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Congenital middle ear cholesteatoma (CMEC) accounts for 2%-5% of all cases of middle ear cholesteatoma. CMEC is rare and diagnostically challenging; therefore, only a few cases are reported in the literature, and the pathophysiology of this condition remains largely unclear. Currently, epidermoid formation, amniotic fluid contamination, lack of the tympanic ring, and squamous metaplasia are among the mechanisms implicated in the pathogenesis of CMEC; however, no single theory satisfactorily explains the pathophysiology of this disorder. We report a case of CMEC in a young male patient, who showed a symmetric, binaural whitish mass posterior to the anterosuperior quadrant of the tympanic membrane. A few reports have described bilateral CMEC; however, no study has reported symmetrical CMEC as observed in this case. Bilateral tympanoplasty concomitant with cholesteatoma removal was performed, and histopathological evaluation of the resected specimen showed closed-type cholesteatoma. In this report, we describe a rare case of symmetric CMEC, which supports the epidermoid formation theory associated with CMEC, together with a literature review.

Background and Objectives A large-scale community-based study of the general population has not been conducted. There have been no studies on the relationship between decreased renal function and the degree of hearing loss. Thus, the purpose was to evaluate the relationship between hearing loss and impaired renal function with a large number of populations.Subjects and Method We performed a cross-sectional population-based cohort study by enrolling 470718 adults, 18 to 80 years old with pure tone audiometry tests who had regular health screening between 2013 and 2018. Hearing loss was defined as a pure-tone average of thresholds at 500, 1000, and 2000 Hz in both right and left ears. Kidney function was evaluated based on eGFR. Chronic kidney disease (CKD) was diagnosed as an eGFR25 dB) and 5.0% had above moderate hearing loss (>40 dB). But those with normal kidney function, 2.0% either had any hearing loss and 0.4% had above moderate hearing loss. The odds ratio (OR) of above moderate hearing loss for participants with CKD was 1.51 (95% confidence interval [CI]: 1.15-2.00, p=0.003) but the OR of mild hearing loss for participants with CKD was 0.82 (95% CI: 0.67- 1.02, p=0.073). The result suggested that CKD and above moderate hearing loss were related even after correcting for potential confounders, but had no statistical significance with mild hearing loss.Conclusion Decreased kidney function is associated with above moderate hearing loss.

Facial palsy can be caused by central and peripheral causes, and it can also be caused by brain tumors or infarction. A 59-year-old male, who lost his right hearing 13 years ago due to Ramsay Hunt syndrome, visited our hospital with facial palsy and dizziness. Initial brain diffusion-weighted magnetic resonance imaging (MRI) showed no abnormal findings, and recurrent Ramsay Hunt syndrome or a neoplastic lesion in the internal auditory canal was suspected. After hospitalization, the patient was administered high-dose steroids, and the videonystagmography showed direction-changing gaze-induced nystagmus, so a brain MRI reexamination was scheduled. While waiting for MRI, the patient complained of neurological symptoms such as diplopia, and right lower pontine infarction was diagnosed on MRI. The patient was transferred to the neurologic department and was discharged on the 10th day after conservative treatment. During the 1-year follow-up, pontine infarction did not recur, and neurological symptoms such as facial palsy gradually improved.

Objectives: This study was performed to investigate the correlation between subjective residual dizziness and objective postural imbalance after successful canalith repositioning procedure (CRP) in benign paroxysmal positional vertigo (BPPV) by using questionnaires and modified Clinical Test of Sensory Integration and Balance (mCTSIB). Methods: A total of 31 patients with BPPV were included prospectively in the study. All included patients were successfully treated after initial CRP and their symptoms and nystagmus disappeared. Two weeks after CRP, all patients were asked to fill out the questionnaire including both Dizziness Handicap Inventory (DHI) and visual analog scale (VAS). We also conducted mCTSIB 2 weeks after CRP. We divided patients into two groups according to VAS: RD (residual dizziness) group, VAS＞0; non-RD group, VAS=0. We compared age, number of CRP, rates associated with three semicircular canals, DHI score and mCTSIB results between two groups. In addition, we analyzed the correlation between DHI score and mCTSIB results. Results: There were no significant differences in age, number of CRP, and rates associated with three semicircular canals between the two groups. RD group showed significantly higher DHI score and abnormal mCTSIB results than the non-RD group (p＜0.05). DHI score and the number of abnormal mCTSIB showed a statistically significant correlation. Conclusions: We demonstrated the correlation between DHI score and mCTSIB after successful CRP for BPPV. It also represents that subjective residual dizziness is correlated with objective postural imbalance even after successful CRP. Therefore, mCTSIB would be a useful test to evaluate both residual dizziness and postural imbalance after CRP in BPPV.

Background: Intratympanic gentamicin injection (ITG) is a well-accepted means to treat intractable Meniere’s disease (MD).Aims/Objectives: To investigate change of vestibule-ocular reflex (VOR) gai...

Background: Although bone morphogenetic protein 6 (BMP6) signaling pathway has been implicated in many types of cancer, its role of tumorigenesis seems to be controversial and its ubiquitin-modifying mechanisms have not been fully addressed. Our study was designed to investigate how BMP6 signaling pathway is regulated by ubiquitin-modifying systems and to address molecular and clinical significance in colorectal cancers. Methods: Human deubiquitnase (DUB) siRNA library was used to screen the specific DUB, named PSMD14, involved in BMP6 signaling pathway. Immunoblot, immunoprecipitation and ubiquitination assays were used to analyze targets of the PSMD14. A role of PSMD14-mediated BMP6 signaling pathway for malignant cancer progression was investigated using in vitro and in vivo model of colorectal cancers as well as clinical samples of colorectal cancer patients. Findings: The deubiquitinase PSMD14 acts as a positive regulator for the initiation of the BMP6 signaling pathway through deubiquitinating K48-linked ALK2 type I receptor ubiquitination mediated by Smurf1 E3 ligase, resulting in increased stability of the ALK2. This role of PSMD14 is independent of its intrinsic role in the 26S proteasome system. Furthermore, either PSMD14 or ALK2 depletion significantly decreases tumorigenesis of HCT116 colorectal cancer cells in a xenograft model as well as cancer stemness/chemoresistance, and expression of the PSMD14 and ALK2 gene are correlated with malignant progression and the survival of colorectal cancer patients. Interpretation: These findings suggest that the PSMD14-ALK2 axis plays an essential role in initiation of the BMP6 signaling pathway and contributes to tumorigenesis and chemoresistance of colorectal cancers. Key words: PSMD14, Deubiqutinase, ALK2 receptor, Smurf1, BMP6, Colorectal cancers

OBJECTIVE: To identify differences in the vestibulo-ocular reflex (VOR) gain value and the peak saccade velocity in the suppression video head impulse test paradigms according to the age of the subject and the direction of the impulse. STUDY DESIGN: Retrospective chart analysis. SETTING: Tertiary referral hospital. PATIENTS/INTERVENTIONS: Between October 2017 and May 2019, we enrolled subjects who had previous histories of dizziness but no dizziness over the last 1 month. MAIN OUTCOME MEASURE: We conducted cervical vestibular-evoked myogenic potential and caloric tests, as well as video head impulse tests. We excluded the subjects who had abnormal cervical vestibular-evoked myogenic potential results (asymmetry ratio of greater than 30%) and abnormal caloric test results (caloric paresis of greater than 25%). RESULTS: We included 647 subjects aged 10 to 87 years. The mean VOR gain and peak saccade velocity were maintained in subjects less than 70 years old (VOR gain, 0.991 ±â€Š0.08, peak saccade velocity, 348.47 ±â€Š142.32). However, the decreases in VOR gain and peak saccade velocity were significant in subjects over 70 years old (VOR gain, 0.928 ±â€Š0.09, peak saccade velocity, 315.51 ±â€Š0.09; p 

Objective To examine the importance of video head impulse test parameter for recovery of symptoms in acute vestibular neuritis (AVN). Study design Prospective study. Setting Tertiary referral hospital. Patients/interventions Twenty-seven patients with AVN were enrolled. We divided patients into two groups according to both dizziness handicap inventory (DHI) score and visual analog scale (VAS) at 6 months: Group F (symptoms free), DHI = 0 and VAS = 0; Group R (symptoms residual), DHI more than zero or VAS more than zero. Main outcome measure All patients underwent video head impulse test paradigm (HIMP), and suppression head impulse test paradigm (SHIMP) initially and at 1 month. Patients were also asked to complete DHI and VAS initially, at 1 month and 6 months. We compared measured parameters between Group F and R. Results In HIMP, Group F showed higher vestibular-ocular reflex (VOR) gain, higher occurrence of covert corrective saccade (CS), lower occurrence and peak velocity of overt CS, and lower PR score than Group R at 1 month. In SHIMP, Group F showed higher VOR gain, higher occurrence and peak velocity of anti-CS, and higher PR score than Group R at 1 month. Conclusions Above parameters of both HIMP and SHIMP at 1 month would be important factors to predict the residual symptoms in chronic phase of AVN.

Background A considerable number of patients with sudden sensorineural hearing loss (SSNHL) have been reported to have dizziness. Objective To analyze vestibular functions and identify the clinical characteristics of SSNHL with dizzinessMETHODS:71 patients with SSNHL who complained of dizziness were investigated retrospectively. The patients underwent vestibular function tests consisting of video-nystagmography, video head impulse test and vestibular evoked myogenic potentials. Results Among 35 patients with spontaneous nystagmus (SN), 21 showed ipsilesional posterior canal gain deficit, 11 showed a gain deficit in the posterior canal only and 9 showed both horizontal and posterior canal gain deficit in video head impulse test. In only one subject with bilateral horizontal canal gain deficit with contralesional SN, AICA infarction was observed.Among 36 patients without SN, 10 were diagnosed as benign paroxysmal positional vertigo and 5 had ipsilesional canal paresis in caloric test. Other 21 patients showed no abnormal signs in vestibular function tests. Conclusions In VFT analysis of SSNHL with dizziness, diverse patterns were identified. In the absence of SN, no definite vestibular organ involvement was the most frequent. But in the case with SN, posterior canal deficit was most common and cerebellar ischemic stroke was rare.

p62/sequestosome-1 is a scaffolding protein involved in diverse cellular processes such as autophagy, oxidative stress, cell survival and death. It has been identified to interact with atypical protein kinase Cs (aPKCs), linking these kinases to NF-&kappa, B activation by tumor necrosis factor &alpha, (TNF&alpha, ). The diverse functions of p62 are regulated through post-translational modifications of several domains within p62. Among the enzymes that mediate these post-translational modifications, little is known about the deubiquitinating enzymes (DUBs) that remove ubiquitin chains from p62, compared to the E3 ligases involved in p62 ubiquitination. In this study, we first demonstrate a role of ubiquitin-specific protease USP20 in regulating p62 stability in TNF&alpha, mediated NF-&kappa, B activation. USP20 specifically binds to p62 and acts as a positive regulator for NF-&kappa, B activation by TNF&alpha, through deubiquitinating lysine 48 (K48)-linked polyubiquitination, eventually contributing to cell survival. Furthermore, depletion of USP20 disrupts formation of the atypical PKC&zeta, RIPK1-p62 complex required for TNF&alpha, B activation and significantly increases the apoptosis induced by TNF&alpha, plus cycloheximide or TNF&alpha, plus TAK1 inhibitor. These findings strongly suggest that the USP20-p62 axis plays an essential role in NF-&kappa, B-mediated cell survival induced by the TNF&alpha, atypical PKC&zeta, signaling pathway.

OBJECTIVE To compare the results of suppression head impulse paradigm (SHIMP) and head impulse paradigm (HIMP) in acute vestibular neuritis (AVN). STUDY DESIGN Retrospective study. SETTING Tertiary otology clinic. PATIENTS AND INTERVENTIONS We tested 21 patients with AVN with the HIMP, SHIMP, and caloric tests, and we analyzed the relationships between the tests' results. MAIN OUTCOME MEASURES For this study, we adopted vestibulo-ocular reflex (VOR) gains in the SHIMP and HIMP, peak saccade velocity (PSV) of SHIMP which is another indicator of residual vestibular function, and canal paresis of caloric test. RESULTS VOR gains showed significant correlation (R = 0.926, p

Objective The purpose of this study was to evaluate and compare the results of cervical vestibular evoked myogenic potential (cVEMP) and video head impulse test (p-vHIT) of posterior semicircular canal considered tools of inferior vestibular nerve function in vestibular neuritis. Study design Prospective cohort study. Setting Tertiary otology clinic. Patients and interventions Seventy-nine patients with vestibular neuritis participated in this study. We analyzed the interaural amplitude difference in cVEMP with a positive rate of p-vHIT according to gain and corrective saccade in the study population. Main outcome measure To evaluate the concordance rate of both tests, we analyzed Fleiss' Kappa value inter-test agreement of cVEMP with p-vHIT. Finally, we performed detailed analysis of the bilaterally absent response on cVEMP according to the p-vHIT results. Results The inter-test agreement between cVEMP and p-vHIT was 69.8% as we also considered the lesion side. This result indicated a statistically fair to good agreement in both tests. In mostly elderly patients with a bilaterally absent response (11 patients) on cVEMP, as a result of vHIT, nine patients with a bilaterally negative response on p-vHIT showed only canal paresis. Two patients showed canal paresis and a unilaterally positive response on p-vHIT. Conclusions Inter-test agreement between cVEMP and p-vHIT assessed in vestibular neuritis was relatively lower than we had predicted. Probably, p-vHIT can provide additional information on the differential diagnosis of dysfunction of the inferior vestibular nerve which is composed of the saccular nerve and the posterior ampullary nerve.

Benign paroxysmal positional vertigo (BPPV) is the most common type of positional vertigo. A canalolithiasis-type of BPPV involving the lateral semicircular canal (LSCC) shows a characteristic direction-changing positional nystagmus (DCPN) which beats towards the lower ear (geotropic) on turning the head to either side in a supine position. Because geotropic DCPN in LSCC canalolithiasis is transient with a latency of a few seconds, the diagnosis can be challenging if geotropic DCPN is persistent without latency. The concept of "light cupula" has been introduced to explain persistent geotropic DCPN, although the mechanism behind it requires further elucidation. In this review, we describe the characteristics of the nystagmic pattern in light cupula and discuss the current evidence for possible mechanisms explaining the phenomenon.

To analyze acute vertigo showing spontaneous nystagmus with negative video head impulse test (vHIT).Retrospective chart analysis.Tertiary referral hospital.Over 16 months, 155 patients were identified with acute vertigo with spontaneous nystagmus. Of these 155, 30 (19.4%) were enrolled in this study because they did not show gain loss or catch-up saccades in both sides of the horizontal vHIT. Results of vestibular function tests (videonystagmography, horizontal vHIT, caloric test, and cervical vestibular-evoked myogenic potential [cVEMP]) and pure tone audiometry were analyzed. For all cases, magnetic resonance imaging with diffusion-weighted imaging was checked.Patients consisted of 17 with Ménière's disease and 7 with sudden sensorineural hearing loss with vertigo (SSNHL_V), and only 3 patients were finally diagnosed as having acute vascular stroke. Except for the loss of hearing on the lesion side, the direction of nystagmus or cVEMP asymmetry showed very different results. All 7 patients with SSNHL_V did not have canal paresis in the caloric test, but cVEMP amplitude was smaller on the lesion side for 6 patients.For patients with acute vertigo presenting spontaneous nystagmus with negative horizontal vHIT, it is important not only to focus on the diagnosis of acute vascular stroke but also to evaluate hearing because of the high possibility of Ménière's disease or SSNHL_V.

Objective: Primary objective of this study was to find a statistical link between the most worldwide comorbidities affecting the elderly population (hypertension, diabetes, osteoarthrosis, osteoporosis and depression) and recurrent episodes of BPPV. Secondary objective was defining possible "groups of risk" for people suffering recurrent positional vertigo related to the presence of a well documented comorbidity. Methods: This was an observational, cross-sectional, multicenter, spontaneous, non-pharmacological study. The data of 1092 patients suffering BPPV evaluated in 11 different Departments of Otolaryngology, Otoneurology and Neurology, referring Centers for positional vertigo evaluation, were retrospectively collected. Results: Regarding evaluated comorbidities (hypertension, diabetes, osteoarthrosis, osteoporosis and depression), data analysis showed the presence of at least one comorbid disorder in 216 subjects (19.8%) and 2 or more in 408 subjects (37.4%). Moreover there was a statistical significant difference between the number of comorbidities and the number of recurrences, otherwise said as comorbidity disorders increased the number of relapses increased too. Conclusion: The presence of a systemic disease may worsen the status of the posterior labyrinth causing a more frequent otolith detachment. This condition increases the risk for patients suffering BPPV to have recurrent episodes, even if correctly managed by repositioning maneuvers. The combination of two or more of aforementioned comorbidities further increases the risk of relapsing BPPV, worsened by the presence of osteoporosis. On the basis of this results it was possible to define "groups of risk" useful for predicting BPPV recurrence in patients with one or more comorbidity. © 2013.

OBJECTIVES Clinicians sometimes treat patients with relatively long-duration geotropic direction-changing positional nystagmus (DCPN), without latency. Recently, the concept of a "light cupula" in the lateral canal that reveals persistent geotropic DCPN has been introduced. In the present study, we investigated the immediate and short-term therapeutic findings in long-duration DCPN. DESIGN The authors prospectively compared the therapeutic efficacy of a canalith-repositioning procedure (CRP) in short- and long-duration geotropic DCPN. RESULTS In patients with long-duration DCPN, the authors found no immediate therapeutic effect, and the number of patients showing short-term effects (on the next day) was very low compared with the comparable figure among those with short-duration DCPN. In addition, no cases exhibited canal conversion after the CRP. CONCLUSION Our results suggest that CRP is not useful in patients with long-duration geotropic DCPN, and the pathogenesis of long-duration geotropic DCPN may not originate from free-floating debris but from deflection of the cupula.

An increasing number of studies on efficient implementation of vivid and realistic displays are being conducted as liquid crystal displays (LCDs) become widely used in TV applications. For vivid displays, the specifications such as wide color gamut (WCG) and high dynamic range (HDR) should be implemented in LCDs. However, the low transmittance rate of the WCG and the significant costs for the peak luminance capability of the HDR are major obstacles. Hence, an RGBW LCD, which is capable of increasing the transmission efficiency, may be a good platform to overcome these problems. In this paper, we estimate the perceived brightness effect of the WCG by using the Helmholtz–Kohlrausch (H–K) effect on RGB and RGBW LCDs. The simulation results showed that the RGBW LCD was more suitable for adopting the WCG than the RGB LCD in terms of the brightness balance of achromatic and chromatic colors, and the results were also confirmed by subjective tests. In addition, we propose an effective method to implement the HDR display based on the RGBW LCD. The data stretch, considering a local adaptation characteristic of a human visual system (HVS), greatly enhanced the details of the dark regions, and the local peak dimming using the white channel analysis and the white channel data itself increased the expressiveness of the peak luminance in irradiative or specular regions to 1500 nits.

Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into mature cells of various cell types. Although the differentiation process of MSCs requires lineage‐specific transcription factors, the exact molecular mechanism that determines MSCs differentiation is not clearly addressed. Here, we demonstrate a Smad4‐Taz axis as a new intrinsic regulator for adipo‐osteogenic differentiation of MSCs and show that this function of Smad4 is independent of the transforming growth factor‐β signal. Smad4 directly bound to the Taz protein and facilitated nuclear localization of Taz through its nuclear localization signal. Nuclear retention of Taz by direct binding to Smad4 increased expression of osteogenic genes through enhancing Taz‐runt‐related transcription factor 2 (Runx2) interactions in the C3H10T1/2 MSC cell line and preosteoblastic MC3T3‐E1 cells, whereas it suppressed expression of adipogenic genes through promoting Taz‐peroxisome proliferator‐activated receptor‐γ (PPARγ) interaction in C3H10T1/2 and preadipogenic 3T3‐L1 cells. A reciprocal role of the Smad4 in osteogenic and adipogenic differentiation was also observed in human adipose tissue‐derived stem cells (hASCs). Consequently, Smad4 depletion in C3H10T1/2 and hASCs reduced nuclear retention of Taz and thus caused the decreased interaction with Runx2 or PPARγ, resulting in delayed osteogenesis or enhanced adipogenesis of the MSC. Therefore, these findings provide insight into a novel function of Smad4 to regulate the balance of MSC lineage commitment through reciprocal targeting of the Taz protein in osteogenic and adipogenic differentiation pathways. Stem Cells 2019;37:368–381, Smad4 directly binds to Taz and induces the retention of Taz in the nucleus, resulting in enhancement of Taz interaction with runt‐related transcription factor 2 or peroxisome proliferator‐activated receptor‐γ. This increased interaction augments the expression of osteogenic genes or reduces the expression of adipogenic genes, respectively. Therefore, Smad4‐Taz axis reciprocally regulates osteogenic and adipogenic differentiation of mesenchymal stem cells.

To evaluate the effects of intratympanic steroid injection (ITS) in light cupula.A total of 47 patients showing persistent geotropic direction-changing positional nystagmus with null point (light cupula) were randomly classified into three groups: ITS (n = 15), vestibular suppressant (VS, n = 16) and canalith repositioning procedure (CRP, n = 16). Positional nystagmus and dizziness severity by dizziness handicap inventory (DHI) and visual analogue scale (VAS) were conducted before and 3 d and 1 week after first treatment to compare the effect of each treatment.DHI and VAS scores had decreased after each treatment; however, there were no differences among the three groups. A week after the first treatment, 7, 6 and 7 patients showed resolution of direction-changing positional nystagmus (DCPN) in the ITS, CRP and VS groups, respectively. There were no significant differences between the three groups. In the ITS group only, however, reversal of the stronger side on head roll test was observed in 6 patients, and 2 of them showed resolution of DCPN at the third day.ITS was not effective for patients with light cupula at 1-week follow-up. However, some patients in the ITS group showed resolution of DCPN at earlier follow-up.

Objectives : We performed a retrospective study to verify the effects of Chungan-tang and acupuncture in acne patients.Methods : This study included patients with facial acne who visited to six branch of clinics in 2014. They were evaluated by Korean Acne Grading System (KAGS) before and after treatment.Results : The average grade of KAGS was 4.02±1.120 at before treatment and 1.30±0.867 at after treatment. 64 patients were classified as three groups by treatment period and KAGS grade significantly decreased in all groups. Six skin symptoms such as heat, blush, dryness, itch, prick, pain also significantly improved.Conclusions : This results may provide that Korean medical treatments including Chungan-tang and acupuncture have effects on improving acne.

Objective The aim of this study was to identify the difference of gain value in the video head impulse test (vHIT) according to the age of the patient and the direction of the impulse. Method All participants were subjected to vHIT with horizontal semicircular canal (HSCC). vHIT with vertical canal (posterior and anterior semicircular canal [PSCC and ASCC]) additionally was performed in 434 participants. Results The mean vestibulo-ocular reflex (VOR) gain was maintained in patients in the HSCC at below 70 years (1.025 ± 0.08) and in the vertical canal at below 80 years (PSCC: 0.965 ± 0.12, ASCC: 0.975 ± 0.14). However, the decrease of VOR gain was significant in patients over 70 years in the HSCC (0.978 ± 0.35, P < .001) and in patients over 80 years in the vertical canal (PSCC: 0.828 ± 0.16, ASCC: 0.851 ± 0.13, P < .001). In addition, a VOR gain of rightward impulse was higher than the leftward impulse, but there was no difference based on the direction of impulse in the vertical impulse test. Conclusion VOR gain declines with increasing age, over 70 years on the horizontal canal, and over 80 years on the vertical canal. Additionally, horizontal VOR gain of rightward impulse was higher than the leftward impulse in right-eye recordings only, but the vertical canal showed no difference of gain according to the direction of impulse. Level of Evidence 2b. Laryngoscope, 2017

Background: To evaluate the association between diabetes mellitus (DM) and the development of incident hearing loss. Methods: Prospective cohort study was performed in 253 301 adults with normal hearing tests who participated in a regular health-screening exam between 2002 and 2014. The main exposure was the presence of DM at baseline, defined as a fasting serum glucose ≥ 126 mg/dL, a self-reported history of DM or current use of anti-diabetic medications. Pre-diabetes was defined as a fasting glucose 100–125 mg/dL and no history of DM or anti-diabetic medication use. Incident hearing loss was defined as a pure-tone average of thresholds at 0.5, 1.0 and 2.0 kHz > 25 dB in both right and left ears. Results: During 1 285 704 person-years of follow-up (median follow-up of four years), 2817 participants developed incident hearing loss. The rate of hearing loss in participants with normal glucose levels, pre-diabetes and DM were 1.8, 3.1 and 9.2 per 1000 person-years, respectively (P < 0.001). The multivariable-adjusted hazard ratios for incident hearing loss for participants with pre-diabetes and DM compared with those with normal glucose levels were 1.04 (95% confidence interval 0.95–1.14) and 1.36 (1.19–1.56), respectively. In spline regression analyses, the risk of incident hearing loss increased progressively with HbA1c levels above 5%. Conclusions: In this large cohort study of young and middle-aged men and women, DM was associated with the development of bilateral hearing loss. DM patients have a moderately increased risk of future hearing loss.

Objectives/Hypothesis To investigate the characteristics of residual symptoms and to evaluate the effects of adjuvant vestibular suppressants on residual symptoms after successful canalith repositioning procedures (CRPs). Study Design Individual randomized controlled trial. Methods One hundred fifty patients with idiopathic benign paroxysmal positional vertigo who achieved successful CRPs on initial visit participated in this study. Dizziness Handicap Inventory (DHI) questionnaires were completed before CRPs. All study populations were divided into three groups after successful CRPs on the initial visit day: the medication (V) group (treated with a vestibular suppressant [dimenhydrinate 50 mg per day]), the placebo (P) group, and the no medication (N) group. One week after successful CRPs, residual symptoms were checked and repeated DHI questionnaires were completed to compare residual symptoms. Results Among the 138 patients who did not show positional nystagmus at follow-up, 67 (48.5%) complained of residual symptoms. The presence of residual symptoms was more prevalent in the P and N group compared with the V group (P = .035, P = .017, respectively). The most frequent residual symptom was lightheadedness (n = 42). Moreover, in the V group, lightheadedness was significantly reduced compared with the P group (P = .029). However, in the analysis of DHI, total and subscale scores did not differ across the three groups before or after successful CRP. Conclusions Vestibular suppressants significantly reduced residual symptoms compared to both placebo and no medication after CRP. However, there was no significant reduction in DHI score compared with the control group, suggesting that the residual symptoms could not be evaluated by DHI score alone. Level of Evidence 1b Laryngoscope 124:2400–2403, 2014

Objectives Our goal was to find the clinical value of cervical vestibular evoked myogenic potential (VEMP) in Meniere's disease (MD) and to evaluate whether the VEMP results can be useful in assessing the stage of MD. Furthermore, we tried to evaluate the clinical effectiveness of VEMP in predicting hearing outcomes. Methods The amplitude, peak latency and interaural amplitude difference (IAD) ratio were obtained using cervical VEMP. The VEMP results of MD were compared with those of normal subjects, and the MD stages were compared with the IAD ratio. Finally, the hearing changes were analyzed according to their VEMP results. Results In clinically definite unilateral MD (n=41), the prevalence of cervical VEMP abnormality in the IAD ratio was 34.1%. When compared with normal subjects (n=33), the VEMP profile of MD patients showed a low amplitude and a similar latency. The mean IAD ratio in MD was 23%, which was significantly different from that of normal subjects (P=0.01). As the stage increased, the IAD ratio significantly increased (P=0.09). After stratification by initial hearing level, stage I and II subjects (hearing threshold, 0-40 dB) with an abnormal IAD ratio showed a decrease in hearing over time compared to those with a normal IAD ratio (P=0.08). Conclusion VEMP parameters have an important clinical role in MD. Especially, the IAD ratio can be used to assess the stage of MD. An abnormal IAD ratio may be used as a predictor of poor hearing outcomes in subjects with early stage MD.

Background: We aimed to investigate the clinical courses and common nystagmus of isolated vertigo patients with vertebrobasilar stroke. Methods: The patients who presented with isolated acute spontaneous vertigo with spontaneous nystagmus (acute vestibular syndrome) at the Emergency Department were retrospectively analyzed. They were referred to the Otolaryngology Department due to the absence of neurologic signs or even of imaging abnormalities after the initial examination at the Emergency Department. Various clinical features, including presenting symptoms, delayed neurologic signs, the site of infarction, and videonystagmographic (VNG) findings were analyzed. Results: Of the 468 cases of acute vestibular syndrome, 23 (4.9%) cases of radiologically proven vertebrobasilar stroke were identified. Of the 23 patients, 17 (74%) showed aggravation of vertigo or delayed neurologic signs during the admission. In the analysis of VNG, 11 (48%) cases of direction-changing gaze-evoked nystagmus, 7 (30%) cases of fixation failure in the caloric test, 6 (27%) cases of periodic alternating nystagmus, and 4 (17%) cases of atypical head-shaking nystagmus were presented. Stroke occurred in the cerebellum (n = 18, 78%), medulla (n = 4, 17%), and pons (n = 1, 4%). Conclusion: In the early stage of vertebrobasilar stroke, an accurate diagnosis was difficult in the Emergency Department even though a radiologic study was performed, but various VNG abnormalities and delayed neurologic signs could help to diagnose whether the origin is central or not.

The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection (ITDI) in acute tinnitus of presumed cochlear origin.A prospective, randomized, placebo-controlled, double-blinded, multicenter study.Between August 2013 and December 2015, 54 patients with unilateral tinnitus were enrolled at four different centers. Patients were assigned either to an ITDI (n = 27) or an intratympanic normal saline injection (ITNI; n = 27) group through block randomization. Intratympanic injections were administered four times over 2 weeks. At 4 weeks after initial injection, we analyzed the improvement rates of tinnitus using the tinnitus handicap Inventory (THI) and visual analogue scale (VAS) for loudness, awareness, and annoyance. We defined improvement as the reduction of more than 7 points or of more than 20% in the final THI score compared to the initial THI score.The initial mean hearing thresholds and VAS and THI scores of the two groups did not differ significantly. At 4 weeks after initial injection, the mean VAS and THI scores of both groups had significantly reduced. However, the improvement rate did not differ significantly between the groups (ITDI, 51.9%; ITNI, 59.3%).The results indicate that ITDI might not be more effective than ITNI for the treatment of acute unilateral tinnitus. Therefore, ITDI should not be considered as the main treatment for patients presenting with acute tinnitus as the primary symptom.1b. Laryngoscope, 128:184-188, 2018.

Objectives Children differ from adults in the expression of dizziness symptoms and the causes of dizziness. In several studies, benign paroxysmal vertigo of childhood (BPVC) and vestibular migraine (VM) were seen exclusively in children with vertigo, but the age threshold used to define ‘children’ varies, and there are few reported studies about adolescents with dizziness. In this study, we investigated the prevalence of vestibular and balance disorders according to age category in a multi-center study (otolaryngology departments of 11 hospitals) of children and adolescents. Methods Children and adolescents aged under 18 who visited the otolaryngology departments of 11 hospitals for dizziness were included. We classified the patients into three categories: preschool (up to and including 6-year-olds), school age (7- to 12-year-olds), and adolescents (13- to 18-year-olds). These patients were reviewed retrospectively based on their clinical charts. Results In the preschool age group, BPVC was most common, followed by VM. In the school-age group, BPVC and VMs were most common, followed by psychogenic vertigo and benign paroxysmal positional vertigo (BPPV). In adolescents, VM was the most common, and Meniere's disease, cardiogenic vertigo, and BPVC, which are seen primarily in adults, were also seen in some adolescents. Conclusion In children and adolescents with dizziness, VM and BPVC were the most common diseases, and prevalence of disease by age showed differing distributions. These findings will help in diagnosing and managing children and adolescents with vertigo.

Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3β (GSK3β), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-β1-induced EMT and metastasis of basal-like breast cancers.

Objectives/Hypothesis To identify the clinical and laboratory characteristics of bilateral vestibulopathy (BVP) on the video head impulse test (vHIT). Study Design Retrospective chart analysis. Methods During 23 months, 1,789 patients with dizziness underwent vHIT in our tertiary referral hospital. Of these patients, 65 (3.6%) patients had bilaterally positive catch-up saccades. Based on the caloric test, 15 (group 1) had bilateral caloric weakness, 13 (group 2) had unilateral caloric weakness, and 37 (group 3) had normal caloric responses on both ears. We collected data on these patients regarding demographics, symptoms, gain, and type of saccade on horizontal canal plane vHIT, as well as gain and time constant on velocity step of the rotatory chair test. Results The average age of group 2 (70.38 ± 11.96 years) and group 3 (69.03 ± 11.01 years) were significantly older than that of group 1 (54.80 ± 11.96 years) (P = 0.029, P = 0.003, respectively). Although all patients had bilaterally positive vHIT, 10 of 15 in group 1 were finally diagnosed as classical BVP by clinical features. On comparison of average gain on bilateral horizontal vHIT, groups 2 (0.71 ± 0.17) and 3 (0.80 ± 0.14) had higher gain compared to group 1 (0.45 ± 0.22) (P = 0.001, P = 0.000, respectively). On velocity step test, time constant and gain of group 3 (11.60 ± 3.07, 0.49 ± 0.13) was significantly higher than those of group 1 (4.92 ± 1.36, 0.22 ± 0.17) (P = 0.000, P = 0.004, respectively). On the receiver operating characteristic curve analysis, vHIT alone seemed to be a discordant method for diagnosis of BVP compared to the caloric and step velocity tests. Conclusion About 3.6% patients with dizziness showed bilateral vestibular ocular reflex deficit during high-frequency acceleration, which was prevalent especially in elderly patients. Also, positive bilateral vHIT does not always correlate with caloric or rotatory chair test results. This may imply that a diverse spectrum of vestibulopathies exist according to the stimulation frequency of deficit. Level of Evidence 4. Laryngoscope, 2016

Evidence of visual-auditory cross-modal plasticity in deaf individuals has been widely reported. Superior visual abilities of deaf individuals have been shown to result in enhanced reactivity to visual events and/or enhanced peripheral spatial attention. The goal of this study was to investigate the association between visual-auditory cross-modal plasticity and speech perception in post-lingually deafened, adult cochlear implant (CI) users. Post-lingually deafened adults with CIs (N = 14) and a group of normal hearing, adult controls (N = 12) participated in this study. The CI participants were divided into a good performer group (good CI, N = 7) and a poor performer group (poor CI, N = 7) based on word recognition scores. Visual evoked potentials (VEP) were recorded from the temporal and occipital cortex to assess reactivity. Visual field (VF) testing was used to assess spatial attention and Goldmann perimetry measures were analyzed to identify differences across groups in the VF. The association of the amplitude of the P1 VEP response over the right temporal or occipital cortex among three groups (control, good CI, poor CI) was analyzed. In addition, the association between VF by different stimuli and word perception score was evaluated. The P1 VEP amplitude recorded from the right temporal cortex was larger in the group of poorly performing CI users than the group of good performers. The P1 amplitude recorded from electrodes near the occipital cortex was smaller for the poor performing group. P1 VEP amplitude in right temporal lobe was negatively correlated with speech perception outcomes for the CI participants (r = -0.736, P = 0.003). However, P1 VEP amplitude measures recorded from near the occipital cortex had a positive correlation with speech perception outcome in the CI participants (r = 0.775, P = 0.001). In VF analysis, CI users showed narrowed central VF (VF to low intensity stimuli). However, their far peripheral VF (VF to high intensity stimuli) was not different from the controls. In addition, the extent of their central VF was positively correlated with speech perception outcome (r = 0.669, P = 0.009). Persistent visual activation in right temporal cortex even after CI causes negative effect on outcome in post-lingual deaf adults. We interpret these results to suggest that insufficient intra-modal (visual) compensation by the occipital cortex may cause negative effects on outcome. Based on our results, it appears that a narrowed central VF could help identify CI users with poor outcomes with their device.

Objectives/Hypothesis: To investigate the clinical characteristics of benign paroxysmal positional vertigo (BPPV) associated with idiopathic sudden sensorineural hearing loss (ISSHL) and to compare them with the characteristics of idiopathic BPPV (i-BPPV). Study Design: Retrospective case series. Methods: We retrospectively analyzed 519 patients with ISSHL and 597 patients with i-BPPV. The ISSHL patients with recent vertigo history before or after admission were tested with video-nystagmography that included the caloric test. BPPV with same-side ISSHL was identified and categorized as secondary BPPV (s-BPPV) using the roll or Dix-Hallpike test. All members of the s-BPPV and i-BPPV groups underwent a daily canalith repositioning procedure (CRP) during the admission periods. We investigated the clinical characteristics, including the number of CRPs performed to achieve successful reposition, canal involvement type, and effect of canal paresis and made comparisons between the s-BPPV and i-BPPV groups. Results: Of the 519 ISSHL patients, 63 (12.1%) were identified as having s-BPPV. Multicanal involvement was more frequent in s-BPPV than i-BPPV patients (P < .001). The mean number of CRPs needed to achieve successful reposition was 4.28 in s-BPPV and 1.34 in i-BPPV (P < .001). The presence of canal paresis was also associated with a greater number of CRPs required for s-BPPV (P < .02). Conclusions: In about 12% of ISSHL patients, s-BPPV was concurrent. More CRPs were required for successful repositioning in patients with s-BPPV than in patients with i-BPPV. Also, the presence of canal paresis in s-BPPV was associated with a greater number of required CRPs. Laryngoscope, 2012