Consensus Statements on the Definition, Classification, and Diagnostic Tests for Tinnitus: A Delphi Study Conducted by the Korean Tinnitus Study Group.

BACKGROUND: Tinnitus is a bothersome condition associated with various symptoms. However, the mechanisms of tinnitus are still uncertain, and a standardized assessment of the diagnostic criteria for tinnitus is required. We aimed to reach a consensus on diagnosing tinnitus with professional experts by conducting a Delphi study with systematic review of the literature. METHODS: Twenty-six experts in managing tinnitus in Korea were recruited, and a two-round modified Delphi study was performed online. The experts evaluated the level of agreement of potential criteria for tinnitus using a scale of 1-9. After the survey, a consensus meeting was held to establish agreement on the results obtained from the Delphi process. Consensus was defined when over 70% of the participants scored 7-9 (agreement) and fewer than 15% scored 1-3 (disagreement). To analyze the responses of the Delphi survey, the content validity ratio and Kendall's coefficient of concordance were evaluated. RESULTS: Consensus was reached for 22 of the 38 statements. For the definition of tinnitus, 10 out of 17 statements reached consensus, with three statements achieving complete agreement including; 1) Tinnitus is a conscious perception of an auditory sensation in the absence of a corresponding external stimulus, 2) Tinnitus can affect one's quality of life, and 3) Tinnitus can be associated with hearing disorders including sensorineural hearing loss, vestibular schwannoma, Meniere's disease, otosclerosis, and others. For the classification of tinnitus, 11 out of 18 statements reached consensus. The participants highly agreed with statements such as; 1) Vascular origin is expected in pulse-synchronous tinnitus, and 2) Tinnitus can be divided into acute or chronic tinnitus. Among three statements on the diagnostic tests for tinnitus only Statement 3, "There are no reliable biomarkers for sensory or emotional factors of tinnitus." reached consensus. All participants agreed to perform pure-tone audiometry and tinnitus questionnaires, including the Tinnitus Handicap Inventory and Tinnitus Questionnaire. CONCLUSION: We used a modified Delphi method to establish a consensus-based definition, a classification, and diagnostic tests for tinnitus. The expert panel reached agreement for several statements, with a high level of consensus. This may provide practical information for clinicians in managing tinnitus.

Therapeutic effect of intraperitoneal dexamethasone on noise-induced permanent threshold shift in mice model.

The purpose of the study was to which investigate whether dexamethasone, which has anti-inflammatory and immune response suppression roles, could treat noise-induced hearing loss caused by damage to hair cells in the cochlea. The experiment used 8-week-old CBA mice exposed to white noise at an intensity of 110 dB SPL for 2 h, with hearing loss confirmed by the auditory brainstem response test. Dexamethasone was administered by intraperitoneal injection for 5 days, and the therapeutic effect was investigated for 3 weeks. The experimental groups were 3 mg/kg of dexamethasone (3 mpk) and 10 mg/kg of dexamethasone (10 mpk), and the control group was a saline-administered group. The results showed that compared to the control group, the hearing threshold value was recovered by 10 dB SPL compared to the saline group from the 14th day in the 3 mpk group. In the 10 mpk group, thresholds were recovered from the 7th day compared to the saline group. This difference was similar at 4 kHz, and in the case of the 10 mpk group, the threshold was recovered by 20 dB SPL compared to the saline group. The study also confirmed the restoration of nerve cell activity and showed a recovery effect of about 20 µV in the amplitude value change in the 10 mpk group. In conclusion, the study suggests that dexamethasone has a therapeutic effect for noise-induced hearing loss by increasing the activity of nerve cells and showing a recovery effect from hair cells damaged by noise.

Efficacy of the Bonebridge BCI602 for Adult Patients with Single-sided Deafness: A Prospective Multicenter Study.

OBJECTIVE: To investigate the safety and efficacy of a novel active transcutaneous bone conduction implant (BCI) device for patients with single-sided deafness (SSD). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral hospitals. METHODS: This prospective multicenter study was conducted at 15 institutions nationwide. Thirty adult (aged ≥19 years) SSD patients were recruited. They underwent implantation of an active transcutaneous BCI device (Bonebridge BCI602). Objective outcomes included aided pure-tone thresholds, aided speech discrimination scores (SDSs), and the Hearing in Noise Test (HINT) and sound localization test results. The Bern Benefit in Single-Sided Deafness (BBSS) questionnaire, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, and the Tinnitus Handicap Inventory (THI) were used to measure subjective benefits. RESULTS: The mean aided pure-tone threshold was 34.2 (11.3), mean (SD), dB HL at 500 to 4000 Hz. The mean total BBSS score was 27.5 (13.8). All APHAB questionnaire domain scores showed significant improvements: ease of communication, 33.6 (23.2) versus 22.6 (21.3), P = .025; reverberation, 44.8 (16.6) versus 32.8 (15.9), P = .002; background noise, 55.5 (23.6) versus 35.2 (18.1), P < .001; and aversiveness, 36.7 (22.8) versus 25.8 (21.4), P = .028. Moreover, the THI scores were significantly reduced [47.4 (30.1) versus 31.1 (27.0), P = .003]. Congenital SSD was a significant factor of subjective benefit (-11.643; 95% confidence interval: -21.946 to -1.340). CONCLUSION: The BCI602 active transcutaneous BCI device can provide functional hearing gain without any adverse effects and is a feasible option for acquired SSD patients with long-term deafness.

Cochlear Implantation in the Elderly: Speech Performance, Associated Factor, Complication, and Surgical Safety.

BACKGROUND AND OBJECTIVES: The guidelines for cochlear implantation (CIs) are expanding, and the number of CI procedures performed on the elderly is increasing. The purpose of this study was to analyze the results and safety of cochlear implantation in the elderly, as well as to evaluate the predictive factors on CI outcomes. SUBJECTS AND METHODS: The study included 56 patients aged ≥40 years, who received CIs between 2009 and 2020. They were divided into two groups: 27 younger adults (40-64 years) and 29 elderly (>64 years). The study compared their pre- and postoperative speech perception and category of auditory performance (CAP) scores, surgical complications, and hospitalization periods. It also evaluated associated factors in the elderly group by examining categorical and continuous variables and postoperative CAP score. RESULTS: There was a significant improvement in speech recognition tests (both word and sentence) and CAP scores in both groups compared to the pre-implantation scores (p<0.001). Postoperative results were slightly lower in the elderly group than in younger adults for sentence recognition and CAP scores, except for word recognition. No significant associated factors were found on postoperative CAP scores, except for etiology. Postoperative CAP significantly improved in the sudden hearing loss group compared to the groups with other etiologies (p=0.045). The elderly group had more comorbidities than that in the younger adult group (p=0.026), but there were no significant differences in postoperative complications and hospitalization periods. CONCLUSIONS: While speech recognition and CAP scores were relatively lower in the elderly group compared to the younger adults, the elderly group showed significant improvements in audiological results after CI. Moreover, CI was safe and well tolerated in elderly patients.

Berberine chloride protects cochlear hair cells from aminoglycoside-induced ototoxicity by reducing the accumulation of mitochondrial reactive oxygen species.

Aminoglycoside, a medicinal category of antibiotics, are used in treatment of Gram-negative bacterial infections. Although they are the most widely-used antibiotics due to their high efficacy and low cost, several main adverse effects have been reported including nephrotoxicity and ototoxicity. Since drug-induced ototoxicity is one of the major etiological causes of acquired hearing loss, we examined cochlear hair cell damages caused by three aminoglycosides (amikacin, kanamycin, and gentamicin), and investigated protective property of an isoquinoline-type alkaloid, Berberine chloride (BC). Berberine, a well-known bioactive compound found from medicinal plants, has been known to have anti-inflammatory, antimicrobial effects. To determine protective effect of BC in aminoglycoside-induced ototoxicity, hair cell damages in aminoglycoside- and/or BC-treated hair cells using ex vivo organotypic culture system of mouse cochlea. Mitochondrial ROS levels and depolarization of mitochondrial membrane potential were analyzed, and TUNEL assay and immunostaining of cleaved caspase-3 were performed to detect apoptosis signals. As the results, it was found that BC significantly prevented aminoglycoside-induced hair cell loss and stereocilia degeneration by inhibiting excessive accumulation of mitochondrial ROS and subsequent loss of mitochondrial membrane potential. It eventually inhibited DNA fragmentation and caspase-3 activation, which were significant for all three aminoglycosides. This study is the first report suggested the preventative effect of BC against aminoglycoside-induced ototoxicity. Our data also suggests a possibility that BC has the potential to exert a protective effect against ototoxicity caused by various ototoxic drugs leading to cellular oxidative stress, not limited to aminoglycoside antibiotics.

Mitochondrial redox system: A key target of antioxidant therapy to prevent acquired sensorineural hearing loss.

Noise (noise-induced hearing loss), and ototoxic drugs (drug-induced ototoxicity), and aging (age-related hearing loss) are the major environmental factors that lead to acquired sensorineural hearing loss. So far, there have been numerous efforts to develop protective or therapeutic agents for acquired hearing loss by investigating the pathological mechanisms of each types of hearing loss, especially in cochlear hair cells and auditory nerves. Although there is still a lack of information on the underlying mechanisms of redox homeostasis and molecular redox networks in hair cells, an imbalance in mitochondrial reactive oxygen species (ROS) levels that enhance oxidative stress has been suggested as a key pathological factor eventually causing acquired sensorineural hearing loss. Thus, various types of antioxidants have been investigated for their abilities to support auditory cells in maintenance of the hearing function against ototoxic stimuli. In this review, we will discuss the scientific possibility of developing drugs that target particular key elements of the mitochondrial redox network in prevention or treatment of noise- and ototoxic drug-induced hearing loss.

Identification of novel missense mutation related with non-syndromic sensorineural deafness, DFNA11 in korean family by NGS.

BACKGOUND: Hereditary hearing loss is one of the most common genetically heterogeneous defects in human. About 70% of hereditary hearing loss is defined as non-syndromic hearing loss showing loss of hearing ability without any other symptoms. Up to date, the identified genes associated with non-syndromic hearing loss are 128, including 52 genes for DFNA and 76 genes for DFNB. Because of high levels of heterogeneity, it is difficult to identify the causative factors for hearing loss using Sanger sequencing. OBJECTIVE: Our aim was to detect causative factors and investigate pathogenic mutations, which co-segregates within the candidate family. METHODS: We used Next Generation Sequencing technique to investigate whole-exome sequences of a Korean family with non-syndromic hereditary hearing loss. The family showed autosomal dominant inheritance pattern. RESULTS: We identified a novel missense variation, c.1978G > A in MYO7A gene, in the family with the autosomal dominant inheritance pattern. c.1978G > A produced Gly660Arg in the motor head domain of Myosin VIIA disrupt the ATP- and actin-binding motif function. CONCLUSION: This study is the first to report pathogenic mutations within MYO7A gene in Korean family and our data would facilitate diagnosing the primary cause of hereditary hearing loss in Korean.

Effect of prehydration solution on hearing threshold after chemotherapy in patients with head and neck cancers: a retrospective study.

BACKGROUND: The study aimed to evaluate the effect of prehydration solution on hearing thresholds after cisplatin chemotherapy. METHODS: In this retrospective cohort study, we reviewed the data of patients who underwent ≥3 courses of cisplatin-based chemotherapy for locally advanced head and neck cancers at a tertiary referral center (n=64). The dextrose solution (DW) group (n=26) received 2 L of normal saline and 1 L of 5% dextrose. The Hartmann solution (HS) group (n=38) received 2 L of normal saline and 1 L of HS. Hearing data were measured 1 day before starting the first course of chemotherapy, and again 20 days after the first, second, and third courses of chemotherapy. The severity of hearing loss was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Thresholds at all frequencies after chemotherapy were greater in the DW group than in the HS group. The increase in thresholds in 1 to 4 kHz after the third course of chemotherapy was greater in the DW group than in the HS group. CTCAE grades after the second and third courses of chemotherapy were greater in the DW group than in the HS group. Logistic regression showed that the odds ratio for CTCAE grade 3 or 4 after the third course of chemotherapy in the DW group was 4.84 on univariate analysis. CONCLUSION: Prehydration using a solution with salt was associated with a decrease in change in hearing thresholds after cisplatin chemotherapy in patients with head and neck cancers.

Factors Affecting the Extrusion Rate and Complications After Ventilation Tube Insertion: A Multicenter Registry Study on the Effectiveness of Ventilation Tube Insertion in Pediatric Patients With Chronic Otitis Media With Effusion-Part II.

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 <15 years diagnosed with otitis media with effusion who received VT insertion were recruited at 15 tertiary hospitals. The primary outcomes were time to extrusion of VT, time to effusion recurrence, and complications. RESULTS: Data from 401 patients were analyzed. After excluding the. RESULTS: of long-lasting tubes (Paparella type II and T-tubes), silicone tubes (Paparella type I) exhibited a significantly longer extended time to extrusion (mean, 400 days) than titanium tubes (collar-button-type 1.0 mm: mean, 312 days; P<0.001). VT material (hazard ratio [HR], 2.117, 95% confidence interval [CI], 1.254-3.572; P=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<0.001). The revision surgery rates were higher among patients aged <7 years than among those aged ≥7 years. CONCLUSION: Silicone tubes (Paparella type I) were less prone to early extrusion than titanium 1.0 mm tubes. VT type, patient age, and effusion composition affected the time to recurrence of effusion.

Atypical Presentation of Enlarged Vestibular Aqueducts Caused by SLC26A4 Variants.

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.

Protective effect of berberine chloride against cisplatin-induced ototoxicity.

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.

Results of Active Middle Ear Implantation in Patients With Mixed Hearing Loss After Middle Ear Surgery: A Prospective Multicenter Study (the ROMEO Study).

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.

Fursultiamine Prevents Drug-Induced Ototoxicity by Reducing Accumulation of Reactive Oxygen Species in Mouse Cochlea.

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.

Prediction of hearing outcomes in chronic otitis media patients underwent tympanoplasty using ossiculoplasty outcome parameter staging or middle ear risk indices.

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.

A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder.

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.

Alterations of functional connectivity in auditory and sensorimotor neural networks: A case report in a patient with cortical deafness after bilateral putaminal hemorrhagic stroke.

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.

Clinical outcomes of otogenic skull base osteomyelitis.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.001). Disease control rate was 34.9% at 1-year and 83.7% at 5-year follow-up. Patient survival rate was 90.6% at 1- and 3-year follow-ups. At the endpoint of follow-up, three patients died. The mean durations from the onset of symptoms to diagnosis were 50 (5-360) and 90 (30-480) days in patients with the controlled disease and in those with the uncontrolled disease, respectively, at the endpoint of follow-up (P = 0.043). CONCLUSION: Comprehensive assessment and aggressive treatment of patients exhibiting symptoms suggestive of SBO would help in the rapid diagnosis of otogenic SBO, resulting in an improvement in prognosis.

Comparison of Ossiculoplasty Outcomes Using Different Materials in the Treatment of Chronic Otitis Media.

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.

Intratympanic steroid injection for sudden sensorineural hearing loss: Impact of injection interval on therapeutic efficacy.

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 (AAOHNS) 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.

KL1333, a derivative of ß-lapachone, protects against cisplatin-induced ototoxicity in mouse cochlear cultures.

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 ß-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.