Despite recent advances in genome engineering technologies, traditional transgenic mice generated on a mixed genetic background of C57BL/6 and 129/Sv mice remain widely used in age-related hearing loss (AHL) research, since C57BL/6 mice exhibit early onset and progression of AHL due to a mutation in cadherin 23-encoding gene (Cdh23753G>A). In these transgenic mice, backcrossing for more than 10 generations results in replacement of the donor background (129/Sv) with that of the recipient (C57BL/6), so that approximately 99.9% of genes are C57BL/6-derived and are considered congenic. However, the regions flanking the target gene may still be of 129/Sv origin, creating a so-called "passenger gene problem" where the normal 129/Sv-derived Cdh23753G allele can travel with the target gene. In this study, we investigated the role of fatty acid-binding protein 7 (Fabp7), which is important for cellular uptake and intracellular trafficking of fatty acids in the cochlea, using traditional Fabp7 knockout (KO) mice on the C57BL/6 background. We found that Fabp7 KO mice showed delayed AHL progression and milder cochlear degeneration. However, the genotype of the Cdh23 region flanking Fabp7 was still that of 129/Sv origin (Cdh23753GG). Our findings reveal the potential risk of contamination for traditional transgenic mice generated on the C57BL/6 background.

The use of viral vectors for inner ear gene therapy is receiving increased attention for treatment of genetic hearing disorders. Most animal studies to date have injected viral suspensions into neonatal ears, via the round window membrane. Achieving transduction of hair cells, or sensory neurons, throughout the cochlea has proven difficult, and no studies have been able to efficiently transduce sensory cells in adult ears while maintaining normal cochlear function. Here, we show, for the first time, successful transduction of all inner hair cells and the majority of outer hair cells in an adult cochlea via virus injection into the posterior semicircular canal. We used a "designer" AAV, AAV2/Anc80L65, in which the main capsid proteins approximate the ancestral sequence state of AAV1, 2, 8, and 9. Our injections also transduced ~10% of spiral ganglion cells and a much larger fraction of their satellite cells. In the vestibular sensory epithelia, the virus transduced large numbers of hair cells and virtually all the supporting cells, along with close to half of the vestibular ganglion cells. We conclude that this viral vector and this delivery route hold great promise for gene therapy applications in both cochlear and vestibular sense organs.

In acquired sensorineural hearing loss, such as that produced by noise or aging, there can be massive loss of the synaptic connections between cochlear sensory cells and primary sensory neurons, without loss of the sensory cells themselves. Because the cell bodies and central projections of these cochlear neurons survive for months to years, there is a long therapeutic window in which to re-establish functional connections and improve hearing ability. Here we show in noise-exposed mice that local delivery of neurotrophin-3 (NT-3) to the round window niche, 24 hours after an exposure that causes an immediate loss of up to 50% loss of synapses in the cochlear basal region, can regenerate pre- and post-synaptic elements at the hair cell / cochlear nerve interface. This synaptic regeneration, as documented by confocal microscopy of immunostained cochlear sensory epithelia, was coupled with a corresponding functional recovery, as seen in the suprathreshold amplitude of auditory brainstem response Wave 1. Cochlear delivery of neurotrophins in humans is likely achievable as an office procedure via transtympanic injection, making our results highly significant in a translational context.

Horizontal basal cells (HBCs) have garnered attention as tissue stem cells of the olfactory epithelium (OE); however, these cells' exact lineage and their contributions to OE regeneration remain unknown. Neural crest-derived cells (NCDCs) have been shown to possess stem cell properties and to participate in the normal development of the OE. However, the contributions of NCDCs to both normal and regenerating adult OE remain unclear. In this study, we investigated the contribution of NCDCs to the OE, focusing particularly on HBCs. Using immunohistochemistry, we observed the OE of P0-Cre/EGFP mice expressing EGFP-tagged NCDCs at several stages of normal development along with regenerated OE following methimazole treatment. We observed EGFP expression in the HBCs, sustentacular cells (SUSs), Bowman's glands, olfactory receptor neurons (ORNs), and olfactory ensheathing cells of 6-week-old mice. No ectopic Cre expression was identified. Although HBCs at late embryonic stages were placode-derived (i.e., EGFP-negative), we found that EGFP+ HBCs alternatively increased with the decrease of placode-derived HBCs during maturation. In regenerated OE, the percentages of neural crest-derived ORNs and SUSs significantly increased compared with normal OE. These results suggest that NCDCs contribute greatly to the adult HBC population and that they are important for the maintenance of the OE.

PURPOSE: Acoustic analysis is an objective and quantitative method in diagnosing speech disorders and evaluating treatment efficacy. Although many reports have used acoustic analysis for oral cancer patients, few studies have focused on the extent of tongue resection. The aim of this study was to evaluate the usefulness of acoustic analysis in the assessment of postoperative speech impairment in oral cancer patients. METHODS: Postoperative speech data as well as Speech Handicap Index (SHI) and 5-point speech intelligibility scale were collected from 65 patients including 31 cases of oral cancer resection without glossectomy, 18 cases of partial glossectomy, and 16 cases of subtotal glossectomy. Speech data were acoustically analyzed by triangular vowel space area, vowel articulation index (VAI), first (F1) and second (F2) formant slopes, and compared according to the extent of tongue resection. RESULTS: The frequency of speech impairment assessed by SHI and 5-point speech intelligibility scale was differed according to the extent of tongue resection. As acoustic analysis, VAI and F1 slope in cases of subtotal glossectomy were significantly smaller than those in cases of partial glossectomy. F2 slope in cases of subtotal glossectomy was significantly smaller than those in the other cases. CONCLUSION: Acoustic analysis was potentially useful as an objective speech assessment for the patients who underwent oral cancer surgery.

OBJECTIVE: Olfactory dysfunction (OD) compromises safety and well-being in humans; however, large-scale Japanese data are lacking. We quantified the prevalence of subjective chronic OD (self-reported olfactory impairment persisting ≥3 months), identified associated health and occupational factors, and evaluated determinants for severity using data from a nationwide web-based survey in Japan. METHODS: We analyzed data from the Japan coronavirus disease 2019 and Society Internet Survey 2023, a stratified, nationwide, cross-sectional survey of community-dwelling residents in Japan. From the initial 33,000 participants, we used the data of 25,569 participants (12,323 men, 13,246 women), after excluding those with implausible responses and missing data, to calculate prevalence. Inverse probability weighting was used to align the sample with the 2019 National Living Conditions Survey. Group differences concerning the presence and severity of OD were tested with χ² or Wilcoxon tests after excluding participants with additional missing data; independent associations were examined using weighted multivariable logistic regression analyses. RESULTS: The weighted prevalence for chronic subjective OD was 1.3 % (95 % confidence interval [CI] 1.1-1.4); age-specific rates ranged from 0.6 % (40-49 years) to 2.1 % (60-69 years). Independent OD correlates included the factors current smoking (odds ratio [OR] 2.09, p = 0.016), homeworking (OR 2.75, p = 0.004), somatic symptoms (Somatic Symptom Scale-8 score ≥ 12; OR 2.66, p = 0.009), dysgeusia (OR 193.2, p < 0.001), current hypertension (OR 3.69, p = 0.005), current bronchial asthma (OR 6.09, p < 0.001), current allergic rhinitis (OR 1.97, p = 0.012), and moderate-severe presenteeism (Work Functioning Impairment Scale score ≥ 21; OR 3.04, p < 0.020). Being a woman was associated with lower OD severity (OR 0.34, p = 0.035, for moderate-severe vs mild), whereas having ≥ 1 day of sick absences in the previous month was associated with higher OD severity (OR 3.17, p = 0.044). CONCLUSION: Subjective OD prevalence in Japan was 1.3 %. Presenteeism was associated with OD and absenteeism was associated with moderate-severe OD. Further studies on the relationship between OD and work productivity are warranted.

BACKGROUND: The three-dimensional (3D) exoscope is an emerging alternative to the operating microscope (OM) in otologic surgery. AIMS: To assess its clinical utility in cholesteatoma surgery. METHODS: Retrospective review of 36 primary cases (21 OM, 15 exoscope) comparing setup time, surgical duration, audiological outcomes, and recurrence. RESULTS: Groups were comparable in background and stage. Setup time was shorter with exoscope (microscope: 20 min, range 18-22, exoscope: 17 min, range 14-20) (p = .002), while other outcomes showed no significant difference. CONCLUSIONS: The 3D exoscope reduced setup time with equivalent surgical and functional outcomes to OM.

OBJECTIVE: This study aimed to investigate the utility of wideband tympanometry (WBT) in diagnosing patulous Eustachian tube (PET) by examining differences in middle ear absorbance and resonant frequency between PET patients and controls. STUDY DESIGN: This is a retrospective observational study. SETTING: This study was conducted at Iwate Medical University Hospital. SUBJECTS AND METHODS: A review of medical records identified 25 ears of 19 PET patients and 18 ears of 9 patients with sensorineural hearing loss or vertigo as a control group. Diagnosis of PET was based on Japan Otological Society criteria. WBT was conducted across frequencies of 226-8000 Hz, measuring ambient pressure absorbance ratios and peak pressure absorbance ratios, as well as resonant frequency (RF) values. RESULTS: The PET group demonstrated significantly lower absorbance at 1000 Hz (P = 0.006) compared with the control group, with no significant differences observed at other frequencies. The RF was significantly reduced in the PET group compared with controls (P < 0.001), indicating alterations in middle ear mechanics associated with PET. The Valsalva maneuver had no significant effect on absorbance values across frequencies. CONCLUSION: WBT is a valuable diagnostic tool for PET, with significant reductions in 1000 Hz absorbance and resonant frequency in PET patients. These parameters may serve as markers for PET, aiding in its differentiation from other middle ear conditions.

INTRODUCTION: Hearing loss is a major problem that negatively impacts human life worldwide. Although factors associated with hearing loss have been widely studied, the impact of hearing loss on social aspects such as work performance in the working-age population remains unclear. To investigate the social and somatic problems associated with hearing loss in working-age individuals, we analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), including a questionnaire concerning social aspects, mental health, physical health, and subjective hearing loss. METHODS: We used the JACSIS 2023 data set, which includes data from 33,000 participants. After excluding participants with inappropriate responses and including those aged 20-64 years, data from 20,691 participants were used for further analysis. We compared various characteristics of the hearing loss group (moderate-to-severe subjective hearing loss) with those of the control group (no subjective hearing loss). RESULTS: A total of 13,745 participants (male: 6,461; female: 7,284) were included in the control group, and 313 participants (male: 150; female: 163) were included in the hearing loss group. Multivariate logistic regression analysis revealed that both male and female participants in the hearing loss group exhibited higher incidences of tinnitus, presenteeism, somatic symptoms, and dyslipidemia compared with the control group. Additionally, subjective hearing loss was one of the independent explanatory variables for presenteeism in the working-age population. CONCLUSIONS: Our findings indicate significant associations between moderate-to-severe subjective hearing loss and various work-related and somatic factors in a working-age population, and encourage future research to assess whether subjective hearing loss independently contributes to presenteeism in the working-age population.

INTRODUCTION: Early detection of hearing impairment in young adults and raising social awareness of preventive measures are essential to mitigate the negative impact on individuals' quality of life and reduce the societal costs associated with hearing impairment. This study investigated the music listening habits of medical college students using audiological function tests to assess their impact on young adults' hearing functions. METHODS: We recruited 77 healthy volunteers who underwent a comprehensive assessment, including a questionnaire on music listening habits, pure-tone audiometry (PTA), tympanometry, extended high-frequency (EHF) audiometry, and loudness discomfort level (LDL) tests. Furthermore, we measured preferred music listening levels (PMLs). The association between music listening habits and PMLs and the results of various auditory function tests were examined. RESULTS: Among the 77 participants, 60 were men, and 17 were women, with a median age of 23 years. All participants exhibited a mean hearing threshold of less than 25 dB HL on PTA. Sixty-six (85.7%) participants used earphones/headphones daily, with a median usage duration of 2.0 hours. The correlations between the duration of earphones/headphones usage, EHF thresholds, and LDLs were not significantly different. The correlation between the duration of earphones/headphones usage and PMLs was weakly positive (r = 0.2772). A stronger positive correlation (r = 0.4625) was observed when focusing on 23 participants with high LDL values. CONCLUSIONS: The positive correlation between the duration of earphones/headphones usage and PMLs suggested that inappropriate music listening habits might synergistically act as risk factors for hearing impairment in young adults.

PURPOSE: To investigate the prevalence and characteristics of bifurcation of the facial nerve (FN) in the mastoid segment using temporal bone CT scans. METHODS: A total of 970 cases (1931 ears) of temporal bone CT scans were reviewed, including 463 females and 498 males, aged 1 to 95 years (interquartile range: 20-69 years). CT imaging with multiplanar reconstruction (MPR) was used to identify and evaluate the bifurcation of the FN. Cases showing branching were confirmed by consensus among three physicians. RESULTS: We identified 10 cases (10 ears) with facial nerve branching in the vertical segment, yielding an incidence rate of 0.52% (10/1931 ears). Every cases were unilateral, predominantly on the left side. Age analysis revealed 1 case (0.22%) in individuals under 20 years and 9 cases (0.61%) in those over 20 years. Bifurcation generally occurred near the middle to lower vertical segment, with the closest proximity to the second genu observed in a 15-year-old patient. CONCLUSIONS: Bifurcation of the FN in the mastoid segment, though rare, can be encountered in otologic surgery. Detailed preoperative imaging evaluations are crucial for surgical planning to minimize the risk of nerve damage. Our findings emphasize the importance of recognizing anatomical variations in the FN for improving surgical outcomes and patient safety.

OBJECTIVE: Dysphagia affects 2.3 %-16 % of the general population and increases with age. It can lead to malnutrition, weight loss, aspiration pneumonia, and emotional symptoms such as anxiety and depression. Mental health disorders impact appetite and muscle mass, further worsening dysphagia. Additionally, cultural and economic factors influence anxiety and depression, which can either result from or contribute to dysphagia. Studies on the relationship between anxiety, depression, and swallowing function using FEES are limited in Asian populations. The Hospital Anxiety and Depression Scale (HADS) is a useful tool for assessing mood disorders. Therefore, in this study, we aimed to investigate the associations among anxiety, depression, and swallowing function in Japanese patients with dysphagia using HADS. METHODS: Data on age; sex; HADS; Eating Assessment Tool-10 (EAT-10); Functional Oral Intake Scale (FOIS); tongue pressure; Hyodo score, a scoring system for evaluating the swallowing function determined by flexible endoscopic evaluation of swallowing (FEES); and videofluoroscopic dysphagia scale (VDS), assessed by videofluoroscopic swallowing study, were collected and analyzed from medical records. Hyodo score consists of four parameters: (1) salivary pooling in the vallecula and piriform sinuses; (2) glottal closure reflex or cough reflex induced by touching the epiglottis or arytenoid; (3) swallowing reflex induced by colored water; and (4) extent of pharyngeal clearance after colored water is swallowed. The Mann-Whitney U test, Fisher's exact test, and multiple logistic regression analyses were used to estimate associations between HADS and swallowing function. RESULTS: No significant relationships were observed between the EAT-10, FOIS, and VDS with HADS scores. Patients with depression were associated with a significantly higher percentage of anorexia complaints (p = 0.047). Lower tongue pressure was observed in patients with depression than in patients without depression (p = 0.002). Patients with anxiety had better swallowing function, as assessed by the Hyodo score (p = 0.047). Fluid clearance, a component of the Hyodo score, was significantly better in patients with anxiety (p = 0.03) even after propensity score matching adjusted for the effects of age, sex, and fluid clearance. CONCLUSION: In patients with anxiety, swallowing function assessed by FEES was favorable, whereas a higher proportion of patients with depression reported decreased appetite, and lower tongue pressure. This discrepancy between subjective dysphagia and FEES findings suggests that patients with anxiety may underestimate their swallowing function.

Transmembrane protein 135 (TMEM135) is a highly conserved 52 kDa protein with five predicted transmembrane domains that colocalizes with mitochondria and peroxisomes. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism across multiple tissues and species; however, its role in the inner ear and auditory system remains unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135FUN025/FUN025 (FUN025) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) thresholds at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing results, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and more modest changes in inner hair cell survival, spiral ganglion neuron density, and stria vascularis integrity in the cochlea. Our results using BaseScope RNA in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, supporting cells, and stria vascularis. Using Volocity software and Costes colocalization analysis, we found that TMEM135 closely colocalizes with mitochondria in hair cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.

OBJECTIVE: Pneumonia is a common complication and a significant cause of mortality following cardiovascular surgery. This study aimed to investigate the incidence and risk factors for pneumonia after thoracic aortic surgery. METHODS: A retrospective review was conducted on the medical records of 380 patients who underwent thoracic aortic surgery between January 2016 and December 2019. Patients were classified into pneumonia and non-pneumonia groups based on postoperative outcomes. Pneumonia was further categorized as aspiration pneumonia, ventilation-associated pneumonia (VAP), or other types. Risk factors were identified through univariate and multivariate analyses. RESULTS: Postoperative pneumonia during hospitalization occurred in 30 patients (7.9 %), including 18 cases of aspiration pneumonia (4.7 %) and 9 cases of VAP (2.4 %). Risk factors identified included hoarseness before surgery, aortic arch replacement, longer anesthesia time, longer intubation duration, necessity for tracheostomy, cerebrovascular disease after surgery, and postoperative recurrent laryngeal nerve paralysis. Multivariate analysis suggested that hoarseness before surgery and the necessity for tracheostomy were independent risk factors for pneumonia during hospitalization. CONCLUSION: This study identified key risk factors for postoperative pneumonia after thoracic aortic surgery. These findings may aid in identifying high-risk patients and implementing preventive strategies to reduce postoperative pneumonia.

OBJECTIVES: Ethanol consumption may lead to various symptoms depending on its concentration in the blood. Acute ethanol intoxication is a major risk factor for bolus -aspiration; however, studies on the effects of acute ethanol intoxication on swallowing are lacking. Therefore, we investigated the effect of acute ethanol intoxication on mice using the videofluoroscopic swallowing study (VFSS) methodology. METHODS: Male C57BL/6 J mice were randomly allocated into three groups: saline injection, 2 g/kg ethanol injection, and 4 g/kg ethanol injection. The VFSS technique was used to analyze the inter-swallow interval, lick-swallow rate, lick rate, bolus area, pharyngeal transit time, bolus speed, and bolus area 3 d before injection (control), 2 h after injection, and 8 h after injection. RESULTS: In the 4 g/kg ethanol injection group, the inter-swallow interval and lick-swallow rate increased after 2 h However, these changes were reversed 8 h after ethanol administration. Additionally, the pharyngeal transit time, bolus speed, and bolus area did not change significantly after ethanol administration. CONCLUSIONS: The present study reveals that ethanol administration delays bolus transport in the mouth but does not affect pharyngeal swallowing reflexes and reflex thresholds. Acute ethanol intoxication specifically impairs the oral function as assessed by the VFSS.

Videofluoroscopic swallow study methodology in mice has recently been established; however, details of developmental and age-related changes remain unclear. This study aimed to reveal the changes in swallowing associated with the entire lifespan of mice using the videofluoroscopic swallow study methodology. We tested six age groups of male C57BL/6J mice (4, 8, 16, 54, 77, and 104 weeks old; n = 5 for each group, respectively). The videofluoroscopic swallow study analyzed the bolus area, pharyngeal transit time, interswallow interval, lick-swallow ratio, and lick rate. Significant age differences were found in the bolus area and lick rate. The bolus area increased significantly as the mice grew older. There was a significant increase in the lick rate from 4 to 8 weeks (P < 0.001) and then a significant decrease from 8 to 104 weeks (P < 0.01). No significant difference was observed between the various stages in the lick-swallow ratio, interswallow interval, or pharyngeal transit time. There was a significant positive correlation between the body weight and bolus area. This study revealed the detailed changes in swallowing at each life stage from swallowing maturation to old age in the mice. Our research may serve as a guide for future studies on swallowing in humans.

With the increase in the older population, the number of individuals with age-related hearing loss is also growing explosively. Therefore, there is an urgent need to identify the detailed pathology of age-related hearing loss and develop novel treatment strategies. In this study, we have investigated the audiological physiology and cochlear pathology of advanced-age CBA/CaJ mice, a strain that resists early pathological hearing loss. The subjects were naturally aged close to their lifespan limit (> two years) under normal in vivo conditions. We used 11 CBA/CaJ mice aged between 129 and 138 weeks to establish an aged group. To compare the electrophysiological function and histological changes, a young group was established using 12 young mice aged between 9 and 14 weeks. The loss of outer hair cells peaked at 11.3 kHz, and the greatest synapse loss was observed in the 5.6 kHz region, which was covered by the dominant frequency in the ambient sound. Furthermore, atrophy and microthrombus formation occurred in the stria vascularis, with endolymphatic hydrops observed in the cochlear apical turn. In the spiral ganglion and cochlear nerve, a reduction in the number of cells was accompanied by morphological changes indicative of cell aging. Increased levels of derivative-reactive oxygen metabolites, an oxidative stress marker, were observed in aged mice. These results indicate that age-related hearing loss involves a combined pathology of acoustic cochlear damage, which is potentially associated with chronic sound exposure and metabolic changes owing to mitochondrial dysfunction and oxidative stress accumulation. Accordingly, these two distinct etiologies must be addressed to prevent and treat age-related hearing loss.

Aspiration pneumonia exacerbates swallowing and respiratory muscle atrophy. It induces respiratory muscle atrophy through three steps: proinflammatory cytokine production, caspase-3 and calpain, and then ubiquitin-proteasome activations. In addition, autophagy induces swallowing muscle atrophy. Nrf2 is the central detoxifying and antioxidant gene whose function in aspiration pneumonia is unclear. We explored the role of Nrf2 in aspiration pneumonia by examining swallowing and respiratory muscle mass and function using wild-type and Nrf2-knockout mice. Pepsin and lipopolysaccharide aspiration challenges caused aspiration pneumonia. The swallowing (digastric muscles) and respiratory (diaphragm) muscles were isolated. Quantitative RT-PCR and Western blotting were used to assess their proteolysis cascade. Pathological and videofluoroscopic examinations evaluated atrophy and swallowing function, respectively. Nrf2-knockouts showed exacerbated aspiration pneumonia compared with wild-types. Nrf2-knockouts exhibited more persistent and intense proinflammatory cytokine elevation than wild-types. In both mice, the challenge activated calpains and caspase-3 in the diaphragm but not in the digastric muscles. The digastric muscles showed extended autophagy activation in Nrf2-knockouts compared to wild-types. The diaphragms exhibited autophagy activation only in Nrf2-knockouts. Nrf2-knockouts showed worsened muscle atrophies and swallowing function compared with wild-types. Thus, activation of Nrf2 may alleviate inflammation, muscle atrophy, and function in aspiration pneumonia, a major health problem for the aging population, and may become a therapeutic target.

OBJECTIVES: To examine the effects of distractor sounds presented to the contralateral ear on speech intelligibility in patients with listening difficulties without apparent peripheral pathology and in control participants. DESIGN: This study examined and analyzed 15 control participants (age range, 22 to 30 years) without any complaints of listening difficulties and 15 patients (age range, 15 to 33 years) diagnosed as having listening difficulties without apparent peripheral pathology in the outpatient clinic of the Department of Otolaryngology-Head and Neck Surgery, Tohoku University Hospital. Speech intelligibility for 50 Japanese monosyllables presented to the right ear was examined under the following three different conditions: "without contralateral sound," "with continuous white noise in the contralateral ear," and "with music stimuli in the contralateral ear." RESULTS: The results indicated the following: (1) speech intelligibility was significantly worse in the patient group with contralateral music stimuli and noise stimuli; (2) speech intelligibility was significantly worse with contralateral music stimuli than with contralateral noise stimuli in the patient group; (3) there was no significant difference in speech intelligibility among three contralateral masking conditions (without contra-stimuli, with contra-noise, and with contra-music) in the control group, although average and median values of speech intelligibility tended to be worse with contralateral music stimuli than without contralateral stimuli. CONCLUSIONS: Significantly larger masking effects due to a contralateral distractor sound observed in patients with listening difficulties without apparent peripheral pathology may suggest the possible involvement of masking mechanisms other than the energetic masking mechanism occurring in the periphery in these patients. In addition, it was also shown that the masking effect is more pronounced with real environmental sounds, that is, music with lyrics, than with continuous steady noise, which is often used as a masker for speech-in-noise testing in clinical trials. In other words, it should be noted that a speech-in-noise test using such steady noise may underestimate the degree of listening problems of patients with listening difficulties in their daily lives, and a speech-in-noise test using a masker such as music and/or speech sounds could make listening problems more obvious in patients with listening difficulties.

BACKGROUND Vestibular paroxysmia is defined by spontaneous, recurrent, short, paroxysmal episodes of vertigo. The authors present a case of vestibular paroxysmia caused by neurovascular compression of the vestibulocochlear nerve due to the subarcuate artery, which was successfully treated with microvascular decompression. OBSERVATIONS A 46-year-old man first experienced vertigo attacks 5 years earlier. The attacks became more frequent, and left-sided tinnitus developed over the past 4 months, prompting a referral to our hospital. Carbamazepine treatment alleviated symptoms but had to be discontinued due to rash. Brain magnetic resonance imaging and angiography revealed that the left anterior inferior cerebellar artery was pressing on the cisternal segment of the left vestibulocochlear nerve. The authors diagnosed vestibular paroxysmia caused by neurovascular compression and performed microvascular decompression. During the operation, a subarcuate artery was identified as the offending vessel, with a prominent indentation on the vestibulocochlear nerve. The vertigo was completely relieved following surgery. LESSONS Neurovascular compression of the vestibulocochlear nerve by the subarcuate artery can result in vestibular paroxysmia. https://thejns.org/doi/abs/10.3171/CASE24239

Transmembrane protein 135 (TMEM135) is a 52 kDa protein with five predicted transmembrane domains that is highly conserved across species. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism in multiple tissues; however, its role in the inner ear or the auditory system is unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135 FUN025/FUN025 ( FUN025 ) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and spiral ganglion neurons in the cochlea. Our results using BaseScope in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, and supporting cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.

BACKGROUND: The effect of wearing masks on olfaction remains unclear. OBJECTIVES: This study aimed to clarify the differences between the effects of no masks, surgical masks, and N95 respirator masks by conducting both identification and threshold olfaction tests. METHODS: Young, healthy volunteers aged ≥ 18 years and < 30 years without awareness of apparent olfactory disorder were included. All participants filled out a questionnaire on olfaction and completed an acuity smell identification test (Open Essence test) and an olfactory threshold test (T&T olfactometry) while wearing no masks, surgical masks, or N95 respirator masks. RESULTS: In the Open Essence tests, the no-mask group score was significantly higher than those of the surgical- and N95-mask groups. Using T&T olfactometry, the median-detection threshold of the no-mask group was significantly lower than that of the surgical-mask group, and the surgical-mask group threshold was significantly lower than that of the N95-mask group. Similar patterns were observed for the median-recognition threshold. CONCLUSIONS: Wearing masks, especially an N95 mask, reduces the ability to detect and identify odors. This disadvantage should be considered by professionals such as healthcare workers, who require proper olfaction to perform appropriate tasks.

OBJECTIVE: The purpose of this study is to compare patient trends in otitis media with effusion (OME) symptoms and diagnoses before and after the COVID-19 pandemic in order to investigate the effects of the coronavirus disease of 2019 (COVID-19). METHODS: A retrospective, multi-center, observational study was carried out between January 2018 and December 2022 at hospitals in the Iwate Prefecture with full-time doctors. All patients were initially separated into two groups, one for the pre-COVID-19 era (from January 2018 to June 2020), and the other for the COVID-19 era (from July 2020 to December 2022). RESULTS: In the pre-COVID-19 era, 132 patients had tympanostomy tubes (TT) placed, while 64 patients had them placed in the COVID-19 era. Between the pre-COVID-19 and COVID-19 eras, there were no statistically significant differences in terms of age, sex, side, craniofacial deformity, or adenoidectomy. Children in elementary school showed a greater decline than those in preschool (42-11 patients in elementary school (74%) and 49 to 32 patients in preschool school (35%); p = 0.025). CONCLUSIONS: The percentage of TT placements for OME dropped to roughly half during the COVID-19 epidemic. This was particularly obvious in elementary school students.

BACKGROUND: Deep neck infections (DNIs) in the cervical fascial planes can cause severe complications such as airway obstruction, mediastinitis, and sepsis. AIMS/OBJECTIVES: This study examines cervical abscess development, its relationship with postoperative swallowing function, and hospital stay duration. MATERIAL AND METHODS: A retrospective case series of 55 DNI patients was divided by hospital stay (<30 days: Group A, ≥30 days: Group B) and swallowing recovery (<6 days: Group C, ≥6 days: Group D). Swallowing was assessed using FOIS; abscesses were categorized via CT and surgery. RESULTS: Longer hospital stays (Group B) were associated with tracheostomy (p = .027) and thoracoscopic mediastinal drainage (p = .038), shorter time between symptom onset and surgery (p = .016), and abscesses in the anterior cervical (p = .007), retropharyngeal space (p = .026), and mediastinal spaces (p = .002). Dysphagia (Group D) was linked to longer hospital stays (p = .006), more abscesses in the anterior cervical (p = .049) and retropharyngeal spaces (p = .009), and higher cases of intubated feeding (p < .001). Streptococcus constellatus was more prevalent in Group D (p = .04), whereas Staphylococcus aureus was less common (p = .043). CONCLUSIONS AND SIGNIFICANCE: Dysphagia is associated with abscesses in the anterior cervical and retropharyngeal spaces and higher Streptococcus constellatus prevalence, indicating delayed oral intake recovery. Thoracoscopic mediastinal drainage and shorter time to surgery were linked to prolonged hospital stays.

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Early detection of dysphagia risk, initiating rehabilitation, and resumption of appropriate diet based on swallowing function is important during deep neck infection (DNI) control. This study aimed to evaluate the extent of cervical abscess development, particularly in the deep neck space, and its relationship to postoperative swallowing function. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A retrospective chart review was performed for all DNI cases treated between April 2015 and April 2021. Deep neck spaces were divided into categories based on computed tomography findings. Functional Oral Intake Scale (FOIS) scores of 4 or higher was defined as normal or slight swallowing disorder and 3 or lower as dysphagia. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Seventeen cases were included in the analysis. Based on FOIS, 14 cases were classified into the dysphagia group at 2 weeks after surgery, 11 cases at 4 weeks, and 8 cases at 8 weeks. There was no significant difference between the location of the abscess and dysphagia at 2 weeks after surgery. Patients with anterior cervical space abscess significantly increased dysphagia 4 weeks (&lt;i&gt;p&lt;/i&gt; = 0.018) and 8 weeks (&lt;i&gt;p&lt;/i&gt; = 0.036) after surgery. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Abscess formation in the anterior cervical space may be associated with prolonged dysphagia after treatment due to inflammation and scarring of the muscles associated with swallowing.

Carbon monoxide (CO) can cause "irreversible" severe-to-profound sensorineural hearing loss. However, there are few reports of detailed hearing test results. Here, we report a case of acute sensorineural hearing loss caused by acute CO poisoning with partial hearing recovery, evaluated by a detailed hearing examination. A 25-year-old woman was brought to the emergency department for attempted suicide. On admission, her consciousness was impaired, and she was treated for severe CO poisoning, including using hyperbaric-oxygen therapy. After regaining consciousness, symptoms of hearing loss and tinnitus were discovered, and a detailed audiological examination revealed bilateral hearing loss, suggesting cochlear damage. Steroids were systemically administered, and her hearing impairment was partially resolved. Sensorineural hearing loss caused by acute CO poisoning includes cochlear pathology and may be partially treatable. The early evaluation of hearing in patients with severe CO poisoning is advisable for early treatment.

OBJECTIVE: Children with cleft palate (CP) are at high risk of developing otitis media with effusion (OME) due to Eustachian tube (ET) dysfunction. Palatoplasty has been reported to decrease the frequency of middle ear disease and improve ET function, and although various techniques have been developed, there is no consensus on the differences in the impact of different techniques on the middle ear. The purpose of this study was to determine the differential effects of palatoplasty on middle ear function and hearing. METHODS: We performed a retrospective observational survey of pediatric patients who underwent palatoplasty for CP between June 2010 and October 2018 at Tohoku University Hospital. Cases were divided into three groups depending on the palatoplasty procedures performed: the push-back palatoplasty group, the two-flap palatoplasty group, and the Furlow double-opposing Z-plasty group. We examined the differences in clinical characteristics between patients who underwent each procedure. The primary outcome variable was tympanic membrane (TM) findings, and the secondary outcome was hearing test results. RESULTS: Children who underwent the two-flap palatoplasty had a higher tympanostomy tube (TT) insertion rate and a higher total number of TT insertions than those who underwent the Furlow double-opposing Z-plasty or the push-back palatoplasty. The TM retraction rate tended to be lower in the Furlow double-opposing Z-plasty group than in the push-back palatoplasty group or the two-flap palatoplasty group. The hearing test results at the last visit were not significantly different among the three groups. CONCLUSIONS: Children who underwent the two-flap palatoplasty had a higher rate of TT insertions, potentially increasing the risk of TM perforation. In contrast, the Furlow double-opposing Z-plasty group had a lower tendency for TM regression, possibly due to improved ET function and reduced incidence of OME. It is important to understand the advantages and disadvantages of each technique before selecting one suitable for the child's cleft and arch width. Additionally, it is important to conduct regular follow-up of TM findings and hearing test results even after palatoplasty.

Inflammatory pleuritis often causes pleural effusions, which are drained through lymphatic vessels (lymphatics) in the parietal pleura. The distribution of button- and zipper-like endothelial junctions can identify the subtypes of lymphatics, the initial, pre-collecting, and collecting lymphatics. Vascular endothelial growth factor receptor (VEGFR)-3 and its ligands VEGF-C/D are crucial lymphangiogenic factors. Currently, in the pleura covering the chest walls, the anatomy of the lymphatics and connecting networks of blood vessels are incompletely understood. Moreover, their pathological and functional plasticity under inflammation and the effects of VEGFR inhibition are unclear. This study aimed to learn the above-unanswered questions and immunostained mouse chest walls as whole-mount specimens. Confocal microscopic images and their 3-dimensional reconstruction analyzed the vasculatures. Repeated intra-pleural cavity lipopolysaccharide challenge induced pleuritis, which was also treated with VEGFR inhibition. Levels of vascular-related factors were evaluated by quantitative real-time polymerase chain reaction. We observed the initial lymphatics in the intercostals, collecting lymphatics under the ribs, and pre-collecting lymphatics connecting both. Arteries branched into capillaries and gathered into veins from the cranial to the caudal side. Lymphatics and blood vessels were in different layers with an adjacent distribution of the lymphatic layer to the pleural cavity. Inflammatory pleuritis elevated expression levels of VEGF-C/D and angiopoietin-2, induced lymphangiogenesis and blood vessel remodeling, and disorganized the lymphatic structures and subtypes. The disorganized lymphatics showed large sheet-like structures with many branches and holes inside. Such lymphatics were abundant in zipper-like endothelial junctions with some button-like junctions. The blood vessels were tortuous and had various diameters and complex networks. Stratified layers of lymphatics and blood vessels were disorganized, with impaired drainage function. VEGFR inhibition partially maintained their structures and drainage function. These findings demonstrate anatomy and pathological changes of the vasculatures in the parietal pleura and their potential as a novel therapeutic target.

Functional endoscopic sinus surgery has become popular worldwide. However, serious complications have been reported with it. A preoperative imaging evaluation is thus essential to avoid complications. The authors compared 0.5 mm slice computed tomography (CT) images reconstructed from sinus CT data with conventional 2 mm slice CT images. The authors evaluated patients who underwent endoscopic surgery. Data regarding age, sex, history of craniofacial trauma, diagnosis, operative procedure, and CT findings of eligible patients were extracted from medical records and retrospectively reviewed. One hundred twelve patients underwent endoscopic surgery during the study period. Six patients (5.4%) had orbital blowout fractures, and half of them could only be identified by 0.5 mm slice CT images. The authors presented the usefulness of 0.5 mm slice CT images in the preoperative imaging evaluation of functional endoscopic sinus surgery. Surgeons should also recognize that a small number of patients have "stealth" (asymptomatic and unrecognized) blowout fractures.

Otitis media, one of the most common childhood diseases, is characterized by inflammation or infection of the middle ear. Due to their ease of access, daily probiotics are recommended for the prevention of early childhood otitis media. This study aimed to assess the impact of probiotics on the incidence of otitis media using a dataset (n = 95,380) from the Japan Environment and Children's Study, a nationwide birth cohort study. After multiple imputations, the association between the incidence of otitis media in early childhood and the daily frequency of yogurt intake in children and mothers was examined using a generalized linear model after adjusting for several confounders. Repeated incidence of otitis media during the 2 years after birth was found in 14,874 participants (15.6%). Based on participants with the lowest frequency of yogurt intake ("almost never") as the reference group, risk ratios for otitis media incidence decreased with higher frequencies of yogurt intake in children at one year of age, but also independently in mothers during pregnancy. The lowest risk ratio (95% confidence interval) for otitis media incidence at six months of age was observed with the most frequent yogurt intake (once/day or more) (0.54 [0.46-0.63]). Additionally, although a similar association was observed in the subgroup of those with cleft lip and/or palate (CL/P), a high-risk group for severe recurrent otitis media, no statistical significance was observed. Thus, increased regular yogurt intake in both children and mothers was associated with a decrease of otitis media during early childhood.

Auditory-evoked responses can be affected by different types of contralateral sounds or by attention modulation. The present study examined the additive effects of presenting visual information about contralateral sounds as distractions during dichotic listening tasks on the contralateral effects of N100m responses in the auditory-evoked cortex in 16 subjects (12 males and 4 females). In magnetoencephalography, a tone-burst of 500 ms duration at a frequency of 1000 Hz was played to the left ear at a level of 70 dB as a stimulus to elicit the N100m response, and a movie clip was used as a distractor stimulus under audio-only, visual-only, and audio-visual conditions. Subjects were instructed to pay attention to the left ear and press the response button each time they heard a tone-burst stimulus in their left ear. The results suggest that the presentation of visual information related to the contralateral sound, which worked as a distractor, significantly suppressed the amplitude of the N100m response compared with only the contralateral sound condition. In contrast, the presentation of visual information related to contralateral sound did not affect the latency of the N100m response. These results suggest that the integration of contralateral sounds and related movies may have resulted in a more perceptually loaded stimulus and reduced the intensity of attention to tone-bursts. Our findings suggest that selective attention and saliency mechanisms may have cross-modal effects on other modes of perception.

Respiratory-related dysphagia and aspiration pneumonia can be attributed to multiple causes. However, reproduction of multiple factor-related respiratory distress and aspiration pneumonia in a single animal model is challenging. To validate animals with vagal nerve palsy as novel models for severe aspiration pneumonia associated with respiratory distress, we investigated the effects of unilateral vagotomy on the swallowing function and severity of pneumonia after forced aspiration in mice. Unilateral vagotomy was performed in C57BL6 male mice that subsequently underwent evaluation of swallowing function by videofluoroscopic swallow study (VFSS) and histological assessments for aspiration pneumonia induced by lipopolysaccharide (LPS). VFSS examinations demonstrated that unilateral vagotomy did not cause apparent aspiration in mice, but it resulted in a significant loss of body weight (BW) due to decreased oral intake. In addition, when aspiration pneumonia was induced by forced administration of LPS, significantly prolonged BW loss and severe infiltration of inflammatory cells associated with aspiration pneumonia were observed in the mice that underwent unilateral vagotomy. In conclusion, the vagotomized mice showed appropriate characteristics as a model of aspiration pneumonia caused by multiple factors, including the paralysis of vocal fold movement and respiratory distress. This model can help elucidate the pathogenesis of aspiration pneumonia and the treatment methods for the respiration-compromised model.

A 46-year-old man who had been diagnosed with eosinophilic otitis media (EOM) and eosinophilic chronic rhinosinusitis was referred to our department. He suffered from bilateral earache, clogged ear sensation, and otorrhea associated with EOM. He had been treated with a myringotomy and a ventilation tube (VT) insertion. However, his symptoms did not improve, and the VT repeatedly fell out. We performed canal wall down mastoidectomy via a retro-auricular incision to remove the presumed cholesterol granuloma (CG) and a long-term VT insertion. The VT fell out repeatedly. Therefore, a large VT that Komune devised was inserted. Four months after reinsertion, there was no evidence of recurrent otorrhea or fallout of a large VT. A large VT insertion could be useful in the severe case of EOM with CG.

Pseudobulbar palsy and bulbar palsy cause dysphagia in patients with amyotrophic lateral sclerosis (ALS). Dysphagia in patients with ALS not only increases the risk of aspiration and pneumonia but also leads to malnutrition and weight loss, which are poor prognostic factors. Gastrostomy is the preferred route of feeding and nutritional support in patients with dysphagia. However, there are no established standards to determine the ideal timing of gastrostomy for patients with ALS. Therefore, we used the videofluoroscopic dysphagia scale (VDS), which objectively quantifies swallowing function, in videofluoroscopic swallowing study (VFSS) to investigate whether this scale at diagnosis can be a useful predictor for the timing of gastrostomy. We retrospectively evaluated 22 patients with ALS who were diagnosed at our hospital. We assessed the VDS scores in all patients within 3 months of diagnosis. A decline in the ALS functional rating scale revised (ALSFRS-R) scores was used as an indicator of disease progression. As a result, we found that the VDS score of the pharyngeal phase and the total VDS score were significantly correlated with the ΔALSFRS-R scores. These scores were also associated with the existing indicators for the timing of gastrostomy, i.e., decreased body weight and percent-predicted forced vital capacity. We demonstrated the noninferiority of the VDS scores relative to the existing indicators. In addition, the VDS score of the pharyngeal phase was significantly correlated with the time from diagnosis to gastrostomy. The VDS score could estimate the timing of gastrostomy in patients with ALS with dysphagia at diagnosis.

BACKGROUND: There has been no report of a detailed long-term study of hearing at defined frequencies. AIMS/OBJECTIVES: This study aimed to evaluate long-term vestibular shwannoma (VS) growth and long-term changes in hearing thresholds at defined frequencies. METHODS: We retrospectively retrieved the medical records of 67 VS patients. Cases that were followed up for more than 5 years were analyzed. RESULTS: Tumor growth was observed in 15 cases (22.4%) and 6 cases underwent gamma knife treatment (9.0%). The longest case of tumor growth and gamma knife treatment was observed 11 years after the initial diagnosis. Hearing thresholds at 500-2000 Hz was significantly different between the no growth and growth group (p < .05). Particularly at 1000 Hz, there was a significant difference between the two groups from an early time-point. CONCLUSIONS AND SIGNIFICANCE: Even a 10-year or longer follow-up of VS may show an increase in tumor growth. Moreover, hearing thresholds, particularly at 1000 kHz, may predict tumor growth when following-up VS patients.

INTRODUCTION: Early detection of dysphagia risk, initiating rehabilitation, and resumption of appropriate diet based on swallowing function is important during deep neck infection (DNI) control. This study aimed to evaluate the extent of cervical abscess development, particularly in the deep neck space, and its relationship to postoperative swallowing function. METHODS: A retrospective chart review was performed for all DNI cases treated between April 2015 and April 2021. Deep neck spaces were divided into categories based on computed tomography findings. Functional Oral Intake Scale (FOIS) scores of 4 or higher was defined as normal or slight swallowing disorder and 3 or lower as dysphagia. RESULTS: Seventeen cases were included in the analysis. Based on FOIS, 14 cases were classified into the dysphagia group at 2 weeks after surgery, 11 cases at 4 weeks, and 8 cases at 8 weeks. There was no significant difference between the location of the abscess and dysphagia at 2 weeks after surgery. Patients with anterior cervical space abscess significantly increased dysphagia 4 weeks (p = 0.018) and 8 weeks (p = 0.036) after surgery. CONCLUSION: Abscess formation in the anterior cervical space may be associated with prolonged dysphagia after treatment due to inflammation and scarring of the muscles associated with swallowing.

Hearing loss is the third most prevalent chronic health condition affecting older adults and age-related hearing loss (ARHL) is the most common form of hearing impairment. Significant sex differences in hearing have been documented in humans and rodents. In general, the results of these studies show that men lose their hearing more rapidly than women. However, the cellular mechanism underlying sex differences in hearing or hearing loss remains largely unknown, and to our knowledge, there is no well-established animal model for studying sex differences in hearing. In the current study, we examined sex differences in body composition, voluntary wheel running activity, balance performance, auditory function, and cochlear histology in young, middle-age, and old CBA/CaJ mice, a model of age-related hearing loss. As expected, body weight of young females was lower than that of males. Similarly, lean mass and total water mass of young, middle-age, and old females were lower than those of males. Young females showed higher voluntary wheel running activity during the dark cycle, an indicator of mobility, physical activity, and balance status, compared to males. Young females also displayed higher auditory brainstem response (ABR) wave I amplitudes at 8 kHz, wave II, III, V amplitudes at 8 and 48 kHz, and wave IV/I and V/I amplitude ratios at 48 kHz compared to males. Collectively, our findings suggest that the CBA/CaJ mouse strain is a useful model to study the cellular mechanisms underlying sex differences in physical activity and hearing.

Ototoxicity is a dose-limiting adverse event for concurrent chemoradiotherapy (CCRT) with high-dose cisplatin for locally advanced head and neck squamous cell carcinoma (HNSCC). Both irradiation to the Eustachian tube (ET) and weight loss are risk factors for patulous ET. The aim of this prospective, observational study was to elucidate the incidences of patulous ET conditions before and after CCRT in HNSCC patients by means of ET function tests. This prospective, observational study was conducted in 27 HNSCC patients who received CCRT with high-dose cisplatin, and ET function tests (sonotubometry and tubo-tympano-aerodynamic graphy) were performed before and 3 months after CCRT. Factors potentially affecting the incidence of patulous ET conditions after CCRT were evaluated. Of the 54 ears from 27 patients investigated, patulous ET conditions were observed in 12 ears (22.2%) from 9 patients (33.3%) before CCRT and 15 ears (27.8%) from 11 patients (40.7%) at 3 months after CCRT. Only patulous ET conditions before CCRT in each ear were significantly associated with patulous ET conditions after CCRT (p = 0.010). This is the first report to describe the incidences of patulous ET conditions before and after CCRT in HNSCC patients. HNSCC patients are potentially at higher risk of patulous ET.

Objective/Hypothesis: Middle ear cholesteatoma is characterized by abnormal growth of the keratinizing squamous epithelium of the temporal bone. d-β-aspartic acid is the major isomer of d-aspartic acid found in elderly tissue. We assessed the immunoreactivity to k-β-aspartic acid of congenital and acquired middle ear cholesteatomas. Study Design: Case-control studies. Material and Methods: Tissue samples were collected from 21 patients comprising 21 ears with congenital middle ear cholesteatoma and 26 patients comprising 29 ears with acquired type. Their clinical and histopathological features were investigated. We divided the middle ear cholesteatoma samples into three layers: the perimatrix, matrix, and cystic contents. The patterns of immunoreactivity to d-β-aspartic acid expression were then assessed immunohistochemically. Results: Two patterns of immunoreactivity to d-β-aspartic acid were detected in middle ear cholesteatoma: infiltrative and diffuse. In congenital middle ear cholesteatoma, d-β-aspartic acid expression was observed throughout all the layers (perimatrix, matrix, and cystic contents), and immunoreactivity to d-β-aspartic acid was dramatically strong in all layers. The expression levels of d-β-aspartic acid to the cystic content and perimatrix were significantly higher in congenital middle ear cholesteatoma than in the acquired type. Conclusions: This study showed the expression levels of d-β-aspartic acid in middle ear cholesteatoma to differ significantly between congenital and acquired middle ear cholesteatoma. Our results indicate that overexpression of d-β-aspartic acid is likely to be involved in the pathogenesis of cholesteatoma, and we speculate that d-β-aspartic acid could be a novel biomarker for, and a therapeutic target in, congenital and acquired middle ear cholesteatoma. Level of Evidence: 4.

Cardiovocal syndrome is left recurrent laryngeal nerve palsy associated with cardiovascular disease. Herein, we report a rare case of left recurrent laryngeal nerve palsy caused by idiopathic pulmonary arterial hypertension. A 40-year-old woman diagnosed with idiopathic pulmonary arterial hypertension was referred to our department for occult infection foci in the ear, nose, and throat (ENT). She had no apparent subjective symptoms in the ENT area, including hoarseness. Flexible laryngoscopy revealed left vocal cord paralysis, and contrast-enhanced computed tomography revealed dilatation of the pulmonary trunk, bilateral pulmonary arteries, and right ventricle, suggesting compression of the left recurrent laryngeal nerve. In our daily practice, when we encounter a left recurrent laryngeal nerve palsy that seems to be endogenous, cardiovascular lesions should be ruled out.

Nasal mucosal melanoma (NMM) is a rare tumor with a poor prognosis. Although an endoscopic resection of malignant nasal tumor now becomes a treatment of choice when the surgical margin can be secured, it is still controversial. We report three cases of NMM that was successfully removed en bloc with clear margins by endoscopic surgery with temporal transseptal access. Cases of a 78-year-old woman, an 83-year-old man, and an 81-year-old man with NMM arising from the inferior turbinate who underwent endoscopic resection of the tumor are discussed in detail. We made temporal transseptal access using septal mucosal flaps. We moved the nasal cavity-occupying tumor to the contralateral side to create a working space to perform endoscopic en bloc resections. This technique is simple yet effective and less invasive than open craniofacial resections for removing malignancies arising from the inferior turbinate.

Although nasal septal abscesses are uncommon, their cosmetic complications can be severe. Hence, prompt diagnosis and treatment are important. Here, we report a case of aseptic nasal septal abscess in a patient with proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA)-positive ulcerative colitis (UC), in which phlebitis was observed and granulomatosis with polyangiitis (GPA) might co-exist. A 27-year-old female suffered from intermittent abdominal pain and diarrhea for several years. She visited our hospital complaining of worsening swelling and pain in the middle forehead and fever lasting 2 weeks. Physical examination and computed tomography revealed severe swelling of the nasal septum. The patient was diagnosed with nasal septal abscess, and incision drainage and biopsy from the bilateral nasal septum were performed, which showed severe ulcerative neutrophilic mucositis with phlebitis. Simultaneously, blood examination yielded slight positivity for PR3-ANCA. Colonoscopy, including biopsy, revealed severe inflammation without vasculitis nor granuloma, which led to the diagnosis with PR3-ANCA-positive UC. Phlebitis in the nasal mucosa and elevated PR3-ANCA suggested co-existing GPA; hence, she was treated with glucocorticoids and rituximab. Following treatment, the nasal septal abscess and digestive symptoms disappeared. She was discharged on day 25 without symptom recurrence or major nasal deformity. For the prevention of nasal deformity due to persistent inflammation, prompt administration of immunosuppressive therapy should be considered with adequate evaluations for systemic diseases, including UC and GPA.

Sinonasal inverted papilloma (IP) is the most common benign tumor in sinonasal cavities. Treatment involves excising the whole tumor, so it is essential to evaluate the extent of the tumor by preoperative radiographic findings. Magnetic resonance imaging (MRI) is superior to computed tomography (CT) for determining a tumor’s location as MRI can discern the difference between mucus and IP. We herein report a 51-year-old man with sinonasal IP treated with endoscopic sinus surgery (ESS). Preoperative MRI showed findings resembling a convoluted cerebriform pattern on T2-weighted imaging, but this site was not enhanced by intravenous gadolinium at all. We preoperatively suspected that this site was not part of the tumor but rather the accumulation of mucus, and indeed, we found no tumor at this site when we performed the surgery. This patient is a valuable example of misleading findings of IP on T2-weighted imaging and underscores the importance of contrast-enhanced T1-weighted imaging to determine the extent of IP.

OBJECTIVE: The objectives of the study were to clarify the characteristics of dysphagia and the incidence of pneumonia in Myotonic dystrophy type 1 (DM1) patients, and to investigate the relationship between the development of pneumonia and the DM1 patient's background, especially concerning swallowing function evaluated by endoscopy. METHODS: The subjects were 88 DM1 patients who underwent swallowing function evaluation. The severity of disease in DM1patients was assessed based on the muscular impairment rating scale (MIRS), and the number of CTG repeats. Patients were divided into two groups; those who developed aspiration pneumonia within two years after swallowing assessment and those who did not develop aspiration pneumonia. Swallowing function was assessed using the food intake level scale (FILS), repetitive saliva swallowing test (RSST), the modified water swallowing test (MWST), and the Hyodo score. RESULTS: Onset of pneumonia within two years of assessment was observed in 22 cases (25%). Age, FILS, and Hyodo score were significantly different between pneumonia and non-pneumonia groups. There was a significant difference in swallowing function tests such as FILS, RSST, and Hyodo score between males and females. The Hyodo score cutoff value for predicting pneumonia within two years was determined by ROC analysis. A cutoff value of 6 was found to have a sensitivity of 0.545 and a specificity of 0.833 (area under the curve=0.722). CONCLUSION: It is important to evaluate the swallowing function of DM1 patients by endoscopy to prevent aspiration pneumonia. In addition, male patients are more likely to deteriorate in swallowing function and should be carefully monitored.

Actinomycosis is a bacterial infection caused by actinomyces. Although almost 50% of cases are related to the head and neck region, those in the nose and paranasal sinuses (PNS) are rare. Actinomycosis of the PNS is presumed to be typically caused by dental caries, dental manipulation, and maxillofacial trauma, which facilitate the penetration of oral pathogens into the sinus, and should thus be treated by the combination of surgical removal and potent antibiotics for at least two months. The current use of these antibiotics might be redundant, considering the nature of actinomycosis of the PNS, which does not invade the mucosal surface. We herein report a 67-year-old female treated with endoscopic sinus surgery (ESS) and diagnosed with actinomycosis of the PNS by pathological findings. She had no history of dental impairment or treatment. She was given routine perioperative prophylactic antibiotics (cefazolin) during the surgery, followed by low-dose clarithromycin. The mucosa of the PNS normalized without any discharge by three months after the operation. The patient is a valuable example that should prompt reconsideration of the commonly accepted pathogenesis and treatment of actinomycosis of the PNS.

OBJECTIVES: To describe cases of patulous Eustachian tube (PET) or patent ET conditions in oculopharyngeal muscular dystrophy (OPMD). PATIENTS: Four cases of PET or patent ET conditions with OPMD. MAIN OUTCOME MEASURES: Clinical case records, objective ET function tests (tubo-tympano-aerodynamic graphy and sonotubometry), and swallowing function (videoendoscopic examination and Food Intake Level Scale) were analyzed. RESULTS: Two cases of definite PET, one case of possible PET, and one case lacking aural symptoms with findings of patent ET. All patients have ptosis, and three cases have dysphagia. Body mass index indicated that three cases were underweight. Magnetic resonance imaging in case 4 showed atrophy and fat replacement of palatine and masticatory muscles. CONCLUSIONS: It is important to consider PET or patent ET conditions when OPMD patients describe aural symptoms.

OBJECTIVE: Head and neck surgeries may cause changes in the nasal airflow, and radiotherapy irreversibly damages paranasal sinus epithelial cells. Some chemotherapeutic drugs have been reported to negatively affect airway ciliary activity in mice, and chronic rhinosinusitis could be an adverse effect of head and neck cancer (HNC) treatment. To evaluate whether HNC treatment is a risk factor for developing sinonasal mucosal thickening that may reflect paranasal sinus inflammation, we compared pre- and post-treatment paranasal sinus computed tomography (CT) images of patients treated for HNC at a single university hospital. METHODS: The patients who received curative treatment for HNC (oral, pharyngeal, and laryngeal cancers) and started receiving first-line therapy between January 2015 and December 2019 were included. Data on age, sex, primary lesion, clinical stage, treatment, smoking history, drinking history, comorbidities (diabetes and chronic lung disease), and pre- and post-treatment (three months and one year after the final treatment) paranasal sinus CT images were analyzed from medical records. Pre- and post-treatment paranasal sinus CT images were scored using the Lund-Mackay (LM) staging system. RESULTS: In total, 245 patients participated in this study. Three months after the final treatment, 80.4% of patients had no change in their total LM scores (p=0.621). Almost 80% of patients who underwent total laryngectomy also had no change in their total LM scores (p=0.833). One-third of patients with nasopharyngeal cancer (NPC) had worse LM scores after treatment (5/15), although no significant difference was observed (p=0.171). None of the various factors collected were significantly related to changes in LM scores three months after the completion of treatment. One year after the final treatment, 211 patients were included and no significant changes in the pre-and post-LM scores were observed in the same analyses, while changes in LM scores were significantly different between T categories (T1-2 vs. T3-4) (p=0.020). CONCLUSION: We found no significant changes in the LM scores after HNC treatment in all the patients, which implies that HNC treatment may not be an apparent risk factor for sinonasal mucosal inflammation.

ABSTRACT: Nasopharyngeal foreign bodies (FBs), which are generally caused by a strong, external force, are seldomly encountered. Removing these FBs is challenging for otorhinolaryngological surgeons because of the vital structures surrounding the nasopharynx, such as the skull base, cranial nerves, and internal carotid artery. Here, the authors report the case of a 69-year-old man referred to our hospital after accidentally cutting his face while using a grinder. Grinder fragments were deeply embedded in the face, thus becoming nasopharyngeal FBs. The authors evaluated three-dimensional volume rendering images and immediately removed these FBs using an endoscopic endonasal transseptal approach under general anesthesia. The postoperative course was uneventful. Using the endoscopic endonasal transseptal approach after evaluating preoperative three-dimensional volume rendering images may help eliminate nasopharyngeal FBs safely.

We report the first case of proteinase 3 (PR3)- antineutrophil cytoplasmic antibody (ANCA)-positive granulomatosis with polyangiitis (GPA) with predominant ears, nose, and throat (ENT) manifestations following COVID-19 vaccination. A 63-year-old woman presented with aural fullness three days after vaccination. She presented with progressive rhinosinusitis and otitis media leading to profound hearing loss within three weeks. Clinical imaging revealed soft-tissue shadows in the paranasal sinuses with multiple pulmonary nodules, and histopathology was consistent with a diagnosis of GPA. It is crucial to be wary of the possibility of GPA in patients who received COVID-19 vaccines due to its rapid disease progression.

Chronic renal failure and diabetes mellitus could also be risk factors of pseudoaneurysm of the internal carotid artery (ICA) due to malignant otitis externa (MOE). Although pseudoaneurysm of the ICA is a rarely encountered disease, it should always be taken into consideration when treating patients of MOE.

Fibroepithelial polyps are benign tumors of mesodermal origin. They rarely occur in the nasal cavity, with only four such cases reported in the relevant English literature. The location was the inferior turbinate in three cases and anterior nasal septum in one case. The etiology has been suggested in other organs; however, it is entirely unknown in the nasal cavity. Pathological findings play an essential role in the diagnosis of fibroepithelial polyps. We report the case of a 76-year-old woman with fibroepithelial polyps originating from the posterior part of the nasal septum. The fibroepithelial polyps were white-yellow lobular masses that differed from a common inflammatory polyp. We made the diagnosis by excluding the other possible tumors based on a pathological examination. This is the first report about fibroepithelial polyps arising from the posterior nasal septum. She had no potential risk factors that might trigger fibroepithelial polyps in the nasal cavity. This case is a valuable example when considering the potential causes (e.g., female hormones and mechanical pressure) of nasal fibroepithelial polyps.

INTRODUCTION: Pharmacogenomic (PGx) testing results provide valuable information on drug selection and appropriate dosing, maximization of efficacy, and minimization of adverse effects. Although the number of large-scale, next-generation-sequencing-based PGx studies has recently increased, little is known about the risks and benefits of returning PGx results to ostensibly healthy individuals in research settings. METHODS: Single-nucleotide variants of three actionable PGx genes, namely, MT-RNR1, CYP2C19, and NUDT15, were returned to 161 participants in a population-based Tohoku Medical Megabank project. Informed consent was obtained from the participants after a seminar on the outline of this study. The results were sent by mail alongside sealed information letter intended for clinicians. As an exception, genetic counseling was performed for the MT-RNR1 m.1555A > G variant carriers by a medical geneticist, and consultation with an otolaryngologist was encouraged. Questionnaire surveys (QSs) were conducted five times to evaluate the participants' understanding of the topic, psychological impact, and attitude toward the study. RESULTS: Whereas the majority of participants were unfamiliar with the term PGx, and none had undergone PGx testing before the study, more than 80% of the participants felt that they could acquire basic PGx knowledge sufficient to understand their genomic results and were satisfied with their potential benefit and use in future prescriptions. On the other hand, some felt that the PGx concepts or terminology was difficult to fully understand and suggested that in-person return of the results was desirable. CONCLUSIONS: These results collectively suggest possible benefits of returning preemptive PGx information to ostensibly healthy cohort participants in a research setting.

BACKGROUND: The palatal augmentation prosthesis (PAP) is an intraoral prosthesis used in the treatment of dysphagia. AIM: The objective of the study is to examine the effect of PAP using tongue pressure and the Videofluoroscopic Dysphagia Scale (VDS) to understand the precise mechanism for improvement in swallowing function with PAP for oral cancer at retrospective survey. METHODS AND RESULTS: Fifteen patients were provided PAPs. Tongue pressure and VDS were evaluated with and without PAP. After intervention with PAP, tongue pressure significantly increased as compared to when without PAP (p < .05). The total mean VDS score with PAP was found to have significantly improved (p < .05). The mean VDS score of the oral phase also significantly improved with the PAP compared to without the PAP group (p < .05). Significant differences (p < .01) were found in each category, such as tongue to palate contact and pyriform sinus residue. CONCLUSION: PAP can improve tongue pressure, tongue to palate contact, and pyriform sinus residue.

OBJECTIVE: The objective is to conduct a questionnaire survey regarding pharyngolaryngeal sensation evaluation in dysphagia to understand the current situation in Japan. METHOD: The questionnaire was sent to the councilor of the Society of Swallowing and Dysphagia of Japan and the Japanese Society of Dysphagia Rehabilitation-Certified Clinician. The prospective questionnaire survey included the questions listed below: Q1: What do you think of the importance of pharyngolaryngeal sensory evaluation? Q2: Select one of the essential swallowing sensations. Q3: Select one of the following regarding the frequency of sensory examination of the larynx. Q4: Select the proportion of cases the sensory test results affect. Q5: As a pharyngolaryngeal sensory evaluation method in swallowing function evaluation, please fill in the table below for the frequency, difficulty, and effectiveness of the following tests, such as gag reflex, touching the larynx by endoscopy, touching the larynx by the probe with endoscopy, cough reflex test, swallowing provocation test. RESULTS: The essential swallowing sensations of mechanical stimulation, chemical stimulation, thermal stimulation were 84.9%, 5.4%, and 9.7%, respectively. The frequency of touching the larynx by endoscopy in the otolaryngology group and cough reflex test in dentistry was significantly higher than the other groups (p < 0.05). The correlation between the frequency and difficulty or effectiveness of the sensory tests indicated that the frequency and difficulty are significantly correlated between each item. CONCLUSION: Our results aid in increasing understanding and selection of pharyngolaryngeal sensation evaluation for dysphagia patients.

OBJECTIVE: To analyze the outcomes of the underwater endoscopic ear surgery (UWEES) technique for closure of cholesteatomatous labyrinthine fistula (LF) with preservation of auditory function. STUDY DESIGN: Retrospective case review study. SETTING: Tertiary referral center. PATIENTS: A total of 12 patients with cholesteatomatous LF. INTERVENTION: Surgical method of closure using UWEES for cholesteatomatous LF to minimize inner ear damage. Artificial cerebrospinal fluid (CSF) was used as the perfusate, except for earlier cases when saline was employed. MAIN OUTCOME MEASURES: Comparison of bone conductance hearing level (BCHL) before and after surgery. A change of BCHL less than 10 dB was defined as successful preservation of bone conductance hearing. RESULTS: All cases of LF were treated successfully by closure using the UWEES technique. Seven cases were type I, one was type IIa, and four were type III according to the Milewski and Dornhoffer classification of LF. The average LF size was 3.1 mm (1-7 mm). Eleven patients were evaluated and their bone conductance hearing was well preserved in all of them (11/11). One patient was too young for preoperative evaluation of BCHL, but hearing preservation was verified 2 years later at the age of 6 years. Remarkably, none of the patients complained of vertigo, except for only a slight manifestation on postoperative day 1. CONCLUSION: The UWEES technique was effective for closure of cholesteatomatous LF with preservation of auditory function.

A 69-year-old woman presented with mild renal dysfunction, proteinuria, and sensorineural hearing loss. A renal biopsy showed focal segmental glomerulosclerosis with thinning of the glomerular basement membrane. There was a positive family history of end-stage kidney disease and hearing loss. Although Alport syndrome was suspected from these features, a genetic test using next-generation sequencer identified a novel missense mutation in LMX1B, c.655C>G: p. (Pro219Ala). In silico analyses predicted the pathogenicity of the mutation. Thus, the present case was diagnosed as LMX1B-associated nephropathy presenting with Alport syndrome-like phenotype, expanding the disease spectrum of LMX1B nephropathy.

ABSTRACT: No study has examined whether magnetic resonance imaging (MRI) alone can be used for evaluating olfactory cleft and ethmoidal sinus in patients with olfactory disorders. Therefore, we analyzed the discrepancies between computed tomography (CT) and MRI in the imaging of the olfactory cleft and ethmoidal sinus. Patients who underwent CT and MRI within 30 days were evaluated. Age, sex, diagnosis, presence of bronchial asthma (BA), peripheral blood eosinophil percentage, and CT and MRI findings were retrospectively reviewed, and the sinuses were assessed on a scale of 0 to 3. Overall, 146 patients with 292 sinuses were enrolled. The ethmoid sinus score and the olfactory cleft score had 77.1% and 72.6% image similarity in CT and MRI. Sex and BA status were not associated with olfactory cleft score discrepancies (sex: P = 0.52, BA: P = 0.41). Magnetic resonance imaging scores tended to be rated higher than the CT scores as age increased, although this difference was not statistically significant (P = 0.09). The higher the peripheral blood eosinophil percentage, the more the magnitude by which the CT score tended to exceed the MRI score; however, this finding was also not statistically significant (P = 0.11). Magnetic resonance imaging scans should be limited to the evaluation of intracranial regions. Scans of olfactory cleft and ethmoid cells are not accurate for the assessment of olfactory dysfunction.

OBJECTIVE: Current interventions of dysphagia are not generalizable, and treatments are commonly used in combination. We conducted a questionnaire survey on nurses and speech therapists regarding dysphagia rehabilitation to understand the current situation in Japan. METHODS: The questionnaire was sent to 616 certified nurses in dysphasia nursing and 254 certified speech-language-hearing therapists for dysphagia. Based on "Summaries of training methods in 2014" by JSDR, 24 local indirect exercises, 11 general indirect exercises, and 13 direct exercises were selected. The Likert scale "How do you feel about each method" was used as follows: A; Frequency, B; Ease, C; Adherence, D; Effectiveness (1-5))?". RESULTS: Two hundred fifty (40%) nurses and 145 (57%) speech-language-hearing therapists (ST) responded to the questionnaire. The direct exercise was associated with a significantly high score in every question. In indirect exercises, "Cervical range of motion exercise," "Orofacial myofunctional exercise," "Lip closure exercise." "Ice massage of pharynx" and "Huffing" were used relatively frequently. "Balloon dilatation therapy" and "Tube exercise" was associated with a relatively high discrepancy for two questions. Frequency" and the sum of "Ease," "Adherence," and "Effectiveness." was significantly correlated for local indirect exercises (r2 = 0.928, P < 0.01), general indirect exercises (r2 = 0.987, P < 0.01), and direct exercises (r2 = 0.996, P < 0.01) (Fig. 5). CONCLUSION: This study examined the current situation of dysphagia rehabilitation in Japan. Our results aid to increase understanding and selection of rehabilitative treatments for dysphagia patients in Japan.

OBJECTIVES: To compare the loudness functions (loudness ratings as a function of sound level) obtained from patients diagnosed as having functional hearing loss (FHL) with those for patients with sensorineural hearing loss (SNHL) and healthy volunteers. DESIGN: Loudness functions for a 1000 Hz tone for patients with FHL and SNHL were assessed based on the categorical loudness scaling method. The data were compared with control data obtained in our facilities. STUDY SAMPLE: 18 patients (33 ears) with FHL and 10 patients (19 ears) with SNHL. RESULTS: For patients with SNHL and healthy volunteers, loudness increased progressively with increasing sound level above the audiometric threshold, with no exceptions. However, for about 70% of the patients with FHL, a different type of loudness function was obtained; the thresholds determined from the loudness function, which were defined as the minimum sound levels at which loudness could be judged, were 10 dB or more lower than the audiometric threshold (>10 dB), and/or the loudness ratings were elevated for a sound at the audiometric threshold. CONCLUSIONS: The results support the hypothesis that patients with FHL often make threshold judgments based on a certain loudness.

BACKGROUND: Fish bones are common foreign bodies in the upper aero-digestive tract, but their clinical features in relation to fish species have not been confirmed. We aimed to clarify the clinical characteristics of fish-bone foreign bodies and their location and removal methods depending on the fish species. STUDY DESIGN: Retrospective, observational, monocentric study. METHODS: From October 2015 to May 2020, 368 patients visited the Department of Otolaryngology-Head and Neck Surgery at Tohoku University Hospital complaining of dysphagia, sore throat, or pharyngeal discomfort after eating fish. We analyzed the patients' sex and age distribution, foreign-body location, type of the fish, and the techniques used for removing the foreign body. RESULTS: Fish bones were confirmed in the upper aero-digestive tract in 270 cases (73.4%), of which 236 (87.4%) involved fish-bone foreign bodies in the mesopharynx. The most frequently involved site was the palatine tonsil (n = 170). Eel was the most frequently observed fish species (n = 39), followed by mackerel (n = 33), salmon (n = 33), horse mackerel (n = 30), and flounder (n = 30). Among the 240 cases in which the bones did not spontaneously dislocate, 109 (45.4%) were treated by endoscopic removal (103 cases) or surgery (6 cases). In pediatric cases (<12 years old), almost all fish bones were found in the mesopharynx (138/139, 99.3%), and 31 cases (22.3%) required endoscopic removal. Flounder fish bones were often lodged in the hypopharynx and esophagus (9/30, 30%), hindering spontaneous dislocation and frequently necessitating endoscopic or surgical removal (19/29, 65.5%). CONCLUSION: The characteristics of fish-bone foreign bodies differed depending on the fish species. Flounder bones were often stuck in the hypopharynx and esophagus and were likely to require more invasive removal methods. Confirming the species of the fish could facilitate appropriate diagnosis and treatment of fish-bone foreign bodies.

Respiratory epithelial adenomatoid hamartomas (REAHs) are rare tumors occurring in the nasal cavity and sinuses, and their etiology is unknown. REAH is a relatively recently established lesion and is often misdiagnosed as nasal polyposis or other tumors. Preoperative endovascular embolization for sinonasal tumors is now widely accepted as an effective method to reduce blood loss, soften the tumor, and facilitate surgical procedures. However, to the best of our knowledge, there are no reports of the requirement for preoperative embolization in the management of REAH. Here, we present a 70-year-old man with an easily bleeding REAH of the olfactory cleft, vascularized by branches of the bilateral internal and external carotid arteries. We removed the tumor endoscopically after preoperative embolization of the bilateral sphenopalatine arteries. Histological investigation revealed an intratumoral hemorrhage accompanying the REAH, with no evidence of a residual or recurrent tumor during the last follow-up at 3 months. In conclusion, accurate preoperative diagnosis and proper preoperative interventions such as embolization are needed for safe and adequate treatment of REAHs that have an abundant blood flow.

A 52-year-old man presented to our emergency department with an acute onset of right-sided facial nerve (FN) palsy of House-Brackmann grade V. Electroneurography (ENoG) was conducted with no response at the right FN, as compared with the left FN (0%). We performed a biopsy of the right middle ear mass and histological studies showed the tumor to be neuroendocrine tumors (NET) of the middle ear. We resected the tumor with canal wall down mastoidectomy and reconstructed the posterior meatal wall with soft tissue. Three months after surgery, the FN paralysis had improved with House-Brackmann grade II. We reviewed cases of NET with FN palsy, and nine patients, including our case, have been reported. Our case is the first report of ENoG for the description of FN palsy due to NET. Although the ENoG value was 0%, it was remarkably improved by surgery. The other cases of NET patients with FN palsy also recovered FN function after surgery. These results suggest that it is recommended to perform the total resection of the tumor to improve the FN function.

Lingual osseous choristoma is a rare benign tumor consisting of normal matured bone tissue. It was first reported in 1913, and less than 100 cases of lingual osseous choristomas, mainly in their twenties and thirties, have been reported in the English literature until now. Here, we report an additional case of lingual osseous choristoma, in an elderly patient, that was incidentally removed by coughing and cured without additional interventions. An 89-year-old male patient was referred to our department for an evaluation of chronic cough. When we examined his oral cavity and pharynx, he expectorated a 10 -mm mass which was histologically diagnosed as an osseous choristoma. We confirmed the well-defined, rounded, high-density mass with a tiny pedicle on the base of the tongue in previous cervical spine CT images. No signs of recurrence were found during the 15-month follow-up examination. Our case serves as a reminder of this rare entity in the diagnosis of tongue masses of the elderly.

OBJECTIVE: Dietary intervention is a practical prevention strategy for age-related hearing loss (AHL). Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) may be effective in prevention of AHL due to their anti-inflammatory and tissue-protective functions. Age-related changes in the hearing function of wild-type and Fat-1 transgenic mice derived from the C57BL/6N strain, which can convert omega-6 PUFAs to n-3 PUFAs and consequently produce enriched endogenous n-3 PUFAs, were investigated to test the efficacy of n-3 PUFAs for AHL prevention. RESULTS: At 2 months, the baseline auditory brainstem response (ABR) thresholds were the same in Fat-1 and wild-type mice at 8-16 kHz but were significantly higher in Fat-1 mice at 4 and 32 kHz. In contrast, the ABR thresholds of Fat-1 mice were significantly lower at 10 months. Moreover, the ABR thresholds of Fat-1 mice at low-middle frequencies were significantly lower at 13 months (12 kHz). Body weights were significantly reduced in Fat-1 mice at 13 months, but not at 2, 10, and 16-17 months. In conclusion, enriched endogenous n-3 PUFAs produced due to the expression of the Fat-1 transgene partially alleviated AHL in male C57BL/6N mice.

Noise exposures causing only transient threshold shifts can destroy auditory-nerve synapses without damaging hair cells. Here, we asked whether virally mediated neurotrophin3 (NT3) overexpression can repair this damage. CBA/CaJ mice at 6 wks were injected unilaterally with adeno-associated virus (AAV) containing either NT3 or GFP genes, via the posterior semicircular canal, 3 wks prior to, or 5 hrs after, noise exposure. Controls included exposed animals receiving vehicle only, and unexposed animals receiving virus. Thresholds were measured 2 wks post-exposure, just before cochleas were harvested for histological analysis. In separate virus-injected animals, unexposed cochleas were extracted for qRT-PCR. The GFP reporter showed that inner hair cells (IHCs) were transfected throughout the cochlea, and outer hair cells mainly in the apex. qRT-PCR showed 4- to 10-fold overexpression of NT3 from 1-21 days post-injection, and 1.7-fold overexpression at 40 days. AAV-NT3 delivered prior to noise exposure produced a dose-dependent reduction of synaptopathy, with nearly complete rescue at some cochlear locations. In unexposed ears, NT3 overexpression did not affect thresholds, however GFP overexpression caused IHC loss. In exposed ears, NT3 overexpression increased permanent threshold shifts. Thus, although NT3 overexpression can minimize noise-induced synaptic damage, the forced overexpression may be harmful to hair cells themselves during cochlear overstimulation.

Recent work shows that acoustic overexposures causing only transient threshold elevation, and no hair cell loss, nevertheless can cause irreversible loss of the synapses between inner hair cells and cochlear nerve fibers (Kujawa and Liberman 2009). This cochlear synaptopathy, which is selective for the subset of sensory fibers with high thresholds and low spontaneous rates (Furman et al. 2013), appeared fully developed at 24-h post-exposure and showed no recovery by 8 weeks. However, prior studies of this synaptopathy counted only pre-synaptic ribbons, did not examine post-exposure times less than 24 h, and did not analyze the spatial patterns of degeneration around the hair cell circumference. Here, we immunostained for pre-synaptic ribbons, post-synaptic terminals and glutamate receptor patches, as well as the hair cell cytoplasm in noise-exposed and control mice to address the dynamics and spatial organization of the synaptopathic process as a function of post-exposure time from 0 h to 2 weeks. Our analysis showed that the loss of synaptic elements is nearly complete immediately after the 2-h exposure, that there is a reversible downregulation of gluR expression in the peripheral terminals which may be part of a protective mechanism, that there may be reversible reorganization of synaptic locations immediately after exposure, and that the spatial patterns are consistent with the idea that low-SR fibers are mainly found on the modiolar face of the hair cell and are the most vulnerable to noise-induced degeneration.

Osteoma of the internal auditory canal (IAC) is an uncommon benign bone tumor. Its imaging features may be similar to other IAC lesions, such as vestibular schwannomas that are benign and usually slow-growing but sometimes life-threatening tumors. Thus, detecting IAC lesions and differentiating osteoma from other IAC lesions are both important clinically. We report a case of misdiagnosis of an IAC osteoma as an IAC schwannoma based on magnetic resonance (MR) imaging using the three-dimensional constructive interference in steady state (CISS) sequence instead of T1-weighted MR imaging with gadolinium. We also review 17 cases of IAC osteomas reported in the past 22 years. A 61-year-old female was admitted to our department with IAC lesion incidentally discovered by the CISS sequence. The lesion was diagnosed as an IAC schwannoma, and was followed up annually under "wait and scan" management. Follow-up T1-weighted MR imaging with gadolinium showed no enhancement of the tumor, and additional computed tomography (CT) of the temporal bone showed a solitary pedunculated bony lesion, resulting in the diagnosis of IAC osteoma. The CISS sequence is useful for detecting small IAC lesions, such as vestibular schwannomas. However, the CISS sequence has limitations for qualitative diagnosis and can misdiagnose osteomas as schwannomas. Use of the CISS sequence without T1-weighted MR imaging with gadolinium for the screening of a lesion of the IAC and cerebellopontine angle should consider the possibility of IAC osteomas, and temporal bone CT or T1-weighted MR imaging with gadolinium should be performed when an IAC lesion is detected.

AIM: Rhino-sinus mucosal involvement is well documented in untreated lepromatous leprosy, but less understood in ex-leprosy patients (i.e. leprosy patients who have been treated and cured) with atrophic rhinitis. MATERIALS AND METHODS: Rhino-sinus abnormalities were investigated in 13 ex-lepromatous leprosy patients with atrophic rhinitis, using interviews enquiring about sinonasal symptoms, nasal endoscopy, nasal swab culture and computed tomography. Endoscopic sinus surgery had been performed in three patients. The clinical course, computed tomography findings and nasal biopsy results of these three patients were evaluated. RESULTS: All patients had turbinate atrophy and 6 of the 13 (46.2 per cent) had septal perforation. Paranasal sinus involvement was noted in 9 of 12 examined patients (75 per cent). The most commonly affected sinus was the maxillary sinus (in 8 of 12; 66.7 per cent). All three patients treated by endoscopic sinus surgery experienced relapse and required further surgery. Maxillary sinus irrigation was effective for reduction of persistent symptoms such as postnasal discharge and crusts. CONCLUSION: Ex-lepromatous leprosy patients with atrophic rhinitis had various rhino-sinus abnormalities and persistent symptoms. These patients had chronic rhinosinusitis because of underlying atrophic rhinitis. These patients required repeated otolaryngological observations together with combined surgery and conservative treatment.

Carcinoma cuniculatum (CC) is a rare variant of low-grade squamous cell carcinoma (SCC), and occurrence in the oral cavity is quite unusual. CC has a papillomatous keratinized surface like verrucous carcinoma, but CC has a propensity for aggressive local invasion, especially into the bone. Therefore, CC can be quite difficult to remove surgically. A 68-year-old man presented with a case of CC mimicking verrucous leukoplakia in the mandibular gingiva. Repeated biopsies showed no malignancy. Local resection was performed, and histological examination revealed the presence of well-differentiated SCC. Additional hemi-mandibulectomy was performed and the final histological diagnosis was CC. Local recurrence was detected at the 14-month follow-up examination. Chemotherapy with docetaxel was not effective, and he died of aspiration pneumonia. CC of the oral cavity is a rare entity and the diagnosis is hard to establish. Misdiagnosis could result in inadequate removal and local recurrence. Complete resection with a safety margin is essential because of the tendency for local invasion.

OBJECTIVES: Vallecular cyst is uncommon in infants. We treated a female infant with vallecular cyst, and curious magnetic resonance imaging findings. We also review 51 other cases of vallecular cyst in infants reported over the past 23 years. CASE REPORT: A three-month-old female infant presented with congenital inspiratory stridor and failure to thrive. Flexible laryngoscopy and ultrasonography revealed a cystic mass in the vallecula. Magnetic resonance imaging findings were initially curious because of artefacts from breathing and swallowing. Marsupialisation of the cyst was performed. Post-operatively, the patient was immediately free of symptoms. CONCLUSION: Magnetic resonance imaging presents various difficulties in infants, but has the best diagnostic effectiveness. We recommend the use of magnetic resonance imaging, flexible fibroscopy and ultrasonography to enable extensive examination of suspected vallecular cysts in infants. Marsupialisation has a recurrence rate of only one in 39 cases, and its safety and effectiveness are well balanced. Thus, prompt marsupialisation of vallecular cyst is the recommended surgical procedure.