Search Results (764)

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Background/Objectives: Despite its significant impact on learning, classroom acoustics and students’ hearing difficulties are often overlooked compared with more visible issues like lighting. Hearing loss—frequently underestimated and invisible—affects both students and teachers, potentially leading to fatigue, reduced participation, and academic challenges. The A.BA.CO. project in Italy was developed to address these issues by promoting improved classroom design, technological solutions, and better auditory communication accessibility in schools. Objective: This article presents the A.BA.CO. project, offering context and an overview of the preliminary analyses conducted by its multidisciplinary team. The goal is to share insights and propose organizational frameworks, technical solutions, and best practices concerning the hearing, communication, and auditory learning challenges experienced by students with hearing impairments. Results: The A.BA.CO. team’s analyses identified key barriers to inclusion for students with (or without) hearing impairments, such as poor classroom acoustics, excessive noise, and suboptimal seating arrangements. The project underscores the importance of improved acoustic environments and the integration of assistive technologies, including speech-to-text systems. The findings highlight the need for interdisciplinary collaboration to design accessible and inclusive educational settings for all learners. Conclusions: Embedding educational audiology within school systems—alongside enhancements in classroom acoustics and the use of assistive technologies and other technological solutions—is essential to ensure that all students, regardless of hearing ability, have equitable access to learning and full participation in educational life. Full article

Pathogenic variants in the MAP1B gene have been associated with neurological impairment, including intellectual disability, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, brain malformations, cognitive hearing loss, short stature, and dysmorphic features. However, few cases with detailed clinical characterization have been reported. We describe a 12-year-old boy carrying a loss-of-function MAP1B variant, presenting with severe elimination disorders despite normal intelligence. He was referred to the genetics service due to persistent elimination issues, including daytime urinary incontinence, nocturnal enuresis, and fecal incontinence. He had normal motor and cognitive development, with an IQ of 99; however, he also presented with ADHD, short stature, microcephaly, and myopia. Brain MRI revealed bilaterial subependymal periventricular nodular heterotopia (PVNH). Audiometry showed normal bilateral hearing. Testing fragile X syndrome (FXS) and karyotype analyses yielded normal results. Whole exome sequencing (WES) revealed a nonsense pathogenic variant in MAP1B (c.895 C>T; p.Arg299*). No other family members showed a similar phenotype; however, a great-uncle and a great-aunt had a history of nocturnal enuresis until age 10. The patient’s deceased mother had short stature and psychiatric disorders, and a history of consanguinity was reported on the maternal side. This case broadens the phenotypic spectrum associated with MAP1B syndrome, suggesting that elimination disorder, frequently reported in FXS, should also be evaluated in MAP1B pathogenic variant carriers. In addition, the presence of short stature also appears to be part of the syndrome. Full article

Background/Objectives: Cochlear implants (CIs) and hearing aids (HAs) have enhanced auditory rehabilitation in elderly individuals, yet limitations in musical perception and psychosocial integration persist. This systematic review aimed to evaluate the effects of music therapy (MT) on the quality of life (QoL), self-esteem, auditory perception, and cognition in older CI and HA users. Methods: A comprehensive search of PubMed was conducted up to March 2022 following PRISMA guidelines. Studies involving participants aged ≥ 60 years with CIs and/or HAs were included. Ten studies (n = 21,632) met eligibility criteria. Data were extracted and assessed using the Newcastle–Ottawa Scale. Results: MT led to improved sound quality, with HISQUI19 scores rising from 60.0 ± 21.8 to 74.2 ± 27.5. Early MT exposure was associated with significantly better MUMU outcomes (p = 0.02). Bilateral CI users showed enhanced stereo detection (52% to 86%), and CI + HA users achieved CNC scores exceeding 95%. Postlingual CI users outperformed prelingual peers in musical discrimination (9.81 vs. 3.48; p < 0.001). Long-term HA use was linked to better a QoL and reduced loneliness. Conclusions: While music therapy appears to support auditory and psychosocial functioning in hearing-impaired older adults, the absence of randomized controlled trials limits causal inference regarding its effects. These results support its integration into hearing rehabilitation strategies for older adults. Full article

Lip-reading, i.e., the ability to recognize speech using only visual cues, plays a fundamental role in audio-visual speech processing, intelligibility, and comprehension. This capacity is integral to language development and functioning; it emerges in early development, and it slowly evolves. By linking psycholinguistics, psychophysics, and neurophysiology, the present narrative review explores the development and significance of lip-reading across different stages of life, highlighting its role in human communication in both typical and atypical development, e.g., in the presence of hearing or language impairments. We examined how relying on lip-reading becomes crucial when communication occurs in noisy environments and, on the contrary, the impacts that visual barriers can have on speech perception. Finally, this review highlights individual differences and the role of cultural and social contexts for a better understanding of the visual counterpart of speech. Full article

Background: Riboflavin transporter deficiency type 2 is an ultra-rare, yet treatable, inborn error of metabolism. This autosomal recessive disorder is caused by pathogenic mutations in the SLC52A2 gene leading to progressive ataxia, polyneuropathy, and hearing and visual impairment. The early initiation of riboflavin therapy can prevent or mitigate the complications. To date, only 200 cases have been reported, mostly in consanguineous populations. The p.Gly306Arg founder mutation, identified in patients of Lebanese descent, is the most frequently reported worldwide. It was described in a homozygous state in a total of 21 patients. Therefore, studies characterizing the phenotypic spectrum of this mutation remain scarce. Methods: A retrospective review of charts of patients diagnosed with riboflavin transporter deficiency type 2 at a tertiary-care reference center in Lebanon was performed. Clinical, biochemical, and molecular profiles were analyzed and compared to reported cases in the literature. Results: A total of six patients from three unrelated families were diagnosed between 2018 and 2023. All patients exhibited the homozygous founder mutation, p.Gly306Arg, with variable phenotypes, even among family members. The median age of onset was 3 years. Diagnosis was achieved by exome sequencing at a median age of 5 years, as clinical and biochemical profiles were inconsistently suggestive. The response to riboflavin was variable. One patient treated with high-dose riboflavin recovered his motor function, while the others were stabilized. Conclusions: This study expands the current knowledge of the phenotypic spectrum associated with the p.Gly306Arg mutation in the SLC52A2 gene. Increased awareness among physicians of the common manifestations of this rare disorder is crucial for early diagnosis and treatment. In the absence of a consistent clinical or biochemical phenotype, the use of next-generation sequencing as a first-tier diagnostic test may be considered. Full article

Transmembrane protein 43 (TMEM43 or LUMA) encodes a highly conserved protein found in the nuclear and endoplasmic reticulum membranes of many cell types and the intercalated discs and adherens junctions of cardiac myocytes. TMEM43 is involved in facilitating intra/extracellular signal transduction to the nucleus via the linker of the nucleoskeleton and cytoskeleton complex. Genetic mutations may result in reduced TMEM43 expression and altered TMEM43 protein cellular localization, resulting in impaired cell polarization, intracellular force transmission, and cell–cell connections. The p.S358L mutation causes arrhythmogenic right ventricular cardiomyopathy type-5 and is associated with increased absorption of lipids, fatty acids, and cholesterol in the mouse small intestine, which may promote fibro-fatty replacement of cardiac myocytes. Mutations (p.E85K and p.I91V) have been identified in patients with Emery–Dreifuss Muscular Dystrophy-related myopathies. Other mutations also lead to auditory neuropathy spectrum disorder-associated hearing loss and have a negative association with cancer progression and tumor cell survival. This review explores the pathogenesis of TMEM43 mutation-associated diseases in humans, highlighting animal and in vitro studies that describe the molecular details of disease processes and clinical, histologic, and molecular manifestations. Additionally, we discuss TMEM43 expression-related conditions and how each disease may progress to severe and life-threatening states. Full article

Objectives: Observational studies have shown that chronic obstructive pulmonary disease (COPD) is associated with an increased risk of hearing impairment. However, causality remains unclear, including with respect to lung function. This study aimed to investigate the associations of lung function and COPD with hearing impairment in the UK Biobank and confirm potential causalities using Mendelian randomization (MR). Methods: Cross-sectional analyses were performed using logistic regression models in a subsample of the UK Biobank. Two-sample MR analyses were performed on summary statistics for forced expiratory volume in one second (FEV1), forced vital capacity (FVC), COPD, and sensorineural hearing loss. Results: FEV1 and FVC were negatively associated with hearing impairment, with odds ratios (95% confidence intervals) of 0.80 (0.77, 0.84) and 0.80 (0.76, 0.83), respectively. COPD was positively associated with hearing impairment, with an odds ratio (95% confidence interval) of 1.10 (1.02, 1.18). In the MR analyses, a negative association was found between FVC and sensorineural hearing loss, with an odds ratio (95% confidence interval) of 0.91 (0.83, 0.99). For FVE1 and COPD, no significant associations were found. Conclusions: The results of this study showed that FVC was causally associated with hearing impairment, suggesting a potential protective effect of FVC on hearing impairment. Full article

The assessment of hearing in children is important, as hearing deficits can impair child development. The Auditory Steady-State Response (ASSR) is an electrophysiological technique that is able to simultaneously evaluate both ears at four frequencies, making it advantageous for testing children where the test time needs to be as short as possible. The objective of this work was to perform a literature review on the effectiveness of ASSR to gauge hearing thresholds in babies, infants, and children, examining its ability to distinguish mild hearing loss from normal cases. This review used PubMed, Web of Science, and Scopus databases from 2014 to 2024. A total of 1226 articles were identified, although only 16 met the previously established inclusion criteria. It was found that ASSR is a reliable diagnostic tool for babies, infants, and children. Recent work appears better able to distinguish mild hearing loss from normal hearing. One unresolved aspect that needs additional attention is the effectiveness of using bone-conducted stimuli. Full article

Background/Objectives: Menière’s disease (MD) is a debilitating disorder with episodic and variable ear symptoms. Diagnosis can be challenging, and evidence for therapeutic approaches is low. Furthermore, patients show a unique and fluctuating configuration of audiovestibular impairment. As a psychometric instrument to assess hearing-specific disability is currently lacking, we evaluated a short form of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) in a cohort of patients with MD. Methods: Data was collected in the context of a multicenter prospective patient registry intended for the long-term follow up of MD patients. Hearing was assessed by pure tone and speech audiometry. The SSQ was applied in the German language version with 17 items. Results: In total, 97 consecutive patients with unilateral MD with a mean age of 56.2 ± 5.0 years were included. A total of 55 individuals (57.3%) were female, and 72 (75.0%) were categorized as having definite MD. The average total score of the SSQ was 6.0 ± 2.1. Cronbach’s alpha for internal consistency was 0.960 for the total score. We did not observe undue floor or ceiling effects. SSQ values showed a statistically negative correlation with hearing thresholds and a statistically positive correlation with speech recognition scores of affected ears. Conclusions: The short form of the SSQ provides insight into hearing-specific disability in patients with MD. Therefore, it may be informative regarding disease stage and rehabilitation needs. Full article

This study analyzes the current state and developmental characteristics of phonological awareness in hearing-impaired preschool children with cochlear implants aged 3 to 5 years in China. The phonological awareness development of hearing-impaired preschool children is assessed via a comparison with normal-hearing preschool children of the same age, utilizing a number of key metrics and statistical analyses to determine any differences in the developmental characteristics between the two groups. The results show that the phonological awareness development of Chinese-speaking hearing-impaired preschool children with cochlear implants follows, for the most part, the progression of their normal-hearing preschool counterparts, albeit at a lower level. Identifying phonological awareness profiles in children with cochlear implants helps improve the accuracy of assessment and supports the development of targeted intervention strategies. This study aims to provide a clearer understanding of their phonological processing abilities. Full article

Background: Elucidating the mechanisms underlying cisplatin-induced ototoxicity is critical for the clinical management of hearing loss. While cisplatin is known to penetrate the inner ear via the blood-labyrinth barrier in the stria vascularis, its precise damaging effects on marginal cells (MCs) and subsequent hearing impairment remain incompletely understood. Pyroptosis, a gasdermin-mediated inflammatory cell death pathway, may play a key role. This study investigated the involvement of gasdermin E (GSDME)-dependent pyroptosis in cisplatin-induced injury to MCs. Methods: An in vitro cisplatin-induced pyroptosis model was established in MCs. GSDME expression was downregulated using small interfering RNA (siRNA), and caspase-3 activity was inhibited pharmacologically. The critical threshold for pyroptosis induction was determined to be 5 μmol/L cisplatin exposure for 24 h, which activated the caspase-3/GSDME signaling pathway. Results: Cisplatin treatment upregulated GSDME and caspase-3 expression in MCs. Both inhibition of GSDME and pharmacological blockade of caspase-3 significantly attenuated cisplatin-induced cellular damage. Notably, caspase-3 suppression reduced GSDME expression, suggesting a positive regulatory relationship between these mediators. Conclusions: GSDME-mediated pyroptosis plays a pivotal role in cisplatin-induced marginal cell injury, with caspase-3 acting as an upstream regulator of GSDME expression. These findings provide a mechanistic foundation for developing novel therapeutic strategies against cisplatin ototoxicity. Full article

Platinum-induced ototoxicity constitutes a significant adverse effect in pediatric oncology, frequently resulting in permanent hearing impairment with profound implications for quality of life, language acquisition, and scholastic performance. This comprehensive review critically evaluates contemporary ototoxicity monitoring practices across various pediatric oncology settings, analyzes current guideline recommendations, and formulates strategies for implementing standardized surveillance protocols. Through examination of recent literature—encompassing retrospective cohort investigations, international consensus recommendations, and functional outcome assessments—we present an integrated analysis of challenges and opportunities in managing chemotherapy-associated hearing loss among childhood cancer survivors. Our findings demonstrate marked heterogeneity in monitoring methodologies, substantial implementation obstacles, and considerable impact on survivors’ functional status across multiple domains. Particularly concerning is the persistent absence of an evidence-based consensus regarding the appropriate duration of audiological surveillance for this vulnerable population. We propose a structured framework for comprehensive ototoxicity management emphasizing prompt detection, standardized assessment techniques, and integrated long-term follow-up care to minimize the developmental consequences of platinum-induced hearing impairment. This approach addresses critical gaps in current practice while acknowledging resource limitations across diverse healthcare environments. Full article

Background/Objectives: Tonal thresholds, typically assessed through pure-tone audiometry (PTA), are central to the audiological evaluation of Ménière’s disease (MD). However, they fail to capture the complexity of real-life speech perception. This study aimed to characterize the relationship between PTA and speech recognition performance in unilateral MD and to determine whether a measurable dissociation exists between hearing sensitivity and verbal processing. We also evaluated frequency-specific audiometric patterns and potential threshold cut-off values associated with speech recognition decline. Methods: A total of 254 ears from 127 patients were included in the study across three groups: the Ménière group (affected and unaffected ears, n = 64 each) and the control group (n = 63). The pure-tone thresholds, speech recognition threshold (SRT), and the maximum word recognition scores (Rmax) were assessed in all participants. Results: Although the Ménière affected and control groups showed comparable pure-tone average (PTA) values (46.33 vs. 38.13 dB, p = 0.439), the affected group demonstrated significantly poorer speech performance (Rmax: 76.25% vs. 87.49%, p < 0.001; SRT: 50.64 vs. 38.45 dB, p = 0.009). The Ménière unaffected group exhibited near-ceiling performance (Rmax: 99.38%, SRT: 18.33 dB) and a mean PTA of 19.59 dB. A strong correlation between PTA and SRT was observed only in the Ménière affected group (r = 0.942, p < 0.001), whereas correlations were moderate in the unaffected (r = 0.671, p < 0.001) and control (r = 0.728, p < 0.001) groups. The ROC analysis revealed that PTA predicted impaired speech recognition with high accuracy in unaffected (AUC = 0.956, p < 0.001) and control (AUC = 0.829, p < 0.001) ears but far less so in affected ears (AUC = 0.784; all p < 0.001), confirming a functional tonal–verbal dissociation in MD. Conclusions: This study demonstrates a functional audiometric dissociation in unilateral Ménière’s disease. Affected ears show poorer speech recognition and require higher intensities despite similar PTA values. The predictive link between thresholds and verbal performance is disrupted. These findings support the need for combined tonal and speech-based assessment in clinical practice. Full article

Implementing neonatal hearing screening has significantly reduced the age at which hearing impairments are detected in children. Nevertheless, objective electrophysiological assessments, such as auditory brainstem response (ABR) or auditory steady-state response (ASSR) testing, are often necessary for children older than six months. These evaluations should be conducted while the child is asleep to obtain accurate and interpretable results, as movement and muscle activity can introduce artifacts that compromise the quality of the recordings. In this narrative review, we evaluate sedation strategies in paediatric procedures, focusing on the efficacy, safety, and practicality of agents/routes for inducing sleep during ABR/ASSR testing. Sedation choices should prioritise patient safety, clinical context, and result reliability and be tailored to the individual’s age, health status, and procedural needs. Full article