Repair of noise-induced damage to stereocilia F-actin cores is facilitated by XIRP2 and its novel mechanosensor domain.

Prolonged exposure to loud noise has been shown to affect inner ear sensory hair cells in a variety of deleterious manners, including damaging the stereocilia core. The damaged sites can be visualized as 'gaps' in phalloidin staining of F-actin, and the enrichment of monomeric actin at these sites, along with an actin nucleator and crosslinker, suggests that localized remodeling occurs to repair the broken filaments. Herein, we show that gaps in mouse auditory hair cells are largely repaired within 1 week of traumatic noise exposure through the incorporation of newly synthesized actin. We provide evidence that Xin actin binding repeat containing 2 (XIRP2) is required for the repair process and facilitates the enrichment of monomeric γ-actin at gaps. Recruitment of XIRP2 to stereocilia gaps and stress fiber strain sites in fibroblasts is force-dependent, mediated by a novel mechanosensor domain located in the C-terminus of XIRP2. Our study describes a novel process by which hair cells can recover from sublethal hair bundle damage and which may contribute to recovery from temporary hearing threshold shifts and the prevention of age-related hearing loss.

Otology-Neurotology 2020 US Workforce Distribution.

Objective: Determine the geographic and per capita distribution of otology-neurotology physician-surgeons within the United States. Study Design: National database review. Setting: United States. Methods: The American Neurotology Society and ENThealth.org membership databases were queried to identify otology-neurotology physician-surgeons within the United States. Physician-surgeons were divided by regional national census areas, state, and by largest population statistical area based on 2019 US Census population estimates. The number of otology-neurotology physician-surgeons per 1 million persons was calculated for each population designation. Results: Four-hundred eighty-two physician-surgeons were identified, representing 49 states and the District of Columbia. The New England division (Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island) was the most concentrated region (1.89), whereas the West-South-Central (Texas, Oklahoma, Arkansas, Louisiana) was the least concentrated region (1.23) per million persons. The highest concentration of physician-surgeons by state is within the District of Columbia (4.25), Vermont (3.21), North Dakota (2.62), Massachusetts (2.61), and New York (2.21) (per million), whereas Mississippi (0.67), Georgia (0.66), Idaho (0.56), New Mexico (0.48), and Wyoming (0.0) were the least concentrated per million persons. Increasing number of physician-surgeons was significantly correlated by state (r2 = 0.9; P < 0.0001), largest statistical area (r2 = 0.88; P < 0.0001), and census region (r2 = 0.95; P < 0.0005). Conclusions: Otology-neurotology physician-surgeons are evenly distributed across the United States; however, certain areas are likely underrepresented. Variability in clinical practice may account for under or overrepresentation not captured in this analysis.

Necroptosis and Apoptosis Contribute to Cisplatin and Aminoglycoside Ototoxicity.

Ototoxic side effects of cisplatin and aminoglycosides have been extensively studied, but no therapy is available to date. Sensory hair cells, upon exposure to cisplatin or aminoglycosides, undergo apoptotic and necrotic cell death. Blocking these cell death pathways has therapeutic potential in theory, but incomplete protection and lack of therapeutic targets in the case of necrosis, has hampered the development of clinically applicable drugs. Over the past decade, a novel form of necrosis, termed necroptosis, was established as an alternative cell death pathway. Necroptosis is distinguished from passive necrotic cell death, in that it follows a cellular program, involving the receptor-interacting protein kinase (RIPK) 1 and RIPK3. In this study, we used pharmacological and genetic interventions in the mouse to test the relative contributions of necroptosis and caspase-8-mediated apoptosis toward cisplatin and aminoglycoside ototoxicity. We find that ex vivo, only apoptosis contributes to cisplatin and aminoglycoside ototoxicity, while in vivo, necroptosis as well as apoptosis are involved in both sexes. Inhibition of necroptosis and apoptosis using pharmacological compounds is thus a viable strategy to ameliorate aminoglycoside and cisplatin ototoxicity.SIGNIFICANCE STATEMENT The clinical application of cisplatin and aminoglycosides is limited due to ototoxic side effects. Here, using pharmaceutical and genetic intervention, we present evidence that two types of programmed cell death, apoptosis and necroptosis, contribute to aminoglycoside and cisplatin ototoxicity. Key molecular factors mediating necroptosis are well characterized and druggable, presenting new avenues for pharmaceutical intervention.

Use of Positive Airway Pressure Following Middle Ear Surgery: A Practice Survey of Otologists.

BACKGROUND: Positive airway pressure (PAP) devices are used as treatment for obstructive sleep apnea (OSA). PAP may increase middle ear pressure which is of interest to otologic surgeons. There is a lack of data to guide management of PAP therapy after middle ear surgery. OBJECTIVE: To elucidate how otologic surgeons manage PAP in their patients after ear surgery. STUDY DESIGN: A survey e-mailed to practicing members of the American Neurotology Society. RESULTS: Among 60 respondents, the most common recommendations to patients were to avoid PAP use for 1 week (40%), return to normal use immediately (23.3%), avoid PAP for 1 month (13.3%), or avoid PAP for 1 day (13.3%) after surgery. Twenty percent of providers reported that they change their advice on the basis of the PAP pressure settings (i.e., shorter hiatus for higher settings). Among respondents, 47% think that they have patients with middle ear issues because of PAP and 13% attributed surgical failures to PAP use. One-third of providers routinely pack the Eustachian tube during surgery. Providers who attributed a negative surgical outcome to PAP use were more likely to routinely pack/plug the Eustachian tube during otologic surgery (p = 0.001). CONCLUSION: Treatment recommendations regarding postoperative PAP treatment for obstructive sleep apnea vary greatly among practicing otologists. Providers who think that an adverse outcome was attributed to PAP use were more likely to prophylactically plug the Eustachian tube during surgery. Future research will provide additional information which will allow a better understanding of the effect of PAP on the middle ear, especially after otologic surgery.

Treatment of glomus jugulare tumors with gamma knife radiosurgery.

OBJECTIVE: Surgical resection, preoperative embolization, radiation therapy, and stereotactic radiosurgery have been used to treat glomus jugulare tumors (GJT). However, the optimal treatment of these tumors remains unclear. The authors report their data on treatment of GJTs with gamma knife radiosurgery (GKS). DESIGN: Retrospective review and pooled analysis. METHODS: Fifteen patients (nine female, six male) were treated with GKS at a single tertiary care institution for GJTs over a 14-year period. Criteria for selection included GKS followed by at least one posttreatment radiographic image, and volumetric analysis was performed. A required 15% change in tumor volume was considered real. Pooled analysis was performed to compare outcomes with other series. RESULTS: The mean total radiologic follow-up was 43.2 months. The mean dose-to-the tumor margin was 14.6 Gy. The mean tumor size at treatment was 7.3 cc and 6.3 cc at last follow-up. After treatment, seven tumors decreased (46.7%), five remained unchanged (33.3%), and three (20%) grew on imaging. Treatment failures received a mean marginal dose of 13.2 Gy compared with 15.1 Gy for treatment successes (P =.08). Overall tumor control rate after GKS in the existing literature with inclusion of the present study is 90.5%. CONCLUSIONS: GKS is an effective treatment option for patients with GJTs, including those with prior surgical resection. Marginal radiation doses greater than 13 Gy may be optimal for tumor control. Longer follow-up will better define the benefits and risks of stereotactic radiosurgery in treating patients with GJT.

Gene transfer in human vestibular epithelia and the prospects for inner ear gene therapy.

Transfer of exogenous genetic material into the mammalian inner ear using viral vectors has been characterized over the last decade. A number of different viral vectors have been shown to transfect the varying cell types of the nonprimate mammalian inner ear. Several routes of delivery have been identified for introduction of vectors into the inner ear while minimizing injury to existing structures and at the same time ensuring widespread distribution of the agent throughout the cochlea and the rest of the inner ear. These studies raise the possibility that gene transfer may be developed as a potential strategy for treating inner ear dysfunction in humans. Furthermore, a recent report showing successful transfection of excised human vestibular epithelia offers proof of principle that viral gene transfer is a viable strategy for introduction and expression of exogenous genetic material to restore function to the inner ear. Human vestibular epithelia were harvested from patients undergoing labyrinthectomy, either for intractable Ménière's disease or vestibular schwannoma resection, and cultured for as long as 5 days. In those experiments, recombinant, multiply-deleted, replication-deficient adenoviral vectors were used to transfect and express a reporter gene as well as the functionally relevant gene, wild-type KCNQ4, a potassium channel gene that when mutated causes the autosomal dominant HL DFNA2.Here, we review the current state of viral-mediated gene transfer in the inner ear and discuss different viral vectors, routes of delivery, and potential applications of gene therapy. Emphasis is placed on experiments demonstrating viral transfection of human inner ear tissue and implications of these findings and for the future of gene therapy in the human inner ear.

Image-guided localization of the internal auditory canal via the middle cranial fossa approach.

OBJECTIVE: We sought to determine the accuracy of an electromagnetic image guidance surgical navigation system in localizing the midpoint of the internal auditory canal (IAC) and other structures of the temporal bone through the middle cranial fossa approach. MATERIALS AND METHODS: Seven fresh cadaveric whole heads were dissected via a middle cranial fossa approach. High-resolution CT scans were used with an InstaTrak 3500 Plus electromagnetic image guidance system (General Electric, Fairfield, CT). We evaluated the accuracy of identifying several middle cranial fossa landmarks including the midpoint of the IAC; the labyrinthine segment of the facial nerve; and the arcuate eminence, the carotid artery, and foramen spinosum. RESULTS: We were able to identify the middle of the IAC within 2.31 mm (range 0.65-7.52 mm, SD 2.39 mm). The arcuate eminence could be identified within 1.86 mm (range 1.49-2.37 mm, SD 0.36 mm). We noted some interference when the handpiece was within 6 to 8 cm of the microscope. CONCLUSION: Although computer-aided navigational tools are no substitute for thorough knowledge of temporal bone anatomy, we found the InstaTrak system reliable in identifying the midpoint of the IAC to within 2.4 mm through a middle fossa approach.

Diagnosis and management of salivary fistula after surgery for congenital aural atresia.

OBJECTIVE: Salivary fistula is an uncommon and unreported yet meaningful complication associated with the repair of congenital aural atresia. The capsule of the parotid gland may be violated during two steps of the operation: the initial dissection around the glenoid fossa or while aligning the auricle with the bony canal at the end of the procedure. We present the first described series of patients with salivary fistula after repair of congenital aural atresia. STUDY DESIGN: Retrospective case review from 1985 to 2004. SETTING: Tertiary referral center. PATIENTS: We included all patients who were diagnosed with a salivary fistula after congenital aural atresia repair. MAIN OUTCOME MEASURE: The diagnosis of a salivary fistula or salivary tissue in the external auditory canal after atresia repair was based on one of the following criteria: 1) identification of a fistula tract or salivary tissue in the external auditory canal, 2) otorrhea positive for amylase, or 3) intermittent otorrhea associated with eating. RESULTS: Of 1,500 patients operated on for aural atresia, we identified 6 with salivary fistula after atresia repair. Salivary fistulas were diagnosed from 15 days to 10 years postoperatively, and the duration ranged from 6 months to 14 years. Treatment included observation, medical management, and surgical intervention. CONCLUSION: Salivary fistulas in the external auditory canal may present with granulation tissue, persistent crusting, or persistent otorrhea; it is therefore necessary to consider salivary fistula when managing these findings in postoperative congenital aural atresia patients. Salivary fistula secondary to repair of congenital aural atresia may be managed conservatively or surgically.

Cochlear implantation in patients with auditory neuropathy of varied etiologies.

OBJECTIVES/HYPOTHESIS: Auditory neuropathy is a relatively recently described pattern of hearing loss characterized by preservation of outer hair cell function despite absent brainstem auditory evoked responses. Intact outer hair cell function is demonstrated by the presence of otoacoustic emissions and/or a measurable cochlear microphonic on electrocochleography, whereas no synchronous neural activity (absent action potentials) is seen on acoustically evoked brainstem auditory evoked response testing. The study reviews the authors' experience with six patients diagnosed with auditory neuropathy, four of whom have undergone cochlear implantation. MATERIALS AND METHODS: A retrospective review of all medical and audiological charts at the University of Virginia Hospitals (Charlottesville, VA) was performed to identify patients who have undergone cochlear implantation or have been diagnosed with auditory neuropathy, or both. RESULTS: Six patients with hearing loss attributable to auditory neuropathy were identified, four of whom have undergone cochlear implantation. Causes varied, including congenital, infectious, and idiopathic origins. Adults demonstrated subjective auditory perception on promontory stimulation, whereas no repeatable brainstem auditory evoked response waveforms could be demonstrated on pediatric promontory stimulation testing. Patients with implants demonstrated implant-evoked brainstem auditory evoked responses and improved audiological performance. CONCLUSIONS: The six cases presented in the study represent varied causes and, probably, varied sites of lesions of auditory neuropathy. Promontory stimulation has been valuable, particularly in adults. Cochlear implantation allows the opportunity to provide a supraphysiological electrical stimulation to the auditory nerve, with the hope of reintroducing synchronous neural activity. Greater confidence and enthusiasm for cochlear implantation in appropriately selected patients with auditory neuropathy are gained through experience with such diverse cases.

Otogenic sigmoid sinus thrombosis: what is the role of anticoagulation?

OBJECTIVES: The treatment of otogenic sigmoid sinus thrombosis with surgery and antibiotics is well established. However, the role of anticoagulation remains unstudied. The study reviews the signs, symptoms, radiological evaluation, surgical treatment, and medical management of patients with otogenic sigmoid sinus thrombosis treated with or without anticoagulation. STUDY DESIGN: Retrospective review of nine patients from 1995 to 2001 with sigmoid sinus thrombosis. METHODS: Patients were identified by a review of all medical and radiological records. Signs, symptoms, diagnostic studies, treatments, and outcomes were recorded. In addition, telephone follow-up was performed. RESULTS Nine patients were identified over a 6-year period from 1995 to 2001. Patients had a mean follow-up time of 9 months (range, 1-24 mo). Of the nine patients identified, eight patients (89%) had tympanostomy tube placement, six patients (67%) had canal wall intact mastoidectomy, and one patient (11%) had canal wall down mastoidectomy. Needle aspiration of the sinus was performed in four of nine patients (44%), and incision of the sinus in two of nine (22%). Treatment with broad-spectrum antibiotics occurred in all patients with a mean duration of 12 days (range, 2-22 d) intravenously and 7 days (range, 0-21 d) orally. Sixty-seven percent of patients (six of nine) were anticoagulated: Five patients received low-molecular-weight heparin, and one patient received heparin-coumadin. No mortality occurred in either the anticoagulated or non-anticoagulated group. One anticoagulated patient did have persistent headaches and otorrhea. CONCLUSIONS: Surgery and antibiotic therapy are the cornerstones of the management of otogenic sigmoid sinus thrombosis. However, the role of anticoagulation remains unclear. Because complications of embolization and persistent sepsis are low in otogenic sigmoid sinus thrombosis patients treated with or without anticoagulation, withholding anticoagulation in selected patients is reasonable. Serial imaging to monitor for thrombus progression is advisable.

Pitfalls in the endoscopic drainage of subperiosteal orbital abscesses secondary to sinusitis.

OBJECTIVE: To review the safety and efficacy of endoscopic drainage of subperiosteal orbital abscesses (SPOAs) secondary to sinusitis and to evaluate risk factors that may be associated with failure. STUDY DESIGN: Retrospective chart review. METHODS: All patients admitted to the University of the Virginia Health System with a diagnosis of SPOA between 1992 and 1999 were reviewed. RESULTS: Seven of the 10 SPOAs identified, each located medially, resolved without complication after endoscopic drainage. The remaining three patients required a second drainage. One patient had an inferiorly located SPOA, which recurred laterally after endoscopic drainage. A second pediatric patient, who did not undergo a routine second-look procedure, developed middle turbinate lateralization and synechiae, which led to recurrent SPOAs. A third patient with a significant history of sinusitis was found to have an ethmoid sinus mucocele extending into the medial and posterior orbit. All patients eventually resolved their symptoms. CONCLUSIONS: Endoscopic drainage of medial SPOAs appears to be safe and effective. However, several risk factors must be recognized when present. Management of these risk factors is discussed.