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Research was conducted to examine the hypothesis that interferon (IFN)-gamma stimulates human Clara cell secretory protein production by human airway epithelial cells. For this study, a human bronchial epithelial cell line (BEAS-2B) was utilized. Results suggest that IFN-gamma can induce increases in steady-state mRNA levels and protein synthesis of human CCSP protein in airway epithelial cells and may modulate airway inflammatory responses.

One component of Oriental medicine diagnosis utilizes the palpation of the radial pulse both for internal medicine and also to help clinicians accurately choose body acupuncture treatment points. In the mid-1980s, an attempt was made to capture diagnostic information with three pressure transducers positioned bilaterally over the radial arteries in such a fashion as to simulate classical Chinese pulse diagnosis (Yoon and Ikezono, 1986 and 1987). The results of this pilot study were subsequently difficult to replicate. In the early 1950s, Paul Nogier in Lyon, France introduced a different pulse diagnostic technique (Nogier, 1976). By touching an acupuncture needle on an active auricular acupuncture point, the radial artery wall over the styloid process changes in tone more prominently than when inactive points on the acuricle are touched. This dermal/cardiovascular reflex of pulse diagnostic technique helps, then to localize salient auricular points to treat regarding a patient's illness. Objective digitalized measurements of the Nogier radial arterial pulse wave were performed by computerized tonometry. This demonstrated that when an active stomach point in the auricle (n = 11) was detected utilizing an imperceptible electric current, the initial upstroke of the pressure wave, the pulse pressure and the peak-to-peak interval of the radial artery pulse wave all increased significantly compared to placebo point electronic detection. Thus, the existence of an active auricular point on the auricle was verified by radial artery tonometry. [ABSTRACT FROM AUTHOR]

To determine the presence and prevalence of regional contraction abnormalities in patients with angina pectoris, radionuclide ventriculography gated to an electrocardiogram was carried out in 22 control subjects (group 1) and in 22 patients with angina pectoris (group 2) with isolated stenosis of the left anterior descending coronary artery. No patients had had previous myocardial infarctions. A computer program subdivided the left ventricle into four regions at a geometric centre, and time-activity curves (30-40 ms/frame) of the global, septal, apical, and lateral regions were computed. There was no significant difference in the ejection fraction in the global or in any of the regions between the two groups. End systole in each region occurred close to global end systole in both groups. In the global region the percentage stroke volume ejected during the first third of systole was not significantly less in group 2 than in group 1. Regional analysis of the segments perfused by the stenosed vessel showed that the percentage stroke volume ejected during the first third of systole in group 2 was significantly less in the septal region and in the apical region compared with that in group 1. In contrast, in the normally perfused lateral region, there was no significant difference in the percentage stroke volume at the first third of systole between the two groups. This indicates that early contraction abnormalities are present in the region perfused by the stenosed vessel in patients with angina pectoris without previous myocardial infarction. Thus analysing the regional change in left ventricular volume during ejection in patients with coronary artery disease can show localised areas of contraction abnormalities during early systole that are not apparent when ventricular contraction is assessed as a whole. [ABSTRACT FROM PUBLISHER]

Objective: A well-known and frequently reported complication after cochlear implantation is the appearance of postoperative vertigo symptoms. Perilymphatic fistula (PLF) is a known cause for hearing loss and vertigo. Cochlin-tomoprotein (CTP) is a cochlear specific protein acting as a marker for PLF. Aim of the present study was to observe, if the postoperatively new occurence of vertigo is caused by a perilymphatic fistula evidenced by CTP marker . Methods: In a prospective analysis 12 cochlear implant patients with the postoperatively new occurence of vertigo underwent a transtympanally revison/resealing surgery. In all patients middle ear fluid was captured and analysed for CTP. Results: In 5 out of 12 patients a positive CTP result was found indicating a PLF. Positive PLF finding did not correlate with the intraoperative visual assumption of a leak. The procedure solves in most of the cases the vertigo problem. Conclusion: Our present finding demonstrates that objectively an insufficent sealing causing perilymphatic fistula occurs frequently in cases of newly postoperative vertigo after cochlea implantation. [ABSTRACT FROM AUTHOR]

Objective: Acute sensorineural hearing loss represents a spectrum of conditions characterized by sudden onset hearing loss. The "Clinical Practice Guidelines for the Diagnosis and Management of Acute Sensorineural Hearing Loss" were issued as the first clinical practice guidelines in Japan outlining the standard diagnosis and treatment. The purpose of this article is to strengthen the guidelines by adding the scientific evidence including a systematic review of the latest publications, and to widely introduce the current treatment options based on the scientific evidence., Methods: The clinical practice guidelines were completed by 1) retrospective data analysis (using nationwide survey data), 2) systematic literature review, and 3) selected clinical questions (CQs). Additional systematic review of each disease was performed to strengthen the scientific evidence of the diagnosis and treatment in the guidelines., Results: Based on the nationwide survey results and the systematic literature review summary, the standard diagnosis flowchart and treatment options, including the CQs and recommendations, were determined., Conclusion: The guidelines present a summary of the standard approaches for the diagnosis and treatment of acute sensorineural hearing loss. We hope that these guidelines will be used in medical practice and that they will initiate further research., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest in this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly established immunodeficiency-related disease. Herein, we report a case of EBVMCU and focus on its cytological usefulness for diagnosis. An 82-year-old man manifested pharyngalgia, dysphagia, and oral pain. His medical history included rheumatoid arthritis that had been treated with methotrexate. Clinically, peritonsillar abscess was suspected, but since neoplastic lesions, including malignant lymphoma (ML), could not be excluded, a series of cytohistological examination was attempted. Despite some alarming findings (e.g., frequent mitoses), fine-needle aspiration and touch imprint cytology consistently revealed a heterogeneous population of lymphoid and plasmacytoid cells with mild nuclear atypia. The final diagnosis of EBVMCU was established based on the permanent histologic specimen; however, retrospectively, cytology was more representative of the benign nature of the lesion than histology, helping a great deal to differentiate it from ML. Cytology can be a useful tool for the correct diagnosis of EBVMCU., (© 2024 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Several surgical techniques have been documented for approaching and repairing superior semicircular canal dehiscence syndrome (SCDS). These techniques encompass the trans-middle cranial fossa, transmastoid, endoscopic approaches, and round window reinforcement (RWR). RWR entails the placement of connective tissue with or without cartilage and around the round window niche, restricting the round window's movement to minimize the 3rd window effect and restore the bony labyrinth closer to its normal state. We employed the multilayer RWR technique, resulting in significant postoperative improvement and long-lasting effects for 3.7 years in 2 cases. Here, we present the clinical findings, surgical procedures, and the effectiveness of multilayer RWR. This technique can be the initial choice for surgical treatments of SCDS due to its high effectiveness, longer-lasting effect, and minimal risk of surgical complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sawada, Matsuda, Tanzawa, Sakamoto, Kudo, Nakashima and Ikezono.)

Purpose: To determine the prevalence of perilymphatic fistula (PLF) in sudden-onset sensorineural hearing loss (SSNHL) patients by employing the Cochlin-tomoprotein (CTP) detection test, a specific diagnostic marker for perilymph. We also analyzed the clinical characteristics associated with hearing outcomes in this cohort., Methods: A total of 74 eligible patients were prospectively enrolled. Following myringotomy, middle ear lavage (MEL) samples underwent the CTP test to identify perilymph leakage. Intratympanic dexamethasone (IT-DEX) therapy was administered, and hearing outcomes were assessed. Control groups comprised patients with chronic otitis media (n = 40) and non-inflammatory middle ears (n = 51) with concurrent MEL sample collection., Results: CTP was positive in 16 (22%) patients. No control samples showed positive results. Multiple regression analysis indicated that age and pre-treatment hearing levels significantly contributed to the CTP value. We found a positive correlation between CTP values, age, and pre-treatment pure-tone averages. Notably, CTP values in SSNHL cases aged 60 and above were significantly higher than in those below 60 years. Patients with positive CTP had significantly worse recovery rates after IT-DEX treatment., Conclusion: This study is the first prospective investigation demonstrating a positive relationship between CTP values, age, and hearing severity in SSNHL, indicating that PLF might be the essential cause of SSNHL, particularly in the elderly. Our findings suggest that IT-DEX may be less effective for PLF-associated SSNHL. Future research could reveal that PLF repair surgery is a viable treatment strategy for SSNHL. This study was registered under the UMIN Clinical Trials Registry (UMIN000010837) on 30/May/2013., (© 2023. The Author(s).)

Objectives: An idiopathic perilymphatic fistula (PLF) can be difficult to diagnose because patients present with sudden sensorineural hearing loss (SSHL) and/or vestibular symptoms without any preceding events. In such cases, we currently test for cochlin-tomoprotein (CTP) to confirm the diagnosis of idiopathic PLF because CTP is only detected in the perilymph. In this study, we report the clinical course of five patients definitively diagnosed with idiopathic PLF who underwent PLF repair surgery using transcanal endoscopic ear surgery (TEES)., Patients and Methods: Five patients were initially treated with intratympanic dexamethasone for SSHL, at which time a CTP test was also performed (preoperative CTP test). Due to refractory hearing loss and/or fluctuating disequilibrium, PLF repair surgery using TEES was performed to seal the oval and round windows using connective tissue and fibrin glue. These patients were diagnosed with definite idiopathic PLF based on pre- or intra-operative CTP test results (negative, < 0.4 ng/mL; intermediate, 0.4-< 0.8 ng/mL; and positive, > 0.8 ng/mL). We evaluated pre- and intra-operative CTP values, intraoperative surgical findings via a magnified endoscopic view, and pre- and post-operative changes in averaged hearing level and vestibular symptoms., Results: Pre- and intra-operative CTP values were positive and intermediate in three patients, positive and negative in one patient, and negative and positive in one patient. None of the patients had intraoperative findings consistent with a fistula between the inner and middle ears or leakage of perilymph. Only two patients showed a slight postoperative recovery in hearing. Four patients complained of disequilibrium preoperatively, of whom two had resolution of disequilibrium postoperatively., Conclusion: A positive CTP test confirms PLF in patients without obvious intraoperative findings. The CTP test is considered more sensitive than endoscopic fistula confirmation. We consider that CTP test results are important indicators to decide the surgical indication for idiopathic PLF repair surgery. In our experience with the five cases, two of them showed improvements in both hearing and vestibular symptoms., Competing Interests: Saitama Medical University, where HaM and TeI are affiliated, holds the patents for the hCTP ELISA test. This fact did not influence the results of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kubota, Ito, Furukawa, Matsui, Goto, Shinkawa, Matsuda, Ikezono and Kakehata.)

Objective: Vertigo is a quite frequent complication after cochlear implantation. Perilymphatic fistula (PLF) is assumed to be one cause of this problem. Cochlin tomoprotein (CTP) is a newly introduced marker for PLF. The present aim was to evaluate the rate of positive CTP testing in cases of newly occurring vertigo after cochlear implantation., Materials and Methods: Twelve patients with vertigo after cochlear implantation and a revisional electrode-sealing procedure underwent intraoperative rinsing of their middle ear. The sample was evaluated for CTP with monoclonal antibody testing. Sixteen controls from six CI patients were taken., Results: 4 out of 12 (33%) cases showed positive CTP testing, indicating that a PLF could be evaluated. In all of the positive CTP cases, surgery decreased the vertigo symptoms. A relation between the subjective visual assessment of a fistula and a positive CTP value was not observed. Controls confirmed the value of the testing., Discussion: CTP detection objectively shows that PLF can occur in patients with vertigo after CI.

Perilymph Fistula (PLF), abnormal communication between the fluid-filled space of the inner ear and the air-filled space of the middle ear, is a significant cause of vestibular and auditory symptoms. This is a retrospective study of 22 cases treated with PLF repair surgery, selected based on our surgical indication. We analyzed the characteristics of these 22 cases and evaluated the efficacy of PLF repair surgery in treating vestibular and auditory symptoms. Cases with antecedent events had significantly shorter intervals before surgery. The postoperative recovery from vestibular symptoms following PLF repair surgery was strikingly rapid, with 82% of cases demonstrating marked improvement within a week, even in chronic cases. Despite the notable absence of a control group in the study, the marked improvements in vestibular symptoms and substantial reductions in Dizziness Handicap Inventory (DHI) scores suggest that the observed benefits are attributable to the surgical intervention. Further, timely surgery showed improvements in hearing, with some benefits also seen in late-stage surgeries. Using the perilymph-specific protein Cochlin-tomoprotein (CTP) as a diagnostic biomarker, we could prove that PLF could be responsible for disequilibrium and related auditory disturbances in these patients. A new hypothesis is proposed that the chronic disequilibrium experienced by many PLF patients is due to enhanced mobility of the utricle and not to endolymphatic hydrops. Further research is needed to fully elucidate PLF's symptoms and treatment efficacy using the surgical indication we developed., Competing Interests: Saitama Medical University, where HM and TI are affiliated, holds the patents for the hCTP ELISA test. This fact did not influence the results of the study. The remaining author has no commercial or financial relationships that could be perceived as potential conflicts of interest., (Copyright © 2023 Matsuda, Hornibrook and Ikezono.)

Background: Empty nose syndrome (ENS) is caused by nasal turbinate surgery. The standard treatment for ENS is an inferior meatus augmentation procedure (IMAP) in which autologous tissue such as auricular cartilage, rib cartilage, or artificial material is transplanted into the nasal cavity. However, some challenges like a very small auricular cartilage are associated with these autologous tissue types. Moreover, since using rib cartilage is a highly invasive technique, the scar on the chest from where the harvesting is done is easily visible, and the artificial material is susceptible to infection. We used autologous dermal fat (ADF) in IMAPs in our study for the following reasons: the quantity of ADF could be increased or reduced as needed, ADF is considered a safer option than rib cartilage because it is harvested from superficial tissue, it is superior in terms of cosmetic appearance to harvested rib cartilage, and it has a lower risk of infection than any artificial material. Objective: The purpose of our study was to investigate the efficacy and safety of IMAPs using ADF. Methods: We included nine patients with ENS who underwent an IMAP using ADF. The patients' backgrounds and responses to the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) were recorded. Changes in each item of the ENS6Q before and after surgery (up to 3 months) were analyzed. Results: The postoperative ENS6Q total score and parameters were significantly better than their preoperative counterparts. Nasal dryness improved slightly less than other symptoms. There were no complications. Conclusions: The IMAP using ADF was effective in improving ENS symptoms; however, some physiological functions were difficult to improve, and dryness persisted. Autologous dermal fat is larger than auricular cartilage, less invasive than rib cartilage, and has a lower risk of infection than artificial material., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Delayed endolymphatic hydrops (DEH) is an inner ear disease that causes recurrent vertigo in the ipsilateral ear or fluctuating hearing in the contralateral ear due to endolymphatic hydrops secondary to preceding deafness. There are few reports of large, multicentre studies investigating the clinical-epidemiological characteristics of DEH., Objective: This study aimed to clarify the characteristics of DEH in Japan., Methods: Clinical data on 662 patients with DEH were analysed by nationwide, multicentre surveys conducted by the Peripheral Vestibular Disorders Research Group of Japan., Results: The proportion of ipsilateral DEH (IDEH) was slightly higher than that of contralateral DEH (CDEH) at 55.4%. The time delay between onset of precedent deafness and onset of DEH was significantly longer for CDEH than for IDEH. The most common cause of precedent deafness was a disease of unknown cause with onset in early childhood (33.1%). Epidemiological characteristics were not significantly different between CDEH with and without vertigo., Conclusion: DEH appearing to be caused by viral labyrinthitis has a high rate of onset within 40 years of precedent deafness. Clinical and epidemiological characteristics of IDEH, CDEH with vertigo, and CDEH without vertigo were very similar., Significance: The clinical-epidemiological characteristics of DEH in Japan were clarified.

Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients., (© 2021. The Author(s).)

Background: Non-contrast FLAIR revealed increased signal within the inner ear in patients with vestibular schwannoma, which is generally assumed to occur in the perilymph; however, the majority of previous studies did not differentiate between the endolymph and perilymph. Therefore, endolymph signal changes have not yet been investigated in detail. The purpose of the present study was three-fold: (1) to assess perilymph signal changes in patients with vestibular schwannoma on heavily T2-weighted (T2W) 3D FLAIR, also termed positive perilymphatic images (PPI), (2) to evaluate signal and morphological changes in the endolymph on PPI, and (3) to establish whether vertigo correlates with the signal intensity ratios (SIR) of the vestibular perilymph or vestibular endolymphatic hydrops., Methods: Forty-two patients with unilateral vestibular schwannoma were retrospectively recruited. We semi-quantitatively and qualitatively evaluated the perilymph signal intensity on the affected and unaffected sides. We also quantitatively examined the signal intensity of the vestibular perilymph and assessed the relationship between vertigo and the SIR of the vestibular perilymph on the affected side. We semi-quantitatively or qualitatively evaluated the endolymph, and investigated whether vestibular hydrops correlated with vertigo., Results: The perilymph on the affected side showed abnormal signal more frequently (signal intensity grade: overall mean 1.45 vs. 0.02; comparison of signal intensity: overall mean 36 vs. 0 cases) and in more parts (the entire inner ear vs. the basal turn of the cochlea and vestibule) than that on the unaffected side. No significant difference was observed in the SIR of the vestibular perilymph with and without vertigo (5.54 vs. 5.51, p = 0.18). The endolymph of the vestibule and semicircular canals showed the following characteristic features: no visualization (n = 4), signal change (n = 1), or vestibular hydrops (n = 10). A correlation was not observed between vestibular hydrops and vertigo (p = 1.000)., Conclusions: PPI may provide useful information on signal and morphological changes in the endolymph of patients with vestibular schwannoma. Further research is warranted to clarify the relationship between vertigo and the MR features of the inner ear., (© 2021. The Author(s).)

Human ACTG1 mutations are associated with high-frequency hearing loss, and patients with mutations in this gene are good candidates for electric acoustic stimulation. To better understand the genetic etiology of hearing loss cases, massively parallel DNA sequencing was performed on 7,048 unrelated Japanese hearing loss probands. Among 1,336 autosomal dominant hearing loss patients, we identified 15 probands (1.1%) with 13 potentially pathogenic ACTG1 variants. Six variants were novel and seven were previously reported. We collected and analyzed the detailed clinical features of these patients. The average progression rate of hearing deterioration in pure-tone average for four frequencies was 1.7 dB/year from 0 to 50 years age, and all individuals over 60 years of age had severe hearing loss. To better understand the underlying disease-causing mechanism, intracellular localization of wild-type and mutant gamma-actins were examined using the NIH/3T3 fibroblast cell line. ACTG1 mutants p.I34M p.M82I, p.K118M and p.I165V formed small aggregates while p.R37H, p.G48R, p.E241K and p.H275Y mutant gamma-actins were distributed in a similar manner to the WT. From these results, we believe that some part of the pathogenesis of ACTG1 mutations may be driven by the inability of defective gamma-actin to be polymerized into F-actin.

MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells.

TECTA is well known as a causative gene for autosomal dominant mid-frequency hearing loss observed in various populations. In this study, we performed next-generation sequencing analysis of a large Japanese hearing loss cohort, including eight hundred and twelve (812) subjects from unrelated autosomal dominant hearing loss families, to estimate the prevalence and phenotype-genotype correlations in patients with TECTA mutations. The prevalence of TECTA mutations in Japanese autosomal dominant sensorineural hearing loss families was found to be 3.2%. With regard to the type of hearing loss, the patients with mutations in the nidogen-like domain or ZA domain of TECTA showed varied audiograms. However, most of the patients with mutations in the ZP domain showed mid-frequency hearing loss. The rate of hearing deterioration in TECTA -associated hearing loss patients and in the normal hearing Japanese control population were the same and regression lines for each group were parallel. We carried out haplotype analysis for four families which had one recurring missense variant, c.5597C>T (p.Thr1866Met). Our results revealed four different haplotypes, suggesting that this mutation occurred independently in each family. In conclusion, TECTA variants represent the second largest cause of autosomal dominant sensorineural hearing loss in Japan. The hearing loss progression observed in the patients with TECTA mutations might reflect presbycusis. The c.5597C>T mutation occurred in a mutational hot spot and is observed in many ethnic populations.

The OTOF gene (Locus: DFNB9), encoding otoferlin, is reported to be one of the major causes of non-syndromic recessive sensorineural hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder (ANSD). In the present study, we performed OTOF mutation analysis using massively parallel DNA sequencing (MPS). The purpose of this study was to reveal the frequency and precise genetic and clinical background of OTOF-related hearing loss in a large hearing loss population. A total of 2,265 Japanese sensorineural hearing loss (SNHL) patients compatible with autosomal recessive inheritance (including sporadic cases) from 53 otorhinolaryngology departments nationwide participated in this study. The mutation analysis of 68 genes, including the OTOF gene, reported to cause non-syndromic hearing loss was performed using MPS. Thirty-nine out of the 2,265 patients (1.72%) carried homozygous or compound heterozygous mutations in the OTOF gene. It is assumed that the frequency of hearing loss associated with OTOF mutations is about 1.72% of autosomal recessive or sporadic SNHL cases. Hearing level information was available for 32 of 39 patients with biallelic OTOF mutations; 24 of them (75.0%) showed profound hearing loss, 7 (21.9%) showed severe hearing loss and 1 (3.1%) showed mild hearing loss. The hearing level of patients with biallelic OTOF mutations in this study was mostly severe to profound, which is consistent with the results of past reports. Eleven of the 39 patients with biallelic OTOF mutations had been diagnosed with ANSD. The genetic diagnosis of OTOF mutations has significant benefits in terms of clinical decision-making. Patients with OTOF mutations would be good candidates for cochlear implantation; therefore, the detection of OTOF mutations is quite beneficial for patients, especially for those with ANSD., Competing Interests: The authors have declared that no competing interests exist.

Perilymphatic fistula is defined as an abnormal communication between the perilymph-filled space and the middle ear, or cranial spaces. The manifestations include a broad spectrum of neuro-otological symptoms such as hearing loss, vertigo/dizziness, disequilibrium, aural fullness, tinnitus, and cognitive dysfunction. By sealing the fistula, perilymphatic fistula is a surgically correctable disease. Also, appropriate recognition and treatment of perilymphatic fistula can improve a patient's condition and hence the quality of life. However, the difficulty in making a definitive diagnosis due to the lack of an appropriate biomarker to detect perilymph leakage has caused a long-standing debate regarding its management. We have reported a clinical test for the diagnosis of perilymphatic fistula by detecting a perilymph specific protein, Cochlin-tomoprotein, as a diagnostic marker using a western blot. The aim of this study is to establish an ELISA-based human Cochlin-tomoprotein detection test and to evaluate its diagnostic accuracy in clinical subjects. The results of ELISA showed good dilution reproducibility. The mean concentration was 49.7±9.4 of 10 perilymph samples. The ROC curve in differentiating the perilymph leakage condition from the normal middle ear was significant (P < 0.001) with an area under the curve (AUC) of 0.918 (95% CI 0.824-0.100). We defined the diagnostic criteria as follows: CTP<0.4 negative; 0.4≦CTP<0.8 intermediate; 0.8≦CTP(ng/ml) positive in the clinical usage of the hCTP ELISA, and sensitivity and specificity were 86.4% and 100%, respectively. We further tested the expression specificity of the Cochlin-tomoprotein by testing blood and CSF samples. The concentration was below the detection limit (0.2 ng/ml) in 38 of the 40 blood, and 14 of the 19 CSF samples. We report the accuracy of this test for the diagnosis of perilymphatic fistula. Using ELISA, we can improve the throughput of the test. Furthermore, it is useful for a large-scale study to characterize the clinical picture and delineate the management of this medical condition.

Perilymphatic fistula (PLF) is defined as an abnormal communication between the fluid (perilymph)-filled space of the inner ear and the air-filled space of the middle ear and mastoid, or cranial spaces. PLF is located in the round or oval window, fractured bony labyrinth, microfissures, anomalous footplate, and can occur after head trauma or barotrauma, chronic inflammation, or in otic capsule dehiscence. This clinical entity was initially proposed more than a century ago, yet it has remained a topic of controversy for more than 50 years. The difficulty of making a definitive diagnosis of PLF has caused a long-standing debate regarding its prevalence, natural history, management and even its very existence. In this present study, we will discuss the symptoms, physiological tests (focusing on vestibular assessment) and imaging studies. Referring to a previous criticism, we will share our classification of PLF into 4 categories. Furthermore, we will summarize a nationwide survey using a novel and widely used biomarker (Cochlin-tomoprotein [CTP]) for PLF diagnosis in Japan and present the results of the new diagnostic criteria. PLF is surgically correctable by sealing the fistula, and appropriate recognition and treatment of PLF can improve hearing and balance, and in turn, improve the quality of life of afflicted patients. Therefore, PLF is an especially important treatable disease for otologists., (© 2018 S. Karger AG, Basel.)

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vertigo and the posterior and/or lateral semicircular canals are usually affected. BPPV is characterized by brief attacks of rotatory vertigo associated with positional and/or positioning nystagmus, which are elicited by specific head positions or changes in head position relative to gravity. In patients with the posterior-canal-type of BPPV, torsional nystagmus is induced by the Dix-Hallpike maneuver. In patients with the lateral-canal-type of BPPV, horizontal geotropic or apogeotropic nystagmus is induced by the supine roll test. The pathophysiology of BPPV is canalolithiasis comprising free-floating otoconial debris within the endolymph of a semicircular canal, or cupulolithiasis comprising otoconial debris adherent to the cupula. The observation of positional and/or positioning nystagmus is essential for the diagnosis of BPPV. BPPV is treated with the canalith repositioning procedure (CRP). Through a series of head position changes, the CRP moves otoconial debris from the affected semicircular canal to the utricle. In this review, we provide the classification, diagnostic criteria, and examinations for the diagnosis, and specific and non-specific treatments of BPPV in accordance with the Japanese practical guidelines on BPPV published by the Japan Society for Equilibrium Research., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Conclusions: The majority of hearing loss due to mumps presents as unilateral profound sensorineural hearing loss, which is refractory to treatment. In rare cases of bilateral total deafness, cochlear implants were beneficial for speech perception. Vaccination against mumps is recommended to prevent mumps-associated hearing loss., Objective: The objective of this study is to investigate the clinical characteristics of hearing loss due to mumps and to evaluate hearing outcomes., Subjects and Methods: The clinical parameters were analyzed under a retrospective multi-institutional study design in patients diagnosed with hearing loss due to mumps at the Otolaryngology departments of 19 hospitals between 1987 and 2016., Results: Sixty-seven patients with hearing loss due to mumps were enrolled. The study population consisted of 35 males and 32 females, ranging in age from 1 to 54, with a median age of 9.5 years. Sixty-three patients presented with unilateral, and 4 with bilateral hearing loss. Profound hearing loss was observed in 65 ears. Only one ear with severe hearing loss showed complete recovery. Four patients with bilateral hearing loss received cochlear implant surgery. Most of the patients with hearing loss due to mumps had no history of vaccination.

The molecular mechanisms underlying age-related hearing loss are unknown, and currently, there is no treatment for this condition. Recent studies have shown that microRNAs (miRNAs) and age-related diseases are intimately linked, suggesting that some miRNAs may present attractive therapeutic targets. In this study, we obtained 8 human temporal bones from 8 elderly subjects at brain autopsy in order to investigate the expression profile of miRNAs in the inner ear with miRNA arrays. A mean of 478 different miRNAs were expressed in the samples, of which 348 were commonly expressed in all 8 samples. Of these, levels of 16 miRNAs significantly differed between young elderly and old elderly subjects. miRNAs, which play important roles in inner ear development, were detected in all samples, i.e., in both young and old elderly subjects, whether with or without hearing loss. Our results suggest that these miRNAs play important roles not only in development, but also in the maintenance of inner ear homeostasis., (© 2017 S. Karger AG, Basel.)

Objectives: To present the cardiovascular risk factors in idiopathic sudden sensorineural hearing loss (SSNHL) patients enrolled in a nationwide epidemiological survey of hearing disorders in Japan., Materials and Methods: We compiled the cardiovascular risk factors in 3073 idiopathic SSNHL subjects (1621 men and 1452 women) and compared their proportions with controls as part of the National Health and Nutrition Survey in Japan, 2014. The cardiovascular risk factors consisted of drinking and smoking habits, a history of five conditions related to cardiovascular disease and body mass index., Results: The proportion of current smokers was significantly higher among men aged 50-59, 60-69 and 70+ and among women aged 30-39, 40-49 and 60-69. The proportion of patients with a history of diabetes mellitus was significantly higher among men aged 50-59, 60-69 and 70+, but not in women. In addition, male and female SSNHL subjects aged 60-69 showed lower proportions of current drinking; and female SSNHL subjects aged 60-69 showed higher proportions of overweight (BMI ≥25 kg/m 2 )., Conclusions: The present cross-sectional study revealed showed significantly higher proportions of current smokers among both men and women as well as those with a history of diabetes mellitus among men across many age groups in patients with idiopathic SSNHL compared with the controls.

Objective: To investigate the positive rate for the Cochlin tomo-protein (CTP: an inner ear-specific protein) detection test among patients with inner ear-related clinical manifestations and evaluate the clinical characteristics of definite perilymphatic fistula (PLF)., Methods: We have performed an ELISA-based CTP detection test using middle ear lavage (MEL) samples from 497 cases of suspected PLF enrolled from 70 clinical centers nationwide between 2014 and 2015. In addition to the CTP-positive rate, audio-vestibular symptoms were compared between CTP-positive and -negative cases., Results: 8-50% of patients in category 1 (trauma, middle and inner ear disease cases), and about 20% of those in categories 2, 3 and 4 (external origin antecedent events, internal origin antecedent events, and without antecedent event, respectively) were positive for CTP. In category 1 cases, the earlier tested samples showed a higher CTP-positive rate, whereas no differences were observed in categories 2, 3 or 4. The characteristic clinical features in the earlier tested cases were nystagmus and fistula sign in CTP test-positive cases in category 1, and streaming water-like tinnitus in those in categories 2, 3 and 4., Conclusion: The present study clarified that CTP detection test-positive patients exist at considerable rates among patients with inner ear-related manifestations.

Objectives: Using a large-scale nationwide survey database, we investigated the epidemiological characteristics for idiopathic SSNHL in Japan., Methods: The subjects for this analysis were patients registered in a Japanese multicentre database between April 2014 and March 2016. A total of 3419 idiopathic SSNHL patients were registered in the database, and the clinical characteristics of the idiopathic SSNHL patients were obtained. Several factors associated with the severity of hearing impairment and prognosis were then investigated. Statistical analysis was performed to clarify the factors associated with the severity of hearing impairment and prognosis., Results: There were significant correlations between the severity of hearing loss and diabetes mellitus, kidney disease, past history of brain infarction, heart disease, age (under 16 years/elderly), and symptoms of vertigo/dizziness. We also analyzed the prognostic factors for idiopathic SSNHL, and found that the severity of hearing loss (Grade 3 or 4), heart disease, aged 65 years or over, time from onset to treatment (over 7 days), and symptoms of vertigo/dizziness were all significantly related to poor prognosis., Conclusion: The present large-scale clinical survey revealed current epidemiological trends for idiopathic sudden sensorineural hearing loss (SSNHL) and various factors associated with the severity of hearing impairment and prognosis.

Objective: To investigate the hearing prognosis of idiopathic sudden sensorineural hearing loss (SSNHL) treated with different initial therapies., Methods: Subjects consisted of patients diagnosed with idiopathic SSNHL within 7 days from onset and showing severe hearing loss (≥60 dB), who were registered in a Japanese multicenter database between April 2014 and March 2016. Subjects were divided into four groups according to initial therapy: (1) steroids, (2) steroids + Prostaglandins (PGs), (3) intratympanic steroids (ITS), and (4) no steroids. Hearing outcomes were compared among the groups., Results: In total, 1305 patients were enrolled. The final hearing level and hearing gain of patients treated with steroids + PGs were significantly higher than those of patients treated with steroids alone or no steroids. The ratio of good prognosis (complete recovery or marked improvement) in patients treated with steroids + PGs was higher than that in patients treated with steroids alone or no steroids. There was no difference in the prognosis of patients treated with steroids alone or no steroids., Conclusion: A large number of patients with idiopathic SSNHL were registered in a multicenter database. PG use in combination with steroid administration was associated with a good hearing prognosis in patients with severe hearing loss.

Objectives: The aim of this study was to investigate the differences between idiopathic sudden sensorineural hearing loss (SSNHL), and acute low-tone sensorineural hearing loss (ALHL) using the results of a nationwide survey database in Japan and to analyze the variables associated with their clinical features and the severity of hearing impairment, treatment, and prognosis., Methods: Participants were patients registered between April 2014 and March 2016 in a multicenter epidemiological survey database involving 30 university hospitals and medical centers across Japan. Statistical analysis was performed to clarify the factors associated with their clinical characteristics and the severity of hearing impairment, treatment, and prognosis., Results: Idiopathic SSNHL and ALHL differed significantly in terms of male-to-female ratio, age distribution, and time from onset to start of treatment. The treatment methods and hearing prognosis also differed markedly between the two diseases. A majority (92%) of idiopathic SSNHL patients were administered some type of corticosteroid, while half of the ALHL patients received corticosteroids and a diuretic agent., Conclusion: The results suggested that idiopathic SSNHL and ALHL belonged to different categories of inner ear disease.

Objectives: To evaluate the differences between acoustic trauma (AT) and other types of acute noise-induced hearing loss (ANIHL), we performed a literature search and case reviews., Methods: The literature search based on online databases was completed in September 2016. Articles on ANIHL and steroid treatment for human subjects were reviewed. The source sounds and treatment sequelae of our accumulated cases were also reviewed. Hearing loss caused by gun-shots and explosions was categorized into the AT group, while hearing loss caused by concerts and other noises was categorized into the ANIHL group., Results: Systemic steroid treatment did not appear to be effective, at least in the AT group, based on both the literature and our case reviews. However, effective recovery after treatment including steroids was observed in the ANIHL group. The difference in hearing recovery between the AT and ANIHL groups was statistically significant (p = .030), although differences in age, days from the onset to treatment and pretreatment hearing levels were not significant., Conclusions: Hearing recovery from AT is very poor, whereas, ANIHL is recoverable to some extent. Therefore, it is essential to differentiate between these two groups for accurate prediction of the hearing prognosis and evaluation of treatment effects.

Objectives: A nationwide epidemiological survey involving 23 hospitals in Japan was conducted and the predictive values of demographic data were examined statistically., Methods: A total of 642 patients from 23 hospitals, including 20 university hospitals, in Japan were enrolled in the study. Age ranged from 8 to 87 years, and all were diagnosed with acute low-tone sensorineural hearing loss (ALHL) between 1994 and 2016. Demographic data for the patients, such as symptoms, gender, mean age, and distribution of ALHL grading, were collected and analyzed in relation to prognosis using Student's t-test, χ 2 test and logistic regression., Results: Female gender (p < .013), younger age (p < .001), low-grade hearing loss (p < .001), and shorter interval between onset and initial visit (p < .004) were significantly predictive of a good prognosis. The prognosis for definite ALHL was significantly better than that for probable ALHL (p < .007)., Conclusions: The severity of initial hearing loss, interval between onset and initial visit and age were important prognostic indicators for ALHL, while female gender was an important prognostic indicator peculiar to ALHL.

Conclusion: Approximately 50% of patients with sPLF based on the clinical diagnosis criteria were definitively diagnosed with CTP-positive sPLF. These results suggest that early surgery within 7 days of the disease onset contributes to improvements in the therapeutic response of hearing loss., Objectives/hypothesis: Idiopathic spontaneous perilymph fistula (sPLF) cannot be diagnosed reliably. It is speculated that this condition occurs in patients with vertigo-accompanied acute sensorineural hearing loss that progresses rapidly in spite of steroid therapy. This study herein evaluated cochlin-tomoprotein (CTP) test results in patients with sPLF who underwent exploratory tympanotomy and considered surgical outcomes with true sPLF., Study Design: Retrospective study., Methods: Twenty-three patients diagnosed with sPLF based on the clinical diagnosis criteria who underwent exploratory tympanotomy were included., Results: CTP test results were positive in 11 cases. In CTP-positive cases, the mean hearing level was 66.5 dB pre-operatively and 42.3 dB post-operatively. The hearing level post-operatively completely recovered in four cases, markedly recovered in three cases, slightly recovered in one case and showed no response in three cases. Hearing level improvements were significantly better in CTP-positive patients who underwent surgery within 7 days of the disease onset than in those treated 8 or more days after the disease onset.