Prestin in Human Perilymph, Cerebrospinal Fluid, and Blood as a Biomarker for Hearing Loss.

OBJECTIVE: Determining the concentration of prestin in human blood, cerebrospinal fluid (CSF), and perilymph (PL), and evaluating its suitability as a clinical biomarker for sensori-neural hearing loss (SNHL). STUDY DESIGN: Human blood, CSF, and PL samples were intraoperatively collected from 42 patients with tumors of the internal auditory canal or with intracochlear tumors undergoing translabyrinthine or middle fossa tumor removal. Prestin concentration was measured using enzyme-linked immunosorbent assay and linear regression analyses were performed to investigate its associations with audiological as well as vestibular test results. SETTING: Tertiary referral center. RESULTS: The median prestin concentration in blood samples of the 42 study participants (26 women, mean ± standard deviation age, 52.7 ± 12.5 years) was 1.32 (interquartile range, IQR, 0.71-1.99) ng/mL. CSF prestin levels were significantly higher with 4.73 (IQR, 2.45-14.03) ng/mL (P = .005). With 84.74 (IQR, 38.95-122.00) ng/mL, PL prestin concentration was significantly higher compared to blood (P = .01) and CSF (P = .03) levels. Linear regression analyses showed significant associations of CSF prestin concentration with preoperative hearing levels (pure-tone average and word recognition; P = .008, R2 = 0.1894; P = .03, R2 = 0.1857), but no correlations with blood or PL levels. CONCLUSION AND RELEVANCE: This study's findings highlight the volatile nature of prestin levels and provide the first insights into this potential biomarker's concentrations in body fluids apart from blood. Future investigations should comprehensively assess human prestin levels with different etiologies of SNHL, prestin's natural homeostasis and systemic circulation, and its temporal dynamics after cochlear trauma. Finally, clinically approved detection kits for prestin are urgently required prior to considering a potential translational implementation of this diagnostic technique.

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.

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.

"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.

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.

How standardised are antibiotic regimens in otologic surgery?

BACKGROUND: Within otologic surgery, a paucity of well-controlled studies assessing the use of systemic antibiotic to reduce surgical site infections exists. Moreover, discrepancies in wound classification of procedures challenge consensus in antimicrobial prescribing patterns. We sought to compare surgeons from two different health systems to examine how surgeons' prescribing habits compared to practice guidelines for numerous otologic procedures. METHODS: An online questionnaire was distributed to 33 Canadian and 32 Austrian surgeons who regularly perform otologic surgery. Current systemic antibiotic prescribing habits for cochlear implantation, cholesteatoma surgery, stapes surgery, and tympanoplasty ± ossiculoplasty were collected. RESULTS: Eighteen of 33 (54.5%) Canadian surgeons provided responses, while 18 of 32 (56.3%) of Austrian surgeons answered. Clear consistency with clinical practice guidelines exists for pre-operative antibiotics use in cochlear implant surgery and infected cholesteatoma surgery. However, for stapes surgery and tympanoplasty ± ossiculoplasty, consensus is lacking for both pre- and post-operative antibiotic prescribing habits. Notable differences between the two countries include post-operative antibiotics for cochlear implant surgery (Austria: 36.4%, Canada: 71.4%) and uninfected cholesteatoma surgery (Austria: 33.3%, Canada: 77.8%). Across all procedures, both induction and post-operative antibiotic administration was not significantly associated with surgeon seniority when stratified by five-year increments. CONCLUSION: The lack of consensus among each country's otologic surgeons underscores the uncertainty in wound classification and thus, adherence to clinical practice guidelines.

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.

Establishment of an optimized guinea pig model of cisplatin-induced ototoxicity.

Background: Cisplatin is among the most effective antineoplastic agents and has revolutionized the treatment of many cancer diseases. However, one of its serious side effects is a progressive and irreversible hearing loss, occurring in both adults and children. For the development of otoprotective therapies that prevent this side effect, cisplatin-induced hearing loss animal models are indispensable. Due to the high toxicity of cisplatin, the establishment of such animal models is a difficult and time-consuming task. Here we introduce the detailed protocol of a sophisticated guinea pig model with a sufficient and permanent hearing loss induced by cisplatin. This manuscript is intended to provide guidance in the development of future cisplatin guinea pig models which may reduce the mortality rate of the animals and help to gain more reproducible results. Methods: Pigmented and unpigmented guineapigs were treated with an intravenous single application of 8 mg/kg cisplatin under general anesthesia. An extensive and long-term intensive care protocol consisting of scheduled application of fluids, antiemetics, analgesics, glucose and supportive feeding among others, was used to ensure wellbeing of the animals. Hearing tests were performed prior to and 5 days after cisplatin application. Animals were then euthanized. Results: The ABR audiometry 5 days after cisplatin application revealed a hearing threshold ranging from 70 dB to 90 dB in the frequencies from 1 kHz to 32 kHz respectively.All animals presented a good health condition despite the treatment with cisplatin. Discussion: The introduced care protocol in this manuscript is intended to serve as a guidance for the establishment of a stable guinea pig model for short- and long-term investigation regarding the inner ear and its protection in the frame work of cisplatin-induced damage.

Functional Outcome After Simultaneous Vestibular Schwannoma Resection and Cochlear Implantation With Intraoperative Cochlear Nerve Monitoring.

OBJECTIVE: Electrically evoked auditory brainstem response audiometry has emerged as a suitable option to intraoperatively assess cochlear nerve function during vestibular schwannoma resection. This study aimed to analyze the functional outcome and implant usage of patients with preserved auditory nerve responses after simultaneous translabyrinthine schwannoma resection and cochlear implantation. STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. METHODS: Patients with unilateral sporadic vestibular schwannoma underwent translabyrinthine tumor resection. Intraoperatively, electrically evoked auditory brainstem response audiometry was performed before and after tumor removal. Cochlear implantation was carried out if positive responses were detected after tumor removal indicating cochlear nerve function. Postoperatively, patients were biannually followed-up to assess aided sound field audiometry and word recognition as well as implant usage. RESULTS: Overall, 26 patients with vestibular schwannoma underwent translabyrinthine schwannoma resection. Out of these patients, 15 had positive cochlear nerve responses after tumor removal and concurrently received a cochlear implant. In 13 patients with histologically confirmed vestibular schwannoma, hearing improved by 23.7 ± 33.2 decibels and word recognition by 25.0 ± 42.4% over a mean follow-up period of 18 months. Overall, 12 included patients were regular cochlear implant users. CONCLUSION: Patients with vestibular schwannoma can benefit substantially from cochlear implantation. Intraoperative assessment of cochlear nerve function using electrically evoked auditory brainstem response audiometry can help to better identify individuals eligible for simultaneous vestibular schwannoma resection and cochlear implantation.

A Novel Preparation Technique for Human Nasal Respiratory Mucosa to Disclose Its Glycosylation Pattern for Bioadhesive Drug Delivery.

To shed some light on glycotargeting as a potential strategy for nasal drug delivery, a reliable preparation method for human nasal mucosa samples and a tool to investigate the carbohydrate building blocks of the glycocalyx of the respiratory epithelium are required. Applying a simple experimental setup in a 96-well plate format together with a panel of six fluorescein-labeled lectins with different carbohydrate specificities allowed for the detection and quantification of accessible carbohydrates in the mucosa. As confirmed by binding experiments at 4 °C, both quantitatively by fluorimetry and qualitatively by microscopy, the binding of wheat germ agglutinin exceeded that of the others by 150% on average, indicating a high content of N-acetyl-D-glucosamine and sialic acid. Providing energy by raising the temperature to 37 °C revealed uptake of the carbohydrate-bound lectin into the cell. Moreover, repeated washing steps during the assay gave a slight hint as to the influence of mucus renewal on bioadhesive drug delivery. All in all, the experimental setup reported here for the first time is not only a suitable approach to estimating the basics and potential of nasal lectin-mediated drug delivery but also meets the needs for answering a broad variety of scientific questions involving the use of ex vivo tissue samples.

Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics.

Hearing impairment is the most common sensory disorder in humans, and yet hardly any medications are licensed for the treatment of inner ear pathologies. Intricate pharmacokinetic examinations to better understand drug distribution within this complex organ could facilitate the development of novel therapeutics. For such translational research projects, animal models are indispensable, but differences in inner ear dimensions and other anatomical features complicate the transfer of experimental results to the clinic. The gap between rodents and humans may be bridged using larger animal models such as non-human primates. However, their use is challenging and impeded by administrative, regulatory, and financial hurdles. Other large animal models with more human-like inner ear dimensions are scarce. In this study, we analyzed the inner ears of piglets as a potential representative model for the human inner ear and established a surgical approach for intracochlear drug application and subsequent apical sampling. Further, controlled intracochlear delivery of fluorescein isothiocyanate-dextran (FITC-d) was carried out after the insertion of a novel, clinically applicable CE-marked cochlear catheter through the round window membrane. Two, six, and 24 hours after a single injection with this device, the intracochlear FITC-d distribution was determined in sequential perilymph samples. The fluorometrically assessed concentrations two hours after injection were compared to the FITC-d content in control groups, which either had been injected with a simple needle puncture through the round window membrane or the cochlear catheter in combination with a stapes vent hole. Our findings demonstrate not only significantly increased apical FITC-d concentrations when using the cochlear catheter but also higher total concentrations in all perilymph samples. Additionally, the concentration decreased after six and 24 hours and showed a more homogenous distribution compared to shorter observation times.

Patient Acceptance of Novel Therapeutic Options for Sensorineural Hearing Loss-A Pilot Study.

OBJECTIVES: Numerous preclinical experiments over the past years have shown the potential of novel therapeutic approaches for sensorineural hearing loss (SNHL) that are now awaiting clinical translation. In this pilot study, we aimed to evaluate the patient acceptance of these future innovative therapies in individuals with SNHL. STUDY DESIGN: Cross-sectional exploratory pilot study. SETTING: Tertiary care academic hospital. PATIENTS: In total, 72 individuals (43 female and 29 male, 59 affected subjects and 13 parents) with different types of SNHL were surveyed between May 2020 and November 2020. INTERVENTION: The interest/willingness to consider new therapeutic options (viral vectors, stem cells, CRISPR/Cas) for themselves or their children was assessed with the help of a questionnaire, and the answers were matched with a quality-of-life score and sociodemographic as well as clinical characteristics. MAIN OUTCOME MEASURE: Acceptance of new therapeutic strategies for SNHL in a representative population. RESULTS: Even with the currently associated treatment uncertainties, 48 patients (66.7%) suffering from SNHL stated that new therapies could be a potential future option for them. Half of these (24 individuals; 33.3%) expressed high acceptance toward the novel strategies. Subjects with a positive attitude toward new therapies in general and viral vectors specifically were significantly older. CONCLUSION: With two-thirds of patients affected by SNHL expressing acceptance toward novel therapies, this pilot study highlights the importance of investigating such attitudes and motivates further translational research to offer additional treatment strategies to this patient population.

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.

Single-incision cochlear implantation and hearing evaluation in piglets and minipigs.

OBJECTIVES: Various animal models have been established and applied in hearing research. In the exploration of novel cochlear implant developments, mainly rodents have been used. Despite their important contribution to the understanding of auditory function, translation of experimental observations from rodents to humans is limited due to the size differences and genetic variability. Large animal models with better representation of the human cochlea are sparse. For this reason, we evaluated domestic piglets and Aachen minipigs for the suitability as a cochlear implantation animal model with commercially available cochlear implants. METHODS: Four domestic piglets (two male and two female) and six Aachen minipigs were implanted with either MED-EL Flex24 or Flex20 cochlear implants respectively, after a step-by-step surgical approach was trained with pig cadavers. Electrophysiological measurements were performed before, during and after implantation for as long as 56 days after surgery. Auditory brainstem responses, electrocochleography as well as electrically and acoustically evoked compound action potentials were recorded. Selected cochleae were further analyzed histologically or with micro-CT imaging. RESULTS: A surgical approach was established using a retroauricular single incision. Baseline auditory thresholds were 27 ± 3 dB sound pressure level (SPL; auditory brainstem click responses, mean ± standard error of the mean) and ranged between 30 and 80 dB SPL in frequency-specific responses (0.5 - 32 kHz). Follow-up measurements revealed deafness within the first two weeks after surgery, but some animals partially recovered to a hearing threshold of 80 dB SPL in certain frequencies as well as in click responses. Electrically evoked compound action potential thresholds increased within the first week after surgery, which led to lower stimulation responses or increase of necessary charge input. Immune reactions and consecutive scalar fibrosis following implantation were confirmed with histological analysis of implanted cochleae and may result in increased impedances. A three-dimensional minipig micro-CT segmentation revealed cochlear volumetric data similar to human inner ear dimensions. CONCLUSIONS: This study underlines the feasibility of cochlear implantation with clinically used cochlear implants in a large animal model with representative inner ear dimensions comparable to humans. To bridge the gap between small animal models and humans in translational research and to account for the structural and size differences, we recommend the minipig as a valuable animal model for hearing research. First insights into the induced trauma in minipigs after cochlear implant surgery and a partial hearing recovery present important data of the cochlear health changes in large animal cochleae.

Intratympanic Substance Distribution After Injection of Liquid and Thermosensitive Drug Carriers: An Endoscopic Study.

OBJECTIVE: In the treatment of inner ear conditions, intratympanic injection emerges as an important drug delivery method. Novel compounds designed for intratympanic injection are routinely loaded in viscous drug carriers. To date, it is unclear if they can freely distribute in the middle ear. The aims of this study were to investigate the middle ear distribution of different drug carriers during intratympanic injection and to determine an optimal injection method for thermosensitive hydrogels. METHODS: Twenty-one human temporal bones were intratympanically injected with fluid drug carriers or poloxamer-407 hydrogels at different tympanic membrane injection sites (inferior, anterior-superior) using different needle types (Whitacre, Quincke). Fluid distribution was evaluated via an endoscopic view. Injection volume, duration, backflow, and overall safety were analyzed. RESULTS: Liquid drug carriers distribute effortlessly in the middle ear, whereas an additional ventilation hole is advantageous when applying thermosensitive hydrogels. The round window is coated with required volumes between 150 and 200 µl, irrespective of the injection position. Required volumes to also coat the stapedial footplate ranged from 310 to 440 µl. Use of the Whitacre-type needle reduced backflow to the ear canal and enabled longer tympanic membrane visibility when no additional ventilation hole was placed. CONCLUSION: Intratympanic injection is a safe and reliable method for the application of thermosensitive hydrogels. The round window niche is readily filled regardless of the injected formulation and injection position. Although fluid drug carriers distribute effortlessly in the middle ear, the placement of an additional ventilation hole might facilitate the application of viscous hydrogels.

The Functional Hearing Gain with an Active Transcutaneous Bone Conduction Implant Does Not Correlate with the Subjective Hearing Performance.

The functional hearing outcome with hearing implants does not always properly reflect the subjective benefit in everyday listening situations. In this study, the functional hearing gain and the impact on the subjective hearing ability and quality of life were assessed in patients with a Bonebridge. A chart review was performed on 45 patients with a Bonebridge who were provided with questionnaires regarding the hearing quality and health-related quality of life during their last clinical visit. The questionnaires consisted of the Speech, Spatial and Qualities (SSQ) and the Health Utility Index Mark 3 (HUI3). Eleven patients had to be excluded due to missing data. A total of 34 patients (37 ears) were included in the study. Aided hearing thresholds were significantly lower compared with the unaided condition, with a mean functional gain of 26.87 dB for patients with mixed/conductive hearing loss (MHL/CHL). Although patients with single-sided deafness (SSD) scored slightly lower on the SSQ compared with patients with MHL/CHL, all included patients reported improved subjective hearing quality with the BB compared with the hearing situation before implantation. No correlation was found between the functional hearing gain and the subdomains of the SSQ. SSD patients scored the HUI3 subdomain "hearing" slightly lower compared with MHL/CHL patients. Although not significant, a relationship was found between the functional gain and the "hearing" subdomain. No correlation was found for the other subdomains of the HUI3. Audiological measurements showed significantly improved hearing thresholds with the Bonebridge. Most importantly, the subjective benefit achieved in everyday listening situations was superior compared with the previous hearing condition. The lack of correlation between subjective questionnaire results and the functional hearing gain shows the importance of assessing both audiological and subjective hearing quality parameters in clinical routine.

Combined Open Surgical and Endoscopic Approach for Management of a Meningoencephalocele After Iatrogenic Perforation of the Anterior Skull Base in a Young Infant.

Traumatic iatrogenic perforation of the anterior skull base is a rare complication following endonasal intubation in preterm infants. Subsequent meningoencephaloceles with concomitant cerebrospinal fluid (CSF) fistulas bear the risk of severe complications, therefore early diagnosis and closure of the skull defect are crucial. However, there is no consensus on the management of such cases of meningoencephaloceles. This case report presents a sophisticated approach of open brain surgery in combination with endonasal endoscopy. A 15-month-old girl presented with a meningoencephalocele and a CSF fistula due to iatrogenic perforation of the left anterior skull base during attempted endonasal intubation after birth. Difficult nasal breathing and an increasing diameter of the skull base defect on imaging controls indicated surgical management. Close multidisciplinary collaboration was essential for diagnosis and decision upon treatment. Open neurosurgical resection and CSF fistula closure combined with endonasal endoscopic removal of the excised meningoencephalocele was performed. Our case report shows that this combined open surgical and endonasal endoscopic approach is a safe procedure in favor of the postoperative outcome and follow-up of the patient.

Triamcinolone acetonide can be detected in cerebrospinal fluid after intratympanic injection.

Intratympanically applied treatments are of increasing interest to the otologic community to treat sudden sensorineural hearing loss or vestibular disorders but also to deliver gene therapy agents, or biologics to the inner ear. Further diversion from the middle ear and perilymph to blood circulation and cerebrospinal fluid via the cochlear aqueduct are one of the limiting factors and so far not understood well enough. In this study, intratympanically applied triamcinolone acetonide was determined in cerebrospinal fluid. Additionally, perilymph was sampled through the round window membrane as well as at the lateral semicircular canal to determine drug levels. Of the twenty-one included patients, triamcinolone acetonide was quantifiable in cerebrospinal fluid in 43% at very low levels (range 0 ng/ml-6.2 ng/ml) which did not correlate with perilymph levels. Drug levels at the two different perilymph sampling sites were within a range of 13.5 ng/ml to 1180.0 ng/ml. Results suggest an equal distribution of triamcinolone acetonide to semicircular canals, which might support the use of triamcinolone acetonide as a treatment option for vestibular pathologies such as Menièrés disease. On the other hand, the distribution to cerebrospinal fluid might be limiting current approaches in gene therapy where a central distribution is unwanted.