Otology & Neurotology - DOD Hearing Center of Excellence: Pharmaceutical Interventions for Hearing Loss (PIHL) Clinical Research Guidance Papers

Introduction to the Pharmaceutical Interventions for Hearing Loss Clinical Research Guidance Papers No abstract available

The Genomic Basis of Noise-induced Hearing Loss: A Literature Review Organized by Cellular Pathways Objective: Using Reactome, a curated Internet database, noise-induced hearing loss studies were aggregated into cellular pathways for organization of the emerging genomic and epigenetic data in the literature. Data Sources: PubMed and Reactome.org, a relational data base program systematizing biological processes into interactive pathways and subpathways based on ontology, cellular constituents, gene expression, and molecular components. Study Selection: Peer-reviewed population and laboratory studies for the previous 15 years relating genomics and noise and hearing loss were identified in PubMed. Criteria included p values <0.05 with correction for multiple genes, a fold change of >1.5, or duplicated studies. Data Extraction and Synthesis: One-hundred fifty-eight unique HGNC identifiers from 77 articles met the selection criteria, and were uploaded into the analysis program at http://reactome.org. These genes participated in a total of 621 cellular interactions in 21 of 23 pathways. Cellular response to stress with its attenuation phase, particularly in response to heat stress, detoxification of ROS, and specific areas of the immune system are predominant pathways identified as significantly "overrepresented" (p values <0.1e-5 and false discovery rates <0.01). Conclusion: Twenty-one of 23 of the designated pathways in Reactome have significant influence on noise-induced hearing loss, signifying a confluence of molecular pathways in reaction to acoustic trauma; however, cellular response to stress, including heat shock response, and other small areas of immune response were highly overrepresented. Yet-to-be-explored genomics areas include miRNA, lncRNA, copy number variations, RNA sequencing, and human genome-wide association study.

Oxidative Damage and Inflammation Biomarkers: Strategy in Hearing Disorders Importance: Excess free radical-induced oxidative stress and inflammatory processes are increasingly recognized as causative factors in hearing and balance disorders. Antioxidant micronutrients neutralize free radicals and, at adequate doses, reduce inflammation and demonstrate benefits in animal models and human trials. Therefore, it is reasonable to expect that biomarkers of oxidative damage and inflammation are appropriate correlative biological outcome parameters in clinical hearing intervention studies. Objective: To provide the otology investigator a selected panel of biomarkers from the large universe of available tests that can be used as reasonable secondary endpoints in hearing and balance research. Background Setting: The tenets of antioxidant science dictate that there are a great variety of free radicals and that they impact different cellular targets. They also demonstrate varying functions in different cellular environments. In addition, oxidative stress and inflammation may cause direct injury to tissues, cell membrane lipids, proteins and mitochondrial, and nuclear DNA. To accommodate these many pathways, the useful categories of potential biomarkers become extensive. The degree of injury is also reflected by separate markers of inflammation and measures of antioxidant levels. Therefore, to provide a reliable indication of oxidative damage, inflammation and antioxidant level, it is necessary to determine a broad spectrum of lipid peroxidation markers, adducts of DNA, oxidation levels of proteins and pro-inflammatory cytokines. Conclusion: This report highlights some of the most clinically relevant and well-studied biomarkers in each category of tissue damage. It also includes those markers with which the authors have had direct positive clinical experience. The outcome from these studies is intended to provide a list of adjunctive measures that can be recommended as a relevant biomarker panel in hearing disorder clinical trials.

Speech-in-Noise Tests and Supra-threshold Auditory Evoked Potentials as Metrics for Noise Damage and Clinical Trial Outcome Measures Objective: In humans, the accepted clinical standards for detecting hearing loss are the behavioral audiogram, based on the absolute detection threshold of pure-tones, and the threshold auditory brainstem response (ABR). The audiogram and the threshold ABR are reliable and sensitive measures of hearing thresholds in human listeners. However, recent results from noise-exposed animals demonstrate that noise exposure can cause substantial neurodegeneration in the peripheral auditory system without degrading pure-tone audiometric thresholds. It has been suggested that clinical measures of auditory performance conducted with stimuli presented above the detection threshold may be more sensitive than the behavioral audiogram in detecting early-stage noise-induced hearing loss in listeners with audiometric thresholds within normal limits. Methods: Supra-threshold speech-in-noise testing and supra-threshold ABR responses are reviewed here, given that they may be useful supplements to the behavioral audiogram for assessment of possible neurodegeneration in noise-exposed listeners. Conclusion: Supra-threshold tests may be useful for assessing the effects of noise on the human inner ear, and the effectiveness of interventions designed to prevent noise trauma. The current state of the science does not necessarily allow us to define a single set of best practice protocols. Nonetheless, we encourage investigators to incorporate these metrics into test batteries when feasible, with an effort to standardize procedures to the greatest extent possible as new reports emerge.

Serial Monitoring of Otoacoustic Emissions in Clinical Trials The purpose of this report is to provide guidance on the use of otoacoustic emissions (OAEs) as a clinical trial outcome measure for pharmaceutical interventions developed to prevent acquired hearing loss secondary to cochlear insult. OAEs are a rapid, noninvasive measure that can be used to monitor cochlear outer hair cell function. Serial monitoring of OAEs is most clearly established for use in hearing conservation and ototoxicity monitoring programs in which they exhibit more frequent and earlier changes compared with pure-tone audiometry. They also show promise in recent human trials of otoprotectants. Questions remain, however, concerning the most appropriate OAE protocols to use and what constitutes a "significant" OAE response change. Measurement system capabilities are expanding and test efficacy will vary across locations and patient populations. Yet, standardizing minimal measurement criteria and reporting of results is needed including documentation of test-retest variability so that useful comparisons can be made across trials. It is also clear that protocols must be theoretically sound based on known patterns of damage, generate valid results in most individuals tested, be accurate, repeatable, and involve minimal time. Based on the potential value added, OAEs should be included in clinical trials when measurement conditions and time permit.

"Measurement" of Tinnitus Chronic tinnitus is the persistent sensation of hearing a sound that exists only inside the head. The prevalence of tinnitus in adults in the United States is estimated at 10 to 15%. For about 20% of these individuals the tinnitus is significantly bothersome. Although myriad therapies for tinnitus are offered (often at significant cost), most are not evidence based. Difficulty in the assessment and further development of interventions for tinnitus stems from the limitations of techniques used to evaluate these interventions. Questionnaires are widely available to "measure" (tinnitus can only be indirectly measured) functional effects of tinnitus, such as difficulty sleeping and concentrating, and negative emotions such as anxiety, depression, and annoyance. Questionnaires have recently been documented for sensitivity to change in response to intervention (i.e., "responsiveness"). All of these questionnaires function well to assess the overall impact of tinnitus. The limitations mentioned pertain primarily to measures of tinnitus perception, which typically include the psychoacoustic measures of tinnitus loudness and pitch matches, tinnitus spectral content, minimum masking levels, and residual inhibition. These measures, which are obtained routinely in many clinics and as part of research studies, have not been validated for being diagnostic, prognostic, discriminative, or responsive. In order for these measures to become clinically meaningful, normative standards are needed, both for baseline measures and for repeated measures of tinnitus perception. Evidence-based intervention for tinnitus requires accurately measuring both the perception of, and reactions to, tinnitus.

Temporary and Permanent Noise-induced Threshold Shifts: A Review of Basic and Clinical Observations Objective: To review basic and clinical findings relevant to defining temporary (TTS) and permanent (PTS) threshold shifts and their sequelae. Data Sources: Relevant scientific literature and government definitions were broadly reviewed. Data Synthesis: The definitions and characteristics of TTS and PTS were assessed and recent advances that expand our knowledge of the extent, nature, and consequences of noise-induced hearing loss were reviewed. Conclusion: Exposure to intense sound can produce TTS, acute changes in hearing sensitivity that recover over time, or PTS, a loss that does not recover to preexposure levels. In general, a threshold shift ≥10 dB at 2, 3, and 4 kHz is required for reporting purposes in human studies. The high-frequency regions of the cochlea are most sensitive to noise damage. Resonance of the ear canal also results in a frequency region of high-noise sensitivity at 4 to 6 kHz. A primary noise target is the cochlear hair cell. Although the mechanisms that underlie such hair cell damage remain unclear, there is evidence to support a role for reactive oxygen species, stress pathway signaling, and apoptosis. Another target is the synapse between the hair cell and the primary afferent neurons. Large numbers of these synapses and their neurons can be lost after noise, even though hearing thresholds may return to normal. This affects auditory processing and detection of signals in noise. The consequences of TTS and PTS include significant deficits in communication that can impact performance of military duties or obtaining/retaining civilian employment. Tinnitus and exacerbation of posttraumatic stress disorder are also potential sequelae.

Guidelines for Auditory Threshold Measurement for Significant Threshold Shift The purpose of this article is to provide guidelines for determining a Significant Noise-Induced Threshold Shift in clinical trials involving human populations. The article reviews recommendations for the standards to be referenced for human subjects, equipment, test environment, and personnel. Additional guidelines for military populations are provided. Guidelines for the calibration of audiometers, sound booth noise levels, and immitance equipment are provided. In addition the guidance provides specific suggestions for the subjects history before study onset, and otoscopy. Test frequencies for threshold determination and methods of threshold determination are reviewed for both air conduction and bone conduction for both baseline testing and later determination of either a temporary (TTS) or permanent threshold shift (PTS). Once a Significant Noise-Induced Threshold Shift has been determined, subjects should be retested, conductive component should be ruled out or addressed, and the subject should be counseled or referred for additional medical evaluation. Guidance for reporting procedures and the computerized study database are described. Finally, experimental designs suggested for noise-induced otoprotection clinical trials are described.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Otology & Neurotology - ACIA: Papers from the 14th Symposium on Cochlear Implants in Children, Nashville, TN

Introduction to the 14th Symposium on Cochlear Implants in Children, Nashville, TN Papers No abstract available

Improving Spoken Language Outcomes for Children With Hearing Loss: Data-driven Instruction Objective: To assess the effects of data-driven instruction (DDI) on spoken language outcomes of children with cochlear implants and hearing aids. Study Design: Retrospective, matched-pairs comparison of post-treatment speech/language data of children who did and did not receive DDI. Setting: Private, spoken-language preschool for children with hearing loss. Subjects: Eleven matched pairs of children with cochlear implants who attended the same spoken language preschool. Groups were matched for age of hearing device fitting, time in the program, degree of predevice fitting hearing loss, sex, and age at testing. Intervention: Daily informal language samples were collected and analyzed over a 2-year period, per preschool protocol. Annual informal and formal spoken language assessments in articulation, vocabulary, and omnibus language were administered at the end of three time intervals: baseline, end of year one, and end of year two. Main Outcome Measures: The primary outcome measures were total raw score performance of spontaneous utterance sentence types and syntax element use as measured by the Teacher Assessment of Spoken Language (TASL). In addition, standardized assessments (the Clinical Evaluation of Language Fundamentals—Preschool Version 2 (CELF-P2), the Expressive One-Word Picture Vocabulary Test (EOWPVT), the Receptive One-Word Picture Vocabulary Test (ROWPVT), and the Goldman–Fristoe Test of Articulation 2 (GFTA2)) were also administered and compared with the control group. Results: The DDI group demonstrated significantly higher raw scores on the TASL each year of the study. The DDI group also achieved statistically significant higher scores for total language on the CELF-P and expressive vocabulary on the EOWPVT, but not for articulation nor receptive vocabulary. Post-hoc assessment revealed that 78% of the students in the DDI group achieved scores in the average range compared with 59% in the control group. Conclusion: The preliminary results of this study support further investigation regarding DDI to investigate whether this method can consistently and significantly improve the achievement of children with hearing loss in spoken language skills.

Speech Recognition of Bimodal Cochlear Implant Recipients Using a Wireless Audio Streaming Accessory for the Telephone Objective: The goals of the present investigation were (1) to evaluate recognition of recorded speech presented over a mobile telephone for a group of adult bimodal cochlear implant users, and (2) to measure the potential benefits of wireless hearing assistance technology (HAT) for mobile telephone speech recognition using bimodal stimulation (i.e., a cochlear implant in one ear and a hearing aid on the other ear). Study Design: A three-by-two-way repeated measures design was used to evaluate mobile telephone sentence-recognition performance differences obtained in quiet and in noise with and without the wireless HAT accessory coupled to the hearing aid alone, CI sound processor alone, and in the bimodal condition. Setting: Outpatient cochlear implant clinic. Subjects: Sixteen bimodal users with Nucleus 24, Freedom, CI512, or CI422 cochlear implants participated in this study. Intervention (s): Performance was measured with and without the use of a wireless HAT for the telephone used with the hearing aid alone, CI alone, and bimodal condition. Main Outcome Measure(s): CNC word recognition in quiet and in noise with and without the use of a wireless HAT telephone accessory in the hearing aid alone, CI alone, and bimodal conditions. Results: Results suggested that the bimodal condition gave significantly better speech recognition on the mobile telephone with the wireless HAT. Conclusions: A wireless HAT for the mobile telephone provides bimodal users with significant improvement in word recognition in quiet and in noise over the mobile telephone.

Cortical Plasticity and Reorganization in Pediatric Single-sided Deafness Pre- and Postcochlear Implantation: A Case Study Hypothesis: The purpose of this study was to examine changes in cortical development and neuroplasticity in a child with single-sided deafness (SSD) before and after cochlear implantation (CI). Background: The extent to which sensory pathways reorganize in childhood SSD is not well understood and there is currently little evidence demonstrating the efficacy of CI in children with SSD. Methods: High-density 128-channel electroencephalography (EEG) was used to collect cortical auditory evoked potentials (CAEP), cortical visual evoked potentials (CVEP), and cortical somatosensory evoked potentials (CSSEP) in a child with SSD, pre-CI and at subsequent sessions until approximately 3 years post-CI in her right ear which occurred at age 9.86 years. Behavioral correlates of speech perception and sound localization were also measured. Results: Pre-CI, high-density EEG showed evidence of delayed auditory cortical response morphology, auditory cortical development strongly contralateral (to the normal hearing ear), evidence of increased cognitive load, and cross-modal reorganization by the visual and somatosensory modalities. The post-CI developmental trajectory provided clear evidence of age-appropriate development of auditory cortical responses, and decreased cross-modal reorganization, consistent with improved speech perception and sound localization. Conclusion: Post-CI, the child demonstrated age-appropriate auditory cortical development and improved speech perception and sound localization suggestive of significant benefits from cochlear implantation. Reversal of somatosensory recruitment was clearly apparent, and only a residual amount of visual cross-modal plasticity remained postimplantation. Overall, our results suggest that CI in pediatric SSD patients may benefit from a highly plastic cortex in childhood.

Does Bilateral Experience Lead to Improved Spatial Unmasking of Speech in Children Who Use Bilateral Cochlear Implants? Hypothesis: In children with bilateral cochlear implants (BiCIs), experience over a 1 to 3-year period can improve speech understanding and spatial unmasking of speech. Background: One reason for providing children with BiCIs is to improve spatial hearing abilities. Little is known about changes in performance with added bilateral experience, and the relation between sound localization and spatial unmasking of speech. Methods: Twenty children with BiCIs participated. Testing was conducted typically within a year of bilateral activation, and at 1, 2, or 3 follow-up annual intervals. All testing was done while children listened with both devices activated. Target speech was presented from front (co-located); interfering speech was from front, right (asymmetrical), or right and left (symmetrical). Speech reception thresholds (SRTs) were measured in each condition. Spatial release from masking (SRM) was quantified as the difference in SRTs between conditions with interferers at 0 degrees and 90 degrees. For 11 of the children, data are also compared with sound localization measures obtained on the same visit to the laboratory but published elsewhere. Results: Change in SRM with bilateral experience varied; some children showed improvement and others did not. Regression analyses identified relationships between SRTs and SRM. Comparison of the SRM with localization data suggests little evidence for correlations between the two spatial tasks. Conclusion: In children with BiCIs spatial hearing mechanisms involved in SRM and sound localization may be different. Reasons for reduced SRM include asymmetry between the ears, and individual differences in the ability to inhibit interfering information, switch and/or sustain attention.

Beyond Early Intervention: Supporting Children With CIs Through Elementary School Background: The development of cochlear implants (CIs) and the broader availability of early intervention, made possible by newborn hearing screening, have raised prospects that deaf children can be mainstreamed at the start of elementary school and fare well with minimal support. This report examines the veracity of that perspective. Methods: This report specifically: (1) reviews progress made by deaf children in spoken language acquisition over the past 25 years; (2) presents data collected from 104 children in the early elementary grades (49 with normal hearing (NH) and 55 with severe-to-profound hearing loss who use CIs); (3) describes language acquisition that typically occurs in elementary school; and (4) highlights intervention strategies for school-age deaf children with CIs. Results: The spoken language skills of deaf children have improved thanks to CIs and early intervention, but remain below those of children with NH. The amount of deficit varies across the language construct examined, with the greatest deficit found for skills dependent upon phonological (speech-sound) sensitivity, and the mildest associated with morphosyntactic (grammatical) skills. There is substantial development in both phonological and morphosyntactic skills that typically occurs during the elementary school years. Conclusion: Both the data and theoretical models of language acquisition indicate that even with the availability of CIs and early intervention, deaf children are behind their peers with NH when they enter school. And there is much language learning that lies ahead for them. Thus, there is a need for us to enhance our intervention with deaf children during the early elementary grades.

Speech Understanding in Children With Normal Hearing: Sound Field Normative Data for BabyBio, BKB-SIN, and QuickSIN Objective: The primary goal was to establish normative data for the Pediatric AzBio "BabyBio," QuickSIN, and BKB-SIN measures in the sound field for children with normal hearing. Setting: Tertiary care hospital; cochlear implant (CI) program. Patients: Forty-one children with normal hearing were recruited across four age groups (5–6, 7–8, 9–10, and 11–12 yr). Interventions: Sentence recognition testing was assessed at four different signal-to-noise ratios (SNRs, +10, +5, 0, and −5 dB) for BabyBio sentences as well as for the BKB-SIN and QuickSIN tests. All measures were presented in the sound field at 60 dBA except QuickSIN, which was presented at 70 dBA. Main Outcome Measures: BabyBio sentence recognition, BKB-SIN SNR-50, and QuickSIN SNR-50 were analyzed to establish sound field norms. Results: BabyBio sentence recognition approached ceiling at all SNRs with mean scores ranging from 86% at −5 dB SNR to 99.3% at +10 dB SNR. Mean QuickSIN SNR-50 was 6.6 dB. Mean BKB-SIN SNR-50 was 1.6 dB with sound field data being consistent with insert earphone normative data in the BKB-SIN manual. Performance for all measures improved with age. Conclusion: Children with normal hearing achieve ceiling-level performance for BabyBio sentence recognition at SNRs used for clinical CI testing (≥0 dB SNR) and approach ceiling level even at −5 dB SNR. Consistent with previous reports, speech recognition in noise improved with age from 5 to 12 years in children with normal hearing. Thus, speech recognition in noise might also increase in the CI population across the same age range warranting age-specific norms for CI recipients. Last, the QuickSIN test could be substituted for the BKB-SIN test with appropriate age-normative data.

Language Development in the First Year of Life: What Deaf Children Might Be Missing Before Cochlear Implantation Objectives: Language development is a multifaceted, dynamic process involving the discovery of complex patterns, and the refinement of native language competencies in the context of communicative interactions. This process is already advanced by the end of the first year of life for hearing children, but prelingually deaf children who initially lack a language model may miss critical experiences during this early window. The purpose of this review is twofold. First, we examine the published literature on language development during the first 12 months in typically developing children. Second, we use this literature to inform our understanding of the language outcomes of prelingually deaf children who receive cochlear implants (CIs), and therefore language input, either before or after the first year. Conclusions: During the first 12 months, typically developing infants exhibit advances in speech segmentation, word learning, syntax acquisition, and communication, both verbal and nonverbal. Infants and their caregivers coconstruct a communication foundation during this time, supporting continued language growth. The language outcomes of hearing children are robustly predicted by their experiences and acquired competencies during the first year; yet these predictive links are absent among prelingually deaf infants lacking a language model (i.e., those without exposure to sign). For deaf infants who receive a CI, implantation timing is crucial. Children receiving CIs before 12 months frequently catch up with their typically developing peers, whereas those receiving CIs later do not. Explanations for the language difficulties of late-implanted children are discussed.

Initial Results With Image-guided Cochlear Implant Programming in Children Hypothesis: Image-guided cochlear implant (CI) programming can improve hearing outcomes for pediatric CI recipients. Background: CIs have been highly successful for children with severe-to-profound hearing loss, offering potential for mainstreamed education and auditory-oral communication. Despite this, a significant number of recipients still experience poor speech understanding, language delay, and, even among the best performers, restoration to normal auditory fidelity is rare. Although significant research efforts have been devoted to improving stimulation strategies, few developments have led to significant hearing improvement over the past two decades. Recently introduced techniques for image-guided CI programming (IGCIP) permit creating patient-customized CI programs by making it possible, for the first time, to estimate the position of implanted CI electrodes relative to the nerves they stimulate using CT images. This approach permits identification of electrodes with high levels of stimulation overlap and to deactivate them from a patient's map. Previous studies have shown that IGCIP can significantly improve hearing outcomes for adults with CIs. Methods: The IGCIP technique was tested for 21 ears of 18 pediatric CI recipients. Participants had long-term experience with their CI (5 mo to 13 yr) and ranged in age from 5 to 17 years old. Speech understanding was assessed after approximately 4 weeks of experience with the IGCIP map. Results: Using a two-tailed Wilcoxon signed-rank test, statistically significant improvement (p < 0.05) was observed for word and sentence recognition in quiet and noise, as well as pediatric self-reported quality-of-life (QOL) measures. Conclusion: Our results indicate that image guidance significantly improves hearing and QOL outcomes for pediatric CI recipients.

Method of Speech Stimulus Presentation Impacts Pediatric Speech Recognition: Monitored Live Voice Versus Recorded Speech Objective: To characterize the potential differences in speech understanding performance on word and sentence tests assessed using live voice and recorded speech measures for pediatric cochlear implant (CI) recipients. Study Design: This clinical study used a combination of retrospective and prospective study designs exploring within-subject performance for recorded versus monitored-live-voice presentation methods on pediatric word and sentence measures. Methods: Word and/or sentence recognition was obtained for 29 pediatric CI recipients using both recorded stimuli and monitored-live-voice (MLV) within a single-test session with a single experimenter for each session. The difference score was calculated for word and sentence measures allowing a comparison across conditions. Setting: Ambulatory. Patients: Pediatric patients aged 4 to 17 years. Intervention(s): Cochlear implants. Main Outcome Measure(s): Speech recognition testing. Results: There was a significant difference between recorded and MLV speech understanding with mean recorded word scores being 13-percentage points lower than those obtained via MLV. Conclusions: The results of this project suggest that the use of MLV for the assessment of speech perception in the pediatric Audiology clinic may overinflate children's performance and thereby runs the risk of failing to identify poorer or at-risk performance.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Otology & Neurotology

The Women in Neurotology (WIN)—A Cross-sectional Survey No abstract available

Hearing Protection, Restoration, and Regeneration: An Overview of Emerging Therapeutics for Inner Ear and Central Hearing Disorders Objective: To provide an overview of biotechnology and pharmaceutical companies active in the field of inner ear and central hearing disorders and their therapeutic approaches. Methods: Scientific and grey literature was searched using broad search terms to identify companies and their hearing-related therapeutic approaches. For each approach its lead indication, product, therapeutic modality, target, mechanism of action and current phase of clinical development was collated. Results: A total of 43 biotechnology and pharmaceutical companies have been identified that are developing therapeutics for inner ear and central hearing disorders. Their therapeutics include drug-, cell- and gene-based approaches to prevent hearing loss or its progression, restore hearing, and regenerate the inner ear. Their therapeutic targets and specific mechanisms of action are wide-ranging, reflecting the complexity of the hearing pathways and the diversity of mechanisms underlying inner ear disorders. While none of the novel products under investigation have yet made it to the clinical market, and a large proportion are still at preclinical phase, many therapeutics have already entered clinical testing with more expected to do so in the next few years. Conclusion: A wide range of novel therapeutics targeting different hearing, balance and tinnitus pathways, and patient populations are approaching the clinical domain. It is important that clinicians involved in the care of patients with hearing loss prepare for what may become a radically different approach to the management of hearing disorders, and develop a true understanding of the new therapies' mechanisms of action, applications, and indications.

A Randomized Cross-over Trial Comparing a Pressure-free, Adhesive to a Conventional Bone Conduction Hearing Device Objectives: The main aim of this study was to compare the average daily wearing time of a conventional bone conduction device with a pressure-free, adhesive bone conduction device. Further, audiologic and quality-of-life outcome parameters were evaluated. Methods: An academic, prospective, randomized cross-over trial was performed at a single center. Thirteen subjects between 12 and 63 years with conductive hearing loss were included. Average daily wearing time and subjective observations were assessed in a diary. Sound field audiometry, Freiburg monosyllables word test, and Oldenburg sentence test in quiet and in noise were carried out after 2 weeks of habituation to each device. AQoL-8D and SSQ-12 questionnaires were completed at baseline and after a 2-week test interval. Results: Median wearing time of the devices was 8.1 hours (5.8–10.2 interquartile range) for the adhesive and 4.3 hours (2.7–7.1) for the conventional bone conduction device, the difference was statistically significant (p = 0.033). There were no statistically significant differences in sound field audiometry, Freiburg monosyllables word test, and Oldenburg sentence test when comparing the two devices. AQoL-8D and SSQ-12 showed a significant improvement with the devices in comparison with baseline, with no significant difference between devices in the total scores. Ten subjects reported pain using the conventional device, two subjects reported skin irritations using the adhesive device. Conclusion: For patients with mixed or conductive hearing loss, the adhesive device is a valuable alternative with a significantly longer daily wearing time.

Optimal Retention Force of Audio Processor Magnets Hypothesis: Audio processor magnets used in transcutaneous active hearing implants vary in retention force. We hypothesized that a range of optimal magnetic retention forces could be derived, based on objective in-situ measurements of individual retention forces. Background: The magnetic force required to retain the proper placement of transcutaneous active hearing implants varies among patients. Currently, audiologists rely on personal experience in deciding which magnet to use. Insufficient force causes frequent loss of the single-unit processors or external coils of behind-the-ear devices, and excessive force causes pain and skin irritations. Methods: We experimentally determined magnetic retention force as a function of the distance between two magnets for different processor-implant magnet combinations. In addition, we studied individual in situ retention forces in 100 patients with hearing devices. Skin status was evaluated by a physician and assessed by patient self-reporting and a questionnaire. Results: Force–distance functions showed that different magnet strengths had differential effects only at distances less than 6 mm. Examiner and patient skin status assessments and comfort scores showed that optimal retention force range was 0.23 to 0.4 N. Conclusion: We found that the currently available magnet types restrict the range of feasible skin flap thicknesses to a maximum of 6 mm. Further we conclude that retention forces between 0.23 and 0.4 N could provide the appropriate trade-off between the risk of losing device fixation and of causing skin irritations. We recommend measuring the retention force in all patients.

Tinnitus Severity Change Following Stapedotomy in Patients With Otosclerosis Objective: To determine whether stapedotomy was effective in reducing tinnitus severity. In addition, the relationship between reduction in tinnitus and improvement in hearing after stapedotomy was analyzed. Study Design: Prospective clinical study. Setting: Tertiary referral center. Patients: A group of 168 otosclerosis patients diagnosed with chronic tinnitus. Intervention: Stapedotomy. Main Outcome Measures: The Tinnitus Functional Index questionnaire (TFI) was used to assess tinnitus severity before surgery, and at 3 and 6 months postoperatively. Pure-tone audiometry was conducted before surgery and 6 months postoperatively. Results: The TFI Total score before the operation was M = 34.5 (standard deviation [SD] = 1.6) points, and decreased 3 months after stapedotomy to M = 17.5 (SD = 1.7), a statistically significant change (T = –8.200; p < 0.001). A weak correlation was found between the pre- and postoperative difference of TFI Total score and air-conduction thresholds (r = 0.21; p = 0.013) as well as between the TFI Total score and the size of the air-bone gap (r = 0.21; p = 0.013). Preoperatively, 86 patients tinnitus was a not or small problem, and for 82 it was moderate to very big. After stapedotomy, 93 (55%) of patients experienced a significant reduction in tinnitus severity. Of the whole group, 62 patients (37%) reported complete disappearance of their tinnitus. No change in tinnitus severity was reported by 63 patients (38%), and an increase was observed by 12 patients (7%). Conclusion: Stapedotomy not only improves hearing but also reduces tinnitus severity. The current results extend knowledge of postoperative results in terms of tinnitus severity, and might benefit patients undergoing tinnitus counseling. It might also be useful to otolaryngologists when making decisions regarding qualification criteria.

Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness—A Double-blind, Randomized, Placebo-controlled Phase 3 Study Objective: To confirm the efficacy and safety of AM-111 (brimapitide), a cell-penetrating c-Jun N-terminal Kinase (JNK) inhibitor, in patients suffering from severe to profound acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). Study design: Prospective, double-blind, randomized, placebo-controlled phase 3 study with follow-up visits on Days 3, 7, 28, and 91. Setting: Fifty-one European and Asian sites (tertiary referral centers, private ENT practices). Patients: Two hundred fifty-six patients aged 18 to 65 years presenting within 72 hours following ISSNHL onset with mean hearing loss ≥ 40 dB and mean threshold ≥ 60 dB at the 3 worst affected contiguous test frequencies. Interventions: Single-dose intratympanic injection of AM-111 (0.4 or 0.8 mg/ml) or placebo; oral prednisolone as reserve therapy if hearing improvement < 10 dB at Day 7. Main outcome measures: Hearing improvement to Day 28 was the primary efficacy endpoint; complete hearing recovery, frequency of reserve therapy used, complete tinnitus remission, improvement in word recognition were secondary endpoints. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events. Results: While the primary efficacy endpoint was not met in the overall study population, post-hoc analysis showed a clinically relevant and nominally significant treatment effect for AM-111 0.4 mg/ml in patients with profound ISSNHL. The study drug and the administration procedure were well tolerated. Conclusions: AM-111 provides effective otoprotection in case of profound ISSNHL. Activation of the JNK stress kinase, AM-111's pharmacologic target, seems to set in only following pronounced acute cochlear injury associated with large hearing threshold shifts.

Systematic Review of Hearing Loss Genes in the African American Population Objective: Literature review of the genetic etiology of hearing loss (HL) in the African American (AA) population. Data Sources: PubMed, EBSCO, and CINAHL were accessed from 1966 to 2018. Review Methods: PRISMA guidelines were followed. Search terms included permutations of "hearing loss," "African American," "black," and "genetic"; "African American" was then cross-referenced against documented HL genes. AA subjects included in multiethnic cohorts of genetic HL testing were identified by searching the key terms "hearing loss" and "ethnic cohort" and "genetic." The Q-Genie tool was used in the quality assessment of included studies. An allele frequency meta-analysis of pathogenic GJB2 variants in the AA population was performed and stratified by hearing status. Results: Four hundred seventeen articles were reviewed, and 26 met our inclusion criteria. Ten studies were included in the GJB2 meta-analysis. In the general AA population, pathogenic GJB2 variants are rare, including the 35delG allele, which displayed a carrier frequency of 0.05%. Pathogenic variants were discovered in seven nonsyndromic HL genes (GJB2, MYO3A, TECTA, STRC, OTOF, MYH14, TMC1), eight syndromic HL genes, and one mitochondrial HL gene. Recent comprehensive genetic testing using custom genetic HL testing platforms has yielded only a 26% molecular diagnosis rate for HL etiologies in the AA population. Conclusions: Investigators should be encouraged to provide an ethnic breakdown of results. Sparse literature and poor diagnosis rates indicate that genes involved in HL in the AA population have yet to be identified. Future explorative investigations using next-generation sequencing technologies, such as whole-exome sequencing, into the AA population are warranted.

Characteristics of Mid-Frequency Sensorineural Hearing Loss Progression Objectives: To characterize the progression of mid-frequency sensorineural hearing loss (MFSNHL) over time. Methods: A retrospective chart review spanning 2012 to 2017 was performed at a tertiary care audiology and neurotology center. Our cohort included 37 patients met the criteria for MFSNHL also known as "cookie bite hearing loss." It was defined as having a 1, 2, and 4 kHz average pure tone audiometry greater than 10 dB in intensity compared with the average threshold at 500 Hz and 8 kHz. Results: Average age at initial presentation was 11.8 years (range, 8 mo to 70 yr). Across all individuals, the average mid-frequency threshold was 47 dB, compared with 27 dB at 500 Hz and 8 kHz. Twenty-three patients (62%) had multiple audiograms with 4-year median follow up time. Average values across all frequencies (0.5, 1, 2, 4, 8 kHz) in the initial audiogram was 37 dB, compared with an average of 39 dB demonstrated on final audiogram. Of those with serial audiograms, only five patients demonstrated threshold changes of 10 dB or more. Of these five patients, only one was found to have clinical worsening of MFSNHL. Conclusions: MFSNHL is an uncommon audiometric finding with unspecified long-term outcomes. We demonstrated that most patients (96%) with MFSNHL do not experience clinical worsening of their hearing threshold over almost 4 years of follow up. Future prospective studies aimed at collecting longer-term data are warranted to further elucidate the long-term trajectory of MFSNHL patients.

Association of Speech Processor Technology and Speech Recognition Outcomes in Adult Cochlear Implant Users Objective: Determine association of advancements in speech processor technology with improvements in speech recognition outcomes. Study Design: Retrospective cohort. Setting: Tertiary referral center. Patients: Adult unilateral cochlear implant (CI) recipients. Intervention: Increasing novelty of speech processor defined by year of market availability. Main Outcome Measures: Consonant-Nucleus-Consonant (CNC) and Hearing in Noise Test (HINT) in quiet. Results: From 1991 to 2016, 1,111 CNC scores and 1,121 HINT scores were collected from 351 patients who had complete data. Mean post-implantation CNC score was 53.8% and increased with more recent era of implantation (p < 0.001, analysis of variance [ANOVA]). Median HINT score was 87.0% and did not significantly vary with implantation era (p = 0.06, ANOVA). Multivariable generalized linear models were fitted to estimate the effect of speech processor novelty on CNC and HINT scores, each accounting for clustering of scores within patients and characteristics known to influence speech recognition outcomes. Each 5-year increment in speech processor novelty was independently associated with an increase in CNC score by 2.85% (95% confidence limits [CL] 0.26, 5.44%) and was not associated with change in HINT scores (p = 0.30). Conclusion: Newer speech processors are associated with improved CNC scores independent of the year of device implantation and expanding candidacy criteria. The lack of association with HINT scores can be attributed to a ceiling effect, suggesting that HINT in quiet may not be an informative test of speech recognition in the modern CI recipient. The implications of these findings with respect to appropriate interval of speech processor upgrades are discussed.

The Effect of Cochlear Coverage on Auditory and Speech Performance in Cochlear Implant Patients Objective: To determine the effect of cochlear coverage on audiological and speech parameters in patients with cochlear implants. Previous work has investigated the effect of tailoring electrode size to a cochlear implant recipient's individual cochlear duct length (CDL). However, no clear relationship has been found between speech development and the extent of electrode insertion, and the benefits of apical stimulation are not yet clear. Methodology: In this retrospective study, we assessed the effect of cochlear coverage on audiological and speech performance. Participants were prelingually deaf children who received cochlear implants between June 2013 and December 2014 under the care of a single cochlear implant surgeon. Cochlear coverage was estimated for each ear according to electrode type, depth of insertion, and the number of active electrodes. Electrode type and length were determined by the individual's CDL, measured by computed tomography (CT), and full insertion was documented intraoperatively. The number of active electrodes was recorded using intraoperative audiological response telemetry. Audiological assessments were obtained 6 months and 1 year postoperatively. Results of the categories of auditory performance-II and speech intelligibility rating scales were obtained after 3 years. Patients were divided into two groups based on their cochlear coverage and their audiological and speech outcomes were compared. Results: Of the 97 children recruited, 47 were girls. Temporal bone CT scans showed the right and left mean CDLs among girls were 27.7 and 27.9 mm, respectively, and 29.2 mm for both ears in boys. For each sex, the right and left CDLs did not differ significantly (p = 0.07). Twenty patients were lost to follow-up, leaving 77 patients (120 ears), which were divided into groups according to cochlear coverage (complete vs. incomplete). Significant between-group differences were not found in assessments of audiology, categories of auditory performances, or speech intelligibility ratings after 3 years. Conclusion: Audiological parameters do not differ according to the degree of cochlear coverage, specifically for low-frequency tones. Speech parameters are also comparable. Therefore, complete cochlear coverage does not appear to provide significant benefit over incomplete coverage for prelingually deaf cochlear implant recipients.

Non-microscopic Middle Ear Cholesteatoma Surgery: A Case Report of a Novel Head-Up Approach Objective: To assess the feasibility of a postauricular transcortical mastoidectomy utilizing an exoscope, which offers 3D stereoscopic visualization. Study Design: Clinical capsule report. Patients: Two consecutive patients with cholesteatoma involvement in the mastoid cavity were included in the study. Intervention: After transcanal endoscopic surgery, postauricular mastoidectomy utilizing a surgical 3D exoscope was performed. Then, the cholesteatoma in the mastoid cavity was removed through the mastoidectomy opening with endoscopes. Results: The postauricular transcortical mastoidectomy utilizing a 3D exoscope was not only feasible, but importantly, the exoscope took little time to switch to and resulted in a smooth workflow. There was no cholesteatoma recurrence at 9 months. Conclusion: During endoscope-based surgery, in patients with cholesteatoma mastoid involvement, we can continue to perform the surgical procedure in a heads-up position utilizing a surgical 3D exoscope. The combination of transcanal endoscopic ear surgery and the postauricular transcortical mastoidectomy utilizing a surgical 3D exoscope is a very novel treatment strategy for cholesteatoma, and it gives us a comfortable and consistent working environment in endoscope-based ear surgery. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Address correspondence and reprint requests to Ryosei Minoda, Middle Ear and Inner Ear Surgical Center, Japan Community Health Care Organization Kumamoto General Hospital, 10-10 Torimachi Yatsushiro, Kumamoto 866-8660, Japan; e-mail: ryminoda@gmail.com The authors have no conflicts of interest to declare. No financial support was received for this work. Supplemental digital content is available in the text. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://journals.lww.com/otology-neurotology). Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Temporal Bone Histopathology of First-Generation Cochlear Implant Electrode Translocation Objective: To evaluate the histopathology of human temporal bones (HTBs) with cochlear implants (CI). Background: Understanding CI translocation injuries is critical for improving outcomes. Material and Methods: Thirteen HTBs from 12 CI patients were studied. Six HTBs exhibited translocation with localized injury (Group 1) and seven HTBs exhibited translocation with significant lateral wall injury (Group 2). There were no significant differences between Group 1 and Group 2 for age at death, age at implantation, and years with CI. Results: Four out of six of Group 1 had round window approach, while all seven of Group 2 had cochleostomy approach. Translocation injuries tended to occur near 180 degrees of angular insertion with a mean of 186.36 ± 51.62 degrees. Average CI insertion length for Group 2 was 21.86 ± 2.55 mm, significantly longer than Group 1 at 18.50 ± 3.33 mm (p = 0.031). Group 1 had an average of 17300 ± 9415 spiral ganglia neurons (SGNs) while Group 2 had significantly fewer SGNs 6714 ± 4269 (p = 0.015). Group 1 average auditory performance of 66.55 ± 27.20% was higher than that of Group 2 of 39.86 ± 15.36%. Group 2 had a high degree of osteoneogenesis and infiltration of cells generally localized to areas of translocation injury and cochleostomy. Conclusion: Translocation injuries tend to occur at an insertion angle of 180 degrees, at 9 to 10 mm. Lateral wall injury and damage to the organ of Corti incites fibrosis, osteoneogenesis, and infiltration, lower SGN count and poorer auditory performance. Longer electrodes were more prone to translocation and higher chance of significant intracochlear injury. Address correspondence and reprint requests to Akira Ishiyama, M.D., Rm 32-28, Rehabilitation Center, 1000 Veteran Ave., Los Angeles, CA 90095; E-mail: ishiyama@ucla.edu IRB# 10-001449 UCLA Supported by NIDCD/NIH: 1U24DC015910-01. NIDCD National Temporal Bone Laboratory at UCLA. Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles. Presented at the American Otologic Society Meeting at the Combined Otolaryngology (COSM) in Washington D.C. on April 21st, 2018. The authors have no conflicts of interest to disclose. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

First Experience With a New Thin Lateral Wall Electrode in Human Temporal Bones Introduction: A modern cochlear implant electrode array design must combine: improved surgical ease of use, structure preservation, particularly important for pediatric application, stable position within the cochlea over time, and a meaningful balance between hearing preservation against addressing sufficient cochlear tissue to support electrical-only hearing. The aim of this study was to investigate a new lateral wall electrode array design from Advanced Bionics on human temporal bones (TBs). Methods: Ten fresh-frozen TBs were implanted with the SlimJ electrode array via the round window. The electrode array is 23 mm long, with a cross-section varying from 0.25 × 0.55 mm at the most apical contact to 0.6 × 0.8 mm at the proximal marker contact. To assess location of the electrode array, the TBs were postoperatively scanned using cone beam computed tomography, and histology was performed to assess intracochlear trauma (Grades 0–4). Results: All electrode arrays were considered easy to insert. The average insertion depth was 432 degrees measured from the round window with a range from 411 to 450 degrees azimuth. Nine out of 10 electrode arrays were inserted fully (<0.5 mm out of the cochlea), one electrode array was left 1.5 mm out of the cochlea. No translocations were observed in all 10 cochleae, slight touching of the basilar membrane at the distal portion of the array was observed in 50% of the cases. Conclusion: The results from the new thin lateral wall electrode array from Advanced Bionics provided consistent scala tympani locations. No translocations were observed and almost all electrode arrays were fully inserted. These results are promising and the new electrode array will be further studied in clinical practice investigating hearing preservation capabilities and speech performance. Address correspondence and reprint requests to Ersin Avci, Ph.D., Advanced Bionics GmbH, 30625 Hannover, Germany; E-mail: ersin.avci@advancedbionics.com E.A. and D.G. are employees of Advanced Bionics GmbH. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Prognostic Factors of Long-Term Hearing Preservation in Small and Medium-Sized Vestibular Schwannomas After Microsurgery Objective: The authors evaluated the long-term hearing outcomes of patients with vestibular schwannoma (VS) to explore appropriate surgical treatment. Study Design: Retrospective study. Setting: Tertiary referral center. Patients: A total of 138 patients diagnosed with small and medium-sized VS with serviceable hearing from January 2006 to December 2015. Interventions: All patients underwent microsurgery via retrosigmoid (RSA) or middle cranial fossa approach (MFA) and were followed up for over 2 years. Main Outcome Measures: Pre- and postoperative hearing, including pure tone audiometry, speech discrimination score, and auditory brainstem response (ABR), were analyzed. Results: The mean tumor size and volume were 16.6 ± 3.4 mm and 1711.8 ± 918.5 mm3, respectively. Preoperative hearing levels were Class A in 42, Class B in 67, and Class C in 29 patients. Patients with a tumor from the superior vestibular nerve (SVN) had better hearing at diagnosis. Postoperative hearing levels were Class A, B, C, and D for 28, 17, 32, and 61 patients. Hearing outcomes were significantly better in patients with normal intraoperative I wave on ABR. Hearing loss within 6 months had a positive effect on postoperative hearing. Better preoperative hearing and tumors from SVN were correlated with better postoperative hearing outcomes. Tumor size, cystic variation, or extension to the fundus of internal auditory canal had no influence on hearing preservation. Conclusions: Better preoperative hearing, shorter hearing loss period, tumors from SVN, and normal intraoperative I wave are prognostic factors for serviceable hearing. RSA and MFA are effective and safe for tumor removal and hearing preservation. Address correspondence and reprint requests to Zhihua Zhang, M.D., Ph.D., Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Zhizaoju Road #639, Shanghai 200011, China; E-mail: zhihuazhang0504@126.com; Hao Wu, M.D., Ph.D., Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Zhizaoju Road #639, Shanghai 200011, China; E-mail: wuhao622@sina.cn The authors declare that the manuscript has not been published previously or is under consideration for publication elsewhere. Its publication is approved by all authors, and if accepted, it will not be published elsewhere in similar form, in any language, without the consent of Lippincott Williams & Wilkins. Each person listed as an author has participated in the study to a significant extent. Funding: This work was supported by grants from the National Natural Science Foundation of China [grant number 81470681, 81570906, and 81870712]. The authors declare that they have no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Association of Intracranial Hypertension With Calvarial and Skull Base Thinning Objective: Determine if patients with increased opening pressure (OP) on lumbar puncture (LP) have thinner calvaria and skull bases. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: Patients (≥18 yr of age) who had a recorded OP on LP and high-resolution computed tomography imaging of the head. Patient age, sex, body mass index were calculated. Intracranial hypertension (IH) was defined with an OP≥25 cm-H2O and low intracranial pressure with an OP<15 cm-H2O. Intervention: Measurement of calvarial, zygoma, and skull base thickness when blinded to OP with three-dimensional slicer and radiologic calipers. Main Outcome Measures: Association of calvarial, skull base, and zygoma thickness with OP and age. Results: Fifty-eight patients were included with a mean (SD) age of 53.1 (16.2) years and average (SD) body mass index of 30.1 (9.1) kg/m2. Patients with IH had thinner mean (SD) calvaria (3.01 [0.81] versus 2.70 [0.58] mm; p = 0.036) and skull bases (5.17 [1.22] versus 4.60 [1.42] mm; p = 0.043) when compared with patients without IH. The mean (SD) extracranial zygoma thickness was similar between the two groups (5.09 [0.76] versus 5.00 [0.73] mm; p = 0.56). General linear model regression demonstrated advancing age was associated with increasing calvarial thickness in patients without IH and calvarial thinning in patients with IH (p = 0.038). Conclusion: IH is independently associated with intracranial bone (calvaria and skull base) thinning and not extracranial (zygoma) thinning. Skull thinning occurs with IH and advancing age. These findings support a possible role of increased ICP in the pathophysiologic development of spontaneous cerebrospinal fluid leaks. Address correspondence and reprint requests to Rick F. Nelson, M.D., Ph.D., Indiana University School of Medicine, 355 West 16th Street Suite 3200, Indianapolis, IN 46202; E-mail: ricnelso@iupui.edu The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Mastoid Cavity Myiasis: A Case Report and Review of the Literature Objective: We report a case study of mastoid cavity aural myiasis in an urban developed setting and review the relevant literature. Data Source: Retrospective case report and review of the English literature via PubMed. Data Selection: English-language articles concerning aural myiasis and mastoid cavity myiasis were included. Data Extraction: Two previous case reports of mastoid cavity myiasis were identified and analyzed. Conclusion: Neglected mastoid cavity care, low socioeconomic status, poor personal hygiene, homelessness, and chronic suppurative otitis media are likely contributing factors to this uncommon presentation occurring in an urban setting. Address correspondence and reprint requests to Jacob Kahane, M.D., Department of Otolaryngology—Head and Neck Surgery, 1701 West Charleston Blvd., Ste. 490, Las Vegas, NV 89102; E-mail: jacob.kahane@unlv.edu The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Different Materials for Plugging a Dehiscent Superior Semicircular Canal: A Comparative Histologic Study Using a Gerbil Model Hypothesis: The choice of the material for plugging a dehiscence of the superior semicircular canal is based on the ease of use and the success of the procedure to permanently relieve symptoms without adverse side effects. Background: Dehiscence of the superior semicircular canal can lead to autophony, conductive hearing loss, and vertigo. Surgical treatment by plugging the canal is a highly effective treatment of the symptoms in many patients, although, the procedure can be associated with some degree of hearing loss in more than or equal to 25% of the patients. The available data indicate that adverse effects may be more frequently observed with bone wax as compared with other materials. Methods: In the present study we compare the tissue reactions induced by plugging the superior semicircular canal with autologous bone pate/bone chips, muscle, fat, artificial bone wax, and teflon in the gerbil model in an attempt to identify the material leading to successful plugging with the least adverse tissue reactions. Results: Our data show that successful plugging was achieved in 100% of the ears by bone pate/bone chips, teflon, and bone wax while the success rate was significantly lower (<50%) following muscle and fat. The proportion of adverse tissue reactions was significantly more pronounced using bone wax as compared with teflon and bone pate/bone chips. Conclusion: The use of teflon or autologous bone as a material for plugging a dehiscent superior semicircular canal should be favored over bone wax, muscle, and fat. Address correspondence and reprint requests to Pingling Kwok, M.D., ENT-Department, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; E-mail: pingling.kwok@ukr.de The work was performed at the ENT-Hospital of the University of Regensburg without receiving any financial support from any third party. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Electrical Impedance as a Biomarker for Inner Ear Pathology Following Lateral Wall and Peri-modiolar Cochlear Implantation Objectives/Hypothesis: Spikes in cochlear implant impedance are associated with inner ear pathology after implantation. Here, we correlate these spikes with episodes of hearing loss and/or vertigo, with a comparison between lateral wall and peri-modiolar electrode arrays. Methods: Seven hundred seventy recipients of Cochlear's slim-straight, lateral wall electrode (CI422), or peri-modiolar (CI512) electrode were investigated for impedance spikes. Impedance fluctuations were defined as a median rise of ≥ 4 kΩ across all intracochlear electrodes from baseline measurements taken 2 weeks after switch-on. Medical records were analyzed from 189 of the 770 patients. Results: The slim straight, lateral wall electrode was found to spike in impedance at a significantly higher rate than the peri-modiolar array (17% vs 12%). The peri-modiolar electrode tended to spike in impedance earlier than the slim-straight electrode. Impedance spikes were found to significantly correlate with medical events (hearing loss, vertigo, or tinnitus). Overall, in the "spike" group, 42 of 75 patients (56%) demonstrated a clinical event during the impedance spike, whereas 26 of 114 patients (22%) of the "non-spike" group had a clinical event. This significant difference existed with both implant types. Conclusion: These results demonstrate a small, but significant increase in impedance spikes in lateral wall electrodes, and support the relationship between spikes in cochlear implant impedances and postoperative inner-ear events, including the loss of residual hearing and vertigo. Monitoring cochlear implant impedance may be a method for early detection, and so the prevention, of these events in the future. Address correspondence and reprint requests to Stephen J. O'Leary, M.D., Ph.D., Department of Surgery-Otolaryngology, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne 3002, Australia. E-mail: sjoleary@unimelb.edu.au Dr C.S. and Dr C.B. are considered to have made equal contributions to this research. S.J.O. is funded by the National Health and Medical Research Council (Australia). This research was conducted at the Royal Victorian Eye and Ear Hospital and funded by the National Health and Medical Research Council (Australia). The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Subtotal Petrosectomy for Cochlear Implant Surgery. Response To Letter To The Editor No abstract available

Sacculus-Utriculus Confluence Criterion (SUCC) No abstract available

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Current Opinion in Otolaryngology & Head and Neck Surgery

Editorial introductions No abstract available

Perspectives on optimizing radiotherapy dose to the dysphagia/aspiration-related structures for patients with head and neck cancer Purpose of review The purpose of this study is to provide an overview on the methodologies, outcomes and clinical implications of studies that have investigated swallowing outcomes after head and neck cancer (HNC) treatment when reducing radiotherapy dose to specific dysphagia/aspiration-related structures (DARS). Recent findings Overall, there is limited recent evidence, with a lack of high-quality studies, which examine the outcomes of DARS-optimized radiotherapy treatment. Large variations exist in the methodology of these studies in regards to which DARS are delineated and how swallowing outcomes are measured. Consequently, there is a wide range of dose limits recommended to a variety of DARS structures. Despite these limitations, there appears to be a general consensus that optimizing dose to the DARS will result in some reduction of dysphagia after radiotherapy without compromising on treatment to the tumour. Summary More rigorous study must be completed to determine the true extent of clinical benefit from this practice. Institutions must take into consideration the limitations of the evidence as well as logistical costs of implementing this technique into practice. However, optimizing dose to the DARS appears to be a well-tolerated practice that may have substantial positive benefits for patients' swallowing function and quality of life after HNC treatment.

Dysphagia in patients with non-head and neck cancer Purpose of review To review the current evidence on dysphagia in non-head and neck cancer, including its cause, prevalence, impact, management, and areas for future research. Recent findings Dysphagia is widely recognised as a common and debilitating side-effect of head and neck cancer (HNC) and its treatment; however, minimal attention has been given to dysphagia in other cancer populations. Detailed data regarding the exact nature and prevalence of dysphagia are limited, in part because of the lack of any validated tools specifically for non-HNC patients. Dysphagia can be due to a variety of different causes in cancer patients. It can have a significant impact on physical and psychological wellbeing, and its management can be complex and multifactorial. Summary Preliminary evidence suggests that the prevalence of dysphagia in non-HNC patients may be high. Cancer patients are vulnerable and survivorship is a key component of cancer care, so further research is essential to better understand the problem and thus provide optimal care and outcomes for patients.

Presbylaryngis: a state-of-the-art review Purpose of review Presbylaryngis is the term used to describe changes in the larynx with ageing. It represents an increasingly common complaint as global populations continue to grow and get older. Presbylaryngis has a significantly negative impact on patients' quality of life and their ability to participate in society. This article will review the relevant literature on the incidence, pathophysiology, clinical evaluation, and treatment modalities for presbylaryngis. Recent findings The recently developed Ageing Voice Index (AVI) constitutes the first validated instrument for voice complaints specifically for the elderly. The evidence suggests that the bedrock of treating presbylaryngis centres on voice therapy. Thus, voice therapy should represent the primary treatment offered with surgery reserved for those failing to adequately respond. However, the comparative effectiveness of the different surgical interventions, namely injection laryngoplasty and thyroplasty, remains undetermined highlighting the need for larger, prospective, comparative studies. Summary Presbylaryngis is characterized by specific changes at the microscopic level resulting in age-related vocal fold atrophy. However, its presence alone does not always result in symptomatic dysphonia and equally, presbyphonia is often multifactorial involving the lower respiratory tract in addition to the larynx. Thus, the role of a multidisciplinary voice clinic for presbylaryngis cannot be overstated.

Surgical and therapeutic advances in the management of voice problems in children and young people Purpose of review The current article reviews advances in both the assessment of paediatric voice disorders, as well as surgical, medical and therapeutic treatments. Recent findings It is important to evaluate the impact of a voice disorder from both the parent and child perspective. Outpatient laryngoscopy with stroboscopy is very possible even in young children; however, high-speed ultrasound is a plausible alternative. High-speed videolaryngoscopy, videokymography and dynamic computed tomography, offer potential for augmenting the assessment of vocal fold vibratory characteristics in children. The evidence to support the efficacy of both indirect and direct voice therapy interventions is growing. The management of vocal fold palsy has advanced to include laryngeal reinnervation. Intubation injury with/without surgical intervention offers challenge and gives rise to voice disorders that may be lifelong. Summary Although assessment and management practices of paediatric voice disorders closely follow those applied to adults, there are important differences and a developmental approach is required when considering both surgical and therapeutic management. Children can benefit from both indirect and direct therapy treatments following an ear, nose and throat assessment which utilizes paediatric instrumentation and considers the health of the entire airway. Underlying medical contributory factors should be explored and treated. Voice disorders due to congenital and acquired changes of the vocal tract may be amenable to surgery.

Management of benign vocal fold lesions: current perspectives on the role for voice therapy Purpose of review Benign vocal fold lesions (BVFLs) cause dysphonia by preventing full vocal fold closure, interrupting vibratory characteristics and increasing compensatory muscle tension. Management includes phonosurgery, voice therapy, pharmacological treatment or more commonly a combination of these interventions. This review aims to present current perspectives on the management of BVFLs, particularly exploring the role of voice therapy. Recent findings The review highlights variation in the management of BVFLs. There is evidence that phonosurgery is a well tolerated and effective intervention for BVFLs. Primary voice therapy can frequently prevent surgery in vocal fold nodules and some types of polyps. Used as an adjunct to phonosurgery, preoperative and postoperative voice therapy can improve patient-reported outcomes and acoustic parameters of the voice. However, heterogeneity of studies and poor descriptions of intervention components prevent a robust analysis of the impact of voice therapy. Summary The current evidence consists of low-level studies using mixed aetiology groups, which compromises internal and external validity. There are a few exceptions to this. Poor reporting and heterogeneous methodologies lead to difficulties determining the components of a voice therapy intervention for this population. Consequently, we are unable to evaluate, which intervention elements are beneficial to patients.

Editorial: Priority setting in otolaryngology in under resourced settings: practical and ethical dilemma No abstract available

Overcoming developing world challenges of cochlear implantation: Chinese perspective Purpose of review Over a short period, China has adopted cochlear implants and emerged as a burgeoning market. This represents a valuable case study for emerging countries in terms of planning, initiating, and growing cochlear implant programs. Recent findings Although many challenges such as funding, establishing infrastructure, and recipient community support have been addressed, many more remain. Consistent rapid escalation in numbers has been driven by push-and-pull factors. Federal, state, and private funding have all played a role. Summary The review highlights the massive need for hearing rehabilitation that currently exists in China. The shortfall can only be addressed by a purposeful and coordinated approach involving government policy, The China Disabled Persons Federation, the industry partnering with hearing and medical professionals and the deaf community.

Priority setting in head and neck oncology in low-resource environments Purpose of review Most information about priority setting comes from developed countries. In low-resource settings, many factors should be considered to select the best candidate for the treatments that are available. The physician is always under pressure to obtain better results in spite of the lower quantity of resources. This exposes physicians to daily ethical dilemmas and increases their anxiety and burnout. Recent findings Most low-resource settings have restrictions in major treatments, and the number of specialized centers that have all the services is low. The surgeon has to navigate through the system as a patient advocate, taking the responsibilities of other health system actors, has to 'negotiate' to design a treatment based on outdated results or to wait for new results and has to decide whether to start or to wait for other treatments to be ready to comply with protocol recommendations. Summary The surgeons face the dilemma of offering the best treatment with scarce resources but with a higher possibility of completion. Finally, we must do the best we can with what we have.

Challenges in the delivery of surgical care for head and neck cancer patients in the Hong Kong Special Administrative Region and China Purpose of review This article aims to explore the ethical dilemmas faced by head and neck surgeons in the Hong Kong Special Administrative Region (HKSAR) and China in the provision of safe, oncological sound and timely care for head and neck cancer patients. Recent findings There is no literature, in particular, in relation to the treatment of head and neck cancer patients and priority setting in head and neck surgery. However, through examining the healthcare provision and sociocultural backgrounds of the HKSAR and China, certain aspects, such as traditional Chinese medicine and medical guan xi (Seeking medical care for personal connections) have been shown to significantly influence the provision of care in China. Medical guan xi facilitates inequity and is problematic in developing a system based on justice, equity, nonmalfeasance and beneficence. In the HKSAR, resource limitations are related to the maldistribution of healthcare between the public and private sectors, resulting in significant time constraints for surgery and oncology care of patients. There is informal application of ethical frameworks for priority setting, however, these have neither been formally supported nor enforced from an administrative level that needs to be addressed. Summary In the HKSAR, there needs to be a strengthening of an ethical framework for priority setting to adhere to justice for our patients and healthcare providers in treating head and neck cancer patients. In China, priority setting is largely set by sociocultural practices that are endemic, in particular, medical guan xi that is inequitable and needs to be addressed to improve the doctor–patient relationship.

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Alexandros Sfakianakis
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