Erratum: Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2.

[This corrects the article DOI: 10.1016/j.omtm.2022.06.012.].

Sinonasal (Schneiderian) Tumors in the Temporal Bone: Case Series and Systematic Review.

BACKGROUND: Neoplasms derived from the sinonasal epithelium are a rare finding in the temporal bone, and their origins are controversial. PURPOSE: To review the characteristics of sinonasal epithelial (previously known as Schneiderian) tumors occurring in the temporal bone. DATA SOURCE: This was a 2-center case series and systematic review of MEDLINE, EMBASE, and the Web of Science through May 2021. STUDY SELECTION: Patients with clinicopathologic evidence of temporal bone involvement by neoplasms of sinonasal epithelial origin were selected, with or without a history of prior primary sinonasal epithelial tumors. DATA ANALYSIS: Clinical, radiologic, and pathologic data were extracted. DATA SYNTHESIS: The systematic review included 56 studies and our 8 unpublished cases, totaling 76 cases of papillomas or squamous cell carcinomas in the temporal bone. Of these, 51% occurred secondary to sinonasal tumors, and 49% occurred primarily. Secondary tumors were usually metachronous (77%), with a median delay of 1 year from sinonasal-to-temporal bone tumor diagnosis. Most cases were unilateral (90%); bilateral temporal bone involvement occurred only as secondary ("trilateral") tumors. Unilateral secondary tumors had ipsilateral (81%) or bilateral (19%) sinonasal counterparts. Secondary tumors were more likely to be malignant (OR, 6.7, P < .001). LIMITATIONS: The review was based on case reports and small case series, which are subject to reporting bias. CONCLUSIONS: The observed tumor patterns support the hypothesis that the Eustachian tube facilitates the spread of sinonasal epithelium-derived neoplasms from the sinonasal cavity to the temporal bone. Transtubal spread of sinonasal epithelium-derived neoplasms should be considered among the rare causes of middle ear masses.

Development and validation of a rabbit model of Pseudomonas aeruginosa non-ventilated pneumonia for preclinical drug development.

Background: New drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa, have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections. Methods: We report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with Pseudomonas aeruginosa by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression. Results: In a rabbit model of non-ventilated pneumonia, endobronchial challenge with live P. aeruginosa strain 6206, but not with UV-killed Pa6206, caused acute respiratory distress syndrome, as evidenced by acute lung inflammation, pulmonary edema, hemorrhage, severe hypoxemia, hyperlactatemia, neutropenia, thrombocytopenia, and hypoglycemia, which preceded respiratory failure and death. Pa6206 increased >100-fold in the lungs and then disseminated from there to infect distal organs, including spleen and kidneys. At 5 h post-infection, 67% of Pa6206-challenged rabbits had PaO2 <60 mmHg, corresponding to a clinical cut-off when oxygen therapy would be required. When administered at 5 h post-infection, humanized dosing regimens of tobramycin and meropenem reduced mortality to 17-33%, compared to 100% for saline-treated rabbits (P<0.001 by log-rank tests). For meropenem which exhibits time-dependent bactericidal activity, rabbits treated with a humanized meropenem dosing regimen of 80 mg/kg q2h for 24 h achieved 100% T>MIC, resulting in 75% microbiological clearance rate of Pa6206 from the lungs. For tobramycin which exhibits concentration-dependent killing, rabbits treated with a humanized tobramycin dosing regimen of 8 mg/kg q8h for 24 h achieved Cmax/MIC of 9.8 ± 1.4 at 60 min post-dose, resulting in 50% lung microbiological clearance rate. In contrast, rabbits treated with a single tobramycin dose of 2.5 mg/kg had Cmax/MIC of 7.8 ± 0.8 and 8% (1/12) microbiological clearance rate, indicating that this rabbit model can detect dose-response effects. Conclusion: The rabbit model may be used to help predict clinical efficacy of new antibacterial drugs for the treatment of non-ventilated P. aeruginosa pneumonia.

Evidence of cochlear neural degeneration in normal-hearing subjects with tinnitus.

Tinnitus, reduced sound-level tolerance, and difficulties hearing in noisy environments are the most common complaints associated with sensorineural hearing loss in adult populations. This study aims to clarify if cochlear neural degeneration estimated in a large pool of participants with normal audiograms is associated with self-report of tinnitus using a test battery probing the different stages of the auditory processing from hair cell responses to the auditory reflexes of the brainstem. Self-report of chronic tinnitus was significantly associated with (1) reduced cochlear nerve responses, (2) weaker middle-ear muscle reflexes, (3) stronger medial olivocochlear efferent reflexes and (4) hyperactivity in the central auditory pathways. These results support the model of tinnitus generation whereby decreased neural activity from a damaged cochlea can elicit hyperactivity from decreased inhibition in the central nervous system.

Experimental drugs for the prevention or treatment of sensorineural hearing loss.

INTRODUCTION: Sensorineural hearing loss results in irreversible loss of inner ear hair cells and spiral ganglion neurons. Reduced sound detection and speech discrimination can span all ages, and sensorineural hearing rehabilitation is limited to amplification with hearing aids or cochlear implants. Recent insights into experimental drug treatments for inner ear regeneration and otoprotection have paved the way for clinical trials in order to restore a more physiological hearing experience. Paired with the development of innovative minimally invasive approaches for drug delivery to the inner ear, new, emerging treatments for hearing protection and restoration are within reach. AREAS COVERED: This expert opinion provides an overview of the latest experimental drug therapies to protect from and to restore sensorineural hearing loss. EXPERT OPINION: The degree and type of cellular damage to the cochlea, the responsiveness of remaining, endogenous cells to regenerative treatments, and the duration of drug availability within cochlear fluids will determine the success of hearing protection or restoration.

Prevention and management of hearing loss in patients receiving ototoxic medications.

Following the efforts of patient advocates, the World Health Organization published updated guidelines for management of multidrug-resistant tuberculosis in 2018 that advised against the routine use of ototoxic second-line injectable drugs (amikacin, capreomycin and kanamycin). Although hearing loss is no longer considered an unavoidable harm for patients with multidrug-resistant tuberculosis, ototoxic medications continue to be used for several infectious and oncological disorders around the world. These drugs contribute to more than a half a million cases of hearing loss worldwide annually. Currently, there are no international standards for preventing and managing hearing loss associated with ototoxic medications. We present recent data on the prevention and management of hearing loss related to these drugs and highlight the variability in care across settings. More importantly, we aim to provide an evidence-based framework for evaluating, screening and preventing ototoxicity. Finally, we identify avenues for future research so that patients no longer have to choose between hearing loss and a disease cure. There remain significant gaps in our understanding about optimal screening and treatment of ototoxic hearing loss. Here we aim to inspire future international guidelines to address gaps in ototoxicity care and establish research agendas for eliminating ototoxic medications.

Sous l'impulsion des défenseurs des droits des patients, l'Organisation mondiale de la Santé a publié une version actualisée des lignes directrices relatives à la prise en charge de la tuberculose multirésistante en 2018, qui déconseille l'usage systématique de médicaments ototoxiques injectables de deuxième intention (amikacine, capréomycine et kanamycine). Bien que la perte auditive ne soit plus considérée comme un risque inévitable chez les patients atteints de tuberculose multirésistante, les médicaments ototoxiques continuent à être largement employés pour traiter de nombreuses maladies infectieuses et oncologiques à travers le monde. Ces médicaments sont impliqués chaque année dans plus de la moitié des cas de déficience auditive dans le monde. Il n'existe actuellement aucune norme internationale consacrée à la prévention et à la prise en charge de la perte auditive causée par des médicaments ototoxiques. Dans le présent document, nous exposons les données récentes à ce propos et soulignons la variabilité des soins prodigués d'une région à l'autre. Nous tentons surtout d'établir, à partir d'éléments concrets, un cadre dédié à l'évaluation, au dépistage et à la prévention de l'ototoxicité. Enfin, nous dégageons des pistes pour de futures études, afin que les patients n'aient plus à choisir entre une perte auditive et un remède. D'importantes lacunes subsistent dans notre compréhension du dépistage et du traitement de la perte auditive d'origine ototoxique. Nous espérons inspirer de futures lignes directrices internationales afin d'y remédier et de développer des programmes de recherche pour supprimer les médicaments ototoxiques.

Tras los esfuerzos de los defensores de pacientes, la Organización Mundial de la Salud publicó en 2018 unas directrices actualizadas para el tratamiento de la tuberculosis multirresistente en las que se desaconsejaba el uso rutinario de medicamentos inyectables de segunda línea ototóxicos (amikacina, capreomicina y kanamicina). Aunque la pérdida de audición ya no se considera un daño inevitable para los pacientes con tuberculosis multirresistente, los medicamentos ototóxicos se siguen administrando para varios trastornos infecciosos y oncológicos en todo el mundo. Estos fármacos contribuyen a más de medio millón de casos de pérdida de audición en todo el mundo cada año. En la actualidad, no existen estándares internacionales para prevenir y tratar la pérdida de audición asociada a los medicamentos ototóxicos. En este documento, se presentan datos recientes sobre la prevención y el tratamiento de la pérdida de audición relacionada con estos fármacos y se destaca la variabilidad de la atención en los distintos entornos. Además, se pretende ofrecer un marco basado en la evidencia para evaluar, detectar y prevenir la ototoxicidad. Por último, se identifican las vías de investigación futura para que los pacientes no tengan que elegir entre la pérdida de audición y la cura de la enfermedad. Siguen existiendo importantes deficiencias en el conocimiento del cribado y el tratamiento óptimos de la pérdida de audición ototóxica. En este sentido, se pretende inspirar futuras directrices internacionales para abordar las deficiencias en la atención a la ototoxicidad y establecer programas de investigación para eliminar los medicamentos ototóxicos.

Voluntary Field Recall of Advanced Bionics HiRes Cochlear Implants: A Single-Institution Experience.

OBJECTIVES: In 2020, Advanced Bionics (AB) announced a recall of two cochlear implant (CI) models, the "HiRes Ultra" and "HiRes Ultra 3D", because of reports of hearing degradation. The present study examines clinical parameters and patient features in cases of device failure and evaluates outcomes after reimplantation. MATERIALS AND METHODS: A series of 52 patients implanted with the recalled devices experienced suspected device failure and subsequently underwent revision CI placement at a tertiary academic medical center between December 2019 and November 2021. RESULTS: Consonant-nucleus-consonant scores and individual phonemes increased significantly between patients' preoperative evaluation and primary cochlear implantation. Performance declined significantly before revision and recovered after revision CI placement. Similarly, pure-tone average thresholds improved between preoperative and primary CI, fell before revision surgery, and were corrected with revision implantation. As a group, patients reached their peak hearing performance significantly faster after revision CI (mean ± standard deviation, 53.4 ± 51.8 d) compared with their primary CI (mean ± standard deviation, 260.6 ± 245.9 d). Electrical field imaging performed by AB and device impedance measurements were found to be abnormal in the basally positioned electrodes (electrodes 9-16). CONCLUSION: Hearing performance degradation is significant in AB Ultra device failures and seems to be linked to the basal-most electrodes in the array. Revision outcomes have been robust, necessitating continued monitoring of affected patients and support for reimplantation procedures. LEVEL OF EVIDENCE: IV.

Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2.

Loss of function of the neurofibromatosis type 2 (NF2) tumor suppressor gene leads to the formation of schwannomas, meningiomas, and ependymomas, comprising ∼50% of all sporadic cases of primary nervous system tumors. NF2 syndrome is an autosomal dominant condition, with bi-allelic inactivation of germline and somatic alleles resulting in loss of function of the encoded protein merlin and activation of mammalian target of rapamycin (mTOR) pathway signaling in NF2-deficient cells. Here we describe a gene replacement approach through direct intratumoral injection of an adeno-associated virus vector expressing merlin in a novel human schwannoma model in nude mice. In culture, the introduction of an AAV1 vector encoding merlin into CRISPR-modified human NF2-null arachnoidal cells (ACs) or Schwann cells (SCs) was associated with decreased size and mTORC1 pathway activation consistent with restored merlin activity. In vivo, a single injection of AAV1-merlin directly into human NF2-null SC-derived tumors growing in the sciatic nerve of nude mice led to regression of tumors over a 10-week period, associated with a decrease in dividing cells and an increase in apoptosis, in comparison with vehicle. These studies establish that merlin re-expression via gene replacement in NF2-null schwannomas is sufficient to cause tumor regression, thereby potentially providing an effective treatment for NF2.

Training Surgeon Scholars: Grant Writing Workshops During Residency.

Surgical residents may have limited experience with grant writing even though it is an important skill for academic physicians. We describe a novel curriculum on the conduct of research and grant literacy delivered at a single otolaryngology training program over 5 years. This workshop series included preparing a draft grant and conducting a mock grant review committee. In a survey of past participants (71% response rate), 91% found the workshops useful for grant writing or reviewing, and many used or planned to use the draft grants for real grant applications. The average number of American Academy of Otolaryngology-Head and Neck Surgery Foundation CORE grants submitted and successfully funded increased among residents at this program in the 4 years after the introduction of the workshop series as compared with the 4 years before. Further improvements continue to be made to the curriculum based on resident feedback.

Intracochlear New Fibro-Ossification and Neuronal Degeneration Following Cochlear Implant Electrode Translocation: Long-Term Histopathological Findings in Humans.

OBJECTIVE: We aim to assess the histopathology of human temporal bones (TBs) with evidence of cochlear implantation (CI) electrode scalar translocation. STUDY DESIGN: Otopathology study. SETTING: Otopathology laboratory. PATIENTS: TBs from patients who had a history of CI and histopathological evidence of interscalar translocation. Specimens with electrode placed entirely within the ST served as controls. INTERVENTION: Histopathological assessment of human TBs. MAIN OUTCOME MEASURES: TBs from each patient were harvested postmortem and histologically analyzed for intracochlear changes in the context of CI electrode translocation and compared to controls. Intracochlear new fibro-ossification, and spiral ganglion neuron (SGN) counts were assessed. Postoperative word recognition scores (WRS) were also compared. RESULTS: Nineteen human TBs with electrode translocation and eight controls were identified. The most common site of translocation was the ascending limb of the basal turn (n = 14 TBs). The average angle of insertion at the point of translocation was 159°â€Š±â€Š79°. Eighteen translocated cases presented moderate fibroosseous changes in the basal region of the cochlea, extending to the translocation point and/or throughout the electrode track in 42%. Lower SGN counts were more pronounced in translocated cases compared to controls, with a significant difference for segment II (p = 0.019). Although final postoperative hearing outcomes were similar between groups, translocated cases had slower rate of improvement in WRS (p = 0.021). CONCLUSIONS: Cochlear implant electrode translocation was associated with greater fibroosseous formation and lower SGN population. Our findings suggest that scalar translocations may slow the rate of improvement in WRS overtime as compared to atraumatic electrode insertions.Level of evidence: IV.

A Subset of Intracanalicular Vestibular Schwannomas Demonstrates Minimal Growth Over a 10-Year Period.

OBJECTIVE: Vestibular schwannomas (VS) commonly undergo magnetic resonance imaging (MRI) surveillance, but long-term data to support the ideal frequency is limited. Herein, we aim to investigate intracanalicular VS growth predictors and long-term growth rates (GR). STUDY DESIGN: Retrospective chart review. SETTING: Two tertiary care centers. PATIENTS: Sporadic intracanalicular VS with initial conservative management and at least two sequential MRIs. INTERVENTION: Serial MRI. MAIN OUTCOME MEASURES: VS were categorized by baseline internal auditory canal tertile sublocalization (fundus, midpoint, porus) and size (≤100, 100-200, >200 mm3). Throughout follow-up, volumetric GR (mm3/yr) were determined (baseline-3 yrs, 3-5 yrs, 5-10 yrs) and treatment rates were assessed. RESULTS: Ninety-nine intracanalicular VS were identified (mean follow-up of 6.1 ±â€Š4.5 yrs). Mean GR before 5-year follow-up were comparable for baseline tertile involvement and size. After 5-year follow-up, mean GR of VS involving the fundus at baseline were lower than those involving the midpoint and fundus (6.17 ±â€Š21.16 and 119.74 ±â€Š117.57 mm3/yr, respectively; p = 0.034). Mean GR of VS with less than or equal to 100 mm3 at baseline (-7.29 ±â€Š25.44 mm3/yr) were lower than those with 100 to 200 mm3 (86.55 ±â€Š103.99 mm3/yr; p = 0.011) and more than 200 mm3 (45.70 ±â€Š35.71 mm3/yr; p = 0.031). Vestibular schwannomas involving the midpoint and fundus had greater treatment rates compared with VS involving only the fundus (p < 0.001). CONCLUSIONS: Baseline tertile involvement and size may predict long-term intracanalicular VS growth where fundal tumors or those less than or equal to 100 mm3 exhibit little long-term growth. Extending surveillance after 5-year follow-up may be reasonable for fundal VS.

A Novel Small Molecule Neurotrophin-3 Analogue Promotes Inner Ear Neurite Outgrowth and Synaptogenesis In vitro.

Sensorineural hearing loss is irreversible and is associated with the loss of spiral ganglion neurons (SGNs) and sensory hair cells within the inner ear. Improving spiral ganglion neuron (SGN) survival, neurite outgrowth, and synaptogenesis could lead to significant gains for hearing-impaired patients. There has therefore been intense interest in the use of neurotrophic factors in the inner ear to promote both survival of SGNs and re-wiring of sensory hair cells by surviving SGNs. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) represent the primary neurotrophins in the inner ear during development and throughout adulthood, and have demonstrated potential for SGN survival and neurite outgrowth. We have pioneered a hybrid molecule approach to maximize SGN stimulation in vivo, in which small molecule analogues of neurotrophins are linked to bisphosphonates, which in turn bind to cochlear bone. We have previously shown that a small molecule BDNF analogue coupled to risedronate binds to bone matrix and promotes SGN neurite outgrowth and synaptogenesis in vitro. Because NT-3 has been shown in a variety of contexts to have a greater regenerative capacity in the cochlea than BDNF, we sought to develop a similar approach for NT-3. 1Aa is a small molecule analogue of NT-3 that has been shown to activate cells through TrkC, the NT-3 receptor, although its activity on SGNs has not previously been described. Herein we describe the design and synthesis of 1Aa and a covalent conjugate of 1Aa with risedronate, Ris-1Aa. We demonstrate that both 1Aa and Ris-1Aa stimulate neurite outgrowth in SGN cultures at a significantly higher level compared to controls. Ris-1Aa maintained its neurotrophic activity when bound to hydroxyapatite, the primary mineral component of bone. Both 1Aa and Ris-1Aa promote significant synaptic regeneration in cochlear explant cultures, and both 1Aa and Ris-1Aa appear to act at least partly through TrkC. Our results provide the first evidence that a small molecule analogue of NT-3 can stimulate SGNs and promote regeneration of synapses between SGNs and inner hair cells. Our findings support the promise of hydroxyapatite-targeting bisphosphonate conjugation as a novel strategy to deliver neurotrophic agents to SGNs encased within cochlear bone.

Aerosol Dispersion During Mastoidectomy and Custom Mitigation Strategies for Otologic Surgery in the COVID-19 Era.

OBJECTIVE: To investigate small-particle aerosolization from mastoidectomy relevant to potential viral transmission and to test source-control mitigation strategies. STUDY DESIGN: Cadaveric simulation. SETTING: Surgical simulation laboratory. METHODS: An optical particle size spectrometer was used to quantify 1- to 10-µm aerosols 30 cm from mastoid cortex drilling. Two barrier drapes were evaluated: OtoTent1, a drape sheet affixed to the microscope; OtoTent2, a custom-structured drape that enclosed the surgical field with specialized ports. RESULTS: Mastoid drilling without a barrier drape, with or without an aerosol-scavenging second suction, generated large amounts of 1- to 10-µm particulate. Drilling under OtoTent1 generated a high density of particles when compared with baseline environmental levels (P < .001, U = 107). By contrast, when drilling was conducted under OtoTent2, mean particle density remained at baseline. Adding a second suction inside OtoTent1 or OtoTent2 kept particle density at baseline levels. Significant aerosols were released upon removal of OtoTent1 or OtoTent2 despite a 60-second pause before drape removal after drilling (P < .001, U = 0, n = 10, 12; P < .001, U = 2, n = 12, 12, respectively). However, particle density did not increase above baseline when a second suction and a pause before removal were both employed. CONCLUSIONS: Mastoidectomy without a barrier, even when a second suction was added, generated substantial 1- to 10-µm aerosols. During drilling, large amounts of aerosols above baseline levels were detected with OtoTent1 but not OtoTent2. For both drapes, a second suction was an effective mitigation strategy during drilling. Last, the combination of a second suction and a pause before removal prevented aerosol escape during the removal of either drape.

Radiologically-proven New Development of Superior Semicircular Canal Dehiscence Associated With Development of Superior Semicircular Canal Dehiscence Syndrome.

OBJECTIVE: This report describes a case of development of radiologic superior semicircular canal dehiscence and reviews the literature for pertinent clinical and radiologic findings in patients with superior semicircular canal dehiscence syndrome (SCDS). PATIENT: A 28-year-old man presented with auditory and vestibular symptoms of SCDS and underwent a high-resolution temporal bone computed tomography scan that showed frank dehiscence of the right superior semicircular canal. Diagnosis of SCDS was further verified with audiometric and cervical vestibular-evoked myogenic potential (cVEMP) thresholds. The patient had previously undergone a computed tomography scan 12 years prior for work-up of sudden sensorineural hearing loss that showed no evidence of superior semicircular canal dehiscence bilaterally. INTERVENTIONS: A combination of diagnostic and therapeutic interventions was conducted consisting of preoperative audiometric and cVEMP thresholds, followed by middle fossa craniotomy for surgical repair of the dehiscence. MAIN OUTCOME MEASURE: Postoperative audiometric and cVEMP thresholds and symptomatic improvement of SCDS after surgical repair of the dehiscence. RESULTS: The patient reported resolution of his clinical symptoms after surgical repair of the dehiscence. Postoperative cVEMP thresholds improved to the normal range and the mild low-frequency conductive hearing loss resolved. CONCLUSIONS: To our knowledge, this case report is the first description of radiologically proven new development of superior canal dehiscence. Further prospective studies that include serial imaging examinations may help with visualizing and understanding the temporal evolution of superior canal dehiscence, and better elucidate the relationship between development/ progression of superior canal dehiscence and onset of clinical symptoms.

Impact of COVID-19 on Presentation of Sudden Sensorineural Hearing Loss at a Single Institution.

The coronavirus disease 2019 (COVID-19) pandemic resulted in widespread unprecedented changes to the health care system. Herein, we sought to assess the impact of the viral outbreak on clinical presentations of sudden sensorineural hearing loss (SSNHL) at a single academic center. Our results demonstrate a decrease in the absolute number of patients presenting with SSNHL to our institution during the initial onset of the COVID-19 pandemic compared to an analogous time frame 1 year prior. However, the ratio of patients with SSNHL compared to total patients evaluated was largely similar during the 2 time periods. Based on data from our institution, the COVID-19 virus does not appear to confer a significantly increased risk for the development of SSNHL.

Demonstration and Mitigation of Aerosol and Particle Dispersion During Mastoidectomy Relevant to the COVID-19 Era.

BACKGROUND: COVID-19 has become a global pandemic with a dramatic impact on healthcare systems. Concern for viral transmission necessitates the investigation of otologic procedures that use high-speed drilling instruments, including mastoidectomy, which we hypothesized to be an aerosol-generating procedure. METHODS: Mastoidectomy with a high-speed drill was simulated using fresh-frozen cadaveric heads with fluorescein solution injected into the mastoid air cells. Specimens were drilled for 1-minute durations in test conditions with and without a microscope. A barrier drape was fashioned from a commercially available drape (the OtoTent). Dispersed particulate matter was quantified in segments of an octagonal test grid measuring 60 cm in radius. RESULTS: Drilling without a microscope dispersed fluorescent particles 360 degrees, with the areas of highest density in quadrants near the surgeon and close to the surgical site. Using a microscope or varying irrigation rates did not significantly reduce particle density or percent surface area with particulate. Using the OtoTent significantly reduced particle density and percent surface area with particulate across the segments of the test grid beyond 30 cm (which marked the boundary of the OtoTent) compared with the microscope only and no microscope test conditions (Kruskall-Wallis test, p = 0.0066). CONCLUSIONS: Mastoidectomy with a high-speed drill is an aerosol-generating procedure, a designation that connotes the potential high risk of viral transmission and need for higher levels of personal protective equipment. A simple barrier drape significantly reduced particulate dispersion in this study and could be an effective mitigation strategy in addition to appropriate personal protective equipment.

Topical fibroblast growth factor-2 for treatment of chronic tympanic membrane perforations.

OBJECTIVE: To determine the efficacy of fibroblast growth factor-2 (FGF-2) in treating chronic nonhealing tympanic membrane (TM) perforations. METHOD: Double-blinded, randomized placebo controlled phase 2 clinical trial for patients with chronic TM perforations of more than 3 months duration with a cross-over arm. Patients received either FGF-2 or placebo (sterile water) saturated gelatin sponge in the perforation after rimming the perforation under topical anesthesia. The perforation was then covered with Tisseel fibrin glue. The primary endpoint was complete closure of the TM perforation. Secondary end points included change in hearing and partial TM closure rates. The TM was examined every 3 weeks with otoendoscopy for closure. The treatment was repeated if there was incomplete closure every 3 weeks up to a total of three treatments per arm. RESULTS: Seventy four patients were recruited for the study. Fifty seven met eligibility criteria and fifty four completed the study. Ten of 14 perforations closed completely in the placebo group (71.4%) and 23 of 40 perforations closed completely in the FGF-2 treatment group (57.5%), P value = .36. Pure tone averages and word recognition scores were not statistically significantly different between study groups post-treatment. After initial complete closure, re-perforation occurred in seven FGF-2 treated patients and two placebo patients making the effective final closure rate 40% for FGF and 57% for placebo, respectively. CONCLUSION: No statistically significant difference in tympanic membrane perforation closure rate was found between the FGF-2 and placebo groups. There were no differences in hearing outcomes between the groups. LEVEL OF EVIDENCE: 1b.

Auditory Quality-of-Life Measures in Patients With Traumatic Brain Injury and Normal Pure Tone Audiometry.

Auditory complaints are commonly reported following traumatic brain injury (TBI). However, few studies have examined patient-reported auditory symptomatology and quality-of-life metrics in individuals with TBI. We hypothesize that following TBI, individuals can experience auditory symptoms even with hearing thresholds in the normal range. Adult patients with normal auditory thresholds and a history of TBI were evaluated for subjective hearing loss, tinnitus, aural fullness, hyperacusis, and autophony. Hearing Handicap Inventory for Adults, Tinnitus Handicap Inventory, and Hyperacusis Questionnaire were administered. Thirty-one patients were prospectively recruited. Twenty-eight TBI participants (90%) reported ≥1 auditory symptoms at the time of survey intake. Mild to severe handicap in the Hearing Handicap Inventory for Adults and Tinnitus Handicap Inventory was reported in 71.4% and 40% of the participants with hearing loss and tinnitus, respectively. Hyperacusis handicap was considered significant in 41.1% of the participants who complained of hyperacusis and completed the survey. Despite normal hearing thresholds, individuals with TBI experience decrements in auditory quality-of-life metrics. Level of evidence: 3.

Peripheral Vestibular Organ Degeneration After Temporal Bone Fracture: A Human Otopathology Study.

OBJECTIVES/HYPOTHESIS: Vestibular symptoms are a common sequela of temporal bone fractures (TBFs). The mechanisms of injury to the peripheral vestibular system following TBF, however, are not well described. Herein, we aimed to investigate the histopathology of the peripheral vestibular system in patients who sustained TBFs. STUDY DESIGN: Retrospective human specimen analysis. METHODS: Specimens from the National Temporal Bone Pathology Registry with (cases) and without (controls) TBFs were evaluated. Specimens were analyzed by light microscopy for vestibular hair cell and/or dendritic degeneration, presence of endolymphatic hydrops, blockage of the endolymphatic duct, and number of Scarpa ganglion cells (ScGCs) in the superior and inferior vestibular nerves. RESULTS: Seven temporal bones (TBs) from five individuals with TBFs, and seven TBs from six age-matched individuals without a history of head injury met inclusion and exclusion criteria. All fractures involved the otic capsule. Severe degeneration of the cristae was identified in the semicircular canals in all TBF cases. The utricular and saccular maculae showed mild to severe degeneration in the TBF cases. Vestibular hydrops (n = 2 TBs) and blockage of the endolymphatic duct (n = 3 TBs) were also present in the TBF cases. There was a decrease of 52.6% in the mean total ScGC count in the TBF cases (n = 3 TBs) compared to age-matched controls (n = 7 TBs, P = .015). There was a mean loss of 53% of the ScGCs in the superior vestibular nerve and a mean loss of 52.3% of the ScGCs in the inferior vestibular nerve compared to age-matched controls (P = .033 and P = .021, respectively). CONCLUSIONS: In a cohort of patients with TBFs, there were distinct peripheral vestibular changes including reduction of ScGCs. LEVEL OF EVIDENCE: NA Laryngoscope, 130:752-760, 2020.