HEARRING group genetic marker study: genetic background of CI patients.

Background: While cochlear implantation (CI) and electric acoustic stimulation (EAS) have a positive outcome in most cases, their effectiveness varies depending on the etiology of the hearing loss. Among the various etiologies, genetic factors are the leading cause of hearing loss and may impact CI and EAS outcomes.

Aims/objectives: To reveal the genetic background of the hearing loss in CI/EAS patients in each ethnic population, we undertook a multi-center study involving the genetic testing of hearing loss in CI/EAS patients from 10 centers.

Post-operative patient perception of decisional regret in cochlear implant recipients.

Importance: Decision regret post-surgery has has been linked to health outcomes for a number of elective procedures but is understudied in cochlear implantation satisfaction. Theunpredictability in outcomes may lead to unmet expectations by the recipient. This study is the first study to investigate the decision regret concept in cochlear implant recipients.

In Silico Localization of Perilymph Proteins Enriched in Meńier̀e Disease Using Mammalian Cochlear Single-cell Transcriptomics.

Hypothesis: Proteins enriched in the perilymph proteome of Meńier̀e disease (MD) patients may identify affected cell types. Utilizing single-cell transcriptome datasets from the mammalian cochlea, we hypothesize that these enriched perilymph proteins can be localized to specific cochlear cell types.

Background: The limited understanding of human inner ear pathologies and their associated biomolecular variations hinder efforts to develop disease-specific diagnostics and therapeutics.

Protection from cisplatin-induced hearing loss with lentiviral vector-mediated ectopic expression of the anti-apoptotic protein BCL-XL.

Cisplatin is a highly effective chemotherapeutic agent, but it can cause sensorineural hearing loss (SNHL) in patients. Cisplatin-induced ototoxicity is closely related to the accumulation of reactive oxygen species (ROS) and subsequent death of hair cells (HCs) and spiral ganglion neurons (SGNs). Despite various strategies to combat ototoxicity, only one therapeutic agent has thus far been clinically approved.

Extracellular vesicles for developing targeted hearing loss therapy.

Substantial efforts have been made for local administration of small molecules or biologics in treating hearing loss diseases caused by either trauma, genetic mutations, or drug ototoxicity. Recently, extracellular vesicles (EVs) naturally secreted from cells have drawn increasing attention on attenuating hearing impairment from both preclinical studies and clinical studies. Highly emerging field utilizing diverse bioengineering technologies for developing EVs as the bioderived therapeutic materials, along with artificial intelligence (AI)-based targeting toolkits, shed the light on the unique properties of EVs specific to inner ear delivery.

CRISPR-Cas9 Engineered Extracellular Vesicles for the Treatment of Dominant Progressive Hearing Loss.

Clinical translation of gene therapy has been challenging, due to limitations in current delivery vehicles such as traditional viral vectors. Herein, we report the use of gRNA:Cas9 ribonucleoprotein (RNP) complexes engineered extracellular vesicles (EVs) for gene therapy. By leveraging a novel high-throughput microfluidic droplet-based electroporation system (μDES), we achieved 10-fold enhancement of loading efficiency and more than 1000-fold increase in processing throughput on loading RNP complexes into EVs (RNP-EVs), compared with conventional bulk electroporation.

Third-generation lentiviral gene therapy rescues function in a mouse model of Usher 1B.

Usher syndrome 1B (USH1B) is a devastating genetic disorder with congenital deafness, loss of balance, and blindness caused by mutations in the myosin-VIIa (MYO7A) gene, for which there is currently no cure. We developed a gene therapy approach addressing the vestibulo-cochlear deficits of USH1B using a third-generation, high-capacity lentiviral vector system capable of delivering the large 6,645-bp MYO7A cDNA. Lentivirally delivered MYO7A and co-encoded dTomato were successfully expressed in the cochlear cell line HEI-OC1.

QoL, CIs, QALYs, and Individualized Rehabilitation: The Clinical and Practical Benefits of Regularly Assessing the Quality of Life of Adult Cochlear Implant Recipients.

This study aimed to report quality of life (QoL) scores in unilateral cochlear implant (CI) users and to generate guidance for clinicians on using QoL measures to individualize CI counselling and rehabilitation and to increase access to CIs as a mode of rehabilitation. Participants (n = 101) were unilateral CI users with single-sided deafness (SSD; n = 17), asymmetrical hearing loss (AHL; n = 26), or bilateral hearing loss (Uni; n = 58). Generic QoL was assessed via the Health Utilities Index (HUI-3), and disease-specific QoL was assessed via the Speech, Spatial, and Qualities of Hearing scale (SSQ12) and Nijmegen CI Questionnaire (NCIQ) at preimplantation and at 6 and 12 months of CI use.

Genotype-Phenotype Correlations in TMPRSS3 (DFNB10/DFNB8) with Emphasis on Natural History.

Background: Mutations in TMPRSS3 are an important cause of autosomal recessive non-syndromic hearing loss. The hearing loss associated with mutations in TMPRSS3 is characterized by phenotypic heterogeneity, ranging from mild to profound hearing loss, and is generally progressive. Clinical presentation and natural history of TMPRSS3 mutations vary significantly based on the location and type of mutation in the gene.

Rescue of auditory function by a single administration of AAV-TMPRSS3 gene therapy in aged mice of human recessive deafness DFNB8.

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients.

Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics.

Hearing impairment is the most common sensory disorder in humans, and yet hardly any medications are licensed for the treatment of inner ear pathologies. Intricate pharmacokinetic examinations to better understand drug distribution within this complex organ could facilitate the development of novel therapeutics. For such translational research projects, animal models are indispensable, but differences in inner ear dimensions and other anatomical features complicate the transfer of experimental results to the clinic.

Rescue of Auditory Function by a Single Administration of AAV- Gene Therapy in Aged Mice of Human Recessive Deafness DFNB8.

Patients with mutations in the gene suffer from recessive deafness DFNB8/DFNB10 for whom cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knock-in mouse model with a frequent human DFNB8 mutation.

Evaluation of Portable Tablet-Based Audiometry in a South Indian Population.

While a comprehensive booth audiogram is the gold standard for diagnosis of hearing loss, access to this may not be available in remote and low resource settings. The aims of this study were to validate a tablet-based audiometer in a tertiary medical center in India and explore its capacity in improving access to hearing healthcare. Subjects presenting to Ear-Nose-Throat clinics for conventional booth audiometry testing were recruited for subsequent tablet-based audiometric testing.

Analysis of Imaging Results for Semisitting Compared with Supine Positioning in the Retrosigmoid Approach for Resection of Cerebellopontine Angle Vestibular Schwannomas.

Objective: To compare the completeness of resection of vestibular schwannomas using three-dimensional segmented volumetric analysis of pre- and postoperative magnetic resonance imaging (MRI) of patients undergoing supine and semisitting positioning for the retrosigmoid approach.

Study Design: Retrospective chart review.

Setting: Tertiary medical center.

Extracellular Vesicles in Inner Ear Therapies-Pathophysiological, Manufacturing, and Clinical Considerations.

(1) Background: Sensorineural hearing loss is a common and debilitating condition. To date, comprehensive pharmacologic interventions are not available. The complex and diverse molecular pathology that underlies hearing loss may limit our ability to intervene with small molecules.

Single-incision cochlear implantation and hearing evaluation in piglets and minipigs.

Objectives: Various animal models have been established and applied in hearing research. In the exploration of novel cochlear implant developments, mainly rodents have been used. Despite their important contribution to the understanding of auditory function, translation of experimental observations from rodents to humans is limited due to the size differences and genetic variability.

Minimally Traumatic Cochlear Implant Surgery: Expert Opinion in 2010 and 2020.

This study aimed to discover expert opinion on the surgical techniques and materials most likely to achieve maximum postoperative residual hearing preservation in cochlear implant (CI) surgery and to determine how these opinions have changed since 2010. A previously published questionnaire used in a study published in 2010 was adapted and expanded. The questionnaire was distributed to an international group of experienced CI surgeons.

Otopathologic and Computed Tomography Correlation of Internal Auditory Canal Diverticula in Otosclerosis.

Introduction: Internal auditory canal (IAC) diverticula, also known as IAC cavitary lesions or anterior cupping of the IAC, observed in otopathologic specimens and high-resolution computed tomography (CT) scans of the temporal bone are thought to be related to otosclerosis. Herein, we examined the usefulness of CT scans in identifying diverticula and determined whether IAC diverticula are associated with otosclerosis on otopathology.

Methods: One hundred five consecutive specimens were identified from the National Temporal Bone Hearing and Balance Pathology Resource Registry.

Olfactory, Auditory, and Vestibular Performance: Multisensory Impairment Is Significantly Associated With Incident Cognitive Impairment.

Background: Dysfunction in the olfactory, auditory, and vestibular systems are commonly seen in aging and are associated with dementia. The impact of sensory loss(es) on cognition is not well understood. Our aim was to assess the relationships between performance on objective multisensory testing and quantify the impact of dysfunction on cognition.

Improving Control of Gene Therapy-Based Neurotrophin Delivery for Inner Ear Applications.

Survival and integrity of the spiral ganglion is vital for hearing in background noise and for optimal functioning of cochlear implants. Numerous studies have demonstrated that supplementation of supraphysiologic levels of the neurotrophins BDNF and NT-3 by pumps or gene therapy strategies supports spiral ganglion survival. The endogenous physiological levels of growth factors within the inner ear, although difficult to determine, are likely extremely low within the normal inner ear.

MicroRNA Profiling in the Perilymph of Cochlear Implant Patients: Identifying Markers that Correlate to Audiological Outcomes.

Hypothesis: MicroRNA (miRNA) expression profiles from human perilymph correlate to post cochlear implantation (CI) hearing outcomes.

Background: The high inter-individual variability in speech perception among cochlear implant recipients is still poorly understood. MiRNA expression in perilymph can be used to characterize the molecular processes underlying inner ear disease and to predict performance with a cochlear implant.

Worldwide Variation in Cochlear Implant Candidacy.

Background: The aim of this study was to find out how candidacy criteria have evolved differently across the globe.

Methods: Candidacy criteria and outcome measurements applied in 19 HEARRING clinics were analyzed.

Results: Candidacy criteria vary between clinics.

Bioinformatic Analysis of the Perilymph Proteome to Generate a Human Protein Atlas.

The high complexity of the cellular architecture of the human inner ear and the inaccessibility for tissue biopsy hampers cellular and molecular analysis of inner ear disease. Sampling and analysis of perilymph may present an opportunity for improved diagnostics and understanding of human inner ear pathology. Analysis of the perilymph proteome from patients undergoing cochlear implantation was carried out revealing a multitude of proteins and patterns of protein composition that may enable characterisation of patients into subgroups.

Suitable Electrode Choice for Robotic-Assisted Cochlear Implant Surgery: A Systematic Literature Review of Manual Electrode Insertion Adverse Events.

Background And Objective: The cochlear implant (CI) electrode insertion process is a key step in CI surgery. One of the aims of advances in robotic-assisted CI surgery (RACIS) is to realize better cochlear structure preservation and to precisely control insertion. The aim of this literature review is to gain insight into electrode selection for RACIS by acquiring a thorough knowledge of electrode insertion and related complications from classic CI surgery involving a manual electrode insertion process.