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.

An Unknown Foreign laryngeal Object: an exotic complication of skull base osteoradionecrosis.

BACKGROUND: Osteoradionecrosis (ORN) of the skull base is a rare complication after head and neck radiation with a broad variety of subsequent complications. METHODS: A 68-year-old woman with a complex oncological history (right-sided sphenoid meningioma; left-sided neck metastasis of a Cancer of Unknown Primary-CUP) was admitted with a right-sided epi-/ oropharyngeal mass and severe pain exacerbations for further evaluation. CT scan revealed an advanced ORN of the skull base with subsequent abruption of the ventral part of the clivus. This dislocated part of the clivus wedged in the oropharynx for 48 h and then moved towards the larynx, resulting in dyspnea and almost complete airway obstruction. RESULTS: Due to the dangerous airway situation, an urgent exploration and removal of the dislocated clivus was necessary. After a potential cervical spine instability was ruled out, the patient's airway was initially secured with an awake tracheotomy and the clivus was removed transorally. The tracheostomy tube was removed during the ongoing inpatient stay, and the patient was discharged with significant pain relief. CONCLUSIONS: The present case illustrates an orphan complication of skull base ORN resulting in a major airway emergency situation.

Short-term safety and effectiveness of the mCLIP partial prosthesis.

PURPOSE: This multicentric, retrospective study aimed to analyze the short-term safety and effectiveness of the mCLIP Partial Prosthesis. METHODS: Patients underwent tympanoplasty with implantation of a mCLIP Partial Prosthesis. Follow-up examination included ear microscopy and pure-tone audiometry to determine the post-operative pure tone average of the frequencies 0.5, 1, 2 and 3 kHz (PTA4). The post-operative PTA4 air bone gap (ABG) was used to evaluate the audiological outcome. A post-operative minimum and maximum follow-up period was not defined. Thus, the follow-up times of each study center were different, which resulted in different follow-up times for the audiological analysis and for adverse events (AE). RESULTS: 72 (66 adults, 6 children) patients were implanted with the mCLIP Partial Prosthesis. 68 (62 adults, 6 children) patients underwent audiological examination; all 72 patients were examined for adverse events. All patients (N = 68): 72.1% of the patients showed a PTA4 ABG of ≤ 20 dB. Individual post-operative bone conduction (BC) PTA4 thresholds were stable in 67 patients. The mean post-operative follow-up time was 78 ± 46 days. Children (N = 6): 5 out of 6 children showed a PTA4 ABG of ≤ 20 dB. None of the children reported a BC PTA4 deterioration of > 10 dB HL after the implantation. The mean post-operative follow-up time was 101 ± 45 days. Adverse events (all patients, N = 72): 15 (14 adults, 1 child) patients had AEs (27 AEs and 2 Follow-Ups). The mean post-operative follow-up time was 375 days. CONCLUSION: Clinical data show satisfactory audiological parameters after implantation of the mCLIP Partial Prosthesis. The prosthesis is safe and effective for implantation in children and adults. TRIAL REGISTRATION NUMBER: NCT05565339, 09 September 2022, retrospectively registered.

"To implant or not to implant": electrically evoked auditory brainstem response audiometry for decision-making in vestibular schwannoma resection with CI.

Vestibular schwannomas (VS) are often associated with debilitating hearing loss. Therefore, preservation and rehabilitation of hearing have become major therapeutic goals of VS management. Recently, cochlear implantation (CI) has been established as an effective treatment option for VS-associated hearing loss. Nevertheless, the integrity and proper function of the cochlear nerve must be evaluated before conducting CI to ensure optimal CI outcomes. Various methods to determine cochlear nerve integrity and functionality have emerged in the last few years. Of these, the use of electrically evoked auditory brainstem response audiometry (eABR) in particular has been proven to be a meaningful tool for monitoring cochlear nerve health during VS surgery. Here, the cochlear nerve can be electrically stimulated using an intracochlear test electrode before, during, and after tumor extirpation. Subsequently, the resulting brainstem responses can be measured and interpreted accordingly to obtain direct information on the cochlear nerve function. This allows for continuous monitoring of cochlear nerve function throughout the course of VS surgery and aids in the decision-making for CI candidacy. Finally, in the case of preserved brainstem responses, CI can be performed instantly after VS extirpation. This simultaneous approach offers several advantages over two-staged procedures and has been shown to be an efficient and safe procedure for restoring hearing after VS removal.

The Effect of Pulse Shape and Interphase Gaps on Speech Perception and Perceived Sound Quality in Electrical Hearing.

BACKGROUND: Stimulation with triphasic pulses has been shown to reduce the occurrence of unwanted facial nerve stimulation (FNS) with cochlear implants (CIs). However, there is little data available on how different pulse shapes affect the hearing outcome with electrical hearing in general. The aim of the study was to evaluate the effects of different stimulation pulse shapes on speech perception in noise, as well as loudness perception and subjective sound quality. METHODS: Twenty experienced cochlear-implant users not suffering from FNS participated in a prospective single-visit study. Based on the subjects' current clinical fitting, six fitting maps with different pulse shapes (biphasic and triphasic) and different interphase gap (IPG) durations (2.1 µs, 10 µs, and 20 µs) were created. First, the loudness was balanced for each configuration by adjusting the stimulation charge amount. Then, speech perception in noise was measured with a German matrix sentence test (Oldenburg Sentence test). The perception of particular sound attributes of speech and music, as well as overall preference, was evaluated with visual analog scales. RESULTS: Similar levels of speech perception were obtained with triphasic stimulation ( P = 0.891) and longer IPGs ( P = 0.361) compared to the subjects' clinical map settings. The stimulation amplitudes for equal loudness were significantly higher with triphasic stimulation compared to biphasic stimulation when keeping the IPG constant. Increasing the IPG had a significantly larger effect on perceived loudness ( P < 0.0001) and charge reduction for equal loudness with triphasic pulses compared to biphasic pulses. Triphasic configuration showed lower overall subjective sound quality ratings than biphasic for speech intelligibility, clarity, naturalness, and overall preference, as well as for music naturalness, and overall preference in the acute setting without adaptation time. Post-hoc pairwise comparisons against the clinical map revealed significantly lower speech naturalness ratings for triphasic with 2.1 µs IPG and for triphasic with 20 µs IPG only. CONCLUSION: Although some sound quality attributes were rated lower compared to the clinical map in the acute test setting, stimulation with triphasic pulses does not affect speech perception in noise and can be considered as a valuable option in CI fitting.

MRI surveillance after translabyrinthine vestibular schwannoma resection and cochlear implantation: is it feasible?

PURPOSE: Cochlear implantation in patients with vestibular schwannomas is of increasing importance and interest. Two remaining challenges are the assessment of conduction of the cochlear nerve and the possibility of postoperative surveillance with magnetic resonance imaging. The aim of the current study was to assess follow-up imaging and determine the visibility of the internal auditory canal after vestibular schwannoma resection and cochlear implantation as well as in patients with persistent vestibular schwannomas and cochlear implants in place. Visibility of the internal auditory canal, cerebellopontine angle, and labyrinth were evaluated and graded. METHODS: For this retrospective study, 15 MR examinations of 13 patients after translabyrinthine vestibular schwannoma resection and ipsilateral cochlear implantation were included. All patients had been implanted with an MED-EL cochlear implant. Magnetic resonance imaging was carried out on a 1.5T device. All patients were prepped according to the manufacturer's recommendations. RESULTS: All 15 examinations were carried out without any adverse event during imaging, such as pain, magnet dislocation, or malfunction. The internal auditory canal and the cerebellopontine angle were sufficiently visible in all cases to allow for vestibular schwannoma follow-up. CONCLUSION: Magnetic resonance imaging surveillance of the internal auditory canal following vestibular schwannoma resection and cochlear implantation is feasible and safe with modern implants with a 1.5T magnetic resonance imaging device using metal artifact reduction sequences. Necessary follow-up imaging should not be a contraindication for cochlear implantation in patients with vestibular schwannomas.

Temporal fluctuations of post-tonsillectomy haemorrhage.

PURPOSE: Although haemorrhage is a common and in some cases life-threatening complication after tonsillectomy, surprisingly little is known about the temporal fluctuations of the onset of bleeding. The purpose of this study was to assess circadian and seasonal rhythms of post-tonsillectomy haemorrhage (PTH) and potential ramifications to educate patients and health care staff. METHODS: This retrospective study carried out at a tertiary referral hospital included paediatric and adult patients requiring emergency surgery due to severe PTH between 1993 and 2019. Medical records were reviewed and patient demographics, details regarding the initial procedure, postoperative day of haemorrhage, and start time of emergency surgery were extracted. Descriptive statistics, Kruskal-Wallis test, Mann-Whitney U test, and Chi-square goodness of fit tests were used to detect potential differences. RESULTS: A total of 300 patients with severe PTH and subsequent emergency surgery were identified. The median postoperative duration until PTH was 6 (range: < 1-19) days. 64.7% (n = 194) of all emergency surgeries had to be performed during evening and night hours (6 pm-6 am) (p < 0.0001). Compared to diurnal incidents, the risk of a nocturnal PTH event increased, the longer ago the initial surgery was (p < 0.0001). No seasonal variations were identified. Age, sex, and details of the initial procedure had no significant influence on the start time according to the surgical protocol. CONCLUSION: The discovered temporal fluctuations of PTH are of relevance for patient awareness and preoperative education. Due to possible life-threatening complications, management of severe PTH requires specific resources and trained medical staff on call.

[Vestibular schwannoma: Diagnosis-Therapy-Aftercare]. / Vestibularisschwannome: Diagnose ­ Therapie ­ Nachsorge.

Vestibular schwannomas can severely impair the quality of life of patients. Next to impaired hearing function, facial palsy is perceived as particularly disturbing in this context. Varying growth rates of these benign tumors complicate a prediction of functional impairment of cranial nerves. Therefore, a regular update on current therapeutic strategies and alternative treatment options is relevant for both physicians and patients.

Radiomics of high-resolution computed tomography for the differentiation between cholesteatoma and middle ear inflammation: effects of post-reconstruction methods in a dual-center study.

OBJECTIVES: To evaluate the performance of radiomic features extracted from high-resolution computed tomography (HRCT) for the differentiation between cholesteatoma and middle ear inflammation (MEI), and to investigate the impact of post-reconstruction harmonization and data resampling. METHODS: One hundred patients were included in this retrospective dual-center study: 48 with histology-proven cholesteatoma (center A: 23; center B: 25) and 52 with MEI (A: 27; B: 25). Radiomic features (co-occurrence and run-length matrix, absolute gradient, autoregressive model, Haar wavelet transform) were extracted from manually defined 2D-ROIs. The ten best features for lesion differentiation were selected using probability of error and average correlation coefficients. A multi-layer perceptron feed-forward artificial neural network (MLP-ANN) was used for radiomics-based classification, with histopathology serving as the reference standard (70% of cases for training, 30% for validation). The analysis was performed five times each on (a) unmodified data and on data that were (b) resampled to the same matrix size, and (c) corrected for acquisition protocol differences using ComBat harmonization. RESULTS: Using unmodified data, the MLP-ANN classification yielded an overall median area under the receiver operating characteristic curve (AUC) of 0.78 (0.72-0.84). Using original data from center A and resampled data from center B, an overall median AUC of 0.88 (0.82-0.99) was yielded, while using ComBat harmonized data, an overall median AUC of 0.89 (0.79-0.92) was revealed. CONCLUSION: Radiomic features extracted from HRCT differentiate between cholesteatoma and MEI. When using multi-centric data obtained with differences in CT acquisition parameters, data resampling and ComBat post-reconstruction harmonization clearly improve radiomics-based lesion classification. KEY POINTS: • Unenhanced high-resolution CT coupled with radiomics analysis may be useful for the differentiation between cholesteatoma and middle ear inflammation. • Pooling of data extracted from inhomogeneous CT datasets does not appear meaningful without further post-processing. • When using multi-centric CT data obtained with differences in acquisition parameters, post-reconstruction harmonization and data resampling clearly improve radiomics-based soft-tissue differentiation.

Speech Segregation in Active Middle Ear Stimulation: Masking Release With Changing Fundamental Frequency.

OBJECTIVES: Temporal fine structure information such as low-frequency sounds including the fundamental frequency (F0) is important to separate different talkers in noisy environments. Speech perception in noise is negatively affected by reduced temporal fine structure resolution in cochlear hearing loss. It has been shown that normal-hearing (NH) people as well as cochlear implant patients with preserved acoustic low-frequency hearing benefit from different F0 between concurrent talkers. Though patients with an active middle ear implant (AMEI) report better sound quality compared with hearing aids, they often struggle when listening in noise. The primary objective was to evaluate whether or not patients with a Vibrant Soundbridge AMEI were able to benefit from F0 differences in a concurrent talker situation and if the effect was comparable to NH individuals. DESIGN: A total of 13 AMEI listeners and 13 NH individuals were included. A modified variant of the Oldenburg sentence test was used to emulate a concurrent talker scenario. One sentence from the test corpus served as the masker and the remaining sentences as target speech. The F0 of the masker sentence was shifted upward by 4, 8, and 12 semitones. The target and masker sentences were presented simultaneously to the study subjects and the speech reception threshold was assessed by adaptively varying the masker level. To evaluate any impact of the occlusion effect on speech perception, AMEI listeners were tested in two configurations: with a plugged ear-canal contralateral to the implant side, indicated as AMEIcontra, or with both ears plugged, indicated as AMEIboth. RESULTS: In both study groups, speech perception improved when the F0 difference between target and masker increased. This was significant when the difference was at least 8 semitones; the F0-based release from masking was 3.0 dB in AMEIcontra (p = 0.009) and 2.9 dB in AMEIboth (p = 0.015), compared with 5.6 dB in NH listeners (p < 0.001). A difference of 12 semitones revealed a F0-based release from masking of 3.5 dB in the AMEIcontra (p = 0.002) and 3.4 dB in the AMEIboth (p = 0.003) condition, compared with 5.0 dB in NH individuals (p < 0.001). CONCLUSIONS: Though AMEI users deal with problems resulting from cochlear damage, hearing amplification with the implant enables a masking release based on F0 differences when F0 between a target and masker sentence was at least 8 semitones. Additional occlusion of the ear canal on the implant side did not affect speech performance. The current results complement the knowledge about the benefit of F0 within the acoustic low-frequency hearing.

The challenging diagnosis and follow-up of skull base osteomyelitis in clinical practice.

PURPOSE: The disease activity of skull base osteomyelitis can be challenging to assess by means of conventional imaging methods and renders monitoring of the disease difficult, especially in areas with restricted access to nuclear medicine imaging. Here, we provide clinically relevant data on the management of skull base osteomyelitis including assessment, treatment, and follow-up strategies with regards to the role of imaging. METHOD: A chart review was performed including 30 patients treated for SBO from 1993 to 2015. Clinical findings, treatment procedures, and complication rates were assessed. Special attention was paid to imaging procedures. RESULTS: The overall mortality rate was 36.7% and increased to 45% when cranial nerve palsies were present. An initial computed tomography (CT) scan was performed in all patients, MRI in 60% and nuclear imaging in 33%. CT scans failed to detect progression or regression in up to 80% after four to nine months. MRI examinations could reveal changes at a higher rate compared to CT. Nuclear medicine functional imaging was most likely to assess disease activity. CONCLUSION: A combination of different imaging modalities is recommended for diagnosing SBO. For the follow-up, MRI is preferable to CT as changes can be detected more readily with MRI. If available, nuclear medicine imaging should guide the decision of treatment discontinuation.

Sustained-Release Triamcinolone Acetonide Hydrogels Reduce Hearing Threshold Shifts in a Model for Cochlear Implantation with Hearing Preservation.

INTRODUCTION: In recent years, the preservation of residual hearing has become a major factor in patients undergoing cochlear implantation (CI). In studies attempting to pharmaceutically improve hearing preservation rates, glucocorticoids (GCs) applied perioperatively in many institutions have emerged as a promising treatment regimen. Although dexamethasone is most commonly used and has been applied successfully by various research groups, recently pharmacological properties have been reported to be relatively unsuitable for topical delivery to the inner ear. Consequently other glucocorticoids merit further evaluation. The aim of this study was therefore to evaluate the otoprotective effects of the topical application of a sustained-release triamcinolone acetonide (TAAC) hydrogel in CI with hearing preservation. METHODS: Normal-hearing pigmented guinea pigs were randomized into a group receiving a single dose of a 6% TAAC poloxamer 407 hydrogel, a group receiving a 30% TAAC hydrogel and a control group. All hydrogel applications were performed 1 day prior to CI. After a cochleostomy was drilled, a specifically designed silicone electrode was inserted into the scala tympani for 5 mm. Frequency-specific compound action potentials of the auditory nerve (0.5-32 kHz) were measured pre- and directly postoperatively as well as on days 3, 7, 14, 21, and 28. Finally, temporal bones were harvested for histological evaluation. RESULTS: Application of the TAAC hydrogels resulted in significantly reduced hearing threshold shifts in low, middle and high frequencies and improved spiral ganglion cell survival in the second turn of the cochlea. Outer hair cell numbers in the basal and second turn of the cochlea were slightly reduced after TAAC application. CONCLUSION: In summary, we were able to demonstrate functional benefits of a single preoperative application of a TAAC hydrogel in a guinea pig model for CI, which persisted until the end of the observational period, that is, 28 days after surgery.

Evaluation of Sustained-Release Steroid Hydrogels in a Guinea Pig Model for Noise-Induced Hearing Loss.

The otoprotective effects of thermoreversible poloxamer 407 hydrogels containing dexamethasone or triamcinolone acetonide were evaluated in an animal model of noise-induced hearing loss. Seven days after noise exposure, hearing threshold shifts at 16 kHz were significantly reduced in the 6% dexamethasone group (p < 0.05). Even though no significant differences in hair cell counts were found, histological analysis revealed a significantly higher spiral ganglion cell density in the first turn of the cochlea in this group (p < 0.05). No otoprotective effects were observed after the application of the triamcinolone acetonide hydrogels. As the findings of this study indicate potential otoprotective effects of sustained topical dexamethasone delivery in the setting of noise-induced hearing loss, this strategy merits further evaluation.

The Role of Preoperative Steroids for Hearing Preservation Cochlear Implantation: Results of a Randomized Controlled Trial.

OBJECTIVES: To determine whether preoperative steroids can improve hearing outcomes in cochlear implantation (CI). METHODS: This is a randomized controlled trial involving 30 postlingual deaf CI patients. Subjects had preoperative thresholds of better than or equal to 80 dB at 125 and 250 Hz, and better than or equal to 90 dB at 500 and 1,000 Hz. The subjects were randomized to a control group, an oral steroid group (receiving 1 mg/kg/day of prednisolone for 6 days prior to surgery), or a transtympanic steroid group (receiving a single dose of 0.5 mL of 10 mg/mL dexamethasone at 24 h prior to surgery). RESULTS: The subjects receiving transtympanic steroids had a significant decrease in the pure tone average over 3 months compared to the control and oral steroid group, which persisted over 12 months (p < 0.05). CONCLUSION: A single dose of preoperative transtympanic steroids prior to CI appears to have a beneficial effect, at least in the short term, with minimal effects seen in the longer term.

Noise trauma and systemic application of the selective glucocorticoid receptor modulator compound A.

BACKGROUND: Selective glucocorticoid receptor modulators (SEGRMs) comprise a novel class of drugs promising both reduced side effects and similar pharmacological potency relative to glucocorticoids, which presently serve as the only clinical treatment for many otologic disorders. In the first otologic SEGRM experiment in an animal model of noise trauma, we compare the effects of Compound A (a SEGRM) and dexamethasone (potent glucocorticoid). METHODS: Forty adult guinea pigs received experimental treatment once daily for ten days. The animals were divided into four cohorts based on the treatment received: Compound A (1 mg/kg or 3 mg/kg), dexamethasone (1 mg/kg) as gold standard, or water as negative control. After five applications, animals were exposed to broadband noise (8-16 kHz) at 115 dB for three hours. Hearing thresholds were determined by recording auditory brainstem responses to clicks and noise bursts (1-32 kHz) and were assessed a week prior to and immediately after exposure, as well as on days 1, 3, 7, 14, 21, and 28. Cochleae were prepared as whole-mounts or embedded and sectioned for histological analysis. RESULTS: Relative to the control treatments, Compound A failed to preserve auditory thresholds post-noise exposure with statistical significance. Histological analyses confirm the physiological result. CONCLUSION: The present findings suggest that Compound A does not have substantial otoprotective capacities in a noise trauma model.

Sustained release of triamcinolone acetonide from an intratympanically applied hydrogel designed for the delivery of high glucocorticoid doses.

The pharmacokinetic properties and tolerability of a triamcinolone acetonide poloxamer 407 hydrogel for intratympanic application were investigated in a guinea pig model. Evaluation of in vivo release kinetics showed very high initial perilymph drug levels, with clinically relevant levels present for a minimum of 10 days. Assessment of auditory brainstem response thresholds showed a minimal, delayed and transient threshold shift, which was apparent on day 3 and resolved by day 10. No relevant histological changes of the middle and inner ear structures were noted, and hair cell counts showed no significant differences between treated and untreated ears. Thus, the triamcinolone-acetonide-loaded poloxamer 407 hydrogel is an effective vehicle for sustained high-dose inner ear glucocorticoid delivery.

FS4, FS4-p, and FSP: a 4-month crossover study of 3 fine structure sound-coding strategies.

OBJECTIVES: The aim of the present study was to compare two novel fine structure strategies "FS4" and "FS4-p" with the established fine structure processing (FSP) strategy. FS4 provides fine structure information on the apical four-electrode channels. With FS4-p, these electrodes may be stimulated in a parallel manner. The authors evaluated speech perception, sound quality, and subjective preference. DESIGN: A longitudinal crossover study was done on postlingually deafened adults (N = 33) who were using FSP as their default strategy. Each participant was fitted with FS4, FS4-p, and FSP, for 4 months in a randomized and blinded order. After each run, an Adaptive Sentence test in noise (Oldenburger Sentence Test [OLSA]) and a Monosyllable test in quiet (Freiburger Monosyllables) were performed, and subjective sound quality was determined with a Visual Analogue Scale. At the end of the study the preferred strategy was noted. RESULTS: Scores of the OLSA did not reveal any significant differences among the three strategies, but the Freiburger test showed a statistically significant effect (p = 0.03) with slightly worse scores for FS4 (49.7%) compared with FSP (54.3%). Performance of FS4-p (51.8%) was comparable with the other strategies. Both audiometric tests depicted a high variability among subjects. The number of best-performing strategies for each participant individually was as follows: (a) for the OLSA: FSP, N = 10.5; FS4, N = 10.5; and FS4-p, N = 12; and (b) for the Freiburger test: FSP, N = 14; FS4, N = 9; and FS4-p, N = 10. A moderate agreement was found in the best-performing strategies of the Speech tests within the participants. For sound quality, speech in quiet, classical, and pop music were assessed. No significant effects of strategy were found for speech in quiet and classical music, but auditory impression of pop music was rated as more natural in FSP compared with FS4 (p = 0.04). It is interesting that at the end of the study, a majority of the participants favored the new coding strategies over their previous default FSP (FSP, N = 13; FS4, N = 13; FS4-p, N = 7). CONCLUSIONS: In summary, FS4 and FS4-p offer new and further options in audio processor fitting, with similar levels of speech understanding in noise as FSP. This is an interesting result, given that the strategies' presentation of temporal fine structure differs from FSP. At the end of the study, 20 of 33 subjects chose either FS4 or FS4-p over their previous default strategy FSP.

Insertion trauma of a novel inner ear catheter for intracochlear drug delivery.

Introduction: Even with recent research advances, effective delivery of a compound to its target cells inside the inner ear remains a challenging endeavor due to anatomical and physiological barriers. Direct intracochlear drug administration with an inner ear catheter (IEC) aims to overcome this obstacle and strives to provide a safe and efficient way for inner ear pharmacotherapy. The goal of this study was to histologically and audiologically evaluate the traumatic properties of a novel IEC for intracochlear drug delivery in a large animal model. Methods: Seven inner ears of piglets that had undergone intracochlear fluorescein isothiocyanate dextran application via an IEC (n = 4) or round window membrane (RWM) puncture with a needle (n = 3) followed by sequential apical perilymph sampling were histologically analyzed. Additionally, obtained objective auditory compound action potential and cochlear microphonic measurements were compared. Cochlear cryosections were stained using hematoxylin and eosin, and preservation of inner ear structures was investigated. Moreover, one cochlea was methylmethacrylate-embedded and analyzed with the IEC in situ. Results: Histological evaluation revealed an atraumatic insertion and subsequent compound application in a majority of IEC-inserted inner ears. Click cochlear compound action potential (CAP) shifts in the IEC groups reached a maximum of 5 dB (1.25 ± 2.5 dB) post administration and prior to perilymph sampling. In comparison, application by RWM puncture generated a maximum click CAP hearing threshold shift of 50 dB (23.3 ± 23.1 dB) coinciding with coagulated blood in the basal cochlear turn in one specimen of the latter group. Furthermore, in situ histology showed an atraumatic insertion of the IEC demonstrating preserved intracochlear structures. Conclusion: The IEC appears to be a promising and efficient way for inner ear drug delivery. The similarities between the porcine and human inner ear enhance the clinical translation of our findings and increase confidence regarding the safe applicability of the IEC in human subjects.