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Abstract Fibrous dysplasia (FD) is a non-malignant condition caused by post-zygotic, activating mutations of the GNAS gene that results in inhibition of the differentiation and proliferation of bone-forming stromal cells and leads to the replacement of normal bone and marrow by fibrous tissue and woven bone. The phenotype is variable and may be isolated to a single skeletal site or multiple sites and sometimes is associated with extraskeletal manifestations in the skin and/or endocrine organs (McCune-Albright syndrome). The clinical behavior and progression of FD may also vary, thereby making the management of this condition difficult with few established clinical guidelines. This paper provides a clinically-focused comprehensive description of craniofacial FD, its natural progression, the components of the diagnostic evaluation and the multi-disciplinary management, and considerations for future research.

Normal hearing requires exquisite cooperation between bony and sensorineural structures within the cochlea. For example, the inner ear secretes proteins such as osteoprotegrin (OPG) that can prevent cochlear bone remodeling. Accordingly, diseases that affe

OBJECTIVE: To evaluate the clinical presentation and outcomes of treatment for patients with chondrosarcomas involving the skull base and temporal bone. STUDY DESIGN: Retrospective review. SETTING: Tertiary medical centre. PATIENTS: Cases of histologically confirmed chondrosarcoma involving the skull base and temporal bones. INTERVENTION: Surgery. MAIN OUTCOME MEASURES: Demographic features of presenting patients; presenting symptoms and signs; surgical approach employed; use of post-operative radiation therapy; histological grade of tumour; and interval of post-operative follow up. RESULTS: Twelve patients were identified with chondrosarcomas involving the skull base, with post-operative follow up ranging from three to 33 years. The average age at presentation was 42 years. The most common presenting symptoms were diplopia, decreased visual acuity and headaches. Five of the 12 patients required multiple surgical procedures. CONCLUSIONS: Patients with chondrosarcoma involving the skull base and temporal bone may present in a variety of ways. Surgical resection, even subtotal, in combination with radiation therapy, can often provide good tumour control over many years for these rare tumours. [ABSTRACT FROM AUTHOR]

Background: The incidence of complications resulting from suppurative otitis media has significantly decreased since the introduction of antibiotics. At the start of the 20th century 50% of all cases of otitis media developed a coalescent mastoiditis. By 1959, the incidence had fallen to 0.4%. Recent studies suggest a current incidence of only 0.24%. Additionally, during the time of Friedrich Bezold (1824-1908), 20% of patients with mastoiditis developed subperiosteal abscess. Interestingly, this has incidence increased; today nearly 50% of patients diagnosed with coalescent mastoiditis have subperiosteal abscess.Objective: To review the contemporary presentation, diagnosis, and management of a spectrum of mastoid abscesses.Design: Retrospective case series.Setting: Hospitals associated with the Department of Otolaryngology/Head and Neck Surgery at the University of California, San Francisco.Patients: Three patients with mastoid abscesses are reported. One patient displayed "classic" Bezold's abscess, with pus escaping the mastoid near the incisura digastrica and tracking along the digastric and sternocleidomastoid muscles into the neck. The second and third patients exhibited temporoparietal swelling secondary to mastoid abscess eroding the root of the zygomatic process, a complication noted by Bezold in 1908 as occurring "in only very rare cases."Results and Conclusions: Since only one third of patients show pathologic tympanic membrane changes, and since complaints of otalgia, fever, and tenderness are inconstant, subperiosteal mastoid abscess is frequently a delayed diagnosis. The clinical presentation, pathogenesis, and routes of abscess spread are presented with photographic and radiographic illustration. Medical and surgical management is reviewed, and methods for accurate diagnosis are emphasized. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effect of visual abstracts versus automated tweets on social media participation in Otology & Neurotology ., Patients: N/A., Interventions: Introduction of visual abstracts developed by the social media editorial team to established automated tweets created by the dlvr.it computer program on the Otology & Neurotology Twitter account., Main Outcome Measures: Twitter analytics including the number of new followers per month, impressions per tweet, and engagements per tweet. The Kruskal-Wallis analysis of variance test was used to compare means., Results: From October 2016 to October 2017 (average of 20 new followers per month), 101 automated tweets averaged 536 impressions and 16 engagements per tweet. The visual abstract was introduced in November 2017. From November 2017 to November 2020 (average of 39 new followers per month), 447 automated tweets averaged 747 impressions and 22 engagements per tweet, whereas 157 visual abstracts averaged 1977 impressions and 78 engagements per tweet. Automated tweets were discontinued in December 2020. From December 2020 to December 2022 (average of 44 new followers per month), 95 visual abstracts averaged 1893 impressions and 103 engagements per tweet. With the introduction of the visual abstract, the average number of followers, impressions per tweet, and engagements per tweet significantly increased (all p -values <0.01; all large effect sizes of 0.16, 0.47, and 0.47, respectively)., Conclusions: Visual abstracts created by a social media editorial team have a positive impact on social media participation in the field of otology and neurotology. The impact is greater than that of social media content generated by Twitter automation tools., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Objective: Evaluate 2-year outcomes after lidocaine/epinephrine iontophoresis and tympanostomy using an automated tube delivery system for pediatric tube placement in-office., Study Design: Prospective, single-arm., Setting: Eighteen otolaryngology practices., Methods: Children age 6 months to 12 years indicated for tympanostomy were enrolled between October 2017 and February 2019. Local anesthesia of the tympanic membrane was achieved via lidocaine/epinephrine iontophoresis and tympanostomy was completed using an automated tube delivery system (the Tula® System). An additional Lead-In cohort of patients underwent tube placement in the operating room (OR) under general anesthesia using only the tube delivery system. Patients were followed for 2 years or until tube extrusion, whichever occurred first. Otoscopy and tympanometry were performed at 3 weeks, and 6, 12, 18, and 24 months. Tube retention, patency, and safety were evaluated., Results: Tubes were placed in-office for 269 patients (449 ears) and in the OR for 68 patients (131 ears) (mean age, 4.5 years). The median and mean times to tube extrusion for the combined OR and In-Office cohorts were 15.82 (95% confidence interval [CI]: 15.41-19.05) and 16.79 (95% CI: 16.16-17.42) months, respectively. Sequelae included ongoing perforation for 1.9% of ears (11/580) and medial tube displacement for 0.2% (1/580) observed at 18 months. Over a mean follow-up of 14.3 months, 30.3% (176/580) of ears had otorrhea and 14.3% (83/580) had occluded tubes., Conclusion: In-office pediatric tympanostomy using lidocaine/epinephrine iontophoresis and automated tube delivery results in tube retention within the ranges described for similar grommet-type tubes and complication rates consistent with traditional tube placement in the OR., (© 2023 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Competing Interests: The authors disclose no conflicts of interest.

Objective: The purpose of this study was to systematically evaluate the literature on the frequency of reporting of sociodemographic data (gender, race, ethnicity, education status, health insurance status, geographic location of residence, and socioeconomic status) among interventional clinical trials involving cochlear implant patients., Databases Reviewed: A systematic search was performed in PubMed, Cochrane Database of Systematic Reviews, Web of Science, and SCOPUS to identify peer reviewed research., Methods: A systematic review was performed, which included original prospective clinical trial research studies involving cochlear implantation and/or interventional trials involving cochlear implant patients. Collected data included funding type, level of evidence, race reporting, ethnicity reporting, socioeconomic status reporting, education level reporting, type of insurance, geographic location, and gender of patients., Results: A total of 644 articles were included for review. Gender was the most reported sociodemographic factor (70% of included studies). Reporting of other data among included studies was low: educational level (6%), socioeconomic status (2%), race (1%), ethnicity (1%), insurance status (0.3%), and geography (1%). The odds of reporting gender (odds ratio [OR] = 1.51), education (OR = 1.81), and geography (OR = 2.72) increased with each subsequent publication date decade; however, this trend was not seen for reporting of race, ethnicity, socioeconomic status, or insurance. The reporting of gender was less likely to be reported in studies with the pediatric participants (OR = 0.62), level II evidence (OR = 0.14), and device programming interventional studies (OR = 0.26)., Conclusion: Reporting of sociodemographic data, other than gender, is low among prospective clinical trials involving cochlear implant patients. The lack of reporting of this key data may limit research rigor and generalizability. Clinical researchers are advised to prospectively collect these data to promote equity in cochlear implant research and clinical care., Competing Interests: Conflicts of interest and source of funding: This work was supported by the National Institute of Health/National Center for Advancing Translational Sciences (UL1TR000117) (CS, NP). MLB is a consultant for MED-EL and Stryker and has received research funding from Advanced Bionics (unrelated to this research). There are no conflicts of interests with the content of this article. The authors have no other financial relationships or conflicts of interest to disclose pertaining to the article., (Copyright © 2022, Otology & Neurotology, Inc.)

Background: From 1821 to 1829, Sir Charles Bell presented cases of facial paralysis from infection, trauma, and unknown causes. As such, "Bell's palsy" initially referred to facial palsy of any etiology. Today, the term is reserved for idiopathic peripheral facial palsy. The objectives of this analysis were to establish when the eponym came to vogue and delineate the semantic shift from its original definition to its current one., Methods: Extensive review of available 19th and 20th century literature mentioning "Bell's palsy" and "Bell's paralysis.", Results: Historical accounts have eponymously attached Bell's name to facial paralysis as early as the 1840s-Bell's palsy was first used to describe cases of facial palsy of any cause. In 1886, Gowers characterized Bell's palsy as a "neuritis usually within the Fallopian Canal," distinguishing it as a separate etiology. Over the next decades, the definition narrowed to peripheral facial paralysis from cold exposure or unknown causes. By the 1940s, its natural history was well described-an acute, unilateral, idiopathic, and usually self-limited peripheral facial palsy., Conclusion: The semantic change of a word over time can tell us a remarkable story of its history and origins. Absence of a discrete lesion, lack of proven treatment, and good prognosis without intervention distinguished Bell's palsy from other causes of facial paralysis. Over time, the definition has narrowed from a facial palsy of any cause to an idiopathic peripheral facial palsy. Recent evidence supporting Bell's palsy as a viral mononeuritis may have driven its recent semantic change toward this specific etiology., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Objectives/hypothesis: To understand the effect of the COVID-19 pandemic on the volume, quality, and impact of otolaryngology publications., Study Design: Retrospective analysis., Methods: Fifteen of the top peer-reviewed otolaryngology journals were queried on PubMed for COVID and non-COVID-related articles from April 1, 2020 to March 31, 2021 (pandemic period) and pre-COVID articles from the year prior. Information on total number of submissions and rate of acceptance were collected from seven top-ranked journals., Results: Our PubMed query returned 759 COVID articles, 4,885 non-COVID articles, and 4,200 pre-COVID articles, corresponding to a 34% increase in otolaryngology publications during the pandemic period. Meta-analysis/reviews and miscellaneous publication types made up a larger portion of COVID publications than that of non-COVID and pre-COVID publications. Compared to pre-COVID articles, citations per article 120 days after publication and Altmetric Attention Score were higher in both COVID articles (citations/article: 2.75 ± 0.45, P < .001; Altmetric Attention Score: 2.05 ± 0.60, P = .001) and non-COVID articles (citations/article: 0.03 ± 0.01, P = .002; Altmetric Attention Score: 0.67 ± 0.28, P = .016). COVID manuscripts were associated with a 1.65 times higher acceptance rate compared to non-COVID articles (P < .001)., Conclusions: COVID-19 was associated with an increase in volume, citations, and attention for both COVID and non-COVID articles compared to pre-COVID articles. However, COVID articles were associated with lower evidence levels than non-COVID and pre-COVID articles., Level of Evidence: 3 Laryngoscope, 132:1364-1373, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

David McDonogh, born into chattel slavery in Louisiana in the early 1800s, accomplished the unfathomable by becoming the first Black otolaryngologist in the United States of America. With tireless determination and profound intellect, Dr McDonogh surmounted immeasurable adversity along his improbable journey to freedom and success as an eye, ear, nose, and throat doctor in New York. His doctorate in medicine was posthumously awarded to his great-great-granddaughter in 2018 by the Columbia University Vagelos College of Physicians and Surgeons. In this History of Otolaryngology piece, we share his extraordinary story.

Purpose: Otolaryngologists are uniquely situated to provide sexual and gender minority (SGM) care, including gender-affirmation (voice/communication, facial surgery) and HIV/AIDS-related conditions. Yet, no research has characterized otolaryngology residency program directors' attitudes toward SGM-related curricula, nor opportunities for supporting training in SGM-related care. Methods: An anonymous cross-sectional e-mail survey was disseminated to 116 otolaryngology residency program directors in July-September 2019. Information collected included current/future curriculum in and attitudes toward SGM care, and program demographics. Data were categorical and analysis utilized chi-square test. Results: The 65 complete responses (56% rate) were nationally representative. Overall, 17% of programs include no SGM-related education. Subjective importance of SGM training ranged from not important at all (3%) to absolutely essential (11%), with mode of average importance (47%); this varied significantly by program geographic setting and population, and program size. The mean percentage of curriculum dedicated to SGM care was 1.0% for didactics and 0.7% for clinical. Curricula include HIV/AIDS-related conditions (58%), facial gender-affirming procedures (50%), culturally informed care (42%), changes with gender-affirming hormones (voice/communication: 48%, facial: 22%), and cancer in SGM patients (42%). Frequently reported barriers were insufficient experienced faculty (52%) and time (42%). Program directors deemed visiting expert lectures (66%), small-group discussion (39%), and online modules (27%) the best ways to incorporate SGM education. Conclusions: More than 80% of otolaryngology residency curricula in a representative national survey include SGM-related education, which represents a limited portion of total curriculum. These results highlight the opportunity for expert lectures and discussion-based and online tool development to facilitate standardized SGM education in otolaryngology residencies., Competing Interests: No competing financial interests exist., (Copyright 2021, Mary Ann Liebert, Inc., publishers.)

Competing Interests: The authors report no relevant conflict of interest in submitting this article for publication. The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of San Antonio Military Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, the Department of Defense, or the U.S. Government.

Objective: To compare surgical characteristics and complications between well drilling (WD) and subperiosteal pocket techniques (SPT) for receiver/stimulator (R/S) fixation of cochlear implant (CI), and conduct cost-effectiveness analysis., Study Design: Retrospective clinical study, decision-analysis model., Setting: Tertiary referral center., Patients: Three-hundred and eighty-eight CI recipients with a minimum of 6-months follow-up., Interventions: CI surgery using either WD or SPT for R/S fixation. A decision-analysis model was designed using data from a systematic literature review., Main Outcome Measures: Surgical operation time, rates of major and minor long-term complications were compared. Incremental cost-effectiveness was also estimated, comparing the two methods of fixation., Results: We compared 179 WD with 209 SPT. Surgery time was significantly shorter in SPT (148 versus 169 min, p = 0.001) and remained significant after adjustment for possible confounders. Higher rates of major complications requiring surgical intervention were found with SPT (10.5% versus 4.5%, p = 0.042), however, the difference was not significant after adjusting for follow-up time (47.8 versus 32.5 months for SPT, WD respectively; p < 0.001). The incremental cost-effectiveness ratio for WD (compared with SPT) was $48,795 per major complication avoided, which was higher than the willingness-to-pay threshold of $47,700 (average cost of 2 h revision surgery)., Conclusions: SPT was found to be faster but potentially risks more complications, particularly relating to device failure. Further long-term studies are required to validate these differences. Based on data from the current literature, neither of the methods is compellingly cost-effective over the other, and surgeons can base their choice on personal preference, comfort, and previous training., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2020, Otology & Neurotology, Inc.)

Objective: To review occupational ergonomic risks for the Otologist and Neurotologist., Data Sources: MEDLINE, OVID, PubMed, and Google Scholar., Study Selection: A search was conducted to identify all studies in the English language that involve ergonomic-related risks for surgeons., Results: Occupational hazards, particularly musculoskeletal disorders (MSDs), are common in the surgical community in general and among Otolaryngologists in particular. Very few studies have been conducted assessing MSDs specific to Otologists and Neurotologists. However, extrapolating from other surgical professions with similar ergonomic postures in the operation room and office, one can infer that cervical and lumbar pain are related to prolonged static sitting and neck flexion when working with a microscope and begins early in training. Early institution of correct ergonomic training is feasible and may be effective. Improved ergonomic habits include upright sitting, avoidance of neck flexion, initiating short breaks, and the use of chairs with arm and back support. Future technologies incorporated into otologic surgery should have improved ergonomic design., Conclusions: Otologists and Neurotologists are exposed to MSDs directly related to their work demands. Incorporating healthy ergonomics into surgical training as well adopting correct posture and the use equipment designed for back support may help mitigate the long-terms risks of MSD.

: This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) "priority" of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19. Interpretation of this guidance document is dependent on local factors including prevalence of COVID-19 in the surgeons' local community. This is not intended to set a standard of care, and should not supersede the clinician's best judgement when managing specific clinical concerns and/or regional conditions.Access to otologic and neurotologic care during and after the COVID-19 pandemic is dependent upon adequate protection of physicians, audiologists, and ancillary support staff. Otolaryngologists and associated staff are at high risk for COVID-19 disease transmission based on close contact with mucosal surfaces of the upper aerodigestive tract during diagnostic evaluation and therapeutic procedures. While many otologic and neurotologic conditions are not imminently life threatening, they have a major impact on communication, daily functioning, and quality of life. In addition, progression of disease and delay in treatment can result in cranial nerve deficits, intracranial and life-threatening complications, and/or irreversible consequences. In this regard, many otologic and neurotologic conditions should rightfully be considered "urgent," and almost all require timely attention to permit optimal outcomes. It is reasonable to proceed with otologic and neurotologic clinic visits and operative cases based on input from expert opinion of otologic care providers, clinic/hospital administration, infection prevention and control specialists, and local and state public health leaders. Significant regional variations in COVID-19 prevalence exist; therefore, physicians working with local municipalities are best suited to make determinations on the appropriateness and timing of otologic and neurotologic care.

Objectives/hypothesis: Evaluate technical success, tolerability, and safety of lidocaine iontophoresis and tympanostomy tube placement for children in an office setting., Study Design: Prospective individual cohort study., Methods: This prospective multicenter study evaluated in-office tube placement in children ages 6 months through 12 years of age. Anesthesia was achieved via lidocaine/epinephrine iontophoresis. Tube placement was conducted using an integrated and automated myringotomy and tube delivery system. Anxiolytics, sedation, and papoose board were not used. Technical success and safety were evaluated. Patients 5 to 12 years old self-reported tube placement pain using the Faces Pain Scale-Revised (FPS-R) instrument, which ranges from 0 (no pain) to 10 (very much pain)., Results: Children were enrolled into three cohorts with 68, 47, and 222 children in the Operating Room (OR) Lead-In, Office Lead-In, and Pivotal cohorts, respectively. In the Pivotal cohort, there were 120 and 102 children in the <5 and 5- to 12-year-old age groups, respectively, with a mean age of 2.3 and 7.6 years, respectively. Bilateral tube placement was indicated for 94.2% of children <5 and 88.2% of children 5 to 12 years old. Tubes were successfully placed in all indicated ears in 85.8% (103/120) of children <5 and 89.2% (91/102) of children 5 to 12 years old. Mean FPS-R score was 3.30 (standard deviation [SD] = 3.39) for tube placement and 1.69 (SD = 2.43) at 5 minutes postprocedure. There were no serious adverse events. Nonserious adverse events occurred at rates similar to standard tympanostomy procedures., Conclusions: In-office tube placement in selected patients can be successfully achieved without requiring sedatives, anxiolytics, or papoose restraints via lidocaine iontophoresis local anesthesia and an automated myringotomy and tube delivery system., Level of Evidence: 2b Laryngoscope, 130:S1-S9, 2020., (© 2020 The Authors. The Laryngoscope published by Wiley Periodicals, Inc. on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Our objective was to compare outcomes in speech and quality of life in those undergoing cochlear implantation for single-sided deafness (SSD), with the aim to characterize the clinical impact of underlying diagnosis in the affected ear and pre-operative hearing status., Study Design: Prospective case series., Setting: Academic Cochlear Implant Center., Patients: 42 adult patients implanted with the diagnosis of SSD., Interventions: Patients were evaluated at 3-, 6-, and 12-months post-operatively using AZBio sentence and speech, and consonant-nucleus-consonant (CNC) depending on appropriate testing level. Our previously validated Comprehensive Cochlear Implant Quality of Life (CCIQ) questionnaire was administered., Main Outcome Measures: Speech perception, quality of life., Results: Subjects were stratified by the underlying diagnosis: Meniere's Disease (MD; n = 10), sudden sensorineural hearing loss (SSNHL; n = 13), and Other (eg TBI, acoustic neuroma, progressive, noise-induced; n = 19). Mean preoperative PTA of the implanted ear was 82dB ± 17; that of the nonimplanted ear was 32dB ± 17. SSNHL and MD demonstrated the highest speech perception score at 3 months (93 and 95%), and "Other" demonstrated the lowest scores at 88%. All 3 groups demonstrated nadir in speech scores at 6 months before improving at 12 months, but the "Other" diagnoses maintained the lowest speech testing across all time points. All 3 groups reported improved quality of life on CCIQ., Conclusions: Subjects with SSNHL and MD demonstrate excellent speech perception and quality of life outcomes after cochlear implantation for SSD. Subjects with "Other" diagnoses underlying their SSD demonstrated lower scores on speech testing but nonetheless reported improved quality of life.

Autosomal recessive genetic forms (DFNB) account for most cases of profound congenital deafness. Adeno-associated virus (AAV)-based gene therapy is a promising therapeutic option, but is limited by a potentially short therapeutic window and the constrained packaging capacity of the vector. We focus here on the otoferlin gene underlying DFNB9, one of the most frequent genetic forms of congenital deafness. We adopted a dual AAV approach using two different recombinant vectors, one containing the 5' and the other the 3' portions of otoferlin cDNA, which exceed the packaging capacity of the AAV when combined. A single delivery of the vector pair into the mature cochlea of Otof -/- mutant mice reconstituted the otoferlin cDNA coding sequence through recombination of the 5' and 3' cDNAs, leading to the durable restoration of otoferlin expression in transduced cells and a reversal of the deafness phenotype, raising hopes for future gene therapy trials in DFNB9 patients., Competing Interests: Conflict of interest statement: W.W.H. and the University of Florida (UF) have a financial interest in the use of AAV therapies, and own equity in a company, Applied Genetic Technologies Corp. (AGTC), that might, in the future, commercialize some aspects of this work, and a joint international patent application (International Patent Application No.: PCT/US2018/031009 - WGS “Whole Genome Sequencing” Ref. U1197.70110WO00) has been submitted by UF and University of California, San Francisco (F.D., W.W.H., O.A.)., (Copyright © 2019 the Author(s). Published by PNAS.)

Contemporary cochlear implants (CI) are generally very effective for remediation of severe to profound sensorineural hearing loss, but outcomes are still highly variable. Auditory nerve survival is likely one of the major factors underlying this variability. Neurotrophin therapy therefore has been proposed for CI recipients, with the goal of improving outcomes by promoting improved survival of cochlear spiral ganglion neurons (SGN) and/or residual hair cells. Previous studies have shown that glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor, and neurotrophin-3 can rescue SGNs following insult. The current study was designed to determine whether adeno-associated virus vector serotype 5 (AAV-5) encoding either green fluorescent protein or GDNF can transduce cells in the mouse cochlea to express useful levels of neurotrophin and to approximate the optimum therapeutic dose(s) for transducing hair cells and SGN. The findings demonstrate that AAV-5 is a potentially useful gene therapy vector for the cochlea, resulting in extremely high levels of transgene expression in the cochlear inner hair cells and SGN. However, overexpression of human GDNF in newborn mice caused severe neurological symptoms and hearing loss, likely due to Purkinje cell loss and cochlear nucleus pathology. Thus, extremely high levels of transgene protein expression should be avoided, particularly for proteins that have neurological function in neonatal subjects.

Hearing loss is a significant public health concern, affecting over 250 million people worldwide. Both genetic and environmental etiologies are linked to hearing loss, but in many cases the underlying cellular pathophysiology is not well understood, highlighting the importance of further discovery. We found that inactivation of the gene Tmtc4 (transmembrane and tetratricopeptide repeat 4), which was broadly expressed in the mouse cochlea, caused acquired hearing loss in mice. Our data showed Tmtc4 enriched in the endoplasmic reticulum, and that it functioned by regulating Ca2+ dynamics and the unfolded protein response (UPR). Given this genetic linkage of the UPR to hearing loss, we demonstrated a direct link between the more common noise-induced hearing loss (NIHL) and the UPR. These experiments suggested a novel approach to treatment. We demonstrated that the small-molecule UPR and stress response modulator ISRIB (integrated stress response inhibitor), which activates eIF2B, prevented NIHL in a mouse model. Moreover, in an inverse genetic complementation approach, we demonstrated that mice with homozygous inactivation of both Tmtc4 and Chop had less hearing loss than knockout of Tmtc4 alone. This study implicated a novel mechanism for hearing impairment, highlighting a potential treatment approach for a broad range of human hearing loss disorders.

Objective: The prevalence of unilateral hearing loss (UHL) in adults has not been well characterized. The objectives of this study are to determine the prevalence of UHL in U.S. adults and its treatment with hearing aids using a nationally representative study., Study Design: Cross-sectional national epidemiologic study (n = 6,242)., Methods: Subjects ≥ 18 years old with audiometric testing in the 2005 to 2006, 2009 to 2010, and 2011 to 2012 cycles of the National Health and Nutrition Examination Study were included. UHL was defined as normal hearing (≤25 decibels hearing level [dB HL] pure tone average [PTA]) in one ear and at least mild hearing loss (>25 dB HL PTA) in the other ear. Hearing aid usage was defined by at least 5 hours per week (2005-2006) or at least seldom (2009-2012) use. Sampling weights were utilized to ensure generalizability to the U.S., Results: The overall prevalence of UHL in adult Americans was 7.2% (95% confidence interval 6.1%-8.6%), with 5.7% (4.8%-6.7%) having mild and 1.5% (0.1%-2.1%) with moderate-or-worse UHL; nearly one-third of the latter reported trouble hearing. The prevalence of hearing aid usage in those with UHL was 2.0% (0.6%-6.7%). Of those with mild UHL, 1.4% (0.2%-8.0%) used hearing aids. Of those with moderate UHL, 4.2% (0.1%-22%) used hearing aids. Among those with UHL and also at least moderate subjective difficulty hearing, only 11% wore hearing aids., Conclusion: UHL is common among U.S. adults. Hearing aid usage is very low, even when there is perceived handicap. Public health education is needed to increase awareness of and auditory rehabilitation for UHL., Level of Evidence: 2. Laryngoscope, 128:1681-1686, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

: The American Otological Society (AOS) has been on the forefront of advancing the science of auditory and vestibular physiology, and art of ear medicine since its founding in 1868. For 150 years, through its publications, the AOS has provided a critical forum to debate these advances, highlighting treatment successes and failures, and served a place to celebrate its history. This historical review provides an overview of the publications of the AOS since its founding: the Transactions of the annual meeting from 1868 through 2006, Treatises on Otosclerosis (1928-1935), the History of the Society from the 100 and 125th anniversary, and the sponsored Society journals-American Journal of Otology (1879-1883, 1979-2000) and Otology & Neurotology (2001-present).

This article is an overview of the care of patients requiring revision surgery for otosclerosis. Preoperative evaluation of the patient including surgical history, audiologic results, and physical findings is discussed, and the causes of failure of primary surgery are reviewed. A discussion of evidence-based surgical technique and postoperative care then follows., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Usher syndrome type III (USH3) characterized by progressive loss of vision and hearing is caused by mutations in the clarin-1 gene (CLRN1). Clrn1 knockout (KO) mice develop hair cell defects by postnatal day 2 (P2) and are deaf by P21-P25. Early onset profound hearing loss in KO mice and lack of information about the cochlear cell type that requires Clrn1 expression pose challenges to therapeutic investigation. We generated KO mice harboring a transgene, TgAC1, consisting of Clrn1-UTR (Clrn1 cDNA including its 5' and 3' UTR) under the control of regulatory elements (Atoh1 3' enhancer/β-globin basal promoter) to direct expression of Clrn1 in hair cells during development and down regulate it postnatally. The KO-TgAC1 mice displayed delayed onset progressive hearing loss associated with deterioration of the hair bundle structure, leading to the hypothesis that hair cell expression of Clrn1 is essential for postnatal preservation of hair cell structure and hearing. Consistent with that hypothesis, perinatal transfection of hair cells in KO-TgAC1 mice with a single injection of AAV-Clrn1-UTR vector showed correlative preservation of the hair bundle structure and hearing through adult life. Further, the efficacy of AAV-Clrn1 vector was significantly attenuated, revealing the potential importance of UTR in gene therapy.

Congenital hearing loss (hearing loss that is present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing screening programmes enable early detection; early intervention will prevent delays in speech and language development and has long-lasting beneficial effects on social and emotional development and quality of life. A diagnosis of hearing loss is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus infection, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular, inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (the conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision making and guide prevention and (genetic) counselling. Management options include specific antimicrobial therapies, surgical treatment of craniofacial abnormalities and implantable or non-implantable hearing devices. An improved understanding of the pathophysiology and molecular mechanisms that underlie hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies.

Age-related hearing impairment (ARHI), one of the most common sensory disorders, can be mitigated, but not cured or eliminated. To identify genetic influences underlying ARHI, we conducted a genome-wide association study of ARHI in 6,527 cases and 45,882 controls among the non-Hispanic whites from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We identified two novel genome-wide significant SNPs: rs4932196 (odds ratio = 1.185, p = 4.0x10-11), 52Kb 3' of ISG20, which replicated in a meta-analysis of the other GERA race/ethnicity groups (1,025 cases, 12,388 controls, p = 0.00094) and in a UK Biobank case-control analysis (30,802 self-reported cases, 78,586 controls, p = 0.015); and rs58389158 (odds ratio = 1.132, p = 1.8x10-9), which replicated in the UK Biobank (p = 0.00021). The latter SNP lies just outside exon 8 and is highly correlated (r2 = 0.96) with the missense SNP rs5756795 in exon 7 of TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. We further tested these SNPs in phenotypes from audiologist notes available on a subset of GERA (4,903 individuals), stratified by case/control status, to construct an independent replication test, and found a significant effect of rs58389158 on speech reception threshold (SRT; overall GERA meta-analysis p = 1.9x10-6). We also tested variants within exons of 132 other previously-identified hearing loss genes, and identified two common additional significant SNPs: rs2877561 (synonymous change in ILDR1, p = 6.2x10-5), which replicated in the UK Biobank (p = 0.00057), and had a significant GERA SRT (p = 0.00019) and speech discrimination score (SDS; p = 0.0019); and rs9493627 (missense change in EYA4, p = 0.00011) which replicated in the UK Biobank (p = 0.0095), other GERA groups (p = 0.0080), and had a consistent significant result for SRT (p = 0.041) and suggestive result for SDS (p = 0.081). Large cohorts with GWAS data and electronic health records may be a useful method to characterize the genetic architecture of ARHI., Competing Interests: The authors have declared that no competing interests exist.

Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by osteocytes, to protect hearing. Understanding the cellular and molecular mechanisms that confer site-specific control of bone remodeling has the potential to elucidate new pathways that are deregulated in skeletal disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)