[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.

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.

Missed Radiological Diagnosis of Otosclerosis in High-Resolution Computed Tomography of the Temporal Bone-Retrospective Analysis of Imaging, Radiological Reports, and Request Forms.

Objectives: Several studies reported low detection rates of otosclerosis in high-resolution computed tomography (HRCT), especially when the scans were reviewed by non-specialized general radiologists. In the present study, we conducted a retrospective review of the detection of otosclerosis in HRCT by general radiologists and the impact of inadequately filled radiological request forms on the detection rate. Methods: Retrospective analysis of hospital records, HRCT reports, and radiological referral notes of 40 patients who underwent stapedotomy surgery for otosclerosis. HRCT imaging data sets were retrospectively reviewed by a blinded experienced neuroradiologist, whose reading served as the gold standard. Results: General radiologists reading HRCT scans had an overall detection rate of otosclerosis of 36.1% in this cohort (13 of 36 available HRCT reports). The neuroradiologist had a much higher detection rate of 82.5% (33 of 40 cases). Interobserver agreement between the general radiologists and the subspecialist neuroradiologist was poor (Cohen's kappa κ = 0.26). General radiologists missed the diagnosis in 15 of the 33 CT-positive scans, corresponding to a missed diagnosis rate of 45.4%. There was a highly significant association between a missed diagnosis and the lack of an explicitly mentioned clinical suspicion of otosclerosis in the request forms (Pearson's chi-squared test, p < 0.005). Conclusion: The diagnosis of otosclerosis is frequently missed by radiologists on HRCT scans of the temporal bone in a clinical setting. Possible reasons include a relative lack of experience of general radiologists with temporal bone imaging as well as the failure of clinicians to unambiguously communicate their suspicion of otosclerosis.

The Diagnostic Yield of Excisional Biopsy in Cervical Lymphadenopathy: A Retrospective Analysis of 158 Biopsies in Adults.

OBJECTIVES: Cervical lymph nodes are the most common site of peripheral lymphadenopathy. The underlying etiologies are usually benign and self-limiting but may include malignancies or other severe life-threatening diseases. The aim of the current study was to investigate the various underlying pathologies of cervical lymphadenopathy as assessed by the diagnostic yield of excisional lymph node biopsies of the neck in a tertiary adult practice. The evaluation was performed in light of previous literature and regional epidemiological patterns. METHODS: Retrospective analysis of hospital charts of 158 adult patients who underwent an excisional biopsy for suspected cervical lymphadenopathy at a tertiary referral head and neck service between January 2017 and December 2019. RESULTS: The most common underlying pathology was unspecific and/or reactive lymphadenitis in 44.5% of specimens, followed by malignant disease in 38.6% of cases. An age above 40 years was significantly correlated with an increased likelihood of malignant disease. Lower jugular and posterior triangle lymph nodes showed higher malignancy rates than other groups (100% and 66.7%, respectively). The overall surgical complication rate was 2.5%. CONCLUSIONS: The results of the current study serve as an indicator of the variety of etiologies causing cervical lymphadenopathy. In particular, given the increasing incidence of malignant diseases in recent decades, the findings should alert physicians to the importance of lymph node biopsy for excluding malignancy in persistent cervical lymphadenopathy especially in older adults. The findings emphasize the value of excisional lymph node biopsy of the neck as a useful diagnostic tool in adult patients with peripheral lymphadenopathy.

The Relationship between the M1/M2 Macrophage Polarization and the Degree of Ossicular Erosion in Human Acquired Cholesteatoma: An Immunohistochemical Study.

The differential involvement of the macrophage activation phenotypes (M1 vs. M2) has been linked to disease severity in various chronic inflammatory disorders. Pharmacologic manipulation of the M1/M2 macrophage polarization has shown therapeutic potential. Cholesteatoma is a destructive chronic middle ear disease with potentially life-threatening complications. The distribution of macrophage polarization phenotypes in middle ear cholesteatoma has not been described. In the present study, human cholesteatoma specimens acquired during tympanomastoidectomy were retrospectively retrieved and immunohistochemically characterized using a combination of antibodies labeling M1 macrophages (CD80), M2 macrophages (CD163), and total macrophages (CD68). The correlations between the immunohistochemical findings and clinical presentation were assessed. The findings revealed that cholesteatomas with more extensive ossicular erosion demonstrated a significantly higher number of M1 (CD80+) cells and a higher M1/M2 ratio than less invasive cholesteatomas (Wilcoxon test, p < 0.05). The extent of ossicular erosion correlated significantly with the M1/M2 ratio (Spearman correlation coefficient ρ = 0.4, p < 0.05). Thus, the degree of ossicular erosion in human acquired cholesteatoma appears to be related to the M1/M2 macrophage polarization. The investigation of macrophage polarization and functions in various clinical presentations of middle ear cholesteatoma is of great interest since it may contribute to the development of pharmaceutical treatment approaches.

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.

Endoscopic ear examination improves self-reported confidence in ear examination skills among undergraduate medical students compared with handheld otoscopy.

Objectives: Handheld otoscopy is the standard tool used to teach ear examination in undergraduate and postgraduate medical education. Previous studies have shown that the undergraduate teaching of ear examination with handheld otoscopes is inadequate, resulting in low self-reported levels of student confidence in their diagnostic skills. With the increase in popularity of endoscopic ear surgery, an increasing number of otolaryngologists are using endoscopes for office examinations of the ear due to the method's superior visualization and excellent image qualities. However, medical students usually do not receive exposure to endoscopic ear examination during their undergraduate curriculum. The aim of this study is to assess our preliminary experience with teaching endoscopic ear examination to undergraduate medical students. Methods: A two-hour-long pilot practical course on basic ear examination was administered to undergraduate medical students with little to no previous experience with ear examination. The course was designed to minimize the duration of campus attendance and patient contact during the COVID-19 pandemic. The course included theoretical didactics, exemplary digital endoscopic images and peer physical practice of ear examination with both a handheld otoscope and a 0-degree endoscope. At the end of the course, the students completed a survey questionnaire consisting of eight questions mainly relating to their subjective confidence level with ear examination using either handheld otoscopes or endoscopes and their overall preference for either examination tool. Results: Most students expressed a preference for ear examination with endoscopes over that with handheld otoscopes and reported an improved confidence level in their diagnostic ability with the former technique. The vast majority of students supported the teaching of endoscopic ear examination to future medical students. Conclusion: The findings of this pilot project report and survey study support the early exposure of novice medical learners to endoscopic ear examination, which may help improve the confidence and diagnostic skill of medical students with regard to ear examination. The findings may have implications for the undergraduate teaching of ear examination in the post-COVID-19 era.

Bilateral Hearing Loss Due to Metastatic Gastric Signet Cell Adenocarcinoma Involving the Internal Auditory Canal and Cerebellopontine Angle.

Intracranial metastases of stomach cancers are very rare and are associated with a poor prognosis. Of those, metastases of gastric cancers in the internal auditory canal and cerebellopontine angle represent an extremely rare subgroup. Such metastatic lesions may be indistinguishable from vestibular schwannomas in imaging studies and clinical presentation. In this report, we describe a case of gastric signet cell adenocarcinoma metastasizing to the internal auditory canal and cerebellopontine angle bilaterally and causing bilateral hearing loss, including a unilateral sudden deafness. Due to the co-detection of multiple other intracranial masses in the magnetic resonance imaging scan, the suspected diagnosis of leptomeningeal metastatic disease was clear, and the patient was referred to palliative whole brain radiotherapy. The case further highlights the importance of prompt diagnosis and treatment of metastatic cerebellopontine angle lesions to prevent permanent neurological sequelae. Metastatic tumors should therefore be considered in the differential diagnosis of cerebellopontine angle lesions, especially in patients with a known history of malignant disease.

Tackling the Mouse-on-Mouse Problem in Cochlear Immunofluorescence: A Simple Double-Blocking Protocol for Immunofluorescent Labeling of Murine Cochlear Sections with Primary Mouse Antibodies.

The mouse is the most widely used animal model in hearing research. Immunohistochemistry and immunofluorescent staining of murine cochlear sections have, thus, remained a backbone of inner ear research. Since many primary antibodies are raised in mouse, the problem of "mouse-on-mouse" background arises due to the interaction between the anti-mouse secondary antibody and the native mouse immunoglobulins. Here, we describe the pattern of mouse-on-mouse background fluorescence in sections of the postnatal mouse cochlea. Furthermore, we describe a simple double-blocking immunofluorescence protocol to label mouse cochlear cryosections. The protocol contains a conventional blocking step with serum, and an additional blocking step with a commercially available anti-mouse IgG blocking reagent. This blocking technique virtually eliminates the "mouse-on-mouse" background in murine cochlear sections, while adding only a little time to the staining protocol. We provide detailed instructions and practical tips for tissue harvesting, processing, and immunofluorescence-labeling. Further protocol modifications are described, to shorten the duration of the protocol, based on the primary antibody incubation temperature. Finally, we demonstrate examples of immunofluorescence staining performed using different incubation times and various incubation temperatures with a commercially available mouse monoclonal primary antibody. © 2020 The Authors. Basic Protocol: Tackling the Mouse-on-Mouse Problem in Cochlear Immunofluorescence: A Simple Double-Blocking Protocol for Immunofluorescent Labeling of Murine Cochlear Sections with Primary Mouse Antibodies.

Bmi1 Loss in the Organ of Corti Results in p16ink4a Upregulation and Reduced Cell Proliferation of Otic Progenitors In Vitro.

The mature mammalian organ of Corti does not regenerate spontaneously after injury, mainly due to the absence of cell proliferation and the depletion of otic progenitors with age. The polycomb gene B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) promotes proliferation and cell cycle progression in several stem cell populations. The cell cycle inhibitor p16ink4a has been previously identified as a downstream target of Bmi1. In this study, we show that Bmi1 is expressed in the developing inner ear. In the organ of Corti, Bmi1 expression is temporally regulated during embryonic and postnatal development. In contrast, p16ink4a expression is not detectable during the same period. Bmi1-deficient mice were used to investigate the role of Bmi1 in cochlear development and otosphere generation. In the absence of Bmi1, the postnatal organ of Corti displayed normal morphology at least until the end of the first postnatal week, suggesting that Bmi1 is not required for the embryonic or early postnatal development of the organ of Corti. However, Bmi1 loss resulted in the reduced sphere-forming capacity of the organ of Corti, accompanied by the decreased cell proliferation of otic progenitors in otosphere cultures. This reduced proliferative capacity was associated with the upregulation of p16ink4a in vitro. Viral vector-mediated overexpression of p16ink4a in wildtype otosphere cultures significantly reduced the number of generated otospheres in vitro. The findings strongly suggest a role for Bmi1 as a promoter of cell proliferation in otic progenitor cells, potentially through the repression of p16ink4a.

Methyl methacrylate embedding to study the morphology and immunohistochemistry of adult guinea pig and mouse cochleae.

BACKGROUND: Histological analysis of the cochlea is required to understand the physiological and pathological processes in the inner ear. In the past, many embedding techniques have been tested in the cochlea to find an optimal protocol that gives both good morphological and immunohistochemical results. Resins provide high quality cochlear morphology with reduced immunogenicity due to the higher polymerization temperature. NEW METHOD: We used Technovit 9100 New(®), a low temperature embedding system based on methyl methacrylate, on adult guinea pig and mouse cochleae to evaluate preservation of the morphology and maintenance of the antigenicity. RESULTS: Conventional toluidine blue staining, as well as immunohistochemical staining with a set of commonly used antibodies, showed highly preserved morphology and immunogenicity of decalcified adult guinea pig and mouse cochleae. COMPARISON WITH EXISTING METHOD(S): We demonstrate both, well-preserved morphology and preservation of antigenicity, superior to other embedding techniques. CONCLUSIONS: Our results showed that the Technovit 9100 New(®) embedding system provided highly preserved morphology and immunogenicity with our protocol in adult guinea pig and mouse cochleae.

Assessing cisplatin-induced ototoxicity and otoprotection in whole organ culture of the mouse inner ear in simulated microgravity.

Cisplatin is a widely used anti-cancer drug. Ototoxicity is a major dose-limiting side-effect. A reproducible mammalian in-vitro model of cisplatin ototoxicity is required to screen and validate otoprotective drug candidates. We utilized a whole organ culture system of the postnatal mouse inner ear in a rotating wall vessel bioreactor under "simulated microgravity" culture conditions. As previously described this system allows whole organ culture of the inner ear and quantitative assessment of ototoxic effects of aminoglycoside induced hair cell loss. Here we demonstrate that this model is also applicable to the assessment of cisplatin induced ototoxicity. In this model cisplatin induced hair cell loss was dose and time dependent. Increasing exposure time of cisplatin led to decreasing EC50 concentrations. Outer hair cells were more susceptible than inner hair cells, and hair cells in the cochlear base were more susceptible than hair cells in the cochlear apex. Initial cisplatin dose determined the final extent of hair cell loss irrespective if the drug was withdrawn or continued. Dose dependant otoprotection was demonstrated by co-administration of the antioxidant agent N-acetyl l-cysteine. The results support the use of this inner ear organ culture system as an in vitro assay and validation platform for inner ear toxicology and the search for otoprotective compounds.

Modeling and analyzing traffic safety perceptions: An application to the speed limit reduction pilot project in Edmonton, Alberta.

To address the speeding problem in residential areas, the City of Edmonton initiated a pilot project to reduce the posted speed limit from 50km/h to 40km/h within six residential communities. This paper investigates the community perceptions of traffic safety within the six pilot communities in two phases: prior to project initiation (pre-pilot) and following the end of the project (post-pilot). This objective was accomplished by analyzing the results of two random dialing telephone surveys comprising 300 residents each. A preliminary analysis showed compatible demographic configurations for the two samples and confirmed that the residents were aware of both the posted speed limits and the adopted speed management controls. For the confirmatory factor analysis (CFA), a two-group (pre-pilot and post-pilot) three-factor model was used to assess the residents' perceptions of the speeding behavior (Speeding), their concerns about traffic safety issues (Concerns), and their perceptions of traffic safety (Safety). Comparing the CFA results of the post-pilot survey versus those of the pre-pilot survey, it was evident that there was a significant decrease in Speeding and Concerns accompanied by a significant increase in Safety. A structural equations model (SEM) was also fitted to the data in order to assess the impact of Speeding and Concerns on Safety. The results showed that Concerns increase significantly with Speeding, and that both factors have significant negative impacts on Safety. However, while the impact of Concerns on Safety was direct, that of Speeding on Safety was largely indirect (i.e., mediated through Concerns). Overall, the multivariate analysis has demonstrated that the pilot project was successful in improving the residents' perceptions of traffic safety in their community.