Takayuki Okano

BACKGROUND/OBJECTIVES: The OTOG gene is responsible for autosomal recessive non-syndromic sensorineural hearing loss and is assigned as DFNB18B. To date, 44 causative OTOG variants have been reported to cause non-syndromic hearing loss. However, the detailed clinical features for OTOG-associated hearing loss remain unclear. METHODS: In this study, we analyzed 7065 patients with non-syndromic hearing loss (mean age 26.4 ± 22.9 years, 2988 male, 3855 female, and 222 without gender information) using massively parallel DNA sequencing for 158 target deafness genes. We identified the patients with biallelic OTOG variants and summarized the clinical characteristics. RESULTS: Among the 7065 patients, we identified 14 possibly disease-causing OTOG variants in 26 probands, with 13 of the 14 variants regarded as novel. Patients with OTOG-associated hearing loss mostly showed congenital or childhood-onset hearing loss. They were considered to show non-progressive, mild-to-moderate hearing loss. There were no symptoms that accompanied the hearing loss in OTOG-associated hearing loss patients. CONCLUSIONS: We confirmed non-progressive, mild-to-moderate hearing loss as the clinical characteristics of OTOG-associated hearing loss. These findings will contribute to a better understanding of the clinical features of OTOG-associated HL and will be useful in clinical practice.

OBJECTIVE: To determine whether the combination of the pharyngeal tonsil grade and palatine tonsil grade results in differences in the apnea-hypopnea index (AHI) and to determine whether each parameter separately (pharyngeal tonsil grade and palatine tonsil grade) results in differences in severe obstructive sleep apnea (OSA). METHODS: This cross-sectional study involved 107 children (mean age, 7.2 years; range, 4-12 years) suspected of having OSA because of snoring or sleep-related complaints. The patients underwent polysomnography, and their palatine and pharyngeal tonsils were graded. RESULTS: In examining whether the palatine tonsils and pharyngeal tonsils could be risk factors for severe OSA, the adjusted odds ratios were 4.42 for palatine tonsil grade 4 versus 1-3 and 10.40 for pharyngeal tonsil grade 4 versus 1-3; both were highly statistically significant. We also found that the AHI when both the pharyngeal and palatine tonsils were grade 4 was higher than the AHI expected for the pharyngeal and palatine tonsils alone. CONCLUSIONS: The combination of grade 4 pharyngeal tonsils and grade 4 palatine tonsils resulted in an AHI much higher than the AHI of other combinations (pharyngeal tonsils grades 1-3 and 4, palatine tonsils grades 1-3 and 4). We believe that grade 4 pharyngeal tonsils and grade 4 palatine tonsils have a great influence on severe OSA and that grade 4 pharyngeal tonsils increase the AHI.

OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of microdebrider adenoidectomy on sleep-disordered breathing among pediatric patients with OSA. METHODS: In the microdebrider group (Group I), there were 30 Japanese OSA patients consisting of 26 boys and 4 girls. For comparison, we had 15 children (13 boys and 2 girls) who underwent classical adenoidectomy (Group II). Patients in Group I were selected from a pool of 95 pediatric Japanese OSA patients and were matched by age, preoperative AHI, and Kaup index with those in Group II.Parameters such as the amount of residual adenoid tissue, bleeding, duration of the procedure, and sleep-related metrics were compared between the two groups. RESULTS: A significant improvement in postoperative AHI was observed in Group I (p<0.05). The prevalence of AHI <1 was significantly higher in Group I compared with Group II (p<0.05). Additionally, the amount of postoperative residual adenoid was significantly less in Group I (3/30 of Grade 3 and 4 adenoid size) than in Group II (7/15, p<0.05). Furthermore, a reduction in postoperative AHI was proportionally associated with a decrease in residual adenoid. CONCLUSIONS: The newly developed microdebrider adenoidectomy technique for pediatric OSA patients with adenotonsillar hypertrophy demonstrated greater accuracy and efficacy in ameliorating sleep apnea symptoms compared with the standard adenoidectomy approach.

OBJECTIVES: In the present study, we performed a detailed analysis of deglutitive dynamics during sleep in patients with obstructive sleep apnea (OSA) using a methodology developed by Sato et al. We hypothesized that the frequency of deglutition would decrease with increasing severity of OSA. The aim of this study is to clarify the involvement of deglutitive dynamics during sleep in OSA by investigating the correlations between deglutition and sleep parameters. METHODS: This study included 30 adult patients with OSA. To analyze deglutition dynamics during sleep, surface electromyography recordings of the suprahyoid and thyrohyoid neck muscles, which are involved in deglutition, were performed simultaneous with conventional polysomnography. The "index of deglutition" was defined as the frequency of deglutition per hour of sleep. We examined correlations between this index and sleep parameters (apnea-hypopnea index [AHI], apnea index, hypopnea index, and lowest blood oxygen saturation). RESULTS: By analyzing the obtained polysomnography and electromyography waveforms, we identified two deglutition patterns with and without respiratory arousal during sleep. We found a significant negative correlation between the index of deglutition in sleep stage 1 and the AHI, with a correlation coefficient of -0.48. (p=0.02). CONCLUSIONS: In the current study, we distinguished deglutition during sleep with and without arousal. In addition we discovered a significant negative correlation between the index of deglutition in sleep stage 1 and the AHI. This new finding will provide a platform for future research on OSA in aspiration pneumonia.

BACKGROUND: There has been a significant increase in scientific investigations of the hearing-dementia association among the research on potentially modifiable risk factors for cognitive impairment. We tested two clinical questions. Analysis 1: does persistent hearing aid (HA) use decrease the decline in cognitive function caused by ageing? Analysis 2: does cognitive function at the time of HA fitting predict future persistent HA use? METHODS: This case-control study performed at two referral centres reported data obtained over a 4.5-year period. We recruited a group of patients with cognitive decline, aged 65 or older with or without hearing loss. The intervention consisted of the use of HAs. The primary outcome measures were adherence to continuous HA use and cognitive function measured using the Japanese version of the Mini-Mental State Examination Test and the Reading Cognitive Test Kyoto. RESULTS: Eighteen HA users and 18 controls were included in the first analysis. HA use was associated with a deceleration of cognitive decline 12 months later. In the second analysis, 11 participants with good adherence to HA use were compared with 12 participants who showed poor adherence to HA use. Among the variables employed in this study, cognitive function measured using the Reading Cognitive Test Kyoto was significantly lower in participants with poor adherence to HA. CONCLUSIONS: HA use in cognitively impaired individuals with hearing loss can slow age-related cognitive decline. Cognitively impaired people with hearing loss who fail to commit to HA use tend to have lower cognitive measurement scores before HA fitting. HA use is generally more challenging as people age and their cognitive abilities decline. Therefore, it is desirable that HAs be used when hearing loss and dementia are in their early stages.

The percentage of macrophage subpopulations based on their origins in the adult cochlea remains unclear. This study aimed to elucidate the origins of cochlear macrophages during the onset phase and development of auditory function. We used three types of mice: wildtype ICR mice, colony-stimulating factor 1 receptor (Csf1r)-deficient mice, and Ms4a3Cre-Rosa tdTomato (Ms4a3tdT) transgenic mice. Macrophages were labeled with ionized calcium-binding adapter molecule 1 (Iba1), which is specific to more mature macrophages, and CD11b, which is specific to monocyte lineage. We investigated the spatial and temporal distribution patterns of resident macrophages in the cochlea during the postnatal and early adult stages. During the adult stages, the rate of monocytes recruited from the systemic circulation increased; moreover, Iba1+/CD11b- cochlear macrophages gradually decreased with age. Fate mapping of monocytes using Ms4a3tdT transgenic mice revealed an increased proportion of bone marrow-derived cochlear macrophages in the adult stage. Contrastingly, the proportion of yolk sac- and fetal liver-derived tissue-resident macrophages decreased steadily with age. This heterogeneity could be attributed to differences in environmental niches within the tissue or at the sub-tissue levels. Future studies should investigate the role of cochlear macrophages in homeostasis, inflammation, and other diseases, including infection, autoimmune, and metabolic diseases.

Abstract Inflammatory bowel disease (IBD) is an autoimmune condition often accompanied by extraintestinal manifestations including arthritis. However, hearing loss as an extraintestinal manifestation of IBD is rarely reported. This study aimed to investigate the clinical characteristics of sensorineural hearing loss associated with IBD. This study included patients with IBD and hearing loss who were registered between October 2005 and September 2022. The patients were diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) by gastroenterologists in addition to sensorineural hearing loss of unknown etiology confirmed by otolaryngologists. Overall, 32 patients aged 10 to 78 years were included, consisting of 9 women, 18 patients with UC, and 14 patients with CD. Hearing loss associated with IBD was more common among men, with a median onset age of 56 years for UC and 33 years for CD. Two patients reported hearing loss in both ears before IBD onset, whereas 38 ears in 30 patients presented hearing loss after IBD onset. Various types of hearing loss were observed in the 42 affected ears. Further, hearing loss typically developed within 10 years of IBD diagnosis in approximately 63% of cases, with a median interval of 9 years among the 32 cases. In some cases, azathioprine and infliximab, therapeutic agents for IBD, were suspected to have contributed to the hearing loss. No other IBD medications were suspected to contribute to the hearing loss in any patient. The pathogenesis of hearing loss in IBD remains unclear; further large-scale investigations are warranted to elucidate the relationship between IBD and sensorineural hearing loss and to better understand the underlying pathophysiology.

OBJECTIVE: This study aimed to longitudinally evaluate speech perception ability and sound-field thresholds with the first, second, or bilateral cochlear implants (CIs) and MAP parameters of second CI in children. METHODS: Eighteen children who underwent bilateral cochlear implantation at Kyoto University Hospital were included. We evaluated speech perception under quiet and noisy conditions using the first, second, or bilateral CIs, CI-aided sound-field thresholds using the first or second CI, and MAP parameter values (C-levels, T-levels, and dynamic range) of the second CI of more than 5 years after the second implantation. RESULTS: Patients with a second CI after 7 years of age had significantly worse speech perception ability with the second CI even long after the surgery than those with a second CI before 7 years of age. CI-aided sound-field thresholds using the first or second CI were similar, regardless of the second implantation timing. Speech perception in noise with bilateral CIs was enhanced by the addition of a second CI, even after 7 years of age. Patients undergoing second cochlear implantation before 3.5 years of age showed significantly higher C-levels and wider dynamic ranges in the second CI MAP parameters. CONCLUSIONS: When the second implantation was performed after 7 years of age, the second CI effects were limited even with long-term use, which is attributed to unstable MAP parameters. The second CI-aided sound-field threshold contributed to the better outcome of bilateral CIs in noise, even if the second implantation was performed at age of ≥7 years.

OBJECTIVE: This study aimed to evaluate the importance of mobile cone-beam computed tomography in detecting tip fold-over of a slim modiolar electrode within the cochlea during surgery. STUDY DESIGN: Retrospective case review. SETTING: Tertiary medical center. METHODS: From January 2020 to June 2022, 33 ears of 30 patients with normal cochlear morphology underwent cochlear implantation with slim modiolar electrodes and intraoperative mobile cone-beam computed tomography imaging. Furthermore, we retrospectively reviewed the medical records and images. RESULTS: The tip fold-over of the electrodes was detected using mobile cone-beam computed tomography in 3 out of 33 ears (9.1%). We could not identify the tip fold-over by scouting plain X-ray images in 2 out of 3 cases before taking the cone-beam computed tomography images. Electrode removal and reinsertion were performed before wound closure and the successful reinsertion was confirmed by mobile cone-beam computed tomography. The folded electrode tips were located at 238.8°, 152°, and 185.8°. CONCLUSION: Intraoperative mobile cone-beam computed tomography is useful in detecting the tip fold-over of the slim modiolar electrodes during surgery. Therefore, it was possible to reinsert the electrodes in all cases before closing the wound, eliminating the need for revision surgeries. Moreover, the analysis of mobile cone-beam computed tomography images may help to elucidate the mechanisms of electrode tip fold-over.

OBJECTIVE: Cleft palate (CP) in children is frequently complicated by otitis media with effusion (OME) due to Eustachian tube dysfunction. Although tympanostomy tube (TT) placement can be beneficial in the treatment of OME to prevent short-term hearing loss, there is no consensus regarding the indications for and timing of TT insertion. The present study was performed to define the safety and effectiveness of simultaneous TT placement with palatoplasty during the language-acquisition period. METHODS: We retrospectively reviewed the medical charts of pediatric patients who underwent palatoplasty for CP in a tertiary medical center, Kyoto University Hospital, from June 2010 to October 2018. The TT retention time was estimated using the Kaplan-Meier method. The incidence of OME recurrence was compared among four Veau classification groups based on the patients' sex, type of CP, median TT retention time, and type of fluid. RESULTS: Seventy-six subjects (150 ears) were enrolled in the study. The median follow-up duration was 48.7 months (range, 18.2-108.0 months) after the first TT placement. A first TT retention time of <20.1 months was a significant risk factor for OME recurrence. Subjects with maxillofacial anomaly complex and subjects with cleft lip and palate and an alveolar cleft showed a significantly higher OME recurrence rate than subjects with clefts only in the hard and/or soft palate. There was no significant difference in the occurrence of sequelae between subjects with only a single TT placement and subjects with more than one TT placement. CONCLUSIONS: Based on the findings of the present study, it is reasonable to perform TT insertion at the same time as palatoplasty on patients who meet the indications. This technique may reduce the number of times the patient requires general anesthesia and maintain good middle ear condition during the period of language acquisition between 1 and 3 years of age.

Glutaraldehyde, a germicide for reprocessing endoscopes that is important for hygiene in the clinic, might be hazardous to humans. Electrolyzed acid water (EAW) has a broad anti-microbial spectrum and safety profile and might be a glutaraldehyde alternative. We sought to assess EAW disinfection of flexible endoscopes in clinical otorhinolaryngological settings and its in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bacteria commonly isolated in otorhinolaryngology. Ninety endoscopes were tested for bacterial contamination before and after endoscope disinfection with EAW. The species and strains of bacteria were studied. The in vitro inactivation of bacteria and SARS-CoV-2 by EAW was investigated to determine the efficacy of endoscope disinfection. More than 20 colony-forming units of bacteria at one or more sampling sites were detected in 75/90 microbiological cultures of samples from clinically used endoscopes (83.3%). The most common genus detected was Staphylococcus followed by Cutibacterium and Corynebacterium at all sites including the ears, noses, and throats. In the in vitro study, more than 107 CFU/mL of all bacterial species examined were reduced to below the detection limit (<10 CFU/mL) within 30 s after contact with EAW. When SARS-CoV-2 was treated with a 99-fold volume of EAW, the initial viral titer (> 105 PFU) was decreased to less than 5 PFU. Effective inactivation of SARS-CoV-2 was also observed with a 19:1 ratio of EAW to the virus. EAW effectively reprocessed flexible endoscopes contributing to infection control in medical institutions in the era of the coronavirus disease 2019 pandemic.

OBJECTIVE: Bone conduction hearing aids are the only non-surgical devices used for conductive hearing loss. However, they are impractical for lifelong use since they require close contact of the transducer with the head skin, causing skin erosion and discomfort. Bone conduction hearing implants and active middle ear implants do not present these issues; however, they require surgery and can sometimes cause issues in the skin surrounding the devices. This study aimed to develop a new bone conduction hearing device that does not exert pressure on the skin or require surgery. METHODS: Our device modified a piezoelectric element by using the skin of a pinna as one of the two electrodes of a conventional piezoelectric device. We compared the sound transmission of a speaker, a conventional piezoelectric device, or the new device to the guinea pig cochlea, a physiological sound transducer to the auditory nerve, in normal and air-conductive hearing loss conditions. RESULTS: The novel device transmitted sound to the cochlea even after causing air-conductive hearing loss. Its bone conduction was more efficient than the speaker and the conventional piezoelectric device. CONCLUSION: We developed a novel type of bone conduction device that efficiently transmits sound to the cochlea by skipping the external auditory canal, tympanic membrane, and middle ear ossicles. This device does not exert pressure on the skin that can result in skin damage, an adverse effect of a conventional bone conduction hearing aid. SIGNIFICANCE: Our novel hearing device can be used as a substitute for current bone-conduction hearing devices.

Macrophages play important roles in tissue homeostasis and inflammation. Recent studies have revealed that macrophages are dispersed in the inner ear and may play essential roles in eliciting an immune response. Autoinflammatory diseases comprise a family of immune-mediated diseases, some of which involve sensorineural hearing loss, indicating that similar mechanisms may underlie the pathogenesis of immune-mediated hearing loss. Autoimmune inner ear disease (AIED) is an idiopathic disorder characterized by unexpected hearing loss. Tissue macrophages in the inner ear represent a potential target for modulation of the local immune response in patients with AIED/autoinflammatory diseases. In this review, we describe the relationship between cochlear macrophages and the pathophysiology of AIED/autoinflammatory disease.

OBJECTIVE: To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue. METHODS: This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study. RESULTS: Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred. CONCLUSION: The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

Sensorineural hearing loss is a common disability often caused by the loss of sensory hair cells in the cochlea. Hair cell (HCs) regeneration has long been the main target for the development of novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration is limited, but the auditory epithelia of non-mammalian organisms retain the capacity for hair cell regeneration. In the avian basilar papilla (BP), supporting cells (SCs), which give rise to regenerated hair cells, are usually quiescent. Hair cell loss induces both direct transdifferentiation and mitotic division of supporting cells. Here, we established an explant culture model for hair cell regeneration in chick basilar papillae and validated it for investigating the initial phase of hair cell regeneration. The histological assessment demonstrated hair cell regeneration via direct transdifferentiation of supporting cells. Labeling with 5-ethynyl-2'-deoxyuridine (EdU) revealed the occurrence of mitotic division in the supporting cells at specific locations in the basilar papillae, while no EdU labeling was observed in newly generated hair cells. RNA sequencing indicated alterations in known signaling pathways associated with hair cell regeneration, consistent with previous findings. Also, unbiased analyses of RNA sequencing data revealed novel genes and signaling pathways that may be related to the induction of supporting cell activation in the chick basilar papillae. These results indicate the advantages of our explant culture model of the chick basilar papillae for exploring the molecular mechanisms of hair cell regeneration.

BACKGROUND: Early detection of cognitive decline allows timely intervention to delay progression of dementia. However, current cognitive evaluation tools often include items delivered via verbal forms of instruction, which can cause poor performance in patients with hearing loss. OBJECTIVE: To develop and validate a cognitive screening battery, the Reading Cognitive Test Kyoto (ReaCT Kyoto), comprising test items given through non-verbal instruction. METHODS: A cross-sectional and multi-center study was conducted in the three medical institutes. ReaCT Kyoto was designed to evaluate domains of "registration," "repetition," "delayed recall," "visuospatial recognition," "orientation in time and place," and "executive function." The Japanese version of the Mini-Mental State Examination Test (MMSE-J) and ReaCT Kyoto were applied by experienced psychotherapists. Concurrent validity was evaluated between the ReaCT Kyoto Test and MMSE-J and between the ReaCT Kyoto Test and physician-diagnosed dementia. RESULTS: ReaCT Kyoto was validated in a sample of 115 participants. The mean age of subjects was 81.0±6.4 years, and the sample comprised 53.0% females. The area under the receiver operating curves was 0.95 for detecting physician-diagnosed dementia. When classifying patients in accordance with presence or absence of hearing loss, the AUCs were 0.93 and 0.97 for those with and without hearing loss, respectively. With a cut-off score of < 29 points for suspected dementia, ReaCT Kyoto correctly classified 90.4% of the subjects as belonging to the group with or without physician-diagnosed dementia. CONCLUSION: ReaCT Kyoto provides an appropriate solution for detection of cognitive impairment in persons with or without hearing loss.

OBJECTIVE: This study aims to evaluate the speech perception with first, second, or bilateral cochlear implants (CI) and to reveal the effects of wearing bilateral CI in children. METHODS: After reviewing the medical records, a total of 19 children who underwent bilateral cochlear implantation serially between 2012 and 2015 at Kyoto University Hospital (tertiary referral center) were included in this study. All patients had no delay in language development. The study group comprised nine boys and ten girls, and their age ranged from 3 years 8 months to 12 years 5 months when they underwent the tests in this study. The mean and median ages were 8 years 6 months and 9 years 2 months, respectively. We measured the appropriate signal/noise ratio (SNR) to test speech perception of Japanese language in noise by testing the hearing ability of unilateral CI patients with or without noise and by surveying the sound environment in a classroom of a mainstream elementary school. Speech perception in quiet and noise and the left-right localization ability were examined using first, second, or bilateral cochlear implants in all patients. RESULTS: Considering the results of hearing ability tests with noise and the SNR of the elementary school classrooms, we decided to use SNR of +10 dB to evaluate the speech perception ability in noise. The speech perception ability using the second CI was significantly worse in patients undergoing second cochlear implantation after 7 years old than in those who underwent surgery before 3.5 years old. Moreover, patients undergoing second cochlear implantation before 7 years old showed significantly better left-right localization of high-frequency sound. CONCLUSIONS: Second cochlear implantation before 7 years old is a critical factor in acquiring beneficial speech perception ability with the second CI and sound localization ability with the bilateral CI.

The development of asymmetric patterns along biologically relevant axes is a hallmark of many vertebrate organs or structures. One example is the sensory epithelium of the mammalian auditory system. Two distinct types of mechanosensory hair cells (inner and outer) and at least six types of associated supporting cells are precisely and asymmetrically arrayed along the radial (medial-lateral) axis of the cochlear spiral. Immunolabeling of developing cochleae indicates differential expression of Glycogen synthase kinase 3β (GSK3β) along the same axis. To determine whether GSK3β plays a role in specification of cell fates along the medial-lateral axis, GSK3 activity was blocked pharmacologically in cochlear explants. Results indicate significant changes in both the number of hair cells and in the specification of hair cell phenotypes. The overall number of inner hair cells increased as a result of both a shift in the medial boundary between sensory and non-sensory regions of the cochlea and a change in the specification of inner and outer hair cell phenotypes. Previous studies have inhibited GSK3 as a method to examine effects of canonical Wnt signaling. However, quantification of changes in Wnt pathway target genes in GSK3-inhibited cochleae, and treatment with more specific Wnt agonists, indicated that the Wnt pathway is not activated. Instead, expression of Bmp4 in a population of GSK3β-expressing cells was shown to be down-regulated. Finally, addition of BMP4 to GSK3-inhibited cochleae achieved a partial rescue of the hair cell phenotype. These results demonstrate a role for GSK3β in the specification of cellular identities along the medial-lateral axis of the cochlea and provide evidence for a positive role for GSK3β in the expression of Bmp4.

OBJECTIVE: To evaluate the electrode status during cochlear implantation (CI) using mobile cone-beam CT (mCBCT). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: Fifty-seven patients (7 bilateral surgeries, 64 ears) who underwent CI and who received intraoperative mCBCT imaging. INTERVENTION: CI and CBCT during surgery. MAIN OUTCOME MEASURE: Electrode location and angular insertion depth determined by intraoperative mCBCT images. RESULTS: There were six cases with cochlear malformation where intraoperative mCBCT was useful to confirm electrode location. Of 58 ears with a normal cochlear morphology, perimodiolar, straight, and mid-scalar electrodes were used in 30 (cochleostomy; 14 advance off-stylet technique cases), 27 (26 round window [RW] insertion, 1 extended round window [ERW] insertion), and 1 (RW insertion) ears, respectively. Complete scala-tympani (ST) insertion was achieved in 35 ears (14 cochleostomy, 21 RW or ERW insertion). The complete ST-insertion rate was significantly higher with RW or ERW insertion than that for cochleostomy insertion (p = 0.03), although cochleostomy insertion using the advanced off-stylet technique had a similar rate to RW or ERW insertion. The angular insertion depth values (average ± standard deviation) for perimodiolar electrodes (354.4 ± 29.44 degrees) were significantly smaller than those for Flex24 (464.8 ± 43.09 degrees) and Flex28 (518.2 ± 61.91 degrees) electrodes (p < 0.05). CONCLUSIONS: Evaluation of CI electrodes using intraoperative mCBCT was comparable to that with fan-beam CT or c-arm-based CBCT. Considering the low radiation dose of mCBCT and its availability in any operation room, mCBCT is the better modality for evaluating cochlear implant electrode arrays.

Resident macrophages reside in all tissues throughout the body and play a central role in both tissue homeostasis and inflammation. Although the inner ear was once believed to be "immune-privileged," recent studies have shown that macrophages are distributed in the cochlea and may play important roles in the immune system thereof. Resident macrophages have heterogeneous origins among tissues and throughout developmental stages. However, the origins of embryonic cochlear macrophages remain unknown. Here, we show that the early development of resident macrophages in the mouse cochlea depends on yolk sac hematopoiesis. Accordingly, our results found that macrophages emerging around the developing otocyst at E10.5 exhibited dynamic changes in distribution and in situ proliferative capacity during embryonic and neonatal stages. Cochlear examination in Csf1r-null mice revealed a substantial decrease in the number of Iba1-positive macrophages in the spiral ganglion and spiral ligament, whereas they were still observed in the cochlear mesenchyme or on the intraluminal surface of the perilymphatic space. Our results demonstrated that two subtypes of resident macrophages are present in the embryonic cochlea, one being Csf1r-dependent macrophages that originate from the yolk sac and the other being Csf1r-independent macrophages that appear to be derived from the fetal liver via systemic circulation. We consider the present study to be a starting point for elucidating the roles of embryonic cochlear resident macrophages. Furthermore, resident macrophages in the embryonic cochlea could be a novel target for the treatment of various inner ear disorders.

In the mammalian cochlea, resident macrophages settle in the spiral ligament, spiral ganglion, and stria vascularis, even at the steady state. Resident macrophages in the cochlea are believed to maintain homeostasis in the inner ear and become active, as part of the front line defense, following inner ear damage. However, the exact roles of cochlear resident macrophages require further clarification. Colony stimulating factor-1 (Csf1) signaling regulates survival, proliferation, and differentiation of resident macrophages and appears to be essential for resident macrophages in the inner ear. To examine the roles of Csf1 signaling in auditory function, we examined the ossicles and inner ear of homozygous Csf1 mutant (Csf1op/op ) mice. The ossicles including the incus and stapes of Csf1op/op mice macroscopically demonstrated bone thickening, and the otic capsules of the inner ear were also thick and opaque. Histological analyses demonstrated that the otic capsules in Csf1op/op mice were thickened and showed spongy bone degeneration. Measurements of the auditory brainstem response revealed significant elevation of thresholds in 4-week old Csf1op/op mice compared with wild-type littermates, indicating that Csf1op/op mice demonstrate hearing loss due to, at least in part, deformity of the ossicles and bone capsule of the inner ear. Furthermore, Csf1op/op mice are deficient in the number of resident macrophages in the spiral ligament and stria vascularis, but not in the spiral ganglion. These data provide evidence that Csf1 signaling is important not only for bone formation in the inner ear, but also for the maintenance of resident macrophages in the spiral ligament and stria vascularis in the adult mouse cochlea.

OBJECTIVES: The experimental studies suggested the hypothesis that the accumulation of advanced glycation end-products (AGEs) could induce hearing impairment. The purpose of this study is to examine the hypothesis among elderly people using an epidemiologic approach. DESIGN: Cross-sectional study. SETTING: Sukagawa City, Fukushima, Japan. PARTICIPANTS: A total of 270 residents aged 75 years or over without dementia, who participated in a health check-up conducted in 2015. MEASUREMENTS: The exposure variable was AGEs, which was assessed using skin autofluorescence (AF) as a proxy measure. The primary outcome was moderate hearing impairment or worse, which was defined as a pure tone average of thresholds ≥41 decibel hearing level at 0.5, 1, 2, and 4 kHz in the better-hearing ear. The secondary outcome was the pure tone average of thresholds as a continuous variable. We estimated the odds ratio using a logistic regression model for the primary outcome and a general linear model for the mean difference in the pure tone average of thresholds for the secondary outcome. Both models were adjusted for relevant confounding factors: age, sex, smoking, diabetes, hypertension, and history of cerebrovascular diseases. RESULTS: The median (interquartile range) AF was 2.2 (2.0, 2.5) arbitrary units (AU). Moderate hearing impairment was reported in 88 participants (32.6%). For the primary outcome, we found significant associations between moderate hearing impairment and AF (adjusted odds ratio per 1 AU, 2.60; 95% confidence interval 1.26-5.35). For the secondary outcome, we also found a significant association between a 1-AU increase in AF and increased pure tone average, with a difference (6.52 dB per 1 AU; 95% confidence interval 2.18-10.86) comparable in magnitude to the increase in pure tone average observed for a 6-year increase in age in our population. CONCLUSIONS: Our study indicated that high levels of AGEs were independently associated with hearing impairment. Modifying levels of AGEs may prevent hearing impairment.