Detection of age-related hearing losses (Arhl) via transient-evoked otoacoustic emissions

Purpose: The objective of the study was to identify subjects presenting hearing deficits, specifically age-related hearing losses (ARHL), via objective assessment methodologies. Materials and Methods: Initially, 259 subjects (165 men, 94 women) were enrolled in the study. After the application of inclusion criteria, the final number was reduced to 88 subjects (49.8 ± 19.1 ys) subdivided into 64 normal and 83 ARHL cases. The subjects were assessed with traditional audiometry tests and with transiently evoked otoacoustic emissions (TEOAEs). Since each ear has its own acoustic signature, the TEOAE analyses were conducted in terms of ears and not subjects. The TEOAE data were processed by traditional and recurrence quantification analyses, leading to the estimation of the WWR (whole waveform reproducibility) and the new RAD2D (2-dimensional radius) parameters. A plot of WWR vs RAD2D was used to optimize the classification of the cases presenting ARHL. Results: By using a WWR value of 70% as a classifier, the sensitivity of TEOAEs was estimated as 75.9% and the specificity as 89.1%. By using the RAD2D parameter (with a cutoff value of 1.78), a sensitivity value of 80.7% and a specificity value of 71.9% were obtained. When both parameters were used, a sensitivity value of 85.5% and a specificity value of 92.2% were estimated. In the latter classification paradigm, the number of false negatives decreased from 20 to 12 out of 83 ears (14%). Conclusion: In adult hearing screening assessments, the proposed method optimizes the identification of subjects with a hearing impairment correlated to the presence of age-related hearing loss

Clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss

Objectives/Hypothesis: The role of antiendothelial cell antibodies in systemic vasculitis has been reported. The. aim of the study was to define the clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss. Study Design: A prospective study in patients with sudden sensorineural hearing loss. Methods: Serum samples were taken from 59 consecutive patients with sudden sensorineural hearing loss at time of presentation and from 28 normal control subjects. Indirect immunofluorescence assay was used to detect antiendothelial cell antibodies. Results: The prevalence of antiendothelial cell antibody detection was 54% (32 of 59 patients), with a statistically significant difference between patients and control subjects (P = .0064). Antiendothelial cell antibody positivity was significantly associated with absent recovery of hearing loss (P = .0020). Conclusions: The cytotoxicity to endothelial cells of the inner ear by antiendothelial cell antibody-positive sera might play a role in causing the stria vascularis damage in immune-mediated sudden sensorineural deafness. The appearance of antiendothelial cell antibody is related to the poor outcome of hearing loss, and its detection could be helpful in the selection of particular patients with sensorineural hearing loss for specific immunosuppressive treatments

Anti-endothelial autoantibodies in patients with sudden hearing loss.

ObjectiveslHypothesis: Sudden hearing loss (HL) can be caused by autoimmune disorders localized to the inner ear or secondary to systemic immune dis- eases. Studies in autoimmune animal strains showing HL have reported changes in the cochlear stria vas- cularis. The authors investigated the presence of an- tiendothelial cell antibodies (AECA) to see if immune- mediated vasculitis may play a role in human sudden HL. Study Design: A prospective study in patients with sudden HL. Methods: Fifteen consecutive pa- tients (mean age, 32 y) affected by sudden HL and 14 normal subjects were included. Patients with familial deafness and metabolic diseases were excluded. Ex- tensive audiovestibular, imaging, microbiological, immunological, and routine examinations were per- formed. AECA were detected on rat kidney tissue sec- tions on the sera collected at -20°C. Results: AECA were positive in 8 of 15 patients (53%) (2 of 5 men and 6 of 10 women), thus differing significantly from the normal control population, in which only 2 of 14 tested AECA positive (P = .023). Conclusions: In pa- tients with sudden HL, immune-mediated vascular damage can have a pathogenetic role and AECA might represent a serological marker of vasculitis. Key Words: Sudden hearing loss, immune-mediated vascular damage, anti-endothelial cell antibodies

Decision Making on Vestibular Schwannoma: Lessons from a Multidisciplinary Board

Background: Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or radiosurgery, microsurgical resection, or wait and scan (WS). We describe the experience of our VS multidisciplinary team (MDT) at a tertiary university referral center created for diagnosis, treatment, and follow-up of VS patients. Methods: We conducted a retrospective study on 132 consecutive patients referred to the MDT and managed by observation (WS), microsurgery, or fractionated sRT. The analysis included patient age, tumor size, hearing level, facial nerve function, tumor control, complications, and quality of life questionnaires. Results: Among the patients, 21% were subjected to microsurgery, 10% to sRT, and 69% to WS. The median follow-up time was 30 months. Outcomes based on different management modalities are described. Statistically significant differences among groups were detected in terms of quality of life (physical domain). Conclusions: MDT may provide the best individualized therapy for VS patients compared with a single gold-standard strategy

Performance and characteristics of the Newborn Hearing Screening Program in Campania region (Italy) between 2013 and 2019

Purpose: Universal newborn hearing screening (UNHS) in the first month of life is crucial for facilitating both early hearing detection and intervention (EHDI) of significant permanent hearing impairment (PHI). In Campania region, UNHS has been introduced in 2003 by the Regional Council Resolution and started on January 2007. The aim of this paper is to update a previous article describing the performance of the program since its implementation in the period between 2013 and 2019. Methods: A longitudinal retrospective study was carried at the Regional Reference Center III on 350,178 babies born in the analysis period. The paper reports the main results of overall coverage, referral rate, lost-to-follow-up rate,yield for PHI and shall determine various risk factor associations with hearing impairment Results: In Campania region, 318,878 newborns were enrolled at I level, with a coverage rate of 91.06%, 301,818 (86.18%) Well Infant Nurseries (WIN) and 17,060 (5.35%) Neonatal Intensive Care Unit (NICU) babies. PHI was identified in 413 children, 288 (69.73%) bilaterally and 125 (30.26%) unilaterally. The overall cumulative incidence rate of PHI was 1.29 per 1000 live-born infants (95% CI 1.17–1.42) with a quite steady tendency during the whole study period. Conclusions: This study confirms the feasibility and effectiveness of UNHS in Campania region also in a setting with major socioeconomic and health organization restrictions.The program meets quality benchmarks to evaluate the progress of UNHS. Nowadays, it is possible to achieve an early diagnosis of all types of HL avoiding the consequences of hearing deprivation

Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling

In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance in vitro and the adverse effect ototoxicity in vivo

Early Noise-Induced Hearing Loss Accelerates Presbycusis Altering Aging Processes in the Cochlea

Several studies identified hearing loss as a risk factor for aging-related processes, including neurodegenerative diseases, as dementia and age-related hearing loss (ARHL). Although the association between hearing impairment in midlife and ARHL has been widely documented by epidemiological and experimental studies, the molecular mechanisms underlying this association are not fully understood. In this study, we used an established animal model of ARHL (C57BL/6 mice) to evaluate if early noise-induced hearing loss (NIHL) could affect the onset or progression of age-related cochlear dysfunction. We found that hearing loss can exacerbate ARHL, damaging sensory-neural cochlear epithelium and causing synaptopathy. Moreover, we studied common pathological markers shared between hearing loss and ARHL, demonstrating that noise exposure can worsen/accelerate redox status imbalance [increase of reactive oxygen species (ROS) production, lipid peroxidation, and dysregulation of endogenous antioxidant response] and vascular dysfunction [increased expression of hypoxia-inducible factor-1alpha (HIF-1α) and vascular endothelial growth factor C (VEGFC)] in the cochlea. Unveiling the molecular mechanisms underlying the link between hearing loss and aging processes could be valuable to identify effective therapeutic strategies to limit the effect of environmental risk factors on age-related diseases

Pioglitazone represents an effective therapeutic target in preventing oxidative/inflammatory cochlear damage induced by noise exposure.

Recent progress in hearing loss research has provided strong evidence for the imbalance of cellular redox status and inflammation as common predominant mechanisms of damage affecting the organ of Corti including noise induced hearing loss. The discovery of a protective molecule acting on both mechanisms is challenging. The thiazolidinediones, a class of antidiabetic drugs including pioglitazone and rosiglitazone, have demonstrated diverse pleiotrophic effects in many tissues where they exhibit anti-inflammatory, anti-proliferative, tissue protective effects and regulators of redox balance acting as agonist of peroxisome proliferator-activated receptors (PPARs). They are members of the family of ligand regulated nuclear hormone receptors that are also expressed in several cochlear cell types, including the outer hair cells. In this study, we investigated the protective capacity of pioglitazone in a model of noise-induced hearing loss in Wistar rats and the molecular mechanisms underlying this protective effects. Specifically, we employed a formulation of pioglitazone in a biocompatible thermogel providing rapid, uniform and sustained inner ear drug delivery via transtympanic injection. Following noise exposure (120 dB, 10 kHz, 1 h), different time schedules of treatment were employed: we explored the efficacy of pioglitazone given immediately (1 h) or at delayed time points (24 and 48 h) after noise exposure and the time course and extent of hearing recovery were assessed. We found that pioglitazone was able to protect auditory function at the mid-high frequencies and to limit cell death in the cochlear basal/middle turn, damaged by noise exposure. Immunofluorescence and western blot analysis provided evidence that pioglitazone mediates both anti-inflammatory and anti-oxidant effects by decreasing NF-\u3baB and IL-1\u3b2 expression in the cochlea and opposing the oxidative damage induced by noise insult. These results suggest that intratympanic pioglitazone can be considered a valid therapeutic strategy for attenuating noise-induced hearing loss and cochlear damage, reducing inflammatory signaling and restoring cochlear redox balance. Copyright \ua9 2018 Paciello, Fetoni, Rolesi, Wright, Grassi, Troiani and Paludetti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Vascular endothelial growth factor (VEGF) expression in noise-induced hearing loss

Noise-induced hearing loss has been associated with alterations in cochlear blood flow. Our study analyzed the expression of Vascular Endothelial Growth Factor (VEGF) and its functional receptors, Flt-1 and Flk-1, in the cochlear structures of noise-exposed and unexposed guinea pigs. VEGF is a prototypical angiogenic agent, with multiple functions on vascular biology, ranging from vascular permeability to endothelial cell migration, proliferation, differentiation, and survival.Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 min. Auditory function was evaluated by electrocochleographic recordings at 2-20 kHz for 7 days. Noise-induced cochlear morphological changes were studied by immunohistochemistry and scanning electron microscopy. The expression of VEGF and its receptors was examined by immunohistochemistry and western blotting analysis. The hearing threshold shift reached a level of 60 dB SPL on day I after trauma and underwent a partial recovery over time, reaching a value of about 20 dB SPL on day 7. Outer hair cell loss was more prominent in the area located 14-16 min from the apex. Increased cochlear VEGF expression was observed in noise-exposed animals, in particular at the level of stria vascularis, spiral ligament, and spiral ganglion cells. No changes were observed in the expression of VEGF-receptors.Our data suggest a role for VEGF in the regulation of the vascular network in the inner ear after acoustic trauma and during auditory recovery, with potentially important clinical and therapeutic implications. (c) 2006 Elsevier B.V. All rights reserved