Intratympanic administration of alpha-lipoic acid-loaded pluronic F-127 nanoparticles ameliorates acute hearing loss.

We used antioxidant-containing nanoparticles (NPs) to treat acute hearing loss. Alpha-lipoic acid (ALA) served as the antioxidant; we employed Pluronic F127 to fabricate NPs. In vitro, ALA-NPs protected cells of the organ of Corti in HEI-OC1 mice, triggering nuclear translocation of NRF2 and increases in the levels of antioxidant proteins, including Nrf2, HO-1, SOD-1, and SOD-2. In vivo, the hearing of mice that received ALA-NP injections into the middle ear cavity was better preserved after induction of ototoxicity than in control animals. The cochlear Nrf2 level increased in test mice, indicating that the ALA-NPs protected hearing via the antioxidant mechanism observed in vitro. ALA-NPs effectively protected against acute hearing loss by activating the Nrf2/HO-1 pathway.

Effects of tympanic membrane perforation, middle ear cavity volume, and mastoid aeration on hearing impairment.

AIMS: To investigate the effects of the location and size of tympanic membrane (TM) perforation and middle ear cavity volume on conductive hearing loss in patients with TM perforation. METHODS: Data were collected via a retrospective medical chart review. RESULTS: We enrolled 128 patients with a mean age of 45.6 ± 10.1 years. The mean perforation size was 21.2 ± 8.6% of the TM area, and the mean air-bone gap (ABG) was 20.2 ± 8.6 dB HL on pure tone audiometry. Patients were divided into two groups based on mean ABG. Patients with a large ABG had a significantly larger TM perforation area and smaller mastoid volume. The TM perforation was most commonly located in the central section. However, regression analyses showed that the proportion of the perforated TM area was the only independent predictor of a large ABG (odds ratio, 1.053; 95% confidence interval, 1.022-1.085; p = 0.001). When we analyzed the frequencies in which hearing loss occurred due to TM perforation, we confirmed that hearing loss occurred mainly in the low-frequency range. CONCLUSION: In patients with TM perforation, conductive hearing loss occurs mainly at low frequencies and in proportion to the size of the TM perforation.

Safety and Effectiveness of Peramivir in Korean Adult Influenza Patients: Prospective Observational Study Based on Post-Marketing Surveillance Data.

BACKGROUND: The safety and clinical effectiveness data of peramivir in the real clinical field are limited. A prospective observational study was conducted based on the post-marketing surveillance data to evaluate the post-marketing safety and effectiveness of peramivir in Korean adults with seasonal influenza. METHODS: Among adults aged 20 years or older who were diagnosed with influenza A or B, patients who started peramivir within 48 hours from the initial symptoms of influenza were enrolled. All adverse events (AEs) that occurred within 7 days after administration of peramivir were checked. For the evaluation of effectiveness, changes in the severity of influenza symptoms and daily living performance were examined before and 7 days after the administration of peramivir. The date on which influenza related symptoms disappeared was checked. RESULTS: A total of 3,024 patients were enrolled for safety evaluation and 2,939 patients were for effectiveness evaluation. In the safety evaluation, 42 AEs were observed in 35 (1.16%) patients. The most common AE was fever. AEs were mostly rated as mild in severity. Serious AEs were observed in 10 patients and two of them died. However, both deaths were considered to be less relevant to peramivir. In the effectiveness evaluation, the severity of influenza symptoms decreased by 10.68 ± 4.01 points and daily living performance was improved 5.59 ± 2.16 points. Influenza related symptoms disappeared on average 3.02 ± 2.39 days after peramivir administration. CONCLUSION: Peramivir showed a tolerable safety profile and acceptable effectiveness in Korean adult patients with seasonal influenza.

Long-Term Effects of Middle Ear Tendon Resection on Middle Ear Myoclonic Tinnitus, Hearing, and Hyperacusis.

OBJECTIVE: To evaluate the therapeutic effects of middle ear tendon resection (METR) on middle ear myoclonic tinnitus (MEMT) and to investigate its long-term effects on hearing and hyperacusis. MATERIALS AND METHODS: Thirty-seven patients with MEMT with a mean age of 33.2 ± 11.8 years were included in this study. METR was performed on all 37 MEMT patients (41 ears) between November 2004 and August 2016. The mean follow-up period was 16.1 months. We examined changes in tinnitus and accompanying stress and depression in patients after surgery, and examined the hearing changes and the occurrence of complications including hyperacusis. RESULTS: After surgery, 34 (91.9%) patients exhibited complete resolution of MEMT during their follow-up period, and 3 patients showed a partial response. The mean Visual Analog Scale (VAS) scores for tinnitus severity, the Tinnitus Handicap Inventory (THI), and stress index decreased significantly after surgery (p < 0.05, paired t test). No patient developed hearing loss or hyperacusis following surgery. Preexisting hyperacusis even improved in most of the patients with intractable MEMT after surgery. Recurrence of the symptom occurred in only 1 patient, who underwent revision surgery with improvement. We observed 1 case of postoperative delayed facial palsy with complete recovery in 2 weeks. CONCLUSIONS: METR seems to be an effective and safe treatment option for intractable MEMT, considering its high control rate of tinnitus and no long-term harmful effects on hearing and hyperacusis.

Prognostic factors for profound sudden idiopathic sensorineural hearing loss: a multicenter retrospective study.

The aim of this study was to assess the outcomes of various treatment modalities for profound idiopathic sudden sensorineural hearing loss (ISSNHL) and confirm the prognostic factors. In total, 191 patients were enrolled after a thorough medical chart review of patients diagnosed with unilateral, profound ISSNHL (≥90 dB). Epidemiological profiles, therapeutic regimens, and the results of pure tone audiometry tests were recorded for all patients. Final recovery was assessed according to Siegel's criteria and by comparing the final hearing level of the affected ear with that of the unaffected ear. The mean follow-up duration and the final hearing level were 75 ± 54 days and 77 ± 24 dB, respectively. None of the evaluated prognostic factors were significantly associated with complete recovery (<25 dB). However, improved hearing in both ears, the absence of dizziness, the use of lipo-prostaglandin E1 (lipo-PGE1), and the use of plasma volume expanders were independently associated with a final hearing level of up to 45 dB (p < 0.05). Steroid dose reduction, worse initial hearing, and non-use of lipo-PGE1 increased the possibility of no recovery. Although the efficacy of oral steroid treatment for profound ISSNHL has been questioned, steroid dose reduction was significantly associated with no recovery. Therefore, adequate oral corticosteroid doses should be considered in the absence of contraindications. In addition, the use of lipo-PGE1 and/or a plasma volume expander seems preferable for better recovery, and their use for the management of profound ISSNHL should be considered.

Prospective, Multicenter Study on Tinnitus Changes after Cochlear Implantation.

OBJECTIVE: To investigate the time course of tinnitus changes in patients receiving cochlear implantation (CI) in a prospective, multicenter setting and to determine related factors. MATERIALS AND METHODS: A total of 79 adult patients who underwent CI were included in this study. We used the same questionnaires sequentially 5 times. The questionnaires included the Visual Analog Scale (VAS) for tinnitus severity, the Tinnitus Handicap Inventory (THI), Beck's Depression Index (BDI), and the Brief Encounter Psychosocial Instrument (BEPSI) for stress assessment. RESULTS: Tinnitus was present in 59 (74.7%) of the 79 study subjects. After CI, tinnitus was eliminated in 10 patients (25%) and improved in 16 patients (40%) of the 40 patients who completed the final questionnaires, and most of the tinnitus reduction occurred in the early period of CI use. In an analysis of psychological functioning with CI, BDI was reduced significantly after CI. Multiple linear regression analysis revealed that preoperative auditory steady-state response (ASSR), THI, and final BDI score were significantly associated with the changes in tinnitus after CI. CONCLUSIONS: Most of the tinnitus reduction occurred within 1 month after CI use, and the changes were significantly associated with THI, ASSR, and BDI scores 6 months after CI. CI is a valuable therapeutic modality in tinnitus of a deafened ear.

Diagnostic value and clinical significance of stress hormones in patients with tinnitus.

Tinnitus has been found to be modulated by stress and is also closely related to the emotional state and the limbic system. In the present study, we evaluated the diagnostic and clinical values of several stress hormones in a large number of tinnitus patients. This study included 344 patients with sensorineural tinnitus and 87 normal controls. A questionnaire about tinnitus was administered to the participants, and blood levels of norepinephrine (NE), epinephrine (Epi), a metabolite of serotonin (5-hydroxyindoleacetic acid, 5-HIAA) and cortisol were compared between groups. In results, the mean values of Beck's depression inventory (BDI), Brief Encounter Psychosocial Instrument (BEPSI), NE, and 5-HIAA levels were higher in the tinnitus group, although there was no statistical significance. But, the proportion of participants with elevated 5-HIAA was significantly higher in the tinnitus group (21.8 vs. 8.0 %, P < 0.05), and the 5-HIAA level significantly correlated with the duration of tinnitus, NE and cortisol. Elevated stress-related hormones, as well as hearing loss, BDI, and BEPSI were the most related factors with tinnitus in multiple regression test with age adjustment. However, levels of stress-related hormones did not correlate with subjective measures including BDI, BEPSI and severity of tinnitus. In conclusion, blood stress hormones seemed to have some diagnostic and clinical value in patients with tinnitus, and serotonin is supposed to be the most important hormone in tinnitus. Further studies about the values of stress and stress hormones in tinnitus patients may lead to new approaches regarding diagnosis and clinical management of the disease.

Renexin as a rescue regimen for noise-induced hearing loss.

Renexin, a compound of cilostazol and ginkgo biloba extract, has been reported to produce neuroprotective effects through antioxidant, antiplatelet, and vasodilatory mechanisms. This study was designed to investigate the protective effects of renexin on hearing, the organ of Corti (OC), and medial olivocochlear efferents against noise-induced damage. C57BL/6 mice were exposed to 110 dB SPL white noise for 60 min and then randomly divided into three groups: high- and low-dose renexin-treated groups and noise only group. Renexin were administered for 7 days: 90 mg/kg to the low-dose, and 180 mg/kg to the high-dose groups. All mice, including the controls underwent hearing tests on postnoise day 8 and were killed for cochlear harvest. We compared the hearing thresholds and morphology of the OC and cochlear efferents across the groups. The renexin-treated groups recovered from the immediate threshold shifts in a dose-dependent manner, while the noise group showed a permanent hearing loss. The renexin-treated ears demonstrated less degeneration of the OC. The diameters of the efferent terminals labeled with α-synuclein were preserved in the high-dose renexin-treated group. In the western blot assay of the cochlear homogenates, the treated groups displayed stronger expressions of α-synuclein than the noise and control groups, which may indicate that noise-induced enhanced activity of the cochlear efferent system was protected by renexin. Our results suggest that pharmacologic treatment with renexin is hopeful to reduce or prevent noise-induced hearing loss as a rescue regimen after noise exposure.

Protective effect of unilateral and bilateral ear plugs on noise-induced hearing loss: functional and morphological evaluation in animal model.

The aim of the following study is to evaluate immediate protective effect of ear plug from noise morphologically and functionally. An 1-month aged 29 male C57BL/6 mice. Subjects were divided into four groups as normal control(G1), bilaterally plugged group (G2), unilaterally plugged group (G3) and noise control group (G4) and later 3 groups were exposed to 110 sound pressure level white noise for 60 min. Immediately after noise exposure, audiologic tests were performed and cochlear morphology and expression levels of a-synuclein in the cochlea were investigated. There were no functional changes in G2 and plugged ears of G3 after noise exposure, whereas unplugged ears of G3 and G4 showed significant hearing loss. In morphological study, there were a significant degeneration of the organ of Corti and mean number and diameter of efferent buttons, in unplugged ears of G3 and G4. Plugged ears of G3 also showed mild changes in morphological study. Reduction of a-synuclein was observed at the efferent terminals or cochlear extracts after noise exposure. The protective effect of ear plug on noise exposure was proven morphologically and functionally in the animal model of noise-induced hearing loss. Further study on cellular or ultrastructural level with ear plug will be needed to reveal more precise mechanism.

Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection.

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.

Tinnitus in patients with profound hearing loss and the effect of cochlear implantation.

The objectives of this study were to characterize the features of tinnitus in patients with profound sensorineural hearing loss and to evaluate the effect of cochlear implantation (CI) on their tinnitus. Medical records were reviewed for 35 patients who underwent CI, and completed tinnitus questionnaire between March 2003 and August 2011. Of them, 22 had tinnitus prior to CI (62.9 %) and the tinnitus group was older than the non-tinnitus group (47.5 ± 15.1 vs. 28.9 ± 15.2). The mean tinnitus handicap inventory (THI) score of the tinnitus group was 50.5 ± 28.7 before surgery, and the mean THI score and visual analogue scale (VAS) scores for loudness, annoyance, effect on life, and awareness decreased significantly after CI, with a mean follow-up period of 10.7 months. Tinnitus was completely eliminated in ten patients (45.5 %) and THI scores decreased in all patients. In a correlation analysis of the decrease in THI scores, preoperative VAS scores for loudness, awareness, effect on life, and annoyance, as well as preoperative THI scores, were highly correlated with the degree of decrease in THI scores postoperatively. The auditory performance of patients older than 40 years did not differ from that of younger patients, but their tinnitus was more improved after CI. In conclusion, tinnitus is a common complaint in patients with cochlear implants, and is more prevalent in elderly implantees. In the present study, CI improved tinnitus in all patients, although the most severe cases had the greatest benefit.

Effect of Aging on Speech Discrimination.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the factors associated with decrease in speech discrimination ability seen in patients with presbycusis and whether aging has a significant effect on the observed decline. SUBJECTS AND METHODS: We retrospectively analyzed the medical records of patients aged >40 years who had undergone pure-tone audiometry, speech audiometry, and auditory brainstem response for hearing loss at our hospital from January 2019 to June 2021, and investigated the factors that correlated with speech discrimination score. RESULTS: We enrolled 103 patients with 120 ears, with a mean age of 65.8±11.9 years. The pure-tone average of the patients' thresholds at 0.5, 1, 2, and 4 kHz was 37.2±27.7 dB HL, and their mean speech discrimination score was 82.5%± 22.3%. A correlation analysis revealed a significant negative correlation between the patients' speech discrimination scores and age. In addition, all variables of pure-tone audiometry and the patients' auditory brainstem responses were significantly correlated with the speech discrimination scores. The pure-tone average had the strongest negative correlation. On analyzing the significant predictors of lower speech discrimination scores, using a multiple linear regression analysis, pure-tone average and age showed significant results. CONCLUSIONS: The speech discrimination ability of older patients with hearing loss significantly decreases with increasing pure-tone average and age.

Effect of Hearing Rehabilitation Therapy Program in Hearing Aid Users: A Prospective Randomized Controlled Study.

OBJECTIVES: Despite sufficient hearing gains, many patients with hearing loss have difficulty using hearing aids due to poor word recognition ability. This study was performed to introduce our hearing rehabilitation therapy (HRT) program for hearing aid users and to evaluate its effect on hearing improvement. METHODS: In this prospective randomized case-control study, 37 participants with moderate or moderate-severe sensorineural hearing loss who had used bilateral hearing aids for more than 3 months with sufficient functional hearing gain were enrolled in this study. Nineteen participants were randomly assigned to the control group (CG) and 18 patients were assigned to participate in our HRT program once a week for 8 consecutive weeks (hearing rehabilitation therapy group [HRTG]). Their hearing results and questionnaire scores for hearing handicap and hearing aid outcomes were prospectively collected and compared between the two groups. RESULTS: After completing 8 weeks of the HRT program, the HRTG showed a significantly greater improvement in scores for consonant-only and consonant-vowel sound perception than the CG (P<0.05). In addition, the HRTG showed a significant improvement in hearing ability as measured by two questionnaires (p<0.05), while no differences were observed in the CG. However, word and sentence recognition test results did not show significant differences between the two groups. CONCLUSION: Even after short-term HRT, patients had subjectively better hearing outcomes and improved phoneme perception ability; this provides scientific evidence regarding a possible positive role for HRT programs in hearing aid users. Further validation in a larger population through a long-term follow-up study is needed.

Efficiency of a dexamethasone nanosuspension as an intratympanic injection for acute hearing loss.

Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of administering dexamethasone nanosuspensions via intratympanic injection because hydrophobic drugs might be more effective in penetrating the inner ear. Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanoparticles in the three nanosuspensions were between approximately 250 and 350 nm in size. To compare the efficiency of Dex-SP and dexamethasone nanosuspension in delivering dexamethasone to the inner ear, the concentrations of dexamethasone in perilymph and cochlear tissues were compared by liquid chromatography-mass spectrometry. The dexamethasone nanosuspensions resulted in significantly higher drug concentrations in perilymph and cochlear tissues than Dex-SP at 6 h; interestingly, animals treated with nanosuspensions showed a 26-fold higher dexamethasone concentrations in their cochlear tissues than animals treated with Dex-SP. In addition, dexamethasone nanosuspension caused better glucocorticoid receptor phosphorylation than Dex-SP both in vitro and in vivo, and in the ototoxic animal model, the nanosuspension showed a significantly better hearing-protective effect against ototoxic drugs than Dex-SP. In the in vivo safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL. In conclusion, a nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection.

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.

Prevalence and significance of high-frequency hearing loss in subjectively normal-hearing patients with tinnitus.

OBJECTIVES: We investigated the incidences of high-frequency hearing loss (HFHL; above 2 kHz) and extended high-frequency hearing loss (EHFHL; above 8 kHz) in patients with tinnitus and subjectively normal hearing, and evaluated their effects on the clinical and audiological features of the patients. METHODS: The sample included 85 patients with sensorineural tinnitus who had normal hearing sensitivity in the frequencies from 250 Hz to 2 kHz, and who had undergone extended high-frequency audiometry between July 2009 and February 2010. We investigated the incidences of HFHL and EHFHL in these patients and analyzed the significance of the hearing losses. RESULTS: The incidence of HFHL or EHFHL was 88%. The proportion of patients with EHFHL, among the patients who had normal hearing sensitivity up to 8 kHz, was about 74%. The patients with normal hearing sensitivity at all test frequencies were significantly younger, had larger otoacoustic emissions, and had tinnitus that was less loud as measured by tinnitus matching than did the subjects with HFHL and/or EHFHL. However, other comparisons of clinical factors in the three groups did not show any differences. CONCLUSIONS: Even if patients with tinnitus do not have any subjective hearing impairment, most of them have HFHL and/or EHFHL. The effects on the clinical features of the patients are still vague.

Tinnitus in patients with chronic otitis media before and after middle ear surgery.

The objective of this study was to investigate the clinical features of tinnitus in patients with chronic otitis media (COM) and to evaluate changes in tinnitus following middle ear surgery in relation to audiologic outcome. Medical records were reviewed for 117 patients with COM who underwent middle ear surgery between March 2009 and March 2010. Of them, 44 patients who pre-operatively reported tinnitus on a tinnitus questionnaire and 28 patients who completed a tinnitus questionnaire 8 weeks after surgery were evaluated to determine the clinical characteristics of tinnitus in patients with COM and any change in tinnitus following middle ear surgery, respectively. New tinnitus symptoms that developed after surgery were also evaluated in previously asymptomatic patients. The pre-operative incidence of tinnitus in patients with COM was 43% (50/117), with 87% of these patients displaying sensorineural tinnitus. After middle ear surgery, tinnitus handicap inventory scores were reduced in 82% of patients (23/28). Mean values of loudness, annoyance, effect on life, and awareness of tinnitus were also significantly reduced. One patient displayed newly developed tinnitus after surgery. Analysis of the relationship between improvement in tinnitus and audiologic outcome demonstrated that the group of patients whose tinnitus handicap inventory was reduced by more than 10 showed significantly greater improvements in mean air-conduction thresholds than did patients in the other group. In conclusion, following middle ear surgery, most patients experienced a reduction in tinnitus and restored hearing, with surgery perceived as an important contributory factor.

Sensorineural Hearing Loss After Surgery to Treat Chronic Otitis Media.

OBJECTIVE: We investigated the incidence of sensorineural hearing loss (SNHL) after chronic otitis media (COM) surgery and determined the associated factors. METHODS: Data were collected via retrospective medical chart review. RESULTS: Of the 192 patients, 82 underwent tympanoplasty, 26 underwent canal wall up mastoidectomy with tympanoplasty, and 84 underwent canal wall down mastoidectomy with tympanoplasty. After surgery, the average air conduction (AC) hearing threshold improved significantly, from 125 to 1000 Hz, but the average high-frequency AC and bone conduction (BC) hearing thresholds deteriorated significantly. In 21 (11%) cases, the BC hearing threshold worsened by more than 15 dB at 4000 Hz. When we compared these 21 cases to patients in whom hearing was preserved, the former group was found to be significantly younger and had a higher frequency of cholesteatomatous otitis media. However, when comparing the severity of inflammation in patients with temporal bone computed tomography, there was no significant difference between the 2 groups. CONCLUSIONS: High-frequency SNHL may develop after surgery to treat COM, especially in young patients with cholesteatoma.

Typewriter tinnitus: An investigative comparison with middle ear myoclonic tinnitus and its long-term therapeutic response to carbamazepine.

OBJECTIVES: Due to its rarity and similar sound, typewriter tinnitus (TT) can be misdiagnosed as middle ear myoclonic tinnitus (MEMT). We aim to clarify the characteristics of TT compared to MEMT, and the long-term therapeutic response to carbamazepine. METHODS: Fourteen patients with TT and 28 patients with MEMT were enrolled. RESULTS: TT patients were older than MEMT patients, and their tinnitus symptoms were mostly unilateral. Tinnitus symptoms, which is associated with dizziness, facial spasm, and head motion, were more common in TT, whereas MEMT were more related to noise. Acoustic reflex decay perturbation and low loudness discomfort level were diagnostic signs in MEMT patients, while decreased level of wave II in ABR was the most reliable sign in TT patients. All TT patients exhibited partial or complete response to carbamazepine, but there was a relapse rate after withdrawal of the drug was 60%. Increase in age and longer duration of symptoms were the risk factors of relapse of TT. CONCLUSION: The different characteristics observed in this study will be helpful to diagnose TT and MENT. Duration of tinnitus was the most important long-term prognostic factor of the carbamazepine trial, which indicates the importance of its earlier diagnosis.

α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway.

The production of reactive oxygen species (ROS) by cisplatin is one of the major mechanisms of cisplatin-induced cytotoxicity. We examined the preventive effect of α-lipoic acid (LA) on cisplatin-induced toxicity via its antioxidant effects on in vitro and ex vivo culture systems. To elucidate the mechanism of the antioxidant activity of LA, NRF2 was inhibited using NRF2 siRNA, and the change in antioxidant activity of LA was characterized. MTT assays showed that LA was safe at concentrations up to 0.5 mM in HEI-OC1 cells and had a protective effect against cisplatin-induced cytotoxicity. Intracellular ROS production in HEI-OC1 cells was rapidly increased by cisplatin for up to 48 h. However, treatment with LA significantly reduced the production of ROS and increased the expression of the antioxidant proteins HO-1 and SOD1. Ex vivo, the organs of Corti of the group pretreated with LA exhibited better preservation than the group that received cisplatin alone. We also confirmed the nuclear translocation of NRF2 after LA administration, and that NRF2 inhibition decreased the antioxidant activity of LA. Together, these results indicate that the antioxidant activity of LA was through the activation of the NRF2/HO-1 antioxidant pathway.