Effect of Non-ablative Medical Therapy on Progression of Hearing Loss in Menière's Disease: A Systematic Review and meta-Analysis.

OBJECTIVE: To systematically review how audiometric data change over time in patients with Menière's disease (MD) undergoing non-ablative medical therapy. DATABASES REVIEWED: Medline (via PubMed), Scopus, Web of Science, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Google Scholar. METHODS: A systematic review and meta-analysis of the literature was performed. Adult patients undergoing non-ablative medical therapy and reported duration of disease or follow-up were included and pooled estimates of pure-tone average (PTA) were tabulated. Studies were excluded if they did not use established MD, did not have pure-tone average (PTA) audiometric data, underwent ear surgery or ablative therapies, and were systematic reviews or case reports. RESULTS: Out of 198 articles meeting full eligibility, 13 studies, involving 950 patients with MD, were included in the review and further analyzed. No effect on progression of PTA from initial diagnosis was seen between the different medical therapies within 2 years of non-ablative medical treatment. There was a significant worsening of PTA after 2 year, regardless of treatment used. High levels of heterogeneity among studies were noted up to 6 months from diagnosis ( I2 = 79%), likely reflecting differences in patient characteristics, treatment regimens, and study design. Overall, the risk of bias was low for the majority of included studies. CONCLUSIONS: Patients diagnosed with MD who are undergoing non-ablative medical therapy should be counseled on the likelihood of worsening of hearing loss over the course of the disease despite elected treatment.

Applications of single-cell sequencing for the field of otolaryngology: A contemporary review.

OBJECTIVES: Single-cell RNA sequencing (scRNA-Seq) is a new technique used to interrogate the transcriptome of individual cells within native tissues that have already resulted in key discoveries in auditory basic science research. Rapid advances in scRNA-Seq make it likely that it will soon be translated into clinical medicine. The goal of this review is to inspire the use of scRNA-Seq in otolaryngology by giving examples of how it can be applied to patient samples and how this information can be used clinically. METHODS: Studies were selected based on the scientific quality and relevance to scRNA-Seq. In addition to mouse auditory system (inner ear including hair cells and supporting cells, spiral ganglion neurons, and inner ear organoids), recent studies using human primary cell samples are discussed. We also perform our own analysis on publicly available, published scRNA-Seq data from oral head and neck squamous cell carcinoma (HNSCC) samples to serve as an example of a clinically relevant application of scRNA-Seq. RESULTS: Studies focusing on patient tissues show that scRNA-Seq reveals tissue heterogeneity and rare-cell types responsible for disease pathogenesis. The heterogeneity detected by scRNA-Seq can result in both the identification of known or novel disease biomarkers and drug targets. Our analysis of HNSCC data gives an example for how otolaryngologists can use scRNA-Seq for clinical use. CONCLUSIONS: Although there are limitations to the translation of scRNA-Seq to the clinic, we show that its use in otolaryngology can give physicians insight into the tissue heterogeneity within their patient's diseased tissue giving them information on disease pathogenesis, novel disease biomarkers or druggable targets, and aid in selecting patient-specific drug cocktails.

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis.

The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell mechanotransduction and hearing. While channels belonging to SV cell types are known to play crucial roles in EP generation, relatively little is known about gene regulatory networks that underlie the ability of the SV to generate and maintain the EP. Using single cell and single nucleus RNA-sequencing, we identify and validate known and rare cell populations in the SV. Furthermore, we establish a basis for understanding molecular mechanisms underlying SV function by identifying potential gene regulatory networks as well as druggable gene targets. Finally, we associate known deafness genes with adult SV cell types. This work establishes a basis for dissecting the genetic mechanisms underlying the role of the SV in hearing and will serve as a basis for designing therapeutic approaches to hearing loss related to SV dysfunction.

Evaluation of Nestin Expression in the Developing and Adult Mouse Inner Ear.

Adult stem cells are undifferentiated cells with the capacity to proliferate and form mature tissue-specific cell types. Nestin is an intermediate filament protein used to identify cells with stem cell characteristics. Its expression has been observed in a population of cells in developing and adult cochleae. In vitro studies using rodent cochlear tissue have documented the potential of nestin-expressing cells to proliferate and form hair and supporting cells. In this study, nestin coupled to green fluorescent protein (GFP) transgenic mice were used to provide a more complete characterization of the spatial and temporal expression of nestin in the inner ear, from organogenesis to adulthood. During development, nestin is expressed in the spiral ganglion cell region and in multiple cell types in the organ of Corti, including nascent hair and supporting cells. In adulthood, its expression is reduced but persists in the spiral ganglion, in a cell population medial to and below the inner hair cells, and in Deiters' cells in the cochlear apex. Moreover, nestin-expressing cells can proliferate in restricted regions of the inner ear during development shown by coexpression with Ki67 and MCM2 and by 5-ethynyl-2'-deoxyuridine incorporation. Results suggest that nestin may label progenitor cells during inner ear development and may not be a stem cell marker in the mature organ of Corti; however, nestin-positive cells in the spiral ganglion exhibit some stem cell characteristics. Future studies are necessary to determine if these cells possess any latent stem cell-like qualities that may be targeted as a regenerative approach to treat neuronal forms of hearing loss.