PurposeTo evaluate adverse events (AEs) associated with teprotumumab in the reatment of thyroid eye disease (TED).MethodsReports involving teprotumumab were extracted from the U.S.FDA Adverse Event Reporting System (FAERS) from the first quarter of 2020 to the first quarter of 2025. After data standardization, disproportionality analyses were performed using multiple signal detection algorithms, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM).ResultsA total of 1,357 reports were identified. Detected signals at the system organ class (SOC) level included ear and labyrinth disorders, eye disorders, social circumstances and reproductive system and breast disorders. A total of 143 Preferred Terms (PTs) met the criteria of four algorithms. Among these, signals within the "Ear and labyrinth disorders" SOC were predominant (n = 598). Tinnitus was the most frequently reported PT (n = 146). The highest disproportionality signals, based on ROR values, were observed for permanent deafness (ROR 10,021.8; 95% CI 5,544.31-18,115.24), autophony (ROR 3,282.12; 95% CI 1,333.19-8,080.12), and patulous eustachian tube (ROR 1,401.68;95% CI 499.54-3,932.99).ConclusionThese findings provide important real-world safety evidence and may support safer clinical use of teprotumumab.

Auditory hypersensitivity, or hyperacusis, is characterized by increased sensitivity to sound and is often associated with tinnitus, yet its underlying mechanisms remain unclear. This study investigated the mechanisms of sodium salicylate-induced auditory hypersensitivity in mice, focusing on neuroinflammation, microglial activation, and neuronal excitability. Male C57BL/6 mice were used to establish the model, and auditory sensitivity was evaluated by behavioral testing. Inflammatory cytokines, excitatory receptor expression, and microglial activation in the auditory cortex were assessed using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence. Sodium salicylate treatment increased auditory sensitivity and was accompanied by elevated pro-inflammatory cytokines, enhanced microglial activation, and upregulation of excitatory receptor subunits. Pharmacological inhibition of microglial activation with minocycline attenuated these changes and improved auditory sensitivity. In addition, modulation of γ-aminobutyric acid (GABA)-mediated inhibitory signaling reduced inflammation, normalized excitatory receptor expression, and alleviated hypersensitivity. These findings suggest that sodium salicylate-induced auditory hypersensitivity involves an interaction between neuroinflammation and neuronal hyperexcitability, and that targeting microglial activation and restoring inhibitory neurotransmission may provide potential therapeutic strategies for hyperacusis and related auditory disorders.

ImportanceTinnitus, affecting 10% to 15% of the global population, is a debilitating condition often linked to hearing loss and neurological disorders. While air pollution is a known risk factor for respiratory and cardiovascular diseases, its association with tinnitus remains underexplored.ObjectiveThis study investigates the association between air pollution, polygenic risk score (PRS), and tinnitus prevalence.DesignCross-sectional analysis.SettingUK Biobank (UKB) population-based cohort.ParticipantsSeventy-nine thousand two hundred seventy-seven individuals from the UKB with available tinnitus, air pollution, and genetic data.ExposuresAir pollution measures (PM2.5, PM2.5-10, PM10, NO2, and NOx). A composite air pollution score was calculated, and PRS was derived from 6 tinnitus-associated single-nucleotide polymorphisms.Main outcome measuresPrevalence, frequency, and severity of tinnitus. Logistic regression models were used, adjusting for sociodemographic, health, and hearing-related covariates.ResultsEach interquartile range increase in air pollution score was associated with higher odds of current tinnitus (OR = 1.06, 95% CI: 1.03-1.08, P < .001), particularly transient tinnitus (OR = 1.04, P = .008). PRS was independently associated with prevalent tinnitus (P < .001), and higher OR were observed among individuals with both high air pollution exposure and high PRS (OR = 1.34, 95% CI: 1.18-1.52, P < .001). Individual pollutants showed weaker associations.ConclusionA joint association of air pollution exposure and genetic susceptibility with tinnitus prevalence was observed in this cross-sectional analysis, highlighting the importance of integrated environmental and genetic assessments in auditory health.RelevanceOur findings emphasize the potential value of integrating environmental and genetic factors for risk stratification of tinnitus in populations.

ImportanceEvidence regarding the mechanism of tinnitus in patients with normal full-frequency hearing remains limited. This study investigated the auditory brainstem response (ABR) waveform patterns in these patients to address this unmet need, which is of considerable assistance in the clinical management of tinnitus with normal hearing.ObjectiveThis study aims to investigate the potential underlying mechanisms of tinnitus with normal full-frequency (125 Hz-16 kHz) hearing threshold by analyzing waveform alterations in ABR among tinnitus patients.DesignCross-sectional study.SettingOtolaryngology outpatient of a tertiary referral hospital.ParticipantsPatients aged 20 to 40 years with unilateral subjective tinnitus and normal hearing (pure-tone thresholds ≤25 dB HL across 0.125-16 kHz) were recruited. Age-matched healthy volunteers with normal full-frequency hearing (0.125-16 kHz) and without tinnitus served as controls.ExposuresParticipants were categorized according to the presence of unilateral subjective tinnitus.Main Outcome MeasuresThe primary outcomes included pure-tone audiometry testing (0.125-16 kHz) and ABR testing using 80 dB nHL click stimuli with alternating polarity (19.9 Hz, 1024 scans).ResultsThe study included 136 adult subjects with normal hearing at all frequencies, including 60 unilateral tinnitus patients and 76 normal volunteers. Results showed no significant differences in ABR waveform characteristics between affected and unaffected ears in unilateral tinnitus patients ((P > .05). However, compared with normal volunteers, unilateral tinnitus patients exhibited significantly prolonged latencies of waves I, III, and V on the tinnitus side (all P < .05), with median differences (95% CI) of 0.08 (0.04-0.11), 0.07 (0.00-0.12), and 0.15 (0.09-0.20), respectively. In addition, the interpeak latency between waves III and V was also prolonged, with a median difference of 0.08 (95% CI: 0.03-0.13).ConclusionTinnitus patients with normal full-frequency hearing exhibit differences in the ABR waves, which may be associated with abnormal middle ear muscle activity. Emotional responses may trigger abnormal middle ear muscle activity via the serotonin system, which in turn affects auditory signal transmission through the trigeminal system, leading to tinnitus and abnormal ABR wave patterns.RelevanceFuture research will focus on the middle ear muscles as a potential breakthrough point, exploring the relationship between abnormal electrical activity in these muscles and tinnitus, as well as the electrical activity of the trigeminal nerve nuclei.Level of Evidence3.

Glomeruli are signal-processing units of the olfactory bulb (OB) that play a key role in many OB computations, including contrast enhancement, gain control, and odorant-selective habituation. In awake mice, we unveil an extremely stable, inhomogeneous map of basal glomerulus-specific activity that serves as the background against which olfactory signal processing occurs. This activity is strongly driven by centrifugal cholinergic inputs; endogenous and airflow-evoked spiking of olfactory sensory neurons; and, to a minor extent, by the odor environment. Moreover, it is brain-state dependent and suppressed under various forms of anesthesia, and is therefore likely attenuated during sleep. These results reveal an important layer in the OB signal-processing network, likely increasing the system's variance and dynamic range via glomerulus-specific functional inhomogeneity.

Reliable drug delivery to the inner ear is still an unmet clinical need, due to the blood cochlear barrier, which effectively protects this highly sensitive organ. To overcome this hurdle, miniaturized, biodegradable implants were prepared (0.3 mm in diameter), which can be administered into the cochlea via a tiny hole drilled into the round window. They were based on poly(lactic-co-glycolic acid) (PLGA) and prepared by hot melt extrusion. Three drugs were incorporated: (i) 20.0% dexamethasone with anti-inflammatory, anti-fibrotic and protective activity for hair cells (being critical for hearing); (ii) 5.7% lidocaine (free base) as local anesthetic drug and therapeutic potential to treat tinnitus or vertigo; and (iii) 2.1% curcuminoids for their anti-inflammatory and anti-oxidant activities. The implants were thoroughly characterized before and after exposure to artificial perilymph in vitro, by DSC, X-ray diffraction, GPC, optical microscopy, TGA and release measurements. In addition, they were implanted into gerbil cochlea, monitoring the resulting local drug concentrations. Importantly, the implants allowed for the simultaneous controlled release of all drugs. In vitro, lidocaine release was fastest (100% after 10 d), followed by dexamethasone (100% after 10 weeks). The slower release of dexamethasone can be explained by saturation effects within the implant. In vivo, drug release was faster, probably because of accelerated polymer degradation due to local drops in pH and/or the presence of esterases (e.g., 100% dexamethasone release in 2 weeks). Curcuminoids were not detectable in the release medium under the given conditions in vitro, nor in the perilymph in vivo, because of their very limited solubility in aqueous media. Visual observation suggests that they were released within 1-2 weeks in vivo (likely partitioning into lipid phases and/or being metabolized). No noteworthy changes in the animals' behavior or signs for tissue inflammation/damage were detected.