Intratympanic steroid treatment can reduce ROS and immune response in human perilymph investigated by in-depth proteome analysis.

Intratympanic (IT) steroid treatment is one of the most widely used and effective treatments for inner ear disorders such as sudden sensorineural hearing loss (SNHL). However, a clear mechanism of IT steroids in inner ear recovery has not yet been revealed. Therefore, we investigated proteome changes in extracted human perilymph after steroid treatment. In this study, we applied a tandem mass spectrometry (MS/MS)-based proteomics approach to discover global proteome changes by comparing human perilymph after steroid treatment with non-treated perilymph group. Using liquid chromatography-MS/MS analysis, we selected 156 differentially expressed proteins (DEPs) that were statistically significant according to Student's t-test. Functional annotation analysis showed that upregulated proteins after steroid treatment are related to apoptosis signaling, as well as reactive oxygen species (ROS) and immune responses. The protein-protein interaction (PPI) clusters the proteins associated with these processes and attempts to observe signaling circuitry, which mediates cellular response after IT steroid treatments. Moreover, we also considered the interactome analysis of DEPs and observed that those with high interaction scores were categorized as having equivalent molecular functions (MFs). Collectively, we suggest that DEPs and interacting proteins in human perilymph after steroid treatment would inhibit the apoptotic and adaptive immune processes that may lead to anti-inflammatory effects.

Altered secretome by diesel exhaust particles and lipopolysaccharide in primary human nasal epithelium.

BACKGROUND: Airway epithelial cells can actively participate in the defense against environmental pathogens to elicit local or systemic inflammation. Diesel exhaust particles (DEP), a main component of urban air pollution with particulate matter, are associated with the occurrence of acute and chronic upper airway inflammatory diseases. OBJECTIVES: We sought to investigate the effect of DEP alone or in combination with lipopolysaccharide on the secretome in the primary human nasal epithelium (PHNE) and to find potential biomarkers to relate DEP exposure to upper airway inflammatory diseases. METHODS: PHNE was cultured at an air-liquid interface to create a differentiated in vivo-like model. Secreted proteins (secretome) on the bottom media of the PHNE were analyzed by mass spectrometry-based label-free quantitative proteomics and ELISA. RESULTS: Considerably more differentially expressed secreted proteins were identified in response to DEP plus lipopolysaccharide than to DEP alone. Some canonical pathways related to inflammation and cancer such as the p53, ß-catenin, and extracellular signal-regulated kinase 1/2 pathways were involved. Among differentially expressed secreted proteins, leukemia inhibitory factor was also detected at a high level in the middle ear effusions of otitis media patients, and the leukemia inhibitory factor level was significantly correlated with daily mean mass concentrations of atmospheric particulate matter averaged over 8 days before sample collection. CONCLUSIONS: Apical stimulation with DEP and lipopolysaccharide can significantly alter the basal secretome in PHNE, and this alteration can be reflected by surrounding inflammation with effusion of fluids in vivo such as middle ear effusions in otitis media patients.

Intratympanic Administration of Dieckol Prevents Ototoxic Hearing Loss.

OBJECTIVE: Systemic administration of dieckol reportedly ameliorates acute hearing loss. In this study, dieckol was delivered to the inner ear by the intratympanic route. The functional and anatomic effects and safety of dieckol were assessed using the rat ototoxicity model. MATERIALS AND METHODS: Dieckol in a high-molecular-weight hyaluronic acid vehicle (dieckol+vehicle group) or vehicle without dieckol (vehicle-only group) were randomly delivered into 12 ears intratympanically. Ototoxic hearing loss was induced by intravenous administration of cisplatin, gentamicin, and furosemide. The hearing threshold and surviving outer hair cells (OHC) were enumerated. Biocompatibility was assessed by serial endoscopy of the tympanic membrane (TM), and the histology of the TM and the base of bulla (BB) mucosa was quantitatively assessed. RESULTS: The hearing threshold was significantly better (difference of 20 dB SPL) in the dieckol+vehicle group than in the vehicle-only group. The number of surviving OHCs was significantly greater in the dieckol+vehicle group than in the vehicle-only group. There were no signs of inflammation or infection in the ear. The thickness of the TM and the BB mucosa did not differ between the two groups. CONCLUSION: Intratympanic local delivery of dieckol may be a safe and effective method to prevent ototoxic hearing loss.

In-depth proteome of perilymph in guinea pig model.

The vast majority of sensorineural hearing loss is caused by impairment of the inner ear cells. Proteomic analysis of perilymph may therefore improve our understanding of inner ear diseases and hearing loss. However, the investigation of the human perilymph proteome was limited due to technical difficulties in perilymph sampling. The guinea pig (Cavia porcellus) is frequently used as an experimental model in preclinical hearing research. In this study, we analyzed samples of perilymph collected from 12 guinea pigs to overcome limited experimental information regarding its proteome. We identified a total of 1413 proteins, establishing a greatly expanded proteome of the previously inferred guinea pig perilymph. This provides a comprehensive proteomic resource for the research community, which will facilitate future molecular-phenotypic studies using the guinea pig as an experimental model of relevance to human inner ear biology.

Reorganized Brain White Matter in Early- and Late-Onset Deafness With Diffusion Tensor Imaging.

OBJECTIVES: Individuals with early- and late-onset deafness showed different functional and morphological brain changes, but white matter alterations in both deaf groups still need to be elucidated. This study aimed to investigate changes in white matter integrity and white matter anatomical connectivity in both early- and late-onset deaf groups compared with hearing group. DESIGN: Diffusion tensor imaging data from 7 early-onset deaf (50.7 ± 6.5 years), 11 late-onset deaf (50.9 ± 12.3 years), and 9 hearing adults (48.9 ± 9.5 years) were preprocessed using FSL software. To find changes in white matter integrity, tract-based spatial statistics was used, which implemented on FSL software. Fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were calculated and compared among the groups with age as a nuisance variable. To find out the effect of onset age or duration of deafness to the white matter integrity, onset-age or duration of deafness was treated as a variable of interest in the general linear model implemented on tract-based spatial statistics. White matter connectivity was constructed by a deterministic tractography and compared among the groups. RESULTS: In comparison to the hearing group, the early-onset deaf group did not show any significant changes but the late-onset deaf group showed decreased FA and increased RD in the several white matter areas. AD in the late-onset deaf group was not significantly different compared with the hearing group. The regions included the corpus callosum, posterior and superior corona radiata, internal capsule, posterior thalamic radiation, superior longitudinal fasciculus, and tapetum of the right hemisphere. Increased RD was also additionally observed in the right external capsule, fornix, and cerebral peduncle. The onset age or duration of deafness was not significantly correlated with the white matter integrity in the early-onset deaf group. In contrast, the onset age showed a significantly positive correlation with the RD, and a negative correlation with the FA, in the late-onset deaf group. The correlated white matter areas were also similar to the findings of comparison with the hearing group. In comparison to the hearing group, the early-onset deaf group did not show altered white matter connectivity, while the late-onset deaf group showed decreased white matter connectivity in between the right lingual and hippocampal areas. CONCLUSIONS: The present results suggest that late-onset deaf adults showed decreased FA and increased RD, and early-onset deaf adults showed no difference compared with the hearing group. In the late-onset deaf adults, onset-age showed a significantly positive correlation with RD and negative correlation with FA. Duration of deafness was not significantly correlated with the changes. Increased RD indicating demyelination occurred in the brain, and the changes were not limited to the auditory cortex but expanded to almost whole brain areas, suggesting significant effect of auditory deprivation on the brain later in life. The altered white matter connectivity in between the right limbic-occipital areas observed in the late-onset deaf group might be caused by altered language functions after auditory deprivation. Future studies are necessary incorporating functional and anatomical aspects of the brain changes in deaf group.

Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model.

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma.

The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.

Dual-site rTMS is More Effective than Single-site rTMS in Tinnitus Patients: A Blinded Randomized Controlled Trial.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an alternative option for treating tinnitus. rTMS is a noninvasive method in which repetitive magnetic stimulation is applied to the cortex; it is considered a therapeutic strategy that modulates the loudness of tinnitus. In this study, we performed a double-blind randomized clinical trial to compare the outcome of tinnitus treatment among (1) dual-site (auditory + prefrontal) rTMS stimulation, (2) auditory cortex only rTMS stimulation (AC), and (3) sham stimulation. The left primary auditory cortex and left dorsolateral prefrontal cortex (DLPFC) were targeted independently of handedness or tinnitus laterality. Dual-site and auditory only groups were treated with a total of 12,000 pulses, 2000 pulses over the AC and 1000 pulses over the DLPFC (group 1), 3000 pulses over the AC only (group 2), and daily for 4 consecutive days. Dual-site group exhibited a significantly better ΔTinnitus Handicap Inventory (ΔTHI) score at 4, 8 weeks and 12 weeks after rTMS treatments compared with pre-treatment. However, there was no effect in the auditory only group. Also, there was no effect in sham group when THI scores were compared with that of the pre-treatment. These results are in line with the former studies that reported a better treatment effect by multiple site rTMS.

Biocompatibility and Therapeutic Effect of 3 Intra-Tympanic Drug Delivery Vehicles in Acute Acoustic Trauma.

INTRODUCTION: The aim of this study was to assess the biocompatibility of several intra-tympanic (IT) drug delivery vehicles and to compare hearing outcomes. MATERIALS AND METHODS: After acute acoustic trauma, rats were treated with IT 10 mg/mL dexamethasone phosphate (D) and divided into the following groups for drug delivery: saline + D (n = 15), hyaluronic acid (HA) + D (n = 17), and methoxy polyethylene glycol-b-polycaprolactone block copolymer (MP) + D (n = 24). RESULTS: No inflammation was found in the saline + D or HA + D groups. The duration of vehicle/drug persistence in the bulla was significantly longer for the MP + D (47.5 days) and HA + D groups (1.8 days) than for the saline + D group (<1 day). The tympanic membrane was significantly thicker in the MP + D group than in the saline + D and HA + D groups. The proportion of ears with good hearing outcome was significantly higher (63.6%) in the HA + D group than in the MP + D group. The number of hair cells in the hearing loss (HL) control group was significantly lower than in the MP + D group. DISCUSSION/CONCLUSION: HA shows great potential as a biocompatible vehicle for D delivery via the IT route, without an inflammatory reaction and with better hearing outcomes. Considering inflammation and hearing, MP may not be a good candidate for IT drug delivery.

Changes in microRNA Expression in the Cochlear Nucleus and Inferior Colliculus after Acute Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) can lead to secondary changes that induce neural plasticity in the central auditory pathway. These changes include decreases in the number of synapses, the degeneration of auditory nerve fibers, and reorganization of the cochlear nucleus (CN) and inferior colliculus (IC) in the brain. This study investigated the role of microRNAs (miRNAs) in the neural plasticity of the central auditory pathway after acute NIHL. Male Sprague-Dawley rats were exposed to white band noise at 115 dB for 2 h, and the auditory brainstem response (ABR) and morphology of the organ of Corti were evaluated on days 1 and 3. Following noise exposure, the ABR threshold shift was significantly smaller in the day 3 group, while wave II amplitudes were significantly larger in the day 3 group compared to the day 1 group. The organ of Corti on the basal turn showed evidence of damage and the number of surviving outer hair cells was significantly lower in the basal and middle turn areas of the hearing loss groups relative to controls. Five and three candidate miRNAs for each CN and IC were selected based on microarray analysis and quantitative reverse transcription PCR (RT-qPCR). The data confirmed that even short-term acoustic stimulation can lead to changes in neuroplasticity. Further studies are needed to validate the role of these candidate miRNAs. Such miRNAs may be used in the early diagnosis and treatment of neural plasticity of the central auditory pathway after acute NIHL.

Treatment Outcome of Auditory and Frontal Dual-Site rTMS in Tinnitus Patients and Changes in Magnetoencephalographic Functional Connectivity after rTMS: Double-Blind Randomized Controlled Trial.

BACKGROUND: Recently, the role of neural modulation in nonauditory cortices via repetitive transcranial magnetic stimulation (rTMS) for tinnitus control has been emphasized. It is now more compelling to consider these nonauditory cortices and the whole "tinnitus network" as targets for tinnitus treatment to achieve a better outcome. OBJECTIVE: We aimed to investigate the effects of active dual-site rTMS treatment in tinnitus reduction using a double-blind randomized controlled trial. METHOD: In study 1, the dual-site rTMS treatment group (n = 17) was treated daily for 4 consecutive days. The sham group (n = 13) also visited the clinic for 4 days; they received sham treatment for the same duration as the dual-site rTMS treatment group. In study 2, the rTMS treatment protocol was exactly the same as in study 1. Magnetoencephalography recordings were performed before and 1 week after the last rTMS treatment. The outcome measure was the Tinnitus Handicap Inventory (THI) score and the visual analog scale score. The effects of treatment were assessed 1, 2, 4, and 8 weeks after rTMS treatment in study 1. Then the mean band power and network changes were compared between pre- and post-treatment values after rTMS in study 2. RESULT: Patients in the dual-site rTMS treatment group exhibited significantly improved THI scores at 2, 4, and 8 weeks after rTMS treatment compared with the pretreatment scores. However, the sham group did not show any significant reduction in THI scores. When the mean band power changes were compared between pre- and post-treatment assessments, an increased oscillation power was observed in the alpha band after rTMS. CONCLUSION: A beneficial effect of rTMS on tinnitus suppression was found in the dual-site active rTMS group, but not in the sham rTMS group.

Endoscopic visualization to the anterior surface of the malleus and tensor tympani tendon in congenital cholesteatoma.

PURPOSE: This study evaluated the feasibility of endoscopy in exposing the anterior surface of the malleus and tensor tympani tendon (ASMT) in children with congenital cholesteatoma (CC), and investigated the outcomes of hearing, postoperative complications, and residual or recurrent disease in endoscopic surgical approach cases. METHODS: A retrospective case review was performed in one tertiary referral center. Twelve children with CC involving the ASMT were recruited, and their medical records were reviewed. All patients underwent either total endoscopic surgery (n = 3) or endoscope-assisted surgery (n = 9), and Potsic staging was adopted to classify CC according to its severity: stage I (n = 8), stage II (n = 2), and stage III (n = 2). The mean follow-up period was 15.5 ± 2.8 months. The visibility of the ASMT by endoscope assistance, audiological results, surgical and postoperative complications, and recidivism of CC were analyzed. RESULTS: The ASMT was well visualized by endoscope assistance in all cases. No patient showed hearing deterioration at 3 months after surgery, and none experienced residual or recurrent disease during the follow-up period. Postoperative complications were not observed. CONCLUSIONS: Total endoscopic or endoscope-assisted surgery could help surgeons directly visualize the ASMT in children, with negligible risks of hearing deterioration, postoperative complications, and recurrent disease. Our study might suggest that endoscopic ear surgery should be considered in patients with CC in the ASMT.

Compensation of Vestibular Function and Plasticity of Vestibular Nucleus after Unilateral Cochleostomy.

Dizziness and vertigo frequently occur after cochlear implantation (CI) surgery, particularly during the early stages. It could recover over time but some of the patients suffered from delayed or sustained vestibular symptoms after CI. This study used rat animal models to investigate the effect of unilateral cochleostomy on the vestibular organs over time. Twenty-seven Sprague Dawley rats underwent cochleostomy to evaluate the postoperative changes in hearing threshold, gain and symmetry of the vestibular ocular response, overall balance function, number of hair cells in the crista, and the c-Fos activity in the brainstem vestibular nucleus. Loss of vestibular function was observed during the early stages, but function recovered partially over time. Histopathological findings demonstrated a mild decrease in vestibular hair cells numbers. Increased c-Fos immunoreactivity in the vestibular nucleus, observed in the early stages after cochleostomy, decreased over time. Cochleostomy is a risk factor for peripheral vestibular organ damage that can cause functional impairment in the peripheral vestibular organs. Altered vestibular nucleus activity may be associated with vestibular compensation and plasticity after unilateral cochleostomy.

Safety assessment of trans-tympanic photobiomodulation.

We evaluated functional and morphological changes after trans-tympanic laser application using several different powers of photobiomodulation (PBM). The left (L) ears of 17 rats were irradiated for 30 min daily over 14 days using a power density of 909.1 (group A, 5040 J), 1136.4 (group B, 6300 J), and 1363.6 (group C, 7560 J) mW/cm(2). The right (N) ears served as controls. The safety of PBM was determined by endoscopic findings, auditory brainstem response (ABR) thresholds, and histological images of hair cells using confocal microscopy, and light microscopic images of the external auditory canal (EAC) and tympanic membrane (TM). Endoscopic findings revealed severe inflammation in the TM of C group; no other group showed damage in the TM. No significant difference in ABR threshold was found in the PBM-treated groups (excluding the group with TM damage). Confocal microscopy showed no histological difference between the AL and AN, or BL and BN groups. However, light microscopy showed more prominent edema, inflammation, and vascular congestion in the TM of BL ears. This study found a dose-response relationship between laser power parameters and TM changes. These results will be useful for defining future allowance criteria for trans-tympanic laser therapies.

Diverse patterns of perilymphatic space enhancement in the rat inner ear after intratympanic injection of two different types of gadolinium: a 9.4-tesla magnetic resonance study.

OBJECTIVE: To compare the quality of perilymphatic enhancement in the rat inner ear after intratympanic injection of two types of gadolinium with a 9.4-tesla micro-MRI. MATERIALS AND METHODS: Gadolinium was injected into the middle ear in 6 Sprague-Dawley rats via the transtympanic route. The left ear was injected with Gd-DO3A-butrol first, and then the right ear was injected with Gd-DOTA. MR images of the inner ear were acquired 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4 h after intratympanic (IT) injection using an Agilent MRI system 9.4T/160/AS. The normalized signal intensity was quantitatively analyzed at the scala vestibuli (SV), scala media, and scala tympani (ST) using a Marosis M-view system. Then the normalized signal intensities (SIs) were compared between the two contrast agents. RESULTS: For Gd-DO3A-butrol, the SI was as low as 1.0-1.5 throughout 1-4 h at the SV and ST of the basal turn. The maximum SI was 1.5 ± 0.5 at the SV (2 h) and 1.3 ± 0.5 at the ST (2 h). For Gd-DOTA, the 1-hour postinjection SI at the basal turn was 2.5 ± 0.5 at the SV, 1.6 ± 0.3 at the ST, and 1.2 ± 0.3 at the scala media. In the apical turn, the maximum SI was reached after 2.5 h. The maximum SI in the apical turn was 1.8 ± 0.4 at the SV (3.5 h), 1.8 ± 0.4 at the ST (4 h), and 1.4 ± 0.3 at the scala media (4 h). CONCLUSIONS: We were able to clearly visualize and separate the ST and SV using IT Gd and 9.4-tesla micro-MRI. We recommend using Gd-DO3A-butrol over Gd-DOTA and to perform the MRI 2.5 h after using IT Gd in the rat inner ear.

Insufficient nutrient intake in individuals with disabling hearing loss and the restoration of nutritional sufficiency in hearing aid users.

Hearing loss affects some nutrient intake. Disabling hearing loss may exacerbate these issues. We aimed to evaluate nutrient intake and assess deficiencies based on functional hearing status. The study included 6907 participants with information on demographic factors, nutrient intake, weight, height, disease status, and hearing level in the eighth Korea National Health and Nutrition Examination Survey, conducted from 2019 to 2021. We categorized the participants into 3 groups based on their functional hearing status: bilateral hearing, unilateral hearing, and disabling hearing loss. The disabling hearing loss group showed lower intake of most major nutrients (P < 0.05), dietary fiber (P < 0.001), and most minerals and vitamins (P < 0.05), with some insufficiencies. The unilateral hearing group showed lower intake only for potassium (P = 0.036) compared to the bilateral hearing group and significantly higher intake of hydration (P = 0.039), dietary fiber (P = 0.039), and calcium (P = 0.009) than the disabling hearing loss group. Nutrient insufficiency in the disabling hearing loss group was more prominent in women, and was partially resolved by using hearing aids. Clinicians and nutritionists should consider undernourishment in these patients, and appropriate interventions for nutrition and hearing aids should be recommended.

Associations between tinnitus and body composition: a cross-sectional study.

The relationship between tinnitus and body composition in specific regions has not been extensively investigated. This study aimed to identify associations between tinnitus and body composition. Individuals with data on physical and otological examination findings, and bioelectrical impedance analysis were included from the ninth Korea National Health and Nutritional Examination Survey. They were divided into a tinnitus group and a non-tinnitus group. Participants with tinnitus were further classified into acute or chronic tinnitus group. The tinnitus group showed significantly higher body fat percentages in each region (arms: P = 0.014; legs: P = 0.029; trunk: P = 0.008; whole body: P = 0.010) and waist circumference (P = 0.007) than the non-tinnitus group, and exhibited lower leg muscle percentage (P = 0.038), total body fluid percentage (P = 0.010), and intracellular fluid percentage (P = 0.009) than the non-tinnitus group in men. Furthermore, men with chronic tinnitus showed a significantly higher trunk fat percentage (P = 0.015) and waist circumference (P = 0.043), and lower intracellular fluid percentage (P = 0.042) than their counterparts without tinnitus. No significant differences in body composition were observed among the groups in the female population. In men, body composition may be associated with tinnitus.

Higher exposure to 1,3-butadiene is associated with more severe hearing loss.

While volatile organic compounds (VOCs) impair various organs, their influence on hearing loss (HL) has not been extensively researched. We aimed to identify the association between VOCs and HL or high-frequency hearing loss (HFHL). We extracted data on age, sex, pure tone audiometry, hypertension, occupational noise exposure, and creatinine-corrected urine VOC metabolite concentrations from the eighth Korea National Health and Nutrition Survey. Among the VOC metabolites, N-acetyl-S-(benzyl)-L-cysteine (BMA, P = 0.004), N-acetyl-S-(phenyl)-L-cysteine (SPMA, P = 0.027), and N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA, P < 0.001) showed associations with HL. Additionally, HFHL exhibited significant associations with BMA (P = 0.005), 3- and 4-methylhippuric acid (3, 4 MHA, P = 0.049), mandelic acid (MA, P = 0.015), SPMA (P < 0.001), N-acetyl-S-(3-hydroxypropyl)-L-cysteine (3-HPMA, P < 0.001), and DHBMA (P < 0.001). After controlling other factors, DHBMA were associated with HL (P = 0.021) and HFHL (P = 0.014) and exhibited a linear association with the mean hearing level (ß = 0.054, P = 0.024) and high-frequency hearing level (ß = 0.045, P = 0.037). Since 1,3-butadiene may act as an ototoxic material, early screening for workers exposed to 1,3-butadiene and reducing exposure to 1,3-butadiene in everyday life may be helpful to prevent further HL.

Efficacy of biologics for eosinophilic otitis media.

BACKGROUND: Eosinophilic otitis media (EOM) is an intractable condition primarily treated with steroids. Recently, biologics targeting IgE or IL-5 have been introduced. OBJECTIVES: This study aimed to evaluate the efficacy of biologics for EOM. MATERIALS AND METHODS: We retrospectively collected data on EOM patients treated from January 2008 to December 2020 from electronic medical records. Patients were classified into the steroid group, treated with systemic or local steroids, and the biologics group, treated with biologics with or without steroids. RESULTS: The otorrhea remission rate was 63.33% in the steroid group, comparable to 58.82% in the biologics group (p = 0.760). Before treatment, the steroid group showed better bone-conduction (BC) thresholds at 0.5 kHz and 1 kHz than the biologics group. Post-treatment, the steroid group improved in air-conduction (AC) threshold and air-bone gap (ABG) at 1 kHz and 2 kHz. The biologics group exhibited stable audiological results. No significant differences were observed post-treatment between the groups, except for the BC threshold at 0.5 kHz, which remained as pre-treatment. CONCLUSIONS AND SIGNIFICANCE: Biologics demonstrated similar efficacy in otorrhea remission as steroids and might help maintain hearing levels. Biologics can be considered for controlling EOM with active otorrhea and reducing systemic steroid use.

Biosafety and potency of high-molecular-weight hyaluronic acid with intratympanic dexamethasone delivery for acute hearing loss.

Objective: This study evaluated the potential of high-molecular-weight hyaluronic acid (HHA) as an intratympanic (IT) drug delivery vehicle for dexamethasone (D) in treating acute hearing loss. We compared the efficacy, safety, and residence time of HHA to the standard-of-care IT drug delivery method. Methods: Endoscopic examinations were used to track tympanic membrane (TM) healing post-IT injection. Micro-computed tomography (CT) was used to gauge drug/vehicle persistence in the bulla air space. Histological analyses covered the middle ear, TM, and hair cell counts. Auditory brainstem responses (ABR) were used to measure hearing thresholds, while high-performance liquid chromatography (HPLC) was employed to quantify cochlear perilymph dexamethasone concentrations. Results: The HHA + D group had a notably prolonged drug/vehicle residence time in the bulla (41 ± 27 days) compared to the saline + D group (1.1 ± 0.3 days). Complete TM healing occurred without adverse effects. Histology revealed no significant intergroup differences or adverse outcomes. Hearing recovery trends favored the HHA + D group, with 85.0% of ears showing clinically meaningful improvement. D concentrations in cochlear perilymph were roughly double in the HHA group. Conclusion: HHA is a promising vehicle for IT drug delivery in treating acute hearing loss. It ensures extended residence time, augmented drug concentrations in targeted tissues, and safety. These results highlight the potential for HHA + D to excel beyond existing standard-of-care treatments for acute hearing loss.