Protective effects of Y-27632 against cisplatin-induced ototoxicity: A zebrafish model Y-27632 and cisplatin-induced ototoxicity.

Cisplatin is an effective chemotherapy agent against various solid malignancies; however, it is associated with irreversible bilateral sensorineural hearing loss, emphasizing the need for drug development to prevent this complication, with the current options being very limited. Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine-threonine protein kinase involved in various cellular processes, including apoptosis regulation. In this study, we used a transgenic zebrafish model (Brn3C: EGFP) in which hair cells within neuromasts are observed in green under fluorescent microscopy without the need for staining. Zebrafish larvae were exposed to cisplatin alone or in combination with various concentrations of Y-27632, a potent ROCK inhibitor. Hair cell counts, apoptosis assessments using the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay, FM1-43FX labeling assay and behavioral analyses (startle response and rheotaxis) were performed to evaluate the protective effects of Y-27632 against cisplatin-induced ototoxicity. Cisplatin treatment reduced the number of hair cells in neuromasts, induced apoptosis, and impaired zebrafish larval behaviors. Y-27632 demonstrated a dose-dependent protective effect against cisplatin-induced hair cell loss and apoptosis. These findings suggest that Y-27632, as a ROCK inhibitor, mitigates cisplatin-induced hair cell loss and associated ototoxicity in zebrafish.

Measuring Optokinetic Reflex and Vestibulo-Ocular Reflex in Unilateral Vestibular Organ Damage Model of Zebrafish.

One-sided vestibular disorders are common in clinical practice; however, their models have not been fully established. We investigated the effect of unilateral or bilateral deficits in the vestibular organs on the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) of zebrafish using in-house equipment. For physical dislodgement of the otoliths in the utricles of zebrafish larvae, one or both utricles were separated from the surrounding tissue using glass capillaries. The video data from VOR and OKR tests with the larvae was collected and processed using digital signal processing techniques such as fast Fourier transform and low-pass filters. The results showed that unilateral and bilateral damage to the vestibular system significantly reduced VOR and OKR. In contrast, no significant difference was observed between unilateral and bilateral damage. This study confirmed that VOR and OKR were significantly reduced in zebrafish with unilateral and bilateral vestibular damage. Follow-up studies on unilateral vestibular disorders can be conducted using this tool.

Exploring Embryo-Ototoxic Effects: Insights into Deodorant-Induced Hair Cell Damage in Zebrafish.

Our study investigated the embryo-ototoxic effects of deodorant2 (DA2) on zebrafish embryos, which serve as valuable model organisms due to genetic and physiological similarities to humans. We focused on understanding DA2's impact on zebrafish hair cells, which are vital for sensory perception and balance regulation. DA2, provided by the Ministry of Environment, Republic of Korea, was used at 460 µg/mL in dimethyl sulfoxide (DMSO), with a 0.43% DMSO solvent control group. Three experiments, each using 10 zebrafish specimens from each group, showed an initial 13% hair cell count reduction in the DA2-exposed group. Subsequent experiments demonstrated reductions of 37% and 22%, each with one mortality case. Statistical analysis revealed a significant 24% hair cell count reduction in the DA2-exposed group. We also assessed DA2's impact on zebrafish behavior. Although not statistically significant, differences in distances traveled (0.33-0.39, 95% confidence interval: -0.46-1.1, p = 0.2033) and latencies (-0.016-0.018, 95% confidence interval: -0.052-0.021, p = 0.1917) hinted at negative effects. These results highlight DA2's ototoxic properties affecting zebrafish auditory systems and behavior. Further investigation into DA2's effects on aquatic organisms and potential mitigation strategies are essential. These findings contribute to understanding DA2's safety profile, benefiting aquatic ecosystems and human health assessments.

Analysis of the association between vestibular schwannoma and hearing status using a newly developed radiomics technique.

PURPOSE: Vestibular schwannoma is a benign tumor originating from Schwann cells surrounding the eighth cranial nerve and can cause hearing loss, tinnitus, balance problems, and facial nerve disorders. Because of the slow growth of the tumor, predicting the hearing function of patients with vestibular schwannoma's is important to obtain information that would be useful for deciding the treatment modality. This study aimed to analyze the association between magnetic resonance imaging features and hearing status using a new radiomics technique. METHODS: We retrospectively analyzed 115 magnetic resonance images and hearing results from 73 patients with vestibular schwannoma. A total of 70 radiomics features from each tumor volume were calculated using T1-weighted magnetic resonance imaging. Radiomics features were classified as histogram-based, shape-based, texture-based, and filter-based. The least absolute shrinkage and selection operator method was used to select the radiomics features among the 70 features that best predicted the hearing test. To ensure the stability of the selected features, the least absolute shrinkage and selection operator method was repeated 10 times. Finally, features set five or more times were selected as radiomics signatures. RESULTS: The radiomics signatures selected using the least absolute shrinkage and selection operator method were: minimum, variance, maximum 3D diameter, size zone variance, log skewness, skewness slope, and kurtosis slope. In random forest, the mean performance was 0.66 (0.63-0.77), and the most important feature was Log skewness. CONCLUSIONS: Newly developed radiomics features are associated with hearing status in patients with vestibular schwannoma and could provide information when deciding the treatment modality.

Audiologic results of total ossicular replacement prosthesis bypassing the stapes suprastructure in canal wall down mastoidectomy.

OBJECTIVES: Sometimes performing PORP adequately is challenging when the stapes is tilted or the suprastructure is partially damaged owing to inflammation or infection. In such cases, the implementation of a TORP bypassing the stapes can be a useful alternative. This study aimed to investigate whether bypassing the stapes suprastructure during total ossicular replacement prosthesis (TORP) affects postoperative complications or audiological outcomes. MATERIAL AND METHODS: Among 104 patients who underwent open cavity mastoidectomy and ossiculoplasty using a titanium prosthesis at Korea University Ansan Hospital between January 2012 and December 2019, we compared the preoperative and postoperative audiological results and surgical complications of 52, 21, and 31 patients who underwent partial ossicular replacement prosthesis (PORP), TORP bypassing the remaining stapes suprastructure, and TORP on the stapes footplate or oval window, respectively. RESULTS: The air-bone gap before surgery was significantly different in the TORP on the stapes footplate group (34.2 ± 12.0 dB) than that in the PORP (22.9 ± 13.8 dB) and TORP bypassing the stapes groups (20.7 ± 11.5 dB, p < 0.001). After surgery, there were no significant differences among the groups (p = 0.818). The air-bone gap difference before surgery was associated with the presence of stapes before surgery (p < 0.001). There was no difference in the proportion of postoperative tympanic perforation, whether it was a revision surgery, malleus status, or the size of perforation of the tympanic membrane among the three groups. CONCLUSION: When performing ossiculoplasty using TORP, bypassing the stapes did not affect surgical and audiologic outcomes.

Hydrophilic and lipophilic statin use and risk of hearing loss in hyperlipidemia using a Common Data Model: multicenter cohort study.

Hearing impairment, the third largest health burden worldwide, currently lacks definitive treatments or preventive drugs. This study compared the effects of hydrophilic and lipophilic statin on hearing loss using a common database model. This retrospective multicenter study was conducted in three hospitals in South Korea (Anam, Guro, Ansan). We enrolled patients with hyperlipidemia with an initial hearing loss diagnosis. Data were collected during January 1, 2022-December 31, 2021 using the Observational Health Data Science and Informatics open-source software and Common Data Model database. The primary outcome was the occurrence of first-time hearing loss following a hyperlipidemia diagnosis, as documented in the Common Data Model cohort database. The measures of interest were hearing loss risk between hydrophilic and lipophilic statin use. Variables were compared using propensity score matching, Cox proportional regression, and meta-analysis. Among 37,322 patients with hyperlipidemia, 13,751 (7669 men and 6082 women) and 23,631 (11,390 men and 12,241 women) were treated with hydrophilic and lipophilic statins, respectively. After propensity score matching, according to the Kaplan-Meier curve, hearing loss risk did not significantly differ among the hospitals. The hazard ratio (HR) of the male patients from Anam (0.29, [95% confidence interval (CI), 0.05-1.51]), Guro (HR, 0.56, [95% CI 0.18-1.71]), and Ansan (hazard ratio, 0.29, [95% CI 0.05-1.51]) hospitals were analyzed using Cox proportional regression. Overall effect size (HR, 0.40, [95% CI 0.18-0.91]) was estimated using meta-analysis, which indicated that hearing loss risk among hydrophilic statin users was less than that among lipophilic statin users and was statistically significant. Men in the hydrophilic statin group had a lower risk of hearing impairment than those in the lipophilic statin group.

A Multicenter Cohort Study on the Association between Metformin Use and Hearing Loss in Patients with Type 2 Diabetes Mellitus Using a Common Data Model.

We attempted to explore the association between metformin use and hearing loss in in a large-scale study. This retrospective multicenter cohort study assessed the data of patients with type 2 diabetes mellitus (DM) aged over 40 years using the Observational Health Data Science and Informatics open-source software and the Common Data Model database from 1 January 2002 to 31 December 2019. Each participant was selected using the ICD-10-CM diagnosis code E11 for type 2 DM with sensorineural hearing loss. The participants were divided into metformin and non-metformin users. The outcome measure was the first occurrence of hearing loss after the diagnosis of DM as measured by the CDM cohort study. A total of 80,596 patients, including 46,152 metformin users and 34,444 non-metformin users from three hospitals were assessed. After calibration, we compared the risk of hearing loss using Kaplan-Meier curves, and found significant differences between the groups. The calibrated hazard ratio in the three hospitals (0.79 [95% confidence interval, 0.57-1.12]) was summarized. These findings suggest that the probability of hearing loss-free survival in the metformin user group is higher than that in the non-metformin user group.

Analysis of hearing prognosis risk factors in pediatric unilateral sudden sensorineural hearing loss.

OBJECTIVES: Pediatric idiopathic sudden hearing loss (PISSNHL) is a rare disease with no established factor affecting its prognosis. In this study, we investigate the risk factors affecting the prognosis of PISSNHL. MATERIAL AND METHODS: Among the patients who visited our hospital from January 2010 to December 2021, the characteristics associated prognosis of 54 patients with unilateral PISSNHL were retrospectively confirmed. RESULTS: Patients' recovery was determined by applying Siegel's criteria (SC) and AAO-HNS criteria (AC). Twenty-seven (50 %) and 29 patients (54.3 %) recovered for SC and AC, respectively. Age, sex, side, duration between onset and treatment, administration of intra-tympanic steroid injection, accompanying symptoms (tinnitus and dizziness), BMI, serum creatinine level, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte count (PLR), lymphocyte count, and platelet count were not significantly different between the recovery group and the poor recovery group (P > 0.05). The patients were divided into five groups according to the initial hearing of the affected ear and again according to their audiogram type. The initial hearing levels, hearing level severity, and the audiogram type were significantly different between the deaf group (>100 dB HL) and the non-deaf group (P < 0.05). CONCLUSION: The prognosis of PISSNHL is closely related to the initial hearing at the onset. If the initial hearing level is <100 dB, the recovery rate is approximately 50 %, therefore requiring active treatment and emotional support. It may also be related to the type of audiometric curve.

Functional Outcomes of Single-Stage Ossiculoplasty in Chronic Otitis Media With or Without Cholesteatoma.

BACKGROUND: Two-stage ossiculoplasty has been widely used for hearing improvement in chronic otitis media with or without cholesteatoma. However, the outcomes of single-stage ossiculoplasty have not been fully clarified.The aim of this study is to determine whether the outcomes of single-stage ossiculoplasty are comparable with those of 2-stage ossiculoplasty in chronic otitis media with or without cholesteatoma. METHODS: Medical records of 191 cases (187 patients) who underwent single-stage ossiculoplasty from January 2011 to May 2018 at our hospital were retrospectively reviewed. RESULTS: Polycel and titanium were used in 56 and 135 cases, respectively. In chronic otitis media without cholesteatoma, the success rate of polycel and titanium partial ossicular replacement prosthesis was 80.7% and 81.6%, respectively. In chronic otitis media with cholesteatoma, the success rate of polycel and titanium partial ossicular replacement prosthesis was 63.6% and 64.6%, respectively, while that of polycel and titanium total ossicular replacement prosthesis was 45.9% and 47.8%, respectively. CONCLUSION: These results suggest that single-stage ossiculoplasty is a suitable option for recovering postoperative hearing in chronic otitis media with or without cholesteatoma. Thus, if middle ear inflammation can be sufficiently treated in the first stage, single-stage ossiculoplasty is a suitable option for chronic otitis media with or without cholesteatoma.

The Effect of Natural Ocean Sound Exposure and Ocean-Side Relaxation on Chronic Tinnitus Patients: A Pilot Study in Korea.

Sound therapy is a treatment modality for tinnitus patients by increasing the background neuronal activity in the auditory system and inducing relative alleviation of the tinnitus. This study was performed to evaluate the efficacy of natural ocean sound exposure and ocean-side relaxation in chronic tinnitus patients. We prospectively enrolled all 18 chronic tinnitus patients (≥6 months) from July to November 2018. All patients completed 90 hours of our programs. The improvement in their subjective tinnitus severity, moods, the quality of life, and sleep was serially assessed using several questionnaires at baseline, immediately, and 1 month after the program. Changes in serum stress hormone levels of the patients were also compared between the baseline and immediately after the program. Average total Tinnitus Handicap Questionnaire score and factor 2 (hearing difficulty related to tinnitus) score significantly improved over time (P = .024 and P = .002). Patient's serum cortisol and epinephrine level did not show significant decrease, and serum norepinephrine and serotonin level significantly increased immediately after our program (P < .001 and P < .001). Natural ocean sound exposure and ocean-side relaxation for short-term period has a potential efficacy on chronic tinnitus patients.

Comparisons among vestibular examinations and symptoms of vertigo in sudden sensorineural hearing loss patients.

OBJECTIVES: Vertigo in sudden sensorineural hearing loss (SSNHL) is hypothesized as an extension of the disease caused by the anatomical proximity of the cochlea and vestibule. The present study aimed to demonstrate the association of vestibular function test (VFT) results with SSNHL disease severity and prognosis. MATERIALS AND METHODS: This study assessed clinical records of 263 SSNHL patients admitted to our hospital, between January 2010 and October 2017. Steroid treatment comprised high-dose intravenous dexamethasone (16 mg/d) or oral methylprednisolone (64 mg/d) for 4 days and tapered oral methylprednisolone for 8 days after discharge. Caloric tests were performed in all patients, and cervical vestibular-evoked myogenic potential (c-VEMP) and ocular VEMP (o-VEMP) tests were performed in 209 and 144 patients, respectively. RESULTS: Ninety six patients had vertigo, and caloric abnormalities were observed in 119 patients. Initial PTA in patients with vertigo were worse than in those without vertigo (63.0 dB vs 72.7 dB, P = .002). Initial PTA in patients with abnormal o-VEMP was worse than in those with normal o-VEMP (61.4 dB vs 73.0 dB, P = .004). PTA improvement after steroid treatment in patients with vertigo was lower than in those without vertigo (25.0 dB vs 20.9 dB, P = .028). PTA improvement after treatment in patients with abnormal caloric results was lower than in those with normal caloric results (26.0 dB vs 18.4 dB, P = .013). CONCLUSION: The functions of vestibular organs, particularly the utricle and lateral semicircular canal, are associated with disease severity and hearing outcome in SSNHL patients.

Clinical Characteristics and Treatment Outcomes of Congenital Cholesteatoma.

OBJECTIVES: Since its introduction in 2002, the staging system for congenital cholesteatoma, as defined by Potsic, has been used widely owing to its simplicity and predictability. The aim of the present study was to analyze the clinical characteristics and surgical treatment outcomes of congenital cholesteatoma and to correlate them with postoperative recurrence. MATERIALS AND METHODS: A retrospective chart review was performed for 38 patients who were diagnosed with congenital cholesteatoma and who underwent surgical resection between August 2007 and November 2014 at the Department of Otorhinolaryngology of our hospital. RESULTS: The mean age of the patients was 7.9±8.2 years, and the number of males and females was 20 and 18, respectively. The mean follow-up period was 30±26 months. Of the 38 patients, 9 (24%) had residual or recurrent cholesteatoma during follow-up examination after primary surgery. The results showed that the size (≥4 mm) of the lesion was significantly correlated with residual or recurrent disease (p=0.026). The disease extent (single vs. multiple quadrant involvement), type (closed vs. open type), and stage; applied surgical method (with mastoidectomy vs. without mastoidectomy); and preoperative hearing level (normal vs. abnormal) were not significantly correlated with residual or recurrent disease. CONCLUSION: The disease extent, type, and stage; applied surgical methods; and preoperative hearing level were not significantly correlated with residual or recurrent disease. The size (≥4 mm) of congenital cholesteatoma was significantly correlated with residual or recurrent disease.

Assessment of hair cell damage and developmental toxicity after fine particulate matter 2.5 µm (PM 2.5) exposure using zebrafish (Danio rerio) models.

OBJECTIVES: Particulate matter (PM) exposure has become one of the most serious problems. The aim of the present study was to evaluate the hair cell damage and possible developmental toxicity caused by PM2.5 exposure using a zebrafish model. METHODS: Zebrafish embryos were exposed to various concentrations of PM2.5. Developmental toxicity was evaluated based on general morphology score (GMS) system and Panzica-Kelly score, and by measurement of body length and heart rate. To evaluate hair cell damage, the average number of total hair cells within four neuromasts exposed to various concentrations of PM2.5 was compared with that of the control group. RESULTS: Morphological abnormalities evaluated by the GMS system and Panzica-Kelly score were rare and body length tended to be shorter in the PM2.5-exposed groups. Heart rate decreased significantly in the PM2.5-exposed group. Additionally, significant hair cell damage was observed after PM2.5 exposure. It was dose-dependent and more severe after a longer period exposure (10 dpf). CONCLUSIONS: In zebrafish embryos, exposure of PM2.5 in the early stages of life decreased heart rate and caused significant hair cell damage in a dose-dependent manner.

The effect of body position on airway patency in obstructive sleep apnea: CT imaging analysis.

PURPOSE: Positional change during sleep influences upper airway patency. However, few studies have used imaging techniques to demonstrate the change. This study aims to determine the effect of positional change on the upper airway space. METHODS: A total of 118 subjects with sleep breathing disorders were analyzed. Participants underwent upper airway CT scans in the supine and lateral decubitus positions (right and left). They were divided into non-obstructive sleep apnea (n = 28) and obstructive sleep apnea (n = 90) groups. We measured the minimal cross-sectional area of the retropalatal/retroglossal spaces and compared the differences of those two spaces in the supine and lateral positions. CT was performed while patients were awake. RESULTS: The minimal cross-sectional area in the OSA group was significantly smaller than non-OSA group in both supine (median[interquartile range], 8.3[0.0-25.1] vs 22.2[1.0-39.6]; P = 0.018) and lateral decubitus positions (5.2[0.0-16.9] vs 21.3[6.1-38.4]; P = 0.002). As the body position of OSA patients shifted from supine to lateral, the retroglossal space increased significantly (67.3[25.1-116.3] vs 93.3[43.4-160.1]; P < 0.001). However, there was no significant difference in the retropalatal space between the supine and lateral decubitus positions. CONCLUSIONS: Positional change from the supine to lateral decubitus position expands the upper airway lumen, especially the retroglossal space. Positional OSA may be related to anatomical change of the upper airway lumen based on body position.