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OBJECTIVE: To evaluate the long-term hearing outcome after translabyrinthine resection of tumors within the internal auditory canal (IAC) with simultaneous cochlear implantation (CI). STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Thirty-seven patients with tumors of the IAC undergoing translabyrinthine tumor surgery as a first-line therapy. INTERVENTIONS: Intraoperatively, electrically evoked auditory brainstem response audiometry (eABR) was performed in all patients to assess cochlear nerve (CN) integrity. In case of preserved CN function after tumor removal, CI was subsequently performed. Postoperatively, patients were regularly followed up to evaluate pure-tone hearing as well as speech recognition with a monosyllabic word comprehension test. MAIN OUTCOME MEASURES: Postoperative hearing thresholds and word recognition scores. RESULTS: Of 37 included patients, 22 (59.46%) had positive eABR responses after tumor removal. Twenty-one of these underwent simultaneous CI directly after tumor surgery and were followed-up for 24.24 ± 19.83 months after surgery. Hearing of these patients significantly improved from 73.87 ± 21.40 dB preoperatively to a mean pure-tone average of 41.56 ± 18.87 dB 1 year (p = 0.0008) and 34.58 ± 2.92 dB 3 years after surgery (p = 0.0157). Speech recognition significantly recovered from 13.33 ± 25.41% to 58.93 ± 27.61% 1 year (p = 0.0012) and 51.67 ± 28.58% 3 years postoperatively (p = 0.0164). CONCLUSIONS: Regardless of tumor histopathology, CI is an effective option to restore patients' hearing after translabyrinthine tumor surgery. After CI, patients hearing can be restored over a long-term period of a minimum of 3 years post-surgery. Furthermore, eABR proves to be a practical tool to evaluate CN function and screen for patients eligible for CI.

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Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Due to the heterogeneity of causes for SNHL, effective treatment options remain scarce, creating an unmet need for novel drugs in the field of otology. Cochlear implantation (CI) currently is the only established method to restore hearing function in profound SNHL and deaf patients. The cochlear implant bypasses the non-functioning sensory hair cells (HCs) and electrically stimulates the neurons of the cochlear nerve. CI also benefits patients with residual hearing by combined electrical and auditory stimulation. However, the insertion of an electrode array into the cochlea induces an inflammatory response, characterized by the expression of pro-inflammatory cytokines, upregulation of reactive oxygen species, and apoptosis and necrosis of HCs, putting residual hearing at risk. Here, we characterize the small molecule AC102, a pyridoindole, for its protective effects on residual hearing in CI. In a gerbil animal model of CI, AC102 significantly improves the recovery of hearing thresholds across multiple frequencies and confines the cochlear trauma to the directly mechanically injured area. In addition, AC102 significantly preserves auditory nerve fibers and inner HC synapses throughout the whole cochlea. In vitro experiments in an ethanol challenged HT22 cell-line revealed significant and dose-responsive anti-apoptotic effects following the treatment of with AC102. Further, AC102 treatment resulted in significant downregulation of the expression of pro-inflammatory cytokines in an organotypic ex vivo model of electrode insertion trauma (EIT). These results suggest that AC102's effects are likely elicited during the inflammatory phase of EIT and mediated by anti-apoptotic and anti-inflammatory properties, highlighting AC102 as a promising compound for hearing preservation during CI. Moreover, since the inflammatory response in CI shares similarities to that in other etiologies of SNHL, AC102 may be inferred as a potential general treatment option for various inner ear conditions.

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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.

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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.

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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.

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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.

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BACKGROUND: Infectious diseases like the common cold, otitis media, or gastroenteritis frequently occur in childhood. In addition to prescription drugs, parents often use supplementary over-the-counter (OTC) products recommended by pharmacists and other non-medical professionals to relieve their children's symptoms. However, the efficacy of such alternative treatments lacks conclusive evidence. The objective of this study was to investigate the use of OTC products and related active ingredients in children, and the motivations behind this choice. METHODS: The present study included 215 children aged between 1 and 14 years with an acute respiratory tract infection, e.g., common cold, bronchitis, otitis media, tonsillitis, or gastroenteritis. During their visit to the pediatric practice, parents filled in a self-administered questionnaire about their child's diagnosis, additional treatment options, and motivations to integrate supplementary medicinal products after their first visit for acute infection or follow-up examination. Children with chronic illnesses and patients visiting for a routine maternal and child health program check-up were excluded. RESULTS: The study included 111 (51.6%) males and 104 (48.4%) females. Median age was 3.00 (IQR 2.0 - 5.0) years. The most common reason for a visit was a respiratory tract infection (78.6%). Out of 215 parents, 182 (84.7%) resorted to non-prescription remedies to alleviate their child's symptoms. Teas (45.1%), and home remedies (43.3%) were the most popular. At total 133 (74.3%) followed recommendations from friends and family regarding additional medications usage. Parents with previous experience with complementary medicine tended to prefer this approach to treat their children (p.adjust = 0.08). CONCLUSION: The use of non-prescription medicine is increasing as well as the range of related information sources. Evidence-based recommendations in this field might improve pediatric care.

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