Actinomycetoma in a patient with pre-existing sensorineural hearing loss: a linezolid-based treatment paradigm.

Mycetoma is a chronic granulomatous infectious disease with a triad of subcutaneous swelling, discharging sinuses and the presence of granules. The infection may occur following minor trauma or penetrating thorn injury. We report a case of a man in his 40s with a history of thorn prick 9 years ago, followed by the formation of painless discharging sinuses on the right foot for the past 2 years. Clinical, local epidemiological, histopathological examination and Gram stain confirmed the diagnosis of actinomycetoma. Prior to initiating the Welsh regimen, a pretreatment assessment of the patient's auditory function was conducted through pure tone audiometry, indicating the existence of pre-existing high-frequency bilateral sensorineural hearing loss. The patient was treated with linezolid as an alternative to amikacin, at a dosage of 600 mg two times per day, leading to complete resolution within 3 weeks. This underscores linezolid's efficacy as a safe and cost-effective alternative for actinomycetoma, without causing ototoxic side effects.

Management of oral manifestations of a child with Heimler Syndrome-2.

Heimler Syndrome 2 (HS-2) is a rare, autosomal recessive mild form of a peroxisomal biogenesis disorder. Though knowledge regarding the disorder is limited, emerging research has found that sensorineural hearing loss, occasional or late onset pigmentation, amelogenesis imperfecta and nail abnormalities are clinical characteristics representative of HS-2.A school-aged male presented to the dental department with a chief complaint of a lack of enamel on multiple teeth. The patient's medical history was significant for patent ductus arteriosus, bilateral sensorineural hearing loss and biallelic mutation of the PEX6 gene. The clinical exam revealed dental crowding, hypoplasia, hypo-calcification of multiple teeth and enlarged pulp chambers of maxillary molars. This case report details the clinical findings associated with HS-2, the comprehensive dental treatment to be rendered to the patient, and critical information to paediatric dentists and general dentists so that they can make proper referrals to medical specialties.

Unraveling the genetic collagen connection: clinical and therapeutic insights on genetic connective tissue disorders.

Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular matrix through interference in the synthesis, development, or secretion of collagen and/or its associated proteins. The clinical phenotype includes multiple signs and symptoms, usually nonspecific but of interest to rheumatologists because of musculoskeletal involvement. The patient´s journey to diagnosis is long, and physicians should include these disorders in their differential diagnoses of diseases with systemic involvement. In this review, insights for the diagnosis and treatment of osteogenesis imperfecta, hypermobility spectrum disorder/Ehlers-Danlos syndrome, Marfan, Loeys-Dietz, and Stickler syndromes are presented.

[Clinical features of congenitally enlarged bony portion of Eustachian tube].

Objective:To investigate the clinical features of patients with congenitally enlarged bony portions of the Eustachian tube（ET）. Methods:The medical history, physical examination, hearing test, temporal bone high resolution computed tomography（HRCT） of six patients（nine ears） with congenitally enlarged bony portion of the ET were retrospectively analyzed. Results:Four patients were men and two were women. The minimum, maximum, and average ages were 5, 21, and（14.7±6.4） years, respectively. Three malformations were bilateral and three were left-sided. Three ears had conductive hearing loss（average bone and air conduction thresholds were 13.7 dB and 71.3 dB）, three had mixed hearing loss（average bone and air conduction thresholds were 27.7 dB and 83.7 dB）, and one had extremely severe sensorineural hearing loss. The average maximum length and width of the enlarged bony ET on temporal bone HRCT were（22.61±2.94） mm and（6.50±2.33） mm, respectively. The enlargement was combined with an external auditory canal malformation in six ears, narrow tympanic cavity in six, tympanic antrum malformation in five, ossicular chain malformation in seven, cochlear malformation in six, helicotrema malformation in three, vestibule widening in two, semicircular canal malformation in three, vestibular window malformation in six, facial nerve abnormality in five, internal auditory meatus malformation in two, low middle cranial fossa in eight, and severe internal carotid artery malformation in one. Conclusion:Bony ET enlargement is a rare congenital middle ear malformation which could combined with other ear malformations. Patients can have no ET dysfunction but different patterns of hearing loss. The defect is usually found unintentionally during imaging, and the HRCT of temporal bone is significant.

[Research progress in targeted delivery of inner ear using nanocarriers].

Various inner ear diseases such as sensorineural deafness and Meniere's disease bring about problems such as speech communication disorders and decreased work efficiency, which seriously affect the life quality of patients. Due to the special anatomical structure and blood-labyrinth barrier in the inner ear, the current drug administration methods are often unable to achieve satisfactory results. Nanocarriers are the forefront and hot spot of nanotechnology research. In recent years, a lot of research progress has been made in the field of targeted delivery of the inner ear, which is expected to be eventually applied to the treatment of clinical diseases of the inner ear. This review focuses on the advantages, main research achievements and limitations of various nanocarriers in the targeted delivery of the inner ear, hoping to provide new ideas for related research.

Socioeconomic and ethnic disparities associated with access to cochlear implantation for severe-to-profound hearing loss: A multicentre observational study of UK adults.

BACKGROUND: Patients with severe-to-profound hearing loss may benefit from management with cochlear implants. These patients need a referral to a cochlear implant team for further assessment and possible surgery. The referral pathway may result in varied access to hearing healthcare. This study aimed to explore referral patterns and whether there were any socioeconomic or ethnic associations with the likelihood of referral. The primary outcome was to determine factors influencing referral for implant assessment. The secondary outcome was to identify factors impacting whether healthcare professionals had discussed the option of referral. METHODS AND FINDINGS: A multicentre multidisciplinary observational study was conducted in secondary care Otolaryngology and Audiology units in Great Britain. Adults fulfilling NICE (2019) audiometric criteria for implant assessment were identified over a 6-month period between 1 July and 31 December 2021. Patient- and site-specific characteristics were extracted. Multivariable binary logistic regression was employed to compare a range of factors influencing the likelihood of implant discussion and referral including patient-specific (demographics, past medical history, and degree of hearing loss) and site-specific factors (cochlear implant champion and whether the hospital performed implants). Hospitals across all 4 devolved nations of the UK were invited to participate, with data submitted from 36 urban hospitals across England, Scotland, and Wales. Nine hospitals (25%) conducted cochlear implant assessments. The majority of patients lived in England (n = 5,587, 86.2%); the rest lived in Wales (n = 419, 6.5%) and Scotland (n = 233, 3.6%). The mean patient age was 72 ± 19 years (mean ± standard deviation); 54% were male, and 75·3% of participants were white, 6·3% were Asian, 1·5% were black, 0·05% were mixed, and 4·6% were self-defined as a different ethnicity. Of 6,482 submitted patients meeting pure tone audiometric thresholds for cochlear implantation, 311 already had a cochlear implant. Of the remaining 6,171, 35.7% were informed they were eligible for an implant, but only 9.7% were referred for assessment. When adjusted for site- and patient-specific factors, stand-out findings included that adults were less likely to be referred if they lived in more deprived area decile within Indices of Multiple Deprivation (4th (odds ratio (OR): 2·19; 95% confidence interval (CI): [1·31, 3·66]; p = 0·002), 5th (2·02; [1·21, 3·38]; p = 0·05), 6th (2·32; [1·41, 3·83]; p = 0.05), and 8th (2·07; [1·25, 3·42]; p = 0·004)), lived in London (0·40; [0·29, 0·57]; p < 0·001), were male (females 1·52; [1·27, 1·81]; p < 0·001), or were older (0·97; [0·96, 0·97]; p < 0·001). They were less likely to be informed of their potential eligibility if they lived in more deprived areas (4th (1·99; [1·49, 2·66]; p < 0·001), 5th (1·75; [1·31, 2·33], p < 0·001), 6th (1·85; [1·39, 2·45]; p < 0·001), 7th (1·66; [1·25, 2·21]; p < 0·001), and 8th (1·74; [1·31, 2·31]; p < 0·001) deciles), the North of England or London (North 0·74; [0·62, 0·89]; p = 0·001; London 0·44; [0·35, 0·56]; p < 0·001), were of Asian or black ethnic backgrounds compared to white patients (Asian 0·58; [0·43, 0·79]; p < 0·001; black 0·56; [0·34, 0·92]; p = 0·021), were male (females 1·46; [1·31, 1·62]; p < 0·001), or were older (0·98; [0·98, 0·98]; p < 0·001). The study methodology was limited by its observational nature, reliance on accurate documentation of the referring service, and potential underrepresentation of certain demographic groups. CONCLUSIONS: The majority of adults meeting pure tone audiometric threshold criteria for cochlear implantation are currently not appropriately referred for assessment. There is scope to target underrepresented patient groups to improve referral rates. Future research should engage stakeholders to explore the reasons behind the disparities. Implementing straightforward measures, such as educational initiatives and automated pop-up tools for immediate identification, can help streamline the referral process.

A single dose of AC102 restores hearing in a guinea pig model of noise-induced hearing loss to almost prenoise levels.

Although sudden sensorineural hearing loss (SSNHL) is a serious condition, there are currently no approved drugs for its treatment. Nevertheless, there is a growing understanding that the cochlear pathologies that underlie SSNHL include apoptotic death of sensory outer hair cells (OHCs) as well as loss of ribbon synapses connecting sensory inner hair cells (IHCs) and neurites of the auditory nerve, designated synaptopathy. Noise-induced hearing loss (NIHL) is a common subtype of SSNHL and is widely used to model hearing loss preclinically. Here, we demonstrate that a single interventive application of a small pyridoindole molecule (AC102) into the middle ear restored auditory function almost to prenoise levels in a guinea pig model of NIHL. AC102 prevented noise-triggered loss of OHCs and reduced IHC synaptopathy suggesting a role of AC102 in reconnecting auditory neurons to their sensory target cells. Notably, AC102 exerted its therapeutic properties over a wide frequency range. Such strong improvements in hearing have not previously been demonstrated for other therapeutic agents. In vitro experiments of a neuronal damage model revealed that AC102 protected cells from apoptosis and promoted neurite growth. These effects may be explained by increased production of adenosine triphosphate, indicating improved mitochondrial function, and reduced levels of reactive-oxygen species which prevents the apoptotic processes responsible for OHC death. This action profile of AC102 might be causal for the observed hearing recovery in in vivo models.

Remote or in-clinic? The effect of service delivery mode on hearing aid output: study protocol for a double-blinded, randomised trial in adults with mild to moderate sensorineural hearing loss.

BACKGROUND: Teleaudiology can potentially improve access to hearing healthcare services. Remote hearing aid fittings offer a new mode of service delivery that removes barriers of geography and access to an audiologist. Real-ear measurements (REMs) are the gold standard for hearing aid output verification but require in-clinic appointments. This study will investigate whether remote hearing aid fittings can provide clinically equivalent outcomes when compared to current, in-clinic, best practice guidelines. RESEARCH DESIGN: A repeated measure, double-blinded crossover design will be used. Participants will be randomly allocated to one of two groups to determine order of intervention, balanced for degree of hearing loss. STUDY SAMPLE: Sixty adults with mild to moderate hearing loss and at least 1 year of experience with hearing aids will be recruited. DATA COLLECTION AND ANALYSIS: Participants will complete two hearing aid fitting protocols, one using an in-clinic fitting process and the other using a remote (at-home) fitting process. In-clinic fittings will include REMs with adjustments to standard (NAL-NL2) prescription targets. The two fitting protocols will then be randomly assigned to participants in a crossover design, so participants and researchers will be blinded to the order of the two fitting protocols. Participants will then have a 4-week period with follow-up appointments for participant-directed gain adjustment. For each fitting protocol, participants will complete objective measurements of final hearing aid output with REMs, speech-in-noise testing, subjective measurements of hearing aid performance, and quality of life measurements. They will then begin an identical period of living with, adjusting, and objective assessment with the other fitting protocol. Data will be analysed as repeated measures with statistical control for potential confounding variables. RESULTS: Data will compare the four-frequency average real-ear aided response (4FREAR) for hearing aids programmed in-clinic and hearing aids programmed remotely, after participant-directed gain adjustments. Secondary measures will assess clinically significant differences in estimated speech intelligibility, hearing-related quality of life, hearing aid benefit, sound quality and preference, and speech-in-noise ability. CONCLUSIONS: This study will inform the development of best practice guidelines for remote hearing aid fittings. If no clinically significant differences are found between in-clinic and remote fit hearing aids, it has the potential to expand teleaudiology initiatives. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN12623000028606p . Date of registration: 12 January 2023.

Early-stage use of hearing aids preserves auditory cortical structure in children with sensorineural hearing loss.

Hearing is critical to spoken language, cognitive, and social development. Little is known about how early auditory experiences impact the brain structure of children with bilateral sensorineural hearing loss. This study examined the influence of hearing aid use and residual hearing on the auditory cortex of children with severe to profound congenital sensorineural hearing loss. We evaluated cortical preservation in 103 young pediatric cochlear implant candidates (55 females and 48 males) by comparing their multivoxel pattern similarity of auditory cortical structure with that of 78 age-matched children with typical hearing. The results demonstrated that early-stage hearing aid use preserved the auditory cortex of children with bilateral congenital sensorineural hearing loss. Children with less residual hearing experienced a more pronounced advantage from hearing aid use. However, this beneficial effect gradually diminished after 17 months of hearing aid use. These findings support timely fitting of hearing aids in conjunction with early implantation to take advantage of neural preservation to maximize auditory and spoken language development.

Novel likely pathogenic variant in the EYA1 gene causing Branchio oto renal syndrome and the exploration of pathogenic mechanisms.

OBJECTIVE: Branchio-oto-renal syndrome (BOR, OMIM#113,650) is a rare autosomal dominant disorder that presents with a variety of symptoms, including hearing loss (sensorineural, conductive, or mixed), structural abnormalities affecting the outer, middle, and inner ear, branchial fistulas or cysts, as well as renal abnormalities.This study aims to identify the pathogenic variants by performing genetic testing on a family with Branchio-oto-renal /Branchio-otic (BO, OMIM#602,588) syndrome using whole-exome sequencing, and to explore possible pathogenic mechanisms. METHODS: The family spans 4 generations and consists of 9 individuals, including 4 affected by the BOR/BO syndrome. Phenotypic information, including ear malformation and branchial cleft, was collected from family members. Audiological, temporal bone imaging, and renal ultrasound examinations were also performed. Whole-exome sequencing was conducted to identify candidate pathogenic variants and explore the underlying molecular etiology of BOR/BO syndrome by minigene experiments. RESULTS: Intra-familial variability was observed in the clinical phenotypes of BOR/BO syndrome in this family. The severity and nature of hearing loss varied in family members, with mixed or sensorineural hearing loss. The proband, in particular, had profound sensorineural hearing loss on the left and moderate conductive hearing loss on the right. Additionally, the proband exhibited developmental delay, and her mother experienced renal failure during pregnancy and terminated the pregnancy prematurely. Genetic testing revealed a novel heterozygous variant NM_000503.6: c.639 + 3 A > C in the EYA1 gene in affected family members. In vitro minigene experiments demonstrated its effect on splicing. According to the American College of Medical Genetics (ACMG) guidelines, this variant was classified as likely pathogenic. CONCLUSION: This study highlights the phenotypic heterogeneity within the same family, reports the occurrence of renal failure and adverse pregnancy outcomes in a female patient at reproductive age with BOR syndrome, and enriches the mutational spectrum of pathogenic variants in the EYA1 gene.

The prevalence and clinical features of MYO7A-related hearing loss including DFNA11, DFNB2 and USH1B.

The MYO7A gene is known to be responsible for both syndromic hearing loss (Usher syndrome type1B:USH1B) and non-syndromic hearing loss including autosomal dominant and autosomal recessive inheritance (DFNA11, DFNB2). However, the prevalence and detailed clinical features of MYO7A-associated hearing loss across a large population remain unclear. In this study, we conducted next-generation sequencing analysis for a large cohort of 10,042 Japanese hearing loss patients. As a result, 137 patients were identified with MYO7A-associated hearing loss so that the prevalence among Japanese hearing loss patients was 1.36%. We identified 70 disease-causing candidate variants in this study, with 36 of them being novel variants. All variants identified in autosomal dominant cases were missense or in-frame deletion variants. Among the autosomal recessive cases, all patients had at least one missense variant. On the other hand, in patients with Usher syndrome, almost half of the patients carried biallelic null variants (nonsense, splicing, and frameshift variants). Most of the autosomal dominant cases showed late-onset progressive hearing loss. On the other hand, cases with autosomal recessive inheritance or Usher syndrome showed congenital or early-onset hearing loss. The visual symptoms in the Usher syndrome cases developed between age 5-15, and the condition was diagnosed at about 6-15 years of age.

Clinical Reasoning: A 24-Year-Old Man With Gait Impairment, Hearing Loss, and Recurrent Fever.

We present a case study of a 24-year-old man who reported mild balance and walking difficulties for 2 years. He had a history of recurrent fever, skin lesions, headache, and elbow pain, but most of these events resolved spontaneously. There was no significant family history. On examination, we observed frontal bossing, sensorineural hearing loss, and gait ataxia. This case underscores the significance of identifying clinical indicators in patients with neurologic symptoms, particularly recurrent fever, to establish a precise and thorough differential diagnosis.

Demographic analysis of hearing impairment based on various parameters in patients with cochlear implant.

Objectives: To analyse the demographic and clinical variables in children having undergone cochlear implant surgery because of deafness. METHODS: The cross-sectional study was conducted from January to November 2022 at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Ear, Nose and Throat Department of Combined Military Hospital, Rawalpindi, and comprised children of eith gender aged up to 10 years who had received cochlear implant. Data was collected through questionnaire-based detailed interviews. Syndromic Hearing Loss, Non-Syndromic Hearing Loss, and Acquired Hearing Loss were identified among the subjects. Data was analysed using SPSS 22. RESULTS: Of the 250 cases, 147(58.8%) were boys, 146(58.4%) were aged 0-5 years, 219(87.6%) had prelingual onset of disease, and 202(80.8%) had a non-progressive disease course. In 203(81.2%) cases, normal developmental milestones were seen. Parental consanguinity was observed in 219(87.6%) cases. However, 63(25.2%) patients had a first-degree relative who had a history of deafness. In 170(68%) cases, hearing loss was hereditary, whereas in 80(32%) it was acquired. Meningitis was the most commonly identified risk factor 55(68.75%). Acquired risk factors and family history had significant association with hearing loss (p<0.05). Speech perception significantly improved in all 219(100%) patients with prelingual hearing loss who underwent cochlear implantation. CONCLUSIONS: Majority of the cases were found to be male, had a prelingual disease onset and a non-progressive disease course. Family history was a significant factor, while meningitis was the most common acquired cause of hearing loss.

Case report of a novel mutation in the TNC gene in Chinese patients with nonsyndromic hearing loss.

RATIONALE: Hereditary hearing loss is known to exhibit a significant degree of genetic heterogeneity. Herein, we present a case report of a novel mutation in the tenascin-C (TNC) gene in Chinese patients with nonsyndromic hearing loss (NSHL). PATIENT CONCERNS: This includes a young deaf couple and their 2-year-old baby. DIAGNOSES: Based on the clinical information, hearing test, metagenomic next-generation sequencing (mNGS), Sanger sequencing, protein function and structure analysis, and model prediction, in our case, the study results revealed 2 heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) and the TBC1 domain family member 24 (TBC1D24) gene (c.1570C>T, p.Arg524Trp). These mutations may be responsible for the hearing loss observed in this family. Notably, the heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) have not been previously reported in the literature. INTERVENTIONS: Avoid taking drugs that can cause deafness, wearing hearing AIDS, and cochlear implants. OUTCOMES: Regular follow-up of family members is ongoing. LESSONS: The genetic diagnosis of NSHL holds significant importance as it helps in making informed treatment decisions, providing prognostic information, and offering genetic counseling for the patient's family.

Diagnóstico genético de la hipoacusia neurosensorial infantil / Genetic diagnosis of childhood sensorineural hearing loss

Introducción: La hipoacusia neurosensorial (HNS) congénita o de inicio precoz es una de las enfermedades hereditarias más frecuentes en nuestro medio y es la deficiencia sensorial más frecuente. Es importante realizar un estudio etiológico de la hipoacusia y el estudio genético mediante la secuenciación de nueva generación (NGS) es la prueba con mayor rendimiento diagnóstico. Nuestro estudio muestra los resultados genéticos obtenidos en una serie de pacientes con HNS congénita/de inicio precoz bilateral. Material y método: Se incluyeron 105 niños diagnosticados de HNS bilateral a los que se les realizó un estudio genético entre los años 2019 y 2022. El estudio genético consistió en una secuenciación masiva del exoma completo, filtrando el análisis para los genes incluidos en un panel virtual de hipoacusia con 244 genes. Resultados: Se obtuvo un diagnóstico genético en 48% (50/105) de los pacientes. Se detectaron variantes patogénicas y probablemente patogénicas en 26 genes diferentes, siendo los genes más frecuentemente afectados el gen GJB2, USH2A y STRC. De las variantes detectadas 52% (26/50) se asociaron a una hipoacusia no sindrómica, 40% (20/50) una hipoacusia sindrómica y 8% restante (4/50) se podían asociar tanto a una hipoacusia sindrómica como no sindrómica. Conclusiones: El estudio genético constituye una parte fundamental del diagnóstico etiológico de la HNS bilateral. Nuestra serie muestra que el estudio genético de la hipoacusia mediante NGS tiene un alto rendimiento diagnóstico y nos proporciona información de gran utilidad en la práctica clínica.(AU)

Introduction: Congenital/early-onset sensorineural hearing loss (SNHL) is one of the most common hereditary disorders in our environment. There is increasing awareness of the importance of an etiologic diagnosis, and genetic testing with next-generation sequencing (NGS) has the highest diagnostic yield. Our study shows the genetic results obtained in a cohort of patients with bilateral congenital/early-onset SNHL. Materials and methods: We included 105 children with bilateral SNHL that received genetic testing between 2019 and 2022. Genetic tests were performed with whole exome sequencing, analyzing genes related to hearing loss (virtual panel with 244 genes). Results: 48% (50/105) of patients were genetically diagnosed. We identified pathogenic and likely pathogenic variants in 26 different genes, and the most frequently mutated genes were GJB2, USH2A and STRC. 52% (26/50) of variants identified produced non-syndromic hearing loss, 40% (20/50) produced syndromic hearing loss, and the resting 8% (4/50) could produce both non-syndromic and syndromic hearing loss. Conclusions: Genetic testing plays a vital role in the etiologic diagnosis of bilateral SNHL. Our cohort shows that genetic testing with NGS has a high diagnostic yield and can provide useful information for the clinical workup of patients.(AU)