A single dose of AC102 restores hearing in a guinea pig model of noise-induced hearing loss to almost prenoise levels.

Although sudden sensorineural hearing loss (SSNHL) is a serious condition, there are currently no approved drugs for its treatment. Nevertheless, there is a growing understanding that the cochlear pathologies that underlie SSNHL include apoptotic death of sensory outer hair cells (OHCs) as well as loss of ribbon synapses connecting sensory inner hair cells (IHCs) and neurites of the auditory nerve, designated synaptopathy. Noise-induced hearing loss (NIHL) is a common subtype of SSNHL and is widely used to model hearing loss preclinically. Here, we demonstrate that a single interventive application of a small pyridoindole molecule (AC102) into the middle ear restored auditory function almost to prenoise levels in a guinea pig model of NIHL. AC102 prevented noise-triggered loss of OHCs and reduced IHC synaptopathy suggesting a role of AC102 in reconnecting auditory neurons to their sensory target cells. Notably, AC102 exerted its therapeutic properties over a wide frequency range. Such strong improvements in hearing have not previously been demonstrated for other therapeutic agents. In vitro experiments of a neuronal damage model revealed that AC102 protected cells from apoptosis and promoted neurite growth. These effects may be explained by increased production of adenosine triphosphate, indicating improved mitochondrial function, and reduced levels of reactive-oxygen species which prevents the apoptotic processes responsible for OHC death. This action profile of AC102 might be causal for the observed hearing recovery in in vivo models.

Unilateral Multifocal Inner Ear and Internal Auditory Canal or Cerebellopontine Angle Cochleovestibular Schwannomas-Genetic Analysis and Management by Surgical Resection and Cochlear Implantation.

OBJECTIVE: To describe the genetic characteristics and the management of two very rare cases of unilateral multifocal inner ear and internal auditory canal or cerebellopontine angle cochleovestibular schwannomas not being associated to full neurofibromatosis type 2-related schwannomatosis. PATIENTS: In a 29-year-old man and a 55-year-old woman with single-sided deafness multifocal unilateral cochleovestibular schwannomas were surgically resected, and hearing was rehabilitated with a cochlear implant (CI). Unaffected tissue was analyzed using next generation sequencing of the NF2 gene. Tumor tissue was analyzed using a 340-parallel sequencing gene panel. MAIN OUTCOME MEASURES: Mutations in the NF2 gene, word recognition score for monosyllables at 65 dB SPL (WRS 65 ) with CI. RESULTS: No disease-causing mutation was detected in the examined sequences in blood leucokytes. All tumor samples revealed, among others, somatic pathogenic NF2 mutations. While the anatomically separate tumors in case 1 were likely molecular identical, the tumors in case 2 showed different genetic patterns. WRS 65 was 55% at 6 years of follow-up and 60% at 4.5 years of follow-up, respectively. CONCLUSIONS: The occurrence of multifocal unilateral cochleovestibular schwannomas without pathogenic variants in NF2 in non-affected blood leucocytes can be associated with mosaic NF2 -related schwannomatosis (case 1), or with likely sporadic mutations (case 2) and may be overlooked due to their extreme rarity. Although challenging, successful hearing rehabilitation could be achieved through surgical resection of the tumors and cochlear implantation.

150 years ago: Schwartze's 1873 mastoidectomy and its implementation over the following 2 years.

BACKGROUND: In 1873, Hermann Schwartze and Adolf Eysell described a new surgical technique for treating mastoid disease using a mallet, chisels, and gouges of various sizes instead of trephines or drill instruments also called "modern mastoidectomy." On the 150th jubilee of this landmark article, we pay tribute by studying the reception and implementation of mastoidectomy in the 2 years following its publication. METHODS: The commentaries published in the otological and medical literature between the second part of 1873 to the end of 1875 were studied with an emphasis on the three specialized otological journals and the otological textbooks that existed during this period. RESULTS AND CONCLUSION: The princeps paper Ueber die künstliche Eröffnung des Warzenfortsatzes ("On the artificial opening of the mastoid process") by Hermann Schwartze and Adolf Eysell published in 1873 was rapidly disseminated in the medical literature for nearly 1 year, and then entered a phase of evaluation followed by a phase of extension and implementation, before finding its definitive place in the history of mastoid process surgery.

Bilateral intracochlear schwannomas: histopathological confirmation and outcomes following tumour removal and cochlear implantation with lateral wall electrodes.

Intracochlear schwannomas (ICS) are very rare benign tumours of the inner ear. We present histopathological proof of the extremely rare bilateral occurrence of intracochlear schwannomas with negative blood genetic testing for neurofibromatosis type 2 (NF2). Bilateral schwannomas are typically associated with the condition NF2 and this case is presumed to have either mosaicism for NF2 or sporadic development of bilateral tumours. For progressive bilateral tumour growth and associated profound hearing loss, surgical intervention via partial cochleoectomy, tumour removal, preservation of the modiolus, and simultaneous cochlear implantation with lateral wall electrode carrier with basal double electrode contacts was performed. The right side was operated on first with a 14-month gap between each side. The hearing in aided speech recognition for consonant-nucleus-consonant (CNC) phonemes in quiet improved from 57% to 83% 12 months after bilateral cochlear implantation (CI). Bilateral intracochlear schwannomas in non-NF2 patients are extremely rare but should be considered in cases of progressive bilateral hearing loss. Successful tumour removal and cochlear implantation utilizing a lateral wall electrode is possible and can achieve good hearing outcomes.

An analysis of the spread of electric field within the cochlea for different devices including custom-made electrodes for subtotal cochleoectomy.

OBJECTIVE: Cochlear implants (CIs) can restore hearing not only in patients with profound hearing loss and deafness, but also in patients following tumour removal of intra-cochlear schwannomas. In such cases, design and placement differ from conventional electrode insertion, in which the cochlea remains filled with fluid. Despite these technical and surgical differences, previous studies have tended to show positive results in speech perception in tumour patients. The purpose of this study is to retrospectively evaluate the ability to predict speech recognition outcomes using individual electric field spreads and to investigate worldwide unique tumour cases. STUDY DESIGN: In a retrospective analysis in a university tertiary center electric field spreads were compared between two groups of electrode designs implanted between 2009 and 2020 i.e., between lateral wall electrodes and custom-made perimodiolar electrode carriers from the same company. The voltage gradients were analysed and grouped with speech recognition results. RESULTS: Differences in electrical field spreads were found between lateral wall electrodes and the custom-made perimodiolar electrodes, whereas a significant influence of electric fields on scores in speech recognition cannot be demonstrated. CONCLUSION: Prediction of speech recognition outcome based on electric field propagation results seems not feasible. Significant differences in field spread between electrode arrays can be clearly demonstrated. This observation and its relevance to hearing treatment and speech recognition should therefore be further investigated in upcoming studies.

The Rate of Eustachian Tube Dysfunction in Adult Patients With Chronic Inflammatory Middle Ear Disease Is Low.

OBJECTIVE: To assess the rate of dilatory (chronic obstructive) eustachian tube dysfunction (ETD) in adult patients scheduled for surgery for chronic inflammatory middle ear disease. PATIENTS: We included adult patients with chronic inflammatory middle ear disease (chronic suppurative otitis media, adhesive otitis media [middle ear atelectasis], cholesteatoma). We excluded patients with pathologies that do not stem from ETD (e.g., noninflammatory chronic middle ear disease [e.g., otosclerosis], tumors, solely external auditory canal conditions), patients scheduled for implantable electronic hearing devices independent of disease, patients with otitis media with effusion and scheduled paracentesis or ventilation tubes only, patients with previous radiotherapy or previous balloon eustachian tuboplasty, and children and patients unable to complete questionnaires. INTERVENTIONS: We evaluated ETD with Valsalva maneuver and in case of negative or unclear Valsalva with the eustachian tube score (ETS). A negative Valsalva maneuver and an ETS score of 5 or lower were used to define dilatory (chronic obstructive) ETD. MAIN OUTCOME MEASURES: Rate of ETD in the included patients. RESULTS: From a total of 482 consecutive patients, 350 patients had positive Valsalva maneuver or ETS score higher than 5. From the 193 patients with negative or unclear Valsalva maneuver, 77 patients had an ETS score of 5 or lower, and 55 rejected further diagnostics with ETS. CONCLUSIONS: Based on a large cohort of adult patients with chronic inflammatory middle ear disease scheduled for middle ear surgery, the majority (82%) seems to have no dilatory (chronic obstructive) ETD that can be detected with current routine clinical methods and tubomanometry. Common pathophysiological explanations should be questioned critically, especially in the context of communication with patients.

[Individual computer-assisted 3D planning for placement of auricular prosthesis anchors in combination with an implantable transcutaneous bone conduction hearing device in patients with aural atresia. German version]. / Individuelle computergestützte 3D-Planung zur Platzierung von Epithesenankern in Kombination mit einem implantierbaren transkutanen Knochenleitungshörgerät bei Patienten mit Ohrfehlbildungen.

BACKGROUND: The simultaneous implantation of the Bonebridge (MED-EL, Innsbruck, Austria), a semi-implantable active transcutaneous bone conduction hearing device and anchors for auricular prostheses can be challenging as both implants contain magnets and compete for the narrow space in the designated implantation area. MATERIAL AND METHODS: A preoperative planning tool (virtual surgery) was used with individual 3D computer models of the skull and implants for finding optimal implant positions for both the floating mass transducer (FMT) and the anchors for the auricular prosthesis. The interaction between the magnetic prosthesis anchors and the FMT was measured by means of static magnetic forces. A retrospective data analysis was conducted to evaluate the surgical and audiological outcome. RESULTS: Between 2014 and 2021 a 3D planning of a simultaneous implantation of the Bonebridge with auricular prosthesis anchors was conducted on 6 ears of 5 patients (3 males, 2 females; age range 17-56 years). The individual preoperative planning was considered very useful for the optimal placement of bone anchors in combination with the Bonebridge. Audiological data showed a clear benefit for hearing 3 months and > 11 months after implantation. No adverse interactions between the magnetic prosthesis anchors and the FMT were observed. In two patients, revision surgery was carried out due to skin inflammation or wound healing problems. No long-term complications were observed 3-5 years after surgery. CONCLUSION: Preoperative 3D planning represents a clear benefit for the simultaneous audiological and esthetic rehabilitation using the Bonebridge and anchors for auricular prostheses.

Individual computer-assisted 3D planning for placement of auricular prosthesis anchors in combination with an implantable transcutaneous bone conduction hearing device in patients with aural atresia.

BACKGROUND: The simultaneous implantation of the Bonebridge (MED-EL, Innsbruck, Austria), a semi-implantable active transcutaneous bone conduction hearing device and anchors for auricular prostheses can be challenging as both implants contain magnets and compete for the narrow space in the designated implantation area. MATERIAL AND METHODS: A preoperative planning tool (virtual surgery) was used with individual 3D computer models of the skull and implants for finding optimal implant positions for both the floating mass transducer (FMT) and the anchors for the auricular prosthesis. The interaction between the magnetic prosthesis anchors and the FMT was measured by means of static magnetic forces. A retrospective data analysis was conducted to evaluate the surgical and audiological outcome. RESULTS: Between 2014 and 2021, a 3D planning of a simultaneous implantation of the Bonebridge with auricular prosthesis anchors was conducted on 6 ears of 5 patients (3 males, 2 females; age range 17-56 years). The individual preoperative planning was considered very useful for the optimal placement of bone anchors in combination with the Bonebridge. Audiological data showed a clear benefit for hearing 3 months and > 11 months after implantation. No adverse interactions between the magnetic prosthesis anchors and the FMT were observed. In two patients, revision surgery was carried out due to skin inflammation or wound healing problems. No long-term complications were observed 3-5 years after surgery. CONCLUSION: Preoperative 3D planning represents a clear benefit for the simultaneous audiological and esthetic rehabilitation using the Bonebridge and anchors for auricular prostheses.

[Objective Audiological Test Procedures: Indications and Differential Diagnostics]. / Objektive audiologische Messverfahren: Indikationen und Differenzialdiagnostik.

Diagnostics of hearing loss comprises subjective and objective methods and is successfully applied since many decades. This article introduces into the methods of impedance audiometry, otoacoustic emissions, auditory evoked potentials and electrically evoked potentials and describes the respective methodologies. Using an exemplary case, in this article we guide through all stages of objective audiological diagnostics and introduce the scientific and technical background, the application and evaluation of the findings of the objective test procedures. An application pathway for objective audiometric diagnostic tools is also described, including newborn hearing screening, differential diagnostics of hearing loss, auditory neuropathy, sudden sensorineural hearing loss, vestibular schwannoma and pediatrics patients. Finally, the application to patients with active middle-ear implants and cochlear implants is described.

Course of social support and associations with distress after partial laryngectomy.

PURPOSE: Social support has been shown to be positively associated with quality of life and adjustment after a cancer diagnosis. The present study investigates the course of social support up to one year after partial laryngectomy and its association with distress. DESIGN: Longitudinal questionnaire study. SAMPLE: A total of 428 patients after partial laryngectomy (mean age: 64, SD = 11, 91% male). METHODS: Patients completed questionnaires before treatment (t1), one week after a partial laryngectomy (t2), 3 months (t3), and one year (t4) thereafter. Social support was evaluated at t2, t3, and t4 using a brief version of the Social Support Questionnaire. Distress was measured at t2, t3, and t4 using the HADS. Descriptive statistics for social support were computed across the three measurement points. Changes were analyzed by Wilcoxon signed-rank tests. Associations with distress were identified using linear regression analyses. FINDINGS: Social support increased between t2 and t3 and decreased to baseline level between t3 and t4. Distress at t2 was associated with social support at t2 (B = -0.15, p < 0.01) and distress at t3 with social support at t3 (B = -0.19, p < 0.01). Distress at t4 was related to social support at t2 (B = -0.10, p = 0.05). CONCLUSIONS: Although perceived social support increases after partial laryngectomy, it decreases again during the course of aftercare. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS OR POLICY: Social support resources should be assessed to identify patients at risk for worse psychological well-being.

Clinical and functional results after implantation of the bonebridge, a semi-implantable, active transcutaneous bone conduction device, in children and adults.

PURPOSE: Aim of the study was to evaluate the surgical, clinical and audiological outcome of 32 implantations of the Bonebridge, a semi-implantable transcutaneous active bone conduction implant. METHODS: In a retrospective cohort study, we analyzed data for 32 implantations in 31 patients (one bilateral case; seven age < 16 years) with conductive or mixed hearing loss, malformations, after multiple ear surgery, or with single-sided deafness as contralateral routing of signal (CROS). RESULTS: Four implantations were done as CROS. Five cases were simultaneously planned with ear prosthesis anchors, and 23 implantations (72%) were planned through three-dimensional (3D) "virtual surgery." In all 3D-planned cases, the implant could be placed as expected. For implant-related complications, rates were 12.5% for minor and 3.1% for major complications. Implantation significantly improved mean sound field thresholds from a preoperative 60 dB HL (SD 12) to 33 dB HL (SD 6) at 3 postoperative months and 34 dB HL (SD 6) at > 11 postoperative months (p < 0.0001). Word recognition score in quiet at 65 dB SPL improved from 11% (SD 20) preoperatively to 74% (SD 19) at 3 months and 83% (SD 15) at > 11 months (p < 0.0001). The speech reception threshold in noise improved from - 1.01 dB unaided to - 2.69 dB best-aided (p = 0.0018). CONCLUSION: We found a clinically relevant audiological benefit with Bonebridge. To overcome anatomical challenges, we recommend preoperative 3D planning in small and hypoplastic mastoids, children, ear malformation, and simultaneous implantation of ear prosthesis anchors and after multiple ear surgery.

Prevalence of oropharyngeal dysphagia in geriatric patients and real-life associations with diseases and drugs.

Risk factors for oropharyngeal dysphagia (OD) in elderly patients are mainly central nervous system (CNS) and structural organic diseases or presbyphagia. We analysed the OD prevalence and association of OD with multimorbidity and polypharmacy using real-life data to complete this spectrum, with a focus on further and iatrogenic risk. This was a cross-sectional retrospective study based on a random sample of 200 patients admitted to a geriatric hospital. Data analysis included diagnoses, the detailed list of drugs, and an intense clinical investigation of swallowing according to Stanschus to screen for OD in each patient. The mean patient age was 84 ± 6.5 years. The prevalence of OD was 29.0%, without an effect of age, but a higher rate was found in men and in nursing home residents and an elevated risk of pneumonia. OD risk was slight in diabetes mellitus and COPD, and pronounced in CNS diseases. A relevant OD association was found, even after adjusting for CNS diseases, with antipsychotics, benzodiazepines, anti-Parkinson drugs, antidepressants, and antiepileptics. Further risk of OD was found with beta-blockers, alpha-blockers, opioids, antiemetics, antivertiginosa or antihistamines, metoclopramide, domperidone, anticholinergics, loop diuretics, urologics, and ophthalmics. From real-life data in patients with and without CNS diseases, we identified drug groups associated with a risk of aggravating/inducing OD. Restrictive indications for these drugs may be a preventative contribution, requiring implementation in dysphagia guidelines and an integrative dysphagia risk scale that considers all associated and cumulative medication risks in addition to diseases.

Rare Diseases and Otorhinolaryngology, Head and Neck Surgery. / Seltene Erkrankungen und Hals-Nasen-Ohren-Heilkunde, Kopf und Halschirurgie.

Rare diseases pose multiple challenges for patients, relatives, physicians, nursing staff, and therapists. Their rarity impedes research and treatments due to medical and economical reasons. Many diseases in the field otorhinolaryngology, head and neck surgery are rare diseases due to their low prevalence. The initiation of the right management processes requires knowledge about diagnostics, resources like centers, networks and registries, about specifics of the physician-patient relationship, follow-up care including communication with family doctors and the role of self-help groups. Of special interest for university hospitals and our scientific society are the specific aspects of research including European networks and research funding, information management, public relations, education, training, financing, and regulations like orphan drugs and clinical trials in small populations.

Optimized preoperative determination of nerve of origin in patients with vestibular schwannoma.

In vestibular schwannoma (VS) patients hearing outcome and surgery related risks can vary and depend on the nerve of origin. Preoperative origin differentiation between inferior or superior vestibular nerve may influence the decision on treatment, and the selection of optimal treatment and counselling modalities. A novel scoring system based on functional tests was designed to predict the nerve of origin for VS and was applied to a large number of consecutive patients. A prospective, double blind, cohort study including 93 patients with suspected unilateral VS was conducted at a tertiary referral centre. Preoperatively before tumor resection a functional test battery [video head-impulse test (vHIT) of all semicircular canals (SCC)], air-conducted cervical/ocular vestibular evoked myogenic potential tests (cVEMP, oVEMP), pure-tone audiometry, and speech discrimination was applied. Sensitivity and specificity of prediction of intraoperative finding by a preoperative score based on vHIT gain, cVEMP and oVEMP amplitudes and asymmetry ratios was calculated. For the prediction of inferior vestibular nerve origin, sensitivity was 73% and specificity was 80%. For the prediction of superior vestibular nerve origin, sensitivity was 60% and specificity was 90%. Based on the trade-off between sensitivity and specificity, optimized cut-off values of - 0.32 for cVEMP and - 0.11 for oVEMP asymmetry ratios and vHIT gain thresholds of 0.77 (anterior SCC), 0.84 (lateral SCC) and 0.80 (posterior SCC) were identified by receiver operator characteristic curves. The scoring system based on preoperative functional tests improves prediction of nerve of origin and can be applied in clinical routine.