Electrical Ear Canal Stimulation as a Therapeutic Approach for Tinnitus-A Proof of Concept Study.

Background: Tinnitus-the perception of sound despite the absence of an external source-can be a debilitating condition for which there are currently no pharmacological remedies. Our proof of concept study focused on the immediate effects of non-invasive electrical stimulation through the ear canal on loudness and tinnitus-induced distress. In addition, we aimed to identify variables that may affect the simulation outcomes. Methods: Sixty-six patients (29 women and 37 men, mean age 54.4 ± 10.4) with chronic tinnitus were recruited to the tertiary referral hospital between December 2019 and December 2021. They underwent 10 min of electrical stimulation through the ear canal for three consecutive days. Visual analog scales measured loudness and tinnitus-induced distress immediately before and after stimulation. Results: After three days of electrical stimulation, tinnitus loudness decreased in 47% of patients, 45.5% reported no change, and 7.6% reported worsening. Tinnitus severity decreased in 36.4% of cases, 59.1% of patients reported no change, and 4.5% reported worsening. Women responded positively to therapy earlier than men. In addition, tinnitus distress decreased in patients with compensated tinnitus but not in those with uncompensated tinnitus. Finally, patients with bilateral tinnitus improved earlier than those with unilateral tinnitus, and the age of the patients did not influence the stimulation results. Conclusions: Our proof of concept study confirms the potential of non-invasive electrical stimulation of the ear as a promising screening approach to identifying patients for more advanced electrostimulation treatment, such as an extracochlear anti-tinnitus implant. These findings have practical implications for tinnitus management, offering hope for improved patient care.

A systematic review of the clinical evidence for an association between type I hypersensitivity and inner ear disorders.

Inner ear disorders have a variety of causes, and many factors can contribute to the exacerbation of cochlear and vestibular pathology. This systematic review aimed to analyze clinical data on the coexistence and potential causal interaction between allergic diseases and inner ear conditions. A search of PubMed and Web of Science identified 724 articles, of which 21 were selected for full-text analysis based on inclusion and exclusion criteria. The epidemiologic evidence found overwhelmingly supports an association between allergic disease and particular inner ear disorders represented by a high prevalence of allergic reactions in some patients with Ménière's disease (MD), idiopathic sudden sensorineural hearing loss (ISSHL), and acute low-tone hearing loss (ALHL). In addition, patients with MD, ISSHL, and ALHL had higher levels of total serum IgE than healthy subjects. Finally, in some cases, changes in cochlear potential may have been induced by antigen exposure, while desensitization alleviated allergy and inner ear-related symptoms. The exact mechanism of interaction between the auditory/vestibular and immune systems is not fully understood, and further clinical and basic research is needed to understand the relationship between the two systems fully.

Sustained Cognitive Improvement in Patients over 65 Two Years after Cochlear Implantation.

This study aimed to evaluate the long-term benefits of cochlear implantation (CI) on cognitive performance, speech perception, and psychological status in post-lingually deafened patients older than 65 (n = 33). Patients were consecutively enrolled in this prospective study and assessed before, one year after, and two years after CI for speech perception, depressive symptoms, perceived stress, and working memory and processing speed. The Wechsler Adult Intelligence Scale (WAIS) was used for the latter. Thirty-three patients (fourteen men and nineteen women) were included. The scores indicating "hearing in quiet" and "hearing with background noise" improved significantly one year after CI and remained so two years after CI. The sound localization scores improved two years after CI. The depressive symptoms and perceived stress scores were low at the study's onset and remained unchanged. Working memory improved significantly two years after CI, while processing speed improved significantly one year after CI and was maintained after that. The improvement in working memory and processing speed two years after CI suggests there is a sustained positive effect of auditory rehabilitation with CI on cognitive abilities.

[Cochlear implant and tinnitus]. / Cochleaimplantat und Tinnitus.

Cochlear implant (CI) treatment is now established as a successful standard of care for auditory rehabilitation of profoundly deaf or severe hearing loss patients. CI candidates with tinnitus also benefit from improved health-related quality of life (HRQoL) and tinnitus burden. Current CI indications include bilateral (double-sided) profound hearing loss and deafness (DSD), unilateral (single-sided) deafness (SSD), and asymmetric hearing loss (AHL). The new and expanded indications for cochlear implants result in different healthcare situations, which may also be associated with differences in tinnitus burden before and after CI treatment. In this article, we discuss the prevalence of tinnitus in different patient groups and the influence of CI on tinnitus prevalence and severity in these groups. In addition, further therapeutic options for tinnitus suppression based on the CI principle are presented, including the development of an anti-tinnitus implant (proof of concept).

Translational Research in Audiology.

The importance of translational research in the medical sciences is growing logarithmically, as this type of research provides the translation of basic research into a clinical product (a drug, therapeutic agent or means of monitoring a disease), as well as the inverse translation of clinical findings into basic research models [...].

Expectations of Polish undergraduate medical students for medical humanities classes: a survey-based pilot study.

BACKGROUND: Medical schools teach Medical Humanities (MH) to provide students with knowledge about the human experience related to health, illness, disease, medicine, and healthcare. Due to the previously observed negative opinions about MH courses, we examined the expectations of medical students in Poland toward humanities subjects. METHODS: We conducted a voluntary, anonymous electronic survey in one medical school (single-center study) and collected data from 166 medical students. The results were analyzed by comparing continuous and categorical variables between groups (gender, year of study, previous participation in MH classes). RESULTS: The students expected to learn how to communicate with patients and their families, especially about difficult topics. They also expected the classes to be active, stress-free, and without passing grades. The preferred MH teacher was a physician, although choosing a psychologist or other qualified person as an MH teacher was also popular. Previous participants in MH courses were more likely to expect such a course to be compulsory than those who had yet to attend it. CONCLUSION: Considering the students' expectations when designing MH classes could increase students' satisfaction with MH courses.

Histamine and Its Receptors in the Mammalian Inner Ear: A Scoping Review.

BACKGROUND: Histamine is a widely distributed biogenic amine with multiple biological functions mediated by specific receptors that determine the local effects of histamine. This review aims to summarize the published findings on the expression and functional roles of histamine receptors in the inner ear and to identify potential research hotspots and gaps. METHODS: A search of the electronic databases PubMed, Web of Science, and OVID EMBASE was performed using the keywords histamine, cochlea*, and inner ear. Of the 181 studies identified, 18 eligible publications were included in the full-text analysis. RESULTS: All four types of histamine receptors were identified in the mammalian inner ear. The functional studies of histamine in the inner ear were mainly in vitro. Clinical evidence suggests that histamine and its receptors may play a role in Ménière's disease, but the exact mechanism is not fully understood. The effects of histamine on hearing development remain unclear. CONCLUSIONS: Existing studies have successfully determined the expression of all four histamine receptors in the mammalian inner ear. However, further functional studies are needed to explore the potential of histamine receptors as targets for the treatment of hearing and balance disorders.

[Prospective comparative analysis of cochlear implant patients with single-sided deafness and asymmetric hearing loss with regard to health-related quality of life, tinnitus distress and psychological comorbidities]. / Prospektive Vergleichsanalyse von CI-Patienten mit einseitiger Taubheit und asymmetrischem Hörverlust hinsichtlich der gesundheitsbezogenen Lebensqualität, Tinnitusbelastung und psychischen Komorbiditäten.

BACKGROUND: Patients with single-sided deafness (SSD) and asymmetric hearing loss (AHL) are increasingly being treated with cochlear implants (CI) due to the demonstrated improvements in auditory abilities and quality of life. To date, there are few published studies in which these two groups are comparatively studied. The aim of the current study was to examine which factors differ between those two patient groups, especially preoperatively. METHODS: A secondary analysis of the previously published raw data of 66 prospectively recruited CI patients (21 SSD/45 AHL) was performed. In addition to the hearing outcome, tinnitus distress (tinnitus questionnaire), health-related quality of life (Nijmegen Cochlear Implant Questionnaire, NCIQ), stress (Perceived Stress Questionnaire, PSQ), and psychological comorbidities (General Depression Scale, ADS­L and Generalized Anxiety Disorder scale, GAD-7) were assessed in SSD and AHL patients pre- and postoperatively. RESULTS: Preoperatively, SSD patients showed significantly higher scores in the NCIQ subdomains "elementary" and "advanced sound perception" than the AHL group. Stress (PSQ) and anxiety symptoms (GAD-7) were significantly higher preoperatively in SSD patients than in AHL patients. After CI, these differences were strongly reduced, with minimal differences being detectable between the groups in the investigated domains postoperatively. CONCLUSION: SSD and AHL patients differ significantly preoperatively in terms of their subjective hearing assessment and psychosocial parameters. In SSD patients, psychological stress factors may have a stronger impact on the quality of life than in AHL patients. These aspects should be taken into account in the preoperative counseling and postoperative rehabilitation.

Universal Recommendations on Planning and Performing the Auditory Brainstem Responses (ABR) with a Focus on Mice and Rats.

Translational audiology research aims to transfer basic research findings into practical clinical applications. While animal studies provide essential knowledge for translational research, there is an urgent need to improve the reproducibility of data derived from these studies. Sources of variability in animal research can be grouped into three areas: animal, equipment, and experimental. To increase standardization in animal research, we developed universal recommendations for designing and conducting studies using a standard audiological method: auditory brainstem response (ABR). The recommendations are domain-specific and are intended to guide the reader through the issues that are important when applying for ABR approval, preparing for, and conducting ABR experiments. Better experimental standardization, which is the goal of these guidelines, is expected to improve the understanding and interpretation of results, reduce the number of animals used in preclinical studies, and improve the translation of knowledge to the clinic.

Identification and Characterization of TMEM119-Positive Cells in the Postnatal and Adult Murine Cochlea.

Transmembrane protein 119 (TMEM119) is expressed in a subset of resident macrophage cells of the brain and was proposed as a marker for native brain microglia. The presence of cells expressing TMEM119 in the cochlea has not yet been described. Thus, the present study aimed to characterize the TMEM119-expressing cells of the postnatal and adult cochlea, the latter also after noise exposure. Immunofluorescent staining of cochlear cryosections detected TMEM119 protein in the spiral limbus fibrocytes and the developing stria vascularis at postnatal Day 3. Applying the macrophage marker Iba1 revealed that TMEM119 is not a marker of cochlear macrophages or a subset of them. In the adult murine cochlea, TMEM119 expression was detected in the basal cells of the stria vascularis and the dark mesenchymal cells of the supralimbal zone. Exposure to noise trauma was not associated with a qualitative change in the types or distributions of the TMEM119-expressing cells of the adult cochlea. Western blot analysis indicated a similar TMEM119 protein expression level in the postnatal cochlea and brain tissues. The findings do not support using TMEM119 as a specific microglial or macrophage marker in the cochlea. The precise role of TMEM119 in the cochlea remains to be investigated through functional experiments. TMEM119 expression in the basal cells of the stria vascularis implies a possible role in the gap junction system of the blood-labyrinth barrier and merits further research.

Degranulation of Murine Resident Cochlear Mast Cells: A Possible Factor Contributing to Cisplatin-Induced Ototoxicity and Neurotoxicity.

Permanent hearing loss is one of cisplatin's adverse effects, affecting 30-60% of cancer patients treated with that drug. Our research group recently identified resident mast cells in rodents' cochleae and observed that the number of mast cells changed upon adding cisplatin to cochlear explants. Here, we followed that observation and found that the murine cochlear mast cells degranulate in response to cisplatin and that the mast cell stabilizer cromoglicic acid (cromolyn) inhibits this process. Additionally, cromolyn significantly prevented cisplatin-induced loss of auditory hair cells and spiral ganglion neurons. Our study provides the first evidence for the possible mast cell participation in cisplatin-induced damage to the inner ear.

A real-life comparison of pulmonary and nasal outcomes in patients with severe asthma and nasal polyposis treated with T2-biologics.

Background: Severe asthma (SA) with comorbid chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with type 2 (T2) inflammatory endotype. Consequently, therapeutic targets are T2 biologics. The present retrospective study aimed to analyze and compare the clinical efficacy of mepolizumab, benralizumab, omalizumab, and dupilumab in patients with SA and comorbid CRSwNP. Methods: 115 adult patients with SA and CRSwNP receiving 1 of the 4 biologics (mepolizumab n = 31; benralizumab n = 27; dupilumab n = 27; omalizumab n = 30) were included in the retrospective open monocentric study. Pulmonary and rhinological parameters were evaluated by Asthma Control Test (ACT), FEV1%, GINA-severity grade, rhinological questionnaires (CRS VAS-scores and sinonasal QoL RSOM-31) before and after 4-6 months of therapy. Results: After 4-6 months of therapy, the Asthma Control Test and FEV1% significantly improved in all biologics groups (p < 0.01). GINA-score significantly improved in the omalizumab group only (p < 0.01). Overall, most nasal scores measured by VAS, total and nasal RSOM-31 subscores improved in all treatment groups (p < 0.05). Interestingly, the most significant differences in pre/post scores were observed in the patients receiving dupilumab, with the most notable improvement for all nasal symptoms, RSOM-31 total score, and RSOM-31 nasal subscore. There were no significant changes in the VAS scores loss of smell in the benralizumab group and postnasal drip in the mepolizumab group. Conclusion: T2-targeting biologics effectively treat asthma in patients with severe asthma and comorbid CRSwNP. However, the efficacy of T2 biologics differs regarding the outcome in CRSwNP.

Extracellular Vesicles in Inner Ear Therapies-Pathophysiological, Manufacturing, and Clinical Considerations.

(1) Background: Sensorineural hearing loss is a common and debilitating condition. To date, comprehensive pharmacologic interventions are not available. The complex and diverse molecular pathology that underlies hearing loss may limit our ability to intervene with small molecules. The current review foccusses on the potential for the use of extracellular vesicles in neurotology. (2) Methods: Narrative literature review. (3) Results: Extracellular vesicles provide an opportunity to modulate a wide range of pathologic and physiologic pathways and can be manufactured under GMP conditions allowing for their application in the human inner ear. The role of inflammation in hearing loss with a focus on cochlear implantation is shown. How extracellular vesicles may provide a therapeutic option for complex inflammatory disorders of the inner ear is discussed. Additionally, manufacturing and regulatory issues that need to be addressed to develop EVs as advanced therapy medicinal product for use in the inner ear are outlined. (4) Conclusion: Given the complexities of inner ear injury, novel therapeutics such as extracellular vesicles could provide a means to modulate inflammation, stress pathways and apoptosis in the inner ear.

Translational Research in Audiology: Presence in the Literature.

Translational research is a process that focuses on advancing basic research-based clinical solutions and is characterized by a structured process accelerating the implementation of scientific discoveries in healthcare. Translational research originated in oncology but has spread to other disciplines in recent decades. A translational project may refer to pharmacological research, the development of non-pharmacological therapies, or to disease monitoring processes. Its stages are divided into basic research focused on the clinical problem (T0), testing the developed means in humans (T1), conducting trials with patients (T2), implementation and dissemination of successful approaches (T3), and improving community health (T4). Many audiological studies are translational in nature. Accordingly, this scoping review aimed to evaluate the use of the terms "translational audiology" and "translational research in audiology" in the literature and examine the goals of the identified studies. PubMed and Web of Science search identified only two publications meeting the search criteria. We conclude that identifying translational audiological studies in the literature may be hampered by the lack of use of the terms "translational audiology" or "translational research". We suggest using these terms when describing translational work in audiology, with a view to facilitating the identification of this type of research and credit it appropriately.

Long-Term Effects of COVID-19 and the Pandemic on Tinnitus Patients.

This study aimed to explore the effect of COVID-19 and the pandemic period on the tinnitus-related complaints of patients with chronic tinnitus. Ninety-six patients who were diagnosed with chronic tinnitus before the pandemic were enrolled in this study. Before the pandemic and in January 2022, all patients used the Visual Analog Scale (VAS) to assess tinnitus loudness, annoyance, and effect on everyday life, sleep, and concentration. Additionally, patients filled the Tinnitus Handicap Inventory (THI) and the Hyperacusis Questionnaire (HQ). In the entire cohort, tinnitus loudness, annoyance, and tinnitus-induced difficulties with concentration as well as THI and HQ scores increased significantly during the two pandemic years. Thirty-seven tinnitus patients contracted COVID-19 between March 2020 and January 2022. These patients were asked to list leading COVID-19 symptoms, changes in tinnitus complaints during and after the disease, and whether their hearing abilities were affected. Three patients in the COVID-19 group confirmed worsening their hearing abilities. There was no decrease in the tinnitus complaint during COVID-19, 24.3% of the infected patients reported exacerbation of tinnitus, and 75.7% said tinnitus remained the same. In the COVID-19-negative group, 13.5% reported tinnitus decrease during the pandemic, 57.6% said it remained the same, and 28.8% reported exacerbation of tinnitus. When split into infected and non-infected groups, a significant increase in tinnitus loudness, tinnitus effect on concentration, and THI scores were seen only in patients who contracted COVID-19, while hyperacusis worsened significantly (p < 0.05) only in COVID-19-negative tinnitus patients. Despite significant differences within the groups, there were no differences found between the groups. This study points to possible different effects of the infection with SARS-CoV-2 and the pandemic period on patients with chronic tinnitus. It also provides evidence for deterioration of preexisting tinnitus as a possible long-term effect of COVID-19.

Lateralization Pattern of the Weber Tuning Fork Test in Longstanding Unilateral Profound Hearing Loss: Implications for Cochlear Implantation.

The Weber tuning fork test is a standard otologic examination tool in patients with unilateral hearing loss. Sound should typically lateralize to the contralateral side in unilateral sensorineural hearing loss. The observation that the Weber test does not lateralize in some patients with longstanding unilateral deafness has been previously described but remains poorly understood. In the present study, we conducted a retrospective analysis of the medical records of patients with unilateral profound hearing loss (single-sided deafness or asymmetric hearing loss) for at least ten years. In this patient cohort, childhood-onset unilateral profound hearing loss was significantly associated with the lack of lateralization of the Weber tuning fork test (Fisher's exact test, p < 0.05) and the absence of tinnitus in the affected ear (Fisher's exact test, p < 0.001). The findings may imply a central adaptation process due to chronic unilateral auditory deprivation starting before the critical period of auditory maturation. This notion may partially explain the poor outcome of adult cochlear implantation in longstanding single-sided deafness. The findings may suggest a role for the Weber test as a simple, quick, and economical tool for screening poor cochlear implant candidates, thus potentially supporting the decision-making and counseling of patients with longstanding single-sided deafness.

Chemokine Expression-Based Endotype Clustering of Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) with (CRSwNP) or without nasal polyps (CRSsNP) is a persistent, heterogeneous inflammatory condition affecting the upper respiratory tract. The present study aimed to improve the characterization of CRS endotypes based on the chemokine and cytokine expression pattern in the CRS tissues. Concentrations of chemokines and cytokines were measured in tissues from nasal biopsies obtained from 66 CRS patients and 25 control subjects using multiplexing or single analyte technologies. Cluster analysis based on the concentration of type-1 (MCP-3/CCL7, MIP-1 α/CCL3), type-2 (IL-5, MCP-3/CCL7, MIP-1 α/CCL3, TARC/CCL17, PARC/CCL18, IP-10/CXCL10, ECP), and type-3 (IL-22) chemokines and cytokines identified six CRS endotypes (clusters). Cluster 1 (type-3) and 2 (type-1) were associated with a low prevalence of nasal polyps, Cluster 3 (type-1, -2, -3) and Cluster 4 (type-2, -3, medium IL-22) with medium, and Cluster 5 (type-2, -3, high Il-22) and Cluster 6 (type-2) with high prevalence of nasal polyps. Asthma was highly prevalent in Cluster-6. Our findings add to the existing knowledge of CRS endotypes and may be useful for the clinical decision-making process. The advancement of biologics therapy for upper respiratory tract disorders rationalizes the personalized diagnostic approach to warrant a successful treatment and monitoring of CRS.

Perception of Medical Humanities among Polish Medical Students: Qualitative Analysis.

Medical humanities (MH) courses are a critical element of the medical curriculum influencing the establishment of a physician in the medical profession. However, the opinion about MH among medical students remains unknown. Interviews from seven focus groups were analysed. The students attended one of three Polish medical schools in Gdansk, Krakow, and Warsaw and were recruited to the discussion focused on the impact of drug manufacturers' presence at medical universities on socialization in the medical profession. Thematic analysis was conducted using the theoretical framework of social constructivism. The students' opinions about the MH classes arose during the analysis. In six groups, students thought that MH courses would be helpful in their future medical practice. However, in four groups, different opinion was expressed that MH courses were unnecessary or even "a waste of time". Factors discouraging students from the MH classes included poorly taught courses (monotonous, uninteresting, unrelated to medical practice, taught by unsuitable lecturers). Secondly, students thought that the time investment in the MH was too extensive. Furthermore, curriculum problems were identified, reflecting the incompatibility between the content of MH courses and teaching semesters. Lastly, some students stated that participation in MH courses should be elective and based on individual interests. Addressing problems recognized in this work could improve the training of future Polish physicians.