Cause Of Sensorineural Hearing Loss Research Articles

Direct reprogramming of fibroblasts into spiral ganglion neurons by defined transcription factors

AbstractDegeneration of the cochlear spiral ganglion neurons (SGNs) is one of the major causes of sensorineural hearing loss and significantly impacts the outcomes of cochlear implantation. Functional regeneration of SGNs holds great promise for treating sensorineural hearing loss. In this study, we systematically screened 33 transcriptional regulators implicated in neuronal and SGN fate. Using gene expression array and principal component analyses, we identified a sequential combination of Ascl1, Pou4f1 and Myt1l (APM) in promoting functional reprogramming of SGNs. The neurons induced by APM expressed mature neuronal and SGN lineage‐specific markers, displayed mature SGN‐like electrophysiological characteristics and exhibited single‐cell transcriptomes resembling the endogenous SGNs. Thus, transcription factors APM may serve as novel candidates for direct reprogramming of SGNs and hearing recovery due to SGN damages.

Identifying DNA Variants in a Turkish Cohort with Inner Ear Anomalies.

To determine the genetic causes of sensorineural hearing loss (SNHL) associated with inner ear anomalies, 11 unrelated Turkish individuals diagnosed with SNHL and an inner ear anomaly using temporal bone computed tomography and inner ear magnetic resonance imaging underwent exome or whole genome sequencing to identify underlying genetic defects. None of the individuals was diagnosed with a recognized syndrome. Four of the 11 probands were homozygous for SLC26A4 variants, c.283G>A, c.845G>A, c.1061T>C, and c.1198delT. Another proband was homozygous for a TECTA variant, c.4163G>A. Patients with variants of the SLC26A4 gene had bilateral enlarged vestibular aqueduct, bilateral incomplete partition type 2 anomaly, bilateral hypoplastic cochlea and bilateral enlarged vestibular aqueduct plus hypoplastic cochlea anomaly. Patients with the variant TECTA gene had bilateral hypoplastic cochlea. This study identified variants of SLC26A4 in 36% of probands with inner ear anomalies. While we identified a variant of the TECTA gene in a proband with cochlear hypoplasia, further studies are needed to see if TECTA variants can cause cochlear malformations.

Antiviral Therapy for Congenital Cytomegalovirus Infection: Does It Prevent Late-Onset Sensorineural Hearing Loss?

Abstract Background Congenital cytomegalovirus (CMV) infection is the leading non-genetic cause of sensorineural hearing loss (SNHL) in children. While SNHL is often present at birth, as many as 20% of infants with congenital CMV infection may develop late-onset hearing loss beyond the neonatal period. Antiviral therapy improves hearing outcomes, but its effect on the occurrence of late-onset SNHL is not fully known. The objective is to describe the prevalence of SNHL at birth and late SNHL among infants and children with congenital CMV infection and assess the impact of antiviral treatment on the occurrence of late-onset SNHL. Methods From 2013 to 2022, infants with congenital CMV infection referred to the NEO-ID Clinic at Nationwide Children’s Hospital (NCH), Columbus, OH underwent complete evaluation including hearing testing. Pertinent demographic, clinical, audiologic, laboratory, and radiographic data were obtained and stored using an electronic database (REDCap). Infants with SNHL at birth or who developed late-onset SNHL beyond a month of age were identified and compared with respect to receipt of antiviral therapy in the neonatal period. Results During the 10-year study period, we enrolled 204 infants with congenital CMV infection: 75% (154/204) had symptomatic disease, while 25% (50/204) had clinically inapparent infection (normal physical examination, growth parameters, and evaluation). Overall, 30% (n=62) had SNHL at birth or on follow-up audiologic evaluation with the majority (95%, 59/62) having symptomatic disease. Of the 62 infants with SNHL, 29% (n=18) had late-onset SNHL in one (n=10) or both (n=8) ears at a median age of 19 months (IQR, 8.5-42 months). Of the 122 infants who received antiviral therapy initiated in the first month of age, 12 (10%) developed late-onset SNHL in one (n=7) or both (n=5) ears. All 12 had symptomatic congenital CMV infection, and 2 received cochlear implants in one ear. Of the 82 infants who did not receive any antiviral therapy, 6 (7%) developed late-onset SNHL (3, unilateral [2, symptomatic]; 3, bilateral [1, symptomatic]) and 2 received cochlear implant. There was no difference in the occurrence of late-onset SNHL in treated (10%) vs. untreated (7%) infants with congenital CMV infection (p=0.6). Conclusion In this cohort of mostly symptomatic infants with congenital CMV infection, antiviral treatment did not reduce the occurrence of late-onset SNHL. Further study on the impact of early antiviral therapy on severity of the SNHL is urgently needed to inform optimal treatment management.

Prenatal and postnatal antiviral therapies for the prevention and treatment of congenital cytomegalovirus infections.

Congenital cytomegalovirus infection (cCMV) is the leading infectious cause of sensorineural hearing loss and lifelong neurodevelopmental disabilities. Studies suggest antiviral therapy can prevent fetal infection after maternal primary infection, as well as halt the progression of hearing loss and neurodevelopmental disabilities in newborns with symptomatic cCMV. With growing worldwide momentum on early detection and diagnosis of cCMV, this review describes the exciting recent advances in antiviral therapies in CMV infected pregnant mothers and babies, as well as emerging evidence on anti-CMV vaccines. New opportunities for prenatal and neonatal interventions have driven a rising interest in screening and identification of asymptomatic CMV infection. Routine screening of pregnant women to identify primary infection in first trimester is now advocated in Western Europe but has yet to be examined from a public health perspective in other regions. Evidence is emerging for maternal valaciclovir therapy to prevent fetal infection after a maternal primary CMV infection in the first trimester of pregnancy. For those infants who are born with symptomatic cCMV, a 6-month course of valganciclovir, started within the first 4 weeks of life, and possibly up to 13 weeks of life, is the current recommended therapy. However, there is unclear evidence for the benefit of treatment for asymptomatic cCMV and cCMV with isolated hearing loss. Research to identify more effective antivirals and an effective CMV vaccine continues. More research is needed to determine the region-specific applicability of the new European recommendations for routine CMV screening in pregnancy. Areas of uncertainty in postnatal management include timing of initiation, duration of treatment and identifying pediatric subgroups that benefit from modification of the standard treatment recommendations.

Differentiation of Spiral Ganglion Neurons from Human Dental Pulp Stem Cells: A Further Step towards Autologous Auditory Nerve Recovery.

The degeneration of spiral ganglion neurons (SGNs), which convey auditory signals from hair cells to the brain, can be a primary cause of sensorineural hearing loss (SNHL) or can occur secondary to hair cell loss. Emerging therapies for SNHL include the replacement of damaged SGNs using stem cell-derived otic neuronal progenitors (ONPs). However, the availability of renewable, accessible, and patient-matched sources of human stem cells is a prerequisite for successful replacement of the auditory nerve. In this study, we derived ONP and SGN-like cells by a reliable and reproducible stepwise guidance differentiation procedure of self-renewing human dental pulp stem cells (hDPSCs). This in vitro differentiation protocol relies on the modulation of BMP and TGFβ pathways using a free-floating 3D neurosphere method, followed by differentiation on a Geltrex-coated surface using two culture paradigms to modulate the major factors and pathways involved in early otic neurogenesis. Gene and protein expression analyses revealed efficient induction of a comprehensive panel of known ONP and SGN-like cell markers during the time course of hDPSCs differentiation. Atomic force microscopy revealed that hDPSC-derived SGN-like cells exhibit similar nanomechanical properties as their in vivo SGN counterparts. Furthermore, spiral ganglion neurons from newborn rats come in close contact with hDPSC-derived ONPs 5 days after co-culturing. Our data demonstrate the capability of hDPSCs to generate SGN-like neurons with specific lineage marker expression, bipolar morphology, and the nanomechanical characteristics of SGNs, suggesting that the neurons could be used for next-generation cochlear implants and/or inner ear cell-based strategies for SNHL.

Exploring the implementation of an educational film within antenatal care to reduce the risk of cytomegalovirus infection in pregnancy: A qualitative study

BackgroundCongenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss and neuro-disability in childhood. In the absence of a licensed vaccine, adoption of hygiene-based measures may reduce the risk of CMV infection in pregnancy, however these measures are not routinely discussed with pregnant women as part of National Health Service (NHS) antenatal care in the United Kingdom (UK).MethodsAn exploratory qualitative study was conducted, underpinned by Normalization Process Theory (NPT), to investigate how an educational intervention comprising of a short film about CMV may best be implemented, sustained, and enhanced in real-world routine antenatal care settings. Video, semi-structured interviews were conducted with participants who were recruited using a purposive sample that comprised of midwives providing antenatal care from three NHS hospitals (n = 15) and participants from professional colleges and from organisations or charities providing, or with an interest in, antenatal education or health information in the UK (n = 15).FindingsMidwives were reluctant to include CMV as part of early pregnancy discussions about reducing the risk of other infections due to lack of time, knowledge and absence of guidance or policies relating to CMV in antenatal education. However, the educational intervention was perceived to be a useful tool to encourage conversations and empower women to manage risk by all stakeholders, which would overcome some identified barriers. Macro-level challenges such as screening policies and lack of official guidelines to legitimise dissemination were identified.DiscussionSuccessful implementation of education about CMV as part of routine NHS care in the UK will require an increase in awareness and knowledge about CMV amongst midwives. NPT revealed that ‘coherence’ and ‘cognitive participation’ between service members are vital to imbed CMV education in routine practice. ‘Collective action’ and ‘reflexive monitoring’ is required to sustain service changes.

A preoperative dose of the pyridoindole AC102 improves the recovery of residual hearing in a gerbil animal model of cochlear implantation

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Due to the heterogeneity of causes for SNHL, effective treatment options remain scarce, creating an unmet need for novel drugs in the field of otology. Cochlear implantation (CI) currently is the only established method to restore hearing function in profound SNHL and deaf patients. The cochlear implant bypasses the non-functioning sensory hair cells (HCs) and electrically stimulates the neurons of the cochlear nerve. CI also benefits patients with residual hearing by combined electrical and auditory stimulation. However, the insertion of an electrode array into the cochlea induces an inflammatory response, characterized by the expression of pro-inflammatory cytokines, upregulation of reactive oxygen species, and apoptosis and necrosis of HCs, putting residual hearing at risk. Here, we characterize the small molecule AC102, a pyridoindole, for its protective effects on residual hearing in CI. In a gerbil animal model of CI, AC102 significantly improves the recovery of hearing thresholds across multiple frequencies and confines the cochlear trauma to the directly mechanically injured area. In addition, AC102 significantly preserves auditory nerve fibers and inner HC synapses throughout the whole cochlea. In vitro experiments in an ethanol challenged HT22 cell-line revealed significant and dose-responsive anti-apoptotic effects following the treatment of with AC102. Further, AC102 treatment resulted in significant downregulation of the expression of pro-inflammatory cytokines in an organotypic ex vivo model of electrode insertion trauma (EIT). These results suggest that AC102’s effects are likely elicited during the inflammatory phase of EIT and mediated by anti-apoptotic and anti-inflammatory properties, highlighting AC102 as a promising compound for hearing preservation during CI. Moreover, since the inflammatory response in CI shares similarities to that in other etiologies of SNHL, AC102 may be inferred as a potential general treatment option for various inner ear conditions.

Hearing Screening for Congenital CytoMegaloVirus-Exploring Parents' Experiences of Completing Targeted Congenital Cytomegalovirus Screening at the Time of Their Infants' Newborn Hearing Screening.

Background/Objectives: Congenital cytomegalovirus (cCMV) is the leading infectious cause of sensorineural hearing loss and neurodevelopmental disabilities, with prompt detection (<21 days of life) required to enable accurate diagnosis and anti-viral treatment where clinically appropriate. International guidelines recommend cCMV screening for infants who do not pass their Universal Newborn Hearing Screening (UNHS). This study aimed to explore parental experiences of targeted cCMV screening through the UNHS in Victoria, Australia between 2019 and 2020 (HearS-cCMV study). Methods: A qualitative study comprising 18 semi-structured interviews with parents who took saliva swabs from their infants who did not pass their UNHS. A maximum variation sampling strategy was used with data analysed using thematic analysis. Results: Four themes described 18 parents' experiences of cCMV screening: (1) parents' lack of CMV awareness prior to cCMV screening; (2) overall positive experience; (3) varied understanding of CMV post screening; and (4) parents were glad to screen their infant for cCMV. Enablers of targeted cCMV screening included the swab being simple and non-invasive, being easier to complete in the hospital than at home, and the screening being well delivered by the staff. Barriers included a potential increase in anxiety, especially with false positives, and the timing of cCMV screening coinciding with their infant not passing UNHS being difficult for some parents. Conclusions: Parent experiences of targeted cCMV screening were positive. Increasing public knowledge of cCMV and training staff members to complete the CMV swab would reduce the risk of false positives and associated parental anxiety. This would facilitate successful routine targeted cCMV screening.

Frequency of Herpes Simplex Virus Types 1 and 2 and Cytomegalovirus in Perilymph and Peripheral Blood Samples of Cochlear-Implanted Children Using the Polymerase Chain Reaction Method

Background and Aim: Inner ear infection with some viruses may be one of the possible causes of Sensorineural Hearing Loss (SNHL). This study aims to determine the frequency of Herpes Simplex Virus 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV) in perilymph and peripheral blood samples of cochlear-implanted children. Methods: In this cross-sectional study, 30 children with severe-to-profound SNHL (aged 1.1–5 years) underwent cochlear implantation surgery. During surgery, their perilymph and peripheral blood samples were collected. The samples were analyzed separately for the presence of herpes HSV-1, HSV-2, and CMV by real-time Polymerase Chain Reaction (PCR) method. The load of IgG and IgM antibodies against these viruses was determined using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Results: The frequency of CMV in perilymph samples was 16.7% (5 patients) and in peripheral blood samples was 3.3% (1 patient). The IgG antibody against CMV and HSV- 1 was positive in 80% and 46.7% of the patients, respectively. The IgM antibody against CMV was positive in 10%. The mean IgM serum antibody load against HSV-1, HSV-2, and CMV was 2.70, 1.70, and 5.47, respectively, and the mean IgG antibody load against these viruses was 56.07, 2.50, and 23.67, respectively. Conclusion: The IgG test is positive in cochlear-implanted children with CMV in their perilymph samples, and the CMV genome is not present in their peripheral blood. This may indicate the previous presence of this virus in the ear and its role in hearing loss. Keywords: Sensorineural hearing loss; perilymph fluid; cytomegalovirus; herpes simplex

From diagnosis to management: current perspectives on congenital cytomegalovirus infection.

Congenital CMV (cCMV) infection is the most common infection of newborns and a leading cause of hearing loss and other neurologic disabilities in children. This review focuses on the diagnosis, presentation and management of cCMV infection. Cytomegalovirus is one of the leading causes of sensorineural hearing loss in children. It also leads to neurodevelopmental disabilities and learning problems throughout childhood in both symptomatic and asymptomatic newborns. Urine and saliva PCR testing are the preferred methods of testing newborn infants for cCMV. In recent years, newborn-targeted and universal screening programs have been implemented in several states and major medical centers with the goal of identifying infected infants at risk for hearing loss. Treatment for infants diagnosed with cCMV infection should be limited to those who are moderately to severely symptomatic at birth with cCMV infection, though treatment may be beneficial for children who are asymptomatic with isolated sensorineural hearing loss. As more children with cCMV are being identified through newborn screening, understanding the clinical presentation and sequelae is important for appropriate management of children with cCMV.

From silence to sound – a case of autoimmune ear disease

Autoimmune inner ear disease (AIED) is a rare rheumatological cause of sensorineural hearing loss, accounting for less than 1% of worldwide hearing loss. It presents with rapidly progressive, unilateral or bilateral SNHL, often fluctuating. The progression is over weeks to months, along with vestibular symptoms. Diagnosing the condition is challenging because no adopted standardized tests are available. Hence, AIED is a challenging diagnosis based on exclusion. Clinical characteristics and how the patients respond to immunosuppressive agents are used for the diagnoses of AIED. Only a few cases have been reported in India till now. Here, we present a rare case of Autoimmune Ear Disease without any underlying systemic autoimmune disease.

Pcolce2 overexpression promotes supporting cell reprogramming in the neonatal mouse cochlea.

Hair cell (HC) damage is a leading cause of sensorineural hearing loss, and in mammals supporting cells (SCs) are unable to divide and regenerate HCs after birth spontaneously. Procollagen C-endopeptidase enhancer 2 (Pcolce2), which encodes a glycoprotein that acts as a functional procollagen C protease enhancer, was screened as a candidate regulator of SC plasticity in our previous study. In the current study, we used adeno-associated virus (AAV)-ie (a newly developed adeno-associated virus that targets SCs) to overexpress Pcolce2 in SCs. AAV-Pcolce2 facilitated SC re-entry into the cell cycle both in cultured cochlear organoids and in the postnatal cochlea. In the neomycin-damaged model, regenerated HCs were detected after overexpression of Pcolce2, and these were derived from SCs that had re-entered the cell cycle. These findings reveal that Pcolce2 may serve as a therapeutic target for the regeneration of HCs to treat hearing loss.

The effects of acute and chronic noise trauma on stimulus-evoked activity across primary auditory cortex layers.

Exposure to intense noise environments is a major cause of sensorineural hearing loss and auditory perception disorders, such as tinnitus and hyperacusis, which may have a central origin. The effects of noise-induced hearing loss on the auditory cortex have been documented in many studies. One limitation of these studies, however, is that the effects of noise trauma have been mostly studied at the granular layer (i.e, the main cortical recipient of thalamic input), while the cortex is a very complex structure, with six different layers each having its own pattern of connectivity and role in sensory processing. The present study aims to investigate the effects of acute and chronic noise trauma on the laminar pattern of stimulus-evoked activity in the primary auditory cortex of the anesthetized guinea pig. We show that acute and chronic noise trauma are both followed by an increase in stimulus-evoked cortical responses, mostly in the granular and supragranular layers. The cortical responses are more monotonic as a function of the intensity level after noise trauma. There was minimal change, if any, in local field potential (LFP) amplitude after acute noise trauma, while LFP amplitude was enhanced after chronic noise trauma. Finally, LFP and the current source density analysis suggest that acute but more specifically chronic noise trauma is associated with the emergence of a new sink in the supragranular layer. This result suggests that supragranular layers become a major input recipient. We discuss the possible mechanisms and functional implications of these changes.NEW & NOTEWORTHY Our study shows that cortical activity is enhanced after trauma and that the sequence of cortical column activation during stimulus-evoked response is altered, i.e. the supragranular layer becomes a major input recipient. We speculate that these large cortical changes may play a key role in the auditory hypersensitivity (hyperacusis) that can be triggered after noise trauma in human subjects.

Droplet Digital PCR (ddPCR) Does Not Enhance the Sensitivity of Detection of Cytomegalovirus (CMV) DNA in Newborn Dried Blood Spots Evaluated in the Context of Newborn Congenital CMV (cCMV) Screening.

Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in children worldwide. Some regions in the United States and Canada have implemented universal newborn screening for cCMV, which requires molecular diagnostic technologies for identifying cCMV, such as PCR testing of newborn dried blood spots (DBS). This study aimed to evaluate the sensitivity of droplet digital PCR (ddPCR) compared to quantitative real-time PCR to detect CMV DNA in newborn DBS. The limit of detection of various ddPCR primer/probe combinations (singleplex UL55-HEX, singleplex UL83-FAM, and multiplex UL55-HEX/UL83-FAM) was evaluated using the National Institute of Standards and Technology's (NIST) CMV quantitative standard. Singleplex UL55-HEX ddPCR exhibited the lowest limit of detection among the primer/probe combinations tested for ddPCR. UL55 ddPCR was then compared to real-time PCR in 49 infants with confirmed cCMV identified through newborn screening for CMV in saliva swabs and confirmed by a urine test. The results showed that ddPCR was only positive for 59% (29 out of 49) of the cCMV infants, while real-time PCR was positive for 80% (39 out of 49). Due to its lower sensitivity and throughput, ddPCR may not be suitable for cCMV newborn screening.

Risk factors and outcomes in patients with cochlear nerve deficiency

IntroductionCochlear nerve deficiency (CND) is a cause of sensorineural hearing loss made by radiologic criteria. There is sparse literature involving audiological outcomes and cochlear implantation (CI) success in patients with CND. MethodsA retrospective chart review of all patients with sensorineural hearing loss at a tertiary children's hospital from 2000 to 2020 was conducted. Patients with CND on radiographic imaging were included and categorized as hypoplastic, aplastic, or indeterminate. ResultsIn this study, 53 patients were identified with CND, totaling 70 ears. Of the 53 patients, 30 (56.6 %) were male, 8 (16.0 %) had a family history of childhood hearing loss, 6 (11.3 %) were born preterm, and 11 (23.4 %) required neonatal intensive care admission. The median maternal age was 29 years old [IQR: 27, 35], and 8 (15 %) patients were born to mothers with diabetes. Of the 70 ears, 49 (70 %) utilized conventional hearing aids, 12 (17.1 %) utilized a bone-anchored hearing aid, and 10 (14.3 %) underwent CI. Of the 10 ears implanted, 4 (40 %) ears had nerves classified as hypoplastic, 3 (30 %) as aplastic, and 3 (30 %) as indeterminate. Improvement in pure tone averages compared to preoperative testing was demonstrated in 8 (80 %), and 6 (60 %) displayed improved speech awareness thresholds. ConclusionThis study demonstrates that there may be an association between CND and maternal diabetes and NICU admission. There are variable results with hearing amplification options in patients with CND, and further research is needed to better describe the role of CI, bone-anchored hearing aids and conventional hearing aids in patients with CND.

Cortisol Sensitizes Cochlear Hair Cells to Gentamicin Ototoxicity Via Endogenous Apoptotic Pathway.

The widespread use of aminoglycosides is a prevalent cause of sensorineural hearing loss. Patients receiving aminoglycosides usually have elevated levels of circulating stress hormones due to disease or physiological stress; however, whether the stress hormone cortisol impacts aminoglycoside-mediated injury of cochlear hair cells has not been fully investigated. House Ear Institute-Organ of Corti 1 (HEI-OC1) cells with or without cortisol pretreatment were exposed to gentamicin, we investigated the effect of cortisol pretreatment on gentamicin ototoxicity by assessing cell viability. Molecular pathogenesis was explored by detecting apoptosis and oxidative stress. Meanwhile, by inhibiting glucocorticoid receptors (GR) and mineralocorticoid receptors (MR), the potential roles of receptor types in cortisol-mediated sensitization were evaluated. Cortisol concentrations below 75 μmol/l did not affect cell viability. However, pretreatment with 50 μmol/l cortisol for 24 hours sensitized hair cells to gentamicin-induced apoptosis. Further mechanistic studies revealed that cortisol significantly increased hair cell apoptosis and oxidative stress, and altered apoptosis-related protein expressions induced by gentamicin. In addition, blockade of either GR or MR attenuated cortisol-induced hair cell sensitization to gentamicin toxicity. Cortisol pretreatment increased mammalian hair cell susceptibility to gentamicin toxicity. Sensitization was related to the activation of the intrinsic apoptotic pathway and excessive generation of reactive oxygen species. Cortisol may exacerbate aminoglycoside ototoxicity.

Dispersed DNA variants underlie hearing loss in South Florida’s minority population

BackgroundWe analyzed the genetic causes of sensorineural hearing loss in racial and ethnic minorities of South Florida by reviewing demographic, phenotypic, and genetic data on 136 patients presenting to the Hereditary Hearing Loss Clinic at the University of Miami. In our retrospective chart review, of these patients, half self-identified as Hispanic, and the self-identified racial distribution was 115 (86%) White, 15 (11%) Black, and 6 (4%) Asian. Our analysis helps to reduce the gap in understanding the prevalence, impact, and genetic factors related to hearing loss among diverse populations.ResultsThe causative gene variant or variants were identified in 54 (40%) patients, with no significant difference in the molecular diagnostic rate between Hispanics and Non-Hispanics. However, the total solve rate based on race was 40%, 47%, and 17% in Whites, Blacks, and Asians, respectively. In Non-Hispanic Whites, 16 different variants were identified in 13 genes, with GJB2 (32%), MYO7A (11%), and SLC26A4 (11%) being the most frequently implicated genes. In White Hispanics, 34 variants were identified in 20 genes, with GJB2 (22%), MYO7A (7%), and STRC-CATSPER2 (7%) being the most common. In the Non-Hispanic Black cohort, the gene distribution was evenly dispersed, with 11 variants occurring in 7 genes, and no variant was identified in 3 Hispanic Black probands. For the Asian cohort, only one gene variant was found out of 6 patients.ConclusionThis study demonstrates that the diagnostic rate of genetic studies in hearing loss varies according to race in South Florida, with more heterogeneity in racial and ethnic minorities. Further studies to delineate deafness gene variants in underrepresented populations, such as African Americans/Blacks from Hispanic groups, are much needed to reduce racial and ethnic disparities in genetic diagnoses.

Sensorineural Hearing Loss in Patients With Chronic Kidney Disease: A Comprehensive Review.

This article aims to ascertain the prevalence of loss of hearing in patients with chronic kidney disease (CKD) and also to examine potential causes of sensorineural hearing loss (SNHL) in patients suffering from CKD. It has been discovered in recent years that there is a relationship between the occurrence of SNHL and CKD. Nowadays many people are suffering from CKD. These patients deal with several otorhinolaryngological issues, such as SNHL, candidiasis, epistaxis, halitosis, dysgeusia, xerostomia, and lip and thyroid malignancies. One of the most frequent otorhinolaryngological complications is audiovestibular system impairment. There are various proposed mechanisms for the appearance of loss of hearing in people suffering from CKD. The kidney and the inner ear have multiple functional and structural similarities, which may be the cause of these problems in CKD patients. In addition, changes in the homeostasis of water and electrolytes can affect the endolymphatic fluid and result in endolymphatic hydrops. Finally, some medications, like aminoglycosides and loop diuretics, are well known for their ototoxicity and are utilized to treat patients with CKD. Only a small number of population-based research have so far been able to show a connection between CKD and audiovestibular system impairment. Some investigationhasshown that CKD patients are more likely than healthy people to experience vestibular impairment. The quality of life of a patient can be reduced by hearing loss. People with hearing loss experience communication issues in daily life, which negatively affects their cognitive and psychosocial functioning. Social isolation and a poor quality of life in terms of health can all result from hearing loss. In addition, decreased renal function has also been linked to poor quality of life, hospitalization, and cognitive dysfunction.

Risk Factors for Natural Hearing Evolution in Newborns With Congenital Cytomegalovirus Infection

Congenital cytomegalovirus (cCMV) is the major cause of congenital nonhereditary sensorineural hearing loss in children. Currently, criteria to identify infants at increased risk for unfavorable hearing outcome are lacking. To identify risk factors associated with cCMV-related hearing improvement, hearing deterioration, and late-onset hearing loss. This multicenter cohort study included patients from 6 secondary and tertiary hospitals enrolled in the Flemish CMV registry (Belgium). Newborns with untreated cCMV infection with at least 4-year audiological follow-up were included. Patients who presented with other possible causes of sensorineural hearing loss were excluded. Data were collected for 15 years (January 1, 2007, to February 7, 2022) and analyzed from September 26, 2022, to January 16, 2023. Primary outcome was hearing evolution (per-ear analysis; described as stable hearing, improvement, or deterioration). The association of gestational characteristics, clinical findings, timing of seroconversion, viral load, and hearing status at birth with hearing evolution was investigated using effect sizes (Cramer V, odds ratio [OR], or Hedges g). Of the 387 children, 205 of 385 with nonmissing data were male (53.2%), 113 (29.2%) had a symptomatic infection, and 274 (70.8%) had an asymptomatic infection. Every child was 4 years or older at final hearing evaluation. A total of 701 of 774 ears (90%) showed stable hearing (normal hearing or stable hearing loss since birth) over time. Late-onset hearing loss (normal hearing at birth followed by hearing loss) was present in 43 of 683 ears (6.3%). Among children with hearing loss present at birth, 24 of 34 ears (70.6%) had hearing deterioration, and 6 of 91 ears (6.6%) had hearing improvement. Prematurity was associated with a higher chance of hearing improvement (OR, 12.80; 95% CI, 2.03-80.68). Late-onset hearing loss was more prevalent in a first trimester infection (OR, 10.10; 95% CI, 2.90-34.48). None of the 104 ears of children with a third trimester seroconversion developed late-onset hearing loss. Findings of this cohort study support that ongoing audiological follow-up for untreated children with congenital hearing loss is important, as the majority of patients had hearing deterioration. The timing of seroconversion was associated with the risk of developing late-onset hearing loss. These insights can aid in parental counseling, patient stratification, and follow-up. Future research should focus on the effect of treatment, the influence of determined risk factors, and the study of eventual new risk factors in patients at high risk to develop hearing loss.

Emerging biotechnologies and biomedical engineering technologies for hearing reconstruction.

Hearing impairment is a global health problem that affects social communications and the economy. The damage and loss of cochlear hair cells and spiral ganglion neurons (SGNs) as well as the degeneration of neurites of SGNs are the core causes of sensorineural hearing loss. Biotechnologies and biomedical engineering technologies provide new hope for the treatment of auditory diseases, which utilizes biological strategies or tissue engineering methods to achieve drug delivery and the regeneration of cells, tissues, and even organs. Here, the advancements in the applications of biotechnologies (including gene therapy and cochlear organoids) and biomedical engineering technologies (including drug delivery, electrode coating, electrical stimulation and bionic scaffolds) in the field of hearing reconstruction are presented. Moreover, we summarize the challenges and provide a perspective on this field.