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.

Enhancing Cochlear Implant Outcomes across Age Groups: The Interplay of Forward Focus and Advanced Combination Encoder Coding Strategies in Noisy Conditions.

Background: Hearing in noise is challenging for cochlear implant users and requires significant listening effort. This study investigated the influence of ForwardFocus and number of maxima of the Advanced Combination Encoder (ACE) strategy, as well as age, on speech recognition threshold and listening effort in noise. Methods: A total of 33 cochlear implant recipients were included (age ≤ 40 years: n = 15, >40 years: n = 18). The Oldenburg Sentence Test was used to measure 50% speech recognition thresholds (SRT50) in fluctuating and stationary noise. Speech was presented frontally, while three frontal or rear noise sources were used, and the number of ACE maxima varied between 8 and 12. Results: ForwardFocus significantly improved the SRT50 when noise was presented from the back, independent of subject age. The use of 12 maxima further improved the SRT50 when ForwardFocus was activated and when noise and speech were presented frontally. Listening effort was significantly worse in the older age group compared to the younger age group and was reduced by ForwardFocus but not by increasing the number of ACE maxima. Conclusion: Forward Focus can improve speech recognition in noisy environments and reduce listening effort, especially in older cochlear implant users.

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.

High-Dose Glucocorticoids for the Treatment of Sudden Hearing Loss.

High-Dose Glucocorticoids for Sudden Hearing LossThis trial compared courses of high-dose intravenous prednisolone or high-dose oral dexamethasone versus standard-dose oral prednisone in adults with idiopathic sudden sensorineural hearing loss. At 30 days, systemic high-dose glucocorticoid therapy was not superior to a lower-dose regimen with respect to change in hearing threshold, and it was associated with a higher risk of side effects.

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.

Influence of the Spread of the Electric Field on Speech Recognition in Cochlear Implant Users.

OBJECTIVE: To investigate the correlation of word recognition with cochlear implant (CI) and spread of the electric field. STUDY DESIGN: Prospective, noninterventional, experimental study. SETTING: A tertiary referral center. PATIENTS: Thirty-eight adult CI users with poor (n = 11), fair (n = 13), and good (n = 16) word recognition performance. MAIN OUTCOME MEASURE: Transimpedances were measured after 37 µs. Word recognition score was recorded at 65 dB SPL for German monosyllables in quiet. Transimpedance half widths were calculated as a marker for spread of the electric field. RESULTS: Narrow and broad spread of the electric field, i.e., small and large half widths, were observed in all word recognition performance groups. Most of the transimpedance matrices showed a pattern of expansion along the diagonal toward the apical electrode contacts. Word recognition was not correlated with transimpedance half widths. CONCLUSIONS: The half width of the spread of the electric field showed no correlation with word recognition scores in our study population.

Influence of Age on Speech Recognition in Noise and Hearing Effort in Listeners with Age-Related Hearing Loss.

The aim of this study was to measure how age affects the speech recognition threshold (SRT50) of the Oldenburg Sentence Test (OLSA) and the listening effort at the corresponding signal-to-noise ratio (SNRcut). The study also investigated the effect of the spatial configuration of sound sources and noise signals on SRT50 and SNRcut. To achieve this goal, the study used olnoise and icra5 noise presented from one or more spatial locations from the front and back. Ninety-nine participants with age-related hearing loss in the 18-80 years age range, specifically in the 18-30, 31-40, 41-50, 51-60, 61-70, and 71-80 age groups, participated in this study. Speech recognition and listening effort in noise were measured and compared between the different age groups, different spatial sound configurations and noise signals. Speech recognition in noise decreased with age and became significant from the age group of 50-51. The decrease in SRT50 with age was greater for icra5 noise than for olnoise. For all age groups, SRT50 and SNRcut were better for icra5 noise than for olnoise. The measured age-related reference data for SRT50 and SNRcut can be used in further studies in listeners with age-related hearing loss and hearing aid or implant users.

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.

[Recommendations of the German Society of Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) for the granting of resident training program authorizations]. / Empfehlungen der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC) für die Erteilung der fachspezifischen Weiterbildungsbefugnis.

The 2018 template for otorhinolaryngology specialist training of the German Medical Association is increasingly implemented by the federal associations. In this regard, the German Society recommended an otorhinolaryngology resident training plan for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) together with the Professional Association of German Otorhinolaryngologists as a suggested guideline for the federal medical associations. In this context, the state medical associations currently work on criteria on the basis of which otorhinolaryngologists and their training institutions can be granted authority for such a certified otorhinolaryngology resident training program.The DGHNO-KHC last made recommendations for the granting of authorizations for specialist training in otorhinolaryngology in 1999. Many contents have changed as a result of the 2018 model specialist training regulations. Therefore, a scientifically formulated proposal for the granting of continuing education authorizations is herewith provided as recommendation to the federal state medical associations.

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.

Treatment of tracheoesophageal fistulas following laryngectomy by customized prostheses-A bicentric case series.

Objective: Tracheoesophageal fistulas (TEF) following laryngectomy cause immense restrictions due to the inability of oral feeding, loss of voice rehabilitation, penetration of saliva, and permanent need of inflatable tracheal cannulas. Patients are consistently in threat of fatal aspiration pneumonias. The failure rate of surgical approaches to close the fistulas is high and an ultima ratio option by customized silicone prostheses can be considered. Methods: A retrospective analysis of 26 patients with a TEF was performed. Results: The fistulas occurred in average 40 months after laryngectomy caused by an enlargement of the voice fistula in 17 patients and problems in wound healing in 6 patients. The mean diameter of the fistula was 32 × 18 mm. Eight patients were treated by a button-shaped and 18 by a tube-shaped prosthesis. Complete oral feeding was possible in 8 and additional feeding by percutaneous endoscopic gastrostomy tube in 16 patients. Voice rehabilitation by voice prostheses was possible in 18 cases. Fifteen patients died in the course of the treatment either due to oncological progression or other reasons. The median follow-up time of the patients alive was 36 months (max 88 months) with 2.2 protheses replacements in mean (max 11). Conclusion: The treatment of TEF by customized prostheses can be considered as an ultima ration option if other approaches had failed. At least, partial oral nutrition and voice rehabilitation as well as protection from aspiration can be achieved in the majority of the patients. Level of Evidence: 4-Case series.

Electrically evoked mismatch negativity responses to loudness and pitch cues in cochlear implant users.

Objective measurements could improve cochlear implant (CI) fitting, especially for CI users who have difficulty assessing their hearing impressions. In this study, we investigated the electrically evoked mismatch negativity (eMMN) brain potential as a mainly preattentive response to pitch and loudness changes. In an electrophysiological exploratory study with 21 CI users, pitch and loudness cues were presented in controlled oddball paradigms that directly electrically stimulated the CI via software. Out of them 17 valid data sets were analyzed. A pitch cue was produced by changing the stimulating CI electrodes (pairs of adjacent electrodes). A loudness cue originated from changing the stimulation amplitude on one CI electrode. MMN responses were measured unsing clinical electroencephalography recording according to a standard recording protocol. At the group level, significant eMMN responses were elicited for loudness cues and for pitch cues at basal electrode pairs but not at apical electrode pairs. The effect of deviance direction was not significant and no stimulus artifacts were observed. Recording an electrically evoked MMN in response to loudness changes in CI users is generally feasible, and is, therefore, promising to support CI fitting procedures in the future. Detection of pitch cues would require a greater electrode distance between selected electrodes for standard and deviant stimuli, especially in apical regions. A routine clinical setup can be used to measure eMMN.

Multicentric study on surgical information and early safety and performance results with the Bonebridge BCI 602: an active transcutaneous bone conduction hearing implant.

AIM: This European multicentric study aimed to prove safety and performance of the Bonebridge BCI 602 in children and adults suffering from either conductive hearing loss (CHL), mixed hearing loss (MHL), or single-sided sensorineural deafness (SSD). METHODS: 33 patients (13 adults and 10 children with either CHL or MHL and 10 patients with SSD) in three study groups were included. Patients were their own controls (single-subject repeated measures), comparing the unaided or pre-operative to the 3-month post-operative outcomes. Performance was evaluated by sound field thresholds (SF), word recognition scores (WRS) and/or speech reception thresholds in quiet (SRT) and in noise (SNR). Safety was demonstrated with a device-specific surgical questionnaire, adverse event reporting and stable pure-tone measurements. RESULTS: The Bonebridge BCI 602 significantly improved SF thresholds (+ 25.5 dB CHL/MHL/SSD), speech intelligibility in WRS (+ 68.0% CHL/MHL) and SRT in quiet (- 16.5 dB C/MHL) and in noise (- 3.51 dB SNR SSD). Air conduction (AC) and bone conduction (BC) thresholds remained stable over time. All adverse events were resolved, with none unanticipated. Mean audio processor wearing times in hours [h] per day for the CHL/MHL group were ~ 13 h for adults, ~ 11 h for paediatrics and ~ 6 h for the SSD group. The average surgical length was 57 min for the CHL/MHL group and 42 min for the SSD group. The versatility of the BCI 602 (reduced drilling depth and ability to bend the transition for optimal placement) allows for treatment of normal, pre-operated and malformed anatomies. All audiological endpoints were reached. CONCLUSIONS: The Bonebridge BCI 602 significantly improved hearing thresholds and speech understanding. Since implant placement follows the patient's anatomy instead of the shape of the device and the duration of surgery is shorter than with its predecessor, implantation is easier with the BCI 602. Performance and safety were proven for adults and children as well as for the CHL/MHL and SSD indications 3 months post-operatively.

[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.

Safety and audiological outcome in a case series of tertiary therapy of sudden hearing loss with a biodegradable drug delivery implant for controlled release of dexamethasone to the inner ear.

Background: Intratympanic injections of glucocorticoids have become increasingly common in the treatment of idiopathic sudden sensorineural hearing loss (ISSHL). However, due to their fast elimination, sustained applications have been suggested for local drug delivery to the inner ear. Materials and methods: The study is based on a retrospective chart review of patients treated for ISSHL at a single tertiary (university) referral center. We included patients who were treated with a solid, biodegradable, poly(D,L-lactic-co-glycolic acid) (PLGA)-based drug delivery system providing sustained delivery of dexamethasone extracochlear into the round window niche (n = 15) or intracochlear into scala tympani (n = 2) for tertiary therapy of ISSHL in patients without serviceable hearing after primary systemic and secondary intratympanic glucocorticoid therapy. We evaluated the feasibility and safety through clinical evaluation, histological examination, and functional tests [pure-tone threshold (PTA), word recognition scores (WRS)]. Results: With adequate surgical preparation of the round window niche, implantation was feasible in all patients. Histologic examination of the material in the round window niche showed signs of resorption without relevant inflammation or foreign body reaction to the implant. In patients where the basal part of scala tympani was assessable during later cochlear implantation, no pathological findings were found. In the patients with extracochlear application, average preoperative PTA was 84.7 dB HL (SD: 20.0) and 76.7 dB HL (SD: 16.7) at follow-up (p = 0.08). The preoperative average maximum WRS was 14.6% (SD: 17.9) and 39.3% (SD: 30.7) at follow-up (p = 0.11). Six patients (40%), however, reached serviceable hearing. The two patients with intracochlear application did not improve. Conclusion: The extracochlear application of the controlled release system in the round window niche and - based on limited observations - intracochlear implantation into scala tympani appears feasible and safe. Due to the uncontrolled study design, conclusions about the efficacy of the treatment are limited. These observations, however, may encourage the initiation of prospective controlled studies using biodegradable controlled release implants as drug delivery systems for the treatment of inner ear diseases.