Differential diagnosis of tinnitus

Tinnitus is a common clinical symptomthat can be debilitating. Risk factors forits development are hearing loss, use of ototoxic drugs, head injury and depression. At the onset of the disease, the likelihood of ear pathology, the presence of anxiety and depression should be considered. There are no effective drug treatments for tinnitus, although a number of scientific studies are ongoing to determine the mechanisms of the development of this condition and to search for possible options for its treatment. When ear pathology is detected, surgical interventions can be effective, but tinnitus associated with this disease persists. Available treatment approaches include hearing aids for diagnosed hearing loss (even mild or unilateral), broadband sound therapy, and counseling. Cognitive-behavioral therapy is indicated for some patients, but availability remains inadequate. The evidence base is most significant for the combination of sound therapy and CBT-based counseling, although clinical trials are complicated by the heterogeneity of the tinnitus patient population.

Hair Cell Protection from Ototoxic Drugs

Hearing loss is often caused by death of sensory hair cells (HCs) in the inner ear. HCs are vulnerable to some ototoxic drugs, such as aminoglycosides(AGs) and the cisplatin.The most predominant form of drug-induced cell death is apoptosis. Many efforts have been made to protect HCs from cell death after ototoxic drug exposure. These mechanisms and potential targets of HCs protection will be discussed in this review.And we also propose further investigation in the field of HCs necrosis and regeneration, as well as future clinical utilization.

Detection of unknown ototoxic adverse drug reactions: an electronic healthcare record-based longitudinal nationwide cohort analysis

Ototoxic medications can lead to significant morbidity. Thus, pre-marketing clinical trials have assessed new drugs that have ototoxic potential. Nevertheless, several ototoxic side effects of drugs may remain undetected. Hence, we sought to retrospectively investigate the potential risk of ototoxic adverse drug reactions among commonly used drugs via a longitudinal cohort study. An electronic health records-based data analysis with a propensity-matched comparator group was carried out. This study was conducted using the MetaNurse algorithm for standard nursing statements on electronic healthcare records and the National Sample Cohort obtained from the South Korea National Health Insurance Service. Five target drugs capable of causing ototoxic adverse drug reactions were identified using MetaNurse; two drugs were excluded after database-based analysis because of the absence of bilateral hearing loss events in patients. Survival analysis, log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio of bilateral hearing loss among patients who were prescribed candidate ototoxic drugs. The adjusted hazard ratio of bilateral hearing loss was 1.31 (1.03–1.68), 2.20 (1.05–4.60), and 2.26 (1.18–4.33) in cimetidine, hydroxyzine, and sucralfate users, respectively. Our results indicated that hydroxyzine and sucralfate may cause ototoxic adverse drug reactions in patients. Thus, clinicians should consider avoiding co-administration of these drugs with other well-confirmed ototoxic drugs should be emphasized.

The crosstalk between the Notch, Wnt, and SHH signaling pathways in regulating the proliferation and regeneration of sensory progenitor cells in the mouse cochlea

Sensory hair cells (HCs) are highly susceptible to damage by noise, ototoxic drugs, and aging. Although HCs cannot be spontaneously regenerated in adult mammals, previous studies have shown that signaling pathways are involved in HC regeneration in the damaged mouse cochlea. Here, we used a Notch antagonist (DAPT), a Wnt agonist (QS11), and recombinant Sonic hedgehog (SHH) protein to investigate their concerted actions underlying HC regeneration in the mouse cochlea after neomycin-induced damage both in vivo and in vitro. With DAPT, the numbers of HCs increased, and supporting cell (SC) proliferation was seen in both the intact and damaged cochlear sensory epithelia, while these numbers were unchanged in the presence of QS11. When simultaneously treated with DAPT and QS11, the number of HCs increased dramatically, and much greater SC proliferation was seen in the cochlear epithelium. In transgenic mice with both Notch1 conditional knockout and β-catenin over-expression, cochlear SC proliferation and HC regeneration were more obvious than in either Notch1 knockout or β-catenin over-expressing mice separately. When cochleae were treated with DAPT, QS11, and SHH together, SC proliferation was even greater, and this proliferation was seen in both the HC region and the greater epithelial ridge. High-throughput RNA sequencing was used to identify the differentially expressed genes between all groups, and the results showed that the SHH and Wnt signaling pathways are involved in SC proliferation. Our study suggests that co-regulation of the Notch, Wnt, and SHH signaling pathways promotes extensive cell proliferation and regeneration in the mouse cochlea.

Autophagy: A Novel Horizon for Hair Cell Protection

As a general sensory disorder, hearing loss was a major concern worldwide. Autophagy is a common cellular reaction to stress that degrades cytoplasmic waste through the lysosome pathway. Autophagy not only plays major roles in maintaining intracellular homeostasis but is also involved in the development and pathogenesis of many diseases. In the auditory system, several studies revealed the link between autophagy and hearing protection. In this review, we aimed to establish the correlation between autophagy and hair cells (HCs) from the aspects of ototoxic drugs, aging, and acoustic trauma and discussed whether autophagy could serve as a potential measure in the protection of HCs.

Progress in protecting vestibular hair cells

Vestibular hair cells are mechanosensory receptors that are capable of detecting changes in head position and thereby allow animals to maintain their posture and coordinate their movement. Vestibular hair cells are susceptible to ototoxic drugs, aging, and genetic factors that can lead to permanent vestibular dysfunction. Vestibular dysfunction mainly results from the injury of hair cells, which are located in the vestibular sensory epithelium. This review summarizes the mechanisms of different factors causing vestibular hair cell damage and therapeutic strategies to protect vestibular hair cells.

Risk Factors for Congenital Deafness in Pediatric Patients Who Underwent Otoaccoustic Emission (OAE) and Auditory Brainstem Response (ABR) Examinations in General Hospital Mohammad Hoesin Palembang, Indonesia

Introduction: Congenital deafness is a hearing loss that occurs at birth. Congenital deafness in neonates can be caused by risk factors during pregnancy and during the birth process. The tests carried out for hearing screening for neonates in hospital up to 1 month old are Otoaccoustic Emission (OAE) and Auditory Brainstem Response (ABR) examinations. Objective: Determining the relationship between family history of deafness, syndromes associated with sensorineural hearing loss, TORCH infection and prenatal syphilis, use of ototoxic drugs during pregnancy, prematurity, low birth weight, asphyxia, and hyperbilirubinemia with the incidence of congenital deafness in children Methods: This cross-sectional study was conducted based on medical record datas from children who underwent OAE and ABR examinations at Dr. Mohammad Hoesin Palembang hospital from January 2019 to February 2021. Results: From the 349 children, 180 (51.6%) had bilateral OAE and ABR pass results, 161 (46.1%) had bilateral referrals and 8 (2.3%) children received unilateral refer results. From 122 children with risk factors, 38 (31.1%) children with bilateral passes, 81 (66.4%) children with bilateral referrals and 3 (2.5 %) children with unilateral refer. From 227 children without risk factors, 142 (62.6 %) children with a bilateral pass, 80 (35.2 %) children with bilateral referrals and 5 (2.2%) children with unilateral refer. The most common risk factor was LBW of 41 (11.7%) children. Chi square test and logistic regression analysis results showed a significant relationship between ototoxic drugs during pregnancy and congenital deafness (p = 0.001) with referral results, the value of Odd Ratio (OR) 9.651. Conclusions: There is a significant relationship between risk factors for ototoxic drugs during pregnancy, TORCH and syphilis infection during pregnancy, asphyxia, congenital syndrome, LBWand hyperbilirubinemia with congenital deafness.

Risk Factors for Congenital Deafness in Pediatric Patients Who Underwent Otoaccoustic Emission (OAE) and Auditory Brainstem Response (ABR) Examinations in General Hospital Mohammad Hoesin Palembang, Indonesia

Introduction: Congenital deafness is a hearing loss that occurs at birth. Congenital deafness in neonates can be caused by risk factors during pregnancy and during the birth process. The tests carried out for hearing screening for neonates in hospital up to 1 month old are Otoaccoustic Emission (OAE) and Auditory Brainstem Response (ABR) examinations. Objective: Determining the relationship between family history of deafness, syndromes associated with sensorineural hearing loss, TORCH infection and prenatal syphilis, use of ototoxic drugs during pregnancy, prematurity, low birth weight, asphyxia, and hyperbilirubinemia with the incidence of congenital deafness in children Methods: This cross-sectional study was conducted based on medical record datas from children who underwent OAE and ABR examinations at Dr. Mohammad Hoesin Palembang hospital from January 2019 to February 2021. Results: From the 349 children, 180 (51.6%) had bilateral OAE and ABR pass results, 161 (46.1%) had bilateral referrals and 8 (2.3%) children received unilateral refer results. From 122 children with risk factors, 38 (31.1%) children with bilateral passes, 81 (66.4%) children with bilateral referrals and 3 (2.5 %) children with unilateral refer. From 227 children without risk factors, 142 (62.6 %) children with a bilateral pass, 80 (35.2 %) children with bilateral referrals and 5 (2.2%) children with unilateral refer. The most common risk factor was LBW of 41 (11.7%) children. Chi square test and logistic regression analysis results showed a significant relationship between ototoxic drugs during pregnancy and congenital deafness (p = 0.001) with referral results, the value of Odd Ratio (OR) 9.651. Conclusions: There is a significant relationship between risk factors for ototoxic drugs during pregnancy, TORCH and syphilis infection during pregnancy, asphyxia, congenital syndrome, LBWand hyperbilirubinemia with congenital deafness.

Hearing loss in a post COVID-19 patient

<p class="abstract">With the advent of COVID-19 pandemic, there has been a myriad of long-term complications in post-COVID patients. In these patients, one of the rare but dreaded symptoms reported is sudden onset sensorineural hearing loss (SNHL) that has been reported mostly during active infection. We followed up with these patients in our outpatient department and came across one patient of SNHL. We conducted a literature search in PubMed and Google Scholar but couldn’t come across any such care report from India. We are hereby reporting the first case of SNHL in a post-hospitalised COVID-19 from India presenting after 3 months of hospital discharge, with no history prior otologic illness, intake of ototoxic drugs or any head injury. Post-COVID patients can present with weird symptoms including hearing loss apart from other commonly reported post COVID 19 sequelae.</p>

Using the Zebrafish Lateral Line to Understand the Roles of Mitochondria in Sensorineural Hearing Loss

Hair cells are the mechanosensory receptors of the inner ear and can be damaged by noise, aging, and ototoxic drugs. This damage often results in permanent sensorineural hearing loss. Hair cells have high energy demands and rely on mitochondria to produce ATP as well as contribute to intracellular calcium homeostasis. In addition to generating ATP, mitochondria produce reactive oxygen species, which can lead to oxidative stress, and regulate cell death pathways. Zebrafish lateral-line hair cells are structurally and functionally analogous to cochlear hair cells but are optically and pharmacologically accessible within an intact specimen, making the zebrafish a good model in which to study hair-cell mitochondrial activity. Moreover, the ease of genetic manipulation of zebrafish embryos allows for the study of mutations implicated in human deafness, as well as the generation of transgenic models to visualize mitochondrial calcium transients and mitochondrial activity in live organisms. Studies of the zebrafish lateral line have shown that variations in mitochondrial activity can predict hair-cell susceptibility to damage by aminoglycosides or noise exposure. In addition, antioxidants have been shown to protect against noise trauma and ototoxic drug–induced hair-cell death. In this review, we discuss the tools and findings of recent investigations into zebrafish hair-cell mitochondria and their involvement in cellular processes, both under homeostatic conditions and in response to noise or ototoxic drugs. The zebrafish lateral line is a valuable model in which to study the roles of mitochondria in hair-cell pathologies and to develop therapeutic strategies to prevent sensorineural hearing loss in humans.