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Giovanna Zimatore,1,2 Marta Cavagnaro,3 Piotr H Skarzynski,4– 6 Anna R Fetoni,7 Stavros Hatzopoulos8 1Department of Theoretical and Applied Sciences, eCampus University, Novedrate, CO 22060, Italy; 2Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy; 3Department of Information Engineering, Electronics and Telecommunication, Sapienza University of Rome, Rome, Italy; 4World Hearing Center, Warsaw, Poland; 5Department of Heart Failure and Cardiac Rehabilitation, Medical University of Warsaw, Warsaw, Poland; 6Institute of Sensory Organs, Kajetany, Poland; 7Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy; 8Clinic of Audiology and ENT, University of Ferrara, Ferrara, ItalyCorrespondence: Giovanna ZimatoreDepartment of Theoretical and Applied Sciences, eCampus University Tel +39 338 959 4393Email giovanna.zimatore@uniecampus.itPurpose: 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 cut-off 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.Keywords: recurrence quantification analysis, early detection, otoacoustic emissions, TEOAEs, determinism, presbycusis

Background/objectives: Bimodal stimulation (BS), which combines the use of a cochlear implant (CI) in one ear and a hearing aid (HA) in the opposite ear, is an established strategy to treat hearing loss by exploiting the unique capabilities of each device. CIs stimulate the auditory nerve by bypassing damaged hair cells, while HAs amplify sounds by requiring a functional hearing residual. The aim of this systematic review is to investigate the advantages and disadvantages of BS such as speech perception in noise., Methods: We examined clinical studies published from October 2020 to July 2024, following the PRISMA guidelines, focusing on the advantages and disadvantages of BS on speech perception in noise in adulthood., Results: BS in adult patients significantly improves speech perception in quiet and noisy environments, especially for those with increased residual hearing. Unilateral CIs and BS perform similarly in quiet conditions, but BS significantly improves speech discrimination in noisy environments if loudness between the two devices is appropriately balanced., Conclusions: Directional microphones and programming software are new technologies that succeed in reducing environmental noise and improving verbal perception outcomes, although their features in the literature are controversial. In addition, the individuals using BS may face temporal mismatches mainly due to differing device latencies, affecting sound localization. Compensating for these mismatches can enhance localization accuracy. However, modulated noise remains a significant obstacle to verbal perception in noise. Valuable assessment tools such as music tests provide further information on hearing performance and quality of life. More research is needed to define certain selection criteria.

Background and Purpose: Cisplatin-induced sensorineural hearing loss is a significant clinical challenge. Although the potential effects of brain-derived neurotrophic factor (BDNF) have previously been investigated in some ototoxicity models, its efficacy in cisplatin-induced hearing loss remains uncertain. This study aimed to investigate the therapeutic potential of recombinant human BDNF (rhBDNF) in protecting cells against cisplatin-induced ototoxicity., Experimental Approach: Using an in vivo model of cisplatin-induced hearing loss, we investigated the beneficial effects of transtympanic administration of rhBDNF in a thermogel solution on hearing function and cochlear injury, using electrophysiological, morphological, immunofluorescence and molecular analyses., Key Results: Our data showed that local rhBDNF treatment counteracted hearing loss in rats receiving cisplatin by preserving synaptic connections in the cochlear epithelium and protecting hair cells (HCs) and spiral ganglion neurons (SGNs) against cisplatin-induced cell death. Specifically, rhBDNF maintains the balance of its receptor levels (pTrkB and p75), boosting TrkB-CREB pro-survival signalling and reducing caspase 3-dependent apoptosis in the cochlea. Additionally, it activates antioxidant mechanisms while inhibiting inflammation and promoting vascular repair., Conclusion and Implications: Collectively, we demonstrated that early transtympanic treatment with rhBDNF plays a multifaceted protective role against cisplatin-induced ototoxicity, thus holding promise as a novel potential approach to preserve hearing in adult and paediatric patients undergoing cisplatin-based chemotherapy., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: Metal carpentry includes a wide range of work activities such as welding and cutting metallic components, use of solvents and paints. Therefore, the employees in these types of activities are mainly exposed to welding fumes and volatile organic solvents. Here, we present an NMR-based metabolomic approach for assessing urinary profiles of workers in the same company that are exposed to two different risk factors., Methods: The study enrolled 40 male subjects exposed to welding fumes, 13 male subjects exposed to volatile organic compounds of a metal carpentry company, and 24 healthy volunteers. All samples were collected, in the middle of the working week at fast. Thirty-five urinary metabolites belonging to different chemical classes such as amino acids, organic acids and amines were identified and quantified. Results were processed by multivariate statistical analysis for identifying significant metabolites for each working group examined, compared to controls., Results: Workers exposed to welding fumes displayed urinary increase in glutamine, tyrosine, taurine, creatine, methylguanidine and pseudouridine associated to oxidative impairment, while workers exposed to volatile organic compounds showed higher urinary levels of branched chain aminoacids., Conclusion: Our work identified specific urinary profile related to each occupational exposure, even if it is below the threshold limit values., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 De Rosa, Giampaoli, Sciubba, Marini, Tranfo, Sisto, Miccheli, Tricarico, Fetoni and Spagnoli.)

Objectives: To describe the new semisynthetic total ossicular replacement prosthesis (New-SSTORP) and to evaluate the New-SSTORP ossiculoplasty results both with the presence and absence of the stapes superstructure., Study Design: Prospective study., Setting: Tertiary referral center., Methods: From April 2023 to May 2023, 18 New-SSTORP ossiculoplasties were performed by the first author. In all patients, the New-SSTORP was interposed between the footplate and the eardrum. The study group was divided into two groups (group A and group B). Group A included 13 patients with the absence of stapes superstructure. Group B included five patients with the presence of stapes superstructure. A successful reconstruction was defined as a postoperative air-bone gap ABG ≤20 dB. For all patients of groups A and B, the last audiometric control considered was performed in January 2024. The mean follow-up was 8½ months. The χ2 test was used to compare results. p < 0.05 was considered significant., Main Outcome Measures: Mean postoperative ABG ≤20 dB., Results: At the end of follow-up, the overall success rate (ABG ≤20 dB) of New-SSTORP ossiculoplasty was obtained in 88.8% (n = 16 of 18) of cases. In group A, the success rate of New-SSTORP ossiculoplasty occurred in 84.6% (n = 11 of 13) of cases, and in group B, the success rate of New-SSTORP ossiculoplasty occurred in 100% (n = 5 of 5) of cases. There was no audiological statistically significant difference between groups A and B (Fisher value is 1; p < 0.05). In all cases, the time for positioning of New-SSTORP was about 5 minutes., Conclusion: The New-SSTORP has a minimal technical challenge for building and placement. The New-SSTORP ossiculoplasty results are very good both with the presence and absence of SS., Competing Interests: Sources of support and disclosure of funding: G.M. has patented the shaft prosthesis and does not have funding to disclose. The remaining authors, disclose no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) may have a heterogeneous response to medical/surgical treatments based on endotypes. Data correlating biomarkers and severity of the disease are lacking. We aimed to determine if IL-5 and calprotectin may be useful in defining severity of disease and identifying uncontrolled patients., Methods: This was a case-control study including 81 patients with diffuse CRSwNP who underwent at least one previous surgery and treated with intranasal steroids. We enrolled 39 uncontrolled patients (SNOT-22 ≥ 40 and two or more cycles of systemic corticosteroids in last year) (Group A) and 42 controlled one (SNOT-22 < 40 and less than two cycles of systemic corticosteroids in last year) (Group B). We analyzed IL-5 and calprotectin in both nasal secretions and nasal polyp tissue., Results: Calprotectin and IL-5 were significantly higher in Group A in both secretions and tissue, and the higher the number of previous surgeries, the higher the levels detected in nasal secretions. At univariate analyses, smoking, asthma, non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NSAID-ERD), blood eosinophilia, neutrophils, and eosinophils at nasal cytology were significantly associated with uncontrolled disease. Multivariate analyses showed that asthma, NSAID-ERD, and IL-5 in nasal secretion/polyp tissue were significantly related to the risk of uncontrolled disease., Conclusions: Our data suggest that asthma, NSAID-ERD, and IL-5 in nasal secretions/tissue may be helpful to identify more severe patients, as they are related to the risk of uncontrolled disease. Nonetheless, high levels of calprotectin and neutrophilia were also observed in uncontrolled patients, especially after multiple surgeries., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Downbeat nystagmus (DBN) is a neuro-otological finding frequently encountered by clinicians dealing with patients with vertigo. Since DBN is a finding that should be understood because of central vestibular dysfunction, it is necessary to know how to frame it promptly to suggest the correct diagnostic-therapeutic pathway to the patient. As knowledge of its pathophysiology has progressed, the importance of this clinical sign has been increasingly understood. At the same time, clinical diagnostic knowledge has increased, and it has been recognized that this sign may occur sporadically or in association with others within defined clinical syndromes. Thus, in many cases, different therapeutic solutions have become possible. In our work, we have attempted to systematize current knowledge about the origin of this finding, the clinical presentation and current treatment options, to provide an overview that can be used at different levels, from the general practitioner to the specialist neurologist or neurotologist., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Marcelli, Giannoni, Volpe, Faralli, Fetoni and Pettorossi.)

Due to its chemical properties, styrene is largely employed in the manufacturing of several products including rubber, polymers and resins, and it is particularly suitable for shipbuilding industry purposes. In this context, the main exposure to styrene occurs in occupational settings. Despite its widespread use, its long-term effects on human health at the occupational level are still unclear. The aim of this pilot study was to evaluate changes in styrene exposure biomarkers related to the metabolic and oxidative stress profiles in the urine of seventeen shipyard workers and seventeen non-exposed subjects. Urinary metabolites were assessed by means of NMR spectroscopy, including mandelic and phenylglyoxylic acids; four oxidative stress biomarkers, namely 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine and 3-nitrotyrosine, were evaluated via HPLC-MS/MS. The metabolic profiles of exposed workers showed both long- and short-term metabolic responses to styrene exposure compared to non-exposed subjects. From the comparison between non-exposed and before-shift workers, only 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were significantly different (long term exposure response). At the same time, comparing the non-exposed group with after-shift workers, we observed lower levels of pseudouridine and 1-methylnicotinamide and higher glutamine levels in after-shift workers. The comparison between before-shift and after-shift workers showed that 8-oxo-7,8-dihydroguanine significantly increased after the shift, suggesting its involvement in the exposure to styrene (short-term exposure response). The obtained results, although preliminary, allow us to lay the basis for further human studies aimed at establishing a global understanding of styrene metabolism.

Introduction: Sensorineural hearing loss (SNHL) has been suggested to be possibly related to congenital toxoplasmosis (CT), although its prevalence varies from 0% to 26%. This variance appears to be dependent especially on early timing of treatment. However, the available data are based on outdated studies conducted on small groups of patients that lack homogeneity. Therefore, to establish evidence-based guidelines for audiologic monitoring in CT, we conducted a comprehensive evaluation of a large case series over a long period of time., Patients and Methods: This is a single-center, retrospective cohort that enrolled all infants and children who were exposed in utero to Toxoplasma gondii and/or congenitally infected between September 1980 and December 2022. They underwent standard serial audiological evaluations to detect possible SNHL at an early stage. The first evaluation was performed during the initial assessment to define the onset of congenital toxoplasmosis, with another evaluation conducted at least at 12 months of life., Results: We collected data from 1,712 patients, and 183 (10.7%) were diagnosed with CT. Among these cases, 78 children (42.6%) presented with symptomatic CT at the onset, exhibiting ocular findings (21.1%), clinical cerebral manifestations (6.1%), and/or abnormal findings on neuroimaging (35.5%). Therapy was administrated at the onset in 164 patients (89.6%) with 115 of them starting treatment prior to 2.5 months of age (0-388, median 32.00 ± 92.352 days of life). Only one patient presented with SNHL at the onset, but this was apparently unrelated to CT. The median number of audiological assessments was 2.2 ± 1.543 (2-10). No patients developed any grade of delayed hearing loss, both in treated and untreated groups. The median age at last audiological evaluation was 2.3 ± 2.18 years (1-8), although the median follow-up period was 12.4 years (±6.3), ranging from 1 to 27 years., Conclusions: Based on these data, it appears that SNHL may be less frequent in CT than previously assumed. We recommend conducting an audiological assessment at the onset (within the first 2.5 months of life) to comprehensively define the type of CT onset, and then conducting another evaluation within 9 months of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Salomè, Malesci, Delle Cave, Amitrano, Gammella, Fanelli, Capone, Capasso, Fetoni and Raimondi.)

Background: Redox imbalance and inflammation have been proposed as the principal mechanisms of damage in the auditory system, resulting in functional alterations and hearing loss. Microglia and astrocytes play a crucial role in mediating oxidative/inflammatory injury in the central nervous system; however, the role of glial cells in the auditory damage is still elusive., Objectives: Here we investigated glial-mediated responses to toxic injury in peripheral and central structures of the auditory pathway, i.e., the cochlea and the auditory cortex (ACx), in rats exposed to styrene, a volatile compound with well-known oto/neurotoxic properties., Methods: Male adult Wistar rats were treated with styrene (400 mg/kg daily for 3 weeks, 5/days a week). Electrophysiological, morphological, immunofluorescence and molecular analyses were performed in both the cochlea and the ACx to evaluate the mechanisms underlying styrene-induced oto/neurotoxicity in the auditory system., Results: We showed that the oto/neurotoxic insult induced by styrene increases oxidative stress in both cochlea and ACx. This was associated with macrophages and glial cell activation, increased expression of inflammatory markers (i.e., pro-inflammatory cytokines and chemokine receptors) and alterations in connexin (Cxs) and pannexin (Panx) expression, likely responsible for dysregulation of the microglia/astrocyte network. Specifically, we found downregulation of Cx26 and Cx30 in the cochlea, and high level of Cx43 and Panx1 in the ACx., Conclusions: Collectively, our results provide novel evidence on the role of immune and glial cell activation in the oxidative/inflammatory damage induced by styrene in the auditory system at both peripheral and central levels, also involving alterations of gap junction networks. Our data suggest that targeting glial cells and connexin/pannexin expression might be useful to attenuate oxidative/inflammatory damage in the auditory system., (© 2023. The Author(s).)

With more than 466 million people affected, hearing loss represents the most common sensory pathology worldwide. Despite its widespread occurrence, much remains to be explored, particularly concerning the intricate pathogenic mechanisms underlying its diverse phenotypes. In this context, metabolomics emerges as a promising approach. Indeed, lying downstream from molecular biology's central dogma, the metabolome reflects both genetic traits and environmental influences. Furthermore, its dynamic nature facilitates well-defined changes during disease states, making metabolomic analysis a unique lens into the mechanisms underpinning various hearing impairment forms. Hence, these investigations may pave the way for improved diagnostic strategies, personalized interventions and targeted treatments, ultimately enhancing the clinical management of affected individuals. In this comprehensive review, we discuss findings from 20 original articles, including human and animal studies. Existing literature highlights specific metabolic changes associated with hearing loss and ototoxicity of certain compounds. Nevertheless, numerous critical issues have emerged from the study of the current state of the art, with the lack of standardization of methods, significant heterogeneity in the studies and often small sample sizes being the main limiting factors for the reliability of these findings. Therefore, these results should serve as a stepping stone for future research aimed at addressing the aforementioned challenges.

Objective: The paediatric caregiver version of the Dizziness Handicap Inventory (DHI-PC) questionnaire is a useful Quality of Life (QoL) evaluation instrument for children experiencing dizziness, vertigo or unsteadiness. Its English version has been validated for use with a paediatric population between 5 and 12 years of age. The aim of this work is to validate the DHI-PC into Italian for both patient assessment and appropriate rehabilitative treatment planning., Materials and Methods: Cross-cultural adaptation of the DHI-PC was performed using standard techniques. Items of the original questionnaire were translated into Italian by two bilingual investigators. Two native English speakers carried out a back translation of the new version that was compared with the original to check that they had the same semantic value. A pre-final version was obtained by an expert committee and was applied in a pilot test., Results: A total of 42 patient caregivers completed the final adapted questionnaire twice with an interval of 2 weeks. Internal consistency was excellent, with Cronbach's alpha = 0.95., Conclusions: Our study showed evidence that the Italian version of DHI-PC is a valid and reliable tool to quantify the degree of dizziness handicap and its application is recommended., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Despite the plethora of studies investigating listening effort and the amount of research concerning music perception by cochlear implant (CI) users, the investigation of the influence of background noise on music processing has never been performed. Given the typical speech in noise recognition task for the listening effort assessment, the aim of the present study was to investigate the listening effort during an emotional categorization task on musical pieces with different levels of background noise. The listening effort was investigated, in addition to participants' ratings and performances, using EEG features known to be involved in such phenomenon, that is alpha activity in parietal areas and in the left inferior frontal gyrus (IFG), that includes the Broca's area. Results showed that CI users performed worse than normal hearing (NH) controls in the recognition of the emotional content of the stimuli. Furthermore, when considering the alpha activity corresponding to the listening to signal to noise ratio (SNR) 5 and SNR10 conditions subtracted of the activity while listening to the Quiet condition-ideally removing the emotional content of the music and isolating the difficulty level due to the SNRs- CI users reported higher levels of activity in the parietal alpha and in the homologous of the left IFG in the right hemisphere (F8 EEG channel), in comparison to NH. Finally, a novel suggestion of a particular sensitivity of F8 for SNR-related listening effort in music was provided., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cartocci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Despite recent advances in biomolecular research that have improved our knowledge of cholesteatoma pathogenesis, the reasons behind its highly variable clinical course are still not clarified. It has been proposed that biological signaling between peri-matrix and matrix cells could play a critical role in disease homeostasis. The aim of our study was to analyze the expression of inflammatory (IL-1β), hyper-proliferative (STAT-3, TGF-β), and angiogenic (VEGF-C, PDGFr) factors in congenital and acquired cholesteatomas (both in adults and children), which might correlate with the clinical features observed. We performed an experimental study on 37 patients (29 males and 8 females, ranging from 4 to 66 years of age) who were diagnosed with cholesteatoma between 2020 and 2021 in our institution. All patients underwent clinical, audiologic, and radiologic assessments. Bone erosion grading and staging of cholesteatoma growth were assessed through preoperative evaluation and intraoperative middle ear findings, according to the PTAM System proposed by the Japan Otological Society (2016). Retro-auricular skin specimens were intraoperatively collected in all patients. Skin and cholesteatoma samples were analyzed through histopathological, western blot, and immunohistochemical evaluations. The expression rate was measured to find out the differences between congenital and acquired cholesteatomas as well as between the adult and pediatric populations. Expression of angiogenic, inflammatory, and proliferative biomarkers is significantly increased in acquired cholesteatomas in children as compared to congenital and acquired forms in adults, in accordance with the higher stage of disease shown by imaging, surgical, and histological features. Our data suggest that pathways already supposed to be involved in the pathogenesis of cholesteatomas could be differently activated in more destructive forms, typically found in children. The identification of potential biomarkers of cholesteatoma aggressiveness could lead to more personalized management (timing of intervention, recurrence prevention) and the future identification of anti-growth/anti-proliferative agents as non-surgery therapeutic options.

Cochlear redox unbalance is the main mechanism of damage involved in the pathogenesis of noise-induced-hearing loss. Indeed, the increased free radical production, in conjunction with a reduced efficacy of the endogenous antioxidant system, plays a key role in cochlear damage induced by noise exposure. For this reason, several studies focused on the possibility to use exogenous antioxidant to prevent or attenuate noise-induce injury. Thus, several antioxidant molecules, alone or in combination with other compounds, have been tested in both experimental and clinical settings. In our findings, we tested the protective effects of several antioxidant enzymes, spanning from organic compounds to natural compounds, such as nutraceuticals of polyphenols. In this review, we summarize and discuss the strengths and weaknesses of antioxidant supplementation focusing on polyphenols, Q-Ter, the soluble form of CoQ10, Vitamin E and N-acetil-cysteine, which showed great otoprotective effects in different animal models of noise induced hearing loss and which has been proposed in clinical trials.

Brain-derived neurotrophic factor (BDNF) has a crucial function in the central nervous system and in sensory structures including olfactory and auditory systems. Many studies have highlighted the protective effects of BDNF in the brain, showing how it can promote neuronal growth and survival and modulate synaptic plasticity. On the other hand, conflicting data about BDNF expression and functions in the cochlear and in olfactory structures have been reported. Several clinical and experimental research studies showed alterations in BDNF levels in neurodegenerative diseases affecting the central and peripheral nervous system, suggesting that BDNF can be a promising biomarker in most neurodegenerative conditions, including Alzheimer's disease, shearing loss, or olfactory impairment. Here, we summarize current research concerning BDNF functions in brain and in sensory domains (olfaction and hearing), focusing on the effects of the BDNF/TrkB signalling pathway activation in both physiological and pathological conditions. Finally, we review significant studies highlighting the possibility to target BDNF as a biomarker in early diagnosis of sensory and cognitive neurodegeneration, opening new opportunities to develop effective therapeutic strategies aimed to counteract neurodegeneration.

Permanent childhood hearing impairment (PCHI) represents the most frequent sensory pathology at birth. PCHI has a relevant psychological impact on the life of both the affected children and their families. Thus, the aim of this work is to explore the degree of parental distress felt by mothers of a deaf or hard-of-hearing child, to determine if this stress is associated with variables related to the children's health (e.g., the severity of hearing loss, presence of other conditions, difficulty with treatment options, difficulty with rehabilitation) or family characteristics such as socio-economic and educational status. The study used the Parenting Stress Index-Short Form (PSI-SF) questionnaire administered to mothers. The results were analyzed in relation to variables such as parents' education level, number of children, severity of hearing loss, presence of other chronic conditions, presence of cognitive delay, familiarity with hearing loss, time of diagnosis, use of prosthetics, and start in a rehabilitation program. The data indicate a correlation between maternal stress levels and low-educational levels, as well as the presence of congenital infections and cognitive delay. These results highlight the need for a comprehensive physical and psychological approach for hearing-impaired children, as stress factors can affect the adherence to effective rehabilitation.

Several studies identified noise-induced hearing loss (NIHL) as a risk factor for sensory aging and cognitive decline processes, including neurodegenerative diseases, such as dementia and age-related hearing loss (ARHL). Although the association between noise- and age-induced hearing impairment has been widely documented by epidemiological and experimental studies, the molecular mechanisms underlying this association are not fully understood as it is not known how these risk factors (aging and noise) can interact, affecting memory processes. We recently found that early noise exposure in an established animal model of ARHL (C57BL/6 mice) accelerates the onset of age-related cochlear dysfunctions. Here, we extended our previous data by investigating what happens in central brain structures (auditory cortex and hippocampus), to assess the relationship between hearing and memory impairment and the possible combined effect of noise and sensory aging on the cognitive domain. To this aim, we exposed juvenile C57BL/6 mice of 2 months of age to repeated noise sessions (60 min/day, pure tone of 100 dB SPL, 10 kHz, 10 consecutive days) and we monitored auditory threshold by measuring auditory brainstem responses (ABR), spatial working memory, by using the Y-maze test, and basal synaptic transmission by using ex vivo electrophysiological recordings, at different time points (1, 4 and 7 months after the onset of noise exposure, corresponding to 3, 6 and 9 months of age). We found that hearing loss, along with accelerated presbycusis onset, can induce persistent synaptic alterations in the auditory cortex. This was associated with decreased memory performance and oxidative-inflammatory injury in the hippocampus, the extra-auditory structure involved in memory processes. Collectively, our data confirm the critical relationship between auditory and memory circuits, suggesting that the combined detrimental effect of noise and sensory aging on hearing function can be considered a high-risk factor for both sensory and cognitive degenerative processes, given that early noise exposure accelerates presbycusis phenotype and induces hippocampal-dependent memory dysfunctions., Competing Interests: Declaration of Competing Interest The authors declare that no commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background and Objectives : Midlife hearing loss (HL) has been considered as a major modifiable risk factor for a later-life progression to dementia. Our aim was to detect a link between precocious sensorineural hearing loss (SNHL) and mild cognitive impairment (MCI) and their association to putative risk factors for a common pathology. Materials and methods: In this study, a retrospective case-control study was carried out. A total of 112 patients were enrolled as following: 81 patients with bilateral SNHL and 31 subjects with normal hearing, whose ages ranged from 50 to 65 years. Both groups performed pure tone audiometry, a tinnitus handicap inventory (THI), Mini-Mental State examination (MMSE), and the Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Results: The mean age was 58 ± 5.2 in SNHL patients and 53.2 ± 4.8 in the control group. The mean pure tone average in the SNHL group was 40.2 ± 18.7 dB HL on the right side and 41.2 ± 17.2 dB HL on the left side, while in the control group it was 12.5 ± 2.8 dB HL on right side and 12.4 ± 3.1 dB HL on left side. About 64% of patients with SNHL exhibited comorbidities, and the most common condition was hypertension. Altered MoCA test scores were significantly related to the pure tone averages in patients with SNHL compared to the control group ( p = 0.0004), while the differences in the HADS-A and HADS-D were not significant. Furthermore, a significant correlation was observed in SNHL patients between an altered MoCA test and hypercholesterolemia ( p = 0.043). Conclusions: Hearing impairment and screening tests to detect MCI should be considered in the midlife in order to carry out strategies to prevent the progression to dementia. Hypertension and hypercholesterolemia are two risk factors in the development of endothelial dysfunction, oxidative stress, and vascular inflammation, and may represent the common pathology linking the inner ear and brain damage.

Experimental and clinical data suggest a tight link between hearing and cognitive functions under both physiological and pathological conditions. Indeed, hearing perception requires high-level cognitive processes, and its alterations have been considered a risk factor for cognitive decline. Thus, identifying common pathogenic determinants of hearing loss and neurodegenerative disease is challenging. Here, we focused on redox status imbalance as a possible common pathological mechanism linking hearing and cognitive dysfunctions. Oxidative stress plays a critical role in cochlear damage occurring during aging, as well as in that induced by exogenous factors, including noise. At the same time, increased oxidative stress in medio-temporal brain regions, including the hippocampus, is a hallmark of neurodegenerative disorders like Alzheimer's disease. As such, antioxidant therapy seems to be a promising approach to prevent and/or counteract both sensory and cognitive neurodegeneration. Here, we review experimental evidence suggesting that redox imbalance is a key pathogenetic factor underlying the association between sensorineural hearing loss and neurodegenerative diseases. A greater understanding of the pathophysiological mechanisms shared by these two diseased conditions will hopefully provide relevant information to develop innovative and effective therapeutic strategies.

Background: Platinum compounds are a group of fundamental chemotherapeutics used in the treatment of solid tumors, but they are burdened by side effects, such as ototoxicity. The objective of this study was to evaluate the incidence of ototoxicity caused by platinum compounds and the risk factors affecting its appearance/progression., Methods: Data from 53 patients who received platinum compounds and who had been off therapy for at least 5 years were analyzed. We collected data relating to audiometry conducted annually from the end of treatment and for at least 5 subsequent years, as well as information concerning the oncological history and comorbidities., Results: At the end of the treatment, 17 patients (32.08%) presented ototoxicity, according to the Boston SIOP Ototoxicity Scale; the risk factors included a higher serum creatinine value at diagnosis, having undergone cranial radiotherapy, and needing magnesium supplementation. After 5 years from the end of the treatment, the number of patients with exhibiting ototoxicity was 31 (58.5%); the factors that influenced the onset/progression of the damage were having undergone radiotherapy (HR 1.23; p < 0.01) and having received therapy with aminoglycosides (HR 1.27; p < 0.01)., Conclusions: Ototoxicity caused by platinum compounds can occur even after the conclusion of the treatments, and the factors affecting its progression are radiotherapy and the aminoglycosides therapy.

Background: Currently, the novel coronavirus (SARS-CoV-2) causes an acute respiratory illness named COVID-19 and is a controversial risk factor for hearing loss (HL). Herein, we aim to describe the associated symptoms and to evaluate hearing function in the COVID-19 pediatric population., Methods: A retrospective cross-sectional observational study was carried out on 37 children who contracted COVID-19 infection with no previous audio-vestibular disorders. Clinical data on the infections were collected, and an audiological assessment of all affected children was performed by using different diagnostic protocols according to their age., Results: Fever, upper respiratory and gastrointestinal manifestations were common presentations of infection. Audiological function was normal in 30 (81.08%) children, while 7 children showed an increased hearing threshold: 6 (16.21%) had transient conductive hearing loss (CHL) due to middle ear effusion and normalized at the follow-up and 1 had sensorineural hearing loss (SNHL). A single child was affected by bilateral SNHL (2.7%); however, he underwent a complete audiological work-up leading to a diagnosis of genetic HL due to a MYO6 gene mutation which is causative of progressive or late onset SNHL., Conclusions: HL needs to be considered among the manifestations of COVID-19 in children, nevertheless, we found cases of transient CHL. The onset of HL during or following COVID-19 infection does not eliminate the indication for maintaining audiological surveillance and audiological work-ups, including genetic diagnosis, to avoid the risk of mistaking other causes of HL.

Purpose: Irreversible bilateral sensorineural hearing loss is a common side effect of platinum compounds. Because of the extended overall survival, a prolonged hearing surveillance and management of hearing impairments are emerging concerns for pediatric oncology., Methods: In this retrospective observational study, we enrolled 38 children out of 116 treated at our institution by chemotherapy (cisplatin and/or carboplatin) with or without irradiation between 2007 and 2014, submitted to hearing monitoring before every cycle of chemotherapy, and who completed a 5-year long-term audiological follow-up. Chemotherapy regimens, demographic findings, cumulative doses, and cranial irradiation were compared., Results: At the end of 5-year follow-up, ototoxicity was significantly increased compared to that observed at the end of chemotherapy (52.5% vs 39.5%, p < 0.001). A late onset of hearing loss was experienced in 13.1% of children, while in 26.3% progressive hearing loss was measured. Deafness at the end of chemotherapy and irradiation were significant prognostic factors for late ototoxicity outcomes (Odds Ratio 7.2-CI 1.67-31.1-p < 0.01 and 5.25-CI 1.26-21.86-p < 0.01 respectively). No significant differences were found between cisplatin and combined treatment (i.e., cisplatin shifted to carboplatin during monitoring for the onset of ototoxicity) and ototoxicity was not associated with platinum compounds cumulative dose (p > 0.05). 13.1% of children needed hearing aids at the end of follow-up., Conclusion: Long-term monitoring of at least 5 years prevents the harmful effects of hearing deprivation identifying late onset/progressive hearing loss after platinum compound chemotherapy in children thanks to early hearing rehabilitation, especially in those who underwent multimodal therapy or subjected to irradiation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the relationship between risk of Benign Paroxysmal Positional Vertigo (BPPV) recurrence and hypothyroidism treated with hormone replacement therapy (HRT)., Methods: 797 patients with idiopathic BPPV were divided into two groups: 250 patients with recurrence of BPPV (R-BPPV) and 547 patients without recurrence (NR-BPPV). Regarding patients with thyroid disease on HRT, we collected serum test results of thyroid-stimulating hormone (TSH), free triiodothyronine f-T3, free thyroxine f-T4, thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab)., Results: Hypothyroidism in long-term HRT was found in 61/250 (24.4%) patients of the R-BPPV group vs 79/547 (14.4%) of the NR-BPPV-group (p = 0.0006). Hashimoto thyroiditis (HT) was associated with recurrence (p < 0.0001). A significant correlation was found between recurrence and level of serum TPO-Ab (p = 0.0117) and TG-Ab (p = 0.0025), but not with mean serum TSH, f-T3 and f-T4., Conclusions: We assume that patients with hypothyroidism in HRT have an increased risk of BPPV recurrence, which is particularly strong for patients with HT and positive thyroid antibodies, suggesting an association between autoimmunity and recurrent vertigo., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Objectives of the present work were to analyze the prevalence of hearing loss in our population of screened newborns during the first 9 years of the universal newborn hearing screening (UNHS) program at University Hospital Sassari (Italy) (AOU Sassari), to analyze the risk factors involved, and to analyze our effectiveness in terms of referral rates and dropout rates. Methods: Monocentric retrospective study whose target population included all the newborns born or referred to our hospital between 2011 and 2019. Results: From 2011 to 2019, a total of 11,688 babies were enrolled in our screening program. In total, 3.9‱ of wellborn babies and 3.58% of neonatal intensive care unit (NICU) babies had some degree of hearing loss. The most frequently observed risk factors among non-NICU babies were family history of hearing loss (3.34%) and craniofacial anomalies (0.16%), among NICU babies were low birth weight (54.91%) and prematurity (24.33%). In the multivariate analysis, family history of hearing loss (p < 0.001), NICU (p < 0.001), craniofacial anomalies (p < 0.001), low birth weight (<1500 g) (p = 0.04) and HIV (p = 0.03) were confirmed as risk factors. Conclusions: Our data are largely consistent with the literature and most results were expected, one relevant exception being the possible role of NICU as a confounding factor and the limited number of risk factors confirmed in the multivariate analysis.

Background: So far, no medical treatment is available for cholesteatoma (C) and the only effective therapy is complete surgical removal, but recurrence is common even after surgical treatment. While C is classically divided into two clinical phenotypes, congenital and acquired, only a few studies have focused on its potential biomarkers. This study aims to revise the literature to identify which biomarkers can define the endotype of C., Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process to identify published experimental articles about molecular biomarkers in C., Results: KGF and its receptor, MMP-9, KRT-1, KRT-10, and MIF might be considered biomarkers of recurrence, whereas Ki-67, TLR-4, RANKL, IL17, MMP-2, MMP-9, IL6, TNF-α, should be considered more specifically as biomarkers of bony erosion., Conclusions: These results are interesting especially from a prognostic point of view, nevertheless more studies are needed to search new biomarkers of C that could completely change not only the therapeutic standards of the disease, but also the clinical history of C itself in the era of precision medicine.

Pathogenic mutations in the Gjb2 and Gjb6 genes, encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, have been linked to the most frequent monogenic hearing impairment, nonsyndromic hearing loss, and deafness DFNB1. It is known that Cx26 plays an important role in auditory development, while the role of Cx30 in hearing remains controversial. Previous studies found that partial deletion of Cx26 can accelerate age-related hearing loss (ARHL), a multifactorial complex disorder, with both environmental and genetic factors contributing to the etiology of the disease. Here, we investigated the role of Cx30 in cochlear-aging processes using a transgenic mouse model with total deletion of Cx30 (Cx30 ΔΔ mice), in which Cx30 was removed without perturbing the surrounding sequences. We show that these mice are affected by exacerbated ARHL, with increased morphological cochlear damage, oxidative stress, inflammation, and vascular dysfunctions. Overall, our data demonstrate that Cx30 deletion can be considered a genetic risk factor for ARHL, making cochlear structures more susceptible to aging processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Paciello, Zorzi, Raspa, Scavizzi, Grassi, Mammano and Fetoni.)

Introduction: The cause of tinnitus improvement in cochlear implant (CI) users is not understood. On the basis that a spatially limited dysfunction in the auditory pathway could cause tinnitus, we used single-channel stimulation to evaluate any variation of tinnitus-perceived loudness and identify the cochlear regions involved., Materials and Methods: It was an observational prospective case-crossover study. After the first mapping, 21 adults with unilateral CI and chronic tinnitus expressed their tinnitus loudness based on the Visual Analog Scale (VAS) score (0-10) at baseline (L 0 ), during a 10 s single-channel stimulation with C-level of electric current (L 1 ) and 30 min after CI activation (L 2 ). Tinnitus reduction [R T = (L 0 - L 1 ) × 100/L 0 ] > 50% was considered significant. VAS outcomes were compared between baseline (L0) and (each) single-channel stimulation (L1) to find the channel with the greatest R T (suppressive channel-SC), whose frequency range revealed the cochlear region involved. Seven patients with asymmetric hearing loss underwent the pitch-matching test to identify the actual frequency evoked by the SC. We compared selective (L 1 ) and non-selective (L 2 ) intracochlear stimulation using paired t -test. Preoperative Tinnitus Handicap Inventory (THI) score was compared with those at 1, 6, and 12 months with paired t -tests to evaluate long-term tinnitus perception., Results: We observed a significant reduction of tinnitus loudness during the experimental procedure [L 0 (6.4 ± 2.4) vs. L 1 (1.7 ± 2.7), p = 0.003]. A total of 15/21 patients (71.4%) had a significant (R T > 50%) and selective improvement, reporting a mean L 1 of 0.4 ± 2.0 ( p = 0.0001). In 10/15 (66.6%) patients, the SC was in the apical turn, within 1,000 Hz; in 5/15 patients (33.4%) within 4,000 Hz. The cochlear region 125-313 Hz was the most affected by tinnitus improvement ( p = 0.0074). Targeted stimulation was more effective than non-selective stimulation [L 1 vs. L 2 (4.3 ± 2.5), p = 0.0022]. In 3/7 patients, the perceived pitch did not fall within the SC frequency ranges. All patients with selective attenuation described tinnitus as monotone. Patients with non-selective attenuation had polyphonic tinnitus and better THI results after 1 year., Conclusion: Targeted intracochlear electrical stimulation improved chronic tinnitus perception, especially in monotone tinnitus, and the apical region was mainly involved. Our results provide new insights into the pathophysiological mechanisms of tinnitus and targets for innovative therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Di Nardo, Di Cesare, Tizio, Paludetti and Fetoni.)

Significance: Cisplatin is an important component of treatment regimens for different cancers. Notwithstanding that therapeutic success often results from partial efficacy or stabilizing the disease, chemotherapy failure is driven by resistance to drug treatment and occurrence of side effects, such as progressive irreversible ototoxicity. Cisplatin's side effects, including ototoxicity, are often dose limiting. Recent Advances: Cisplatin ototoxicity results from several mechanisms, including redox imbalance caused by reactive oxygen species production and lipid peroxidation, activation of inflammation, and p53 and its downstream pathways that culminate in apoptosis. Considerable efforts in research have targeted development of molecular interventions that can be concurrently administered with cisplatin or other chemotherapies to reduce side effect toxicities while preserving or enhancing the antineoplastic effects. Evidence from studies has indicated some polyphenols, such as curcumin, can help to regulate redox signaling and inflammatory effects. Furthermore, polyphenols can exert opposing effects in different types of tissues, that is, normal cells undergoing stressful conditions versus cancer cells. Critical Issues: This review article summarizes evidence of curcumin antioxidant effect against cisplatin-induced ototoxicity that is converted to a pro-oxidant activity in cisplatin-treated cancer cells, thus providing an ideal chemosensitivity combined with otoprotection. Polyphenols can modulate the adaptive responses to stress in the cisplatin-exposed cochlea. These adaptive effects can result from the interaction/cross talk between the cell's defenses, inflammatory molecules, and the key signaling molecules of signal transducers and activators of transcription 3 (STAT-3), nuclear factor κ-B (NF-κB), p53, and nuclear factor erythroid 2-related factor 2 (Nrf-2). Future Directions: We provide molecular evidence for alternative strategies for chemotherapy with cisplatin addressing the otoprotection and chemosensitization properties of polyphenols. Antioxid. Redox Signal . 36, 1229-1245.

Background: An early hearing detection and intervention program (EHDI) is the first step for the habilitation of children with permanent hearing impairment (PHI). Actually, early intervention programs have increasingly shifted toward family involvement, emphasizing that the child's family should take an active role in the habilitation process. Therefore, familiar empowerment is the best way to improve a child's emerging abilities. The aim of this study was to investigate parental self-efficacy beliefs and involvement as well as the language skills of deaf or hard of hearing DHH children who were habilitated with hearing aids and followed using the T.A.T.A web app (NeonaTal Assisted TelerehAbilitation), an example of asynchronous telepractice., Methods: The study describes the early stages of the habilitation program of 15 PHI children followed through the T.A.T.A. web app, which empowers families through a weekly questionnaire submitted during the first 270 to 360 days of their child's life, for 14 weeks. The family involvement rate scale (FIRS) was used to evaluate parental compliance, and all children received in-person visits at the beginning and at the end of the training period., Results: The children showed greater auditory perceptual skills at the end of the training period on the basis of both the Infant Listening Progress Profile (ILiP) score and the Categories of Auditory Performance (CAP) and FIRS scales. In other words, the auditory skills improved with age as well as with parental participation., Conclusions: The T.A.T.A. web app promotes a proactive management and a tailored habilitation through an active familiar involvement, easily achieved in clinical routine and in emergency settings without additional costs.

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., (© 2021. The Author(s).)