exhibited 2.32- and 1.78-fold higher odds for HL compared to those of the Low and Middle tertiles, respectively. There were positive associations between RDW and AHT values.High RDW was associated with increased odds of hearing impairment in the Korean population with CKD.

We designed and implemented an electromagnetic transducer for implantable bone conduction hearing aids. The proposed transducer is smaller than previous bone conduction transducers for easy implantation and was designed using high permeability metals to produce large electromagnetic forces. In addition, the number of cantilever beams was changed from two to three to minimize distortion of the transducer, potentially due to twisting of the cantilever beam. The proposed transducer consists of a titanium cover with three screw holes, a metal ring, a circular plate, a vibrational membrane with a three-cantilever structure, a metal plate and cylinder, a permanent magnet, top and bottom coils, and a cylindrical titanium case. The transducer was optimally designed based on analysis of electromagnetic and mechanical vibrations, and the target resonance frequency was derived by controlling the variable elements of the vibrational membrane. The transducer was manufactured based on the results of finite element analysis, and the validity of the design was verified by comparing the results of vibration measurement experiments and a simulation. Finally, to evaluate the performance of the proposed transducer, the transducer was attached to the mastoid of participants and functional near-infrared spectroscopy was used to measure brain activation changes of the auditory cortex due to vibration stimulation.

Drug-induced hearing loss is a major type of acquired sensorineural hearing loss. Cisplatin and aminoglycoside antibiotics have been known to cause ototoxicity, and excessive accumulation of intracellular reactive oxygen species (ROS) are suggested as the common major pathology of cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Fursultiamine, also called thiamine tetrahydrofurfuryl disulfide, is a thiamine disulfide derivative that may have antioxidant effects. To evaluate whether fursultiamine can prevent cisplatin- and kanamycin-induced ototoxicity, we investigated their preventive potential using mouse cochlear explant culture system. Immunofluorescence staining of mouse cochlear hair cells showed that fursultiamine pretreatment reduced cisplatin- and kanamycin-induced damage to both inner and outer hair cells. Fursultiamine attenuated mitochondrial ROS accumulation as evidenced by MitoSOX Red staining and restored mitochondrial membrane potential in a JC-1 assay. In addition, fursultiamine pretreatment reduced active caspase-3 and TUNEL signals after cisplatin or kanamycin treatment, indicating that fursultiamine decreased apoptotic hair cell death. This study is the first to show a protective effect of fursultiamine against cisplatin- and aminoglycoside antibiotics-induced ototoxicity. Our results suggest that fursultiamine could act as an antioxidant and anti-apoptotic agent against mitochondrial oxidative stress.in cochlear hair cells.

BACKGROUND: This paper describes the design and implementation of a dual-coil type electromagnetic actuator for implantable bone conduction hearing devices. OBJECTIVE: The structure of the proposed actuator was designed to generate maximum Lorentz force via the dual-coil method with a closed magnetic circuit. To satisfy the indications required by implantable bone conduction hearing devices, high output was generated within a specific frequency range using a vibrational membrane with a cantilever. METHODS: The structure of the membrane consists of a fixed ring, a circular plate, and two cantilevers connected symmetrically. Variable elements of the vibrational membrane affecting the actuator frequency characteristics were analyzed through mathematical modeling and finite element analysis, based on the analysis used to derive the optimum structure of the vibrational membrane. The components of the actuator were fabricated through chemical etching and computer numerical control process, and the bone conduction actuator was fabricated through the precision assembly process. RESULTS: The output characteristics of the implemented actuator were measured using a laser Doppler vibrometer. As a result of measurement, the proposed actuator generated mechanical resonance at 1.2 kHz. CONCLUSIONS: By comparing the measured results with the finite element analysis results, we confirmed the validity of the proposed actuator design.

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has ushered in a new era of gene therapy. In this study, we aimed to demonstrate precise CRISPR/Cas9-mediated genome editing of the splicing mutation c.919-2A > G in intron 7 of the SLC26A4 gene, which is the second most common causative gene of congenital hearing loss. We designed candidate single-guide RNAs (sgRNAs) aimed to direct the targeting of Staphylococcus aureus Cas9 to either exon 7 or exon 8 of SLC26A4. Several of the designed sgRNAs showed targeting activity, with average indel efficiencies ranging from approximately 14% to 25%. The usage of dual sgRNAs delivered both into Neuro2a cells and primary mouse embryonic fibroblasts resulted in the successful removal of large genomic fragments within the target locus. We subsequently evaluated genome editing in the presence of artificial donor templates to induce precise target modification via homology-directed repair. Using this approach, two different donor plasmids successfully introduced silent mutations within the c.919-2A region of Slc26a4 without evident off-target activities. Overall, these results indicate that CRISPR/Cas9-mediated correction of mutations in the Slc26a4 gene is a feasible therapeutic option for restoration of hearing loss.

Rationale: Mutations of SLC26A4 that abrogate pendrin, expressed in endolymphatic sac, cochlea and vestibule, are known to cause autosomal recessive sensorineural hearing loss with enlargement of the membranous labyrinth. This is the first study to demonstrate the feasibility of gene therapy for pendrin-related hearing loss. Methods: We used a recombinant viral vector to transfect Slc26a4 cDNA into embryonic day 12.5 otocysts of pendrin-deficient knock-out (Slc26a4∆/∆ ) and pendrin-deficient knock-in (Slc26a4tm1Dontuh/tm1Dontuh ) mice. Results: Local gene-delivery resulted in spatially and temporally limited pendrin expression, prevented enlargement, failed to restore vestibular function, but succeeded in the restoration of hearing. Restored hearing phenotypes included normal hearing as well as sudden, fluctuating, and progressive hearing loss. Conclusion: Our study illustrates the feasibility of gene therapy for pendrin-related hearing loss, suggests differences in the requirement of pendrin between the cochlea and the vestibular labyrinth, and documents that insufficient pendrin expression during late embryonal and early postnatal development of the inner ear can cause sudden, fluctuating and progressive hearing loss without obligatory enlargement of the membranous labyrinth.

Congenital intratympanic membrane cholesteatoma (ITMC) is a rare type of congenital cholesteatoma located within the tympanic membrane. This lesion tends to increase in size over time. The development of ITMC can cause several complications such as hearing impairment, dizziness, facial palsy, and intracranial complications, similar to any other cholesteatoma. The treatment of congenital cholesteatoma requires the removal of the lesion through surgery, because disease progression induces bony destruction of the nearby tissue. Most patients presenting with this cholesteatoma type are also treated with primary surgical removal. However, we recently experienced a case of an ITMC that showed a natural transition to an external auditory canal cholesteatoma.

Significance Auditory neuropathy spectrum disorder (ANSD) is a confounding auditory disease in which the subjects respond to sound but have difficulties in speech discrimination. Herein, we examined two Asian families with hereditary late-age–onset ANSD. By linkage analysis and exome sequencing, we identified the TMEM43-p.(Arg372Ter) variant as the etiology of the disease. To examine the mechanism of TMEM43 on ANSD, we generated a knock-in mouse with the p.(Arg372Ter) variant that recapitulated the progressive hearing loss phenotype of the two families. We discovered that variation in TMEM43 impairs the connexin-linked function of mediating passive conductance current in cochlear glial cells. Based on the pathology involving cochlear glial cells, we performed cochlear implant on the human patients, and their speech discrimination ability was restored., Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, TMEM43, mainly expressed in GLSs. We identify p.(Arg372Ter) of TMEM43 by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.

Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, TMEM43, mainly expressed in GLSs. We identify p.(Arg372Ter) of TMEM43 by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.

Purpose Ossiculoplasty outcome parameter staging (OOPS) and middle ear risk index (MERI) are the most commonly used indices for predicting prognosis of patients with chronic otitis media (COM). This study aimed to verify the efficiency of OOPS and MERI scores in predicting outcomes of patients with COM who underwent tympanoplasty. Methods We retrospectively reviewed the data of patients who underwent tympanoplasty (n = 526). OOPS, and MERI scores were collected. Hearing data were measured 1 day preoperatively, and 3 and 12 months postoperatively. Operation success was defined according to the Korean Society of Otology guidelines. Results For calculation of success, the ROC values of MERI were 0.551 at 12 months. ROC values of OOPS were 0.637 at 12 months. There were no significant differences in hearing variables among the three groups according to MERI. There were significantly favorable outcomes in hearing variables in the low-risk group in OOPS. The mean OOPS score was greater in patients with success than those with non-success. Otorrhea, ossicle status, and status of mucosa as variables in both indices were associated with success. The type of mastoidectomy as a variable in OOPS alone was associated with success. Absence of hypertension, presence of ossiculoplasty, and use of incus as ossiculoplasty material were associated with poor success rate. Conclusion Compared with MERI, the OOPS index was more closely associated with the hearing outcomes, which may be due to the extent of inflammation in the OOPS index.

Objectives. This study was conducted to evaluate the user satisfaction, efficacy, and safety of round window (RW) vibroplasty using the Vibrant Soundbridge (VSB) in patients with persistent mixed hearing loss after mastoidectomy.Methods. The study included 27 patients (mean age, 58.7 years; age range, 28–76 years; 11 men and 16 women) with mixed hearing loss after mastoidectomy from 15 tertiary referral centers in Korea. The VSB was implanted at the RW. The Korean translation of the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire and the Korean version of the International Outcome Inventory for Hearing Aids (K-IOI-HA) questionnaire were used to evaluate user satisfaction as the primary outcome. The secondary outcome measures were audiological test results and complication rates.Results. The mean scores for ease of communication (61.3% to 29.7% to 30.2%), reverberation (62.1% to 43.1% to 37.4%), and background noise (63.3% to 37.7% to 34.3%) subscales of the APHAB questionnaire significantly decreased after VSB surgery. The mean K-IOI-HA scores at 3 and 6 months after surgery were significantly higher than the mean preoperative score (18.6 to 27.2 to 28.1). The postoperative VSB-aided thresholds were significantly lower than the preoperative unaided and hearing aid (HA)-aided thresholds. There was no significant difference between preoperative unaided, preoperative HA-aided, and postoperative VSB-aided maximum phonetically balanced word-recognition scores. None of the 27 patients experienced a change in postoperative bone conduction pure tone average. One patient developed temporary facial palsy and two developed surgical wound infections.Conclusion. RW vibroplasty resulted in improved satisfaction and audiological test results in patients with mixed hearing loss after mastoidectomy, and the complication rate was tolerable.

Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have never been clearly associated with progressive deafness. Herein, we present a novel deafness locus mapped to chromosome 3p25.1 and a new auditory neuropathy spectrum disorder (ANSD) gene TMEM43 mainly expressed in GLSs. We identify p.R372X of TMEM43 by linkage analysis and exome sequencing in two large Asian families. The knock-in (KI) mouse with p.R372X mutation recapitulates a progressive hearing loss with histological abnormalities exclusively in GLSs. Mechanistically, TMEM43 interacts with Cx26 and Cx30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.R372X mutation is introduced. Based on the mechanistic insights, cochlear implant was performed on two patients and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a novel deafness gene and its causal relationship with ANSD.

Cisplatin (CP) is a chemotherapeutic drug used to treat cancerous solid tumors, but it causes serious side effects, including ototoxicity. The major cause of CP-induced ototoxicity is increased levels of mitochondrial reactive oxygen species (ROS). In this study, we examined the effect of 2-Isopropyl-3H-naphtho(1,2-d)imidazole-4,5-dione (KL1333), a β-lapachone derivative, on CP-induced ototoxicity using ex vivo organotypic culture system of cochlea. Hair cell damages in CP-treated cochlear explants with or without KL1333 were compared by immunohistochemistry. CP-induced oxidative stress and the preventive effect of KL1333 were analyzed by measuring intracellular ROS levels and depolarization of mitochondrial membrane potential. Activation of apoptosis signaling pathway was detected using TUNEL assay and immunostaining of cleaved caspase-3. As the results, it was found that KL1333 pretreatment significantly decreased stereocilia degeneration and hair cell loss, and prevented an increase in mitochondrial ROS levels in response to CP. Immunohistochemical examinations of cochlear explants revealed greater caspase-3 immunopositivity in the CP group than in controls, while the KL1333 + CP group showed significantly less immunopositivity than the CP group (P < 0.05). Thus, it appeared that KL1333 protected hair cells in the organ of Corti from CP-induced apoptosis by decreasing mitochondrial damages due to the production of mitochondrial ROS. This study is the first report showed the preventive effect of KL1333 against CP-induced ototoxicity. Although further studies should be performed to determine if KL1333 could maintain anticancer effect of CP, our data cautiously suggests that the antioxidant KL1333 can be used as an effective anti-apoptotic agent to prevent ototoxicity caused by CP-induced oxidative stress, and may prove useful in preventing hearing loss caused by CP.

Objective To compare the effect of injection time intervals of intratympanic (IT) dexamethasone (DEX) in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods Seventy-five adults with ISSNHL were grouped into four groups according to the IT DEX interval. In addition to concurrent oral steroid medication for two weeks, patients received IT DEX injections every 1, 2, 3, and four days, respectively. (Group 1, Group 2, Group 3, and Group 4). We evaluated the treatment outcomes according to modified criteria from “Clinical Practice Guideline: Sudden Hearing Loss” of the American Academy of Otolaryngology-Head and Neck Surgery (AAO HNS) to justify treatment success. Results There were no significant differences in demographic and baseline audiometric data. The mean of pure tone audiometry (PTA) and speech discrimination score (SDSs) were significantly improved after oral steroid and IT DEX treatment in all four groups. Group 1 showed significantly higher improvement than Group 4 in PTA after treatment. There was a significantly higher complete recovery (CR) rate in Group 1 than Group 4. Conclusion We found a statistically significant difference in the complete hearing recovery rate and audiometric results (PTA) between the group with a daily interval of injections and the group with a four-day time interval. Therefore, daily time intervals in intratympanic steroid injection may be considered as an option for better improvement of hearing in patients with ISSNHL.

Enlarged vestibular aqueduct is the most common inner ear malformation in pediatric patients with sensorineural hearing loss. Here, we report a new presentation of enlarged vestibular aqueduct in a Korean family. The family consists of two parents and five daughters, and the first and second daughters were diagnosed with bilateral enlarged vestibular aqueducts. The third daughter, who showed no signs of hearing deterioration, came to medical attention with incomplete Horner syndrome. Evaluations for localization of Horner syndrome on the patient and Sanger sequencing of SLC26A4 on the family members were performed. Although auditory brainstem response and pure tone audiometry of the third daughter were normal, temporal bone computed tomography demonstrated bilateral enlarged vestibular aqueducts. Sanger sequencing of SLC26A4 revealed compound heterozygous variants c.2168A>G and c.919-2A>G in the first, second, and third daughters. Diagnosis of enlarged vestibular aqueduct is often delayed because the degree of hearing loss can vary, and a considerable phenotypic variability can be shown even in family members with the same SLC26A4 variations. Fluctuations of CSF pressure into the cochlear duct and recurrent microruptures of the endolymphatic membrane could result in damage of sympathetic nerve supplying to the inner ear, which could explain the mechanism of Horner syndrome associated with enlarged vestibular aqueduct.

The-state-of-art CRISPR/Cas9 is one of the most powerful among the approaches being developed to rescue fundamental causes of gene-based inheritable diseases. Several strategies for delivering such genome editing materials have been developed, but the safety, efficacy over time, cost of production, and gene size limitations are still under debate and must be addressed to further improve applications. In this study, we evaluated branched forms of the polyethylenimine (PEI) - branched PEI 25 kDa (BPEI-25K) - and found that it could efficiently deliver CRISPR/Cas9 plasmids. Plasmid DNA expressing both guide RNA and Cas9 to target the Slc26a4 locus was successfully delivered into Neuro2a cells and meditated genome editing within the targeted locus. Our results demonstrated that BPEI-25K is a promising non-viral vector to deliver the CRISPR/Cas9 system in vitro to mediate targeted gene therapy, and these findings contribute to an understanding of CRISPR/Cas9 delivery that may enable development of successful in vivo techniques.

OBJECTIVES The aim of this multicenter registry study was to investigate the effectiveness of ventilation tube insertion and the microbiology of otitis media with effusion (OME) in children. This part I study was conducted to evaluate the microbiological profile of children with OME who needed ventilation tube insertion. METHODS Patients

Objectives Few studies have evaluated the accurate association between hearing loss (HL) and albuminuria in patients with or without diabetes mellitus (DM). The aim of our study was to identify the clinical effects of albuminuria on HL with or without DM. Methods This study included 9,762 patients from the Korean National Health and Nutrition Examination Survey between 2011 and 2013. Participants were divided into 4 groups based on DM and urine albumin/creatinine ratio levels: group 1 included participants with neither DM nor albuminuria, group 2 included participants without DM and with albuminuria, group 3 included patients with DM and without albuminuria, and group 4 included patients with both DM and albuminuria. The low- or mid-frequency and high-frequency, and average hearing threshold values were obtained. Results There were 7,508, 545, 1,325, and 384 participants in groups 1, 2, 3, and 4, respectively. Univariate and multivariate analyses showed that the 3 hearing thresholds in group 1 were the lowest and those in group 4 were the highest among the 4 groups. No significant differences were observed in those thresholds between groups 2 and 3. Group 4 was associated with HL compared with the other groups, but moderate to severe HL was not associated with DM or albuminuria. Conclusion The presence of albuminuria was associated with a modest effect on hearing thresholds regardless of presence of DM.

Hereditary hearing loss (HHL) is a common genetically heterogeneous disorder, which follows Mendelian inheritance in humans. Because of this heterogeneity, the identification of the causative gene of HHL by linkage analysis or Sanger sequencing have shown economic and temporal limitations. With recent advances in next-generation sequencing (NGS) techniques, rapid identification of a causative gene via massively parallel sequencing is now possible. We recruited a Korean family with three generations exhibiting autosomal dominant inheritance of hearing loss (HL), and the clinical information about this family revealed that there are no other symptoms accompanied with HL. To identify a causative mutation of HL in this family, we performed whole-exome sequencing of 4 family members, 3 affected and an unaffected. As the result, A novel splicing mutation, c.763+1G>T, in the solute carrier family 17, member 8 (SLC17A8) gene was identified in the patients, and the genotypes of the mutation were co-segregated with the phenotype of HL. Additionally, this mutation was not detected in 100 Koreans with normal hearing. Via NGS, we detected a novel splicing mutation that might influence the hearing ability within the patients with autosomal dominant non-syndromic HL. Our data suggests that this technique is a powerful tool to discover causative genetic factors of HL and facilitate diagnoses of the primary cause of HHL.

Cisplatin (cis-diaminedichloridoplatinum(II), cis-[PtCl2(NH3)2]) is an effective chemotherapeutic agent in the treatment of several types of malignant solid tumors but its clinical use is associated with ototoxicity. Several studies have investigated the effect of antioxidants on cisplatin-induced ototoxicity in mice. The triazole KPR-A020 has been shown to play a protective role against mitochondrial dysfunction by reducing the production of mitochondrial reactive oxygen species (ROS). The effect of KPR-A020 on cisplatin-induced ototoxicity was examined using cultures of cochlear explants. Healthy mice were randomly divided into 4 groups: control, treated with cisplatin alone (CP), treated with cisplatin and KPR-A020 (CP + KPR-A020), and treated with KPR-A020 alone (KPR-A020). The cochlear explants were harvested for histological and immunohistochemical examinations. Biochemical analyses of the explants revealed that pre-treatment with KPR-A020 prevented an increase in mitochondrial ROS levels. Moreover, the CP + KPR-A020 group showed better hair cell survival than the CP group. Immunohistochemical examinations of cochlear explants stained with anti-caspase-3 revealed greater immunopositivity in the CP group. The CP + KPR-A020 group showed significantly less immunopositivity than the CP group (P < 0.05). Thus, it appears that KPR-A020 protects hair cells in the organ of Corti from cisplatin-induced toxicity by decreasing the production of mitochondrial ROS. The results of this study suggest that KPR-A020 can be used as an antioxidant and antiapoptotic agent to prevent hearing loss caused by cisplatin induced-oxidative stress.

Objectives We aimed to identify the causative mutation for siblings in a Korean family with nonsyndromic hearing loss (HL) and enlarged vestibular aqueduct (EVA). The siblings were a 19-year-old female with bilateral profound HL and an 11-year-old male with bilateral moderately severe HL. Methods We extracted genomic DNA from blood samples of the siblings with HL, their parents, and 100 controls. We performed mutation analysis for SLC26A4 using direct sequencing. Results The two siblings were compound heterozygotes with the novel mutation p.I713LfsX8 and the previously described mutation p.H723R. Their parents had heterozygous mono-allelic mutations. Father had p.I713LfsX8 mutation as heterozygous, and mother had p.H723R mutation as heterozygous. However, novel mutation p.I713LfsX8 was not detected in 100 unrelated controls. Conclusion Both mutations identified in this study were located in the sulfate transporter and anti-sigma factor antagonist domain, the core region for membrane targeting of SulP/SLC26 anion transporters, which strongly suggests that failure in membrane trafficking by SLC26A4 is a direct cause of HL in this family. Our study could therefore provide a foundation for further investigations elucidating the SLC26A4-related mechanisms of HL.

Objectives We aimed to identify the causative mutation for siblings in a Korean family with nonsyndromic hearing loss (HL) and enlarged vestibular aqueduct (EVA). The siblings were a 19-year-old female with bilateral profound HL and an 11-year-old male with bilateral moderately severe HL. Methods We extracted genomic DNA from blood samples of the siblings with HL, their parents, and 100 controls. We performed mutation analysis for SLC26A4 using direct sequencing. Results The two siblings were compound heterozygotes with the novel mutation p.I713LfsX8 and the previously described mutation p.H723R. Their parents had heterozygous mono-allelic mutations. Father had p.I713LfsX8 mutation as heterozygous, and mother had p.H723R mutation as heterozygous. However, novel mutation p.I713LfsX8 was not detected in 100 unrelated controls. Conclusion Both mutations identified in this study were located in the sulfate transporter and anti-sigma factor antagonist domain, the core region for membrane targeting of SulP/SLC26 anion transporters, which strongly suggests that failure in membrane trafficking by SLC26A4 is a direct cause of HL in this family. Our study could therefore provide a foundation for further investigations elucidating the SLC26A4-related mechanisms of HL.

Background and objectives The recent increase in the reported incidence of congenital cholesteatoma (CC) may be secondary to the widespread use of otoendoscopy as well as an increased awareness of these lesions among primary care physicians. However, little research about CC has been conducted in a large group of patients. This study aimed to analyze the clinical characteristics of CC including the annual number of patients, symptoms, age at diagnosis, stage and type of disease, surgical techniques, recurrence, and postoperative complications. Subjects and methods Retrospective chart review was performed for patients who met the inclusion criteria between January 1997 and June 2012. Results Ninety-three patients underwent surgery for CC. The age at operation ranged from 12 months to 17 years (mean age, 6.1 years). The number of patients was less than 4 per year until 2005, but increased to more than 10 per year since 2008. CC was most commonly reported as an incidental finding (58.1%). The operative procedures included the transcanal myringotomy approach (46.2%), canal wall up mastoidectomy (37.6%), tympanoplasty (8.6%), and canal wall down mastoidectomy (7.5%). The recurrence rate was 20.4% and the complication rate was 12.9%. No patients with stage I CC had complications. Conclusions This study showed that the incidence of CC has recently increased notably. Most patients with stage I and II CC were completely cured by transtympanic surgery, and complication and recurrence rates increased according to the extent of disease. Early detection of CC is important to facilitate minimally invasive surgery and to reduce complication and recurrence rates.

Objectives Previous studies examining the association between osteoporosis (OP) and hearing loss (HL) have shown conflicting results. The objective of the present study was to examine the association between hearing impairment and OP in postmenopausal women, using appropriate statistical analyses. Methods Total 1,009 participants were included in the current study. The propensity score matched (PSM) cohort was defined as the cohort including participants diagnosed with OP and participants without OP. Three statistical models were developed where model 1 was unadjusted, model 2 included age, and model 3 included age, body mass index, alcohol intake, smoking habit, diabetes mellitus, hypertension, high density lipoprotein cholesterol, triglyceride level, vitamin D, and alkaline phosphatase. Results There were 776 and 233 participants in the groups diagnosed without and with OP, respectively. For propensity score matching, 233 pairs were selected from the 776 participants without OP. In the total cohort, using statistical models 2 and 3, no significant difference in the four hearing thresholds was identified between the 2 groups. Logistic regression indicated that, in model 3, participants with OP had a 1.128 (P=0.323) increased risk HL. A significant HL risk was not observed in participants with OP. Using statistical model 3, there were no significant associations among lumbar spine or femoral neck T-scores and changes in the hearing thresholds. In the PSM cohort, statistical models also showed similar results. Conclusion The current study did not demonstrate and association between bone mineral density and hearing impairment in the study population of postmenopausal Korean women.

The aim of this study was to determine and evaluate the association between potassium intake and hearing thresholds in the Korean adult population. Data from the Korean National Health and Nutrition Examination Survey were analyzed. Participants were divided into tertiles on the basis of their potassium intake as follows: low, middle, and high. Pure-tone audiometry was performed using an automated audiometer. We calculated as the average threshold at the low-frequency pure-tone average (0.5 and 1 kHz), mid-frequency pure-tone average (2 and 3 kHz), and high-frequency pure-tone average (4 and 6 kHz). The average hearing threshold (AHT) was calculated as the pure-tone average of the thresholds at 0.5~3 kHz. Hearing loss (HL) was defined as an AHT of >40 dB in the better ear. There were 1975 participants each in the low, middle, and high tertile groups. The four different average hearing thresholds significantly decreased with an increase in the potassium intake tertile. Multivariate analysis revealed that the four different average hearing thresholds were significantly lower in the high tertile group than in the other two groups. In addition, univariate and multivariate linear regression analyses showed that the potassium intake level was inversely associated with each of the four different average hearing thresholds. Analyses of participants matched based on propensity scores and participants not matched based on propensity scores yielded similar results. The results of this study suggest that high potassium intake levels were associated with a lower prevalence of HL and lower hearing thresholds in the Korean adult population.

One of most important factors for messenger RNA (mRNA) transcription is the spliceosomal component U1 small nuclear RNA (snRNA), which recognizes 5' splicing donor sites at specific regions in pre-mRNA. Mutations in these sites disrupt U1 snRNA binding and cause abnormal splicing. In this study, we investigated mutations at splice sites in SLC26A4 (HGNC 8818), one of the major causative genes of hearing loss, which may result in the synthesis of abnormal pendrin, the channel protein encoded by the gene. Seventeen SLC26A4 variants with mutations in the U1 snRNA binding sites were assessed by minigene splicing assays, and 11 were found to result in abnormal splicing. Interestingly, eight of the 11 pathogenic mutations were intronic, suggesting the importance of conserved sequences at the intronic splice site. The application of modified U1 snRNA effectively rescued the abnormal splicing for most of these mutations. Although three were cryptic mutations, they were rescued by cotransfection of modified U1 snRNA and modified antisense oligonucleotides. Our results demonstrate the important role of snRNA in SLC26A4 mutations, suggesting the therapeutic potential of modified U1 snRNA and antisense oligonucleotides for neutralizing the pathogenic effect of the splice-site mutations that may result in hearing loss.

Supplemental Digital Content is available in the text, Rationale: Cortical deafness is a rare auditory dysfunction caused by damage to brain auditory networks. The aim was to report alterations of functional connectivity in intrinsic auditory, motor, and sensory networks in a cortical deafness patient. Patient concerns: A 41-year-old woman suffered a right putaminal hemorrhage. Eight years earlier, she had suffered a left putaminal hemorrhage and had minimal sequelae. She had quadriparesis, imbalance, hypoesthesia, and complete hearing loss. Diagnoses: She was diagnosed with cortical deafness. After 6 months, resting-state functional magnetic resonance imaging (rs-fMRI) and diffuse tensor imaging (DTI) were performed. DTI revealed that the acoustic radiation was disrupted while the corticospinal tract and somatosensory track were intact using deterministic tracking methods. Furthermore, the patient showed decreased functional connectivity between auditory and sensorimotor networks. Interventions: The patient underwent in-patient stroke rehabilitation therapy for 2 months. Outcomes: Gait function and ability for activities of daily living were improved. However, complete hearing impairment persisted in 6 months after bilateral putaminal hemorrhagic stroke. Lessons: Our case report seems to suggest that functional alterations of spontaneous neuronal activity in auditory and sensorimotor networks are related to motor and sensory impairments in a patient with cortical deafness.