Tinnitus reduction after active bone-conduction implantation in patients with single-sided deafness: a prospective multicenter study.

PURPOSE: Single-sided deafness (SSD) presents significant challenges for patients, including compromised sound localization, reduced speech recognition, and often, tinnitus. These issues are typically addressed using interventions such as cochlear implantation (CI) and bone conduction implant (BCI). However, evidence regarding the efficacy of BCI in reducing tinnitus in SSD patients remains limited. This study explored the ability of a novel active transcutaneous BCI (Bonebridge BCI602) to alleviate tinnitus in SSD patients. STUDY DESIGN: Prospective cohort multicenter study. SETTING: Tertiary referral hospitals. METHODS: A prospective multicenter study of 30 SSD patients was conducted. The patients were divided into two groups: those with (n = 19) and without (n = 11) tinnitus. Audiometric assessments, subjective questionnaires including the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Bern Benefit in Single-Sided Deafness (BBSS), and tinnitus evaluations with the Tinnitus Handicap Inventory (THI) and tinnitogram were conducted before and after BCI surgery. RESULTS: THI scores after surgery were significantly reduced in SSD patients with tinnitus. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups; however, the former group exhibited a significantly greater improvement in the APHAB questionnaire score. According to tinnitograms, the loudness of tinnitus decreased, particularly in patients with ipsilateral tinnitus. Patients with residual hearing had greater reductions in their THI scores. However, three patients without residual hearing had a relative worsening of tinnitus after surgery. CONCLUSION: The Bonebridge BCI602 effectively reduced tinnitus in SSD patients, particularly in those with residual hearing. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups. These findings demonstrate the therapeutic potential of BCI for managing SSD and associated tinnitus.

The Impact of Lateral Relaxing Incision on Middle Ear Function in Cleft Palate Repair.

Children with cleft palate are susceptible to otitis media with effusion. This study aimed to investigate the effect of lateral relaxing incision (RI) on middle ear function in cleft palate patients who underwent palatoplasty using double-opposing Z-plasty (DOZ). This is a retrospective study of patients who underwent bilateral ventilation tube insertion concurrently with DOZ, wherein RI was selectively performed on the right side of the palate (Rt-RI group) or not (No-RI group). The frequency of VTI, duration of the first ventilation tube retention, and hearing outcomes at the last follow-up were reviewed. Outcomes were compared using the χ 2 test and t test. A total of 126 treated ears from 63 non-syndromic children (18 male, 45 female) with cleft palate were reviewed. The mean age at surgery was 15.8±6.17 months. There were no significant differences in the frequency of ventilation tube insertion between the right and left ears within the Rt-RI group or between the Rt-RI and no-RI groups in the right ear. Subgroup analysis for ventilation tube retention time, auditory brainstem response thresholds, and air-conduction pure tone averages showed no significant differences. In the DOZ, the use of RI had no significant effects on middle ear outcomes during 3 years of follow-up. Relaxing incision seems to be safe without concern for middle ear function in children with cleft palate.

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.

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.

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.

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.

A molecular mechanism of nickel (II): reduction of nucleotide excision repair activity by structural and functional disruption of p53.

Nickel is a major carcinogen that is implicated in tumor development through occupational and environmental exposure. Although the exact molecular mechanisms of carcinogenesis by low-level nickel remain unclear, inhibition of DNA repair is frequently considered to be a critical mechanism of carcinogenesis. Here, we investigated whether low concentrations of nickel would affect p53-mediated DNA repair, especially nucleotide excision repair. Our results showed that nickel inhibited the promoter binding activity of p53 on the downstream gene GADD45A, as a result of the disturbance of p53 oligomerization by nickel. In addition, we demonstrated that nickel exposure trigger the reduction of GADD45A-mediated DNA repair by impairing the physical interactions between GADD45A and proliferating cell nuclear antigen or xeroderma pigmentosum G. Notably, in the GADD45A-knockdown system, the levels of unrepaired DNA photoproducts were higher than wild-type cells, elucidating the importance of GADD45A in the nickel-associated inhibition of DNA repair. These results imply that inhibition of p53-mediated DNA repair can be considered a potential carcinogenic mechanism of nickel at low concentrations.

Environmental cadmium exposure is associated with elevated risk of chronic otitis media in adults.

OBJECTIVES: Chronic otitis media (COM) is caused by an infection of the middle ear, although it may also be associated with environmental pollutants. Recent reports found that cadmium exposure could be toxic to middle ear cell lines, but the role of cadmium in the development of COM in humans has not been examined to date. We hypothesised that environmental cadmium exposure was associated with an increased risk of COM in the general population. METHODS: We analysed cross-sectional data for 5331 adults of 20 years of age or above, obtained from the Korea National Health and Nutrition Examination Survey 2010-2012. We examined the association between blood cadmium levels and COM diagnosed by an otolaryngologist. RESULTS: The highest quartile group of cadmium blood concentration was associated with an OR of 3.33 (95% CI 1.78 to 7.53) for COM, after adjusting for potential confounding factors. Doubling blood cadmium concentration resulted in an OR of 1.58 (95% CI 1.19 to 2.08) for COM. These associations were robust on sensitivity analyses after excluding current smokers and former smokers and after excluding subjects with a potential history of occupational exposure to cadmium. CONCLUSIONS: The results of our study suggest that environmental cadmium exposure is associated with increased risk of COM, and further studies are warranted to understand the pathogenetic mechanism by which COM is caused by cadmium exposure.

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.

Bacterial Species and Antibiotic Sensitivity in Korean Patients Diagnosed with Acute Otitis Media and Otitis Media with Effusion.

Changes over time in pathogens and their antibiotic sensitivity resulting from the recent overuse and misuse of antibiotics in otitis media (OM) have complicated treatment. This study evaluated changes over 5 years in principal pathogens and their antibiotic sensitivity in patients in Korea diagnosed with acute OM (AOM) and OM with effusion (OME). The study population consisted of 683 patients who visited the outpatient department of otorhinolaryngology in 7 tertiary hospitals in Korea between January 2010 and May 2015 and were diagnosed with acute AOM or OME. Aural discharge or middle ear fluid were collected from patients in the operating room or outpatient department and subjected to tests of bacterial identification and antibiotic sensitivity. The overall bacteria detection rate of AOM was 62.3% and OME was 40.9%. The most frequently isolated Gram-positive bacterial species was coagulase negative Staphylococcus aureus (CNS) followed by methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Streptococcus pneumonia (SP), whereas the most frequently isolated Gram-negative bacterium was Pseudomonas aeruginosa (PA). Regardless of OM subtype, ≥ 80% of CNS and MRSA strains were resistant to penicillin (PC) and tetracycline (TC); isolated MRSA strains showed low sensitivity to other antibiotics, with 100% resistant to PC, TC, cefoxitin (CFT), and erythromycin (EM); and isolated PA showed low sensitivity to quinolone antibiotics, including ciprofloxacin (CIP) and levofloxacin (LFX), and to aminoglycosides. Bacterial species and antibiotic sensitivity did not change significantly over 5 years. The rate of detection of MRSA was higher in OME than in previous studies. As bacterial predominance and antibiotic sensitivity could change over time, continuous and periodic surveillance is necessary in guiding appropriate antibacterial therapy.

Diesel exhaust particle-induced airway responses are augmented in obese rats.

Air pollutants and obesity are important factors that contribute to asthma. The aim of this study was to assess the airway responsiveness and inflammation in Otsuka-Long Evans Tokushima Fatty (OLETF) obese rats and Long Evans Tokushima-Otsuka (LETO) nonobese rats exposed to diesel exhaust particles (DEPs). Otsuka Long Evans Tokushima fatty rats and LETO rats were exposed intranasally to DEP and then challenged with aerosolized DEP on days 6 to 8. Body plethysmography, bronchoalveolar lavage (BAL), and histology were performed. Enhanced pause (Penh) was measured as an indicator of airway resistance on day 9 and samples were collected on day 10. After exposure to DEP, the OLETF group exhibited a greater increase in Penh compared to that in the LETO group. Moreover, the BAL fluid in mice showed an increase in the total and differential cell counts in the DEP-exposed OLETF group compared to that in the DEP-exposed LETO group. Histological assessment of lung tissue from each group revealed that the DEP-exposed OLETF group tended to have increased inflammatory cell infiltrations in the prebronchial area. Increased peroxisome proliferator-activated receptor γ, coactivator 1ß messenger RNA was observed in the lungs of obese rats compared to that in nonobese rats following DEP exposure. These data indicate that the DEP-exposed OLETF group had increased airway responses and inflammation compared to the DEP-exposed LETO group, indicating that diesel particulates and obesity may be co-contributors to asthma.

Transcutaneous auricular vagus nerve stimulation can modulate fronto-parietal brain networks.

Objective: Recent studies have shown that transcutaneous vagal nerve stimulation (tVNS) holds promise as a treatment for neurological or psychiatric disease through the ability to modulate neural activity in some brain regions without an invasive procedure. The objective of this study was to identify the neural correlates underlying the effects of tVNS. Methods: Twenty right-handed healthy subjects with normal hearing participated in this study. An auricle-applied tVNS device (Soricle, Neurive Co., Ltd., Gyeongsangnam-do, Republic of Korea) was used to administer tVNS stimulation. A session consisted of 14 blocks, including 7 blocks of tVNS stimulation or sham stimulation and 7 blocks of rest, and lasted approximately 7 min (1 block = 30 s). Functional magnetic resonance imaging (fMRI) was performed during the stimulation. Results: No activated regions were observed in the fMRI scans following both sham stimulation and tVNS after the first session. After the second session, tVNS activated two clusters of brain regions in the right frontal gyrus. A comparison of the activated regions after the second session of each stimulation revealed that the fMRI following tVNS exhibited four surviving clusters. Additionally, four clusters were activated in the overall stimulated area during both the first and second sessions. When comparing the fMRI results after each type of stimulation, the fMRI following tVNS showed four surviving clusters compared to the fMRI after sham stimulation. Conclusion: tVNS could stimulate some brain regions, including the fronto-parietal network. Stimulating these regions for treating neurological or psychiatric disease might require applying tVNS for at least 3.5 min.

Feasibility of Easy to Use and Inexpensive Three-Dimensional Printed Educational Model of Temporal Bone: Practiced Without Drilling.

OBJECTIVE: Three-dimensional (3D) printed temporal bone model draws great attention as a promising alternative for conventional cadaveric model in education of otologic surgery. However, its high price and requirement for specialized tools hinder widespread use. We devised a simple educational model based on lattice structure to overcome these problems and compared it with a commercial model. METHODS: We converted high-resolution temporal bone computed tomography images into stereolithography format, and printed it using the G005 3D printing system from CUBICON©. In this process, the part to be drilled out was made of lattice structure. We evaluated the model by a questionnaire prepared in advance, and compared the results with those of a commercial model. RESULTS: We created an educational 3D printed temporal bone lattice model one-tenth the cost of commercial temporal bone. Our model reproduced the important structures of the temporal bone, produced less dust, and had similar strength and grinding sensation compared to the commercial model. The surface texture and reproducibility were comparable to the commercial model. Although most of structures were remodeled more elaborately in the commercial model than our model, our model demonstrated significant potential as a cost-effective educational tool for medical students and residents. CONCLUSION: 3D printed temporal bone lattice model has potential for widespread use due to low cost and easy accessibility. Further improvements in the fine structures of the temporal bone are necessary to enhance its utility as an educational model.

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.

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.

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.

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.

Effect of diesel exhaust particles on RANK/RANKL expression in in vivo and in vitro models of middle ear inflammation.

OBJECTIVE: Increasing evidence suggests a link between middle ear inflammation and the development of diesel exhaust particles (DEPs). Chronic middle ear inflammation can lead to bone damage and remodeling. This study aimed to explore the impact of DEPs on the expression of interleukin (IL)-6 and RANKL under conditions of middle ear inflammation. METHODS: DEPs were collected by burning fuel in a diesel engine at the Gwangju Institute of Science and Technology. Human middle ear epithelial cells were cultured to 70-80% confluence in culture plates and then treated with DEPs at concentrations of 0, 5, 10, 20, 40, and 80 µg/mL for 24 h. Cell viability was assessed manually. B6.SJL mice, aged 9 weeks, were exposed to DEPs at a concentration of 200 µg/m3 for 1 h daily over a period of 28 days. The expression levels of IL-6, tumor necrosis factor α, RANKL, and RANK were evaluated using hematoxylin and eosin staining and western blot analysis of the harvested middle ear samples. RESULTS: The viability of human middle ear epithelial cells was found to decrease in a dose-dependent manner after 24 h. The mRNA expression level of IL-6 exhibited the most significant increase at the 48-h mark. In contrast, the mRNA expression levels of RANKL and RANK showed a marked increase as early as 6 h post-exposure, with both genes subsequently displaying a time-dependent decrease. Histological analysis revealed that the middle ear mucosa was thicker in the group exposed to DEPs compared to the control group. Additionally, the protein expression levels of IL-6 and RANKL were elevated in the DEP-exposed group relative to the normal control group. CONCLUSIONS: We confirmed the expression of osteoclast-related proteins in the mouse middle ear. These results imply that air pollutants might affect RANKL/RANK signaling, which is associated with bone remodeling.