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Objectives: This study aimed to establish the minimal clinically important difference (MCID) and assess the responsiveness of the Chinese version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn)., Study Design: Prospective multicenter study., Setting: Four Chinese tertiary referral centers admitting patients nationwide., Patients: 230 adult patients with chronic otitis media (COM) undergoing tympanoplasty., Intervention: Patients were required to complete the ZCMEI-21-Chn to measure health-related quality of life both preoperatively and postoperatively. An anchor-based method was used to determine the MCID of the derivative cohort by including the Global Rating of Change Questionnaire as an anchor. The generalizability and consistency with functional outcomes of the MCID estimates were externally examined in a validation cohort using a receiver operating characteristic curve analysis., Results: A total of 161 and 69 patients were included in the derivative and validation cohort. The mean preoperative and postoperative ZCMEI-21-Chn total scores were 28.4 (standard deviation [SD] 14.5) and 17.5 (SD 12.6). The mean change in ZCMEI-21-Chn score was 10.9 (SD 14.3, p < 0.001). The MCIDs of the ZCMEI-21-Chn for improvement and deterioration were estimated at 13 (SD 13.0) and -7 (SD 12.9), accordingly. For patients who have reported an improved health-related quality of life, a cutoff value of 15.6 dB HL for elevation of the air-conducted hearing threshold was noticed. However, change of clinical importance judged according to MCID and Japan Otological Society criteria disagreed with each other, notably with a Cohen's kappa ( κ ) of 0.14 ( p = 0.21) in the validation cohort., Conclusion: This study is the first to establish the MCID of a COM-specific questionnaire in Chinese. For the COM population undergoing surgical intervention, MCID values of 13 for improvement and -7 for deterioration are recommended. The results were externally validated to be generalizable to nationwide usage, yet distinguishable from the audiological criteria. The availability of the MCID greatly adds to the clinical utility of the ZCMEI-21-Chn by enabling a clinically meaningful interpretation of its score changes., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Pathology repositories worldwide store millions of celloidin-processed human brain and temporal bone (TB) sections vital for studying central nervous system diseases and sensory organs. However, accessing these sections for modern molecular-pathological research, like immunohistochemistry, is hindered by the challenge of removing celloidin without damaging tissue. In this study, we explored the use of polyethylene glycols (PEGs), a class of non-hazardous, ethylene glycol oligomers, combined with an improved section mounting technique, to gently and effectively dissolve celloidin from sections archived for up to 40 years. Optimizing our protocol involved exploring celloidin dissolution kinetics in PEGs of varying molecular weights and terminations, as well as different temperatures. Low molecular weight PEGs, particularly PEG 200, were the most efficient celloidin solvent. Nuclear magnetic resonance (NMR) spectroscopy of celloidin-PEG 200 dissolution products revealed no chemical alterations, suggesting pure solvation without chemical modification. Because the solvation of celloidin in PEG was inhibited by proteins, we further developed a protein-free mounting protocol allowing complete celloidin removal in 30 to 60 minutes by immersing in PEG 200. In summary, our approach overcomes major methodological hurdles, rendering decades-old archival celloidin sections viable for immunohistochemical and other molecular biological techniques, while enhancing safety and workflow efficiency.

Purpose: In cochlear implantation with flexible lateral wall electrode arrays, a cochlear coverage (CC) range between 70% and 80% is considered ideal for optimal speech perception. To achieve this CC, the cochlear implant (CI) electrode array has to be chosen according to the individual cochlear duct length (CDL). Here, we mathematically analyzed the suitability of different flexible lateral wall electrode array lengths covering between 70% and 80% of the CDL., Methods: In a retrospective cross-sectional study preoperative high-resolution computed tomography (HRCT) from patients undergoing cochlear implantation was investigated. The CDL was estimated using an otosurgical planning software and the CI electrode array lengths covering 70-80% of the CDL was calculated using (i) linear and (ii) non-linear models., Results: The analysis of 120 HRCT data sets showed significantly different model-dependent CDL. Significant differences between the CC of 70% assessed from linear and non-linear models (mean difference: 2.5 mm, p < 0.001) and the CC of 80% assessed from linear and non-linear models (mean difference: 1.5 mm, p < 0.001) were found. In up to 25% of the patients none of the existing flexible lateral wall electrode arrays fit into this range. In 59 cases (49,2%) the models did not agree on the suitable electrode arrays., Conclusions: The CC varies depending on the underlying CDL approximation, which critically influences electrode array choice. Based on the literature, we hypothesize that the non-linear method systematically overestimates the CC and may lead to rather too short electrode array choices. Future studies need to assess the accuracy of the individual mathematical models., (© 2023. The Author(s).)

Background: Chronic otitis media (COM) can lead to significant impairment of health-related quality of life (HRQoL) due to symptoms such as otorrhea, pain, hearing loss, tinnitus, or dizziness. A systematic assessment of HRQoL in COM is becoming increasingly important as it complements (semi-)objective outcome parameters in clinical practice and research. HRQoL is measured by means of patient-reported outcome measures (PROMs). There are two disease-specific validated PROMs available for COM in German-the Chronic Otitis Media Outcome Test (COMOT-15) and the Zurich Chronic Middle Ear Inventory (ZCMEI-21)-which have become increasingly popular in recent years., Objective: The purpose of this narrative review is to present the current state of research on measuring HRQoL in COM before and after surgical procedures., Results and Conclusion: Hearing is the most important factor influencing HRQoL in COM. Surgical procedures usually result in a clinically relevant improvement in HRQoL in COM with or without cholesteatoma. However, if cholesteatoma is present, its extent does not correlate with HRQoL. While HRQoL plays a secondary role in establishment of the indication for surgical therapy in COM with cholesteatoma, it plays an important role in terms of relative surgical indications, e.g., a symptomatic open mastoid cavity after resection of the posterior canal wall. We encourage the regular use of disease-specific PROMs preoperatively as well as during follow-up to assess HRQoL in COM in individual patients, in research, and in the context of quality monitoring., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Competing Interests: The authors disclose no conflicts of interest.

We aimed to determine the prevalence of radiological temporal bone features that in previous studies showed only a weak or an inconsistent association with the clinical diagnosis of Meniere's disease (MD), in two groups of MD patients (n = 71) with previously established distinct endolymphatic sac pathologies; i.e. the group MD-dg (ES degeneration) and the group MD-hp (ES hypoplasia). Delayed gadolinium-enhanced MRI and high-resolution CT data were used to determine and compare between and within (affected vs. non-affected side) groups geometric temporal bone features (lengths, widths, contours), air cell tract volume, height of the jugular bulb, sigmoid sinus width, and MRI signal intensity alterations of the ES. Temporal bone features with significant intergroup differences were the retrolabyrinthine bone thickness (1.04 ± 0.69 mm, MD-hp; 3.1 ± 1.9 mm, MD-dg; p < 0.0001); posterior contour tortuosity (mean arch-to-chord ratio 1.019 ± 0.013, MD-hp; 1.096 ± 0.038, MD-dg; p < 0.0001); and the pneumatized volume (1.37 [0.86] cm 3 , MD-hp; 5.25 [3.45] cm 3 , MD-dg; p = 0.03). Features with differences between the affected and non-affected sides within the MD-dg group were the sigmoid sinus width (6.5 ± 1.7 mm, affected; 7.6 ± 2.1 mm, non-affected; p = 0.04) and the MRI signal intensity of the endolymphatic sac (median signal intensity, affected vs. unaffected side, 0.59 [IQR 0.31-0.89]). Radiological temporal bone features known to be only weakly or inconsistently associated with the clinical diagnosis MD, are highly prevalent in either of two MD patient groups. These results support the existence of diverse-developmental and degenerative-disease etiologies manifesting with distinct radiological temporal bone abnormalities., (© 2023. The Author(s).)

Objectives: Enlarged vestibular aqueduct (EVA) is a common finding associated with inner ear malformations (IEM). However, uniform radiologic definitions for EVA are missing and various 2D-measurement methods to define EVA have been reported. This study evaluates VA volume in different types of IEM and compares 3D-reconstructed VA volume to 2D-measurements., Methods: A total of 98 high-resolution CT (HRCT) data sets from temporal bones were analyzed (56 with IEM; [cochlear hypoplasia (CH; n = 18), incomplete partition type I (IPI; n = 12) and type II (IPII; n = 11) and EVA (n = 15)]; 42 controls). VA diameter was measured in axial images. VA volume was analyzed by software-based, semi-automatic segmentation and 3D-reconstruction. Differences in VA volume between the groups and associations between VA volume and VA diameter were assessed. Inter-rater-reliability (IRR) was assessed using the intra-class-correlation-coefficient (ICC)., Results: Larger VA volumes were found in IEM compared to controls. Significant differences in VA volume between patients with EVA and controls (p < 0.001) as well as between IPII and controls (p < 0.001) were found. VA diameter at the midpoint (VA midpoint) and at the operculum (VA operculum) correlated to VA volume in IPI (VA midpoint: r = 0.78, VA operculum: r = 0.91), in CH (VA midpoint: r = 0.59, VA operculum: r = 0.61), in EVA (VA midpoint: r = 0.55, VA operculum: r = 0.66) and in controls (VA midpoint: r = 0.36, VA operculum: r = 0.42). The highest IRR was found for VA volume (ICC = 0.90)., Conclusions: The VA diameter may be an insufficient estimate of VA volume, since (1) measurement of VA diameter does not reliably correlate with VA volume and (2) VA diameter shows a lower IRR than VA volume. 3D-reconstruction and VA volumetry may add information in diagnosing EVA in cases with or without additional IEM., (© 2022. The Author(s).)

Purpose: A narrow bony internal auditory canal (IAC) may be associated with a hypoplastic cochlear nerve and poorer hearing performances after cochlear implantation. However, definitions for a narrow IAC vary widely and commonly, qualitative grading or two-dimensional measures are used to characterize a narrow IAC. We aimed to refine the definition of a narrow IAC by determining IAC volume in both control patients and patients with inner ear malformations (IEMs)., Methods: In this multicentric study, we included high-resolution CT (HRCT) scans of 128 temporal bones (85 with IEMs: cochlear aplasia, n = 11; common cavity, n = 2; cochlear hypoplasia type, n = 19; incomplete partition type I/III, n = 8/8; Mondini malformation, n = 16; enlarged vestibular aqueduct syndrome, n = 19; 45 controls). The IAC diameter was measured in the axial plane and the IAC volume was measured by semi-automatic segmentation and three-dimensional reconstruction., Results: In controls, the mean IAC diameter was 5.5 mm (SD 1.1 mm) and the mean IAC volume was 175.3 mm 3 (SD 52.6 mm 3 ). Statistically significant differences in IAC volumes were found in cochlear aplasia (68.3 mm 3 , p < 0.0001), IPI (107.4 mm 3 , p = 0.04), and IPIII (277.5 mm 3 , p = 0.0004 mm 3 ). Inter-rater reliability was higher in IAC volume than in IAC diameter (intraclass correlation coefficient 0.92 vs. 0.77)., Conclusions: Volumetric measurement of IAC in cases of IEMs reduces measurement variability and may add to classifying IEMs. Since a hypoplastic IAC can be associated with a hypoplastic cochlear nerve and sensorineural hearing loss, radiologic assessment of the IAC is crucial in patients with severe sensorineural hearing loss undergoing cochlear implantation., (© 2022. The Author(s).)

Background: Endolymphatic sac tumors are rare neoplasia characterized by slow growth. However, their clinical impact should not be underestimated, considering their potential for local aggressive behavior and strong association with von Hippel-Lindau syndrome. Therefore, early detection with emerging theragnostic examinations such as 68 Ga-DOTATATE-PET/CT might improve patient management and reduce morbidity., Methods: We report the clinicopathological features of seven endolymphatic sac tumors. In this cohort, we performed immunohistochemical analysis of somatostatin receptor 2A (SSTR2A) and prostate specific membrane antigen (PSMA) protein expression patterns; two targets providing rationale for novel imaging modalities such as PSMA- or SSTR-targeted PET., Results: The tumor cells of all cases were negative for prostate specific membrane antigen and somatostatin receptor 2A, however immunolabeling was consistently detected in intratumoral endothelial cells of endolymphatic sac tumors for PSMA (7/7 cases, 100%), and for SSTR2A (5/7 cases, 71%)., Conclusions: Our results show a high rate of PSMA and SSTR2A expression in the tumor vasculature of endolymphatic sac tumors. PSMA and SSTR2A can be targeted with appropriate radioligands for diagnostic and therapeutic purposes. This finding provides a rationale for prospective clinical studies to test this approach as a sensitive screening tool for patients with suspected endolymphatic sac tumors including an improved management of von Hippel-Lindau syndrome., (© 2022. The Author(s).)

Background: Perfect hearing is crucial to the practice of various professions, such as instrument makers, musicians, sound engineers, and other professions not related to music, such as sonar technicians. For people of these occupational groups, we propose the term "professional ear user" (PEU) in analogy to "professional voice user". PEUs have special requirements for their hearing health, as they have well-known above-average auditory perceptual abilities on which they are professionally dependent., Objective: The purpose of this narrative review is to summarize selected aspects of the prevention, diagnosis, and treatment of ear disorders in PEUs., Results and Conclusion: Prevention of hearing disorders and other ear diseases includes protection from excessive sound levels, avoidance of ototoxins and nicotine, and a safe manner of cleaning the outer auditory canal. Diagnosing hearing disorders in PEUs can be challenging, since subclinical but relevant changes in hearing cannot be reliably objectified by conventional audiometric methods. Moreover, the fact that a PEU is affected by an ear disease may influence treatment decisions. Further, physicians must be vigilant for non-organic ear diseases in PEUs. Lastly, measures to promote comprehensive ear health in PEUs as part of an educational program and to maintain ear health by means of a specialized otolaryngology service are discussed. In contrast to existing concepts, we lay the attention on the entirety of occupational groups that are specifically dependent on their ear health in a professional setting. In this context, we suggest avoiding a sole focus on hearing disorders and their prevention, but rather encourage the maintenance of a comprehensive ear health., (© 2022. The Author(s).)

Low-frequency sensorineural hearing loss (SNHL) is a rare hearing impairment affecting frequencies below 1000 Hz, previously associated with DIAPH1, WSF1, MYO7A, TNC, SLC26A4 or CCDC50 genes. By exome sequencing, we report a novel nonsense variant in CENPP gene, segregating low-frequency SNHL in five affected members in a Swiss family with autosomal dominant inheritance pattern. Audiological evaluation showed up-sloping audiometric configuration with mild-to-moderate losses below 1000 Hz, that progresses to high-frequencies over time. Protein modeling shows that the variant truncates five amino acids at the end, losing electrostatic interactions that alter protein stability. CENPP gene is expressed in the supporting cells of the organ of Corti and takes part as a subunit of the Constitutive Centromere Associated Network in the kinetochore, that fixes the centromere to the spindle microtubules. We report CENPP as a new candidate gene for low-frequency SNHL. Further functional characterization might enable us to elucidate its molecular role in SNHL., (© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)

Objective: To determine the prevalence of endolymphatic hydrops (EH) in cochlear implant (CI) candidates with idiopathic profound sensorineural hearing loss (SNHL) and its influence on the preservation of audiovestibular function after cochlear implantation., Study Design: Prospective case series., Setting: Tertiary referral center., Patients: CI candidates with idiopathic progressive SNHL, but without classic EH-associated symptoms., Interventions: Delayed intravenous gadolinium-enhanced inner ear fluid-attenuated inversion recovery magnetic resonance imaging as well as pure-tone audiograms, video head impulse tests, and vestibular evoked myogenic potentials before and 4 weeks after cochlear implantation., Main Outcome Measures: Prevalence of EH before cochlear implantation, audiovestibular function before and after surgery in hydropic and nonhydropic ears., Results: Thirty-two ears in 16 CI candidates were included. Nine ears (28%) with EH were detected. Although preoperative hearing thresholds, utricular function, and semicircular canal function were not different between the two groups, saccular function was reduced in hydropic ears. Ten subjects received a unilateral CI. Of these, 3 (30%) showed EH on the implanted side. There was no difference regarding postoperative hearing loss between the two groups, but the results point toward a higher vulnerability of hydropic ears with respect to loss of otolith function after cochlear implantation., Conclusions: This is the first study showing that EH can be assumed in about one third of CI candidates with idiopathic profound SNHL, but no classic EH-associated symptoms. Preliminary results suggest that EH has no influence on the preservation of cochlear function but could be a risk factor for loss of otolith function after cochlear implantation., Competing Interests: Financial disclosures/conflicts of interest: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

A "gold standard" for quantitatively diagnosing inner ear malformations (IEMs) and a consensus on normative measurements are lacking. Reference ranges and cutoff values of inner ear dimensions may add in distinguishing IEM types. This study evaluates the volumes of the cochlea and vestibular system in different types of IEM., Study Design: Retrospective cohort., Setting: Tertiary academic center., Patients: High-resolution CT scans of 115 temporal bones (70 with IEM; cochlear hypoplasia [CH]; n = 19), incomplete partition (IP) Types I and III (n = 16), IP Type II with an enlarged vestibular aqueduct (Mondini malformation; n = 16), enlarged vestibular aqueduct syndrome (n = 19), and 45 controls., Interventions: Volumetry by software-based, semiautomatic segmentation, and 3D reconstruction., Main Outcome Measures: Differences in volumes among IEM and between IEM types and controls; interrater reliability., Results: Compared with controls (mean volume, 78.0 mm3), only CH showed a significantly different cochlear volume (mean volume, 30.2 mm3; p < 0.0001) among all types of IEM. A cutoff value of 60 mm3 separated 100% of CH cases from controls. Compared with controls, significantly larger vestibular system volumes were found in Mondini malformation (mean difference, 22.9 mm3; p = 0.009) and IP (mean difference, 24.1 mm3; p = 0.005). In contrast, CH showed a significantly smaller vestibular system volume (mean difference, 41.1 mm3; p < 0.0001). A good interrater reliability was found for all three-dimensional measurements (ICC = 0.86-0.91)., Conclusion: Quantitative reference values for IEM obtained in this study were in line with existing qualitative diagnostic characteristics. A cutoff value less than 60 mm3 may indicate an abnormally small cochlea. Normal reference values for volumes of the cochlea and vestibular system may aid in diagnosing IEM., (Copyright © 2022, Otology & Neurotology, Inc.)

Objective: The aim of the present study was to identify patients who developed acute unilateral peripheral vestibulopathy (AUPVP) after COVID-19 vaccination., Methods: For this single-center, retrospective study, we screened the medical records of our tertiary interdisciplinary neurotology center for patients who had presented with AUPVP within 30 days after COVID-19 vaccination (study period: 1 June-31 December 2021). The initial diagnosis of AUPVP was based on a comprehensive bedside neurotological examination. Laboratory vestibular testing (video head impulse test, cervical and ocular vestibular evoked myogenic potentials, dynamic visual acuity, subjective visual vertical, video-oculography, caloric testing) was performed 1-5 months later., Results: Twenty-six patients were diagnosed with AUPVP within the study period. Of those, n = 8 (31%) had developed acute vestibular symptoms within 30 days after COVID-19 vaccination (mean interval: 11.9 days, SD: 4.8, range: 6-20) and were thus included in the study. The mean age of the patients (two females, six males) was 46 years (SD: 11.7). Seven patients had received the Moderna mRNA vaccine and one the Pfizer/BioNTech mRNA vaccine. All patients displayed a horizontal(-torsional) spontaneous nystagmus toward the unaffected ear and a pathological clinical head impulse test toward the affected ear on initial clinical examination. Receptor-specific laboratory vestibular testing performed 1-5 months later revealed recovery of vestibular function in two patients, and heterogeneous lesion patterns of vestibular endorgans in the remaining six patients., Discussion and Conclusions: The present study should raise clinicians' awareness for AUPVP after COVID-19 vaccination. The relatively high fraction of such cases among our AUPVP patients may be due to a certain selection bias at a tertiary neurotology center. Patients presenting with acute vestibular symptoms should be questioned about their vaccination status and the date of the last vaccination dose. Furthermore, cases of AUPVP occurring shortly after a COVID-19 vaccination should be reported to the health authorities to help determining a possible causal relationship., 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 reviewer SH declared a shared parent affiliation with the authors to the handling editor at the time of review., (Copyright © 2022 Schmid, Bächinger, Pangalu, Straumann and Dlugaiczyk.)

Purpose: Evaluating the current health state in chronic otitis media (COM), audiologic results are complemented by subjective outcomes, such as health-related quality of life (HRQoL). Two disease-specific instruments assessing HRQoL in COM in German-speaking patients exist, i.e., the chronic otitis media outcome test (COMOT-15) and the Zurich chronic middle ear inventory (ZCMEI-21). Since the psychometric properties of these questionnaires in a concurrent application are unknown, the aim of this study was to compare the COMOT-15 and the ZCMEI-21., Methods: HRQoL was assessed in adult COM patients using the COMOT-15 and the ZCMEI-21. Psychometric properties were determined, including response distribution, concurrent validity, internal consistency, correlation to hearing and gender differences., Results: In 173 patients (mean age 51.5 years), both questionnaires showed normally distributed scores without strong floor and ceiling effects. The total scores and subscores of both questionnaires exhibited satisfactory internal consistency (Cronbach's α 0.7-0.9) with the exception of the COMOT-15 hearing subscore (α = 0.94) and the ZCMEI-21 medical resource subscore (α = 0.66). Fair correlations between the air conduction pure-tone average and the total scores were found (COMOT-15: r = 0.36, p < 0.0001; ZCMEI-21: r = 0.34, p < 0.0001)., Conclusion: In the first study comparing the COMOT-15 and the ZCMEI-21, both questionnaires exhibited satisfactory psychometric properties with several subtle differences. The COMOT-15 has a strong focus on hearing with a probably redundant content of the hearing subscore and may be suited for hearing-focused research questions. The ZCMEI-21 provides a comprehensive assessment of the COM symptom complex and may therefore also be used in research settings, where ear discharge, vertigo or pain should be covered., (© 2021. The Author(s).)

Background: Surgical treatment of vestibular schwannoma (VS) leads to acute ipsilateral vestibular loss if there is residual vestibular function before surgery. To overcome the sequelae of acute ipsilateral vestibular loss and to decrease postoperative recovery time, the concept of preemptive vestibular ablation with gentamicin and vestibular prehabilitation before surgery has been developed ("vestibular prehab")., Objective: Studying postural stability during walking and handicap of dizziness over a 1-year follow-up period in VS patients undergoing vestibular prehab before surgical treatment of VS., Methods: A retrospective review of consecutive patients with a diagnosis of a VS undergoing surgical therapy from June 2012 to March 2018 was performed. All patients were included with documentation of the length of hospital duration and the Dizziness Handicap Inventory (DHI) and the Functional Gait Assessment (FGA) assessed preoperatively as well as 6 weeks and 1 year postoperatively., Results: A total 68 VS patients were included, of which 29 patients received preoperative vestibular ablation by intratympanic injection of gentamicin. Mean VS diameter was 20.2 mm (SD 9.4 mm) and mean age at surgery was 49.6 years (SD 11.5 years). Vestibular prehab had no effect on DHI and FGA at any time point studied., Conclusions: We found no effect of vestibular prehab on postural stability during walking and on the handicap of dizziness. These findings add to the body of knowledge consisting of conflicting results of vestibular prehab. Therefore, vestibular prehab should be applied only in selected cases in an experimental setting.

Introduction: Surgical obliteration is the treatment of choice for symptomatic mastoid cavities. Various methods and materials are available. Allogeneic material is easily available but can lead to wound infections due to rejection, granulation and inflammatory reactions. Consequently, autologous material is often preferred due to its good biocompatibility. The aim of this study was to compare the long-term outcomes of patients after mastoid cavity obliteration with allogeneic and autologous material with regard to the occurrence of recurrent cholesteatoma, the number of revision surgeries and the impact of surgery on the health-related quality of life., Methods: Patients who underwent mastoid cavity obliteration with an allogeneic material (hydroxyapatite matrix [HMM]) were retrospectively included in the study. In a prospective part, patients who underwent mastoid cavity obliteration with autologous reconstruction material (AutoM) were included. In addition to a detailed chart review, all patients underwent pure tone audiometry and completed the Zurich Chronic Middle Ear Inventory (ZCMEI-21) at the postoperative examination to assess health-related disease-specific quality of life., Results: A total of 22 patients with a mean age of 56.9 (SD 18.7 years) receiving HMM (mean follow-up interval: 88.3 months [SD 21.9 months]) and 25 patients with a mean age of 52.4 years (SD 13.7 years) receiving AutoM (mean follow-up interval: 13.5 months [SD 9.5 months]) were included in the study. The revision-free rate for audiological indication after one year was 100% for HMM and 85% for AutoM. The recurrence-free rate at one year was 95% for HMM and 100% for AutoM. 55% of the patients with alloplastic material and 8% of the patients with autologous material required revision surgery due to ear discharge or recurrent cholesteatoma. The groups did not differ in terms of postoperative hearing outcome or postoperative quality of life., Discussion: Obliteration of mastoid cavities is a surgical challenge. There was no relevant difference between the materials used in terms of recurrence rate, hearing and health-related quality of life within the 13.5-month observation period of both groups. The lack of subjective symptoms together with the high rate of recurrent cholesteatoma and revision indications emphasises the need for regular clinical follow-up including ear microscopy in chronic middle ear disease and strongly suggests regular follow-up examinations., Competing Interests: Die Autoren geben an, keine Interessenkonflikte zu haben. Vorresultate der Studie wurden bereits auf Englisch publiziert (Weiss et al., Otol Neurotol 41:e55 – e63, 2020)., (Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany.)

Purpose: Different types of chronic middle ear disease (CMED) present with differing severity of single symptoms, such as discharge, vertigo or hearing loss, which impair health-related quality of life (HRQoL). Here, we aimed to (i) investigate characteristics of HRQoL and (ii) evaluate the association between HRQoL and hearing among different types of CMED., Methods: In this prospective longitudinal cohort study, we included adult patients undergoing surgical treatment for CMED. Primary outcomes included HRQoL assessed by the Zurich Chronic Middle Ear Inventory (ZCMEI-21) and hearing assessed by pure-tone audiometry., Results: In the included 108 patients (51% females), CMED were chronic otitis media (COM) with (n = 46) or without (n = 22) cholesteatoma, persistent mastoid cavity (with [n = 15] or without [n = 10] recurrent cholesteatoma), revision ossiculoplasty for hearing restoration (n = 14), and postinflammatory meatal fibrosis (n = 1). Preoperatively, the mean ZCMEI-21 score showed statistically significant differences among different types of CMED (p = 0.007) with persistent mastoid cavity without cholesteatoma exhibiting the highest score (34.1, SD 7.7) indicating poor HRQoL. At a mean follow-up period of 183 days, no statistically significant differences in the ZCMEI-21 scores among different types of CMED were observed (p = 0.67)., Conclusion: This study objectifies differences in HRQoL among different types of CMED. In patients with indication for functional surgery only, e.g., persistent mastoid cavity without cholesteatoma, the worst HRQoL was observed. Yet, in these types of CMED, HRQoL guides decision for treatment. Moreover, differences in HRQoL among different types of CMED were not closely associated with hearing, but largely depended on other symptoms, such as discharge or vertigo., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Meniere's disease (MD) progresses from unilateral to bilateral disease in up to 50% of patients, often chronically and severely impairing balance and hearing functions. According to previous studies, 91% of bilateral MD patients demonstrate bilateral hypoplasia of the endolymphatic sac (ES) upon histological and radiological examination of their inner ears. Here, we seek to validate a radiological marker for ES hypoplasia that predicts the risk for future progression to bilateral MD in individual patients. Methods: Patients with unilateral MD and radiological evidence for ES hypoplasia in either the clinically affected inner ear (cohort MD uni -hp uni ) or both inner ears (cohort MD uni -hp bi ) were included. Given our hypothesis that ES hypoplasia critically predisposes the inner ear to MD, we expected progression to bilateral MD only in the MD uni -hp bi cohort. To investigate eventual progression to bilateral MD, clinical, audiometric, and imaging data were retrospectively collected over follow-up periods of up to 31 years. Results: A total of 44 patients were included in the MD-hp uni ( n = 15) and MD uni -hp bi ( n = 29) cohorts. In line with our radiology-based predictions, none (0/15) of the MD-hp uni patients exhibited progression to bilateral MD, whereas 20/29 (69%) MD-hp bi patients have already progressed to bilateral MD. Using the Kaplan-Meier estimator, bilateral disease progression would be observed in 100% of MD-hp bi patients 31 years after the initial diagnosis with an estimated median time to bilateral progression of 12 years. The nine MD-hp bi patients who, so far, remained with unilateral disease demonstrated a median time since initial (unilateral) MD diagnosis of only 6 years and are thus still expected to progress to bilateral disease. Conclusion: Progression to bilateral MD adheres to predictions based on the radiological presence or absence of ES hypoplasia. This prognostic tool, if validated by prospective long-term studies, will provide clinically relevant information about a patient's future disease burden and will help to select more personalized treatment regimens., 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 © 2021 Bächinger, Schuknecht, Dlugaiczyk and Eckhard.)

Competing Interests: Die Autoren geben an, keine Interessenkonflikte zu haben. Vorresultate der Studie wurden bereits auf Englisch publiziert (Weiss et al., Otol Neurotol 41:e55 – e63, 2020).

Purpose: To establish a standardized reporting system of cholesteatoma, the ChOLE classification has recently been introduced. We here aimed to systematically investigate the association between the ChOLE classification and (i) hearing, (ii) recidivism rate, and (iii) postoperative complications. These data may increase the utility of the ChOLE classification in clinical practice and research by stratifying patients according to expected outcomes or risks for complications., Methods: In this prospective multicentric study, we included adult patients undergoing tympanomastoid surgery due to cholesteatoma. Main outcome measures included the association of the ChOLE classification system with (i) audiometric data including air conduction (AC) and bone conduction (BC) pure-tone average (PTA), and the air-bone gap (ABG), (ii) recidivism and complication., Results: A total of 160 patients suffering from cholesteatoma were included. ChOLE stage distribution was stage I in 23 (14%), stage II in 128 (80%), and stage III in 9 (6%) patients. The ChOLE stage was associated with the postoperative AC PTA (p = 0.05) and the postoperative BC PTA (p = 0.02). Further, the status of the ossicular chain after surgery (ChOLE subdivision "O") was associated with both the postoperative ABG (p = 0.0001) and the postoperative AC PTA (p = 0.003). Moreover, we found an association between complications (ChOLE subdivision "L) and both the postoperative BC PTA (p = 0.04) and the postoperative ABG (p = 0.04). No association between the ChOLE stage was found to both cholesteatoma recidivism and surgical complications., Conclusion: The ChOLE classification is a new system to classify cholesteatomas. We provide evidence that hearing outcomes vary among different ChOLE stages. In particular, hearing outcomes are associated with the ChOLE subdivision "O" and "L". Thus, the ChOLE classification system has a predictive value regarding hearing outcomes.

Purpose: Aural fullness is a common symptom of middle ear diseases, most importantly Eustachian tube dysfunction (ETD). Yet, aural fullness may also be caused by inner ear disorders, such as hydropic ear diseases. Here, we report our experience with endolymphatic hydrops (EH) mimicking ETD. Furthermore, we review the literature related to (i) EH as a differential diagnosis of symptoms suggesting ETD and (ii) the pathophysiology and treatment of aural fullness due to inner ear disorders., Methods: We retrospectively included adult patients with aural fullness as chief complaint and radiographically diagnosed EH. Hearing and Eustachian tube function were assessed using audiometry, tympanometry, and tubomanometry. Primarily suspected ETD was treated by balloon dilatation of the Eustachian tube (BDET). The endolymphatic space of the inner ear was imaged using gadolinium-enhanced MRI (Gd-MRI) including a 3D-real inversion-recovery sequence after intravenous gadolinium administration., Results: We report three affected ears of two patients (two females, age 42 and age 51) with aural fullness as chief complaint. Audiometry of main speech frequencies was normal in all affected ears. In one ear, there was a type A tympanogram and in two ears, there was a type B tympanogram. In both patients, medical treatment for ETD and BDET were unsuccessful. Gd-MRI of the inner ears revealed cochlear EH in 3/3 ears affected by aural fullness, but not in the unaffected ear., Conclusion: EH may underlay cases with aural fullness and could in these cases explain unsuccessful treatment for ETD. As ETD is often treated by invasive procedures, distinguishing ETD from EH as the underlying cause of aural fullness is important. Our findings raise the question whether Gd-MRI to rule out EH is indicated in patients with unexplained aural fullness, in particular after unsuccessful interventional treatment for ETD.

Hypothesis: Epithelial ion transport pathologies of the endolymphatic sac (ES) are associated with large vestibular aqueduct syndrome (LVAS)., Background: LVAS is defined by the pathognomonic features of a widened bony vestibular aqueduct (VA) and an enlarged ES. The underlying cause of its associated cochleovestibular symptoms remains elusive. Disturbances in epithelial ion transport in the enlarged ES, affecting inner ear fluid regulation, were proposed as a possible pathophysiology. However, although respective epithelial ion transport pathologies have been demonstrated in the enlarged ES from transgenic LVAS mouse models, these pathologies have not been investigated in human LVAS cases., Methods: Histological and immunohistochemical analysis of the enlarged ES epithelium in postmortem temporal bones from two individuals with a clinical diagnosis of LVAS., Results: The enlarged ES epithelium demonstrated an overall atypical epithelial differentiation and a lack of the immunolocalization of signature ion transport proteins. Notably, in both cases, a rudimentary branch of the ES with a typically differentiated ES epithelium was present., Conclusions: The described cellular and molecular pathologies of the enlarged ES in humans provide evidence of epithelial transport pathology as one potential cause of cochleovestibular symptoms in LVAS. The present findings also emphasize the clinical relevance of already established LVAS mouse models.

Objectives: To investigate the association between the "ChOLE" classification, hearing outcomes and disease-specific health-related quality of life (HRQoL)., Methods: In two tertiary referral centers, patients requiring primary or revision surgery for cholesteatoma were assessed for eligibility. Audiometric assessment was performed pre- and postoperatively. The ChOLE classification was determined intraoperatively and via the preoperative CT scan. HRQoL was assessed pre- and postoperatively using the Zurich Chronic Middle Ear Inventory (ZCMEI-21)., Results: A total of 87 patients (mean age 45.2 years, SD 16.2) were included in this study. ChOLE stage I cholesteatoma was found in 8 (9%), stage II cholesteatoma was found in 65 (75%), and stage III cholesteatoma was found in 14 (16%) patients. Postoperatively, the mean air-bone gap (0.5, 1, 2, 3 kHz) was significantly smaller than before surgery (14.3 dB vs. 23.0 dB; p = 0.0007). The mean ZCMEI-21 total score significantly decreased after surgery (26.8 vs. 20.7, p = 0.004). No correlation between the ZCMEI-21 total score and both the ChOLE stage and the extent of the cholesteatoma (ChOLE subdivision "Ch") was found. A trend towards worse HRQoL associated with a poorer status of the ossicular chain (ChOLE subdivision "O") was observed. The audiometric outcomes were not associated with the extent of the cholesteatoma. The ChOLE subdivision describing the ossicular status showed a strong association with the pre- and postoperative air conduction (AC) thresholds. Further, the ZCMEI-21 total score and its hearing subscore correlated with the AC thresholds., Conclusion: The ChOLE classification does not show a clear association with HRQoL measured by the ZCMEI-21. The HRQoL neither seems to be associated with the extent of the disease nor with the ossicular chain status. Yet, surgical therapy significantly improved HRQoL by means of reduced ZCMEI-21 total scores, which were strongly associated with the AC thresholds. Intraoperative assessment of a cholesteatoma using the ChOLE classification and HRQoL complement each other and provide useful information.

Signal transducer and activator of transcription 1 (STAT1) is known to be an important player in inflammatory responses. STAT1 as a transcription factor regulates the expression of multiple proinflammatory genes. Inflammatory response is one of the common effects of ototoxicity. Our group reported that hair cells of STAT1 knockout (STAT1-KO) mice are less sensitive to ototoxic agents in-vitro. The effect of inflammatory responses in STAT1-KO mice has primarily been studied challenging them with several pathogens and analyzing different organs of those mice. However, the effect of STAT1 ablation in the mouse inner ear has not been reported. Therefore, we evaluated the cochlear function of wild type and STAT1-KO mice via auditory brain stem response (ABR) and performed histopathologic analysis of their temporal bones. We found ABR responses were affected in STAT1-KO mice with cases of bilateral and unilateral hearing impairment. Histopathologic examination of the middle and inner ears showed bilateral and unilateral otitis media. Otitis media was characterized by effusion of middle and inner ear that varied between the mice in volume and inflammatory cell content. In addition, the thickness of the middle ear mucosae in STAT1-KO mice were more pronounced than those in wild type mice. The degree of middle and inner ear inflammation correlated with ABR threshold elevation in STAT1-KO mice. It appears that a number of mice with inflammation underwent spontaneous resolution. The ABR thresholds were variable and showed a tendency to increase in homozygous and heterozygous STAT1-KO mice. These findings suggest that STAT1 ablation confers an increased susceptibility to otitis media leading to hearing impairment. Thus, the study supports the new role of STAT1 as otitis media predisposition gene., Competing Interests: The authors have declared that no competing interests exist.

Background: The demand for assessing health-related quality of life (HRQoL) in chronic otitis media (COM) is increasing globally. The currently available Chinese-language patient-reported outcome measurement (PROM) specific for COM includes merely a limited range of related symptoms and dimensions. Hence, in this study, we aim to translate, culturally adapt, and validate the Zurich Chronic Middle Ear Inventory (ZCMEI-21) in Chinese, to enable a comprehensive evaluation of the patients' subjective health outcome in COM., Methods: We sampled and surveyed 223 COM patients at three tertiary referral centers in China, using the Chinese translation of ZCMEI-21 (ZCMEI-21-Chn) and the EQ-5D questionnaire, a generic measure of HRQoL. Confirmatory factor analysis (CFA) was performed to investigate the structural model fit to the dataset. Cronbach's α and test-retest reliability coefficient were calculated to establish reliability, and correlation was tested between ZCMEI-Chn scores and EQ-5D scores for convergent validity., Results: A total of 208 adult patients with COM were included, with a mean age of 46 years (SD 14 years) and a male proportion of 41% (85/208). A modified bifactor model with ω H of 0.65 and ECV of 0.47 was found to fit the scale scores, indicating fair general factor saturation and multidimensionality of the instrument. ZCMEI-21-Chn demonstrated good reliability (Cronbach's α = 0.88, test-retest reliability = 0.88). The total scores of ZCMEI-21-Chn had a moderate correlation with a question directly addressing HRQoL (r = 0.40, p < 0.001), EQ-5D descriptive system score (r = 0.57, p < 0.001), and EQ-5D visual analogous scale (r = 0.30, p < 0.001)., Conclusions: The ZCMEI-21-Chn is valid, reliable and culturally adapted to Chinese adult patients with COM. This study offers clinicians an efficient and comprehensive instrument to quantify COM patients' self-reported health outcomes, which could facilitate the standardization of HRQoL data aggregation in COM on a global scale.

Objective: To assess the change in health-related quality of life (HRQoL) in patients undergoing mastoid cavity obliteration., Methods: Patients who had undergone canal wall-down mastoidectomy for chronic otitis media with creation of a persistent mastoid cavity and underwent revision tympanomastoid surgery including mastoid cavity obliteration using autologous material were included. Audiological measurements including air conduction (AC) and bone conduction (BC) pure-tone averages (PTA) and the air-bone gap (ABG) were assessed. Health-related Quality of Life (HRQoL) was assessed by the Zurich Chronic Middle Ear Inventory (ZCMEI-21) pre- and postoperatively., Results: A total of 25 patients (16 females and 9 males; mean age 51.6 years, 14 right and 11 left ears) were included. Patients were reexamined after a mean follow-up period of 9.2 months (SD = 6.5) after obliteration of the mastoid cavity. Compared to the preoperative visit, patients showed a significantly reduced AC PTA at the postoperative visit (mean difference: - 4.1; SD = 10.4, p = 0.045). The mean ZCMEI-21 score changed from 31.7 (SD = 14.5) preoperatively to 17.4 (SD = 15.1) postoperatively (mean difference: - 14.3; SD = 19.1; p = 0.0002). The mean ZCMEI-21 score changes were neither correlated to the AC PTA shift (p = 0.60) nor to the ABG shift (p = 0.66)., Conclusions: This is the first study reporting a highly significant and clinically important improvement in HRQoL after mastoid cavity obliteration in a prospective setting. The improvement in HRQoL was not correlated to the hearing improvement. As a clinical implication, we provide evidence for a substantial subjective benefit of the surgical obliteration of a symptomatic mastoid cavity and, therefore, encourage this surgical procedure.

Aim: To determine the minimal clinically important difference (MCID) of the Zurich Chronic Middle Ear Inventory (ZCMEI-21), a questionnaire assessing health-related quality of life (HRQoL) in chronic otitis media (COM)., Methods: In this longitudinal study, 103 patients completed the ZCMEI-21 before and after surgery for chronic otitis media. An anchor-based method including a global rating of change (GRC) was used to assess the MCID of the ZCMEI-21., Results: A total of 103 patients were included. The mean preoperative and postoperative ZCMEI-21 scores were 28.6 (SD 13.6), and 21.8 (SD 12.8), respectively. The mean change was 6.8 (SD 0.8; p < 0.0001). A significant correlation between the ZCMEI-21 scores and the GRC was found (r =  - 0.5; p < 0.001). Using the anchor-based method, the MCID of the ZCMEI-21 was estimated at 5.3 (SD 12.0)., Conclusions: Knowledge of values indicating a clinically relevant change in patient-reported outcome measures is important when interpreting effects of different treatment modalities. This is the first study assessing the MCID of a questionnaire measuring HRQoL in COM, i.e. the ZCMEI-21. We recommend a MCID of 5 in COM patients undergoing surgical treatment. This information substantially increases the usefulness of the ZCMEI-21 as an outcome measure in COM as changes can be assessed with regard to their clinical meaningfulness.

Objective: To assess long-term results and present experience with a high-porosity hydroxyapatite ceramic for obliterating large open mastoid cavities., Study-Design: Cross-sectional cohort study., Setting: Tertiary academic referral center., Patients: All patients who underwent tympanomastoid surgery for chronic middle ear disease or revision surgery with reduction of an open mastoid cavity using a highly porous hydroxyapatite matrix material (HMM) between May 2005 and June 2013 were assessed for eligibility. Twenty three patients (56.9 ± 18.3 yr) were included., Intervention: Primary middle ear surgery or revision surgery using a HMM., Main Outcome Measures: Pure-tone average, computed tomography (CT), and magnetic resonance imaging (MRI) to investigate osseoinduction, osseointegration and presence of cholesteatoma, current quality of life assessed by Zurich Chronic Middle Ear Inventory and change in quality of life post-intervention assessed by the Glasgow Benefit Inventory., Results: Patients were reexamined after a mean follow-up period of 88.3 months (SD 21.4 mo) after obliteration of the open mastoid cavity with HMM. Compared with visit 1, patients showed a significantly reduced ABG at visit 2 (29.22 dB ± 2.71 dB versus 12.77 dB ± 3.46 dB).CT scan was carried out in 21 patients (91%) patients and 17 patients (74%) underwent MRI.Revision surgery was required in a total of 17 cases (74%). In four patients recurrent cholesteatoma was found at follow up., Conclusions: Poor cavity obliteration, a high rate of revision surgery and difficult differentiation between recurrent cholesteatoma and granulation tissue in CT scan was observed.

An exceptionally low calcium (Ca 2+ ) concentration in the inner ear endolymph ([Ca 2+ ] endolymph ) is crucial for proper auditory and vestibular function. The endolymphatic sac (ES) is believed to critically contribute to the maintenance of this low [Ca 2+ ] endolymph . Here, we investigated the immunohistochemical localization of proteins that are presumably involved in the sensing and transport of extracellular Ca 2+ in the murine ES epithelium. Light microscopic and fluorescence immunolabeling in paraffin-embedded murine ES tissue sections (male C57BL/6 mice, 6-8 weeks old) demonstrated the presence of the calcium-sensing receptor CaSR, transient receptor potential cation channel subtypes TRPV5 and TRPV6, sarco/endoplasmic reticulum Ca 2+ -ATPases SERCA1 and SERCA2, Na + /Ca 2+ exchanger NCX2, and plasma membrane Ca 2+ ATPases PMCA1 and PMCA4 in ES epithelial cells. These proteins exhibited (i) membranous (apical or basolateral) or cytoplasmic localization patterns, (ii) a proximal-to-distal labeling gradient within the ES, and (iii) different distribution patterns among ES epithelial cell types (mitochondria-rich cells (MRCs) and ribosome-rich cells (RRCs)). Notably, in the inner ear membranous labyrinth, CaSR was exclusively localized in MRCs, suggesting a unique role of the ES epithelium in CaSR-mediated sensing and control of [Ca 2+ ] endolymph . Structural loss of the distal ES, which is consistently observed in Meniere's disease, may therefore critically disturb [Ca 2+ ] endolymph and contribute to the pathogenesis of Meniere's disease.

Aminoglycoside ototoxicity is common in clinical practice but reliable protective agents currently do not exist. Aminoglycoside regimens causing ototoxicity in different laboratory animals are under investigation. The assessment method used most commonly to determine auditory effects is the auditory brainstem response (ABR). Distortion product otoacoustic emissions (DPOAE) have been used less frequently. A precise recommendation on the specific method to assess peripheral auditory function before and after aminoglycoside toxicity in mice does not exist. In order to evaluate various mouse models for ototoxic injury caused by various aminoglycoside regimens, there is a need for performing preliminary tests in small cohorts before large experiments. The aim of our study was to investigate different aminoglycoside regimens that cause substantial ototoxic damage in vivo . Aminoglycosides are safe and produce a detectable hearing threshold shift in a small cohort of mice that can be used as a model for preliminary tests. Different ototoxic regimens were assessed by ABR and DPOAE measurements pre- and post-treatment. Further, the sensory cell loss was quantified by counting hair cells in the cochlea. It was revealed that an ototoxic regimen with kanamycin twice daily for 15 consecutive days is safe, well tolerated and produces an early significant hearing threshold shift detected by DPOAE in a small cohort of mice. The study compared ABR and DPOAE in mentioned regimens for the first time and illustrated that DPOAE is well suited for detecting hearing threshold shifts in high frequencies before ABR threshold shifts occur in accordance with predominating outer hair cell damage mainly in the basal turn of the cochlea.

Objective: To evaluate the quality of perceived sound after stapedotomy over a 1-year follow-up period focussing on incidence of dysacusis, particularly distorted sound perception (DSP). DSP was assessed by (i) determination of the frequencies and hearing level that such perceptions are elicited by pure tones (pure-tone-evoked distorted sound perception, PTE-DSP), a novel psychoacoustic measurement introduced in this paper, and (ii) assessment of patient-reported occurrence of DSP using the Amsterdam Post Operative Sound Evaluation (APOSE) questionnaire (APOSE-DSP)., Design: Prospective study., Study Sample: Patients (n = 23) with otosclerosis undergoing stapedotomy., Results: An air-bone gap of <20 dB was achieved in 100% of the patients. Three weeks postoperatively, 48% of the patients reported measured PTE-DSP and 39% of the patients experienced APOSE-DSP. The PTE-DSP significantly decreased during the 1-year follow-up period (p = 0.03). Postoperatively, APOSE-DSP was associated with a smaller benefit (improvement in air conduction; p = 0.03), yet, a lower bone conduction pure-tone average was associated with PTE-DSP (p = 0.006)., Conclusions: DSP after stapedotomy is associated with a smaller benefit 3 months after stapedotomy. DSP commonly occur after stapedotomy, but decrease over time. This is important information to be included in patient counselling before stapedotomy.

Hypothesis: The vestibular aqueduct (VA) in Menière's disease (MD) exhibits different angular trajectories depending on the presenting endolymphatic sac (ES) pathology, i.e., 1) ES hypoplasia or 2) ES degeneration., Background: Hypoplasia or degeneration of the ES was consistently found in inner ears affected by MD. The two etiologically distinct ES pathologies presumably represent two disease "endotypes," which may be associated with different clinical traits ("phenotypes") of MD. Recognizing these endotypes in the clinical setting requires a diagnostic tool., Methods: 1) Defining the angular trajectory of the VA (ATVA) in the axial plane. 2) Measuring age-dependent normative data for the ATVA in postmortem temporal bone histology material from normal adults and fetuses. 3) Validating ATVA measurements from normative CT imaging data. 4) Correlating the ATVA with different ES pathologies in histological materials and CT imaging data from MD patients., Results: 1) The ATVA differed significantly between normal adults and MD cases with ES degeneration, as well as between fetuses and MD cases with ES hypoplasia; 2) a strong correlation between ATVA measurements in histological sections and CT imaging data was found; 3) a correlation between the ATVA, in particular its axial trajectory in the opercular region (angle αexit), with degenerative (αexit < 120°) and hypoplastic ES pathology (αexit > 140°) was demonstrated., Conclusion: We established the ATVA as a radiographic surrogate marker for ES pathologies. CT-imaging-based determination of the ATVA enables endotyping of MD patients according to ES pathology. Future studies will apply this method to investigate whether ES endotypes distinguish clinically meaningful subgroups of MD patients.

Objectives: To translate and validate the Zurich Chronic Middle Ear Inventory (ZCMEI-21) for the English language in order to provide an English instrument to assess health-related quality of life in chronic otitis media (COM)., Design: Pilot translation study including cognitive debriefings, prospective multicentre cross-sectional psychometric validation study., Setting: Four tertiary referral centres in three different English-speaking countries (UK, USA and Australia)., Participants: Adult patients suffering from COM., Main Outcome Measures: The English translation of the ZCMEI-21 (ZCMEI-21-E) and the five-level version of the EQ-5D questionnaire. The EQ-5D, which constitutes a generic measure of health-related quality of life, consists of a descriptive system score and a visual analogue scale. Statistical outcomes included single-item descriptive statistics, internal consistency (Cronbach's α) as an indicator of reliability, as well as construct validity., Results: A total of 124 patients suffering from COM were included. The mean age was 50.1 years (SD 16.9 years), and 72 (58.1%) were males. The Cronbach's α of the ZCMEI-21-E was 0.91, suggesting an excellent internal consistency. The Spearman's correlation coefficient of the ZCMEI-21-E total score was 0.55 (P < 0.0001) for convergent construct validity with EQ-5D descriptive system score and 0.57 (P < 0.0001) with the EQ-5D visual analogue scale., Conclusions: The ZCMEI-21-E is a new validated questionnaire that provides clinicians with a short, comprehensive and reliable instrument to quantify health-related quality of life in patients suffering from COM. The ZCMEI-21-E may be of use in clinical routine as well as in outcome research and monitoring., (© 2018 John Wiley & Sons Ltd.)

Two histopathological subtypes of Meniere's disease (MD) were recently described in a human post-mortem pathology study. The first subtype demonstrated a degenerating distal endolymphatic sac (ES) in the affected inner ear (subtype MD-dg); the second subtype (MD-hp) demonstrated an ES that was developmentally hypoplastic. The two subtypes were associated with different clinical disease features (phenotypes), suggesting that distinct endotype-phenotype patterns exist among MD patients. Therefore, clinical endotyping based on ES pathology may reveal clinically meaningful MD patient subgroups. Here, we retrospectively determined the ES pathologies of clinical MD patients ( n = 72) who underwent intravenous delayed gadolinium-enhanced inner ear magnetic resonance imaging using previously established indirect radiographic markers for both ES pathologies. Phenotypic subgroup differences were evidenced; for example, the MD-dg group presented a higher average of vertigo attacks (ratio of vertigo patterns daily/weekly/other vs. monthly, MD-dg: 6.87: 1; MD-hp: 1.43: 1; p = 0.048) and more severely reduced vestibular function upon caloric testing (average caloric asymmetry ratio, MD-dg: 30.2% ± 30.4%; MD-hp: 13.5% ± 15.2%; p = 0.009), while the MD-hp group presented a predominantly male sex ratio (MD-hp: 0.06:1 [f/m]; MD-dg: 1.2:1 [f/m]; p = 0.0004), higher frequencies of bilateral clinical affection (MD-hp: 29.4%; MD-dg: 5.5%; p = 0.015), a positive family history for hearing loss/vertigo/MD (MD-hp: 41.2%; MD-dg: 15.7%; p = 0.028), and radiographic signs of concomitant temporal bone abnormalities, i.e., semicircular canal dehiscence (MD-hp: 29.4%; MD-dg: 3.6%; p = 0.007). In conclusion, this new endotyping approach may potentially improve the diagnosis, prognosis and clinical decision-making for individual MD patients.

Objective: There are no instruments available to comprehensively assess health-related quality of life (HRQoL) in chronic otitis media (COM) in Italian-speaking countries. The Zurich chronic middle ear inventory (ZCMEI-21) is a well-established instrument for the assessment of HRQoL in COM. The objective of this study was to translate and cross-culturally adapt the ZCMEI-21 into Italian and validate this questionnaire for measuring HRQoL in patients with COM., Study Design: Prospective multicenter study., Setting: Three University hospitals (northern Italy, central Italy, southern Italy)., Patients: Adult patients suffering from COM (n = 128)., Intervention: Following international guidelines, the ZCMEI-21 was translated into Italian (ZCMEI-21-It). Validation was performed by psychometric test statistics. Moreover, ZCMEI-21-It total and subscale scores were compared and correlated with 1) the scores of the original validation study, 2) to a question that directly addresses HRQoL, and 3) to the scores of the EQ-5D-5L, a generic questionnaire assessing HRQoL., Results: From three study centers, a total of 128 patients with COM were included. Cronbach's α was 0.86 indicating a high reliability. Between the ZCMEI-21-It total score and the question that directly addresses HRQoL, we found a strong correlation (r = 0.62, p < 0.0001). Between the ZCMEI-21-It total score and the EQ-5D-5L scores, we expectedly found moderate correlations (descriptive system score: r = 0.39, p < 0.0001; visual analog scale: r = 0.30, p = 0.008)., Conclusion: We translated the ZCMEI-21 questionnaire into Italian and validated the ZCMEI-21-It in a prospective multicenter study. The ZCMEI-21-It is the first instrument that comprehensively assesses relevant dimensions of HRQoL in Italian-speaking patients affected by COM.

Objective: In the assessment of chronic otitis media (COM) and its treatment, patient-reported outcomes are becoming increasingly important. The aim of the present study was to translate and validate the Zurich chronic middle ear inventory (ZCMEI-21) in Japanese in order to provide the first Japanese-language instrument for measuring health-related quality of life (HRQoL) in COM., Methods: The ZCMEI-21 was translated into Japanese according to published guidelines. In order to assess validity, the ZCMEI-21-Jap total score was compared to a question directly addressing HRQoL as well as the five-level version of the EQ-5D questionnaire, a generic measure of HRQoL., Results: Demographic data and validity were assessed in a total of 91 COM patients. The ZCMEI-21-Jap total and subscale scores were well comparable to those of the original validation study. Cronbach's α of the ZCMEI-21-Jap was 0.85, indicating an excellent internal consistency. The ZCMEI-21-Jap total score showed a strong correlation (r=0.68, p<0.0001) to the question directly addressing HRQoL and, as expected, only a moderate correlation to the EQ-5D scores (r=0.49, p<0.0001 for descriptive system score and r=0.44, p<0.0001 for VAS score)., Conclusion: We successfully translated the ZCMEI-21 into Japanese and were able to obtain sufficient information during the validation process for the use of the ZCMEI-21-Jap to quantify HRQoL in patients with COM. With the current study, we aim to take a step forward towards an international standardization of reporting HRQoL in COM., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aminoglycosides have detrimental effects on the hair cells of the inner ear, yet these agents indisputably are one of the cornerstones in antibiotic therapy. Hence, there is a demand for strategies to prevent aminoglycoside-induced ototoxicity, which are not available today. In vitro data suggests that the pleiotropic growth factor erythropoietin (EPO) is neuroprotective against aminoglycoside-induced hair cell loss. Here, we use a mouse model with EPO-overexpression in neuronal tissue to evaluate whether EPO could also in vivo protect from aminoglycoside-induced hearing loss. Auditory brainstem response (ABR) thresholds were measured in 12-weeks-old mice before and after treatment with kanamycin for 15 days, which resulted in both C57BL/6 and EPO-transgenic animals in a high-frequency hearing loss. However, ABR threshold shifts in EPO-transgenic mice were significantly lower than in C57BL/6 mice (mean difference in ABR threshold shift 13.6 dB at 32 kHz, 95% CI 3.8-23.4 dB, p = 0.003). Correspondingly, quantification of hair cells and spiral ganglion neurons by immunofluorescence revealed that EPO-transgenic mice had a significantly lower hair cell and spiral ganglion neuron loss than C57BL/6 mice. In conclusion, neuronal overexpression of EPO is protective against aminoglycoside-induce hearing loss, which is in accordance with its known neuroprotective effects in other organs, such as the eye or the brain., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Because existing patient-reported outcome measures (PROMs) specific for chronic otitis media (COM) are lacking certain relevant symptoms and dimensions of health-related quality of life (HRQoL), we aimed to develop and validate a new questionnaire for comprehensively measuring HRQoL in adult patients with COM. An expert panel and patients were involved in developing the first version of the Zurich chronic middle ear inventory, containing 33 items (ZCMEI-33). An electronic application was chosen not only to provide maximal data quality, but also to facilitate and accelerate data analysis. Item reduction was performed by testing the questionnaire in a first cohort (n = 85). Using sequential statistical analysis, the ZCMEI-33 was reduced to 21 items (ZCMEI-21). Subsequently, the ZCMEI-21 was validated in a second cohort (n = 76). Validation revealed a Cronbach's α of 0.91, indicating excellent internal consistency. Moreover, the ZCMEI-21 was able to discriminate between patients with COM and healthy participants (p < 0.0001), thus possessing good discrimination validity. Assessing criterion validity, the ZCMEI-21 total score was compared to a question directly addressing HRQoL and the EQ-5D descriptive system score, a generic measure of HRQoL. Whereas the ZCMEI-21 total score and the EQ-5D descriptive system score were only moderately correlated (r = 0.60, p < 0.0001), the ZCMEI-21 total score and the question directly addressing HRQoL showed a strong correlation (r = 0.74, p < 0.0001). In conclusion, sufficient information on reliability and validity was obtained to propagate the application of the ZCMEI-21 to quantify HRQoL in patients with COM.

A 21-year-old male suffering from severe throat pain after being hit by a bullet in Syria claimed that he was shot through his eye and that the bullet subsequently descended behind his throat. Even though the first medical report stated that this course is implausible, meticulous workup provided evidence that the bullet might have entered the parapharyngeal space in a more cranial position than the one it was found eight months later. Our case highlights that bullets are able to move within the body, rendering ballistic reconstruction difficult. However, after removal of the bullet the patient's symptoms completely resolved.