[RECURRENT AND VIRTUAL EDUCATION FOR ALL DISCIPLINES AND OCCUPATIONS IN THE ALLERGY REALM : A SURVEY OF THE PARTICIPANTS FROM THE INITIATIVE 'OUTREACH LECTURES' TO CREATE EDUCATIONAL OPPORTUNITIES].

BACKGROUND: In the enhancement of allergy care involving multidisciplinary and multiple medical departments, there is a perceived need for education that targets not only specialists but also non-specialists. However, research on the need for and methods of such education remains inadequate. OBJECTIVE: To design a remote allergy care education program for all medical practitioners and to validate its necessity and utility. METHODS: The Empowering Next Generation Allergist/immunologist toward Global Excellence Task Force (ENGAGE-TF), supported by the Japanese Society of Allergology, initiated a virtual educational program called 'Outreach Lectures' in collaboration with Keio University and Fukui University. This initiative was widely promoted through social media and various institutions, and a survey was conducted through its mailing list. RESULTS: 1139 responses were obtained. More than half were physicians from non-allergy specialties, representing a diverse range of healthcare professions. Over 70% expressed being 'very satisfied,' and over 60% found the difficulty level 'appropriate.' Free-form feedback revealed differences in learning focus based on profession and learning approach based on years of experience. CONCLUSION: The high participation rate (90%) of non-specialist physicians underscores the demand for addressing allergic conditions in primary care. The effectiveness of virtual / recurrent education, particularly for healthcare professionals with over 11 years of experience, was implied. Further follow-up investigation focusing on quantitative and objective assessment of educational effectiveness is indispensable.

Upper Respiratory Symptoms as Long COVID: Insight from a Multicenter Cohort Study.

Objective: This study aimed to investigate the clinical features of long COVID cases presenting with upper respiratory symptoms, a topic not yet fully elucidated. Study Design: Prospective cohort study. Setting: A multicenter study involving 26 medical facilities in Japan. Methods: Inclusion criteria were patients aged ≥18 years old with a confirmed COVID-19 diagnosis via severe acute respiratory syndrome coronavirus 2 polymerase chain reaction or antigen testing, who were hospitalized at the participating medical facilities. Analyzing clinical information and patient-reported outcomes from 1009 patients were analyzed. The outcome measured the degree of initial symptoms for taste or olfactory disorders and assessed the likelihood of these symptoms persisting as long COVID, as well as the impact on quality of life if the upper respiratory symptoms persisted as long COVID. Results: Patients with high albumin, low C-reactive protein, and low lactate dehydrogenase in laboratory tests tended to experience taste or olfactory disorders as part of long COVID. Those with severe initial symptoms had a higher risk of experiencing residual symptoms at 3 months, with an odds ratio of 2.933 (95% confidence interval [CI], 1.282-6.526) for taste disorders and 3.534 (95% CI, 1.382-9.009) for olfactory disorders. Presence of upper respiratory symptoms consistently resulted in lower quality of life scores. Conclusion: The findings from this cohort study suggest that severe taste or olfactory disorders as early COVID-19 symptoms correlate with an increased likelihood of persistent symptoms in those disorders as long COVID.

Tests of human auditory temporal resolution: preliminary investigation of ZEST parameters for amplitude modulation detection.

Auditory temporal resolution plays a critical role in the everyday experience of listening to complex acoustic patterns. Amplitude modulation detection thresholds are widely used to measure auditory temporal resolution. In an attempt to develop a standardized clinical test of auditory temporal resolution, we used ZEST (Zippy Estimation by Sequential Testing, a Bayesian threshold estimation procedure, to measure amplitude modulation detection thresholds. ZEST utilizes prior knowledge about a listener's thresholds, as represented by a probability density function of the thresholds, and psychometric functions of the listener's responses. This paper reports a preliminary study in which ZEST parameters that could be used for measurements of amplitude modulation detection thresholds were sought. For this purpose, we created histograms of the detection thresholds for a wide range of modulation frequencies, measured the psychometric functions of amplitude modulation detection, and performed computer simulations of ZEST threshold estimation. The results suggested that, with appropriately-set parameters, ZEST allows for the accurate estimation of amplitude modulation detection thresholds within 20 trials.

Barrier Factors of Adherence to Dupilumab Self-Injection for Severe Allergic Disease: A Non-Interventional Open-Label Study.

Purpose: The status of dupilumab self-injection at home is not well understood. We therefore aimed to identify the barriers to adherence to dupilumab self-injection. Patients and Methods: This non-interventional open-label study was conducted between March 2021 and July 2021. Patients with atopic dermatitis, bronchial asthma, and chronic rhinosinusitis with nasal polyps receiving dupilumab, from 15 sites, were requested to complete a self-administered questionnaire regarding the frequency and effectiveness of dosing as well as their use and satisfaction with dupilumab. Barriers to adherence were assessed using the Adherence Starts with Knowledge-12. Results: We included 331 patients who used dupilumab for atopic dermatitis (n = 164), chronic rhinosinusitis with nasal polyps (n = 102), and bronchial asthma (n = 65). The median efficacy of dupilumab scored 9.3 on the visual analog scale. Overall, 85.5% of the patients self-injected dupilumab, and 70.7% perfectly complied with the established injection dates. The pre-filled pen was significantly superior to the conventional syringe in terms of usability, operability, ease of pushing the plunger, and patient satisfaction. However, the pre-filled pen caused more pain during self-injection than did the syringe. Multivariate logistic regression analysis showed that adherence decreased with longer dupilumab treatment duration (p = 0.017) and was not associated with age, sex, underlying disease, or device type. There was a difference in responses related to "inconvenience/forgetfulness" between the good and poor adherence groups. Conclusion: The pre-filled dupilumab pen was superior to the syringe in terms of usability, operability, ease of pushing the plunger, and satisfaction. Repetitive instructions are recommended for preventing poor adherence to dupilumab self-injection.

Association Between Multiple Sclerosis and the Symptoms of Vertigo and Facial Nerve Palsy.

Patients with vertigo and facial nerve palsy as initial symptoms are rarely diagnosed with multiple sclerosis. A 43-year-old woman presented to our department with symptoms of vertigo and right facial nerve palsy (Yanagihara 16-point system [total score, 40] or House- Brackmann grade IV [obvious facial weakness]). On the day of the visit, she presented with right eye abduction, left eye adduction, and complaints of diplopia. Based on magnetic resonance imaging findings, she was diagnosed with clinically isolated syndrome, which is an early manifestation of multiple sclerosis. She was treated with intravenous methylprednisolone. Otolaryngologists often suspect Hunt's syndrome in patients who present with facial nerve palsy combined with vertigo. However, herein, we report our experience with an extremely rare case of a patient with atypical nystagmus symptoms, eye movement disorder, and diplopia secondary to facial palsy and vertigo, who presented with a clinical course different from that of Hunt's syndrome.

Efficacy of transtympanic infusion of dexamethasone into the tympanic cavity in mice with acute sensorineural hearing loss associated with cytomegalovirus infection.

BACKGROUND: There is no report on acute sensorineural hearing loss with congenital cytomegalovirus (cCMV) infection in basic experiments. AIMS/OBJECTIVES: The aim of this study was to evaluate the effect of dexamethasone, an anti-inflammatory steroid, on acute sensorineural hearing loss in the mouse cytomegalovirus (MCMV) infection model mice. MATERIAL AND METHODS: Sensorineural hearing loss model mice were divided into two groups, one with and one without intratympanic dexamethasone. Dexamethasone was injected into the tympanic cavity of only the right ear, and hearing ability was assessed at the ages of three, six, and eight weeks by auditory brainstem response measurement. RESULTS: Among the 23 mice intratympanically injected with dexamethasone (15 µg/mouse) at the age of three weeks, five (21.7%) had a hearing improvement of at least 10 dB and 18 (78.3%) had no improvement at the age of six weeks. Among the 19 mice that did not receive a dexamethasone injection, one (5.3%) showed improvement and 18 (94.7%) showed no improvement (p = 0.129). CONCLUSIONS AND SIGNIFICANCE: In this study, transtympanic infusion of dexamethasone into the tympanic cavity was effective in some mice with sensorineural hearing loss, suggesting that, in addition to angiogenesis, anti-inflammatory activity might be a mechanism of treatment for hearing loss.

In Vivo Imaging Analysis of an Inner Ear Drug Delivery in Mice: Comparison of Inner Ear Drug Concentrations Over Time.

Treatment for inner ear regeneration and protection needs local injection of steroid or new drug for inner ear regeneration into the round window membrane (RWM) in cochlea, but a systemic injection is not available due to its systemic side effects. However, pharmacokinetics of therapeutic agents or steroid locally injected into the inner ear is not well known. Hence, we introduce a new method for the real-time observation of drug delivery in transgenic animals in vivo. We exemplify mice which contain a firefly luciferase (FLuc) gene expression cassette regulated by the murine glial fibrillary acidic protein (GFAP) promoter. Luciferin delivered into the inner ear of those mice reacts with FLuc that is expressed in the GFAP-expressing cells in the cochlear nerve and spiral ganglion, and the resulting bioluminescence is detected by a camera. Using this system, we show the imaging of pharmacokinetic differences between local and systemic (intravenous and subcutaneous) injections of the inner ear.

Transcanal endoscopic ear surgery for management of ossicular malformation: clinical outcomes of 17 cases.

BACKGROUND: In recent years, transcanal endoscopic ear surgery (TEES) is known as an innovative and minimally invasive surgery. AIMS: To clarify the usefulness of TEES for the ossicular malformation, we performed a retrospective study. MATERIAL AND METHODS: We examined cases of ossicular malformation performed using TEES at our hospital between April 2015 and April 2020. RESULTS: The hearing level results were countable for 16 cases. Post-operative hearing levels were significantly improved. Transient nausea, tongue paralysis, and taste disorders were observed; however, no other complications were observed. In 2015-2018, some of the cases required the assistance of a surgical microscope. In contrast, all the cases were performed by TEES after 2019 using a powered device to curve the canal. CONCLUSIONS AND SIGNIFICANCE: TEES requires considerable training, and the sensation of depth is difficult to acquire. However, this less invasive method is also helpful for ossicular malformation cases.

Delayed facial palsy after cochlear implantation caused by reactivation of Herpesvirus: A case report and review of the literature.

Cochlear implantation has many complications; however, delayed facial palsy is relatively rare. In this report, we present the case of a 60-year-old woman with delayed facial palsy after cochlear implantation. Eleven days after the operation, the patient complained of right facial palsy (Yanagihara score 6, House-Brackmann [HB] grade VI). Herpes virus reactivation and local bacterial infection were considered as possible causes of the facial paralysis. A blood test revealed an increase in viral antibody titer, and the patient was diagnosed as having herpes virus reactivation. She was treated with antiviral therapy for the facial palsy until resolution. Slight mouth weakness continued even at 1.5 months (Yanagihara score 34, HB II) but eventually resolved at 3 months (Yanagihara score 40, HB I). Delayed facial palsy is a rare but serious complication that can occur with viral reactivation regardless of the competence of the surgical procedure. Therefore, it is important to inform patients preoperatively regarding the risk of not only immediate but also delayed postoperative facial paralysis.

Comprehensive and long-term surveys of COVID-19 sequelae in Japan, an ambidirectional multicentre cohort study: study protocol.

INTRODUCTION: The rapid spread of COVID-19 posed a global burden. Substantial number of people died of the disease in the acute phase of infection. In addition, a significant proportion of patients have been reported to suffer from post-acute phase symptoms, sequelae of COVID-19, which may negatively influence the quality of daily living and/or socioeconomic circumstances of the patients. However, no previous study has comprehensively and objectively assessed the quality of life of patients by using existing international scales. Further, evidence of socioeconomic consequences among patients with COVID-19 is scarce. To address the multidimensional issues from sequelae of COVID-19, evidence from comprehensive surveys beyond clinical perspectives is critical that investigates health, and social determinants of disease progression as well as socioeconomic consequences at a large scale. METHODS AND ANALYSIS: In this study, we plan to conduct a nationwide and comprehensive survey for the sequelae of COVID-19 in a total of 1000 patients diagnosed at 27 hospitals throughout Japan. This study will evaluate not only the health-related status of patients from clinical perspectives but also the Health-related Quality of Life (HRQoL) scores, socioeconomic status and consequences to discuss the sequelae of the disease and the related risk factors. The primary endpoint is the frequency of long-term complications of COVID-19 infection. The secondary endpoints are risk factors for progression to sequelae of COVID-19 infection. The study will provide robust and important evidence as a resource to tackle the issues from the sequelae of COVID-19 from the multi-dimensional perspectives. ETHICS AND DISSEMINATION: This trial was approved by the Keio University School of Medicine Ethics Committee (20200243, UMIN000042299). The results of this study will be reported at a society meeting or published in a peer-reviewed journal.

Comparison of Drug Availability in the Inner Ear After Oral, Transtympanic, and Combined Administration.

Although combination of oral and transtympanic drug therapy (CT) has been proved more effective and safer for idiopathic sudden sensorineural hearing loss (ISSNHL) by some clinical trials, there are few laboratory researches on the pharmacokinetics in the inner ear following CT on account of structural limitations of the inner ear. The aim of the present study was to investigate the pharmacokinetic behaviors of CT in the inner ear of mice. Eighteen transgenic GFAP-Luc mice which express luciferase in cochlear spiral ganglion cells were divided into oral administration (OR) group, transtympanic injection route (TT) group and CT group, and luciferin was delivered into the inner ear of these mice through oral, transtympanic or combined routes, respectively. A new in vivo imaging system was used to observe luciferin/luciferase signals and the compare the pharmacokinetics of different administration routes in the inner ear of mice. Bioluminescence signals were observed in the inner ear 3.3 ± 2.6 min after CT, significantly earlier than that of OR group (15.8 ± 7.4 min). CT owned the longest reaching-peak time and largest area under the curve (AUC) among three groups. Compared to TT, CT had longer biological half-life and higher AUC value, but did not displayed stronger peak value. There were significant differences in the peak values between OR group and TT group and between OR group and CT group. This study suggests that the OR route is less effective than the TT or CT route, and combination of OR and TT can deliver more drugs into the inner ear and confer a longer therapeutic window, but cannot increase drug intensity.

Eosinophilic annular erythema showing eosinophil cytolytic ETosis successfully treated with benralizumab.

A 56-year-old woman presented with repeated swelling of the lips and face. She had a history of childhood asthma; she had a recurrence of asthma when she was 54 years old and was taking inhaled corticosteroids, and other antiasthma drugs. The swelling of her lips and face improved temporarily with oral corticosteroids (OCS), but recurred soon after discontinuing OCS. Her peripheral blood eosinophil count was 632/µL (9.3%), and her serum was negative for myeloperoxidase-anti-neutrophil cytoplasmic antibody and serine proteinase3-anti-neutrophil cytoplasmic antibody. Hematoxylin and eosin staining of her back skin revealed abundant eosinophilic infiltrate around the vascular area of the shallow dermis layer, but no evidence of vasculitis and we diagnosed her as eosinophilic annular erythema (EAE). Punctate staining of galectin-10, chromatolytic eosinophils, and net-like DNA was also evident in close proximity to the free granules, indicating extracellular vesicles and eosinophil extracellular traps (ETosis). We started daily OCS to control her asthma and skin eruption/oedema. Three months after administering daily OCS, benralizumab was initiated for withdrawal from OCS dependence and treatment of severe asthma. After initiation of benralizumab, her skin and subcutaneous tissue symptoms promptly improved. OCS was discontinued, and no edematous erythema has been observed since then. Bronchial asthma has also been well-controlled. This is the first report on the evidence of eosinophil ETosis in the dermis of EAE patients and the efficacy of benralizumab in a patient with EAE. Benralizumab may be a useful drug for treating refractory EAE with severe eosinophilic asthma.

Three cases of otitis media caused by Mycobacterium abscessus subsp. abscessus: Importance of medical treatment and efficacy of surgery.

This study aimed to assess the clinical presentation, antibiotic therapy, surgery, and outcomes in patients with otitis media caused by Mycobacterium abscessus subsp. abscessus and discuss the efficacy of surgery. This is a retrospective case review of three patients diagnosed with otomastoiditis caused by M. abscessus subsp. abscessus. All patients had refractory otorrhea. One patient had granulation tissue in the tympanic membrane. They received medical treatment and underwent surgery. Otorrhea was resolved several months after the initiation of long-term multiantibiotic therapy in all cases. The timing of surgery varied among patients. Before initiating antibiotic therapy, mastoidectomy was performed to achieve definitive diagnosis in two patients, and wound dehiscence developed in these patients. Two patients underwent debridement after the initiation of multiantibiotic therapy. After antibiotic administration, tympanoplasty was performed to improve hearing in one patient. All patients achieved culture negativity after treatment, and no recurrences have been noted. From three cases, it is suggested that the mainstay of treatment for M. abscessus subsp. abscessus is long-term multiantibiotic therapy, and surgery itself may have little effect on achieving ear dryness. Thus, in most patients, drug therapy should be prioritized. Considering postoperative complications, surgery before achieving ear dryness should be avoided, except in emergency cases. In addition, if the diagnosis is not confirmed by repeated bacteriological tests, mastoidectomy should be performed to collect specimens. Tympanoplasty for hearing loss or eardrum perforation is recommended after discontinuation of medications.

Analysis of Pharmacokinetics in the Cochlea of the Inner Ear.

Hearing loss affects >5% of the global population and therefore, has a great social and clinical impact. Sensorineural hearing loss, which can be caused by different factors, such as acoustic trauma, aging, and administration of certain classes of drugs, stems primarily from a dysfunction of the cochlea in the inner ear. Few therapeutic strategies against sensorineural hearing loss are available. To develop effective treatments for this disease, it is crucial to precisely determine the behavior of ototoxic and therapeutic agents in the microenvironment of the cochlea in live animals. Since the 1980s, a number of studies have addressed this issue by different methodologies. However, there is much less information on pharmacokinetics in the cochlea than that in other organs; the delay in ontological pharmacology is likely due to technical difficulties with accessing the cochlea, a tiny organ that is encased with a bony wall and has a fine and complicated internal structure. In this review, we not only summarize the observations and insights obtained in classic and recent studies on pharmacokinetics in the cochlea but also describe relevant analytical techniques, with their strengths, limitations, and prospects.

Multicenter phase III trial of regenerative treatment for chronic tympanic membrane perforation.

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

Surgical treatment of otosclerosis using a unique stapes prosthesis without a hook.

BACKGROUND: During stapes surgery, the Teflon wire piston prosthesis is prone to postoperative 'slips' and subsequent necrosis and fracture of the long process of the incus. AIMS/OBJECTIVE: We invented and used a novel cup-shaped apatite prosthesis to reduce the incidence of necrosis of the long process of the incus and analysed the postoperative results. MATERIAL AND METHODS: Thirty-one ears in 25 patients with otosclerosis who underwent stapes surgery with our apatite prosthesis were evaluated. RESULTS: The air conduction improved by 24.0 dB (the average) from pre- to post-operation. Additionally, 84.8% of patients achieved an air-bone gap of ≤10 dB for the 4-frequency measurements (p < .01). CONCLUSIONS: Our findings indicate that our new prosthesis was associated with a good postoperative prognosis in patients with otosclerosis. SIGNIFICANCE: Our unique prosthesis yielded good outcomes for the treatment of otosclerosis even in the short term.

Pros and Cons of the Exoscope for Otologic Surgery.

Introduction. There are a few discussions regarding usefulness of an exoscope in otologic surgery compared to a traditional microscope. Objective. The pros and cons of using a newly developed exoscope (ORBEYE™) during microotologic surgery were evaluated. Methods. The usefulness of the ORBEYE™ exoscope was retrospectively assessed in 6 otologic surgeries by 8 surgeons postoperatively. A questionnaire comprising 20 questions was designed and used for evaluation. Results. All the otologic surgeons agreed that the exoscope is useful as an educational tool; the exoscope had the highest score in the questionnaire (average: 4.75). The question "Will the ORBEYETM exoscope replace the conventional tympanoplasty or stapes surgery?" had the lowest score (average: 3.13). Conclusions. The quality of the images and movies in the exoscope was considered to be high and improved; therefore, the exoscope was considered as a useful educational tool in otologic surgery. Similar to otologic endoscopic surgery, all the members such as the operator and assistants could head up and share 1 image.

Molecular Mechanisms and Biological Functions of Autophagy for Genetics of Hearing Impairment.

The etiology of hearing impairment following cochlear damage can be caused by many factors, including congenital or acquired onset, ototoxic drugs, noise exposure, and aging. Regardless of the many different etiologies, a common pathologic change is auditory cell death. It may be difficult to explain hearing impairment only from the aspect of cell death including apoptosis, necrosis, or necroptosis because the level of hearing loss varies widely. Therefore, we focused on autophagy as an intracellular phenomenon functionally competing with cell death. Autophagy is a dynamic lysosomal degradation and recycling system in the eukaryotic cell, mandatory for controlling the balance between cell survival and cell death induced by cellular stress, and maintaining homeostasis of postmitotic cells, including hair cells (HCs) and spiral ganglion neurons (SGNs) in the inner ear. Autophagy is considered a candidate for the auditory cell fate decision factor, whereas autophagy deficiency could be one of major causes of hearing impairment. In this paper, we review the molecular mechanisms and biologic functions of autophagy in the auditory system and discuss the latest research concerning autophagy-related genes and sensorineural hearing loss to gain insight into the role of autophagic mechanisms in inner-ear disorders.

In Vivo Real-Time Simultaneous Examination of Drug Kinetics at Two Separate Locations Using Boron-Doped Diamond Microelectrodes.

Methylcobalamin, which is used for the clinical treatment of patients with neuropathy, can have an impact on the sensorineural components associated with the cochlea, and it is possible that the auditory threshold in a certain population of patients with deafness may be recovered. Nonetheless, it remains uncertain whether the action site of methylcobalamin is localized inside or outside the cochlea and which cellular or tissue element is targeted by the drug. In the present work, we developed a method to realize in vivo real-time simultaneous examination of the drug kinetics in two separate locations using boron-doped diamond microelectrodes. First, the analytical performance of methylcobalamin was studied and the measurement protocol was optimized in vitro. Then, the optimized protocol was applied to carry out real-time measurements inside the cochlea and the leg muscle in live guinea pigs while systemically administering methylcobalamin. The results showed that the methylcobalamin concentration in the cochlea was below the limit of detection for the microelectrodes or the drug did not reach the cochlea, whereas the compound clearly reached the leg muscle.

Single nucleotide polymorphisms in tinnitus patients exhibiting severe distress.

The association between distress caused by tinnitus and psychological factors such as depression and anxiety has been examined and reported. However, prognostic factors remain poorly understood because there are only a few reports on genetic associations. We theorized there might be an association between the grade of tinnitus distress and the genetic background related to psychological factors which might lead us to identify prognostic markers. We enrolled 138 patients who had suffered from tinnitus for over 3 months. Using Tinnitus Handicap Inventory (THI) scores, we examined the association between tinnitus distress and a genetic background related to depression or anxiety. A significant association between single nucleotide polymorphism rs131702 of the Breakpoint Cluster Region (BCR) gene and the severe THI score was identified. In addition, there was an association with the severity of the State-Trait Anxiety Inventory, an index of state anxiety severity. No association was found with the Self-Rating Depression Scale, an index of depression severity. It is reported that rs131702 of BCR in Japanese patients are related to bipolar II depression characterized by fluctuation between abnormal mood states of mania and depression. Our results indicate that rs131702 of BCR is independent of depression in this study and is, therefore, a prognostic factor unique to tinnitus. We conclude that the severity of tinnitus is associated with genes related to depression.