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Introduction: Stereotactic radiosurgery (SRS) is a precise, single-session irradiation technique commonly used to treat vestibular schwannomas. However, SRS can lead to irreversible hearing loss, most probably due to irradiation-induced damage to the nearby inner ear. Currently, no preventive or therapeutic options exist, highlighting the need for the development and experimental testing of novel treatments. To enable this research, we developed a protocol for inducing unilateral hearing loss in mice through targeted unilateral cochlear irradiation. Material and methods: We used 6-week-old C57BL/6J mice and administered precise unilateral irradiation in the vicinity of the cochlea using a Leksell Gamma Knife® Icon device. The precision and reproducibility of the targeted area were ensured through radiological imaging for each mouse using the integrated cone beam CT scan and co-registering these images with MRI and CT mouse atlas images. To ensure meaningful translational data, we placed a single 4 mm isocenter lateral to the cochlea with the 80% isodose line passing through the modiolus to deliver 8 (n = 3), 16 (n = 5), 24 (n = 8), and 32 (n = 8) Gy. Auditory brainstem responses (ABR) were measured one day prior to irradiation (baseline) and at one and four weeks post-irradiation. Statistical analysis was performed using two-way repeated measures ANOVA with Bonferroni correction. Results: In all experimental groups, the irradiation dose received by the non-irradiated cochlea was less than 15% of that received by the irradiated cochlea. In the 32 Gy group, irradiation of cochlea yielded significant threshold shifts, compared to the non-irradiated ear, at 22.6 and 32 kHz on day 7 and to a greater degree on day 28. Similar but less pronounced effects were observed in the 24 Gy group. Furthermore, we observed a unilateral decrease in the p-p and wave I amplitudes, following 72-78 dB SPL click stimulation, in both groups. No hearing loss was detected in the 8 and 16 Gy groups. Histopathological studies are ongoing. Conclusions: Targeted near-cochlear irradiation in mice induces unilateral dose-dependent high-frequency hearing loss, evidenced by increased threshold shifts and decreased ABR wave I amplitudes. This model provides a valuable tool for exploring the radiobiological mechanisms underlying SRS-induced hearing loss and for testing potential radioprotec-tive agents. [ABSTRACT FROM AUTHOR]

Cochlear hair cells and their associated auditory neurons do not regenerate after injury, leading to irreversible sensorineural hearing loss. This lack of regenerative potential of cochlear progenitors is a major obstacle to developing efficient in vitro models, delaying new therapeutic advancements for hearing loss treatment. Consequently, from early preclinical stages, testing new treatments relies on animal-based models, resulting in low throughput, significant variability, and limited predictive value. We have recently identified the signaling pathways that can reprogram stemness in senescent auditory neuroprogenitors. By synergistically targeting the WNT and TGFβ/Smad pathways using small molecules or genetic means, we achieved virtually unlimited expansion of auditory neuroprogenitors in vitro. This reprogramming does not compromise their ability to differentiate into mature and functional auditory neurons, even after 40 passages and a thousand-fold amplification. The so-called phoenix auditory neuroprogenitors can be frozen and thawed, leading to the creation of a cell bank and offering an efficient alternative to animal-based models. The phoenix platform provides numerous advantages, including suitability for high-throughput technologies, low experimental variability, single-cell resolution, and a significant reduction in the number of animals used. Furthermore, it maintains the phenotype of auditory neurons in a primary culture-like setup. Initially developed using mouse neural cells, we are currently implementing this model with human fetal otic neural stem cells. This re-programming method represents a significant breakthrough in overcoming a major bottleneck in auditory research. The phoenix platform offers an efficient, high-throughput, cost-effective, and 3R-compatible approach for in vitro screening of potential otoprotective and otoregenerative drug candidates. In addition, the precise investigation of the mechanisms leading to phoenix proliferation opens new avenues in the field of inner ear regeneration. [ABSTRACT FROM AUTHOR]

The accumulation of reactive oxygen species (ROS) in cells and tissues contributes to the development and the progression of numerous diseases such as cancers, metabolic syndromes, or sensorineural disorders. NAPDH oxidases, a family of enzymes which sole function is to produce reactive oxygen species (ROS), appeared as relevant therapeutic targets in the treatment of oxidant-mediated pathologies. More specifically, the NOX3 isoform is only expressed in the inner ear and, although its physiological role in the cochlea is not known, there is increasing evidence that NOX3 is involved in different forms of acquired hearing loss. Thus, the inhibition of NOX3 would provide an efficient otoprotec-tive strategy, notably by preventing ROS-induced damages to the auditory synapse. This project aims at discovering NOX3 small molecule inhibitors for the prevention of acquired sensorineural hearing loss. We developed a cell-based high-throughput screen using an inducible system allowing the expression of NOX3 upon 24 h treatment with tetracy-cline. NOX3 activity was assessed through the detection of generated extracellular superoxide radical anion (O2*-) using the colorimetric assay WST-1. The non-specific NOX inhibitor diphenyleneiodonium chloride (DPI) was used as a reference compound for maximal inhibition. Among the 15,511 compounds screened, 115 showed an inhibitory activity on NOX3 equal to or higher than 50% and were considered as hits. These hits were further tested in dose-response using WST-1 and validated using orthogonal assays detecting hydrogen peroxide (Amplex Red/HRP and CBA fluorometric assays) and cytotoxicity. The specificity of the validated hits for NOX3 over the 6 other isoforms was also assessed. This critical early drug discovery step paves the way to the development of new small molecule therapeutics for the prevention of sensorineural hearing loss. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether odontogenic maxillary sinusitis, either alone (OMSw/oFB) or in combination with fungus ball (OMSwFB), is associated with specific clinical characteristics and treatment outcomes compared to non-odontogenic maxillary sinusitis., Materials and Methods: A retrospective cohort study was performed on patients who underwent surgical treatment for chronic maxillary sinusitis between 2013 and 2021. OMSw/oFB and OMSwFB patients, were selected as the study group, while patients diagnosed with non-odontogenic maxillary sinusitis (non-OMS) were enrolled as the control group. Predictor variables were OMSw/oFB and OMSwFB. Outcomes were clinical presentation, postoperative complications, and treatment outcome. Descriptive, bivariate, and multiple logistic regression statistics were calculated, and the significance level was set at P ≤ 0.05., Results: The sample included 200 patients with a mean age of 49.6 ± 20.1 years and 57.5 % were men. Of the 200 patients, 123 (61.5 %) had non-OMS, 55 (27.5 %) had OMSw/oFB, and 22 (11 %) had OMSwFB. Multivariate analysis showed that OMSw/oFB was associated with more successful treatment rates (OR = 8.19, p < 0.01), whereas OMSwFB was associated with a less favorable outcome (OR = 0.27, p = 0.03). Age was associated with an unfavorable outcome in both OMS groups (OR: 0.98, p = 0.03 and p = 0.03, respectively), but no significant associations with other outcomes were found., Conclusion: This study suggests that OMSwFB is a recalcitrant form of OMS associated with a higher risk of persistent symptoms and less favorable outcome. These patients should be informed about the challenging nature of the disease and closely monitored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal of Stomatology, Oral and Maxillofacial Surgery] and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Although most patients with post-traumatic olfactory dysfunction (PTOD) undergo MRI, there is no consensus about its diagnostic or prognostic value. The aims were: 1) to classify the extent of post-traumatic neurodegeneration; 2) to determine its relationship with chemosensory dysfunction (smell, taste, trigeminal); and 3) to establish whether MRI can predict olfactory improvement., Methodology: We conducted a retrospective cohort study based on a series of 56 patients with PTOD. All patients underwent validated psychophysical tests of their smell, taste, and trigeminal functions, otorhinolaryngologic evaluation, and MRI. An experienced radiologist blinded to patient data evaluated 40 chemosensory-relevant brain regions according to a four-point scale (0=no lesion to 3=large lesion). Follow up data after 4 years (on average) were available in 46 patients., Results: The cluster analysis showed 4 brain lesion patterns that differed in lesion localization and severity. They are associated with diagnostic categories: anosmia, hyposmia and normosmia. Two clusters were highly specific for anosmia (100% specificity)and could accurately predict this condition (100% positive predictive value). No clusters were associated with trigeminal or taste dysfunction. Regarding improvement, 72.7% of patients in the cluster with mild lesions experienced subjective and measurable olfactory improvement whereas this was only the case in 21.7-37.5% of patients with larger lesions. The odds of subjective smell improvement were 5.9 times higher in patients within the milder cluster compared to larger ones., Conclusions: The analysis of brain lesions in PTOD allows corroboration of smell test results and prediction of subjective and measurable improvement.

Background: Chemosensory dysfunction (olfaction, taste, and trigeminal) affects quality of life, potentially impacting eating behaviors. We investigated which factors are associated with weight loss in patients with smell and taste disorders., Methods: Retrospective study of consecutive adult patients seen in the smell and taste clinic during a 10-year period. Patients were asked about smell, flavor and taste impairment. Psychophysically, smell was assessed with Sniffin' Sticks, flavor with a retronasal test, and taste with Taste Strips., Results: A total of 554 patients (313 females) were included with a median age of 51 years (IQR 23). Seventy-six (13.7%) reported involuntary weight loss (median 6 kg, IQR 6) due to chemosensory disorders. The odds of losing weight were 2.1 times higher when patients reported subjective changes in flavor perception. Parosmia was a significant predictor of weight loss. Patients with symptoms lasting longer than two years were less likely to present with weight loss. Post-traumatic chemosensory dysfunction was a significant predictor of losing weight. On psychophysical testing, the probability of a patient losing weight increased by 8% for every 1-unit reduction in Taste Strips score., Conclusion: Factors associated with weight loss were self-reported changes in flavor perception, parosmia, duration of symptoms for less than two years, head injury, and psychophysically measured low Taste Strips score. These data help to identify patients at risk of weight loss from smell or taste impairment.

Background Cognitive behavioral therapy (CBT) is the current standard treatment for chronic severe tinnitus; however, preliminary evidence suggests that real-time functional MRI (fMRI) neurofeedback therapy may be more effective. Purpose To compare the efficacy of real-time fMRI neurofeedback against CBT for reducing chronic tinnitus distress. Materials and Methods In this prospective controlled trial, participants with chronic severe tinnitus were randomized from December 2017 to December 2021 to receive either CBT (CBT group) for 10 weekly group sessions or real-time fMRI neurofeedback (fMRI group) individually during 15 weekly sessions. Change in the Tinnitus Handicap Inventory (THI) score (range, 0-100) from baseline to 6 or 12 months was assessed. Secondary outcomes included four quality-of-life questionnaires (Beck Depression Inventory, Pittsburgh Sleep Quality Index, State-Trait Anxiety Inventory, and World Health Organization Disability Assessment Schedule). Questionnaire scores between treatment groups and between time points were assessed using repeated measures analysis of variance and the nonparametric Wilcoxon signed rank test. Results The fMRI group included 21 participants (mean age, 49 years ± 11.4 [SD]; 16 male participants) and the CBT group included 22 participants (mean age, 53.6 years ± 8.8; 16 male participants). The fMRI group showed a greater reduction in THI scores compared with the CBT group at both 6 months (mean score change, -28.21 points ± 18.66 vs -12.09 points ± 18.86; P = .005) and 12 months (mean score change, -30 points ± 25.44 vs -4 points ± 17.2; P = .01). Compared with baseline, the fMRI group showed improved sleep (mean score, 8.62 points ± 4.59 vs 7.25 points ± 3.61; P = .006) and trait anxiety (mean score, 44 points ± 11.5 vs 39.84 points ± 10.5; P = .02) at 1 month and improved depression (mean score, 13.71 points ± 9.27 vs 6.53 points ± 5.17; P = .01) and general functioning (mean score, 24.91 points ± 17.05 vs 13.06 points ± 10.1; P = .01) at 6 months. No difference in these metrics over time was observed for the CBT group ( P value range, .14 to >.99). Conclusion Real-time fMRI neurofeedback therapy led to a greater reduction in tinnitus distress than the current standard treatment of CBT. ClinicalTrials.gov registration no.: NCT05737888; Swiss Ethics registration no.: BASEC2017-00813 © RSNA, 2024 Supplemental material is available for this article.

In the recent past, inclusion criteria for cochlear implant surgery expanded to patients with ever more residual acoustic hearing in the low frequencies. By applying the meticulous hearing preservation surgical strategy and specifically designed atraumatic electrode arrays, residual hearing can be preserved to a meaningful extent in a large majority of patients. In this paper, we describe two female patients suffering from mechanically evoked tinnitus after hearing preservation cochlear implantation surgery with MEDEL flex electrodes. The occurrence of audible perceptions through mechanical stimulation in the region of the external ear is believed to be due to the direct transmission of movements via the electrode array to the basilar membrane of the inner ear. In both cases, the mechanically evoked tinnitus led to revision surgery with immobilization of the array in the mastoid cavity. Despite eliminating the tinnitus, the revision surgery led to a loss of residual hearing in one patient, whereas the relatively poor residual hearing in the other revision case remained unchanged. The presence of mechanically evoked tinnitus seems to be associated with increased fragility of inner ear structures and hearing function, possibly due to direct mechanical contact of the electrode array with the basilar membrane. Consequently, the electrode array needs to be carefully immobilized in the mastoid cavity at a distance from soft tissue to prevent mechanical damage of inner ear structures, particularly in female patients with fine muscular tissue.

Olfactory disorders became known by large parts of the population since the Covid-19 pandemic. The causes of olfactory dysfunctions are manifold. Similar to other sensory impairments the disruption can be qualitative or quantitative. Quantitative olfactory disorders such as anosmia or hyposmia are well explored, whereas the knowledge on qualitative disorders such as parosmia or phantosmia is still limited. This article gives an update on the current clinical knowledge and workup of parosmia and phantosmia., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Purpose of the Review: This study aims to summarize the current state of the art of how taste disorders are clinically best managed., Recent Findings: Taste disorders are distressing for the concerned patients since eating and drinking become bothersome or impossible. Apart from nutritional problems, quality of life is impaired. Still, diagnosis and treatment of taste disorders are elusive, and general knowledge about taste and its affection is little within the population and the medical community. This review stresses the importance of accurate workup and diagnosis of taste disorders in order to offer an effective treatment. Yet unclear aspects of taste disorders are discussed, and interesting findings regarding the treatment of taste disorders are reviewed. A special focus is given to current pharmacological options on how to treat taste disorders., Summary: Despite impressive insights into the gustatory function and molecular logic of taste receptor cells, there is currently poor clinical knowledge on the pathophysiology of taste disorders in humans. Diagnosing, measuring, and treating gustatory disorders remain restricted to a handful of specialized smell and taste centers worldwide. Despite interesting work on potential drugs treating taste disorders, many of the reported medications lack controlled and randomized trials confirming their efficacy in taste dysfunction. Future efforts need to be focused on the treatment of taste disorders., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2022.)

Single sided deafness diminishes speech understanding in noise and sound localization and thereby globally auditory performance. Most patients also suffer from tinnitus and indicate reduced quality of life. Patients have the choice to adapt to the new situation without treatment, to restore pseudostereophonic hearing by contralateral routing of signal (CROS) hearing aids or to restore binaural hearing using a cochlear implant in the deaf ear. This article summarizes the physiological base of binaural hearing and treatment options for single sided deafness with a special emphasis on the cochlear implant., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objectives: Many patients complain about olfactory fluctuation (OF), which is a symptom commonly attributed to sinonasal disease. Data-based evidence for its association with sinonasal disease is scarce. The aim of the study is to identify explanatory variables associated with OF and to analyze its predictive value regarding sinonasal disease., Study Design: We performed a retrospective study based on patients with olfactory dysfunction., Methods: We analyzed data from 482 patients attending the smell and taste outpatient clinic with full psychophysical workup and structured questions regarding their symptoms. The questionnaire included items on OF and chronic nasal symptoms. Clinical investigators filled out the second part of this questionnaire that included information about nasal endoscopy, psychophysical tests of orthonasal olfaction (Sniffin' Sticks), retronasal olfaction, and putative etiology of olfactory dysfunction., Results: OF was more prevalent in sinonasal disease (42.4%) compared to other putative etiologies of olfactory dysfunction such as postinfectious (28%) or posttraumatic (11.7%) (X2 [5, n = 440] = 24.98; P < .0001). OF was strongly associated with Sniffin' Sticks score categories (anosmia, hyposmia, normosmia) (X2 [2, n = 424] = 39.21; P < .0001; Cramer's V = 0.30; P < .0001) and presence of "chronic nasal symptoms" (X2 [1, n = 437] = 22.71; P < .0001; Cramer's V = 0.23; P < .0001). The accuracy in predicting putative sinonasal disease etiology when OF was present depended strongly on the clinical context., Conclusion: Olfactory fluctuation is a symptom mostly but not exclusively associated with sinonasal disease, elevated Sniffin' Sticks test scores, and is frequently accompanied by other nasal complaints. Its presence is valuable information for clinicians to be integrated into the clinical context when doing patients' workup., Level of Evidence: 4 Laryngoscope, 130:2442-2447, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)